bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of obesity on resection margins in patients with pancreatic ductal adenocarcinoma treated with neoadjuvant chemotherapy.
Authors: Asawa Palash , Vusqa Urwat Til , Karna Rahul , Shah Shivani , Sweeney Ryan , Jayakrishnan Thejus , Srinivasamaharaj Srividya , Samhouri Yazan , Monga Dulabh K. 
Published: June 2022

e16229 Background: Obesity has been associated with decreased survival in patients with pancreatic ductal adenocarcinoma (PDAC). However, exact reasons remain unclear. Reduced response to chemotherapy because of obesity-induced desmoplasia has been proposed as a mechanism for the suboptimal response to treatment and therefore worse outcome. To this end, we attempted to determine the effect of obesity on the efficacy of neoadjuvant chemotherapy in patients with resectable and potentially resectable PDAC who underwent surgical resection. We assessed rates of microscopic tumor-free margins as a surrogate for treatment response. Methods: We performed a retrospective review of all patients diagnosed with PDAC from 2017-2019 at Allegheny Health Network. Obesity was defined as BMI > 30 kg/m2. Patients with resectable and potentially resectable disease who eventually received surgical treatment were included.Demographics, treatment details, and surgical pathology results were reviewed. Two-sided Mann-Whitney U test and Fischer’s exact test were used to evaluate differences between groups with continuous and categorical variables, respectively. A p value of < 0.05 was considered as level of significance. Results: Out of 121 patients who received and completed treatment at our institution, 29 patients underwent neoadjuvant chemotherapy followed by surgical resection. Most patients were female (61%), Caucasians (90%), had stage I (76%) and potentially resectable disease (72%). Eleven (38%) patients were categorized as obese and remaining non-obese. Among patients who underwent surgery after neoadjuvant chemotherapy, 10 out of 11 patients (90.9%) had microscopic tumor-free margins in the obese group when compared to 17 out of 18 patients (94.4%) in the non-obese group. (Table). Conclusions: Our study revealed no significant difference in obese patients compared to non-obese patients in terms of tumor-free margins assessed microscopically after surgical resection. Our study is limited by its small sample size, retrospective nature, and unidentifiable confounding factors that could potentially affect outcomes. Larger scale studies are needed to investigate the effect of obesity on treatment outcomes in resectable and potentially resectable pancreatic cancer patients treated with neoadjuvant chemotherapy.[Table: see text]
Venous segmental resection in locally advanced pancreatic tumors.
Authors: Gevorkyan Yuriy A. , Katelnitskaya Oksana V. , Kit Oleg I. , Maslov Andrey A. , Soldatkina Natalya V. , Petrov Dmitriy S. , Kolesnikov Vladimir E. , Savchenko Dmitriy A. , Tolmakh Roman E. , Dashkov Andrey V. , Ilchenko Sergei A. , Trifanov Vladimir S. , Kolesnikov Evgeniy N. 
Published: June 2022

e16243 Background: Surgical treatment is considered the main treatment for pancreatic cancer improving the patient survival. The most common obstacle to surgery with R0 resection is the involvement of the great vessels. Recently, venous resections have been increasingly performed for this type of tumors. Our purpose was to evaluate radicality of surgical treatment and postoperative morbidity in patients with locally advanced pancreatic cancer. Methods: The study included patients with locally advanced pancreatic cancer (T3 N0-1 M0) with damage to the venous segment (portal vein system) confirmed by CT angiography. Results: Over a 5-year period, 73 (18.9%) of 386 operated-on patients with pancreatic cancer underwent surgeries for pancreatic ductal adenocarcinoma with venous resection. The frequency of wedge venous resection was 24.7% (18), segmental resection with end-to-end anastomosis - 46.6% (34), prosthetics - 26% (19), prosthetics with replantation of the splenic vein - 2.7% (2). The postoperative morbidity rate was 30.1%. Within 30 days after surgery, the mortality rate reached 5.5% (4 patients). The main causes were bleeding and thrombosis of the reconstruction area. Only patients with venous segment replacement developed thrombotic complications. Microscopically complete resection was performed in 87.7% of cases (64 patients). During the follow-up period, the 1-year survival rate reached 90%, and the recurrence-free rate was 93%. Conclusions: Surgical treatment for locally advanced pancreatic tumors with damage to the portal vein system shows an acceptable rate of postoperative complications due to the vascular stage, and a high rate of reaching a negative resection margin. Initial assessment of the need for venous resection is required in patients with pancreatic tumors, as well as expanding the extent of surgical intervention due to venous resection to achieve R0 resections.
Timing of onset of systemic treatment in asymptomatic patients with metastatic pancreatic cancer: An international expert survey and case-vignette study.
Authors: Augustinus Simone , Van Laarhoven Hanneke W.M. , Cirkel Geert A. , de Groot Jan Willem , Groot Koerkamp Bas , Macarulla Teresa , Melisi Davide , O'Reilly Eileen Mary , van Santvoort Hjalmar , Mackay Tara , Besselink Marc G , Wilmink Johanna 
Published: June 2022

e16256 Background: The number of asymptomatic patients diagnosed with metastatic pancreatic cancer (mPDAC) is increasing, mostly due to increased use of imaging. Traditionally, systemic therapy is started immediately on disease detection. However, one perspective is that delaying therapy may preserve/maintain quality of life for longer. The impact on survival is unknown. The aim of this study was to gain further insights into current perspectives and clinical decision making regarding timing of start of systemic treatment in asymptomatic patients with mPDAC. Methods: An online survey (11 questions and 9 case vignettes) was sent to all first and last authors of published clinical trials on mPDAC over the past 10 years and medical oncologists of the Dutch Pancreatic Cancer Group. Differences in preferred treatment (i.e. immediate vs. delayed) between continents and years of experience (i.e. < 5 years, 5-10 years, > 11 years) were analyzed using the Fisher’s exact test. Results: Seventy-eight of 291 (27%) medical oncologists responded from 15 countries over 4 continents (62% Europe, 23% North America, 10% Asia, and 5% Australia). Most respondents worked in an academic hospital (73%) and reported more than 11 years’ experience (76%). The majority (63%) preferred immediate start of chemotherapy after diagnosis of metastastic disease. Thirty-two percent favored delayed treatment; 5% at symptom occurrence, 5% at objective disease progression, and 22% either at symptom occurrence or objective disease progression (whichever comes first). For the case vignettes, immediate treatment was preferred in 6/9 cases (67%). In the 3 remaining cases, delayed treatment was favored (case context: just one small lung metastasis, older age, significant comorbidities). The recommended timing of treatment (i.e. immediate or delayed treatment) was different between continents in 1/9 cases (11%, p = 0.012) and between years of experience in 5/7 cases (56%, all p < 0.001); medical oncologists from Europe and with < 5 years of experience preferred delayed treatment more often. Conclusions: This international survey based on case-vignettes indicated that immediate treatment was mostly preferred in asymptomatic patients with mPDAC. However, in one-third of cases, delayed treatment initiation was favored (e.g., due to patient selection and oncologists preference). The relation between timing of systemic treatment initiation and outcome in mPDAC is unknown and warrants further investigation.
Initial clinical results of the first commercial clinical blood test dedicated to the early detection of pancreatic ductal adenocarcinoma (PDAC).
Authors: King Thomas C. 
Published: June 2022

e16258 Background: The IMMray® PanCan-d blood test for early detection of PDAC has been commercially available in 45 U.S. states since the laboratory’s licensure in August 2021. This is the first clinically-available blood test dedicated to the early detection of PDAC, combining an 8-plex biomarker signature with CA19-9 in a proprietary algorithm. Here we report the initial results of this assay. Methods: All orders received and results reported were reviewed for the IMMray PanCan-d test between August 4, 2021 and February 11, 2022. Serum specimens were processed at the Immunovia, Inc. laboratory in Marlborough, Massachusetts. Demographic information of individuals undergoing testing is based on the completed test requisition submitted by their health care providers. All information was de-identified prior to this analysis. Results: The median age of those tested was 59 years and 46% were male. 76% of patients were referred because of a history of familial pancreatic cancer. Germline mutation prevalence is reported in the table below. 12% of patients had IPMNs or mucinous cystic neoplasms, 2% had chronic pancreatitis and 3% had new onset Diabetes Mellitus. Table. Demographics of Individuals Tested with the IMMray PanCan-d test 80.5% of IMMray PanCan-d results were negative, 1.1% were high-risk signature present, and 11.5% were borderline. These results are fully consistent with validation studies for this assay in high-risk surveillance populations (Brand RE et al Clin Transl Gastroenterol, doi: 10.14309/ctg.0000000000000468). 6.9% of individuals tested had a CA19-9 value of less than 2.5 U/ml, which we identify as presumptively Lewis null (le/le) and CA19-9 non-secretors. Given that CA19-9 contributes significantly to calculated decision values for the IMMray PanCan-d test, individuals with a CA19-9 less than 2.5 U/ml receive a result of test not performed. Conclusions: The commercial availability of a biomarker assay for the early detection of PDAC resulted in a testing population with demographics and referral criteria similar to that of PDAC high-risk surveillance programs in the U.S. IMMray PanCan-d test results were as expected based on prior validation studies.[Table: see text]
Retrospective analysis of management and outcomes of patients with malignant biliary obstruction.
Authors: Chan Abigail Sy , Chandler Natasha , Dong Brian , Rios Perez Cristian Daniel , Xue RuoBing , Hu Huirong , Kong Maiying , Sharma Vivek R. 
Published: June 2022

e16266 Background: Malignant biliary obstruction (MBO) is commonly associated with pancreaticobiliary cancers (PBCa). It increases the risk for cholangitis, hepatic failure, and deconditioning, which delays systemic therapy. This study aims to identify predictors associated with MBO outcomes after biliary decompression. Methods: This single-center, retrospective study analyzed patients with MBO from 2016-2020 who underwent biliary drainage. Patient demographics, cancer history, intervention type, and date of last follow up were obtained. Descriptive statistics were used to summarize relevant variables. Baseline characteristics were compared using Chi squared tests. Kruskal Wallis test was used to identify whether there were significant difference among multiple groups. Results: Of the 59 patients included, mean age was 62 years and 75% had PBCa. Baseline characteristics were presented in Table. The mean survival time from MBO diagnosis was 227 days (range: 16-1446). Overall, 39% survived at the end of 6 months follow up. Of the 29 patients who received chemotherapy after decompression, they were younger (57 vs 66 years old, p = 0.004). History of prior chemotherapy was significantly associated with increased 180-day mortality (OR 0.75, CI 0.58-0.97, p = 0.033). There were no differences based on sex, race, primary cancer, stage, intervention type or bilirubin levels in chemotherapy initiation or 6-month survival. In those with MBO as initial presentation of cancer, they were older, had pancreatic or biliary cancer, non-metastatic disease, unresected primary tumors, treatment-naïve, and no survival difference compared to later MBO presentation. Conclusions: Diagnosis of MBO is significantly associated with mortality (61% at 6-months) in our patient population, similar to historical controls of 40-60%. This data suggests that younger patients and those treatment naïve were associated with receipt of subsequent therapy and better 6-month survival, respectively.[Table: see text]
A systemic review and meta-analysis of FOLFIRINOX vs gemcitabine plus nab-paclitaxel in the neoadjuvant treatment of localized pancreatic cancer.
Authors: Fatima Zainab , Alhabhbeh Ammar , Darweesh Mohammad , Laswi Hisham , Manthri Sukesh 
Published: June 2022

e16272 Background: Localized pancreatic adenocarcinoma (PDAC) includes resectable, borderline resectable, and locally advanced cancers. In potentially resectable pancreatic cancer, the role of neoadjuvant therapy is evolving and guidelines from expert groups are conflicting. Although limited, randomized trials have shown that neoadjuvant chemotherapy (NCT) can provide survival benefits in patients with localized PDAC. Studies have compared FOLFIRINOX (FFN) with Gemcitabine plus nab-Paclitaxel (G-nP) as first-line NCT for PDAC, but no consensus has been established. As a result, we performed an updated meta-analysis to assess the difference in overall survival between two chemotherapy regimens. Methods: PubMed, EMBASE, and Cochrane databases were systematically reviewed from inception to December 2021 to identify studies comparing FFN with G-nP in the neoadjuvant settings for localized PDAC. The primary outcome was the overall survival of patients and secondary endpoints were RECIST partial or complete response, resection rate and R0 resection. The effectiveness of FOLFIRINOX and G-nP in terms of overall survival in patients with localized PDAC was compared using hazard ratios (HR) and 95% confidence intervals (CI). In addition, the heterogeneity of the studies was evaluated using Cochrane's Q test of heterogeneity and the I2 statistic. Pooled analysis of HR was performed with Stata 17 METAN using random effect model and P of 0.05 was considered statistically significant. Results: We identified 10 studies that met our inclusion criteria. All studies were retrospective and 5 of them were carried out in the United States. The total numbers of patients preoperatively treated with FOLFIRINOX versus G-nP were 988 and 719, respectively. In this meta-analysis compared to G-nP, neoadjuvant FFN was associated with significant prolonged overall survival (HR = 0.72, 95% CI: 0.63–0.82, P < 0.001). FFN group had a significantly higher RECIST partial and complete response rate than the G-nP group, with an OR of 1.65 (95 % CI 1.02-2.68, p = 0.04). For resection rate and R0 resection, FFN group had ORs of 1.65 (95% CI 0.94-2.90, p = 0.08) and 1.91 (95% CI 0.95-3.81, P = 0.07) respectively, both outcomes were statistically insignificant. Conclusions: Results of our meta-analysis show that for localized pancreatic cancer, neoadjuvant treatment with FFN was associated with better survival than G-nP. One limitation to our current study was that all included studies were designed retrospectively. Further randomized clinical trials are needed to explore the ideal neoadjuvant chemotherapy for PDAC.[Table: see text]
Frequency of loco-regional complications and their IMPACT on hospitalization outcomes in patients with pancreatic cancer.
Authors: Shah Mihir , Kumi Dennis Danso , Deenadayalan Vaishali , Ahuja Kriti , Abate Elias , Goyal Aakash , Gupta Shweta 
Published: June 2022

e16278 Background: Despite advances in medicine, pancreatic cancer continues to have a grim prognosis. It is not well studied if certain loco-regional complications pose higher prognostic risk than others and thus may be useful in estimating longevity and targeting care. Methods: National Inpatient Sample (NIS) was queried to identify adult patients with underlying pancreatic cancer between 2016-2018. Relative frequency and diagnosis of locoregional complications as principal diagnosis in these patients were identified and top 5 loco-regional complications were studied and compared for all-cause mortality, mean length of stay (LOS), mean total hospital charges (THC). Statistics were performed using the t-test, univariate and multinomial logistic regression. Results: There were 112,230 adult hospitalizations for pancreatic cancer. Top 5 loco-regional complications were cancer pain (8.6%), upper GI bleeding (UGIB) (8.4%), gastroduodenal obstruction (5.7%), failure to thrive (5%) and acute liver failure (2.8%). Mortality rate of all pancreatic cancer admissions was 7% and all loco-regional complications studied were associated with significant increased odds of mortality, the highest in patients with acute liver failure (AOR- 5.33, p < 0.001). All Loco-regional complications studied were associated with statistically significant increased LOS with the highest among patients admitted with UGIB (p < 0.001). UGIB was also associated with the highest THC whiles cancer pain admissions had a lower charge (p < 0.001). Conclusions: Among Loco-regional complications in pancreatic cancer that were studied, cancer associated pain was the most frequent while acute liver failure was the most fatal (5x higher odds of mortality). UGIB was associated with the longest hospital LOS (6 more days) and the highest THC (over $100,000 extra per admission) whereas cancer associated pain was associated with the shortest length of stay and lowest total charge. Further efforts are needed to improve outpatient pain management in pancreatic cancer patients to prevent these admissions.[Table: see text]
MiR-198 sensitizes pancreatic cancer to gemcitabine treatment through downregulation of VCP-mediated autophagy maturation.
Authors: Marín-Müller Christian , Li Dali , Lu Jian-Ming , Liang Zhengdong , Vega-Martínez Osvaldo , Fisher William , Chen Changyi , Yao Qizhi Cathy 
Published: June 2022

e16290 Background: The mechanism of human pancreatic ductal adenocarcinoma (PDAC) resistance to nucleoside analog and first-line chemotherapy drug gemcitabine is not clearly understood, but some studies have associated it with increased autophagy. In cancer biology, autophagy plays dual roles as it can promote tumor suppression during early stages, but in established tumors, it plays a crucial role in tumor growth by enhancing survival under metabolic and therapeutic stress. We have previously found that miR-198 acts as a tumor suppressor in PDAC through the targeting of a network of tumorigenic factors, including the Valosin-containing protein (VCP), which has been reported to play an important role in autophagy. In this study, we investigate whether the repression of VCP through miR-198 replacement disrupts the autophagy process and sensitizes PDAC cells to gemcitabine treatment. Methods: MIAPaCa2 cells with forced overexpression of mesothelin (MSLN) and AsPC-1 cell lines and, CDX and PDX mouse models were used for gemcitabine sensitization studies. For miR-198 replacement, a miR-198 expression vector-loaded lactic co-glycolic-acid-modified polyethylenimine polyplex (LPNP-p198) was used. Autophagy disruption experiments were run over miR-198 and/or VCP overexpressing cell lines. Nude mice were used for subcutaneous and orthotopic CDX models and SCID/Beige were used for the subcutaneous PDX model. Results: Cell lines were treated with LPNP-p198 in combination with gemcitabine and cell growth was significantly inhibited when compared to gemcitabine alone. Additionally, it was determined that miR-198 disrupts the autophagy maturation process and, that it is then restored by overexpression of VCP. LPNP-p198 can effectively enter tumor cells and induce tumor sensitization in vivo, resulting in an 80-90% reduction of tumor burden and metastatic spread in the LPNP-p198 plus gemcitabine group when compared to controls, with the concomitant downregulation of VCP expression in the tumor tissue. In addition, this group had the fewest mice with jaundice, ascites, and metastases to the abdominal cavity, spleen, liver, and kidney. Finally, to address the potential of the observed effect in the context of the heterogenic nature of PDAC, we confirmed our findings in a PDX mouse model, where a marked reduction in tumor burden was observed in the LPNP-p198 plus gemcitabine group compared to controls. Conclusions: Our findings indicate that miR-198 replacement disrupts the autophagy maturation process and sensitizes PDAC cells to gemcitabine through VCP repression, indicating a potential therapeutic strategy for targeting gemcitabine-resistant PDAC and, establishing the use of LPNPs as a prototype for effective nucleic acid delivery in vitro and in vivo, with potential to be used from bench to clinic.
Systematic investigation of immune-related lncRNA landscape reveals a potential long non-coding RNA signature for predicting prognosis in kidney renal clear cell carcinoma.
Authors: Liu Kepu , Li Zhibin , Ruan Dongli , Wang Huilong , Wang Wei , Zhang Geng 
Published: June 2022

e16510 Background: Increasing evidence has revealed that long non-coding RNAs (lncRNAs) play a crucial role in cancer immunity. However, the comprehensive landscape of immune infiltration-associated lncRNAs and their potential roles in the prognosis and diagnosis of kidney renal clear cell carcinoma (KIRC) remains largely unexplored. Methods: The transcriptomics data, expression profiles, and clinical information of KIRC patients were obtained from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. Novel lncRNAs were identified by a custom pipeline. The infiltration of immune cells was calculated by ssGSEA. K-means consensus method was used to cluster KIRC samples in different groups. Immune-related lncRNAs were obtained by differential expression analysis based on these groups. Univariate Cox regression, LASSO regression, and multivariate Cox regression analysis were performed on GEO datasets to construct an immune-related lncRNAs signature for predicting the prognosis of KIRC. And then, validated the prognostic signature in TCGA data. Results: Based on 261 samples from KIRC patients, tens of thousands of novel lncRNA genes were identified. KIRC samples were clustered into three immune clusters based on the infiltration of immune cells. Based on these groups, 241 immune-related lncRNAs were obtained. Moreover, a large part of immune-related lncRNAs could be detected in urinary samples of KIRC. Through a series of analyses, three immune-related lncRNAs were identified as a prognostic signature for KIRC. KIRC patients in the high-risk group had a shorter OS than those in the low-risk group both in the training set (P < 0.001) and TCGA data (P < 0.001), respectively. The AUC was 0.9 in the training set. Univariate and multivariate Cox regression analysis confirmed that the immune-related lncRNAs signature could be an independent prognostic factor both in the training set and TCGA data. Conclusions: All these findings provide a more comprehensive lncRNAs catalog for investigating the lncRNAs and provide a novel approach for the effective prediction of clinical outcomes in KIRC.