Hepatic arterial infusion chemotherapy followed by sorafenib in patients with advanced hepatocellular carcinoma (HICS 55): an open label, non-comparative, phase II trial.

BACKGROUND: In patients with advanced hepatocellular carcinoma (HCC), evidence is unclear as to whether hepatic arterial infusion chemotherapy (HAIC) or sorafenib is superior. We performed a prospective, open-label, non-comparative phase II study to assess survival with HAIC or HAIC converted to sorafenib. METHODS: Fifty-five patients were prospectively enrolled. Patients received HAIC as a second course if they had complete response, partial response, or stable disease (SD) with an alpha fetoprotein (AFP) ratio < 1 or a des-γ-carboxy prothrombin (DCP) ratio < 1. Patients were switched to sorafenib if they had SD with an AFP ratio > 1 and a DCP ratio > 1 or disease progression. The primary endpoint was the 1-year survival rate. Secondary endpoints were the 2-year survival rate, HAIC response, survival rate among HAIC responders, progression-free survival, and adverse events. RESULTS: Of the 55 patients in the intent-to-treat population, the 1-year and 2-year survival rates were 64.0 and 48.3%, respectively. After the first course of HAIC, one (1.8%) patient showed complete response, 13 (23.6%) showed partial response, 30 (54.5%) had SD, and 10 (18.1%) patients had progressive disease. Twenty-three patients (41.8%) had SD with AFP ratios < 1 or DCP ratios < 1, and 7 (12.7%) had SD with AFP ratios > 1 and DCP ratios > 1. Thirty-seven patients (68.5%) were responders and 17 (30.9%) were non-responders to HAIC. In responders, the 1-year and 2-year survival rates were 78 and 62%, respectively. CONCLUSION: Given the results of this study, this protocol deserves consideration for patients with advanced HCC. This trial was registered prospectively from December 12. 2012 to September 1. 2016.

A trial of the use of patency capsules in combination with overnight capsule endoscopy.

BACKGROUND: The PillCam® patency capsule (PPC) was developed to minimize the risk of capsule retention during capsule endoscopy (CE). Typically, the use of patency capsules prior to CE requires patients to be monitored over a period of time. To reduce the need for frequent outpatient visits during PPC examination and CE, we developed the overnight CE (ON-CE) procedure. METHODS: Between October 2012 and January 2014, a total of 19 patients (15 males and 4 females, mean age 48.4 years) were administered PPC to assess the patency of the small intestine prior to ON-CE at JA Onomichi General Hospital in Hiroshima, Japan. RESULTS: PPC confirmed patency of the small intestine in 15 of the 19 patients. Of these 15 patients, 14 proceeded to ON-CE. The CE was cancelled in 1 patient and the cecal intubation time exceeded 8 h in another patient. For the remaining 12 patients, the mean small intestine observation coverage was 92.3% and the mean cecal intubation time was 325 min. There were no adverse events and the discharge of the capsule was confirmed in all cases. CONCLUSION: When patency of the gastrointestinal tract was confirmed with the PPC, ON-CE was performed safely and effectively.

Percutaneous transhepatic sclerotherapy for recurrent bleeding ileal varices diagnosed by capsule endoscopy and computed tomography during percutaneous transhepatic venography.

We report a case of acute uncontrolled gastrointestinal bleeding in a patient with liver cirrhosis. A 64-year-old man was admitted to our hospital for further investigation of blood in stools. Preliminary examination by computed tomography (CT) as well as upper and lower endoscopy could not detect the bleeding source. Exploratory laparotomy was considered difficult due to potential easy bleeding and adhesions caused by past abdominal surgery. The hemoglobin level was normalized by blood transfusion. Capsule endoscopy (CE) identified ileal varices. The top of these ileal varices was red, prompting their identification as the source of bleeding. Percutaneous transhepatic venography (PTV) confirmed the presence of many varices in the branch of the superior mesenteric vein, although the bleeding source could not be identified. CT during PTV identified varices protruding into the ileal lumen, which were managed subsequently by percutaneous transhepatic sclerotherapy (PTS). The procedure stopped the bleeding completely. CE proved less invasive and effective in detecting obscure gastrointestinal bleeding. CT during PTV followed by PTS is suitable for diagnosis and treatment of bleeding varices in patients with portal hypertension.

ITPA polymorphism effects on decrease of hemoglobin during sofosbuvir and ribavirin combination treatment for chronic hepatitis C.

BACKGROUND: Polymorphisms in the inosine triphosphatase (ITPA) gene is associated with anemia induced by peg-interferon (PEG-IFN) plus ribavirin (RBV) treatment for patients with chronic hepatitis C virus (HCV) infection. However, the effect of ITPA polymorphism on sofosbuvir plus RBV treatment is unknown. METHODS: Two hundred and forty-four patients with chronic HCV genotype 2 infection without decompensated liver cirrhosis were treated with sofosbuvir plus RBV for 12 weeks. The effects of ITPA polymorphism on hemoglobin levels and RBV dose reduction and treatment response were analyzed. ITPA (rs1127354) was genotyped using the Invader assay. Multivariate regression analysis was performed to identify factors associated with sustained virological response (SVR). RESULTS: Overall, SVR12 was achieved in 231 (94.7%) patients, based on intention to treat analysis. During the therapy, reduction of hemoglobin levels was significantly greater in ITPA genotype CC patients than CA/AA patients. Therefore, the cumulative proportion of patients with RBV dose reduction was significantly higher and total dose of RBV was significantly lower in patients with CC genotype compared to CA/AA genotypes. SVR12 rates were similar between ITPA genotypes CC and CA/AA (94.7 and 94.4%, respectively, P = 0.933). Multivariate logistic regression analysis identified FIB4 index <3.25 (odds ratio [OR], 9.388 for ≥3.25; P = 0.005) and low body weight (OR, 1.059, for high body weight; P = 0.017) as independent predictors for SVR12. CONCLUSIONS: ITPA polymorphism influences hemoglobin levels and incidence of RBV dose reduction during sofosbuvir plus RBV therapy. However, ITPA genotype CC patients can expect a curative effect equivalent to CA/AA patients for chronic HCV genotype 2 infection.

Current treatment strategies for pancreatic cancer in the elderly.

Pancreatic cancer, which is responsible for >90% of exocrine pancreatic tumours, is typically a disease of the elderly (> or =70 years of age). However, older patients are less likely to be staged than younger patients despite having a worse overall 5-year survival rate than their younger counterparts. Various radiological, ultrasonographic and endoscopic investigations are used not only as diagnostic tools but also to accurately stage the cancer for possible surgery. Many patients with pancreatic cancer have mutations of the K-ras oncogene, and various tumour suppressor genes are also inactivated. Pancreas resection can be performed in elderly resectable patients without excess mortality, even in those >80 years of age. However, treatment for locally advanced, unresectable and metastatic pancreatic cancer is palliative. Fluorouracil-based chemoradiation for locally advanced or unresectable cancer, and gemcitabine for patients with metastatic disease, can result in clinical benefits. Placement of a stent in the biliary tract has been shown to improve symptoms of obstructive jaundice or ascites, as well as quality of life. As molecular targets are identified, interventions with targeted specific agents may improve tumour control. However, further studies will be needed to demonstrate whether or not various agents targeting signal transduction pathways or nuclear transcription factors are useful for elderly patients with advanced pancreatic cancer.

[Antimicrobial susceptibility and beta-lactamase producibility of bacteria clinically isolated during the period from December 1999 to February 2000].

Antimicrobial susceptibility and beta-lactamase producibility were tested in 848 clinical strains collected at 8 hospitals in Kanagawa prefecture during the period from December 1999 to February 2000. Positive rates of beta-lactamase used the nitrocefin method (Cefinase) were 21.9% of Staphylococcus aureus, 10.0% of Haemophilus influenzae, and 99.0% of Moraxella catarrhalis. Furthermore, on the acidometric method (P/Case test) penicillinase (PCase), cephalosporinase (CEPase), and both of PCase and CEPase were found to be positive in 19.0%, 16.0%, and 16.0% for Escherichia coli, 6.2/0/3.1% for Klebsiella pneumoniae, 0/66.3/26.5% for Enterobacter cloacae, 2.8/57.7/15.5% for Serratia marcescens, and 4.0/15.0/22.0% for Pseudomonas aeruginosa, respectively. Based on the assessment of minimal inhibitory concentrations (MICs) of antibacterial agents among beta-lactamase producing strains, there were 5 strains (4 strains of K. pneumoniae and 1 strain of E. coli) that may be ESBLs producing bacteria out of a total of 466 strains of Enterobacteriaceae and P. aeruginosa. During this process, 1 strain of class-B beta-lactamase-producing E. cloacae was isolated. MRSA were found in 79.2% of S. aureus, and BLNAR were found in 8.9% of H. influenzae.

[Gemcitabine in elderly patients with unresectable pancreas cancer].

The efficacy and safety of gemcitabine at a starting dose of 1,000 mg/m2 administrated once a week for 3 weeks with 1 week's rest was investigated in elderly 11 patients with unresectable pancreatic cancer. Objective response was not documented. However, pain intensity, analgesic consumption and Karnofsky Performance Status (KPS) were frequently improved. In total, a clinical benefit was observed in 8 out of 11 (73%) patients. Toxicity was mild and well tolerated. These results suggest that gemcitabine had a superior clinical benefit and a mild toxicity profile. Gemcitabine should be the standard treatment in elderly patients with unresectable pancreatic cancer.

[A case of mucosal Schwann cell hamartoma].

A 40-year-old man was referred to our hospital because of a positive fecal occult blood test. Colonoscopy revealed many small whitish nodules in the mucosa of the sigmoid colon. Specimens endoscopically resected from the lesions revealed spindle cell proliferation in the lamina propria. Immunohistochemical study revealed strong and diffuse positivity for S-100 protein. Results of staining for neurofilament protein and epithelial membrane antigen were negative. The neurogenic tumors were diagnosed as mucosal Schwann cell hamartoma. No clinical features of multiple endocrine neoplasia type 2B or neurofibromatosis type 1 were found in the present case.

A case of Helicobacter pylori-negative depressed type gastric adenoma.

A 75-year-old woman was referred to our hospital for further examination of gastric antral abnormal endoscopic findings. Endoscopic study of the stomach revealed a depressed lesion in the gastric antrum. Atrophic findings were not recognized in the background gastric mucosa, and Helicobacter pylori infection was not detected by histology, an urea breath test, a rapid urease test and serological test. A diagnosis of adenoma was given histopathologically from the resected specimens. As a result of immunohistological study, the phenotype of the tumor was not classified as either gastric type or intestinal type. CDX2 was positive in part of the tumor.