Hiroki Yoshita

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.

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.

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.

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.

Multiple Colon Ulcers with Typical Small Intestinal Lesions Induced by Non-Steroidal Anti-Inflammatory Drugs

The diagnosis of NSAID-induced colon ulcers is difficult when the distribution or endoscopic findings are not typical. An 83-year-old woman was transferred to our hospital for hemorrhagic diarrhea. Colonoscopy showed multiple ulcers in the entire colon, particularly longitudinal ulcers in the transverse colon. These were unusual for NSAID-induced colopathy, although she had been on meloxicam. However, capsule endoscopy revealed multiple scars and erosions, characteristic of NSAIDs users. The final diagnosis was NSAID-induced enteropathy, and all lesions were in remission after meloxicam discontinuation. We herein emphasize the value of an endoscopic assessment of the entire digestive tract in the diagnosis of NSAID-induced mucosal lesions.

Multiple Synchronous Sporadic Gastrointestinal Stromal Tumors in the Stomach and Jejunum

A 77-year-old patient was admitted to our hospital for the further examination of melena. A computed tomography scan detected two submucosal tumors (SMTs) in the stomach and jejunum. Double-balloon endoscopy revealed the presence of a delle on the jejunal SMT, suggesting that the SMT was the origin of the gastrointestinal bleeding. Both tumors were surgically resected and subsequently diagnosed via histology as gastrointestinal stromal tumors (GISTs). Furthermore, the two GISTs had different mutations in the c-kit gene, suggesting that they were derived from different clonal origins. This report depicts an extremely rare case of multiple synchronous sporadic GISTs in the stomach and jejunum.

Preventive effect of Rikkunshito, a traditional Japanese medicine, on chemotherapy-induced nausea and vomiting with cisplatin: Case series

Supportive therapies are important to treat chemotherapy‐induced nausea and vomiting (CINV). Rikkunshito, a Kampo medicine, has been reported to be effective against cisplatin‐induced anorexia in rats. In the present study, we evaluated the preventive effect of Rikkunshito for CINV in patients receiving high‐dose cisplatin chemotherapy.

Su1982 Favorable Prognostic Factors in Advanced Gastric Cancer Patients Ineligible for Criteria of the Clinical Trial

Background/Aims: According to Correas hypothesis, adenoma at stomach plays a role in gastric carcinogenesis as a precursor. Since endoscopic resection including endoscopic submucosal dissection for premaligant or cancerous lesion has been generally accepted as one of treatment options, endoscopist may have a chance to get the pathologic results showing early gastric cancer arising from adenoma (EGC-AFA). However there have been few reports about clinicopathologic characteristics of EGC-AFA. The aim of this study was to evaluate characteristics of EGC-AFA compared to de novo EGC treated by endoscopic resection. Methods: Between January 2008 and December 2011, 1005 EGCs form 981 S-524 AGA Abstracts patients by endoscopic resectionwere enrolled.We retrospectively reviewed clinicopathologic data of 1005 EGC lesions. Among them 161 lesions (16%) were EGC-AFA and 844 (84%) were de novo EGC. Results: There was no significant difference of age, sex, location of tumor, and gross morphology on EGD between two groups. Synchronous cancer was significantly more frequent in EGC-AFA than in de novo EGC (19.3% vs 10.3%, p=0.001). The tumor size of EGC-AFA measured on EGD was significantly larger than that of de novo EGC (16.6±9.9mm vs 14.5±7.3mm, p=0.004). However, there was no significant difference of actual tumor size on pathologic specimen. The frequency of pathologic discrepancy between biopsy specimen and resected one was higher in EGC-AFA than in de novo EGC (36.6% vs 24.2%, p=0.01). In pathologic characteristics, the differentiated type adenocarcinoma has been shown more frequent in EGC-AFA than de novo EGC (95% vs 88%, p= 0.009), and the submucosal invasion according to T stage (T1b) was significantly less frequent in EGC-AFA than in de novo EGC (12.4% vs 18.0%, p=0.001). Conclusion: The observation of co-existence of adenoma and carcinoma in one specimen is not uncommon. Due to association of adenomatous changes around cancerous lesion, misdiagnosis rate at biopy specimen higher in EGC-AFA and the size measurement of EGC-AFA might be exaggerated on EGD examination. The features of more differentiation and less invasiveness would give more favorable prognosis to EGC-AFA. The endoscopist should pay attention on synchronous ormetachronous lesions on follow up endoscopic examinationwhen encountered EGC-AFA.