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Tumor budding is a histological characteristic defined as the presence of small clusters of cancer cells at the invasion front. Its significance in duodenal adenocarcinoma (DA) has not been fully described.A single-center, retrospective study was conducted. Patients who underwent curative surgery for histologically diagnosed DA from January 2006 to December 2018 at Kansai Medical University Hospital were included. Tumor budding was counted per 0.785 mmIn total, 47 patients were included. The 5-year overall survival and relapse-free survival rates were 77% and 72%, respectively. High tumor budding was seen in 15 patients (32%). Excluding patients with superficial type (pT1) DA (n = 22), high tumor budding [hazard ratio (HR) 13.4, p = 0.028], regional lymph node metastasis (HR 19.9, p = 0.039), and adjuvant chemotherapy (HR 0.056, p = 0.036) were independent factors related to the overall survival in multivariate analyses. Distant metastases occurred significantly more often in patients who had high tumor budding than in others (p = 0.039).The data suggest that high tumor budding is a predictor of a poor prognosis in resected DA.

Active hexose-correlated compound (AHCC) is a standardized extract from cultured Lentinula edodes mycelia, used as a potent biological response modifier in cancer treatment. We evaluated the nutritional effect of AHCC, given during neoadjuvant therapy, to patients with pancreatic ductal adenocarcinoma (PDAC). Thirty patients with resectable or borderline-resectable PDAC received neoadjuvant therapy with gemcitabine plus S-1. We compared, retrospectively, the outcomes of 15 patients who received AHCC combined with neoadjuvant therapy with those of 15 patients who did not receive AHCC combined with neoadjuvant therapy. The median changes of the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutrition index (PNI) were significantly better in the AHCC group. The relative dose intensity of neoadjuvant therapy was also significantly higher in the AHCC group. Thus, AHCC may improve the nutritional status during neoadjuvant therapy of patients with pancreatic ductal adenocarcinoma. To validate these results and examine the long-term impact of AHCC, a prospective phase II study for PDAC is ongoing.

Background Eosinophilic granulomatosis with polyangiitis (EGPA) is an anti-neutrophil antibody (ANCA)-associated necrotizing vasculitis, which predominantly affects small to medium vessels, and is associated with asthma and eosinophilia. EGPA has two different pathogenic aspects: eosinophilic granulomatous inflammation and ANCA-associated inflammation. A recent histological study of peripheral nerves showed that not only ANCA-associated inflammation but also eosinophil-associated vascular occlusion leads to ischemia. Endobronchial involvement is relatively common especially in the patients with granulomatosis with polyangiitis but rare in patients with EGPA. Central nervous system (CNS) involvement is also rare in patients with EGPA, the pathogenesis and relationship between these two rare conditions have not been elucidated. Case presentation A 62-year-old woman was admitted with numbness, purpura, and eosinophilia. She had a 3-year-history of bronchial asthma. Chest computed tomography showed left lower lobe collapse, and brain magnetic resonance imaging indicated occipital lobe infarction. Skin biopsy findings led to the diagnosis of EGPA. ANCA test results were negative. All symptoms improved after initiating glucocorticoids. However, atelectasis and brain infarction relapsed with increasing eosinophil counts. Atelectasis quickly disappeared with increasing glucocorticoid dose, and glucocorticoid could be reduced to a maintenance dose after the initiation of mepolizumab. Conclusion Both atelectasis and brain infarction might develop not only via ANCA-associated inflammation but also via eosinophilic inflammation.

To evaluate the status of surgical training in Japan through a national-level needs assessment. A survey was sent to all 909 graduating residents (GRs) and their 611 program directors (PDs) for the year 2016. A working group of surgical educators from around the country was formed under the education committee of the Japan Surgical Society. The survey items were developed by consensus of this working group. The survey investigated the knowledge and problems of the current curriculum, and the status of the current residency training. The response rates were 56.3% of the GRs and 76.8% of the PDs. Among the participants, 47.6% of the GRs and 29.4% of the PDs believed that the residency curriculum did not match the clinical experience. Over 80% of the GRs and PDs agreed on the importance of training outside of the OR, whereas only 13% of the GRs had received such training regularly. Trainees also reported a lower satisfaction rate about the opportunity to train outside of the OR. This national-level needs assessment of surgical training in Japan identified several gaps in the curriculum. These results provide valuable data to assist the ongoing efforts for surgical residency curriculum improvement.

After initial pancreatic resection, local recurrence of pancreatic cancer (PC) or new primary PC can develop in the remnant. There are limited data available regarding this so-called remnant PC. The aim of this retrospective study was to clarify the clinical features and establish a treatment strategy for remnant PC. A multicenter retrospective study with the Kyushu Study Group of Clinical Cancer was carried out. Clinical data from 50 patients who developed remnant PC were analyzed. RAS mutation analysis of the initial tumor and of remnant PC was performed in 17 cases. The initial pancreatic resections were performed for 37 invasive ductal carcinomas, and for 13 other tumors. Thirty-seven patients underwent a second pancreatectomy for remnant PC (resected group), while thirteen patients were not operated (unresected group). The median overall survival times were 42.2 months in the resected group and 12.3 months in the unresected group (HR 0.374; 95% CI 0.17–0.83). In RAS mutation analysis, 14 cases had at least 1 missense variant of KRAS, HRAS, or NRAS in the initial pancreatic tumor and/or remnant PC. The same missense variants between the initial tumor and remnant PC were discovered only in KRAS of one patient, and in HRAS of one patient. No case had completely consistent missense variants between the initial tumor and remnant PC. This study found that repeated pancreatectomy for remnant PC can prolong patient survival, and RAS mutation analysis indicated that many remnant PCs are developed from metachronous multifocal origins.

Although recurrence after hepatectomy for colorectal liver metastases (CRLM) is common, the optimal treatment strategy remains unclear. The aims of this study were to clarify the impact of repeat surgery and identify the predictive factors for repeat surgery. Among the 170 patients who underwent potentially curative surgery for CRLM, 113 developed recurrence. The predictive factors for the performance of repeat surgery were identified and a predictive model was constructed. The patterns of recurrence were as follows; single site [n = 100 (liver, n = 61; lung, n = 22; other, n = 17)], multiple site (n = 13). Repeat surgery was performed in 54 patients (47.8%) including re-hepatectomy (n = 25), radiofrequency ablation (n = 12), and resection of the extrahepatic recurrent disease (n = 17), and their overall survival (OS) was significantly better than that of those who could not (5-year OS 60.7 vs 19.5%, P

To establish if the number of pancreatic acinar cells at the pancreatic cut end is a predictor of postoperative pancreatic fistula (POPF). The number of acinar cells was assessed histologically in 121 consecutive patients who underwent pancreaticoduodenectomy (PD) between April, 2012 and July, 2016. POPF developed in 23 of the 121 patients. Univariate analysis revealed that male sex, long operating time, high volume of blood loss, soft remnant pancreas, large pancreatic duct, and the number of pancreatic acinar cells were significantly associated with POPF. Multivariate analysis revealed that male sex (p = 0.022) and the number of pancreatic acinar cells (p

Background: Inflammation and immune characteristics of the tumour microenvironment have therapeutic significance. The aim of this study was to investigate the clinical impact on disease progression in human extrahepatic cholangiocarcinoma (ECC). Methods: A total of 114 consecutive ECC patients with curative resection between 2000 and 2014 were enrolled. Tumour infiltrating CD66b+ neutrophils (TANs; tumour associated neutrophils), CD163+ M2 macrophages (TAMs; tumour associated macrophages), CD8+ T cells, and FOXP3+ regulatory T cells (Tregs) were assayed by immunohistochemistry, and their relationships with patient clinicopathological characteristics and prognosis were evaluated. Results: Tumour associated neutrophils were inversely correlated with CD8+ T cells (P=0.0001) and positively correlated with Tregs (P=0.001). High TANs (P=0.01), low CD8+ T cells (P=0.02), and high Tregs (P=0.04) were significantly associated with poor overall survival (OS). A high-risk signature, derived from integration of intratumoural inflammatory and immune cells, was significantly associated with poor recurrence-free survival (P=0.01) and OS (P=0.0008). A high-risk signature was correlated with postoperative distant metastases. Furthermore, a high-risk signature was related to the resistance to gemcitabine-based chemotherapy used after recurrence. Conclusions: Our data showed that tumour infiltrating inflammatory and immune cells may play a pivotal role in ECC progression and a high-risk signature predicted poor prognosis in ECC patients.

Pancreatic neuroendocrine tumors (PNETs) are clinically malignant, having metastatic potential. Histological tumor grade is an accepted indicator of malignant potential, but noninvasive prognostic markers have not yet been identified. This study assessed whether the preoperative neutrophil-to-lymphocyte ratio (NLR) could predict clinical outcomes of PNET patients. Fifty-eight patients who underwent curative resection for PNETs between 2001 and 2015 were retrospectively evaluated. The correlations between the preoperative NLR and clinicopathological parameters, including patient baseline clinical characteristics, tumor progression, and postoperative oncological outcome were evaluated. A high preoperative NLR was significantly associated with large tumor size (P = 0.0015) and high tumor grade (P

Background Carcinosarcoma is a rare tumor that includes both carcinoma and sarcoma components. It develops commonly in the female reproductive tract, most often in the uterus. However, as there are a small number of similar cases in the English literature, we would like to present a rare case of a carcinosarcoma in Vater’s papilla. Case presentation A 76-year-old female patient was preoperatively diagnosed with a papillary adenocarcinoma in Vater’s papilla by endoscopic biopsy. The patient underwent subtotal stomach-preserving pancreaticoduodenectomy, and postoperative pathological examination diagnosed the carcinosarcoma. The patient received adjuvant chemotherapy with gemcitabine, but multiple liver metastases were found 3 months after the operation. Though chemotherapy with gemcitabine and cisplatin was introduced, she died owing to tumor progression 7 months after the operation. Conclusion Because carcinosarcoma of Vater’s papilla is a rare disease, a suitable treatment strategy has been unclear. We also present a review of the English literature regarding carcinosarcoma of Vater’s papilla.

Pancreatico-digestive anastomosis is important in ensuring the safety of pancreaticoduodenectomy. This study compared the postoperative complications of a newly developed method of inserting end-to-side pancreaticojejunostomy with the conventional pancreaticojejunostomy after pancreaticoduodenectomy. From April 2012 to December 2015, 108 consecutive patients underwent pancreaticoduodenectomy at Kumamoto University Hospital. A modified child’s reconstruction was performed with the inserting or conventional pancreaticojejunostomy. The clinical course and the incidence of postoperative complications were retrospectively evaluated. Five patients were excluded, four who underwent hepato-pancreatoduodenectomy and one who did not require pancreaticojejunostomy because of an atrophic pancreatic remnant. Of the 103 patients that were included in the analysis, 41 and 62 underwent surgery with the inserting and conventional methods, respectively. The incidence of postoperative Clavien–Dindo grade > II complications was similar in the two groups [36.6 % (15/41) vs 27.4 % (17/62)]. However, the rates of grade C postoperative pancreatic fistula [7.3 % (3/41) vs 0 % (0/62) P = 0.030] and re-operation for postoperative complications [14.6 % (6/41) vs 3.2 % (2/62), P = 0.034] were significantly higher in the inserting group than in the conventional group. There were no in-hospital deaths in either group. The conventional pancreaticojejunostomy is safer than the end-to-side inserting pancreaticojejunostomy, as the latter is associated with a risk of severe complications. Improvements in pancreatico-digestive anastomosis techniques are required.

Dysregulation of lipid and amino acid metabolism in patients with liver diseases results in obesity-related carcinogenesis and decreased levels of branched-chain amino acids (BCAA), respectively. This study assessed the clinical and prognostic impact of visceral fat amount (VFA) and its association with amino acid metabolism in patients with hepatocellular carcinoma (HCC). In this study, 215 patients who underwent hepatic resection for HCC were divided into two groups based on VFA criteria for metabolic abnormalities in Japan. Computed tomography was used to measure VFA at the third lumbar vertebra in the inferior direction. Of the 215 patients, 132 had high and 83 had low VFA. High VFA was significantly associated with older age and higher body mass index (BMI), subcutaneous fat amount, and BCAA, but not with liver function, nutrient status, or tumoral factors. VFA was positively correlated with BMI (P

The relationship between intraoperative blood loss (IBL) and prognosis has been reported for some types of cancer, but not for pancreatic cancer, which has one of the highest mortality rates of any cancer. We conducted this study to analyze the relationship between IBL and clinical outcome for patients undergoing radical surgery for pancreatic cancer. The subjects of this study were 144 patients who underwent curative pancreatectomy for invasive pancreatic cancer between 2002 and 2014. Clinicopathological characteristics were recorded and prognostic factors were identified by univariate and multivariate analyses. Large IBL was significantly associated with advanced tumor stage, a long operation time, a large tumor, portal vein resection, and blood transfusion. According to univariate analysis, IBL was also significantly associated with overall survival (OS) and relapse-free survival (RFS); however, it was not an independent prognostic factor for OS and RFS in multivariate analysis. According to multivariate analysis, lymph node metastasis and R-status were independent prognostic factors for OS and RFS. A subgroup analysis of patients who received no blood transfusion showed similar results. Minimizing IBL is very important; however, the present study found that positive lymph node metastasis and R-status were stronger independent prognostic factors for pancreatic cancer.

Intraductal papillary mucinous neoplasm (IPMN), the most common pancreatic cystic neoplasm, is known to progress to invasive ductal adenocarcinoma. IPMNs commonly harbor activating somatic mutations in GNAS and KRAS, primarily GNAS(R201H) and KRAS(G12D). GNAS encodes the stimulatory G-protein α subunit (Gsα) that mediates a stimulatory signal to adenylyl cyclase to produce cyclic adenosine monophosphate (cAMP), subsequently activating cAMP-dependent protein kinase A. The GNAS(R201H) mutation results in constitutive activation of Gsα. To study the potential role of GNAS in pancreatic tumorigenesis in vivo, we generated lines of transgenic mice in which the transgene consisted of Lox-STOP-Lox (LSL)-GNAS(R201H) under the control of the CAG promoter (Tg(CAG-LSL-GNAS)). These mice were crossed with pancreatic transcription factor 1a (Ptf1a)-Cre mice (Ptf1a(Cre/+)), generating Tg(CAG-LSL-GNAS);Ptf1a(Cre/+) mice. This mouse line showed elevated cAMP levels, small dilated tubular complex formation, loss of acinar cells and fibrosis in the pancreas; however, no macroscopic tumorigenesis was apparent by 2 months of age. We then crossed Tg(CAG-LSL-GNAS);Ptf1a(Cre/+) mice with LSL-Kras(G12D) mice, generating Tg(CAG-LSL-GNAS);LSL-Kras(G12D);Ptf1a(Cre/+) mice. We used these mice to investigate a possible cooperative effect of GNAS(R201H) and Kras(G12D) in pancreatic tumorigenesis. Within 5 weeks, Tg(CAG-LSL-GNAS);LSL-Kras(G12D);Ptf1a(Cre/+) mice developed a cystic tumor consisting of marked dilated ducts lined with papillary dysplastic epithelia in the pancreas, which closely mimicked the human IPMN. Our data strongly suggest that activating mutations in GNAS and Kras cooperatively promote murine pancreatic tumorigenesis, which recapitulates IPMN. Our mouse model may serve as a unique in vivo platform to find biomarkers and effective drugs for diseases associated with GNAS mutations.

Background: The inactivation of the Hippo pathway lead to TAZ (PDZ-binding motif)/YAP (yes-associated protein) overexpression, and is associated with worse prognostic outcomes in various cancers including hepatocellular carcinoma (HCC). Although there are several reports of microRNA (miR) targeting for YAP, miR targeting for TAZ remains unclear. The aim of this study is to identify the miR targeting TAZ expression in HCC. Methods: MicroRNA expression was analysed using the Human miFinder 384HC miScript miR PCR array, and was compared between low and high TAZ expression cell lines. Then, we extracted miR-9-3p as a tumour-suppressor miR targeting TAZ. We examined the functional role of miR-9-3p using miR-9-3p mimic and inhibitor in HCC cell lines). Results: In HCC cell lines and HCC clinical samples, there was the inverse correlation between miR-9-3p and TAZ expressions. TAZ expression was induced by treatment of miR-9-3p inhibitor and was downregulated by treatment of miR-9-3p mimic. Treatment of miR-9-3p mimic inhibited cell proliferative ability with downregulated phosphorylations of Erk1/2, AKT, and β-catenin in HLF. Inversely, treatment of miR-9-3p inhibitor accelerated cell growth compared with control in HuH1. Conclusions: MicroRNA-9-3p was identified as the tumour-suppressor miR targetting TAZ expression in HCC cells.

The purpose of this study was to determine the relationship between serum zinc (Zn) level and clinicopathological profiles in patients with hepatocellular carcinoma (HCC). Furthermore, we investigate the influence of serum Zn level on the long-term prognosis after hepatectomy. A retrospective analysis was conducted of 310 patients who underwent initial hepatectomy for HCC. The correlation between serum Zn level and preoperative liver functional indicator, pathological features, including the degree of hepatic fibrosis, and perioperative outcome were evaluated. The patients were divided into two groups (serum Zn ≤ 65 mg/dL; n = 71 and Zn > 65 mg/dL; n = 239), and their long-term prognosis were compared. There were strong correlations between preoperative serum Zn level and serum albumin (r = 0.47, P

A replaced common hepatic artery (RCHA) originating from the superior mesenteric artery is a rare anomaly, and cancer of the head of the pancreas can easily invade the RCHA. Interruption of the hepatic arterial flow at the time of pancreaticoduodenectomy (PD) is associated with an increased risk of hepatic and biliary ischemia, which may consequently result in complications such as stenosis of the biliary-enteric anastomosis, and in biliary fistulae. Hence, PD accompanied by dissection and reconstruction of the RCHA is necessary. We here report a case of pancreatic head cancer with invasion of the RCHA. We performed a PD with dissection and reconstruction of the RCHA using the left gastric artery and proximal stump of the RCHA, without any serious complications. We conclude that for PD in patients with an RCHA, careful study of preoperative images is necessary, and that microsurgery for arterial reconstruction is beneficial for these patients.

Pancreatic cancer is a risk factor for the development of portal vein thrombosis because pancreatic lesions sometimes compress and/or directly invade the portal vein. We herein present a case of pancreatic cancer with widespread thrombosis of the portal vein system. A 52-year-old male was admitted to our hospital with epigastralgia. An abdominal contrast-enhanced computed tomography scan demonstrated a non-enhanced low-density tumor in the head of the pancreas and widespread thrombus formation in the superior mesenteric and portal veins. 18F-FDG positron emission tomography showed uptake in the tumor but not in the thrombi. We diagnosed the patient with pancreatic cancer with widespread portal venous thrombosis without tumor thrombi, and pancreaticoduodenectomy with reconstruction of the portal vein was performed. Histological examinations showed that the majority of the emboli consisted of blood thrombi including a few tumor cells. Although the patient ultimately died due to multiple liver metastases, he lived for 19 months after the surgery. The present case indicates that performing radical pancreatic resection in patients with pancreatic cancer is possible, even when widespread portal venous thrombosis is present.

Patients with unresectable pancreatic and biliary cancers sometimes need decompression due to obstruction of the gastrointestinal tract and/or biliary tract. The aim of this study was to determine the prognostic factors associated with an indication for palliative bypass surgery in patients with unresectable pancreatic and biliary cancers. Between April 2005 and September 2011, 37 patients with unresectable pancreatic and biliary cancers underwent palliative bypass surgery. Prognostic factors were searched for among clinical characteristics, operation-related factors, and tumor-related factors using a prospective database. The median survival time (MST) of these patients was 4.6 months, with a 6-month survival rate of 40.5 %. A multivariate Cox proportional hazards regression analysis revealed that mGPS >2 was the only independent prognostic factor for bypass surgery. Patients with an mGPS of 2 had an MST of 1.7 months, and they had a significantly worse prognosis than mGPS 0–1 patients with an MST of 6.3 months. The mGPS is useful for predicting survival after surgical decompression due to gastrointestinal obstruction in patients with unresectable pancreatic and biliary cancers. Patients with a poor mGPS may not be indicated for palliative bypass surgery.

Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2). When present in PRC2, EZH2 catalyzes trimethylation on lysine 27 residue of histone H3, resulting in epigenetic silencing of gene expression and cancer progression. We investigated the expression and function of EZH2 in intrahepatic and extrahepatic cholangiocarcinoma (ICC and ECC).The influence of EZH2 on cell growth and apoptosis was assessed by knockdown experiments. Target gene of EZH2 was searched by quantitative RT-PCR. Clinical significance of EZH2 in 86 cholangiocarcinoma patients (45 ICC and 41 ECC) who underwent curative surgery was examined by immunohistochemistry.In vitro analysis, knockdown of EZH2 reduced cell growth, induced G1 arrest, and induced apoptosis, as confirmed by Annexin V staining and increased sub-G1 populations in cholangiocarcinoma cell lines. The expression levels of p16 (INK4a) and p27 (KIP1) were remarkably increased by knockdown of EZH2 in these cell lines. In immunohistochemical study, EZH2 upregulation correlated with tumor diameter (p = 0.0103) in ICC, lymph node metastasis (p = 0.0292) in ECC, and Ki67 index in both ICC (p = 0.0364) and ECC (p = 0.0017). In addition, EZH2 expression was correlated with poor prognosis in both ICC (p = 0.0447) and ECC (p = 0.0227).The current study demonstrated relationships between EZH2 expression and acceleration of the cell cycle and antiapoptosis, and poor prognosis in cholangiocarcinoma. These results suggest that EZH2 may represent a potential therapeutic target in patients with cholangiocarcinoma.

During hepatic resection, accurate estimation of remnant liver volume and hepatic function is crucial for avoiding postoperative liver failure. The purpose of this study was to identify preoperative factors related to postoperative liver dysfunction according to the percentage of future liver remnant volume (%FLR).A total of 625 patients who underwent hepatectomy were enrolled in this study. Total bilirubin level50 μmol/L and/or prothrombin time index50 % on postoperative day 5 were used as criteria for postoperative liver dysfunction (PLD). Patients were classified into 3 groups according to the %FLR: 35-60 (n = 116), 60-80 (n = 157), and80 (n = 351). Multivariate logistic regression analysis was performed to identify factors related to postoperative liver dysfunction in each group.Among the patients with 35-80 %FLR, the morbidity and mortality rates were significantly higher in patients with PLD than in patients without PLD. There was no postoperative death in patients with80 %FLR . Multivariate analysis showed that PLD was associated with receptor index (LHL15) ≤0.93 (odds ratio [OR] = 7.96) in patients with 35-60 %FLR. The sensitivity and specificity for PLD were 87.5 and 96.1 %, respectively. In patients with 60-80 %FLR, PLD was associated with platelet count10.0 × 10(4)/mL (OR = 6.12). The sensitivity and specificity for PLD were 73.3 and 96.2 %, respectively.LHL15 ≤0.93 and platelet count10.0 × 10(4)/mL are pivotal indicators for predicting PLD in patients with 35-60 %FLR and 60-80 %FLR, respectively.

Over the past 100 years, advances in surgical techniques and perioperative management have reduced the morbidity and mortality after pancreaticoduodenectomy (PD). Many techniques have been proposed for the reconstruction of the pancreaticodigestive anastomosis to prevent the development of a postoperative pancreatic fistula (POPF), but which is the best approach is still highly debated. We carried out a systematic review to determine and compare the effectiveness of various methods of anastomosis after PD. A meta-analysis and most randomized controlled trials (RCTs) showed that the mortality, POPF rate and incidence of other postoperative complications were not statistically different between the pancreaticogastrostomy and pancreaticojejunostomy (PJ) groups. One RCT showed that a binding PJ significantly decreased the risk of POPF and other postoperative complications compared with conventional PJ. External duct stenting reduced the risk of clinically relevant POPF in a meta-analysis and RCTs. The prophylactic use of octreotide after PD does not result in a reduced incidence of POPF. In conclusion, our findings suggest that the successful management of pancreatic anastomoses may depend more on the meticulous surgical technique, surgical volume, and other management parameters than on the type of technique used. However, some new approaches, such as binding PJ, and the use of external stents should be considered in further RCTs.

Clinical determinants of liver regeneration induced by portal vein embolization (PVE) and hepatectomy remain unclear. The aims of this study were to investigate how liver regeneration occurs after PVE followed by hepatectomy and to determine which factors strongly promote liver regeneration. Thirty-six patients who underwent both preoperative PVE and major hepatectomy were enrolled in this study. Percentage of future liver remnant volume before PVE (%FLR-pre) was compared with the remnant liver volume after PVE (%FLR-post-PVE) and on postoperative day 7 after hepatic resection (%FLR-post-HR). Clinical indicators contributing to liver regeneration induced by both PVE and hepatectomy were examined by logistic regression analysis. PVE and hepatectomy caused a two-step regeneration. FLR-pre, FLR-post-PVE, and FLR-post-HR were 448, 579, and 761 cm3, respectively. The %FLR-pre was significantly associated with liver regeneration induced by both PVE and hepatectomy (r = 0.63, p

Reactive fibroinflammatory pseudotumor located in the pancreas is a rare condition. However, we experienced three cases of reactive fibroinflammatory pseudotumor of the pancreas over the previous 2 years. Immunohistochemical staining of immunoglobulin G4 (IgG4) confirmed that Cases 1 and 3 involved IgG4-related disease and that Case 2 did not. In Cases 1 and 3, the masses were formed through autoimmune reaction and were diagnosed as autoimmune pancreatitis (AIP). In Case 2, because only a few IgG4-positive cells were found, it was difficult to diagnose AIP or IgG4-related disease. Reactive fibroinflammatory pseudotumors can develop without the involvement of any autoimmune mechanisms. There seems to be partial overlap between reactive fibroinflammatory pseudotumors and AIP.

Diabetes and obesity are associated with non-alcoholic steatohepatitis and an increased incidence of hepatocellular carcinoma (HCC). TAZ and YAP are equivalently placed downstream effectors of the Hippo pathway with oncogenic roles in human cancers. Statins are commonly used to patients with metabolic problems as hypercholesterolemia. Statins also have anti-cancer properties, and the cross-talk between mevalonate pathway and Hippo pathway was known. The aim of this study is to confirm the statin's anti-cancer effects on HCC cells and its survival benefits in HCC patients with curative surgery. TAZ expression level in HCC cell lines was analyzed by western blot. Two cell lines (HLF and HuH1) were used in this study. Then the mechanism of statin's anti-proliferative effect was examined in HLF and HuH1 cells. In clinical setting, overall survival and recurrence-free survival (RFS) rate were examined in comparison between statin intake and statin non-intake group. The proliferation assay using four different statins (atorvastatin, pravastatin, fluvastatin, simvastatin). Simvastatin and fluvastatin showed very strong growth suppressive effects, and induced apoptosis in HLF cells, but not HuH1 cells. TAZ expression was suppressed in HLF cells by fluvastatin and simvastatin treatment. The similar change pattern was confirmed in p-ERK1/2 and ERK. In HuH1 cells, such expression change was not confirmed. In clinical setting, statin intake was significantly associated with longer RFS in the HCC patients with hepatectomy (P = 0.038). The statin had the anti-proliferative effects and induced apoptosis in HCC cells and improved the prognosis of HCC patients.

The treatment outcome of extrahepatic cholangiocarcinoma remains insufficient because it is difficult to obtain accurate diagnosis of tumor spreading and effective treatment agent is quite limited in spite of substantial current efforts, all of which have been unsuccessful except for gemcitabine plus cisplatin. The patient was a 60-year-old female who had developed hilar cholangiocarcinoma and underwent extrahepatic bile duct resection. Although it was conceivable that it would be the R1 resection, the patient wanted to receive limited resection to avoid postoperative complication mainly because she was depressed. In histology, interstitial spreading of tumor was appreciated at the surgical margin of bile duct. The patient did not accept to receive the additional treatment after the surgery and hardly visited the hospital to take the periodical test for monitoring the residual cancer cells. As expected, the local relapse of tumor was appreciated 1 year after the R1 surgery. She chose radiotherapy and agreed with subsequent S-1 treatment for 26 months. Consequently, elevated CA19-9 was decreased, and local relapse has been successfully controlled for more than 7 years after the relapse of tumor. Here, we report quite a rare case in terms of long survivor after chemoradiotherapy on locally relapsed unresectable hilar cholangiocarcinoma.

Sorafenib is an oral multikinase inhibitor with anti-proliferative and anti-angiogenic effects and is used worldwide for the treatment of advanced or metastatic hepatocellular carcinoma (HCC). While the significant survival benefit of sorafenib in patients with advanced HCC was demonstrated, various treatment-related adverse events might happen. Of them, the incidence of drug-related severe liver dysfunction rarely occurs (

In patients undergoing pancreaticoduodenectomy, leakage from the pancreatic anastomosis remains an important cause of morbidity and contributes to prolonged hospitalization and mortality. Recently, a new end-to-end pancreaticojejunostomy technique without the use of any stitches through the pancreatic texture or pancreatic duct has been developed. In this novel anastomosis technique, the pancreatic stump is first sunk into deeply and tightened with a purse string in the bowel serosa. We modified this method in an end-to-side manner to complete the insertion of the pancreatic stump into the jejunum, independent of the size of the pancreas or the jejunum. We tested this new anastomosis technique in four pilot patients and compared their outcomes with four control patients who underwent traditional pancreaticojejunostomy. No severe pancreatic fistulas were observed in either group. There were no differences in morbidity or hospital stay between the groups. This new method can be performed safely and is expected to minimize leakage from pancreaticojejunostomies.

The causes of strangulated small bowel obstruction (SSBO) include a fibrous cord, torsion, and internal hernia. We conducted this study to define the clinical features of SSBO.We reviewed the clinical course and preoperative data of 74 patients treated for SSBO in Kumamoto Regional Medical Center between January 2004 and September 2010.Twenty-one patients had no history of laparotomy. Computed tomography (CT) showed high positivity (86.3 %) of closed loops in the involved intestine. Postoperative complications developed in 23 patients, representing a morbidity rate of 31.1 %. Forty-four patients underwent resection of non-viable small intestine (non-viable group), and 30 did not require resection of the intestine (viable group). There were four hospital deaths in the non-viable group. The overall mortality rate and the mortality rate in the non-viable group were 5.4 and 9.1 %, respectively.These findings indicate that SSBO can occur without a history of laparotomy, CT is useful in its diagnosis, and its associated morbidity and mortality are high.

Purpose: Mortality rates after pancreatic resection are now lower than 5% in high-volume centers; however, morbidity remains high. This stresses the importance of identifying accurate predictors of operative morbidity after pancreatic resection. The Estimation of Physiologic Ability and Surgical Stress (E-PASS) scoring system was developed for a comparative audit of general surgical patients. Our previous study confirmed its usefulness for predicting morbidity after pancreaticoduodenectomy. In the present study, we evaluated whether the E-PASS scoring system can predict the occurrence of complications after distal pancreatectomy (DP). Methods: The subjects were 46 patients who underwent DP for pancreatic disease. We studied correlations between the incidence of postoperative complications and the preoperative risk score (PRS), surgical stress score (SSS), and comprehensive risk score (CRS) of the E-PASS scoring system. Results: A collective total of 20 postoperative complications developed in 13 (28.3%) of the 46 patients. All E-PASS scores, particularly PRS and CRS, were significantly higher in the patients with postoperative complications than in those without complications. The complication rate increased with increasing PRS, SSS, and CRS scores. Conclusion: The E-PASS scoring system is useful for predicting morbidity after DP.

In Japan, forests associated with shrines and temples are recognized as important components of urban green space, which can potentially function as centers for ecosystem conservation in rapidly urbanizing Japanese cities. In addition to their ecological value, shrine/temple forests have social value, providing recreational and aesthetic needs to residents of urban areas. We review the historical development of shrine/temple forests in Japan and discuss current conservation issues from both ecological and sociological perspectives. Generally, shrine forests are minimally managed and public access is discouraged, whereas temple forests are intensively managed for public display. Shrines tend to be spatially scattered across the landscape but associated with specific geographical features, whereas temples tend to be clustered. Their wide and random distribution in urban areas suggests that shrine forests can potentially be used as stepping stones in the urban green space network, whereas spatially clustered temple forests can be integrated to form large areas of green space. Species diversity of shrine/temple forests declines with decreasing area. The distribution pattern of species is not completely nested, indicating that although conservation of large forest fragments may be effective for maintaining landscape-level biodiversity, smaller forest fragments and adjacent precincts are sometimes significant because rare species occasionally inhabit them. Active management and ecological restoration, such as removal of invasive species, are also important to maintain the desirable near-natural forest conditions. A working group including the owner, community, regional government, and ecologists should be involved in creating an effective, long-term management plan. Because social and cultural values are diverse, basic ecological studies of shrine/temple forests would contribute a scientific basis that fosters public confidence in the process.

Clinically, we often encounter cancer patients who also have cardiovascular disease such as coronary artery disease. We experienced a case of severe coronary artery disease and a large hepatocellular carcinoma in a 69-year-old man. To reduce the risk of a perioperative cardiovascular event during mesohepatectomy, an elective intra-aortic balloon pump (IABP) was used. After an uneventful recovery, the patient was discharged on day 15. While IABP is frequently introduced in cardiac surgery, there have been few reports of its use during liver surgery. Here, we present IABP-assisted major hepatectomy as an option in a patient with both cancer and coronary artery disease.

The right hepatic artery usually branches from the common hepatic artery, however, there are cases showing anatomic variations. We present 41-year-old female patient with gallbladder cancer. In this case, the accessory right hepatic artery branched from the gastroduodenal artery, passed in front of the common bile duct and fed into the anterior segment of the liver. Cholecystectomy and resection of the extrahepatic bile duct with hepaticoenterostomy were performed successfully, preserving the accessory right hepatic artery. There are few reports presenting such an extremely rare anomaly of hepatic arteries in the English literature. Additionally, we herein present a review of the English literature regarding anatomic variations of right hepatic artery.

The characteristic histological feature of pancreatic mucinous cystic neoplasm (MCN) is ovarian-like stroma (OS) underlying the epithelium and existence of estrogen receptors and progesterone receptors in the nucleus of OS. We experienced a case of pancreatic MCN which was activated during pregnancy and confirmed the existence of estrogen receptors and progesterone receptors. In cases with potential factors for malignancy, surgical resection of MCN may be needed during pregnancy. On the other hand, in cases without these, as female sex hormones may have an influence on the behavior of pancreatic MCN during pregnancy, the timing of surgery should be decided on a case-by-case basis, taking into consideration the status of the malignancy, the stage of the pregnancy, and the condition of the mother and fetus.

Acute gastric volvulus is a torsion of the stomach by more than 180° and a life-threatening condition. We present a 50-year-old male patient with acute abdominal pain who has Down syndrome/trisomy 21. Computed tomography showed a significant distended stomach with features of a severe gastric volvulus. Emergency operation in form of reduction and gastropexy was performed. We are not aware of any similar cases published in the English literature, where as gastric volvulus occurred in a patient with Down syndrome.

Despite years of intensive research on copper oxide superconductors with high transition temperatures (T-c), the driving force of superconductivity has not yet been clarified. Angle-resolved photoemission spectroscopy (ARPES)(1-3) measurements have uncove

The 2010 World Health Organization (WHO) classification proposed the grading of pancreatic neuroendocrine tumors (PNET) on the basis of proliferation, using the mitotic counts and/or Ki-67 index, although a surgical method according to grading has so far been indicated. Most patients with nonfunctioning PNET are not diagnosed until the appearance of tumor-related symptoms, because they have no hormonal symptoms, and the size of the tumor correlates well with its malignant potential in most cases. We herein present the case of a 67-year-old female with an asymptomatic very small pancreatic tumor. She was diagnosed as having nonfunctioning PNET on the basis of a cytological examination, and underwent a subtotal stomach-preserving pancreaticoduodenectomy. On the basis of histological examinations she was diagnosed as having a G1 PNET, 8 mm in diameter, with lymph node metastasis. Our findings suggest that standard surgery with substantial lymph node sampling should be performed for nonfunctioning PNET in order to ensure a complete resection, even if a tumor is minute and/or G1.

Afferent loop necrosis after Roux-en-Y cholangiojejunostomy biliary reconstruction is rare. We present the case of a 36-year-old woman with acute necrotic afferent loop obstruction. The peripheral area of the Roux-en-Y limb, including the cholangiojejunostomy portion, was twisted just proximal to the cholangiojejunostomy. Cholangiojejunostomy was completely separated due to necrosis of the Roux-en-Y jejunum. In addition to the case report, we discuss features of cholangiojejunostomy that require special attention.