Diagnosis of mild chronic pancreatitis (Cambridge classification):Comparative study using secretin injection-magnetic resonance cholangiopancreatography and endoscopic retrograde pancreatography

AIM:To investigate the usefulness of secretin injection-MRCP for the diagnosis of mild chronic pancreatitis. METHODS:Sixteen patients having mild chronic pancreatitis according to the Cambridge classification and 12 control subjects with no abnormal findings on the pancreatogram were examined for the diagnostic accuracy of secretin injection-MRCP regarding abnormal branch pancreatic ducts associated with mild chronic pancreatitis (Cambridge Classification), using endoscopic retrograde cholangiopancreatography (ERCP) for comparison. RESULTS:The sensitivity and specificity for abnormal branch pancreatic ducts determined by two reviewers were respectively 55%-63% and 75%-83% in the head, 57%-64% and 82%-83% in the body, and 44%-44% and 72%-76% in the tail of the pancreas. The sensitivity and specificity for mild chronic pancreatitis were 56%-63% and 92%-92%, respectively. Interobserver agreement (κ statistics) concerning the diagnosis of an abnormal branch pancreatic duct and of mild chronic pancreatitis was good to excellent. CONCLUSION:Secretin injection-MRCP might be useful for the diagnosis of mild chronic pancreatitis.

Interplay of neuropilin-1 and semaphorin 3A after partial hepatectomy in rats

AIM:To elucidate the role of neuropilin-1(Nrp-1) and semaphorin 3A(Sema3A) in sinusoidal remodeling during liver regeneration in rats.METHODS:Male Wistar/ST rats at 7 wk of age,weighing about 200 g,were used for all animal experiments.In vivo,at 24,48,72,96,144 and 192 h after twothirds partial hepatectomy(PHx),the remnant livers were removed.Liver tissues were immunohistochemically stained for Nrp-1,Sema3A and SE-1,a liver sinusoidal endothelial cell(SEC) marker.Total RNA of the liver tissue was extracted and reversely transcribed into cDNA.The mRNA expression of Sema3A was analyzed by quantitative real-time polymerase chain reaction and normalized to that of ribosomal protein S18.In vitro,SECs were isolated from rat liver and cultured in endothelial growth medium containing 20 ng/mL vascular endothelial cell growth factor.Migration of SECs in primary culture was assessed by cell transwell assay with or without recombinant Sema3A.Apoptotic cells were determined by a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling method.RESULTS:In vitro,immunohistochemistry study revealed that Sema3A and Nrp-1 were constitutively expressed in hepatocytes and SECs,respectively,in normal rat liver tissues.Nrp-1 expression in SECs was quantified by the percentage of immunostained area with antiNrp-1 antibody in relation to the area stained with SE-1.Between 24 h and 96 h following resection of liver,Nrp-1 expression in SECs was transiently increased.Compared with the baseline(5.2% ± 0.1%),Nrp-1 expression in SECs significantly increased at 24 h(17.3% ± 0.7%,P < 0.05),48 h(39.1% ± 0.6%,P < 0.01),72 h(46.9% ± 4.5%,P < 0.01) and 96 h(29.9% ± 3.8%,P < 0.01) after PHx,then returned to the basal level at termination of liver regeneration.Interestingly,the expression of Sema3A was inversely associated with that of Nrp-1 in liver after PHx.Sema3A mRNA expression was significantly reduced by about 75% over the period 24-144 h after PHx(P < 0.05),and returned to basal levels at 192 h after PHx.In vitro,SECs isolated from rats after PHx(PHx-SECs) were observed to migrate to the lower chamber of the cell transwell system after incubation for 24 h,but not cells from normal rats(CONT-SECs),indicating that mobility of PHx-SECs increases as compared with that of CONT-SECs.Moreover,recombinant Sema3A significantly attenuated migration in PHx-SECs in primary culture(vehicle-treated 100% ± 7.9% vs Sema3A-treated 42.6% ± 5.4%,P < 0.01),but not in CONT-SECs.Compared with CONTSECs,the apoptotic rate of PHx-SECs decreased by 78.3%(P < 0.05).There was no difference in apoptosis between CONT-SECs that were treated with vehicle and Sema3A.However,in PHx-SECs,apoptosis was induced by the presence of 5 nmol Sema3A for 24 h(vehicle-treated 21.7% ± 7.6% vs Sema3A-treated 104.3% ± 8.9%,P < 0.05).In addition,immunohistochemistry confirmed the increased expression of Nrp-1 in PHx-SECs,while it was noted to a lesser extent in CONT-SECs.CONCLUSION:The interplay of Nrp-1 and Sema3A shown in our results may lead to a better understanding of interaction between sinusoidal remodeling and SECs during liver regeneration.

Two distinct pathways of p16 gene inactivation in gallbladder cancer

AIM: To examine the mechanism of inactivation of the p16 gene in gallbladder cancer,and to investigate p16 alterations and their correlation with clinicopathological features. METHODS: Specimens were collected surgically from 51 patients with gallbladder cancer. We evaluated the status of protein expression,loss of heterozygosity (LOH),homozygous deletion and promoter hypermethylation using immunohistochemistry,microsatellite analysis,quantitative real-time polymerase chain reaction (PCR) and methylation-specific PCR,respectively. In addition,mutations were examined by direct DNA sequencing. RESULTS: Homozygous deletions of the p16 gene exon2,LOH at 9p21-22,p16 promoter hypermethylation,and loss of p16 protein expression were detected in 26.0% (13/50),56.9% (29/51),72.5% (37/51) and 62.7% (32/51),respectively. No mutations were found. LOH at 9p21 correlated with the loss of p16 protein expression (P < 0.05). Homozygous deletion of the p16 gene,a combination LOH and promoter hypermethylation,and multiple LOH at 9p21 were significantly correlated with the loss of p16 protein expression (P < 0.05). LOH at 9p21 and promoter hypermethylation of the p16 gene were detected in 15.4% (2/13) and 92.3% (12/13) of the tumors with homozygous deletion of the p16 gene,respectively. P16 alterations were not associated with clinicopathological features. CONCLUSION: Our results suggest that LOH and homozygous deletion may be two distinct pathways in the inactivation of the p16 gene. Homozygous deletion,a combination of LOH and promoter hypermethylation,and multiple LOH are major mechanisms of p16 inactivation in gallbladder cancer.

A case of gallbladder carcinoma associated with pancreatobiliary reflux in the absence of a pancreaticobiliary maljunction:A hint for early diagnosis of gallbladder carcinoma

有胆囊墙的进步变厚的一个 62 岁的人访问了我们的门诊病人诊所。在胆总管的胆汁的淀粉酶水平是 19,900 IU/L，胆囊的是 127,000 IU/L，尽管内视镜后退 cholangiopancreatography 没揭示 pancreaticobiliary maljunction。组织学表明了胆囊的中等区分的腺癌。Pancreatobiliary 倒流和联系胆囊癌在现在的盒子中被证实，当 pancreaticobiliary maljunction 不在时。pancreatobiliary 倒流并且胆囊墙的进步变厚的更早的察觉可能导致了胆囊的更早的切除术并且改进了这个病人的差的预后。

Gallbladder carcinoma associated with pancreatobiliary reflux

AIM: To detect the patients with and without pan-creaticobiliary maljunction who had pancreatobiliary reflux with extremely high biliary amylase levels.METHODS: Ninety-six patients, who had diffuse thickness (> 3 mm) of the gallbladder wall and were suspected of having a pancreaticobiliary maljunction on ultrasonography, were prospectively subjected to endoscopic retrograde cholangiopancreatography, and bile in the common bile duct was sampled. Among them, patients, who had extremely high biliary amylase levels (>10 000 IU/L), underwent cholecystectomy, and the clinicopathological findings of those patients with and without pancreaticobiliary maljunction were examined.RESULTS: Seventeen patients had biliary amylase levels in the common bile duct above 10 000 IU/L, including 11 with pancreaticobiliary maljunction and 6 without pancreaticobiliary maljunction. The occurrence of gallbladder carcinoma was 45.5% (5/11) in patients with pancreaticobiliary maljunction, and 50% (3/6) in those without pancreaticobiliary maljunction.CONCLUSION: Pancreatobiliary reflux with extremely high biliary amylase levels and associated gallbladder carcinoma could be identified in patients with and without pancreaticobiliary maljunction, and those patients might be detected by ultrasonography and bile sampling.

Identification of cerebral response to balloon distention of the bile duct

AIM: To identify the brain loci that process human biliary sensation. METHODS: In 6 patients (age range: 42-74 years; 4 men), who underwent percutaneous transhepatic biliary drainage (PTBD), the distal biliary tract was stimulated by repeatedly inflating the balloon of the PTBD catheter so that it reached volumes that produced a definite painless sensation. The functional magnetic resonance imaging (fMRI) of the cortical response to biliary sensation was examined. RESULTS: Biliary balloon stimulation elicited activation of the insular cortex, prefrontal cortex, and somato- sensory cortex (P < 0.001). CONCLUSION: Biliary balloon stimulation evoked a cerebral cortical response detectable by fMRI.