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Background: Neoadjuvant chemotherapy (NAC) represents a promising alternative to pancreatic ductal adenocarcinoma (PDAC) planned resection, but the survival impact remains undefined. To assess the feasibility and survival outcomes of NAC with gemcitabine and S1 (GS) for PDAC planned resection by prospective study., Methods: Patients with resectable or borderline resectable PDAC received 2 cycles of NAC-GS and were offered curative resection followed by gemcitabine adjuvant. The primary endpoint was 2-year overall survival (OS). Adverse events during NAC, radiological and tumor marker responses, resection rate, and surgical safety were evaluated as secondary endpoints (UMIN000004148)., Results: We enrolled 104 patients between 2010 and 2012, with 101 patients treated using NAC-GS as the full analysis set (FAS). Of the 101 patients, 88% received the planned 2 cycles of NAC. Grade 3 neutropenia was common (35%). Radiological partial response and decreased carbohydrate antigen 19-9 concentration (> 50% decrease) were noted in 13% and 41%, respectively. R0/1 resections with M0 were performed in 65 patients without surgical mortality. Of the 65 patients, 44 received planned gemcitabine adjuvant for 6 months as the on-protocol cohort. The primary endpoint for the 2-year OS rate was 55.9% in the FAS (n = 101) and 74.6% in the on-protocol cohort (n = 44)., Conclusions: NAC-GS was feasible and actively prolonged survival following PDAC planned resection. Randomized control trials are needed to further clarify the survival benefit of NAC-GS in addition to surgery followed by adjuvant therapy.

Background: The prognosis of pancreatic cancer patients with metastatic para-aortic lymph node (PALN) has been reported to be extremely poor. In general, PALN metastasis has been considered as a contraindication for pancreatic resection. The aim of this study was to reevaluate the postoperative prognostic value of PALN metastasis in pancreatic cancer and to determine the validity of pancreatic surgery., Methods: Retrospective multicenter analysis of 882 patients who have undergone curative-intent pancreatic resection with pathological evaluation of PALNs for pancreatic ductal adenocarcinoma between 2001 and 2012 was conducted. Clinicopathological data and outcomes were evaluated with univariate and multivariate analysis., Results: In total, 102 (12.4 %) patients had positive metastasis in PALN. Patients with metastatic PALN had significantly poorer survival than those without (17 vs. 23 months; p < 0.001). Multivariable analysis of 822 patients identified adjuvant chemotherapy, primary tumor status, regional lymph node metastasis, portal vein invasion, pre- and post-operative serum CA19-9 levels, and tumor grade as independent prognostic factors. In contrast, PALN metastasis did not have a significant prognostic value. Furthermore, the multivariate prognostic analysis in patients with PALN metastasis revealed that adjuvant chemotherapy and the number of metastatic PALN were significantly associated with long-term survival. Lung metastasis as initial recurrence was observed more often in patients with PALN metastasis in comparison with those without., Conclusions: Some pancreatic cancer patients with metastatic PALN may survive for longer than expected after pancreatectomy. Adjuvant chemotherapy and the number of metastatic PALN were critical factors for long-term survival of those patients.

Pancreaticobiliary maljunction (PBM) is a congenital malformation in which the pancreatic and bile ducts join anatomically outside the duodenal wall. Japanese clinical practice guidelines on how to deal with PBM were made in 2012, representing a world first. According to the 2013 revision to the diagnostic criteria for PBM, in addition to direct cholangiography, diagnosis can be made by magnetic resonance cholangiopancreatography (MRCP), 3-dimensional drip infusion cholangiography computed tomography, endoscopic ultrasonography (US), or multiplanar reconstruction images by multidetector row computed tomography. In PBM, the common channel is so long that sphincter action does not affect the pancreaticobiliary junction, and pancreatic juice frequently refluxes into the biliary tract. Persistence of refluxed pancreatic juice injures epithelium of the biliary tract and promotes cancer development, resulting in higher rates of carcinogenesis in the biliary tract. In a nationwide survey, biliary cancer was detected in 21.6% of adult patients with congenital biliary dilatation (bile duct cancer, 32.1% vs. gallbladder cancer, 62.3%) and in 42.4% of PBM patients without biliary dilatation (bile duct cancer, 7.3% vs. gallbladder cancer, 88.1%). Pathophysiological conditions due to pancreatobiliary reflux occur in patients with high confluence of pancreaticobiliary ducts, a common channel ≥6 mm long, and occlusion of communication during contraction of the sphincter. Once the diagnosis of PBM is established, immediate prophylactic surgery is recommended. However, the surgical strategy for PBM without biliary dilatation remains controversial. To detect PBM without biliary dilatation early, MRCP is recommended for patients showing gallbladder wall thickening on screening US under suspicion of PBM.

Background: Pancreatobiliary reflux (PBR) can occur in individuals without pancreaticobiliary maljunction. The aim of this study was to elucidate the incidence of PBR in individuals with a normal pancreaticobiliary junction and its impact on the biliary tree., Methods: Data were prospectively collected from 15 centers on 420 patients with a morphologically normal pancreaticobiliary junction who had undergone bile sampling and measurement of the biliary amylase level. We investigated the incidence and predictive factors for high biliary amylase levels (HBAL), as well as the relationship of HBAL with biliary malignancy., Results: Twenty-three patients (5.5%) showed HBAL (≥10,000 IU/L). Univariate analysis showed that risk factors for the elevation of biliary amylase levels were the existence of a relatively long common channel (≥5 mm), acute pancreatitis, and papillitis. Multivariate analysis revealed that only the existence of a relatively long common channel was a significant factor for PBR. Biliary amylase levels in patients with a relatively long common channel were significantly higher than in patients without a long common channel (12,333 vs. 2,070 IU/L, P = 0.001). The incidence of HBAL (P < 0.001), as well as the overall biliary amylase levels (P = 0.007) were significantly higher in patients with gallbladder cancer than in those without gallbladder cancer., Conclusions: The PBR was frequently observed in individuals with a relatively long common channel. Patients showing HBAL with normal pancreaticobiliary junction are at high risk for gallbladder cancer.

Portal annular pancreas (PAP) is a rare anatomical anomaly in which the pancreatic parenchyma surrounds the superior mesenteric vein and portal vein (PV) annularly. This anomaly requires careful consideration in pancreatic resection. A case is presented and the technical issues are discussed. A 61-year-old female was referred to the hospital for suspected papilla Vater adenocarcinoma. Preoperative computed tomography showed that the PV was annularly surrounded by pancreatic parenchyma. Surgery revealed the uncinate process extended extensively behind the PV and fused with the pancreatic body. The pancreas was first divided above the PV, and it was divided again in the body after liberating the PV from pancreatic annulation. The postoperative course was uneventful without pancreatic fistula. It is safer to divide the pancreatic body on the left of the fusion between the uncinate process and the pancreatic body to reduce the risk of pancreatic fistula in pancreaticoduodenectomy for PAP.

The common bile duct and the main pancreatic duct open into the duodenum, where they frequently form a common channel. The sphincter of Oddi is located at the distal end of the pancreatic and bile ducts; it regulates the outflow of bile and pancreatic juice. In patients with a pancreaticobiliary maljunction, the action of the sphincter does not functionally affect the junction. Therefore, in these patients, two-way regurgitation (pancreatobiliary and biliopancreatic reflux) occurs. This results in various pathological conditions of the biliary tract and the pancreas. Biliopancreatic reflux could be confirmed by: operative or postoperative T-tube cholangiography; CT combined with drip infusion cholangiography; histological detection of gallbladder cancer cells in the main pancreatic duct; and reflux of bile on the cut surface of the pancreas. Biliopancreatic reflux occurs frequently in patients with a long common channel. Although the true prevalence, degree, and pathophysiology of biliopancreatic reflux remain unclear, biliopancreatic reflux is related to the occurrence of acute pancreatitis. Obstruction of a long common channel easily causes bile flow into the pancreas. Even if no obstruction is present, biliopancreatic reflux can still result in acute pancreatitis in some cases.

During laparoscopic cholecystectomy (LC), misidentification of the cystic duct, which causes major bile duct injuries, can result from wrong or incomplete dissection of Calot's triangle. Therefore, the critical view of safety has been accepted as a safe method for gaining a sufficient view of Calot's triangle before transecting the cystic duct. However, even in cases without aberrant anatomy of the bile duct, bile duct injury can occur by a wrong approach to a critical view of safety. Additionally, in cases of badly inflamed gallbladders, it is often hard to achieve a critical view of safety, because Calot's triangle is often solid and cannot be expanded. In our standardized procedure, which is based on exposing the inner layer of the subserosal layer (the ss-i layer), the critical view of safety can be safely achieved. We have safely performed LC, using our standardized procedure, for many cases with cholecystitis with highly inflamed gallbladders. In this article, focusing especially on prevention of bile duct injuries, we present our standardized procedure to achieve the critical view of safety along with histological findings.

Current literature suggests that early laparoscopic cholecystectomy (LC) for acute cholecystitis (AC) can be safely performed within 72 h of symptom onset. However, for various reasons, in clinical practice, fibrosed gallbladders are frequently encountered during early LC for AC. The subserosal layer of the gallbladder wall can be divided into an inner and an outer layer. The inner layer has an abundant vasculature and some fibrous tissue; it abuts the muscularis propria. The outer layer consists of abundant fat tissue; it abuts the serosa or the liver parenchyma. In both patients with AC and those without cholecystitis, dissection of the gallbladder in the outer layer facilitates removal of the gallbladder without tearing the gallbladder or injuring the liver parenchyma behind the liver bed. However, in patients with AC lasting 72 h or more, the subserosal layer becomes solid and thick due to inflammatory cell infiltration and fibrotic change. Thus, adequate dissection of the outer layer becomes difficult. However, there is a layer between the inner and outer layers that can be dissected bluntly and easily. Thus, we could dissect the gallbladder from its liver bed safely, surely, and quickly by using our original technique which was validated by histological examination.

We report on a 65-year-old man who received asynchronous bilateral adrenalectomy for adrenal metastasis of hepatocellular carcinoma. Fifteen months after curative resection of right hepatic lobe for hepatocellular carcinoma, a metastatic lesion of the left adrenal gland was detected and left adrenalectomy was performed. Ten months after the second operation, a metastatic lesion in the right adrenal gland, associated with tumor thrombus in the inferior vena cava, was revealed. Transcatheter arterial embolization of the arteries feeding the metastatic tumor was performed, but its effects were incomplete. As there was the tumor thrombus in the inferior vena cava and no other intrahepatic recurrence or extrahepatic metastasis was found, resection of the right adrenal gland with tumor thrombus, without the employment of veno-venous bypass, was performed, followed by postoperative hormonal supplementation. Changes in the patient's alpha-fetoprotein level were clinically useful for the detection of the metastatic lesions and the evaluation of therapeutic effects. Metastasis to adrenal gland from hepatocellular carcinoma should be actively managed, and the appropriate surgical treatment selected, if intrahepatic recurrence and/or other extrahepatic metastasis are controlled. To achieve higher curability and better outcome in patients with bilateral adrenal metastasis of hepatocellular carcinoma, bilateral total adrenalectomy is indicated, accompanied by effective postoperative hormonal supplementation.

The case of a 74-year-old female patient who underwent a right hepatic lobectomy for hepatocellular carcinoma (HCC) which developed in primary biliary cirrhosis (PBC) is reported herein. During a follow-up examination for Parkinson's disease, an elevation of hepatobiliary tract-related enzymes and alpha-fetoprotein was uncovered. Diagnostic imagings showed a hypervascular, solitary, and encapsulated tumor measuring about 7 cm in diameter located mainly in the posterior segment. Positive antimitochondrial and antinuclear antibodies and a preoperative liver biopsy strongly suggested well differentiated HCC developed in PBC (Scheuer's classification stage II). Since the natural prognosis of PBC estimated by the Mayo risk score was fairly good and the liver function indicated sufficient tolerance for major hepatic resection, and preoperative computed tomography (CT) volumetry showed the atrophy of the right hepatic lobe, a right hepatic lobectomy was performed. A pathological examination revealed well encapsulated, moderately differentiated HCC with, in part, well-differentiated HCC in the tumor and stage II PBC in the noncancerous region. CT volumetry performed at postoperative day 14 showed a 146% enlargement of the remnant liver. An early detection of HCC and PBC by strict screening would prevent a limitation of surgical therapy due to a deteriorated liver function.

We report a patient with cholangiocellular carcinoma with tumor thrombi in the main portal trunk who has survived for 9.5 years after hepatic resection. A 57-year-old woman underwent an extended left lobectomy, and resection of the caudate lobe plus the main portal trunk for a liver tumor that had a portal tumor thrombus in the main portal trunk. The portal vein was reconstructed with an autologous vein graft obtained from the external iliac vein. Histological examination of the resected specimen revealed moderately differentiated tubular adenocarcinoma compatible with cholangiocellular carcinoma. Factors contributing to the patient's long-term survival are discussed. Aggressive surgical resection can be effective even for such an advanced case of cholangiocellular carcinoma.