Michiya Kobayashi

A 57-year-old woman presented with a chief complaint of right lower abdominal pain. Abdominal radiography and plain abdominal computed tomography revealed a mass with extensive calcification. A colonoscopy demonstrated a 20-mm-sized mass lesion protruding into the intestinal lumen from the ileocecal valve’s lower lip. The mass was covered with normal mucosa without erosions. Endoscopic ultrasonography indicated that the tumor originated from or beneath the proper muscle layer. To treat the pain, eliminate the obstruction risk, and obtain a definitive diagnosis, the patient chose surgical resection. Laparoscopic-assisted ileocecal resection was performed under the diagnosis of a submucosal ascending colon tumor. Macroscopically, the tumor showed no gross epithelial abnormalities. However, it was filled with fecal material and had an orifice of approximately 3 mm on the proximal side of the tumor. Histopathologically, the cyst wall consisted of an entire colonic structure, and continuity was noted between the cystic lesion’s wall and the ascending colon’s wall, leading to a diagnosis of diverticular expansion due to fecal matter. No malignancies were detected. A diverticulum can collect feces and protrude into the colonic lumen, resembling colonic submucosal tumors with calcification. Although rare, this condition should be included in the differential diagnosis of colon tumors.

It has been suggested that the therapeutic efficacy of S-1 + cisplatin (SP) and capecitabine + cisplatin (XP) may differ depending on the histology of the tumor, but no clear evidence exists. Individual participant data were obtained from three randomized phase II trials in which such patients received either SP (S-1 [40–60 mg twice daily for 21 days] plus cisplatin [60 mg/m² on day 8], every 5 weeks) or XP (capecitabine [1000 mg/m² twice daily for 14 days] plus cisplatin [80 mg/m² on day 1], every 3 weeks). A total of 162 patients were included, with 79 patients in the SP arm and 83 patients in the XP arm. Although there was also no difference between arms in ORR according to histological classification, differentiated tumors showed a significantly better OS (but not PFS) for SP versus XP that was associated with a deeper tumor shrinkage. Undifferentiated tumors showed a consistently better OS, and PFS for SP versus XP, likely because cases without tumor shrinkage tended to be fewer for SP. Our data thus showed that SP was superior to XP in this setting, but there were qualitative differences in therapeutic efficacy dependent on tumor histology.

Our aim was to clarify the incidence of bowel obstruction associated with a feeding jejunostomy (BOFJ) after thoracoscopic esophagectomy and its association to characteristics and postoperative change in body weight. We reviewed 100 consecutive patients who underwent thoracoscopic esophagectomy with gastric tube reconstruction and placement of a jejunostomy feeding catheter for esophageal cancer. The incidence of BOFJ was evaluated and the change in body weight after surgery was compared between patients with and without BOFJ. BOFJ developed in 17 patients. Compared to patients without BOFJ, those with BOFJ had a higher preoperative body mass index (23.3 kg/m2 versus 20.9 kg/m2, P = 0.022), and greater postoperative body weight loss rate: 3 month, decrease to 84.2% of initial body weight versus 89.3% (P = 0.002). Patients with BOFJ had shorter distance between the jejunostomy and midline (40 mm versus 48 mm, P = 0.011) compared to patients without BOFJ. On multivariate analysis, higher preoperative body mass index (odds ratio (OR) = 9.248; 95% confidence interval (CI) = 1.344–63.609; p = 0.024), higher postoperative weight loss at 3 months (OR = 8.490; 95% CI = 1.765–40.837, p = 0.008), and shorter distance between the jejunostomy and midline (OR = 8.160; 95% CI = 1.675–39.747, p = 0.009) were independently associated with BOFJ. Patients of BOFJ had greater preoperative body mass, shorter distance between jejunostomy and midline, and greater postoperative weight loss.

Although number of elderly patients with metastatic colorectal cancer (mCRC) is rapidly increasing, this population is often underrepresented in clinical trials. Recently, a phase II trial demonstrated that capecitabine and oxaliplatin (XELOX) combined with bevacizumab XELOX plus bevacizumab was effective and well tolerated by elderly patients with mCRC who reside in Western countries. The aim of this study was to evaluate the safety and efficacy of XELOX plus bevacizumab for Japanese patients aged ≥75 years with mCRC. This prospective, open-label phase II trial recruited patients aged ≥75 years with previously untreated mCRC between March 2010 and January 2012. Treatment consisted of 7.5 mg/kg of intravenous bevacizumab and 130 mg/m2 of oxaliplatin on day 1 of each cycle combined with 2000 mg/m2 of oral capecitabine per day on days 1–14 of each cycle. Treatment was repeated every 3 weeks until disease progression or termination of the study. The primary endpoint was progression-free survival; the secondary endpoints were toxicity, overall response rate, time-to-treatment failure, and overall survival. Thirty-six patients (male 58 %; median age 78 years; colon cancer 67 %) met all eligibility criteria and received at least one course of the planned treatment. The median time-to-treatment failure was 7.0 months. Twelve patients (33.3 %) experienced adverse effects (AEs) ≥ grade 3 and frequent AEs ≥ grade 3, including neutropenia (22.2 %) and neuropathy (13.9 %). Hypertension was the most frequent AE ≥ grade 3 associated with bevacizumab (11.1 %). Low baseline creatinine clearance associated significantly with the incidence of AEs ≥ grade 3. Response and disease control rates were 55.6 and 91.7 %, respectively. Median progression-free and overall survival times were 11.7 months (95 % confidence interval, 8.0–13.4 months) and 22.9 months, respectively. XELOX combined with bevacizumab was well tolerated by selected Japanese patients aged ≥75 years with mCRC patients, and controlled clinical trials are now required to determine the survival benefit.

The level of plasma diamine oxidase (DAO) activity is associated with the maturation and integrity of small intestinal mucosa. This study in rats investigated whether a decreased level of plasma DAO could reflect the severity of mucosal injury due to intravenous 5-fluorouracil (5-FU) treatment. The beneficial effect of soluble dietary fiber (SDF) on preventing diarrhea after 5-FU treatment was also examined. To induce diarrhea, 5-FU (50 mg/kg/day for four days) was administered via the tail vein with or without SDF supplementation. After 5-FU treatment, the majority of rats developed moderate to severe diarrhea, and levels of plasma DAO activity significantly decreased compared to those of control group (P < 0.05). Scanning electron microscopy revealed disarrangement of the small intestinal villi. Contrarily, the rats supplemented with SDF had diarrhea less frequently (50.0 vs. 91.7 %, P = 0.025) on day five, and DAO activity levels were significantly higher than in those rats administered 5-FU alone (8.25 ± 5.34 vs. 5.50 ± 4.32, P = 0.023). In conclusion, plasma DAO activity decreases in response to severe intestinal mucosal injury after 5-FU treatment, and SDF supplementation might be a practical and useful treatment for reducing the intestinal toxicity of 5-FU.

Background: Adjuvant chemotherapy for stage III colon cancer is internationally accepted as standard treatment with established efficacy. Several oral fluorouracil (5-FU) derivatives with different properties are available in Japan, but which drug is the most appropriate for each patient has not been established. Although efficacy prediction of 5-FU derivatives using expression of 5-FU activation/metabolism enzymes in tumors has been studied, it has not been clinically applied. Methods/design: The B-CAST study is a multicenter, prospective cohort study aimed to identify the patients who benefit from adjuvant chemotherapy with each 5-FU regimen, through evaluating the relationship between tumor biomarker expression and treatment outcome. The frozen tumor specimens of patients with stage III colon cancer who receives postoperative adjuvant chemotherapy are examined. Protein expression of thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) are evaluated using enzyme-linked immunosorbent assay (ELISA). mRNA expression of TP, DPD, thymidylate synthase (TS) and orotate phosphoribosyl transferase (OPRT) are evaluated using reverse transcription polymerase chain reaction (RT-PCR). The patients’ clinical data reviewed are as follow: demographic and pathological characteristics, regimen, drug doses and treatment duration of adjuvant therapy, types and severity of adverse events, disease free survival, relapse free survival and overall survival. Then, relationships among the protein/mRNA expression, clinicopathological characteristics and the treatment outcomes are analyzed for each 5-FU derivative. Discussion: A total of 2,128 patients from the 217 institutions were enrolled between April 2009 and March 2012. The B-CAST study demonstrated that large-scale, multicenter translational research using frozen samples was feasible when the sample shipment and Web-based data collection were well organized. The results of the study will identify the predictors of benefit from each 5-FU derivative, and will contribute to establish the “personalized therapy” in adjuvant chemotherapy for colon cancer. Trial registration: ClinicalTrials.gov: NCT00918827, UMIN Clinical Trials Registry (UMIN-CTR) UMIN000002013

Is there diversity among UGT1A1 polymorphism in Japan

In this paper we report a technique for laparoscopic lymph node (LN) dissection for descending and proximal sigmoid colon cancer with the preservation of the superior rectal artery (SRA) to maintain the blood supply to the distal sigmoid colon. Five (5) cases were included from November 2004 to March 2005. For D3 LN dissection, the root of inferior mesenteric artery was exposed with ultrasonic cutting and coagulating surgical device to avoid bleeding. The arterial wall was then exposed with a spatula-type electric cautery down to the left colic artery (LCA). The LCA was then clipped and cut while preserving the SRA. The inferior mesenteric vein was divided at the caudal side of the LCA and prior to joining to the splenic vein. All cases underwent a LN dissection laparoscopically. There were no cases of complications originating from the LN dissection. Although long-term outcomes should be investigated, our results indicate that this is a safe, applicable method.