Pancreatic Carcinoma Research Articles

Abstract A059: Serum EphA2 proteolytic fragment is a potent biomarker for diagnosing a very early stage of ductal pancreatic carcinoma

Abstract Erythropoietin-producing hepatocellular receptor A2 (EphA2) is a receptor tyrosine kinase, and its expression increases with malignant progression of cancer. Therefore, EphA2 is believed to be a candidate for molecular cancer therapy and many candidate drugs targeting EphA2 have been developed, but their effects are limited. The reason is its complex signaling functions. In fact, EphA2 has a tumor suppressor function regulated by the stimulation of the Ephrin-A ligand, while in the absence of ligand stimulation, it has a prooncogenic function in collaboration with EGFR and its downstream signaling molecules. The opposite functions of EphA2 make it difficult to develop it as a cancer drug target. We have previously demonstrated that a type-1 matrix membrane metalloprotease (MT1-MMP) at cancer cell surface interacted with EphA2 and selectively cleaved its N-terminal ligand binding site, converting it into a prooncogenic signaling transmitter (Koshikawa N et al., Cancer Research, 2015). We also found that the N- terminal fragment of EphA2 (termed EphA2-NF) released by MT1-MMP cleavage increased in sera from patients with gastric cancer and ductal pancreatic carcinoma (PDC) (Koshikawa N et al., Cell Death & Disease, 2017). In this study, we compare the expression of EphA2-NF in serum from a healthy donor (HD: 150 cases), patients with chronic pancreatic disease (87 cases), and PDC (578 cases) by automated chemiluminescence immunoassay with a specific EphA2-NF monoclonal antibody. As a result, PDC cases, including stage I/II PDC, show significantly higher levels of EphA2-NF than HD (Sato et al. Cancer Research Communications, 2023). Furthermore, PDC occurred in the intraductal papillary mucinous neoplasm (IPMN) cases with high levels of EphA2-NF during follow-up observation. Therefore, to verify that the EphA2 proteolytic cleavage occurred in the PDC onset, we analyzed 50 surgical resected tissues from patients with PDC and IPMN to detect the N and C-terminal regions of EphA2 by immunohistochemical staining. Interestingly, PDC, including early stage PDC cases, lacked the N-terminus of EphA2. Furthermore, the deletion of N-terminus of EphA2 was observed in all tested cases pathologically diagnosed as intraductal papillary mucinous adenocarcinoma (IPMC) (Sato S et al., Cancer Research Communications, 2023). These results suggest that serum EphA2-NF has the potential to revolutionize the early detection and management of PDC, providing a valuable tool to diagnose the disease in very early stages when treatment results may be more favorable. Collaborators: Masatoshi Nakagawa, Eisaku Yoshida and Toru Yoshimura (Research and Development, Abbott Japan LLC) Citation Format: Naohiko Koshikawa, Shinya Sato, Kouki Nio, Takeshi Terashima, Makoto Ueno, Taro Yamashita. Serum EphA2 proteolytic fragment is a potent biomarker for diagnosing a very early stage of ductal pancreatic carcinoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A059.

Investigation of the efficacy of siRNA-mediated KRAS gene silencing in pancreatic cancer therapy

Aim Pancreatic carcinoma is an aggressive cancer that progresses without many symptoms. The difficulty of early diagnosis and an inadequate response to traditional treatments also cause the survival rate of pancreatic cancer to be low. Current research is focusing on methods of diagnosis and treatment, such as gene therapy, to increase survival rates. Small interfering ribonucleic acid (siRNA) has emerged as a promising advanced therapeutic strategy for cancer treatment. This study sought to silence the KRAS gene in the human pancreatic carcinoma cell line using a complex of small interfering ribonucleic acid (siRNA) and gold nanoparticles (AuNP). Methods In this study, 25 nM siRNA and gold nanoparticles at 0.5 mg/ml, 0.25 mg/ml, and 0.125 mg/ml concentrations were used to silence the KRAS gene in the CAPAN-1 cell line. Real-time PCR analysis, agarose gel electrophoresis, and double staining were carried out, and xCelligence real-time cell analysis (RTCA) was used to measure proliferation. Results The PCR analysis revealed crossing point (CP) values of actin beta (ACTB) ranging from 33.04 to 35.98, which was in the expected range for all samples. The interaction between the gold nanoparticle/siRNA complex in the double staining analysis revealed that the most effective concentration of gold nanoparticle was 0.125 mg/ml. The WST-1 technique showed that siRNA/AuPEI cells in application groups had a viability rate of over 90%, indicating no toxicity or side effects. The xCELLigence RTCA® showed that at hour 72, there was a significant difference in proliferation in the 0.5 mg/mL PEI/AuNP-siRNA, 0.25 mg/mL PEI/AuNP-siRNA, and 0.125 mg/mL PEI/AuNP-siRNA application groups compared to the control and siRNA groups (p < 0.05). By hour 96, all three groups were statistically different from the control and siRNA groups in terms of proliferation (p < 0.05). Conclusions The results of this analysis suggest that the AuPEI/siRNA complex can be effectively used to silence the target gene, but more studies are needed to verify these results.

The role of chemotherapy in the management of pancreatic acinar cell carcinoma

AbstractIntroductionPancreatic acinar cell carcinoma (pACC) is a rare malignancy with unique clinical and molecular features. The role of chemotherapy in pACC management is not well established.MethodsThe National Cancer Database (NCDB) for pACC was used. Cox regression was used in resected pACC patients to identify significant overall survival (OS) predictors. Patients were then divided based on these risk factors into propensity‐matched group of surgery versus surgery + chemotherapy and Kaplan–Meier analysis was performed with log‐rank tests to compare OS.ResultsThe NCDB 2004–2020 included 1592 pACC patients, 1553 were selected. Median age was 66 and 1090 (70.2%) were males. 622 (40.1%) received chemotherapy only, 257 (16.5%) had surgery only, and 365 (23.5%) had both. 189 Patients who received surgery were only matched to peers who had surgery + chemotherapy. The median OS for surgery only was 57.8 ± 6.0 versus 54.2 ± 9.9 months for surgery + chemotherapy (p = 0.836). Cox regression identified nodal and margin status as independent predictors of OS. Therefore, subgroups of patients with node‐negative, node‐positive, margin‐negative, and margin‐positive resections were similarly matched 1:1 for the receipt of surgery only versus surgery + chemotherapy. Only patients with node‐positive disease had a significant OS benefit with the addition of chemotherapy (44.2 ± 7.3 vs. 27.5 ± 10.5 months; p = 0.036).ConclusionOur analysis suggests that surgical resection remains the cornerstone of therapy for pACC. Node status and margin status are the primary prognosticators. The addition of chemotherapy provides an OS benefit only in node‐positive disease.

Possible inhibition effects of resveratrol on pancreatic tumorigenesis in the azaserine‐rat model

Resveratrol, which is thought to have a preventive effect on the formation of different types of cancer, is abundant in grapes and other foods. Resveratrol has been shown to have anti‐cancer effects by in vitro andin vivo studies, however this is the first time its effect on atypical acinar cell foci (AACF), known as precursor forms of pancreatic carcinoma, has been experimentally investigated. Male Sprague Dawley rats, each consisting of 5 experimental groups (Cont, AzCont, AzRes10, AzRes15, and AzRes20), 10 of which were 14 days old, were used in the study. In the azaserine groups (AzCont, AzRes10, AzRes15, and AzRes20), it was investigated how the development of Atypical Cell Foci (AACF) resulting from intraperitoneal injection (i.p.) of azaserine (30 mg/kg bw) in 14‐day‐old rats was affected by dietary restoration. Male rats in the resveratrol group (AzRes10, AzRes15, and AzRes20) were fed diets containing 10%, 15%, or 20% mmol resveratrol for an 8‐month experimental period 1 week after the last azaserine injection. Pancreas preparations prepared from histological sections were examined for AACF burden and analyzed via a video image analyzer. One‐way analysis of variance (ANOVA) non‐parametric statistical analyses were performed to test whether there was a difference between the averages of the experimental and control groups. The AACF load in the azaserine group (AzCont) compared to the control group (Cont) was found to be statistically significant in all categories (p < 0.05). The calculated estimated mean AACF volume (mm3) values and the AACF ratio as a percentage of the calculated organ volume were statistically significantly lower in all resveratrol groups (AzRes10, AzRes15, and AzRes20) compared to the azaserine control group (AzCont). The calculated estimated mean AACF volume (mm3) values and the AACF ratio as a percentage of the calculated organ volume were statistically significantly lower in all resveratrol groups (AzRes10, AzRes15, and AzRes20) compared to the azaserine control group (AzCont) (p < 0.05). In addition, the calculated estimated mean AACF diameter (mm) in the AzRes10 and AzRes15 groups, in the AzRes15 group the calculated estimated mean AACF number in the whole organ and the calculated average AACF number per unit area were found to be statistically significant compared to the azaserine control group (AzCont) (p < 0.05). According to the results of our study, it has been shown that atypical acinar cell foci (AACF) formed in the exocrine pancreas of rats with azaserine can be reduced by a diet containing resveratrol. It was determined that the tumor burden decreased statistically significantly (p ≤ 0.05) in resveratrol‐treated rats. Accordingly, it is thought that the inhibitory effects of resveratrol may contribute to studies that reduce the occurrence of pancreatic cancer.

S-1/irinotecan/oxaliplatinchemotherapy achieved a pathological complete remission in advanced pancreatic carcinoma.

Chemotherapy has been developed for many years for malignancies, including advanced pancreatic cancer, downsizing the primary site, thereby enabling complete cure with the combination of conversion surgery. Pathological complete remission from operation samples was usually identified as a promising indication for a good prognosis for many carcinomas. Several case reports consisting of pathological complete remission after chemotherapy application have been reported but no case of pathological complete remission that resulted from successful extensive resection by surgery after S-1, irinotecan, and oxaliplatin (SIROX) chemotherapy. A 48-year-old male patient was hospitalized due to abdominal pain which turned out to be a 25mm-sized advanced uncinate process of pancreatic cancer with possible duodenum invasion and hepatic metastasis. The tumor had decreased after administering 23 sessions of modified SIROX chemotherapy, and he underwent pylorus-preserving pancreaticoduodenectomy with portal vein resection. He was successfully managed with conservative treatment and discharged 12days postoperatively despite his postoperative weakness. He had been taking S-1 pills for 6months and until now, 3years postoperatively, with no relapse. The final pathology reported complete tumor regression. Therefore, we emphasize the oncologic significance of chemotherapy in the uncinate process of pancreatic cancer and the potential role of conversion surgery.

Rate And Grade of Postoperative Pancreatic Fistula After Modified Blumgart Pancreaticojejunostomy in Pancreaticoduodenectomy

Introduction: Pancreaticoduodenectomy (PD), commonly known as the Whipple procedure, is the standard surgical approach for treating pancreatic and periampullary cancers. Despite advancements in surgical techniques, postoperative pancreatic fistula (POPF) remains one of the most significant complications following PD, contributing to increased morbidity. This study aims to evaluate the development and severity of POPF in patients undergoing PD with the Modified Blumgart Pancreaticojejunostomy. Methods: This Cross-sectional Observational study was carried out among the indoor patients of surgery units in Dhaka Medical College & Hospital, Dhaka, from January 2023 to December 2023. All patients who experienced Pancreatoduodenectomy in the Surgery department of Dhaka Medical College & Hospital during the study period were considered as the study population. A total of 30 patients were selected as study subjects by purposive sampling technique. Consent from patients and relevant authorities was taken. Univariate and multivariate analysis of the data was carried out using a statistical analysis software program. Descriptive analysis of continuous variables was carried out and showed as the means ± SD. Result: This study involved 30 patients, with the majority (36.6%) aged between 40-50 years and male predominance (63.3%). Most patients (50%) were diagnosed preoperatively with periampullary carcinoma, followed by pancreatic carcinoma (40%). Postoperative pancreatic fistula occurred in 13.3% of patients, with the majority (75%) being Grade B fistulas, and 25% classified as Grade A. No Grade C fistulas were observed. Conclusion: Placing sutures between the pancreatic tissue and the jejunum carries a risk of pancreatic juice leakage due to needle holes or injury to the pancreatic tissue, particularly in patients with a soft pancreas. Therefore, this study suggests that an anastomosis technique utilizing fewer sutures may be more advantageous. The original Blumgart anastomosis employed four to six trans pancreatic/jejunal seromuscular sutures, whereas our approach utilized only one to three. Additionally, the modified Blumgart technique ensured complete coverage of the pancreatic stump with jejunal serosa through the modified lateral suture that penetrates the seromuscular layer of the jejunum

Delta-radiomics Approach Using Contrast-enhanced and Non-contrast-enhanced Computed Tomography Images for Predicting Distant Metastasis in Patients with Borderline Resectable Pancreatic Carcinoma

PurposeTo predict distant metastasis (DM) in patients with borderline resectable pancreatic carcinoma (BRPC) using delta-radiomics features calculated from contrast-enhanced computed tomography (CECT) and non-CECT images. MethodsAmong 250 patients who underwent radiotherapy at our institution between February 2013 and December 2021, 67 patients were deemed eligible. A total of 11 clinical features and 3,906 radiomics features were incorporated. Radiomics features were extracted from CECT and non-CECT images and the differences between these features were calculated, resulting in delta-radiomics features. The patients were randomly divided into the training (70%) and test (30%) datasets for model development and validation. Predictive models were developed with clinical features (clinical model), radiomics features (radiomics model), and a combination of the abovementioned features (hybrid model) using Fine–Gray regression (FG) and random survival forest (RSF). Optimal hyperparameters were determined using stratified five-fold cross-validation. Subsequently, the developed models were applied to the remaining test datasets, and the patients were divided into the high- or low-risk groups based on their risk scores. Prognostic power was assessed using the concordance index (C-index) with 95% confidence intervals obtained through 2,000 bootstrapping iterations. Statistical significance between the two groups was assessed using Gray's test. ResultsAt a median follow-up period of 23.8 months, 47 (70.1%) patients developed DM. The C-indices of the FG-based clinical, radiomics, and hybrid models were 0.548, 0.603, and 0.623, respectively, in the test dataset, whereas those of the RSF-based models were 0.598, 0.680, and 0.727, respectively. The RSF-based model, including delta-radiomics features, significantly divided the cumulative incidence curves into two groups (P<0.05). The feature map of the gray-level size-zone matrix showed that the difference in feature values between CECT and non-CECT images correlated with the incidence of DM. ConclusionsDelta-radiomics features obtained from CECT and non-CECT images using RSF successfully predict the incidence of DM in patients with BRPC.

Intraductal papillary mucinous neoplasm: Overview of management.

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is increasingly being diagnosed incidentally on imaging. Ithas malignant potential, making it vitalto establish the correct diagnosis, assessits malignant risk and follow a management strategy to prevent development of invasive carcinoma ofthe pancreas. This review focuses on the epidemiology, natural history, risk factors, diagnosis and management of IPMN of the pancreas, and will provide practical points for general practitioners. IPMN of the pancreas can transform into invasive pancreatic carcinoma at a low rate of approximately 2%/year. Upon diagnosis of IPMN, it is risk stratified based on the presence of worrisome or high-risk stigmata, which guides further management. Management needs to be individualised based on IPMN and patient factors due to limitations with the current diagnostic tools.

Intricate roles of estrogen and estrogen receptors in digestive system cancers: a systematic review.

Gender disparities are evident across different types of digestive system cancers, which are typically characterized by a lower incidence and mortality rate in females compared to males. This finding suggests a potential protective role of female steroid hormones, particularly estrogen, in the development of these cancers. Estrogen is a well-known sex hormone that not only regulates the reproductive system but also exerts diverse effects on non-reproductive organs mediated through interactions with estrogen receptors (ERs), including the classic (ERα and ERβ) and non-traditional ERs [G protein-coupled estrogen receptor (GPER)]. Recent advances have contributed to our comprehension of the mechanisms underlying ERs in digestive system cancers. In this comprehensive review we summarize the current understanding of the intricate roles played by estrogen and ERs in the major types of digestive system cancers, including hepatocellular, pancreatic, esophageal, gastric, and colorectal carcinoma. Furthermore, we discuss the potential molecular mechanisms underlying ERα, ERβ, and GPER effects, and propose perspectives on innovative therapies and preventive measures targeting the pathways regulated by estrogen and ERs. The roles of estrogen and ERs in digestive system cancers are complicated and depend on the cell type and tissue involved. Additionally, deciphering the intricate roles of estrogen, ERs, and the associated signaling pathways may guide the discovery of novel and tailored therapeutic and preventive strategies for digestive system cancers, eventually improving the care and clinical outcomes for the substantial number of individuals worldwide affected by these malignancies.

Ferrocenyl β-Diketonate Compounds: Extended Ring Systems for Improved Anticancer Activity.

A library of ferrocenyl β-diketonate compounds with varying degrees of aromatic functionality have been synthesized and fully characterized. This includes cyclic voltammetry and the analysis of four new structures by single crystal X-ray diffraction. The compounds cytotoxic potential has been determined by MTT screening against pancreatic carcinoma (MIA PaCa-2), ovarian adenocarcinoma (A2780), breast adenocarcinomas (MDA-MB-231 and MCF-7) and normal epithelial retinal (ARPE-19). The compounds show a general trend, where increasing the number of aromatic rings in the molecule yields an increase in cytotoxicity and follows the trend anthracenyl > naphthyl > phenyl > methyl. The compounds are particularly sensitive to the triple negative cancer cell line MDA-MB-231, and the potential modes of action have been studied by production of reactive oxygen species using fluorescence microscopy and cell morphology using Scanning Electron Microscopy. All assays highlight the ferrocenyl β-diketonate with an anthracenyl substituent to be the lead compound in this library. The decomposition was also observed within cells, to give a cytotoxic fluorescent molecule, which has been visualized by confocal microscopy.

Intestinal obstruction following antituberculosis therapy in a patient with pancreatic carcinoma and pulmonary tuberculosis: a case report

IntroductionIntestinal obstruction is a common complication in patients with advanced malignancies, often attributed to the disease itself or as a side effect of opioid analgesics used for pain management. However, the occurrence of intestinal obstruction following antituberculosis therapy is rare.Case presentationWe report a unique case of a 58-year-old Asian male diagnosed with stage IV pancreatic carcinoma and pulmonary tuberculosis. The patient was initiated on a regimen of ethambutol hydrochloride, pyrazinamide, rifampicin, and isoniazid tablets (II) for tuberculosis, alongside morphine for the management of severe cancer-related pain. Subsequently, he developed symptoms indicative of intestinal obstruction. Despite discontinuation of morphine, the patient’s symptoms persisted until he autonomously ceased all medications, leading to a rapid improvement in his condition. This unexpected resolution highlighted the antituberculosis drugs as the probable cause of his intestinal obstruction.ConclusionsThis case underscores the importance of considering antituberculosis drugs as a potential cause of intestinal obstruction, especially in patients who do not respond to conventional management strategies for drug-induced gastrointestinal side effects. It also emphasizes the need for heightened vigilance and monitoring when prescribing these medications to patients with advanced malignancies, to promptly identify and address rare but significant side effects.

Multiparametric quantitative MRI of healthy adult pancreas: correlations with gender and age

BackgroundThe pancreas plays an important role in the nutrition and metabolism of the whole body. Many disease processes including obesity, diabetes mellitus (DM), acute or chronic pancreatitis, and pancreatic carcinoma result in abnormality of pancreas morphology and function. Magnetic resonance imaging (MRI) provides quantitative parameters including T1, T2, and apparent diffusion coefficient (ADC) values for evaluating normal and abnormal pancreas. Based on the normal range of these quantitative parameters, pancreatic abnormality could be detected early. However, the range and the relationship of T1, T2, and ADC values with gender and age groups using the same dataset have not been explored.PurposeTo establish the ranges of MRI tissue and functional parameters, including T1, T2, and ADC values, in healthy adult pancreas and their correlations with gender, subregion, and age.Materials and methodsThe T1, T2, and ADC values of healthy pancreas in 86 adults were measured using a 3.0-T MRI scanner. The average T1, T2, and ADC values were obtained in the whole pancreas and subregions (head, neck, body, and tail). Their correlations with gender and age were investigated.ResultsThe T1, T2, and ADC values of the whole pancreas from all subjects were 870.07 ± 61.86 ms, 44.07 ± 6.14 ms, and 1.072 ± 0.212 × 10−3 mm2/s, respectively. T2 values were significantly different between genders (P &amp;lt; 0.05). No significant differences were found between subregions. The T1, T2, and ADC values differed significantly among the age groups (P &amp;lt; 0.05). The T1 value revealed a moderately positive correlation, while the T2 and ADC values displayed negative correlations with age (r = 0.31, −0.45, and −0.39, respectively). The combination of T1, T2, and ADC values achieved the highest AUC value and showed a significant difference compared to T1, T2, and ADC values alone in predicting age older than 45 years.ConclusionThis study established the normal ranges of T1, T2, and ADC. We found that T2 is different between men and women, and T1, T2, and ADC are age-dependent. These results could be useful for quantitative MRI of pancreatic disease.

Pancreatic exocrine carcinoma in a lohmann brown chicken

A 23-month-old lohmann brown breed chicken showed symptoms of anorexia, depression and diarrhea before dying. It presented to the pathology laboratory for necropsy. The necropsy confirmed serosal, white and nodular widespread tumor infiltrations in different sizes in the intestines and periton adjacent to the pancreas. In the histological examination, poorly differentiated epithelial cells were seen to form tubular structures in the pancreatic tissue located between the duodenum. According to pathology, this case was diagnosed as pancreatic exocrine carcinoma. This case report provides histologic descriptions of the pancreatic exocrine carcinoma in a chicken that have been reported extremely rare in poultry and pet birds.

Histological variants of pancreatic ductal adenocarcinoma: a survival analysis.

Pancreatic ductal adenocarcinoma (PDAC) can be classified into distinct histological subtypes based on the WHO nomenclature. The aim of this study was to compare the prognosis of conventional PDAC (cPDAC) against the other histological variants at the population level. The Surveillance, Epidemiology and End Results (SEER) database was used to identify patients with microscopically confirmed PDAC. These patients were divided into 9 histological subgroups. Overall survival was assessed using the Kaplan-Meier method and Cox regression models stratified by tumor histology. A total of 159,548 patients with PDAC were identified, of whom 95.9% had cPDAC, followed by colloid carcinoma (CC) (2.6%), adenosquamous carcinoma (ASqC) (0.8%), signet ring cell carcinoma (SRCC) (0.5%), undifferentiated carcinoma (UC) (0.1%), undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) (0.1%), hepatoid carcinoma (HC) (0.01%), medullary carcinoma of the pancreas (MCP) (0.006%) and pancreatic undifferentiated carcinoma with rhabdoid phenotype (PUCR) (0.003%). Kaplan-Meier curves showed that PUCR had the worst prognosis (median survival: 2 months; 5-year survival: 0%), while MCP had the best prognosis (median survival: 41 months; 5-year survival: 33.3%). In a multivariable Cox model, several histological subtypes (i.e. CC, ASqC, SRCC, UCOGC) were identified as independent predictors of overall survival when compared to cPDAC. PDAC is a heterogenous disease and accurate identification of variant histology is important for risk stratification, as these variants may have different biological behavior.

Increased Proportion of the Squamous Cell Carcinoma Components Is Associated with Aggressive Behavior and a Worse Prognosis in Resected Pancreatic Adenosquamous Carcinoma.

Pancreatic adenosquamous carcinoma (PASC) is a subtype of pancreatic cancer with a poorer prognosis than pancreatic ductal carcinoma (PDAC). The pathogenesis of this histological subtype has not been fully explained due to its rarity. Of the 245 patients who underwent pancreatic resection for pancreatic cancer, six (2.3%) were diagnosed with PASC. They were retrospectively allocated to Group A (≥ 50% adenocarcinoma components) or Group S (≥ 50% squamous cell carcinoma components). The six patients with PASC were all males between the ages of 63 and 77years, with tumors of 12 to 52mm in diameter. Tumors were located in the pancreatic head (n = 2) and the pancreatic tail (n = 4). Relative to Group A, all three patients in Group S had larger tumors diameters, ≥ 40mm with invasion to other organs. Cancer-specific survival of Group S was worse than that of the PDAC group (median survival, 1.5years vs. 4.1years). All patients in Group A were alive at the end of follow-up. Recurrence-free survival of Group S was inferior to that of the PDAC group (median survival, 0.2years vs. 1.8years; Group A, not defined). Immunohistochemistry revealed the MIB-1 positivity rate in squamous cell carcinoma regions was 1.8 times higher than that in adenocarcinoma regions in the same specimens. In PASC patients, an increased proportion of squamous cell carcinoma components was associated with aggressive behavior and a worse prognosis. This was due to the high MIB-1 positivity rate of squamous cell carcinoma components.

Anatomical variants of the jejunal veins and their technical implications in pancreaticoduodenectomy: a systematic review and meta-analysis.

One of the most common causes of bleeding during pancreaticoduodenectomy (PD) is dissection of the pancreatic head from the superior mesenteric vein (SMV) and superior mesenteric artery (SMA). Knowledge of the anatomical variants of the veins draining the proximal jejunum may allow a better control of bleeding during detachment of the uncinate process and pancreatic head from the mesenteric pedicle and division of the mesopancreas. The aim of this systematic review and meta-analysis is to evaluate the anatomical variations of the first jejunal vein (FJV) and jejunal trunk (FJT). Fourteen studies (1,888 patients) were included. We performed a systematic review of the available Literature according to the PRISMA guidelines. The analysis has shown that the posterior course of the FJT and FJV represents the most frequent topographical location (PPE 79.6%) with the anterior jejunal trunk (JT) having a lower rate (PPE 20.4%). Few articles reported the variations with separate trunks for the first and second jejunal vein. A thorough preoperative radiological assessment of the anatomical variation of FJT and FJV may confer some advantage to establish the best therapeutic strategy and the best surgical approach in case of pancreatic head carcinoma, as it can allow a better estimate of the extent of the neoplasm and improve the accuracy of surgical dissection with potential for reduced bleeding.

Application of LEF-1 immunohistochemical staining in the diagnosis of solid pseudopapillary neoplasm of the pancreas

IntroductionSolid pseudopapillary neoplasm (SPN) is a tumor of young females with gain-of-function mutation in catenin beta 1 gene involved in Wnt signal transduction pathway. Beta-catenin immunohistochemistry (IHC) is used to diagnose SPN. Lymphoid enhancer-binding factor 1 (LEF-1) has been recognized in the transactivation of Wnt pathway. We aim to study LEF-1 IHC in SPN and other pancreatic tumors and compare it with beta-catenin IHC. MethodsWe retrieved cases of SPN, pancreatic neuroendocrine tumor (PanNET), serous cystadenoma (SCA), ductal adenocarcinoma (PDAC) and acinar cell carcinoma (ACC) from 2011 to 2023. Formalin-fixed, paraffin-embedded blocks with adequate tumor were cut and stained with beta-catenin (B-Catenin-1 clone) and LEF-1 (EP310 clone) IHC. Cases were reviewed by two pathologists independently. Nuclear staining with LEF-1 and beta-catenin was considered as positive. ResultsOur cohort consisted of 111 cases [SPN = 59 (42 resections, 11 FNA, 6 biopsies), PDAC = 24, PanNET = 22, SCA = 5, ACC = 1]. For SPN cases male to female ratio was1:8. Age ranged from 9 to 81 years (average: 32 years). Pancreatic tail was the most common location (47 %) followed by head (28 %), body (19 %) and neck (6 %). Tumor size ranged from 1.0 to 12.2 cm (average: 5 cm). Among the SPN cases 57/59 demonstrated strong nuclear LEF-1 staining. 2/49 cases were negative for LEF-1 (both pathologist in agreement). All SPN tumors demonstrated nuclear staining with beta-catenin. Among the non-SPN tumors, beta-catenin showed nuclear staining in 2/52 cases (2 PDAC). The remaining 50 cases were negative for nuclear beta-catenin and demonstrated variable staining pattern with interpretation variability between the two pathologists. The sensitivity and specificity for LEF-1 were 97 % and 100 %, respectively, while for beta-catenin, they were 100 % and 96 % respectively. ConclusionCrisp nuclear staining of LEF-1 without background staining makes diagnostic interpretation relatively easy and accurate compared to beta-catenin IHC. This is further helpful for small biopsy samples to help differentiate SPN from mimickers such as PanNET. None of the non-SPN cases displayed nuclear LEF-1 rendering it a valuable adjunct to beta-catenin in the diagnostic evaluation of SPN.

The umblicus says it all

Abstract Introduction/Objective Umbilical nodules can be divided into benign and malignant. Malignant lesions of the umbilicus are very rare. They can arise from primary tumors or secondary to abdominal and pelvic malignancies. Literature review suggests that these umbilical lesions can present as primary tumor in 38% of the cases, endometriosis in 32%, and metastatic lesions in 30%. Umbilical metastasis is one of the main characteristic signs of extensive neoplastic disease and is known as Sister Mary Joseph’s nodule (SMJN). It is a very rare finding and the incidence of SMJN is 1- 3% in people diagnosed with intra-abdominal or pelvic malignancies. Methods/Case Report A 31-year-old male with no past medical history presented to the emergency room with 3 months history of umbilical nodule and 60 pounds weight loss. He experienced early satiety, abdominal pain, nausea and generalized fatigue. CT abdomen showed hepatomegaly with numerous hypoattenuating lesions throughout the liver with peripheral enhancement, and hypoattenuating mass within the pancreatic tail and body measuring approximately 2.1 x 5.8 cm that appears contiguous with hilar splenic lesion. CT chest showed multiple pulmonary metastases with prominent precarinal and subcarinal lymph nodes. Serologic tests revealed elevated Alpha fetoprotein, ALP, ALT, and CA19-9. Patient underwent umbilical nodule core biopsy and right liver core biopsy. Microscopic evaluation of the specimens revealed pancreatic acinic cell carcinoma with two different morphological variants. Umbilical nodule with glandular pattern and liver lesion with trabecular pattern. Immunohistochemical stains were performed with tumor cells positive for CK 7, Trypsin and BCL-10 and negative for Glypican 3, CK 20, AFP and CD56. The prognosis is poor, with an average survival time of about 19 months. After the diagnosis patient underwent chemotherapy. Results (if a Case Study enter NA) NA Conclusion Umbilical nodules can be diagnosed with careful clinical and histopathological evaluation. The prognosis of patients presenting with SMJN is generally poor as it is a sign of advanced malignancy. Sometimes it may be the first and only sign of an internal neoplasm. Therefore, this is an important differential diagnosis to consider.

Cytokine-armed vaccinia virus promotes cytotoxicity toward pancreatic carcinoma cells via activation of human intermediary CD56dimCD16dim natural killer cells.

Pancreatic ductal adenocarcinoma (PDAC) remains a particularly aggressive disease with few effective treatments. The PDAC tumor immune microenvironment (TIME) is known to be immune suppressive. Oncolytic viruses can increase tumor immunogenicity via immunogenic cell death (ICD). We focused on tumor-selective (vvDD) and cytokine-armed Western-reserve vaccinia viruses (vvDD-IL2 and vvDD-IL15) and infected carcinoma cell lines as well as patient-derived primary PDAC cells. In co-culture experiments, we investigated the cytotoxic response and the activation of human natural killer (NK). Infection and virus replication were assessed by measuring virus encoded YFP. We then analyzed intracellular signaling processes and oncolysis via in-depth proteomic analysis, immunoblotting and TUNEL assay. Following the co-culture of mock or virus infected carcinoma cell lines with allogenic PBMCs or NK cell lines, CD56+ NK cells were analyzed with respect to their activation, cytotoxicity and effector function. Both, dose- and time-dependent release of danger signals following infection weremeasured. Viruses effectively entered PDAC cells, emitted YFP signals and resulted in concomitant oncolysis. The proteome showed reprogramming of normally active core signaling pathways in PDAC (e.g., MAPK-ERK signaling). Danger-associated molecular patterns were released upon infection and stimulated co-cultured NK cells for enhanced effector cytotoxicity. NK cell subtyping revealed enhanced numbers and activation of a rare CD56dimCD16dim population. Tumor cell killing was primarily triggered via Fas ligands rather than granule release, resulting in marked apoptosis. Overall, the cytokine-armed vaccinia viruses induced NK cell activation and enhanced cytotoxicity toward human PDAC cells in vitro. We could show that cytokine-armed virus targets the carcinoma cells and thus hasgreat potential to modulate the TIME in PDAC.

Molecular and Clinical Features of Pancreatic Acinar Cell Carcinoma: A Single-Institution Case Series

Objectives: Acinar cell carcinoma (ACC) accounts for about 1% of pancreatic cancers. The molecular and clinical features of ACC are less characterized than those of pancreatic ductal adenocarcinoma. Methods: We retrospectively evaluated the clinical and molecular features of ACC patients who underwent germline and/or somatic molecular testing at The University of Texas MD Anderson Cancer Center from 2008 to 2022 and two cases from 2023–2024 who underwent RNA and TME analysis by Boston Gene. Patient information was extracted from our institutional database with the approval of the Institutional Review Board. Results: We identified 16 patients with available molecular testing results. Fourteen patients had metastatic disease, one had borderline resectable disease, and one had localized resectable disease at diagnosis. Fifteen patients were wild type for KRAS (one patient had unknown KRAS status). Somatic/germline mutations of DNA damage repair genes (BRCA1/2, PALB2, and ATM) were present in 5 of 12 patients tested for these genes. One patient was found to have RET fusion and responded favorably to selpercatinib for over 42 months. The median overall survival (OS) was 24 months for patients with metastatic disease. One of the additional two cases who underwent BostonGene testing was found to have NTRK1 fusion. RNA and TME analysis by Boston Gene of the two cases reported immune desert features and relatively lower RNA levels of CEACAM5, CD47, CD74, and MMP1 and higher RNA levels of CDH6 compared with PDAC.