bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early evidence of pancreatic enzyme insufficiency in patients with gastric neoplasia.
Authors: Shah Raj N , Zakhour Joud , Karam Wissam , Alqam Anas , Dean Tanner , Nabbout Nassim H. 
Published: July 2024

e16037 Background: The incidence and association of Exocrine Pancreatic Insufficiency (EPI) in patients with gastric neoplasms has not been well reported. Malnutrition and cachexia occur commonly in patients with advanced gastric cancer (AGC), significantly affecting the quality of life and prognosis in these patients. EPI is one of the factors associated with malnutrition and can cause increased morbidity and mortality. ( [1] ) While an association between pancreatic tumors and EPI has been well established, such an association has not been well studied with gastric tumors. Methods: We queried the HERON database for the number of patients diagnosed with Malignant neoplasms of the stomach using International Classification of Disease (ICD) code C16 who then developed EPI, represented by ICD codes K87, K86.6, and K89.9. We conducted a comparative analysis involving individuals diagnosed with gastric neoplasia but lacking a preceding diagnosis of EPI. Specifically, we examined two distinct groups within this cohort: those individuals who were subsequently diagnosed with EPI and those who were not. Additionally, our study incorporated a comparison with the broader general population, utilizing the same database. We used CHI squared testing, odds ratio, and Cramer’s V for statistical analysis. Results: We identified ICD codes in the whole database of 1566102 patients from the database inception to Jan 1, 2024. Out of these, 1609 patients had the diagnosis of gastric neoplasms in the database. 21 patients had the diagnosis of PEI occurring following the diagnosis of gastric neoplasm. 3148 patients developed EPI without gastric neoplasms. The association was statistically significant with a p-value of < / = .001. The odds ratio reported was 6.58 (95% CI = 4.27-10.13). The Cramer’s V was 0.007. Conclusions: The findings reveal preliminary evidence within our cohort of a significant association between the diagnosis of gastric malignant neoplasm and subsequent development of EPI. However, the strength of this association, as indicated by Cramer’s V, is comparatively low. This could be attributed to various factors, including possible missed diagnosis related to limited physician awareness. To delve deeper into this early evidence, a prospective study should be initiated, and physician should pay special attention to this underreported condition. The study should also investigate subgroup variables such as the patient's age, gender, carcinoma stage at diagnosis, nutritional status before and after treatment, as well as the type and duration of treatment, including chemotherapy and radiotherapy. ( [2] ).
Analysis of factors affecting complete pathological remission after neoadjuvant immunocombination chemotherapy treatment for locally advanced esophageal squamous carcinoma.
Authors: Liao Ziyi , Ma Daiyuan 
Published: July 2024

e16061 Background: Chemotherapy combined with immunotherapy for locally advanced esophageal squamous carcinoma has achieved a high rate of complete pathological remission, which is conducive to a better prognosis for patients; however, not all ESCC patients benefit from ICI therapy, so finding validated prognostic markers of efficacy will help us to screen for populations that are superior to neoadjuvant immunotherapy. Methods: Patients with locally advanced esophageal squamous carcinoma treated with neoadjuvant immune-combination chemotherapy followed by radical surgery from January 2019 to June 2023 at our institution were collected. The grouping was based on whether pathologic complete remission (pCR) was achieved after neoadjuvant therapy. Clinical and treatment-related data as well as hematologic, inflammatory, and nutritional indices within 1 week before neoadjuvant therapy and within 1 week after 2 cycles of neoadjuvant immune-combination chemotherapy treatment were collected from all patients, and univariate and multivariate analyses were performed to assess independent predictors of pCR. Results: Patients in both pCR and Non-pCR groups were more likely to obtain pCR if they had pre-treatment BMI > 21Kg/m2 vs BMI ≤21Kg/m2, number of neoadjuvant therapy cycles ≥3 cycles vs number of neoadjuvant therapy cycles = 2 cycles, and CYFRA21-1ng/ml < 3.28 vs ≥3.28 before neoadjuvant therapy (p < 0.05). Patients with albumin ≥40.10g/L vs albumin < 40.10g/L, NLR < 2.50 vs NLR ≥2.50, and NRI ≥98.06 vs NRI < 98.06 were more likely to achieve pCR before treatment in both groups (p < 0.05). SII ≥521.75 VS SII < 521.75 was more likely to achieve pCR after 2 cycles of treatment (p < 0.05). Univariate analysis of the comparison of dynamic changes in nutritional inflammatory indexes during treatment between the two groups of patients showed that pCR was more likely to be achieved in patients with persistently elevated eosinophil counts and NLR after 2 cycles of neoadjuvant immune-combination chemotherapy treatment (p < 0.05). The results of multifactorial analysis showed that pre-treatment BMI, SII after 2 cycles of treatment, and dynamic changes in eosinophils during neoadjuvant therapy were independent influences on complete pathological remission after neoadjuvant immune-combination chemotherapy treatment (p < 0.05). Conclusions: Complete pathological remission after neoadjuvant immune-combination chemotherapy treatment for esophageal squamous carcinoma was significantly correlated with the patient's pre-treatment BMI, Post-treatment SII, and eosinophil dynamics during treatment.
Influence of neoadjuvant regimen on the prognosis of locally advanced gastric and gastroesophageal junction cancer with HER2 overexpression.
Authors: Zhao Lingdi , Liu Xiao , Chen Guanglong , Ma Baozhen , Huang Jinxi , Jiang Zhiqiang , Hou Xinfang , Li Ning , Qin Peng , Zhang Yong , Wang Zibing , Li Zhi , Gao Quanli 
Published: July 2024

e16082 Background: The relative high recurrence rate in locally advanced gastric or gastroesophageal junction (G/GEJ) cancer with Her2 overexpression after surgery, along with the absence of a standard neoadjuvant treatment protocol, necessitates exploration of novel approaches for this patient population. Methods: In this study, we conducted a retrospective analysis of clinical characteristics, postoperative pathological results, and survival data for patients who underwent neoadjuvant treatment and subsequent surgery at our center from September 2020 to December 31, 2022. The inclusion criteria were as follows: 1) pathologically confirmed adenocarcinoma of the G/GEJ; 2) diagnosed as cT3-4 or N+ by enhanced CT and endoscopic ultrasound; 3) Her2 immunohistochemistry 3+ or 2+ with Fish positive in biopsy specimens; 4) discussed in a multidisciplinary team for the need for neoadjuvant treatment; 5) received 2-4 cycles of neoadjuvant therapy; 6) underwent radical D2 surgery; 7) had complete follow-up data. Results: Seventy-three patients met the inclusion criteria, with 19 receiving chemotherapy + anti-PD-1, 10 receiving chemotherapy + anti-Her2, and 44 receiving chemotherapy alone. Their pCR rates were 31.6%, 10%, and 2.3%, respectively (P = 0.003); MPR rates were 42.1%, 30%, and 11.4% (P = 0.022). As of the last follow-up on December 31, 2023, the median DFS for the chemotherapy group was 18.1 months (95% confidence interval 14.9-21.3); median DFS for the other two groups had not been reached. DFS analysis revealed differences in median DFS among different neoadjuvant treatment regimens (P = 0.025); further pairwise comparisons indicated that this difference mainly stemmed from the chemotherapy + anti-Her2 group compared to the chemotherapy group. Conclusions: In locally advanced gastric and gastroesophageal junction cancer with Her2 overexpression, neoadjuvant chemotherapy combined with anti-Her2 treatment improves the pCR rate and prolongs DFS compared to neoadjuvant chemotherapy alone.
Correlation of plasma GDF15 with aging, organ disfunction, sarcopenia, and postoperative infectious complication in patients with esophageal cancer.
Authors: Ozawa Yohei , Okamoto Hiroshi , Taniyama Yusuke , Sato Chiaki , Ishida Hirotaka , Abe Takaaki , Kamei Takashi 
Published: July 2024

e16088 Background: The age of cancer incidence is increasing every year. Along with it, cancer patients getting has more comorbidity and decreasing muscle strength which may lead to increase postoperative complications. Especially, since esophageal cancer (EC) patients have heavy drinking and smoking history and high age of morbidity, they usually have multiple comorbidities and so that they particularly have high incidence of cachexia. A novel inflammatory marker known as growth differentiation factor 15 (GDF15) has been recently reported relation with cancer cachexia. This study conducted to evaluate correlation between clinical data which suggested cachexia of EC patients and plasma GDF15. Methods: Eighty-one esophageal cancer patients who first visited our outpatient ward from July 2021 to March 2023 were enrolled in this study. After obtaining consent for the study, plasma samples collected before starting any treatment for the cancer. The quantification of GDF15 was performed by ELISA. Clinical information was collected from clinical record including age, comorbidities, biochemical data, Controlling Nutritional Status (CONUT) score, and Skeletal Mass Index (SMI). GDF15 was then evaluated for clinical impact by comparison with postoperative results. Mann-Whitney U test, student-t test, ANOVA were used appropriately to analyze the relationship between the GDF-15 and patient characteristics and post operative complications. Multivariate analysis ware used logistic regression analysis. P-values < 0.05 were considered statistically significant for all statistical analyses. Results: Mean age was 68.3-year-old and 80.3% of these were male. Malnutrition patients diagnosed by using CONUT were 24 (29.6%) and sarcopenia patients diagnosed by using SMI were 21 (25.9%). The median value of GDF15 was 1165 pg/mL with its range were from 298 to 9100 pg/mL. Plasma GDF15 was statistically correlated with age ( P< 0.001), performance status ( P= 0.046), prevalence of hypertension ( P= 0.045) and/or diabetes ( P= 0.018), serum level of aspartate aminotransferase (AST) ( P< 0.001)/ γ-glutamyltransferase (γ-GTP) ( P< 0.001)/ creatinine ( P= 0.004)/ blood sugar ( P= 0.028), and SMI ( P= 0.003). Seventy-two patients underwent curative surgery, and no perioperative death was observed. The patients who occurred anastomotic leakage and infectious complication observed statistically higher GDF15 than those without (P = 0.030, P = 0.016). Optimal cut-off value was detected as 940 ng/mL for detecting infectious complication by ROC-curve with AUC value of 0.68. Conclusions: This study showed GDF15 is potentially suggesting deterioration of general condition, which came from aging, organ disfunction, and decreasing muscle mass, which may lead to cachexia in EC patients. In addition, higher GDF15 patients have risk of postoperative infectious complication.
Outcomes of R-MPV followed by ara-c in primary central nervous system lymphoma: A single-center retrospective analysis.
Authors: Khurshid Aatif , Paranji Sreshta , Kapur Rohan , Weber Alec , Cohen Michelle , Vegunta Rathnamitreyee , Seiter Karen , Liu Delong , Ahmed Tauseef , Sweeney Richard , Steinberg Amir S. 
Published: July 2024

e19046 Background: Primary central nervous system lymphoma (PCNSL) lymphoma is a rare non-Hodgkin’s Lymphoma. Currently, there is no uniform consensus in the optimal management of PCNSL. In patients that can tolerate systemic therapy, induction therapy is typically done with a high-dose methotrexate-based regimen, due to evidence of better penetration of the blood brain barrier. One such regimens is high dose methotrexate combined with rituximab, procarbazine, and vincristine (R-MPV). Options for consolidation therapy include high-dose systemic therapy with stem cell rescue (ASCT), whole brain radio therapy (WBRT) and high-dose cytarabine (ara-c) with or without etoposide (EA). At our institution we utilize an R-MPV induction approach with some form of ara-c consolidation without etoposide. We aimed to execute a retrospective cohort study to analyze outcomes of this approach. Methods: All the patients diagnosed with PCNSL who received an induction regimen of R-MPV from 10/01/2020 to 06/01/2023 were included. Data was then gathered by chart review of the electronic medical record. Treatment outcomes were evaluated based on imaging with brain MRIs and PET scans. Central findings such as complete response (CR) rate, progression free survival (PFS) and overall survival (OS) were ascertained. Results: 10 charts were reviewed. 9 out of the 10 patients had a histological presentation consistent with diffuse large B-cell lymphoma; 1 patient had a diagnosis of B-cell lymphoma. In terms of demographics, the patients ages ranged from 54 to 83 years, with a median of 74 years. Complete response was achieved in 5 out of the 10 patients (CR rate of 50%), and no relapse was noted in any of these patients. 2 out of the 10 patients progressed on treatment, with 1 dying from progression of the disease. The median follow-up for patients who were still alive was 24 months. 2-year PFS was 80%, and 2-year OS was 90%. Median PFS and OS were not reached. Mean PFS and OS were 28 months and 30.5 months respectively. Conclusions: Based on our study results, the CR rate we observed for R-MPV appears consistent with existing literature on this regimen and other methotrexate-based induction regimens. Our results for R-MPV with ara-c consolidation provides similar outcomes to existing studies on treatment with different methotrexate-based induction and consolidation with ASCT, particularly the 80% PFS we observed. This percent PFS also appears similar to studies of consolidation with ara-c and EA, and superior to PFS with WBRT. Overall, these results are reassuring as in a specific set of older patients who might not be candidates for ASCT, our specific nonmyeloablative approach could be worthwhile. However, our study does have the limitation of being a single center retrospective perspective. [Table: see text]
Combination therapy with the oncolytic virus CF33-CD19 and blinatumomab for the treatment of advanced solid tumors.
Authors: Li Daneng , Seiz Amanda , Fein Seymour H. , Byon John Chong Han , Wilkinson Grey A , Woodard Paul Paul 
Published: July 2024

TPS2687 Background: CF33-CD19 is a novel chimeric vaccinia virus that selectively replicates in tumor cells and can provoke anti-tumor immunity. CF33-CD19 expresses a truncated and non-signaling CD19 protein on the surface of infected tumor cells before virus-mediated tumor lysis, labeling them for CD19-targeted therapies. Preclinical studies with CF33-CD19 have shown that combination therapy with CD19 targeting chimeric antigen receptor T cells is more effective than either monotherapy in murine xenograft and syngeneic models [1]. Likewise, combination therapy with bispecific T-cell engagers (BiTE)s that bind CD3-positive T cells and infected solid tumor cells that express de novo CD19, showed pronounced recruitment of T cells to the tumor microenvironment, resulting in tumor growth inhibition in mouse models. CD19xCD3 targeting BiTEs such as blinatumomab may offer an off-the-shelf alternative to adoptive cell therapies. This phase I study, called OASIS, dose escalates CF33-CD19 administered intravenously (IV) or intratumorally (IT) combined with blinatumomab in adults with advanced or metastatic solid tumors. Methods: The OASIS study (NCT06063317) is enrolling patients with advanced or metastatic solid tumors with ≥ 2 prior lines of therapy. Patients who have received prior treatment with a poxvirus based oncolytic virus or a bispecific CD19-directed CD3 T-cell engager are excluded. A safety run-in will evaluate the safety of CF33-CD19 monotherapy administered IT or IV before initiating the combination therapy regimen. Combination therapy will be administered in 28-day cycles with CF33-CD19 on days 1 and 15. Following viral transduction to promote de novo CD19 expression, blinatumomab is given on days 2-9 and 16-23 via a 7-day continuous infusion. Patients > 45 kg will receive 9 mcg of blinatumomab during the first week of cycle 1, then 28 mcg during the third week of cycle 1 and subsequent cycles. The study consists of two parts. Part 1 follows a 3+3 dose escalation scheme independently of each route of CF33-CD19 administration (IT and IV) with dose levels of CF33-CD19 ranging from 1.0x107 to 3.0x109 PFU. Part 2 is a cohort expansion in select indications at the optimal dose. The co-primary endpoints are safety and identification of the recommended phase 2 dose. Secondary endpoints include objective response rate according to RECIST v1.1 and iRECIST. Enrollment began in October 2023. 1. Park et al. Sci Transl Med. 2020 Sep 2;12(559):eaaz1863. doi: 10.1126/scitranslmed.aaz1863. PMID: 32878978. Clinical trial information: NCT06063317 .
Final Results From a Phase I Trial and Expansion Cohorts of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced/Metastatic Genitourinary Tumors
Authors: Apolo Andrea B. , Girardi Daniel M. , Niglio Scot A. , Nadal Rosa , Kydd Andre R. , Simon Nicholas , Ley Lisa , Cordes Lisa M. , Chandran Elias , Steinberg Seth M. , Lee Sunmin , Lee Min-Jung , Rastogi Shraddha , Sato Nahoko , Cao Liang , Banday A. Rouf , Boudjadi Salah , Merino Maria J. , Toubaji Antoun , Akbulut Dilara , Redd Bernadette , Bagheri Hadi , Costello Rene , Gurram Sandeep , Agarwal Piyush K. , Chalfin Heather J. , Valera Vladimir , Streicher Howard , Wright John Joseph , Sharon Elad , Figg William D. , Parnes Howard L. , Gulley James L. , Saraiya Biren , Pal Sumanta K. , Quinn David , Stein Mark N. , Lara Primo N. , Bottaro Donald P. , Mortazavi Amir 
Published: July 2024

PURPOSE
Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma (mUC), metastatic renal cell carcinoma (mRCC), and rare genitourinary (GU) tumors in a dose-escalation phase I study. We report the final data analysis of the safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the phase I patients and seven expansion cohorts.

METHODS

This is an investigator-initiated, multicenter, phase I trial. CaboNivo doublet expansion cohorts included (1) mUC, (2) mRCC, and (3) adenocarcinoma of the bladder/urachal; CaboNivoIpi triplet expansion cohorts included (1) mUC, (2) mRCC, (3) penile cancer, and (4) squamous cell carcinoma of the bladder and other rare GU tumors (ClinicalTrials.gov identifier:
NCT02496208
).

RESULTS
The study enrolled 120 patients treated with CaboNivo (n = 64) or CaboNivoIpi (n = 56), with a median follow-up of 49.2 months. In 108 evaluable patients (CaboNivo n = 59; CaboNivoIpi n = 49), the ORR was 38% (complete response rate 11%) and the median duration of response was 20 months. The ORR was 42.4% for mUC, 62.5% for mRCC (n = 16), 85.7% for squamous cell carcinoma of the bladder (n = 7), 44.4% for penile cancer (n = 9), and 50.0% for renal medullary carcinoma (n = 2). Grade ≥ 3 treatment-related adverse events occurred in 84% of CaboNivo patients and 80% of CaboNivoIpi patients.

CONCLUSION
CaboNivo and CaboNivoIpi demonstrated clinical activity and safety in patients with multiple GU malignancies, especially clear cell RCC, urothelial carcinoma, and rare GU tumors such as squamous cell carcinoma of the bladder, small cell carcinoma of the bladder, adenocarcinoma of the bladder, renal medullary carcinoma, and penile cancer.
A Cadaveric Feasibility Study of the Biportal Endoscopic Transfrontal Sinus Approach: A Minimally Invasive Approach to the Anterior Cranial Fossa
Authors: Saez-Alegre Miguel , Torregrossa Fabio , Jean Walter C. , Morshed Ramin A. , Piper Keaton , Link Michael J. , Van Gompel Jamie J. , Peris Celda Maria , Pinheiro Neto Carlos D. 
Published: July 2024

BACKGROUND AND OBJECTIVES:
The trans-sinus transglabellar and bifrontal approaches offer direct access to the anterior cranial fossa. However, these approaches present potential drawbacks. We propose the biportal endoscopic transfrontal sinus (BETS) approach, adapting endoscopic endonasal approach (EEA) techniques for minimally invasive access to the anterior fossa, reducing tissue manipulation, venous sacrifice, and brain retraction.

METHODS:
Six formalin specimens were used. BETS approach involves 2 incisions over the medial aspect of both eyebrows from the supraorbital notch to the medial end of the eyebrow. A unilateral pedicled pericranial flap is harvested. A craniotomy through the anterior table of the frontal sinus (FS) and a separate craniotomy through the posterior table are performed. Two variants of the approach (preservative vs cranialization) are described for opening and reconstruction of the FS based on the desired pathology to access. Bone flap replacement can be performed with titanium plates and filling of the external table defect with bone cement.

RESULTS:
Like in EEA, this approach provides access for endoscope and multiple working instruments to be used simultaneously. The approach allows wide access to the anterior cranial fossa, subfrontal, and interhemispheric corridors, all the way up to the suprachiasmatic corridor and through the lamina terminalis to the third ventricle. BETS provides direct access to the anterior fossa, minimizing the level of frontal lobe retraction and providing potentially less tissue disruption and improved cosmesis. Cerebrospinal fluid fistula risk remains one of the major concerns as the narrow corridor limits achieving a watertight closure which can be mitigated with a pedicled flap. Mucocele risk is minimized with full cranialization or reconstruction of the FS.

CONCLUSION:
The BETS approach is a minimally invasive approach that translates the concepts of EEA to the FS. It allows excellent access to the anterior cranial fossa structures with minimal frontal lobe retraction.