Diagnostic Accuracy of the Initial Endoscopy for Ampullary Tumors.

BACKGROUND/AIMS: Ampullary tumors come in a wide variety of malignant forms. We evaluated the diagnostic accuracy of endoscopy for ampullary tumors, and analyzed the causes of misdiagnosis. METHODS: We compared endoscopic imaging and biopsy results to final diagnoses. Types of endoscope, numbers of biopsy specimens taken, and final diagnoses were evaluated as possible factors influencing diagnostic accuracy. RESULTS: Final diagnoses were 19 adenocarcinomas, 18 normal or papillitis, 11 adenomas, two adenomyomas, one paraganglioma, and one neuroendocrine tumor. The diagnostic accuracy of endoscopic imaging or the initial biopsy was identical (67.3%). At least one test was concordant with the final diagnosis in all except two cases. Compared with the final diagnosis, endoscopic imaging tended to show more advanced tumors, whereas the initial biopsy revealed less advanced lesions. The diagnostic accuracy of the initial biopsy was influenced by the type of endoscope used and the final diagnosis, but not by the number of biopsies taken. CONCLUSIONS: Endoscopy has limited accuracy in the diagnosis of ampullary tumors. However, most cases with concordant endoscopic imaging and biopsy results are identical to the final diagnosis. Therefore, in cases where both of these tests disagree, re-evaluation with a side-viewing endoscope after resolution of papillitis is required.

HDAC inhibitors induce epithelial-mesenchymal transition in colon carcinoma cells.

The effects of histone deacetylase (HDAC) inhibitors on epithelial-mesenchymal transition (EMT) differ in various types of cancers. We investigated the EMT phenotype in four colon cancer cell lines when challenged with HDAC inhibitors trichostatin A (TSA) and valproic acid (VPA) with or without transforming growth factor-ß1 (TGF-ß1) treatment. Four colon cancer cell lines with different phenotypes in regards to tumorigenicity, microsatellite stability and DNA mutation were used. EMT phenotypes were assessed by the expression of E-cadherin and vimentin using western blot analysis, immunofluorescence, quantitative real-time RT-PCR following treatment with TSA (100 or 200 nM) or VPA (0.5 mM) with or without TGF-ß1 (5 ng/ml) for 24 h. Biological EMT phenotypes were also evaluated by cell morphology, migration and invasion assays. TSA or VPA induced mesenchymal features in the colon carcinoma cells by a decrease in E-cadherin and an increase in vimentin expression at the mRNA and protein levels. Confocal microscopy revealed membranous attenuation or nuclear translocation of E-cadherin and enhanced expression of vimentin. These responses occurred after 6 h and increased until 24 h. Colon cancer cells changed from a round or rectangular shape to a spindle shape with increased migration and invasion ability following TSA or VPA treatment. The susceptibility to EMT changes induced by TSA or VPA was comparable in microsatellite stable (SW480 and HT29) and microsatellite unstable cells (DLD1 and HCT116). TSA or VPA induced a mesenchymal phenotype in the colon carcinoma cells and these effects were augmented in the presence of TGF-ß1. HDAC inhibitors require careful caution before their application as new anticancer drugs for colon cancers.

H2 Receptor-Mediated Relaxation of Circular Smooth Muscle in Human Gastric Corpus: the Role of Nitric Oxide (NO).

This study was designed to examine the effects of histamine on gastric motility and its specific receptor in the circular smooth muscle of the human gastric corpus. Histamine mainly produced tonic relaxation in a concentration-dependent and reversible manner, although histamine enhanced contractility in a minor portion of tissues tested. Histamine-induced tonic relaxation was nerve-insensitive because pretreatment with nerve blockers cocktail (NBC) did not inhibit relaxation. Additionally, K(+) channel blockers, such as tetraethylammonium (TEA), apamin (APA), and glibenclamide (Glib), had no effect. However, N(G)-nitro-L-arginine methyl ester (L-NAME) and 1H-(1,2,4)oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC), did inhibit histamine-induced tonic relaxation. In particular, histamine-induced tonic relaxation was converted to tonic contraction by pretreatment with L-NAME. Ranitidine, the H2 receptor blocker, inhibited histamine-induced tonic relaxation. These findings suggest that histamine produced relaxation in circular smooth muscle of human gastric smooth muscle through H2 receptor and NO/sGC pathways.

Differential expression of E-cadherin, ß-catenin, and S100A4 in intestinal type and nonintestinal type ampulla of Vater cancers.

BACKGROUND/AIMS: Epithelial-mesenchymal transition (EMT)-related proteins may exhibit differential expression in intestinal type or pancreatobiliary type ampulla of Vater carcinomas (AVCs). We evaluated the expression of E-cadherin, ß-catenin, and S100A4 in intestinal and nonintestinal type AVCs and analyzed their relationships with clinicopathological variables and survival. METHODS: A clinicopathological review of 105 patients with AVCs and immunohistochemical staining for E-cadherin, ß-catenin, and S100A4 were performed. The association between clinicopathological parameters, histological type, and expression of EMT proteins and their effects on survival were analyzed. RESULTS: Sixty-five intestinal type, 35 pancreatobiliary type, and five other types of AVCs were identified. The severity of EMT changes differed between the AVC types; membranous loss of E-cadherin and ß-catenin was observed in nonintestinal type tumors, whereas aberrant nonmembranous ß-catenin expression was observed in intestinal type tumors. EMT-related changes were more pronounced in the invasive tumor margin than in the tumor center, and these EMT-related changes were related to tumor aggressiveness. Among the clinicopathological parameters, a desmoplastic reaction was related to overall survival, and the reaction was more severe in nonintestinal type than in intestinal type AVCs. CONCLUSIONS: Dysregulation of E-cadherin, ß-cadherin, and S100A4 expression may play a role in the carcinogenesis and tumor progression of AVCs.

Epithelial-mesenchymal transition-related protein expression in biliary epithelial cells associated with hepatolithiasis.

BACKGROUND AND AIM: Epithelial-mesenchymal transition (EMT) of biliary epithelial cells (BECs) plays major roles in many cholangiopathies. This study evaluated whether EMT of BECs has a role in hepatolithiasis-induced biliary fibrosis and types of BECs that are involved. METHODS: The expression of EMT-related proteins and epidermal growth factor receptor was evaluated by immunohistochemistry of liver tissues from 102 patients with hepatolithiasis, 32 patients with post-hepatitis cirrhosis, and 48 normal livers. Antibodies against E-cadherin, ß-catenin, and cytokeratin were used to identify epithelial cells and antibodies against vimentin, S100A4, podoplanin, and α-smooth muscle actin (α-SMA) were used to identify mesenchymal cells. The relationship between clinical and histological parameters and immunohistochemistry findings in BECs, and the surrounding stroma were evaluated. RESULTS: Loss of E-cadherin and acquisition of S100A4 and vimentin were observed in BECs. In all BECs, cytokeratin and ß-catenin expression were unchanged, while podoplanin and α-SMA were not expressed. Although hepatic fibrosis was more severe in post-hepatitis cirrhosis, EMT of BECs was more widespread in hepatolithiasis. In hepatolithiasis, EMT-related proteins were more highly expressed in small bile ducts than in medium or large bile ducts. Their expression was associated with the severity of biliary fibrosis and the expressions of epidermal growth factor receptor. Expression of α-SMA in fibroblasts from the portal space was closely linked to pathological changes in small bile ducts and EMT-related protein expressions in BECs. CONCLUSIONS: Proliferating cholangiocytes that form small bile ducts may contribute to cholangiopathies in hepatolithiasis through an EMT-like phenomenon or through interactions with stromal myofibroblasts.

Clinical, pathological, and immunohistochemical features of adenomyoma in the ampulla of vater.

BACKGROUND/AIMS: Ampullary adenomyoma is a benign lesion whose malignant potential has yet to be confirmed. Despite its benign nature, adenomyoma is frequently misdiagnosed as a carcinoma or adenoma and is overtreated by extensive surgery. This study was performed to analyze the clinical, pathological, and immunohistochemical features of adenomyomas in the ampulla of Vater. METHODS: Nine cases of adenomyoma in the ampulla of Vater, diagnosed in Chungbuk National University Hospital between 2008 and 2011, were enrolled in this study. We reviewed the clinical data on the symptoms, laboratory data, and radiologic findings of the abdominal computed tomography and endoscopic retrograde cholangiopancreatography. For pathological analysis, all the slides were reviewed by one pathologist, and immunohistochemical stainings with antibodies against cytokeratin 7 (CK7), cytokeratin 20 (CK20), α-smooth muscle actin (α-SMA), and Ki-67 antigen were performed. RESULTS: All the cases were CK7 positive and CK20 negative. A strong cytoplasmic expression of α-SMA was confirmed in all cases. The Ki-67 index was less than 1% in eight cases and 5% in one case. Four cases underwent endoscopic papillectomy, and one case received surgical ampullectomy during colorectal cancer surgery. Five cases that underwent endoscopic or surgical treatment remained symptom-free for three years. Four cases that were closely observed with repeated endoscopic examinations exhibited no interval changes in the papillary lesions. CONCLUSIONS: Endoscopic biopsy and immunohistochemistry can aid in the diagnosis of ampullary adenomyomas. Endoscopic papillectomy or surgical ampullectomy is adequate for the treatment of symptomatic ampullary adenomyomas.

Podoplanin, α-smooth muscle actin or S100A4 expressing cancer-associated fibroblasts are associated with different prognosis in colorectal cancers.

The interactions between the tumor microenvironment and tumor cells determine the behavior of the primary tumors. Whether cancer-associated fibroblasts (CAF) have a tumor progressive or a protective role likely depends on the type of tumor cells and the CAF subpopulation. In the present study, we analyzed the prognostic significance of CAF subpopulations in colorectal cancer (CRC). CAF phenotypes were analyzed in 302 CRC patients by using antibodies against podoplanin (PDPN), α-smooth muscle actin (α-SMA), and S100A4. The relationship between the CAF phenotypes and 11 clinicopathological parameters were evaluated and their prognostic significance was analyzed from the disease-free and overall survival times. We observed that at the tumor invasive front, PDPN CAFs were present in 40% of the cases, and S100A4 or α-SMA CAFs were detected in all the cases. PDPN/S100A4 and α-SMA/S100A4 dual-stained CAFs were observed in 10% and 40% of the cases, respectively. The PDPN(+) CAFs were associated with 6 favorable clinicopathological parameters and prolonged disease-free survival time. The PDPN(-)/α-SMA(high) CAFs were associated with 6 aggressive clinicopathological parameters and tended to exhibit shorter disease-free survival time. On the other hand, the PDPN(-)/S100A4(high) CAFs were associated with 2 tumor progression parameters, but not with disease prognosis. The PDPN(+) CAF phenotype is distinct from the α-SMA or S100A4 CAFs in that it is associated with less aggressive tumors and a favorable prognosis, whereas the PDPN(-)/α-SMA(high) or PDPN(-)/S100A4(high) CAFs are associated with tumor progression in CRC. These findings suggest that CAFs can be a useful prognostic biomarker or potential targets of anti-cancer therapy in CRC.

Mechanism of Relaxation Via TASK-2 Channels in Uterine Circular Muscle of Mouse.

Plasma pH can be altered during pregnancy and at labor. Membrane excitability of smooth muscle including uterine muscle is suppressed by the activation of K(+) channels. Because contractility of uterine muscle is regulated by extracellular pH and humoral factors, K(+) conductance could be connected to factors regulating uterine contractility during pregnancy. Here, we showed that TASK-2 inhibitors such as quinidine, lidocaine, and extracellular acidosis produced contraction in uterine circular muscle of mouse. Furthermore, contractility was significantly increased in pregnant uterine circular muscle than that of non-pregnant muscle. These patterns were not changed even in the presence of tetraetylammonium (TEA) and 4-aminopyridine (4-AP). Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretchactivated channels in myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed increased immunohistochemical expression of TASK-2. Therefore, TASK-2, seems to play a key role during regulation of myometrial contractility in the pregnancy and provides new insight into preventing preterm delivery.

Combined aberrant expression of E-cadherin and S100A4, but not ß-catenin is associated with disease-free survival and overall survival in colorectal cancer patients.

BACKGROUND/AIMS: Epithelial-to-mesenchymal transition (EMT) in cancers is related to metastasis, recurrence, and poor prognosis. We evaluated whether EMT-related proteins can act as prognostic biomarkers in colorectal cancer (CRC) patients. METHODS: We evaluated the expression of E-cadherin, ß-catenin, and S100A4 by immunohistochemistry (IHC) in 333 CRC tissues from the tumor center and invasive margin. Tumor budding, cell grade, tumor stage, type of tumor growth, peritumoral lymphocyte infiltration (TLI), and perineural- or lymphovascular invasion were evaluated as pathological parameters. mRNA levels of E-cadherin, N-cadherin, ß-catenin, and S100A4 from 68 specimens from the same set were analyzed by real time quantitative RT-PCR. RESULTS: Loss of E-cadherin, nuclear ß-catenin, and gain of S100A4 were higher in the invasive margin than in the tumor center. Loss of E-cadherin was associated with cell grade, macroscopic type, perineural invasion, and tumor budding, ß-catenin with microsatellite instability and tumor site, and S100A4 with growth type, macroscopic type, AJCC stage, lymphovascular invasion, and perineural invasion. The aberrant expression of E-cadherin and S100A4 not ß-catenin in the invasive margin was a significant and independent risk factor for disease-free and overall-survival by multivariate analysis, along with AJCC stage and perineural invasion. mRNA levels of ß-catenin and S100A4 were correlated with the IHC findings at the tumor invasive margin. E-cadherin and N-cadherin showed a weak inverse correlation. CONCLUSIONS: The combination of loss of E-cadherin and gain of S100A4 in the tumor invasive margin can be used to stratify patients with the same AJCC stage into different survival groups.

High k(+)-induced relaxation by nitric oxide in human gastric fundus.

This study was designed to elucidate high K(+)-induced relaxation in the human gastric fundus. Circular smooth muscle from the human gastric fundus greater curvature showed stretch-dependent high K(+) (50 mM)-induced contractions. However, longitudinal smooth muscle produced stretch-dependent high K(+)-induced relaxation. We investigated several relaxation mechanisms to understand the reason for the discrepancy. Protein kinase inhibitors such as KT 5823 (1 µM) and KT 5720 (1 µM) which block protein kinases (PKG and PKA) had no effect on high K(+)-induced relaxation. K(+) channel blockers except 4-aminopyridine (4-AP), a voltage-dependent K(+) channel (K(V)) blocker, did not affect high K(+)-induced relaxation. However, N(G)-nitro-L-arginine and 1H-(1,2,4)oxadiazolo (4,3-A)quinoxalin-1-one, an inhibitors of soluble guanylate cyclase (sGC) and 4-AP inhibited relaxation and reversed relaxation to contraction. High K(+)-induced relaxation of the human gastric fundus was observed only in the longitudinal muscles from the greater curvature. These data suggest that the longitudinal muscle of the human gastric fundus greater curvature produced high K(+)-induced relaxation that was activated by the nitric oxide/sGC pathway through a K(V) channel-dependent mechanism.

Interstitial cells of Cajal (ICC)-like-c-Kit positive cells are involved in gastritis and carcinogenesis in human stomach.

This study was executed to prove the existence of c-Kit-positive interstitial cells of Cajal (ICC)-like cells [c-Kit (+) ICC-like cells] and their possible role associated with gastric inflammation and/or carcinogenesis in human gastric mucosa. c-Kit (+) ICC-like cells were observed throughout all the layers of the gastric fundus along the greater curvature. Dense fusiform cell bodies with many processes were found in each layer. We also studied the c-Kit-positive immunoreactivity distribution pattern in the mucosa. c-Kit (+) cells were found mainly around the epithelial repair zone of the normal gastric fundus/corpus and of the fundus/corpus with non-metaplastic chronic gastritis. Notably, they were found attached to the epithelia of the repair zone in non-metaplastic chronic gastritis. In chronic gastritis with intestinal metaplasia, they were found scattered everywhere in the stroma of the gastric mucosa and did not attach to the metaplastic epithelium. We found c-Kit (+) ICC-like cells in human mucosa. They were present mainly in the stroma around the repair zone of the glands in chronic gastritis as well as in normal mucosa, whereas they seemed to redistribute over the whole mucosa in gastritis with intestinal metaplasia. These cells around the repair zone were found to be tightly attached to epithelial cells, but not to metaplastic epithelial cells. Thus, c-Kit (+) ICC-like cells appear to have a role in the epithelial recovery process and may be associated with carcinogenesis of human gastric mucosa.

Nitric Oxide-mediated Relaxation by High K in Human Gastric Longitudinal Smooth Muscle.

This study was designed to elucidate high-K(+)induced response of circular and longitudinal smooth muscle from human gastric corpus using isometric contraction. Contraction from circular and longitudinal muscle stripes of gastric corpus greater curvature and lesser curvature were compared. Circular smooth muscle from corpus greater curvature showed high K(+) (50 mM)-induced tonic contraction. On the contrary, however, longitudinal smooth muscle strips showed high K(+) (50 mM)-induced sustained relaxation. To find out the reason for the discrepancy we tested several relaxation mechanisms. Protein kinase blockers like KT5720, PKA inhibitor, and KT5823, PKG inhibitor, did not affect high K(+)-induced relaxation. K(+) channel blockers like tetraethylammonium (TEA), apamin (APA), glibenclamide (Glib) and barium (Ba(2+)) also had no effect. However, N(G)-nitro-L-arginine (L-NNA) and 1H-(1,2,4) oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC) and 4-AP (4-aminopyridine), voltage-dependent K(+) channel (K(V)) blocker, inhibited high K(+)-induced relaxation, hence reversing to tonic contraction. High K(+)-induced relaxation was observed in gastric corpus of human stomach, but only in the longitudinal muscles from greater curvature not lesser curvature. L-NNA, ODQ and K(V) channel blocker sensitive high K(+)-induced relaxation in longitudinal muscle of higher portion of corpus was also observed. These results suggest that longitudinal smooth muscle from greater curvature of gastric corpus produced high K(+)-induced relaxation which was activated by NO/sGC pathway and by K(V) channel dependent mechanism.

Regional Distribution of Interstitial Cells of Cajal (ICC) in Human Stomach.

We elucidated the distribution of interstitial cells of Cajal (ICC) in human stomach, using cryosection and c-Kit immunohistochemistry to identify c-Kit positive ICC. Before c-Kit staining, we routinely used hematoxylin and eosin (HE) staining to identify every structure of human stomach, from mucosa to longitudinal muscle. HE staining revealed that the fundus greater curvature (GC) had prominent oblique muscle layer, and c-Kit immunostaining c-Kit positive ICC cells were found to have typical morphology of dense fusiform cell body with multiple processes protruding from the central cell body. In particular, we could observe dense processes and ramifications of ICC in myenteric area and longitudinal muscle layer of corpus GC. Interestingly, c-Kit positive ICC-like cells which had morphology very similar to ICC were found in gastric mucosa. We could not find any significant difference in the distribution of ICC between fundus and corpus, except for submucosa where the density of ICC was much higher in gastric fundus than corpus. Furthermore, there was no significant difference in the density of ICC between each area of fundus and corpus, except for muscularis mucosa. Finally, we also found similar distribution of ICC in normal and cancerous tissue obtained from a patient who underwent pancreotomy and gastrectomy. In conclusion, ICC was found ubiquitously in human stomach and the density of ICC was significantly lower in the muscularis mucosa of both fundus/corpus and higher in the submucosa of gastric fundus than corpus.

Cholestatic hepatitis and thrombocytosis in a secondary syphilis patient.

The incidence of acute hepatitis in syphilis patient is rare. First of all, our patient presented with hepatitis comorbid with thrombocytosis. To our knowledge, this is only the second report of syphilitic hepatitis with thrombocytosis. The 42-yr-old male complained of flu-like symptoms and skin eruptions on his palms and soles. Laboratory findings suggested an acute hepatitis and thrombocytosis. Serologic test results were positive for VDRL. He recovered from his symptoms and elevated liver related enzymes with treatment. Because syphilitic hepatitis can present without any typical signs of accompanying syphilis, syphilis should be considered as a possible cause in acute hepatitis patients.

[Histopathologic analysis of adenoma and adenoma-related lesions of the gallbladder].

BACKGROUND/AIMS: In order to determine the malignant potential of gallbladder adenoma for progression to carcinoma, we evaluated the histopathologic features of adenoma and adenoma-related lesions on cholecystectomized specimens. METHODS: Among 1,847 cholecystectomized specimens, 63 specimens from 26 benign adenomas, 9 carcinomas in situ (CIS), and 28 invasive carcinomas were selected. A pathologist reviewed all specimens and selected benign adenomas, CIS in the adenoma, and adenoma residue in invasive carcinomas. Adenomas and adenoma-related lesions were classified according to morphology (tubular, tubulopapillary, and papillary) and the consisting epithelium (biliary, pyloric metaplasia, and intestinal metaplasia). The age and the size of the benign adenomas and carcinomas in the adenoma were also compared. RESULTS: Adenoma and adenoma-related lesions were found in 34 out (1.8%) of all resected gallbladder. Among 9 CIS and 28 invasive carcinomas, adenoma-related lesions were detected in 7 and 1 case, respectively. All eight carcinomas arising in the adenoma were well-differentiated solitary tumors. The diameters of the carcinomas in the adenoma were, on average, larger than that of the benign adenomas (1.8 cm vs. 0.9 cm, p=0.01). The patients with carcinomas in the adenoma were, on average, older than those with benign adenomas, although the difference was insignificant (57 years vs. 47 years, p=0.09). The morphology and consisting epithelium did not differ between the benign adenomas and carcinomas in the adenoma. The malignant transformation occurred in 23.5% of adenomas. CONCLUSIONS: Gallbladder adenoma is a rare disease, although malignant transformation occurs frequently. Adenoma is a precancerous lesion and the adenoma-carcinoma sequence is one of the gallbladder cancer carcinogenesis.

[A case of congenital hepatic fibrosis presented with recurrent acute cholangitis].

Acute cholangitis usually develops in congenital hepatic fibrosis (CHF), accompanied by cystic dilated bile ducts. However, it can also develop in simple CHF and may lead to critical course. A 30-year old man presented with recurrent acute cholangitis without bile duct dilatation. He visited the hospital for febrile sense and abdominal pain in the right upper quadrant. He had been admitted several times for hepatosplenomegaly and cholangitis since childhood and received a liver biopsy 15 years ago. Abdominal computed tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP) revealed hepatosplenomegaly and a mildly dilated bile duct without stones or biliary cysts. His condition improved after conservative treatment. However, during a two-month follow up period, the patient experienced three episodes of acute cholangitis. A liver biopsy was performed and showed periportal fibrosis and intrahepatic ductular dysplasia, characteristics of congenital hepatic fibrosis. The periportal fibrosis and the infiltration of inflammatory cells were aggravated compared to 15 years ago. There was no evidence of hepatic cirrhosis. He was diagnosed with congenital hepatic fibrosis with recurrent acute cholangitis without intrahepatic duct dilatation, and conservatively treated with antibiotics.

A case of idiopathic adulthood ductopenia.

Idiopathic adulthood ductopenia (IAD) is a chronic cholestatic liver disease of unknown etiology characterized by adult onset, an absence of autoantibodies, inflammatory bowel disease, and a loss of interlobular bile ducts. In the present report, a case fulfilling the IAD criteria is described. A 19-year-old man was admitted to the hospital for persistent elevation of transaminases and alkaline phosphatase without clinical symptoms. Viral hepatitis markers and autoantibodies were absent. The patient had a normal extrahepatic biliary tree and had no evidence of inflammatory bowel disease. A liver biopsy specimen showed absence of interlobular bile ducts from 58% of the portal tracts. He was diagnosed with IAD and was treated with ursodeoxycholic acid.

Metachronous bile duct cancer nine years after resection of gallbladder cancer.

We report a rare case of a 74-year-old man with metachronous gallbladder cancer and bile duct cancer who underwent curative resection twice, with the operations nine years apart. At the age of 65 years, the patient underwent a cholecystectomy and resection of the liver bed for gallbladder cancer. This was a well-differentiated adenocarcinoma, with negative resection margins (T2N0M0, stage IB). Nine years later, during a follow-up examination, abdominal computed tomography and MRCP showed an enhanced 1.7 cm mass in the hilum that extended to the second branch of the right intrahepatic bile duct. We diagnosed this lesion as a perihilar bile duct cancer, Bismuth type IIIa, and performed bile duct excision, right hepatic lobectomy and Roux-en-Y hepaticojejunostomy. The histological diagnosis was a well-differentiated adenocarcinoma with one regional lymph node metastasis (T1N1M0, stage IIB). Twelve months after the second operation, the patient is well, with no signs of recurrence. This case is compared with 11 other cases of metachronous biliary tract cancer published in the world medical literature.

Successful Hemostasis with Recombinant Activated Factor VII in a Patient with Massive Hepatic Subcapsular Hematoma.

Recombinant activated coagulation factor VII (rFVIIa) is known to be effective in the management of acquired deficiencies of factor VII and platelet function defects. But recently, rFVIIa has been successfully used to treat ongoing bleeding in disseminated intravascular coagulopathy (DIC) condition. The patient reported here was suspected to be suffering from toxic hepatitis on admission. After percutaneous liver biopsy, bleeding occurred and did not stop even after right hepatic artery embolization. The patient developed a severe hemorrhage that resulted in hypovolemic shock, hemoperitoneum, and a massive subcapsular hematoma. The patient then developed DIC due to massive transfusion, as well as acute liver necrosis. The patient was given 400 mug/kg of rFVIIa. Recombinant factor VIIa was administered in an attempt to control the bleeding. This stabilized the hemoglobin levels of the patient. The patient gradually recovered in 4 months. In conclusion, this case suggests that rFVIIa can be successfully used for the hemostasis of uncontrolled bleeding in DIC.