Shoichi Fujii

Postoperative morbidity and mortality after mesorectal excision with and without lateral lymph node dissection for clinical stage II or stage III lower rectal cancer (JCOG0212): results from a multicentre, randomised controlled, non-inferiority trial

BACKGROUND Mesorectal excision is the international standard surgical procedure for lower rectal cancer. However, lateral pelvic lymph node metastasis occasionally occurs in patients with clinical stage II or stage III rectal cancer, and therefore mesorectal excision with lateral lymph node dissection is the standard procedure in Japan. We did a randomised controlled trial to confirm that the results of mesorectal excision alone are not inferior to those of mesorectal excision with lateral lymph node dissection. METHODS This study was undertaken at 33 major hospitals in Japan. Eligibility criteria included histologically proven rectal cancer of clinical stage II or stage III, with the main lesion located in the rectum with the lower margin below the peritoneal reflection, and no lateral pelvic lymph node enlargement. After surgeons had confirmed macroscopic R0 resection by mesorectal excision, patients were intraoperatively randomised to mesorectal excision alone or with lateral lymph node dissection. The groups were balanced by a minimisation method according to clinical N staging (N0 or N1, 2), sex, and institution. Allocated procedure was not masked to investigators or patients. This study is now in the follow-up stage. The primary endpoint is relapse-free survival and will be reported after the primary analysis planned for 2015. Here, we compare operation time, blood loss, postoperative morbidity (grade 3 or 4), and hospital mortality between the two groups. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00190541. FINDINGS 351 patients were randomly assigned to mesoretcal excision with lateral lymph node dissection and 350 to mesorectal excision alone, between June 11, 2003, and Aug 6, 2010. One patient in the mesorectal excision alone group underwent lateral lymph node dissection, but was analysed in their assigned group. Operation time was significantly longer in the mesorectal excision with lateral lymph node dissection group (median 360 min, IQR 296-429) than in the mesorectal excision alone group (254 min, 210-307, p<0·0001). Blood loss was significantly higher in the mesorectal excision with lateral lymph node dissection group (576 mL, IQR 352-900) than in the mesorectal excision alone group (337 mL, 170-566; p<0·0001). 26 (7%) patients in the mesorectal excision with lateral lymph node dissection group had lateral pelvic lymph node metastasis. Grade 3-4 postoperative complications occurred in 76 (22%) patients in the mesorectal excision with lateral lymph node dissection group and 56 (16%) patients in the mesorectal excision alone group. The most common grade 3 or 4 postoperative complication was anastomotic leakage (18 [6%] patients in the mesorectal excision with lateral lymph node dissection group vs 13 [5%] in the mesorectal excision alone group; p=0·46). One patient in the mesorectal excision with lateral lymph node dissection group died of anastomotic leakage followed by sepsis. INTERPRETATION Mesorectal excision with lateral lymph node dissection required a significantly longer operation time and resulted in significantly greater blood loss than mesorectal excision alone. The primary analysis will help to show whether or not mesorectal excision alone is non-inferior to mesorectal excision with lateral lymph node dissection. FUNDING National Cancer Center, Ministry of Health, Labour and Welfare of Japan.

The clinicopathological features of colorectal mucinous adenocarcinoma and a therapeutic strategy for the disease

BackgroundThe guidelines established by the National Comprehensive Cancer Network do not describe mucinous histology as a clinical factor that should influence the therapeutic algorithm. However, previous studies show conflicting results regarding the prognosis of colorectal mucinous adenocarcinoma. In this study, we described the clinicopathological features of mucinous adenocarcinoma in Japan, to identify optimal therapeutic strategies.Methods144 patients with mucinous and 2673 with non-mucinous adenocarcinomas who underwent primary resection in two major centers in Yokohama, Japan were retrospectively evaluated for clinicopathological features and treatment factors. A multivariate analysis for overall survival followed by the comparison of overall survival using Cox proportional hazard model were performed.ResultsPatients with mucinous adenocarcinoma had larger primary lesions, higher preoperative CEA levels, a deeper depth of invasion, higher rates of nodal and distant metastasis, and more metastatic sites. A multivariate analysis for overall survival revealed a mucinous histology to be an independent prognostic factor. In the subgroup analysis stratified by stage, Patients diagnosed as StageIII and IV disease had a worse survival in mucinous adenocarcinoma than non-mucinous, while survival did not differ significantly in patients diagnosed as Stage0-II disease. In StageIII, local recurrence in rectal cases and peritoneal dissemination were more frequently observed in patients with a mucinous histology.ConclusionsOur study indentified that mucinous adenocarcinoma was associated with a worse survival compared with non-mucinous in patients with StageIII and IV disease. In rectal StageIII disease with mucinous histology, additional therapy to control local recurrence followed by surgical resection may be a strategical alternative. Further molecular investigations considering genetic features of mucinous histology will lead to drug development and better management of peritoneal metastasis

Impact of body mass index and visceral adiposity on outcomes in colorectal cancer

Aim:  Obesity and visceral obesity are closely related to the development of colorectal cancer, as well as other metabolic complications. We investigated the prognostic significance of body mass index (BMI) and visceral obesity in 273 patients with resectable colorectal cancer.

Upper abdominal body shape is the risk factor for postoperative pancreatic fistula after splenectomy for advanced gastric cancer: a retrospective study.

BackgroundPostoperative pancreas fistula (POPF) is a major complication after total gastrectomy with splenectomy. We retrospectively studied the effects of upper abdominal shape on the development of POPF after gastrectomy.MethodsFifty patients who underwent total gastrectomy with splenectomy were studied. The maximum vertical distance measured by computed tomography (CT) between the anterior abdominal skin and the back skin (U-APD) and the maximum horizontal distance of a plane at a right angle to U-APD (U-TD) were measured at the umbilicus. The distance between the anterior abdominal skin and the root of the celiac artery (CAD) and the distance of a horizontal plane at a right angle to CAD (CATD) were measured at the root of the celiac artery. The CA depth ratio (CAD/CATD) was calculated.ResultsPOPF occurred in 7 patients (14.0%) and was associated with a higher BMI, longer CAD, and higher CA depth ratio. However, CATD, U-APD, and U-TD did not differ significantly between patients with and those without POPF. Logistic-regression analysis revealed that a high BMI (≥25) and a high CA depth ratio (≥0.370) independently predicted the occurrence of POPF (odds ratio = 19.007, p = 0.002; odds ratio = 13.656, p = 0.038, respectively).ConclusionSurgical procedures such as total gastrectomy with splenectomy should be very carefully executed in obese patients or patients with a deep abdominal cavity to decrease the risk of postoperative pancreatic fistula. BMI and body shape can predict the risk of POPF simply by CT.

Perivascular epithelioid cell tumor of the rectum: report of a case and review of the literature

We report a case of perivascular epithelioid cell tumor arising in the rectum of a 55-year-old woman. The tumor was treated by transanal endoscopic microsurgery. After 1 year follow-up, the patient is alive with no radiologic or endoscopic evidence of recurrence. Perivascular epithelioid cell tumor is a rare mesenchymal tumor characterized by co-expression of melanocytic and smooth muscle markers. This rare tumor can arise in various organs, including the falciform ligament, uterus, uterine cervix, liver, kidney, lung, breast, cardiac septum, pancreas, prostate, thigh, and gastrointestinal tract. Perivascular epithelioid cell tumor of the gastrointestinal tract is very rare, with only 23 previously reported cases. We review the literature on perivascular epithelioid cell tumors arising in the gastrointestinal tract.

Capecitabine versus S-1 as adjuvant chemotherapy for patients with stage III colorectal cancer (JCOG0910): an open-label, non-inferiority, randomised, phase 3, multicentre trial

BACKGROUND Adjuvant chemotherapy with oral fluoropyrimidine alone after D3/D2 lymph node dissection improves disease-free survival and overall survival in patients with stage III colon cancer. Adjuvant S-1 has been shown to be non-inferior to uracil and tegafur plus leucovorin in terms of disease-free survival. This study aims to confirm the non-inferiority of S-1 compared with capecitabine as adjuvant treatment in patients with stage III colorectal cancer. METHODS This study was an open-label, non-inferiority, randomised, phase 3, multicentre trial done in 56 Japanese centres to assess the non-inferiority of S-1 to capecitabine as adjuvant chemotherapy. Eligible patients were aged 20-80 years with stage III colorectal adenocarcinoma, as defined by the presence of an inferior margin of the primary tumour above the peritoneal reflection; R0 resection; and colectomy with D3 or D2 lymph node dissection. Patients were randomly assigned (1:1) to receive eight courses of capecitabine (1250 mg/m2 orally twice daily, days 1-14, every 21 days) or four courses of S-1 (40 mg/m2 orally twice daily, days 1-28, every 42 days). Randomisation was done via phone call, fax, or web-based systems to the Japan Clinical Oncology Group Data Center and used a minimisation method with a random component adjusted by institution, tumour location (colon vs rectosigmoid and upper rectum), number of positive lymph node metastases (≤3 vs ≥4), and surgical technique (conventional vs non-touch isolation). The primary endpoint was disease-free survival with a non-inferiority margin for the hazard ratio (HR) set at 1·24, analysed by intention to treat. This trial was registered with UMIN Clinical Trial Registry, number UMIN000003272. FINDINGS Between March 1, 2010, and Aug 23, 2013, 1564 patients were randomly assigned to capecitabine (n=782) or S-1 (n=782), all of whom were included in the efficacy analysis; 777 patients in the capecitabine group and 768 in the S-1 group were included in the safety analysis. At the prespecified second interim analysis after final accrual, 258 (48%) of 535 required events were reported, and the Data and Safety Monitoring Committee recommended early publication because S-1 could not show non-inferiority compared with capecitabine for disease-free survival. With a median follow-up of 23·7 months (IQR 14·1-35·2), 3-year disease-free survival was 82·0% (95% CI 78·5-85·0) for the capecitabine group and 77·9% (74·1-81·1) for the S-1 group (HR 1·23, 99·05% CI 0·89-1·70; one-sided pnon-inferiority=0·46). The most frequent grade 3 or higher adverse events in the capecitabine group were hand-foot skin reactions (123 [16%] of 777 patients), and in the S-1 group were diarrhoea (64 [8%] of 768 patients) and neutropenia (61 [8%]). There was one (<1%) treatment-related death in each group. INTERPRETATION Adjuvant capecitabine remains one of the standard treatments for stage III colorectal cancer in Japan; S-1 is not recommended. FUNDING National Cancer Center and Ministry of Health, Labour and Welfare of Japan.

Prospective study of patient satisfaction and postoperative quality of life after laparoscopic colectomy in Japan.

This prospective cohort study was designed to compare the short‐term and intermediate health‐related quality of life of Japanese patients after laparoscopic colectomy (LC) or open colectomy (OC) for colonic cancer.

Long-Term Outcomes After Colectomy in Patients With Familial Adenomatous Polyposis

The aim of this study was to evaluate the long-term prognosis of patients who underwent colectomy for familial adenomatous polyposis. The clinical data of 29 familial adenomatous polyposis patients who underwent colectomy were retrospectively reviewed. Five patients died of causes that included colorectal cancer (CRC), desmoid tumor, cancer of the small intestine, and pancreatitis. The 30-year survival rate was 72%. Among the 15 patients who had CRC at primary surgery, the 5-year survival rate was 100% in stages 0, I, and II, and 75% in stage IIIA. Stage I desmoid tumor showed slow or no growth, whereas a stage IV tumor showed rapid growth and was fatal. Extracolonic malignancies were seen in the small intestine, stomach, duodenum, thyroid, kidney, breast, and ovary. Among 8 patients with ileorectal anastomosis, 4 had a second primary rectal cancer and 6 had a salvage reoperation. None of the patients who underwent either stapled or handsewn ileal pouch–anal anastomosis had second primary rectal cancers. ...

Abstract 830: Clinical significance of measuring serum p53 antibodies in synchronous multiple colorectal cancer and double cancer patients

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Aims: The clinical significance of measuring serum p53 antibodies in colorectal cancer patients was evaluated. Patients and Methods: Preoperative serum tumor markers including CEA, CA19-9 and p53 antibody were examined in 264 patients (stage I: 68, II: 73, III; 81) who were given diagnoses of colon and/or rectal cancer in Yokohama City University Hospital from 2007 to 2008. Correlativity of tumor markers to clinical findings was investigated. Results: In the overall patients, range, median and positive ratio of each tumor marker are shown in Table [1][1]. Positive ratio of CEA and CA19-9 gradually increased according to clinical stage of the tumor, however, those of p53 showed almost the same concentration in any stage. Then, in stage I patients, positive ratio of p53 was higher than CEA and CA19-9 (p=0.0005). Thirty five cases (13.3%) of patients had synchronous or metachronous double or triple colorectal cancers. In that group, positive ratio of p53 was 48.3%, and median serum concentration of p53 was 0.915U/ml (0.15-295). Positive ratio and serum concentration of p53 of double or triple colorectal cancer patients were significantly higher than that of single cancer patients (p=0.0375). Conclusions: Serum concentration of p53 is sensitive, especially in early stage of colorectal cancer compared with other tumor markers. Colorectal cancer patients who showed high concentration of p53 have to be carefully checked for occult 2nd gastrointestinal tumor. View this table: 1 Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 830. [1]: #T1