Showing papers in "Journal of Hepato-biliary-pancreatic Sciences in 2014"

A novel difficulty scoring system for laparoscopic liver resection.

Abstract: Early on, laparoscopic liver resection (LLR) was limited to partial resection, but major LLR is no longer rare. A difficulty scoring system is required to guide sur- geons in advancing from simple to highly technical laparo- scopic resections. Subjects were 90 patients who had undergone pure LLR at three medical institutions (30 patients/institution) from January 2011 to April 2014. Sur- gical difficulty was assessed by the operator using an index of 1-10 with the following divisions: 1-3 low difficulty, 4-6 intermediate difficulty, and 7-10 high difficulty. Weighted kappa statistic was used to calculate the concordance between the operators' and reviewers' (expert surgeon) dif- ficulty index. Inter-rater agreement (weighted kappa statis- tic) between the operators' and reviewers' assessments was 0.89 with the three-level difficulty index and 0.80 with the 10-level difficulty index. A 10-level difficulty index by linear modeling based on clinical information revealed a weighted kappa statistic of 0.72 and that scored by the extent of liver resection, tumor location, tumor size, liver function, and tumor proximity to major vessels revealed a weighted kappa statistic of 0.68.We proposed a new scoring system to predict difficulty of various LLRs preoperatively. The calculated score well reflected difficulty.

Multicenter retrospective study of endoscopic ultrasound-guided biliary drainage for malignant biliary obstruction in Japan.

Abstract: Background Endoscopic ultrasound-guided biliary drainage (EUS-BD) is considered to be an effective salvage procedure for failed endoscopic retrograde cholangiopancreatography in patients with unresectable malignant biliary obstruction. The aim of this retrospective study was to evaluate the efficacy and feasibility of EUS-BD. Methods From November 2006 to May 2012, a total of 64 patients who underwent EUS-BD (44 EUS-guided choledochoduodenostomy [EUS-CDS] and 20 EUS-guided hepaticogastrostomy [EUS-HGS]) at seven tertiary-care referral centers in Japan were included. The primary outcome was the technical success rate, and the secondary outcomes were the incidence of complications, stent dysfunction rate, time to stent dysfunction, and overall survival. Results The technical success rate for both EUS-CDS and EUS-HGS was 95%. The reasons for technical failure were two failed dilations of the anastomosis in EUS-CDS and one puncture failure in EUS-HGS. The stent dysfunction rate and 3-month dysfunction-free patency rate were 21% and 80% for EUS-CDS and 32% and 51% for EUS-HGS. There were 12 (six in EUS-CDS and six in EUS-HGS) procedure-related complications (19%): five cases of bile leakage (3/2), three stent misplacements (1/2), one pneumoperitoneum (1/0), two cases of bleeding (1/1), one perforation (1/0), and one biloma (0/1). Bile leakage was more frequently observed in patients who underwent plastic stent placement (11%) than in those with covered metal stents (4%). Conclusions This Japanese multicenter study revealed a high success rate in EUS-BD. However, the complication rate was as high as that in previous series. Covered metal stents may be useful to reduce bile leakage in EUS-BD.

Roles of liver fluke infection as risk factor for cholangiocarcinoma.

Abstract: Several factors are known to be associated with risk of cholangiocarcinoma (CCA) and infection with the liver flukes, Opisthorchis viverrini and Clonorchis sinensis, has often been singled out as the leading risk factor in east and southeast Asia. In this review, current knowledge of their biology, life cycle, and pathogenesis of O. viverrini, and its role as a carcinogenic parasite are presented. The trends of age-specific incidence of liver cancer in Khon Kaen, northeast Thailand are considered and compared with the prevalence profiles of O. viverrini. Potential impacts of the liver fluke control program particularly by mass drug administration (MDA) and public health education in the past and a recent drop of incidence of CCA are discussed in relation to primary prevention and control of this fatal bile duct cancer.

International experience for laparoscopic major liver resection.

Abstract: Although minor laparoscopic liver resections (LLRs) appear as standardized procedures, major LLRs are still limited to few expert teams. The aim of this study was to report the combined data of 18 international centers performing major LLR. Variables evaluated were number and type of LLR, surgical indications, number of synchronous colorectal resections, details on technical points, conversion rates, operative time, blood loss and surgical margins. From 1996 to 2014, a total of 5388 LLR were carried out including 1184 major LLRs. The most frequent indication for laparoscopic right hepatectomy (LRH) was colorectal liver metastases (37.0%). Seven centers used hand assistance or hybrid approach selectively for LRH mostly at the beginning of their experience. Seven centers apply Pringle's maneuver routinely. The conversion rate for all major LLRs was 10% and mean operative time was 291 min. Mean estimated blood loss for all major LLR was 327 ml and negative surgical margin rate was 96.5%. Major LLRs still remain challenging procedures requiring important experience in both laparoscopy and liver surgery. Stimulating the younger generation to learn and accomplish these techniques is the better way to guarantee further development of this surgical field.

Laparoscopic hepatectomy is theoretically better than open hepatectomy: preparing for the 2nd International Consensus Conference on Laparoscopic Liver Resection.

Abstract: Six years have passed since the first International Consensus Conference on Laparoscopic Liver Resection was held. This comparatively new surgical technique has evolved since then and is rapidly being adopted worldwide. We compared the theoretical differences between open and laparoscopic liver resection, using right hepatectomy as an example. We also searched the Cochrane Library using the keyword "laparoscopic liver resection." The papers retrieved through the search were reviewed, categorized, and applied to the clinical questions that will be discussed at the 2nd Consensus Conference. The laparoscopic hepatectomy procedure is more difficult to master than the open hepatectomy procedure because of the movement restrictions imposed upon us when we operate from outside the body cavity. However, good visibility of the operative field around the liver, which is located beneath the costal arch, and the magnifying provide for neat transection of the hepatic parenchyma. Another theoretical advantage is that pneumoperitoneum pressure reduces hemorrhage from the hepatic vein. The literature search turned up 67 papers, 23 of which we excluded, leaving only 44. Two randomized controlled trials (RCTs) are underway, but their results are yet to be published. Most of the studies (n = 15) concerned short-term results, with some addressing long-term results (n = 7), cost (n = 6), energy devices (n = 4), and so on. Laparoscopic hepatectomy is theoretically superior to open hepatectomy in terms of good visibility of the operative field due to the magnifying effect and reduced hemorrhage from the hepatic vein due to pneumoperitoneum pressure. However, there is as yet no evidence from previous studies to back this up in terms of short-term and long-term results. The 2nd International Consensus Conference on Laparoscopic Liver Resection will arrive at a consensus on the basis of the best available evidence, with video presentations focusing on surgical techniques and the publication of guidelines for the standardization of procedures based on the experience of experts.

Clinicopathological features and prognosis of mucin-producing bile duct tumor and mucinous cystic tumor of the liver: a multi-institutional study by the Japan Biliary Association

Abstract: Background The aim of this study was to determine the clinicopathological features and surgical outcomes of mucinous cystic neoplasm of the liver (MCN) and mucin-producing intraductal papillary neoplasm of the intrahepatic bile duct (M-IPNB). Methods We performed a multi-institutional, retrospective study of patients with MCN or M-IPNB pathologically defined by the presence or absence of an ovarian-like stroma. Results The M-IPNB and MCN were diagnosed in 119 and nine patients, respectively. MCN was observed in female patients, while M-IPNB produced symptoms of cholangitis. M-IPNBs were classed as low or intermediate grade in 53 cases, high grade in 23 and invasive carcinoma in 43. Fifty-one of the M-IPNBs were the pancreatobiliary type (PT), 33 were the intestinal type (IT), 23 were the oncocytic type (OT), and 12 were the gastric type (GT). The 1-, 5- and 10-year survival rates for the 105 patients with M-IPNB were 96%, 84% and 81%, respectively, while the 5-year survival rate for patients with MCN was 100%. OT and GT M-IPNB had better 10-year survival rates than PT and IT M-IPNB. Conclusions Although MCN has different features from M-IPNB, both diseases have a good prognosis after resection. The cellular type of M-IPNB appears to predict outcome.

Nationwide survey for primary sclerosing cholangitis and IgG4-related sclerosing cholangitis in Japan

Abstract: Background We previously conducted nationwide surveys for primary sclerosing cholangitis (PSC) in Japan, and demonstrated several characteristic features of Japanese PSC patients, yet patients with IgG4-related sclerosing cholangitis (IgG4-SC) might be misdiagnosed as PSC. Since the clinical diagnostic criteria of IgG4-SC were established in 2012, we again conducted a nationwide survey to investigate the characteristics of PSC and IgG4-SC lacking pancreatic involvement. Methods The design was a questionnaire-based, multi-center retrospective study. The enrolled subjects were patients with PSC and IgG4-SC without pancreatic involvement diagnosed after 2005. Results We enrolled 197 PSC and 43 IgG4-SC patients without pancreatic lesions. The male dominance was significantly evident in IgG4-SC (P = 0.006). In patients with PSC, two peaks in age distribution were clearly observed. IgG4-SC was not detected in any patient younger than 45 years of age. At presentation, serum albumin and IgM were significantly higher in PSC, while serum IgG and IgG4 were significantly elevated in IgG4-SC. Inflammatory bowel disease (IBD) was detected in only 68/197 PSC patients (34%). The prognosis of IgG4-SC was considerably better than that of PSC. Conclusion We confirmed several interesting clinical details of PSC in Japanese patients: two peaks in the age distribution and lower prevalence of IBD.

Case series of 17 patients with cholangiocarcinoma among young adult workers of a printing company in Japan

Abstract: Background An outbreak of cholangiocarcinoma occurred among workers in the offset color proof-printing department at a printing company in Japan. The aim of this study was to clarify the characteristics of the patients with cholangiocarcinoma. Methods This was a retrospective study conducted in 13 Japanese hospitals between 1996 to 2013. The clinicopathological findings of cholangiocarcinoma developed in 17 of 111 former or current workers in the department were investigated. Most workers were relatively young. Results The cholangiocarcinoma was diagnosed at 25–45 years old. They were exposed to chemicals, including dichloromethane and 1,2-dichloropropane. The serum γ-glutamyl transpeptidase activity was elevated in all patients. Dilated intrahepatic bile ducts without tumor-induced obstruction were observed in five patients. The cholangiocarcinomas arose from the large bile ducts. The precancerous or early cancerous lesions, such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile ducts, as well as non-specific bile duct injuries, such as fibrosis, were observed in various sites of the bile ducts in all eight patients for whom operative specimens were available. Conclusions The present results showed that cholangiocarcinomas occurred at a high incidence in relatively young workers of a printing company, who were exposed to chemicals including chlorinated organic solvents.

Volume analyzer SYNAPSE VINCENT for liver analysis

Abstract: In recent years, there has been an active movement to ensure the greater safety of actual surgeries, by simulating it preoperatively with the use of three-dimensional image visualization technologies. Along with this movement, the Ministry of Health, Labour and Welfare has named "Image-supported navigation in hepatectomy" as part of advanced medical techniques. This method aims to improve the safety during a surgery by calculating the volume of the liver dominated by each blood vessel or simulating, prior to surgery, the volume of resection zone or the remaining liver volume. These calculations and simulations are carried out using the three-dimensional images produced by extractions of the liver, vascular and tumor regions from the computed tomography images, which were collected using the tomography apparatus prior to hepatectomy. In order to facilitate the achievement of such preoperative simulations, the volume analyzer SYNAPSE VINCENT (VINCENT, hereafter) by Fujifilm, in its Liver Analysis Application, comes equipped with unique features. This paper will introduce the technologies behind those unique features and provide a direction for future research and developments.

Diagnostic criteria for pancreaticobiliary maljunction 2013.

Abstract: Pancreaticobiliary maljunction is a congenital malformation in which the pancreatic and bile ducts join anatomically outside the duodenal wall. The diagnostic criteria for pancreaticobiliary maljunction were proposed in 1987. The committee of The Japanese Study Group on Pancreaticobiliary Maljunction (JSGPM) for diagnostic criteria for pancreaticobiliary maljunction began to revise the diagnostic criteria from 2011 taking recently advanced diagnostic imaging techniques into consideration, and the final revised version was approved in the 36(th) Annual Meeting of JSPBM. For diagnosis of pancreaticobiliary maljunction, an abnormally long common channel and/or an abnormal union between the pancreatic and bile ducts must be evident on direct cholangiography, such as endoscopic retrograde cholangiopancreatography, percutaneous transpehatic cholangiography, or intraoperative cholangiography; magnetic resonance cholangiopancreatography; or three-dimensional drip infusion cholangiography computed tomography. However, in cases with a relatively short common channel, it is necessary to confirm that the effect of the papillary sphincter does not extend to the junction by direct cholangiography. Pancreaticobiliary maljunction can be diagnosed also by endoscopic ultrasonography or multi-planar reconstruction images provided by multi-detector row computed tomography. Elevated amylase levels in bile and extrahepatic bile duct dilatation strongly suggest the existence of pancreaticobiliary maljunction.

Oncological benefit of preoperative endoscopic biliary drainage in patients with hilar cholangiocarcinoma.

Abstract: Due to advances in endoscopic equipment and techniques, preoperative endoscopic biliary drainage (EBD) has been developed to serve as an alternative to percutaneous transhepatic biliary drainage (PTBD). This study sought to clarify the benefit of EBD in comparison to PTBD in patients who underwent radical resections of hilar cholangiocarcinoma. One hundred and forty-one patients underwent radical surgery for hilar cholangiocarcinoma between 2000 and 2008 were retrospectively divided into two groups based on the type of preoperative biliary drainage, PTBD (n = 67) or EBD (n = 74). We investigated if the different biliary drainage methods affected postoperative survival and mode of recurrence after median observation period of 82 months. The survival rate for patients who underwent EBD was significantly higher than those who had PTBD (P = 0.004). Multivariate analysis revealed that PTBD was one of the independent factors predictive of poor survival (hazard ratio: 2.075, P = 0.003). Patients with PTBD more frequently developed peritoneal seeding in comparison to those who underwent EBD (P = 0.0003). PTBD was the only independent factor predictive of peritoneal seeding. In conclusion, EBD might confer an improved prognosis over PTBD due to prevention of peritoneal seeding, and is recommended as the initial procedure for preoperative biliary drainage in patients with hilar cholangiocarcinoma.

Comparison of inflammation-based prognostic scores as predictors of tumor recurrence in patients with hepatocellular carcinoma after curative resection.

Abstract: Background Various inflammation-based prognostic scores, including the Glasgow prognostic score (GPS), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), prognostic index (PI), and prognostic nutritional index (PNI), have been associated with survival in patients with several types of cancer. This study compared the ability of these scores to predict recurrence-free survival (RFS) in patients with hepatocellular carcinoma (HCC) after curative hepatectomy. Methods Data were collected prospectively from 113 patients who underwent curative resection for HCC from January 2003 to December 2012. Clinicopathological variables including preoperative inflammation-based prognostic scores were analyzed. Univariate and multivariate analyses were performed to identify factors predictive of RFS. Results Univariate analysis showed that NLR (P < 0.0001) and PI (P = 0.0194) were significantly associated with RFS. Multivariate analysis showed that NLR (hazard ratio [HR]; 2.58, P = 0.0020), tumor differentiation (HR; 9.55, P < 0.0001), serosal invasion (HR; 2.24, P = 0.0112), and vascular invasion (HR; 2.18, P = 0.0106) were independently correlated with RFS. Conclusions Preoperative NLR is an independent predictor of RFS in patients with HCC after curative hepatectomy, and is superior to the other inflammation-based prognostic scores.

Molecular mechanism of cholangiocarcinoma carcinogenesis.

Abstract: Cholangiocarcinoma (CCA) is a highly malignant cancer of the biliary tract with a poor prognosis, which often arises from conditions causing long-term inflammation, injury, and reparative biliary epithelial cell proliferation. Several conditions are known to be major risk factors for cancer in the biliary tract or gallbladder, including primary sclerosing cholangitis, liver fluke infection, pancreaticobiliary maljunction, and chemical exposure in proof-printing workers. Abnormalities in various signaling cascades, molecules, and genetic mutations are involved in the pathogenesis of CCA. CCA is characterized by a series of highly recurrent mutations in genes, including KRAS, BRF, TP53, Smad, and p16(INK4a) . Cytokines that are affected by inflammatory environmental conditions, such as interleukin-6 (IL-6), transforming growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α), and platelet-derived growth factor (PDGF), play an important role in cancer pathogenesis. Prominent signaling pathways important in carcinogenesis include TGF-β/Smad, IL-6/STAT-3, PI3K/AKT, Wnt, RAF/MEK/MAPK, and Notch. Additionally, some microRNAs regulate targets in critical pathways of CCA development and progression. This review article provides the understanding of the genetic and epigenetic mechanism(s) of carcinogenesis in CCA, which leads to the development of new therapeutic targets for the prevention and treatment of this devastating cancer.

Circulating miR-192 in liver fluke-associated cholangiocarcinoma patients: a prospective prognostic indicator.

Abstract: Background This study aimed to investigate the miR-192 levels in patients' sera of liver fluke-associated cholangiocarcinoma (CCA) for a prospective prognostic indicator. Methods MicroRNA polymerase chain reaction (PCR) array was performed using pooled serum samples from 11 CCA patients and nine healthy subjects. Selected miRNAs were verified for the differential levels in both sera and tumor tissues (of patients and Opisthorchis viverrini (Ov)-induced CCA model) using TaqMan miRNA expression assay. Results Our results demonstrated that miR-192 was significantly higher in the serum of CCA patients than that in healthy subjects giving a sensitivity of 74% and specificity of 72% (area under the curve [AUC] = 0.803; 95% confidence interval [CI], 0.708–0.897, P < 0.0001). Serum miR-192 examined in Ov infected subjects and subjects with periductal fibrosis were increased but not statistically significantly when compared with healthy subjects. High levels of serum miR-192 were significantly correlated with lymph node metastasis (P = 0.047) and shorter survival compared with individuals with low levels of serum miR-192 (hazard ratio [HR] 2.076, 95% CI 1.004–4.291, P = 0.049). We also found that the expression levels of miR-192 appeared to be elevated in both CCA tissues of patients and in Ov-induced CCA tissues of a hamster model. Conclusions This finding indicates that elevated levels of miR-192 may be involved in CCA genesis and have a potential utility as a noninvasive prognostic indicator for CCA patients.

Role of Intercostal Trocars on Laparoscopic Liver Resection for Tumors in Segments 7 and 8

Abstract: Performing laparoscopic liver resection for lesions located in segment 7 and 8 is technically difficult, as the operative field is far from the conventional trocar site, and the liver impedes free motion of the laparoscopic instru- ment. Inserting the port through the intercostal space (ICS) may facilitate liver resection for these lesions. From January 2012 to July 2013, five patients (four men and one woman) underwent laparoscopic S7 or 8 segmentectomy for liver metastasis and hepatocellular carcinoma (HCC). Ports were inserted at the 7th and 9th ICS, respectively, in addition to conventional abdominal ports. The mean age was 58 ± 10 (45-74) years; operation time, 197 ± 68 (110-300) minutes; blood loss, 161 ± 138 (40-320) ml; and length of hospital stay, 7 ± 3 (4-12) days. Pathologic findings revealed three, one, and one case(s) of colon cancer metastasis, breast cancer metastasis, and HCC, respectively. The mean tumor size and tumor-free margin were 2.2 ± 1.1 cm and 5.8 ± 1.9 mm, respectively. There were no postoperative compli- cations. Laparoscopic liver resection using intercostal trocars could be a useful method for tumors located in segments 7 and 8 of the liver in selected patients.

Hepatolithiasis: analysis of Japanese nationwide surveys over a period of 40 years

Abstract: The aims of the present study are to clarify the changes in clinicopathologic features, diagnosis and treatment for hepatolithiasis, and propose an appropriate management strategy in Japan. The research group conducted nationwide surveys seven times in the past over a period of 40 years. Furthermore, a cohort was followed up in 2010. We analyzed the clinical features, diagnosis tools, treatment procedures, outcomes, and predictive factors for cholangiocarcinoma. Surgery was the primary method for hepatolithiasis up to 1998, and the frequency of its use has decreased since then. In 2011, 66.7% of hepatolithiasis patients were treated using nonsurgical approaches. In addition, endoscopic retrograde cholangiography (ERC) with stone extraction was the most frequently performed procedure (22.7%). However, the incidences of residual stone and recurrent stone after ERC with stone extraction were higher than those after percutaneous transhepatic cholangioscopic lithotomy and surgery. Bile duct stricture and dilatation during follow up were significant risk factors for stone recurrences. In the cohort study, stone removal only and age >65 years were significant factors for the development of cholangiocarcinoma. In patients without a history of cholangioenterostomy, left-lobe-type stones were a risk factor, and hepatectomy reduced the risk of the development of cholangiocarcinoma significantly. Nonsurgical treatment may be performed as the first-line treatment for hepatolithiasis. Surgery should be performed on patients who were treated incompletely after nonsurgical treatment. However, hepatectomy may be recommended for patients with left-lobe-type stones and without a history of cholangioenterostomy.

International Survey on Technical Aspects of Laparoscopic Liver resection: a web‐based study on the global diffusion of laparoscopic liver surgery prior to the 2nd International Consensus Conference on Laparoscopic Liver Resection in Iwate, Japan

Abstract: The technique of laparoscopic liver resection (LLR) has been greatly improved since the first international consensus conference. Our aim was to evaluate the worldwide spread of LLR prior to the 2nd International Consensus Conference on Laparoscopic Liver Resection in Iwate, Japan (4-6 October 2014). The International Survey on Technical Aspects of Laparoscopic Liver resection was designed to assess dissemination of LLR, indications, and the surgical techniques. The anonymous questionnaire was e-mailed to liver surgeons worldwide. A total of 448 liver surgeons responded to the survey. The peak age range of surgeons performing LLR was 41-50 years. Japan had by far the largest number of respondents (n = 223), followed by the US (n = 38) and France (n = 20). In Japan, the majority of surgeons performing LLR belonged to community hospitals, where LLR has been increasingly used since its implementation in 2009 or later, comprising up to 40% of all liver resection cases. In contrast, in North America and Europe, LLR was mostly performed at academic medical centers. LLR has undergone global dissemination after the first international consensus conference in 2008. Japan has experienced unparalleled, explosive diffusion characterized by the adoption of LLR at middle-tier, regional institutions.

Endoscopic ultrasonography-guided transhepatic antegrade stone removal in patients with surgically altered anatomy: case series and technical review (with videos).

Abstract: Recently, endoscopic ultrasonography (EUS)-guided transhepatic antegrade interventions have been introduced in patients with a surgically altered anatomy. Herein, we focused on and reviewed EUS-guided transhepatic antegrade stone removal (EUS-TASR) in patients with a surgically altered anatomy and native papilla. The basic technique of EUS-TASR involves the following steps: (1) EUS-guided needle puncture; (2) guidewire placement; (3) tract dilation; (4) balloon sphincteroplasty; (5) stone removal; and (6) stent placement if needed. Based on reports in the literature including our cases, the complete stone extraction rate is 71.4% (10/14) including five of our cases (60% success rate) at one session without serious complications. In conclusion, EUS-TASR appears to be feasible and useful in selected patients although its application may be limited depending on anatomical factors and current devices used.

Proposal of a new staging system for mass-forming intrahepatic cholangiocarcinoma: a multicenter analysis by the Study Group for Hepatic Surgery of the Japanese Society of Hepato-Biliary-Pancreatic Surgery

Abstract: Background Recently, the Liver Cancer Study Group of Japan (LCSGJ) staging system for intrahepatic cholangiocarcinoma (ICC) was followed by a proposal of the American Committee on Cancer (AJCC)/International Union Against Cancer (UICC) system. The present study aimed to assess the accuracy of both systems to predict survival after curative resection for mass-forming ICC and to establish a new staging system based on survival analysis results. The present study was conducted as a project study of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. Methods Clinical data from 233 patients who underwent curative resection for mass-forming ICC were retrospectively reviewed. Survival analysis was performed to identify predictors of postoperative outcomes, and a new staging system was established. The survival stratification of our proposed system was compared with two previous staging systems. Results A N0M0 cohort analysis demonstrated that tumor size, tumor number, and vascular invasion were independently associated with survival after curative resection for mass-forming ICC, whereas serosal and periductal invasion were not. Of patients with nodal metastases, patients with T4 tumor had significantly lower overall survival rate than patients with T1, T2, or T3 tumor. Thus, we proposed a new staging system as follows: serosal invasion was excluded from the LCSGJ T categories, and patients with nodal metastases were divided into stage IVA or IVB according to T classification. The new system better stratified survival after curative resection for mass-forming ICC than the two previous systems. Conclusions The AJCC/UICC staging system failed to stratify the Japanese patients with mass-forming ICC. The new staging system provided better survival prediction in the patients who underwent curative resection for mass-forming ICC, although further studies are necessary to evaluate the impact of tumor size on survival.

Histological confirmation of periductal fibrosis from ultrasound diagnosis in cholangiocarcinoma patients.

Abstract: Cholangiocarcinoma (CCA) has no specific clinical signs and symptoms and non-specific bio- and tumor-markers in the early disease stage. Usually patients present to tertiary care with advanced disease stage. In order to detect early cases of CCA that may present as a mass, dilatation of intrahepatic duct or combination, ultrasonography is accepted as a powerful imaging tool. A smaller mass or bile duct segmental dilatation requires further imaging for characterization, including computerized tomography (CT) or magnetic resonance imaging (MRI). We examined whether liver echo pattern was correlated with high risk for CCA in an endemic area of Opisthorchis viverrini (Ov). Ov infestation caused chronic inflammation of the biliary tree by periductal fibrosis (PDF), which may subsequently lead to CCA development. In our study, a World Health Organization classification of pattern of increased periportal echo (IPE) for schistosomiasis was applied. Two CCA patients gave consent for operation. Histopathological diagnosis showed both had cholangiocarcinoma with periductal fibrosis of the non-tumorous area of the liver. Ultrasonography was used to compare the non-tumorous area with parenchymal echo pattern and was shown to have an early CCA detection role and a surveillance role in an endemic area of Ov by detection of PDF.

Peroral pancreatoscopy using the SpyGlass system for the assessment of intraductal papillary mucinous neoplasm of the pancreas.

Abstract: Background Peroral pancreatoscopy (POPS) using a mother–baby endoscope system is often useful for assessment of intraductal papillary mucinous neoplasm (IPMN) of the pancreas with main pancreatic duct (MPD) involvement, but is not widely used for several reasons. The aim of this study was to evaluate the usefulness of the SpyGlass Direct Visualization System for assessment of IPMN. Methods Seventeen patients diagnosed with possible IPMN with MPD dilation underwent peroral pancreatoscopy using the SpyGlass system at our institution. The quality of visualization and the sensitivities of cytological and pathological investigations for diagnosing malignant lesions were evaluated. Results Peroral pancreatoscopy was performed using the SpyScope in 12 patients and an endoscopic retrograde cholangiopancreatography (ERCP) catheter in five patients. Sufficient visualization was achieved in 92% of cases using the SpyScope and 40% of cases using the ERCP catheter. Biopsy under direct visualization was successful in seven patients. Biopsy specimens showed adenocarcinoma in one patient, benign neoplastic epithelium in five patients, and regenerative changes in one patient; and had 25% sensitivity and 100% specificity for detecting malignancy. SpyGlass pancreatoscopy with irrigation cytology had 100% sensitivity and 100% specificity for detecting malignancy. SpyGlass pancreatoscopy was useful for determining the operative excision line in three patients. There were no severe procedure-related adverse events. Conclusions Peroral pancreatoscopy using the SpyGlass system seems to be feasible and useful for assessment of IPMN with a dilated MPD.

Analysis of risk factors for recurrence after curative resection of well-differentiated pancreatic neuroendocrine tumors based on the new grading classification

Abstract: Background It is difficult to predict the malignant potential of pancreatic neuroendocrine tumors (PNETs) precisely. This study investigated the validity of a new grading system adopted by the World Health Organization 2010 classification to determine risk factors for recurrence of PNETs. Methods Data of 70 patients with PNETs who underwent curative resection were retrospectively examined by uni- and multivariate analyses. Histopathological findings were re-reviewed by experienced pathologists. NET G1 was defined as mitotic count <2 per 10 high power fields (HPF) and/or ≤2% Ki67 index, and NET G2 as 2–20 mitosis per 10 HPF and/or 3–20% Ki67 index. Results There were 58 patients with NET G1 and 12 with NET G2. Incidence of recurrence was 11.4%. Univariate analysis demonstrated significant risk factors for recurrence including NET G2 of histological grade (P = 0.0089), male gender (P = 0.0333), tumor size ≥ 20 mm (P = 0.0117), lymph node metastasis (P = 0.0004), liver metastasis (P < 0.0001), lymphatic invasion (P = 0.046), and neural invasion (P = 0.0002). By multivariate analysis, histological grade (hazard ratio; 59.76, P = 0.0022) and neural invasion (hazard ratio; 147.49, P = 0.0016) were significantly associated with recurrence of PNETs. Conclusions This study confirmed the prognostic relevance of the new grading classification and that evaluation of perineural invasion and histological grade should be considered as prognostic predictors in well-differentiated PNETs (NET G1 and G2).

Indications for portal vein embolization in perihilar cholangiocarcinoma.

Abstract: Preoperative portal vein embolization (PVE) is often performed as a routine procedure before extended hepatectomy to minimize postoperative liver failure. However, the indications for PVE in perihilar cholangiocarcinoma (PCCA), which differ between institutions, remain controversial. In the present study, we examined the indications for PVE in patients with PCCA. A comprehensive meta-analysis of PVE was performed using the PubMed, Medline, and Cochrane databases. The present study, which included 3033 patients (45 publications), compared the results of 836 cases in the PCCA group and 2197 cases in the other hepatic tumor (OHT) group. In the PCCA group, percent future remnant liver (%FRL) and ratio of %FRL to indocyanine green (ICG) were used as criteria in 71% and 25% of cases, respectively, and a %FRL < 40% was used as indication for PVE in 90% of cases. The rates of resection of the bile duct, simultaneous pancreaticoduodenectomy, and reconstruction of the portal vein and hepatic artery were high in the PCCA group (P < 0.001). Mortality after hepatectomy was 3.7% in the PCCA group and 1.9% in the OHT group (P < 0.001). The indication for PVE in PCCA patients is %FRL < 40% in many institutions. The indications for PVE in PCCA patients should be distinguished from those in other hepatic tumors because of the complex surgery required for PCCA.

Comparison of the BISAP scores for predicting the severity of acute pancreatitis in Chinese patients according to the latest Atlanta classification

Abstract: Background The bedside index of severity in acute pancreatitis (BISAP) is a new, convenient, prognostic multifactor scoring system. As there were no studies designed to validate this system according to the latest Atlanta classification in China and more data are needed before clinical application, we compared BISAP, the Acute Physiology and Chronic Health Evaluation (APACHE) II and Ranson scoring systems in predicting the severity, pancreatic necrosis and mortality of acute pancreatitis (AP) using the latest 2012 Atlanta classification in a tertiary care center in China. Methods The medical records of all patients with AP admitted to our hospitals between January 2010 and June 2013 were reviewed retrospectively. Severe AP was defined as the persistence of organ failure for more than 48 h. The capacity of the BISAP, APACHE II and Ranson's score system to predict severity, pancreatic necrosis and mortality was evaluated using linear-by-linear association. The predictive accuracy of the BISAP, APACHE II and Ranson's score was measured as the area under the receiver operating characteristic curve (AUC). Results Of 155 patients enrolled in the study, 16.7% were classified as having severe AP, and six (3.2%) died. There were statistically significant trends for increasing severity (P < 0.001), PNec (P < 0.001) and mortality (P < 0.001) with increasing BISAP. The AUC for severity predicted by BISAP was 0.793 (95% confidence interval [CI] 0.700–0.886), APACHE II 0.836 (95% CI 0.744–0.928) and by Ranson score was 0.903 (95% CI 0.814–0.992). The AUC for PNec predicted by BISAP was 0.834 (95% CI 0.739–0.929), APACHE II 0.801 (95% CI 0.691–0.910) and by Ranson score was 0.840 (95% CI 0.741–0.939). The AUC for mortality predicted by BISAP was 0.791 (95% CI 0.593–0.989), APACHE II 0.812 (95% CI 0.717–0.906) and by Ranson score was 0.904 (95% CI 0.829–0.979). Conclusions BISAP score may be a valuable source for risk stratification and prognostic prediction in Chinese patients with AP. A prospective and multicenter validation study is required to confirm our results and further our recognition of BISAP scores in AP.

Hypoxia inducible factor-1 alpha plays a pivotal role in hepatic metastasis of pancreatic cancer: an immunohistochemical study

Abstract: Background Hypoxia is an important condition to promote angiogenesis that is essential to tumor progression, including pancreatic ductal adenocarcinoma (PDAC). We evaluated whether the immunohistochemistry for hypoxia inducible factor-1α (HIF-1α) was correlated with hepatic metastases in PDAC. Methods We examined the expression of HIF-1α, vascular endothelial growth factor-A (VEGF-A), thymidine phosphorylase (TP) and basic fibroblast growth factor (bFGF) in a total of 100 paraffin-embedded PDAC primary tumors using immunohistochemical staining, and assessed their clinicopathologicalcorrelations.Wedeterminedmicrovessel count (MVC) and apoptotic index (AI), and assessed their correlations with hepatic metastases. Student’s t-test, the Mann‐Whitney U-test, and Spearman correlation coefficients were used to validate the model, and regression analysis was used to test the model. Results Hypoxia inducible factor-1α expression induced the expression of multiple angiogenic factors, leading to a higher MVC and a lower AI. HIF-1α expression (P = 0.0087) and angiogenic factors (P = 0.0079) were significantly associated with not only the microvessel status (P = 0.022) but also the high incidence of hepatic metastasis (P = 0.02), resulting in the worse survival of PDAC patients (P < 0.05). Conclusions Hypoxia inducible factor-1α plays a pivotal role in hepatic metastasis through its association with the expression of angiogenic factors in PDAC patients. These results may contribute future therapeutic strategies to prevent pancreatic cancer metastasis.

Lymph node dissection for intrahepatic cholangiocarcinoma: a critical review of the literature to date.

Abstract: Definite policy or evidence in regards to the lymph node dissection (LND) for intrahepatic cholangiocarcinoma (ICC) does not exist at present. We review and summarize the current knowledge about LND for ICC in reference to the literature to date. A Pubmed search was done to find the relevant literature. Only English literature from 2000 to 2013 was retrieved, using key words "intrahepatic cholangiocarcinoma" and "lymph node". In all selected articles, those which included a description of the difference in the survival results between the presence of lymph node metastasis (LNM), execution rate of LND, or institutional policy for LND were included in this review. In all reviewed articles, survival results of the LNM-positive group, evaluated by the 5-year survival rate, median survival time, or recurrence-free survival time were clearly worse than the LNM-negative group. However, the execution rate of LND was not often assessed, and therefore precise evaluation for the efficacy of LND is still controversial. Randomized controlled trials under the definite LND policy should be conducted to obtain precise survival results and clinical evaluation criteria for LND.

Review of hepatopancreatoduodenectomy for biliary cancer: an extended radical approach of Japanese origin.

Abstract: Cholangiocarcinomas exhibit various modes of local extension, and some tumors can only be completely resected by hepatopancreatoduodenectomy (HPD), which is defined as the resection of the whole extrahepatic biliary system with the adjacent liver and pancreatoduodenum. Since Takasaki et al. introduced HPD for locally advanced gallbladder cancer in 1980, Japanese hepatobiliary surgeons have aggressively challenged this extended procedure for advanced biliary tumors. Early experiences with HPD were frequently associated with liver failure and sequential mortality, leading to an underestimation of the survival benefit of HPD. However, with improvements in surgical techniques and perioperative patient care, including portal vein embolization, over the last two decades, the mortality rate after HPD has gradually decreased. Recent studies have demonstrated a favorable survival in cholangiocarcinoma, provided that R0 resection is achieved. In contrast, HPD for gallbladder cancer remains controversial because of the extremely poor survival, although the study populations have been limited. HPD can be performed with low mortality and offers a better probability of long-term survival in patients with cholangiocarcinoma. We should consider HPD to be a standard approach for laterally advanced cholangiocarcinomas that are otherwise unresectable.

Histological features of precancerous and early cancerous lesions of biliary tract carcinoma

Abstract: Biliary tract carcinoma develops within the intrahepatic or extrahepatic biliary tree and gallbladder. Primary sclerosing cholangitis, hepatolithiasis, congenital choledochal cyst, liver fluke infection, pancreatobiliary maljunction, toxic exposures and hepatitis virus infection are risk factors for the development of human biliary carcinoma. The precise molecular abnormalities of biliary carcinogenesis are still unknown, but chronic inflammatory conditions induce the production of reactive oxygen or nitrogen species leading to DNA damage. Recent studies indicate that cholangiocarcinoma of the large bile duct may arise in premalignant lesions such as biliary intraepithelial neoplasm (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB). BilIN and IPNB are generally confined to the large and septal-sized bile duct. BilINs are occasionally observed in non-biliary liver cirrhosis as well as chronic biliary disease. In contrast, the precursor lesion of intrahepatic cholangiocarcinoma of the small bile duct type remains unclear. We herein demonstrated the histological characteristics of different tumor development pathways from premalignant lesion to carcinoma in different sites of the biliary tree.

Systematic review and meta-analysis of minimally invasive techniques for the management of cholecysto-choledocholithiasis.

Abstract: Background The optimal management of patients with symptomatic gallstones and possible or proven common bile duct (CBD) stones and gallstones is still evolving. Today a number of options exist: preoperative endoscopic retrograde cholangiopancreatography (pre-op ERCP), laparoscopic cholecystectomy (LC) combined with intraoperative endoscopic sphincterotomy (IOES), laparoscopic common bile duct exploration (LCBDE) and postoperative ERCP (post-op ERCP). This meta-analysis was done to compare these management options and determine if any single option was clearly superior. Methods A systematic search was conducted using several electronic databases. The search revealed 15 randomized controlled trials (RCTs). Six comparing pre-op ERCP with LCBDE, five comparing pre-op ERCP with IOES, two comparing IOES with LCBDE and two comparing post-op ERCP with LCBDE, comprising a total of 1992 patients. Results The pre-op ERCP group had a significantly higher incidence of ERCP related complications (odds ratio: 2.40, 95% confidence interval: 1.21–4.75). Conclusions The evidence provided by this meta-analysis suggests that both of these approaches would appear comparable. To fully address which would be the better approach would require an RCT as discussed above.

Tips for anatomical hepatectomy for hepatocellular carcinoma by the Glissonean pedicle approach (with videos)

Abstract: Couinaud described three fundamental approaches at the hepatic hilus in liver surgery. The Glissonean pedicle approach at the hepatic hilus is one of these procedures and provides anatomical hepatectomy for hepatocellular carcinoma (HCC). The Glissonean pedicle approach was introduced by Couinaud and Takasaki in the early 1980s. The key of the Glissonean pedicle approach is clamping the pedicle first, secondly confirming the territory, which includes the HCC, and finally dissecting the liver parenchyma. This procedure prevents intrahepatic metastasis of HCC, which spreads along the portal vein and improves the overall survival after surgery. Another key feature is that we do not have to consider any variations of the vascular elements in the hepatoduodenal ligament under the hilar plate. This procedure allows an approach to the tertiary branches, which feed a smaller anatomical area than Couinaud's segment. We refer to this area as a cone unit of the liver. The procedure is also available in laparoscopic hepatectomy and provides new knowledge of the surgical anatomy, especially for small anatomical liver resection in the cirrhotic liver.