Role of intraoperative enteroscopy for surgical decision making with Crohn's disease.

BACKGROUND: This study aimed to assess the role of intraoperative enteroscopy (IOE) in determining surgical treatment. METHODS: The IOE procedure was performed for 30 patients with Crohn's disease. The degree of stricture and the presence of active ulcer were examined. Preoperative diagnoses and intraoperative findings obtained by inspection and palpation were noted and compared with the IOE findings. RESULTS: Of the 78 intestinal strictures observed by IOE (42%), 33 were not found by preoperative examination. Of the 45 strictures confirmed by IOE to be severe (<15 mm in diameter), 8 were judged to be mild (15-25 mm in diameter) or were not even identified by intraoperative inspection and palpation. Active ulcer was found at 12 of 33 mild strictures, and all 12 strictures were surgically corrected. Of 11 severe strictures detected by IOE at previous surgical sites, 9 were found preoperatively, and 4 were judged to be mild on the basis of inspection and palpation. Stricture was found at the ileocecal valve by IOE in seven patients, but was not diagnosed preoperatively in two of these patients. CONCLUSION: Intraoperative enteroscopy provides useful information regarding the status of the lumen in patients with Crohn's disease.

Enhanced expression of hepatocyte growth factor activator inhibitor type 2-related small peptide at the invasive front of colon cancers.

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

Suppressor of cytokine signalling 1 in lymphocytes regulates the development of intestinal inflammation in mice.

BACKGROUND AND AIMS: Imbalance between pro- and anti-inflammatory cytokines produced by intestinal T cells induces inflammatory bowel diseases (IBD). However, the importance of regulation of cytokine signalling in IBD has not been fully clarified. We have demonstrated that suppressor of cytokine signalling 1 (SOCS1) is expressed in inflamed tissues in an experimental colitis model. In the present study, we investigated the role of SOCS1 in colitis models to clarify the mechanism of IBD development. METHODS: Intestinal T cells in transgenic mice expressing high levels of SOCS1 in lymphocytes (SOCS1Tg mice) were characterised by flow cytometric analysis and cytokine production from intestinal T cells was determined by ELISA. 2,4,6-Trinitrobenzene sulphonic acid (TNBS) induced colitis was induced in SOCS1Tg mice and severity was compared with control littermates by measurement of survival rates. Intracellular signalling was assessed by western blotting analysis. RESULTS: SOCS1Tg mice developed colitis spontaneously with age. Young SOCS1Tg mice less than 15 weeks of age, before the onset of colitis, were susceptible to TNBS induced colitis. Intestinal T cells of SOCS1Tg mice showed increased interferon gamma and tumour necrosis factor alpha production and decreased transforming growth factor beta production. Expression of cytotoxic T lymphocyte associated antigen 4 (CTLA-4), a negative regulator of T cell activation, in SOCS1Tg mice was severely impaired at the protein level although mRNA levels of CTLA-4 in SOCS1Tg mice were comparable with those in control mice. CONCLUSIONS: Our data suggest that SOCS1 plays an important role in the regulation of colitis by controlling intestinal T cell activation mediated through CTLA-4 expression.

Constitutive IL-8 expression in cancer cells is associated with mutation of p53.

We previously reported that most cancer cell lines constitutively express various cytokines including IL-8. But how IL-8 gene expression is regulated in cancer cells is still unclear. p53 tumor suppressor gene plays an important role in the regulation of transcription and is mutated in cancer cell lines. We investigated whether p53 status affects the constitutive expression of IL-8 in human cancer cells. SUIT-2 and RERF-LCOK cancer cells constitutively produced high levels of IL-8 in culture medium. Both cell lines were shown to carry a p53 mutation, and constitutive NF-kappaB transcriptional activity. To analyze whether p53 status mediates IL-8 expression, the effect of wild-type p53 (wt-p53) gene transfer on activation of NF-kappaB was determined in both cell lines. ELISA showed that the IL-8 concentration in medium decreased dose dependently by transient expression of wt-p53. Western-blot analysis showed no marked change in NF-kappaB protein levels in cell nuclei. EMSA showed no repression of NF-kappaB binding activity after transient expression of wt-p53. In contrast, luciferase reporter studies indicated that transcriptional activity of NF-kappaB is suppressed by transfection of wt-p53. These results show that wt-p53 gene transfer inhibits IL-8 production and NF-kappaB transcription activity in cancer cells and suggest that constitutive IL-8 production in cancer cells is associated with mutation of p53.

FR167653 improves survival and pulmonary injury after partial hepatectomy under ischemia/reperfusion in rats.

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.

Immunohistochemical detection of 8-hydroxy-2'-deoxyguanosine in gallbladder epithelium of patients with pancreaticobiliary maljunction.

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.

Quality of life after pylorus-preserving pancreatoduodenectomy.

BACKGROUND: With increasing numbers of long-term survivors after pylorus-preserving pancreatoduodenectomy (PPPD), postoperative quality of life (QOL) has become a great concern. However, few reports are available on data of the postoperative changes in QOL after PPPD. METHODS: A total of 20 patients were studied regarding QOL before and at short term (within 2 months), intermediate term (6 months), and long term (1 year) after PPPD, using a questionnaire. The questionnaire consisted of 13 physical and 10 psychosocial items. The medical records were also reviewed to evaluate objective nutritional status. Factors predicting delayed recovery of QOL were examined at intermediate term by univariate and multivariate analyses. RESULTS: Overall and physical QOL scores returned to the preoperative level at intermediate term after PPPD, showing parallel changes with the objective nutritional status. However, the scores of psychosocial condition, which reflected the patient's mental health, remained low even at long term. QOL scores at intermediate term in patients with pancreatic carcinoma were significantly lower than those with other diseases. Univariate analysis showed that preoperative body weight loss, impaired preoperative pancreatic exocrine function, long operative time, intraoperative radiotherapy, pancreatic carcinoma, and postoperative diarrhea were factors predicting the delayed recovery of QOL. Multivariate analysis revealed that preoperative pancreatic exocrine function significantly affected the delayed recovery of QOL. CONCLUSIONS: Preoperative supplement of pancreatic enzymes together with perioperative mental care would improve QOL at long term after PPPD.

Laparoscopically assisted resection of choledochal cyst and Roux-en-Y reconstruction.

UNLABELLED: Laparoscopic surgery for a congenital choledochal cyst was accomplished in five of eight adult patients for whom it was attempted (63%). Creation of a Roux-en-Y jejunal limb by midline minilaparotomy and hepaticojejunostomy using a laparoscopic sewing instrument facilitated the procedure. BACKGROUND: Congenital choledochal cyst is a good indication for laparoscopic surgery. However, only two case reports are available at this writing. METHODS: Eight adult patients, ages 19 to 61 years (mean, 32.6 years), underwent laparoscopically assisted resection of the choledochal cyst and Roux-en-Y hepaticojejunostomy. RESULTS: The whole procedure was accomplished in five patients (63%). The duration of the procedure ranged from 525 to 680 min (average, 616 min). Open conversion in three patients was necessitated by severance of a small common hepatic duct because of disorientation caused by previous laparoscopic cholecystectomy, electrocautery injury to the common channel distal to the anomalous pancreaticobiliary junction, or heavy adhesion around the cyst secondary to recent severe cholangitis. Creation of a Roux-en-Y jejunal limb by midline minilaparotomy and hepaticojejunostomy using a laparoscopic sewing instrument facilitated the procedure. CONCLUSIONS: Laparoscopically assisted resection of the choledochal cyst and hepaticojejunostomy are technically feasible and deserve further clinical trials.

Hepatectomy and marked retention of indocyanine green and bromosulfophtalein.

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.

Surgical bypass versus metallic stent for unresectable pancreatic cancer.

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.

Carcinoma arising in choledochocele.

BACKGROUND AND STUDY AIMS: Choledochocele has a potential for carcinogenesis, but no report has described malignant changes of the choledochocele in relation to pancreaticobiliary reflux because its anatomic form does not fit the criteria of pancreaticobiliary malunion (PBM). The aims of this study were to analyze the amylase level in bile in patients with choledochocele and to clarify whether the presence of a choledochocele predisposed to carcinoma. PATIENTS AND METHODS: Records of 2826 patients who had undergone endoscopic retrograde cholangiopancreatography between 1995 and 1999 were reviewed for the presence of choledochocele and/or periampullary carcinoma. As an evidence of pancreaticobiliary reflux, amylase activity was examined in common duct bile obtained at surgery or by endoscopy. The prevalence of periampullary carcinoma was compared between patients with and without choledochocele. RESULTS: A total of 11 patients were diagnosed as having a choledochocele. The amylase level in bile was higher in patients with choledochocele (120,922 +/- 62,269 IU/l; n = 4) than in previously examined patients with functioning gallbladders (15 +/- 24 IU/l; n = 10, P = 0.005). The prevalence of periampullary carcinoma in patients with choledochocele (27%, 3/11) was significantly higher than that in those without choledochocele (0.9%, 26/2815; P<0.0002). CONCLUSION: The bile analysis of the present study presents one possible explanation for the predisposition to carcinoma in choledochocele as bile containing amylase may stagnate in the choledochocele and then carcinoma may develop in the inner epithelium of the choledochocele by the same mechanism as that leading to carcinogenesis in patients with PBM.

Comparison of laparoscopic versus open cholecystectomy in patients with cardiac valve replacement.

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.

Periampullary choledochoduodenal fistula in ampullary carcinoma.

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.

Liver metastasis from gallbladder carcinoma: anatomic correlation with cholecystic venous drainage demonstrated by helical computed tomography during injection of contrast medium in the cholecystic artery.

BACKGROUND: The current study evaluated whether the sites of liver metastasis from gallbladder carcinoma are correlated with areas of cholecystic venous drainage (CVD) utilizing helical computed tomography (CT) during the injection of contrast medium into the cholecystic artery (cholecystic artery CT). METHODS: Cholecystic artery CT scans were performed in 26 patients with gallbladder carcinoma. Liver metastases were examined retrospectively in these patients on CT, and the sites of liver metastasis and CVD were compared closely. The patients were divided into concurrent (those who had metastasis at the time of cholecystic artery CT), early postoperative metastasis (those who developed metastasis within 6 months after surgery), and late postoperative metastasis (those who developed metastasis more than 6 months after surgery) groups. The frequency of metastasis related to CVD was compared between the three groups. RESULTS: A total of 32 metastases were identified in 11 patients, 21 of which were related to CVD. Six patients were included in the concurrent metastasis group; 18 of 20 tumors were found to be related closely to CVD. There were two patients in the early postoperative metastasis group; all three of the tumors detected were found to be closely related to CVD. Three patients were subclassified as being in the late postoperative metastasis group; none of the nine tumors detected appeared to be in areas associated with CVD. CONCLUSIONS: The sites of liver metastases were found to be well correlated with the areas with CVD, particularly in the concurrent and early postoperative metastasis groups. CVD may be a useful marker of potential areas of liver metastasis from gallbladder carcinoma, particularly in patients with early stage metastasis.

Surgical treatment of patients with T2 gallbladder carcinoma invading the subserosal layer.

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: assessing the grade of malignancy from natural history.

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.

Which is a less invasive pancreatic head resection: PD, PPPD, or DPPHR?

Less invasive pancreatic head resection, such as pylorus preserving pancreatoduodenectomy (PPPD) and duodenum preserving pancreatic head resection (DPPHR) has been introduced for the treatment of pancreatoduodenal lesions, especially for benign conditions, in consideration of postoperative quality of life. Surgical stress and exocrine and endocrine function of the residual pancreas were examined in 44 patients with PPPD, 10 with conventional pancreatoduodenectomy (PD) and six with DPPHR. 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 (OGTT), N-benzol-L-tyrosyl-p-aminobenzoic acid (BT-PABA) excretion value (a pancreatic exocrine function test), and volume of postoperative pancreatic juice drainage were compared among the three different variants of pancreatectomy. Operation time and operative blood loss in PD were largest of the three, followed by PPPD and DPPHR. Postoperative elevation of serum CRP on postoperative day (POD) 2 or 3 was similar among the three different types of operation. Fasting blood sugar concentrations were not different among the three groups at short- and long-term after the operation, while the 120-min value of the GTT showed a marked elevation at long-term only after PPPD. The volume of pancreatic juice drainage increased up to POD 4 and became constant thereafter. The total amount of pancreatic juice drainage from POD 4 to 13 was smallest in PD (637 ml) followed by PPPD (1,255 ml) and DPPHR (1,431 ml). The BT-PABA value declined after PD (-20.3%, P = 0.0437) and PPPD (-20.2%, P = 0.0239) at short term, but not after DPPHR (8.2%). These findings suggest that the early impairment of the pancreatic exocrine function after PD and PPPD but not after DPPHR may indicate that the invasiveness of pancreatic head resection to the pancreatic functions is greater in PD and PPPD than in DPPHR.

Therapeutic efficacy of G207, a conditionally replicating herpes simplex virus type 1 mutant, for gallbladder carcinoma in immunocompetent hamsters.

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.

Is peripapillary choledochoduodenal fistula an indication for endoscopic sphincterotomy?

BACKGROUND: Most patients with a peripapillary choledochoduodenal fistula undergo fistulotomy by endoscopic sphincterotomy for the treatment of bile duct stones. However, whether sphincterotomy should be performed in patients with the fistula but without stones is controversial. METHODS: Among 165 patients in whom a benign peripapillary choledochoduodenal fistula was diagnosed at ERCP, the clinical outcome was retrospectively analyzed and compared between those who underwent fistulotomy by endoscopic sphincterotomy (group 1) and those whose fistula was left untreated (group 2). All patients with hepatolithiasis, residual stones, biliary diversion, or transduodenal papilloplasty were excluded (32, leaving 133). Fistulas were divided into types I and II according to the location of the fistula (Ikeda classification). RESULTS: Follow-up data collected during a median period of 124 months were available for 127 of 133 patients (95%), 76 in group 1 and 53 in group 2. Late complications were bile duct stone recurrence (17 patients), acute cholangitis (7 patients), and biliary carcinoma (2 patients). The incidence of stone recurrence was not significantly different between the 2 groups (p = 0.1). In group 2, 4 patients (8%) with an untreated type II fistula had 1 to 3 episodes of presumed reflux cholangitis, which resolved quickly with conservative treatment. CONCLUSIONS: Endoscopic sphincterotomy is not always necessary for peripapillary choledochoduodenal fistulas if bile duct stones are absent because reflux cholangitis is a relatively rare complication that can be easily managed.

Lower activity of CCAAT/enhancer-binding protein and expression of cyclin E, but not cyclin D1, activating protein-1 and p21(WAF1), after partial hepatectomy in obstructive jaundice.

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.