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Background: Hepatocyte growth factor activator inhibitor type 2-related small peptide (H2RSP) is a small nuclear protein abundantly expressed in the gastrointestinal epithelium. However, its functions remain unknown. Aims: To investigate the expression and localisation of H2RSP in normal, injured and neoplastic human intestinal tissue. Methods: Immunohistochemical examination and in situ hybridisation for H2RSP were performed using normal and diseased intestinal specimens. Its subcellular localisation and effects on the cellular proliferation and invasiveness were examined using cultured cells. Results: In the normal intestine, H2RSP was observed in the nuclei of surface epithelial cells and this nuclear localisation was impaired in regenerating epithelium. In vitro, the nuclear translocation of H2RSP was observed along with increasing cellular density, and an overexpression of H2RSP resulted in a reduced growth rate and enhanced invasiveness. H2RSP expression was down regulated in well-differentiated colorectal adenocarcinomas. However, a marked up regulation of the cytoplasmic H2RSP immunoreactivity was observed in cancer cells at the invasive front. These cells showed low MIB-1 labelling, an enhanced p16 expression and nuclear β-catenin. The number of H2RSP-positive cells in the invasive front of well- differentiated adenocarcinomas was considerably higher in the cases with lymph node metastases than in node-negative ones. Conclusion: In the normal intestine, the nuclear accumulation of H2RSP is a marker of differentiated epithelial cells. Although H2RSP was down regulated in colorectal adenocarcinomas, a paradoxical up regulation was observed in actively invading carcinoma cells. H2RSP immunoreactivity at the invasive front may serve as a marker of invasive phenotype of well-differentiated colon cancers. [ABSTRACT FROM AUTHOR]

Background: Although an antecolic duodenojejunostomy was reported to reduce post-operative delayed gastric emptying (DGE) compared with a retrocolic duodenojejunostomy after a pylorus-preserving pancreaticoduodenectomy (PPPD), the long-term effects of these procedures have rarely been studied. The aim of this prospective, randomized, clinical trial was to investigate the influence of the reconstruction route on post-operative gastric emptying and nutrition., Methods: Reconstruction was performed in 116 patients with an antecolic duodenojejunostomy (A group, n = 58) or a vertical retrocolic duodenojejunostomy (VR group, n = 58). Post-operative complications, including DGE, gastric emptying variables assessed by (13) C-acetate breath test and nutrition, were compared between the two groups for 1 year post-operatively., Results: The incidence of DGE was not significantly different between the procedures (A group: 12.1%; VR group: 20.7%, P = 0.316). At post-operative month 1, gastric emptying was prolonged in the VR versus the A group but not significantly so. At post-operative month 6, gastric emptying was accelerated significantly in the A versus the VR group. Post-operative weight recovery was significantly better in the VR versus the A group at post-operative month 12 (percentage of pre-operative weight, A group: 93.8 ± 1.2%; VR group: 98.5 ± 1.3%, P = 0.015)., Conclusions: A vertical retrocolic duodenojejunostomy was an acceptable procedure for the lower incidence of DGE and may contribute to better weight gain affected by moderate gastric emptying., (© 2013 International Hepato-Pancreato-Biliary Association.)

Purpose: This study aimed at demonstrating the feasibility of retrospectively fused (18)F FDG-PET and MRI (PET/MRI fusion image) in diagnosing pancreatic tumor, in particular differentiating malignant tumor from benign lesions. In addition, we evaluated additional findings characterizing pancreatic lesions by FDG-PET/MRI fusion image., Methods: We analyzed retrospectively 119 patients: 96 cancers and 23 benign lesions. FDG-PET/MRI fusion images (PET/T1 WI or PET/T2WI) were made by dedicated software using 1.5 Tesla (T) MRI image and FDG-PET images. These images were interpreted by two well-trained radiologists without knowledge of clinical information and compared with FDG-PET/CT images. We compared the differential diagnostic capability between PET/CT and FDG-PET/MRI fusion image. In addition, we evaluated additional findings such as tumor structure and tumor invasion., Results: FDG-PET/MRI fusion image significantly improved accuracy compared with that of PET/CT (96.6 vs. 86.6 %). As additional finding, dilatation of main pancreatic duct was noted in 65.9 % of solid types and in 22.6 % of cystic types, on PET/MRI-T2 fusion image. Similarly, encasement of adjacent vessels was noted in 43.1 % of solid types and in 6.5 % of cystic types. Particularly in cystic types, intra-tumor structures such as mural nodule (35.4 %) or intra-cystic septum (74.2 %) were detected additionally. Besides, PET/MRI-T2 fusion image could detect extra benign cystic lesions (9.1 % in solid type and 9.7 % in cystic type) that were not noted by PET/CT., Conclusions: In diagnosing pancreatic lesions, FDG-PET/MRI fusion image was useful in differentiating pancreatic cancer from benign lesions. Furthermore, it was helpful in evaluating relationship between lesions and surrounding tissues as well as in detecting extra benign cysts.

Background: Multifunctional redox protein human thioredoxin (TRX-1) is reduced by thioredoxin reductase (TRX-R). The aim of the present study was to examine the distribution of TRX-1 and TRX-R expressions in gallbladder carcinoma (GBC) to clarify their usefulness as prognostic factors after surgical resection., Methods: Immunohistochemical staining for TRX-1 and TRX-R was performed in GBC tissue from 38 patients who underwent surgical resection, and TRX-1/TRX-R localization in relation to outcome was examined., Results: TRX-1 protein levels were significantly higher in GBC samples than in cholecystolithiasis samples (P = 0.0174). TRX-1 expression was observed in 100% (38/38) of tumour samples and in the nucleus in 76% (29/38), with nuclear expression in the invasion front observed in 45% (13/29). TRX-R expression was only detected in the cytoplasm of cancer cells and in the invasion front in 28 samples. In all of the samples, the depth of tumour invasion, lymph node metastasis, surgical margin, curability and nuclear expression of TRX-1 in the invasion front were significant prognostic factors by univariate analysis. In 27 selected patients who underwent curative resection, both TRX-1 nuclear expression and TRX-R cytoplasmic expression in the invasion front was a significantly prognostic factor., Conclusion: TRX-1 nuclear expression in the GBC invasion front is a significant prognostic marker. Patients with both TRX-1 nuclear expression and TRX-R cytoplasmic expression in the tumour invasion front should be observed carefully even if after curative resection., (© 2012 International Hepato-Pancreato-Biliary Association.)

This study aimed to investigate whether the initial indication for surgery or type of surgery (strictureplasty or resection) performed determines recurrence patterns in patients with Crohn disease. Recurrence patterns of 41 patients (31 patients: only resection and anastomosis of the intestine, and 10 patients: strictureplasty with/without resection and anastomosis) who underwent operation for recurrent Crohn disease (June 2002-December 2010) were evaluated. Strictureplasty for nonperforating disease was performed at 17 sites, and reoperation was required at 11 sites (10 sites for nonperforating disease and 1 site for perforating disease). There was a significant difference in the recurrence pattern in patients who underwent resection and anastomosis (P < 0.01) and in patients who underwent strictureplasty with resection and anastomosis (P < 0.05) between sites at which resection and anastomosis was performed for nonperforating and for perforating disease. Initial indication for surgery, but not the type of surgery, appeared to determine recurrence patterns.

Objective: Predicting liver functional reserve is important before partial hepatectomy. However, it is difficult to predict using morphologic imaging modalities, such as CT and MRI. In this study, we assess the usefulness of galactosyl human serum albumin (GSA) scintigraphy in predicting liver function recovery., Methods: We performed 99mTc-GSA scintigraphy before operation in 56 patients. Each patient was administered 185 MBq of 99mTc-GSA by intravenous injection. Serial images were taken immediately after the administration for 40 min. SPECT images were obtained to make a functional map. We calculated the functioning parameter residual GSA-Rmax (GSA-RL) using analysis software developed by Dr.N. Shuke. In addition, we compared GSA-RL with the morphological parameter residual liver volume (RLV-CT) calculated by conventional CT and serum albumin (Alb) or cholinesterase (ChE). We analyzed the correlation between imaging parameters and the postoperative recovery periods of serum albumin (r-Alb) and cholinesterase (r-ChE) and the values at 1 and 3 months for serum albumin (1M-Alb, 3M-Alb) and cholinesterase (1M-ChE, 3M-ChE)., Results: We found significant correlations between GSARL and r-Alb, r-ChE, 1M-Alb, 3M-Alb, 1M-ChE and 3M-ChE, but not between RLV-CT and the same parameters., Conclusion: The GSA-RL calculated by 99mTc GSASPECT was a useful parameter for predicting postoperative liver function recovery that should be implemented before partial hepatectomy.

Antigen binding to the B-cell receptor (BCR) of pre-mature B lymphocytes induces their apoptotic cell death, but binding to the BCR of mature B lymphocytes triggers activation and proliferation. Binding to pre-mature B lymphocytes is thought not only to function as a mechanism to exclude B-cell clones that possess the ability to react with self-antigen, but also to act as a defense mechanism in auto-immune diseases. Cross-linking of BCR of pre-mature B-cell lines, including the chicken DT40 cell line, with anti-immunoglobulin IgG induces apoptotic cell death. Treatment with phorbol 12-myristate 13-acetate/ionomycin, which mimics BCR stimulation, is used to study intracellular signal transduction of B lymphocytes. Here, by analyzing the E2A-deficient DT40 cell line, E2A(-/-), we show that E2A deficiency prevents certain levels of apoptotic cell death mediated by BCR signaling. In addition, E2A deficiency-linked BCR signaling controls the mimicked pre-mature B-cell apoptosis by PMA/ionomycin through elevated survivin plus inhibitor of apoptosis 2 levels, and reduced caspase-3 and caspase-8 activities, resulting in increased amounts of ICAD (inhibitor of caspase-activated DNase), compared with those in the presence of E2A, followed by reduction of DNA fragmentation. These findings will contribute to the resolution of molecular mechanisms of negative selection of B cells and also auto-immune diseases.

Modification of transcription factors by anticancer agents plays an important role in both apoptotic and survival signaling. Here we report that both DNA topoisomerase I and II inhibitors such as SN-38 and etoposide, but not cisplatin, 5-fluorouracil or actinomycin D, can induce phosphorylation of the transcription factor Sp1. Furthermore, DNA topoisomerase inhibitors were shown to transactivate GC-box-dependent promoters such as the SV40 and vascular endothelial growth factor promoters. The phosphorylated form of Sp1 was detectable within 30 min of etoposide treatment and was greatly diminished by the presence of the PI3K inhibitor wortmannin and by DNA-dependent protein kinase (DNA-PK) knockdown. We also confirmed that the phosphorylated form of DNA-PK was increased by treatment with both etoposide and SN-38. Taken together, these findings demonstrate a novel genomic response to anticancer agents that induce Sp1 phosphorylation, and might contribute to tumor progression and drug resistance.

The effects of two-thirds partial hepatectomy on bile acid metabolism have not been well established. This study investigated the changes in microsomal enzymes activities during liver regeneration. The cholesterol 7alpha-hydroxylase (7alpha-hydroxylase) and 3beta-hydroxy-delta5-C27-steroid dehydrogenase (3beta-dehydrogenase) activities in male Wistar rats were determined using high-performance liquid chromatography (HPLC). Cytochrome P450 (P450) and cytochrome b5 (b5) levels and NADPH cytochrome c reductase activities were also determined after hepatectomy. 7alpha-Hydroxylase activities were not reduced on days 3, 5, or 7 compared to those of sham-operated rats, but there was a significant decrease (by 60%) of 3beta-dehydrogenase activity compared to that of sham-operated groups (p <0.01) on days 3, 5, and 7 after hepatectomy. While 7alpha-hydroxylase activity had recovered by day 3 after hepatectomy, 3beta-dehydrogenase activity had not, even on day 7. These results suggest that the mechanisms of regulation of these 2 bile acid metabolizing enzymes are significantly different during liver regeneration.

MRP1 is a 190-kDa membrane glycoprotein that confers multidrug resistance to tumor cells. The accumulated evidence has proved that GSH interacts with MRP1 and stimulates drug transport. However, the mechanism of GSH-dependent drug transport by MRP1 remains unclear. In this study, we used limited tryptic digestion of MRP1 in isolated membrane vesicles, in the presence and absence of GSH, to investigate the influence of GSH on MRP1 conformation. We found that GSH inhibited the generation of an approximately 35-kDa C-terminal tryptic fragment (including a C-terminal His tag) termed C2 from MRP1. This effect of GSH was not because of direct inhibition of trypsin activity, and agosterol A enhanced the inhibitory effect of GSH. The main cleavage site in MRP1 for the generation of the C2 fragment by trypsin resided between TMD2 and NBD2 of MRP1. Limited tryptic digestion of membrane vesicles expressing various truncated and co-expressed MRP1 fragments in the presence and absence of GSH revealed that GSH inhibited the production of the C2 fragment only in the presence of the L(0) region of MRP1. Thus the L(0) region is required for the inhibition of trypsinization of the C-terminal half of MRP1 by GSH. These findings, together with previous reports, suggest that GSH induces a conformational change at a site within the MRP1 that is indispensable for the interaction of MRP1 with its substrates.

Drug-induced modifications of transcription factors play important roles in both apoptosis and survival signaling. The data presented here show that the DNA topoisomerase II poison TAS-103 transactivated the SV40 promoter in a GC-box-dependent manner and induced Sp1 acetylation in cells expressing p300. This activity was not observed in cells lacking p300. TAS-103 treatment also enhanced the p300 content of the nucleus and the interaction of p300 with Sp1. Cellular susceptibility to TAS-103 was correlated with p300 expression but not with topoisomerase II expression. Furthermore, the presence of p300 significantly sensitized cancer cells to TAS-103 but not to cisplatin. Taken together, these findings demonstrate novel genomic responses to anticancer agents that modulate Sp1 acetylation and Sp1-dependent transcription in an apoptotic pathway.

Background: In Japan, postoperative relapse occurs within five years in 9.2 to 16% of patients whose breast cancers have not metastasized to lymph nodes at the time of initial surgery(node-negative, n0). Attempts to find molecular markers able to classify n0 breast cancers in terms of postoperative prognosis have not been successful., Methods: To identify molecular indicators of prognosis for this type of cancer, we used a cDNA microarray consisting of 25,344 human genes to investigate expression profiles of 12 primary breast cancers from patients whose tumors recurred within five years after surgery(5Y-R) and 12 from patients who survived disease-free for more than five years (5Y-F)., Results: Sets of genes characterizing each group in terms of expression patterns in the tumors were selected by Mann-Whitney and random-permutation tests: these panels included 21 genes expressed highly in 5Y-R tumors than in 5Y-F tumors, and 37 with higher expression in the 5Y-F group than in the 5Y-R group., Conclusions: We established a scoring system to prediction of postoperative prognosis which was 100% accurate as to the actual clinical outcomes of the 24 cases and therefore might be useful for predicting prognosis of n0 breast cancers in a clinical setting. The prognostic score system clearly separated the two groups without any overlap, and accurately predicted prognosis in 6 additional cases. Moreover, the extensive list of tumor-related genes identified in these experiments provides valuable information about progression of breast cancer and suggests potential target molecules for therapy of n0 breast cancers.

We have previously demonstrated significantly decreased immunoreactivity of hepatocyte growth factor activator inhibitor type 1 (HAI-1), an integral membrane protein that exhibits potent inhibitory activity against hepatocyte growth factor activator (HGFA) and matriptase, in colorectal adenocarcinomas. In this report, we describe further detailed analysis of HAI-1 expression in colorectal adenocarcinoma by using three kinds of anti-HAI-1 antibodies, each of which recognizes a distinct epitope of the HAI-1 molecule, and also by in-situ hybridization for HAI-1 mRNA. The results indicated that the decreased immunoreactivity of HAI-1 in colorectal carcinoma cells is largely a result of enhanced ectodomain shedding of HAI-1 in these cells. In contrast, immunoreactivity of mature membrane-form HAI-1 was paradoxically en-hanced in cancer cells at the invasion front, showing intense cell-stroma interactions and/or sprouting invasion. This finding indicates that these invading cells showed decreased ectodomain shedding of HAI-1 and consequently might require the existence of the membrane-form HAI-1. Of particular interest was the observation of a possible inverse correlation between paradoxical up-regulation of membrane-form HAI-1 expression and membrane-associated E-cadherin in these cells. These membrane-form HAI-1-positive sprouting cancer cells were also negative for MIB-1 immunohistochemically, indicating a low-proliferating population. All these results suggest that HAI-1 may mediate diverse functions in regard to the progression of colorectal carcinomas, and the immunoreactivity of membrane-form HAI-1 may serve as a marker of invading cancer cells.

Mitochondrial sterol 27-hydroxylase (EC 1.14.13.15) is an important enzyme, not only in the formation of bile acids from cholesterol intermediates in the liver but also in the removal of cholesterol by side chain hydroxylation in extrahepatic tissues. The enzyme has been assayed by complicated methods using radiolabeled substrates or deuterium-labeled tracers. These methods may be inaccurate for measuring enzyme activity, because the amount of electron-transferring proteins may be insufficient for maximal velocity. To solve this problem, after solubilization of the enzyme from rat liver mitochondria with n-octyl-beta-d-glucopyranoside (OGP), we measured the enzyme activity by incubating the solubilized enzyme with saturated amounts of electron-transferring proteins. In our assay system, using 7alpha-hydroxy-4-cholesten-3-one (HCO) as a substrate, we could easily measure the product, 7alpha,27-dihydroxy-4-cholesten-3-one, with HPLC monitoring absorbance at 240 nm. The product formation was proportionate to the time up to 5 min and the protein concentration up to 0.5 mg of protein/ml. The maximal velocity of the enzyme was 1.1 nmol/min/mg of protein, which was 4- to 16-fold higher than previously reported values. A simple and accurate assay method for sterol 27-hydroxylase in rat liver mitochondria is herein described.

A 71-year-old Japanese woman complained of right upper abdominal fullness and pain. Computed tomography revealed a huge cyst in the right lobe of the liver, measuring 16 cm in diameter. She underwent laparoscopic deroofing of the liver cyst. On operation, needle aspiration of the cyst yielded clear serous fluid without any bile contamination. However, after the cyst was deroofed with laparoscopic coagulating shears, bile leakage was recognized from a tiny orifice in the cyst cavity. A catheter was inserted via the orifice for cholangiography, which demonstrated a communication with the biliary tract. The orifice was easily closed with a laparoscopic suturing device. Operation time was 5 hours and 30 minutes, and blood loss was 300 grams. Pathological examination of the liver cyst was consistent with a simple cyst. The postoperative course was uneventful, and the patient has had no recurrence to date at 13 months. Laparoscopic deroofing is a recommended treatment for a liver cyst even in the presence of cystobiliary communication.

Objective: To evaluate the effects of truncal vagotomy at the diaphragmatic level on the sphincter of Oddi (SO) motility., Summary Background Data: Cholelithiasis is a well-known late complication after gastrectomy and/or vagotomy. The mechanism of gallstone formation is only partly understood, and few studies address the effects of vagotomy on SO cyclic motility in conscious subjects., Methods: In conscious dogs, SO motility was recorded by retrograde infusion manometry through a duodenal cannula before and after bilateral truncal vagotomy at the diaphragmatic level. Effects of cholecystokinin-octapeptide and feeding were also evaluated before and after vagotomy., Results: SO cyclic motility and the gastroduodenal migrating motor complex continued to occur during postvagotomy fasting. Intermittent inhibitions of the SO and duodenal contractions disappeared during phase 3 of the migrating motor complex. SO basal pressure significantly decreased, whereas the amplitude significantly increased. Cholecystokinin-octapeptide inhibited SO contractions before and after vagotomy. The amplitude of SO contractions increased and their frequency decreased after feeding; however, these effects disappeared after vagotomy., Conclusions: SO cyclic motility and the effects of feeding change after truncal vagotomy at the diaphragmatic level. These facts may at least partly explain gallstone formation after gastric surgery and/or vagotomy.

Objective: To analyze factors affecting the recovery course of phase 3 activity of the gastric migrating motor complex after pylorus-preserving pancreatoduodenectomy (PPPD) and investigate effects of the recovery of gastric phase 3 on gastric emptying after feeding., Summary Background Data: Whether early recovery of gastric phase 3 during fasting would predict early recovery of the fed-state gastric emptying function after PPPD has not been well documented., Methods: Manometric recording from the gastric antrum was repeated at a weekly interval until the first appearance of gastric phase 3 in 57 patients after PPPD. Twenty-three clinical parameters were assessed as possible factors affecting the recovery course of gastric phase 3 by simple and multiple regression analyses. A gastric emptying study after feeding of a test meal was performed by the acetaminophen method and the values were compared between patients with and without gastric phase 3 after PPPD., Results: The mean period before the first appearance of gastric phase 3 was 38 days. Among 23 parameters, only lymph node dissection along the hepatoduodenal ligament significantly delayed recovery of gastric phase 3 after PPPD by univariate and multivariate analyses. The presence or absence of gastric phase 3 in the early postoperative period did not influence gastric emptying after feeding in the intermediate period after PPPD., Conclusions: Avoiding lymph node dissection along the hepatoduodenal ligament, if applicable, may contribute to early recovery of gastric phase 3 after PPPD. The recovery state of gastric phase 3 during fasting, however, is not necessarily consistent with the degree of improvement of gastric emptying after feeding.

Background: With progress in molecular biology, the presence of telomerase activity, P53 mutation and Ki-ras codon 12 point mutation has been reported in malignant tumours of the liver, pancreas and biliary tree. The purpose of this paper is to clarify the clinical implications of finding these three biomarkers in the peripheral blood of affected patients., Methods: Telomerase activity, P53 mutation, and Ki-ras codon 12 point mutation in the peripheral blood were examined among 86 patients with hepato pancreato biliary disease, both benign and malignant, and the results were compared with clinical findings., Results: Of 20 patients with benign conditions, only one patient with intraductal papillary adenoma showing severe dysplasia exhibited a biomarker (telomerase activity) in the peripheral blood. In total, there were 66 patients with various HPB carcinomas. Of 56 cancer patients studied pre-operatively, 16 were positive for more than one biomarker, 13 were positive for telomerase activity, 4 for P53 mutation (three at exon 7 and another at exon 8), and 2 for Kiras codon 12 point mutation (both in the second letter). Twelve of the 16 biomarker-positive patients had stage IV disease as opposed to 23 of 40 biomarker-negative patients. The resectability rate of the cancer was 38% in positive patients and 50% in negative patients. The one-year survival rate after resection was zero in positive patients and 15% in negative patients, but the difference was not significant (P=0.65). Of 32 patients with liver metastasis at the time of the molecular examination, eight were positive and 24 negative. Of 34 patients without liver metastasis, nine were positive and 25 negative. The development of subsequent liver metastases in those without them at the start was not significantly different in those with and without biomarkers (56 vs 36%: P=0.31)., Conclusions: The three novel biomarkers of the peripheral blood seemed to be of little value for screening of early malignant HPB neoplasms but may help to predict liver metastasis.

Gallbladder cancer is an extremely difficult disease to cure once metastases occur. In this paper, we explored the potential of G207, an oncolytic, replication-competent herpes simplex virus type 1 mutant, as a new therapeutic means for gallbladder cancer. Gallbladder carcinoma cell lines (four human and one hamster) showed nearly total cell killing within 72 h of G207 infection at a m.o.i. of 0.25 to 2.5 in vitro. The susceptibility to G207 cytopathic activity correlated with the infection efficiency demonstrated by lacZ expression. Intraneoplastic inoculation of G207 (1 x 10(7) pfu) in immunocompetent hamsters bearing established subcutaneous KIGB-5 tumors caused a significant inhibition of tumor growth and prolongation of survival. Repeated inoculations (three times with 4-day intervals) were significantly more efficacious than a single inoculation. In hamsters with bilateral subcutaneous KIGB-5 tumors, inoculation of one tumor alone with G207 caused regression or growth reduction of uninoculated tumors as well as inoculated tumors. In athymic mice, however, the anti-tumor effect was largely reduced in inoculated tumors and completely abolished in remote tumors, suggesting large contribution of T-cell-mediated immune responses to both local and systemic anti-tumor effect of G207. These results indicate that G207 may be useful as a new strategy for gallbladder cancer treatment.

A 49-year-old man with a history of acute pancreatitis was hospitalized with a diagnosis of pancreatic pseudocyst. Ultrasonography, computed tomography, and magnetic resonance imaging all demonstrated a homogeneous cyst, 9 x 4 cm in size, at the tail of the pancreas without mural nodules or septa. Because an intestinal structure was identified between the cyst and stomach preoperatively by computed tomography and endoscopic ultrasonography, laparoscopic cystogastrostomy was carried out instead of percutaneous or endoscopic cyst drainage. The cyst was exposed by dissecting the lesser omentum and found to have no adhesion to the surrounding tissues. Anastomosis was performed using an endoscopic linear stapler via small cystotomy and gastrotomy openings on the lesser curvature, which were then sutured laparoscopically. The postoperative course was uneventful. Laparoscopic surgery is recommended as a safe, reliable, and minimally invasive treatment for managing pancreatic pseudocyst.

Objective: To examine the differences in regeneration rates and functions of the liver at the time of and after hepatectomy in obstructive jaundiced rats with preoperative external and internal biliary drainage., Summary Background Data: The significance of biliary drainage before surgery is controversial in patients with obstructive jaundice., Methods: After biliary obstruction for 7 days, rats were randomly divided into three groups: obstructive jaundice and hepatectomy (OJ-Hx), external biliary drainage and hepatectomy (ED-Hx), and internal biliary drainage and hepatectomy (ID-Hx). The OJ-Hx group underwent hepatectomy without biliary drainage; the other two groups underwent hepatectomy after biliary drainage for 7 days. At the time of hepatectomy, all rats were provided with internal biliary drainage. On days 0, 1, 2, 3, and 7 after hepatectomy, the DNA synthesis rate and the concentrations of adenine nucleotides and malondialdehyde in the liver were determined as markers of the hepatic regeneration rate, energy status, and lipoperoxide concentration, respectively. Portal endotoxin concentrations were measured and serum hyaluronic acid concentrations were determined as an indicator of hepatic endothelial function., Results: The relative liver weight was significantly higher in the ID-Hx group than in the OJ-Hx group on days 1, 3, and 7 after hepatectomy and than in the ED-Hx group on days 1 and 2. The rate of hepatic DNA synthesis was significantly higher in the ID-Hx group than in the OJ-Hx and ED-Hx groups on day 1. The rate was similar in the ED-Hx and ID-Hx groups on day 2 but was significantly higher than in the OJ-Hx group. The hepatic malondialdehyde concentration was significantly higher on day 1 in the ED-Hx group than in the other two groups. It was lowest in the ID-Hx group throughout the study. Both biliary drainage procedures lowered the portal endotoxin concentration and serum hyaluronic acid concentration at the time of hepatectomy. The serum hyaluronic acid concentration was lowest in the ID Hx group. Hepatic adenine triphosphate concentrations and energy charge levels were similar among the three groups., Conclusion: Although both external and internal biliary drainage before hepatectomy improved serum liver function tests, portal endotoxin concentration, and serum hyaluronic acid concentration at the time of surgery, preoperative internal biliary drainage was superior to external drainage, as evidenced by the better liver regeneration and function after hepatectomy.

A case of bile duct injury during laparoscopic cholecystectomy finally necessitating right hepatic lobectomy is reported to re-emphasize the importance of preoperative and intraoperative assessment of the biliary tree. A 47-year-old Japanese woman underwent laparoscopic cholecystectomy for cholecystolithiasis. On postoperative day 5, fever and right hypochondralgia developed, and CT revealed fluid collection at the right hypochondrium. Percutaneous drainage was performed, and subsequent fistulography revealed a communication of the cystic cavity with the right posterior bile duct, which suggested injury of the aberrant hepatic duct. Conservative therapy, including the adaptation of fibrin glue, was performed, but closure of the fistula and cavity was not obtainable. Finally, a right hepatic lobectomy was performed four months after cholecystectomy. In this case, endoscopic retrograde cholangiopancreatography was unsuccessful preoperatively, and intraoperative cholangiography was not done. This case report re-emphasizes that the preoperative and intraoperative examination of the biliary tree is mandatory to avoid bile duct injury.

Objective: To study the recovery course of gastric emptying after Billroth I pylorus-preserving pancreatoduodenectomy (PPPD) and therapeutic effects of cisapride., Methods: To examine gastric emptying, acetaminophen was given, admixed in a pasty liquid meal, to 16 patients undergoing PPPD before surgery and at 1, 3, 6, 9, and 12 months after surgery. Cisapride was given orally to 10 patients before they received the acetaminophen regimen. Electrogastrography was performed at 2 weeks to 1 month after surgery in eight patients and at 6 to 12 months after surgery in seven patients., Results: Gastric emptying was delayed but returned to the preoperative level by 6 months after surgery. Pretreatment with cisapride accelerated gastric emptying during months 1 to 6 but not during months 6 to 12 after surgery. Electrogastrography frequently showed tachygastria 2 weeks to 1 month after surgery, but seldom 6 to 12 months after surgery., Conclusions: After Billroth I PPPD, gastric emptying is delayed but recovers by 6 months after surgery. Tachygastria may play a part in the pathogenesis of delayed gastric emptying, but it can be treated with cisapride.

The relationship between complex cystic ducts and cholelithiasis has seldom been investigated quantitatively. Thus we attempted a retrospective survey on two case series with and without cholelithiasis in a university hospital. A total of 500 patients who underwent endoscopic retrograde cholangiography were reviewed, 250 of whom had cholelithiasis and another 250 no gallstones. They were sampled at random during the period from 1979 through 1993. Parameters including the length, inner diameter and configuration of the cystic duct, and the angle formed by the cystic duct, and the axis of the gallbladder were compared between the groups with or without cholelithiasis. The patients with gallstones has significantly (p < 0.001) longer and narrower cystic ducts (a mean of 48 mm and 4 mm in length and diameter, respectively) than did those without stones (a mean of 28 mm and 7 mm, respectively). Moreover, patients with gallstones showed a significantly (p < 0.001) more acute angle between the gallbladder and the cystic duct than those without (a mean angle of 84 degrees and 119 degrees respectively). The overall frequency of the disfigurements of the cystic duct was significantly higher in the group with gallstones (99%) than in the group without (29%). The results therefore suggested that complex cystic ducts are associated with cholelithiasis.

To reevaluate the current features of spontaneous internal biliary fistulas, we reviewed 1,929 consecutive patients who had been treated for biliary tract diseases during the recent 12-year period. Thirty-three patients had internal biliary fistulas and the incidence was 1.9%. Of 33 patients, 20 were women and 13 were men with the average age 63 years, and their mean duration of illness was 4 years. A total of 37 fistulas were found and the most common type was choledochoduodenal (62%), followed by cholecystoduodenal (19%), cholecystocholedochal (11%) and cholecystocolonic (8%) fistulas. Internal biliary fistulas of thirty-one patients were caused by biliary stones and those of two patients by malignant tumors. All of the 17 bile samples examined were bacteria positive and the majority of calculi were brown pigment stones. All of the choledochoduodenal fistulas were correctly diagnosed by endoscopic retrograde cholangiography. In 14 patients with cholecystoenteric or cholecystocholedochal fistulas, direct evidence of the internal fistula was obtained only in 7 patients (50%) preoperatively. Pneumobilia, a small atrophic gallbladder adherent to the neighboring organs and a history of spontaneous disappearance of jaundice in elderly patients may indicate the presence of a cholecystoentric fistula. Since the preoperative diagnostic rate for internal biliary fistula involving the gallbladder is still low, care is necessary before and at the time of surgery especially during laparoscopic cholecystectomy for elderly patients with cholelithiasis.

Pancreatic arteriovenous malformation is a rare condition that may cause gastrointestinal bleeding. A 66-year-old man with large arteriovenous malformation at the pancreatobiliary region is described. The patient had recurrent episodes of hemobilia after cholecystectomy performed for the treatment of cholelithiasis. Enlargement of the arteriovenous malformation was documented by angiography performed before and after the cholecystectomy. Bleeding from the biliary tract was successfully controlled by transarterial embolization. Cholecystectomy may have caused a hemodynamic change at the pancreatobiliary region, leading to the enlargement of the lesion and hemobilia.

The effects of treatment with chenodeoxycholic acid (CDCA) or ursodeoxycholic acid (UDCA) on nucleation time, biliary lipid concentration, and vesicular lipid composition were studied. Gallbladder bile was collected at the time of surgery from 33 cholesterol gallstone patients who were divided into three groups: 16 untreated, 9 pretreated with CDCA (400 mg/day), and 8 pretreated with UDCA (600 mg/day) for 1-3 weeks before surgery. Control bile samples were also collected from nine patients without cholelithiasis. Nucleation time was prolonged significantly in both CDCA- and UDCA-treated groups [12.6 +/- 8.5 (SD) and 21.0 +/- 0 days, respectively] compared with the untreated gallstone group (3.3 +/- 3.2 days). Both treatments significantly decreased the proportion and concentration of both cholesterol and phospholipids present in the vesicular phase. Treatment with UDCA decreased the cholesterol saturation index more than did CDCA at the dose used in this study. In the CDCA-treated group, patients without much change in cholesterol saturation index (greater than 1.0) showed a prolongation of the nucleation time with a significant decrease in vesicular cholesterol concentration, indicating a shift of cholesterol from vesicles to micelles. UDCA-treated patients and CDCA-treated patients with decreased cholesterol saturation index (less than 1.0) showed a greater effect. The authors conclude that UDCA prolongs the nucleation time mainly by decreasing the cholesterol saturation index, whereas CDCA does so by the dual effect of lowering the cholesterol saturation index and shifting cholesterol from vesicles to micelles.

Our previous studies have shown a protective effect of propylthiouracil (PTU) pretreatment against the toxicity of cyclophosphamide (CP). The present study was undertaken to investigate the mechanism of the PTU protection. CP is metabolized by the cytochrome P-450 drug-metabolizing enzyme system in the liver to alkylating metabolites, to active antineoplastic agents, and to acrolein, the most toxic and least antineoplastic metabolite. Measurements of CP metabolites in blood and urine during a 4-hr i.v. infusion of CP (50 mg/kg body weight/hr) showed urinary acrolein excretion to be 2.5 times higher in control rats as compared to PTU-treated rats. Since it has been reported that urinary acrolein levels are directly related to the frequency and severity of hemorrhagic cystitis, it is concluded from our observations that prevention of hemorrhagic cystitis is probably mediated by the PTU effect on lowering urinary acrolein concentration and excretion. Serum alkylating activity was significantly higher in the PTU-pretreated rats, which may enhance the antineoplastic potential of CP.