Detection of aberrant crypt foci with image-enhanced endoscopy.

Background and study aims Conventional detection of aberrant crypt foci (ACF) with dye-spraying and magnifying observation is labor- and skill-intensive. We performed a prospective non-inferiority study to investigate the utility of image-enhanced endoscopy (IEE) for detection of ACF. Patients and methods Patients with a history of colorectal neoplasm were eligible. The number of ACF in the lower rectum was counted first using IEE magnification with narrow-band imaging (NBI) or blue-laser imaging (BLI), and subsequently using the methylene blue method. The primary endpoint was the ACF detection rate with IEE, i. e., the number of ACF detected with IEE relative to the number of ACF detected with methylene blue. The secondary endpoints were bowel preparation time, ACF detection time, and the detection rate with NBI or BLI. Results A total of 40 patients were enrolled (NBI 20 and BLI 20). The overall detection rate for ACF with IEE was 81.7 % (503/616; 95 %CI 78.8 - 84.6 %), meeting the primary endpoint. The detection rate for ACF with BLI (84.9 %, 258/304) was significantly higher than with NBI (78.5 %, 245/312; P  < 0.05). Both bowel preparation time and ACF detection time were significantly shorter with IEE versus the methylene blue method ( P  < 0.01, respectively). The detection rates for dysplastic and non-dysplastic ACF with IEE were 84.4 % (27/32) and 80.3 % (469/584), respectively. Conclusion IEE is able to detect ACF during colonoscopy with sensitivity non-inferior to that of the conventional methylene blue method. IEE is simpler than the methylene blue method and is therefore a potentially useful new tool for ACF detection.

Panitumumab in combination with irinotecan plus S-1 (IRIS) as second-line therapy for metastatic colorectal cancer.

BACKGROUND: Irinotecan plus S-1 (IRIS) is the only oral fluoropyrimidine-based regimen reported to be non-inferior to FOLFIRI and widely used in clinical practice for metastatic colorectal cancer (mCRC) patients. However, the combination of IRIS plus an anti-EGFR agent has not been evaluated previously. This study aimed to investigate the feasibility and efficacy of IRIS with panitumumab as second-line therapy for wild-type KRAS mCRC. METHODS: Main inclusion criteria were patients with wild-type KRAS mCRC refractory to one prior chemotherapy regimen for mCRC, ECOG PS 0-2, and age ≥20 years. Patients received panitumumab (6 mg/kg) and irinotecan (100 mg/m(2)) on days 1 and 15 and S-1 (40-60 mg according to body surface area) twice daily for 2 weeks, repeated every 4 weeks. The primary endpoint was the feasibility of the therapy. The secondary endpoints were response rate (RR), progression-free survival (PFS), and overall survival (OS). RESULTS: A total of 36 patients received protocol treatment in eight centers. Of these, 23 patients (63.9 %) completed protocol treatment, demonstrating achievement of the primary endpoint. The most frequent grade 3/4 toxicities were diarrhea (16.7 %), acne-like rash (13.9 %), and neutropenia (11.1 %). The overall RR was 33.3 % (12/36). Of these patients, five underwent conversion surgery. Median PFS and OS were 9.5 months (95 % CI 3.5-15.4 months) and 20.1 months (95 % CI 16.7-23.2 months), respectively. CONCLUSION: IRIS plus panitumumab has an acceptable toxicity profile and a promising efficacy in patients with previously treated wild-type KRAS mCRC. Accordingly, this regimen can be an additional treatment option for second-line chemotherapy in wild-type KRAS mCRC.

A phase I/II study of fixed-dose-rate gemcitabine and S-1 with concurrent radiotherapy for locally advanced pancreatic cancer.

PURPOSE: This study was conducted to identify the maximum-tolerated dose (MTD) of fixed-dose-rate gemcitabine (FDR-gem) administered concurrently with S-1 and radical radiation for locally advanced pancreatic cancer (LAPC) and to provide efficacy and safety data. METHODS: Patients with unrespectable pancreatic cancer confined to the pancreatic region were treated with FDR-gem (300-400 mg/m(2), 5 mg/m(2)/min) on days 1, 8, 22, and 29 and 60 mg/m(2) of S-1 orally on days 1-14, 22-35. A total radiation dose of 50.4 Gy (1.8 Gy/day, 28 fractions) was delivered concurrently. RESULTS: Twenty-five patients were enrolled; all were evaluable for toxicity assessment. In phase I, eight patients were treated in sequential cohorts of three to five patients per dose level. The MTD was reached at level 2, and dose-limiting toxicities were neutropenia and thrombocytopenia. The recommended doses were 300 mg/m(2) of gemcitabine and 60 mg/m(2) of S-1 daily. The overall response rate was 25% and disease control rate (partial response plus stable disease) was 92%. The progression-free survival was 11.0 months. The median overall survival and 1-year survival rates were 16.0 months and 73%, respectively. CONCLUSION: The combination of FDR-gem and S-1 with radiation is a feasible regimen that shows favorable antitumor activity with an acceptable safety profile in patients with LAPC.

Trastuzumab in combination with docetaxel/cisplatin/S-1 (DCS) for patients with HER2-positive metastatic gastric cancer: feasibility and preliminary efficacy.

PURPOSE: We previously reported that a triplet combination of docetaxel, cisplatin, and S-1 (DCS) is active against metastatic gastric cancer with a very high response rate of 87.1 % in a phase II study. Recently, the efficacy of trastuzumab (T-mab) for the treatment of HER2-positive gastric cancer has been reported. Therefore, we investigated the feasibility and preliminary efficacy of DCS + T-mab (DCS-T) for unresectable HER2-positive metastatic gastric cancer. METHODS: Patients received oral S-1 (40 mg/m(2) b.i.d.) on days 1-14, intravenous cisplatin (60 mg/m(2)), docetaxel (50 mg/m(2)), and T-mab (8 mg/kg in the first cycle and 6 mg/kg in the second cycle and thereafter) on day 8 every 3 weeks. RESULTS: The study included 16 patients: median age, 60 (34-76) years; males/females, 11:5; intestinal-type/diffuse-type histology, 11:5; and HER2 3+/2+(FISH+), 13:3. The completion rate until the third cycle was 87.5 % (14/16) (95 %CI 71.3-103.7 %). Adverse events of grade 3/4 severity during the first 3 cycles were: leukopenia/neutropenia, 50.0:75.0 %; febrile neutropenia, 12.5 %; diarrhea, 12.5 %; and stomatitis, 12.5 %. All of these side effects were manageable and well controlled. There were no treatment-related deaths. The overall response rate was 93.8 % (15/16), and the response rate in patients with measurable lesions was 100 % (15/15). The median cycle to response was only 1 (1-3 cycles). Non-curative factors disappeared in 56.3 % (9/16) of patients, and conversion surgery (R0 resection) was performed in all these cases. Pathological response rates in primary and metastatic lesions were 88.9 % (8/9) and 100 % (9/9), respectively. The median PFS and OS were not reached during the median follow-up time of 18.3 months ranged from 11.0 to 34.3 months. CONCLUSIONS: DCS-T was feasible in patients with unresectable HER2-positive metastatic gastric cancer. The observed response was very promising and warrants further investigation. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000005603.

Mucosectom2-short blade for safe and efficient endoscopic submucosal dissection of colorectal tumors.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) in the colon has rapidly come into widespread use. However, as complications such as bleeding and perforation often occur, and the procedure time is longer for ESD than for endoscopic mucosal resection (EMR), development of safer and more reliable devices are required especially for colorectal ESD. We report on a new device, the Mucosectom2-short blade (M2-SB) for colorectal ESD and describe its safety and efficacy. PATIENTS AND METHODS: The study included 30 patients with lesions diagnosed as colorectal tumor: a nongranular-type laterally spreading tumor (LST) larger than 20 mm or a granular-type LST larger than 30 mm, or lesions that were evaluated as being difficult to remove even by piecemeal EMR. RESULTS: All lesions were resected en bloc using this new device, with free lateral and vertical margins. The procedure time was 61 minutes and there was no bleeding or perforation related to the procedure. CONCLUSION: The M2-SB seems to be a safe and efficient tool for colorectal ESD.

[A case of idiopathic omental bleeding treated successfully with transarterial embolization].

A 58-year-old man was brought to our hospital with left upper abdominal pain which suddenly appeared on the previous evening. An abdominal CT scan showed localized retention of ascites, a slightly high density mass under the left upper abdominal wall, with a high density area detected within the mass, which was suggestive of leakage of contrast medium from peripheral branches of the omental artery. From these findings intraperitoneal hemorrhage caused by bleeding from the greater omentum was suspected. Angiographic examination of the abdomen indicated extravasation of contrast medium from blood vessels of the right gastroepiploic artery. Transarterial embolization was carried out and permanent hemostasis was achieved. Injury, anticoagulant, neoplasms, varix, torsion of the omentum, and segmental arterial mediolysis (SAM) etc have been reported as causes of omental bleeding, but none of these were found in our case. We diagnosed the present case as idiopathic omental bleeding.