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This study investigated the utility of imaging features, such as rim enhancement on contrast-enhanced CT (CECT), in predicting the prognosis of pancreatic ductal adenocarcinoma (PDAC). This retrospective study included 158 patients (84 men; mean age, 68 years) with pathologically confirmed PDAC. The following imaging features were evaluated on CECT by two radiologists: tumor size, tumor attenuation, and the presence of rim enhancement. Cox proportional hazards analysis was performed to identify the imaging and clinicopathological features for predicting disease-free survival (DFS) and overall survival (OS). Pathological features were compared with the presence of rim enhancement. Among the 158 patients, 106 (67%) underwent curative surgery (surgery group) and 52 (33%) received conservative treatment (non-surgery group). Rim enhancement was observed more frequently in the non-surgery group than in the surgery group (44% vs. 20%; p < 0.001). Rim enhancement showed significant associations with shorter DFS and OS in the surgery group (hazard ratios (HRs), 3.03 and 2.99; p < 0.001 and p = 0.003, respectively), whereas tumor size showed significant associations with shorter OS (HR per 1 mm increase, 1.08; p < 0.001). PDACs with rim enhancement showed significant associations with higher histological tumor grades (p < 0.001). PDAC with rim enhancement on CECT could predict poorer prognosis and more aggressive tumor grades. [ABSTRACT FROM AUTHOR]

Background: Recent evidence suggests that the presence of microbiome within human pancreatic ductal adenocarcinoma (PDAC) tissue potentially influences cancer progression and prognosis. However, the significance of tumor-resident microbiome remains unclear. We aimed to elucidate the impact of intratumoral bacteria on the pathophysiology and prognosis of human PDAC. Methods: The presence of intratumoral bacteria was assessed in 162 surgically resected PDACs using quantitative polymerase chain reaction (qPCR) and in situ hybridization (ISH) targeting 16S rRNA. The intratumoral microbiome was explored by 16S metagenome sequencing using DNA extracted from formalin-fixed paraffin-embedded tissues. The profile of intratumoral bacteria was compared with clinical information, pathological findings including tumor-infiltrating T cells, tumor-associated macrophage, fibrosis, and alterations in four main driver genes (KRAS, TP53, CDKN2A/p16, SMAD4) in tumor genomes. Results: The presence of intratumoral bacteria was confirmed in 52 tumors (32%) using both qPCR and ISH. The 16S metagenome sequencing revealed characteristic bacterial profiles within these tumors, including phyla such as Proteobacteria and Firmicutes. Comparison of bacterial profiles between cases with good and poor prognosis revealed a significant positive correlation between a shorter survival time and the presence of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus. The abundance of these bacteria was correlated with a decrease in the number of tumor-infiltrating T cells positive for CD4, CD8, and CD45RO. Conclusions: Intratumoral infection of anaerobic bacteria such as Bacteroides, Lactobacillus, and Peptoniphilus is correlated with the suppressed anti-PDAC immunity and poor prognosis. [ABSTRACT FROM AUTHOR]

Background: Abundant collagen deposition is a hallmark of pancreatic ductal adenocarcinomas (PDACs). This study clarified the interactive relationship between tumor-stromal collagen, molecular and immune characteristics, and tumor pr ogression in human PDAC. Methods: We performed a comprehensive examination using an integrative molecular pathological epidemiology database on 169 cases with resected PDAC. The amount of tumor-stromal collagen was quantified through digital imaging analysis for Elastica van Gieson-stained whole-section tumor slides. We analyzed the association of tumor-stromal collagen with gene alterations (KRAS, TP53, CDKN2A/p16, and SMAD4), immune parameters (CD4+ tumor-infiltrating lymphocytes [TILs], CD8+ TILs, FOXP3+ TILs, and tertiary lymphoid structures), and patient prognosis. Results: Low amounts of tumor-stromal collagen were associated with poor differentiation (multivariable OR = 3.82, 95%CI = 1.41–12.2, P = 0.008) and CDKN2A/p16 alteration (OR [95%CI] = 2.06 [1.08–4.02], P = 0.03). Tumors with low collagen levels had shorter overall survival (HR [95%CI] = 2.38 [1.59–3.56], P < 0.0001). In the S-1 and gemcitabine (GEM) treatment groups, low tumor-stromal collagen was linked to poor prognosis of patients with PDAC (S-1 group: multivariable HR [95%CI] = 2.76 [1.36–5.79], P = 0.005; GEM group: multivariate HR [95%CI] = 2.91 [1.34–6.71], P = 0.007). Additionally, low amounts of tumor-stromal collagen were also linked to low levels of CD4+ TILs (P = 0.046), CD8+ TILs (P = 0.09), and tertiary lymphoid structures (P = 0.001). Conclusions: Tumor-stromal collagen deposition may play a crucial role in modulating tumor-immune microenvironment and determining response to adjuvant chemotherapy and patient survival outcomes. [ABSTRACT FROM AUTHOR]

Purpose: The therapeutic strategy for borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) has remained unestablished because the preoperative prognostic factors have not been determined. Methods: One hundred eighty-four consecutive PDAC patients who underwent upfront surgery with a curative resection between January 2000 and June 2013 at Kobe University Hospital were retrospectively studied. The PDAC patients were stratified into resectable (R)-PDAC ( n = 147) and BR-PDAC patients ( n = 37). We evaluated the independent prognostic significance of the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) in the BR-PDAC patients. Results: BR-PDAC patient survival was significantly worse than R-PDAC patient survival (median survival time: 22.1 months vs. 24.3 months; 5-year survival rate 6 vs. 21 %; P = 0.042). The median survival in BR-PDAC patients with a preoperative NLR of >3 ( n = 12) was 10.2 months, while that in patients with preoperative NLR of ≤3 ( n = 25) was 24.9 months ( P = 0.002). Moreover, the median survival in BR-PDAC patients with a preoperative PLR of >225 ( n = 8) was 10.2 months, while that in patients with a preoperative PLR of ≤225 ( n = 29) was 24.7 months ( P = 0.003). Preoperative NLR >3 (HR = 2.980, 95 % CI 1.251-6.920; P = 0.015) and PLR >225 (HR = 3.050, 95 % CI 1.169-7.468; P = 0.024) were independent prognostic factors in BR-PDAC patients. Conclusions: Higher preoperative NLR and PLR can be independent predictive risk factors in BR-PDAC patients following curative resection. [ABSTRACT FROM AUTHOR]

Objectives: Small proline-rich protein 1A (SPRR1A) is recognized as a squamous differentiation marker but is also upregulated in some non-squamous cancers. However, its expression in pancreatic ductal adenocarcinoma (PDAC) has not been investigated. This study elucidated the expression of SPRR1A in PDAC and its effect on the prognosis and malignant behavior of PDAC. Methods: We examined the SPRR1A expression by immunohistochemistry in 86 surgical PDAC cases and revealed the relationship between its expression and the prognosis of the PDAC patients. Furthermore, we overexpressed SPRR1A in pancreatic cancer cell lines (PK-1 and Panc-1) and assessed the phenotype and gene expression changes in vitro. Results: Among the 84 cases, excluding 2 with squamous differentiation, 31 (36.9%) had a high SPRR1A expression. The overall survival (median 22.1 months vs. 33.6 months, p = 0.0357) and recurrence-free survival (median 10.7 months vs. 15.5 months, p = 0.0298) were significantly lower in the high-SPRR1A-expression group than in the low-SPRR1A-expression group. A multivariate analysis indicated that a high SPRR1A expression (HR 1.706, 95% CI 1.018 to 2.862, p = 0.0427) and residual tumor status (HR 2.687, 95% CI 1.487 to 4.855, p = 0.00106) were independent prognostic factors. The analysis of TCGA transcriptome data demonstrated that the high-SPRR1A-expression group had a significantly worse prognosis than the low-SPRR1A-expression group, which supported our data. SPRR1A overexpression in PK-1 and Panc-1 did not result in remarkable changes to in vitro phenotypes, such as the cell proliferation, chemo-resistance, EMT, migration or global gene expression. Conclusion: Increased expression of SPRR1A is associated with a poor prognosis in PDAC and may serve as a novel prognostic marker. However, our in vitro study suggests that the SPRR1A expression may be a consequence, not a cause, of the aggressive behavior of PDAC. [ABSTRACT FROM AUTHOR]

Background: It remains controversial whether preoperative cholangitis affects long-term outcomes after resection in patients with extrahepatic bile duct cancer.Methods: A total of 107 patients with extrahepatic bile duct cancer who underwent resection with curative intent from 2008 to 2014 were retrospectively reviewed. Patients were categorized into two groups according to the presence or absence of preoperative cholangitis. Clinicopathological variables and long-term outcomes were compared in the two groups.Results: In the preoperative cholangitis group, the rate of preoperative biliary drainage, the number of tube changes and/or additions, and the rate of lymph node metastasis were higher compared to the no-cholangitis group. Overall survival and disease-free survival were significantly worse in the cholangitis group compared to the no-cholangitis group (p = 0.022, p = 0.007). A poorer prognosis was not observed with an increasing grade of cholangitis in Tokyo Guidelines 2013 (p = 0.09). A multivariate logistic regression analysis revealed that the preoperative cholangitis was an independent prognostic factor for extrahepatic bile duct cancer.Conclusion: Preoperative cholangitis is an independent prognostic factor in patients with extrahepatic bile duct cancer regardless of the severity of the cholangitis. [ABSTRACT FROM AUTHOR]

Background: Borderline resectable pancreatic cancer (BRPC) is frequently associated with positive surgical margins and a poor prognosis because the tumor is in contact with major vessels. This study evaluated the relationship between the margin-negative (R0) resection rate and findings indicating peripancreatic vascular invasion on multidetector computed tomography (MDCT) imaging after neoadjuvant chemoradiotherapy (NACRT) in patients with BRPC.Methods: Twenty-nine BRPC patients who underwent laparotomy after neoadjuvant S-1 with concurrent radiotherapy were studied retrospectively. Peripancreatic major vessel invasion was evaluated based on the length of tumor-vessel contact on MDCT. The R0 resection rates were compared between the progression of vascular invasion (PVI) group and the non-progression of vascular invasion (NVI) group.Results: There were 3 patients with partial responses (10%), 25 with stable disease (86%), and 1 with progressive disease (3%) according to the RECISTv1.1 criteria. Regarding vascular invasion, 9 patients (31%) were classified as having PVI, and 20 patients (69%) were classified as having NVI. Of the 29 patients, 27 (93%) received an R0 resection, and all the PVI patients received an R0 resection (9/9; R0 resection rate = 100%) while 90% (18/20) of the NVI patients underwent an R0 resection. The exact 95% confidence interval of risk difference between those R0 resection rates was - 10.0% [- 31.7-20.4%].Conclusions: Patients with BRPC after NACRT achieved high R0 resection rates regardless of the vascular invasion status. BRPC patients can undergo R0 resections unless progressive disease is observed after NACRT.Trial Registration: UMIN-CTR, UMIN000009172 . Registered 23 October 2012. [ABSTRACT FROM AUTHOR]