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A 66-year-old Japanese woman was admitted to our hospital for jaundice. Abdominal computed tomography(CT) showed dilatation of the intra- and extra-hepatic bile duct, and a hypovascular lesion measuring 30mm in diameter in the head of the pancreas. This tumor was in contact with the(superior mesenteric vein: SMV)and(inferior vena cava: IVC), but there were no obvious signs of invasion. Upper gastrointestinal endoscopy showed obstruction of the duodenum. We chose to perform an upfront surgery, considering the patient's general condition being stable and the difficulties associated with endoscopic biliary drainage. During surgery, stiff attachment between the tumor and IVC was identified and wedge resection of the IVC wall was performed. SMV resection and end-to-end reconstruction were also carried out. Pathological studies of the surgical specimen revealed direct invasion by the pancreatic adenocarcinoma into the adventitia of the IVC. The postoperative course was uneventful, and the patient was discharged from the hospital on the 27th postoperative day; she underwent adjuvant chemotherapy(S-1 100mg/day)and is still alive without tumor recurrence, 21 months after surgery. Cases of resected pancreatic adenocarcinoma directly invading the IVC are rare. In this case, pancreaticoduodenectomy along with wedge resection of the IVC wall could safely be performed, and no complications were observed. There is a need for further accumulation of similar cases.

Intrahepatic cholangiocarcinomas were classified into two types based on their microscopic appearance. Tumors with histologic similarities to hilar cholangiocarcinomas (predominantly ductal adenocarcinomas with minor tubular components, if present, restricted to the invasive front) were defined as the perihilar type, whereas the others were classified as peripheral cholangiocarcinomas. Among the 47 cases examined in the present study, 26 (55%) were classified as the perihilar type, whereas 21 (45%) were the peripheral type. The perihilar type had higher pT stages and more frequently showed a periductal-infiltrating gross appearance and microscopic perineural infiltration than peripheral cholangiocarcinomas. The presence of low-grade biliary intraepithelial neoplasia in the adjacent bile ducts was only found in perihilar cholangiocarcinomas (6/21, 29%). The immunophenotype also differed between the two types with MUC5AC and MUC6 being more commonly expressed in the perihilar type. One-third of perihilar cholangiocarcinomas lacked the expression of SMAD4, suggesting SMAD4 mutations, whereas the loss of BAP1 expression and IDH1 mutations were almost restricted to the peripheral type (35 and 15%, respectively). Patients with perihilar cholangiocarcinoma had worse overall survival than those with peripheral cancer (P=0.027). A multivariate analysis identified the histologic classification as an independent prognostic factor (P=0.005, HR=3.638). Comparisons between intrahepatic and hilar cholangiocarcinomas also revealed that the molecular features and prognosis of perihilar cholangiocarcinomas were very similar to those of hilar cholangiocarcinomas. In conclusion, this histology-based classification scheme of intrahepatic cholangiocarcinomas will be useful and clinically relevant because it represents different underlying molecular features and has an independent prognostic value.

It remains controversial whether preoperative cholangitis affects long-term outcomes after resection in patients with extrahepatic bile duct cancer. 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. 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. Preoperative cholangitis is an independent prognostic factor in patients with extrahepatic bile duct cancer regardless of the severity of the cholangitis.

The present study aimed to elucidate whether the stemness molecule, CD133, is expressed in well-differentiated pancreatic neuroendocrine tumors (PanNETs; World Health Organization grades 1 and 2) and establish its clinical relevance using 2 separate cohorts. In the first series (n = 178) in which tissue microarrays were available, immunohistochemistry revealed that CD133 was expressed in 14 cases (8%). CD133+ PanNETs had higher TNM stages (P < .01), more frequent lymphovascular invasion (P = .01), and higher recurrence rates (P = .01). In the second cohort (n = 56), the expression of CD133 and CK19 was examined in whole tissue sections. CD133 and CK19 were positive in 10 (18%) and 36 (64%) cases, respectively. CD133 expression correlated with higher pT scores (P < .01), the presence of microscopic venous infiltration (P = .03), and shorter disease-free periods (P < .01). When cases were divided into grade 1 and 2 neoplasms, patients with CD133+ PanNET continued to have shorter disease-free periods than did those with CD133- tumors in both groups (P < .01 and P = .02, respectively). Although CK19+ cases had shorter disease-free periods than did CK19- cases in the whole cohort (P = .02), this difference was less apparent in subanalyses of grade 1 and 2 cases. CD133 expression also appeared to be an independent predictive factor for tumor recurrence in a multivariate analysis (P = .018). The CD133 phenotype was identical between primary and metastatic foci in 17 of 18 cases from which tissues of metastatic deposits were available. In conclusion, the combination of CD133 phenotyping and World Health Organization grading may assist in stratifying patients in terms of the risk of progressive clinical courses.

Background and aim Lymph node metastasis predicts poorer prognoses in patients with invasive intraductal papillary mucinous neoplasms of the pancreas (IPMNs). Factors associated with lymph node metastasis of invasive IPMN remain unclear. Therefore, this study aimed to define factors associated with lymph node metastasis of invasive IPMN. Methods Between June 2000 to August 2015, 156 consecutive patients with IPMN underwent surgical resection at Kobe University Hospital, and were enrolled in this study. The relationship between lymph node metastasis and clinical characteristics, including imaging studies and serum tumor markers, was evaluated. A multivariate logistic regression analysis was performed to assess the relationship between serum tumor markers and the presence of lymph node metastasis of IPMN, adjusted for clinical characteristics. Results Lymph node metastasis was observed in 7.7% (12/156) of IPMNs via a pathological examination. The multivariate logistic regression analysis revealed that serum SPan-1 was associated with the presence of lymph node metastasis of IPMN (odds ratio [OR] = 7.32; 95% confidence interval [CI] = 1.10 to 56.0; P = 0.04). In addition, survival was poorer among serum SPan-1-positive patients than SPan-1 negative patients (Log-rank test; P = 0.0002). Lymph node enlargement was detected preoperatively on computed tomography scans in only 16.7% (2/12) of cases that were positive for lymph node metastasis. Conclusions Elevated serum SPan-1 was associated with lymph node metastasis in this cohort of patients who underwent resection for invasive IPMN.

A 68-year-old woman underwent Miles' surgery with a diagnosis of a rectalgastrointestinalstromaltumor (GIST)in 2004. In 2005 and 2006, she developed liver metastases that were surgically removed, but once again in June 2006, she presented with liver metastasis, and imatinib therapy(400mg/day)was administered. In October 2016, she was diagnosed with progression of liver metastasis, and a tumor in the pancreatic body was identified on a CT scan. The patient was referred to our institution for treatment. We performed right hepatectomy and distalpancreatectomy in January 2017. Immunohistochemically, the recurrent tumor was positive for c-kit and CD34, and the diagnosis of GIST was confirmed. The pathological diagno- sis was a high-risk GIST showing 43mitoses per 50 high-power fields. Imatinib therapy(400mg/day)was administered after surgery. She is currently alive without recurrence.

The biological behavior of well-differentiated neuroendocrine tumors of the pancreas (PNETs) is difficult to predict. This study was designed to determine whether involvement of the main pancreatic duct (MPD) serves as a poor prognostic factor for PNETs. The involvement of the MPD in PNETs was defined as ductal stenosis inside the tumor mass associated with distal MPDs more than twofold larger in diameter than the proximal ducts. We examined the correlation between MPD involvement and other clinicopathological parameters, including nodal metastasis and recurrence-free survival, in 101 patients treated consecutively at three referral centers in Japan. All patients underwent surgical resection. MPD involvement was observed in 13 of the 101 cases (13%) and was associated with multiple unfavorable clinicopathological features (e.g., larger tumor size, higher histological grade, more frequent nodal metastasis, and higher recurrence rates). Patients with MPD involvement also showed significantly worse recurrence-free survival than did those without ductal involvement (P

Aims The aim of this study was to achieve a better definition of intraductal papillary neoplasms of the bile duct (IPNBs). Methods and results Biliary tumours that showed predominantly intraductal papillary growth were provisionally classified as IPNBs (n = 25) and papillary cholangiocarcinomas (n = 27). IPNB was defined as a neoplasm that is confined to the epithelium or is regularly arranged in a high-papillary architecture along thin fibrovascular stalks, whereas the term ‘papillary cholangiocarcinoma’ was used for tumours with more complex papillary structures (e.g. irregular papillary branching or mixed with solid–tubular growth). In our consecutive cohort of biliary neoplasms, 5% were classified as IPNBs, and 10% as papillary cholangiocarcinomas. IPNBs differed from papillary cholangiocarcinomas by less advanced invasion, gross mucin overproduction (72% versus 7%), and their prevalent location (84% of IPNBs in intrahepatic/hilar ducts; 70% of papillary cholangiocarcinomas in extrahepatic ducts). Gastric-type and oncocytic-type tumours were only detected in IPNBs. Expression of mucin core proteins and cytokeratin 20 significantly differed between the two groups. KRAS and GNAS were wild-type genotypes in all but one case of KRAS-mutated IPNB. Patients with IPNB had better recurrence-free survival than those with papillary cholangiocarcinoma (P = 0.007). In multivariate analysis, in which several other prognostic factors (e.g. stromal invasion and lymph node metastasis) were applied, the classification of the two papillary tumours was an independent prognostic factor (P = 0.040). Conclusions Given the significant contrast in clinicopathological features between IPNBs and papillary cholangiocarcinomas, it may be more appropriate to use the diagnostic term ‘IPNB’ for selected tumours that show regular papillary growth, separately from papillary cholangiocarcinomas.

Background Microscopic venous and lymphatic invasion is a known prognostic factor for various cancers, but its prognostic relevance for pancreatic neuroendocrine tumors (PNETs) is unclear. Methods Thirty-two consecutive patients with PNET who had complete resection were included in this study. Venous and lymphatic invasion was identified on elastic tissue or immunohistochemical staining, and correlated with other clinicopathological factors, including recurrence-free survival. Results Venous and lymphatic invasion was identified in nine (28%) and three (9%) patients, respectively. Tumors with venous invasion were of significantly larger size, higher Ki-67 index, and higher mitotic counts. Patients with venous invasion showed significantly worse prognosis than those without venous invasion ( P = 0.001). Five of nine patients (56%) with venous invasion had tumor recurrence, while a relapse was found in one case in patients without venous invasion (n = 23). Lymphatic invasion was not correlated with any other clinicopathological parameters including lymph node metastasis and recurrence-free survival. Predictive factors for recurrence in univariate analysis included microscopic venous invasion, tumor size ≥ 20 mm, non-functionality, and WHO grades. In multivariate analysis where WHO grades and microscopic venous invasion were applied, venous invasion remained a significant predictor of poor recurrence-free survival ( P = 0.021). Conclusions Microscopic venous invasion may serve as a predictive factor for tumor recurrence in patients with resectable PNET. The combination of WHO grades and microscopic venous invasion may assist in the stratification of the patients for risk of tumor recurrence.

This study aimed to evaluate the efficacy of stereotactic body radiotherapy (SBRT) compared with three-dimensional conformal radiotherapy (3DCRT). Forty-three patients with portal vein tumor thrombosis (PVTT)/inferior vena cava tumor thrombosis (IVCTT) treated with SBRT (27 with CyberKnife (CK) and 16 with TrueBeam (TB)) from April 2013 to December 2014, and 54 treated with 3DCRT from June 2008 to March 2013 were evaluated. Dosimetric parameters, response to radiotherapy (RT) and survival outcomes were compared in total SBRT vs. 3DCRT, CK vs. 3DCRT and TB vs. 3DCRT, respectively. The median biologically effective dose 10 (BED10) values in total SBRT, CK, TB and 3DCRT were 73.4 Gy10, 75.0 Gy10, 60.5 Gy10 and 58.5 Gy10, respectively (P < 0.001 in total SBRT vs. 3DCRT, P < 0.001 in CK vs. 3DCRT, P = 0.004 in TB vs. 3DCRT). The tumor response rates were 67%, 70%, 62% and 46%, respectively (P = 0.04, P = 0.04, P = 0.25). The 1-year overall survival rates were 49.3%, 56.7%, 38.1% and 29.3%, respectively (P = 0.02, P = 0.02, P = 0.30), and the 1-year local progression rates were 20.4%, 21.9%, 18.8% and 43.6%, respectively (P = 0.01, P = 0.04, P = 0.10). The use of SBRT made it possible to achieve a higher BED10 compared with the use of 3DCRT. Improvements in local control and survival were achieved in the CK group and the total SBRT group. Our results suggest that SBRT may have the potential to be the standard RT technique for the treatment of PVTT/IVCTT.

We assessed the predictive value of the preoperative neutrophil-to-lymphocyte ratio (NLR) in patients who underwent a two-stage treatment combining reductive surgery and percutaneous isolated hepatic perfusion for multiple hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).Forty-two patients underwent the two-stage treatment between January 2000 and December 2014 at Kobe University Hospital (Hyogo, Japan). The NLR was calculated from lymphocyte and neutrophil counts in the preoperative routine blood test. Clinical data and overall survival were compared statistically and multivariate analysis was done to identify prognostic factors.The median survival of patients with a preoperative NLR 2.3 was 14.9 months (n = 13), whereas that of patients with a preoperative NLR ≤ 2.3 was 26.1 months (n = 29; P = 0.022). A preoperative NLR 2.3 was an independent prognostic factor in patients with multiple HCC with PVTT [hazard ratio (HR) 2.329; 95 % confidence interval (CI) 1.058-5.667; P = 0.036].Based on the results of this study, an elevated preoperative NLR is an independent predictive risk factor for patients undergoing two-stage treatment for multiple HCC with PVTT.

Objectives The aim of this study was to determine the incidence rate and clinical features of second primary pancreatic ductal carcinoma (SPPDC) in the remnant pancreas after pancreatectomy for pancreatic ductal carcinoma (PDC). Methods Data of patients undergoing R0 resection for PDC at a single high-volume center were reviewed. SPPDC was defined as a tumor in the remnant pancreas after R0 resection for PDC, and SPPDC met at least one of the following conditions: 1) the time interval between initial pancreatectomy and development of a new tumor was 3 years or more; 2) the new tumor was not located in contact with the pancreatic stump. We investigated the clinical features and treatment outcomes of patients with SPPDC. Results This study included 130 patients who underwent surgical resection for PDC between 2005 and 2014. Six (4.6%) patients developed SPPDC. The cumulative 3- and 5-year incidence rates were 3.1% and 17.7%, respectively. Four patients underwent remnant pancreatectomy for SPPDC. They were diagnosed with the disease in stage IIA or higher and developed recurrence within 6 months after remnant pancreatectomy. One patient received carbon ion radiotherapy and survived 45 months. One patient refused treatment and died 19 months after the diagnosis of SPPDC. Conclusions The incidence rate of SPPDC is not negligible, and the cumulative 5-year incidence rate of SPPDC is markedly high. Post-operative surveillance of the remnant pancreas is critical for the early detection of SPPDC, even in long-term survivors after PDC resection.

We herein examined the immunohistochemical expression of 2 hepatocyte-specific transporters (bile salt export pump [BSEP] and multidrug-resistance protein 3 [MDR3]) in hepatocellular carcinomas (HCCs, n=54), intrahepatic cholangiocarcinomas (n=34), combined hepatocellular and cholangiocarcinomas (n=23), and hepatoid carcinomas originated from extrahepatic organs (n=27) to compare their diagnostic values with those of arginase-1 (ARG1) and hepatocyte paraffin-1 (HepPar-1). BSEP was expressed in 91% of HCCs and MDR3 in 83%. Although their sensitivities were slightly lower than those of ARG1 (96%) and HepPar-1 (93%), the 2 transporters appeared to be more specific for HCCs. ARG1 and HepPar-1 were expressed in intrahepatic cholangiocarcinomas (9% and 6%) and hepatoid carcinomas (22% and 44%, respectively), whereas BSEP and MDR3 were entirely negative in these neoplasms, except for 1 case of BSEP-positive hepatoid carcinoma of the esophagus. The highly specific expression of BSEP and MDR3 in hepatocytes was recapitulated in additional examinations of combined hepatocellular and cholangiocarcinomas, in which the expression of the transporters was restricted to morphologically hepatocellular areas. In contrast, ARG1 and HepPar-1 were also variably positive in areas of biliary or indeterminate differentiation. We also applied BSEP and MDR3 immunohistochemistry to 8 biopsy cases of poorly differentiated primary liver cancer, in which the original diagnosis was not conclusive. The diagnosis of HCC was retrospectively suggested in 2 cases expressing both BSEP and MDR3. In conclusion, given the highly specific expression of BSEP and MDR3 in HCCs, immunohistochemistry for these transporters will be useful not only for determining hepatocellular differentiation in primary liver cancers but also for discriminating HCCs from hepatoid carcinomas.

Background Postpancreatectomy hemorrhage (PPH) is a life-threatening complication of pancreatic surgery. The shift from surgical to radiological intervention was recently reported in retrospective cohort studies, but it has remained controversial as to which emergent intervention provides optimal management. Methods All 553 patients who underwent standard pancreatic resection at Kobe University Hospital between January 2003 and December 2013 were included. Patient data and complication data were identified from a prospective database. Results The overall incidence of PPH was 6% (35 of 553 patients). Ten patients underwent endoscopic intervention or observation monitoring, or suffered hemorrhagic sudden death. Among the remaining 25 PPH patients, primary surgical intervention was successful in the 6 hemodynamically unstable PPH patients. Primary radiological intervention could successfully stop the bleeding in 15 of the 17 patients with late-PPH. Nine patients who had bleeding from the hepatic artery after pancreaticoduodenectomy were rescued by endovascular embolization of the artery-trunk. The in-hospital mortality of PPH was 20% (7 of 35). Four of the 5 PPH patients who died following any intervention eventually died due to the other complications associated with prolonged pancreatic fistula. Conclusions The leading treatment has been radiological intervention. Endovascular embolization of the hepatic artery-trunk can be securely performed only if blood flow to the liver by an alternate route is confirmed. To reduce mortality of PPH patients, it is necessary to prevent other complications associated with pancreatic fistula following hemostasis. Proactive surgical intervention such as abscess drainage or remnant pancreatectomy is a key consideration.

Although several publications have reported donor morbidities, deterioration of liver function, which may cause posthepatectomy liver failure (PHLF), was not assessed specifically. The incidence of PHLF proposed by the International Study Group of Liver Surgery (ISGLS-PHLF) was analyzed among 257 living donors. ISGLS-PHLF was defined by an increased international normalized ratio and hyperbilirubinemia on or after postoperative day 5. ISGLS-PHLF was identified in 21 donors (8 %), of which 18 (85.7 %) were grade A, 2 (9.5 %) were grade B, and 1 (4.8 %) was grade C. The average hospital stay without ISGLS-PHLF was 15 ± 1 days, which extended along with increasing grades (p = 0.03). In univariate analysis, right hepatectomy was significantly associated with the incidence of ISGLS-PHLF (p = 0.02), and right hepatectomy (p = 0.002) and operation time (p = 0.01) in multivariate analysis. Of 176 right lobe donors, 19 (10.8 %) developed ISGLS-PHLF, of which 16 (84.2 %) were grade A, 2 (10.5 %) were grade B, and 1 (5.3 %) was grade C. Operation time was significantly associated with the incidence of ISGLS-PHLF in univariate (p = 0.002) and multivariate (p = 0.003) analyses. Right lobe donation surgery is associated with a higher incidence of ISGLS-PHLF.

A 69-year-old woman who was identified the tumor of the pancreas tail by CT scan for postoperative inspection of breast cancer. Pancreas tail cancer with para-aortic lymph node metastases was diagnosed by close inspection. She consulted a different hospital to receive their second opinion. She was diagnosed of sarcoidosis from points with lymphadenopathy in hilar region and para-aorta for 3 years and uveitis. The patient was referred to our institution for treatment. We performed distal pancreatectomy in March, 2014. No.16 lymph nodes were cancer-negative, but lymph nodes around the pancreas were cancer positive. Abdominal CT, 9 months after surgery, showed lymph node swelling. We recommended a definitive diagnosis by EUS-FNA, but she refused the inspection. She was checked by CT scan regularly afterwards and is alive without recurrence 39 months after the operation. Diagnosis for lymph node metastases is difficult for a malignant tumor when the sarcoidosis coexisted.

The therapeutic strategy for borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) has remained unestablished because the preoperative prognostic factors have not been determined. 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. 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. Higher preoperative NLR and PLR can be independent predictive risk factors in BR-PDAC patients following curative resection.

To compare the prognostic factors and outcomes after hepatic resection among patients with hepatitis B virus (HBV)-positive, hepatitis C virus (HCV)-positive, and negative for hepatitis B surface antigen and hepatitis C antibody, so-called "NBNC"-hepatocellular carcinoma (HCC) using the data from a nationwide survey.The incidence of NBNC-HCC is rapidly increasing in Japan.A total of 11,950 patients with HBV-HCC (n = 2194), HCV-HCC (n = 7018), or NBNC-HCC (n = 2738) who underwent a curative hepatic resection were enrolled in this study. The clinicopathological features were compared among the groups. The significant prognostic variables determined by univariate analysis were subjected to a multivariate analysis using a Cox proportional hazard regression model.Liver function in the HCV-HCC group was significantly worse than that in the HBV-HCC and NBNC-HCC groups. The NBNC-HCC group had significantly more advanced HCC than the HCV-HCC group. The 5-year overall survival rates after hepatectomy in the HBV-HCC, HCV-HCC, and NBNC-HCC groups were 65%, 59%, and 68%, respectively. The 5-year recurrence-free survival (RFS) rates in these 3 groups were 41%, 31%, and 47%, respectively. Stratifying the RFS rates according to the TNM stage showed that the NBNC-HCC group had a significantly better prognosis than the HBV-HCC group in stages II, III, and IVA, and a significantly better prognosis than the HCV-HCC group in stages I and II. Multivariate analysis revealed a significantly better RFS rate in the NBNC-HCC group.The findings of this nationwide survey indicated that patients with NBNC-HCC had a significantly lower risk of HCC recurrence than those with HBV-HCC and HCV-HCC.

Background/Objectives: The recent guideline for intraductal papillary mucinous neoplasms (IPMNs) focuses on morphological features of the lesion as signs of malignant transformation, but ignores the background pancreatic parenchyma, including features of chronic pancreatitis (CP), which is a risk factor for pancreatic malignancies. Endoscopic ultrasonography frequently reveals evidence of CP (EUS-CP findings) in the background pancreatic parenchyma of patients with IPMNs. Therefore, we investigated whether background EUS-CP findings were associated with malignant IPMN. Methods: The clinical data of 69 consecutive patients with IPMNs who underwent preoperative EUS and surgical resection between April 2010 and October 2014 were collected prospectively. The association of EUS-CP findings (total number of EUS-CP findings; 0 vs. ≥1) with invasive IPMN was examined. The association of EUS-CP findings with pathological changes of the background pancreatic parenchyma (atrophy/inflammation/fibrosis) was also examined. Results: Among patients with EUS-CP findings, invasive intraductal papillary mucinous carcinoma (IPMC) was significantly more frequent than among patients without EUS-CP findings (42.5% [17/40] vs. 3.4% [1/29], p = 0.0002). In addition, patients with EUS-CP findings had higher grades of pancreatic atrophy and inflammation than patients without EUS-CP findings (atrophy: 72.5% [29/40] vs. 34.5% [10/29], p = 0.003; inflammation: 45.0% [18/40] vs. 20.7% [6/29], p = 0.04). Conclusions: In IPMN patients, detection of EUS-CP findings in the background pancreatic parenchyma was associated with a higher prevalence of invasive IPMC. Accordingly, EUS examination should not only assess the morphological features of the lesion itself, but also EUS-CP findings in the background parenchyma.

Background and aims Small hypovascular hepatocellular carcinoma (HCC) ≤2 cm is biologically less aggressive than hypervascular one, however, the optimal treatment is still undetermined. The efficacy of surgical resection (SR), radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI) was evaluated. Methods The 853 (SR, 176; RFA, 491; PEI, 186) patients were enrolled who met Child-Pugh A/B, single hypovascular HCC ≤2 cm pathologically proven, available tumour differentiation and absence of macrovascular invasion and extrahepatic metastasis. Overall and recurrence-free survivals were compared in original and a propensity score weighted pseudo-population with 732 patients. Results The median follow-up time and tumour size were 2.8 years and 1.47 cm respectively. In original population, multivariate Cox regression showed no significant difference for overall survival among three groups. In pseudo-population, Cox regression also revealed no significant difference for overall survival among them, although SR (HR, 0.56; 95% CI, 0.36-0.86) and RFA (HR, 0.75; 95% CI, 0.57-1.00) groups had significantly lower recurrence than PEI group. The overall survival rates at 3 and 5 years for the SR, RFA and PEI groups were 94%/70%, 90%/75% and 94%/73% respectively. Corresponding recurrence-free survival rates were 64%/54%, 59%/41% 48%/33% respectively. Subgroup analysis revealed no significant survival benefit of SR compared with non-SR. No treatment-related death occurred. Conclusions For patients with single hypovascular HCC ≤2 cm, no significant difference for overall survival was first identified among 3 treatment groups. The SR or RFA could be recommended, and PEI would be alternative to RFA.

Background Inflammation-induced carcinogenesis in pancreatic ductal adenocarcinoma (PDAC) has been reported; however, its involvement in PDAC with intraductal papillary mucinous neoplasm (IPMN) remains unclear. We herein investigated the relationship between pancreatic atrophy and inflammation and the incidence of PDAC concomitant with IPMN. Methods This study included 178 consecutive patients who underwent surgical resection for PDAC with IPMN (N = 21) and IPMN (N = 157) between April 2001 and October 2016. A multivariable logistic regression analysis was conducted to assess the relationship between pancreatic inflammation and atrophy and the incidence of PDAC concomitant with IPMN, with adjustments for clinical characteristics and imaging features. Pathological pancreatic inflammation and atrophy were evaluated in resected specimens. Results High degrees of pancreatic inflammation and atrophy were not associated with the incidence of PDAC with IPMN (multivariable odds ratio [OR] = 0.5, 95% confidence interval [CI] = 0.07 to 3.33, P = .52, adjusted by clinical characteristics, OR = 0.9, 95% CI = 0.10 to 5.86, P = .91, adjusted by imaging studies; OR = 0.2, 95% CI = 0.009 to 1.31, P = .10, adjusted by clinical characteristics, OR = 0.2, 95% CI = 0.01 to 1.43, P = .12, adjusted by imaging studies, respectively). Conclusions Pancreatic inflammation and atrophy were not associated with pancreatic cancer concomitant with IPMN.

Background: Topical hemostatic agents are useful when hepatic hemorrhage is difficult to control. The aim of this study was to evaluate the hemostatic efficacy and safety of a biodegradable polyurethane-based adhesive, MAR VIVO-107 (MAR), in comparison with a clinically used fibrin glue. Methods: Thirty female New Zealand white rabbits were randomly assigned to 3 study groups as follows: MAR (n = 10), fibrin glue (n = 10), and saline groups (n = 10). After standardized partial liver resection was performed, each agent was immediately applied to the wound area. Bleeding time until hemostasis and blood loss were recorded. After 7 days, body weight, hematology parameters, and serum levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase were measured. Simultaneously, the severity of intra-abdominal adhesion was evaluated. Results: The mean bleeding time in the MAR (38 ± 10 s) and fibrin glue groups (65 ± 17 s) was significantly shorter than that in the saline group (186 ± 12 s). Similarly, the mean blood loss in the MAR (9 ± 3 g) and fibrin glue groups (9 ± 3 g) was significantly less than that in the saline group (23 ± 4 g). No significant differences in bleeding time and blood loss were found between the MAR and fibrin glue groups. The postoperative survival rate was 100% in all the groups. Body weight as well as hematological and serum biochemical values on day 7 were within the small and physiological range when compared with the preoperative baseline values, and significant differences were not detected among the MAR, fibrin glue, and saline groups. The severities of adhesion were similar between the 3 groups. Conclusion: Our data demonstrated that MAR was not inferior to fibrin glue in terms of hemostatic efficacy and safety.

A 44-year-old woman underwent surgical resection and received preoperative and postoperative chemotherapy for conventional osteosarcoma in the right fibular head. Three years later, follow-up PET-CT revealed accumulation ofFDG in the tail ofthe pancreas. Contrast-enhanced computed tomography showed a 13mm well-circumscribed hypovascular tumor. EUS showed a heterogeneous solid tumor, which was diagnosed as metastasis ofosteosarcoma to the pancreas. Laparoscopic spleen preserving distal pancreatectomy(LAP-SPDP)was performed. Pathologically, the tumor was diagnosed as metastasis ofconventional osteosarcoma to the pancreas. Cells from pancreas islet tissue were detected in the tumor, suggesting invasion ofthe tumor into the pancreatic body and surrounding adipose tissue. Although postoperative chemotherapy was administered, lung metastasis was detected 1.1 years after surgery. Laparoscopic partial resection of the lung metastasis was performed, and the patient is still alive. Metastasis ofosteosarcoma to the pancreas is rare, and there is no report oflaparoscopic approach as a treatment. Herein, we report a case with several references.

A 66-year-old woman presented to the Department of Gynecology in our institution in 2005 with peritoneal recurrence of ovarian fibrosarcoma. Originally, combined modality therapy including repeated surgical resection and somatic chemotherapy was performed. A peritoneal recurrence was found near the pancreatic head. She was referred to our department in October 2015, and underwent pancreaticoduodenectomy. The tumor was severely adhesive to the portal vein and combined portal venous resection was performed. Histological examination of tumor specimens revealed tumor invasion to the adjacent pancreatic parenchyma and portal vein. No evidence of recurrence was detected after a follow-up of 8 months. We suggest that in cases with peritoneal recurrence of ovarian tumors, radical resection might be considered, taking into account the biologic behavior of the tumor.

Objectives The effect of smoking status on the incidence of pancreatic ductal adenocarcinoma (PDAC) concomitant with intraductal papillary mucinous neoplasm (IPMN) has not been clarified. This study investigated the association of smoking status with PDAC concomitant with IPMN. Methods The subjects were 124 consecutive patients undergoing resection of IPMNs (intraductal papillary mucinous adenoma (IPMA): N = 77, invasive IPMN: N = 31, and PDAC with IPMN: N = 16) between April 2008 and October 2015. The associations between smoking status (never/former/current smoker) or cumulative pack-years (0-19/20-39/≥40) and the incidence of PDAC concomitant with IPMN or invasive IPMN were evaluated. Results Current smoking, not former smoking, was associated with the incidence of PDAC concomitant with IPMN (PDAC with IPMN vs IPMN alone; P = 0.004, PDAC with IPMN vs IPMA; P = 0.004, PDAC with IPMN vs invasive IPMN; P = 0.04, respectively), but not that of invasive IPMN (invasive IPMN vs IPMA; P = 0.85). Cumulative pack-years were higher in patients who had PDAC concomitant with IPMN than in patients with invasive IPMN (P = 0.04). Cumulative pack-years were not associated with smoking status (current vs former). Conclusions Current smoking, not former smoking, was associated with the incidence of PDAC concomitant with IPMN. Cessation of smoking may be recommended for patients with IPMN.

Acute graft-versus-host-disease (aGVHD) is a rare complication in the setting of pancreas-kidney transplantation (PKT). We herein describe the case of a 37-year-old male with severe type 1 diabetes with chronic renal failure who received simultaneous PKT from a female donor. Diarrhea developed on postoperative day (POD) 10. Subsequently, fever and liver dysfunction occurred on POD 32. Skin rashes appeared with pain and itching on his trunk and extremities on POD 40. As pancytopenia occurred on POD 63, bone marrow biopsies demonstrated profound hypoplastic marrow. On POD 69, we eventually made a definitive diagnosis of aGVHD because skin biopsies revealed the XX chromosome signal in a fluorescence in situ hybridization analysis. Thereafter, 100 mg of prednisolone was administered for 5 days. Although every symptom was temporarily improved, on POD 156, the patient expired from the septic pneumonia without any effects of antibiotics. Clinician should be aware that PKT has the potential to induce aGVHD.

Although preoperative biliary drainage in jaundiced patients is controversial, external biliary drainage (EBD) is beneficial for infection control in patients with biliary cancers. When EBD is performed, additional bile replacement (BR) has the benefit of improving impaired intestinal barrier function, but the detailed mechanism remains unknown. We examined the effect of bile replacement on immune functions over the duration of BR in jaundiced patients. Fifteen patients were enrolled into this prospective study. BR was started soon after the total serum bilirubin concentration reached 5.0 mg/dl and was continued for 14 days. Drained bile was given two times orally (2 × 100 ml/day). Concanavalin A (Con A)- and phytohemagglutinin (PHA)-stimulated lymphocyte proliferation and serum diamine oxidase (DAO) activity were measured before starting and during BR. Twenty patients with EBD and no BR were analyzed as a control group. Serum liver enzymes, prothrombin time–international normalized ratio (PT-INR), and responses to Con A and PHA gradually improved over the 14 days of BR, but percentages of lymphocytes and DAO levels did not. PT-INR, and Con A and PHA responses did not improve during EBD in the control group. PT-INR significantly decreased in patients with a greater fraction of their drained bile replaced. Our results indicate that preoperative BR using as large a quantity of bile as possible is useful for improving blood coagulability and cellular immunity in patients with EBD.

Background and Objectives Pylorus-preserving pancreatoduodenectomy (PPPD) has been associated with a high incidence of delayed gastric emptying (DGE). There are few studies comparing DGE associated with PPPD and subtotal stomach-preserving pancreatoduodenectomy (SSPPD). Moreover, differences between the procedures with respect to long-term results have not been reported. A prospective randomized study was conducted to compare perioperative complications and long-term nutritional status with PPPD and SSPPD. Methods One hundred patients with periampullary lesions were randomized to receive either PPPD (n = 50) or SSPPD (n = 50). All patients were followed up for 3 years after surgery or to the time of recurrence to evaluate nutritional status for the study. The effects of the procedure, age, and malignancy on changes in nutritional indicators were estimated with linear mixed models. This study was registered at UMIN Clinical Trials Registry (UMIN 000012337). Results The incidence of DGE assessed by the International Study Group of Pancreatic Surgery was 20% with PPPD and 12% with SSPPD (P = 0.414). There were no significant differences between the two procedures on postoperative serum albumin levels, serum total cholesterol levels, and body mass index during the 3-year follow-up period. Conclusions SSPPD is equally effective in DGE occurrence rate and long-term nutritional status comparing to PPPD. J. Surg. Oncol 2014; 109:690–696. © 2014 Wiley Periodicals, Inc.

To examine the prognostic factors and outcomes after several types of treatments in patients with hepatocellular carcinoma (HCC) negative for hepatitis B surface antigen and hepatitis C antibody, so-called "non-B non-C HCC" using the data of a nationwide survey.The proportion of non-B non-C HCC is rapidly increasing in Japan.A total of 4741 patients with non-B non-C HCC, who underwent hepatic resection (HR, n = 2872), radiofrequency ablation (RFA, n = 432), and transcatheter arterial chemoembolization (TACE, n = 1437) as the initial treatment, were enrolled in this study. The exclusion criteria included extrahepatic metastases and/or Child-Pugh C. Significant prognostic variables determined by a univariate analysis were subjected to a multivariate analysis using a Cox proportional hazard regression model.The degree of liver damage in the HR group was significantly lower than that in the RFA and TACE groups. The HR and TACE groups had significantly more advanced HCC than the RFA group. The 5-year survival rates after HR, RFA, and TACE were 66%, 49%, and 32%, respectively. Stratifying the survival rates, according to the TNM stage and the Japan Integrated Staging (JIS) score, showed the HR group to have a significantly better prognosis than the RFA group in the stage II and in the JIS scores "1" and "2." The multivariate analysis showed 12 independent prognostic factors. HR offers significant prognostic advantages over TACE and RFA.The findings of this large prospective cohort study indicated that HR may be recommended, especially in patients with TNM stage II and JIS scores "1" and "2" of non-B non-C HCC.

Objective To clarify the clinical significance of resection of lymph node metastases in patients' hepatocellular carcinoma (HCC). Background Although the presence of lymph node metastasis form HCC has been considered as a systemic disease, prognosis after resection of them remains unknown. Methods From the database of a Japanese nationwide survey, 14,872 patients of HCC treated by surgical resection between 2000 and 2005 were enrolled. We modified the current Japanese staging system for HCC, by further dividing stage IVA into stage IVAnon-n1 and stage n1, according to the absence or presence of pathologically proven lymph node metastasis. Thus, the patients classified into 6 disease stages, that is, I (n=1494), II (n=8056), III (n=4243), IVAnon-n1 (n=701), n1 (n=112), and IVB (n=266), and their long-term outcomes were compared. Results The median follow-up period was 20.6 months. The 3-year overall survival rates of the patients with stage IVAnon-n1, stage n1, and stage IVB were 51.6%, 38.9% and 27.2%, respectively. A multivariate analysis showed that stage IVAnon-n1 would have a similar impact on the survival as stage n1 (hazard ratio: 0.88, 95% confidence interval: 0.59-1.33, P=0.555), and that stage n1 still represented one class less advanced than stage IVB (hazard ratio: 0.52, 95% confidence interval: 0.34-0.80, P=0.003). Conclusions The prognosis of patients with histologically node-positive HCC was similar to that of patients with locally advanced HCC (stage IVA), which supports the validity of the current Japanese staging system and also partially validates the system proposed by the UICC/AJCC.

Posthepatectomy liver failure (PHLF) is a major complication after hepatectomy. As there was no standardized definition, the International Study Group of Liver Surgery (ISGLS) defined PHLF as increased international normalized ratio and hyperbilirubinemia on or after postoperative day 5 in 2010. We evaluated the impact of the ISGLS definition of PHLF on hepatocellular carcinoma (HCC) patients. We retrospectively analyzed 210 consecutive HCC patients who underwent curative hepatectomy at our facility from 2005 to 2010. The median follow-up period after hepatectomy was 35.2 months. Thirty-nine (18.6 %) patients fulfilled the ISGLS definition of PHLF. Overall survival (OS) rates at 1, 3, and 5 years in patients with/without PHLF were 69.1/93.5, 45.1/72.5, and 45.1/57.8 %, respectively (P = 0.002). Recurrence-free survival (RFS) rates at 1, 3, and 5 years in patients with/without PHLF were 40.9/65.9, 15.7/38.3, and 15.7/20.3 %, respectively (P = 0.003). Multivariate analysis revealed that PHLF was significantly associated with both OS (P = 0.047) and RFS (P = 0.019). Extent of resection (P

Background: The efficacy of hepatic arterial infusion chemotherapy for the treatment of advanced hepatocellular carcinoma (HCC) remains unclear. Methods: The outcome of 476 patients with HCC who underwent hepatic arterial infusion chemotherapy with 5-fluorouracil and cisplatin (HAIC) were compared with 1466 patients who did not receive active therapy. Results: A survival benefit of the therapy after adjusting for known risk factors was observed (hazard ratio, 0.48; 95% CI, 0.41–0.56; P

Background & Aims There are no accurate and reliable tools for diagnosis of early stage pancreatic ductal adenocarcinoma (PDA) or small metastatic lesions. It is also a challenge to differentiate PDA from focal mass-forming pancreatitis (FMP). There is controversy regarding the efficacy of 18-fluorodeoxyglucose positron-emission tomography (FDG-PET) in the diagnosis of PDA. We investigated whether FDG-PET provides information that, combined with data from other imaging techniques, can aid in decision making for patients with suspected PDA. Methods We performed a retrospective analysis of data collected from 232 consecutive patients with suspected PDA at Kobe University Hospital from January 2006 through June 2012. All patients underwent a diagnostic imaging protocol that included multidetector row computed tomography, superparamagnetic iron oxide–enhanced magnetic resonance imaging, and FDG-PET. Based on endoscopic ultrasonography, fine-needle aspiration biopsy, or endoscopic retrograde cholangiopancreatography analyses, 218 patients had PDA (89 underwent resection and 129 did not) and 14 patients had FMP (8 had focal mass-forming chronic pancreatitis and 6 had focal mass-forming autoimmune pancreatitis). Results FDG-PET detected 50% of stages 0 and I, 91.9% of stage II, 100% of stage III, and 96.8% of stage IV tumors. Detection was affected significantly by tumor size ( P = .024) and T stage ( P = .023) in resected tumors. Multidetector row computed tomography detected significantly more liver metastases than FDG-PET. Few para-aortic lymph node or peritoneal metastases were detected by FDG-PET. FDG-PET correctly identified 11 of the 14 patients with FMP (5 of 8 with focal mass-forming chronic pancreatitis and 6 of 6 with focal mass-forming autoimmune pancreatitis). Conclusions FDG-PET is not effective in detecting early stage PDA and small metastases, or in differentiating PDA from FMP. Combining FDG-PET with current diagnostic techniques for PDA did not provide any decisive information, therefore it should not be included in this analysis.

A 25-year-old woman was referred to our hospital with persistent upper abdominal pain. Preoperative imaging studies revealed a hilar bile duct stricture with portal venous encasement, and the patient underwent curative resection involving extended left hepatectomy and segmental portal vein resection. The pathological findings demonstrated a well-differentiated tubular adenocarcinoma of the bile duct with regional lymph node metastasis (stage IIIB according to the UICC TNM classification), as well as the overexpression of p53 proteins and the K-ras gene mutation in tumor cells. The patient has shown no evidence of recurrence in the 10 months since the operation. Although there are several reports of relatively young adults with cholangiocarcinoma, the majority of such patients demonstrate either an anomalous arrangement of the pancreaticobiliary duct system or primary sclerosing cholangitis. The absence of any morphological abnormalities in this patient's biliary system implicates de novo carcinogenesis as the most likely cause of the cholangiocarcinoma.

Background & Aims The treatment of choice for early or moderately advanced hepatocellular carcinoma (HCC) with good liver function remains controversial. We evaluated the therapeutic impacts of surgical resection (SR), percutaneous ethanol injection (PEI), and radiofrequency ablation (RFA) on long-term outcomes in patients with HCC. Methods A database constructed on the basis of a Japanese nationwide survey of 28,510 patients with HCC treated by SR, PEI, or RFA between 2000 and 2005 was used to identify 12,968 patients who had no more than 3 tumors (⩽3cm) and liver damage of class A or B. The patients were divided into SR (n=5361), RFA (n=5548), and PEI groups (n=2059). Overall survival and time to recurrence were compared among them. Results Median follow-up was 2.16years. Overall survival at 3 and 5years was respectively 85.3%/71.1% in the SR group, 81.0%/61.1% in the RFA, and 78.9%/56.3% in the PEI. Time to recurrence at 3 and 5years was 43.3%/63.8%, 57.2%/71.7%, and 64.3%/76.9%, respectively. On multivariate analysis, the hazard ratio for death was significantly lower in the SR group than in the RFA (SR vs. RFA:0.84, 95% confidence interval, 0.74–0.95; p =0.006) and PEI groups (SR vs. PEI:0.75, 0.64–0.86; p =0.0001). The hazard ratios for recurrence were also lower in the SR group than in the RFA (SR vs. RFA:0.74, 0.68–0.79; p =0.0001) and PEI groups (SR vs. PEI:0.59, 0.54–0.65; p =0.0001). Conclusions Our findings suggest that surgical resection results in longer overall survival and shorter time to recurrence than either RFA or PEI in patients with HCC.

The purpose of this study was to assess the efficacy of arterial-dominant phase images of gadolinium–ethoxybenzyl–diethylenetriamine pentaacetic acid (EOB)-enhanced magnetic resonance imaging (MRI) for evaluation of arterial blood supply in hepatocellular carcinoma (HCC) in comparison with that of multiphasic dynamic computed tomography (CT). This study comprised 30 patients (22 men and 8 women, mean age: 68.0 years) with 40 pathologically proven HCCs (well differentiated: 3, moderately differentiated: 30, poorly differentiated: 7, mean diameter: 45.1 mm), all of whom underwent EOB-enhanced MRI and dynamic CT preoperative assessment. Regions of interest were placed over HCCs and the adjacent normal liver, and signal intensities or CT values were measured by two experienced abdominal radiologists on the arterial-dominant phase images of EOB-enhanced MRI and dynamic CT images. HCC-to-liver contrasts [Michelson's contrast: CM=(SHCC− SLiver)/(SHCC+ SLiver)] were calculated and compared among the modalities. HCC-to-liver contrasts were also visually scored on a 5-point scale and compared. The mean CM and visual score for dynamic CT were significantly higher than those for EOB-enhanced MRI. Good agreements were obtained among the two observers. Dynamic CT is a more suitable modality than EOB-enhanced MRI for evaluation of arterial blood supply in HCC. This should be taken into account for diagnosis and management of HCC.

Background In the present study, we conducted a multicenter nationwide survey to investigate the effects of preoperative fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) on the prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). Methods From 16 Japanese LT centers, data were collected on 182 recipients with HCC who underwent living donor liver transplantation (LDLT) between February 2005 and November 2013. PET-positive status was defined as increased uptake of FDG in the tumor compared to the surrounding non-tumor liver tissue. The median follow-up after LDLT was 54.5 months (range 1–125 months). Results Postoperative HCC recurrence occurred in 23 patients. Multivariate analysis revealed that exceeding the Milan criteria (MC), alpha-fetoprotein (AFP) level ≥115 ng/ml, and PET-positive status were significant and independent risk factors for recurrence. In the over-MC group, a subgroup of patients with AFP level

Background Operative clips used to ligate vessels in abdominal operation usually are made of titanium. They remain in the body permanently and form metallic artifacts in computed tomography images, which impair accurate diagnosis. Although biodegradable magnesium instruments have been developed in other fields, the physical properties necessary for operative clips differ from those of other instruments. We developed a biodegradable magnesium-zinc-calcium alloy clip with good biologic compatibility and enough clamping capability as an operative clip. In this study, we verified the safety and tolerability of this clip for use in canine cholecystectomy. Methods Nine female beagles were used. We performed cholecystectomy and ligated the cystic duct by magnesium alloy or titanium clips. The chronologic change of clips and artifact formation were compared at 1, 4, 12, 18, and 24 weeks postoperative by computed tomography. The animals were killed at the end of the observation period, and the clips were removed to evaluate their biodegradability. We also evaluated their effect on the living body by blood biochemistry data. Results The magnesium alloy clip formed much fewer artifacts than the titanium clip, and it was almost absorbed at 6 months postoperative. There were no postoperative complications and no elevation of constituent elements such as magnesium, calcium, and zinc during the observation period in both groups. Conclusion The novel magnesium alloy clip demonstrated sufficient sealing capability for the cystic duct and proper biodegradability in canine models. The magnesium alloy clip revealed much fewer metallic artifacts in CT than the conventional titanium clip.

Background: The present study aimed to elucidate prognostic values of baseline plasma chromogranin A (CgA) concentrations in patients with resectable, well-differentiated pancreatic neuroendocrine tumors (PNETs). Methods: Preoperative CgA levels in 21 patients with PNET were correlated with clinicopathological factors and patients’survival. Results: Plasma CgA levels ranged 2.9–30.8 pmol/mL (median 6.0), and were significantly elevated in patients with post-operative recurrence (P = 0.004). Using the receiver operating characteristic curve, the optimal cutoff value to predict tumor recurrence was determined as 17.0 pmol/mL. This threshold identified patients with recurrence with 60% sensitivity, 100% specificity, and 90% overall accuracy. Patients with higher CgA levels showed worse recurrence-free survival than those with low CgA levels, both in total (P < 0.001) and in G2 patients (P = 0.020). Conclusions: Combined plasma CgA concentrations and WHO grading may assist in better stratification of PNET patients in terms of the risk of recurrence.

Patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) invading the portal trunk (Vp4) are poor surgical candidates because of the technical difficulties involved. To overcome the limitations, we developed a technique of back-flow thrombectomy (BFT) based on the inherent portal hemodynamics and the macroscopic form of PVTT. Forty-six patients with multiple HCC and Vp4 PVTT underwent hepatectomy with tumor thrombectomy. We used the BFT to treat 24 patients, 18 of whom had PVTT in the contralateral second portal branch. The form of PVTT was classified macroscopically into the floating and expansive types. The rate of complete removal by BFT of PVTT in the contralateral second portal branch was 89%. The patency rates at the thrombectomy site in all 46 patients and in the 24 BFT patients, 3 months after hepatectomy were 93 and 90%, respectively. The median OS of all 46 patients was 15 months, with 1- and 3-year OS rates of 58.5 and 17.1%, respectively. The median OS of the 24 patients treated with BFT vs. the 22 not treated with BFT was 14 and 15 months, respectively. BFT can expand the therapeutic time window for patients with HCC and deep-seated PVTT and may improve their survival.

Alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) are frequently used as tumor markers in hepatocellular carcinoma (HCC). The authors hypothesized different patient populations with varying tumor sizes would influence the predictive power of tumor markers for survival in HCC patients. The authors investigated the influence of tumor size on predictive powers of AFP and DCP. 181 patients underwent hepatectomy for HCC from 2003 to 2008 at Kobe University Hospital. Tumor markers were measured before and at 1 month post-hepatectomy. The Cox proportional-hazards model revealed that preoperative serum AFP was associated with survival; its effects depended on tumor size. Hazard ratios (HRs) for preoperative AFP were maximum for medium-sized HCC, and for DCP, HRs were maximum in small-sized tumors. Post-hepatectomy, both tumor markers were associated with survival, revealing significant interactions with tumor size. HRs for postoperative AFP were greater than 1 for relatively wide range tumors (3-11 cm). HRs for postoperative DCP increased with tumor size, with a strong prognostic predictive power for tumors5 cm. The predictive power of serum tumor markers varied by tumor size in HCC patients. By selecting the appropriate tumor marker, its predictive power can be improved.

BACKGROUND Portal vein thrombus (PVT) has been an absolute contraindication for liver transplantation because of technical difficulties and inadequate vessel graft supply. With recent surgical innovations many difficulties have been overcome and PVT is no longer a contraindication to liver transplantation. MATERIAL AND METHODS From June 2000 to December 2014, 72 patients underwent living donor liver transplantation at Kobe University Hospital, with a focus on the high-grade PVT cases and analysis of modified PV reconstruction technique and clinical course. RESULTS Four recipients (5.6%) developed Yerdel classification grade III PVT and 2 recipients (2.8%) developed grade IV PVT. There were no statistically significant differences between the severity of PVT grades by sex (p=0.77), recipient age (p=0.49), model for end-stage liver disease (MELD) score (p=0.68), graft-recipient weight ratio (GWRW) (p=0.15), graft type of right or left lobe (p=0.55), original liver disease (p=0.09), or intra-operative bleeding (p=0.21). Four grade III recipients were anastomosed with SMV, and 2 grade IV recipients were anastomosed with coronary vein, both of which were interpositioned with vein grafts. Only 1 recipient had died of hepatocellular carcinoma recurrence by 1.5 years after liver transplantation, and all 5 remaining severe PVT recipients survived. Overall 1- and 5-year survival rates for grade 0, I, and II recipients were 78.8% and 62.4%, respectively; 75.0% and 75.0%, respectively, for grade III recipients; and 100% and 100%, respectively, for grade IV recipients (p=0.54). CONCLUSIONS High-grade PVT had comparable survival without the recurrence of PVT after living donor liver transplantation.

Background Despite evidence suggesting a role of chronic pancreatitis in pancreatic carcinogenesis, its relationship with invasive intraductal papillary mucinous neoplasms (IPMN) remains unclear. Low levels of pancreatic enzymes are predictive markers of advanced chronic pancreatitis. We investigated whether low pancreatic enzyme levels were associated with a higher incidence of invasive IPMN. Methods This study included 146 consecutive patients who underwent surgical resection of IPMN between April 2001 and October 2014. Multivariable logistic regression analysis was conducted to assess the association between serum pancreatic enzymes and the incidence of invasive IPMN, with adjustment for clinical characteristics including alcohol consumption. The association of serum pancreatic enzymes with pathological pancreatic atrophy and inflammation in areas adjacent to or distant from the tumor was also evaluated. Results Low serum levels of pancreatic amylase and lipase were associated with a higher incidence of invasive IPMN (multivariable odds ratio [OR] = 9.6, 95% confidence interval [CI] = 2.99 to 35.1, P = 0.0001; OR = 14.2, 95% CI = 2.77 to 112, P = 0.001, respectively). Low serum pancreatic amylase and lipase levels were also associated with higher grade pancreatic atrophy in areas adjacent to the tumor ( P = 0.011 and P = 0.017, respectively) and in areas distant from the tumor ( P = 0.0002 and P = 0.001, respectively). Furthermore, low serum pancreatic amylase and lipase levels were associated with higher grade inflammation in areas distant from the tumor ( P P = 0.001, respectively). Conclusions Low serum pancreatic enzymes may be a predictive marker of invasive IPMN. Excessive alcohol consumption did not influence the association of low pancreatic enzyme levels with invasive IPMN.

Radiographic intraoperative cholangiography (R-IOC) has been widely used to reduce the incidence of biliary complications in living donor hepatectomy (LDH), but it has some drawbacks including radiation exposure and difficulty with handling a C-arm machine for generating 3D images and delineating thin caudate branches. We recently developed contrast-enhanced intraoperative ultrasonic cholangiography (CE-IOUSC) as a tool for biliary navigation in hepatobiliary surgery. We compared the feasibility and usefulness of CE-IOUSC and R-IOC in LDH for visualizing the biliary system and facilitating bile duct division. Seven consecutive patients who underwent LDH using CE-IOUSC and R-IOC between January 2013 and December 2015 in our institute were enrolled. The detectability of each hepatic duct, biliary configuration types, and caudate branches around the cutting point of the hepatic duct was compared. The detectability of each hepatic duct and biliary configuration types was 100%, 100%, 86%, and 100% in drip infusion cholangiography-computed tomography, R-IOC, and 3D/2D CE-IOUSC, respectively. 2D CE-IOUSC could detect caudate branches draining into the cutting side of the hepatic duct, similar to R-IOC (p

Background: Perioperative management for patients receiving long-term anticoagulant (AC) and antiplatelet (AP) therapy is a great concern for surgeons. This single-center retrospective study evaluated the risks of hemorrhage and thromboembolism after hepato-biliary-pancreatic (HBP) surgery in such patients. Methods: Between 2009 and 2014, 886 patients underwent HBP surgery. Patients were categorized into the AC (n = 39), AP (n = 77), or control (n = 770) group according to the administration of antithrombotic drugs. Perioperative management of AC and AP therapies followed the guidelines of the Japanese Circulation Society. The incidences of hemorrhage and thromboembolism were compared among groups. We used 1:1 propensity score matching and compared the incidences between the matched pairs. Results: There were 0, 1 (1.3%), and 26 (3.4%) hemorrhagic complications in the AC, AP, and control groups, respectively (p = 0.16). There were 0, 1 (1.3%), and 6 (0.8%) thromboembolic complications in the AC, AP, and control groups, respectively (p = 0.66). There was no significant difference in hemorrhagic and thromboembolic complications between the propensity-matched pairs. Conclusion: The incidences of hemorrhage and thromboembolism after HBP surgery in patients receiving long-term AC and AP therapies are within acceptable ranges.

A 69-year-old woman was admitted to a nearby clinic complaining of abdominal pain. Abdominal CT showed a 10 cm diameter huge cystic lesion in the body and tail of the pancreas. The patient was referred to our institution for treatment. Endoscopic ultrasonography (EUS) revealed a cystic mass with a solid lesion. Endoscopic retrograde pancreatography(ERP) demonstrated mucous at the opening of the papilla of Vater and dilatation of the pancreatic duct with a solid nodule. Contrast radiography revealed a fistula from the tumor to the jejunum. A biopsy specimen from the lesion showed adenocarcinoma. Intraoperative findings showed a tumor occupying the pancreas body and tail with suspected invasion to the stomach, jejunum, and transverse colon. We performed distal pancreatectomy with partial resection of stomach, jejunum, and colon. Pathological findings showed an invasive type of IPMC, with invasion to the subserosal layer of the stomach and colon and the mucous layer of the jejunum. While IPMC is recognized as a slow growing malignancy, some cases of invasive carcinoma with fistulation into adjacent organs have been reported. To our knowledge, a case of IPMC penetrating to 3 adjacent organs is rare.

A 61-year-old woman was referred to our hospital for surgery for gallstones. She was diagnosed as having gallbladder cancer after a detailed radiologic examination. At the first laparotomy, gallbladder cancer with bulky invasion to the liver and multiple liver metastases were observed. Gemcitabine plus cisplatin (GC) administration was chosen. After 7 administration of GC, we changed GC to gemcitabine alone due to blood toxicity. After 7 months of chemotherapy, although CT findings showed regression of the liver invasion and the liver metastases, the serum CA19-9 level gradually increased. Because there were no obvious distant metastases on detailed radiologic examination, we performed surgery for the primary lesion after obtaining informed consent. Pathological examination demonstrated fibrosis without viable cancer cells in the metastatic liver tumor. Gemcitabine was administered as post-operative adjuvant chemotherapy. Twelve months after surgery, there was no sign of recurrence.

Introduction Pancreatogenic diabetes after pancreatectomy is of growing importance due to the increasing life expectancy of pancreatectomized patients. Although reduction of pancreatic volume is thought to affect glucose metabolism, a consistent relationship has yet to be determined. This study aimed to investigate functional consequences of distal pancreatectomy (DP) in preoperatively non-diabetic patients. Methods This study included 61 non-diabetic patients who underwent DP. Clinical data were obtained, and the percent resected volume (PRV) of each pancreas was determined via multi-detector row computed tomography volumetry. Results During the follow-up period (median 26 months), 22 patients (36 %) developed new-onset diabetes within a median onset time of 8 months (range 0.5–42 months) postoperatively. The remaining 39 patients also showed impaired glucose metabolism. Multivariate analysis identified preoperative hemoglobin A1c ≥ 5.7 % (odds ratio 15.6, p = 0.001) and PRV > 44 % (odds ratio 11.3, p = 0.004) as independent risk factors for new-onset diabetes. Conclusions Key determinants of postoperative glycemic control include preoperative functional reserve of the endocrine pancreas and the volume reduction of pancreatic parenchyma. Our findings enable reliable preoperative evaluation of the risk of postoperative diabetes and appropriate postoperative surveillance, which is helpful for early intervention in high risk patients.

Purpose We conducted the study to assess the feasibility and efficacy of gemcitabine-concurrent proton radiotherapy (GPT) for locally advanced pancreatic cancer (LAPC). Materials and methods Of all 50 patients who participated in the study, 5 patients with gastrointestinal (GI)-adjacent LAPC were enrolled in P-1 (50Gy equivalent [GyE] in 25 fractions) and 5 patients with non-GI-adjacent LAPC in P-2 (70.2GyE in 26 fractions), and 40 patients with LAPC regardless of GI-adjacency in P-3 (67.5GyE in 25 fractions using the field-within-a-field technique). In every protocol, gemcitabine (800mg/m 2 /week for 3weeks) was administered concurrently. Every patient received adjuvant chemotherapy including gemcitabine after GPT within the tolerable limit. Results The median follow-up period was 12.5months. The scheduled GPT was feasible for all except 6 patients (12%) due to acute hematologic or GI toxicities. Grade 3 or greater late gastric ulcer and hemorrhage were seen in 5 patients (10%) in P-2 and P-3. The one-year freedom from local-progression, progression-free, and overall survival rates were 81.7%, 64.3%, and 76.8%, respectively. Conclusion GPT was feasible and showed high efficacy. Although the number of patients and the follow-up periods are insufficient, the clinical results seem very encouraging.

Paroxysmal nocturnal hemoglobinuria (PNH) makes patients susceptible to intravascular hemolysis and thrombosis, and it can be life-threatening in stressful situations. Eculizumab, a humanized monoclonal antibody that inhibits the complement protein C5, has been evaluated as a novel therapy for PNH. We herein describe the case of a 59-year-old Japanese woman with classic PNH, who had been successfully treated with eculizumab, but who later developed acute cholecystitis/cholangitis from gallstones. Although the severe obstructive jaundice requiring endoscopic therapy following cholecystectomy was complicated, critical intravascular hemolysis and thrombosis were not observed. Therefore, utilizing eculizumab during the peri-operative management of PNH patients should be carefully taken into consideration.