Clinical T2N0 Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy plus Local Excision.

INTRODUCTION: Total mesorectal excision is the standard treatment for clinical T2 (cT2) rectal cancer; however, this procedure can result in postoperative dysfunction, decreased quality of life, and stoma creation in some patients. We investigated neoadjuvant chemoradiotherapy (nCRT) plus local excision (LE) as an alternative treatment strategy for patients with cT2N0 rectal cancer. METHOD: Fifty-six patients with cT2N0M0 rectal cancer who exhibited the following characteristics (an anal verge of ≤8 cm, tumor size of <30 mm, well- or moderately differentiated adenocarcinoma on biopsy) underwent LE following nCRT. Chemoradiotherapy was administered at 40 or 45 Gy in 20-25 fractions with concurrent oral UFT (tegafur/uracil; 400 mg/m2) or S-1 (tegafur/gimeracil/oteracil; 80 mg/m2). RESULTS: Fifty-five patients (98%) completed nCRT as planned. Histologically, the excision margin was negative in all patients, and four patients with ypT3 disease underwent total mesorectal excision. Recurrence was observed in 15 patients (27%), local recurrence in 7 (13%), and distant recurrence in 10 (18%). The salvage surgery was possible for the local recurrence group. The 5-year disease-free and overall survival rates were 68.4% and 84.9%, respectively. Multivariate analysis showed that only the tumor regression grade (TRG) was an independent risk factor for recurrence (p = 0.025). Although 7 (26%) out of 27 patients with a TRG of 3 or 4 developed local recurrence and 6 (22%) had distant metastasis, 25 patients with a TRG of 1 or 2 did not exhibit local recurrence, and only 1 (4%) experienced distant metastasis. CONCLUSION: nCRT plus LE may be an alternative treatment for patients with cT2N0 rectal cancer who achieved a TRG of 1 or 2. However, additional treatment was required in patients who achieved a TRG of 3 or 4.

Classification of rectal cancer according to recurrence types - comparison of Japanese guidelines and Western guidelines.

BACKGROUND: Rectal cancer is characterized by more local recurrence (LR) and lung metastasis than colon cancer. However, the diagnosis of rectal cancer is not standardized as there is no global consensus on its definition and classification. The classification of rectal cancer differs between Japanese and Western guidelines. AIM: To clarify the characteristics of rectal cancer by comparing the tumor location and characteristics of rectal cancer with those of colon cancer according to each set of guidelines. METHODS: A total of 958 patients with Stage II and III colorectal cancer were included in the analysis: 607 with colon cancer and 351 with rectal cancer. Localization of rectal cancers was assessed by enema examination and rigid endoscopy. According to Japan guidelines, rectal cancer is classified as Rb (below the peritoneal inversion), Ra (between the inferior margin of second sacral vertebrae and Rb) or RS (between Ra and sacral promontory). RESULTS: There were no significant differences between RS rectal cancer and colon cancer in the rates of liver and lung metastasis or LR. Lung metastasis and LR were significantly more common among Rb rectal cancer (in Japan) than in colon cancer (P = 0.0043 and P = 0.0002, respectively). Lung metastases and LR occurred at significantly higher rates in rectal cancer measuring ≤ 12 cm and ≤ 10 cm than in colon cancers (P = 0.0117, P = 0.0467, P = 0.0036, P = 0.0010). Finally, the rates of liver metastasis, lung metastasis, and LR in rectal cancers measuring 11 cm to 15 cm were 6.9%, 2.8%, and 5.7%, respectively. These were equivalent to the rates in colon cancer. CONCLUSION: High rectal cancer may be treated with the same treatment strategies as colon cancer. There was no difference in the classification of colorectal cancer between Japan and Western countries.

Rainbow of KIBOU (ROK) study: a Breast Cancer Survivor Cohort in Japan.

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.

Impact of modifiable lifestyle factors on outcomes after breast cancer diagnosis: the Setouchi Breast Cancer Cohort Study.

The primary purpose of this large cohort study is to investigate the effects on breast cancer outcomes of modifiable lifestyle factors after breast cancer diagnosis. These factors include physical activity, smoking, alcohol consumption, obesity and weight gain after diagnosis, alternative medicine and dietary factors. Women diagnosed with Stage 0 to III breast cancer are eligible for participation to this study. Lifestyle, use of alternative medicine, psychosocial factors, reproductive factors and health-related quality of life will be assessed using a questionnaire at the time of breast cancer diagnosis (baseline), and 1, 2, 3 and 5 years after diagnosis. Clinical information and breast cancer outcomes will be obtained from a breast cancer database. The primary endpoint will be disease-free survival. Secondary endpoints are overall survival, health-related quality of life, breast cancer-related symptoms and adverse events. Patient recruitment commenced in February 2013. Enrollment of 2000 breast cancer patients is planned during the 5-year recruitment period. The concept of the study is described in this article.

Prospective study of transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: an Asian cooperative study between Japan and Korea.

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.

Randomized clinical trial of adjuvant chemotherapy with intraperitoneal and intravenous cisplatin followed by oral fluorouracil (UFT) in serosa-positive gastric cancer versus curative resection alone: final results of the Japan Clinical Oncology Group trial JCOG9206-2.

PURPOSE: To evaluate the survival benefit of adjuvant chemotherapy after curative resection in serosa-positive gastric cancer, a multicenter phase III clinical trial was conducted in Japan. PATIENTS AND METHODS: From January 1993 to March 1998, 268 patients were randomized to adjuvant chemotherapy (135 patients) or surgery alone (133 patients). All patients underwent gastrectomy with D2 or greater lymph node dissection. The chemotherapy regimen consisted of intraperitoneal cisplatin soon after abdominal closure, postoperative intravenous cisplatin (day 14) and 5-fluorouracil (day 14-16), and daily oral FU (UFT) starting 4 weeks after surgery for 12 months. The primary endpoint was overall survival. Relapse-free survival and site of recurrence were secondary endpoints. RESULTS: Fifty-two patients (38.5%) in the adjuvant chemotherapy arm completed the chemotherapy regimen. There were 4 (1.49%) treatment-related deaths, 1 in the surgery-alone and 3 in the adjuvant chemotherapy arm (2 did not receive chemotherapy). Grade 4 toxicity was observed in 3 patients in the surgery-alone and 2 patients in the adjuvant chemotherapy arm. There was no significant difference in 5-year overall survival (62.0% adjuvant chemotherapy vs. 60.9% surgery-alone, P = 0.482) and 5-year relapse-free survival rates (57.5% adjuvant chemotherapy vs. 55.6% surgery-alone; P = 0.512). CONCLUSION: There was no benefit in overall and relapse-free survival with this adjuvant chemotherapy regimen for patients with macroscopically serosa-positive gastric cancer after curative resection.

A placebo-controlled 3-year study of a calcium blocker on visual field and ocular circulation in glaucoma with low-normal pressure.

PURPOSE: To study the 3-year effect of oral nilvadipine, a calcium antagonist, on visual field performance and ocular circulation in open-angle glaucoma (OAG) with low-normal intraocular pressure (IOP). DESIGN: A randomized, placebo-controlled, double-masked, single-center trial. PARTICIPANTS: Patients with OAG who were younger than 65 years and had untreated IOP consistently of 16 mmHg or less. INTERVENTION: Oral nilvadipine (2 mg twice daily) or placebo was assigned randomly to patients fulfilling the criteria by the minimization method of balancing the groups according to age, refraction, and the mean deviation (MD) value (Humphrey Perimeter 30-2 SITA Standard Program; Humphrey Instruments, Inc., San Leandro, CA) of the eye with less negative MD. No topical ocular hypotensive drugs were prescribed. Visual field testing was performed every 3 months; fundus examination and IOP, blood pressure, and pulse rate measurements were carried out every month; and quantitative indexes of circulation in the optic disc rim (NB(ONH)) and choroid in the foveal area (NB(fovea)) were determined using the laser speckle method at 0, 3, 6, 12, 18, 24, 30, and 36 months. MAIN OUTCOME MEASURES: The time courses of MD, NB(ONH), and NB(fovea) in the eye with less negative MD. RESULTS: Thirty-three patients were enrolled; 17 were assigned to nilvadipine and 16 were assigned to placebo; 13 in each group completed the study. No significant intergroup difference was seen in age, refraction, or baseline values of any of the parameters. During the 3-year period, the IOP averaged 12.6 mmHg in the nilvadipine group and 12.8 mmHg in the placebo group (P>0.1), and no significant change from baseline or intergroup difference was seen in blood pressure or pulse rate. The estimated slope of change in the MD was less negative in the nilvadipine than in the placebo group (-0.01 vs. -0.27 decibels/year; P = 0.040). The NB(ONH) and NB(fovea) values remained increased compared with baseline for the study period by approximately 30% to 40% only in the nilvadipine group, and the intergroup difference was significant (P = 0.003 for NB(ONH) and P = 0.007 for NB(fovea)). CONCLUSIONS: Nilvadipine (2 mg twice daily) slightly slowed the visual field progression and maintained the optic disc rim, and the posterior choroidal circulation increased over 3 years in patients with OAG with low-normal IOP.

Validity of a self-administered food frequency questionnaire (FFQ) and its generalizability to the estimation of dietary folate intake in Japan.

BACKGROUND: In an epidemiological study, it is essential to test the validity of the food frequency questionnaire (FFQ) for its ability to estimate dietary intake. The objectives of our study were to 1) validate a FFQ for estimating folate intake, and to identify the foods that contribute to inter-individual variation of folate intake in the Japanese population. METHODS: Validity of the FFQ was evaluated using 28-day weighed dietary records (DRs) as gold standard in the two groups independently. In the group for which the FFQ was developed, validity was evaluated by Spearman's correlation coefficients (CCs), and linear regression analysis was used to identify foods with large inter-individual variation. The cumulative mean intake of these foods was compared with total intake estimated by the DR. The external validity of the FFQ and intake from foods on the same list were evaluated in the other group to verify generalizability. Subjects were a subsample from the Japan Public Health Center-based prospective Study who volunteered to participate in the FFQ validation study. RESULTS: CCs for the internal validity of the FFQ were 0.49 for men and 0.29 and women, while CCs for external validity were 0.33 for men and 0.42 for women. CCs for cumulative folate intake from 33 foods selected by regression analysis were also applicable to an external population. CONCLUSION: Our FFQ was valid for and generalizable to the estimation of folate intake. Foods identified as predictors of inter-individual variation in folate intake were also generalizable in Japanese populations. The FFQ with 138 foods was valid for the estimation of folate intake, while that with 33 foods might be useful for estimating inter-individual variation and ranking of individual folate intake.

Green tea consumption and subsequent risk of gastric cancer by subsite: the JPHC Study.

OBJECTIVE: To investigate the relationship between green tea consumption and subsequent risk of gastric cancer at different anatomical subsites in a population-based prospective study. METHODS: The Japan Public Health Center-based prospective study (JPHC Study) was established in 1990 for Cohort I and in 1993 for Cohort II. Among 72,943 subjects (34,832 men and 38,111 women), 892 gastric cancer cases (665 men and 227 women) were identified from 1990 to 2001. RESULTS: While no association between green tea consumption and gastric cancer was observed among men, a decreased risk of gastric cancer was observed among women after adjustment for potential confounding factors. This result was more remarkable when only the tumors in the distal portion were analyzed; for that subsite, the relative risk was 0.51 (95% confidence interval 0.30-0.86) in the highest category of green tea consumption (5 or more cups per day versus less than 1 cup per day) (p for trend = 0.01). The null association for upper-third gastric cancer was consistent for both sexes. CONCLUSIONS: An inverse association between green tea consumption and distal gastric cancer was observed among women. More prospective studies with detailed information are needed to confirm the role of green tea in the occurrence of gastric cancer.

Demographics, lifestyles, health characteristics, and dietary intake among dietary supplement users in Japan.

BACKGROUND: The associations between supplement use and certain demographics, lifestyles, health characteristics, and dietary intakes have not been studied in a large population in non-Western societies. The objective of our study was to investigate the association between supplement use and demographics, lifestyles, health characteristics, and dietary intake in a population-based cohort study in Japan. METHODS: Subjects were the 78 531 participants (45-74 years) who completed a self-administered questionnaire in 1995 or 1998 in a 5-year follow-up survey by the Japan Public Health Center-based prospective Study on cancer and cardiovascular disease. The questionnaire included enquiries about supplement use, occupation, height, weight, smoking, alcohol, physical activity, dietary behaviours, working hours, subjective stress, as well as intakes for 138 foods. RESULTS: The supplement users were likely to have formerly smoked or never smoked. Female supplement users were likely to consume alcohol moderately. The prevalence of users was higher in the elderly, the self-employed, those with lower body mass index, greater physical activity, lower frequency of eating prepared food, higher frequency of eating out, and higher stress level in both sexes after mutual adjustment. Mean intakes of energy and nutrients were lower for users than for non-users. CONCLUSION: The demographics, lifestyles, health characteristics, and dietary intakes may need to be adjusted when evaluating the effect of dietary supplements on disease because they can become potential confounding factors.

Randomized trial of adjuvant chemotherapy with mitomycin, Fluorouracil, and Cytosine arabinoside followed by oral Fluorouracil in serosa-negative gastric cancer: Japan Clinical Oncology Group 9206-1.

PURPOSE: To evaluate the survival benefit of adjuvant chemotherapy after curative resection in serosa-negative gastric cancer patients (excluding patients who were T1N0), we conducted a multicenter phase III clinical trial in which 13 cancer centers in Japan participated. PATIENTS AND METHODS: From January 1993 to December 1994, 252 patients were enrolled into the study and allocated randomly to adjuvant chemotherapy or surgery alone. The chemotherapy comprised intravenous mitomycin 1.33 mg/m2, fluorouracil (FU) 166.7 mg/m2, and cytarabine 13.3 mg/m2 twice weekly for the first 3 weeks after surgery, and oral FU 134 mg/m2 daily for the next 18 months for a total dose of 67 g/m2. The primary end point was relapse-free survival. Overall survival and the site of recurrence were secondary end points. RESULTS: Ninety-eight percent of patients underwent gastrectomy with D2 or greater lymph node dissection. There were no treatment-related deaths and few serious adverse events. There was no significant difference in relapse-free and overall survival between the arms (5-year relapse-free survival 88.8% chemotherapy v 83.7% surgery alone; P =.14 and 5-year survival 91.2% chemotherapy v 86.1% surgery alone; P =.13, respectively). Nine patients (7.1%) in the chemotherapy arm and 17 patients (13.8%) in the surgery-alone arm had cancer recurrence. CONCLUSION: There was no statistically significant relapse-free or overall survival benefit with this adjuvant chemotherapy for patients with macroscopically serosa-negative gastric cancer after curative resection, and there was no statistical difference between the two arms relating to the types of cancer recurrence. We do not recommend adjuvant chemotherapy with this regimen for this population in clinical practice.