Spontaneous clearance of serum HCV-RNA after splenectomy in a patient with HCV-related liver cirrhosis and portal hypertension: a case report.

BACKGROUND: Spontaneous clearance of chronic hepatitis C virus (HCV) is rare in adults. A T-lymphocyte response is thought to be involved in HCV-RNA clearance. Splenectomy reportedly has a beneficial effect on T cell immune function in patients with cirrhosis. To the best of our knowledge, the present report is the first to describe spontaneous clearance of serum HCV-RNA within 1 year after splenectomy in a patient with cirrhosis. CASE PRESENTATION: A 55-year-old man with HCV cirrhosis was transferred to our institution with advanced pancytopenia, splenomegaly, and gastric varices. He had a 1-year history of ascites, edema, and general fatigue. The patient had a Child-Pugh score of 8 and serological type 1 HCV; the HCV-RNA level was 4.7 log IU/mL. Contrast-enhanced computed tomography showed gastric varices and marked splenomegaly (estimated spleen volume of 2175 mL). Esophagogastroduodenoscopy revealed enlarged gastric varices with no red color sign, and the varices were larger than those 1 year prior. He was diagnosed with decompensated HCV-related liver cirrhosis and portal hypertension. We considered direct-acting antiviral (DAA) therapy; however, DAA therapy was not approved in Japan for patients with decompensated cirrhosis at that time. Hand-assisted laparoscopic splenectomy was performed to improve the worsening portal hypertension. Further, we planned the initiation of DAA therapy after surgery, when such therapy would become available. DAA therapy was approved 1 year after splenectomy. At that time, we measured the HCV-RNA level before the initiation of DAA therapy; unexpectedly, however, serum HCV-RNA was not detectable, and the virus continued to disappear during the following 4 years. His liver function (total bilirubin, albumin, and prothrombin time) and pancytopenia improved during the 5 years postoperatively. The serum aspartate and alanine aminotransferase levels normalized between 1 and 5 years postoperatively. Esophagogastroduodenoscopy showed no change in the gastric varices during the 5 years after surgery. The patient remained asymptomatic and continued to do well. CONCLUSIONS: We have presented a case of spontaneous clearance of HCV-RNA after splenectomy in a patient with cirrhosis and portal hypertension. Splenectomy may be associated with disappearance of HCV-RNA based on previous reports. More cases should be accumulated and evaluated.

Analysis of the relationship between the amplitude of aortic wall motion and heart function.

PURPOSE: Because the posterior wall of the aorta and left atrium are interlocked, the amplitude of motion of the aortic wall (AMAW) may reflect cardiac and vessel functions. This study examined the relationship between cardiac and vessel functions and AMAW. METHODS: Patients with cardiovascular diseases or patients undergoing health examinations who visited a participating hospital and underwent echocardiography and brachial-ankle pulse-wave velocity (baPWV) examinations were registered. The correlations between echocardiographic indices, ankle-brachial index, and baPWV and AMAW on M-mode echocardiography were analyzed. RESULTS: Overall, 184 patients were enrolled. Heart rate (r = - 0.1587), ejection fraction (EF; r = 0.3240), wall thickness (r = - 0.1598), peak early diastolic mitral annular velocity (E) to peak early diastolic mitral annular velocity ratio (e'; r = - 0.2463), and baPWV (r = - 0.1928) significantly correlated with AMAW. In the stratified multiple regression analysis, E/e' (standardized partial regression coefficients = - 0.1863) and mean baPWV (standardized partial regression coefficients = - 0.1917) in patients with an EF of ≥ 60% (n = 114) significantly correlated with AMAW. In patients with an EF of < 60% (n = 70), E/e' (standardized partial regression coefficients = - 0.2443) significantly correlated with AMAW. CONCLUSION: Because E/e' correlated with AMAW in patients with an EF of < 60% or ≥ 60%, AMAW might be an indicator of left atrial pressure elevation. Moreover, because AMAW correlated with baPWV in patients with an EF of ≥ 60%, changes in the restricted left atrial volume might influence diastolic dysfunction. AMAW may be related to cardiac and vessel functions.

Adult pancreatic hemangioma: A case report.

Vascular neoplasms of the pancreas are extremely rare and usually manifest as symptomatic, cystic lesions. This study presents a case that includes the clinicopathologic information used to discriminate pancreatic hemangioma from other types of cystic lesion of the pancreas. A 40-year-old female visited hospital with a chief complaint of abdominal pain. The serum CEA and CA19-9 levels of the patient were within the normal limits. An abdominal computed tomography scan and magnetic resonance imaging showed a 100-mm mass lesion in the body and tail of the pancreas, and the tumor extended toward the retroperitoneum and surrounded the splenic vein. The lesion was subsequently resected. Macroscopically, it was a multiloculated cyst with intracystic hemorrhage. Microscopically, the lesion was composed of numerous, heterogeneous cysts lined by a flattened single layer of cells without significant atypia. Notably, numerous neoplastic vessels extended into the interlobular septa of the pancreas and surrounded the main pancreatic duct. Immunohistochemical analysis showed that the lining cells expressed CD31 and CD34. The lesion was diagnosed as adult pancreatic hemangioma. Surgical treatment may be required when a direct contact between the lesion and the pancreatic tissue is demonstrated using imaging.

Efficacy and safety of a 14-day administration of tolvaptan in the treatment of patients with ascites in hepatic oedema.

OBJECTIVE: To investigate the efficacy and safety of 14 days' orally administered tolvaptan as adjunctive treatment for hepatic oedema in Japanese liver cirrhosis patients with insufficient response to conventional diuretics, with the option to increase dose in those who did not respond initially. METHODS: This multicentre, single-arm, phase 3 study allocated patients with liver cirrhosis and persistent ascites to 7-day treatment with 7.5 mg/day tolvaptan followed by an additional 7 days' treatment. Responders at day 7 (achieving ≥ 1 kg body-weight reduction) continued on 7.5 mg/day tolvaptan; nonresponders (<1 kg body-weight reduction) received 15 mg/day tolvaptan. Conventional diuretic treatment continued throughout. The primary endpoint was change in body weight from baseline, as a marker of ascites volume. RESULTS: A total of 51 patients received 7.5 mg/day tolvaptan for 7 days, which caused a significant reduction in mean body weight (55% response rate). During the second 7-day treatment period, 30 patients received 7.5 mg/day tolvaptan and 13 patients received tolvaptan 15 mg/day: response rates were 43% and 23%, respectively. Two serious adverse events were observed. Serum sodium was within normal range. CONCLUSIONS: Tolvaptan therapy for 14 days (with possible dose increase as necessary), in combination with conventional diuretics, effectively reduced body weight in patients with hepatic oedema.

Efficacy, safety, and survival factors for sorafenib treatment in Japanese patients with advanced hepatocellular carcinoma.

BACKGROUND: Sorafenib, an oral multikinase inhibitor, was approved for the treatment of advanced hepatocellular carcinoma (HCC), but has not been adequately evaluated for safety and effectiveness in Japanese patients with advanced HCC. AIMS: The purpose of this study was to prospectively assess the efficacy, safety, and risk factors for survival in patients with advanced HCC treated with sorafenib. METHODS: Between May 2009 and December 2010, 96 Japanese patients with advanced HCC (76 male, 20 female, mean age: 70.4 years) were treated with sorafenib. Eighty-eight patients had Child-Pugh class A, and 8 patients had Child-Pugh class B liver cirrhosis. Barcelona Clinic Liver Cancer stage B and C were found in 64 and 32 patients, respectively. RESULTS: Twelve patients demonstrated partial response to sorafenib therapy, 43 patients had stable disease, and 33 patients had progressive disease at the first radiologic assessment. The most frequent adverse events leading to discontinuation of sorafenib treatment were liver dysfunction (n = 8), hand-foot skin reaction (n = 7), and diarrhea (n = 4). The median survival time and time to progression were 11.6 and 3.2 months, respectively. By multivariate analysis, des-γ-carboxy prothrombin serum levels and duration of treatment were identified as independent risk factors for survival. CONCLUSIONS: This study showed that sorafenib was safe and useful in Japanese patients with advanced HCC. In addition, this study demonstrated that sorafenib should be administered as a long-term treatment for advanced HCC regardless of therapeutic effect and dosage.

Multicenter phase II randomized study evaluating dose-response of antiperistaltic effect of L-menthol sprayed onto the gastric mucosa for upper gastrointestinal endoscopy.

AIM: Peppermint oil solution was found to be effective for reducing gastric spasm during upper gastrointestinal endoscopy. The aim of the present study was to assess whether the gastric peristalsis-suppressing effect is dose-dependently induced by L-menthol, the major constituent of peppermint oil, and to determine the recommended dose of an L-menthol preparation. METHODS: In this phase II, multicenter, double-blind, dose-response study, 131 eligible patients were randomly assigned to receive 20 mL of 0.4% L-menthol (n = 32), 0.8% L-menthol (n = 35), 1.6% L-menthol (n = 30), or placebo (n = 34). The primary efficacy measure was the proportion of subjects with no peristalsis in two time periods, 75 to 105 s after treatment and immediately before the completion of endoscopy. RESULTS: The peristalsis-suppressing effect of L-menthol increased dose dependently (5.6%, 32.0%, 47.4% and 52.9% in the 0%, 0.4%, 0.8% and 1.6% groups, respectively: P < 0.001, one-tailed Cochran-Armitage trend test). As compared with the placebo group, the proportion of subjects with no peristalsis after administration was significantly higher in the 0.8% group (P = 0.015) and 1.6% group (P = 0.009). Adverse events in the L-menthol dose groups occurred with similar frequencies in the placebo group. CONCLUSION: L-menthol suppresses peristalsis in a dose-dependent manner, and the dose-response reaches a plateau at 0.8% L-menthol. Further Phase III studies are needed to establish the superiority of 0.8% L-menthol over placebo.

[Survival benefits of chemotherapy for unresectable biliary tract cancer--a multicenter retrospective analysis].

There is no agreement on the standard chemotherapeutic regimen for biliary tract cancer(BTC), although multi-drug regimens such as gemcitabine and/or S-1 have been tested in clinical trials. This study retrospectively reviewed data from patients with BTC who were seen at hospitals in the Kitakyushu and Fukuoka areas between 2005 and 2006, and examined the effect of systemic chemotherapy regimen on survival benefits in patients with unresectable BTC. Chemotherapy may benefit patients with BTC any age group, regardless of the primary site.

[Case of overwhelming postsplenectomy infection (OPSI) with chronic hepatitis type C during peginterferon/ribavirin combination therapy].

A 61-year-old woman with a past history of splenectomy was admitted to our hospital because of high fever and loss of consciousness during interferon therapy for the treatment of chronic hepatitis type C. She died of multiple organ failure, and disseminated intravascular coagulation shortly after admission. The results of blood culture and the autopsy revealed sepsis due to streptcoccus pneumonia. The neutropenia and immunosuppression by interferon therapy induced overwhelming postsplenectomy infection (OPSI), a potentially rapidly fatal septicemia. When we perform treatment with immunosuppression such as interferon therapy or anticancer drug therapy to splenectomised patients, it is necessary to carry out pnemococcus vaccination. Splenectomy is performed for patients with thrombocytopenia of chronic hepatitis type C before interferon therapy. To avoid OPSI, partial splenic arterial embolization was discussed.

[Phase I/II study of combination chemotherapy with gemcitabine and UFT for advanced pancreatic cancer in a multi-center trial].

The aim of this phase I/II study was to evaluate the tolerability and efficacy of combination chemotherapy with gemcitabine (GEM) and UFT for advanced pancreatic cancer. In phase I study UFT was given orally every day for 14 days and GEM was infused on day 1 and 8 at three dose levels (800, 900, 1,000 mg/m(2)/week) every 21 days. GEM 1,000 mg/m(2) and UFT 400 mg/m(2) did not reach the maximum tolerated dose. We decided that the recommended dose (RD) was GEM 1,000 mg/m(2)and UFT 400 mg/m(2). In phase II study 27 patients were enrolled and received GEM and UFT at RD. The tumor response rate was 17.6%, and the median survival was 221 days, which was very similar to that of GEM monotherapy. Due to adverse events, especially liver dysfunction, protocol therapy was discontinued in 12 patients. This study could not revealed the superiority of the GEM monotherapy.

[Multi-center trial of gemcitabine for 49 patients with advanced pancreatic cancer].

Forty-nine patients with unresectable pancreatic cancer (stage IV disease) received gemcitabine in a multi-center trial in the Fukuoka pancreatic cancer chemotherapy group, Japan. No complete remissions, 5 partial remissions (10%) and 25 no changes (51%) were obtained. Gemcitabine could maintain QOL. Main toxicities were hematologic, especially neutropenia. Neutropenia tended to appear in early administration. Non-hematologic toxicities were anorexia, nausea/vomiting, and skin rash. The mean overall survival period was 7.5 months. Carcinomatous ascites and/or pleural effusion resulted in a poor prognosis (average survival 3.1 months). Gemcitabine could be given without severe toxicities in outpatient clinics. These results suggested that gemcitabine is currently a first-line therapeutic agent for advanced pancreatic cancer.