Literature review in cases with exacerbation of ulcerative colitis induced by treatment with interferon and/or ribavirin.

Ulcerative colitis (UC) is an immune disorder of the gastrointestinal tract which has been reported to be precipitated by interferon (IFN) therapy. We describe the results of a literature review of cases in which the development or exacerbation of UC was coincident with IFN and/or ribavirin (RIB) treatment for chronic hepatitis C. We summarized the studies on the effectiveness of IFN for UC or Crohn's disease, which were primarily carried out in Europe and the USA. In the nine reported cases of UC exacerbation by IFN therapy in Japan, seven involved IFN-α, one involved IFN-α2b plus RIB, and the other involved IFN-ß; thus cases induced by IFN-α were more common. The period between the initiation of IFN treatment and the development or exacerbation of UC varied widely among the reported cases (from 1 day to 4.5 years). The reports have all assumed a cause-and-effect correlation between IFN treatment and UC. However, although combination therapy of IFN and RIB has become widespread in Japan, UC development or exacerbation induced by IFN has not increased concurrently. Conversely, numerous studies reporting the effectiveness of IFN for treating UC and Crohn's disease have been published in Europe and the USA. One reason for this finding may be the difference in the balance of T helper cell 1 and T helper cell 2 between populations.

Successful treatment of mucosa-associated lymphoid tissue lymphoma in a patient with gastric and rectal lesions with metachronous and ectopic development.

A 75-year-old female, who had an abnormal stomach x-ray finding, was admitted to the hospital for further examination and therapy. Upper GI endoscopy showed reddish and swollen folds on the greater curvature of the gastric body and a biopsy was of this lesion revealed malignant lymphoma (small cell type or mucosa-associated lymphoid tissue (MALT) lymphoma suspected). The patient was infected with Helicobacter pylori (H. pylori), however, in response to the patient's wishes, a total gastrectomy, omentectomy and splenectomy were performed and the histological diagnosis was gastric MALT lymphoma. Two courses of CHOP therapy (cyclophosphamide (CPM) 750 mg/m(2)/day, day 1, adriamycin (ADM) 50 mg/m(2)/day, day 1, vincristine sulfate (VCR) 1.4 mg/m(2)/day, day 1, prednisolone 100 mg/body, day 1-5) were administered as adjuvant chemotherapy. A colonoscopic examination performed about 4.5 yr after the operation revealed rectal submucosal tumors and the biopsied specimens were diagnosed as malignant lymphoma. A transanal focal resection was performed and the histological diagnosis was metachronous and ectopic development of MALT lymphoma. The histological finding was similar to the gastric lesion. About 4 and 7 yr after the first development of rectal MALT lymphoma, MALT lymphomas developed repeatedly in the rectal lesion, however, these were resected repeatedly and no developmenthas occurred during the past two years. This report presents a very rare case of metachronous and ectopic MALT lymphoma development in the gastric and rectal lesions.

[A case of superior mesenteric artery occlusion associated with idiopathic chronic cold agglutinin disease].

A 64-year-old man who had been given a diagnosis of idiopathic chronic cold agglutinin disease in a medical clinic suffered from Raynaud's phenomenon and acrocyanosis in winter. He was admitted to our hospital with unbearable abdominal pain. Blood tests showed liver dysfunction with jaundice and severe acidosis. Abdominal angiogram and contrast-enhanced CT revealed superior mesenteric artery occlusion. These findings suggest that thrombosis due to cold agglutinin disease could be the cause of superior mesenteric artery occlusion.

Advanced gastric cancer patient with peritonitis carcinomatosa successfully treated with a combination therapy of paclitaxel and TS-1, but relapsed with multiple bone metastasis and died from rapidly progressive meningitis carcinomatosa--advanced gastric cancer with metachronous peritonitis carcinomatosa and meningitis carcinomatosa.

A 59-year-old man diagnosed as gastric cancer with peritonitis carcinomatosa was treated with paclitaxel and TS-1; 60 mg/m(2)/day of paclitaxel was given on days 1 and 8, and 60-80 mg/m(2)/day of TS-1 was given for 2 weeks. Six courses of combination therapy were administered, and the ascites disappeared completely. Because multiple bone metastases occurred, we attempted combination therapy with cisplatin and irinotecan hydrochloride; 50 or 30 mg/m(2)/day of cisplatin was given on day 1 or day 15, and 70 mg/m(2)/day of irinotecam hydrochloride was given on days 1 and 15. The patient achieved a remarkable response, however, intrameningeal dissemination occurred and he died from rapidly progressive meningitis carcinomatosa.

Features of hepatocellular carcinoma in cases with autoimmune hepatitis and primary biliary cirrhosis.

AIM: To characterize the clinical features of hepatocellular carcinoma (HCC) associated with autoimmune liver disease, we critically evaluated the literature on HCC associated with autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). METHODS: A systematic review of the literature was conducted using the Japana Centra Revuo Medicina database which produced 38 cases of HCC with AIH (AIH-series) and 50 cases of HCC with PBC (PBC-series). We compared the clinical features of these two sets of patients with the general Japanese HCC population. RESULTS: On average, HCC was more common in men than in women with AIH or PBC. While many patients underwent chemolipiodolization (CL) or transcatheter arterial embolization (TAE) (AIH-series: P = 0.048 (vs operation), P = 0.018 (vs RFA, PEIT); PBC-series: P = 0.027 (vs RFA, PEIT), others refused therapeutic interventions [AIH-series: P = 0.038 (vs RFA, PEIT); PBC-series: P = 0.003 (vs RFA, PEIT)]. Liver failure was the primary cause of death among patients in this study, followed by tumor rupture. The survival interval between diagnosis and death was fairly short, averaging 14 +/- 12 mo in AIH patients and 8.4 +/- 14 mo in PBC patients. CONCLUSION: We demonstrated common clinical features among Japanese cases of HCC arising from AIH and PBC.

Synchronous development of HCC and CCC in the same subsegment of the liver in a patient with type C liver cirrhosis.

As a result of having undergone computed tomography (CT), a 75-year-old woman with type-C liver cirrhosiswas shown to have two tumors on the ventral and dorsal sides of subsegment 3 (S3). The tumor on the ventral side was diagnosed as a classic hepatocellular carcinoma (HCC), while that on the dorsal side was considered atypical for a HCC. Although the indocyanine green (ICG) findings indicated poor hepatic reserve, the prothrombin time (PT) was relatively good. An operation was performed in February 2007; however, this resulted in exploratory laparotomy. Dynamic CT performed 12 mo after the operation revealed that the tumor on the dorsal side of S3 had apparently increased. The marginal portion of the tumor was shown to be in the early and parenchymal phases, while the internal portion was found to have grown only slightly in the delayed phase. We diagnosed this tumor as a cholangiocellular carcinoma (CCC). S3 subsegmentectomy was performed in April 2008. The tumor on the ventral side was pathologically diagnosed as a moderately differentiated HCC, and that on the dorsal side was diagnosed as a CCC. We can therefore report a rare case of synchronous development of HCC and CCC in the same subsegment of the liver in a patient with type-C liver cirrhosis. We also add a literature review for all the reported cases published in Japan and around the world, and summarize the features of double cancer exhibiting both HCC and CCC.

Pelioid-type hepatocellular carcinoma with numerous eosinophilic infiltrations in a patient with primary biliary cirrhosis.

A 65-year-old woman with liver injury was referred to our hospital in 1992. She was diagnosed with primary biliary cirrhosis (PBC) of Scheuer's histological classification stage IV. She was treated with 600 mg/day of ursodeoxycholic acid. A 1-cm mass in S7 was detected in August 1995. The serum alpha-fetoprotein (AFP) level increased to 1288 ng/mL in January 1996. Angiography showed a cotton wool-like appearance in the delayed phase. Because the size of the tumor appeared to be increasing and the serum AFP levels increased with high levels of L3 fraction, a pelioid-type hepatocellular carcinoma (HCC) was strongly suspected. Hepatic artery infusion with SMANCS and partial resection of S7 and S8 of the liver were performed in March 1996. The pathological diagnosis for theresected liver tumor was pelioid-type HCC. The serum AFP level decreased to 50 ng/mL after the operation, but relapsed HCC was detected in S6 and S7. Angiography in September 1996 revealed multiple hypervascular lesions, and hepatic artery infusion with SMANCS was again performed; however, we were unable to suppress the progression of the relapsed HCC. The patient died due to an intra-abdominal rupture of relapsed HCC and subsequent liver failure in December 1996. We report a rare case of pelioid-type HCC with numerous eosinophilic infiltrations arising from PBC.

[A case of advanced gastric cancer with obstructive jaundice due to multiple liver metastasis successfully treated with the following combination therapy of CPT-11 and cisplatin after combination therapy of paclitaxel and TS-1].

A 60-year-old man, who had been admitted to another hospital with complaints of constipation, abdominal fullness and appetite loss, was referred to our hospital for further examination and therapy. The patient was diagnosed as advanced gastric cancer (type-3) with multiple liver metastasis and obstructive jaundice. He was treated with combination therapy of paclitaxel and TS-1 (60 mg/m(2)/day of paclitaxel was iv administered on day 1 and 8, and TS-1 of 80 mg/m(2)/day was orally administered for 2 weeks followed by one drug-free week), and showed a remarkable response. However, because of ascites, elevated serum CEA level and resistance in the liver metastasis and gastric region, we attempted two courses of combination therapy with high-dose CPT-11 and cisplatin (70 mg/m(2)/day of CPT-11 was administered iv on day 1 and 15, and 80 mg/m(2)/day of cisplatin on day 1 followed by two drug-free weeks) which showed a remarkable response. Two courses of combination therapy with low-dose CPT-11 and cisplatin (60 mg/m(2)/day of CPT-11 and 30 mg/m(2)/day of cisplatin were administered iv on day 1 and 15 followed by two drug-free weeks) on an outpatient basis. However, the patient showed resistance to the latter combination therapy, increased ascites due to suspicious peritonitis carcinomatosa and obvious re-growth of the metastatic tumors in the liver. He died on May 23, 2006, about ten months after initial diagnosis. We reported a case of successful treatment of combination chemotherapy for advanced gastric cancer with obstructive jaundice due to progressive multiple metastatic tumors in the liver and obtained comparative long-term survival maintaining high quality of life.

[A case of exacerbation of ulcerative colitis induced by combination therapy with PEG-interferon alpha-2b and ribavirin for chronic hepatitis C].

A 55-year-old man with chronic hepatitis C had diarrhea with bloody stool in July, 2003 and ulcerative colitis was suspected. However, he quickly improved. He was treated with percutaneous radiofrequency ablation therapy for adenomatous hyperplasia in S5 of the liver in December, 2004. After the ablation therapy, he was treated with combination therapy of PEG-interferon alpha-2b and ribavirin for chronic hepatitis C. Because exacerbation of ulcerative colitis appeared 10 weeks after beginning of the treatment for hepatitis C, the combination therapy of PEG-interferon and ribavirin was discontinued. He was treated with mesalazine and steroid therapy for ulcerative colitis, and improved. We report the first case in Japan of the exacerbation of ulcerative colitis induced by the combination therapy of PEG-interferon and ribavirin for chronic hepatitis C.

Sustained biochemical remission after interferon treatment may closely be related to the end of treatment biochemical response and associated with a lower incidence of hepatocarcinogenesis.

Clinical background and incidence of hepatocellular carcinoma (HCC) of patients with chronic hepatitis C who obtained biochemical remission without eradication of virus (biochemical response) after interferon (IFN) treatment was retrospectively analyzed for 755 patients. Annual incidence of HCC was significantly lower in the patients with biochemical response and sustained response than that of the patients that did not show these responses. Logistic regression analysis showed that only the normalization of alanine aminotransferase (ALT) value at the end of IFN treatment was a significant factor for biochemical response. Annual incidence of HCC was significantly lower in the patients who obtained normalization of ALT values at the end of treatment than those who did not. Patients who were younger, who had a lower level of activity and fibrosis indices in histology, higher platelet count, and who were given more higher total dose of IFN were more likely to attain normalization of ALT levels at the end of treatment, and this was related to biochemical response. Low incidence of HCC in patients who obtained normalization of ALT values at the end of treatment was likely because they were in the earlier stage of chronic hepatitis. Active treatment of chronic hepatitis C with interferon in the early phase of the disease may bring about a biochemical response in some patients, even if sustained virological response is not obtained.

Interferon inhibits progression of liver fibrosis and reduces the risk of hepatocarcinogenesis in patients with chronic hepatitis C: a retrospective multicenter analysis of 652 patients.

A retrospective multicenter analysis of 652 patients with chronic hepatitis C who have been treated with interferon (IFN) was performed to assess the effects of IFN on the clinical course and development of HCC. During a mean follow-up of 54.8 months, hepatocellular carcinoma (HCC) developed in 7.0% of the patients. The rate was significantly higher in the patients who did not respond to IFN treatment than in those with sustained virological response and those who obtained a normalization of alanine aminotransferase levels despite the presence of HCV RNA (incomplete response) (P < 0.01). Using multivariate Cox's proportional hazard model, alcohol abuse (P < 0.05) and a higher level of fibrosis (P < 0.05) before treatment were the significant background factors associated with HCC development in the patients who did not respond to IFN. Interestingly, a significant increase in the rate of HCC development occurred in patients who had a histological finding of progressive fibrosis (F3). In addition, patients with low histological staging scores were likely to have an incomplete response, even if a sustained virological response was not obtained. IFN produced an improvement in histological activity and fibrosis stage in the second biopsy specimens irrespective of the clinical outcome when compared against untreated subjects.