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Small cell carcinoma usually involves the lung and rarely affects the biliary tract, especially the cystic duct. In this article we report a case of small cell carcinoma of the cystic duct in a 46-year-old Japanese man. The patient presented with abdominal pain and jaundice. Imaging showed a small nodule in the cystic duct invading the common bile duct with dilatation of the proximal biliary tree. The hepatic artery and portal vein were free from invasion. Extended right hepatic lobectomy, cholecystectomy, and resection of the extrahepatic proximal bile ducts were performed together with lymph node dissection under the tentative diagnosis of carcinoma of the cystic duct. Histopathologic examination of the resected specimen revealed small cell carcinoma arising in the cystic duct and extending into the common bile duct. The postoperative clinical course was uneventful, and the patient is doing well without any signs of recurrence 1 year after the operation. To our knowledge this is the first documented case of a small cell carcinoma arising in the cystic duct.

Cholesterol 7alpha-hydroxylase (cholesterol-NADPH oxidoreductase, EC 1.14.13.17, 7alpha-hydroxylating) is known to have extremely sensitive sulfhydryl group(s). It is believed that a cysteine residue that has a sulfhydryl group plays an important role in the decrease of this enzyme activity. The amino acid sequences of cholesterol 7alpha-hydroxylase of five different mammalian species, human, rat, rabbit, hamster and mouse, revealed that these mammalian species contain eight cysteine residues that are well conserved. To identify which cysteine residues are responsible for the extremely high lability, we used the technique of the site-directed mutagenesis. Eight mutated genes of human cholesterol 7alpha-hydroxylase in which one codon for a cysteine residue was changed to that for alanine were prepared and expressed in COS-1 cells. The protein mass and enzyme activity of cholesterol 7alpha-hydroxylse obtained from these eight mutated genes were determined. While all mutated genes expressed the enzyme mass, two mutated genes did not express protein capable of catalyzing 7alpha-hydroxylation of cholesterol: in one mutant a codon for the 7th cysteine residue (Cys 444) was substituted to that for alanine and in the other mutant a codon for the 8th cysteine residue (Cys 476) was changed similarly. These results suggest that the 7th and 8th cysteine residues are important for expression of the enzyme activity. Based on the fact that Cys 444 exists in the heme binding region, Cys 476 was suggested to be responsible for enzyme lability.

Background/aims: There have been many supportive data that the postoperative changes in nutritional status are more favorable after pylorus-preserving pancreatoduodenectomy than after Whipple resection; however, few reports are available on the postoperative changes in subjective quality of life after pancreatoduodenectomy. The aim of this study was to compare the postoperative change in quality of life after pylorus-preserving pancreatoduodenectomy and Whipple resection., Methodology: A total of 36 patients (31 with pylorus-preserving pancreatoduodenectomy and five with Whipple resection) were studied regarding quality of life before and at short term (within two months) and at long term (six months to one year) after surgery, using a questionnaire. The questionnaire consisted of 13 physical and 10 psychosocial items. The medical records were also reviewed to evaluate their objective nutritional status. Postoperative changes in quality of life and nutritional status were compared between the pylorus-preserving pancreatoduodenectomy and Whipple groups., Results: Overall and physical quality of life scores dropped at short term and then recovered at long term in the pylorus-preserving pancreatoduodenectomy group, but showed a persistently low value even at long term in the Whipple group. The change in physical quality of life showed almost parallel changes with the nutritional status in both groups. However, the scores of psychosocial quality of life, which reflected the patient's mental status, remained low even at long term in both pylorus-preserving pancreatoduodenectomy and Whipple groups., Conclusions: Quality of life is more favorable after pylorus-preserving pancreatoduodenectomy than after Whipple resection, but long-standing mental health care is necessary in patients with pyloruspreserving pancreatoduodenectomy and Whipple resection.

We previously reported a novel small gene, designated hepatocyte growth factor activator inhibitor type 2 (HAI-2) related small peptide (H2RSP), in the process of the search for splicing variant forms of HAI-2 by 3(')-rapid amplification of cDNA ends method [Biochem. Biophys. Res. Commun. 288 (2001) 390]. Human H2RSP gene consisted of four exons spanning approximately 1kbp and was located in 11kbp downstream of HAI-2 gene. In this study, we cloned and characterized the mouse counterpart of H2RSP gene, which was located in 6.6kbp downstream of mouse HAI-2 gene, and analyzed the transcripts generated from both genes. Similar to human, mouse H2RSP mRNA (0.5kb) was detected abundantly in various tissues including the gastrointestinal tract, and has nuclear localization signal (NLS) in the lysine-rich region (exon 4), which was well-conserved between human and mouse genes. However, chimeric mRNA transcribed from both HAI-2 (exons 1-7) and H2RSP (exons 2-4) genes, which was found in the kidney, prostate, and placenta of human by Northern blot analysis, was not detected in mouse tissue even by a reverse transcription-polymerase chain reaction (RT-PCR). Instead of the chimeric mRNA, a novel splicing variant lacking putative transmembrane domain of HAI-2 was found in mouse but not in human as a putative secrete form of HAI-2. These results suggest that the organization of H2RSP and HAI-2 gene complex is well-conserved, but the usage of these genes was quite different between human and mouse.

Survival time of 73 patients with undiagnosed gallbladder carcinoma incidentally found after cholecystectomy treated between 1982 and 2000 was evaluated in relation to various variables, with special reference to the significance of the radical second resection. The most significant prognostic factor was the depth of tumor invasion as assessed by univariate and multivariate analyses (odds ratio 3.40, 95% CI 1.65-7.00, p < 0.001). None of the 23 pT1 patients received radical second resection, and all of them were doing well without recurrence at their last follow-up examination. The 3-year survival rate was 68% for patients with pT2 and 14% for patients with pT3. Patient characteristics for the 18 pT2 patients who underwent radical second resection were similar to the characteristics of the 25 pT2 patients who did not; nor did postoperative survival times differ significantly. Survival time was not correlated with the interval from initial to second surgery or the type of initial cholecystectomy (open vs laparoscopic). In 11 patients with pT2 whose surgical margin was judged positive at initial cholecystectomy, the radical second resection significantly lengthened survival time. Radical second resection tended to prolong the median survival period from 7 to 15 months in 7 patients with pT3, although the difference was not significant. In conclusion, patients with pT1 undiagnosed carcinoma need no further treatment. The redo surgery was found to prolong survival only in patients with pT2 with positive surgical margin at initial cholecystectomy.

We herein report a 64-year-old Japanese woman with cystadenocarcinoma of the liver without mesenchymal stroma which had been followed up by imagings for 12 years. A small round cyst grew from 1cm to 4 cm in diameter during 10 years. Thereafter, solid components were first detected in the unilocular cystic mass, which showed very rapid growth. Extended right lobectomy with right caudate lobectomy was performed. The histopathological diagnosis was cystadenocarcinoma of the liver without mesenchymal stroma. In this communication, we describe the progressive morphologic changes, shown on imagings, from a benign hepatic cyst to cystadenocarcinoma of the liver without mesenchymal stroma, and we briefly discuss the carcinogenesis of cystadenocarcinoma of the liver.

Objective: Our aim was to evaluate the performance of helical CT as an aid in the preoperative diagnosis of the spread of carcinomas of the gallbladder., Materials and Methods: Two radiologists retrospectively reviewed both hard-copy and soft-copy (on a monitor with multiplanar reconstruction capability) versions of helical CT scans (3-mm collimation and 3-mm reconstruction) of 21 patients who had undergone surgical resection for carcinomas of the gallbladder. The local spread of the disease was evaluated according to the TNM system, and the results were correlated to the pathologic findings. Inter- and intraobserver differences were checked with kappa statistics. Results of the consensus interpretations were used to calculate sensitivity, specificity, and accuracy of helical CT., Results: No significant inter- or intraobserver differences were found in any T category evaluation. The sensitivities of the hard-copy consensus interpretations in the diagnosis of T1, T2, T3, and T4 lesions were 33%, 64%, 80%, and 100%, respectively; specificities of hard-copy interpretations were 94%, 80%, 81%, and 95%, respectively. For soft-copy (monitor) consensus interpretations, the sensitivities for the diagnosis of T1, T2, T3, and T4 lesions were 33%, 73%, 80%, and 100%, respectively; the specificities of soft-copy interpretations were 94%, 80%, 88%, and 95%, respectively. Overall accuracy of the hard-copy interpretation was 83%; the overall accuracy of the soft-copy interpretation was not significantly different-86%., Conclusion: Helical CT provided 83-86% accuracy in the diagnosis of the local extent of carcinomas of the gallbladder, showing acceptable sensitivity and specificity for the T2 and more advanced lesions but poor sensitivity for the T1 lesions. Use of a monitor with multiplanar reconstructions of the CT data did not significantly improve the diagnostic accuracy.

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.

A total of 31 Japanese patients who underwent pylorus-preserving pancreatoduodenectomy from January 1998 through September 2000 were studied regarding quality of life and nutritional status before and within two months (short term) and six months to one year (long term) after surgery. Quality of life was estimated using a questionnaire consisting of 23 items (13 physical and 10 psychosocial domains). Nutritional status was assessed by body weight, hemoglobin concentration, serum concentration of albumin and cholesterol, and pancreatic function. These data were compared between 18 patients with end-to-end (Imanaga) and 13 with end-to-side (Traverso) gastrointestinal reconstruction. In both groups, physical quality of life scores dropped at short term, and then returned to the normal level at long term after operation, showing mostly parallel changes with the parameters of nutritional status. However, the scores of psychosocial conditions, which reflected the patient's mental health, remained low even at long term in both groups. The values of these parameters showed no statistical difference between the two groups at each time point. Postoperative quality of life and nutritional status were not different between Imanaga and Traverso reconstructions after pylorus-preserving pancreatoduodenectomy and mental health care would be necessary for at least one year after operation in both groups.

Tumor infiltrating lymphocytes (TILs) are candidates for adoptive cellular immunotherapy. Here we report on a patient whose TILs presented unusual lymphocyte antigens. Pleural effusions were collected from a 47-year-old man with recurrent cholangio cell carcinoma and malignant effusion. Effusion-associated lymphocytes (EALs) were separated by Ficoll-Hypaque gradient, and the EAL phenotype was determined by flow cytometry. The percentage of positive cells was determined for each lymphocyte-related differentiation antigen. The percentages of CD3+, CD19+, and CD16+ lymphocyte subpopulations among EALs were 20%, 7%, and 3%, respectively. Nearly 70% of EALs were CD3-/CD19-/CD56-/CD16- cells. The phenotypes of peripheral blood lymphocytes (PBLs) collected simultaneously from the patient's peripheral blood were CD3+ (52%), CD19+ (20%), and CD16+ (20%). When EALs were cultured in medium without pleural effusion, T cell-related antigens, but not B cell- or natural killer (NK) cell-related antigens, were newly expressed on EALs, and this expression reached a plateau after 48 h in culture. The proportions of CD3+, CD19+, and CD16+ cells were 69%, 7%, and 3%, respectively. However, when EALs were cultured in medium with pleural effusion, increased expression of T cell-related antigens was not observed; the proportions of CD3+, CD19+, and CD16+ cells were 16%, 6%, and 1%, respectively. Neither total cell numbers nor cellular viability of EALs changed significantly after in-vitro culture, suggesting that significant proliferation or death of EALs did not occur during the culture period. Co-culture of the patient's PBLs with autologous pleural effusion for 96 h did not alter the expression of lymphocyte-related antigens on the PBLs. These results indicate that expression of T cell-related antigens, but not B cell- or NK cell-related antigens, on EALs was blocked temporarily by the malignant pleural effusion. This is the first report concerning the existence of a large quantity of unclassified lymphocytes in which the T cell-related antigens were reversibly masked in the malignant pleural effusion.

Background: The importance of bile in liver regeneration after hepatectomy is unknown, although we have recently shown that preoperative internal biliary drainage is superior to external biliary drainage for liver regeneration in obstructive jaundiced rats. This study examined the hypothesis that the presence or absence of bile in the intestinal tract modulates cyclins and cyclin-dependent kinases after hepatectomy in rats., Methods: In male Wistar rats, bile was drained externally (ED group) or into the duodenum (ID group) for 7 days before 70% hepatectomy. Relative liver weight, DNA synthesis rate, and proliferating cell nuclear antigen labeling index were determined at the time of hepatectomy (day 0) and on days 1, 3, and 7 after hepatectomy. Posthepatectomy expressions of cyclin D1 and E and of cyclin D1- and E-associated kinases were serially analyzed. Hepatic function tests were performed., Results: No significant difference in liver function was found between the 2 groups at hepatectomy except for the lower albumin level in the ED group. The relative liver weight was lower in the ED group than in the ID group on day 3 after hepatectomy (ED, 2.58% +/- 0.06%; ID, 2.84% +/- 0.08%; P <.05). Both the DNA synthesis rate and proliferating cell nuclear antigen labeling index in the ED group (77 +/- 36 disintegrations per minute/microg DNA and 8.3% +/- 1.9%, respectively) were lower than those in the ID group (262 +/- 50 disintegrations per minute/microg DNA and 21.6% +/- 5.6%, respectively) on day 1 after hepatectomy (P <.05, respectively). Cyclin D1-associated kinase activity and cyclin D1 expression were not significantly different between the 2 groups. Cyclin E-associated kinase activity was lower in the ED group than in the ID group at 18 hours after hepatectomy (ED, 84% +/- 17%; ID, 146% +/- 28% of the value at 0 hour in the ID group; P <.05), although expressions of cyclin E and p27 binding to cyclin E were not significantly different between the 2 groups., Conclusions: These results suggest that the absence of bile in the intestine delays liver regeneration associated with cyclin E-associated kinase inactivation after hepatectomy.

Background: The correlation between diabetes mellitus and pancreatic carcinoma is well documented, but no criteria have been established for the efficient selection of a high-risk group among patients with diabetes mellitus., Methods: Eighty-seven patients were selected prospectively from outpatients with diabetes and underwent endoscopic retrograde pancreatography (ERP) according to the authors' original criteria, including the onset of diabetes after age 55 years, deterioration of diabetes or loss of body weight despite strict medical control, elevation of serum amylase and/or CA19-9 levels, and pancreatobiliary abnormalities on routine ultrasonography. The patients were divided into two groups according to the time from the onset of diabetes to ERP: Patients in Group A had recent-onset diabetes (within 3 years), and Group B patients had diabetes for > 3 years., Results: A total of 86 patients (excluding 1 patient with unsuccessful ERP who had undergone previous Billroth-2 gastrectomy) were enrolled. There were 33 males and 53 females, age 40-90 years, with a mean age of 65.1 years. ERP demonstrated pancreatic carcinoma, although it was advanced disease in all patients, at an extremely high rate of 7.0% (6 of 86 patients) with no serious complications. The prevalence of pancreatic carcinoma in Group A (13.9%; 5 of 36 patients) was significantly greater compared with Group B (2.0%; 1 of 50 patients; P = 0.0442). ERP with an indwelling balloon catheter and subsequent pancreatic juice sampling was performed in 49 patients, yielding positive cytology in 1 patient with pancreatic tail carcinoma, whereas measurements of carcinoembryonic antigen and CA19-9 levels in pancreatic juice were of no use in the diagnosis of pancreatic carcinoma., Conclusions: Selective ERP in patients with diabetes who were at high risk did not lead to the early diagnosis of pancreatic carcinoma, although this study showed that the 3-year period after the onset of diabetes was critical. A more aggressive diagnostic approach within this period in diabetic patients with the authors' criteria may contribute to the earlier diagnosis of pancreatic carcinoma., (Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10493)

We have previously demonstrated that there are two subgroups of patients with different types of biliary bile acid output after relief of obstructive jaundice by percutaneous transhepatic biliary drainage (PTBD). The reason for two groups is not clear but is possibly the difference in hepatic reserve function. The aim of this study was to examine the relation of biliary bile acid output to the hepatic ATP level and biliary excretion rate of indocyanine green (ICG) in humans. Patients whose bile could be collected through a PTBD tube participated in this study. The mean serum total bilirubin concentration was 12.7 mg/dl at the time of PTBD, decreasing to 1.1 mg/dl before surgery. These patients underwent curative resection for cancer of the bile duct, duodenal papilla, or pancreatic head after the relief of hyperbilirubinemia. Bile was collected at 1-hour intervals for 5 hours after intravenous administration of ICG (0.5 mg/kg) within a few days before surgery, and a small liver tissue sample was obtained immediately after laparotomy without using ischemic procedures. The concentrations of total bile acid and ICG in bile, the bile flow rate, and the bile acid output and ICG excretion rate in bile over 5 hours were determined. ATP concentrations in liver tissue were determined by high performance liquid chromatography. Results of hepatic ATP levels were correlated with the bile acid output and ICG excretion rate into bile. Both the biliary bile acid output (micromoles per 5 hours) and ICG excretion rate (percent of injected dose of ICG) over 5 hours were significantly correlated with the hepatic ATP level (p = 0.0190 and p = 0.0084, respectively). Neither the bile flow rate nor the serum liver function tests were related to the hepatic ATP level. Significant correlation was found between the bile acid output and the ICG excretion rate (p = 0.0127). Biliary bile acid output reflects the hepatic ATP level. Determination of the biliary bile acid output and ICG excretion may provide useful parameters for evaluating the hepatic energy status, which is essential for organ viability.

Transcriptional activation of nuclear factor (NF)-kappaB, signal transducers and activators of transcription (STAT) 3, activating protein (AP)-1 and CCAAT/enhancer-binding protein (C/EBP) plays an important role in liver regeneration by modulating cell cycle regulators. The regeneration of cirrhotic liver after hepatectomy is inhibited despite intact expression of growth factors. To elucidate the mechanism involved, regeneration responses in growth factor receptors, transcription factors, and cell cycle regulators after two-thirds hepatectomy were compared between rats with thioacetamide-induced cirrhotic and normal liver. The expression of c-met and epidermal growth factor receptor analyzed by RT-PCR and immunohistochemistry did not differ between the two groups. The activities of C/EBP and AP-1 evaluated by electrophoretic mobility shift assay were significantly inhibited in the cirrhotic group compared with those in the control group, but not those of NF-kappaB and STAT3. The expression of cyclin-D1, -E, and -A assessed by Western blot analysis was significantly decreased in the cirrhotic group compared with the control group. The level in p21(Cip1) or p27(Kip1) did not differ between the two groups. The liver regeneration estimated by the rates of [(3)H]thymidine incorporation into DNA and staining of proliferating cell nuclear antigen was significantly lower in the cirrhotic rats than in the controls. In conclusion, downregulation of cyclin -D1, -E, and -A expression, which may be induced by impaired activities of C/EBP and AP-1, is responsible for the decreased regenerative capacity of cirrhotic liver after partial hepatectomy., ((c)2002 Elsevier Science (USA).)

Background/aims: To examine whether serum hepatocyte growth factor and interleukin-6 levels are early parameters of postoperative liver dysfunction after hepatectomy., Methodology: The serum levels of hepatocyte growth factor and interleukin-6 were measured in 16 hepatectomized patients on the day of surgery (before surgery, immediately after hepatectomy, after completion of surgery) and on postoperative days 1, 3, and 5. Serum liver function tests were determined for 14 days after surgery and their results were correlated with serum interleukin-6 and hepatocyte growth factor levels., Results: Serum interleukin-6 and hepatocyte growth factor levels were elevated after surgery and these values were higher in patients who underwent hepatectomy greater than lobectomy in magnitude. The mean maximum value of interleukin-6 appeared on day 0 and was earlier than that of hepatocyte growth factor, which was found on day 1. Serum total bilirubin and alanine aminotransferase levels reached the maximum within 5 days after surgery. Multiple regression analysis showed that serum levels of interleukin-6 and hepatocyte growth factor on day 0 after surgery were significantly correlated with the postoperative maximum total bilirubin level (P < 0.0001). The maximum interleukin-6 level but not hepatocyte growth factor significantly correlated with the postoperative maximum bilirubin level (P < 0.02)., Conclusions: Both the serum interleukin-6 and hepatocyte growth factor levels are likely early indicators of postoperative liver dysfunction in patients after hepatectomy.

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/aims: Activation of reticuloendothelial system functions by the treatment with OK-432 has been reported to enhance liver regeneration. However, its effect on liver regeneration has not been studied after hepatectomy under ischemia/reperfusion which is in clinical use. The aim was to examine the effect of OK-432 on regeneration and energy status of the liver after hepatectomy under ischemia/reperfusion in rats., Methodology: Rats were randomly divided into two groups; OK-432 pretreatment and saline treatment (control) group. In the OK-432 group, OK-432 (2.5 mg/kg body weight) was administered intraperitoneally 24 hours before hepatectomy. In the control group, the same volume of physiological saline was administered in the same manner. Seventy percent hepatectomy was performed in both groups during the second 15-minute ischemia period after an initial 15-minute ischemia and 15-minute reperfusion periods. The survival after hepatectomy, relative liver weight, deoxyribonucleic acid synthesis rate, and hepatic adenine nucleotide and energy charge levels were examined immediately after hepatectomy and on postoperative days 1, 2, 3, and 7. Serum levels of total bilirubin, glutamic pyruvic transaminase, and hyaluronic acid were also measured., Results: All rats survived and the relative liver weight and deoxyribonucleic acid synthesis rate were not significantly different in the two groups. Serum total bilirubin and glutamic pyruvic transaminase levels were not significantly different in both groups. The serum concentration of hyaluronic acid immediately after hepatectomy was significantly higher in the OK-432 group than in the control group. The pretreatment with OK-432 had no significant effect on the levels of adenine nucleotides and energy charge in the liver., Conclusions: Under ischemia/reperfusion, pretreatment with OK-432 has no significant effect on regeneration and energy status of the liver after hepatectomy.

Extramedullary plasmacytoma is a rare variant of plasma cell tumor involving organs outside the bone marrow. The vast majority of extramedullary plasmacytomas present as a secondary tumor of systemic myelomatosis of the bone marrow. We experienced a patient with extramedullary plasmacytomas of the head and tail of the pancreas presenting as secondary masses from extramedullary plasmacytoma of the maxillary sinus that had been treated 5 years previously. A 38-year-old Japanese man had undergone radiation therapy for an extramedullary plasmacytoma of the maxillary sinus 5 years before the current presentation. He experienced severe upper abdominal pain in November 1999, when laboratory data showed elevation of the serum amylase level. Computed tomography showed two isodensity masses, in the head and tail of the pancreas. Angiography showed two hypervascular masses, one in the head and the other in the tail of the pancreas, and encasement of the portal vein trunk junction. Laparotomy was performed, with the tentative diagnosis of extramedullary plasmacytoma of the pancreas, in order to obtain a definite diagnosis. Intraoperative biopsy revealed that the two pancreatic masses were extramedullary plasmacytomas. External radiation therapy was performed after the operation. When a pancreatic mass is noticed in patients with a history of plasmacytoma, secondary extramedullary plasmacytoma of the pancreas should be considered as a differential diagnosis.

Autoimmune pancreatitis is a rare type of pancreatitis that is characterized by diffuse swelling of the pancreas and irregular stenosis of the pancreatic ductal system ("sclerosing" pantreatitis), caused by autoimmune processes. Previous reports have shown the complete form of the disease, but very few have presented follow-up imagings from the beginning to the complete form. We, herein, report a case of autoimmune pancreatitis starting as a localized form. A-56-year-old Japanese man developed obstructive jaundice. Ultrasonography showed a hypoechoic mass in the head of the pancreas, and endoscopic retrograde pancreatography (ERP) showed localized stenosis of the pancreatic duct in the head of the pancreas. Computed tomography (CT) showed enlargement, with a capsule-like rim, in the head of the pancreas. Internal biliary tube drainage was performed to relieve the obstructive jaundice. The patient was followed-up under the tentative diagnosis of localized "mass-forming" pancreatitis. Four months after the drainage, CT showed diffuse swelling of the pancreas, with a capsule-like rim, and ERP demonstrated diffuse irregular narrowing of the pancreatic duct. Glucose intolerance was noted for the first time. Steroid was given as a diagnostic treatment for autoimmune pancreatitis. Two months after initiation of the steroid treatment, the ERP findings were normal, and CT showed a normal pancreas. The biliary tube was removed, and the glucose intolerance was subsequently alleviated. To summarize, we report a case of autoimmune pancreatitis starting as localized "mass-forming" pancreatitis with a peripheral rim on imagings. It is very important to be well aware of the presence of the localized form of autoimmune pancreatitis.

Pancreas divisum is an embryologic anomaly of the pancreas that is characterized by a lack of fusion of the dorsal and ventral pancreatic ducts. It is rarely associated with pancreatic neoplasms. We report herein a rare association of pancreas divisum and serous cystadenoma of the pancreas. A 46-year-old Japanese woman presented with epigastralgia. Ultrasonography, computed tomography (CT) and magnetic resonance cholangiopancreatography revealed a multilocular cystic mass, measuring 7 cm in diameter, with a central stellate scar, in the body and tail of the pancreas. Angiography demonstrated a relatively hypervascular mass, suppressing the splenic vein. No arterial encasement was evident. Endoscopic retrograde pancreatography through the major papilla demonstrated only the duct of Wirsung; cannulation into the minor papilla was unsuccessful. In addition, CT showed a mildly dilated main pancreatic duct draining into the minor papilla. Distal pancreatectomy and splenectomy were performed, with the tentative diagnosis being serous cystic neoplasm of the pancreas, possibly malignant, and pancreas divisum. The cut surface of the resected specimen had a honeycomb-like appearance and the specimen consisted of multiple cysts of various sizes. Histopathological examination showed multiple cysts lined by a single layer of flat or cuboidal epithelial cells with glycogen in the cytoplasm. There was no evidence of malignancy. The histopathological diagnosis was serous cystadenoma of the pancreas. To the best of our knowledge, only three cases of serous cystadenoma of the pancreas associated with pancreas divisum have been reported. We report the fourth case of such an association, and briefly review the literature.

Background: Early gastric stasis is a frequent complication of pylorus-preserving pancreatoduodenectomy (PPPD). However, few reports have addressed this phenomenon in relation to the type of gastrointestinal reconstruction. We compared gastrointestinal motility and gastric juice output after two different types of gastrointestinal reconstruction following PPPD, end-to-side duodenojejunostomy after pancreaticojejunostomy and hepaticojejunostomy (group 1) and end-to-end duodenojejunostomy before pancreaticojejunostomy and hepaticojejunostomy (group 2)., Method: In a total of 25 patients, 10 in group 1 and 15 in group 2, who underwent PPPD, manometry was repeated to assess gastric and jejunal motility until the first occurrence of phase III activity of gastric cyclic motor activity (CMA). The plasma level of motilin was measured in each phase of the gastric CMA and compared between the two groups. The daily volume of gastric juice output through a gastrostomy tube was also recorded for comparison., Result: There was no significant difference in the time period for recovery of gastric phase III activity and gastric juice output between the two groups. However, abnormal contractions with an increased basal pressure appeared frequently in the afferent jejunal loop only in group 1. The plasma motilin level after PPPD showed no apparent cyclic change even after the recovery of gastric phase III in either group., Conclusion: Gastrointestinal reconstructive procedures have almost no effect on the recovery of gastric CMA. The plasma motilin concentration does not play a major role in the recovery of gastric CMA in the early postoperative period after PPPD.

Background/aims: Association of cholangiocellular carcinoma in patients with hepatolithiasis has been reported. However, its incidence depending on the kind of stones is obscure. The aim was to examine the association rate of cholangiocellular carcinoma in patients with hepatolithiasis with a special reference to the kind of intrahepatic stones., Methodology: One hundred and thirty-nine patients with hepatolithiasis who have been treated from 1973 to 1997 were retrospectively reviewed to examine the characteristics of cholangiocellular carcinoma. The type and location of intrahepatic calculi were analyzed., Results: Cholangiocellular carcinoma was found in 8 of 139 patients, the incidence being 5.8%. The incidence of carcinoma was more than twice in patients whose stones were located in intrahepatic bile duct only (9.3%; 5/54) than in those located in both intrahepatic and extrahepatic bile duct (3.5%; 3/85). Of 121 patients excluding 18 whose calculi were not available for classification, the kind of intrahepatic calculi was brown pigment in 106 patients (87.6%), cholesterol in 10 (8.3%), black pigment in 4, and fatty acid calcium in one. Cholangiocellular carcinoma was associated in 3 (2.8%) of 106 patients with brown pigment stones, 3 (30%) of 10 with cholesterol stones, in one with fatty acid calcium stones, and one patient whose stone was not available for analysis. The association rate of cancer was significantly (P < 0.01) higher in patients with cholesterol stones than those with brown pigment stones. One patient survived for 24 months after left lobectomy but the others died within six months., Conclusions: An early and attentive evaluation for the possible presence of cholangiocellular carcinoma is mandatory not only in patients with brown pigment stones but also in those with intrahepatic cholesterol stones.

We report a 74-year-old Japanese woman with a spontaneously vanishing pseudocyst in the remnant pancreas after pylorus-preserving pancreatoduodenectomy for intraductal papillary-mucinous adenoma of the pancreas. A cystic lesion appeared in the remnant pancreas 6 months after the operation and had disappeared 3 months later. When a cystic lesion is encountered in the remnant pancreas after pancreatectomy for mucin-hypersecreting tumor of the pancreas, pseudocyst, as well as recurrence, should be considered in the differential diagnosis. Additional resection would likely cause considerable morbidity, with loss of endocrine and exocrine functions.

There have been numerous reports that mucinous cystadenoma of the pancreas can transform to mucinous cystadenocarcinoma after cystenterostomy, but few authors have reported morphological changes long after cystenterostomy for mucinous cystadenoma. A 41-year-old Japanese woman had undergone cystgastrostomy at a nearby hospital 11 years before undergoing the treatment reported here. The preoperative diagnosis at the time of cystgastrostomy was a pancreatic cyst. At laparotomy a cyst, measuring 10cm in diameter, was found in the body and tail of the pancreas. The histopathological diagnosis of the cyst wall was mucinous cystadenoma of mild dysplasia. Computed tomography 10 years after the cystgastrostomy showed that the cyst had decreased in diameter from 10 cm to 5cm. Gastroscopy showed a scar at the cystgastrostomy site in the stomach. A complete resection of the mucinous cystadenoma was done, 11 years after the cystgastrostomy, because of the malignant potential. The resected specimen showed mucinous cystadenoma of mild dysplasia with structural and cellular atypia similar to that in the previous specimen. There was no malignant change. The patient was discharged after an uneventful postoperative course and no recurrence has been evident for 6 months to date. This case showed imaging and histopathological evidence of the slow-growing nature of mucinous cystadenoma of the pancreas.

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.

In the era of laparoscopic surgery, treatment strategies for common bile duct stones remain controversial. Laparoscopic choledochotomy is usually indicated only when transcystic duct exploration is not feasible. However, laparoscopic choledochotomy provides complete access to the ductal system and has a higher clearance rate than the transcystic approach. In addition, primary closure of the choledochotomy with a running suture and absorbable clips facilitates the procedure. Therefore, to avoid postoperative biliary stenosis, all patients with bile duct stones can be indicated for choledochotomy, except for those with nondilated common bile duct. Placement of a C-tube also provides access for the clearance of possible retained stones by endoscopic sphincterotomy as a backup procedure. C-tube placement, in contrast to T-tube insertion, is advantageous in terms of a relatively short hospital stay. In conclusion, laparoscopic choledochotomy with C-tube drainage is recommended as the treatment of choice for patients with common bile duct stones.

Background: FR167653 is a potent suppressant of production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta, which play an important role in hepatic and pulmonary injury due to ischemia/reperfusion of the liver and in liver regeneration after hepatectomy. We examined the effects of FR167653 on hepatectomy under ischemia/reperfusion in rats., Methods: After initial 15-min ischemia and 5-min reperfusion, 70% hepatectomy was performed during the second 15-min ischemia period in FR167653-treated (FR group) and saline-treated (saline group) rats. The survival rate, relative liver weight, TNF-alpha, IL-1 beta, DNA synthesis rate of the remnant liver, and histological change and adhesion molecule (ICAM-1) of the lung were examined. Serum glutamic pyruvic transaminase and hepatic malondialdehyde were also measured., Results: Expressions of TNF-alpha and IL-1 beta in the remnant liver were significantly inhibited in the FR group compared to the saline group. The survival was significantly better and pulmonary damage was less in the FR group after hepatectomy under ischemia/reperfusion. ICAM-1 expression of the lung was not altered after hepatectomy and was not significantly different between the two groups. Liver regeneration and injury were not significantly different between the two groups., Conclusion: FR167653 does not affect liver injury and regeneration after hepatectomy under ischemia/reperfusion, while it ameliorates pulmonary injury and improves the survival.

Objectives: Pancreaticobiliary maljunction, an anomalous union of the pancreatic duct with the common bile duct, is a risk factor for biliary carcinoma. We hypothesized that, in patients with pancreaticobiliary maljunction, persistent regurgitation of pancreatic juice into the biliary tract induces oxidative DNA damage. We assessed the expression of an oxidative DNA base-modified product, 8-hydroxy-2'-deoxyguanosine, in gallbladder epithelium., Design: Eleven noncancerous gallbladders from patients with pancreaticobiliary maljunction, 12 gallbladder carcinomas from patients without pancreaticobiliary maljunction and 14 noncancerous gallbladders from patients without pancreaticobiliary maljunction (control) were studied., Methods: Immunohistochemistry was performed for 4-hydroxy-2-nonenal-modified protein (as a marker for lipid peroxidation), 8-hydroxy-2'-deoxyguanosine and p53 gene product., Results: Stronger cytoplasmic staining of 4-hydroxy-2-nonenal-modified protein was observed in the gallbladder epithelium from patients with pancreaticobiliary maljunction than in epithelium from gallbladder cancer patients or from control subjects with normal gallbladders. Clear, strong nuclear staining of 8-hydroxy-2'-deoxyguanosine was observed in the gallbladder epithelial cells from patients with pancreaticobiliary maljunction. Densitometric quantitation revealed significantly higher expression of 8-hydroxy-2'-deoxyguanosine in gallbladder epithelial cells from patients with pancreaticobiliary maljunction (index 27.3 +/- 3.1) than in cells from patients with gallbladder carcinoma (11.4 +/- 1.5; P < 0.05) or from control subjects with normal gallbladder (6.4 +/- 1.0; P < 0.05). Positivity of p53 was 27% in gallbladder epithelium associated with pancreaticobiliary maljunction, 75% in gallbladder carcinoma epithelium and 0% in control epithelium., Conclusions: These results suggest that reactive oxygen species are produced in the gallbladder of patients with pancreaticobiliary maljunction and that oxidative DNA injury is related to carcinogenesis in these patients.

A 61-year-old man was admitted to our hospital with right lateral abdominal pain. The patient had chronic hepatitis type B and type C and was diagnosed as hepatocellular carcinoma in the anterior-superior segment of the liver by ultrasonography and abdominal computed tomography. Although laboratory examinations were within normal limits, the indocyanine green retention rate at 15 min was as high as 72.0% and the bromosulfophtalein retention rate at 45 min 17.3%. We additionally performed technetium-99m-galactosyl human serum albumin liver scintigraphy and liver biopsy, both of which indicated only mild chronic liver damage, indicating that the liver function is adequate for surgery. After partial hepatectomy, a pathological examination revealed well to moderately differentiated hepatocellular carcinoma with only mild chronic inflammation in adjacent liver tissue. The indocyanine green retention rate at 15 min is the best discriminating preoperative test for evaluating hepatic functional reserve, but when marked retention of both indocyanine green and bromosulfophtalein show the discrepancy with normal routine liver function tests, technetium-99m-galactosyl human serum albumin liver scintigraphy and liver biopsy are helpful diagnostic methods for assessing the preoperative hepatic function.

In order to re-evaluate the importance of the enterohepatic circulation of bile acid in the regulation of the activities of hepatic cholesterol 7alpha-hydroxylase, bile acid metabolism was examined in internal biliary bypass models of rats. A polyethylene tube was inserted into the common bile duct and another side of the tube was placed in the duodenum (DD), lower jejunum (JD), cecum (CeD), or transverse colon (CoD) as internal biliary bypass models and in the urinary bladder as an external biliary drainage (ED). After bile diversion for 7 days in each group, hepatic cholesterol 7alpha-hydroxylase activities, bile acid concentrations in bile, serum, and portal vein, biliary bile acid compositions, and intestinal absorption rates of infused labeled taurocholic acid were analyzed. Hepatic cholesterol 7alpha-hydroxylase activity was similar in the JD group compared with the DD group, however, it was significantly up-regulated in the CeD (227% of the DD group), CoD (312%), and ED groups (316%). Biliary, serum, and portal bile acid concentrations were not significantly changed in the DD, JD, and CeD groups but those were significantly lower in the CoD and ED groups compared with the DD group. The proportion of the secondary bile acids was significantly increased in the CeD group and was decreased in the CoD and ED groups. The absorption rate of taurocholic acid was almost 100%, 56%, and 23% in the JD, CeD, and the CoD group, respectively. As the cholesterol 7alpha-hydroxylase activity was not significantly changed in the JD group and the predominance of secondary bile acids did not suppress the enzyme activity in the CeD group, the luminal factor, which is absorbed in the presence of bile acids, and the bile acid metabolites are not likely the regulatory factor. The cholesterol 7alpha-hydroxylase activity seems to be primarily regulated by the intestinal absorption of bile acids and partly by the intestinal mucosal factor which is linked to the intestinal bile acid absorption.

For a pancreatic body or tail tumor, distal pancreatectomy with splenectomy (DPS) is a standard operation. Spleen-preserving distal pancreatectomy (SPDP) was introduced in order to preserve the organ and thus provide the patient with a better quality of life. Clinical data were compared between 38 Japanese patients with DPS and 9 with SPDP for benign tumors or tumor-like lesions at the body or tail of the pancreas at preoperative, early postoperative (< 3 months after operation), and late postoperative periods (>6 months after operation). The preoperative findings were not different between the two groups except for the significantly higher serum amylase levels in the SPDP group. Operation time, operative blood loss, and length of postoperative hospital stay were not different between the two groups. Pancreatic fistula occurred in 3 (8%) of the 38 patients in the DPS group and in 1 (11%) of the 9 patients in the SPDP group, abdominal abscess in 5 (13%) of the 38 patients in the DPS group and none (0%) in the 9 patients in the SPDP group. At short-term, clinical findings were not different between the two groups except for a significantly greater platelet count in the DPS group than in the SPDP group (46.8 x 10(4)/microl versus 29.6 x 10(4)/microl, P = 0.0081). At long-term after the operation, clinical findings, including the platelet count, were not different between the two groups. Computed tomography revealed a pseudocyst in 9 (53%) of 17 patients examined in the DPS group and in 3 (75%) of 4 patients examined in the SPDP group at short-term after operation. All patients with pseudocysts were asymptomatic. Two asymptomatic patients (one in the DPS group and one in the SPDP group) first developed a pseudocyst at long-term after the operation. The alteration of glucose tolerance was similar between the two groups. Postoperative pancreatic exocrine function (the N-benzol-L-tyrosyl-p-aminobenzoic acid test) was not different between the two groups. These data suggest that SPDP with preservation of the splenic vessels can be satisfactorily performed without elongating operative time and postoperative hospital stay or increasing risk of postoperative complications, with the exception of increased platelet count in the DPS group at short-term after the operation. Thus, SPDP is worth considering as one of the options for the treatment of benign lesions of the body or tail of the pancreas.

Background: Because T2 carcinoma of the gallbladder that invades perimuscular connective tissue without extension beyond serosa or into the liver has a hope for longterm survival, we attempted to clarify significant prognostic factors with respect to tumor- and surgery-related variables., Study Design: Of 65 patients with gallbladder carcinoma who had undergone surgical resection from 1983 to 1999, 28 had T2 carcinoma histologically proved. The significance of variables for survival was examined by the Kaplan-Meier method and log-rank test followed by multivariate analyses using Cox's proportional hazard model., Results: There were 17 patients with stage II carcinoma (T2 N0 M0), 6 with stage III (T2 N1 M0), and 5 with stage IVB. Lymph node metastasis was present in 11 patients (39%) and it reached to the peripancreatic head region (N2) in 5 of them. Lymphatic, venous, and perineural invasions were found in 68%, 57%, and 43%, respectively. With respect to tumor factors, the absence of perineural invasion (Odds ratio [OR] 16.77, 95% confidence interval [CI] 2.17-129.94, p = 0.0069), absence of lymph node metastasis (OR 15.00, 95% CI 2.08-108.33, p = 0.0073), and stage II (II versus III and IVB, OR 15.00, 95% CI 2.08-108.33, p = 0.0073) were significant factors related to good postoperative survival in the multivariate analysis. Surgical procedure (radical resection versus cholecystectomy, OR 4.31, 95% CI 1.34-13.82, p = 0.0142) and surgical margin (OR 7.41, 95% CI 2.19-25.13, p = 0.0013) were significant factors in the univariate analysis. Cancer-free surgical margins provided a significantly better survival (5-year survival rate, 62%); none with cancer-positive surgical margins survived for more than 27 months. In the multivariate analysis, surgical procedure was significant (OR 25.49, 95% CI 1.62-400.72, p = 0.021). Radical surgery, including extended cholecystectomy (resection of the gallbladder together with the gallbladder bed of the liver) and anatomic resection of liver segment 5 and of the lower part of segment 4, gave a significantly better 5-year survival rate than cholecystectomy (59% versus 17%). The 5-year survival rate after radical resection in patients with stage II was 75%; that in patients with stage III and IVB was 33%., Conclusions: Results suggest that radical surgery is the treatment of choice for patients with T2 carcinoma of the gallbladder. The presence of lymph node metastasis, perineural invasion, or both suggests the necessity of additional treatment after radical surgery.

Intraductal papillary-mucinous tumor of the pancreas is a spectrum of conditions ranging from benign to malignant, and very few papers have referred to the natural history of this disease. In this communication the indicators of malignancy were examined from a viewpoint of natural history. Follow-up computed tomographies (CTs) more than 6 months after the diagnosis were reviewed in 17 Japanese patients with intraductal papillary-mucinous tumor of the pancreas. They were divided into two groups by the presence or absence of morphological progressive changes by the follow-up CTs, and the clinicopathological features were compared between the two groups to examine possible malignant indicators. The 17 patients consisted of seven patients in the no-change group and ten in the progressive group. The distribution of the patients was not different with regard to age; gender; or presence or absence of pancreatitis, diabetes mellitus, or unique findings of the ampulla of Vater between the two groups. The dilatation of the main pancreatic duct (> or = 3 mm) was more frequent in the progressive group: (eight of ten patients; 80%) than in the no-change group (two of seven patients; 29%) (P = 0.03). Six (86%) of the seven tumors in the no-change group were located in the branch duct, whereas five (50%) of the ten in the progressive group were situated in the main pancreatic duct. Histopathologic diagnoses of the resected specimens of the four in the no-change group examined were intraductal papillary-mucinous adenoma in three and adenoma with moderate dysplasia in one, whereas the diagnoses in the six in the progressive group examined were adenoma in two, adenoma with moderate dysplasia in two, and carcinoma (invasive) in two. The patients with intraductal papillary-mucinous tumor of the pancreas with a dilatation of the main pancreatic duct at the time of diagnosis should be followed up more carefully than those without dilatation. Once progressive morphological changes are detected by the follow-up CTs surgical resection should be considered because of possible malignancy.

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.

Background: Bilirubin oxidative metabolites (BOMs) are generated from bilirubin as a result of its scavenging action against free radicals. During sepsis, excess amounts of free radicals are produced, and they play an important role in the pathophysiological process. We studied whether urinary excretion of BOMs would increase under septic conditions in humans and compared BOM levels with other well-established clinical parameters of inflammation., Methods: In 19 septic patients and 28 nonseptic control patients, the BOM concentrations in urine were measured by enzyme-linked immunosorbent assay with an anti-bilirubin antibody., Results: Urinary BOM levels in septic patients were much higher than those in control patients (21.6 +/- 2.5 vs 1.4 +/- 0.4 micromol/g creatinine, P < 0.001). Although there was a linear correlation between urinary BOM and serum total bilirubin levels (r = 0.392, P = 0.008), serum bilirubin levels were not significantly higher in the septic group than in the control group (P = 0.072). BOM levels correlated with body temperature (r = 0.801, P < 0.001), white blood cell counts in the peripheral blood (r = 0.590, P < 0.001), serum C-reactive protein (r = 0.653, P < 0.001), and the acute physiological and chronic health evaluation (APACHE II) score (r = 0.467, P = 0.003)., Conclusions: These results demonstrated a urinary increase in BOMs in septic patients. This increase indicates that urinary BOM level is a possible marker for continuous monitoring of sepsis severity in clinical practice., (Copyright 2001 Academic Press.)

CCAAT/enhancer-binding protein (C/EBP)-alpha stabilizes p21(WAF1), whereas activating protein-1 (AP-1) and C/EBP-beta enhance cyclin D1 and cyclin E expression, respectively, during the progress of liver regeneration. In this study, we investigated the differences in the transcription factors and cell cycle regulators between obstructive jaundiced and control rats before and after hepatectomy accompanied with a release of biliary obstruction by internal biliary drainage. The expressions and activities of C/EBP-alpha and -beta were significantly decreased in the jaundiced group concomitant with the significantly lower cyclin E expression after hepatectomy than in the controls. The activities of AP-1, cyclin D1 and p21(WAF1) were not significantly different between the two groups. These results suggest that obstructive jaundice inhibits hepatic expression and activity of C/EBP, resulting in the impaired cyclin E expression that is partly responsible for the cell cycle dysfunction after hepatectomy., (Copyright 2001 Academic Press.)

Most patients with ampullary carcinoma have obstructive jaundice without cholangitis. We experienced a patient with ampullary carcinoma who presented with obstructive jaundice and cholangitis, probably because of an accompanying periampullary choledochoduodenal fistula. A 77-year-old Japanese man had jaundice, high fever, and upper abdominal pain and was diagnosed, at another hospital, with obstructive cholangitis. On admission to our hospital, his symptoms and signs had subsided spontaneously. Abdominal ultrasonography showed cholecystolithiasis and dilatation of the common bile duct. Duodenoscopy showed an ulcerating tumor at the oral prominence of the ampulla of Vater and a periampullary choledochoduodenal fistula at the bottom of the ulcer. Biopsy from the fistula showed well differentiated adenocarcinoma. With a diagnosis of ampullary carcinoma with fistula formation, the patient underwent pylorus-preserving pancreatoduodenectomy. The diagnosis was confirmed by histology. This communication presents a unique case of ampullary carcinoma that caused obstructive jaundice, which subsided spontaneously but was associated with cholangitis caused by the divergent effects of the periampullary choledochoduodenal fistula formed by the carcinoma.

To evaluate the benefits and safety of laparoscopic cholecystectomy (LC) in patients with cardiac valve replacement (which frequently leads to cholelithiasis), 12 patients with cholelithiasis associated with cardiac valve replacement were studied. The patients were divided into two groups, of 6 patients each, according to the type of operation performed, open cholecystectomy (OC) or LC. The postoperative course was monitored with respect to laboratory data on postoperative days (POD) 1, 3, and 7. The mean duration of operation, blood loss, days to food resumption, length of hospital stay, and morbidity were compared between the two groups. Significant differences (P < 0.05) were found between the OC and LC groups in white blood cell counts on POD 1 (12 980 +/- 3040/mm3 vs 8300 +/- 1590/mm3), days to food resumption (2.7 +/- 0.4 days vs 1.0 +/- 0.7 days), and length of postoperative stay (15.8 +/- 1.0 days vs 10.8 +/- 1.6 days). There were no complications in the LC group, but 1 patient in the OC group had heart failure postoperatively. Our findings indicate the efficacy and safety of LC in patients with cardiac valve replacement.

From 1984 to 1998, a total of 2158 patients underwent hepatobiliary and pancreatic surgery, and 12 patients developed liver abscess after hepatobiliary and pancreatic surgery; thus, the incidence of liver abscess was 0.6%. The main reasons for liver abscess were anastomotic stricture in 5 patients, obstruction of percutaneous transhepatic biliary drainage (PTBD) tube in 3 patients, and portal vein and hepatic artery obstruction due to intraoperative radiation in 1 patient, transportal chemotherapy in 1 patient, chemo-lipiodolization in 1 patient, and unknown in 1 patient. Ten of the 12 patients initially underwent percutaneous transhepatic abscess drainage of whom 2 patients subsequently received surgical drainage. The other 2 patients were treated with antibiotics only. Eight of the 12 patients were cured, but 4 patients died. The reasons for death were sepsis in 3 patients and liver failure due to portal vein and hepatic artery obstruction in 1 patient. Our results indicate that liver abscess should be taken into consideration for patients with risk factors.

With the development of interventional radiology and endoscopy, the practice of inserting expandable metallic stents for malignant jaundice has become widespread. Many studies have compared surgical bypass with polyethylene stents, or metallic stents with polyethylene stents. However, few data are available on the comparison of surgical bypass and metallic stents. The aim of this study was to compare the patient's postprocedure course and the cost performance of surgical bypass and metallic stents in patients with unresectable pancreatic cancer. The parameters analyzed were the rates of procedural and therapeutic success, duration of hospital stay, prevalence of early and late complications, cost performance, and prognosis. The rates of procedural and therapeutic success were excellent with both palliative treatments. With surgical bypass, there was a low prevalence of late complications, but duodenal obstruction sometimes occurred in patients without gastric bypass. With metallic stents, there was shorter hospitalization and lower cost, but a higher prevalence of late complications. Stent occlusion tended to occur in patients with uncovered metallic stents. There was no difference in the prognosis between the two palliative treatments. Thus, in consideration of the poor prognosis of pancreatic cancer, in patients with unresectable pancreatic cancer, insertion of covered metallic stents would be preferable to surgical bypass, because of the subsequent short hospitalization and the low cost. On the other hand, in patients with a relatively long expected prognosis, or in those with existing duodenal obstruction, biliary bypass with gastrojejunostomy may provide an advantage.

The role of radical resection in the treatment of gallbladder carcinoma was examined with special reference to lymph node metastasis using two classifications: one proposed by the American Joint Committee on Cancer (AJCC) and the other by the Japanese Society of Biliary Surgery (JSBS). Histologic evaluations for the depth of tumor invasion (T), lymph node metastasis (N), stage, and follow-up for a mean period of 38 months (range 4-185 months) were completed in 52 patients with gallbladder carcinoma who underwent surgical resection from 1982 to 1997. The definition of T was similar in the two classifications. The extent of nodal involvement (N, AJCC; n, JSBS), stage, and survival were examined. In the absence of lymph node metastasis, the 5-year survival rate reached 71%. The 5-year survival rate in patients with involved nodes confined to the hepatoduodenal ligament, posterosuperior pancreaticoduodenal region, or along the common hepatic artery (N1 and part of N2 by AJCC; nl and n2 by JSBS) approximated 28%. In contrast, postoperative survival was poor in the presence of more extensive nodal involvement (rest of N2 by AJCC; n3 and n4 by JSBS), with no 2-year survivors. The definition of stage I was the same in both classifications, and all patients in this stage are alive. The 5-year survival rates in stages II and III by the AJCC were 70.7% and 22.4%, respectively, and those by JSBS 61.9% and 23.1%, respectively. Thus the survival rates in stages I to III were essentially similar irrespective of the staging system. Stage IV showed significantly worse survival than stage III by the JSBS classification. In contrast, the differentiation of stage IV from III by the AJCC was not significant because of the better survival in stage IV that contained any T with nodal involvement in the posterosuperior pancreaticoduodenal region and along the common hepatic artery. Radical resection should be considered for patients with stage I to III disease defined by either classification and applied to the tumor invasion up to T3 with nodal involvement confined to the hepatoduodenal ligament, posterosuperior pancreaticoduodenal region, and along the common hepatic artery. The role of radical surgery seems to be limited in patients with more extensive tumor invasion or lymph node metastasis.

Gastric stasis is a frequent complication of pylorus-preserving pancreatoduodenectomy (PPPD). We demonstrated that it might be attributable to delayed recovery of phase III activity of the gastric migrating motor complex due to low concentrations of plasma motilin caused by resection of the duodenum. Leucine 13-motilin is effective for treating gastric stasis, but it is not yet available for clinical use. Whether erythromycin would improve early gastric stasis after PPPD was tested clinically and by manometry. A manometric tube assembly and a gastrostomy tube were inserted in the stomach of 10 patients at PPPD for pressure recording from the gastric antrum and jejunum and for gastric juice drainage, respectively. After baseline recording, erythromycin 5 mg/kg was given intravenously on day 14 and saline as a placebo on day 17 every 4 hours four times a day. The daily volume of gastric juice output and the gastric motility index were measured. The mean period until the return of gastric phase III was 31 +/- 1 days. Erythromycin significantly increased the gastric motility index from 7.9 +/- 1.3 mmHg to 15.7 +/- 1.8 mmHg (p = 0.0005), whereas saline did not (7.2 +/- 1.6 mmHg to 6.5 +/- 1.2 mmHg; p = 0.21). Erythromycin significantly decreased the gastric juice output from 1,080 +/- 190 ml to 738 +/- 199 ml (p < 0.0001), but the saline injections did not (1,064 +/- 174 ml to 1,115 +/- 189 ml; p = 0.35). Erythromycin, a universally available motilin agonist, is a safe, effective, potent drug for the treatment of early gastric stasis after PPPD.

Background: For a pancreatic body tumor, distal pancreatectomy (DP) has been a standard operation. Segmental resection (SR) of the pancreas has been introduced as a less invasive procedure in consideration of preservation of the pancreatic functions and postoperative quality of life. Surgical stress and exocrine and endocrine functions of the residual pancreas were compared between DP and SR., Methods: Clinical findings including serum levels of C reactive protein (CRP), fasting blood sugar, a 120 min value of the 75 g oral glucose tolerance test, and N-benzol-L-tyrosyl-p-aminobenzoic acid excretion value (a pancreatic exocrine function test) were compared between 47 patients with DP and 10 with SR performed for benign pancreatic diseases., Results: Operation time was longer in SR (356 min) than in DP (272 min; P = 0.0123). Operative blood loss and peri-operative blood transfusion were not different between the two groups. Serum levels of CRP increased after the operation, reaching the peak on postoperative day 2 or 3, and decreased thereafter The peak of serum CRP level was similar between the two groups (13.4+/-1.8 mg/dl in SR and 14.8+/-1.1 mg/dl in DP). Postoperative hospital stay in 10 patients with SR (65 days) was significantly longer than that in 47 with DP (33 days; P = 0.0001). When postoperative complications were compared between the two groups, the incidence of pancreatic fistula was significantly higher in SR (4/10 [40%]) than in DP (4/46 [9%]; P = 0.0103). Abdominal abscess was seen in 30% of SR and in 11% of DP. Postoperative intra-abdominal hemorrhage was seen only in one patient with SR After DP, glucose tolerance deteriorated at short-term in nine of 24 patients examined and at long-term in two of five patients examined. Only one patient showed improvement of glucose intolerance at short-term after the operation. On the other hand, SR showed no alteration of the pancreatic endocrine and exocrine functions in eight patients examined., Conclusions: SR is superior to DP from the view-point of preservation of the pancreatic functions, although SR has a longer operation time, a longer hospital stay and a higher incidence of postoperative complications.

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: Frequent P53 mutations and Ki-ras codon 12 point mutations have been reported in pancreatic cancer. Pancreatic cancer often recurs in the liver and/or lymph nodes shortly after a surgical resection. The purpose of this study is to elucidate the occurrence of microcirculating cancer cells and micrometastasis in pancreatic cancer., Methods: P53 mutations and Ki-ras codon 12 point mutations were examined in the main tumor, liver, portal vein, and peripheral arterial blood, and para-aortic lymph nodes of patients with pancreatic cancer using molecular examinations., Results: P53 mutations in the main tumor were present in nine (29%) of 31 patients with pancreatic cancer, whereas a Ki-ras codon 12 point mutation was evident in 18 (62%) of 29 examined patients. The peripheral arterial and portal vein blood and liver were positive for gene abnormalities in one (5%) of 21, in none (0%) of 19, and in one (1%) of 20, respectively. A P53 mutation in the main tumor was evident in none (0%) of seven stage I or II carcinomas and in nine (38%) of 24 stage III or IV cases, whereas a Ki-ras codon 12 point mutation was present in four (67%) of six stage I or II cases and in 14 (61%) of 23 stage III or IV cases. In addition, 15 (71%) of 21 patients with gene abnormalities (Ki-ras codon 12 point and/or p53 mutation) in the main tumor showed lymph node metastasis at surgery, whereas five (42%) of 12 without gene abnormalities did not demonstrate lymph node metastasis. Two (29%) of six patients with gene abnormalities in the main tumor and without metastatic disease at surgery developed liver metastasis within 6 months after surgery, whereas all five (100%) without the gene abnormalities and metastatic disease at surgery did not develop the metastasis, with the sensitivity being 100%, specificity 44%, the predictive value of the positive test 36%, and the predictive value of the negative test 100%. Two patients who had gene abnormalities in the para-aortic lymph node were free from histopathological metastasis and these two patients developed para-aortic lymph node metastasis within 6 months after surgery., Conclusions: A molecular examination of Ki-ras codon 12 and p53 mutations therefore enables us to predict, to some degree, the occurrence of liver and lymph node metastasis in pancreatic carcinoma.

Gallstones formed after gastrectomy are bilirubinate stones probably associated with biliary stasis and infection. Effects of proximal duodenal transection performed during gastrectomy on interdigestive sphincter of Oddi cyclic motility possibly relevant to this phenomenon were investigated in four conscious dogs. Although the cyclic change in sphincter motility was still in concert with the duodenal migrating motor complex after duodenal transection, the mean period was shortened (p < 0.02), and the frequency (p < 0.005) and amplitude (p < 0.001) of sphincter phasic waves during phase III were decreased. The cyclic variation of basal pressure disappeared, and the mean basal pressure throughout the cycle was significantly reduced (p < 0.003). Transient inhibition of sphincter and duodenal contractions normally seen during phase III disappeared. Duodenal transection reversed the response of the sphincter to cholecystokinin-octapeptide from inhibition to stimulation and from reduction of the basal pressure to elevation. These data suggest that duodenal transection produces significant changes in interdigestive sphincter of Oddi motility, possibly contributing to augmented duodenobiliary reflux and then lithogenesis. Myoneural continuity between the stomach and sphincter of Oddi at the proximal duodenum may play an important role in maintaining normal biliary dynamics.

Background: Correlation between various gastrointestinal events and particular aspects of the migrating motor complex has been reported. This study correlates postcholecystectomy pain to variations in biliary pressure associated with the duodenal motor cycle., Methods: In 18 patients with postcholecystectomy pain and 10 control subjects, biliary and duodenal pressures were recorded simultaneously with microtransducers. After recording a spontaneous cycle, morphine was administered to induce a premature phase III and spasm of the sphincter of Oddi, and then cerulein was administered to stop the spasm., Results: Transient but significant elevations of biliary pressure occurred at duodenal phase III in both groups, but a greater percentage of the patients developed pain during phase III (89% vs. 20%, p<0.01). Morphine produced premature phase III and biliary pressure elevation, which were accompanied by pain more frequently in the patients than in the control subjects (78% vs. 30%, p<0.05). Biliary pressure dropped after the cerulein injection, relieving the pain in 13 of 14 patients and in 2 of 3 control subjects who had morphine-induced pain. The phase III-related pain was relieved by endoscopic sphincterotomy in 14 of 15 patients., Conclusions: The cyclic elevation of biliary pressure in coordination with phase III of the duodenal motor cycle may contribute to the development of pain in patients with postcholecystectomy biliary dyskinesia.

Background: Modulation of Kupffer cell functions by treatment with gadolinium chloride protects the liver against reperfusion injury. However, its effect on liver regeneration after hepatectomy under ischemia/reperfusion has not been studied. Using a common clinical ischemia/reperfusion technique, we examined the effect of gadolinium on liver regeneration after hepatectomy in rats., Methods: After an initial 15-minute ischemia and 15-minute reperfusion, 70% hepatectomy was performed during the second 15-minute ischemia period in gadolinium-pretreated (gadolinium group) and saline solution--pretreated (control group) rats. The 24-hour survival rate, relative liver weight, DNA synthesis rate, and hepatic adenosine triphosphate level were examined immediately after hepatectomy and on postoperative days (PODs) 1, 2, 3, and 7. Serum levels of total bilirubin, glutamic pyruvic transaminase, and endotoxin were also measured., Results: The 24-hour survival rate was significantly lower in the gadolinium group (67%) than in the control group (100%). On POD 1, the relative liver weight and DNA synthesis rate were significantly lower in the gadolinium group than in the control group. On POD 1, serum total bilirubin and endotoxin levels were significantly higher in the gadolinium group than in the control group. Immediately after hepatectomy, the hepatic adenosine triphosphate level was significantly lower in the gadolinium group than in the control group., Conclusions: Under ischemia/reperfusion, gadolinium pretreatment impairs liver regeneration and energy status after hepatectomy and decreases postoperative survival.

The effects of octreotide, a synthetic somatostatin analogue, were examined in 43 Japanese patients with pylorus-preserving pancreatoduodenectomy. The 43 patients were divided into two groups: 13 patients to whom a daily dose of 100 microg of octreotide was administered continuously and subcutaneously for the first 10 postoperative days (octreotide group); and 30 patients to whom octreotide was not administered (control group). Within 10 postoperative days, pancreatoenterostomy leakage was evident in one (7.7%) of the 13 patients in the octreotide group, but in five (16.7%) of the 30 patients in the control group. The total amount of the pancreatic juice drained externally during the first 10 postoperative days was 848+/-200 ml in the octreotide group and 1152+/-180 ml in the control group. When limited to 20 patients who underwent pancreatoenterostomy with total tube drainage, the amount of pancreatic juice in 10 patients in the octreotide group examined was 796+/-232 ml, which was significantly lower than the 1690+/-334 ml in 10 patients in the control group examined (P < 0.05). Of the 10 patients in the octreotide group, the amount of pancreatic juice during postoperative days 6-10 when octreotide was given was reduced to 382+/-104 ml compared to 445+/-108 ml during postoperative days 11-15 when octreotide was not administered (P < 0.05). These findings suggest that subcutaneous injection of octreotide, 100 microg per day during the first 10 postoperative days, inhibits pancreatic exocrine secretion and decreases pancreatoenterostomy leakage.

We examined the usefulness of preoperative chemotherapy using 5-FU and low-dose CDDP in patients with stage IVb gastric cancer. Between 1996 and 1998, seven patients with stage IVb gastric cancer who received preoperative chemotherapy achieved complete or partial response. One course of the chemotherapy was as follows: arterial or venous infusion of 5-FU (500 or 250 mg/day on day 1-5) and low-dose CDDP (5-10 mg/day on day 1-5) for three weeks. In addition to preoperative chemotherapy, biological response modifiers such as OK-432 and lentinan were used. We evaluated the response with abdominal or chest CT and tumor markers. Although preoperative chemotherapy did not improve the survival rate significantly, the prognosis of these patients seemed to be relatively good. Only slight side effects were found. These results suggest that preoperative chemotherapy using 5-FU and low-dose CDDP may be useful for patients with stage IVb gastric cancer.