Real-world efficacy of daclatasvir and asunaprevir with respect to resistance-associated substitutions

AIM To investigate daclatasvir(DCV) and asunaprevir(ASV) efficacy in hepatitis C(HCV) patients, with respect to resistance-associated substitutions(RASs).METHODS A total of 392 HCV-infected patients from multiple centers were included in this study. We evaluated their clinical courses and sustained virologic responses(SVR) according to pretreatment factors(gender, age, history of interferon-based regimens, platelet counts, level of viremia, pretreatment NA5A:L31, and Y93 substitutions). We also analyzed the pretreatment and post-treatment major RASs of NS3:D168, NS5A:L31 and Y93 substitutions using a direct-sequencing method in 17 patients who were unable to achieve SVR at 12 wk after treatment completion(SVR12).RESULTS The overall SVR12 rate was 88.3%. Thirty-one patients discontinued treatment before 24 wk because of adverse events, 23 of whom achieved SVR12. There were no significant differences in SVR12 rates with respect to gender, age, history of interferon-based regimens, and platelet counts. The SVR12 rate in patients with viral loads of ≥ 6.0 log IU/m L was significantly lower than those with viral loads of < 6.0 log IU/m L(P < 0.001). The SVR12 rate in patients with Y93 substitution-positive was significantly lower than those with Y93 substitution-negative(P < 0.001). The L31 substitution-positive group showed a lower SVR12 rate than the L31 substitution-negative group, but the difference was not statistically significant. Seventeen patients who did not achieve SVR12 and had available pretreatment and post-treatment sera had additional RASs in NS3:D168, NS5:L31, and Y93 substitution at treatment failure.CONCLUSION Combination of DCV and ASV is associated with a high SVR rate. Baseline RASs should be thoroughly assessed to avoid additional RASs after treatment failure.

Efficient hemostatic method for endoscopic submucosal dissection of colorectal tumors

AIM:To evaluate a new hemostatic method using hemostatic forceps to prevent perforation and perioperative hemorrhage during colonic endoscopic submucosal dissection(ESD).METHODS:We studied 250 cases,in which ESD for colorectal tumors was performed at the Kyoto Prefectural University of Medicine or Nara City Hospital between 2005 and 2010.We developed a new hemostatic method using hemostatic forceps in December 2008 for the efficient treatment of submucosal thick vessels.ESD was performed on 126 cases after adoption of the new method(the adopted group)and the new method was performed on 102 of these cases.ESD was performed on 124 cases before the adoption of the new method (the unadopted group).The details of the new method are as follows:firstly,a vessel was coagulated using the hemostatic forceps in the soft coagulation mode according to the standard procedure,and the coagulated vessel was removed using the forceps in the"endocut" mode without perioperative hemorrhage.Secondly,the partial surrounding submucosa was dissected using the forceps in the endocut mode.In the current study,we evaluated the efficacy of this method.RESULTS:Coagulated vessels were successfully removed using the hemostatic forceps in all 102 cases without severe perioperative hemorrhage.Moderate perioperative hemorrhage occurred in five cases(4.9%);however,it was stopped by immediately reuse of the hemostatic forceps.The partial surrounding submucosa was dissected using the forceps in all 102 cases.In the adopted group,the median operation time was 105 min.The proportion of endoscopic en bloc resection was 92.8%(P<0.01)compared to 80.6%in the unadopted group.The postoperative hemorrhage and perforation rates were 2.3%and 2.3%.The rate of perforation was significantly lower than that in the unadopted group (9.6%,P<0.01).We evaluated the ease of use of this method by allowing our three trainees to performed ESD on 46 cases,which were accomplished without any severe hemorrhage.CONCLUSION:The new method effectively treated submucosal thick vessels and shows promise for the prevention of perforation and perioperative hemorrhage in colonic ESD.

Image-enhanced endoscopy for diagnosis of colorectal tumors in view of endoscopic treatment

Recently,image-enhanced endoscopy(IEE) has been used to diagnose gastrointestinal tumors.This method is a change from conventional white-light(WL) endoscopy without dyeing solution,requiring only the push of a button.In IEE,there are many advantages in diagnosis of neoplastic tumors,evaluation of invasion depth for cancerous lesions,and detection of neoplastic lesions.In narrow band imaging(NBI) systems(Olympus Medical Co.,Tokyo,Japan),optical filters that allow narrow-band light to pass at wavelengths of 415 and 540 nm are used.Mucosal surface blood vessels are seen most clearly at 415 nm,which is the wavelength that corresponds to the hemoglobin absorption band,while vessels in the deep layer of the mucosa can be detected at 540 nm.Thus,NBI also can detect pit-like structures named surface pattern.The flexible spectral imaging color enhancement(FICE) system(Fujifilm Medical Co.,Tokyo,Japan) is also an IEE but different to NBI.FICE depends on the use of spectral-estimation technology to reconstruct images at different wavelengths based on WL images.FICE can enhance vascular and surface patterns.The autofluorescence imaging(AFI) video endoscope system(Olympus Medical Co.,Tokyo,Japan) is a new illumination method that uses the difference in intensity of autofluorescence between the normal area and neoplastic lesions.AFI light comprises a blue light for emitting and a green light for hemoglobin absorption.The aim of this review is to highlight the efficacy of IEE for diagnosis of colorectal tumors for endoscopic treatment.

Comparison of peg-interferon, ribavirin plus telaprevir vs simeprevir by propensity score matching

AIM: To compare efficacy of telaprevir(TVR) and simeprevir(SMV) combined with pegylated interferon(PEG-IFN) and ribavirin(RBV) while treating chronic hepatitis C(CHC). METHODS: In all, 306 CHC patients were included in this study. There were 159 patients in the TVR combination therapy group and 147 patients in the SMV combination therapy group. To evaluate pretreatment factors contributing to sustained virological response at 12 wk(SVR12), univariate and multivariate analyses were performed in TVR and SMV groups. To adjust for patient background between TVR and SMV groups, propensity score matching was performed. Virological response during treatment and SVR12 were evaluated.RESULTS: Overall rates of SVR12 [undetectable serum hepatitis C virus(HCV) RNA levels] were 79.2% and 69.4% in TVR and SMV groups, respectively. Patients in the SMV group were older, had higher serum HCV RNA levels, lower hemoglobin, higher prevalence of unfavorable interleukin-28B(IL28B) genotype(rs8099917), and poorer response to previous PEG-IFN and RBV treatment. Propensity score matching was performed to adjust for backgrounds(n = 104) and demonstrated SVR12 rates of 74.0% and 73.1% in the TVR and SMV groups, respectively. In the TVR group, discontinuation rates were higher because of adverse events; however, breakthrough and nonresponse was more frequent in the in SMV group. Multivariate analysis revealed IL28 B genotype(rs8099917) as the only independent predictive factor of SVR12 in both groups.CONCLUSION: SVR12 rates were almost identical following propensity score matching.

Gastric carcinoma originating from the heterotopic submucosal gastric gland treated by laparoscopy and endoscopy cooperative surgery

Gastric carcinoma is derived from epithelial cells in the gastric mucosa. We reported an extremely rare case of submucosal gastric carcinoma originating from the heterotopic submucosal gastric gland(HSG) that was safely diagnosed by laparoscopy and endoscopy cooperative surgery(LECS). A 66-year-old man underwent gastrointestinal endoscopy, which detected a submucosal tumor(SMT) of 1.5 cm in diameter on the lesser-anterior wall of the upper gastric body. The tumor could not be diagnosed histologically, even by endoscopic ultrasound-guided fine-needle aspiration biopsy. Local resection by LECS was performed to confirm a diagnosis. Pathologically, the tumor was an intra-submucosal well differentiated adenocarcinoma invading 5000 μm intothe submucosal layer. The resected tumor had negative lateral and vertical margins. Based on the Japanese treatment guidelines, additional laparoscopic proximal gastrectomy was curatively performed. LECS is a less invasive and safer approach for the diagnosis of SMT, even in submucosal gastric carcinoma originating from the HSG.

Safe procedure in endoscopic submucosal dissection for colorectal tumors focused on preventing complications

Endoscopic submucosal dissection (ESD) is efficient for en bloc resection of large colorectal tumors. However, it has several technical difficulties, because the wall of the colon is thin and due to the winding nature of the colon. The main complications of ESD comprise postoperative perforation and hemorrhage, similar to endoscopic mucosal resection (EMR). In particular, the rate of perforation in ESD is higher than that in EMR. Perforation of the colon can cause fatal peritonitis. Endoscopic clipping is reported to be an efficient therapy for perforation. Most cases with perforation are treated conservatively without urgent surgical intervention. However, the rate of postoperative hemorrhage in ESD is similar to that in EMR. Endoscopic therapy including endoscopic clipping is performed and most of the cases are treated conservatively without blood transfusion. In blood examination, some degree of inflammation is detected after ESD. For the standardization of ESD, it is most important to decrease the rate of perforation. Adopting a safe strategy for ESD and a suitable choice of knife are both important waysof preventing perforation. Moreover, appropriate training and increasing experience can improve the endoscopic technique and can decrease the rate of perforation. In this review, we describe safe procedures in ESD to prevent complications, the complications of ESD and their management.

Direct cholangioscopy combined with doubleballoon enteroscope-assisted endoscopic retrograde cholangiopancreatography

Double-balloon enteroscope (DBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) is an effective endoscopic approach for pancreatobiliary disorders in patients with altered gastrointestinal anatomy. Endoscopic interventions via DBE in these postoperative settings remain difficult because of the lack of an elevator and the use of extra-long ERCP accessories. Here, we report the usefulness of direct cholangioscopy with an ultra-slim gastroscope during DBE-assisted ERCP. Three patients with choledocholithiasis in postoperative settings (two patients after Billroth Ⅱ gastrojejunostomy and one patient after Roux-en-Y gastrojejunostomy) were treated. DBE was used to gain access to the papilla under carbon dioxide insufflation, and endoscopic sphincterotomy was performed with a conventional sphincterotome. For direct cholangioscopy, the enteroscope was exchanged for an ultra-slim gastroscope through an incision in the overtube, which was inserted directly into the bile duct. Direct cholangioscopy was used to extract retained bile duct stones in two cases and to confirm the complete clearance of stones in one case. Bile duct stones were eliminated with a 5-Fr basket catheter under direct visual control. No adverse events were noted in any of the three cases. Direct cholangioscopy with an ultra-slim gastroscope facilitates subsequent treatment within the bile duct. This procedure represents another potential option during DBE-assisted ERCP.

Pseudomembranous colitis presenting as acute colonic obstruction without diarrhea in a patient with gastric Burkitt lymphoma

Pseudomembranous colitis (PMC) usually manifests asfever and diarrhea in hospitalized patients treated withsystemic antibiotics. We described a case of PMC withintestinal obstruction but without diarrhea. A 60-yearold man was hospitalized for chemotherapy for the treatment of Burkitt lymphoma of the stomach. The patient became febrile and complained of crampy abdominal pain during the post-chemotherapy nadir. Plain abdominal radiography showed some intestinal gas and niveau. Because stool cytotoxin assay for clostridium difficile was positive and colon fiberscopic examination showed a pseudomembrane at the left side of the colon,and a diagnosis of PMC was made. Treatment with intracolonic vancomycin administration by colonoscopy and nasoileus tube was successful. Physicians should take into account the possibility of bowel obstruction due to PMC occurring in patients undergoing chemotherapy and perform emergency colonoscopy examination of suspected cases.

A Review of Non-operative Treatments for Hepatocellular Carcinoma with Advanced Portal Vein Tumor Thrombus

Portal vein tumor thrombus (PVTT) frequently occurs with the progression of hepatocellular carcinoma (HCC) and is an important factor in determining the prognosis of HCC.In many cases of HCC with advanced PVTT,treatment is difficult because the tumor has considerable extension into the liver,and portal hypertension is a frequent complication.The standard therapy for unresectable HCC with advanced PVTT is sorafenib therapy in patients with good hepatic function.However,the outcomes of sorafenib therapy are not completely satisfactory,making the development of another therapy an urgent task.Therefore,this review aims to summarize non-operative treatments for HCC with advanced PVTT and discuss future perspectives based on those therapies,including therapies still being developed.

在早 colorectal 癌症的内视镜的切除术的组织学的评估的重要性

The diagnostic criteria for colonic intraepithelial tumors vary from country to country.While intramucosal adenocarcinoma is recognized in Japan,in Western countries adenocarcinoma is diagnosed only if the tumor invades to the submucosa and accesses the muscularis mucosae.However,endoscopic therapy,including endoscopic mucosal resection(EMR)and endoscopic submucosal dissection(ESD),is used worldwide to treat adenoma and early colorectal cancer.Precise histopathological evaluation is important for the curativeness of these therapies as inappropriate endoscopic therapy causes local recurrence of the tumor that may develop into fatal metastasis.Therefore,colorectal ESD and EMR are not indicated for cancers with massive submucosal invasion.However,diagnosis of cancer with massive submucosal invasion by endoscopy is limited,even when magnifying endoscopy for pit pattern and narrow band imaging and flexible spectral imaging color of enhancement are performed.Therefore,occasional cancers with massive submucosal invasion will be treated by ESD and EMR.Precise histopathological evaluation of these lesions should be performed in order to determine the necessity of additional therapy,including surgical resection.

Epidemiology of hepatocellular carcinoma in nonalcoholic fatty liver disease

Along with the changes in our food culture and lifestyle,conditions such as obesity,diabetes mellitus,and metabolicsyndrome have been on the rise,and the incidence of nonalcoholic fatty liver disease(NAFLD),which is closelyrelated to these diseases,has also increased rapidly.Despite being a risk factor for the development of hepatocellularcarcinoma(HCC),NAFLD has no established screening method,and HCC originating from NAFLD often tends to be discovered in its advanced and symptomatic stages,which has become an important clinical problem.Even though the carcinogenicity rate among the entire population of NAFLD patients is not high compared to that of patients with viral hepatitis,since HCC also often develops from non-cirrhotic livers,it is difficult to narrow down the cases that need to be under surveillance.Going forward,it will be important to clarify the clinical characteristics and genetic background of NAFLD-related HCC and establish not only a useful surveillance method but also preventive methods.