Yukinori Imai

Guideline on the use of new anticancer drugs for the treatment of Hepatocellular Carcinoma 2010 update

The “Guideline on the Use of New Anticancer Drugs for the Treatment of Hepatocellular Carcinoma” was prepared by the Study Group on New Liver Cancer Therapies established by the “Research Project on Emergency Measures to Overcome Hepatitis” under the auspices of the Health and Labour Sciences Research Grant. The Guideline brings together data collected by the Study Group on the use and incidence of adverse events in 264 patients with advanced hepatocellular carcinoma (HCC) treated using sorafenib and in 535 patients with advanced HCC treated using miriplatin at 16 participating institutions up until 22 December 2010, as well as referring to the published studies, academic presentations, and reports from the private sector. The aim of this Guideline is to facilitate understanding and current thinking regarding the proper usage of new anticancer drugs towards actual use in therapy. In terms of the format, the Guideline presents “clinical questions” on issues pertaining to medical care, makes “recommendations” on diagnosis and treatment in response to each of these clinical questions, and provides a rationale for these recommendations in the form of “scientific statements”.

Development of rare resistance-associated variants that are extremely tolerant against NS5A inhibitors during daclatasvir/asunaprevir therapy by a two-hit mechanism

The virologic characteristics of resistance‐associated variants (RAVs) developing in patients receiving dual oral therapy with daclatasvir/asunaprevir, including those with previous triple therapy with simeprevir, were evaluated.

Development of rare RAVs that are extremely tolerant against NS5A inhibitors during daclatasvir/asunaprevir therapy Via a Two-Hit mechanism.

The virologic characteristics of resistance‐associated variants (RAVs) developing in patients receiving dual oral therapy with daclatasvir/asunaprevir, including those with previous triple therapy with simeprevir, were evaluated.

Therapeutic strategy for patients with bleeding rectal varices complicating liver cirrhosis

Although rupture of rectal varices is rarely encountered, it may provoke massive and fatal hemorrhage in patients with liver cirrhosis. We examined the clinical features of patients showing bleeding from rectal varices to establish a suitable therapeutic strategy for the lesions.

Long‐Term Outcome of 154 Patients Receiving Balloon‐Occluded Retrograde Transvenous Obliteration for Gastric Fundal Varices

This study aims to clarify the long‐term outcome of therapeutic strategies including balloon‐occluded retrograde transvenous obliteration (B‐RTO) for patients with gastric fundal varices.

Balloon-occluded retrograde transvenous obliteration using a microballoon catheter for intractable gastric fundal varices.

Balloon‐occluded retrograde transvenous obliteration (B‐RTO) is recognized as the standard therapy for patients with gastric fundal varices in Japan; however, the procedure is difficult when drainage veins other than the gastrorenal shunt developed. The efficacy and safety of B‐RTO using a microballoon catheter for such patients were evaluated.

A case of liver cirrhosis due to hepatits C virus infection complicating giant anorectal varices treated with balloon-occluded retrograde transvenous obliteration.

A 73-year-old man with liver cirrhosis due to hepatitis C virus infection was admitted to our hospital because of massive bleeding from external varices. Colonoscopic examination revealed that giant anorectal varices had developed between the anus and rectal ampulla, and had ruptured at the perianal site. On three-dimensional computed tomography imaging, the feeding and drainage vessels of the varices were identified as the inferior mesenteric vein and right inferior hemorrhoidal vein, respectively. Endoscopic therapies were not employed for the bleeding varices, because the blood flow volume of the feeding vessel was extremely large. Balloon-occluded retrograde transvenous obliteration (B-RTO) was therefore carried out through the drainage vessels. The variceal blood flow disappeared after B-RTO therapy, and the varices decreased in size with thrombus formation verified by colonoscopy. Bleeding from the external varices also ceased. B-RTO therapy may be an effective approach for giant anorectal varices presenting as a complication in liver cirrhosis patients in whom the main drainage vessels can be determined.

Transcatheter arterial chemoembolization for hepatocellular carcinoma: Comparison of the therapeutic efficacies between miriplatin and epirubicin.

The therapeutic efficacy of transcatheter arterial chemoembolization (TACE) using miriplatin was evaluated in comparison with that using epirubicin in patients with hepatocellular carcinoma (HCC).

Usefulness of gastroesophageal reflux scintigraphy using the knee-chest position for the diagnosis of gastroesophageal reflux disease.

ObjectivesThe aim of this study is to evaluate the usefulness of gastroesophageal reflux (GER) scintigraphy using the knee-chest (KC) position for the diagnosis of gastroesophageal reflux disease (GERD).MethodsThe study subjects were 37 patients with GERD and 8 healthy volunteers (control group). Endoscopically observed esophageal mucosal breaks were evaluated with the Los Angeles classification. For GER scintigraphy, the subjects ingested liquid yogurt labeled with99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA) and water. Imaging was performed in the supine and KC position, and GER was graded as 1-4 according to the extent of GER assessed by scintigraphy.Results GER scintigraphy revealed no reflux in the control group (specificity: 100%). In the supine position, gastroesophageal reflux was observed in 49% of the patients with GERD, compared to 76% in the KC position. 21 of 23 (91%) patients with erosive esophagitis were shown to have GER with scintigraphy. GER scintigraphy revealed severe reflux (grade 3 or 4) (83%, 10/12) in the patients who had severe mucosal breaks (LA grade C or D). GER scintigraphy detected grade 1 or 2 reflux in 7 of the 14 patients who were endoscopically negative. There was a correlation between the endoscopically determined severity of mucosa and the reflux grade which was determined with GER scintigraphy.ConclusionGER scintigraphy can detect gastroesophageal reflux with a high sensitivity in the KC position and might be a useful method in the screening and assessment of the severity of this disease. This method would be useful for the diagnosis of GERD in endoscopically negative patients.

“Reversi‐type virologic failure” involved in the development of non‐structural protein 5A resistance‐associated variants (RAVs) in patients with genotype 1b hepatitis C carrying no signature RAVs at baseline

The therapeutic efficacy of daclatasvir/asunaprevir was inferior in patients with non‐structural protein 5A (NS5A)‐R30Q mutant hepatitis C virus strains at baseline, compared with those with wild‐type strains, even though the half maximal effective concentration of NS5A inhibitors was lower in mutant strains than in wild‐type strains. In these patients, R30Q and Y93H mutant strains, which are highly resistant to NS5A inhibitors, emerged at virologic failure. The mechanisms involved in such virologic failure were examined.