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Showing papers in "Journal of Hepato-biliary-pancreatic Sciences in 2011"


Journal ArticleDOI
TL;DR: The four predictive risk factors identified here can provide useful information useful for tailoring postoperative management of clinically relevant pancreatic fistula (grade B/C) after pancreaticoduodenectomy.
Abstract: Background/purpose It is important to predict the development of clinically relevant pancreatic fistula (grade B/C) in the early period after pancreaticoduodenectomy (PD). This study has been carried out as a project study of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHPBS) to evaluate the predictive factors associated with clinically relevant pancreatic fistula (grade B/C).

189 citations


Journal ArticleDOI
TL;DR: 3D reconstructions were obtained from simple spiral computed tomography slides using OsiriX, an open source processing software package dedicated to DICOM images and projected on the patient's body to enhance spatial perception during surgical intervention (augmented reality).
Abstract: New technologies can considerably improve preoperative planning, enhance the surgeon’s skill and simplify the approach to complex procedures. Augmented reality techniques, robot assisted operations and computer assisted navigation tools will become increasingly important in surgery and in residents’ education. We obtained 3D reconstructions from simple spiral computed tomography (CT) slides using OsiriX, an open source processing software package dedicated to DICOM images. These images were then projected on the patient's body with a beamer fixed to the operating table to enhance spatial perception during surgical intervention (augmented reality). Changing a window's deepness level allowed the surgeon to navigate through the patient's anatomy, highlighting regions of interest and marked pathologies. We used image overlay navigation for laparoscopic operations such cholecystectomy, abdominal exploration, distal pancreas resection and robotic liver resection. Augmented reality techniques will transform the behaviour of surgeons, making surgical interventions easier, faster and probably safer. These new techniques will also renew methods of surgical teaching, facilitating transmission of knowledge and skill to young surgeons.

146 citations


Journal ArticleDOI
TL;DR: In patients with HCC with macroscopic PVTT treated by partial hepatectomy with or without portal thrombectomy, the PVTT classification better stratified and predicted prognosis than the TNM staging, CLIP scoring system, and JIS scoring systems, which were unrefined and inadequate for this group of patients.
Abstract: We aimed to correlate the survival of patients with hepatocellular carcinoma (HCC) with macroscopic portal vein tumor thrombus (PVTT) who underwent partial hepatectomy with or without portal thrombectomy with our PVTT classification. Currently, different staging systems for HCC are widely used in clinical practice. However, they lack the refinement in giving prognosis and guiding surgical treatment once macroscopic PVTT is present. A retrospective study was carried out, in a single tertiary center, from January 2001 to December 2004 on 441 patients who underwent partial hepatectomy with or without portal thrombectomy for HCC with macroscopic PVTT. Overall survival was examined to determine whether it was correlated with our PVTT classification, and with the TNM staging, Cancer of the Liver Italian Program (CLIP) scoring system, and the Japan Integrated Staging (JIS) scoring system. With our PVTT classification, the numbers (percentages) of patients with types I, II, III, and IV PVTT were 144 (32.7%), 189 (42.9%), 86 (19.5%), and 22 (5.0%), respectively. The corresponding 1-, 2-, and 3-year overall survival rates for types I to IV PVTT were 54.8, 33.9, and 26.7%; 36.4, 24.9, and 16.9%; 25.9, 12.9, and 3.7%; and 11.1, 0, and 0%, respectively (log-rank of the survival curves P < 0.0001). Using the TNM system, the majority of patients were classified as stage III (n = 379 or 85.9%). Similarly, the majority of patients (n = 388 or 88.0%) were classified as having CLIP scores of 2 (n = 143, or 32.4%), 3 (n = 171, or 38.8%), and 4 (n = 74, or 16.8%). The 1-, 2-, and 3-year overall survivals for these 3 CLIP scores were very similar. Using the JIS score, the majority of patients (n = 372 or 84.4%) were classified with a JIS score of 2. The 1-, 2-, and 3-year overall survivals of patients with a JIS score of 2 were worse than those of the patients with a JIS score of 1 (this was expected) as well as being worse than those with a JIS score of 3 (this was unexpected). Thus, the latter 3 systems of classification were not refined enough, and they were inadequate for stratifying HCC with macroscopic PVTT treated with partial hepatectomy with or without thrombectomy. In patients with HCC with macroscopic PVTT treated by partial hepatectomy with or without thrombectomy, our PVTT classification better stratified and predicted prognosis than the TNM staging, CLIP scoring system, and JIS scoring system, which were unrefined and inadequate for this group of patients.

139 citations


Journal ArticleDOI
TL;DR: A non-smooth tumor margin in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI is useful to predict MPVI, IM, and early recurrence of HCC after hepatectomy.
Abstract: The value of the hepatobiliary phase of gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in patients with hepatocellular carcinoma (HCC) has not been evaluated in detail. Between 2008 and 2009, 61 patients with HCC within the Milan criteria underwent Gd-EOB-DTPA-enhanced MRI and hepatectomy. The tumor margin was determined preoperatively based on hepatobiliary phase images. Microscopic portal vein invasion (MPVI), intrahepatic metastasis (IM), and recurrence of HCC within 1 year after hepatectomy were evaluated in 24 patients with non-smooth margins at the periphery of the tumor and 37 patients with smooth margins. The number of patients with MPVI and IM of HCC was significantly higher among those with non-smooth margins (42 and 38%, respectively) than among those with smooth margins (3%; p = 0.0002 and 5%; p = 0.0042, respectively). A non-smooth margin was identified as a significant predictor of MPVI (odds ratio 18.814, p = 0.024) and IM (odds ratio 6.498, p = 0.036) of HCC on multivariate analysis. Furthermore, a non-smooth margin was identified as a significant predictor of recurrence within 1 year after hepatectomy (odds ratio 4.306, p = 0.04) on multivariate analysis. A non-smooth tumor margin in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI is useful to predict MPVI, IM, and early recurrence of HCC after hepatectomy.

120 citations


Journal ArticleDOI
TL;DR: The mechanisms of liver regeneration must be elucidated and leveraged for the sufficient treatment of liver diseases.
Abstract: Liver regeneration is a necessary process that most liver damage depends on for recovery. Regeneration is achieved by a complex interactive network consisting of liver cells (hepatocytes, Kupffer cells, sinusoidal endothelial cells, hepatic stellate cells, and stem cells) and extrahepatic organs (thyroid gland, adrenal gland, pancreas, duodenum, and autonomous nervous system). The restoration of liver volume depends on hepatocyte proliferation, which includes initiation, proliferation, and termination phases. Hepatocytes are “primed” mainly by Kupffer cells via cytokines (IL-6 and TNF-alpha) and then “proliferation” and “cell growth” of hepatocytes are induced by the stimulations of cytokines and growth factors (HGF and TGF-alpha). Liver regeneration is achieved by cell proliferation and cell growth, where the IL-6/STAT3 and PI3-K/PDK1/Akt pathways play pivotal roles, respectively. IL-6/STAT3 pathway regulates hepatocyte proliferation via cyclin D1/p21 and protects against cell death by upregulating FLIP, Bcl-2, Bcl-xL, Ref1, and MnSOD. PI3-K/PDK1/Akt is known to be responsible for regulation of cell size via its downstream molecules such as mTOR in addition to being known for its survival, anti-apoptotic and anti-oxidative properties. Although the molecular mechanisms of liver regeneration have been actively studied, the mechanisms of liver regeneration must be elucidated and leveraged for the sufficient treatment of liver diseases.

108 citations


Journal ArticleDOI
TL;DR: Preoperative carbohydrate antigen (CA) 19-9, intrahepatic metastasis, and nodal involvement were the significant independent predictors of poor prognosis by multivariate analysis.
Abstract: The aim of this study was to clarify the prognostic factors of intrahepatic cholangiocarcinoma (ICC) following hepatectomy and to examine the impact of lymph node metastasis on survival. This study was therefore carried out as a Project Study of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. Three hundred and forty-one patients who underwent hepatectomy for ICC between 1995 and 2004 at the 9 institutions of the Medical University Hospitals were analyzed retrospectively. Multivariate regression analyses and a Kaplan–Meyer analysis were performed to identify prognostic factors. Pathological lymph node metastasis was one of the significant factors affecting overall survival (hazard ratio 2.10, p < 0.001) based on the multivariate analysis. Among the patients who underwent extended lymphadenectomy beyond the hepatoduodenal ligament, the median survival of 121 patients with nodal involvement was 12.2 months. Only seven patients with nodal involvement have survived for more than 4 years. In the present study, preoperative carbohydrate antigen (CA) 19-9, intrahepatic metastasis, and nodal involvement were the significant independent predictors of poor prognosis by multivariate analysis. Further prospective studies may thus be needed to confirm these findings, because this study has a limitation in that it was a retrospective study with multicenter data collection.

100 citations


Journal ArticleDOI
TL;DR: Robotic surgery is feasible and can be safely performed in patients with complicated HBP pathologies, and further evaluation with clinical trials is required to validate its real benefits.
Abstract: Robotic surgery has emerged as one of the most promising surgical advances since its launch at the turn of the millennium. Despite its worldwide acceptance in many different surgical specialties, the use of robotic assistance in the field of hepatobiliary and pancreatic (HBP) surgery remains relatively unexplored. This article aims to evaluate the efficacy and outcomes of robotic HBP surgery in a single surgical center. Between May 2009 and December 2010, all patients admitted to our unit for robotic HBP surgery were evaluated. A retrospective analysis of a prospectively maintained database on clinical outcomes was performed. There were 55 robotic HBP operations performed during the study period. There were 27 robotic liver resections (left lateral sectionectomies n = 17, left hepatectomy n = 1, other segmentectomies n = 2 and wedge resections n = 7), 12 robotic pancreatic procedures (Whipple’s operations n = 8, spleen-preserving distal pancreatectomies n = 2, double bypass n = 1 and cystojejunostomy n = 1) and 16 biliary procedures (biliary enteric bypass n = 9, bile duct exploration and related procedures n = 7). The median postoperative hospital stays for robotic liver resections, biliary procedures and pancreatic operations were 5.5 days (range 3–11 days), 6 days (range 4–11 days) and 12 days (range 6–21 days), respectively. Morbidities for liver resection, biliary procedures and pancreatic operations were 7.4, 18 and 33%, respectively. There was no mortality in our series. Robotic surgery is feasible and can be safely performed in patients with complicated HBP pathologies. Further evaluation with clinical trials is required to validate its real benefits.

86 citations


Journal ArticleDOI
TL;DR: The plastic stent and the self-expandable metallic stent (SEMS) are used for EUS-BD and how these stents are chosen is focused on.
Abstract: Endoscopic ultrasonography-guided biliary drainage (EUS-BD) has been carried out as an alternative to the percutaneous or surgical approach when endoscopic retrograde cholangiopancreatography fails. However, there is no standard technique or device for EUS-BD. In this review, we focus on how we choose the stents and described our tips on this EUS-BD technique. The plastic stent (PS) and the self-expandable metallic stent (SEMS) are used for EUS-BD. The latter is further divided into the fully covered SEMS (FCSEMS), partially covered SEMS (PCSEMS), and uncovered SEMS (UCSEMS) types. Although PS is not expensive, the duration of stent patency is short. SEMS is expensive but the duration of stent patency is long. With UCSEMS, basically there is no stent malpositioning; however, if the gap between the bile duct and the GI tract becomes displaced, bile leakage from the mesh of the stent is likely to occur. Though there is no bile leakage with FCSEMS, the side branch of the bile duct may become occluded, and migration and dislocation sometimes occur. PCSEMS is basically similar to FCSEMS. When EUS-BD was first developed, drainage by PS was common, although reports on drainage by SEMS have increased recently.

85 citations


Journal ArticleDOI
TL;DR: Histopathological examination demonstrated severe inflammatory cell infiltration in the cecum and ascending colon, whereas the degree was mild in the rectum/descending colon, and characteristic clinical, colonoscopic, and histopathological findings.
Abstract: Purpose Only a few studies have documented the characteristics of inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC). We aimed to clarify the clinical and histopathological characteristics of IBD associated with PSC (PSC-IBD).

81 citations


Journal ArticleDOI
TL;DR: Endoscopic treatment of post-LT AS using a removable FCSEMS is technically feasible, safe, and effective and this dedicated method may play an increasing role in the future management of benign biliary strictures.
Abstract: Background Endoscopic management of biliary anastomotic stricture (AS) following liver transplantation (LT) remains challenging There are no dedicated self-expandable metal stents (SEMS) for this setting

65 citations


Journal ArticleDOI
TL;DR: Pancreatic cancer patients with deep jaundice and expected delay prior to curative intent surgery are potential candidates for temporary biliary drainage, and placement of self-expandable metal stents could reduce stent-related complication rates such as early occlusion because of prolonged patency.
Abstract: Background Pancreatic cancer is a common digestive cancer with high mortality, and surgical resection is the only potential curative treatment option Pancreatic head cancer is usually accompanied by biliary obstruction, which potentially increases surgical complications following pancreaticoduodenectomy Thus, preoperative biliary drainage has long been advocated

Journal ArticleDOI
TL;DR: Optimal management and better outcome of pancreaticoduodenal injuries seem to be associated with shorter operative time, and with simple and fast damage control surgery (DCS), in contrast to definitive surgical procedures.
Abstract: Abdominal trauma rarely causes injuries involving the duodenum and pancreas. Associated injuries occur in 46% of all pancreatic injuries. The morbidity and mortality of pancreaticoduodenal injuries remain high. The present study is a retrospective review of our experience from 1989 to 2008 in the surgical treatment of traumatic pancreaticoduodenal injuries. Mortality, morbidity, prognostic factors, and the value of surgical techniques were analyzed. In our level I Trauma Center, between 1989 and 2008, 55 patients had a pancreaticoduodenal injury. In 68.5% of cases pancreatic injuries were found, 20.4% had duodenal injury, and 11.1% suffered combined pancreaticoduodenal injuries; 85.3% of the patients had blunt abdominal trauma, while 14.9% had penetrating injuries. We treated 78.1% of the patients with external drainage and/or simple suture; distal pancreatectomy was performed in 9% of cases and duodenal resection with anastomosis (3.7%) and diversion procedures (3.7%) were performed in an equal number of patients. Age, American Association for the Surgery of Trauma (AAST) grade, organ involved, hemodynamic status, intraoperative cardiac arrest, and operative time remained strongly predictive of mortality on multivariate analysis. The AAST grade represented, on multivariate analysis, the only independent prognostic factor predictive of overall morbidity. In the past decade we have used feeding jejunostomy more frequently, with a reduction of mortality and operating time, due also to a better approach from a dedicated trauma team. Optimal management and better outcome of pancreaticoduodenal injuries seem to be associated with shorter operative time, and with simple and fast damage control surgery (DCS), in contrast to definitive surgical procedures.

Journal ArticleDOI
TL;DR: The Tokyo Guidelines should be used more widely for the diagnosis of acute cholangitis and cholecystitis in the twenty-first century and various efforts should be made to improve the sensitivity and specificity of the diagnostic criterion.
Abstract: Three years have passed since the publication of the Tokyo Guidelines for the management of acute cholangitis and cholecystitis, and we believe that the time has come to assess their validity. In this study, we validated the diagnostic accuracy of these criteria in 74 patients with an initial diagnosis of acute cholangitis and 81 patients with an initial diagnosis of acute cholecystitis. We also statistically compared the accuracy of the diagnosis made based on the Tokyo Guidelines with that based on the presence of Charcot’s triad for acute cholangitis and Murphy’s sign for acute cholecystitis with use of the sign test to assess differences. The results revealed that the diagnostic sensitivity and specificity of the Tokyo Guidelines for suspected or definitive acute cholangitis were 72.1 and 38.5%, respectively, and the corresponding values for definitive cholangitis alone were 63.9 and 69.2%, respectively. For definitive acute cholecystitis, the diagnostic sensitivity and specificity of the Tokyo Guidelines were 84.9 and 50.0%, respectively. The accuracy of diagnosis based on the Tokyo Guidelines was significantly higher than that based on the presence of Charcot’s triad (acute cholangitis, p < 0.001 by the sign test) or Murphy’s sign (acute cholecystitis, p < 0.001 by the sign test). It was therefore concluded that the Tokyo Guidelines should be used more widely for the diagnosis of acute cholangitis and cholecystitis in the twenty-first century. Hereafter, various efforts should be made to improve the sensitivity and specificity of the diagnostic criterion of the Tokyo Guidelines.

Journal ArticleDOI
TL;DR: EUS-GBD holds high potential as an alternative gallbladder decompression procedure, however, because current experience is limited, multicenter trials for the accurate evaluation of this procedure appear to be necessary in the near future.
Abstract: Background/purpose Endoscopic ultrasonography-guided gallbladder drainage (EUS-GBD) has been developed as an alternative drainage method in patients with acute cholangitis. Here, we describe two successful EUS-GBD cases and review the literature on this topic.

Journal ArticleDOI
TL;DR: This work presents the initial experience of single-port laparoscopic liver surgery using a LaparoEndoscopic Single Site (LESS) approach with the TriPort System to perform a left lateral sectionectomy via a single supraumbilical incision in a patient with a single colorectal metastasis.
Abstract: Background/purpose Laparoscopic liver surgery is attracting wider interest for the treatment of benign and malignant neoplasms. Laparoscopy is a safe and feasible approach for lesions located in the left liver lobe. As the emphasis on minimizing the technique continues, single-port access surgery is quickly evolving. We present our initial experience of single-port laparoscopic liver surgery using a LaparoEndoscopic Single Site (LESS) approach with the TriPort System (ASC; Advanced Surgical Concepts, Bray, Ireland) to perform a left lateral sectionectomy via a single supraumbilical incision.

Journal ArticleDOI
TL;DR: The spontaneous rupture of a hepatic hemangioma is to be considered an exceptional event and preventive surgery should be considered only for lesions of at least 11-cm size in special cohorts of patients.
Abstract: The risk of spontaneous bleeding or rupture of liver hemangiomas still remains unknown. The aim of this review was to analyze the problem of spontaneous bleeding or rupture in liver hemangiomas and to identify factors leading to bleeding in these cases. A MEDLINE search was undertaken to identify articles in English, French, German, Italian, and Spanish from 1898 to 2010. Basic data such as age and sex of patients were collected. Additional data such as risk factors or causes of rupture were also analyzed. Cases were divided into spontaneous and non-spontaneous ruptures. A total of 97 cases are described. In 51 of the 97 patients (52.6%) a non-spontaneous rupture was identified. Only in 46 out of the 97 cases (47.4%) was a spontaneous rupture found. Non-spontaneous rupture was significantly more frequent in patients aged <40 years than in older ones (p = 0.0099). Mean size of the ruptured lesions was 11.2 cm (range 1–37 cm). Massive bleeding occurred in 88 patients (90.7%). Reported mortality over the past 20 years has been significantly lower than before (p < 0.001). The overall mortality for the period under study was ~35%. The spontaneous rupture of a hepatic hemangioma is to be considered an exceptional event. Preventive surgery should be considered only for lesions of at least 11-cm size in special cohorts of patients.

Journal ArticleDOI
TL;DR: The current technique for both invagination pancreaticojejunostomy and duct-to-mucosa pancreatico-enteric anastomosis is focused on, recognizing that careful surgical technique, surgeon experience, and surgical volume are factors that are important in yielding the best outcomes.
Abstract: Following the resectional aspect of pancreaticoduodenectomy, three anastomoses are used to reestablish gastrointestinal continuity. The pancreatic–enteric anastomosis is by far the most problematic, and has been considered by many the Achilles heel of the pancreaticoduodenal resection. Multiple clinical trials have been published focusing on improving outcomes of the pancreatic–enteric anastomosis, including elements such as the use of prophylactic octreotide, the use of sealants, stenting of the pancreatic duct, and surgical technique. There are two widely used methods to accomplish an end-to-side pancreaticojejunostomy (PJ) after pancreaticoduodenectomy: either invagination PJ or duct-to-mucosa PJ. Two prospective randomized trials have evaluated these techniques, the first a trial by Bassi and co-authors, and the second a trial by Berger et al. In this article we will focus on our current technique for both invagination pancreaticojejunostomy and duct-to-mucosa pancreaticojejunostomy, recognizing that careful surgical technique, surgeon experience, and surgical volume are factors that are important in yielding the best outcomes.

Journal ArticleDOI
TL;DR: A case series of MCA for severe biliary stricture or obstruction, which could not be treated with conventional therapies, is described and the MCA technique is a revolutionary method of performing choledochocholedochostomy and cholingochoenterostomy interventionally in patients with biliary obstruction.
Abstract: Magnetic compression anastomosis (MCA) is a revolutionary, minimally invasive method of performing choledochoenterostomy or choledochocholedochostomy without using surgical techniques in patients with biliary stricture or obstruction. Herein, we describe a case series of MCA for severe biliary stricture or obstruction, which could not be treated with conventional therapies. Two patients with biliary obstruction were treated using MCA for choledochocholedochostomy and choledochoenterostomy at Tokyo Medical University Hospital and Tokyo Medical University Hachioji Medical Center. Endoscopically, a samarium–cobalt (Sm–Co) rare-earth magnet was placed at the superior site of obstruction through the percutaneous transhepatic biliary drainage route and another Sm–Co magnet was placed at the inferior site of obstruction. A comprehensive computer-aided literature search for MCA was performed up to September 2009 by using MEDLINE and EMBASE. MCA techniques enabled complete anastomosis in both cases without procedure-related complications. The MCA technique is a revolutionary method of performing choledochocholedochostomy and choledochoenterostomy interventionally in patients with biliary obstruction, for whom the conventional endoscopic procedure is not available, or in candidates who are deemed unsuitable for surgery.

Journal ArticleDOI
TL;DR: The need for PBD to treat jaundice in HCA patients scheduled for major surgical resection of the liver and that major surgery should be performed only after the recovery of hepatic function is suggested.
Abstract: The controversy over whether and how to perform preoperative biliary drainage (PBD) in patients with hilar cholangiocarcinoma (HCA) remains unsettled. Arguments against PBD before pancreatoduodenectomy have recently been gaining momentum. However, the complication-related mortality rate is as high as 10% for patients with HCA who have undergone major liver resection, and liver failure is a major cause of postoperative death. This suggests the need for PBD to treat jaundice in HCA patients scheduled for major surgical resection of the liver and that major surgery should be performed only after the recovery of hepatic function. No definite criteria or guidelines outlining indications for PBD are currently available. In patients with HCA, PBD may be performed by either percutaneous transhepatic biliary drainage (PTBD) or endoscopic biliary drainage (EBD). No consensus, however, has been reached regarding which drainage method is more appropriate. No reported study has compared the effectiveness of PTBD, endoscopic biliary stenting (EBS), and endoscopic nasobiliary drainage (ENBD) in patients with HCA. This review summarizes the results of our study comparing the three methods and outlines the preoperative endoscopic management of segmental cholangitis (SC) in HCA patients undergoing PBD.

Journal ArticleDOI
TL;DR: Borderline resectable pancreatic cancer (BRPC) had a poorer prognosis with more local failure than resectal PC although prognosis of BRPC was significantly better than that of unresectable PC.
Abstract: Borderline resectable pancreatic cancer (BRPC) appears to be most frequently related to a positive surgical margin and has a poor prognosis after resection. However, few reports are available on differences in tumor characteristics and prognoses among resectable pancreatic cancer (PC), BRPC, and unresectable PC. Records of 133 patients resected for pancreatic ductal adenocarcinoma and 185 patients treated as locally advanced PC (LAPC) were reviewed. Twenty-four patients who initially underwent resection (BRPC-s) and 10 patients who were initially treated as LAPC (BRPC-n) met the criteria for BRPC. Prognosis of BRPC was significantly better than that of unresectable PC, but was significantly worse than that of resectable PC. BRPC-s showed more frequent nerve plexus invasion (P < 0.01), portal vein invasion (P < 0.01), and loco-regional recurrence (P = 0.03) than resectable PC. The positive surgical margin rate was not significantly higher in BRPC-s (29%) than in resectable PC (19%) (P = 0.41). BRPC had a poorer prognosis with more local failure than resectable PC although prognosis of BRPC was significantly better than that of unresectable PC. Considering the tumor and treatment characteristics, multidisciplinary treatment including resection is required for BRPC.

Journal ArticleDOI
TL;DR: Allopurinol, through its known xanthine oxidase inhibitory effect, as only one of the potential mechanisms, has demonstrated its potential application in protecting the liver during ischemia and reperfusion.
Abstract: Allopurinol was first introduced, in 1963, as a xanthine oxidase inhibitor when it was investigated for concomitant use with cancer chemotherapy drugs. Today it is used in gout and hyperuricemia. Due to its additive benefit in preventing oxidative damage, attention has shifted towards the use of allopurinol in organ ischemia and reperfusion. Currently, the mechanism by which allopurinol exerts a protective benefit in ischemia reperfusion related events is not fully understood. There are various theories: it may act by inhibiting the irreversible breakdown of purine substrates, and/or by inhibiting the formation of reactive oxygen species, and/or by protecting against damage to the mitochondrial membrane. This work focuses on liver ischemia and reperfusion injury in an effort to better understand the mechanisms associated with allopurinol and with this pathological entity. The current research, mainly in animal models, points to allopurinol having a protective benefit, particularly if used pre-ischemically in liver ischemia reperfusion injury. Furthermore, after reviewing allopurinol dosing and administration, it was found that 50 mg/kg is statistically the most effective dose in attenuating liver ischemia reperfusion injury. Owing to the limited number of samples, the time of administration did not show statistical difference, but allopurinol was often beneficial when given around 1 h before ischemia. In conclusion, allopurinol, through its known xanthine oxidase inhibitory effect, as only one of the potential mechanisms, has demonstrated its potential application in protecting the liver during ischemia and reperfusion.

Journal ArticleDOI
TL;DR: Nafamostat mesilate reduced peritoneal metastasis and prolonged survival of pancreatic cancer-bearing mice and increased the sensitivity of anoikis.
Abstract: Background Constitutive activation of nuclear factor kappa-B (NF-κB) contributes to the aggressive behavior of pancreatic cancer. Over-expression of downstream target genes of NF-κB such as intercellular adhesion molecule-1 (ICAM-1), interleukin-8 (IL-8), vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) leads to the promotion of cell adhesion, angiogenesis, invasion and metastasis. We previously reported that nafamostat mesilate, a synthetic serine protease inhibitor, blocks NF-κB activation in pancreatic cancer. We hypothesized that nafamostat mesilate may inhibit cell adhesion, angiogenesis, invasion and metastases in peritoneal dissemination of pancreatic cancer.

Journal ArticleDOI
TL;DR: DPPHR for benign or premalignant lesions is a difficult procedure with a higher complication rate than PPPD, but was without mortality, which allows better long-term results.
Abstract: Background/purpose Pylorus-preserving pancreaticoduodenectomy (PPPD) is the treatment of choice for benign or premalignant pancreatic head lesions. Duodenum-preserving pancreatic head resection (DPPHR) has been reported in only 132 patients. This study aimed to compare the long-term results of DPPHR and PPPD.

Journal ArticleDOI
TL;DR: The results suggested that HIFU treatment might be effective in controlling local tumor and may have the possibility of becoming one of the combination therapies for treating pancreatic carcinoma in the future.
Abstract: Introduction Pancreatic carcinoma has one of the poorest prognoses among malignant tumors. Many pancreatic carcinoma patients who undergo common treatments, such as surgery, radio-chemotherapy and chemotherapy, gained little benefit because of the histological characteristics.

Journal ArticleDOI
TL;DR: The chemotactic interaction between CCR7 and its ligand, CCL21, may be a critical event during progression in pancreatic cancer, and its underlying mechanism may be induction of angiogenesis and lymphangiogenesis regulated by this chemOTactic interaction.
Abstract: In this study, we report the influence of CCL21 and its receptor, CCR7, on the progression of pancreatic cancer and illuminates the correlation between the CCL21/CCR7 axis and the angiogenesis and lymphangiogenesis of pancreatic adenocarcinoma (PAC). A total of 30 patients with pancreatic cancer was involved in the current study. The expression of CCL21 and CCR7 in cancerous tissues, paracancerous tissues and normal pancreas were investigated using real-time PCR, Western blot and immunohistochemistry, respectively. In addition, we assessed microvessel density (MVD) and microlymphatic vessel density (MLVD) in tumor tissues using immunohistochemistry. Compared to paracancerous tissues and normal pancreas, CCL21 expression in cancerous tissues was detected at a significantly low level. In contrast, the CCR7 expression was considerably higher in cancerous tissues than in normal pancreas and paracancerous tissues. Additionally, a significant correlation between the expression pattern of the CCL21/CCR7 axis and clinicopathological features, such as lymph node metastasis, was identified. Furthermore, we found that CCL21 expression was significantly associated with MVD but not significantly associated with MLVD, while CCR7 expression was significantly associated with MLVD but not significantly associated with MVD. The chemotactic interaction between CCR7 and its ligand, CCL21, may be a critical event during progression in pancreatic cancer, and its underlying mechanism may be induction of angiogenesis and lymphangiogenesis regulated by this chemotactic interaction.

Journal ArticleDOI
TL;DR: Endoscopic bilateral stenting using newly designed metallic stents is feasible, safe, and effective in patients with unresectable malignant hilar biliary obstruction.
Abstract: Whether unilateral or bilateral drainage should be performed for malignant hilar biliary obstruction is controversial. Moreover, endoscopic placement of bilateral metallic stents is difficult and complicated. New metallic stents, such as the Niti-S Y-type stent (Y-stent), BONASTENT M-Hilar, and Niti-S large cell D-type stent (LCD), have recently been developed for bilateral stent-in-stent procedures to facilitate contralateral stent deployment through the interstices of the first metallic stent. We review the features and efficacy of these metallic stents designed for bilateral drainage in patients with hilar biliary obstruction. The newly designed stents examined exhibited high technical success rates, low stent-related complications, and good stent patency. Endoscopic reinterventions for occluded stents could be performed easily, particularly in patients with bilateral LCD placement. Endoscopic bilateral stenting using newly designed metallic stents is feasible, safe, and effective in patients with unresectable malignant hilar biliary obstruction.

Journal ArticleDOI
TL;DR: Although this stent is not radiopaque and the number of cases was small in this experimental study, endoscopic stenting using this novel, braided, self-expandable, biodegradable, pancreatic and biliary stent was feasible in the pig model.
Abstract: Recently, biodegradable pancreatic stents have been designed and placed in vivo and in vitro. The aim of this study is to investigate the feasibility of endoscopic stenting using the novel, braided, self-expandable, biodegradable, pancreatic and biliary stent in a pig model. A braided, self-expandable, biodegradable stent was endoscopically placed into the pancreatic duct and bile duct in 4 pigs. Eventually, necropsy was performed to evaluate the stent placement after the procedure. Pancreatic and biliary stents were successfully inserted and easily deployed across the papilla into the main pancreatic duct and bile duct, respectively, in all the animals under endoscopic and fluoroscopic guidance. Necropsy performed immediate following stent placement, found that stents had been placed across the papilla and stent expansion had occurred in all cases. Although this stent is not radiopaque and the number of cases was small in this experimental study, endoscopic stenting using this novel, braided, self-expandable, biodegradable, pancreatic and biliary stent was feasible in the pig model. Further animal studies to evaluate the short-term patency, tissue reactivity and degradability of the stents are warranted.

Journal ArticleDOI
TL;DR: Selective lymphadenectomy of LNM from HCC was a feasible and efficacious procedure, and survival rates can be expected to improve after selective lymph Adenectomy of single LNM.
Abstract: Background No consensus has been reached on the feasibility and efficacy of surgery for lymph node metastases (LNM) from hepatocellular carcinoma (HCC).

Journal ArticleDOI
TL;DR: In this article, the authors describe total laparoscopic pancreaticoduodenectomy (PD) undertaken using the da Vinci Surgical System® (Intutive Surgical).
Abstract: Robotic surgery is the most advanced development in minimally invasive surgery. However, the number of reports on robot-assisted endoscopic gastrointestinal surgery is still very small. In this article, we describe total laparoscopic pancreaticoduodenectomy (PD) undertaken using the da Vinci Surgical System® (Intutive Surgical). Three patients underwent robotic PD between November 2009 and February 2010. Following resection of the pancreatic head, duodenum, and the distal stomach, intracorporeal anastomosis was accomplished by Child’s method of reconstruction, which includes a two-layered end-to-side pancreaticojejunostomy, an end-to-side choledochojejunostomy, and a side-to-side gastrojejunostomy. The time required for surgery was 703 ± 141 min, and blood loss was 118 ± 72 mL. The average hospital stay period was 26 ± 12 days. As a postoperative complication, pancreatic juice leak occurred in one case, but it was managed with conservative treatment. Of the three patients, one had cancer of the papilla of Vater, one had cancer of the pancreatic head, and one had a solid pseudopapillary neoplasm. In all cases, the surgical margin was negative for tumor. Robot-assisted PD required a long time, but organ removal with less bleeding was able to be safely performed owing to the high degree of freedom associated with the forceps manipulation and the magnified view. Similarly, pancreatojejunostomy could certainly be conducted. No major postoperative complications were found. Accumulation of da Vinci PD experience in the future will lead to safer and faster PD.

Journal ArticleDOI
TL;DR: Increased expression of p53R2 may predict gemcitabine resistance, and upregulated RNR activity may influence gemcitABine resistance in cholangiocarcinoma cells.
Abstract: Gemcitabine is a promising drug for cholangiocarcinoma treatment. However, the kinetics and metabolism of this drug in cholangiocarcinoma treatment are not well defined. We aimed to investigate the potential clinical role of gemcitabine metabolism-related genes in the gemcitabine sensitivity of cholangiocarcinoma and identify and characterize novel gemcitabine resistance-related genes. Expressions of genes related to gemcitabine sensitivity and gemcitabine metabolism were measured in 10 cholangiocarcinoma cell lines, and the association between gene expression and gemcitabine sensitivity was evaluated. Furthermore, gemcitabine-resistant cell lines were established from YSCCC cells and subjected to genome-wide microarray analysis. The 2-fold upregulated and downregulated genes were then subjected to pathway analysis. p53R2 mRNA expression was significantly higher in gemcitabine-resistant cell lines (IC50 > 1000 nM), and all subunits of ribonucleotide reductase were upregulated in the established gemcitabine-resistant cell lines. Microarray analysis revealed that the upregulated genes in the resistant cells belonged to the glutathione and pyrimidine metabolism pathways, and that the downregulated genes belonged to the N-glycan biosynthesis pathway. Increased expression of p53R2 may predict gemcitabine resistance, and upregulated RNR activity may influence gemcitabine resistance in cholangiocarcinoma cells. Glutathione pathway-related genes were induced by continuous exposure to gemcitabine and may contribute to gemcitabine resistance.