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This work describes the fabrication and characterization of hydroxypropyl cellulose (HPC)-based biomimetic bundled gel fibres. The bundled gel fibres were reinforced with multiwalled carbon nanotubes (MWCNTs). A phase-separated aqueous solution with MWCNT and HPC was transformed into a bundled fibrous structure after being injected into a co-flow microfluidic device and applying the sheath flow. The resulting MWCNT-bundled gel fibres consist of multiple parallel microfibres. The mechanical and electrical properties of MWCNT-bundled gel fibres were improved and their potential for tissue engineering applications as a cell scaffold was demonstrated.

Background Many studies have shown that lifestyle factors such as diet, physical activity are related to the incidence of cancer. However, there are few studies on the association between lifestyle factors and cancer prognosis. To investigate the influence of lifestyle factors and psychosocial factors on prognosis, we started a prospective study of women with breast cancer, the Rainbow of KIBOU study-Breast (ROK Study-B) in 2007. As of February 2018, more than 6300 women have been enrolled, thus making this one of the world’s largest cancer patient cohort studies. Based on the know-how obtained from this study, we started another new cohort study for colorectal cancer patient (ROK Study-C). Methods The ROK Study-C is a prospective observational study for colorectal cancer survivors at the National Cancer Center Hospital. Participants fill in several self-administrated questionnaires about lifestyle, psychosocial factors (including posttraumatic growth and benefit finding, support), and quality of life (QOL) 5 times in total: at diagnosis, 3 and 6 months, 1 and 5 years after surgery. CT-scans will be collected to assess body composition and obesity. We also use blood and cancer tissue from the Biobank. The primary endpoint is disease-free survival. The secondary endpoints are overall survival and health-related QOL. The planned sample size is 2000 and the follow-up period is 5 years after the last enrollment. Discussion Recruitment began in December 2015 and the study is still ongoing. The ROK Study-C will contribute to improvements in patient prognosis and yield important evidence for colorectal cancer survivorship.

Purpose: We examined the relationship between fecal occult blood test (FOBT) screening behavior and beliefs regarding FOBT screening in order to formulate effective measures to improve FOBT screening rates. Method: In June 2010, we conducted a cross-sectional questionnaire survey of 600 randomly selected individuals aged 40–60 years who were registered participants of Refine, which was an internet research company to cooperate with this study. We assessed CRC knowledge, perceived risk of CRC, perceived severity of CRC, concern for CRC, beliefs of FOBT screening, FOBT screening behavior, and demographic variables. Result: There were 592 valid responses (from 294 males and 298 females; mean age 53.96 ± 8.39) in the final analysis. A total of 266 (44.9%) underwent FOBT in the year preceding the survey. Factor analysis relating to the beliefs of obtaining FOBT demonstrated five factors (α = 0.829) including: (1) perceived barrier, (2) subjective norms, (3) low importance, (4) descriptive norms, and (5) non-ne...

Aim Many studies have evaluated the risk factors for anastomotic leakage after laparoscopic anterior resection. In this study in order to increase the tightness of anastomoses and prevent bleeding from their staple lines, a linear stapler with pre-attached bioabsorbable polyglycolic acid (PGA) felt was used for rectal transection, and the short-term surgical outcomes were evaluated. Patients and methods A prospective registry of 62 patients with rectosigmoidal or rectal carcinoma who initially underwent laparoscopic anterior resection using PGA felt for rectal transection was reviewed. Results The overall frequency of anastomotic leakage was 1.6% (1/62), and none of the patients developed postoperative staple line bleeding or other adverse events related to the use of PGA felt. Conclusion The frequency of anastomotic leakage was relatively low, and therefore the use of a linear stapler with pre-attached bioabsorbable PGA felt might reduce the risk of adverse events related to anastomosis, especially anastomotic leakage.

A case of spontaneous regression of transverse colon cancer is reported. A 64-year-old man was diagnosed as having cancer of the transverse colon at a local hospital. Initial and second colonoscopy examinations revealed a typical cancer of the transverse colon, which was diagnosed as moderately differentiated adenocarcinoma. The patient underwent right hemicolectomy 6 weeks after the initial colonoscopy. The resected specimen showed only a scar at the tumor site, and no cancerous tissue was proven histologically. The patient is alive with no evidence of recurrence 1 year after surgery. Although an antitumor immune response is the most likely explanation, the exact nature of the phenomenon was unclear. We describe this rare case and review the literature pertaining to spontaneous regression of colorectal cancer.

Background Endoscopic submucosal dissection (ESD) has recently provided a new treatment strategy for large colorectal neoplasms, as an alternative to laparoscopy-assisted colectomy (LAC). Prospective comparative data on the perioperative course of ESD vis-à-vis LAC are scarce. Methods We prospectively evaluated the perioperative course of colorectal ESD in 300 patients. We evaluated en bloc and curative resection, procedure duration, postoperative parameters [white blood cell count (WBC), C-reactive protein (CRP), and hemoglobin], pain, recovery duration (time to achieve full mobilization, normal diet, and length of hospitalization), and complications. We also prospectively evaluated 190 patients undergoing LAC as a control group. Results The median size of the lesions was 30 mm for ESDs (LACs: 20 mm). The median procedure time was 90 min for ESDs (LACs: 185 min). Postoperative pyrexia was reported in 4 % of ESDs (LACs: 54 %). Only 4 % of ESDs required analgesia (LACs: 61 %). Between the preoperative period and postoperative day 1, the mean difference in WBC and CRP was +1,300/μl for ESDs (LACs: +3,100/μl), and +0.91 mg/dl for ESDs (LACs: +3.96 mg/dl), respectively. A ≥2 g/dl decrease in hemoglobin was observed in 5 % of ESDs (LACs: 30.0 %). Complications were seen in 7 % of ESDs (LACs: 15 %). The rate of delayed bleeding and perforation was 5 and 1.7 % of ESDs, respectively. Although only one of them required laparotomy for peritonitis caused by delayed perforation, others could be managed endoscopically. Additional LAC was required in 16 ESDs due to redefined risk for lymph node metastases. The median hospital stay was 5 days for ESDs (LACs: 10 days). These were consecutive patients with prospective data collection. Conclusions Colorectal ESD is effective, minimally invasive and safe in terms of periperative clinical course. Colorectal ESD provides advantages for treatment of large adenomas and early cancers with no risk of lymph node metastasis.

Introduction Laparoscopic approaches are increasingly being used in patients with colorectal cancer, but the feasibility of laparoscopic resection of synchronous colorectal cancers in separate specimens remains unknown. In such cases, it is necessary to consider the site of port placement, sequence of dissection, choice of specimen extraction sites, specimen handling, and extracorporeal anastomosis sites. Moreover, the need for complete mesenteric dissection in two areas, removal of two separate specimens containing malignancies, and two anastomoses elicit unique questions related to technical considerations. The aim of this study was to determine the feasibility of laparoscopic resection of two separate specimens containing malignancies for multiple synchronous colorectal cancers. Methods Between June 2001 and January 2013, 1341 patients with colorectal cancer underwent laparoscopic surgery at our institution. Of them, 11 patients underwent laparoscopy-assisted combined resection of two separate colorectal specimens for multiple synchronous primary colorectal cancers. We retrospectively reviewed their surgical outcomes. Results All procedures were completed laparoscopically without perioperative mortality. Patients underwent right-sided colon resection for right-sided cancer and left-sided or rectal resection for left-sided colon or rectal cancer. The median duration of surgery was 296 min, and the median blood loss was 65 mL. Median time to first postoperative liquid and solid intake was 1 day and 3 days, respectively. Most patients were discharged on postoperative day 8. With regard to postoperative complications, two patients had a surgical-site infection. Conclusion Laparoscopic resection of two separate colorectal specimens for multiple synchronous primary colorectal cancers is a feasible and safe procedure.

The aim of the present study was to determine the feasibility of simultaneous resection of colorectal cancer by laparoscopy and a pulmonary lesion through minithoracotomy. Four patients underwent laparoscopic resection of colorectal cancer followed by pulmonary resection. The mean operative duration was 390 min and the mean blood loss was 133 mL. The postoperative course was uneventful. The indication for simultaneous resection of colorectal cancer by the laparoscopic approach and a pulmonary lesion is controversial. This method is safe and feasible in selected patients, but whether colorectal resection or pulmonary surgery is performed first should be determined on a case-by-case basis.

Background Guidelines for rectal cancer treatment differ in Japan, Europe, and the United States. Neoadjuvant chemoradiotherapy (CRT) has been used to control lateral lymph nodes (LLNs) in the West. The usefulness of LLN dissection (LLND) has been discussed in Japan, and a randomized study stated the possible advantage of local control. However, it is still unclear whether adding LLND to CRT is beneficial. Methods To investigate the effectiveness of LLND on rectal cancer patients who underwent neoadjuvant CRT, we retrospectively collected magnetic resonance images (MRIs) in a cohort of 1500 patients with cStage II/III lower rectal cancer below the peritoneal reflection and centrally reviewed MRIs. We measured short-axis LLN sizes on pre- and post-CRT images and evaluated patients’ prognosis according to LLN size and whether LLND was performed. Results MRIs were collected from 752 patients, of whom 189 underwent neoadjuvant CRT. Both pre- and post-CRT MRIs were available in 155 patients, of whom 66 underwent LLND (LLND group) and 89 did not (non-LLND group). The LLND and non-LLND group showed the following differences: positive circumferential resection margin by MRI after CRT: 53.0% vs. 32.6%; positive extramural venous invasion: 36.4% vs. 24.7%; laparoscopic surgery: 39.4% vs. 88.8%; and mean pre-CRT LLN size: 5.2 mm vs. 3.6 mm. Five-year relapse-free survival (5y-RFS) was 73.8% and 66.1% in the LLND and non-LLND groups, respectively (p = 0.38). Two local recurrences occurred in the LLND group. In stratified analysis, 5y-RFS of 40 patients whose LLN size was ≥5 mm in pre-CRT images was 77.8% in the LLND group and 46.2% in the non-LLND group (p = 0.06). On the other hand, 115 patients whose LLN size was Conclusions Our data indicated that adding LLND to CRT may have survival benefits on those who had LLN size of ≥ 5 mm before CRT. Stratification by short-axis LLN size using pre-CRT MRIs may facilitate optimal multidisciplinary treatment strategies for low rectal cancer. Legal entity responsible for the study Department of Surgery, Kyoto University Graduate School of Medicine. Funding The Japanese Foundation for Research and Promotion of Endoscopy, The Japan Society of Clinical Oncology, and Kondou Kinen Medical Foundation. Disclosure All authors have declared no conflicts of interest.

It is a great honor to comment on the article entitled “Prognostic impact of hypochloremia in patients with stage I to III colorectal cancer after radical resection” by Qingguo Li and his colleagues in the Diseases of Colon and Rectum (1).

3578 Background: The usefulness of lateral lymph node dissection (LLND) for lower rectal cancer has been discussed. Concerning relapse-free survival (RFS), in the JCOG0212 trial, the non-inferiority of avoiding LLND for rectal cancer without LLN enlargement of ≥10 mm was not shown; however, the superiority of LLND was also not demonstrated. Methods: To examine whether the difference in dissection effect could be demonstrated by the size of LLN, magnetic resonance imaging (MRI) for the central review of pre-registered patients with stages II/III lower rectal cancer below the peritoneal reflection was performed, and the prognosis of the patients were prospectively investigated as a cohort. The relationship between LLND and RFS was also evaluated. Results: MR images of 738 cases (mean distance from anal verge: 4.5 cm) were evaluated. Twenty patients with LLN enlargement of ≥10 mm were excluded from the analysis. Overall, of 718 patients, 310 did not undergo LLND (non-LLND group), whereas the other 408 underwent LLND (LLND group). The lymph node sizes of ≥5 mm were observed in 10.0% and 21.1% of patients in the non-LLND and LLND groups, respectively. Although there was some bias in the background characteristics of the two groups (non-LLND vs. LLND; median age 66 vs. 61 years; laparoscopic surgery 64.2% vs. 17.9%; preoperative treatment 39.4% vs. 27.9%; circumferential resection margin evaluated by MRI 37.3% vs. 49.9%; and postoperative complications 33.2% vs. 44.4%), almost no difference in the 5-year RFS was observed (63.4% vs. 67.5%).The LLND group had significantly more favorable with ≥5 mm LLN (non-LLND 51.6% vs. LLND 69.0% P = 0.023) than with < 5 mm LLN (non-LLND 64.7%; LLND 67.0%). Conclusions: Oncological benefit of LLND was suggested in patients with enlarged lateral nodes on MRI using a large cohort of clinical stage II/III lower rectal cancer.

Background: Obesity is reported to be associated with worse prognosis in early breast cancer. However, there is little data regarding the impact of low BMI on survival in patients with breast cancer. As obesity is rare and low BMI is relatively common in Japanese population compared to Caucasians, Japanese cohort is suitable to assess the impact of low BMI on survival in patients with early breast cancer. Recently an exploratory analysis of a small Japanese randomized phase II trial (JFMC 34-0601) suggested that low BMI was associated with a decreased overall response rate to neoadjuvant endocrine therapy with exemestane. We further explored the impact of low BMI on survival in patients with early breast cancer using a dataset of randomized phase III trials in Japan. Methods: Patients included in prospective randomized phase III trial N-SAS BC02 and BC03 were retrospectively analyzed. N-SAS BC02 investigated four arms of adjuvant chemotherapy consisted of taxane alone or in combination with anthracycline-containing regimen (median follow up of 6.1 years). NSAS BC03 compared anastorozole with tamoxifen as adjuvant endocrine therapy (median follow up of 6.4 years). The correlation of BMI and overall survival was exploratory analyzed. This study was supported by the Public Health Research Center Foundation CSPOR. Results: A total of 1726 patients were included in our study. Median age was 56 (24 – 82) years, 71.2% of tumors were ER positive, and 9.7% were HER2 overexpressed. Lymph node metastases were observed in 76% of patients. Mean value of BMI was 23.3 and only 4.6% of patients had BMI over 30. 33.1% of patients had BMI under 22 and 4.8% had BMI under 18.5. In the univariate Cox proportional hazard model, lower BMI was significantly associated with worse prognosis (BMI27, HR 0.55, 95% CI 0.32 – 0.93, p = 0.025). The same trend was observed in multivariate analysis (HR 0.61, p = 0.064). Conclusion: We confirmed that obese patients were relatively rare in Japanese patients with early breast cancer. In this non-obese population, lower BMI was correlated with worse prognosis. However these results should be cautiously interpreted. Our findings suggest that there may be an optimal BMI in patients with early breast cancer and it should be confirmed by another cohort. Citation Format: Yoichi Naito, Yasuo Ohashi, Isao Yokota, Toru Watanabe, Hiroji Iwata, Shozo Ohsumi, Shinji Ohno, Yasuo Hozumi, Seiichiro Yamamoto, Masato Takahashi, Tomohiko Aihara, Hirofumi Mukai. Low body mass index (BMI) is associated with poor survival in Japanese patients with early breast cancer; an exploratory analysis of prospective randomized phase III trials N-SAS BC02 and 03 [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-21.

A 72-year-old male visited a local hospital on presentation of melena. Colonoscopy revealed a protruded lesion in the ascending colon, and computed tomography revealed a 20 cm retroperitoneal tumor. Biopsy failed to provide a definitive diagnosis of the colonic lesion. He was diagnosed as having a retroperitoneal liposarcoma and an ascending colon tumor using computed tomography, and referred to our hospital. Biopsy of the ascending colon lesion showed spindle cells with fibrosis. On immunohistochemical staining, tumor cells were positive for cyclin-dependent kinase 4 and murine double minute 2, and the lesion was diagnosed as a well-differentiated or dedifferentiated liposarcoma. The retroperitoneal liposarcoma, which had infiltrated the ascending colon, was resected along with the right colon and the right kidney. Macroscopically, the tumor had infiltrated the ascending colon, forming a multinodular solid mass in the lumen and the right kidney. Microscopic finding of the main tumor revealed a well-differentiated liposarcoma, and that of the colonic lesion revealed a dedifferentiated liposarcoma with nuclei of different sizes and shapes and increased spindle cell morphology. The right kidney and ureter were surrounded by tumor cells but were not infiltrated, and there was no lymph node involvement. The diagnosis of retroperitoneal liposarcoma is often difficult because symptoms appear only after the tumor becomes very large. Some retroperitoneal liposarcomas are found on computed tomography by chance. The clinical course of this case was very rare because of the presentation of melena as the first symptom and the detection of an invasive mass in the ascending colon using colonoscopy.

OBJECTIVE Though the fecal occult blood test is used for colorectal cancer screening worldwide, it does not have a particularly high sensitivity for detecting colorectal cancer. Here we investigated the applicability of the fecal microRNA test to fecal samples that had been used for a previous fecal occult blood test and stored under various conditions. METHODS Five colorectal cancer patients and five healthy volunteers were enrolled. Fecal samples were stored for 0-5 days at 4°C, room temperature or 37°C. Total RNA was extracted from the fecal occult blood test residuum and microRNA expression was analyzed by real-time reverse transcription polymerase chain reaction. RESULTS There were no remarkable differences either in colorectal cancer patients or in controls with regard to the concentration of RNA extracted from the fecal occult blood test residuum in any of the storage groups compared with the samples prepared on day 0 (Group 0). Ribosomal RNA stored at room temperature or 37°C degraded rapidly. In contrast, the ribosomal RNA stored at 4°C remained intact for at least 5 days. The microRNAs in samples stored at 4°C and room temperature were conserved; however, the microRNAs stored at 37°C were significantly degraded compared with Group 0 (P < 0.05). In the residuum stored at 4°C up to 5 days, the relative quantification of miR-106a normalized with miR-24 in colorectal cancer patients was significantly higher than those in healthy volunteers (P < 0.05). In contrast, the quantification of normalized miR-106a was remarkably low in samples stored at room temperature and 37°C. CONCLUSIONS Fecal microRNA of sufficient quality for reverse transcription polymerase chain reaction analysis was extracted from the fecal occult blood test residuum stored at 4°C for up to 5 days.

Purpose To evaluate the safety and efficacy of transcatheter arterial chemoembolization used for the treatment of unresectable hepatocellular carcinoma (HCC) with an Asian cooperative prospective study between Japan and Korea. Materials and Methods Patients with unresectable HCC unsuitable for curative treatment or with no prior therapy for HCC were enrolled. The patients underwent transcatheter arterial chemoembolization with emulsion of Lipiodol and anthracycline agent, followed by embolization with gelatin sponge particles, which was repeated on an as-needed basis. The primary endpoint was 2-year survival rate, and the secondary endpoints were adverse events and response rate. Results The 2-year survival rate of 99 patients was 75.0% (95% confidence interval, 65.2%–82.8%). The median time-to-progression was 7.8 months, and the median overall survival period was 3.1 years. Of 99 patients, 42 (42%) achieved a complete response, and 31 (31%) had a partial response. The response rate was 73% using modified Response Evaluation Criteria in Solid Tumors. The grade 3–4 toxicities included increased alanine aminotransferase level in 36%, increased aspartate aminotransferase level in 35%, thrombocytopenia in 12%, and abdominal pain in 4% of patients. All other toxicities were generally transient. Conclusions Asian transcatheter arterial chemoembolization demonstrated sufficient safety and reasonable efficacy as a standard treatment for unresectable HCC. These results could be useful as reference data for future trials of transcatheter arterial chemoembolization.

Clinical progressive disease (cPD) occurs during neoadjuvant chemotherapy (NAC) in 3%-5% of triple-negative breast cancer (TNBC) patients. We aimed to identify the histopathological and immunohistochemical parameters that are correlated with the TNBC that showed cPD. We identified 22 TNBCs that showed cPD during NAC (cPD group) and 80 TNBCs that did not receive NAC (control group). Using surgically resected tumor specimens, we performed histopathologic examinations and immunohistochemical analysis of 11 molecules that appeared relevant to epithelial-mesenchymal transition (EMT), and basal-like, molecular apocrine and other features. Metaplastic carcinomas (MPCs) and high proliferation (≥50 mitoses per 10 high-power fields or ≥50% Ki-67 score) were more frequent in the cPD than in the control (41% vs 3%, P

Background Although there are a large number of epidemiological studies investigating the etiological role of lifestyle factors in breast cancer, there are few studies on the association between lifestyle factors and breast cancer prognosis. To investigate the influence of lifestyle factors such as diet and physical activity, use of complementary and alternative medicine, and psychosocial factors on prognosis, we designed a large-scale cohort study of female breast cancer patients in Japan. Methods The planned sample size is 7200. The cohort is being conducted in collaboration with several clinical trials, a cancer registry, and daily practice. Information on clinical factors, treatment, and follow-up will be obtained from the clinical trials and participating hospitals. A self-administered questionnaire is given to subjects before, immediately after, or 1 to 5 years after surgery. Blood and tissue samples are also collected. The primary endpoint is disease-free survival. The secondary endpoints are overall survival and health-related quality of life. The follow-up period will be at least 5 years after the last participant is enrolled. Recruitment began in November 2007. Current status As of April 2017, there are 5852 patients enrolled in the study along with 1430 biological samples and the study is still ongoing. The number of subjects enrolled in the study is already the largest in the world. Conclusions The ROK study will provide much important evidence for breast cancer survivorship.

Objectives This study examined both the frequency of appearance-related symptoms and distress resulting from these symptoms in cancer patients receiving chemotherapy. Methods Self-report questionnaires were distributed to 753 outpatients receiving ≧4 weeks of treatment at an outpatient chemotherapy center. Valid responses were returned by 638 patients (response rate, 84.7%). Participants were questioned about 57 appearance-related symptoms (AS) and 23 non-appearance-related physical symptoms (non-AS); psychological well-being was assessed using a shortened version of the Derriford Appearance Scale 59. Results Questionnaire responses were obtained from 264 male and 374 female patients (mean age, 59.5 years; range, 18–85 years). Most respondents (80.3%) were concerned with changes in appearance resulting from treatment. By sex and disease type, women suffered more than men, and treatment for breast cancer created the greatest distress for women. Conclusion Cancer patients are concerned about a variety of AS, and these may result in greater distress than non-AS. AS-related information and care are increasingly being sought in advance of treatment. Copyright © 2013 John Wiley & Sons, Ltd.

Background and Objectives We conducted a phase II study to evaluate the safety and efficacy of preoperative chemotherapy with S-1 + cisplatin followed by gastrectomy in patients with linitis plastica (type 4) or large ulcero-invasive-type (type 3) gastric cancer. Methods Eligibility criteria included histologically proven adenocarcinoma of the stomach; clinically resectable gastric cancer of type 4 or type 3. Patients received two 28-day courses of preoperative chemotherapy of S-1 (80–120 mg/body, p.o., days 1–21) and cisplatin (CDDP; 60 mg/m2, i.v., day 8). Primary endpoints were completion of protocol treatment and incidence of treatment-related death (TRD). Results Among the 49 eligible patients with the median age of 61 years, 36 completed the protocol treatment comprising two courses of preoperative chemotherapy and R0/1 resection (73.5% completion, 80% CI, 63.7–81.7%). One TRD was observed during the first course of chemotherapy. Median survival and 3-year overall survival were 17.3 months and 24.5%, respectively. Conclusions Preoperative chemotherapy with S-1 + CDDP followed by gastrectomy is a safe and promising treatment for type 4 and large type 3 gastric cancers. Based on the results of this study, we are now conducting a phase III study (JCOG0501) to confirm the superiority of this treatment. J. Surg. Oncol. 2013;107:741–745. © 2013 Wiley Periodicals, Inc.

Summary Background Although benefits of laparoscopic surgery compared with open surgery have been suggested, the long-term survival of patients undergoing laparoscopic surgery for colon cancer requiring Japanese D3 dissection remains unclear. We did a randomised controlled trial to establish non-inferiority of laparoscopic surgery to open surgery. Methods We did an open-label, multi-institutional, randomised, two-arm phase 3 trial in 30 hospitals in Japan. Patients aged 20–75 years who had histologically proven colon cancer; tumours located in the caecum or ascending, sigmoid, or rectosigmoid colon; T3 or deeper lesions without involvement of other organs, node stages N0–2, and metastasis stage M0; and tumour size of 8 cm or smaller were included. Only accredited surgeons did surgery as an operator or instructor. Patients were randomly assigned (1:1) preoperatively to undergo D3 resection either by an open route or a laparoscopic route, via phone call or fax to the Japan Clinical Oncology Group (JCOG) Data Center. Randomisation used a minimisation method with a biased-coin assignment according to tumour location (caecum, ascending vs sigmoid, rectosigmoid) and institution. The primary endpoint was overall survival and was analysed by intention to treat. The non-inferiority margin for the hazard ratio (HR) was set at 1·366. This study is registered with UMIN Clinical Trials Registry, number C000000105, and ClinicalTrials.gov, number NCT00147134. Findings Between Oct 1, 2004, and March 27, 2009, 1057 patients were randomly assigned to either open surgery (n=528) or laparoscopic surgery (n=529). 5-year overall survival was 90·4% (95% CI 87·5–92·6) for open surgery and 91·8% (89·1–93·8) for laparoscopic surgery. Laparoscopic D3 surgery was not non-inferior to open surgery for overall survival (HR 1·06, 90% CI 0·79–1·41; p non-inferiority =0·073). 65 (13%) patients in the open surgery group and 53 (10%) patients in the laparoscopic surgery group had grade 2–4 adverse events. Grade 2–4 adverse events included diarrhoea (15 [3%] in the open surgery group vs 14 [3%] in the laparoscopic surgery group), paralytic ileus (six [1%] vs nine [2%]), and small intestine bowel obstruction (16 [3%] vs 11 [2%]). Two treatment-related deaths occurred in the open surgery group: one patient died 7 days after surgery (probably due to myocardial infarction), and one patient died from febrile neutropenia, pneumonia, diarrhoea, and gastrointestinal haemorrhage during postoperative chemotherapy. Interpretation Laparoscopic D3 surgery was not non-inferior to open D3 surgery in terms of overall survival for patients with stage II or III colon cancer. However, because overall survival in both groups was similar and better than expected, laparoscopic D3 surgery could be an acceptable treatment option for patients with stage II or III colon cancer. Funding National Cancer Center Research and Development Fund, Grant-in-Aid for Cancer Research, and Health and Labour Sciences Research Grant for Clinical Cancer Research from the Ministry of Health, Labour and Welfare of Japan.

The aim of the present study was to examine the technical and oncological feasibility of laparoscopic surgery (LAP) in elderly patients with a history of abdominal surgery. We conducted a propensity score-matched case–control study of colorectal cancer (CRC) patients aged ≥80 years that were treated at 41 hospitals between 2003 and 2007. We included 601 patients who had a history of abdominal surgery and underwent curative and elective surgery for stage 0 to III CRC. After the matching procedure, 153 patients were included in each cohort. The surgical outcomes of LAP and open surgery (OS) were compared. P-values of

To clarify the role of splenectomy in total gastrectomy for proximal gastric cancer.Splenectomy in total gastrectomy is associated with increased operative morbidity and mortality, but its survival benefit is unclear. Previous randomized controlled trials were underpowered and inconclusive.We conducted a multiinstitutional randomized controlled trial. Proximal gastric adenocarcinoma of T2-4/N0-2/M0 not invading the greater curvature was eligible. During the operation, surgeons confirmed that R0 resection was possible with negative lavage cytology, and patients were randomly assigned to either splenectomy or spleen preservation. The primary endpoint was overall survival (OS) and the secondary endpoints were relapse-free survival, operative morbidity, operation time, and blood loss. The trial was designed to confirm noninferiority of spleen preservation to splenectomy in OS with a noninferiority margin of the hazard ratio as 1.21 and 1-sided alpha of 5%.Between June 2002 and March 2009, 505 patients (254 splenectomy, 251 spleen preservation) were enrolled from 36 institutions. Splenectomy was associated with higher morbidity and larger blood loss, but the operation time was similar. The 5-year survivals were 75.1% and 76.4% in the splenectomy and spleen preservation groups, respectively. The hazard ratio was 0.88 (90.7%, confidence interval 0.67-1.16) (1.21); thus, the noninferiority of spleen preservation was confirmed (P = 0.025).In total gastrectomy for proximal gastric cancer that does not invade the greater curvature, splenectomy should be avoided as it increases operative morbidity without improving survival.

Background: The potential for infertility caused by treatment is one of the important quality-of-life issues in young breast cancer (YBC) patients. Insufficient communication and partnership between oncologists and reproductive specialists has been identified as a major barrier to meeting their needs. However, the perception of reproductive specialists towards fertility preservation (FP) of YBC has not been evaluated. Objective: To investigate the perception and needs of reproductive specialists towards FP of YBC patients. Methods: A cross-sectional survey was developed and sent to 423 certified reproductive specialists registered to the Japan Society for Reproductive Medicine to self-evaluate their perceptions and practices regarding FP in YBC patients. Results: Two hundred reproductive specialists (47%) responded to the survey. 99% responded that reproductive specialists should be engaged in FP of YBC patients. 46% responded that cancer treatment is more important than childbirth even if the patient was recurrence-free five years after primary treatment. 83% responded that they would like to treat YBC patients. Respondents affiliated with private clinics were more likely to accept both fertilized egg and unfertilized egg preservation than those affiliated with academic or general hospitals (p < 0.01). 58% responded that ovulation induction methods should be modified in YBC patients. The choice of ovulation induction methods varied both in non-cancer women and YBC patients, however, the frequency of the use of letrozole was significantly higher (p < 0.01) and that of LHRH-agonist short protocol was significantly less (p < 0.05) in the management of breast cancer patients than in the practice of non-cancer women. 70% of the reproductive specialists responded that they were anxious in treating YBC patients. Concerns for greater or unknown risk of disease recurrence (66%), insufficient knowledge about breast cancer (47%), and lack of patient's spouse/partner (24%) were identified as major barriers in supporting FP for YBC patients. Conclusion Reproductive specialists recognize the needs of FP in YBC patients and are willing to participate and support care for YBC. Affiliation of reproductive specialists was related to positive attitude towards to egg preservation. Various concerns regarding FP among reproductive specialists indicate the need for evidence that supports the safety of FP for YBC patients and guidelines that facilitate the practice and communication of oncologists and reproductive specialists. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-11-02.

Objective: Progression-free survival is an often-used endpoint in clinical trials comparing preoperative therapy and surgery-first therapy. Because the surgery date is always later in the preoperative arm than in the surgery-first arm, it is difficult to define progression-free survival optimally. We evaluated three progression-free survival definitions that used different methods to handle incomplete resection. Methods: The three definitions specify the event date of incomplete resection (IR) as follows: ‘IR ¼ event’ method, date of surgery; ‘IR not event’ method, date of radiological or clinical progression after incomplete resection; landmark method, landmark time. According to these definitions, the theoretical strengths and weaknesses of the three definitions are investigated. Three patterns of progression-free survival and overall survival were estimated using the data of the Japan Clinical Oncology Group studies. Results: Theoretically, ‘IR ¼ event’ inflates alpha error while ‘IR not event’ method and landmark method reduce the statistical power under the alternative hypothesis. In JCOG9907, hazard ratios for the three definitions were: ‘IR ¼ event’, 0.80 (95% confidence interval, 0.59‐1.07; P ¼ 0.13); ‘IR not event’, 0.81 (95% confidence interval, 0.60‐1.09; P ¼ 0.16); landmark, 0.80 (95% confidence interval, 0.59‐1.07; P ¼ 0.15). No P value of any methods corresponded with the positive result for overall survival (P ¼ 0.03). In the preoperative arms of the four studies, maximum differences in median and percentage of 1 year progressionfree survival among the three definitions were 0‐6.4 months and 1.2‐5.2%. Conclusions: Progression-free survival sometimes fails as a surrogate of overall survival, and differences among results obtained with various progression-free survival definitions can be large. Overall survival should be used as primary endpoint in studies evaluating preoperative therapy.

This study evaluated the risk factors for anastomotic leakage after laparoscopic surgery for rectal cancer using a stapling technique.The total prospective registry of 111 patients with rectal cancer who initially underwent laparoscopic low anterior resection using a stapling technique was reviewed. Univariate and multivariate analyses were carried out to identify relevant risk factors.Overall anastomotic leakage rate was 5.4% (6/111). Univariate analysis demonstrated that body mass index (BMI) (P=0.0377) was significantly associated with anastomotic leakage. After univariate analysis, the variables of BMI and the size of the circular stapler (P=0.0923) were selected for multivariate analysis, as their P values were0.2, and multivariate analysis demonstrated that BMI was independently predictive of developing anastomotic leakage (P=0.0458).Laparoscopic surgery for rectal cancer using a stapling technique can be performed safely without increasing the risk of anastomotic leakage, and increased BMI might be a potential risk factor for anastomotic leakage.

Laparoscopic intersphincteric resection (Lap ISR) is not yet an established technique and its safety and feasibility are unclear. Our aim was to clarify the safety and feasibility of Lap ISR for clinical stage 0/I rectal cancer (Lap RC) in a prospective multicenter study of laparoscopic surgery in Japan.To examine the technical and oncological feasibility of laparoscopic surgery for rectal cancer, we conducted a confirmatory phase II trial to evaluate laparoscopic surgery for preoperative clinical stage 0/I rectal cancer. Eligibility criteria included histologically proven carcinoma, size ≤ 8 cm, age 20-75 years, no bowel obstruction, and no prior chemotherapy or radiotherapy. Between February 2008 and September 2010, 495 patients with rectal cancer underwent laparoscopic surgery at 43 institutions. Patients' background characteristics and operative and postoperative outcomes were recorded prospectively.Seventy-seven patients (15.6 %) underwent Lap ISR. A diverting stoma was created in 69 patients (89.6 %). Conversion to open surgery occurred in 4 patients (5.2 %): 2 patients were converted because of uncontrollable bleeding, and the other 2 patients because of the need for pelvic side wall lymphadenectomy. There was no mortality. Median operative time was 345 min (range = 198-565), median amount of blood loss was 100 ml (range = 0-1760), and three patients (3.9 %) were transfused intraoperatively. The median number of dissected lymph nodes was 14 (range = 3-33), and all (proximal, distal, and vertical) pathological cut margins were negative. Postoperative complications of grade 2 or more were detected in 17 patients (22.1 %), including anastomotic leakage in 5 (6.4 %), bowel obstruction in 5 (6.5 %), and surgical site infection in 2 (2.6 %). Abdominal drainage and diverting stoma were necessary in two patients (2.6 %) due to anastomotic leakage. Median length of postoperative hospital stay was 13 days (range = 7-167).Lap ISR was feasible and safe for clinical stage 0/I rectal cancer with favorable short-term outcome.

Satoru Murata1, Yoshikatsu Koga2, Yoshihiro Moriya3, Takayuki Akasu3, Shin Fujita3, Seiichiro Yamamoto3, Yasuo Kakugawa4, Yosuke Ohtake4, Norio Saito1, Yasuhiro Matsumura21Colorectal Surgery Division, Department of Surgical Oncology, National Cancer Center Hospital East, Kashiwa, Japan 2Investigative Treatment Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan 3Department of Surgery, National Cancer Center Hospital, Tokyo, Japan 4Cancer Screening Division, National Cancer Center Research Center for Cancer Prevention and Screening, Tokyo, JapanBackground: Several methods for the early detection of colorectal cancer to reduce its mortality rate have been reported. Here, we investigated the potential of a fecal micro RNA test for the early detection of colorectal cancer.Methods: Patients with colorectal cancer (n = 299) and healthy volunteers (n = 116) with no abnormalities detected by screening colonoscopy were enrolled in this case-control study. Micro RNA expression in the colonocytes of patients with colorectal cancer (n = 47) and in healthy volunteers (n = 35) were analyzed in the training set, and the micro RNA expression in the colonocytes of patients with colorectal cancer (n = 252) and healthy volunteers (n = 81) was validated in the validation set.Results: In the training study, significant differences in the relative expression level of miR-17-92 cluster, -106a, -135, and -146a were observed between patients with colorectal cancer and healthy volunteers (P < 0.01). The area under the receiver operating characteristic curve using miR-17, -18a, -19a, -19b, -20a, -92a, -106a, -135b, and -146a was more than 0.7. The overall sensitivity and specificity in the training study using these micro RNAs was 70.2% (33/47) and 74.3% (26/35), respectively. The overall sensitivity and specificity in the validation study was 67.5% (170/252) and 75.3% (61/81), respectively.Conclusion: We have developed a fecal micro RNA test for exfoliated colonocytes for colorectal cancer screening. Further comparative study of this test for colorectal cancer screening is needed.Keywords: colorectal cancer, fecal micro RNA, colonocytes, cancer screening, fecal RNA test

Yamaguchi T, Taniguchi H, Fujita S, Sekine S, Yamamoto S, Akasu T, Kushima R, Tani T, Moriya Y & Shimoda T (2012) Histopathology 61, 162–169 Clinicopathological characteristics and prognostic factors of advanced colorectal mucinous adenocarcinoma Aims: Mucinous adenocarcinoma (MUC) is a histological variant of colorectal adenocarcinoma. The aim of the present study was to characterize clinicopathological features and identify prognostic factors of MUCs. Methods and results: A total of 181 patients with MUC who underwent surgery between 1975 and 2003 were reviewed. The clinicopathological features of these patients were compared with those of 4125 non-MUC patients. Univariate and multivariate analyses were conducted to identify significant prognostic factors in 102 patients with pT3 or pT4 tumour who underwent curative surgery. Patients with MUCs tended to present with more advanced clinical stages. The overall 5-year survival rate of MUC patients was lower than that of non-MUC patients; however, no prognostic difference was found when patients with the same clinical stages were compared. Multivariate analysis revealed male sex, bowel obstruction and infiltrating growth type as independent prognostic factors. Five-year cancer-specific survival rates for MUC patients with ≤1, 2 and 3 risk factors identified by multivariate analysis were 95.5%, 52.1% and 0.0%, respectively (P

Activation of the EGFR, KRAS, and ALK oncogenes defines 3 different pathways of molecular pathogenesis in lung adenocarcinoma. However, many tumors lack activation of any pathway (triple-negative lung adenocarcinomas) posing a challenge for prognosis and treatment. Here, we report an extensive genome-wide expression profiling of 226 primary human stage I–II lung adenocarcinomas that elucidates molecular characteristics of tumors that harbor ALK mutations or that lack EGFR, KRAS, and ALK mutations, that is, triple-negative adenocarcinomas. One hundred and seventy-four genes were selected as being upregulated specifically in 79 lung adenocarcinomas without EGFR and KRAS mutations. Unsupervised clustering using a 174-gene signature, including ALK itself, classified these 2 groups of tumors into ALK-positive cases and 2 distinct groups of triple-negative cases (groups A and B). Notably, group A triple-negative cases had a worse prognosis for relapse and death, compared with cases with EGFR, KRAS, or ALK mutations or group B triple-negative cases. In ALK-positive tumors, 30 genes, including ALK and GRIN2A, were commonly overexpressed, whereas in group A triple-negative cases, 9 genes were commonly overexpressed, including a candidate diagnostic/therapeutic target DEPDC1, that were determined to be critical for predicting a worse prognosis. Our findings are important because they provide a molecular basis of ALK-positive lung adenocarcinomas and triple-negative lung adenocarcinomas and further stratify more or less aggressive subgroups of triple-negative lung ADC, possibly helping identify patients who may gain the most benefit from adjuvant chemotherapy after surgical resection. Cancer Res; 72(1); 100–11. ©2011 AACR.

Introduction The aim of the study is to evaluate the current status of treatment-related death (TRD) in lung cancer patients. Methods We retrospectively analyzed the incidence and risk factors of TRD in lung cancer patients who received chemotherapy and/or thoracic radiotherapy using logistic regression analyses. Results Between January 2001 and December 2005, 1225 (222 small cell and 1003 non-small cell lung cancers) patients received chemotherapy and/or thoracic radiotherapy as the initial treatment. Of these, 43 patients receiving chemotherapy followed by thoracic radiotherapy were included into both the chemotherapy-alone and radiotherapy-alone groups. There were a total of 23 (1.9%) TRDs. Chemotherapy-related deaths occurred in 7 of 927 (0.8%) patients, including 4 from drug-induced lung injury, 2 from pneumonia, and 1 from unknown cause. Concurrent chemoradiotherapy-related deaths occurred in 12 of 245 (4.9%) patients, including 11 from radiation pneumonitis and 1 from pneumonia. Thoracic radiotherapy-related deaths occurred in 4 of 96 (4.2%) patients. The incidence of chemotherapy-related death was correlated with poor performance status (odds ratio [OR]: 11.4, 95% confidence interval [CI]: 3.53–37.1), the presence of hypoxia (OR: 19.3, CI: 6.06–61.7), hyponatremia (OR: 45.5, CI: 13.4–154), and treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (OR: 8.56, CI: 2.48–29.5), whereas the incidence of concurrent chemoradiotherapy-related death was correlated with pulmonary fibrosis (OR: 22.2, CI: 5.61–87.8). Radiotherapy results were not analyzed because there were too few patients. Conclusions TRD occurred in 1.9% of the patients as a result of treatment-related lung injury in the majority of the cases.

Purpose We developed and evaluated a simple, robust and valid self-administered questionnaire for the estimation of physical activity (PA). Here, we examined the validity of this questionnaire in subjects with differing sex, ages, occupations and living circumstances.

Recent genome-wide association studies (GWASs) have identified polymorphisms in several genes associated with lung cancer risk. Nevertheless, functional polymorphisms in DNA repair and metabolic genes that had been reported as being associated with risk for lung cancer, particularly for lung squamous cell carcinoma (SQC), were not examined in those studies. Therefore, significance of these functional polymorphisms was evaluated in a population, in which polymorphisms in the GWAS genes showed associations with lung SQC risk.Polymorphisms in three DNA repair genes, TP53, MDM2, and OGG1, and two metabolic genes, CYP1A1 and GSTM1, were examined for associations with lung SQC risk in a hospital-based case-control study consisting of 377 cases and 325 controls, which had been previously subjected to association studies on GWAS genes, CHRNA3, TERT, and HLA-DQA1.Genotypes for two DNA repair genes, TP53 and OGG1, showed significant associations with SQC risk (p0.05), and those for two GWAS genes, CHRNA3 and HLA-DQA1, showed significant associations with SQC risk (P0.05) with odds ratios between 1.65 (95% confidence interval = 1.06-2.57 for OGG1) and 2.57 (95% confidence interval = 1.03-6.87 for CHRNA3). Marginally significant associations were also observed for MDM2 and CYP1A1 genes. Interactions among these polymorphisms on SQC risk were not observed.Association of functional polymorphisms in DNA repair and metabolic genes with lung SQC risk was appreciated. This result indicates the necessity of reevaluation for the significance of functional polymorphisms in DNA repair and metabolic genes on lung cancer risk in other populations subjected to GWASs.

Objective. The study aims to investigate the association between leisure-time physical activity and breast cancer risk in consideration of tumor estrogen-receptor/progesterone-receptor status. Methods. We conducted a population-based prospective cohort study among 53,578 women in the Japan Public Health Center-based Prospective Study. Leisure-time physical activity was assessed by self-reported questionnaires. A Cox proportional hazards regression model was used to derive relative risks and 95% confidence intervals. Results. From 1990–1993 to the end of 2007, 652 cases were identified. The breast cancer rates (per 100,000 person-years) in the sedentary groups (≤ 3 days/month) was 84 in overall, 97 in premenopausal and 75 in postmenopausal women. We observed a statistically significant inverse association between leisure-time physical activity and breast cancer risk (relative risk ≥ 3 days/week vs. ≤ 3 days/month = 0.73; 95% confidence interval 0.54–1.00; p trend 0.037), particularly in estrogen receptor+progesterone receptor+ (relative risk 0.43; 0.19–1.00; p trend 0.022), and this inverse trend was apparent among postmenopausal women (relative risk 0.25; 0.06–1.06; p trend 0.041). An inverse trend was also observed between daily total physical activity and postmenopausal estrogen receptor+progesterone receptor+ risk ( p = 0.046). Among body mass index ≥ 25 kg/m 2 group, leisure-time physical activity was associated with decreased risk (relative risk ≥ 1 day/week vs. ≤ 3 days/month = 0.65; 0.43–0.97; p trend 0.033 ). Conclusion. Active participation in leisure-time physical activity may contribute to a decrease in breast cancer risk, particularly for postmenopausal estrogen receptor+progesterone receptor+ tumors.

653 Background: In curative resection of sigmoid colon and rectal cancer, it is unclear whether D3 lymph node dissection preserving left colic artery (LCA) (Group A) is beneficial compared to D3 without preserving LCA (Group B) in terms of clinical outcomes. Preservation of LCA is expected to maintain blood supply which results in preventing anastomotic leakage, intestinal paralysis, and so on. Methods: The data of JCOG0404 (which is a randomized controlled trial comparing open to laparoscopic surgery for stage II/III colon cancer) were used. Eligibility criteria in JCOG0404 included histologically proven colon cancer; T3 or deeper lesion without involvement of other organs; N0-2 and M0. D3 lymph node dissection with or without preserving LCA was identified according to the photographs of the resected field collected for central surgical review in JCOG0404. The short and long-term outcomes were compared between each procedure. Results: Among all randomized 1057 patients in JCOG0404, 631 patients who received assigned sigmoid colectomy and anterior resection were included in the subgroup analysis. The number of patients were 135 in Group A and 496 in Group B. The patient backgrounds did not differ between groups. The median operative time, median blood loss, and the proportion of grade 1 or more anastomotic leakage and intestinal paralysis were not remarkably different (Group A vs. Group B: 185 min vs 186 min, 60 ml vs. 50 ml, 3.0% vs. 5.0%, and 2.2% vs. 3.8%). However, overall postoperative complication occurred more in Group B than in Group A (9.6% and 21.6%, p = 0.022). In terms of efficacy, 5-year relapse-free survival (RFS) and overall survival (OS) tended to be better in Group A than Group B (RFS: 83.7% and 80.5%, HR 1.25 (95% CI 0.79-1.96), OS: 96.3% and 91.1%, HR 2.47 (95% CI 1.13-5.40)). Conclusions: Short and long-term outcomes were better in Group A than Group B. It was considered that D3 lymph node dissection preserving LCA could be alternative treatment for D3 lymph node dissection. Clinical trial information: C000000105.

Objective: Male smoking prevalence is still high in Japan, and quantitative information for tobacco control is scarce. The aim of the present study was to project cancer mortality among Japanese males under different future scenarios of smoking prevalence. Methods: The target population comprised Japanese males aged 40–79 years in 2007, whose smoking prevalence was 35%. On the basis of the pooled data from three large-scale cohort studies in Japan, the effects of age, years of smoking and years after smoking cessation on the time to all-cancer or lung cancer death were estimated by an accelerated failure time model. The parameter estimates were used to project the annual number of deaths from all cancers and lung cancer by running simulations for different future scenarios of smoking prevalence. Each scenario was evaluated by the cumulative number of avoided deaths when compared with the status quo and by the percent change (from the baseline year) in agestandardized rate of mortality. Results: Reducing the smoking prevalence from 35% in 2007 to 0% in 2017 was estimated to avoid 333 900 all-cancer deaths and 171 100 lung cancer deaths in 20 years. Even when we shortened the projection period to 10 years, these numbers of avoided deaths would be 81 100 and 38 800, respectively. The age-standardized rate of all-cancer mortality was estimated to decrease by 9.6% in 10 years and 18.1% in 20 years. Conclusions: Reducing the prevalence of smoking among males would be effective in reducing the cancer burden even within 10 years in countries with a high male smoking prevalence.

Background/Aims: To evaluate the short-term surgical outcomes of laparoscopic intersphincteric resection (ISR) for lower rectal cancer, and to compare them with a case-control series of open ISR. Methods: Between July 2002 and March 2011, 29 patients with lower rectal cancer underwent laparoscopic ISR, and 22 of 29 patients who underwent laparoscopic ISR were compared with the control open ISR group of patients matched for age, gender, operative procedure and pathological stage. Results: There was no perioperative mortality, 8 complications occurred in 7 patients, and the morbidity rate was 24.1% (7/29). Leakage occurred in 1 patient (3.4%) in the laparoscopic ISR group. Regarding the matched case-control study, the operative time was significantly longer (p = 0.0007), but blood loss was significantly lower (p = 0.0003) in the laparoscopic ISR group. The median postoperative hospital stay was 8 days in the laparoscopic ISR group, which was significantly shorter than in the open ISR group (14 days). Postoperative complication rates were similar. In the laparoscopic ISR group, the levels of C-reactive protein on postoperative days 1–3 were significantly lower than in the open ISR group. Conclusions: Laparoscopic ISR for lower rectal cancer provides benefits in the early postoperative period without increasing morbidity or mortality.

Background Surgical indication for stage IV colorectal cancer patients with bilobar hepatic metastases may be controversial. Methods Retrospective cohort analysis was performed using data of 200 patients who underwent surgical resections for synchronous metastases of colorectal cancer between 1990 and 2005. Of these, 80 patients had solitary, 43 had unilobar multiple, and 77 had bilobar metastases. Prognostic factors of the 77 bilobar metastases were evaluated using multivariate analysis. The survival was compared with that of 95 patients undergoing chemotherapy for unresectable bilobar hepatic metastases. Results Univariate and multivariate analyses revealed that the number of metastasis (≥6) [relative risk (RR), 2.7; P = 0.002] and depth of invasion (T4) (RR, 2.0; P = 0.04) were predictors of survival of the 77 patients. The survival of 11 T4 cancer patients with six or more metastases was poor, but significantly better than that of 95 patients with unresectable bilobar metastases (P = 0.04). Conclusion Surgical resection in stage IV colorectal cancer patients having bilobar hepatic metastases was justified in the present setting. J. Surg. Oncol. 2010;102:784–788. © 2010 Wiley-Liss, Inc.

We tested the hypothesis that polymorphisms in cytochrome P450c17alpha (CYP17), aromatase (CYP19), 17beta-hydroxysteroid dehydrogenase type I (17beta-HSD1) and sex hormone-binding globulin (SHBG) genes may modify the association between isoflavone intake and breast cancer risk. We conducted hospital-based, case-control studies in Nagano, Japan and Sao Paulo, Brazil. A total of 846 pairs (388 Japanese, 79 Japanese Brazilians, and 379 non-Japanese Brazilians) completed validated food frequency questionnaires. Four single nucleotide polymorphisms (SNPs) in CYP17 (rs743572), CYP19 (rs10046), 17beta-HSD1 (rs605059), and SHBG (rs6259) genes were genotyped. We found no association between the 4 SNPs and breast cancer risk. In combination analyses of isoflavone intake and SNPs, an inverse association between intake and risk was limited to women with at least one A allele of the rs605059 polymorphism for all 3 populations, albeit without statistical significance. For the rs6259 polymorphism, the inverse association was limited to postmenopausal Japanese with the GG genotype (odds ratio [OR] for highest vs. lowest tertile = 0.50, 95% confidence interval [CI] = 0.29-0.87; P for trend0.01), and to non-Japanese Brazilians with at least one A allele (OR for consumers vs. nonconsumer = 0.21, 95% CI = 0.06-0.77). We found no remarkable difference for the rs743572 and rs10046 polymorphisms. Our findings suggest that polymorphisms in the 17beta-HSD1 and SHBG genes may modify the association between isoflavone intake and breast cancer risk.

This study aims to search for independent predictors of lateral node metastasis in low rectal cancers. We analyzed 1,046 patients who underwent curative resection for lower rectal cancer in our prospectively collected database. All lymph nodes were dissected from the fresh specimen, and their locations were documented prospectively according to the classification by the Japanese Society of Cancer of the Colon and Rectum. More than 35% of the patients had demonstrated upward nodal metastasis in the direction of the inferior mesenteric vessels, while 11% demonstrated lateral node metastasis, which was present in 17.3% of patients with T3 and T4 lesions. Multivariate analysis revealed five factors to be statistically significant independent predictors of lateral node metastasis: female sex, tumors that were not well differentiated, pathological T3 and above, positive microscopic lymphatic invasion, and positive mesorectal nodes. Using the variables sex, differentiation, T stage, and mesorectal nodes as risk factors, because these could be elucidated preoperatively, the presence of lateral node metastasis was then analyzed according to the number of positive risk factors. When there were fewer than three positive factors, the risk of lateral nodal spread was low (4.5%). When three or more risk factors were positive, the odds of lateral node metastasis were more than 7.5 times higher (p

Adenocarcinoid tumor most commonly occurs in the appendix and a tumor arising in the rectum is extremely rare. A 58-year-old man underwent total pelvic exenteration with extended lateral lymph node dissection for rectal adenocarcinoid tumor invading the urethra with lateral lymph node metastasis. Microscopically and immunohistochemically, the tumor consisted of carcinoid-like components and signet-ring-cell-carcinoma-like components, and an adenocarcinoid tumor was diagnosed. Postoperatively, the patient received combination chemotherapy of fluorouracil and leucovorin as an adjuvant therapy. Three years and 5 years after the initial surgery, the patient developed left groin and left external iliac lymph node recurrences, and lymphadenectomy was performed each time. As a result, the patient is alive more than 5 years after the initial surgery. There is no consensus on the indication of surgical treatment for adenocarcinoid tumor. However, in advanced cases, an aggressive surgical procedure might result in long-term survival when resectable.