Shinichi Sameshima

Irinotecan plus S-1 (IRIS) versus fluorouracil and folinic acid plus irinotecan (FOLFIRI) as second-line chemotherapy for metastatic colorectal cancer: a randomised phase 2/3 non-inferiority study (FIRIS study)

BACKGROUND Fluorouracil and folinic acid with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) are widely used as first-line or second-line chemotherapy for metastatic colorectal cancer. However, infusional fluorouracil-based regimens, requiring continuous infusion and implantation of an intravenous port system, are inconvenient. We therefore planned an open-label randomised controlled trial to verify the non-inferiority of irinotecan plus oral S-1 (a combination of tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate; IRIS) to FOLFIRI as second-line chemotherapy for metastatic colorectal cancer. METHODS Between Jan 30, 2006, and Jan 29, 2008, 426 patients with metastatic colorectal cancer needing second-line chemotherapy from 40 institutions in Japan were randomly assigned by a computer-based minimisation method to receive either FOLFIRI (n=213) or IRIS (n=213). In the FOLFIRI group, patients received folinic acid (200 mg/m(2)) and irinotecan (150 mg/m(2)) and then a bolus injection of fluorouracil (400 mg/m(2)) on day 1 and a continuous infusion of fluorouracil (2400 mg/m(2)) over 46 h, repeated every 2 weeks. In the IRIS group, patients received irinotecan (125 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 progression-free survival, with a non-inferiority margin of 1.333. Statistical analysis was on the basis of initially randomised participants. This study is registered with ClinicalTrials.gov, number NCT00284258. FINDINGS All randomised patients were included in the primary analysis. After a median follow-up of 12.9 months (IQR 11.5-18.2), median progression-free survival was 5.1 months in the FOLFIRI group and 5.8 months in the IRIS group (hazard ratio 1.077, 95% CI 0.879-1.319, non-inferiority test p=0.039). The most common grade three or four adverse drug reactions were neutropenia (110 [52.1%] of 211 patients in the FOLFIRI group and 76 [36.2%] of 210 patients in the IRIS group; p=0.0012), leucopenia (33 [15.6%] in the FOLFIRI group and 38 [18.1%] in the IRIS group; p=0.5178), and diarrhoea (ten [4.7%] in the FOLFIRI group and 43 [20.5%] in the IRIS group; p<0.0001). One treatment-related death from hypotension due to shock was reported in the FOLFIRI group within 28 days after the end of treatment; no treatment-related deaths were reported in the IRIS group. INTERPRETATION Progression-free survival with IRIS is not inferior to that with FOLFIRI in patients receiving second-line chemotherapy for metastatic colorectal cancer. Treatment with IRIS could be an additional therapeutic option for second-line chemotherapy in metastatic colorectal cancer. FUNDING Taiho Pharmaceutical Co Ltd and Daiichi Sankyo Co Ltd.

Surgical resections of ulcerative colitis associated with dysplasia or carcinoma

BackgroundUlcerative colitis (UC) patients have an increased risk of colorectal dysplasia and carcinoma. The purpose of this study was to analyze the clinical features and surgical treatment of ulcerative colitis associated with dysplasia or carcinoma.MethodsWe operated on 41 UC patients since April 2000. Twelve of the cases were associated with dysplasia or carcinoma. Ten patients were male and two were female; the median age was 58.0 years, and the average duration of disease was 19.2 years. Nine cases were pancolitis type and three were left-sided type. Six cases were remission-relapsing type and six were chronic inflammation type. In 10 of 12 cases, dysplasia or carcinoma was diagnosed before the operations. Nine cases were primary operations and two were second-time operations.ResultsAmong ten patients who underwent primary operations, four patients had open surgery and six patients had hand-assisted laparoscopic surgery (HALS). Seven patients received anus/anal sphincter-preserving operations with reconstruction by the ileal pouch technique. Ileal pouch anal-canal anastomosis (IPACA) was performed in five cases and ileal pouch anal anastomosis (IPAA) in two cases. Abdomino-peritoneal resection was performed in two cases, proctcolectomy with permanent ileostomy in one case, and right hemicolectomy in one case. A 39-year-old patient was unresectable due to dissemination of the carcinoma. A 55-year-old patient who underwent IPACA showed night soiling postoperatively. Other patients who received IPAA and IPACA showed favorable anal function postoperatively. Histological examination showed low-grade dysplasia in two cases, high-grade dysplasia in three cases, and adenocarcinoma in seven cases. In the seven cases of adenocarcinoma, four, two, and one cases were stage 1, 3, and 4 according to TNM classification. Three of five cases with dysplasia were detected by surveillance colonoscopy. All patients with carcinoma were symptomatic and did not undergo surveillance colonoscopy.ConclusionsIPACA by HALS was safely performed as an anal-preserving operation in UC patients with dysplasia or carcinoma. Non-anal-preserving operations for aged patients showed a preferable postoperative course. Surveillance colonoscopy is essential for detecting dysplasia before the development of carcinoma.

Rectal cancer associated with chronic lymphocytic leukemia

It has been reported that chronic lymphocytic leukemia (CLL) often occurs concomitantly with other malignant neoplasms. However, because CLL is rare in Japan, there are only a limited number of reports of the occurrence of malignant neoplasia in Japanese patients with CLL. We report here the simultaneous occurrence of rectal cancer and CLL in a 57-year-old man. Because the clinical stage of CLL was Rai system I, we decided, in accordance with the National Cancer Institute–Sponsored Working Group guidelines, to monitor him without therapy for CLL until evidence of disease progression, and we performed abdominoperineal resection of the rectum for the cancer. The small rectal tumor was associated with aggressive lymphangiosis carcinomatosa, and multiple nodal metastases were observed in the pool of CLL cells. He died of rectal cancer 7 months after the operation, and autopsy revealed extensive metastases of the cancer. Cellular and humoral immunity is often impaired in patients with CLL, and the defective immunity in this patient may have had an etiological role in the development and rapid progression of the cancer. In the follow-up of CLL patients, we must always be aware of the possible existence of a second malignant disease. Particular attention should be paid to those with defective immunity, and screening should be performed, especially for pulmonary and gastrointestinal malignancies.

Focal Lymphoid Hyperplasia of the Terminal Ileum Presenting Mantle Zone Hyperplasia with Clear Cytoplasm. A Report of Three Cases

We report three unusual cases of focal lymphoid hyperplasia of the ileocecal valve. The gross specimens showed thickening of the ileocecal valve. Low power magnification showed a dense lymphoid infiltrate in the mucosa and submucosa. This condition was characterized by reactive lymphoid follicles with large reactive germinal centers surrounded by a pale cuff of mantle zone lymphocytes presenting a marginal zone distribution pattern. These cells had intermediate- to- medium-sized round or slightly indented nuclei and a broad rim of clear cytoplasm. However, immunohistochemical study demonstrated that both the mantle zone lymphocytes and the pale cuff of the lymphoid cells were CD20+, sIgM+, sIgD+, CD5−, CD10−, CD23−, CD43−, Bcl-2+, Bcl-6−, CyclinD1−. The polytypic nature of these cells was demonstrated by immunohistochemistry and polymerase chain reaction. This unusual mantle cell hyperplasia with clear cytoplasm associated with focal lymphoid hyperplasia in middle-aged and elderly patients should be differentiated from the extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue type or mantle cell lymphoma showing a marginal zone distribution pattern. To avoid overdiagnosis and overtreatment, it is suggested that immunophenotypic and genotypic studies might be required, and careful attention should be paid to the morphologic examination.

Portal encasement: Significant CT findings to diagnose local recurrence after pancreaticoduodenectomy for pancreatic cancer

BACKGROUND/OBJECTIVES To demonstrate the utility of portal encasement as a criterion for early diagnosis of local recurrence (LR) after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). METHODS A total of 61 patients who underwent PD for PDAC were included in this retrospective study. Portal stenosis was evaluated by sequential postoperative computed tomography (CT) scans and correlated with disease recurrence. In addition to the conventional LR diagnostic criterion of a growing soft tissue mass, LR was evaluated using portal encasement as an additional diagnostic criterion. Portal encasement was defined as progressive stenosis of the portal system accompanied by a soft tissue mass, notwithstanding the enlargement of the mass. RESULTS Benign portal stenosis was found on the first postoperative CT imaging in 16 patients. However, stenosis resolved a median of 81 days later in all but one patient whose stenosis was due to portal reconstruction during PD. Portal encasement could be distinguished from benign portal stenosis based on the timing of emergence of the portal stenosis. Portal encasement developed in 13 of the 19 patients with LR, including 6 patients in whom the finding of portal encasement led to the diagnosis of LR a median of 147 days earlier with our diagnostic criterion compared with the conventional diagnostic criteria. CONCLUSIONS Portal encasement should be considered as a promising diagnostic criterion for earlier diagnosis of LR after PD for PDAC.

Laparoscopic surgery to remove a cage that migrated to the retroperitoneal space during posterior lumbar interbody fusion: A case report

Cage migration into the retroperitoneal space during posterior lumbar interbody fusion rarely occurs. Here, we report a patient who underwent laparoscopic surgery to remove a migrated cage from the retroperitoneal space.

A Case of Poorly Differentiated Adenocarcinoma with Signet Ring Cell Carcinoma of the Duodenal Bulb: A Case Report

Duodenal cancers are rare. Histopathologically, most duodenal cancers are adenocarcinoma. Signet ring cell carcinoma (SRCC) is a rare tumor more commonly found in the stomach than at other sites in the digestive tract. SRCC is extremely uncommon in the duodenum, with most of these tumors occurring in the ampulla. Until now, there are few case reports of duodenal cancers with SRCC. To accumulate case reports, we report a rare case of nonampullary duodenal bulb SRCC. A 74-year-old man was admitted to our hospital with melena. Esophagogastroduodenoscopy (EGD) showed a duodenal bulb ulcer. He was treated with a proton pump inhibitor. However, 1 month later, he was readmitted to our hospital with epigastric pain and nausea. A second EGD examination showed an ulcer at the duodenal bulb. Biopsies taken from the ulcer showed SRCC. Distal gastrectomy and duodenal bulb resection were performed. Histologic examination of the specimen showed a type 4 lesion located from the duodenal bulb to the pyloric antrum. The tu...

An effective new method for the placement of an anti-adhesion barrier film using an introducer in laparoscopic surgery

Postoperative small bowel obstruction (SBO) is one of theserious complications of abdominopelvic surgery. One ofthe major causes of SBO is the formation of intra-ab-dominal adhesions. The rate of SBO is reportedly 2–6 % inlaparoscopic surgery, although it is lower than in laparo-tomy [1, 2]. Furthermore, peritoneal and bare pelvic floordefects after resection of the rectum are observed afterabdominoperineal resection for rectal cancer, and theycause postoperative wide adhesions of the small intestine tothe pelvic floor. An anti-adhesion barrier film (Sepra-film