Complex glandular pattern is an aggressive morphology that predicts poor prognosis of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant neoplasm with various morphologies. Recognition of histological patterns that can predict prognosis is important in pathological examination. Recently, the complex glandular pattern was defined as a morphology associating the poor prognosis in lung adenocarcinoma. We investigated the significance of the complex glandular pattern in PDAC by performing a retrospective analysis. Among 240 consecutive cases of conventional PDACs, 21 cases in which complex glandular pattern constituted >50 % of the total tumor volume (CG-PDACs) were identified. The prevalence of CG-PDAC was 8.8 % among all preoperative therapy-naïve and surgically resected conventional PDACs. Compared to the control PDACs (n = 95), the CG-PDACs were characterized by significantly higher prevalence of small- to medium-sized artery invasion (71.4 % vs. 14.7 %, p < 0.0001), intratumoral necrosis (59.1 % vs. 16.8 %, p < 0.0001), tumor budding (mean: 15.5 vs. 12.5 per 0.785 mm2, p = 0.04), significantly higher Ki67 proliferative index (mean: 75.0 % vs. 54.7 %, p < 0.0001), and the HNF1α-/KRT81+ (quasi-mesenchymal) immunophenotype (42.9 % vs. 19.0 %, p = 0.004). In Kaplan-Meier analyses, the CG-PDAC patients achieved significantly worse disease-free survival (DFS) and overall survival (OS) compared to the control PDAC patients; the respective median DFS and OS were 6.3 and 17.7 months for CG-PDACs, and 22.6 and 52.8 months for control PDACs. A multivariate Cox regression analysis showed that predominance of complex glandular pattern was an independent prognostic factor (hazard ratio: 2.95; 95 % confidence interval: 1.46-5.98; p = 0.003). Our results provide new insights into the complex glandular pattern in conventional PDACs as a novel and potentially useful prognostic factor.

[A Case of Perihilar Cholangiocarcinoma with Postoperative Hepatic Encephalopathy Due to Portosystemic Shunt Treated by Percutaneous Embolization].

An 83-year-old woman developed jaundice, and was diagnosed as perihilar cholangiocarcinoma. Abdominal contrast- enhanced CT revealed coexisting portosystemic shunt between portal vein and inferior vena cava, however, her blood ammonia level was normal. She underwent right hemihepatectomy and caudate lobectomy combined with extrahepatic bile duct resection and portal vein resection. Postoperatively, hyperammonemia refractory to conservative treatment was observed. The blood ammonia level increased to 180µg/dL and she was suffered from grade Ⅲ hepatic encephalopathy on the 20th postoperative day. CT showed an increase in the diameter of the portosystemic shunt, while there was only a slight increase in the remnant left lobe of the liver. These findings indicated that hepatic encephalopathy was caused by increased portosystemic shunt blood flow and decreased portal venous flow. Hepatic encephalopathy was rapidly improved by percutaneous transhepatic portosystemic shunt obliteration.

Association of tumors having Epstein-Barr virus in surrounding lymphocytes with poor prognosis.

Infection with certain viruses is an important cause of cancer. The Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium recently analyzed the whole-genome sequencing (WGS) data from 2656 cases across 21 cancer types, and indicated that Epstein-Barr virus (EBV) is detected in many different cancer cases at a higher frequency than previously reported. However, whether EBV-positive cancer cases detected by WGS-based screening correspond to those detected by conventional histopathological techniques is still unclear. In this study, to elucidate the involvement of EBV in various cancers, we reanalyzed the WGS data of the PCAWG cohort combined with the analysis of clinical samples of gastric and pancreatic cancer in our cohort. Based on EBV copy number in each case, we classified tumors into three subgroups: EBV-High, EBV-Low, and EBV-Negative. The EBV-High subgroup was found to be EBV-positive in the cancer cells themselves, whereas the EBV-Low subgroup was EBV-positive in the surrounding lymphocytes. Further, the EBV-Low subgroup showed a significantly worse prognosis for both gastric cancer and across cancer types. In summary, we classified tumors based on EBV copy number and found a unique cancer subgroup, EBV-positive in the surrounding lymphocytes, which was associated with a poor prognosis.

Integrated environmental, lifestyle, and epigenetic risk prediction of primary gastric neoplasia using the longitudinally monitored cohorts.

BACKGROUND: DNA methylation accumulates in non-malignant gastric mucosa after exposure to pathogens. To elucidate how environmental, methylation, and lifestyle factors interplay to influence primary gastric neoplasia (GN) risk, we analyzed longitudinally monitored cohorts in Japan and Singapore. METHODS: Asymptomatic subjects who underwent a gastric mucosal biopsy on the health check-up were enrolled. We analyzed the association between clinical factors and GN development using Cox hazard models. We further conducted comprehensive methylation analysis on selected tissues, including (i) mucosae from subjects developing GN later, (ii) mucosae from subjects not developing GN later, and (iii) GN tissues and surrounding mucosae. We also use the methylation data of mucosa collected in Singapore. The association between methylation and GN risk, as well as lifestyle and methylation, were analyzed. FINDINGS: Among 4234 subjects, GN was developed in 77 subjects. GN incidence was correlated with age, drinking, smoking, and Helicobacter pylori (HP) status. Accumulation of methylation in biopsied gastric mucosae was predictive of higher future GN risk and shorter duration to GN incidence. Whereas methylation levels were associated with HP positivity, lifestyle, and morphological alterations, DNA methylation remained an independent GN risk factor through multivariable analyses. Pro-carcinogenic epigenetic alterations initiated by HP exposure were amplified by unfavorable but modifiable lifestyle choices. Adding DNA methylation to the model with clinical factors improved the predictive ability for the GN risk. INTERPRETATION: The integration of environmental, lifestyle, and epigenetic information can provide increased resolution in the stratification of primary GN risk. FUNDING: The funds are listed in Acknowledgements section.

Hepatobiliary-pancreatic surgery for patients with a prepancreatic postduodenal portal vein: a case report and literature review.

BACKGROUND: Prepancreatic portal vein (PPV) is a congenital anatomical variant of the portal vein (PV). PPVs are extremely rare and generally classified into two categories, prepancreatic preduodenal portal vein and prepancreatic postduodenal portal vein (PPPV). Prepancreatic preduodenal portal veins are rare, with approximately 100 reported cases globally; PPPVs are even more atypical, with less than 20 documented cases globally. Despite the extremely low occurrence, PPPV knowledge and recognition are important, especially for hepatobiliary-pancreatic (HBP) surgeries, such as pancreaticoduodenectomy (PD) for patients of a PPPV. Here, we report a case of PPPV and a literature review. CASE PRESENTATION: A 73-year-old-male with ampullary carcinoma underwent PD at our hospital. Preoperative enhanced CT revealed an abnormal L-shaped PV, identified as a PPPV. Both the PPPV and the postpancreatic "normal" superior mesenteric vein (SMV) divaricated from the SMV at the caudal side of the pancreas. A splenic vein and inferior mesenchymal vein flowed into the postpancreatic "normal" PV, which encircled the common bile duct and potentially flowed into the liver, forming a cavernous transformation at the hilar plate. During surgery, we attempted to isolate the PV from the pancreas and common bile duct. However, it was difficult to isolate from the pancreas. The PPPV was so fragile that bleeding from the PPPV became uncontrollable. To remove the tumor, we resected the PPPV and reconstructed a "normal" PV as an autogenous graft. To maintain intraoperative hepatic blood flow and avoid small bowel congestion, an antithrombogenic bypass catheter was placed between the SMV and umbilical vein during reconstruction. After surgery, several complications occurred, such as PV thrombosis and hyperammonemia. The patient was discharged on postoperative day 45. CONCLUSIONS: PPPV is a rare vascular variant but is easily diagnosed preoperatively due to its distinct shape on CT imaging. However, isolating the PPPV from the pancreas and bile duct is incredibly difficult and potentially associated with increased operative risks and postoperative complications. PV resection rather than isolation is a potential solution to reduce the risk of hemorrhage, even in the absence of invasion.

[A Case of Jejunal Ectopic Pancreatic Cancer with Small Bowel Obstruction].

Were port a caseof an 82-year-old man who presented with vomiting. Computed tomography(CT)revealed a jejunum tumor and small bowel obstruction. Enteroscopy revealed a protruded lesion and biopsy indicated adenocarcinoma. PET-CT revealed nothing without jejunal tumor. Therefore, with a preoperative diagnosis of primary small bowel cancer, we performed operation. Surgery indicated peritoneal disseminations and a jejunal tumor 40 cm distal from the ligament of Treitz, and we performed small bowel partial resection. Pathological examination revealed adenocarcinoma originating from a Heinrich type I ectopic pancreas in the jejunum. Ectopic pancreatic cancer in the jejunum is rare, and we review case reports in the literature.

[A Case of Early-Onset Rapidly Progressive Cerebral Infarction with Trousseau's Syndrome in a Patient with Pancreatic Cancer Undergoing Surgery].

Trousseau's syndrome refers to cerebral infarction associated with hypercoagulability caused by cancer. Here, we report a case of Trousseau's syndrome in a patient with pancreatic cancer undergoing surgery. A 71-year-old woman was diagnosed with pancreatic head cancer with portal vein invasion; she underwent pancreaticoduodenectomy combined with portal vein resection. Pathological examination showed poorly differentiated adenocarcinoma with para-aortic lymph nodal metastasis. Although the patient had an uneventful postoperative course, she suddenly developed right hemiplegia and dysarthria 6 weeks after surgery, resulting in multiple cerebral infarctions scattered over both hemispheres. Owing to elevated D-dimer and CA125 levels as well as multiple liver metastases, the patient was diagnosed with Trousseau's syndrome and treated using heparin-based anticoagulant therapy. However, her cerebral infarction progressed rapidly and she died within 35 days of admission. Therefore, Trousseau's syndrome should be suspected when a patient with cancer is diagnosed with cerebral infarction, and anticoagulation therapy with heparin should be promptly initiated.