Endoscopic treatment for portal hypertension: what's new in the last 12 months?
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Biomedical subjects
Publications and source records attributed to H Imazu.
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BACKGROUND: It has been shown that expression of the potent angiogenic factor, vascular endothelial growth factor (VEGF), and its receptors, flt-1 (VEGFR-1) and KDR/Flk-1 (VEGFR-2), increased during the development of liver fibrosis. AIMS: To elucidate the in vivo role of interaction between VEGF and its receptors in liver fibrogenesis. METHODS: A model of CCl(4) induced hepatic fibrosis was used to assess the role of VEGFR-1 and VEGFR-2 by means of specific neutralising monoclonal antibodies (R-1mAb and R-2mAb, respectively). R-1mAb and R-2mAb were administered after two weeks of treatment with CCl(4), and indices of fibrosis were assessed at eight weeks. RESULTS: Hepatic VEGF mRNA expression significantly increased during the development of liver fibrosis. Both R-1mAb and R-2mAb treatments significantly attenuated the development of fibrosis associated with suppression of neovascularisation in the liver. Hepatic hydroxyproline and serum fibrosis markers were also suppressed. Furthermore, the number of alpha-smooth muscle actin positive cells and alpha1(I)-procollagen mRNA expression were significantly suppressed by R-1mAb and R-2mAb treatment. The inhibitory effect of R-2mAb was more potent than that of R-1mAb, and combination treatment with both mAbs almost completely attenuated fibrosis development. Our in vitro study showed that VEGF treatment significantly stimulated proliferation of both activated hepatic stellate cells (HSC) and sinusoidal endothelial cells (SEC). VEGF also significantly increased alpha1(I)-procollagen mRNA expression in activated HSC. CONCLUSIONS: These results suggest that the interaction of VEGF and its receptor, which reflected the combined effects of both on HSC and SEC, was a prerequisite for liver fibrosis development.
While gallbladder carcinoma is occasionally associated with pancreaticobiliary maljunction, spontaneous necrosis of carcinoma is extremely rare. We herein present a case of spontaneous necrosis of gallbladder carcinoma associated with direct invasion of viable cancer cell nests to the muscularis propria and subserosal layer located beneath the primary nodules. A 65-year-old Japanese man was admitted to a local hospital, complaining of repeated discomfort in the right hypochondrium. Ultrasonography and computed tomography scanning revealed cholecystitis associated with gallstones. Cholecystectomy was performed, and operative cholangiography demonstrated pancreaticobiliary maljunction. The resected gallbladder showed multiple mixed stones filled with necrotic debris and bile sludge. Scrutiny of the mucosal surface revealed multiple small necrotic nodules in the fundus, which were histologically confirmed to be necrotic remnants of a cancerous glandular structure. Small nests of papillary adenocarcinoma were found beneath the nodules in the muscularis propria and in the venous structure located in the connective tissues next to the divided margin of the gallbladder bed. Resection of S4a and S5 of the liver and resection of the extrahepatic bile duct was then performed to remove the remaining cancerous tissues and/or micrometastasis in the liver and bile duct. The biliary tree was reconstructed with a hepaticoduodenostomy. No cancer nests or any precancerous lesions were found in the additionally resected specimens. This case indicates a unique morphological feature of gallbladder carcinoma associated with pancreaticobiliary maljunction, which provides some insight into the pathogenesis of spontaneous necrosis of gallbladder carcinoma.
Although retroperitoneal or psoas abscess is an unusual clinical problem, the insidious and occult characteristics of this abscess sometimes cause diagnostic delays, resulting in considerably high morbidity and mortality. In particular, psoas abscess caused by perforated colon carcinoma is uncommon. We report a case of psoas abscess caused by a carcinoma of the cecum. A 72-year-old Japanese woman was admitted to our hospital, with pain in the right groin and buttock. The pain had appeared 6 months before admission, and the symptoms had then been relieved by oral antibiotics. On March 25, 1999, inflammatory signs in the right buttock indicated localized cellulitis, and incision and drainage was performed at a local hospital. The patient was referred to our hospital on the same day. On admission to our hospital, computed tomography (CT) scan revealed a thick right-sided colonic wall and enlargement of the right ileopsoas muscle. Barium enema and colonofiberscopy revealed an ulcerated tumor occupying the entire circumference of the cecum. A retroperitoneal abscess and fistula had been formed by the retroperitoneal perforation of cecum carcinoma: surgical resection was performed after remission of the local inflammatory signs. Operative findings indicated that the cancerous lesion and its surrounding tissues were firmly attached to the right iliopsoas and major psoas muscle, and en-bloc resection, including adjacent muscular tissue, was performed. The fact that carcinoma of the colon could be a cause of psoas abscess and cellulitis in the gluteal region should be considered when an unexplained psoas abscess is diagnosed.
BACKGROUND/AIMS: Endothelin-1 has been suggested to play a key role in cirrhotic portal hypertension, but a role of its receptors in vivo is not fully elucidated. METHODS: Biliary cirrhosis was induced by bile duct ligation. Expressions of endothelin-1 and its receptors were evaluated by radioimmunoassay and/or reverse-transcription polymerase chain reaction. Hemodynamics were studied using endothelin receptor agonist or antagonist. RESULTS: Portal pressure and hepatic endothelin-1 concentrations progressively increased in parallel after bile duct ligation. Gene expression of hepatic prepro-endothelin-1 and endothelin B receptor enhanced after bile duct ligation, while that of endothelin A receptor was unchanged. Intraportal administration of endothelin-1 or endothelin B receptor agonist sarafotoxin 6c (0.5 nmol/kg, respectively) progressively raised portal pressure in both sham and cirrhotic rats. Portal hypertensive effect of sarafotoxin 6c was more intense in cirrhotic rats than sham animals. Neither endothelin A receptor antagonist FR139317 (1 mg/kg) nor endothelin B receptor antagonist BQ788 (1 mg/kg) alone ameliorated cirrhotic portal hypertension. Only the combined endothelin A and B blockade was associated with a decrease in portal pressure in cirrhotic rats. CONCLUSIONS: These results indicate that endothelin-1 plays a major role in cirrhotic portal hypertension through endothelin receptor subtype B together with subtype A in vivo.
We present two patients with bleeding episodes from gastric fundal varices. The gastric fundal varices were treated by balloon catheter-assisted endoscopic sclerotherapy using alpha-cyanoacrylate monomer. The varices were successfully obliterated with no complications or hemodynamic changes to the gastrorenal shunts. This procedure may be considered a novel, feasible approach to the treatment of gastric fundal varices in the future.
We report the case of a 53-year-old man with a long history of ulcerative colitis in whom an elevated lesion in the epithelium of the affected transverse colon was initially diagnosed as a benign inflammatory polyp by endoscopic biopsies. After 4 years of follow-up, because the tumor had enlarged and villous components were endoscopically observed on the surface, a colonic resection was performed. The tumor was found to consist of hyperplastic colonic epithelium associated with multiple mucinous cysts lined with dysplastic colonic epithelial cells. Moreover, the mucinous cysts were primarily located beneath the submucosal layer and appeared to intrude into the muscularis propria of the colonic wall. This lesion had a unique pathological feature, presumably indicating neither benign inflammatory epithelium nor a neoplastic lesion of the colonic epithelium. Mucinous cysts lined with colonic epithelial components in the muscularis propria suggest a loss of normal integrity of the colonic wall. Areas of the epithelial cell lining of the mucinous cysts showed apparent structural and nuclear atypia and positive expression for p53, suggesting that this portion of the specimen was dysplastic epithelium. These pathological findings may indicate one longitudinal aspect of tumor development which could provide evidence of premalignant change or initial pathological features during the long-standing course of ulcerative colitis.
We report a case of hyperplastic polyp of the gallbladder in a 6-year-old girl, successfully treated by laparoscopic cholecyctectomy after a 2-year follow-up from the original diagnosis. On her first admission, serum amylase level was very high, so that congenital pancreaticobiliary maljunction (PBM) was suspected. Although it became clear afterwards that the high serum amylase level was derived from a mumps infection, the diagnosis of PBM was not excluded until intraoperative cholangiography was conducted. The tumor in the gallbladder had doubled in size in 2 years. It was not possible to obtain biopsy specimens for histological diagnosis, so the risk of the tumor being malignant could not be completely excluded until surgical resection had been carried out. In spite of the rapid tumor growth, no neoplastic features were seen in the tumor by histopathological examination of the resected specimen; thus, a diagnosis of a hyperplastic polyp of the gallbladder was made.
Despite the relatively common incidence of sacrococcygeal dermoids, rectal cysts are uncommon. We report the case of a submucosal dermoid cyst occurring in the rectum. A 30-year-old woman visited the Gynecology Department because of pregnancy. A pelvic tumor was accidentally found during the checkup after miscarriage. A barium enema showed an anterior shift of the rectum by the presence of the tumor. Computed tomography and magnetic resonance imaging revealed a tumor located posterior to the rectum occupying almost the entire pelvic cavity, and the tumor was resected. The tumor was located in the submucosal layer of the posterior rectal wall and was well circumscribed. The resected tumor was a cyst entirely covered with a fibrous and firm capsule, which was filled with an amorphous white creamy substance. The histological findings showed the cyst consisting of a keratinizing stratified squamous epithelium with sebaceous gland and hair follicles, which was compatible with benign cystic teratoma. Primary rectal teratoma is very rare and only 36 cases have been reported in the literature worldwide. Furthermore, while the majority of cases were polypoid-shaped dermoid cysts protruding into the rectal lumen, only 3 cases were submucosal dermoid cysts. Therefore, such cases are considered to be extremely rare.
While the liver and lung are primary targets for distant metastasis from colorectal carcinoma, metastasis in other distant sites is rarely found. We report herein an unusual case of metastasis to the skeletal muscle of the right forearm from an adenocarcinoma of the transverse colon. A 60-year-old man was originally admitted to our hospital for surgical treatment of an intestinal obstruction caused by a transverse colon carcinoma. Transverse colon resection along with lymph node dissection was performed and no evidence of distant metastatic foci was found. Angiography-enhanced computed tomography scanning done 14 months after the first operation revealed multiple hepatic metastases which were resected. A metastasis was subsequently detected in the right extensor carpi ulnaris muscle 2 years after the primary resection, and a major part of the right extensor carpi ulnaris and the extensor digiti minimi muscle were resected, warranting a sufficient margin of 5 cm of normal tissue from the tumor. Reattachment of the residual muscles into the ulna was performed. Metastases to bone and/or soft tissues from colorectal carcinomas are extremely rare and to our knowledge, only eight other cases have been reported in the world literature. This low incidence may be related to the anatomical characteristics and/or the biochemical environment of the skeletal muscle, but it is also possible that the true incidence is underestimated. Recent improvements in interventional radiological procedures may facilitate a diagnosis of skeletal muscle metastasis being made more frequently.
Angiomyomatous hamartoma is a rare disease with a predisposition for the inguinal lymph nodes. A 51-year-old male patient visited a local hospital because of a right inguinal mass, measuring 3 x 4 cm in size, which was resected. The resected specimen showed irregularly distributed thick-walled vessels in the hilum, extending into the medulla and focally into the cortex of the node, eventually becoming more dispersed and associated with smooth muscle cells splaying into sclerotic stroma. These findings are compatible with an angiomyomatous hamartoma. Another tumor-like mass appeared shortly after the resection at the same location, but was not an angiomyomatous hamartoma, rather it was composed of edematous stromal tissue with proliferating smooth muscle cells. The stromal component included thick-walled blood vessels and lymphatics. Although it could not be determined whether these associated changes in the surrounding stroma are a cause or an effect of angiomyomatous hamartoma, they indicate the clinical difficulty in determining an appropriate area of resection and may provide clues to the pathogenesis of angiomyomatous hamartoma.
BACKGROUND AND STUDY AIMS: Endoscopic injection sclerotherapy (EIS) and endoscopic variceal ligation (EVL) are used worldwide as the treatment for esophageal varices. We evaluated portal hemodynamics using magnetic resonance angiography (MRA) in these two forms of treatment. PATIENTS AND METHODS: The study was carried out in 50 cirrhotic patients. MRA was performed to identify the hepatofugal supply vein selectively for esophageal varices. Those who showed a positive MR angiogram for the supply vein were randomly allocated to one of two groups, using the sealed envelope method, and underwent either EIS or EVL. On the other hand, those with a negative angiogram received only EVL. EIS was done to embolize esophageal varices as well as their feeders by intravariceal injection of sclerosant under fluoroscopic guidance. RESULTS: A positive MR angiogram of the hepatofugal left gastric vein as the supply vein was observed in 41 patients. Nine patients showed negative MRA results. Among those with positive angiograms, the rate of eradication of the left gastric vein was higher in the EIS-treated group than in the EVL treated group (50% vs. 8.6%). After either treatment, the recurrence-free rate for high risk esophageal varices was higher in patients with complete eradication of the left gastric vein than in those without (88% vs. 35%). In patients with negative angiogram results, who only underwent EVL, high risk esophageal varices did not reappear over a long period. CONCLUSION: MRA is useful for evaluating portal hemodynamics. With the aim of avoiding recurrence of esophageal varices, EIS was suitable for patients who had a hepatofugal supply vein for the varices because recurrence could be prevented by embolization of the supply vein. EVL may be expected to be efficacious in patients where no image of a hepatofugal supply vein is found on MRA.
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To investigate the molecular mechanisms of the high incidence of carcinogenesis in the biliary epithelium of patients with pancreaticobiliary maljunction, we examined p53 gene mutations, loss of heterozygosity of p53, and overexpression of p53 gene product in the cancerous and noncancerous biliary epithelium of 27 patients with pancreaticobiliary maljunction. Mutations of the p53 gene were examined by polymerase chain reaction-single strand conformation polymorphism and a direct sequencing method. Loss of heterozygosity of the p53 gene was determined using a double-targeted fluorescence in situ hybridization method. Expression of p53 gene product was examined using immunohistochemical staining. Mutations of the p53 gene were found in 4 of 5 biliary carcinomas (80%) and in 10 of 26 noncancerous biliary lesions (38.5%). Point mutations of the p53 gene were detected at codons 207, 212, and 217 on exons 5 through 8. The incidence of p53 gene mutations on exons 5, 6, 7, and 8 was 12. 9%, 36.4%, 0.0%, and 13.8%, respectively. Loss of heterozygosity of p53 was shown in 72% of the cells obtained from the cancerous lesion, and in an average of 14% obtained from the noncancerous lesions. Overexpression of p53 protein was found in 57.1% of carcinoma, and in 31.3% of the noncancerous lesions. These results suggest that p53 gene mutations are involved in the carcinogenesis of biliary epithelium in patients with pancreaticobiliary maljunction.
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A 65-year-old woman was admitted to our hospital with the diagnosis of gallbladder tumor. Right extended hepatic lobectomy plus lymph node dissection of the hepatoduodenal ligament and left hepaticojejunostomy with Roux-en-Y reconstruction was performed in July, 1993. The gallbladder tumor was histologically proven to be squamous cell carcinoma. Seventeen months later, the patient experienced dyspnea and pitting edema of the lower legs and was admitted, in December 1994, with a diagnosis of heart failure. Despite intensive cardiac support, she died 12 days after the second admission. Autopsy revealed multiple cardiac tumors in the left and right ventricles, left atrium, left coronary artery, and left diaphragm. Histologically, these tumors were shown to be squamous cell carcinoma, considered to have metastasized from the primary gallbladder carcinoma. As neither local recurrence of the gallbladder carcinoma nor any lymph node metastasis was found, the cardiac metastasis of the gallbladder carcinoma may have occurred via the hematogenous route. Although rare, this route of cardiac metastasis of gallbladder carcinoma may be an important aspect of distant metastasis, which should be monitored for during follow-up after resection of the primary tumor.
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It is well known that the frequency of an associated gallbladder cancer in patients with pancreaticobiliary maljunction (PBM) without congenital choledochal dilation (CCD) is very high, while that of bile duct cancer with CCD is remarkably high, and that of bile duct malignancy without CCD is low. However, recent statistical evaluations have demonstrated that the coincidence rates of gallbladder and bile duct cancer with CCD are 11.5% and 4.6%, respectively, whereas without CCD the rates are 57.1% and 4.1%, respectively. Rates of bile duct cancer with CCD are comparable to those without CCD. We have performed biliary reconstruction after resection of extrahepatic bile ducts along with the gallbladder for PBM patients who had neither CCD nor cancer. Our surgical strategy for these patients without CCD with PBM was assessed from K-ras point mutations and overexpression of p53 protein in the epithelia of the cancerous portions and non-neoplastic portions of the gallbladder and bile duct affected by PBM regardless of choledochal dilatation. The mutation rate in the non-neoplastic gallbladder epithelium without CCD was 80%, that of the bile duct without CCD 57%, not significantly different from the 50% and 40%, respectively, with CCD. The frequency of p53 overexpression in the non-neoplastic bile duct epithelium without CCD was 14%, comparable to the 11% in gallbladder epithelium with CCD. Judging from the statistical data and the molecular biological data, resection of an extrahepatic bile duct with the gallbladder should be the treatment of choice for carcinogenesis prevention.