Rupture of hepatic aneurysm complicating hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) for which hepatic arterial coil embolization was effective.

A 74-year-old woman was transferred to our hospital for further examinations because of abdominal fullness and abnormal levels of serum liver/biliary enzyme persisting for 3 weeks. She had anemia and dilatation of many capillary vessels in her fingers, palms, and tongue in addition to reporting frequent incidences of nasal bleeding in herself and her family. Abdominal ultrasonography detected a cystic lesion in the right hepatic lobe, connected to a dilated tortuous hepatic artery. A low-echoic hepatic phyma was also detected in the back of the cystic lesion. Abdominal computed tomography and magnetic resonance imaging indicated that the cystic lesion was an aneurysm and the low-echoic phyma was a hematoma. Hepatic arteriography confirmed a hepatic aneurysm, tortuous dilatation of the hepatic artery, and the complication of an arteriovenous shunt in the liver. Taking all of these findings into consideration, this case was diagnosed as hereditary hemorrhagic telangiectasia (HTT) complicated by a hepatic aneurysm causing intrahepatic hematoma. To prevent re-rupture of the aneurysm, we performed a hepatic arterial coil embolization. After therapy, no blood flow to the aneurysm was detected by ultrasonic color Doppler method and the hematoma gradually diminished. There have been no reports of a case in which hepatic arterial embolization was effective for HHT-associated hepatic aneurysm causing intrahepatic hematoma. This very rare case provides important clinical information regarding abdominal vascular complications of HTT and a less invasive treatment for them.

Systemic extrapancreatic lesions associated with autoimmune pancreatitis.

OBJECTIVES: Autoimmune pancreatitis (AIP) is often associated with systemic extrapancreatic lesions. We studied 31 cases of AIP to clarify the diversity of associated systemic extrapancreatic lesions and the differences between AIP with and without systemic extrapancreatic lesions. METHODS: The clinical features and courses were compared by age, sex, and blood chemistry between those with and without systemic extrapancreatic lesions. In addition, we reviewed the available literature on systemic extrapancreatic lesions with AIP. RESULTS: Seven of the 31 cases of AIP had associated systemic extrapancreatic lesions, which were diagnosed simultaneously with AIP; however, 1 case presenting with various extrapancreatic lesions was diagnosed independently of the AIP lesion. Patients with systemic extrapancreatic lesions needed maintenance steroid therapy for AIP in 4 cases and systemic extrapancreatic lesions in 2 cases; the ratio of cases requiring maintenance steroid therapy was significantly higher among those with systemic extrapancreatic lesions (6/8) than those without (7/23). There were no significant differences between groups with regard to age, sex, extent of narrowing of the main pancreatic duct, and enlargement of the pancreas. gamma-globulin, IgG, and IgG4 levels were significantly higher in patients with AIP with systemic extrapancreatic lesions than those without. The systemic extrapancreatic lesions associated with AIP found in the literature were Sjögren syndrome, ulcerative colitis, retroperitoneal fibrosis, sialadenitis, thyroiditis, and idiopathic thrombocytopenic purpura. CONCLUSIONS: The results of this study suggest that, when encountering a case of AIP with elevated levels of gamma-globulins, IgG, and IgG4, an effort should be made to detect other systemic extrapancreatic abnormalities and initiate steroid administration.

FTY720, an immunosuppressant, attenuates chronic pancreatitis in rats by suppressing T-cell infiltration.

OBJECTIVES: FTY720, a novel synthetic immunosuppressant, decreases peripheral blood lymphocytes by accelerating their homing to the peripheral and mesenteric lymph nodes and Peyer's patches. We previously reported that tacrolimus, another immunosuppressant, attenuates chronic pancreatitis by suppressing T-cell infiltration in male Wistar Bonn/Kobori rats but also may cause toxicity. To assess the effects of FTY720 on the development of pancreatic inflammation and fibrosis in the same model, the agent dissolved in physiologic saline was subcutaneously injected to 10-week-old male WBN/Kob rats for 10 weeks. METHODS: Parameters for inflammation and fibrosis were assessed and interferon-gamma and transforming growth factor-beta1 mRNA in the pancreas were determined by RT-PCR. RESULTS: Treatment with FTY720 attenuated gross alterations in the pancreas, including pigmentation and atrophy. This protective effect was quantitatively confirmed by significant increase in pancreatic weights and decreases in pancreatic myeloperoxidase activity (an index of granulocyte infiltration), pancreatic hydroxyproline content (an index of collagen deposition), ratio of fibrous tissue, and histologic scores. The obvious infiltration of CD4- and CD8-positive T cells into the pancreas in the saline group was almost completely prevented by administration of FTY720, which also suppressed overexpression of interferon and transforming growth factor-beta1 mRNA in the pancreas. CONCLUSION: We conclude that FTY720 prevents pancreatic inflammation and fibrosis by suppressing infiltration of CD4- and CD8-positive T cells and by downregulating induction of interferon and transforming growth factor-beta1 mRNA in the pancreas.

Intrahepatic biliary papilloma morphologically similar to biliary cystadenoma.

A 37-year-old man presented complaining of epigastralgia. Abdominal ultrasonography revealed the presence of a papillary tumor (9 mm in diameter) in the cystic lesion (18 mm in diameter) in hepatic segment 4, which was accompanied by mild intrahepatic bile duct dilatation. Although abdominal computed tomography also showed the cystic lesion, it did not show papillary tumors inside the lesion. Endoscopic retrograde cholangiography showed the communication between the cystic lesion and the left hepatic duct. In addition, mucus was observed in the common bile duct. When transpapillary intraductal ultrasonography was performed through the left hepatic duct using a fine ultrasonic probe, a hyperechoic papillary and lobulated tumor was clearly shown in the cystic lesion. The wall of the cyst was smooth and there was no sign of tumor infiltration. Based on these findings, biliary cystadenoma was diagnosed and an extended left lobectomy was carried out. However, pathological findings postoperatively revealed that the lesion was a localized biliary papilloma, developing and extending to the intrahepatic duct. This case is rare and there have been no published reports describing a biliary papilloma morphologically similar to biliary cystadenoma.

Clinical differences between primary sclerosing cholangitis and sclerosing cholangitis with autoimmune pancreatitis.

OBJECTIVES: Sclerosing cholangitis (SC) with autoimmune pancreatitis (AIP) is similar to primary sclerosing cholangitis (PSC) with regard to cholangiographic findings, but only the former responds well to steroid therapy. This report concentrates on the clinical differences between these diseases. METHODS: The presenting complaint or abnormality, associated disease, cholangiographic findings, pancreatic changes, treatment, and clinical course were studied for several cases of PSC (n = 27) and SC with AIP (n = 20). RESULTS: SC with AIP as a diagnosis occurs abruptly with obstructive jaundice compared with PSC where diagnosis is often based on findings of asymptomatic liver test abnormalities. In addition, inflammatory bowel disease is only associated with PSC. The most prominent features of cholangiograms for the SC with AIP cases were stenosis of the lower common bile duct. However, sclerosing changes in the intra- and extrahepatic bile ducts or hilar hepatic region were observed for half of the cases. Only PSC showed stage III or IV liver biopsy findings. IgG4 was significantly higher in SC with AIP. CONCLUSIONS: SC with AIP and PSC are different clinical entities.

Combination therapy with an angiotensin-converting enzyme inhibitor and an angiotensin II receptor blocker synergistically suppresses chronic pancreatitis in rats.

We recently demonstrated that both lisinopril and candesartan, an angiotensin-converting enzyme inhibitor and angiotensin II type 1 receptor blocker, respectively, attenuate pancreatic inflammation and fibrosis in male Wistar Bonn/Kobori (WBN/Kob) rats. The purpose of the present study was to assess whether combination therapy with low doses of both, ineffective when given alone, might synergistically exert protective effects. Lisinopril, candesartan, or a combination of both in drinking water was administered to 10-week-old male WBN/Kob rats for 10 weeks. Parameters of inflammation and fibrosis, positive immunostaining for alpha-smooth muscle actin, and gene expression of cytokine and growth factors were assessed, as well as circulating renin-angiotensin system components. Dose-dependent effects of combination therapy were also investigated. Only combination therapy attenuated gross alterations in the pancreas, as quantitatively confirmed by increases in pancreatic weights and decreases in myeloperoxidase activity, hydroxyproline content, histologic scores, relative fibrosis area, and relative area of alpha-smooth muscle actin-positive cells. Combination therapy suppressed up-regulation of tumor necrosis factor-alpha, platelet-derived growth factor-receptor beta, and transforming growth factor-beta1 mRNA in the pancreas. Dose dependence of combination therapy was recognized with reference to improvement in these parameters. The conclusions are that combination therapy synergistically alleviated pancreatic inflammation and fibrosis in male WBN/Kob rats. This effect may be related to suppression of tumor necrosis factor-alpha, platelet-derived growth factor-receptor beta, and transforming growth factor-beta1 mRNA. Compared with the either therapy alone, combination therapy with an angiotensin-converting enzyme inhibitor and an angiotensin II type 1 receptor blocker may be more beneficial for treating chronic pancreatitis.

Cholangiography can discriminate sclerosing cholangitis with autoimmune pancreatitis from primary sclerosing cholangitis.

BACKGROUND: Sclerosing cholangitis with autoimmune pancreatitis has a cholangiographic appearance that is similar to that of primary sclerosing cholangitis, but only the former responds well to corticosteroid therapy. It, therefore, is necessary to distinguish between these two diseases. Cholangiography is the reference standard for the diagnosis of primary sclerosing cholangitis. The present study compared the characteristic findings for these two types of sclerosing cholangitis. METHODS: Cholangiograms from patients with primary sclerosing cholangitis (n = 29) and sclerosing cholangitis with autoimmune pancreatitis (n = 26) were studied with regard to length and region of stricture formation, and other characteristic findings. RESULTS: Band-like stricture, beaded or pruned-tree appearance, and diverticulum-like formation were significantly more frequent in primary sclerosing cholangitis. In contrast, segmental stricture, long stricture with prestenotic dilatation and stricture of the distal common bile duct were significantly more common in sclerosing cholangitis with autoimmune pancreatitis. Discriminant analysis based on these findings correctly identified 27 of 28 patients with primary sclerosing cholangitis and 25 of 26 patients with sclerosing cholangitis with autoimmune pancreatitis. It also identified a patient with an incorrect diagnosis of primary sclerosing cholangitis who proved, on review of a surgical specimen, to have findings consistent with lymphoplasmacytic sclerosing cholangitis. CONCLUSIONS: Characteristic cholangiographic features allow discrimination of sclerosing cholangitis with autoimmune pancreatitis and lymphoplasmacytic sclerosing cholangitis without pancreatitis from primary sclerosing cholangitis.

Intracystic hemorrhage of a simple liver cyst mimicking a biliary cystadenocarcinoma.

Simple liver cysts are rarely complicated by intracystic hemorrhage. We encountered a case of simple liver cyst that was morphologically similar to biliary cystadenocarcinoma, which was complicated by asymptomatic intracystic hemorrhage and successfully treated by right lobectomy. A large cystic lesion of the liver was detected in a 57-year-old woman during a mass screening health check. Abdominal ultrasonography (US) revealed that the cystic lesion, containing many hyperechoic papillary structures, occupied almost the entire region of the right hepatic lobe. In addition, a round mural nodule, measuring approximately 5 cm in diameter, was detected in the cystic wall. Abdominal computed tomography (CT) revealed that the inner part of the cystic lesion showed homogeneous low density, but CT did not show the round nodule detected by US. On T1-weighted sequence of magnetic resonance imaging (MRI), the lesion showed homogeneous high signals, together with a low-signal tumorous lesion in the cystic wall. T2-weighted sequence of MRI showed unhomogeneous high signals, together with high signals in the tumorous part. These findings did not exclude the possibility of a malignant cystic tumor, such as biliary cystadenocarcinoma. Therefore, right lobectomy was performed. Histological examinations of resected tissue specimens revealed that the lesion was a liver cyst containing a large amount of blood clot, and that the tumorous lesion detected by US and MRI was a large mass of blood clot which was partly liquefied. This case indicates the diagnostic importance of the morphological discordance between CT and US or MRI findings for liver cyst containing a large amount of blood clot.

Exophytic pedunculated gastrointestinal stromal tumor with remarkable cystic change.

A 59-year-old man with bloody stools, and previously diagnosed with sigmoid colon carcinoma, visited our hospital. Preoperative abdominal ultrasonography (US) showed another tumor, with an uneven irregular surface, measuring about 9 x 5 cm, below the left hypochondrium. The tumor consisted of several cysts. Abdominal computed tomography (CT) showed a multicystic tumor attached to the stomach, and its septum and marginal region were intensely stained on contrast imaging. On magnetic resonance imaging (MRI), low and markedly high signals were revealed in the tumor on T1-weighted and T2-weighted sequences, respectively. Contrast imaging of the upper digestive tract showed extramural compression of the greater curvature of the antral stomach by the tumor. The tumor was partially imaged by endoscopic ultrasonography (EUS), but continuity to the stomach was not confirmed. On abdominal angiography, the tumor was slightly stained via the gastroepiploic arteries. Surgical treatment was performed to excise both the gastric tumor and the sigmoid colon carcinoma. The gastric tumor was removed with gastric wall tissue where the tumor was attached to a 2-cm pedicle. It was multicystic, contained watery fluid, and had a smooth outer surface. Histologically, the tumor consisted of multiple irregular cysts without epithelial lining, and solid epitheloid cell nests in between. The tumor cells had clear or eosinophilic cytoplasm and round nuclei. No mitotic figures were seen. The tumor cells in the pedicle were connected with the muscularis propriae of the stomach. Immunohistochemistry showed c-kit-positive, CD34-positive smooth muscle actin (SMA)-negative, and S-100-negative staining of tumor cells. The final diagnosis was gastrointestinal stromal tumor (GIST).