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Metastases to cranial base meningiomas. Clinical presentations and surgical outcomes. Literature overview.

Tumour-to-meningioma metastasis (TTMM) is an uncommon phenomenon, however repeatedly found in the literature. Meningiomas occur to be the most frequent target of metastatic expansion of systemic cancers. Meningiomas often vary in symptoms and treatment, and this largely depends on the tumour location. Due to their variable locations, they can be classified as convexity meningiomas, which includes falcine and parasagittal tumours, and cranial base, which includes tumours located in the olfactory groove, sphenoid wing, petrous bone and other cranial base locations. The aim of this study was to analyse all data regarding metastases to cranial base meningiomas. We performed a literature search to locate all cases of metastases to cranial base meningiomas in PubMed and Medline databases using the following key words metastasis to meningioma, meningioma metastasis, and cranial base meningioma. We collected patient and cancer parameters, exact meningioma location and clinical presentations including characteristics which may suggest TTMM. We found 100 articles describing 111 patients of metastasis to cranial base meningioma. Among these articles, 55 cases (49.55%) included metastases to non-skull base meningiomas. In 24 cases (21.62%), the location of meningioma was not precisely described or other data were unavailable, in particular histopathological examination. The most common location of TTMM was sphenoid wing, which was found in 9 patients. The other locations included cerebellopontine angle in 5 patients, and tuberculum sellae in 3 cases. 81.25% cases of TTMM were reported in women, and the most common cancer origins were the breast (28.3%), lung (18.7%), kidney (9.38%) and prostate (9.38%). In two cases the metastatic origin was unclear, and in 15.6% of cases the patients were in remission for more than 1 year. In 78.1% of cases patients presented focal deficits, followed by increased intracranial pressure, and seizures. In almost one-third of cases, TTMM first appeared from a previously unknown cancer. Rapid clinical presentation of cranial nerve palsies may suggest the dual nature of intracranial pathology. The metastasis to cranial base meningioma should be suspected in patients with oncological background, regardless of meningioma parameters or cancer status.

Dendronized DNA Chimeras Harness Scavenger Receptors To Degrade Cell Membrane Proteins.

Bispecific chimeras bridging cell membrane proteins with lysosome-trafficking receptors (LTRs) provide an effective therapeutic approach through lysosomal degradation of disease-relevant targets. Here, we report a novel dendronized DNA chimera (DENTAC) strategy that uses a dendritic DNA to engage cell surface scavenger receptors (SRs) as LTR. Using bioorthogonal strain-promoted alkyne-azide cycloaddition to conjugate the dendritic DNA with protein binder, the resulting DENTAC is able to traffic the protein target into the lysosome for elimination. We demonstrated the utility of DENTAC by degrading oncogenic membrane nucleolin (NCL) and epidermal growth factor receptor (EGFR). The anti-cancer application of NCL-targeting DENTAC was validated in a mouse xenograft model of lung cancer. This work thus presents a new avenue for rapid development of potent degraders against membrane proteins, with also broad research and therapeutic prospects.

Synthesis, Antiproliferative Evaluation, and Molecular Docking Study of Novel Longifolene-Derived Tetraline Fused Thiazole-Amide Derivatives.

Twenty novel longifolene-derived tetraline fused thiazole-amide compounds were synthesized from longifolene, a renewable natural resource. Their structures were characterized by FT-IR, NMR, ESI-MS, and elemental analysis. The in vitro antiproliferative activity of these compounds against SK-OV-3 ovarian cancer cell lines, MCF-7 human breast cancer cell lines, HepG2 human liver cancer cell lines, A549 human lung adenocarcinoma cell lines, and T-24 human bladder cancer cell lines was tested by MTT assay. Compounds 6a-6c displayed significant and broad-spectrum antiproliferative activity against almost the tested cancer cell lines with IC

Estimating stage-specific sensitivity for cancer screening tests.

When evaluating potential new cancer screening modalities, estimating sensitivity, especially for early-stage cases, is critical. There are methods to approximate stage-specific sensitivity in asymptomatic populations, both in the prospective (active screening) and retrospective (stored specimens) scenarios. We explored their validity via a simulation study. We fit natural history models to lung and ovarian cancer screening data that permitted estimation of stage-specific (earlylate) true sensitivity, defined as the probability subjects screened in the given stage had positive tests. We then ran simulations, using the fitted models, of the prospective and retrospective scenarios. Prospective sensitivity by stage was estimated as screen-detected divided by screen-plus interval-detected cancers, where stage is defined as stage at detection. Retrospective sensitivity by stage was estimated based on cancers detected within specified windows before clinical diagnosis with stage defined as stage at clinical diagnosis. Stage-specific true sensitivities estimated by the lung cancer natural history model were 47% (early) and 63% (late). Simulation results for the prospective setting gave estimated sensitivities of 81% (early) versus 62% (late). In the retrospective scenario, earlylate sensitivity estimates were 35%57% (1-year window) and 27%49% (2-year window). In the prospective scenario, most subjects with negative early-stage screens presented as other than early-stage interval cases. Results were similar for ovarian cancer, with estimated prospective sensitivity much greater than true sensitivity for early stage, 84% versus 25%. Existing methods for approximating stage-specific sensitivity in both prospective and retrospective scenarios are unsatisfactory improvements are needed before they can be considered to be reliable.

Cancer Cells Employ the Most Prolific RNA Editors A Closer Look at the Single-Cell Level.

Adenosine-to-inosine (A-to-I) RNA editing is a major source of nucleotide diversification that has significant mechanistic implications in cancer progression and treatment response. However, its activity and prevalence have not yet been systematically determined at a single-cell resolution. Chan and colleagues revealed widespread A-to-I RNA editing events in single cancer cells through an in-depth analysis of a public lung adenocarcinoma single-cell transcriptome dataset. Edits significantly enriched in cancer cells compared to other cell types have the potential to inhibit innate immune response and to predict poor therapeutic response and prognosis in patients treated with targeted therapies. See related article by Chan et al., p. 374.

Co-delivery of gemcitabine and paclitaxel plus NanoCpG empowers chemoimmunotherapy of postoperative cold triple-negative breast cancer.

Triple-negative breast cancer (TNBC) due to lack of clear target and notorious cold tumor microenvironment (TME) is one of the most intractable and lethal malignancies. Tuning cold TME into hot becomes an emerging therapeutic strategy to TNBC. Herewith, we report that integrin-targeting micellar gemcitabine and paclitaxel (ATN-mGP, ATN sequence Ac-PhScNK-NH

Balloon kyphoplasty as palliative care for painful pathological spinal fracture followed by lung cancer metastasis A cohort study.

Pathological spine fractures caused by metastases of lung cancer have brought great suffering to patients. Percutaneous kyphoplasty (PKP) has been considered a preferred alternative for painful spinal metastases. The clinical efficacy and safety of PKP for metastatic spinal lesions are urgently to be evaluated. A cohort study was conducted on 54 cases with pathologic spine fractures caused by metastasis of lung cancer. The correction of kyphosis was assessed by the Cobb angle. The life dependence and quality of the patients were evaluated by the Barthel Index of activities of daily living (ADL) and the quality-adjusted life year (QALY). Patients survival was carefully recorded. PKP significantly corrected the kyphosis compared with conservative treatment. The ratio of moderate dependence after fracture was clearly increased by PKP. QALY indicated a better life quality brought by PKP. However, PKP could not improve the survival rate of patients. PKP can be used as an effective palliative care treatment for patients with metastatic pathologic spinal fractures of lung cancer.

A population-based investigation How to identify high-risk T1-2N0 esophageal cancer patients

Newly diagnosed T1-2N0 esophageal cancer (EC) is generally deemed as early local disease, with distant metastases (DM) easily overlooked. This retrospective study aimed to describe the metastatic patterns, identify risk factors and established a risk prediction model for DM in T1-2N0 EC patients. A total of 4623 T1-2N0 EC patients were identified in the Surveillance, Epidemiology and End Results (SEER) database from 2004 to 2018. Multivariable logistic regression was used to identify risk factors for DM. A nomogram was developed for presentation of the final model. Of 4623 T1-2N0 patients, 4062 (87.9%) had M0 disease and 561 (12.1%) had M1 disease. The most common metastatic site was liver ( We identified independent predictive factors for DM, as well as for BoM, BrM, LiM and LuM. Above all, a practical and convenient nomogram with a great accuracy to predict DM probability for T1-2N0 EC patients was established.

Remote Adipose Tissue-Derived Stromal Cells of Patients with Lung Adenocarcinoma Generate a Similar Malignant Microenvironment of the Lung Stromal Counterpart.

Cancer alters both local and distant tissue by influencing the microenvironment. In this regard, the interplay with the stromal fraction is considered critical as this latter can either foster or hamper the progression of the disease. Accordingly, the modality by which tumors may alter distant niches of stromal cells is still unclear, especially at early stages. In this short report, we attempt to better understand the biology of this cross-talk. In our autologous stromal experimental setting, we found that remote adipose tissue-derived mesenchymal stem cells (mediastinal AMSC) obtained from patients with lung adenocarcinoma sustain proliferation and clonogenic ability of A549 and human primary lung adenocarcinoma cells similarly to the autologous stromal lung counterpart (LMSC). This effect is not observed in lung benign diseases such as the hamartochondroma. This finding was validated by conditioning benign AMSC with supernatants from LAC for up to 21 days. The new reconditioned media of the stromal fraction so obtained, was able to increase cell proliferation of A549 cells at 14 and 21 days similar to that derived from AMSC of patients with lung adenocarcinoma. The secretome generated by remote AMSC revealed overlapping to the corresponding malignant microenvironment of the autologous local LMSC. Among the plethora of 80 soluble factors analyzed by arrays, a small pool of 5 upregulated molecules including IL1-

Delayed Presentation of Air Embolism Within Cerebral Arteries Following Computed Tomography-Guided Lung Biopsy.

Computed tomography (CT)-guided percutaneous core needle biopsy of the lung is a frequently performed interventional radiological procedure. Most complications are minor and self-resolving. However, a rare but potentially fatal complication is that of systemic air embolism, especially when to the cerebral or coronary arteries. This study reports a case of delayed (12 hours after initial biopsy) air embolism in the cerebral arteries that resulted from an otherwise uncomplicated biopsy of a lung nodule. It is vital for early diagnostic confirmation and appropriate treatment if possible, though maximal efforts at prevention are still recommended.

Development of a Novel Predictive-Prognostic Scoring Index for Immune Checkpoint Inhibitors in Advanced Non-small Cell Lung Cancer.

Immune checkpoint inhibitors (ICIs) have become the standard of care for the treatment of patients with driver mutation absent advanced non-small cell lung cancer (NSCLC). The present study aimed to develop a reliable, reproducible, and practical scoring system to prognosticate and predict response to ICI response in patients with advanced NSCLC. All patients who were diagnosed as having unresectableadvanced stage NSCLC and were treated with at least one cycle of ICIs at the Medical Oncology Departments of Dr. Burhan Nalbantoğlu State Hospital (Nicosia, Cyprus) and Near East University Hospital (Nicosia, Cyprus) were included in the study. The association between variables and OS was evaluated using a Cox proportional hazards regression model. Variables with a P-value less than 0.05 in the univariate analysis were included in the multivariate model. A prognostic scoring system was developed.  Survival estimates were calculated using the Kaplan-Meier method. The value of the Concordance index (C-index) and the area under the curve (AUC) was used to evaluate the discriminative ability of scoring systems. One hundred fifty consecutive patients with unresectablemetastatic NSCLC who received PD-1 inhibitors between March 2017 and November 2022 were included. In the multivariate Cox regression model, serum lactate dehydrogenase (LDH), C-reactive protein (CRP) levels, and Eastern Cooperative Oncology Group Performance Status (ECOG PS) were significantly associated with OS. We generated a new score using CRP ³1.0 mgdL, ECOG PS ³2, and LDH level >ULN. Relative weight was based on the HRs of multivariate analyses (CRP ³1.0 mgdL 2 points, ECOG PS ³2 2.5 points, and LDH level >ULN 1.5 points). The cohort was divided into three risk groups based on the sum of factors present 0-2.5 (good risk), 3.5-4.5 (intermediate risk), or 6 (poor risk). The median OS was 18.9, 7.4, and 2.9 months for good, intermediate, and poor risk categories, respectively (log-rank test, p<0.001). The Harrell C-index of CEL to predict OS and PFS was 0.73 and 0.69, respectively, indicating significant predictability. The AUC of the scoring index for predicting the responses was 0.765 (95% CI 0.685-0.845). The CEL score is a promising prognostic and predictive index consisting of serum CRP levels (C), ECOG PS (E), and serum LDH levels (L). This represents another step forward in the treatment of patients with advanced NSCLC.

Cross-talk between cuproptosis and ferroptosis regulators defines the tumor microenvironment for the prediction of prognosis and therapies in lung adenocarcinoma.

Cuproptosis, a newly identified form of programmed cell death, plays vital roles in tumorigenesis. However, the interconnectivity of cuproptosis and ferroptosis is poorly understood. In our study, we explored genomic alterations in 1162 lung adenocarcinoma (LUAD) samples from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) cohort to comprehensively evaluate the cuproptosis regulators. We systematically performed a pancancer genomic analysis by depicting the molecular correlations between the cuproptosis and ferroptosis regulators in 33 cancer types, indicating cross-talk between cuproptosis and ferroptosis regulators at the multiomic level. We successfully identified three distinct clusters based on cuproptosis and ferroptosis regulators, termed CuFeclusters, as well as the three distinct cuproptosisferroptosis gene subsets. The tumor microenvironment cell-infiltrating characteristics of three CuFeclusters were highly consistent with the three immune phenotypes of tumors. Furthermore, a CuFescore was constructed and validated to predict the cuproptosisferroptosis pathways in individuals and the response to chemotherapeutic drugs and immunotherapy. The CuFescore was significantly associated with the expression of miRNA and the regulation of post-transcription. Thus, our research established an applied scoring scheme, based on the regulators of cuproptosisferroptosis to identify LUAD patients who are candidates for immunotherapy and to predict patient sensitivity to chemotherapeutic drugs.

Natural killer cells suppress cancer metastasis by eliminating circulating cancer cells.

Despite significant advances in cancer treatment, the metastatic spread of malignant cells to distant organs remains a major cause of cancer-related deaths. Natural killer (NK) cells play a crucial role in controlling tumor metastasis however, the dynamics of NK cell-mediated clearance of metastatic tumors are not entirely understood. Herein, we demonstrate the cooperative role of NK and T cells in the surveillance of melanoma metastasis. We found that NK cells effectively limited the pulmonary seeding of B16 melanoma cells, while T cells played a primary role in restricting metastatic foci growth in the lungs. Although the metastatic foci in the lungs at the endpoint were largely devoid of NK cells, they played a prominent role in promoting T cell recruitment into the metastatic foci. Our data suggested that the most productive interaction between NK cells and metastatic cancer cells occurred when cancer cells were in circulation. Modifying the route of administration so that intravenously injected melanoma cells bypass the first liver passage resulted in significantly more melanoma metastasis to the lung. This finding indicated the liver as a prominent site where NK cells cleared melanoma cells to regulate their seeding in the lungs. Consistent with this notion, the liver and the lungs of the tumor-bearing mice showed dominance of NK and T cell activation, respectively. Thus, NK cells and T cells control pulmonary metastasis of melanoma cells by distinct mechanisms where NK cells play a critical function in shaping T cell-mediated

The lung, the niche, and the microbe Exploring the lung microbiome in cancer and immunity.

The lung is a complex and unique organ system whose biology is strongly influenced by environmental exposure, oxygen abundance, connection to extrapulmonary systems

Identification and validation of a muscle failure index to predict prognosis and immunotherapy in lung adenocarcinoma through integrated analysis of bulk and single-cell RNA sequencing data.

It was previously reported that the production of exerkines is positively associated with the beneficial effects of exercise in lung adenocarcinoma (LUAD) patients. This study proposes a novel scoring system based on muscle failure-related genes, to assist in clinical decision making. A comprehensive analysis of bulk and single cell RNA sequencing (scRNA-seq) of early, advanced and brain metastatic LUAD tissues and normal lung tissues was performed to identify muscle failure-related genes in LUAD and to determine the distribution of muscle failure-related genes in different cell populations. A novel scoring system, named MFI (Muscle failure index), was developed and validated. The differences in biological functions, immune infiltration, genomic alterations, and clinical significance of different subtypes were also investigated. First, we conducted single cell analysis on the dataset GSE131907 and identified eight cell subpopulations. We found that four muscle failure-related genes (BDNF, FNDC5, IL15, MSTN) were significantly increased in tumor cells. In addition, IL15 was widely distributed in the immune cell population. And we have validated it in our own clinical cohort. Then we created the MFI model based on 10 muscle failure-related genes using the LASSO algorithm, and MFI remained an independent prognostic factor of OS in both the training and validation cohorts. Moreover, we generated MFI in the single-cell dataset, in which cells with high MFI received and sent more signals compared to those with low MFI. Biological function analysis of both subtypes revealed stronger anti-tumor immune activity in the low MFI group, while tumor cells with high MFI had stronger metabolic and proliferative activity. Finally, we systematically assessed the immune cell activity and immunotherapy responses in LUAD patients, finding that the low MFI group was more sensitive to immunotherapy. Overall, our study can improve the understanding of the role of muscle failure-related genes in tumorigenesis and we constructed a reliable MFI model for predicting prognosis and guiding future clinical decision making.

Definitive intensity modulated proton re-irradiation for lung cancer in the immunotherapy era.

As immunotherapy has improved distant metastasis-free survival (DMFS) in Non-Small Cell Lung Cancer (NSCLC), isolated locoregional recurrences have increased. However, management of locoregional recurrences can be challenging. We report our institutional experience with definitive intent re-irradiation using Intensity Modulated Proton Therapy (IMPT). Retrospective cohort study of recurrent or second primary NSCLC or LS-SCLC treated with IMPT. Kaplan-Meier method and log-rank test were used for time-to-event analyses. 22 patients were treated from 2019 to 2021. After first course of radiation (median 60 Gy, range 45-70 Gy), 45% received adjuvant immunotherapy. IMPT re-irradiation began a median of 28.2 months (8.8-172.9 months) after initial radiotherapy. The median IMPT dose was 60 GyE (44-60 GyE). 36% received concurrent chemotherapy with IMPT and 18% received immunotherapy after IMPT. The median patients IMPT lung mean dose was 5.3 GyE (0.9-13.9 GyE) and 5 patients had cumulative esophagus max dose >100 GyE with 1-year overall survival (OS) 68%, 1-year local control 80%, 1-year progression free survival 45%, and 1-year DMFS 60%. Higher IMPT (HR 1.4 95% CI 1.1-1.7, p0.01) and initial radiotherapy mean lung doses (HR 1.3 95% CI 1.0-1.6, p0.04) were associated with worse OS. Two patients developed Grade 3 pneumonitis or dermatitis, one patient developed Grade 2 pneumonitis, and seven patients developed Grade 1 toxicity. There were no Grade 4 or 5 toxicities. Definitive IMPT re-irradiation for lung cancer can prolong disease control with limited toxicity, particularly in the immunotherapy era.

Cuproptosis-related lncRNA signatures Predicting prognosis and evaluating the tumor immune microenvironment in lung adenocarcinoma.

Cuproptosis, a unique kind of cell death, has implications for cancer therapy, particularly lung adenocarcinoma (LUAD). Long non-coding RNAs (lncRNAs) have been demonstrated to influence cancer cell activity by binding to a wide variety of targets, including DNA, RNA, and proteins. Cuproptosis-related lncRNAs (CRlncRNAs) were utilized to build a risk model that classified patients into high-and low-risk groups. Based on the CRlncRNAs in the model, Consensus clustering analysis was used to classify LUAD patients into different subtypes. Next, we explored the differences in overall survival (OS), the tumor immune microenvironment (TIME), and the mutation landscape between different risk groups and molecular subtypes. Finally, the functions of LINC00592 were verified through Patients in various risk categories and molecular subtypes showed statistically significant variations in terms of OS, immune cell infiltration, pathway activity, and mutation patterns. Cell experiments revealed that LINC00592 knockdown significantly reduced LUAD cell proliferation, invasion, and migration ability. The development of a trustworthy prediction model based on CRlncRNAs may significantly aid in the assessment of patient prognosis, molecular features, and therapeutic modalities and may eventually be used in clinical applications.

CCKAR is a biomarker for prognosis and asynchronous brain metastasis of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the most common histological type of lung cancer, and brain metastasis (BM) is the most lethal complication of NSCLC. The predictive biomarkers and risk factors of asynchronous BM are still unknown. A total of 203 patients with NSCLC were enrolled into our cohort and followed up. The clinicopathological factors such as tumor size, T stage, lymphatic invasion, metastasis and asynchronous BM were investigated. CCKAR expression in NSCLC and resected BM was assessed by IHC, and CCKAR mRNAs in NSCLC and para-tumor tissues were estimated by qRT-PCR. The correlations between CCKAR expression, BM and other clinicopathological factors were assessed by chi-square test, and prognostic significance of CCKAR was estimated by univariate and multivariate analyses. CCKAR was highly expressed in NSCLC tissues compared with para-tumor tissues. CCKAR expression in NSCLC was significantly associated with asynchronous BM. The BM percentages for NSCLC patients with low and high CCKAR were surprisingly 5.2% and 66.6%, respectively. CCKAR expression and BM were unfavorable factors predicting unfavorable outcome of NSCLC. Moreover, CCKAR expression in NSCLC was an independent risk factor of asynchronous BM. CCKAR is a prognostic biomarker of NSCLC. CCKAR expression in NSCLC is positively associated with asynchronous BM, and is a risk factor of asynchronous BM from NSCLC.

Metabolomics profiling in prediction of chemo-immunotherapy efficiency in advanced non-small cell lung cancer.

To explore potential metabolomics biomarker in predicting the efficiency of the chemo-immunotherapy in patients with advanced non-small cell lung cancer (NSCLC). A total of 83 eligible patients were assigned to receive chemo-immunotherapy. Serum samples were prospectively collected before the treatment to perform metabolomics profiling analyses under the application of gas chromatography mass spectrometry (GC-MS). The key metabolites were identified using projection to latent structures discriminant analysis (PLS-DA). The key metabolites were used for predicting the chemo-immunotherapy efficiency in advanced NSCLC patients. Seven metabolites including pyruvate, threonine, alanine, urea, oxalate, elaidic acid and glutamate were identified as the key metabolites to the chemo-immunotherapy response. The receiver operating characteristic curves (AUC) were 0.79 (95% CI 0.69-0.90), 0.60 (95% CI 0.48-0.73), 0.69 (95% CI 0.57-0.80), 0.63 (95% CI 0.51-0.75), 0.60 (95% CI 0.48-0.72), 0.56 (95% CI 0.43-0.67), and 0.67 (95% CI 0.55-0.80) for the key metabolites, respectively. A binary logistic regression was used to construct a combined biomarker model to improve the discriminating efficiency. The AUC was 0.86 (95% CI 0.77-0.94) for the combined biomarker model. Pathway analyses showed that urea cycle, glucose-alanine cycle, glycine and serine metabolism, alanine metabolism, and glutamate metabolism were the key metabolic pathway to the chemo-immunotherapy response in patients with advanced NSCLC. Metabolomics analyses of key metabolites and pathways revealed that GC-MS could be used to predict the efficiency of chemo-immunotherapy. Pyruvate, threonine, alanine, urea, oxalate, elaidic acid and glutamate played a central role in the metabolic of PD patients with advanced NSCLC.

Identification of KIT and BRAF mutations in thyroid tissue using next-generation sequencing in an Ecuadorian patient A case report.

The incidence of thyroid cancer has increased worldwide. Ecuador presents the highest incidence among Latin American countries and the second around the world. Genetic alteration is the driving force for thyroid tumorigenesis and progression. The change from valine (V) to glutamic acid (E) at codon 600 of the BRAF gene (BRAF A woman in her early fifties, self-identified as mestizo, from Otavalo, Imbabura-Ecuador had no systemic diseases and denied allergies, but she had a family history of a benign thyroid nodule. Physical examination revealed a thyroid gland enlargement. The fine-needle aspiration biopsy indicated papillary thyroid cancer. The patient underwent a successful total thyroidectomy with an excellent recovery and no additional treatments after surgery. Using Next-Generation sequencing a heterozygous mutation in the BRAF gene, causing an amino acid change Val600Glu was identified. Similarly, in the KIT gene, a heterozygous mutation resulting in an amino acid change Leu678Phe was detected. Moreover, an ancestry analysis was performed, and the results showed 3.1% African, 20.9% European, and 76% Native American ancestry. This report represents the genetic characteristics of papillary thyroid cancer in an Ecuadorian woman with a mainly Native American ethnic component. Further studies of pathological variants are needed to determine if the combined demographic and molecular profiles are useful to develop targeted treatments focused on the Ecuadorian population.

Arrhythmogenic superior vena cava manifesting after a right-sided pneumonectomy and mediastinal lymph node dissection.

No case of AF ablation after right-sided pneumonectomy has been reported, presumably because the pneumonectomy renders the ablation procedure more difficult than lobectomy because of the marked mediastinal displacement. In the case of catheter ablation of AF after right-sided pneumonectomy, it is extremely important to insert a mapping catheter not only into the PV but also into the SVC to accurately diagnose the site of abnormal electrical activity.

Protein-energy malnutrition and worse outcomes after major cancer surgery A nationwide analysis.

Protein-energy malnutrition (PEM) has been recognized as a poor prognostic factor in many clinical issues. However, nationwide population studies concerning the impact of PEM on outcomes after major cancer surgery (MCS) are lacking. We aimed to evaluate the postoperative outcomes associated with PEM following MCS. By using the Nationwide Inpatient Sample database, data of patients undergoing MCS including colectomy, cystectomy, esophagectomy, gastrectomy, hysterectomy, lung resection, pancreatectomy, or prostatectomy were analyzed retrospectively from 2009 to 2015, resulting in a weighted estimate of 1,335,681 patients. The prevalence trend of PEM, as well as mortality and major complications after MCS were calculated. Multivariable regression analysis was applied to estimate the impact of PEM on postoperative outcomes after MCS. PEM showed an estimated annual percentage increase of 7.17% (95% confidence interval (CI) 4-10.44%) from 2009 to 2015, which contrasts with a 4.52% (95% CI -6.58-2.41%) and 1.21% (95% CI -1.85-0.56%) annual decrease in mortality and major complications in patients with PEM after MCS. PEM was associated with increased risk of mortality (odds ratio (OR)2.26 95% CI 2.08-2.44 P < 0.0001), major complications (OR2.46 95% CI 2.36-2.56 P < 0.0001), higher total cost ($35814 $22292, $59579 vs. $16825 $11393, $24164, P < 0.0001), and longer length of stay (14 9-21 days vs. 4 2-7 days, P < 0.0001), especially in patients underwent prostatectomy, hysterectomy and lung resection. PEM was associated with increased worse outcomes after major cancer surgery. Early identification and timely medical treatment of PEM for patients with cancer are crucial for improving postoperative outcomes.

MicroRNAs improve cancer treatment outcomes through personalized medicine.

MicroRNAs (miRNAs) are short non-coding RNAs that repress or degrade mRNA targets to downregulate genes. In cancer occurrence, the expression of miRNAs is altered. Depending on the involvement of a certain miRNA in the pathogenetic growth of a tumor, It may be up or downregulated. The oncogenic action of miRNAs corresponds with upregulation, which leads to tumor proliferation and spread meanwhile the miRNAs that have been downregulated bring tumor-suppressive outcomes. Oncogenes and tumor suppressor genes are among the genes whose expression is under their control, demonstrating that classifying them solely as oncogenes or tumor suppressor genes alone is not only hindering but also incorrect. Apart from basic tumors, miRNAs may be found in nearly all human fluids and can be used for cancer diagnosis as well as clinical outcome prognostics and better response to treatment strategies. The overall variance of these tiny non-coding RNAs influences patient-specific pharmacokinetics and pharmacodynamics of anti-cancer medicines, driving a growing demand for personalized medicine. By now, microRNAs from tumors biopsies or blood are being widely investigated as substantial biomarkers for cancer in time diagnosis, prognosis, and, progression. With the rise of COVID-19, this paper also attempts to study recent research on miRNAs involved with deaths in lung cancer COVID patients. With the discovery of single nucleotide polymorphisms, personalized treatment via microRNAs has lately become a reality. The present review article describes the highlights of recent knowledge of miRNAs in various cancers, with a focus on miRNA translational applications as innovative potential diagnostic and prognostic indicators that expand person-to-person therapy options.

A Case of Multiple Lung Metastases of Pancreatic Cancer with 50 Months Survival by Sequential Chemotherapy.

We hereby report a case in which a patient with multiple lung metastases of pancreatic cancer continued chemotherapy and maintained good performance status(PS)for 48 months after recurrence. But her disease progressed rapidly after withdrawal of chemotherapy, resulting in her death in a short period of time. The patient was a 66-year-old woman who underwent a substomach preserving pancreaticoduodenectomy for pancreatic head cancer at the age of 60 years. She was diagnosed as fT3N1M0, fStage ⅡB. During postoperative adjuvant chemotherapy S-1, multiple lung metastases were noted on CT scan 2 years after surgery. Thereafter, she was treated with gemcitabine(GEM)alone, GEM plus nab-paclitaxel(GnP), nal-CPT-11 plus 5-FU plus Leucovorin, and FOLFIRINOX for 48 months sequentially. Each of which achieved a best overall response SD or better. However, Trousseau syndrome developed following community-acquired pneumonia during chemotherapy withdrawal due to myelosuppression. The disease progressed rapidly and resulted in her death 50 months after relapse. The results suggest that chemotherapy may have contributed significantly to disease control in this case.

A Case of Hypertrophic Pulmonary Osteoarthropathy Associated with Pulmonary Pleomorphic Carcinoma.

Hypertrophic pulmonary osteoarthropathy(HPO)is a tumor-associated syndrome that features the triad of clubbed fingers, periosteal bone growth in long bones, and arthritis, and is often associated with an adenocarcinoma or squamous cell carcinoma. This report presents details of a case of HPO associated with pleomorphic carcinoma, which was relieved by treatment. A 47-year-old woman was presented with a complaint of generalized arthralgia. A physical examination showed swollen joints in the body and clubbed fingers. Chest CT revealed a mass shadow in the left upper lobe and ultrasound- guided biopsy findings led to a diagnosis of non-small cell lung cancer. Furthermore, bone scintigraphy indicated symmetrical accumulation in bones and joints throughout the body. A right upper lobectomy was performed along with combined chest wall resection and mediastinal lymph node dissection with an open chest, and the presence of lung cancer complicated with HPO was indicated. Pathological examination results revealed a diagnosis of pleomorphic carcinoma(pT4N0M0, Stage ⅢA). Systemic arthralgia was resolved on the first postoperative day. One year after surgery, a solitary brain metastasis developed and was removed, with no recurrence at the time of writing. Joint symptoms related to HPO can be expected to improve with treatment of pulmonary lesions, thus aggressive procedures for diagnosis and treatment are desirable.

A Case of Drug-Induced Interstitial Pneumonia after Dose-Dense AC Therapy.

The patient is a 67-year-old female. She was diagnosed with left breast cancer cT2N1M0, Stage ⅡB, Luminal B-like, and was desided dose-dense AC therapy(ddAC)plus dose-dense paclitaxel therapy(ddPTX)as preoperative chemotherapy. After completing 4 courses of ddAC and visiting to start the first course of ddPTX, she presented with symptoms of fatigue and shortness of breath on exertion. Chest X-ray showed no abnormality and echocardiography showed decreased left ventricular wall motion, leading to a diagnosis of doxorubicin-induced cardiac dysfunction. Preoperative chemotherapy was discontinued and surgery was decided. Two weeks later, CT imaging was performed for preoperative evaluation, which showed the appearance of diffuse pale ground-glass opacity in the bilateral lung fields, and a diagnosis of drug-induced interstitial pneumonia was made. After 3 weeks of steroid treatment, the symptoms improved and the ground-glass opacity disappeared on CT imaging. We were keenly aware that interstitial pneumonia can develop with pale ground-glass opacity that is difficult to diagnose without CT imaging, and that the need for CT should always be considered.

Successful Treatment with TACE and RFA for a Hepatocellular Carcinoma Case with Lung Metastasis.

We report a hepatocellular carcinoma(HCC)case with lung metastasis that was successfully treated with transarterial chemoembolization(TACE)and percutaneous radiofrequency ablation(RFA). A man in his 60s took right robe liver resection for HCC after TACE for its rupture. Lung metastasis occurred at S12 and S6 in the left lung, and an adverse event interrupted standard molecular target therapies. Because extrahepatic metastasis had been seen only in these two locations for a long time, TACE was performed for both metastases. The feeders for both lesions were each intercostal artery, and controlling the drug inflow was necessary to avoid drug influx into the spinal cord branches when S6 metastasis was treated. The viable lesion remained in the S6 lesion, so RFA was added for both lung metastases. 100% tumor necrosis has been observed since the RFA.

A Case of Successful Collective Treatment of Rectal Cancer Diagnosed by Liver Abscess.

A 67-year-old woman was found to have multiple liver abscess and pneumonia. Liver abscess was improved after percutaneous transhepatic abscess drainage(PTAD). A diagnosis of rectal cancer was made by colonoscopy and the patient underwent colostomy for rectal cancer on February 2018. Laparoscopic low anterior resection was performed on July 2019 after mFOLFOX plus bevacizumab(BEV)14 courses. Lower leaf partial lung resection was performed on September 2019 and upper leaf partial resection was performed on September 2020 for lung metastasis. The patient is currently alive without relapse after 21 months. Liver abscess was caused by portal vein infection of rectal cancer. Effective chemotherapy with surgery was successful.

Surgical Resection of Pulmonary Oligometastases of Ampullary Cancer-A Case Report and Review of Seven Cases.

A 62-year-old woman underwent a subtotal stomach-preserving pancreatoduodenectomy for ampullary carcinoma (T3bN0M0, Stage Ⅱb). Histopathologically, the tumor was a tubular adenocarcinoma with mixed features, predominantly the intestinal type, following which adjuvant chemotherapy was not performed. Computed tomography performed 32 months after surgery showed a tumor measuring 6.7 mm in diameter at the apex of the right lung. The tumor had gradually increased in size and measured 10 mm in diameter, 47 months postoperatively. Since other metastatic lesions were absent, partial resection of the right lung under video-assisted thoracic surgery was performed 48 months postoperatively. Histopathological testing confirmed a diagnosis of lung metastasis from the resected specimen of ampullary carcinoma without mediastinal lymph node metastasis. Adjuvant chemotherapy was not performed, and recurrence was not observed even after 53 months following the partial lung resection. Previously, 7 resected cases of solitary lung metastasis from ampullary cancer have been reported. The histopathological sub-type of these 7 cases were intestinal type in 5 and pancreatobiliary type in 2 cases, respectively. No mortality or recurrence was observed for 8-119 months in any of the 7 cases(median, 19 months). In conclusion, owing to the good prognosis, solitary lung metastasis from an ampullary cancer can be classified as an oligometastatic disease, based on the concept proposed by Hellman and Weichselbaum.

Two Cases of Elderly Patients with Giant Intrahepatic Cholangiocarcinoma Treated with Multidisciplinary Therapy including Ablation Therapy.

Case 1 consisted of an 86-year-old male diagnosed with intrahepatic cholangiocarcinoma(ICC), approximately 11 cm in diameter, at segment S78 of the liver. A total of 4 percutaneous radiofrequency ablations(PRFA)and 3 hepatic arterial infusion chemotherapies(HAIC)of 5-FU were performed. He died after developing lung metastases 27 months after the initial treatment. Case 2 was an 85-year-old female diagnosed with ICC, 8 cm in diameter, at the posterior segment of the liver, with lymph node metastasis. She underwent HAIC of 5-FU and S-1 as well as gemcitabine-based systemic chemotherapy. The main tumor developed 10 months after the initial treatment, and PRFAs were subsequently performed twice for the main lesion. Although the tumor markers gradually decreased, she died of jaundice 33 months after the initial treatment. As one of the multidisciplinary therapies for the giant ICC, ablation therapy may be safe and effective in elderly patients.

A Case of Advanced Breast Cancer in Which Mohs Paste and Systemic Drug Therapy Allowed Local and Disease Control.

Local control of disintegrating advanced breast cancer is often difficult because of the exudate, bleeding, and the foul odor. The current author encountered a case of large breast cancer with ulceration in which drug therapy and local control with Mohs paste allowed disease control. The patient was a 61-year-old woman. There was a large ulcerated lump in her right breast, and exudate, bleeding, and a foul odor were present. The woman was diagnosed with hormone-sensitive mucinous carcinoma based on a biopsy, and diagnostic imaging revealed axillary lymph node metastasis and multiple metastases in both lungs. Mohs paste was used locally, and local control was achieved after 1 month. A year and a half after the start of systemic drug therapy, the breast lump disappeared, and lung metastases and lymph node metastasis had almost disappeared. A CR has been maintained 3 years and 5 months later. Mohs paste was extremely useful in achieving local control of exudation and bleeding from exposed unresected cancer. This was an excellent treatment in the patients terminal stages and as part of local treatment in combination with systemic drug therapy.

A Case of Pancreatic Invasive Micropapillary Carcinoma That Survived Seven Years after Resection and Chemotherapy.

We present the case of a 47-year-old man who underwent a subtotal stomach-preserving pancreaticoduodenectomy for pancreatic head cancer. Histopathological diagnosis revealed that the majority of the cancer was an invasive micropapillary carcinoma(IMPC). Postoperative adjuvant chemotherapy using S-1 was continued for 4 years, at the end of which, multiple lymph node metastases were identified. Therefore, gemcitabine plus S-1 therapy was initiated. The treatment reduced the lymph node in size and resulted in the maintenance of a partial response for a year and a half. However, increased lymph node metastases recurred, and multiple lung metastases were noted. The patient died 7 years and 2 months after the resection of the primary lesion. Although pancreatic IMPC has a poor prognosis, long-term survival may be achieved by resection of the primary region, the administration of adjuvant chemotherapy and management of recurrent lesions by chemotherapy.

Long-Term Survival of a Patient with Hepatocellular Carcinoma after Surgical Resection of Metachronous Hilar Lymph Node Metastases.

The recurrence of hepatocellular carcinoma(HCC)is primarily due to intrahepatic metastases. Additionally, extrahepatic HCC metastases most commonly occurs in the lungs, lymph nodes, adrenal glands, and bones. Systemic chemotherapy is the standard treatment for extrahepatic metastases. Although several reports on surgical resection of lymph node metastases (LNM) in patients with HCC have been published, its clinical benefits remain controversial. We report a case in which surgical resection of LNM was performed in a patient with HCC. The patient was a 74-year-old woman diagnosed with HCC and non-B non-C chronic hepatitis, for which she underwent a laparoscopic partial hepatectomy. The pathological diagnosis was St-A, 1.6×1.4 cm, confluent multinodular type, pT1N0M0, fStage Ⅰ. Nine months later, 2 LNM on the liver hilum were detected and managed with sorafenib. Sorafenib was discontinued after 2 months due to the development of Grade 3 hand-foot syndrome. Since no new lesions were detected on follow-up, lymph node resection was performed. The patient remains disease-free 4.5 years postoperatively.

A Case of Rectal Cancer with Protein-Losing Gastroenteropathy.

We report a case receiving laparoscopic surgical resection of rectal cancer with protein-losing gastroenteropathy. A 58- year-old man was referred to our hospital because of melena, diarrhea, and anorexia. He showed septic shock, anemia, and hypoproteinemia. CT scan showed a rectal tumor with regional lymph node swelling and a cavernous lung lesion with a pulmonary embolus. Ninety-five days after admission to intensive care, he was introduced to our department because of the disappearance of a lung lesion indicating a lung abscess. Colonoscopy showed a cauliflower-like type 1 rectal cancer lesion. He experienced laparoscopic low anterior resection 121 days after admission. He was discharged without problems 66 days after the operation. After 8 months of surgery and no chemotherapy, he had no recurrence of rectal cancer. Colon cancer with protein-losing gastroenteropathy is rare and shows a typical cauliflower-like type 1 tumor appearance. Hypoproteinemia can be improved after resection of colon cancer.

A Case of Long-Term Survival by Multidisciplinary Surgical Treatment for Metastatic Multi-Organ Metastasis after Radical Resection of Esophageal Cancer.

A 78-year-old man with advanced thoracic esophageal cancer underwent radical esophagectomy after neoadjuvant chemotherapy with cisplatin plus 5-FU. He had left adrenal metastasis 10 months after surgery and removed it, but 3 months later he had liver metastases. After 2 courses of chemotherapy with nedaplatin plus 5-FU, resection was performed. One course of nedaplatin plus 5-FU for adjuvant chemotherapy was added, but the patient was followed up without another chemotherapy after surgery because of intestinal obstruction due to infection and increase of the lymphatic cyst in the abdominal cavity. Six months after the liver resection, nodules appeared in the right lung, and 4 months later, multiple nodules extending to both lungs were observed. Therefore, it was judged that there were multiple lung metastases, and administration of nivolumab was started. He has been 3 years since the recurrence of esophageal cancer and 17 months after the start of nivolumab administration, but the recurrence lesion is only progressing to lung metastasis.

A Resected Case of Mesenteric Nodal Metastases from Small Cell Lung Carcinoma.

A 65-year-old woman with small cell lung carcinoma(T2N2M0, Stage ⅢA)underwent chemoradiation therapy. During the follow-up study after the partial response of chemoradiation therapy, the serum level of ProGRP was elevated. X-ray computed tomography(CT)showed a 8 cm long mesenteric mass adjacent to ileocecal vessels, which indicated high level of standardized uptake value(SUV)max(12.6)by fluorodeoxyglucose-positron emission tomographycomputed tomography( FDG-PETCT). No gastrointestinal malignancy was observed. Mesenteric nodal metastasis from lung carcinoma was primarily diagnosed, however, possible malignant lymphoma was differentiated. Surgical resection was planned as a diagnostic treatment, thus laparoscopic ileocecal resection was performed. The resected specimen presented a fused mass of several lymph nodes. Histopathology found consistent with mesenteric nodal metastases from small cell lung carcinoma. After surgery, adjuvant chemotherapy was administered. Spontaneous metastasis in the mesenteric lymph node from lung cancer is extremely rare. A case report and a review of the literature is presented.

Eight Cases of Breast Cancer That Relapsed More Than Ten Years after Initial Treatment.

Recurrence is more common for breast cancer than other solid tumors. In the last 5 years, we experienced 8 cases that relapsed more than 10 years after initial treatment. All cases were hormone-sensitive and HER2-negative. The Ki-67 percentage score was less than 15% in 7 cases. The age range at recurrence was 56-93 years(mean, 74.6 years), and the time to recurrence was 10-14 years and 20 or more years in 6 and 2 cases(mean, 14.6 years), respectively. The triggers for diagnosis were subjective symptoms, follow-up, and examination for other diseases in 3, 3, and 2 cases, respectively. The recurrence sites included the axilla, pleuralung, liverlung, skin, and chest wall in 3, 2, 1, 1, and 1 case, respectively. Treatment included an aromatase inhibitor(AI)and AI plus CDK46 inhibitor in 5 and 3 cases, respectively. The post-recurrence treatment period was 6-31 months(mean, 21.6 months), with 4 cases of PR, 3 cases of SD, and 1 case of death from other disease. There were 3 cases of axillary recurrence and 1 case each of neuropathic pain, upper limb edema, and local pain all were alleviated by the treatment. In 2 cases, the pleural effusion decreased without chest tube drainage. Hormone receptor- positive late-relapse cases are generally highly therapeutically sensitive with favorable prognosis. In many cases, AI alone was selected considering patient age, side effects, treatment costs, and other factors.

A Case of De Novo Stage Ⅳ Her2-Positive Breast Cancer with Cardiac Tamponade Caused by Cancerous Pericarditis.

The patient was a 58-year-old woman. She was diagnosed with cT4b, cN3c, cM1, cStage Ⅳ, Her2 positive breast cancer with liver, lung and bone metastases. Seven days after the first visit, she came to our hospital for dyspnea. Chest X-ray, chest CT, and echocardiography showed a decrease in EF to 50.6% due to a large amount of pericardial effusion, and she was diagnosed with cardiac tamponade. On the same day, pericardial drainage was performed urgently. The cytopathology of pericardial fluid was malignant, that is to say, she was diagnosed with cancerous pericarditis. Pericardial drainage relieved respiratory distress, and echocardiography showed disappearance of pericardial fluid and improvement of EF up to 80.4%. Docetaxel plus trastuzumab plus pertuzumab therapy was started 10 days after pericardial drainage as first-line treatment. After starting chemotherapy, the response has continued for 6 months without re-accumulation of pericardial fluid.

Two Cases of Stage Ⅳ Colorectal Cancer with Long-Term Survival following Single-Agent Chemotherapy with Capecitabine-A Case Reports.

We experienced 2 cases of Stage Ⅳ colorectal cancer obtained long-term survival by chemotherapy with only capecitabine. Case 1 Seventy-one-years-old male was performed open sigmoid colectomy, D2 dissection for sigmoid colon cancer. Pathological diagnosis was pT4aN2aM0, pStage Ⅲc. Capecitabine plus oxaliplatin(CAPOX)was performed as adjuvant chemotherapy for 6 months consequently. Two-years after operation, peritoneal dissemination was found, and CAPOX plus bevacizumab(BEV)was started. Due to appearance of renal disfunction and proteinuria, only capecitabine was continued. Since then, 60 months have been passed without disease progression. Case 2 Seventy-six-years-old female was diagnosed as ascending colon cancer with multiple lung metastases. She had initially given systematic chemotherapy with CAPOX plus BEV. Grade 2 adverse effect(numbness and diarrhea)appeared, then the chemotherapy was discontinued. Seven months later, bowel obstruction due to tumor growth was appeared, and open right-hemi colectomy, with D3 dissection was performed for relief of symptoms. Pathological diagnosis was pT3N1bM1a, pStage Ⅳa. With her request, chemotherapy was performed with only capecitabine. Although lung metastasis was slowly progressed, for 72 months she has maintained good general condition since the chemotherapy with only capecitabine was started.

Resection of Multiple Metastases after Liver Resection from Colon Cancer-A Case Report.

A 49-year-old female was underwent laparoscopic right hemicolectomy for ascending colon cancer and liver metastasis. Then, she was underwent laparoscopic hepatectomy. She received BEV plus mFOLFOX6 therapy as postoperative adjuvant chemotherapy, but she had liver recurrence. She received FOLFOXIRI therapy. Although tumor tended to progressive, it was localized, so laparoscopic hepatectomy was performed again. She received AFL plus FOLFIRI therapy. Fourteen months after hepatic resection, disseminated nodules and lung metastases were found. However, both of peritoneal dissemination, and lung metastasis were localized, so it was judged that peritoneal dissemination and lung metastasis could be resectable. Then, peritoneal dissemination resection and sigmoid colectomy were performed, and then lung resection was performed to perform R0 resection. R0 resection and multimodal therapy for simultaneous and heterotopic metastases of colorectal cancer can contribute to provide a long-term prognosis.

A Case of Hepatocellular Carcinoma with Erythrocytosis.

Hepatocellular carcinoma is associated with a relatively high rate of paraneoplastic syndrome, but the frequency of erythrocytosis is low. We report a case of hepatocellular carcinoma with preoperative erythrocytosis and hypererythropoietinemia. The case is a 50-year-old man who has been cured by interferon treatment for hepatitis C 20 years ago(SVR). He visited our hospital with the complaint of right hypochondrial pain, and was diagnosed with hepatocellular carcinoma, which occupied S857 of the liver, and showed erythrocytosis and high erythropoietin(Epo)as tumor-related symptoms. A right hepatic lobectomy was performed, and the patient was discharged 13 days after the operation. The red blood cell count and Epo were normalized immediately after the operation. One year and 2 months after the operation, multiple lung metastases recurred, and chemotherapy is currently underway. Hepatocellular carcinoma with erythrocytosis and hypererythropoietinemia has been reported to have a poor prognosis, and multimodal treatment and strict surveillance are considered necessary.

Cases of Advanced Colorectal Cancer with Nephrotic Syndrome after FOLFIRI plus Ramucirumab Administration.

We report 2 Cases of advanced colorectal cancer that developed nephrotic syndrome after ramucirumab(RAM)administration. Case 1 A 54-year-old woman with rectal cancer, liver and lung metastases, and peritoneal dissemination underwent sigmoid colon double-barrel colostomy for perforation management. The patient received 15 postoperative CAPOX plus bevacizumab(Bev)courses. FOLFIRI plus RAM was introduced as the second-line treatment. After 2 courses, the patient showed marked proteinuria and hypoalbuminemia and was diagnosed with nephrotic syndrome. The patients condition improved promptly with administrating diuretics and antihypertensive drugs. Case 2 A 72-year-old man underwent sigmoid colon cancer resection with duodenal infiltration. Despite the treatment, a tumor was identified at the radial margin(RM1), with a positive cytological test(CY1)result. Therefore, postoperative mFOLFOX6 plus Bev was administered for 17 courses. FOLFIRI plus RAM was introduced as the second-line treatment due to residual tumor growth. After 2 courses, the patient showed accentuated proteinuria and was diagnosed with nephrotic syndrome and heart failure. The patients condition improved after administrating diuretics, antihypertensive drugs, and V2-receptor antagonists. In both cases, marked proteinuria was observed after shifting to second-line treatment with two RAM administrations. Therefore, monitoring nephrotic syndrome development during the early RAM introduction stage is essential.

A Case of Long-Term Survival without Recurrence following Resection of Hepatic and Pulmonary Metastases of Gastric Cancer.

A 78-year-female underwent distal gastrectomy for gastric cancer. The final diagnosis was moderately differentiated tubular adenocarcinoma, T4a, N2, M0, Stage ⅢB. Four years later, S6 hepatic metastasis and S9 pulmonary metastasis were detected. After 10 courses of S-1 plus oxaliplatin therapy, she received partial hepatectomy(S6). One year after hepatectomy, she underwent partial pulmonary resection for lung metastasis in the left lung(S9). Histopathological findings revealed the lung tumor was a pulmonary metastasis from gastric cancer with a small primary lung adenocarcinoma. There has been no recurrence for 30 months since the last operation.

Blue Light Inhibits Proliferation of Metastatic Cancer Cells by Regulating Translational Initiation A Synergistic Property with Anticancer Drugs.

The aim of this study was to examine the inhibitory effect of blue light (BL) on the proliferation of metastatic cancer cells and synergistic properties with chemo-drugs. BL significantly inhibited the proliferation of B cell lymphoma (A20 and RAMOS) cells in a dose-dependent manner. Anti-proliferative effect of BL irradiation was identified to be associated with the inhibition of proliferating-cell nuclear antigen expression and cell cycle by decreasing S-phase cells. Consistent with its inhibitory effects, BL irradiation at 20 Jcm

Metal Nanoparticles as Novel Agents for Lung Cancer Diagnosis and Therapy.

Lung cancer is one of the most common malignancies worldwide and contributes to most cancer-related morbidity and mortality cases. During the past decades, the rapid development of nanotechnology has provided opportunities and challenges for lung cancer diagnosis and therapeutics. As one of the most extensively studied nanostructures, metal nanoparticles obtain higher satisfaction in biomedical applications associated with lung cancer. Metal nanoparticles have enhanced almost all major imaging strategies and proved great potential as sensor for detecting cancer-specific biomarkers. Moreover, metal nanoparticles could also improve therapeutic efficiency via better drug delivery, improved radiotherapy, enhanced gene silencing, and facilitated photo-driven treatment. Herein, the recently advanced metal nanoparticles applied in lung cancer therapy and diagnosis are summarized. Future perspective on the direction of metal-based nanomedicine is also discussed. Stimulating more research interests to promote the development of metal nanoparticles in lung cancer is devoted.

Treatments and whole exon sequencing of a case with multiple primary lung cancer.

The number of patients with synchronous multiple primary lung cancer (sMPLC) has increased recently. However, diagnosing and selecting the appropriate therapeutic strategy for this type of disease is not simple. This report presented a case of sMPLC with lymph node metastasis. With no smoking and cancer history, this patient had seven nodules in the right lung and underwent single-portal video-assisted thoracoscopic surgery (VATS). In addition, she received four cycles of chemotherapy after the operation. Whole exon sequencing (WES) was performed in five resected tissue samples (four tumors and one lymph node). We conducted genomic profiling and clone evolution analysis of the five samples. Gene detection helped to confirm that the metastasis lymph node was transferred from one nodule. There was apparent heterogeneity of gene mutations among the five samples of the patient, with only one shared neurofilament heavy polypeptide (NEFH) mutation. A dominant substitution of C > TG > A was found in all the samples. Pyclone model was used to calculate all tissues cellular prevalence (CP) values, and NEFH mutations were thought to be the ancestral clones. During the follow-up period, residual lesions showed no apparent changes and limited response to chemotherapy. This report showed an essential role in genomic detection and selecting the appropriate treatment of sMPLC. Surgery remains the primary treatment strategy for this type of disease, and the occurrence and development of sMPLC need more in-depth research.

Comparison of the efficacy and safety of rivaroxaban and low-molecular-weight heparin in Chinese lung cancer patients with nonhigh-risk pulmonary embolism.

Data that guide selection of differing anticoagulant regimens for specific cancer-associated venous thromboembolism (VTE) are lacking. We aimed to compare the efficacy and safety of rivaroxaban and low-molecular-weight heparin (LMWH) against nonhigh-risk pulmonary embolism (PE) in Chinese lung cancer patients. Four hundred forty-six Chinese lung cancer patients with nonhigh-risk PE who initiated treatment with rivaroxaban or LMWH were identified from Zhongshan Hospital database from 2016 to 2020. The primary outcomes were the composite event of VTE recurrence or major bleeding, and all-cause mortality. The secondary outcomes were VTE recurrence, major bleeding and clinically relevant non-major bleeding (CRNMB). Propensity score matching was used to balance baseline covariates. We conducted sensitivity analysis by stabilized inverse probability of treatment weighting and competing risk analysis by a Fine and Gray subdistribution hazard model. In propensity score-matched cohorts, rivaroxaban was similar to LMWH in the risks of the composite outcome (hazard ratio (HR), 0.73 95% confidence interval (CI), 0.45-1.21 P 0.22), VTE recurrence (HR, 0.69 95% CI, 0.36-1.34 P 0.28), major bleeding (HR, 0.79 95% CI, 0.37-1.68 P 0.54) and CRNMB (HR, 1.13 95% CI, 0.62-2.09 P 0.69). All-cause mortality was significantly lower in rivaroxaban group than LMWH group (HR, 0.52 95% CI, 0.36-0.75 P < 0.001). The primary and secondary outcomes favored rivaroxaban over LMWH in all the subgroups expect for central PE and intermediate-risk PE. The sensitivity analysis yielded similar results, and competing risk analysis was in accordance with the primary findings. Rivaroxaban might be a promising alternative to LMWH as initial treatment for nonhigh-risk PE in lung cancer patients.

Relationship between brain metastasis and thyroid transcription factor 1.

Brain metastases (BMs) are common in lung adenocarcinomas (ACs). Thyroid transcription factor 1 (TTF-1) is important in the diagnosis of AC. This study aimed to examine the relationship between TTF-1 and BM for the first time in literature. The data of 137 patients with AC that developed BM between 2009 and 2020 were retrospectively analyzed. A total of 137 patients, 120 (87.6%) male, and 17 (12.4%) female were examined. Their mean age was 59.78 ± 0.82 years. The Eastern Cooperative Oncology Group (ECOG) performance score was 0-1 (< 2) for 39 (28.5%) patients and 2-4 (≤ 2) for 98 (71.5%). TTF-1 was positive in 100 (73%) patients and negative in 37 (27%). More than five BMs were present in 102 (74.4%) patients and less than five in 35 (25.6%). All the patients received whole-brain radiotherapy. None of the patients was suitable for surgery or radiosurgery. The median survival time was 6.4 95% confidence interval (CI), 5.67-7.1 months. The survival time was 7 (95% CI, 5.91-8.09) months for the TTF-1 () patients and 5.8 (95% CI, 4.1-7.5) months for the TTF-1 (-) patients. In the univariate analysis, there was a significant relationship between survival time and age (p 0.047), TTF-1 (p 0.024), and ECOG performance score (p 0.002). The multivariance analysis revealed a significant relationship between survival and TTF-1 (p 0.034) and ECOG score (p 0.007). We found a correlation between survival time and ECOG performance score and TTF-1. TTF-1 can be used as a biomarker to monitor prognosis in the follow-up and treatment of patients with AC that develop BM.

Postoperative circulating tumor DNA can refine risk stratification in resectable lung cancer results from a multicenter study.

Circulating tumor DNA (ctDNA) has potential as a promising biomarker for molecular residual disease detection in lung cancer. As the next-generation-sequencing standardized panel for ctDNA detection emerges, its clinical utility needs to be validated. We prospectively recruited 184 resectable lung cancer patients from four medical centers. Serial postoperative ctDNAs were analyzed by a standardized panel. A total of 427 postoperative plasma samples from 177 eligible patients were enrolled. ctDNA positivity after surgery was an independent predictor for disease recurrence and preceded radiological recurrence by a median of 6.6 months (range, 0.7-27.0 months). ctDNA-positive or -negative patients with tumors of any stage had similar disease-free survival (DFS). Patients who received targeted therapy had significantly improved DFS than those not receiving adjuvant therapy or receiving chemotherapy, regardless of baselinepreadjuvant ctDNA status. According to whether the ctDNA variants were detected in its matched tissue, they were classified into tissue-derived and non-tissue-derived. Patients with detectable postoperative ctDNA with tissue-derived mutations had comparable DFS with those with non-tissue-derived mutations. Collectively, we demonstrated that postoperative ctDNA has the potential to stratify prognosis and optimize tumor stage in resectable lung cancer. ctDNA variants not identified in tissue samples should be considered in molecular residual disease testing.

A palmitate-rich metastatic niche enables metastasis growth via p65 acetylation resulting in pro-metastatic NF-κB signaling.

Metabolic rewiring is often considered an adaptive pressure limiting metastasis formation however, some nutrients available at distant organs may inherently promote metastatic growth. We find that the lung and liver are lipid-rich environments. Moreover, we observe that pre-metastatic niche formation increases palmitate availability only in the lung, whereas a high-fat diet increases it in both organs. In line with this, targeting palmitate processing inhibits breast cancer-derived lung metastasis formation. Mechanistically, breast cancer cells use palmitate to synthesize acetyl-CoA in a carnitine palmitoyltransferase 1a-dependent manner. Concomitantly, lysine acetyltransferase 2a expression is promoted by palmitate, linking the available acetyl-CoA to the acetylation of the nuclear factor-kappaB subunit p65. Deletion of lysine acetyltransferase 2a or carnitine palmitoyltransferase 1a reduces metastasis formation in lean and high-fat diet mice, and lung and liver metastases from patients with breast cancer show coexpression of both proteins. In conclusion, palmitate-rich environments foster metastases growth by increasing p65 acetylation, resulting in a pro-metastatic nuclear factor-kappaB signaling.

Integrative multi-omics networks identify PKCδ and DNA-PK as master kinases of glioblastoma subtypes and guide targeted cancer therapy.

Despite producing a panoply of potential cancer-specific targets, the proteogenomic characterization of human tumors has yet to demonstrate value for precision cancer medicine. Integrative multi-omics using a machine-learning network identified master kinases responsible for effecting phenotypic hallmarks of functional glioblastoma subtypes. In subtype-matched patient-derived models, we validated PKCδ and DNA-PK as master kinases of glycolyticplurimetabolic and proliferativeprogenitor subtypes, respectively, and qualified the kinases as potent and actionable glioblastoma subtype-specific therapeutic targets. Glioblastoma subtypes were associated with clinical and radiomics features, orthogonally validated by proteomics, phospho-proteomics, metabolomics, lipidomics and acetylomics analyses, and recapitulated in pediatric glioma, breast and lung squamous cell carcinoma, including subtype specificity of PKCδ and DNA-PK activity. We developed a probabilistic classification tool that performs optimally with RNA from frozen and paraffin-embedded tissues, which can be used to evaluate the association of therapeutic response with glioblastoma subtypes and to inform patient selection in prospective clinical trials.

Phagocytosis in the retina promotes local insulin production in the eye.

The retina is highly metabolically active, relying on glucose uptake and aerobic glycolysis. Situated in close contact to photoreceptors, a key function of cells in the retinal pigment epithelium (RPE) is phagocytosis of damaged photoreceptor outer segments (POS). Here we identify RPE as a local source of insulin in the eye that is stimulated by POS phagocytosis. We show that Ins2 messenger RNA and insulin protein are produced by RPE cells and that this production correlates with RPE phagocytosis of POS. Genetic deletion of phagocytic receptors (loss of function) reduces Ins2, whereas increasing the levels of the phagocytic receptor MerTK (gain of function) increases Ins2 production in male mice. Contrary to pancreas-derived systemic insulin, RPE-derived local insulin is stimulated during starvation, which also increases RPE phagocytosis. Global or RPE-specific Ins2 gene deletion decreases retinal glucose uptake in starved male mice, dysregulates retinal physiology, causes defects in phototransduction and exacerbates photoreceptor loss in a mouse model of retinitis pigmentosa. Collectively, these data identify RPE cells as a phagocytosis-induced local source of insulin in the retina, with the potential to influence retinal physiology and disease.

USP13 promotes breast cancer metastasis through FBXL14-induced Twist1 ubiquitination.

Epithelial-to-mesenchymal transition (EMT) is an important cause of high mortality in breast cancer. Twist1 is one of the EMT transcription factors (EMT-TFs) with a noticeably short half-life, which is regulated by proteasome degradation pathways. Recent studies have found that USP13 stabilizes several specific oncogenic proteins. As yet, however, the relationship between Twist1 and USP13 has not been investigated. Co-Immunoprecipitation, GST-pulldown, Western blot, qRT-PCR and immunofluorescence assays were used to investigate the role of USP13 in de-ubiquitination of Twist1. Chromatin immunoprecipitation and Luciferase reporter assays were used to investigate the role of Twist1 in inhibiting USP13 reporter transcription. Scratch wound healing, cell migration and invasion assays, and a mouse lung metastases assay were used to investigate the roles of USP13 and Twist1 in promoting breast cancer metastasis. We found that Twist1 can be de-ubiquitinated by USP13. In addition, we found that the protein levels of Twist1 dose-dependently increased with USP13 overexpression, while USP13 knockdown resulted in a decreased expression of endogenous Twist1. We also found that USP13 can directly interact with Twist1 and specifically cleave the K48-linked polyubiquitin chains of Twist1 induced by FBXL14. We found that the effect of USP13 in promoting the migration and invasion capacities of breast cancer cells can at least partly be achieved through its regulation of Twist1, while Twist1 can inhibit the transcriptional activity of USP13. Our data indicate that an interplay between Twist1 and USP13 can form a negative physiological feedback loop. Our findings show that USP13 may play an essential role in breast cancer metastasis by regulating Twist1 and, as such, provide a potential target for the clinical treatment of breast cancer.

Air pollution associated with incidence and progression trajectory of chronic lung diseases a population-based cohort study.

No prior study has examined the effects of air pollution on the progression from healthy to chronic lung disease, subsequent chronic lung multimorbidity and further to death. We used data from the UK Biobank of 265 506 adults free of chronic lung disease at recruitment. Chronic lung multimorbidity was defined as the coexistence of at least two chronic lung diseases, including asthma, chronic obstructive pulmonary disease and lung cancer. The concentrations of air pollutants were estimated using land-use regression models. Multistate models were applied to assess the effect of air pollution on the progression of chronic lung multimorbidity. During a median follow-up of 11.9 years, 13 863 participants developed at least one chronic lung disease, 1055 developed chronic lung multimorbidity and 12 772 died. We observed differential associations of air pollution with different trajectories of chronic lung multimorbidity. Fine particulate matter showed the strongest association with all five transitions, with HRs (95% CI) per 5 µgm Our study provides the first evidence that ambient air pollution could affect the progression from free of chronic lung disease to incident chronic lung disease, chronic lung multimorbidity and death.

Endobronchial Hamartoma Treated with Bronchoscopic Microwave Tissue Coagulation and Electrosurgical SnaringReport of a Case.

A 35-year-old man had chronic cough and was treated as asthma at local doctor. Since the symptoms was not improved, chest computed tomography( CT) was performed and an approximately 5 mm nodule with calcification was found in the left main bronchi. He was referred to our hospital for treatment. Bronchoscopic examination revealed a polypoid lesion in the membranous part of the left main bronchus. Since transbronchial biopsy revealed no malignant findings, bronchoscopic resection using microwave tissue coagulation and electrosurgical snaring was performed safely under the general anesthesia. The tumor was histologically diagnosed as endobronchial hamartoma.

Surgical Treatment of Congenital Absence of the Pericardium Found by Chance at Pulmonary SurgeryReport of a Case.

Absence of the pericardium is generally asymptomatic rare congenital disorder. However, it may be life-threatening problem due to cardiac deviation or herniation after the pulmonary resection. We described a case of complete defect of the pericardium found at surgery for metastatic lung cancer. Since the left lower lobectomy was necessary, the pericardium was reconstructed with an ePTFE sheet. Postoperative course was uneventful without any symptoms at two years post-surgery.

Surgical Technique and Prognosis of Limited Resection in High-risk Patients with Primary Lung Cancer.

To identify adaptations of limited resection for poor-risk patients with primary lung cancer and the efficacy of ensuring an adequate surgical margin. A total of 139 poor-risk patients who underwent limited resection for their primary lung cancer in our institution between 2005 and 2020 were included. The efficacy of ensuring a surgical margin was determined by analyzing the rate of recurrence, and the prognosis was analyzed via the Kaplan-Meier method. Wedge resection was performed for 105 patients, and segmentectomy was performed for 34 patients. Recurrence was observed in 29 (20.8%) patients, while stump recurrence was observed in only 4( 3.8%) patients with wedge resection. The median surgical margin was 15 mm, which was equal to the median tumor size, and all histopathological margins were negative. An analysis of the 68 patients excluding those with multiple lung cancer showed that the pathological stage was not related to the prognosis. Surgical death and severe complications were not observed, and only 3 patients died of lung cancer during the observational period of 3.4 years. Limited resection improves the patients prognosis and ensures an adequate surgical margin to control recurrence.

Analysis of Surgical Margin Recurrence Following Segmentectomy for Early-stage Non-small Cell Lung Cancer.

Surgical margin recurrence following segmentectomy is a critical issue because it may have been avoided by lobectomy. Between January 2000 and December 2018, we retrospectively investigated 199 patients who underwent segmentectomy for c-StageⅠ non-small cell lung cancer at our hospital. Recurrence occurred in 20 cases, of which 3 cases had surgical margin recurrence. In our previous study, the recurrence risk factor after segmentectomy was radiologic solid tumor size( cut-off value 1.5 cm). Of the 130 patients in the low-risk group with radiologic solid tumor size of less than 1.5 cm, five had any recurrence, three of which had surgical margin recurrence. In the high-risk group with radiologic solid tumor size of 1.5 cm or more, no surgical margin recurrence was observed. Three cases of surgical margin recurrence were accompanied by lepidic components, and the tumors were difficult to identify intraoperatively and were located close to adjacent areas. Surgical margin recurrence may be avoided by carefully considering the segments to be resected and improving the method for identifying the intersegmental plane.

Robot-assisted Segmentectomy for Lung Cancer.

The role of segmentectomy for lung cancer is expected to increase owing to the results of Japan Clinical Oncology Group (JCOG) 0802. Moreover, the major advantage of robot-assisted thoracic surgery (RATS) is that it allows high precision of dissection. The surgical approach comprised the placement of four robotic ports on the lower intercostal space with an assistant hole. While performing robotic surgery without haptic sensation, it is considered safe to dissect the bronchus first followed by the interlobar and intersegmental plane dissection at the end. In our institution, 52 lung cancer segmentectomies were performed between April 2020 and April 2022, out of which 8 (15.4%)were robot-assisted. The median operating time and console time for RATS were 233 and 182 minutes, respectively, showing a trend towards significantly longer operating time as compared to thoracoscopic segmentectomy( 184 vs. 233 minutes, p0.007). There were no significant differences in the time to drain removal, the incidence of complications, or pain scores at discharge. Although robotic surgery provides the surgeon with better view and greater precision, it does not decrease the operation time and pain. However, robot-assisted surgery is expected to deliver greater benefits to the patient with technological advances in devices and surgical techniques.

Introduction of Robot-assisted Lung Segmentectomy.

Robot-assisted lung segmentectomy will be covered by insurance starting 2020. The results of the Japan Clinical Oncology Group( JCOG) 0802 trial have been reported, and the use of robot-assisted lung segmentectomy is expected to increase in the future. We present an introduction to robot-assisted lung segmentectomy at our institution using actual cases. Our facility constructs vascular three-dimensional (3D) images from computed tomography( CT) images as a preoperative simulation. Robot-assisted surgery is performed with the da Vinci Xi, using four arms with carbon dioxide insufflation through an assist hole in the anterior thoracic region of the fifth intercostal space, with a focus on the eighth intercostal space. The port placement and forceps used are the same as for lobectomy. Interdigitations are identified with intravenous indocyanine green after dissecting the pulmonary arteriovenous veins. After that, the da Vinci Xi firefly is activated, and the non-resected lungs are fluorescently stained to identify the inter-areas, and the inter-areas which are separated with an automatic suture device.

Ingenuities of Segmentectomy for Small Lung Cancer in Uniportal Video-assisted Thoracic Surgery.

Our department has been performing uniportal thoracoscopic lobectomy since April 2019 and now also performs segmentectomy for small malignant tumors. A skin incision of approximately 4 cm is created between the anterior fifth intercostal space on the left and right sides. Based on our experience, uniportal segmentectomy does not follow the learning curve unique to segmentectomy. For dissection of segmental surface, an automatic suture is used to prevent pulmonary fistulas. If the cutting line between the segments is straight, dissection can be performed easily even in uniportal surgery, in which the automatic suturing device is inserted from one direction. For inter-area identification, we use an air-containing collapsed line with normal ventilation, after which thoracoscopic indocyanine green( ICG) imaging is introduced. However, there have been cases in which a difference in inter-area identification occurred between ICG identification and the air-containing collapsed line. As such, it is better to utilize both methods in cases with masses close to the inter-areas.

Thoracoscopic Segmentectomy Using Three-dimensional Image Simulation of the Pulmonary Artery Perfusion Area and Indocyanine Green( ICG) Intravenous Injection Method.

When performing segmentectomy, we aim to keep adequate distance from the tumor using three-dimensional( 3D) images of the pulmonary artery perfusion area and the indocyanine green( ICG) injection method. The effectiveness and improvement of this method were examined. We retrospectively investigated 50 consecutive patients who underwent segmentectomy with this method. In simulation, we measured the predicted margin distance( PMD) on a 3D image. Then, we measured the actual margin distance (AMD) on resected specimens fixed in formalin. We compared these two distances and evaluated factors influencing shorter AMD. The median AMD was 1.7 cm, and there was no positive margin case. The median ratio of AMDPMD was 0.73. In multivariate analysis, shorter PMD and no resection of subsegment bronchi next to the tumor were significant factors associated with shorter AMD( p<0.001, p0.014). Our method was effective for segmentectomy. For adequate AMD, a longer PMD in simulation and subsegmental bronchi resection next to the tumor should be considered.

Segmentectomy for Lung Cancer Using Indocyanine Green( ICG).

The most important issues in the segmentectomy for lung cancer, are the accurate establishment of the suture line and to reduce local recurrence at the resection margin. There are two methodsbronchial dominance as an indicator and intravenous indocyanine green (ICG) as an indicator of blood flow dominance. We have been performing identification by ICG since 2020. After the pulmonary arteriovenous and bronchus are resected, ICG is injected intravenously, and the borders between fluorescent and non-fluorescent area is identified using a ICG thoracoscope, and are resected using an electro-surgical unit or stapler. After that, additional ICG is administered, pulmonary blood flow is checked, and if an uncontaminated area is identified, an additional resection is performed. We have retrospectively reviewed 16 cases of ICG method for lung cancer( all at clinical stageⅠ) performed since January 2020, and no recurrence has been observed. We present the details of these cases and report the usefulness of the ICG fluorescence system.

Development of Virtual-assisted Lung Mapping.

The Japan Clinical Oncology Group (JCOG) 0802West Japan Oncology Group (WJOG) 4607L trial has recently reported that in small lung cancer, segmentectomy has a higher overall survival rate than lobectomy, increasing the significance of sublobar resection. However, local recurrence is a major concern after sublobar resection, and an insufficient surgical margin is a significant risk factor for locoregional recurrence. Therefore, since 2014, we have performed virtual-assisted lung mapping (VALMAP), a preoperative bronchoscopic multiple-spot dye-marking technique, using indigo carmine as a preoperative localization technique to identify hardly detectable pulmonary nodules and confirm the adequacy of the surgical margin. However, conventional VAL-MAP (VAL-MAP 1.0) faced some chal-lenges. One issue is that approximately 10% marks were invisible and unidentifiable due to patient factors or technical issues. Another problem was that, in some cases requiring large resection depth, VAL-MAP did not lead to successful resection with adequate surgical margin. Thus, we have invented several novel techniques to solve these issues. VAL-MAP dual staining is a technique using indocyanine green (ICG) as well as indigo carmine that has improved the success rate of marking detection during surgery without causing additional complications. VAL-MAP 2.0 is a proximal mapping technique that involves the use of a coil, enabling three-dimensional mapping and making sublobar resection more accurate, particularly for a deeply located tumor.

Pulmonary Nodule Localization by Pleural Marking Using Virtual Thoracoscopic Imaging.

Percutaneous or transbronchial markings are performed to localize pulmonary nodules preoperatively. We present a novel intraoperative procedure that utilizes virtual thoracoscopic imaging-assisted pleural marking. In this procedure, a virtual thoracoscopic image is created preoperatively, and the coordinates of the pleural point above the tumor are determined. The pleural marker is intraoperatively placed on the coordinates, and dye is transferred to the visceral pleura with two lung ventilations. We present the specific procedures and countermeasures for cases when nodules are not palpable. Additionally, we present a comparison between the various methods of preoperative marking and this method.

Intraoperative Margin Assessment during Thoracoscopic Sublobar Resection Using Radiofrequency Identification Microchip.

We developed a novel wireless localization technique with radiofrequency identification( RFID) markers to enable precise localization of deeply located small lung lesions. Electromagnetic navigational bronchoscopy was used to place RFID markers as close to tumors as possible. Without palpating the lung, operators located the marker using a detection probe, following tone changes in accordance with the marker-probe distance. In this section, we present a novel wireless localization technique using an RFID marker for accurate localization of small lung lesions.

Retrograde S(9)10 Segmentectomy without Interlobar Fissurelectomy.

With increase of patients with a small-sized lung cancer, there is an increasing need for minimally invasive lung segmentectomy that can preserve respiratory function. We perform S(9)10 segmentectomy with retrograde dissection of the pulmonary vein, bronchus, pulmonary artery, in order, without interlober fissurelectomy and staple dissection of the peripheral lung parenchyma. Seven patients who underwent retrograde S(9)10 segmentectomy between June, 2021 and May, 2022 in our hospital were retrospectively reviewed. No patient was converted to the open thoracotomy, without any complications including prolonged air leakage. The average operation time was 171 minutes( range 125 to 221), amount of bleeding was 25 ml( range 0 to 75). Median duration of chest tube insertion was 4 days( range 3 to 6), length of stay after surgery was 6 days (range 5 to 9). Pathologic stage showed pT1mi in 3 patients, pT1a in 3 patients, pT2a in 1 patient. No local recurrence was seen at this time. Retrograde S(9)10 segmentectomy is feasible and facilitates interlobar procedure at the time of repeated segmentectomy or completion lobectomy.

Digital Innovation for Lung Segmentectomy for Early-stage Small Lung Cancer.

In recent years, the number of cases of small-size lung cancer(<2 cm) has increased with the widespread of computed tomography (CT) in medical checkup and comprehensive medical checkup. Although lobectomy has been the standard surgical treatment for early-stage small-size lung cancer, it has become possible to evaluate the CT findings of small tumors in terms of ground-glass areas and solid areas, and it has become clear that the former has a low histological malignancy while the latter has a high malignancy. Lung cancers with high ground-glass opacity have low malignant potential and are therefore being aggressively treated by limited resection. The number of lung segmentectomies is expected to increase in the future, and accurate identification of pulmonary intersegmental planes is important in this operation. Especially in thoracoscopic surgery, where the field of view and surgical operation are limited, tumor localization and intersegmental planes identification are particularly important and require preoperative and intraoperative planning. In order to perform safe and reliable lung segmentectomy, we create a three-dimensional (3D) lung model by Synapse Vincent for preoperative simulation of pulmonary vascular, tumor location, and intersegmental plane. In addition, preoperative simulations are performed using wearable goggles to freely move the 3D lung model in a virtual reality (VR) space. Intraoperatively, in addition to indocyanine green (ICG)-based intersegmental identification, digital assistance is used for tumor and intersegmental identification using mixed reality( MR) goggles. We describe the current status and future prospects of segmentectomy in our institution.

Novel Surgical Techniques for Lung Segmentectomy of Malignant Lung Tumors.

For a long time, lobectomy and lymph node dissection have been the standard surgery for treating non-small cell lung cancer. Recently, segmentectomy has been introduced as an alternative surgical procedure for treating early-stage lung cancer. Moreover, a growing number of segmentectomies are performed due to the increasing number of elderly patients, and the expansion of indications, including early- stage lung cancer with a ground glass nodule or peripheral nodule under 2 cm in diameter. However, the use of segmentectomy remains under debate. We have been performing thoracoscopic lung segmentectomy for malignant lung tumors since 2003. The number of surgeries has increased over the past few years, since robot-assisted lung resection of the right lobe became covered by health insurance in April 2018. In addition, lung segmentectomy is performed for lung metastases of malignant tumors in other organs. In deciding on the surgical approach, the increased technical difficulty of segmentectomy compared to lobectomy, owing to the anatomical complexity of the peripheral vessels and bronchi, needs to be considered, and novel surgical procedures and preoperative planning based on three-dimensional computed tomography( CT) images are necessary. We describe the preoperative management and surgical techniques used in approximately 250 lung segmentectomy procedures performed at our hospital up to May 2022, with no conversion to thoracotomy.

Dawn of Radical Segmentectomy for Small Sized Peripheral Non-small Cell Lung Cancer.

The result of prospective, randomized, controlled, trial, Japan Clinical Oncology Group (JCOG) 0802 West Japan Oncology Group( WJOG) 4607L, has been published in April 2022. The superiority in overall survival for patients who underwent segmentectomy for small sized peripheral non-small cell lung cancer( NSCLC)( whole tumor size≤2 cm, CT ratio>0.5) compared with those undergoing lobectomy has been demonstrated for the first time in the world. Segmentectomy might become a standard surgical procedure for such tumors. Consequently, the opportunity to perform segmentectomy will increase. Developing techniques for segmentectomy is an urgent issue for general thoracic surgeons because segmentectomy generally requires more advanced surgical technique than lobectomy. In particular, the radical segmentectomy is an anatomically limited resection with hilar and mediastinal lymph node dissection. That means anatomically accurate resection of the pulmonary segment. There are a lot of points to be mastered in operative indications based on tumor size, phenotype, and location, understandings of anatomy, surgical techniques, transition to lobectomy, and so on. In this article, we would like to share some tips on segmentectomy primarily focusing on the surgical techniques.

Molecular dynamics simulations suggest Thiosemicarbazones can bind p53 cancer mutant R175H.

Cancer pathologies are associated with the unfolding and aggregation of most recurring mutations in the DNA Binding Domain (DBD) of p53 that coordinate the destabilization of protein. Substitution at the 175th codon with arginine to histidine (R175H, a mutation of large to small side-chain amino acid) destabilizes the DBD by 3 kcalmol and triggers breasts, lung cancer, etc. Stabilizing the p53 mutant by small molecules offers an attractive drug-targeted anti-cancer therapy. The thiosemicarbazone (TSC) molecules NPC and DPT are known to act as zinc-metallochaperones to reactivate p53R175H. Here, a combination of LESMD simulations for 10 TSC conformations with a p53R175H receptor, single ligand-protein conformation MD, and ensemble docking with multiple p53R175H conformations observed during simulations is suggested to identify the potential binding site of the target protein in light of their importance for the direct TSC - p53R175H binding. NPC binds mutant R175H in the loop region L2-L3, forming pivotal hydrogen bonds with HIS175, pi‑sulfur bonds with TYR163, and pi-alkyl linkages with ARG174 and PRO190, all of which are contiguous to the zinc-binding native site on p53DBD. DPT, on the other hand, was primarily targeting alternative binding sites such as the loop-helix L1H2 region and the S8 strand. The similar structural characteristics of TSC-bound p53R175H complexes with wild-type p53DBD are thought to be attributable to involved interactions that favour binding free energy contributions of TSC ligands. Our findings may be useful in the identification of novel pockets with druggable properties.

Hyaluronate decorated polyethylene glycol linked poly(lactide-co-glycolide) nanoparticles encapsulating MUC-1 peptide augmented mucosal immune response in Balbc mice through inhalation route.

NSCLC (Non-Small Cell Lung Cancer) clutches highest mortality rate in man and women globally. The present study was conducted to target MUC-1 peptide (M-1) into antigen presenting cells by cargo the peptide into hyaluronic acid decorated polyethylene glycol linked poly (D, l-lactide-co-glycolide) nanoparticles (M-1-PL-co-GA-PEG-sHA-NPs) for generating mucosal immunity through inhalation (i.h.) route. The mean particle size and surface charge of M-1-PL-co-GA-PEG-sHA-NPs was measured to be 136.2 ± 18.38-nm and - 28.34 ± 6.77-mV, respectively, prepared by non-aggregated emulsion-diffusion evaporation method. The 28.42% percentage release of M-1 peptide from M-1-PL-co-GA-PEG-NPs was observed to be at 2 h and 95.29% at 8 h while the percentage release of M-1 peptide from M-1-PL-co-GA-PEG-sHA-NPs was observed to be 26.02% at 4 h and 97.95% at 24 h that proved the prolonged release of antigen. M-1-PL-co-GA-PEG-sHA-NPs demonstrated higher (P < 0.05) cellular uptake of 86.2% in RAW 264.7 cells in comparison to 27.6% of M-1-PL-co-GA-PEG-NPs. In addition, M-1-PL-co-GA-PEG-sHA-NPs induced remarkably (P < 0.05) elevated release of 80.6-pgml of TNF-α in comparison to 5-pgml by culture medium and 57.9-pgml of TNF-α by M-1-PL-co-GA-PEG-NPs. Similarly, M-1-PL-co-GA-PEG-sHA-NPs persuade remarkably (P < 0.05) elevated release of 225-pgml of IL-1β in comparison to 47-pgml by culture medium and 161.9-pgml of IL-1β by M-1-PL-co-GA-PEG-NPs. M-1-PL-co-GA-PEG-sHA-NPs might have been endocytosed through receptor mediated pathway owing to presence of sHA. Mice immunized through i.h. route with M-1-PL-co-GA-PEG-sHA-NPs induced strong (P < 0.05) IgA antibody titre as compared to M-1-PL-co-GA-PEG-NPs and M-1 peptide in dose-dosage regimen. M-1-PL-co-GA-PEG-sHA-NPs nanovaccine warrants further analysis in xenograft model of NSCLC to showcase its antitumor capability.

The complexity of EGFR exon 19 deletion and L858R mutant cells as assessed by proteomics, transcriptomics, and metabolomics.

Most lung adenocarcinoma-associated EGFR tyrosine kinase mutations are either an exon 19 deletion (19Del) or L858R point mutation in exon 21. Although patients whose tumors contain either of these mutations exhibit increased sensitivity to tyrosine kinase inhibitors, progression-free and overall survival appear to be longer in patients with 19Del than in those with L858R. In mutant-transfected BaF3 cells, 19Del and L858R were compared by multi-omics analyses including proteomics, transcriptomics, and metabolomics. Proteome analysis identified increased plastin-2, TKT, PDIA5, and ENO1 expression in L858R cells, and increased EEF1G expression in 19Del cells. RNA sequencing showed significant differences between 19Del and L858R cells in 112 genes. Metabolome analysis showed that amino acids, adenylate, guanylate, NADPH, lactic acid, pyruvic acid glucose 6-phosphate, and ribose 5-phosphate were significantly different between the two mutant cells. Because GSH was increased with L858R, we combined osimertinib with the GSH inhibitor buthionine sulfoximine in L858R cells and observed synergistic effects. The complexity of EGFR 19Del and L858R mutant cells was demonstrated by proteomics, transcriptomics, and metabolomics analyses. Therapeutic strategies for lung cancer with different EGFR mutations could be considered because of their different metabolic phenotypes.

Cancer Diagnoses and Use of Radiation Therapy among Persons Experiencing Homelessness.

Persons experiencing homelessness (PEH) have low rates of cancer screening and worse cancer mortality compared to persons not experiencing homelessness. Data regarding cancer diagnosis and treatment in PEH are limited. We investigated cancer prevalence and utilization of radiation therapy (RT) in PEH. Patients presenting between January 1, 2014 and September 27, 2021 at a large metropolitan hospital system were assessed for homelessness via intake screening or chart search. PEH data were cross-referenced with the institutions cancer database to identify PEH with cancer diagnoses. Demographic, clinical, and treatment variables were abstracted. Of a total of 9,654 (9,250 evaluable) PEH with a median age of 42 years, 81 patients (0.88%) had at least one cancer diagnosis and five had multiple diagnoses, for a total of 87 PEH with at least one cancer diagnosis. The median age at diagnosis was 60 years. 43% were female and 51% were Black. 43% presented with advanced or metastatic disease. Lung (17%), prostate (15%), leukemialymphoma (13%), and headneck (9%) were the most common diagnoses. 17% underwent surgery alone, 13% chemotherapy alone, 14% radiation therapy (RT) alone, and 6% hormone therapy alone. 8% of patients underwent no treatment, and 43% underwent multimodality therapy. 58% of treated patients never achieved disease-free status. Of the 31 patients who received RT, 87% received EBRT. Most patients (70%) received hypofractionated regimens. For patients who had multifraction treatment, the treatment completion rate was 85%, significantly lower than the departmental completion rate of 98% (p < .00001). In a large cohort of PEH in a metropolitan setting, cancer diagnoses were uncommon and were frequently advanced-stage. Most patients underwent single-modality treatment or no treatment at all. Despite use of hypofractionation, the RT completion rate was low, likely reflecting complex barriers to care. Further interventions to optimize cancer diagnosis and treatment in PEH are urgently needed.

CT-based emphysema characterization per lobe A proof of concept.

The Fleischner society criteria are global criteria to visually evaluate and classify pulmonary emphysema on CT. It may group heterogeneous disease severity within the same category, potentially obscuring clinically relevant differences in emphysema severity. This proof-of-concept study proposes to split emphysema into more categories and to assess each lobe separately, and applies this to two general population-based cohort samples to assess what information such an extension adds. From a consecutive sample in two general population-based cohorts with low-dose chest CT, 117 participants with more than a trace of emphysema were included. Two independent readers performed an extended per-lobe classification and assessed overall severity semi-quantitatively. An emphysema sum score was determined by adding the severity score of all lobes. Inter-reader agreement was quantified with Krippendorff Alpha. Based on Fleischner society criteria, 69 cases had mild to severe centrilobular emphysema, and 90 cases had mild or moderate paraseptal emphysema (42 had both types of emphysema). The emphysema sum score was significantly different between mild (10.7 ± 4.3, range 2-22), moderate (20.1 ± 3.1, range 15-24), and severe emphysema (23.6 ± 3.4, range 17-28, p < 0.001), but ranges showed significant overlap. Inter-reader agreement for the extended classification and sum score was substantial (alpha 0.79 and 0.85, respectively). Distribution was homogenous across lobes in never-smokers, yet heterogenous in current smokers, with upper-lobe predominance. The proposed emphysema evaluation method adds information to the original Fleischner society classification. Individuals in the same Fleischner category have diverse emphysema sum scores, and lobar emphysema distribution differs between smoking groups.

Belgian observational survival data (incidence years 2004-2017) and expenditure for innovative oncology drugs in twelve cancer indications.

The Food and Drug Administration and European Medicines Agency typically approve market access for cancer drugs based on surrogate end-points, which do not always translate into substantiated improvements in outcomes that matter the most to patients, i.e. survival and quality of life. These drugs often, also, have a high price tag. We assessed whether there was an increase in cancer drug expenditure for a broad selection of indications, and whether this correlates with increased overall survival. This cohort study used Belgian Cancer Registry data from 125,692 patients (12 cancer indications, incidence period 2004-2017), which was linked to reimbursement and survival data. This reliably represents the Belgian situation. One-to-five year observed survival probability, median survival time, oncology drug expenditure and mean oncology drug cost per patient were reviewed. In almost all indications, total expenditure and average treatment cost for oncology drugs increased over the years (2004-2017). In contrast, mixed findings are observed for the evolution in overall survival probability and median survival time. While an absolute improvement in the 3-year survival probability of about 10% is noticed in non-small-cell lung cancer and chronic myeloid leukaemia, improvements in about half of the other indications are limited or even absent. The Belgian observational data indicate that assuming innovative oncology drugs always add value in terms of improved survival is often unjustified. The literature also highlights the problem of using surrogate end-points, and the lack of comparative evidence showing an added value of oncology drugs for both survival and quality of life at market approval or during the post-marketing phase. Comparative studies should be conducted in the pre-marketing phase that are suitable for registration purposes, aid reimbursement decisions and support physicians and patients when making treatment decisions.

Guideline Application in Real world multi-Institutional Based survey of Adjuvant and first-Line pancreatic Ductal adenocarcinoma treatment in Italy. Primary analysis of the GARIBALDI survey.

Information about the adherence to scientific societies guidelines in the real-world therapeutic management of oncological patients are lacking. This multicenter, prospective survey was aimed to improve the knowledge relative to 2017-2018 recommendations of the Italian Association of Medical Oncology (AIOM). Treatment-naive adult patients with pancreatic adenocarcinoma were enrolled. Group A received adjuvant therapy, group B received primary chemotherapy, and group C had metastatic disease. The results on patients accrued until 31 October 2019 with a mature follow-up were presented. Since July 2017, 833 eligible patients of 923 (90%) were enrolled in 44 Italian centers. The median age was 69 years (range 36-89 years 24% >75 years) 48% were female 93% had Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or 1 group A 16%, group B 30% group C 54% 72% Nord, 13% Center, 15% South. In group A, guidelines adherence was 68% 95% confidence interval (CI) 59% to 76% 53% of patients received gemcitabine and 15% gemcitabine capecitabine median CA19.9 was 29 (range 0-7300 not reported 15%) median survival was 36.4 months (95% CI 27.5-47.3 months). In group B, guidelines adherence was 96% (95% CI 92% to 98%) 55% of patients received nab-paclitaxel gemcitabine, 27% FOLFIRINOX, 12% gemcitabine, and 3% clinical trial median CA19.9 was 337 (range 0-20220 not reported 9%) median survival was 18.1 months (95% CI 15.6-19.9 months). In group C, guidelines adherence was 96% (95% CI 94% to 98%) 71% of patients received nab-paclitaxel gemcitabine, 16% gemcitabine, 8% FOLFIRINOX, and 4% clinical trial liver and lung metastases were reported in 76% and 23% of patients, respectively median CA19.9 value was 760 (range 0-1374500 not reported 9%) median survival was 10.0 months (95% CI 9.1-11.1 months). The GARIBALDI survey shows a very high rate of adherence to guidelines and survival outcome in line with the literature. CA19.9 testing should be enhanced nutritional and psychological counseling represent an unmet need. Enrollment to assess adherence to updated AIOM guidelines is ongoing.

A phase II study (WJOG12819L) to assess the efficacy of osimertinib in patients with EGFR mutation-positive NSCLC in whom systemic disease (T790M-negative) progressed after treatment with first- or second-generation EGFR TKIs and platinum-based chemotherapy.

Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) that is an established standard treatment option for chemotherapy-naive patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). However, of such patients who have received prior treatment with a first- or second-generation EGFR TKI, only approximately half are eligible for osimertinib therapy because its indication as second-line treatment and beyond is limited to metastatic NSCLC that is positive for the T790M resistance mutation of the EGFR gene. This study was initiated at the request of a dedicated network for patients with lung cancer in Japan. We conducted a phase II study to assess the efficacy of osimertinib in patients with EGFR mutation-positive NSCLC in whom systemic disease (T790M-negative) progressed after treatment with first- or second-generation EGFR TKIs and platinum-based chemotherapy. The primary end point was response rate (assessed by a central imaging reviewer). From August 2020 to February 2021, 55 patients from 15 institutions were enrolled in the study. The overall response for primary analysis was achieved in 16 patients (29.1 % 95 % CI, 17.6-42.9), which exceeded the threshold response rate necessary for analysis. Stable disease was found in 16 patients (29.1 %), and progressive disease, in 18 (32.7 %). The median length of progression-free survival (PFS) was 4.07 months (95 % CI 2.10-4.30), and the rate of 12-month PFS was 17.3 %. Osimertinib demonstrated modest antitumor activity against progressive EGFR T790M-negative disease.

PKM2PDK1 dual-targeted shikonin derivatives restore the sensitivity of EGFR-mutated NSCLC cells to gefitinib by remodeling glucose metabolism.

Pyruvate kinase 2 (PKM2) and pyruvate dehydrogenase kinase 1 (PDK1) are two key enzymes in tumor glucose metabolism pathway that not only promote tumor growth and proliferation through accelerating aerobic glycolysis, but also contribute to drug resistance of non-small cell lung cancer (NSCLC). Considering that targeting PKM2 or PDK1 alone seems insufficient to remodel abnormal glucose metabolism to achieve significant antitumor activity, we proposed a two-step approach that regulates PKM2 and PDK1 synchronously. Firstly, we found that the combination of ML265 (PKM2 activator) and AZD7545 (PDK1 inhibitor) could synergistically inhibit proliferation and induce apoptosis in H1299 cells. Base on this, we designed a series of novel shikonin (SK) thioether derivatives as PKM2PDK1 dual-target agents, among which the most potent compound E5 featuring a 2-methyl substitution on the benzene ring exerted significantly increased inhibitory activity toward EGFR mutant NSCLC cell H1975 (IC

Indoor radon survey in Whitehorse, Canada, and dose assessment.

Radon-222 (222Rn) and its decay products are the primary sources of the populations exposure to background ionizing radiation. Radon decay products are the leading cause of lung cancer for non-smokers and the second leading cause of lung cancer after smoking for smokers. A community-driven long-term radon survey was completed in 232 residential homes in different subdivisions of Whitehorse, the capital of the Yukon, during the heating season from November to April in 2016 - 2017 and in 2017-2018. Radon concentrations were measured on the ground floors in living rooms and bedrooms. The arithmetic and geometric means of indoor radon activity concentrations in different subdivisions of Whitehorse ranged from 52 ± 0.6 Bq m-3 and 37 ± 2.3 Bq m-3 in the Downtown area of Whitehorse to 993.0 ± 55.0 Bq m-3 and 726.2 ± 2.4 Bq m-3 in Wolf Creek. Underlying geology and the glacial surfaces may partly explain these variations of indoor radon concentrations in subdivisions of Whitehorse. A total of 78 homes (34.0%) had radon concentrations higher than 100 Bq m-3, 47 homes (20.5%) had concentrations higher than 200 Bq m-3, and 33 homes (14.4%) had concentrations higher than 300 Bq m-3. The indoor radon contribution to the annual effective inhalation dose to the residents ranged from 3.0 mSv in the Downtown area to 51.0 mSv in Wolf Creek. The estimated annual average dose to adults in Whitehorse, Yukon, is higher than the worlds average annual effective dose of 1.3 mSv due to inhalation of indoor radon. The annual radon inhalation effective dose was assessed using the radon measurements during the winter, hence the assessed dose may be overestimated. Cost-efficient mitigation methods exist to reduce radon in existing buildings, and to prevent radon entry into new buildings.

How do Plastic Surgeons use the Metaverse A Systematic Review.

In 2021, metaverse became a buzzword. The metaverse is a digital virtual world in which people can live as a digital virtual identity. In the metaverse, people can participate in making rules and create their own worlds. As plastic surgeons in the new era, we have been thinking about the application of the metaverse in plastic surgery. Therefore, we carried out this study to systematically review the current published articles on the application of metaverse in medicine, so as to provide a reference for the rational and effective application of metaverse by plastic surgeons in the future. The researchers searched the Wanfang, Weipu, China National Knowledge Infrastructure (CNKI), PubMed, the Cochrane Library, and the Embase database. The retrieval time was set from the database establishment to April 2022. All studies on the use of the metaverse in medicine were included in our study. A total of 4 studies were included in this study. According to our study, the metaverse is mostly used for skill training for residents and medical students. The metaverse was used for the first time to train doctors in lung cancer surgery at Seoul National University Bundang Hospital, Korea. Augmented reality in the metaverse has also been used to aid surgery and to address a variety of medical and mental health problems for patients. At present, the application of metaverse is still in the preliminary stage of exploration, and the practical effect of metaverse on plastic surgery needs to be observed and evaluated. Although there are still many problems in the metaverse, the new medical model of plastic surgery supported by the metaverse is worth looking forward to.

Combination toripalimab and bevacizumab for an elderly urothelial carcinoma patient with brain metastasis who failed rapidly after radiotherapy a case report and literature review.

Brain metastasis is a rare refractory event in patients with urothelial carcinoma. Platinum-based chemotherapy is the recommended first-line standard therapy for all metastasis urothelial carcinoma patients eligible for cisplatin or carboplatin. Patients ineligible for platinum may receive immunotherapy. No clear evidence exists that UC with brain metastasis is sensitive to immunotherapy, and the optimal treatment for patients with BM is uncertain. We evaluated the safety and efficacy of combined immunotherapy and antivascular therapy in an elderly patient with urothelial carcinoma with brain metastasis, and summarize the currently available evidence. First, she underwent a left nephrectomy and left ureterectomy and recovered well postoperatively. The postoperative pathologic findings were consistent with urothelial carcinoma. Approximately 2 years later, the patient developed impaired limb movement on the right side and underwent MRI, which revealed lesions in the left frontal lobe and suggested brain metastasis. The brain metastasis responded to local radiotherapy but progressed again in a short time. Then, the patient was administered toripalimab at 240 mg combined with bevacizumab at 300 mg every 3 weeks. After 1cycle of treatment, the patient achieved a quick response, and symptoms improved significantly. Repeat evaluation imaging demonstrated that the lesions in the brain and lung were significantly smaller and evaluation showed partial response. The treatment was well tolerated and the patient remained in partial response until the last follow-up by July 2022, 6 months after the initiation of treatment. This case suggests that immune checkpoint blockade combined with antivascular therapy might be a new possibility for patients with metastatic urothelial carcinoma, including brain metastases.

First-line crizotinib therapy is effective for a novel SEC31A-anaplastic lymphoma kinase fusion in a patient with stage IV lung adenocarcinoma a case report and literature reviews.

Anaplastic lymphoma kinase (ALK) fusion was found in 3-7% of all patients with nonsmall cell lung cancer. The efficacy of ALK-tyrosine kinase inhibitor (ALK-TKI) in EML4-ALK has been extensively studied, whereas little evidence is available on its efficacy in rare ALK fusions. Here, we report the performance of crizotinib in a 50-year-old male lung adenocarcinoma patient with a novel rare SEC31A-ALK fusion. Computed tomography (CT) scan revealed multiple patchy high-density shadows in both lungs. The larger ones are located near the spine in the right lung lower lobe (55 × 34 mm) and the left hilar region (45 × 26 mm), with multiple enlarged mediastinal and axillary lymph nodes. Biopsy by bronchoscopy revealed invasive adenocarcinoma. The pathological stage of T4N3M1b (clinical stage IVA) was confirmed. Next-generation sequencing revealed SEC31A exon20ALK exon20 fusion, ABCB1 amplification, FGF19 amplification, DAXX p.S213L, MUTYH p.R19(germline mutation and pathogenic) with tumor mutational burden at 3.2 mutationsMb, microsatellite stable, proficient mismatch repair and PD-L1 positive immunohistochemistry, tumor proportion score(TPS) 1-49% (TPS 25%). Based on these findings, crizotinib was recommended for the first-line treatment at 250 mg twice daily. The first CT assessment after 2-month therapy showed partial response (PR) for the two larger lesions, multiple shadows and nodules in both lungs and the mediastinal and axillary lymph nodes. Crizotinib at 250 mg twice a day was applied in the following 9 months. Assessment at every 3 months (up to 1-year after diagnosis) showed further absorption for all lesions (continuous PR). We reported a novel rare ALK fusion SEC31A EXON20ALK exon20 and showed the effectiveness of crizotinib against the fusion. This study provided strong evidence for the efficacy of ALK-TKI for rare ALK fusion.

CircRNA circPOLA2 overexpression suppresses cell apoptosis by downregulating PTEN in glioblastoma.

The oncogenic role of circPOLA2 has only been explored in lung cancer, whereas the role of which in glioblastoma (GBM) is unclear. Our research explored the involvement of circPOLA2 in GBM. CircPOLA2 and phosphatasetensinhomolog (PTEN) mRNA levels in GBM and paired nontumor tissues collected from 58 GBM patients were analyzed by real-time quantitative PCR (RT-qPCR). CircPOLA2 and PTEN were overexpressed in GBM cells to study their interaction by RT-qPCR and Western blot. The roles of circPOLA2 and PTEN in regulating GBM cell apoptosis were explored using cell apoptosis assay. Our data revealed that circPOLA2 was upregulated and PTEN was downregulated in GBM. PTEN showed an inverse correlation to circPOLA2 across GBM tissues, In GBM cells, circPOLA2 overexpression decreased PTEN accumulation, but PTEN overexpression failed to significantly affect circPOLA2 expression. Moreover, PTEN reduced the inhibitory effects of circPOLA2 on GBM cell apoptosis. CircPOLA2 is overexpressed in MCL and might promote GBM cell apoptosis through downregulating PTEN.

Aumolertinib effectively reduces clinical symptoms of an EGFR L858R-mutant non-small cell lung cancer case coupled with osimertinib-induced severe thrombocytopenia a case report.

Replacement of first-generation or second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with third-generation EGFR-TKIs remains the current standard of care for T790M mutations in patients with non-small cell lung cancer. Osimertinib is one of the first third-generation EGFR-TKIs to be approved and is also the most widely studied in clinical research. There has been widespread concern about the adverse effects of osimertinib such as cardiotoxicity and interstitial lung disease, but few articles have reported severe thrombocytopenia after osimertinib treatment. This article reports a 64-year-old woman with non-small cell lung cancer initially diagnosed with cT2aN1M1a, EGFR p.L858R, who developed disease progression and T790M after 32 months of first-line treatment with gefitinib (250 mgday) before switching to second-line treatment with osimertinib (80 mgday). Severe thrombocytopenia and active bleeding occurred after treatment with osimertinib, which improved with recombinant human thrombopoietin and platelet transfusion. Treatment was replaced with aumolertinib (110 mgday). After platelet stabilization with aumolertinib treatment in combination with chest radiotherapy, this patient had progression-free survival for 9 months and overall survival for over 45 months. In conclusion, from our experience, aumolertinib has good efficacy and mild adverse effects, and is a good choice for non-small cell lung cancer patients with T790M, especially for patients at high risk of thrombocytopenia.

A case of lung adenocarcinoma with MET∆ex14 mutation regressed after preoperative treatment with savolitinib, and successfully underwent radical resection.

Non-small cell lung carcinoma (NSCLC) is a complex disease, with many different potential gene mutations that drive its formation, occurrence, and development. It is estimated that about 3% of NSCLC patients are accompanied by MET exon 14 skipping (METex14) mutations, and the prognosis of such patients is generally poor, which forms a formidable challenge for us. Savolitinib (Orpathys) is the first highly selective MET inhibitor in China. Here, we presented an NSCLC patient with MET∆ex14 mutation, who was initially uncertain whether existed intrapulmonary metastasis and recently underwent percutaneous coronary intervention for acute myocardial infarction and received savolitinib 600 mg once a day. The tumor was significantly shrunk 6 months later, and no metastatic lesions were found. Eventually, it was determined that the patient was in the early stage of lung cancer. After experts consultation and evaluation, the patient accepted radical tumor resection and recovered well. Therefore, savolitinib is an important treatment strategy for NSCLC patients with MET∆ex14 mutation, who was not suitable for surgery. Our experience may provide supporting evidence and guidance for implementing an effective therapeutic strategy for similar cases.

Neoadjuvant target therapy with ensartinib in lung adenocarcinoma with EML4-ALK fusion variant a case report and literature review.

Although neoadjuvant target therapy has been used to treat patients with non-small-cell lung cancer (NSCLC), most of these patients have mutations in the epidermal growth factor receptor (EGFR) gene. Few patients to date have received neoadjuvant target therapy for NSCLC containing variants in genes encoding anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs). Herein, we present a 51-year-old man with a lung mass in the left lower lobe with enlarged mediastinal lymph nodes. He was diagnosed with NSCLC after needle lung biopsy, with next-generation sequencing showing an echinoderm microtubule-associated protein-like 4 gene-anaplastic lymphoma kinase (EML4-ALK) fusion variant. The patient received neoadjuvant ensartinib, a second-generation ALK-TKI, for 5 months, followed by successful lobectomy through uniportal video-assisted thoracic surgery and adjuvant ensartinib. To our knowledge, few patients with ALK-positive NSCLC had received neoadjuvant treatment with ensartinib. Findings in this patient may widen indications for neoadjuvant target therapy in the treatment of resectable stage II-IIIA ALK-positive NSCLC.

The NIH-led research response to COVID-19.

Investment, collaboration, and coordination have been key.

M2 macrophage-derived exosomal miR-1911-5p promotes cell migration and invasion in lung adenocarcinoma by down-regulating CELF2 -activated ZBTB4 expression.

Lung adenocarcinoma (LUAD) is one of the most aggressive, lethal cancers, comprising around 40% of lung cancer cases. Metastases are the primary cause of LUAD deaths. The mechanism underlying metastatic LUAD and tumor microenvironment remain largely unknown. To explore the effect of M2 macrophage-derived exosomes on LUAD progression. Quantitative-PCR (q-PCR) and western blot were used to measure the expression of RNAs and proteins separately. Co-culture experiments wound healing and Transwell invasion assays were performed to evaluate the effect of M2 macrophage-derived exosomes on LUAD cell migration and invasion. RNA pulldown and luciferase reporter, RNA-binding immunoprecipitation (RIP), and mRNA stability assays were conducted to explore the downstream mechanism of exosomal microRNA-1911-5p (miR-1911-5p). M2 macrophage-derived exosomes accelerated the migration and invasion of LUAD cells. M2 macrophages-secreted exosomal miR-1911-5p enhanced cell migration and invasion in LUAD. Mechanically, miR-1911-5p targeted CUGBP- and ETR-3-like family 2 (CELF2) to downregulate zinc finger and BTB domain containing 4 (ZBTB4) in LUAD. Additionally, miR-1911-5p promoted LUAD progression via ZBTB4. The present study demonstrated that M2 macrophage-derived exosomal miR-1911-5p facilitates the migration and invasion of LUAD cells by inhibiting CELF2-activated ZBTB4, which might offer insight into LUAD treatment.

Electrophysiological evaluation of an anticancer drug gemcitabine on cardiotoxicity revealing down-regulation and modification of the activation gating properties in the human rapid delayed rectifier potassium channel.

Gemcitabine is an antineoplastic drug commonly used in the treatment of several types of cancers including pancreatic cancer and non-small cell lung cancer. Although gemcitabine-induced cardiotoxicity is widely recognized, the exact mechanism of cardiac dysfunction causing arrhythmias remains unclear. The objective of this study was to electrophysiologically evaluate the proarrhythmic cardiotoxicity of gemcitabine focusing on the human rapid delayed rectifier potassium channel, hERG channel. In heterologous hERG expressing HEK293 cells (hERG-HEK cells), hERG channel current (IhERG) was reduced by gemcitabine when applied for 24 h but not immediately after the application. Gemcitabine modified the activation gating properties of the hERG channel toward the hyperpolarization direction, while inactivation, deactivation or reactivation gating properties were unaffected by gemcitabine. When gemcitabine was applied to hERG-HEK cells in combined with tunicamycin, an inhibitor of N-acetylglucosamine phosphotransferase, gemcitabine was unable to reduce IhERG or shift the activation properties toward the hyperpolarization direction. While a mannosidase I inhibitor kifunensine alone reduced IhERG and the reduction was even larger in combined with gemcitabine, kifunensine was without effect on IhERG when hERG-HEK cells were pretreated with gemcitabine for 24 h. In addition, gemcitabine down-regulated fluorescence intensity for hERG potassium channel protein in rat neonatal cardiomyocyte, although hERG mRNA was unchanged. Our results suggest the possible mechanism of arrhythmias caused by gemcitabine revealing a down-regulation of IhERG through the post-translational glycosylation disruption possibly at the early phase of hERG channel glycosylation in the endoplasmic reticulum that alters the electrical excitability of cells.

Zoledronic acid-associated osteonecro sis of the jaw in patients with EGFR-sensitive mutant lung cancer two case reports.

Bone metastasis from lung cancer predicts a decrease in the quality of life and a shortening of survival for patients. While controlling the primary disease, active prevention and treatment of skeletal-related events (SREs) are crucial. The use of bisphosphonates as a basic drug for bone metastases from lung cancer has been increasing also, the corresponding adverse effects have emerged. The case is here reported of two cases of osteonecrosis of the jaw associated with zoledronic acid treatment were reported in patients with epidermal growth factor receptor -sensitive mutation non-small-cell lung cancer(NSCLC) and discussed the clinical features, early recognition and interventions.

Microfluidic study of retention and elimination of abnormal red blood cells by human spleen with implications for sickle cell disease.

The spleen clears altered red blood cells (RBCs) from circulation, contributing to the balance between RBC formation (erythropoiesis) and removal. The splenic RBC retention and elimination occur predominantly in open circulation where RBCs flow through macrophages and inter-endothelial slits (IESs). The mechanisms underlying and interconnecting these processes significantly impact clinical outcomes. In sickle cell disease (SCD), blockage of intrasplenic sickled RBCs is observed in infants splenectomized due to acute splenic sequestration crisis (ASSC). This life-threatening RBC pooling and organ swelling event is plausibly triggered or enhanced by intra-tissular hypoxia. We present an oxygen-mediated spleen-on-a-chip platform for in vitro investigations of the homeostatic balance in the spleen. To demonstrate and validate the benefits of this general microfluidic platform, we focus on SCD and study the effects of hypoxia on splenic RBC retention and elimination. We observe that RBC retention by IESs and RBC-macrophage adhesion are faster in blood samples from SCD patients than those from healthy subjects. This difference is markedly exacerbated under hypoxia. Moreover, the sickled RBCs under hypoxia show distinctly different phagocytosis processes from those non-sickled RBCs under hypoxia or normoxia. We find that reoxygenation significantly alleviates RBC retention at IESs, and leads to rapid unsickling and fragmentation of the ingested sickled RBCs inside macrophages. These results provide unique mechanistic insights into how the spleen maintains its homeostatic balance between splenic RBC retention and elimination, and shed light on how disruptions in this balance could lead to anemia, splenomegaly, and ASSC in SCD and possible clinical manifestations in other hematologic diseases.

Novel LINC01923-anaplasticlymphoma kinase rearrangement identified in advanced lung adenocarcinoma with durable response to ensartinib a case report.

Anaplastic lymphoma kinase (ALK) rearrangements are one of the most common mutations in nonsmall cell lung cancer. Majority of the ALK rearrangements were sensitive to crizotinib, yet some rare fusion types may less benefit. The patient with LINC01923-ALK fusion was treated with crizotinib for 1 week and developed an adverse rash reaction. Replaced with second-line treatment with esatinib, the patient had a partial response in the primary site and achieved a complete response in the brain metastases. The patient was treated successfully with ensartinib leading to a progression-free survival of 6 months (and counting). This is the first report on one lung adenocarcinoma patient with a novel LINC01923-ALK fusion beneficial from ensartinib, which provides more knowledge for ALK fusion spectrum.

The determinants of health-related quality of life among patients with newly diagnosed lung cancer in Taiwan A cross-sectional study.

Although considered one of the most important prognostic factors for lung cancer patients, the health-related quality of life (HRQOL) of the newly diagnosed lung cancer population remains scarcely focused on in the literature. Therefore, we aimed to identify the determinants of HRQOL among newly diagnosed lung cancer patients in Taiwan. Two hundred and fifty patients newly diagnosed with lung cancer were recruited from a medical center in northern Taiwan through convenience sampling. Four structured questionnaires, including the Taiwanese version of the MD Anderson symptom inventory (MDASI-T), the Taiwanese version of the Pittsburgh Sleep Quality Index (PSQI-T), the International Physical Activity Questionnaire-Short Form (IPAQ-SF), and the World Health Organization Quality of Life-BREF (WHOQOL-BREF), were used to collect data. Further, a multivariate stepwise linear regression was conducted to determine the independent risk factors for HRQOL. A p-value of less than 0.05 was considered statistically significant. The patients (mean age was 61.04 years, 51.2% male, 94.0% non-small cell lung cancer, 56.4% stage IIIB-IV) had moderate levels of HRQOL among the physical, psychological, social, and environmental domains, as well as overall QOL. HRQOL was not correlated with married status, religion, and comorbidity. Gender, age, family income, smoking status, cancer stage, ECOG PS scores, PA, symptom burden (severity and interference), and PSQI global scores were correlated with HRQOL. Notably, symptom severity was the dominant negative predictor affecting the psychological and environmental domains of QOL (β -4.313 and -3.500, respectively), accounting for 23.2% and 14.6% of the variance, respectively. On the other hand, symptom interference was the dominant negative predictor affecting the physical and social domains of QOL, as well as overall QOL (β -3.592, -1.984, and -0.150, respectively), accounting for 44.4%, 15.0%, and 24.1% of the variance, respectively. Newly diagnosed lung cancer patients suffered symptom severity and interference that significantly impaired their HRQOL particularly, symptom interference affected the physical domain of QOL. Healthcare professionals should pay more attention to cancer-related symptom severity, symptom interference, and HRQOL changes when caring for newly diagnosed lung cancer patients.

Successful osimertinib rechallenge after severe thrombocytopenia caused by osimertinib combined with sitagliptin a case report.

Osimertinib is recommended as the first-line treatment of advanced non-small cell lung cancer (NSCLC) in adults. The most commonly reported adverse events for osimertinib are skin effects, diarrhea, nausea, decreased appetite, fatigue, paronychia, and stomatitis. Severe thrombocytopenia is rarely reported. We present a case of severe thrombocytopenia in a 70-year-old NSCLC patient caused by osimertinib combined with sitagliptin. After remission of thrombocytopenia, the patient was well tolerated with osimertinib re-administration in the absence of sitagliptin. We speculated that declined platelet count might be related to the interaction between osimertinib and sitagliptin by acting with a synergistic effect on platelets. Osimertinib rechallenge can be considered after discontinuing drugs that may contribute to platelet decline if possible, and making a careful assessment of complete blood count and risk of bleeding.

Translating and Adapting the DISCERN Instrument Into a Simplified Chinese Version and Validating Its Reliability Development and Usability Study.

There is a wide variation in the quality of information available to patients on the treatment of the diseases afflicting them. To help patients find clear and accessible information, many scales have been designed to evaluate the quality of health information, including the Patient Education Materials Assessment Tool the Suitability Assessment of Materials for evaluation of health-related information for adults and DISCERN, an instrument for judging the quality of written consumer health information on treatment choices. These instruments are primarily in English. Few of them have been translated and adapted into simplified Chinese tools for health information assessment in China. This study aimed to translate and adapt DISCERN into the first simplified Chinese version and validate the psychometric properties of this newly developed scale for judging the quality of patient-oriented health information on treatment choices. First, we translated DISCERN into simplified Chinese using rigorous guidelines for translation and validation studies. We tested the translation equivalence and measured the content validity index. We then presented the simplified Chinese instrument to 3 health educators and asked them to use it to assess the quality of 15 lung cancer-related materials. We calculated the Cohen κ coefficient and Cronbach α for all items and for the entire scale to determine the reliability of the new tool. We decided on the simplified Chinese version of the DISCERN instrument (C-DISCERN) after resolving all problems in translation, adaptation, and content validation. The C-DISCERN was valid and reliable the content validity index was 0.98 (4748, 98% of the items) for clarity and 0.94 (4548, 94% of the items) for relevance, the Cronbach α for internal consistency was .93 (95% CI 0.699-1.428) for the whole translated scale, and the Cohen κ coefficient for internal consistency was 0.53 (95% CI 0.417-0.698). C-DISCERN is the first simplified Chinese version of the DISCERN instrument. Its validity and reliability have been attested to assess the quality of patient-targeted information for treatment choices.

Association of Radiation and Procarbazine Dose With Risk of Colorectal Cancer Among Survivors of Hodgkin Lymphoma.

Hodgkin lymphoma (HL) survivors have higher rates of colorectal cancer, which may be associated with subdiaphragmatic radiation therapy andor alkylating chemotherapy. Although radiation dose-response associations with breast, lung, stomach, pancreatic, and esophageal cancer after HL have been demonstrated, the association of radiation therapy with colorectal cancer remains unclear. To quantify the rate of colorectal cancer according to radiation dose to the large bowel and procarbazine dose among HL survivors. A nested case-control study examined 5-year HL survivors at 5 hospital centers in the Netherlands. Participants had been diagnosed with HL in 1964 to 2000, when they were 15 to 50 years of age, and were followed for a median of approximately 26 years. Survivors of HL who developed colorectal cancer and survivors who were selected as controls were individually matched on sex, age at HL diagnosis, and date of HL diagnosis. Data were analyzed from July 2021 to October 2022. Mean radiation doses to the large bowel were estimated by reconstructing individual radiation therapy treatments on representative computed tomography data sets. Excess rate ratios (ERRs) were modeled to evaluate the excess risk associated with each 1-gray increase in radiation dose, and potential effect modification by procarbazine was explored. The study population included 316 participants (mean SD age at HL diagnosis, 33.0 9.8 years 221 69.9% men), 78 of whom were HL survivors who developed colorectal cancer (cases) and 238 who did not (controls). The median (IQR) interval between HL and colorectal cancer was 25.7 (18.2-31.6) years. Increased colorectal cancer rates were seen for patients who received subdiaphragmatic radiation therapy (rate ratio RR, 2.4 95% CI, 1.4-4.1) and those who received more than 8.4 gm2 procarbazine (RR, 2.5 95% CI, 1.3-5.0). Overall, colorectal cancer rate increased linearly with mean radiation dose to the whole large bowel and dose to the affected bowel segment. The association between radiation dose and colorectal cancer rate became stronger with increasing procarbazine dose the ERR per gray to the whole bowel was 3.5% (95% CI, 0.4%-12.6%) for patients who did not receive procarbazine, and increased 1.2-fold (95% CI, 1.1-1.3) for each 1-gm2 increase in procarbazine dose. This nested case-control study of 5-year HL survivors found a dose-response association between radiation therapy and colorectal cancer risk, and modification of this association by procarbazine. These findings may enable individualized colorectal cancer risk estimations, identification of high-risk survivors for subsequent screening, and optimization of treatment strategies.

Association between the patients symptom burden and their family caregivers benefit finding in non-small cell lung cancer receiving combined chemotherapy.

The aim of the study is to explore the relationship between the patients symptom burden and their family caregivers benefit finding in non-small cell lung cancer (NSCLC) receiving combined chemotherapy. A cross-sectional study on 181 NSCLC patients receiving combined chemotherapy and their family caregivers was conducted at two comprehensive hospitals from December 2021 to August 2022 in China. The patients completed the self-designed questionnaire, The Chinese Version of M.D. Anderson Symptom Inventory (MDASI) and Lung Cancer Module of the M.D. Anderson Symptom Inventory (MDASI-LC), while caregivers completed the self-designed questionnaire, Benefit Finding Scale (BFS). The mean symptom burden score of NSCLC patients receiving combined chemotherapy was 71.55 (SD 22.19), and the median score of fatigue was 6 (IQR, 4, 7). Fatigue was the most severe symptom. The mean benefit finding score of family caregivers was 56.09 (SD 16.25). Among the dimensions of the benefit finding scale, the personal growth dimension scored the highest. The mean score of personal growth dimension was 18.31 (SD 5.47). The scores of symptom burden of NSCLC patients and the benefit finding of family caregivers were significantly different in patients clinical data stage of tumor, tumor metastasis, duration of illness, self-care ability, leukocyte count (WBC), blood platelet (PLT), hemoglobin content (Hb), Na The symptom burden of patients is adversely correlated with the benefit finding of family caregivers in NSCLC receiving combined chemotherapy the lighter the symptom burden of patients, the higher the benefit finding of family caregivers. Therefore, appropriate nursing measures should be taken for fatigue, lack of appetite, and other symptoms. A variety of ways should be taken to promote family caregivers to participate in patient symptom management, so as to achieve the goal of reducing the burden of patients symptoms and improving the level of family caregivers benefit finding.

Extracranial metastasis sites correlate to the incidence risk of brain metastasis in stage IV non-small cell lung cancer a population-based study.

The aim of this study was to analyse the correlation of extracranial metastasis sites (ECMs) to the incidence risk of brain metastasis (BMs) in stage IV non-small cell lung cancer (NSCLC). 18349 newly diagnosed patients were retrospectively analysed, and 4919 pairs of cases were matched by propensity score matching in a 11 ratio. Alternative factors were analysed by multivariable logistic regression analysis. And the interaction analysis and subgroup analysis were carried out. The incidences of Brain, Lung, Liver, Bone, Multiple and Other metastasis were 26.9%, 20.2%, 4.6%, 19.9%, 16.9% and 38.3%, respectively. Results suggested that Age, Race, Histological type, Grade, T stage, N stage and Organ metastasis site were risk factors (p < 0.05). The interaction analysis suggested interaction effects between the Primary site, T stage, N stage and Organ metastasis site. The subgroup analysis showed that the Organ metastasis site and the risk of BMs were statistically significant except that the Overlapping subgroup (p 0.267) of the Primary site. And the incidence risk of BMs in Lung metastasis, Liver metastasis and Bone metastasis groups was lower than that in other metastasis group (OR 1, p < 0.05). There was no significant difference between the Multiple metastasis group and the other metastasis group (OR 1.091, p 0.169). Advanced age, non-AsianPacific Islander, non-squamous cell carcinoma, poorly differentiated grade, and higher TN stage were risk factors for increased BMs in stage IV NSCLC, and the ECMs were associated with the risk of BMs.

The incidence and risk factors for acute kidney injury in patients treated with immune checkpoint inhibitors.

Recent observational studies reported acute kidney injury (AKI) events in over 10% of the patients treated with immune checkpoint inhibitors (ICIs). However, these studies included patients treated in high-resource settings and earlier lines. Therefore, we aimed to assess the AKI rates and predisposing factors in ICI-treated patients from a limited resource setting. We evaluated 252 patients with advanced cancer for this retrospective cohort study. AKI events were defined by Kidney Disease Improving Global Outcomes criteria. The median age was 59 years. The melanoma (18.3%), non-small cell lung cancer (14.7%) and renal cell carcinoma (22.6%) patients comprised over half of the cohort. During the follow-up, 45 patients (17.9%) had at least one AKI episode. In multivariable analyses, patients with chronic kidney disease (CKD) odds ratio (OR), 3.385 95% confidence interval (CI), 1.510-7.588 P 0.003, hypoalbuminemia (OR, 2.848 95% CI, 1.225-6.621 P 0.015) or renin-angiotensin-aldosterone system (RAAS) inhibitor use (OR, 2.236 95% CI, 1.017-4.919 P 0.045) had increased AKI risk. There was a trend towards increased AKI risk in patients with diabetes (OR, 2.042 95% CI, 0.923-4.518 P 0.78) and regular proton pump inhibitors use (OR, 2.024 95% CI, 0.947-4.327 P 0.069). In this study, we observed AKI development under ICIs in almost one in five patients with cancer. The increased AKI rates in CKD, hypoalbuminemia or RAAS inhibitor use pointed out a need for better onco-nephrology collaboration and efforts to improve the nutritional status of ICI-treated patients.