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Introduction and Aim: Pancreas Ductal Adenocarcinomas (PDACs) are among the leading causes of cancer-related death. Tyrosine kinase receptors (TKRs) are responsible for cell plasticity, chemoresistance, immunosuppression and metastasis potential. Axl is a receptor of the TKR family, and it has come to the fore in cancer treatment in the last decade. This study aimed to investigate the relationship of immunohistochemical Axl expression with histological features and its prognostic importance in PDACs. Materials and Methods: Fifty-three patients who were operated on for PDAC between 2006-2017 were evaluated retrospectively. Features of tumors; size, lymphovascular invasion (LVI), perineural invasion (PNI), resection margin (RM), lymph node metastasis (LNM), differentiation, tumor-infiltrating lymphocyte, stage and overall survival were recorded. Immunohistochemically, membranous and or cytoplasmic staining was considered positive for Axl. Statistically, Pearson Chi-Square, Cox regression and Kaplan Mayer tests were used in the SPSS 21.0 program. Results: Axl was positive in 28 patients (52.8%). Axl positivity was found to be associated with the presence of LVI (P = 0.009) and LNM (P = 0.002) and was an independent prognostic factor in short survival (P = 0.006). Conclusion: It was found that increased expression of Axl, which is known to increase EMT-mediated metastasis in carcinogenesis, may be an indicator of local spread and poor prognosis in PDAC patients. In this respect, it can be promising as a targeted molecule in PDAC patient's individualized treatments.

ObjectivesTo assess factors associated with radical resection (R0) of pancreatic ductal adenocarcinoma (PDAC) after induction treatment with FOLFIRINOX.MethodsPatients with either locally advanced (LA) and borderline resectable (BR) PDAC undergoing surgical exploration after FOLFIRINOX were retrospectively enrolled. Two pancreatic radiologists reviewed the CT blinded to the final outcome and assessed chemotherapy response and resectability. Patients were then divided into R0 resected (group A) and not resected/R1 resected (group B), which were compared.ResultsOf 59 patients included, 19 were defined as unresectable (32%), 33 borderline resectable (56%) and 7 resectable (12%) during the blind radiological evaluation after FOLFIRINOX. Once in a surgical setting, 27% were non-resectable, whereas 73% received surgical resection with a 70% R0 rate. Consequent sensitivity and specificity were 86% and 29%. At imaging review, significant decreases in longest tumour dimension were observed in both groups: from 32 mm (95% CI 15–55) to 21 (10–44) in group A and from 34 (18–70) to 26 (7–60) in group B, p < 0.05. However, a significant increase in tumour attenuation in all phases was only observed for R0 resected, from 52 HU (26–75) to 65 (35–92) in arterial phase (p < 0.001) and from 62 (36–96) to 78 (40–120) in the venous (p = 0.001).ConclusionAfter neoadjuvant FOLFIRINOX, CT predicted resectability with acceptable sensitivity but low specificity. The observation of increased tumour attenuation at CT scan after FOLFIRINOX treatment might represent a reliable predictor of R0 resection.Key Points• CT drives the assessment of PDAC resectability after FOLFIRINOX• CT predicts resectability with acceptable sensitivity but low specificity• Significant increase in tumour attenuation was only observed for R0 resected PDAC• Tumour attenuation after FOLFIRINOX represents a reliable predictor of R0 resection

Background and Objectives High mortality in pancreas ductal adenocarcinoma (PDAC) is related to delayed diagnosis and lack of cost‐effective early detection strategies. Retrospective studies have demonstrated an association between PDAC and acute pancreatitis (AP). Herein, we explore the incidence of PDAC in patients with non‐biliary and non‐alcoholic AP. Methods A population‐based, retrospective cohort study was conducted utilizing TriNetX (Cambridge, MA). Patients ≥40 years with AP (ICD‐10‐CM code: K85) and without biliary AP (K85.1), alcohol‐induced AP (K85.2) or chronic pancreatitis (K86.0, K86.1), were identified. The primary outcome was incidence of PDAC (C25) in patients at defined intervals following AP. We compared the rate of early‐stage diagnosis (stage 1–2) and surgical resection among patients with and without preceding AP. Results The incidence of PDAC ranged from 2.16% (1 year) to 3.43% (5 years). Patients with PDAC and AP in preceding year were more likely to undergo surgical resection relative to those without AP (10.1% vs. 6.3%, risk ratio 1.62: 95% confidence interval, CI 1.47–1.79). Early‐stage diagnosis of PDAC was more frequent in patients with preceding AP; however, difference was insignificant (p = 0.48; 95% CI 0.64–2.58). Conclusion AP is infrequently associated with PDAC and can precede a diagnosis of PDAC in a minority of patients without another known etiology of pancreatitis. Patients with a recent AP are more likely to undergo surgical resection of PDAC and a trend toward diagnosis at an earlier stage compared to patients with PDAC and without AP. The impact of AP‐related PDAC on survival is unknown. Understanding the risk of pancreatic cancer following an acute pancreatitis diagnosis is a critical component to early intervention for pancreatic cancer in this high‐risk population as multiple data sets have demonstrated that early detection can lead to an increased percentage of patients diagnosed with stage I disease, and hence an improved chance for cure.

Objective: This systematic review analyzes the anatomical variants in the pancreas and its ductal system to report on their association with pancreatic pathologies. Methods: We conducted a search of the MEDLINE, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS databases from their inception to July 2023. The methodological quality was assessed with the Anatomical Quality Assessment (AQUA) tool. Finally, the pooled prevalence was estimated using a random effects model. Results: 55 studies were found that met the eligibility criteria. The overall prevalence of pancreas divisum (PD) was 18% (95% CI = 15–21%). The prevalence of PD associated with pancreatitis was 30% (95% CI = 1–61%). Conclusions: An anatomical variant of the pancreas such as PD may be the cause of bile duct obstruction, resulting in various clinical complications, such as pancreatitis. Hence, knowing this variant is extremely important for surgeons, especially for those who treat the gastroduodenal region.

OBJECTIVE: The balance between malignant tumor cells and the connective tissue surrounding them determines the aggressiveness of the tumor. We aimed to understand the effects of mesothelin (MSLN) and fibulinl (FBLN1) expressions on survival in pancreas ductal adenocarcinoma (PDCA), and also whether these proteins have prognostic value for PDCA. METHODS: Of 80 patients in total, 40 who underwent the Whipple procedure for diagnosed PDCA between 2009 and 2016, and 40 patients with diagnosed pancreatitis as the control group, were included in the present study. Immunohistochemically, MSLN, and FBLN1 expressions were evaluated retrospectively. We assessed the relationship between the degree of MSLN, FBLN1 expression, clinical-pathological features, and survival rates in PDCA cases. RESULTS: The median follow-up duration was 11.4 (3-41) months. All of the patients for MSLN and FBLN1 were immune reactive. We detected a significant difference in MSLN expression between patients with PDCA and control groups, but not in FBLN1 expression. MSLN, FBLN1 expressions were categorized as lower-higher (L/H) groupings. There was no difference in the median overall survival (OS) of patients in the MSLN groups. The L-FBLN1 group had a median OS of 18 months (95% CI: 9.51-26.48) versus 14 months (95% CI: 13.021-14.97) in the H-FBLN1 group (interconnective tissue) (p=0.035). According to Kaplan-Meier analysis, L-FBLN1 expression in the tumor microenvironment was associated with longer survival in PDCA. The FBLN1 expression in the tumor microenvironment was shown to be significantly inversely related to OS (p=0.05). CONCLUSION: The FBLN1 expression, which is in the tumor microenvironment of PDCA, may serve as a prognostic biomarker. Keywords: Fibulin1; mesothelin; pancreas ductal adenocarcinoma; prognosis; tumor microenvironment.

While combined immunotherapy and anti-angiogenic therapy have demonstrated efficacy in renal cell carcinoma, non-small cell lung cancer and hepatocellular carcinoma, the efficacy of first-line treatment for pancreatic ductal adenocarcinoma (PDAC) with germline BRCA2 mutation remains unproven. We described a BRCA2-mutated patient with PDAC who presented with posterior cardiac metastasis 8 months after surgery. After receiving four cycles of anlotinib combined with tislelizumab, abdominal CT scans indicated a complete response. The patient sustained this response for over 14 months on the combination regimen, with no reported adverse events. In conclusion, the combination of tislelizumab and anlotinib may offer a viable therapeutic option for recurrent metastatic BRCA2-mutated PDAC.

Background In preoperative staging for patients with a ductal adenocarcinoma of the pancreatic head (PDAC), resectability is anatomically characterized by the possible clearance of the medial vascular grove. Borderline resectable PDAC patients who retain an increased risk of infiltration to the portomesenteric system and/or arterial vasculate are candidates for neoadjuvant therapy. However, redefined pathological analysis revealed the dorsal resection margin to be similar at risk for R1 resection. Mesopancreatic excision (MPE) aims to secure the integrity of the dorsal and ventral resection margins. The existence of the mesopancreas (MP) is inevitable, since the pancreas is of a secondary retroperitoneal nature and the dorsal as well as ventral fascial coverings define the peripancreatic compartment anatomy. It remains unknown if the MP area is only infiltrated in high-risk PDAC patients or if MPE during pancreatoduodenectomy should be employed for localized PDAC patients as well. Methods Patients who underwent upfront pancreatoduodenectomy were included. CRM evaluation and analysis of the MP was standardized in all patients. Patients were sub-grouped by the infiltration status of the vascular groove (localized disease: LOC). In LOC patients there was evidently no cancerous infiltration into the medial vascular groove (true + primary resectable). Results Two hundred eighty-four consecutive patients who underwent pancreatoduodenectomy were included (169 LOC patients). In LOC patients the MP infiltration rate remained high but was significantly lower when compared to advanced PDAC patients (MP + 69.2% vs. 83.5%, p  =  0.005 ). In LOC patients, CRM resection status of the dorsal resection status remained significantly affected by the MP infiltration status (R0CRM– 80.5% vs. 62.8%, p  =  0.019 ). Conclusion These important findings clearly show underestimated tumor extensions into the mesopancreas even in localized, primary resectable PDAC patients who are currently amenable for upfront resection. Synergistically to total mesorectal or mesocolic excision, which is applied to all stages of colorectal disease, MPE is justified in primary resectable patients as well. Therefore, MPE should be employed in all PDAC patients. Since the infiltration status of the mesopancreas was a significant factor for incomplete resection in primary resectable PDAC patients, neoadjuvant treatment options for must be discussed.

Background The implementation of the pathologic CRM (circumferential resection margin) staging system for pancreatic head ductal adenocarcinomas (hPDAC) resulted in a dramatic increase of R1 resections at the dorsal resection margin, presumably because of the high rate of mesopancreatic fat (MP) infiltration. Therefore, mesopancreatic excision (MPE) during pancreatoduodenectomy has recently been promoted and has demonstrated better local disease control, fueling the discussion of neoadjuvant downsizing regimes in MP + patients. However, it is unknown to what extent the MP is infiltrated in patients with distal pancreatic (tail/body) carcinomas (dPDAC). It is also unknown if the MP infiltration status affects surgical margin control in distal pancreatectomy (DP). The aim of our study was to histopathologically analyze MP infiltration and elucidate the influence of resection margin clearance on recurrence and survival in patients with dPDAC. Furthermore, the results were compared to a collective receiving MPE for hPDAC. Method Clinicopathological and survival parameters of 295 consecutive patients who underwent surgery for PDAC ( n  = 63 dPDAC and n  = 232 hPDAC) were evaluated. The CRM evaluation was performed in a standardized fashion and the specimens were examined according to the Leeds pathology protocol (LEEPP). The MP area was histopathologically evaluated for cancerous infiltration. Results In 75.4% of dPDAC patients the MP fat was infiltrated by vital tumor cells. The rates of MP infiltration and R0CRM– resections were similar between dPDAC and hPDAC patients ( p  =  0.497 and 0.453 respectively ). MP– infiltration status did not correlate with CRM implemented resection status in dPDAC patients ( p  =  0.348 ). In overall survival analysis, resection status and MP status remained prognostic factors for survival. In follow up analysis. surgical margin clearance in dPDAC patients was associated with a significant improvement in local recurrence rates (5.2% in R0CRM– resected vs. 33.3 in R1/R0CRM + resected, p  =  0.002 ). Conclusion While resection margin status was not affected by the MP status in dPDAC patients, the high MP infiltration rate, as well as improved survival in MP– dPDAC patients after R0CRM– resection, justify mesopancreatic excision during splenopancreatectomy. Larger scale studies are urgently needed to validate our results and to study the effect on neoadjuvant treatment in dPDAC patients.

BackgroundThe role of surgery for circumscribed synchronous hepatic lesions of the pancreatic ductal adenocarcinoma (PDAC) remains controversial. Thus, the aim of our study was to compare survival outcome (OS) after surgery of patients with hepatic metastases (M1surg) to patients with only localized disease.MethodsCorrelation analysis of clinicopathological data and OS after resection of M1surg patients and patients with localized PDACs (M0) was performed. Patients were included for survival analysis only if a complete staging including perineural, venous and lymphatic invasion was available.ResultsOut of the study collective, 35 patients received extended surgery (M1surg), whereas 131 patients received standardized surgery for localized disease (M0). Length of hospitalization and mortality was similar in both groups. FOLFIRNOX as an adjuvant treatment regime was administered in ~ 23 and ~ 8% of M1surg and M0 patients, respectively. In subgroup analysis of R0 resected patients and in multivariate analysis of the total cohort, there was no difference in overall survival between both groups. Only the resection status (R1 vs R0) and venous invasion (V1) were identified as independent prognostic factors. Site of recurrence in R0 resected M1surg patients and in M0 patients were homogenously distributed.ConclusionThis is the first study demonstrating a survival benefit after extended surgery for synchronously hepatic-metastasized PDACs. We found no difference in survival outcome of metastasized patients when compared to patients with localized disease. FOLFIRINOX as an adjuvant treatment regime for resected M1surg presumably is worthwhile. Larger multicenter studies are still needed to validate our results.

Background: Survival after surgery for pancreatic ductal adenocarcinoma (PDAC) remains poor. Thus, novel therapeutic concepts focus on the development of targeted therapies. In this context, inhibitor of apoptosis protein (IAP) survivin is regarded as a promising oncotherapeutic target. However, its expression and prognostic value in different tumour compartments of PDAC have not been studied. Methods: Immunohistochemical analysis of survivin in different PDAC tumour compartments from 236 consecutive patients was correlated with clinicopathological variables and survival. Results: In comparison to healthy pancreatic tissue high nuclear (p < 0.001) and high cytoplasmic (p < 0.01) survivin expression became evident in the tumour centre, along the invasion front and in lymph node metastases. Cytoplasmic overexpression of survivin in tumour centres was related to the presence of distant metastasis (p = 0.016) and UICC III/IV stages (p = 0.009), while high cytoplasmic expression at the invasion front grouped with venous infiltration (p = 0.022). Increased nuclear survivin along the invasion front correlated with perineural invasion (p = 0.035). High nuclear survivin in tumour centres represented an independent prognostic factor for overall survival of pancreatic tail carcinomas (HR 13.5 95%CI (1.4–129.7)) and correlated with a limited disease-free survival in PDAC (HR 1.80 95%CI (1.04–3.12)). Conclusion: Survivin is associated with advanced disease stages and poor prognosis. Therefore, survivin will help to identify patients with aggressive tumour phenotypes that could benefit from the inclusion in clinical trials incorporating survivin inhibitors in PDAC.