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Background/aims: The aim of this study was to investigate the effect of 1α,25-dihydroxyvitamin D3 on proliferation of human pancreatic cancer cell lines and to identify related cell cycle regulatory proteins with antiproliferative effects., Methodology: Human pancreatic cancer cell lines SUIT-2 and its four sublines, and Panc-1, AsPC-1, and MiaPaCa-2 were treated with1α,25-dihydroxyvitamin D3. The number of cells was measured by the MTT method, and the cell cycle regulatory proteins were then analyzed by Western blotting., Results: Eight human pancreatic cancer cell lines expressed vitamin D receptor (VDR) mRNA. 1α,25-dihydroxyvitamin D3 inhibited proliferation of SUIT-2 and its sublines. We found p21 to be upregulated after 24 hours in S2-028, the cell line in which proliferation was most inhibited by 1α,25-dihydroxyvitamin D3., Conclusions: 1α,25-dihydroxyvitamin D3 inhibited proliferation of pancreatic cancer cells and is involved in the upregulation of cyclin-dependent kinase inhibitor p21.

Background/aims: Hepatocellular carcinoma (HCC) patients often have low platelet count (LPC). The aim of this study was to determine unique features of HCC patients with LPC., Methodology: HCC patients who underwent surgery were divided into two groups: LPC group (platelet count ≤100,000/mm³, n=84) and control group (platelet count >100,000/mm³, n=240). Surgical outcomes, risk factors for postoperative complications and prognostic factors were retrospectively compared., Results: HCC patients with LPC had poorer liver function, smaller tumors, less anatomical resection and more frequent postoperative liver failure than control group patients. Postoperative survival was not different between the two groups. Tumor invasion to the main branch or trunk of portal vein (Vp3, 4) was the only risk factor for postoperative substantial complications in the LPC group. Postoperative survival was worse in patients with tumor diameter ≥4 cm or multiple tumors and in those who underwent preoperative transcatheter arterial chemoembolization (TACE) in the LPC group by multivariate analysis. Among them, preoperative TACE were not prognostic factors in the control group., Conclusions: In HCC patients with LPC, Vp3, 4 patients should be carefully monitored after surgery and preoperative TACE is not recommended for long-term postoperative survival.

Background/aims: Although fecal diversion is reported to improve the quality of life (QOL) of the patients with active perianal disease, the effect of the concomitant abdominal surgery was not well studied. The aim of this study was to investigate factors that impair postoperative QOL of patients with Crohn's disease., Methodology: A SF-36v2 questionnaire was mailed to patients who underwent abdominal operation between January 2001 and February 2007. Patients were also asked about the medical therapy they were receiving., Results: Data from 50 patients were analyzed. Univariate analyses revealed that patients with active perianal disease had lower scores for role physical, bodily pain and social functioning than did patients without it. Social functioning and role emotional scores were lower in patients older than 40 years than in those younger. The physical component summary score was significantly affected in patients with active perianal disease. Fecal diversion had no effect on QOL after abdominal surgery for Crohn's disease. Multivariate analysis showed that the physical component summary score was significantly lower in patients with active perianal disease than in patients without it., Conclusions: Active perianal disease is an important factor that impairs QOL in patients who have undergone surgery for intestinal Crohn's disease.

Background/aims: The aim of this study was to investigate the effect of thrombin and the thrombin receptor protease-activated receptor (PAR)-1 on adhesion of human pancreatic cancer cell lines to extracellular matrices (ECMs) and to identify related integrins with these effects., Methodology: Human pancreatic cancer cell lines SUIT-2 and its four sublines, and Panc- 1, AsPC-1 and MiaPaCa-2 were treated with thrombin, PAR-1 agonist TRAP-6, PAR-1 antagonist SCH79797, or anti-integrin ±vβ3, ±vβ5 and β1 monoclonal antibodies. Cells were incubated for 45 minutes on micro titer plates that were pre-coated with ECMs (fibronectin, laminin, vitronectin, type IV collagen). The number of adherent cells was measured by the MTT method., Results: Eight human pancreatic cancer cell lines expressed PAR-1. Thrombin significantly enhanced adhesion of SUIT-2 and its sublines and MiaPaCa-2 to vitronectin, especially in the SUIT-2 subline S2-007. We obtained similar results on S2-007 cells through treatment with TRAP-6. However, SCH79797 inhibited the effect of thrombin. Furthermore, anti-integrin β1 antibody conspicuously inhibited 1U/mL thrombin-induced enhancement of adhesion to vitronectin., Conclusions: Thrombin significantly enhanced adhesion of pancreatic cancer cells to vitronectin through PAR- 1 depending on the presence of integrin β1. Suppression of thrombin action by anti-integrin β1 antibody will become a useful therapy against pancreatic cancer.

Background/aims: Delayed gastric emptying (DGE) is a specific, worrisome complication after pancreaticoduodenectomy (PPPD), whereas subtotal stomach-preserving pancreaticoduodenectomy (SSPPD) that excises the pylorus ring seems to be effective in reducing DGE. This study compared gastric emptying and nutritional status between PPPD and SSPPD over 1 year., Methodology: From June 2003 to December 2007, 41 patients (PPPD: 33, SSPPD: 8) were enrolled in this study to evaluate differences in gastric emptying and nutritional status at 1, 3, 6, 9 and 12 months after pancreaticoduodenectomy. Gastric emptying was evaluated by 13C-acetate breath test. Nutritional status (body weight, serum levels of total protein, albumin and total cholesterol) was similarly assessed., Results: At 1 month, gastric emptying evaluated at T1/2 (half-emptying time) was significantly prolonged in the PPPD but not in the SSPPD compared to the preoperative level. Thereafter, T1/2 was decreased and showed function significantly better preserved at 3, 6 and 12 months after PPPD than after SSPPD. Body weight recovery was significantly better at 6 and 12 months after PPPD than after SSPPD. Other nutritional parameters were better preserved in the PPPD during 1-year follow-up., Conclusions: PPPD seems to be a more suitable surgical procedure than SSPPD in regard to gastric emptying and nutritional status.

Background/aims: The aim of this study was to clarify the role of bile duct resection without hepatectomy (hilar resection) in hilar cholangiocarcinoma., Methodology: We retrospectively compared surgical results for hilar cholangiocarcinoma between 8 patients treated with hilar resection and 21 patients treated with hepatectomy., Results: All hilar resections were performed for Bismuth type I or II tumors with T2 or less lesions, whereas hepatectomy was done for type III or IV tumors excluding one type II tumor. R0 resection was equally achieved in both groups (62.5% in hilar resection group and 76.2% in hepatectomy group, p=0.469) and overall 5-year survival rates were comparable (21.9% vs. 23.6%, p=0.874). With respect to gross tumor appearance, R0 resection was achieved in all patients with papillary tumor in both groups with the excellent 5-year survivals (100% vs. 100%). In patients with nodular and flat tumors, R0 resection was achieved less frequently in the hilar resection vs. hepatectomy group (50% vs. 77.8%) mainly due to failure to clear the proximal ductal margin, resulting in poorer 5-year survival (0% vs. 18.7%)., Conclusions: Hilar resection may be indicated for papillary T1 or 2 tumors in Bismuth type I or II cholangiocarcinoma.

Background/aims: To investigate the efficacy of infliximab for complicated perianal Crohn's disease with special reference to maintenance therapy., Methodology: Between June 2002 and April 2009, 20 patients (15 men and 5 women, aged 31.4±2.9 years old (mean ± standard error)) with complicated fistulizing anal Crohn's disease underwent seton placement. For the induction therapy, intravenous infusion of infliximab was given 3 times after surgical treatment. Thereafter, infliximab was given every 8 weeks as maintenance therapy. Patients were followed-up for 31.8±4.2 months after the first infliximab infusion. The number of the infliximab treatments given was 13.6±2.5., Results: After induction therapy, complete response (CR) was observed in 8 patients (40%), partial response (PR) in 9 and progress disease (PD) in 3. With (n=17) or without (n=3) maintenance therapy following the induction therapy, CR was observed in 15 of 20 patients (75%). Of the 17 patients who received maintenance therapy, CR was of observed in 13 patients, of whom 7 patients showed PR or PD before maintenance therapy., Conclusions: Seton drainage and infliximab therapy is effective in the patients with fistulizing perianal Crohn's disease. Maintenance infliximab therapy might be effective in patients with perianal Crohn's disease.

Background/aims: Differences in hepatic organic anion transporters were compared in rats to identify a causative factor for early stage acute hepatic failure after 70% or 90% hepatectomy (Hx)., Methodology: Male Wistar rats (8 weeks, 250-330g) were randomly assigned to one of two groups for 70% Hx or 90% Hx, and sacrificed at 0, 6, 12, 24, 48, or 72 hours after Hx. Posthepatectomy expression of the bile salt export pump (Bsep), multidrug resistance proteins 2 and 3 (Mrp2, Mrp3), sodium-dependent taurocholate co-transporting polypeptide (Ntcp), and organic anion transporting polypeptides 1 and 2 (Oatp1, Oatp2) were analyzed by Northern blotting. Serum liver function tests were also performed., Results: Postoperative survival rates at 72 hours after 70% and 90% Hx were 100% and 50%, respectively. mRNA expression of Bsep and Mrp3 was increased after 90% Hx, while decreased after 70% Hx. These values were significantly greater at 12 and 24 hours after 90% Hx than after 70% Hx (p < 0.05). In contrast, Mrp2 expression was downregulated to a half of the preoperative level after 90% Hx, while increased after 70% Hx. mRNA expression of uptake transporters (Ntcp, Oatp1, Oatp2) was decreased after 70% Hx and 90% Hx with a similar extent. Total serum bilirubin and bile acid levels were significantly increased after both hepatectomy procedures with a greater extent after 90% Hx., Conclusions: Alteration of mRNA expression of Bsep, Mrp2 and Mrp3 may be characteristic behavior in the early stage of acute liver failure.

Background/aims: Lymph node metastasis (pN) is one of the most significant prognostic factors in patients with gastric cancer. The pN classification of the Japanese Gastric Cancer Association (JGCA) is based on the anatomical site of metastatic nodes from the primary tumor, whereas that of the International Union Against Cancer (UICC) is based on the number of nodes involved. The purpose of this study was to determine which system is more useful for predicting patient outcomes., Methodology: From 1992 to 2002, a total of 318 patients at our hospital underwent surgical resection with lymph node dissection for primary gastric cancer. Their medical records were examined, and the overall survival rates were compared between the two pN classification systems., Results: Under the JGCA system, there was a significant difference in patient survival between pN0 and pN1 and between pN1 and pN2 but not between pN2 and pN3. Under the UICC-TNM system, there was a significant difference in patient survival between all pN classes. When the JGCA-pN1 and JGCA-pN2 classes were regrouped as UICC-pN1 and UICC-pN2-3, respectively, the survival rate was still better for the UICC-pN1 class than for the UICC-pN2-3 class., Conclusions: The better differentiation of outcomes by the UICC-pN system suggests that the number of metastatic lymph nodes is more important than the anatomical site in predicting outcomes.

Background/aims: The purpose of the present study was to evaluate the attitude of medical students to laparosocopic surgery., Methodology: Two hundred and seven medical students completed a questionnaire regarding their visualization of, understanding of, and interest in observation of laparoscopic surgery via laparoscopic monitor (laparoscopic observation) and of open surgery, either directly (open direct observation), or via video monitor observation (open monitor observation). They were also asked about their willingness to become an operator (operator). Responses to each item were given as Likert-type scores ranging from 1 to 5., Results: The visualization score was significantly lower for open direct observation than for open monitor observation (P<0.001) and laparoscopic observation (P<0.001), with the significantly lower score for open monitor observation than for laparoscopic observation (P<0.001). The understanding score was significantly lower for open direct observation than for open monitor observation (P<0.01) and laparoscopic observation (P<0.01). Interest scores did not differ between the three observation methods. The operator score was significantly higher for open surgery than for laparoscopic surgery., Conclusions: Laparoscopic surgery provides good visualization of the operative field. However, students' interest in laparoscopic surgery is similar to those of open surgery.

Melanoma is a malignancy originating from melanocytes. The primary melanoma usually occurs on the skin, retina, anal canal or occasionally at other organs such as the esophagus, penis or vagina. Although melanoma represents about one-third of all metastatic lesions in the gastrointestinal tract, metastasis of melanoma to the GI tract, detected radiologically or endoscopically, is relatively rare. In most cases of malignant melanoma, recurrence and death occur within 10 years after treatment of the primary lesion. We herein report a case showing a recurrence 17 years after extirpation of primary malignant melanoma in the foot. A 65-year-old man, with a history of extirpation of a malignant melanoma in the sole of his foot 17 years before, presented with anorexia and severe anemia, and multiple duodenal tumors were pointed out with upper gastrointestinal endoscopy. Histologic examination of the endoscopic biopsy specimen revealed proliferation of large polygonal cells with distinct nucleoli, and malignant melanoma was diagnosed immunohistochemically. Further examination, including computed tomography and positron emission tomography with fluorodeoxyglucose, revealed systemic metastasis.

Background/aims: To provide medical students with good visualization and understanding of surgical procedures, we used video monitoring (Monitor) in the operating room and slide (Slide) and video (Video) presentation in the conferences. The purpose of this study was to evaluate the effect of these visual aids on surgical education., Methodology: One hundred and twenty-nine fifth- and sixth-year medical students completed a questionnaire regarding their visualization of, understanding of, and interest in all surgical procedures observed and procedures pertaining to their assigned patients. The score was collected on a Likert-type scores ranged from 1 for "poor" to 5 for "excellent"., Results: Visualization and understanding scores were significantly lower for direct observation than for Monitor (p<0.01 and p<0.001), Slide (p<0.001 and p<0.001) and Video (p<0.001 and p<0.001). Interest scores did not differ between observation methods. For all observation methods, understanding of and interest in the surgical procedures were significantly greater in relation to assigned patients than in relation to all patients observed., Conclusions: Video monitoring and slide and video presentations enhance students' understanding of and interest in surgical procedures. Contributing to the care of assigned patient also increases understanding of and interest in general surgery.

Background/aims: Almost all patients with stage II colorectal cancer are spared adjuvant chemotherapy, yet a considerable number of these patients die from the disease. The aim of this retrospective study was to identify factors negatively affecting survival of patients with stage II colorectal cancer treated by curative resection., Methodology: Study subjects were 88 patients who had undergone curative resection for stage II colorectal cancers at Miyazaki University Hospital during the period from 1987-1999. Patients were followed up for a minimum of 5 years or until death. The influence of clinical and pathologic variables on 5-year cancer-specific survival was assessed by uni variate and multivariate analyses., Results: The 5-year cancer-specific survival rate was 83.4%. Univariate analysis showed circular tumor growth to be significantly associated with decreased survival (p=0.0047). Furthermore, multivariate analysis showed that circular tumor growth significantly affected long-term cancer-specific survival of patients with stage II colorectal cancer (hazard ratio 1.184, p=0.025)., Conclusions: Circular tumor growth is an independent prognostic factor for patients with stage II colorectal cancer. The long-term prognosis of stage II colorectal cancer patients with circular-type carcinoma appear to be poor.

A 53-year-old Japanese female was referred to Miyazaki University hospital for the surgical treatment of gastric cancer. She had no symptoms and the presence of the complex cystic gallbladder with multiple and linear hyperechogenic septa was incidentally found by ultrasonography. Multicystic lesion of gallbladder was also observed on DIC-CT and MRCP. Neither the bile duct nor the pancreatic duct was dilated. The papilla of the Vater was of normal appearance endoscopically. Pathological study of the biopsy specimen from the type 3 tumor of the stomach showed poorly differentiated adenocarcinoma. Distal partial gastrectomy and cholecystectomy were performed. The gross examination of the gallbladder confirmed the presence of multiple thin septa with honeycomb appearance. Cancer cells were not observed histologically and final diagnosis was the multiseptate gallbladder. The postoperative course was uneventful. We herein report a rare case of multiseptate gallbladder showing the findings on DIC-CT and MRCP.

Background/aims: Hepatectomy combined with colectomy is the preferred treatment for patients with synchronous colorectal cancer and hepatic metastasis. However, the effects on hepatic reserve function of combining colectomy with hepatectomy are unclear. The purpose of this study was to determine liver regeneration and functions after hepatectomy with and without colectomy., Methodology: 23 rats underwent 70% hepatectomy (Hx group) and 23 rats underwent 70% hepatectomy with ileocecal resection (HCx group), and 6 rats just after surgery (day 0) underwent simple celiotomy. On days 0, 1, 2, 3 and 7 after surgery, the remnant liver weight, DNA synthesis rate, malondialdehyde concentration, hepatic Adenosine monophosphate, ADP, ATP, serum hyaluronic acid concentration and endotoxin level in the portal blood were measured., Results: In HCx group, the hepatic DNA synthesis rate on day 1 (p < 0.01) and the liver weight on day 7 (p < 0.05) were significantly lower, hepatic malondialdehyde concentration on days 1 and 2 (p < 0.05) was significantly higher and serum hyaluronic acid and portal endotoxin levels on day 1 were significantly higher (p < 0.01 and p < 0.05, respectively)., Conclusion: Addition of colectomy to hepatectomy impairs regeneration and endothelial cell function of the remnant liver; the impairment is associated with increased levels of portal endotoxin and hepatic lipoperoxide.

Background/aims: Gastrointestinal stromal tumor (GIST) is recently defined as a tumor expressing c-kit and sometimes showing liver metastasis. We investigated the outcomes of gastric GIST with special attention to the effect of repeated treatment for the patients with liver metastases., Methodology: Fourteen gastric GISTs were retrospectively reviewed and the significance of the NIH stratification system was examined., Results: Liver metastasis was found in 4 of the 14 patients with gastric GISTs. Three of the 4 patients had metachronous liver metastases and underwent repeated hepatectomies after the initial operation for gastric GIST. The other patient had a synchronous liver metastasis and underwent total gastrectomy and partial resection of the liver as the initial treatment. Two of the 4 patients have received treatments 6 times, including hepatic resection, microwave coagulation therapy (MCT), radiofrequency ablation (RFA), or by imatinib. All 4 patients with hepatic metastases are alive after the first hepatectomy with a mean survival time of 64.8 months with or without imatinib treatment. None classified to very low risk and low risk groups by the NIH system showed liver metastasis, while 43% of the patients classified to the high risk showed liver metastasis., Conclusions: Repeated surgical and medical treatments for liver metastases from gastric GIST improve survival. Special attention should be paid to be the high risk group categorized by the NIH classification system.

Background/aims: With the aim of preventing delayed gastric emptying (DGE) after pylorus-preserving pancreatoduodenectomy (PPPD), the new reconstruction method namely vertical retrocolic duodenojejunostomy in which the stomach and duodenum are brought down through the left side of the transverse mesocolon in a straight line thereby allowing these organs apart from the excised and anastomosed field and food passage by gravity is presented., Methodology: The preoperative and intraoperative factors, and short-term outcomes with special reference to DGE were compared between the two groups, PPPD (n = 12) and standard pancreatoduodenectomy (PD, n = 9). PD was similarly carried out except for hemigastrectomy for comparison. DGE was defined as a need for nasogastric tube decompression for 10 days or more., Results: Preoperative and intraoperative factors were not significantly different between the two groups. DGE was absent in both groups because nasogastric tube was removed within 7 days in all patients with a mean of postoperative day 3 in both groups. The days until liquid diet in the PPPD group were similar, but those until regular diet were significantly faster compared with the PD group. Postoperative hospital stay was similar between the two groups., Conclusions: The current reconstruction method may minimize DGE after PPPD.

Background/aims: Various staging systems containing both the tumor and liver function factors for hepatocellular carcinoma (HCC) have been proposed. The aim of this study was to evaluate the appropriate staging system in patients received hepatic resection for HCC., Methodology: The prognosis of the 235 patients who had undergone hepatectomy in these 15 years were analyzed according to the 7 staging systems, the Cancer of the Liver Italian Program (CLIP) score, the Barcelona Clinic Liver Cancer (BCLC) staging, the Groupe d'Etude et de Traitment du Carcinome Hépatocellulaire (GETCH) classification, the Chinese University Prognostic Index (CUPI) grade, the Japan Integrated Staging (JIS) score, modified JIS (mJIS) score, and Tokyo score. The capabilities to differentiate the postoperative survival between the neighboring score in each staging system were examined. Statistical analyses of the log-rank test, linear trend test, likelihood ratio (LR) test, Akaike Information Criteria (AIC), and Harrels' c-index were used., Results: The patients were widely distributed in the most of the staging system with the exceptions of GETCH classification and CUPI grade where almost all patients were classified to only the two groups. CLIP, JIS, mJIS, and Tokyo scores significantly differentiated the postoperative survival rate between 2 or 3 neighboring scores, whereas other staging systems only did between one. Statistical evaluations of prognostic stratification by the LR test, AIC, and Harrels' c-index showed that the JIS score system was the best among the 7 staging systems., Conclusions: JIS score is the best staging system for HCC in patients who undergo hepatectomy.

Background/aims: To investigate the effects of preoperative pancreatic function on gastric emptying, body weight, and quality of life after pylorus-preserving pancreatoduodenectomy., Methodology: Thirty-one patients who underwent pylorus-preserving pancreatoduodenectomy were divided into 2 groups according to preoperative pancreatic exocrine and endocrine function (normal vs. abnormal). Gastric emptying, body weight, and quality of life were evaluated before surgery, 1-2 months after surgery (short-term), and 6-12 months after surgery (long-term)., Results: Short-term body weight was significantly decreased in comparison to preoperative body weight regardless of preoperative exocrine and endocrine pancreatic function. Body weight returned to the preoperative level by 12 months after surgery in patients with normal preoperative pancreatic function but not in patients with abnormal pancreatic function. In both groups, gastric emptying was delayed at 1-2 months after surgery and then returned to the preoperative value by 12 months. Short-term quality of life did not differ from preoperative quality of life in either group, but long-term quality of life improved to beyond the preoperative level in both groups., Conclusions: Preoperative pancreatic function appears to significantly influence long-term body weight after pylorus-preserving pancreatoduodenectomy.

Hepatic angiosarcoma is a non-epithelial malignant tumor and a rare primary neoplasm accounting for only a 0.1% of primary liver malignant tumors. Hepatic angiosarcoma progresses rapidly; therefore, most cases are discovered at an advanced stage, and less than 20% of the patients have received surgery. The lack of specific symptoms and radiological findings leads to the delay of diagnosis resulting in the poor prognosis. To the best of our knowledge, only three patients have been reported to survive for more than one year after hepatic resection for angiosarcoma. We herein report a patient with hepatic angiosarcoma, 4 cm in size, who underwent hepatic resection after confirming the diagnosis as angiosarcoma by the intraoperative frozen section examination. The patient is still alive for more than 16 months postoperatively without any signs of recurrence.

Background/aims: Although the size and number of the metastatic liver tumors have been considered to be prognostic factors after hepatectomy in patients with colorectal liver metastases, the importance of these parameters is still controversial. The aim of this study was to evaluate the importance of the new factor, namely, the sum of longest diameters of the metastatic liver tumors (SLD)., Methodology: The medical records of 59 patients who had undergone hepatic resection for colorectal liver metastases were abstracted and these patients were completely followed-up., Results: The overall 5-year survival rate after hepatectomy was 38.5%, and median survival time was 25.9 months. The significant prognostic factors by the univariate analysis were the extents of vessel permeation and lymph node metastasis of primary colorectal carcinoma, the presence of extrahepatic metastasis, the longest diameter and SLD of the liver tumor, surgical margin of the liver, and the serum level of carcinoembryonic antigen. Multivariate analysis showed that SLD (P=0.026) and extrahepatic distant organ metastasis (P=0.008) were the independent prognostic factor., Conclusions: SLD is a useful and significant predictor for survival after hepatectomy in patients with colorectal liver metastases.

Background/aims: The differentiation between benign and malignant jaundice is sometimes difficult even with modern diagnostic modalities. With recent advances in molecular biology, Ki-ras point mutation in codon 12 and p53 mutation have been reported as novel biomarkers of hepatobiliary and pancreatic carcinoma. The purpose of this study was to compare exfoliative bile cytology and biomarkers of the bile in patients with hepatobiliary and pancreatic diseases., Methodology: Cytologic examination and novel biomarkers, point mutations of codon 12 of Ki-ras and p53 mutations, were examined in the biliary tract bile aspirated through percutaneous transhepatic biliary drainage (PTBD) tube in 30 Japanese patients with benign and malignant hepatobiliary and pancreatic diseases., Results: Sensitivity of the exfoliative bile cytology for malignant conditions was 31% and specificity 100%, while sensitivity of molecular markers of the bile was 25% and specificity 93%. When the cytologic examination and genetic study were in conjunction, sensitivity increased to 50% and specificity remained 93%., Conclusions: These findings suggest that genetic examinations of the bile, when used in conjunction with cytology, may improve the diagnostic yield for suspected malignant tumors of the hepatobiliary and pancreatic system.

The metabolism of orally administered dehydroepiandrosterone (DHEA) by male and female golden Syrian hamsters was examined by quantification of DHEA and dehydroepiandrosterone sulfate (DHEAS) in gallbladder bile, urine and feces using high-performance liquid chromatography (HPLC). Plasma levels of DHEA and DHEAS were also determined by radioimmunoassay (RIA). After 5 days of oral DHEA administration (100 mg/kg body weight twice a day), RIA showed that plasma levels of DHEA and DHEAS were increased approximately 3-6 and 4-5 times, respectively, compared to controls. More than 95 % of circulating DHEA (S) in the peripheral blood was DHEAS. There was no significant sex difference in DHEAS plasma levels between male and female animals in the DHEA-supplemented group. However, 0.2 - 0.3 % of ingested DHEA was conjugated to DHEAS and excreted in urine by females, whereas less than 0.002 % was excreted in urine by males (p < 0.005). DHEAS was excreted in bile by males after DHEA supplementation, and the sex differences in DHEAS levels observed in bile were statistically significant (male, 18.7 +/- 7.5 vs. female, 5.6 +/- 3.1 micromol/l) (p < 0.005). Small amounts of ingested DHEA were excreted in an unchanged state in feces, and no sex difference was observed. These results suggest that there is a considerable sex difference in the conjugation and excretion of orally administered DHEA in the hamster.

Background/aims: Changes in bile acid synthesis during liver regeneration after hepatectomy is little known in humans. Since it has been reported that the serum 7 alpha-hydroxycholesterol levels reflect the hepatic bile acid synthesis and that the determination of bile acid synthesis is useful to assess the liver regeneration rate, we determined the serum 7 alpha-hydroxycholesterol level during liver regeneration after hepatectomy in clinical patients., Methodology: The serum 7 alpha-hydroxycholesterol levels were determined by gas-liquid chromatography-mass spectrometry-selected ion monitoring method before and on days 1, 3, 5, 7, 14 and 21 after hepatectomy in twenty consecutive patients., Results: The 7 alpha-hydroxycholesterol levels became lower between days 1 and 7, were increased on day 14, and then decreased on day 21 after hepatectomy. The patients with preoperative external biliary drainage showed a higher serum 7 alpha-hydroxycholesterol level than those without biliary drainage before hepatectomy. The former showed lower serum 7 alpha-hydroxycholesterol levels than the latter throughout the 21 days after hepatectomy. In patients whose liver resection rate was more than 50%, the serum 7 alpha-hydroxycholesterol levels were kept lower until 21 days after hepatectomy compared with those whose liver was excised less than 50%., Conclusions: It is concluded that the patients who had preoperative biliary drainage or major hepatic resection seem to have less hepatic reserve capacity for bile acid synthesis after hepatectomy.

Background/aims: The outcome of advanced gallbladder carcinoma is dismal despite aggressive surgery. The aim of this study was to evaluate the surgical outcome and prognostic factors for patients with gallbladder carcinoma and to identify patients who may benefit from radical surgery., Methodology: Fifty-six patients who underwent surgical resection of gallbladder carcinoma were retrospectively reviewed. Their tumor markers, operative management, pathological factors and survival were analyzed., Results: The serum carcinoembryonic antigen level was elevated in 9 of 51 patients (18%) with data available as was the serum carbohydrate antigen 19-9 level in 14 of 47 patients (30%). Univariate analysis showed that jaundice, serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels, the number, size, macroscopic type, and histological grade of the tumor, the depth of tumor invasion (pT), pathological stage, lymph node metastasis (pN), lymphatic invasion, vascular invasion, perineural infiltration, curability of lymph node dissection and surgical margins have prognostic significance for survival. Multivariate analysis revealed jaundice, high histological grade, pT3 or pT4, and surgical margins were independent prognostic factors for survival., Conclusions: Preoperative serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels are potential predictors and informative for survival. There are still difficulties to treat gallbladder carcinoma infiltrating beyond subserosa or revealing jaundice.

Background/aims: To investigate the therapeutic efficacy of intraoperative radiation for carcinomas of the bile duct and ampulla of Vater., Methodology: Postoperative morbidity, mortality and survival of patients undergoing surgical resection of ampullary cancer (n = 19) and bile duct cancer (n = 28) were retrospectively compared between two groups with and without intraoperative radiation., Results: Background items (age, gender, preoperative laboratory data, operative time and bleeding volume, tumor stage) did not differ significantly between the two groups. The predominant postoperative complication was leakage of pancreatic juice, which occurred in similar rates in both groups. No significant differences were noted in the 3-year survival rates between the resection plus intraoperative radiation group and resection alone group (60.0% (n = 5) vs. 50.1% (n = 13) for ampullary cancer; 0% (n = 4) vs. 27.1% (n = 24) for bile duct cancer, respectively). The main causes of recurrence were distant metastasis for ampullary cancer and microscopic residue of carcinoma for bile duct cancer., Conclusions: The combination of intraoperative radiation and resection may add no significant benefit to patients with ampullary and bile duct cancer when compared with resection alone.

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.

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.

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.

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.

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.

Background/aims: Even with the recent advances of diagnostic and therapeutic modalities, the clinical course of patients with pancreatic cancer remains dismal. Five-year survivors are rare, cure is exceptional, and the operative mortality rate is significant. In this study, univariate and multivariate retrospective analyses were performed with regard to the prognostic parameters to clarify the problems in order to improve survival rates after surgical resection., Methodology: Clinical courses of 60 Japanese patients with pancreatic cancer who underwent surgical resection in one Japanese University Hospital were reviewed to scrutinize the influence of 22 prognostic (9 host-side, 5 operative and 8 tumor-side) factors. A special reference was made on intra-operative radiation therapy, portal vein resection, lymph node dissection around the aorta, and conventional pancreatoduodenectomy versus pylorus-preserving pancreatoduodenectomy in pancreatic head cancer., Results: Univariate analysis showed that operation time, comprehensive stage, comprehensive curability, histopathologic grade of differentiation and histopathologic venous invasion were statistically significant factors. Multivariate Cox regression analysis regarding the 5 profound factors showed that histopathologic grade of differentiation and histopathologic venous invasion were independently significant factors. The 1- and 3-year survival rates of 18 patients with intra-operative radiation therapy were 56% and 39%, while those of 36 patients without intra-operative radiation therapy were 54% and 18%. The 1- and 3-year survival rates of 43 patients with PV0,1 were 58% and 28%, while those of 17 with PV2,3 were 50% and 10%. Three patients with PV2 in 1 and PV3 in 2 underwent a portal vein resection. Two of the 3 patients were dead from liver metastasis 3 and 5 months after a surgical resection of liver metastasis. The 1- and 3-year survival rates of 17 with radical lymph node dissection including the para-aortic area were 61% and 26%, while those of 27 without para-aortic lymph node dissection were 66% and 25%. Of the 17 patients, the para-aortic lymph node was metastasized in 1 patient. The 1- and 3-year survival rates of 31 with pancreatoduodenectomy were 53% and 18%, while the 1- and 3-year survival rates with pylorus preserving pancreatoduodenectomy were 68% and 28%, respectively., Conclusions: These findings suggest that the clinical outcome after surgical resection of pancreatic carcinoma depends on tumor-side factors not operative parameters or host-side parameters. The clinical course seems to rely upon the nature of pancreatic cancer not upon the operative procedure.

Background/aims: The Ki-ras gene located at 12p, encodes the GTP binding protein involving the signal transduction system and concerns cell proliferation and differentiation., Methodology: Pancreatic tissues were obtained from 37 patients with various pancreatic diseases. Ki-ras codon 12 point mutation and p53 (exon 5-8) mutation were examined in 3 patients with chronic pancreatitis, 9 mucinous adenoma of the pancreas (2 with mucinous cystadenoma and 7 with intraductal papillary-mucinous adenoma), 22 pancreatic ductal carcinoma, and 3 serous cystadenoma., Results: On usual pancreatic exocrine ductal lesions, Ki-ras point mutation was evident in 0% (0/3) of chronic pancreatitis, in 56% (5/9) of mucinous adenoma, and in 57% (12/21) of ductal carcinoma, the mutation being located in the second letter in 18 and in the 1st letter in 2. One Ki-ras codon 12 positive pancreatic cancer showed Ki-ras codon 12 point mutation in the surrounding pancreas (2nd letter mutation in both areas). p53 mutation was present in 0% (0/1) of chronic pancreatitis, in 0% (0/8) of mucinous adenoma, while it was evident in 29% (6/21) of pancreatic ductal carcinoma, the mutation being situated in exon 5 in 3, in exon 6 in 1, and in exon 7 in 2. In 3 patients with serous cystadenoma, there was no mutation in Ki-ras codon 12 or p53 (exon 5-8)., Conclusions: These findings suggest that Ki-ras point mutation is involved in the early events of pancreatic ductal carcinoma, while p53 mutation is intricated in the late phase of pancreatic ductal carcinogenesis and the histogenesis of serous cystadenoma is different from that of pancreatic exocrine ductal lesions including mucinous adenoma and ductal carcinoma.

A successful resection rate for diffuse bile duct carcinoma is low. Major hepatectomy combined with pancreatoduodenectomy is a possible choice for curative resection, but the post-operative mortality rate after such an extensive surgery has been reported to be high. The main reason for post-operative death is liver failure. With the aid of pre-operative portal vein embolization, major hepatectomy (left lobectomy and extended right lobectomy with caudate lobectomy) and pylorus-preserving pancreatoduodenectomy was successfully applied to 2 patients with diffuse bile duct carcinoma as a one-stage surgery. We herein report these 2 cases discussing the usefulness of pre-operative portal vein embolization.

Background/aims: The postoperative course of patients with bile duct carcinoma after surgical resection remains dismal. The purpose of this study was to examine the mode of spread from the original site of the carcinoma and its prognostic significance., Methodology: A total of 46 Japanese patients with extrahepatic bile duct carcinoma who underwent surgical resection from January 1976 to August 1995 were retrospectively reviewed., Results: Out of 24 patients with upper bile duct carcinoma, 16 (67%) were papillary or well differentiated tubular adenocarcinoma of the polypoid or nodular type on gross configuration, whereas 7 of 11 patients (64%) with lower bile duct carcinoma had moderately differentiated tubular adenocarcinoma or poorly differentiated adenocarcinoma of the annular constrictive or diffusely infiltrating type (p < 0.01). A noteworthy feature was perineural invasion (18/24, 75%) in the former group. Lymphatic permeation and venous invasion were seen in 50% and 38% of the former group and these were present in 73%, and in 73% of the latter (p < 0.01). Lymph node metastasis was most frequent in patients with lower bile duct carcinoma (5/11, 45%). Periductal spread along the bile duct toward the liver was more frequent and extensive in the infiltrating type than in the polypoid, nodular, or annular constrictive type. Carcinoma of the polypoid type often extended along the mucosa and rarely through the periductal layer. The mean distance between the edge of carcinoma invasion estimated by cholangiography and that proved by histology on the resected specimens was 6.1 +/- 6.1 mm in the hepatic and 6.2 +/- 9.1 mm in the duodenal direction. In all 11 patients with lower bile duct carcinoma, surgical margins were free of cancer cells, while they were affected by malignant cells in 17 of 24 patients with upper bile duct carcinoma. Univariate log-rank analysis showed that venous invasion, perineural infiltration, and the presence or absence of cancer cells at the cut edge of the bile duct in the hepatic direction and at the resection margins in the transverse direction were significant prognostic factors. Multivariate Cox regression analysis revealed that cancer cells at the edge of the bile duct in the hepatic direction constitute a significant and independent prognostic variant., Conclusions: Extrahepatic bile duct carcinoma should be excised to a distance of 1.5 cm from the edge of the carcinoma as estimated on cholangiography to achieve cancer-free margins, especially at the resected margins in the hepatic direction.

The effect induced by endoscopic sphincterotomy on biliary lipids and bile acid composition was examined by following up the seven patients prior to early (1-2 week) and late (0.5-1 year) after the endoscopic sphincterotomy. The concentrations of total bile acids, phospholipid and cholesterol were essentially constant throughout the one-year observation period. Cholesterol saturation indices were not significantly altered. No bile acid concentration changed significantly. The results indicate that endoscopic sphincterotomy has little undesirable effect on the biliary lipids and bile acid compositions over an observed period.