Shinya Kajiura

Endoscopic submucosal dissection for superficial esophageal neoplasms using the stag beetle knife

Endoscopic submucosal dissection (ESD) is an accepted standard treatment for early gastric cancer but is not widely used in the esophagus because of technical difficulties. To increase the safety of esophageal ESD, we used a scissors-type device called the stag beetle (SB) knife. The aim of this study was to determine the efficacy and safety of ESD using the SB knife. We performed a single-center retrospective, uncontrolled trial. A total of 38 lesions were excised by ESD from 35 consecutive patients who were retrospectively divided into the following two groups according to the type of knife used to perform ESD: the hook knife (hook group) was used in 20 patients (21 lesions), and the SB knife (SB group) was used in 15 patients (17 lesions). We evaluated and compared the operative time, lesion size, en bloc resection rate, pathological margins free rate, and complication rate in both groups. The operative time was shorter in the SB group (median 70.0 minutes [interquartile range, 47.5-87.0]) than in the hook group (92.0 minutes [interquartile range, 63.0-114.0]) (P = 0.019), and the rate of complications in the SB group was 0% compared with 45.0% in the hook group (P = 0.004). However, the lesion size, en bloc resection rate, and pathological margins free rate did not differ significantly between the two groups. In conclusion, ESD using the SB knife was safer than that using a conventional knife for superficial esophageal neoplasms.

Predictive value of optimal morphologic response to first-line chemotherapy in patients with colorectal liver metastases.

Background: It has been reported that morphologic response to preoperative chemotherapy is an independent prognostic factor in patients who undergo hepatic resection of colorectal liver metastases (CLM). The aim of this study was to evaluate the predictive value of morphologic response to first-line chemotherapy in patients with CLM. Methods: We assessed 41 patients with CLM who received fluorouracil-based chemotherapy with or without bevacizumab as the first-line chemotherapy between April 2006 and June 2012. Three blinded radiologists evaluated computed tomography images and classified them as optimal, incomplete or no response according to the morphologic criteria. Response to systemic chemotherapy was also evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST). Predictive factors associated with progression-free survival (PFS) were identified in multivariate analysis. Results: Twenty-three patients (56%) received chemotherapy with bevacizumab, while 18 patients (44%) received chemotherapy without bevacizumab. Optimal morphologic response was observed in 11 patients (48%) treated with bevacizumab and in 5 patients (28%) treated without bevacizumab (p = 0.19). Eight patients (20%) underwent hepatic resection after chemotherapy. The median follow-up period was 31.3 months. The median PFS was 13.3 months for patients with optical morphologic response and 8.7 months in those with incomplete/no morphologic response (p = 0.0026). On multivariate analysis, performance status and morphologic response were significant independent predictors of PFS. Conclusion: Optimal morphologic response was significantly associated with PFS in patients with CLM who were treated with fluorouracil-based chemotherapy as the first-line chemotherapy.

Long-Term Follow-Up Outcome of Imatinib Mesylate Treatment for Recurrent and Unresectable Gastrointestinal Stromal Tumors

Background: The follow-up study of up to 71 months of a randomized phase II B2222 trial has demonstrated a long-term survival in patients with recurrent or unresectable gastrointestinal stromal tumors (GISTs). One subset of the patients (17.7%) has been alive for over 9 years with continuous imatinib mesylate (imatinib) treatment. Here, we report the retrospective analysis of recurrent or unresectable GIST patients with imatinib treatment at our institution. Methods: We summarized the data of 20 patients with recurrent or unresectable GIST treated with imatinib. Results: Patients were followed for a median of 40 months (range 2.5–103) under imatinib treatment. The median progression-free survival (PFS) was 89 months and overall survival for 8 years was 67%. Fifteen patients showed continuous partial response or stable disease with imatinib treatment. The median PFS was 45 months and the median size of the primary tumor was 7.6 cm (range 2.8–18). Four patients showed progressive disease. The median PFS was 56 months and the median size of the primary tumor was 11.9 cm (range 6.7–19). Grade 3 or 4 adverse events occurred in neutropenia (10%), anemia (15%) and renal dysfunction (5%). However, all patients were well managed by supportive treatment and none were discontinued from imatinib treatment due to toxicity or adverse events. Conclusion: Imatinib had a high efficacy in patients with unresectable and recurrent GIST during long-term follow-up. All patients were well managed by supportive treatment against adverse events and they were able to take imatinib without discontinuation. The management of adverse events was a key factor for achieving a long-term survival. In addition, the potential risk of imatinib-resistant GISTs tends to depend on the size of the primary GISTs.

Treatment outcome of advanced pancreatic cancer patients who are ineligible for a clinical trial

Objective The aim of this study was to evaluate the outcome of patients with advanced pancreatic cancer in clinical practice, and assess whether chemotherapy provided a clinical benefit for patients who did not meet the eligibility criteria of the clinical trial. Methods We retrospectively analyzed the medical records of 75 patients who received first-line chemotherapy for pancreatic cancer between April 2006 and September 2011. Patients were treated with gemcitabine (GEM) alone, S-1 (tegafur, gimeracil, and oteracil potassium) alone, or GEM plus S-1. Patients were divided into the clinical trial eligible group (arm eligible) or the ineligible group (arm ineligible). We evaluated the efficacy and the safety of the chemotherapy. Results A total of 23 patients out of 75 (31%) belonged to the ineligible group, for the following reasons: 20 patients had poor performance status, eight had massive ascites, one had synchronous malignancy, and one had icterus. The median progression-free survival (PFS) was 3.5 months, and the median overall survival (OS) was 6.7 months in all patients. In arm eligible, median PFS was 4.5 months, and median OS was 10.5 months. In arm ineligible, median PFS was 1.1 months, and median OS was 2.9 months. Conclusion The outcome of the patients who did not meet the eligibility criteria was very poor. It is important to select the patients that could benefit from either chemotherapy or optimal supportive care.

Fragmented CagA protein is highly immunoreactive in Japanese patients.

Background:  High‐molecular‐weight cell‐associated proteins (HM‐CAP) assay is the most popular serological immunoassay worldwide and has been developed from US isolates as the antigens. The accuracy is reduced when the sera are from adults and children in East Asia including Japan. To overcome the reduced accuracy, an enzyme immunoassay using Japanese strain–derived HM‐CAP (JHM‐CAP) was developed, in which the antigens were prepared by exactly the same procedure as HM‐CAP. The performance of JHM‐CAP was better than that of HM‐CAP in Japanese adults as well as in children. The higher sensitivity was because of the presence of 100‐kDa protein that was absent in the preparation of HM‐CAP antigen.

Amrubicin Monotherapy for Patients with Platinum-Refractory Gastroenteropancreatic Neuroendocrine Carcinoma

Objective. Patients with gastroenteropancreatic neuroendocrine carcinoma (NEC) have a poor prognosis. Platinum-based combination chemotherapy is commonly used as first-line treatment; however, the role of salvage chemotherapy remains unknown. This study aimed to analyze the efficacy and safety of amrubicin monotherapy in patients with platinum-refractory gastroenteropancreatic NEC. Methods. Among 22 patients with advanced gastroenteropancreatic NEC, 10 received amrubicin monotherapy between September 2007 and May 2014 after failure of platinum-based chemotherapy. The efficacy and toxicity of the treatment were analyzed retrospectively. Results. Eight males and two females (median age, 67 years (range, 52–78)) received platinum-based chemotherapy, including cisplatin plus irinotecan (n = 7, 70%), cisplatin plus etoposide (n = 2, 20%), and carboplatin plus etoposide (n = 1, 10%) before amrubicin therapy. Median progression-free survival and overall survival after amrubicin therapy were 2.6 and 5.0 months, respectively. Two patients had partial response (20% response rate), and their PFS were 6.2 months and 6.3 months, respectively. Furthermore, NEC with response for amrubicin had characteristics with a high Ki-67 index and receipt of prior chemotherapy with cisplatin and irinotecan. Grade 3-4 neutropenia and anemia were observed in four and five patients, respectively. Conclusion. Amrubicin monotherapy appears to be potentially active and well-tolerated for platinum-refractory gastroenteropancreatic NEC.

A study of the changes in the cause of peptic ulcer bleeding.

AIM To clarify the frequency of and changes in the cause of peptic ulcer bleeding. METHODS This study retrospectively evaluated the out- and inpatients who underwent endoscopy between 2002 to 2008. The subjects were patients presenting with peptic ulcer bleeding. The details of these patients were obtained from their endoscopic reports and medical records. RESULTS The rates of Helicobacter pylori (H. pylori) infection were significantly low (P = 0.039), while the proportion of nonsteroidal antiinflammatory drugs (NSAIDs) users and vascular disease significantly increased over the period studied (P = 0.034 and P = 0.04, respectively). However, there was no significant difference in the proportion of low-dose aspirin users (P = 0.832). CONCLUSION Its found that the primary cause of peptic ulcer bleeding changed from H. pylori infection to use of NSAIDs over the 7-year period of study. It seems that the number of low-dose aspirin users has increased with the increase in the proportion of vascular disease. It is necessary to take measures to prevent peptic ulcer bleeding among NSAIDs and low dose aspirin users.

Transient receptor potential vanilloid 4 (TRPV4) silencing in Helicobacter pylori-infected human gastric epithelium

Helicobacter pylori (HP) infection induces methylation silencing of specific genes in gastric epithelium. Various stimuli activate the nonselective cation channel TRPV4, which is expressed in gastric epithelium where it detects mechanical stimuli and promotes ATP release. As CpG islands in TRPV4 are methylated in HP‐infected gastric epithelium, we evaluated HP infection‐dependent changes in TRPV4 expression in gastric epithelium.

Phase I Study of Docetaxel Plus Nedaplatin in Patients With Metastatic or Recurrent Esophageal Squamous Cell Carcinoma After Cisplatin Plus 5-Fluorouracil Treatment:

Objectives:To date, no second-line chemotherapy regimen for esophageal squamous cell carcinoma (SCC) has been established. This clinical trial aimed to assess the optimum dose of docetaxel plus nedaplatin (cis-diammine-glycolate platinum) as second-line chemotherapy. Methods:Patients with metastatic or recurrent esophageal SCC after treatment with cisplatin plus 5-fluorouracil received docetaxel (50 or 60 mg/m2) plus nedaplatin (70 mg/m2) on day 1 every 4 weeks. The recommended dose was based on dose-limiting toxicities defined during the first cycle. Results:From February 2009 to November 2011, 9 patients were enrolled in the study. Their median age was 62 years (range, 58 to 72 y). Six patients had undergone radiotherapy and 4 had undergone surgical resection of primary lesions. Dose-limiting toxicities were observed in 2 patients at dose level 1 (60 mg/m2 docetaxel, 70 mg/m2 nedaplatin) but not at dose level 0 (50 mg/m2 docetaxel, 70 mg/m2 nedaplatin). Thus, the maximum tolerated dose was established at dose level 1. No severe nonhematological toxicity was observed. No patient achieved complete response, but 2 (22%; 95% confidence interval, 0%-49%) achieved partial response and 3 had stable disease. Median progression-free and overall survival times were 2.1 and 9.5 months, respectively. Conclusions:Docetaxel plus nedaplatin chemotherapy seems to be a safe and feasible second-line regimen for the treatment of esophageal SCC. We recommend the administration of 50 mg/m2 docetaxel (day 1) plus 70 mg/m2 nedaplatin (day 1) every 4 weeks in a phase II study.

Neuroendocrine Carcinoma of the Stomach: A Response to Combination Chemotherapy Consisting of Ramucirumab Plus Paclitaxel

Extrapulmonary neuroendocrine carcinoma (NEC) is a rare disease, and there is no standard chemotherapy. A 73-year-old man was diagnosed with advanced gastric NEC. He received chemotherapy of irinotecan plus cisplatin, and amrubicin monotherapy. After failure of second-line chemotherapy, he received ramucirumab plus paclitaxel; this treatment was chosen because vascular endothelial growth factor 2 was strongly expressed in the tumor endothelial cells. After two cycles, his NEC had markedly reduced in size, and he continued with this treatment for over eight months. In this case, the combination of an anti-angiogenic inhibitor and a cytotoxic agent was highly effective for gastric NEC.