bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of venous thromboembolic complications in patients with pancreatic cancer.
Authors: Katelnitskaya Oksana V. , Kit Oleg I. , Frantsiyants Elena M. , Gevorkyan Yuriy A. , Kaymakchi Oleg Yu. , Snezhko Aleksandr V. , Soldatkina Natalya V. , Kolesnikov Vladimir E. , Dashkov Andrey V. , Poluektov Sergey I. , Aleksandrovich Maksim K. , Kaymakchi Dmitry O. , Pavlov Vladislav K. , Vereshchak Maksim A. , Savchenko Dmitriy A. , Tolmakh Roman E.
Published: June 2021

e16220

Background: Patients with pancreatic cancer are at high risk for venous thrombosis. Thrombotic episodes are most often recorded at the tumor diagnosis, surgical treatment and chemotherapy courses, or the disease recurrence. This complication postpones the beginning of treatment of the underlying disease and increases the mortality rate of cancer patients. The purpose of the study was to reveal the relationship between clinical characteristics and disorders of hemostasis indicators in patients with pancreatic cancer, and to identify predictors of venous thrombosis. Methods: 246 patients diagnosed with pancreatic cancer were recruited in 2019. The most common histological tumor type was pancreatic ductal adenocarcinoma (91.9%). The most common tumor site was the head of the pancreas (68.3%). Almost half of the patients were initially diagnosed with stage IV cancer (TanyNanyM1). Surgery was performed in 28% of patients. VTEC incidence during the 12-month follow-up period was 15.4%. Results: Analysis of the clinical characteristics and initial hemostasis parameters in patients with and without venous thrombosis revealed that the risk of thrombosis was higher in patients with larger tumors and the presence of distant metastases. High levels of D-dimers at diagnosis doubled the risk of venous thrombosis during antitumor treatment. Conclusions: The most significant predictors of venous thrombosis in patients with pancreatic cancer are tumor size, stage IV, and initially high levels of D-dimer. The study of hemostasis indicators at the stage of diagnosis of pancreatic cancer (D-dimer) can help to identify patients with a high risk of VTEC, for whom anticoagulant prophylaxis with a low hemorrhagic risk is advisable.
New method of hepatic artery reconstruction after its injury or resection.
Authors: Katelnitskaya Oksana V. , Kit Oleg I. , Gevorkyan Yuriy A. , Snezhko Aleksandr V. , Kaymakchi Oleg Yu. , Kolesnikov Evgeniy N. , Soldatkina Natalya V. , Kolesnikov Vladimir E. , Dashkov Andrey V. , Poluektov Sergey I. , Aleksandrovich Maksim K. , Kaymakchi Dmitry O. , Pavlov Vladislav K. , Vereshchak Maksim A. , Savchenko Dmitriy A. , Tolmakh Roman E.
Published: June 2021

e16221

Background: Restoration the hepatic arterial blood flow is required in traumatic or iatrogenic damage to the hepatic artery and its branches, as well as in the planned resection of the hepatic artery with subsequent reconstruction. Various ways have been proposed to solve this problem: ligation of the hepatic artery and its branches, which is associated with an extremely high mortality rate, reaching 70%, and the need for extensive liver resections; portal vein arteriolization; transposition of the splenic artery with its severe complications (heart attack, abscess) or hepatic artery replacement sometimes are not available and imply aggressive anticoagulant therapy, which is often challenging after extensive oncological interventions. Prosthetic vascular grafts are associated with a high risk of infection. We propose replacement of the common hepatic artery defect by transposition of the left gastric artery and end-to-end anastomosis between the proximal end of the left gastric artery and the distal end of the hepatic artery. Methods: The proposed method was applied in 7 cancer patients - 4 cases of iatrogenic damage to the common hepatic artery in lymph node dissection of the hepatoduodenal ligament and 3 resection of the common hepatic artery with tumor infiltration. The mean age of patients was 53 years. 2 patients had surgery for gastric cancer, 5 - pancreatic cancer. Results: The vascular reconstruction lasted for 17 minutes. No thrombotic complications of the reconstruction area or liver necrosis in the postoperative period were registered. The main advantages of this method were the absence of synthetic materials or deficit blood supply to neighboring organs, and no need for extensive mobilization of the great vessels in other areas (renal artery, abdominal aorta). Conclusions: The proposed method for reconstruction of the hepatic artery allows performing a simple and adequate restoration of the hepatic arterial blood flow, reduced time of the vascular stage of the surgery and reduced incidence of postoperative complications associated with the vascular stage - reduced time of liver ischemia and reduced risk of thrombosis in the reconstruction area.
Relative dose intensity (RDI) of nab-P in gem+nab-P combination in pancreatic cancer treatment and the prognostic role of baseline NLR.
Authors: Varayathu Hrishi , Kurian Lincil , Murugan Anju , Mathew Hephzibah Sara , Rani Sonia , Thomas Beulah Elsa , Sangi Lalram , Somayaji Shalaka , Mathew Smruthy Ann , Gupta Sunny Kumar , Tripathi Priyank , Mufti Suhail Sayeed , Naik Radheshyam , Ajaikumar Basavalinga Sadasivaiah
Published: June 2021

e16269

Background: Combination of Gem+Nab-P is considered as a dose intense regimen which exhibits synergistic cytotoxic activity and equally effective in increasing survival as FOLFIRINOX regimen in pancreatic cancer. However, number of patients who tolerates such dose intense regimen is found to be less in Indian population. The importance of maintaining optimum RDI is well-known however a low RDI may reflect a poor tolerability. Therefore, the present study aimed to identify desired relative dose intensity and explore the potential of baseline NLR as a prognostic biomarker. Methods: A retrospective chart review was performed of 26 patients with a median age of 65.5 years who received this drug combination either as first-line or second-line treatment for pancreatic adenocarcinoma at a single institution. Treatment outcome was measured using overall survival and toxicities were classified according to CTCAE guidelines. The thresholds for RDI of Gem and Nab-P, and baseline NLR cut-off for predicting survival was calculated by constructing ROC curves. Results: Median overall survival was 11.5 months. Median RDI of Gem and Nab-P was found to be 79% (30-94) and 71% (39 –114) respectively. We estimated a RDI cut-off of 67% in Nab-P and 68% in Gem and observed a statistically significant favorable outcome in patients who received Nab-P with RDI > 67% ( p-0.021). No significant relationship of Gem RDI with outcome was observed. Median overall survival was found to be higher in patients with a baseline NLR < 2.35, patients on D1, D8, D15 treatment regimen and those who received Nano particle bound paclitaxel. Complete assessment of study subjects are enlisted in the table. Grade 3 neuropathy, fatigue, and hyponatremia were reported in 2, 5 and 4 patients respectively. Grade 2 skin rashes and neuropathy were seen in 3 patients each. Conclusions: Our study concludes that tolerability of Gem+Nab P is a concern and it is expected to exhibit a durable response only if it achieves an optimum RDI of Nab-P. The study indicates varied efficacy in different pharmaceutical preparations of paclitaxel favoring the use of nano-particle formulations. The study also indicates that baseline NLR is an important prognostic biomarker in pancreatic cancer[Table: see text]
Lipid and neutrophil accumulation and active inflammasome in high BMI tumor regions of human pancreatic ductal adenocarcinoma.
Authors: Khattab Ahmed , Patruni Sunita , Garciafigueroa Yesica , Phillips Brett , Engman Carl , Khatoon Nazia , Shankar Karthik , Rizvi Ali , Miller Stacey , Zheng Lei , Giannoukakis Nick , Monga Dulabh K.
Published: June 2021

e16271

Background: Obesity is an established risk factor for cancer and cancer-related mortality. Adipocytes may act as a “damage” signal resulting in the accumulation of innate immune cells, fueling an inflammatory micro-environment. Among the innate immune cells, tumor-associated neutrophils (TANs) are confirmed to accumulate inside the tumor. As obesity is a significant risk factor for a poorer prognosis in pancreatic ductal adenocarcinoma (PDAC), we hypothesize that obesity-driven adipose fuels the progression of PDAC in a TAN and inflammasome-facilitated manner. This may happen through several mechanisms, including genomic instability of aggressive PDAC clonal populations. Methods: Tissue from resected tumors of PDAC patients (n = 44) with a body-mass index (BMI) > 27 (obese [n = 21]) and BMI < 22 (normal [n = 23]) were incubated with anti-human CD66b antibodies and detected using standard immunofluorescent microscopy techniques. Images were acquired in a Zeiss Axioplan microscope workstation and analyzed by ZEN and Metamorph software. Results: We identified the presence of adipocytes in all tissue sections and CD66b+ neutrophils in all tissue sections of normal BMI patients and in 81% of high BMI patients. There is a significantly greater density of adipocytes in the tumor environment when compared to adjacent normal areas, suggesting that these cells are acting as a damage signal. We have also shown that there are fewer total cells per area in the tumor region, suggesting a disorganization that may allow more adipose tissue to form in these areas of high BMI patients. Our novel data also shows that high BMI results in a significantly higher neutrophil count in tumor specific tissue when compared to patients with a low BMI. These data suggest an association between BMI and inflammasome accumulation in the tumor environment. Conclusions: Our data uniquely shows that CD66b+ neutrophils tend to accumulate inside PDAC in high BMI patients and this is associated with intra-tumoral active inflammasomes. The higher concentrations of these inflammasomes in higher BMI patients may be of mechanistic relevance in understanding how inflammation induces progression of PDAC. A larger cohort of tissues from PDAC obtained from low and high BMI individuals will be needed to test our hypothesis and to begin to decipher the role of obesity on inflammation and PDAC progression.
Circulating tumor DNA as a prognostic factor in peritoneal carcinomatosis after hyperthermic intraperitoneal chemotherapy.
Authors: Li Zongyuan , Pu Xiaolin , Jiang Hua
Published: June 2021

e16280

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) is the main treatment for peritoneal carcinomatosis (PC).However, It is still a major problem to predict the efficacy of HIPEC. Some studies have shown that peritoneal cancer index (PCI) can be used to predict the efficacy of HIPEC, but the invasiveness and inaccuracy are shortcomings. Therefore, we need a minimally invasive and accurate prediction biomarker. Many studies have confirmed that circulating tumor DNA (ctDNA) can accurately predict the efficacy and prognosis of various solid tumors. This study aimed to evaluate the predictive value of ctDNA from ascites and plasma for HIPEC. Methods: Eligible PC patients should be defintive diagnosed by pathology or cytology. Each patient was treated with HIPEC for 4 times, with an interval of 3 days each time. Plasma and ascites samples were collected before HIPEC and after the last HIPEC. All samples were detected by next generation sequencing (NGS). The molecular tumor burden index (mTBI) and main clone variant allele fraction (VAF) changes were used as the prediction indexes of efficacy. In addition, The changes of common tumor markers such as CEA during the same period were used as controls. Results: A total of 19 patients with PC were enrolled from November 2018 to January 2020. Firstly, the mTBI changes of 14 patients whom had plasma samples at two time points (baseline and postHIPEC)were analyzed. Among them, 3 patients had no gene mutation were detected in two time points. There were significant differences in mTBI before and after HIPEC in the remaining 11 patients (Wilcoxon， p = 0.026). the median Ascites progression free survival (PFS) was 3.35 months (95% CI: 2.34 – 5.13 months), and the median overall survival (OS) was 5.93 months (95% CI: 4.93 – 11.17 months). The mTBI decline was significantly positively correlated with ascites PFS (Spearman r = 0.673, p = 0.023) and moderately positively correlated with OS (Spearman r = 0.510, p = 0.109). The highest VAF in plasma samples was defined as the main clone mutation. The main clone VAF decline was moderately positively correlated with ascites PFS (Spearman r = 0.588, p = 0.057) and slightly positively correlated with OS (Spearman r = 0.386, p = 0.241). As the controls, We found that the common tumor markers decline was no correlated with ascites PFS(Spearman r = 0.091, p = 0.790) and OS (Spearman r = 0.287, p = 0.396). We further analyzed the correlation of VAF between ascites and plasma co-mutation genes in 12 patients. The VAF of co-mutated genes in plasma and ascites was positively correlated (Spearman r = 0.794, p = 0.001). Conclusions: Plasma ctDNA can be used as a biomarker for predicting the efficacy of HIPEC for peritoneal carcinomatosis, and its accuracy is significantly higher than comon tumor markers. However, a larger sample size study are needed to validate our results.
Is it anemia an independent prognostic factor of patients with renal cell carcinoma? A university hospital experience.
Authors: Bighetti Bruna , Seo Giuliana , Leite Pamela Reinaldo , Jesus Thais , Luz Gyovanna , Santoro Ilka Lopes , Tadokoro Hakaru , Padua Tiago
Published: June 2021

e16501

Background: Clear cell carcinoma (RCC) is the most common histologic type of renal cancer. It is well established that, for this specific histology, six main prognostic factors interact into a score and can categorize it into three different prognostic groups: favorable-risk, intermediate-risk, and poor-risk. These six factors are anemia, thrombocytosis, neutrophilia, hypercalcemia, Karnofsky performance status < 80%, and < 1 year from diagnosis to treatment. The objective of this study is to evaluate if any of these prognostic factors can independently predict a worse prognosis. Methods: We conducted a retrospective study with 51 patients treated in our national reference institution. The great majority of them were RCC. We analyzed the overall survival (OS) of each one of the six classic risk factors adding to that the body mass index (BMI), the presence of metastasis at diagnosis time, and comorbidities. Results: The analysis of most of the indexed parameters did not show a statistical difference, but anemia and the presence of metastasis at the time of diagnosis. We found that the anemia itself denotes a Hazard Ratio (HR) of 2,35 (p = 0,034). Moreover, if it is adjusted for age and sex, the HR reduces at 1,149, sustaining its statistical significance yet. The presence of metastasis at the time of diagnosis is translated as an HR = 2,029 (p = 0,049), bringing into light something already known in clinical practice, but still, a lower risk compared to anemia. Conclusions: The six classic risk factors for RRC survival pooled together can interact and predict the OS and patient’s prognosis. Our study suggests that the anemia itself can predict independently a worst-case scenario, which emphasizes the importance of this analysis upfront. A larger prospective cohort is warranted to further understanding this framework.
Relationship between neutrophils/lymphocytes and tumor infiltrating lymphocytes stroma in patients with invasive muscle bladder cancer and the response to treatment.
Authors: Richardet Martin Eduardo , Ferreira Maria gimena , Paradelo Martin , Acosta Luciana Paola , Molina Matias , Magi Ignacio , Richardet Eduardo
Published: June 2021

e16513

Background: The bladder cancer is a malignant disease. It has been related to tobacco consumption, fat diet, high body mass index (BMI) and urinary tract infections. As a result of the activation the pro-inflammatory pathways. Neutrophil to lymphocyte radio (NLR) and the infiltrating lymphocytes of the tumor stroma (TILs) have been shown to have a significant prognostic value in different tumors. The primary aim is to analyze the role of TILs and RNL as a predictive factor, in patients with MIBC and objective response rate (ORR). The secondary aim is to evaluate the relationship beteween BMI, tabaquism and ORR, in the same group of pts. Methods: A total of 35 pts with MIBC was included. All pts received neoadjuvant treatment, with cisplatin and gemcitabine. Also, TILs was determined as the percentage of mononuclear inflammatory cells in the total stromal area counted in 5 high-power fields (CGA, X 400), on the invasive front of the tumor. The NLR was obtained before treatment and value of cut-off was 2.6. the evaluation of ORR was calculated used the T-Test and Chi Square test. Results: Of the total of 35 patients. 15 patients obtained complete response (CR), 6 pts partial response (PR), 5 pts stable disease (SD) and 9 pts disease progression (DP). In 21 tumor sample was observed an intense TILS. These patients obtained a better ORR 42.6 % vs 21.7% with low TILs in his tumor samples. The difference was statistically significant (p: 0.001). Regarding NLR, only 9 pts presented response with NLR > 2,6 vs 12 pts with response and RNL < 2.6. The difference was not statistically significant. When analyzing the smoking and response. We could observe response of 69.6% in smoking pts vs Non- smoking the response was 41.7%. Regarding BMI, 21 pts with response of 27% and 14 patient without response 25.9%. But the differences were not significant in any groups. Conclusions: We conclude that the presence of TILS in tumor samples, in patients with MIBC, could be a predictive factor against the response to neoadjuvant treatment. With the other variables, smoking and BMI, we did not observed influence in ORR. We will keep working to obtain a greater number of patients. Then we could have a better analysis and statistical power.
Analysis of metabolism-related gene signature for prognosis prediction of clear cell renal cell carcinoma.
Authors: Cao Dalong , Liao Yuchen , Wang Guoqiang , Cai Shangli , Shi Guohai
Published: June 2021

e16580

Background: Clear cell renal cell carcinoma (ccRCC) is characterized by a dysregulation of changes in cellular metabolism. However, the prognostic value of metabolism-related genes in ccRCC have not been systematically profiled. In this study, a candidate prognostic gene signature of metabolism in ccRCC was explored. Methods: The clinical and gene expression profiles of ccRCC patients were downloaded from the TCGA, GEO and three clinical trials (CheckMate 009, CheckMate 010, CheckMate 025), and the metabolism-related gene set was downloaded from MSigDB. Differential expression analysis and LASSO Cox regression with binomial deviance minimization criteria were applied to identify and build a metabolism-based signature. The prognostic significance of the signature was further evaluated with the Receiver Operating Characteristic (ROC) curve analysis. Univariate and multivariate Cox regression analysis was performed to evaluate the impact of each variable on OS. Furthermore, the prediction power of the signature has been validated using different ccRCC cohort. Results: In this study, a signature of 8 metabolism-related genes (ANGPT2, ATP6V1B1, CACNA1E, CD163L1, EPN2, HOXD11, PROS1, SHOX2) was constructed as being significantly associated with overall survival (OS) among patients with ccRCC, which differentiated ccRCC patients into high- and low-risk subgroups. The Kaplan-Meier (KM) analysis showed that the survival rate of the low-risk patients was significantly higher than that of the higher-risk patients (hazard ratio (HR) in training set, 0.25 [95% CI, 0.14-0.44; P < 0.001]; testing set, 0.28 [95% CI, 0.10-0.76; P = 0.008]; validation cohort (clinical trials), 0.47 [95% CI, 0.33-0.68; P < 0 .001]; validation cohort (GSE29609), 0.25, [95% CI, 0.08-0.88; P = 0 .01]). ROC curve analysis of the prognostic signature showed that the areas under curve (AUC) for the 1-, 3-, and 5-year OS in all cohort were more than 0.70 (AUC of the signature for 3 year in the training set and validation cohort were 0.816 and 0.708, respectively, and 0.807 and 0.702, respectively, for the 5- year OS). Further more, a nomogram based on the signature was constructed and showed an accurate prediction for prognosis in ccRCC. Conclusions: Taken together, we identified the key metabolism-related genes and constructed a robust prognostic signature for the prognostic predictor of ccRCC patients, which maybe help personalized management of ccRCC patients.
A prospective phase 2/3 study of PSMA-targeted 18F-DCFPyL-PET/CT in patients (pts) with prostate cancer (PCa) (OSPREY): A sub-analysis of disease staging changes in PCa pts with recurrence or metastases on conventional imaging.
Authors: Durack Jeremy C. , Alva Ajjai Shivaram , Preston Mark A , Pouliot Frederic , Saperstein Lawrence , Carroll Peter R. , Pienta Kenneth J. , Rowe Steven P. , Patnaik Akash , Probst Stephan , Stambler Nancy , Jensen Jessica , Wong Vivien , Siegel Barry A. , Morris Michael J.
Published: June 2021

e17003

Background: Conventional imaging and bone scintigraphy are suboptimal modalities for identifying PCa. PSMA-based imaging is highly promising for PCa detection. 18F-DCFPyL is a novel PSMA-targeted radiopharmaceutical for positron emission tomography (PET) that may be useful in staging of PCa. The diagnostic performance, detection rate, and potential impact of 18F-DCFPyL on staging of pts with high-risk PCa have been previously reported. Here we report on the impact of 18F-DCFPyL on staging of pts with PCa recurrence or metastases on conventional imaging. Methods: 18F-DCFPyL-PET/CT was evaluated in 117 men with radiologic evidence of local recurrence or metastatic disease on baseline anatomical imaging (CT, MRI) or whole-body bone scintigraphy and in whom at least one lesion was deemed amenable to biopsy. A single dose of 9 mCi (333 MBq) of 18F-DCFPyL was administered via intravenous injection, followed by PET/CT acquisition 1 to 2 hours thereafter. Based on TNM staging: prostatic (T), pelvic LN (N), extra-pelvic LN (M1a), bone (M1b) and other visceral organs/soft tissue (M1c), 18F-DCFPyL-PET/CT detection rates including lesion counts were systematically analyzed. Three central, blinded, and independent readers evaluated the 18F-DCFPyL scans. Results: In this study, 82 (70%) patients had baseline radiographic M1 stage disease (14 patients with M1a, 50 patients with M1b, 18 patients with M1c) and 33 (28%) patients were M0 stage at baseline by central conventional imaging review; two patients were unevaluable. 18F-DCFPyL-PET/CT up-staged 58% (19/33) of pts from M0 to M1, of whom 91% (10/11) who underwent an extra-pelvic biopsy were confirmed to have M1 disease by pathology, including 9 patients with M1b and 1 patient with M1a. Of the patients who were staged M1 at baseline, 18F-DCFPyL-PET/CT upstaged 16% (10/64; M1a to M1b or M1c: n = 4; M1b to M1c: n = 6) of pts to a higher M1 sub-stage and down-staged 22% (18/82) to M0. Conclusions: 18F-DCFPyL-PET/CT identified M1 disease in the majority of patients examined who otherwise had locoregional disease. These data suggest that 18F-DCFPyL-PET/CT may be a useful tool in properly staging men with both metastatic and nonmetastatic relapsed disease, which could lead to superior treatment paradigms than currently exist using conventional imaging. Clinical trial information: NCT02981368.
Association of basophil to lymphocyte ratio (BLR) with clinical outcomes in metastatic hormone sensitive prostate cancer.
Authors: Smith Katherine Emilie Rhoades , Wan Limeng , Liu Yuan , Brown Jacqueline T , Russler Greta , Yantorni Lauren Beth , Caulfield Sarah , Carthon Bradley Curtis , Kucuk Omer , Nazha Bassel , Master Viraj A. , Bilen Mehmet Asim
Published: June 2021

e17049

Background: There is limited biomarker data available for metastatic hormone sensitive prostate cancer (mHSPC). Inflammatory markers found on routine clinical lab data, including leukocyte to lymphocyte ratios calculated from complete blood counts (CBC), is associated with clinical outcomes (CO) in different malignancies. We investigated the association between basophil-to-lymphocyte ratio (BLR) and CO in a racially diverse patient population with mHSPC. Methods: We performed a retrospective multicenter review from Winship Cancer Institute at Emory University and Georgia Cancer Center for Excellence at Grady Memorial Hospital (2014 – 2020). Demographics, disease characteristics, and laboratory data were collected at the start of upfront therapy with either docetaxel (DOC) or abiraterone (ABI). Overall survival (OS) and progression-free survival (PFS) were used to measure CO. Results: Included were 165 patients with mHSPC with a median follow-up time of 22.6 months. 89 (53.9%) were Black and 76 (46.1%) were Non-Black (White, Asian, or Hispanic). 106 (63%) had Gleason scores of 8-10 and 105 (63.6%) were classified as high-volume disease (per CHAARTED trial criteria). 92 (55.8%) received DOC and 73 (44.2%) received ABI. Worse CO were associated with high BLR at an optimal cut of 0.0265 (range 0 – 0.81 , mean of 0.03, standard deviation 0.09). Elevated BLR is associated with decreased OS (HR 3.51, 1.79 – 6.91, p <0.001) and PFS (HR 1.85, 1.14 – 3.00, p 0.013) in multivariable analyses (MVA). High BLR and low BLR groups were similar except for age as a continuous variable, which was associated with high BLR. Otherwise, there were no significant difference for all reported clinical characteristics, including drug (DOC vs ABI), race (Black vs Non-Black), Gleason, disease volume (per CHARRTED criteria), ECOG, or BMI. Conclusions: In mHSPC, high baseline BLR is associated with worse OS and PFS. Our results are the first to identify that BLR is associated with CO in mHSPC. Further study is needed to validate BLR as a potential biomarker.[Table: see text]
The outcomes of ‘8’suture suspension laparoscopic radical hysterectomy for early-stage cervical carcinoma.
Authors: Lu Huaiwu , Zhang Yuhao , Xu Miaochun , Huo Chuying , Lin Zhongqiu
Published: June 2021

e17519

Background: The mainly causes may due to the use of uterine manipulator and unprotected vaginal incision. To avoid these disadvantages, we modified the procedures by using ‘8’ suture suspension of the uterine instead of the uterine manipulator and vagino-purse-string suture before cutting of the vaginal. The aim of this study is to evaluate surgical data and oncological outcome of LRH without uterine manipulator based‘8’suture suspension method for early-stage cervical cancer. Methods: Patients with cervical cancers who underwent‘8’ suture suspension LRH in our center between January 2018 to August 2020 were retrospective analyzed. Without the use of uterine manipulator, a 2-0 absorbable suture was used to make an‘8’suture at the fundus of the uterine, and then make a coil. Another suture was passed through the coil to manipulate the uterus towards suitable directions. When separating the rectovaginal space, a needle with suture was pierced into the abdominal cavity from the abdominal wall above the pubic symphysis and passed through the coil to pull the uterus upwards and forwards, which was remove when separating the vesicovaginal space. Before cutting of the vaginal, a vagino-purse-string suture was made to prevent the tumor exposure in the abdominal cavity. Surgical data, postoperative complications, relapse rate and disease-free survival rate were evaluated. All operations were performed by the same surgical team. Results: A total of 48 cervical cancer patients were included in this study. Eight patients were stage IA2, 37 patients were stage IB and 3 patients were stage IIA1. There were 37 patients with squamous carcinoma while 11 with adenocarcinomas. The mean operative time was 199min (ranged from 120 to 290min). The median time of hospital stay after surgery was 7 days (ranged from 4 to 17 days). The mean blood loss volume was 40ml (ranged from 5 to 200 ml). The mean of number of removed lymph nodes are 30. The median time of removing urinary tube was 18 days (ranged from 12 to 25 days). The median time of postoperative exhaust time was 3 days(ranged from 2 to 4 days). There were no intraoperative complications, while postoperative complications were observed in 4 patients with fever. The median follow- up times were 16 months. During the follow-up time, there were no recurrence. Conclusions: The‘8’suture suspension LRH is a feasible and safe surgical procedure for early stage cervical cancer, with acceptable surgical and oncological outcomes in the hands of well-trained and experienced laparoscopic surgeons.[Table: see text]
Frequency of homologous recombination repair alterations in ovarian cancer in Chinese population.
Authors: Yang Tongtong , Liu Huanhuan , Li Mingwei , Zhang Yanrui , Zhang Yun , Liang Xiayuan , Zhou Tao , Lou Feng , Cao Shanbo , Wang Huina
Published: June 2021

e17531

Background: Ovarian Cancer (OC) is the most lethal cancer of all gynecological malignancies.Circulating tumor DNA (ctDNA) has received substantial attention in recent years resulting from the non-invasive, safe and effective method with considerable potential for clinical diagnosis and treatment management in patients with OC. Here, we assessed the mutational feature in homologous recombination repair (HRR) using ctDNA in OC. Methods: Plasma ctDNA was isolated from blood of patients and then was analyzed by AcornMed Biotechnology NGS-based assay for 808 genes panel for genomic alterations. The somatic and germline pathogenic mutations were identified in 12 HRR genes (ATM, BRCA1, BRCA2, BRIP1, CHEK1, CHEK2, FANCA, PALB2, RAD51B, RAD51C, RAD51D, RAD54L). Results: At our institution, 85 patients underwent NGS analysis of ovarian cancer specimens. The median age was 57 (range from 26 to 83). Twenty-six patients(42.34%) harbored a mutation in at least 1 of the HRR genes in their tumor. The most commonly altered HRR gene was BRCA1 (18.25%), followed by BRCA2 (8.76%), ATM (5.84%), RAD51D(3.65%), CHEK2 (2.92%), FANCA(2.19%) and RAD51C (0.73%). To determine the difference of mutation landscape in HRR between Chinese and western populations, we compared prevalence and spectrum in cases between our cohort and the cohort of Heeke et al 1(Table). Prevalence of HRR were different from the Western cases(42.34% vs 20%, P＜0.05). Of note, BRCA1, BRCA2, ATM and CHEK2 alterations rate was higher in our cohort, and BRIP1 and PALB2 were only detected in the western cohort. Conclusions: CtDNA can characterize the mutational feature of HRR in OC. Around 42.3% of patients with OC harbour germline or somatic HRR mutations. The expanded use of PARP inhibitors in HRR deficient tumours using a signature of HRR by ctDNA in clinical practice requires validation.[Table: see text]
MicroRNAs as predictors of future endometrial malignancies in endometrial hyperplasia without atypia.
Authors: Lai Chyong-Huey , Lin Chiao-Yun , Wu Ren-Chin , Yang Lan-Yan , Tseng Hsiao-Jung , Tang Yun-Hsin , Jung Shih-Ming , Ueng Shir-Hwa , Huang Huei-Jean , Chao Angel
Published: June 2021

e17563

Background: The histological criteria of predicting risk of progression of endometrial hyperplasia (EH) to endometrial cancer (EC) is based on the degree of architectural crowding and nuclear atypia. We aim to investigate the cumulative rate of progression to EC in simple or complex hyperplasia without atypia (SH/CH-nonA) and the molecular biomarkers for risk of developing EC in women with SH/CH-nonA. Methods: EH tissues of EC patients with preceding SH/CH-nonA (case) were compared to SH/CH-nonA patients without progression to EC (control) using miRNA array, followed by reverse transcription and quantitative real-time polymerase chain reaction (RT-qPCR), and verified in an independent cohort. Results: The 10-year and 15-year cumulative rates were 8% and 10%, respectively by the hospital medical records. The median time from EH to EC was 8.71 years (range, 0.55-19.84). Twenty miRNAs (p < 0.05, fold change > 4) were significantly different in SH/CH-nonA cases (n = 6) compared to SH/CH-nonA controls (n = 12) by miRNA array. Multiplex RT-qPCR validation (51 SH/CH-nonA controls and 19 SH/CH-nonA cases) selected miR30a-3p, miR141, miR200a, and miR200b. Area under the curve values for tissue miR30a-3p (p = 0.043), miR141(p = 0.003), miR-200a (p < 0.001), and miR200b (p = 0.004) in discriminating cases from controls were 0.658, 0.734, 0.811, and 0.710, and the sensitivity and specificity rates were 56.9% and 76.5%, 73.7% and 74.5%, and 68.4% and 100%, 47.4% and 100%, respectively. Conclusions: MiR30a-3p, miR141, miR-200a, and miR200b are useful tissue biomarkers for predicting future risk of developing EC for patients with SH/CH-nonA.
Invasive Paget’s disease of the breast versus genitalia versus skin: What are the demographic and prognostic differences?
Authors: Moon Ashley S. , Liao Cheng-I , Chen Hsiu-Min , Lee Danny , Chan John
Published: June 2021

e17577

Background: Invasive extramammary Paget’s disease is most commonly in the vulva but can also occur in other genitalia as well as primary skin locations (face, scalp, neck, trunk, extremities). We aim to determine the clinicopathologic and prognostic factors of invasive Paget’s disease of the breast, genitalia and skin. Methods: Data on patients with invasive Paget’s disease of the breast, genitalia and skin were collected between 2001 and 2015 from the National Cancer Data Base Participant Use File 2016. Univariate, multivariate analyses, and Kaplan-Meier survival analysis were performed by SAS. Results: 10, 122 female patients were eligible, of which 7, 051 had invasive disease (breast n = 5, 105, genitalia n = 1, 717, skin n = 229) and the remainder had in situ disease. Median age for invasive disease was 63 years for breast, 73 years for genitalia and 75 years for skin. Among Whites, the proportion of invasive Paget’s of breast, genitalia, and skin was 70.8%, 25.8%, 3.4%; Blacks 93.8% breast, 5.3% genitalia and 0.9% skin; Asian/Pacific Islanders 65.0% breast, 31.8% genitalia and 3.2% skin. Among treatment institutions, academic centers treated 30.2% of invasive breast, 48.9% genitalia and 51.5% skin. Surgery was performed in 89.4% of invasive breast compared to 21.1% genitalia and 46.7% skin. Radiotherapy was administered to 25.3% of invasive breast, 3.0% genitalia and 15.3% skin. Chemotherapy was given to 28.0% of breast, 1.9% genitalia and 5.7% skin. Early stage (I or II) disease was diagnosed in 70.8% of invasive breast, 63% genitalia and 30.6% skin. Five-year OS from any cause for patients with invasive Paget’s disease of breast, genitalia and skin was 81.9%, 83.8%, and 69.9%, respectively. In univariate analysis, older age (HR 3.75, 95% CI 3.27-4.31, p < 0.001), Black race (HR 1.21, 95% CI 1.00-1.46, p = 0.046), history of other cancer (HR 1.53, 95%CI 1.36-1.71, p < 0.001), higher comorbidity score (HR 2.12, 95%CI 1.88-2.39, p < 0.001), higher stage (HR 4.25, 95%CI 3.73-4.85, p < 0.001), and no surgical treatment (HR 3.47, 95% CI 2.87-4.19, p < 0.001) were associated with worse survival. In multivariate analysis, invasive Paget’s of the skin was associated with the worst survival (HR 1.56, 95% CI 1.19-2.05, p = 0.001). For all three types of invasive Paget’s disease, better prognosis was associated with Asian/Pacific Islander race (HR 0.49, 95% CI 0.31-0.80, p = 0.004), income ≥ $63, 000 (HR 0.83, 0.70-0.98, p = 0.028) and treatment at an academic/research center (HR 0.78, 0.62-0.99, p = 0.037). Conclusions: Invasive Paget’s disease of the breast is 3-fold more common than genitalia with younger age at diagnosis. Most are diagnosed at early stages with good prognosis. Blacks have a higher proportion of invasive Paget’s disease of the breast than other races. Invasive Paget’s disease of primary skin had the poorest prognosis.
Cytokines performance during nivolumab treatment: A subgroup analysis of NIVACTOR study.
Authors: Denaro Nerina , Paccagnella Matteo , Galizia Danilo , Falletta Antonella , Abbona Andrea , Gammaitoni Loretta , Fiorino Erika , De Zarlo Lorena , Bossi Paolo , Sangiolo Dario , Licitra Lisa F. , Aglietta Massimo , Merlano Marco Carlo
Published: June 2021

e18008

Background: Nivolumab is approved for 2nd line R/M SCCHN, but only ̃20% of patients will benefit. Therefore, there is an unmet need for predictive markers. Nivactor is a prospective real-life study of nivolumab in SCC-HN. We report an ancillary study on circulating cytokines in a subgroup of patients from Nivactor. Methods: We analysed changes of circulating cytokines (IL-2/4/5/6/8/10/12/13/15, CCL-2/4/22, CXCL-10, IFN-γ, TGF-β, TNF-α, VEGF) during nivolumab therapy at baseline (T0), cycle 3 (T1), cycle 7 (T2) and at disease progression (TPD). ROC analysis identifies cytokines that correlate best with PFS and OS and calculate cut-off points. Cox analysis was performed to assess HR. Hierarchical Clustering on Principal Components (HCPC) was performed to cluster pts and then compared clusters for good or poor PFS and OS. Correction for multiplicity was applied. Results: 19 pts were analysed. Using ROC analysis, we were able to identify cut-off values correlated with PFS at T0 only for IL-6 and IL-10. Similarly, we identified IL-6, IL-10, TGF-β and VEGF cut-off for OS. Then we performed Cox analysis dividing the population based on the identified cut-offs and we found that pts with IL-6 or IL-10 lower than cut off had a significant better PFS and OS (p = 0.049 and p = 0.003 for PFS, respectively; p = 0.029 and p = 0.006 for OS, respectively). TGF-β lower than cut-off correlates with better OS (p = 0.02). Interestingly, pts with all the 3 cytokines below the cut-off show the best OS. Finally, we performed a multivariate analysis using HCPC to identify 4 clusters of pts. Cluster 2 has the best PFS and OS than all other cluster considered together (p = 0.001 and p = 0.004 respectively). Patients in cluster 2 show at T0 lower IL-6/10/15 and at T1 lower IL-5/10 and higher IFN-γ compared to the others. Longitudinal analysis among the 3 time points shows that the increase of IFN-γ, IL-5 and IL-10 between T0 and T1 correlates with better PFS (p = 0.01, p = 0.03, p = 0.02, respectively); only IFN-γ and IL-5 correlates with better OS (p = 0.04; p = 0.02, respectively). Conclusions: ROC analysis can identify cytokines whose basal level may predict patients that could benefit from nivolumab treatment: low IL-6 and IL-10 positively influence both PFS and OS. Low TGF-β does not correlate with PFS but only with better OS and can be considered a pure prognostic marker. Longitudinal analysis offers information on the effect of treatment on circulating cytokines, and show that the subgroup of pts with better PFS exhibits an increase of inflammatory cytokines values.
NTRK, ALK and RET rearrangements in salivary gland cancer.
Authors: Kutukova Svetlana , Imyanitov Evgeny , Beliak Natalia P. , Ivaskova Julia V. , Razumova Alexandra
Published: June 2021

e18023

Background: We investigated the prevalence of rare genes rearrangements in salivary gland adenocarcinomas and the impact of these fusions on overall survival (OS) and progression free survival (PFS). Methods: For 51/60 (85.0%) patients with different types salivary gland adenocarcinomas (stage I-IVA), sufficient tumor tissue was available for molecular characterization by polymerase chain reaction (PCR) and has been tested for NTRK, ALK, ROS1, RET and MET deletion. OS and PFS curves were estimated with the Kaplan-Meier method and compared using the log-rank test. Results: Two cases (3.92%) of NTRK translocation were found, both are a classic rearrangement of ETV6ex5; NTRK3ex15. Of the other alterations, 2 cases (3.92%) of unbalanced ALK expression. However, it was not possible to establish the option of rebuilding. In addition, were found 2 cases (3.92%) of highly balanced expression of NTRK2 and ALK, and one case (1.96%) of high expression of ROS1. RET mRNA expression was detected in 13 of 48 cases (27.08%). NTRK, RET, ALK and ROS1 fusions were equally common in both men and women (p = 0.89), not depending on age (0.76). All patients bearing ALK, RET and NTRK fusions had shorter overall survival - 13.2 months, 95% confidence interval [CI] 13.0 to 32.0 months in multivariable model 105.0 moth (95% CI 105.0-105.0) in patient's group without mutations (p = 0.1817); and shorter PFS: 5.0 month (95% CI 5.0-16.0) vs not reached PFC in group (mean of PFS 63.15±5.58; 95% CI 52.20-74.09) without mutations (p = 0.0467). ALK fusion is an independent poor prognosis factor affecting on OS: p = 0.0168, hazard ratio (HR) = 8.65 (95% CI 1.47-50.77); and poor prognosis factor affecting on PFS: p = 0.0170, HR = 7.13 (95% CI 1.42-35.80). Conclusions: ALK, NTRK, ROS1 and RET mutations define a new rare subtype of salivary gland adenocarcinomas with enormously poor prognosis. The presence ALK-mutation is an independent poor prognosis factorб negatively affecting both overall survival and progression-free survival. It’s advisable to consider the possibilities of using ALK, NTRK and RET inhibitors in this cohort of patients.
Comparison of diagnostic characteristics between sentinel lymph node biopsy (SLNB) and radio-guide elective neck dissection (RGEND) in patients with T1-2N0 oral tongue cancer.
Authors: Kotov Maxim , Radzhabova Zamira , Novikov Sergey
Published: June 2021

e18037

Background: Elective neck dissection remains the standard treatment for cN0 oral cancer due to the high incidence of occult lymph node (LN) metastases. Sentinel lymph node biopsy (SNB) might be a less morbid alternative to neck dissection. Diagnostic value of SLNB depends on the number of sampled LNs. We aimed to compare the diagnostic features of SNB and RGEND in patients with T1-2N0 oral tongue cancer. Methods: A prospective study was conducted in patients with cT1-2N0M0 oral tongue squamous cell carcinoma treated between January 2016 and December 2020. The procedure included SLNB ollowed by immediate extent ipsilateral neck dissection. SLNB included accumulated radiotracer LNs, which located close to the primary tumor. RGEND included LNs accumulated radiotracer with all LNs located at the same level. Pathology assessment was performed and diagnostic characteristics were compared between SLNB and RGEND. Results: A total of 38 patients were enrolled. The mean age was 55.7±13,1. Twenty-four patients had unilateral lymph flow and 14 had bilateral. Sentinel LNs were located at levels IIa-III. Occult metastases were found in 15,8% (n = 6) of patients. The median number of LNs in the sample was 3 (IQR: 1-5). The sensitivities of SLNB and RGEND were 50% (95%CI: 15.7 - 84.3) and 100% (95%CI: 54.7-100), respectively, p-value = 0.001. Specificity was similar among groups: 100% (95%CI: 88-100) and 100% (95%CI: 89.1-100. SLNB had accuracy of 89.5% (95%CI: 77.2 - 97), and RGEND 100% (95% CI: 90.7-100), p-value = 0.001. Positive predictive value (PPV) was similar among groups. Negative predictive value (NPV) was 88.2% (95% CI: 78.9 - 93.7) in SLNB and 100% (95%CI: 91-100) in RGEND groups. p-value = 0.001. Conclusions: SLNB and RGEND have high rates of specificity, accuracy, PPV, and NPV, regardless of sampling size. RGEND has the highest sensitivity in patients with cT1-2N0 oral tongue cancer.
Trainings needs of allied health professionals caring for sexual and gender minority adolescents and young adults with cancer: A qualitative analysis.
Authors: Alpert Ash B. , Gampa Vikas , Vadaparampil Susan Thomas , Quinn Gwendolyn P.
Published: June 2021

e18532

Background: Little is known about the training needs of allied health professionals who provide reproductive health counseling and other support services to sexual and gender minority (SGM) adolescent and young adult (AYA) people with cancer. Methods: A 28-item electronic survey with 4 qualitative items was distributed to 601 allied health professionals who had participated in a training focused on reproductive health needs in AYA people with cancer. Open-ended questions invited respondents to describe personal experiences, reservations, and suggestions for improving SGM AYA cancer care. Using an interpretive description methodology, two investigators independently analyzed qualitative survey responses noting thematic saturation. Together, they refined themes, resolving disagreements with consensus. Interrater reliability was 88%. Results: 321 people participated in the survey and 190 answered open-ended questions. Themes included: 1) an ecosystem exists around patients’ interactions with clinicians and institutions; 2) institutional and individual assumptions result in stigmatization of SGM AYA people with cancer; 3) accommodating patients and providing clinicians with relevant education and experiences are initial steps to decrease stigma; and 4) improving the care for SGM AYA people with cancer may require transformative approaches that incorporate intersectional frameworks and challenge current systems. Conclusions: Improving the quality of care for SGM AYA people with cancer will require systemic and institutional change as well as educational interventions.
Patterns of presentation among New Zealand Māori with pancreatic cancer at Lakes District Health Board.
Authors: Camburn Laura , Hari Dass Prashanth
Published: June 2021

e18553

Background: New Zealand (NZ) Māori have higher rates of pancreatic cancer than other ethnic groups in NZ. Lakes District Health board (LDHB) has one of the highest proportion of Māori patients within New Zealand, 34.7% compared to 15.7% nationally. We aimed to review the patterns of presentation of patients diagnosed with pancreatic cancer at LDHB between ethnicities. Methods: Patients diagnosed with pancreatic cancer at LDHB between 01 Jul 2014 to 31 Mar 2020 were identified using the faster cancer treatment data and regional hospice referral data. This was cross checked against surgical and oncology referrals. Electronic notes were reviewed to collect data on ethnicity, patient demographics, & presentation. Results: 69 patients were identified; 25 Māori patients and 44 New Zealand European (NZE) patients. The mean age at diagnosis was 63.4 years for Māori and 73.4 years for NZE patients. 22 (88%) Māori patients were below the age of 75 at diagnosis compared to 24 (55%) NZE patients. In both groups there were more affected males than females. Risk factors such as positive smoking history, obesity and diabetes were more prevalent in Māori patients (80% v 43%, 40% v 16%, 44% v 20% respectively). Māori were more likely to present with metastatic disease compared to non-Māori at presentation (64% v 52%). Conclusions: Māori pancreatic cancer patients in our region were more likely to present younger with metabolic syndrome and more advanced disease compared to NZE patients.
Excess body weight association with various cancer: A United States population-based study 2021.
Authors: Alkrekshi Akram , Arroyo Suarez Raul , Kassem Ahmad Nader
Published: June 2021

e18558

Background: Excess body weight (EW) is a rising healthcare issue affecting over two-thirds of the United States (US) population, and it is a risk factor for various cancer. Methods: We used Explorys, IBM, a US database that includes ̃ 73 million patients. We evaluated non-gastrointestinal cancers prevalence based on age (18-64 and ≥ 65 years; for female cancers 18-49 and ≥ 50 years), race; Caucasians (C) and African-Americans (AA), and weight; normal weight (N) with BMI 18.5- 24.9 kg/m2 and EW for BMI ≥ 25 kg/m2. Compared to NW, the odds ratio (OR) and 95% confidence interval (CI) for multiple cancer rates in the EW group were calculated. p-value of <0.001 was considered significant (S) and > 0.001 as non-significant (NS). Results: A population of 26.9 million was included. C 85.6%, AA 14.4%. See table. Conclusions: A strong association between EW and urological cancers (prostate, bladder, renal), non-Hodgkin's lymphoma, multiple myelomas (MM), breast cancer, endometrial cancer, ovarian cancer in C 18-64 yrs but not in C ≥ 65 yrs with the exception for kidney cancer. A similar finding in AA 18-64 yrs for cancers of prostate, renal, breast, uterus, and MM compared to AA ≥ 65 yrs. EW is possibly more oncogenic earlier in life, especially in C.[Table: see text]