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BackgroundThe present study aimed to determine the ability of diagnosing malignancy and predicting malignant transformation in patients with IPMN using carcinoembryonic antigen (CEA) level in the pancreatic juice.MethodsWe enrolled patients with IPMN who underwent endoscopic retrograde pancreatography (ERP) between 2002 and 2018. We examined the ability of diagnosing malignancy in 63 patients who underwent surgery (surgical group). Furthermore, we examined the value of predicting malignant transformation in 52 patients who underwent follow-up for over 1 year after ERP (follow-up group).ResultsIn the surgical group, the overall sensitivity and specificity of CEA level (≥ 97 ng/ml) in the pancreatic juice for diagnosing malignancy were 45% and 100%, respectively. The specificity was excellent for all IPMN types; however, the sensitivity was highest in main duct type, followed by mixed type and branch duct type. In the follow-up group, malignant transformation was observed in four patients (7.7%) during the follow-up, and the median time until malignant transformation was 58 months. High CEA level in the pancreatic juice demonstrated a statistically significant difference in multivariate analysis and was found to be an independent predictor of malignant transformation (hazard ratio 17; P = 0.02). The cumulative malignant transformation rate was significantly higher in the high CEA group than that in the low CEA group (5-year cumulative malignant transformation rates, 69% vs. 0%, P < 0.001).ConclusionsCarcinoembryonic antigen level in the pancreatic juice is useful not only in diagnosing malignancy but also in predicting future malignant transformations in IPMN patients receiving follow-up.

PurposePostoperative pancreatic fistula (POPF) is one of the major complications in patients who undergo distal pancreatectomy (DP). Recently, dividing the pancreas by stapler is a commonly performed technique, however, POPF still occurs. Therefore, the purpose of this study was to investigate the risk factors for POPF after DP using a triple-row stapler.MethodsA total of 75 patients underwent DP using a triple-row stapler (Endo GIA™ Reloads with Tri-Staple™ Technology 60 mm; COVIDIEN, North Haven, CT, USA) at Yamanashi University from December 2012 to December 2016. The clinical risk factors for POPF after DP using a triple-row stapler were identified based on univariate and multivariate analyses.ResultsClinical POPF (ISGPF Grade B and C) was seen in 7 of 75 patients (9.3%). The body mass index (BMI) was significantly higher in the patients with POPF (26.8 ± 0.5 kg/m2) compared with the patients without POPF (21.4 ± 0.4 kg/m2; a cut-off value; 25.7 kg/m2). In addition, the patients with POPF were significantly younger than the patients without POPF (56.4 ± 5.6 vs 67.0 ± 1.5; a cut-off value was 57.0 years old).ConclusionsBMI and age were found to be significant risk factors for POPF after DP using a triple-row stapler.

AimTo investigate the relationship between the intrahepatic expression of podoplanin (PDPN) and Kupffer cells (KCs) in ischemia–reperfusion (I/R) liver damage.MethodsC57Bl/6 mice were injected with 200 µl of clodronate liposomes (macrophage depletion; MDP group) to deplete KCs or control liposomes (control group) via the ophthalmic vein plexus 24 h prior to ischemia. Animals were subjected to 90 min of partial hepatic ischemia (70%), followed by reperfusion, and were then killed at designated time points. Serum and liver tissues were harvested for further analyses.ResultsSerum ALT levels, mortality rates, and the percentage of necrotic area in liver sections were significantly higher in the MDP group than in the control group. PDPN was expressed in the lymphatic epithelium, interlobular bile duct epithelium, and in some hepatocytes in each group. Its expression in hepatocytes was down-regulated in the MDP group. The accumulation of platelets in the sinusoid was reduced 6 h after I/R in the MDP group. Tissue HGF and IGF-1 levels decreased in the MDP group.ConclusionsThese results suggest that KCs play a key role in the activation of platelets through direct contact with PDPN-positive hepatocytes in I/R livers.

Frequency and characteristics of metachronous occurrence of multifocal intraductal papillary mucinous neoplasms (IPMNs) or distinct pancreatic ductal adenocarcinomas (PDACs) in the remnant pancreas during follow-up evaluation after pancreatectomy for IPMNs have not been well known. The aim of this study was to investigate the outcomes after resection of IPMNs, especially focusing on the metachronous occurrence of multifocal IPMNs and distinct PDACs. Medical records of 172 patients who underwent resection of IPMNs were reviewed retrospectively, and the data regarding the occurrence of metachronous IPMNs or PDACs in the remnant pancreas during a mean postoperative follow-up period of 64 months were collected. The incidence including synchronous and metachronous multifocal occurrence of IPMNs was 20% (34 of 172), and that of distinct PDACs was 9.9% (17 of 172). Ten metachronous IPMNs developed in the remnant pancreas after a mean time of 23 postoperative months (range, 12–84 mo), and 2 with main duct IPMNs (both were carcinoma in situ) required remnant pancreatectomy. Six distinct PDACs developed in the remnant pancreas after a mean time of 84 postoperative months (range, 12–150 mo). Four of them were found to have a tumor with a size of less than 2 cm, whereas the remaining 2 PDACs were found to be unresectable more than 10 years after resection of IPMNs. Intense long-term follow-up evaluation is necessary for the early detection of metachronous occurrence of distinct PDACs as well as malignant IPMNs after resection of IPMNs.

Tissue biopsies are the gold-standard for investigating the molecular characterization of tumors. However, a “solid” biopsy is an invasive procedure that cannot capture real-time tumor dynamics and may yield inaccurate information because of intratumoral heterogeneity. In this review, we summarize the current state of knowledge about surgical treatment-associated “liquid” biopsy for patients with digestive organ tumors. A liquid biopsy is a technique involving the sampling and testing of non-solid biological materials, including blood, urine, saliva, and ascites. Previous studies have reported the potential value of blood-based biomarkers, circulating tumor cells, and cell-free nucleic acids as facilitators of cancer treatment. The applications of a liquid biopsy in a cancer treatment setting include screening and early diagnosis, prognostication, and outcome and recurrence monitoring of cancer. This technique has also been suggested as a useful tool in personalized medicine. The transition to precision medicine is still in its early stages. Soon, however, liquid biopsy is likely to form the basis of patient selection for molecular targeted therapies, predictions regarding chemotherapy sensitivity, and real-time evaluations of therapeutic effects.

INTRODUCTION: Acinar cell carcinoma (ACC) is a rare malignant tumor arising from pancreatic exocrine cells. While it typically originates in the pancreas, ectopic occurrences, especially in the duodenum, are extremely uncommon. Few reports exist of duodenal ACC, particularly those presenting as large tumors.CASE PRESENTATION: An 83-year-old man presented with melena. Endoscopy and imaging revealed a large mass, approximately 7 cm in size, extending from the duodenal bulb to the descending portion of the duodenum. Contrast-enhanced CT showed no evidence of extramural invasion or distant metastasis. Although biopsy confirmed malignancy, a definitive diagnosis could not be established preoperatively. The patient underwent pancreaticoduodenectomy. Postoperative histopathological examination, including immunohistochemical staining positive for trypsin, confirmed the diagnosis of pancreatic-type ACC, likely arising from ectopic pancreatic tissue in the duodenum.CONCLUSIONS: We report a rare case of a giant pancreatic-type ACC of the duodenum, which was strongly suspected to have arisen from ectopic pancreatic tissue. This case highlights the diagnostic challenges associated with pancreatic-type ACC of the duodenum and adds valuable information to the limited literature on this rare entity.

Background The present study aimed to examine the correlation between preoperative carcinoembryonic antigen levels in pancreatic juice (PJ‐CEA) and the histological subtype of intraductal papillary mucinous neoplasm (IPMN). Methods We enrolled IPMN patients who underwent endoscopic retrograde pancreatography between March 2002 and March 2018. Clinical factors associated with IPMN histological subtypes of 67 patients who underwent surgery were analyzed. Furthermore, the relationship between CEA immunohistochemistry findings and histological subtypes was investigated. Results Median PJ‐CEA were 15 ng/ml in the gastric type, 150 ng/ml in the intestinal type, and 175 ng/ml in the pancreatobiliary type. Both intestinal and pancreatobiliary types had significantly higher PJ‐CEA than the gastric type (p = 0.001). In the analysis of histological subtype predictors, high PJ‐CEA (≥63 ng/ml) only showed a significant difference in multivariate analyses (95% confidence interval 4.8–70.2; p < 0.001). Immunohistochemistry findings revealed significantly higher CEA expression in the non‐gastric type than in the gastric type (p < 0.001). The non‐gastric type showed a significantly worse prognosis than the gastric type (p = 0.017). Conclusion PJ‐CEA was an independent predictor of IPMN histological subtypes in a preoperative setting. High PJ‐CEA predict the non‐gastric type, while low PJ‐CEA predict the gastric type.

Background The goal of this study was to understand gene expression signatures of hepatocellular carcinoma (HCC) recurrence in subjects with hepatitis C virus (HCV) infection. Recurrence-free survival (RFS) following curative resection of HCC in subjects with HCV is highly variable. Traditional clinico-pathological endpoints are recognized as weak predictors of RFS. It has been suggested that gene expression profiling of HCC and nontumoral liver tissue may improve prediction of RFS, aid in understanding of the underlying liver disease, and guide individualized patient management. Frozen samples of the tumors and nontumoral liver were obtained from 47 subjects with HCV-associated HCC. Additional nontumoral liver samples were obtained from HCV-free subjects with metastatic liver tumors. Gene expression profiling data was used to determine the molecular signature of HCV-associated HCC and to develop a predictor of RFS. Results The molecular profile of the HCV-associated HCC confirmed central roles for MYC and TGFβ1 in liver tumor development. Gene expression in tumors was found to have poor predictive power with regards to RFS, but analysis of nontumoral tissues yielded a strong predictor for RFS in late-recurring (>1 year) subjects. Importantly, nontumoral tissue-derived gene expression predictor of RFS was highly significant in both univariable and multivariable Cox proportional hazard model analyses. Conclusions Microarray analysis of the nontumoral tissues from subjects with HCV-associated HCC delivers novel molecular signatures of RFS, especially among the late-recurrence subjects. The gene expression predictor may hold important insights into the pathobiology of HCC recurrence and de novo tumor formation in cirrhotic patients.

The aim of this study was to investigate the populations and functions of hepatic and splenic macrophages (Mfs) in non-alcoholic fatty liver disease (NAFLD). Experiment 1: Wild-type and STAM mice were given chow or high-fat diets for designated periods. In isolated Mfs, phagocytosis and cytokine production were assessed. Immunohistochemistry for CD68 and F4/80 and expression of CD14 and CD16 were assessed. Experiment 2: Bone marrow cells harvested from enhanced green fluorescent protein (EGFP) mice were transplanted into wild-type mice with or without splenectomy after total body irradiation that was kept on methionine- and choline-deficient diets. Experiment 1: The number of CD68-positive cells and the percentage of F4/80-positive/CD68-positive cells increased with the progression of NAFLD. Production of TNF-α and IL-6 by hepatic Mfs was greater than that by splenic Mfs in mice with NASH. The number of CD14 CD16 Mfs increased in the spleen and decreased in the liver in animals that had progressed to NASH. Furthermore, the number of CD14 CD16 hepatic Mfs was increased in animals that had progressed to NASH with fibrosis. Experiment 2: EGFP-positive cells were observed in the liver after transplantation. In the splenectomy group, EGFP-positive Mfs were also observed; however, the number was significantly less than that in the sham operation group. The populations and functions of hepatic and splenic Mfs are altered during the progression of NAFLD. In addition, increased hepatic Mfs during the progression of NAFLD may migrate from bone marrow to the liver via the spleen.

Background and aims Although patients with cholecystocholedocholithiasis are generally referred to cholecystectomy after endoscopic sphincterotomy (ES) and common bile duct clearance, we often have a conflict whether cholecystectomy is necessary in very elderly patients with comorbid diseases. The aim of this study is to assess whether cholecystectomy in very elderly patients is justified after ES. Patients and methods Patients with cholecystocholedocholithiasis who underwent ES and stone extraction and were followed-up for more than 10 years were retrospectively reviewed. We divided these patients into two groups: the elderly group (equal to or more than 80 years old) and young group (less than 80 years old) and compared late biliary complications and mortality. Results The 10-year cumulative incidence of overall biliary complications was significantly lower in cholecystectomized patients than in patients with gallbladder in situ in the young group (7.5 vs. 21.7%, p  = 0.0037), but not different in the elderly group (8.3 vs. 7.4%, p  = 0.92). When each complication was evaluated separately, the rate of recurrent common bile duct stones (CBDS) was not different, but that of acute cholecystitis was significantly lower in the elderly group than in the young group (4.1 vs. 22.6%, p  = 0.011). Conclusions In very elderly patients the incidence of acute cholecystitis is low even when the gallbladder is preserved after endoscopic treatment of CBDS, with a similar risk of CBDS recurrence. Thus, it may not be necessary to recommend cholecystectomy after ES for CBDS in very elderly patients.