Search

Objective: Breast cancer is the most common type of cancer in women worldwide. Although the incidence of breast cancer is still on an increasing trend, there are few studies concerning breast cancer risk factors in Japan. Therefore, we conducted an Internet survey investigating the prevalence of risk factors for breast cancer. Methods: We conducted an Internet survey using opt-in panels in women aged from 20 to 70 years. The survey items consisted of potential and proven risk factors for breast cancer such as age at menarche, menopausal status, premenopausal use of oral contraceptives, postmenopausal use of hormones, parity, height, alcohol consumption and family history of breast cancer. Results: Subjects comprised 2002 persons who were matched for sex, age and residential area with the National Census in 2005. Statistically significant trends were observed for most factors: age at menarche is becoming lower, age at first birth is higher, height is higher, the proportion of women who have given birth is smaller and the proportion of women who drink alcohol is larger. Conclusions: We showed a clear increase in the prevalence of risk factors for breast cancer. Based on the results, the incidence of breast cancer in Japan may be increasing for at least a few decades.

The aim of this study was to evaluate the short-term surgical outcomes of laparoscopic abdominoperineal resection (APR) for rectal cancer, by comparing it with a case-control series of open APR.Fourteen patients with rectal cancer who underwent laparoscopic APR between August 2004 and November 2011 were compared with the open APR group of 14 patients matched for age, gender, and surgical procedure.There were no cases of conversion to laparotomy in the laparoscopic APR group and no mortality in either of the groups. The median operation was longer (P = 0.002), but the median amount of blood loss was smaller (P = 0.019), in the laparoscopic APR group. The median length of hospital stay of the laparoscopic APR group was 8 days, shorter than that of the open APR group (16 days, P0.001). The changes of the WBC count and serum CRP level after operations were significantly smaller in the laparoscopic APR group (P0.05). There were no significant differences between the groups in terms of the perioperative morbidity and readmission rates within 30 days.Patients undergoing laparoscopic APR had superior perioperative outcomes to those undergoing open APR, except for the longer operation.

BACKGROUND/AIMS We examined the clinicopathological characteristics of rectal cancer patients with lateral pelvic lymph node (LPLN) metastasis in order to clarify their associated prognostic factors. METHODOLOGY A total of 91 rectal cancer patients with LPLN metastasis who underwent curative resection at the National Cancer Center Hospital between 1985 and 2004 were reviewed. RESULTS The five-year overall survival rate and disease-free survival rate of the studied patient were 39% and 27%, respectively. Univariate analysis showed that tumor differentiation, lymphatic invasion, venous invasion, mesenteric lymph node status and LPLN status were significant prognostic factors. Multivariate analysis showed that tumor differentiation, mesenteric lymph node status and LPLN status were significant prognostic factors. Among 15 patients with LPLN metastasis and without mesenteric lymph node metastasis, 11 patients (73.3%) with one or two LPLN metastases survived more than five years. Among 12 patients with four or more LPLN metastases, two(16.7%) survived more than five years. CONCLUSIONS Tumor differentiation, mesenteric lymph node status and LPLN status are significant prognostic factors of patients with LPLN metastasis. Because some patients with LPLN metastasis survive for a long period, LPLN dissection should be considered for them.

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.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/m(2), i.v., day 8). Primary endpoints were completion of protocol treatment and incidence of treatment-related death (TRD).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.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.

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.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 (P0.001).Mucinous adenocarcinoma represents a distinct clinicopathological entity. Sex, bowel obstruction and growth patterns might be useful prognostic factors to identify patients with a high risk of recurrence after curative resection of advanced MUCs.

This study examined both the frequency of appearance-related symptoms and distress resulting from these symptoms in cancer patients receiving chemotherapy.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.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.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.

Background Fertility is one of the key aspects of quality of life for breast cancer patients of childbearing age. The objective of this study was to describe fertility-related practice for young breast cancer patients in Japan and to identify healthcare provider factors that contribute to physicians’ behavior towards fertility preservation. Methods A cross-sectional survey was developed in order for Japanese breast cancer specialists (n = 843) to self-evaluate their knowledge, attitude, and behavior regarding fertility preservation. Survey items included questions regarding knowledge of and attitude toward fertility issues in cancer patients, fertility-related practice, potential barriers for the discussion of fertility with patients, and responding physicians’ socio-demographic background. Results Four hundred and thirty-four (52%) breast oncologists responded to the survey. Female and younger oncologists (age less than 50 years) had significantly higher probability of referring patients to reproductive specialists. Physicians who had better knowledge score and positive attitudes toward fertility preservation were more likely to discuss potential fertility issues with cancer patients. This was significantly associated with consultation and referral to reproduction specialists when encountering fertility issues with cancer patients. Risk of recurrence, lack of collaborating reproductive specialists, and time constraints in the clinic were identified as major barriers to discussion of fertility preservation with breast cancer patients. Conclusion Female and younger physicians as well as physicians working in a multidisciplinary environment had positive attitudes and behavior towards fertility preservation in breast cancer patients. The development of comprehensive and interdisciplinary programs for healthcare providers is necessary to meet the expectations and fertility needs of breast cancer patients.

In cancer screening, it is essential to undertake effective screening with appropriate methodology, which should be supported by evidence of a reduced mortality rate. At present, mammography is the only method for breast cancer screening with such evidence. However, mammography does not achieve sufficient accuracy in breasts with high density at ages below 50. Although ultrasonography achieves better accuracy in Breast Cancer detection even in dense breasts, the effectiveness has not been verified. We have planned a randomized controlled trial to assess the effectiveness of ultrasonography in women aged 40–49, with a design to study 50 000 women with mammography and ultrasonography (intervention group), and 50 000 controls with mammography only (control group). The participants are scheduled to take second round screening with the same modality 2 years on. The primary endpoints are sensitivity and specificity, and the secondary endpoint is the rate of advanced breast cancers.

To reduce the colorectal cancer (CRC) mortality rate, we have reported several CRC screening methods using colonocytes isolated from feces. Expression analysis of oncogenic microRNA (miRNA) in peripheral blood was recently reported for CRC detection. In the present study, we conducted miRNA expression analysis of exfoliated colonocytes isolated from feces for CRC screening. Two hundred six CRC patients and 134 healthy volunteers were enrolled in the study. miRNA expression of the miR-17-92 cluster, miR-21, and miR-135 in colonocytes isolated from feces as well as frozen tissues was analyzed by quantitative real-time PCR. The expression of the miR-17-92 cluster, miR-21, and miR-135 was significantly higher in CRC tissues compared with normal tissues. The exfoliated colonocytes of 197 CRC patients and 119 healthy volunteers were analyzed because of the presence of sufficient miRNA concentration. miR-21 expression did not differ significantly between CRC patients and healthy volunteers (P = 0.6). The expression of miR-17-92 cluster and miR-135 was significantly higher in CRC patients than in healthy volunteers (P < 0.0001). The overall sensitivity and specificity by using miRNA expression was 74.1% (146/197; 95% confidence interval, 67.4-80.1) and 79.0% (94/119; 95% confidence interval, 70.6-85.9), respectively. Sensitivity was dependent only on tumor location (P = 0.0001). miRNA was relatively well conserved in exfoliated colonocytes from feces both of CRC patients and healthy volunteers. miRNA expression analysis of the isolated colonocytes may be a useful method for CRC screening. Furthermore, oncogenic miRNA highly expressed in CRC should be investigated for CRC screening tests in the future. Cancer Prev Res; 3(11); 1435–42. ©2010 AACR.

Purpose To identify polymorphisms in DNA repair genes that affect responses to platinum-based doublet chemotherapy in patients with non–small-cell lung cancer (NSCLC). Patients and Methods In total, 640 patients with NSCLC who received platinum-based doublet chemotherapy in the National Cancer Center Hospital in Japan from 2000 to 2008 and whose responses were evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) participated in a study of the association between response and genotypes for 30 single nucleotide polymorphisms (SNPs) in 27 DNA repair genes. Candidate SNPs were selected in a discovery set of 201 patients, and their associations were validated in an independent set of 439 patients by prespecified P value criteria. Results Homozygotes for the minor allele TP53-72Pro of the Arg72Pro SNP in the TP53 gene showed a better response rate (54.3%) than those for the major allele TP53-72Arg (29.1%; P = 4.4 × 10−5) irrespective of therapeutic regimens, and minor allele homozygotes had significantly longer progression-free and overall survivals than major allele homozygotes (hazard ratio [HR], 0.85; 95% CI, 0.74 to 0.98; P = .020; and HR, 0.86; 95% CI, 0.74 to 0.99; P = .039). Minor allele carriers for SNP Lys940Arg in the poly (ADP-ribose) polymerase 1 (PARP1) gene showed a better response rate to the paclitaxel regimen (45.8%) than to the gemcitabine regimen (10.5%; P for interaction = .019). Conclusion Polymorphisms in the TP53 and PARP1 genes are involved in inter-individual differences in the response to platinum-based doublet chemotherapy in patients with NSCLC.

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. 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. 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). 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.

Estrogen has been indicated to play an etiological role in the development of lung adenocarcinoma (ADC), particularly bronchioloalveolar carcinoma (BAC), a type of ADC that develops from a benign adenomatous lesion, atypical adenomatous hyperplasia (AAH). Polymorphisms in the CYP19A1 gene cause interindividual differences in estrogen levels. Here, 13 CYP19A1 single-nucleotide polymorphisms (SNPs) were examined for associations with lung AAH risk. AAH is detected as ground-glass opacity (GGO) by computed tomography (CT) examination, and this study consisted of 100 individuals diagnosed with GGO in their lungs among 3088 CT-based cancer screening examinees and 424 without. Minor allele carriers for the rs3764221 SNP showed an elevated risk for GGO [odds ratio (OR) = 1.72, P = 0.017]. Associations of this SNP with risks for lung AAH and BAC in the lungs were next examined using 359 ADC cases whose resected lung lobes were subjected to a histological examination for AAH accompaniment and the presence of BAC components and 330 controls without cancer. The ORs were also increased for lung ADC accompanied by AAH (OR = 1.74, P = 0.029) as well as lung ADC with BAC components (OR = 1.41, P = 0.091). The minor allele was associated with an increased circulating estradiol level (P = 0.079) in a population of 363 postmenopausal women without cancer. These results indicate that CYP19A1 polymorphisms are involved in the risk for lung AAH and BAC in the lungs by causing differences in estrogen levels.

Background The high frequency of local recurrence occurring after endoscopic piecemeal resection (EPMR) for large colorectal tumors is a serious problem. However, almost all of these cases of local recurrence can be detected within 1 year and cured by additional endoscopic resection. We report a rare case of recurrent advanced colonic cancer diagnosed 11 years after initial EPMR treatment. Case presentation A 65-year-old male was diagnosed with a sigmoid colon lesion following a routine health check-up. Total colonoscopy revealed a 12 mm type 0-Is lesion in the sigmoid colon, which was diagnosed as an adenoma or intramucosal cancer and treated by EPMR in 1996. The post-resection defect was closed completely using metallic endoclips to avoid delayed bleeding. In 2007, at the third follow up, colonoscopy revealed a 20 mm submucosal tumor (SMT) like recurrence at the site of the previous EPMR. The recurrent lesion was treated by laparoscopic assisted sigmoidectomy with lymph node dissection. Conclusion When it is difficult to evaluate the depth and margins of resected tumors following EPMR, it is important that the defect is not closed in order to avoid tumor implantation, missing residual lesions and to enable earlier detection of recurrence. It is crucial that the optimal follow-up protocol for EPMR cases is clarified, particularly how often and for how long they should be followed.

This prospective study used antibody suspension bead arrays to identify biomarkers capable of predicting post-operative recurrence with distal metastasis in patients with colorectal cancer. One hundred colorectal cancer patients who underwent surgery were enrolled in this study. The median follow-up period was 3.9 years. The pre-operative plasma concentrations of 24 angiogenesis-related molecules were analyzed with regard to the TNM stage and the development of post-operative recurrence. The concentrations of half of the examined molecules (13/24) increased significantly according to the TNM stage (P < 0.05). Meanwhile, a multivariate logistic regression analysis revealed that the concentrations of vascular cell adhesion molecule 1 (VCAM-1) and plasminogen activator inhibitor-1 (PAI-1) were significantly higher in the post-operative recurrence group. The VCAM-1 and PAI-1 model discriminated post-operative recurrence with an area under the curve of 0.82, a sensitivity of 0.75, and a specificity of 0.73. A leave-one-out cross-validation was applied to the model to assess the prediction performance, and the result indicated that the cross-validated error rate was 12.5% (12/96). In conclusion, our results demonstrate that antibody suspension bead arrays are a powerful tool to screen biomarkers in the clinical setting, and the plasma levels of VCAM-1 and PAI-1 together may be a promising biomarker for predicting post-operative recurrence in patients with colorectal cancer.

Background: Young age at onset of smoking is a known risk factor for cancer; however, few studies have investigated the risk of cancer associated with onset of smoking during adolescence in Japan.Methods: We analyzed a portion of the data from a population-based cohort of 40 897 subjects aged 40 to 69 years with a history of smoking and no history of cancer at baseline.Results: During a 14-year follow-up period, 4386 total cancers and 681 lung cancers were newly diagnosed. As compared with smokers who started smoking after the age of 20 years, those who started before the age of 17 years smoked a significantly larger number of cigarettes per day for a significantly longer duration; they also had a significantly higher risk of lung cancer. The hazard ratios in men and women were 1.48 (95% confidence interval, 1.11–1.96) and 8.07 (2.34–27.85), respectively. After further adjustment for smoking amount, the associations remained significant. There was a statistically significant inverse correlation between lung cancer risk and age at onset of smoking in male current smokers whose baseline age was 50 to 59 years; no such association was detected among other age strata.Conclusions: There was no clear evidence of increased risk of cancer due to adolescent smoking. However, adolescent smoking appeared to indirectly increase lung cancer risk because it was associated with a longer duration and larger amount of smoking.

Adenocarcinoma (ADC) is the commonest histological type of lung cancer, and its weak association with smoking indicates the necessity to identify high-risk individuals for targeted screening and/or prevention. By a genome-wide association study (GWAS), we identified an association of polymorphisms in the 6p21.31 locus containing four human leukocyte antigen (HLA) class II genes with lung ADC risk. DQA1 � 03 of the HLA-DQA1 gene was defined as a risk allele with odds ratio (OR) of 1.36 [95% confidence interval (CI) 5 1.21‐1.54, P 5 5.3 3 10 27 ] by analysis of 1656 ADC cases and 1173 controls. DQA1 � 03 and the minor allele for a polymorphism, rs2736100, in TERT, another lung cancer susceptibility locus identified in recent GWASs on Europeans and Americans, were indicated to independently contribute to ADC risk with per allele OR of 1.43 (95% CI 5 1.31‐1.56, P 5 7.8 3 10216). Individuals homozygous both for the DQA1 � 03 and minor TERTalleles were defined as high-risk individuals with an OR of 4.76 (95% CI 5 2.53‐9.47, P 5 4.2 3 1027). The present results indicated that individuals susceptible to lung ADC can be defined by combined genotypes of HLA-DQA1 and TERT.

Background: The strength of the association between brain tumors in children and residential power-frequency magnetic fields (MF) has varied in previous studies, which may be due in part to possible misclassification of MF exposure. This study aimed to examine this association in Japan by improving measurement techniques, and by extending measurement to a whole week.Methods: This population-based case-control study encompassed 54% of Japanese children under 15 years of age. After excluding ineligible targeted children, 55 newly diagnosed brain tumor cases and 99 sex-, age-, and residential area-matched controls were included in the analyses. The MF exposures of each set of matching cases and controls were measured in close temporal proximity to control for seasonal variation; the average difference was 12.4 days. The mean interval between diagnosis and MF measurements was 1.1 years. The weekly mean MF level was defined as the exposure. The association was evaluated using conditional logistic regression analysis that controlled for possible confounding factors.Results: The odds ratios (95% CI) for exposure categories of 0.1 to 0.2, 0.2 to 0.4, and above 0.4 µT, against a reference category of

Background Locally advanced gastric cancer with extensive lymph node metastasis is usually considered unresectable and so treated by chemotherapy. This trial explored the safety and efficacy of preoperative chemotherapy followed by extended surgery in the management of locally advanced gastric adenocarcinoma. Methods Patients with gastric cancer with extensive lymph node metastasis received two or three 28-day cycles of induction chemotherapy with irinotecan (70 mg/m2 on days 1 and 15) and cisplatin (80 mg/m2 on day 1), and then underwent gastrectomy with curative intent with D2 plus para-aortic lymphadenectomy. Primary endpoints were 3-year overall survival and incidence of treatment-related death. Results The study was terminated because of three treatment-related deaths when 55 patients had been enrolled (mortality rate above 5 per cent). Two deaths were due to myelosuppression and one to postoperative complications. Clinical response and R0 resection rates were 55 and 65 per cent respectively. The pathological response rate was 15 per cent. Median overall survival was 14·6 months and the 3-year survival rate 27 per cent. Conclusion This multimodal treatment of locally advanced gastric cancer provides reasonable 3-year survival compared with historical data, but at a considerable cost in terms of morbidity and mortality.

The prognosis of unresectable hepatic colorectal metastases is poor even if chemotherapy is administered. The purpose of this study was to evaluate the long-term efficacy of hepatic arterial infusion (HAI) chemotherapy and hepatectomy following HAI for such condition.Seventy-two patients with unresectable hepatic colorectal metastases received continuous HAI of 5-fluorouracil.The overall response rate was 38%. The median survival of all patients was 18 months. The overall 3-year survival rate was 18%. Seven patients (10%) survived more than 58 months. Of the eight patients with a complete response, seven developed liver and/or lung metastases, and of these, one patient undergoing additional hepatectomy has been disease-free and the other six receiving chemotherapy died of disease. Another complete-response case died of liver abscess. Of the 19 patients with a partial response, six could undergo hepatectomy after HAI. The overall 5-year survival rate of seven patients undergoing hepatectomy was 71%, whereas for patients without hepatectomy, the rate was 0%.Most patients showing response after HAI for unresectable hepatic colorectal metastases had relapses. The long-term prognosis of patients undergoing hepatectomy after HAI was favorable. Therefore, when HAI makes liver metastases resectable, they should be resected.

To clarify the risk factors of lateral pelvic lymph node (LPLN) metastasis of rectal cancer, we examined associations between LPLN status and clinicopathological factors including LPLN status diagnosed by computed tomography (CT). We reviewed a total of 210 patients with advanced rectal cancer, of which the lower margin was located at or below the peritoneal reflection, who underwent preoperative CT with 5-mm-thick sections and lateral pelvic lymph node dissection at the National Cancer Center Hospital between February 1998 and March 2006. Forty-seven patients (22.4%) had LPLN metastasis. Multivariate analysis showed that LPLN status diagnosed by CT, pathological regional lymph node status, tumor location, and tumor differentiation were significant risk factors for LPLN metastasis. Among 45 patients with well-differentiated adenocarcinoma who were LPLN-negative and in whom CT had found no regional lymph node metastasis, none had LPLN metastasis. On the other hand, among 13 patients with moderate or less differentiated lower rectal adenocarcinoma who were LPLN-positive and in whom CT had revealed regional lymph node metastasis, 12 (92.3%) had LPLN metastasis. LPLN status diagnosed by CT, pathological regional LN status, tumor location, and tumor differentiation are significant risk factors for LPLN metastasis. Using these factors, patients can be classified as having a low or high risk of LPLN metastasis.

Endometriosis of the appendix is rare, and we present a case of endometriosis of the appendix with adhesion to right ovarian cyst presenting as intussusception of a mucocele of the appendix in a 35-year-old woman with no associated sign of endometriosis. Colonoscopy revealed intussusception-like change and mucosal defect in the mucosa at the orifice of the appendix. Abdominal computed tomography showed a low-density lesion, which seemed to be right ovarian cyst. However, as the appendix was located near this site, differentiation between ovarian cyst and mucocele of the appendix was difficult. Laparoscopic examination disclosed blue berry spots on the Douglas cul-de-sac and right ovarian cyst, and the appendix was atrophied and hardened and tightly adhered to the right ovary. Laparoscopic appendectomy and partial cecectomy was performed, and on pathologic examination, thickening and fibrosis of the muscle layer owing to endometriosis were judged to have caused intussusception-like changes.

Background: We reported on a novel diagnostic method for colorectal cancer (CRC) using a DNA-based analysis of isolated colonocytes from feces. The aim of the present study was to investigate with real-time PCR and direct sequencing analysis whether the cancer cells could be detected in feces stored under different conditions after evacuation. Methods: Feces were collected from patients with CRC. Feces were divided into 21 pieces and each piece was manipulated at time after arrival (zero time) and after storage of 24, 48 and 72 h at 4 or 378C. Colonocytes were isolated from each separate fecal sample, and DNA and RNA were extracted from the colonocytes. We investigated the relationship between storage conditions and content of extracted DNA or RNA with real-time PCR. We also clarified the gene alterations regarding APC and p53 genes under different storage conditions with direct sequence analysis. Results: Though the amount of genomic DNA and total RNA recovered from colonocytes isolated from each fecal piece decreased significantly at 378C at any storage time compared with 0 h, the gene alterations were detected independent of any storage conditions. Conclusions: The colonocytes recovery rate from feces was unchanging for 3 days as long as the feces were kept at 48C. However, the identical point mutation to one obtained in cancer tissue was detected in the corresponding exfoliated colonocytes even after storage for 72 h at 378C, which suggests that exfoliated CRC cells maintain their configuration in feces at least 3 days after evacuation.

The purpose of this study was to evaluate whether implementation of a clinical pathway (CP) reduces length of stay after laparoscopic surgery for colorectal carcinoma.We retrospectively reviewed 330 patients with colorectal carcinoma who underwent laparoscopic surgery between 2002 and 2006. The patients were divided into 2 groups: no clinical pathway patients in 2002-03 (Group A) and those managed with clinical pathway in 2004-06 (Group B). Patients in Group B were planned to be discharged and return home within postoperative day 8, with use of CP.There was no mortality in either group. In Group B, the rate of patients who started solid food within postoperative day 3 was significantly higher than in Group A for both colon carcinoma (96.7 vs. 82.8%, p = 0.001) and rectal carcinoma (94.2 vs. 65.5%, p = 0.001). The rate of patients discharged within postoperative day 8 was significantly higher in Group B than in Group A (98.5 vs. 64.8%, p = 0.001), although there were more advanced cases in Group B.The implementation of clinical pathway has led to the standardization of patient care and considerable decrease in length of stay after laparoscopic surgery for colorectal carcinoma.

Purpose This study evaluated whether the presence of epidermal growth factor receptor (EGFR) mutations is a predictive marker for survival benefit from gefitinib and/or a prognostic marker in patients with advanced lung adenocarcinoma. Patients and Methods Overall survival (OS) was compared between patients with advanced lung adenocarcinoma who began first-line systemic therapy before and after gefitinib approval in Japan (January 1999 to July 2001 and July 2002 to December 2004, respectively). Deletional mutations in exon 19 or the L858R mutation in exon 21 of EGFR were evaluated using high-resolution melting analysis. Results EGFR mutations were detected in 136 (41%) of the 330 patients included in this study. OS was significantly longer among the EGFR-mutant patients treated after gefitinib approval compared with the OS of patients treated before gefitinib approval (median survival time [MST], 27.2 v 13.6 months, respectively; P < .001), whereas no significant survival improvement was observed in patients without EGFR mutations (MST, 13.2 v 10.4 months, respectively; P = .13). A significant interaction between the presence of EGFR mutations and a survival improvement was seen (P = .045). Among patients treated before gefitinib approval, those with EGFR mutations lived longer than those without EGFR mutations (MST, 13.6 v 10.4 months, respectively; P = .034). The response rates to first-line cytotoxic chemotherapy were not significantly different between patients with and without EGFR mutations (31% v 28%, respectively; P = .50). Conclusion EGFR mutations significantly predict both a survival benefit from gefitinib and a favorable prognosis in patients with advanced lung adenocarcinoma.

Early detection of colorectal cancer (CRC) is desired for reducing its mortality rate. Recently, the feasibility of a new method for isolating colonocytes from feces was demonstrated, followed by direct sequencing analysis for detecting colorectal cancer. In the present study, gene expression analysis was conducted using quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). One hundred and sixty-six patients with CRC and 134 healthy volunteers were enrolled. Messenger RNA expressions of CEA, MMP7, MYBL2, PTGS2 and TP53 in the colonocytes isolated from feces were analyzed by quantitative real-time RT-PCR. Beta-2-microglobulin, used for internal control, could not be detected in approximately 25% each of the CRC patients (39/166) and healthy volunteers (33/134). CEA expression did not differ significantly between CRC patients and healthy volunteers (P = 0.21). MMP7, MYBL2, PTGS2 and TP53 gene expressions were significantly higher in CRC patients than in healthy volunteers (P < 0.001). The overall sensitivity and specificity using these gene expressions were 58.3% (74/127, 95% CI; 49.2-67.0) and 88.1% (89/101, 95% CI; 80.2-93.7), respectively. The sensitivity was dependent on the tumor location (P = 0.01) and tumor size (P = 0.02), but not the tumor depth (P = 0.06) or cancer stage (P = 0.37). Gene expression analysis of colonocytes isolated from feces may be a useful method for CRC screening, if the number of isolated colonocytes is sufficiently high for analysis by quantitative real-time PCR. Therefore, improvement of the colonocyte retrieval system from feces may be necessary for the technique to be developed for clinical use.

Purpose: Epidermal growth factor receptor (EGFR) mutations, especially in-frame deletions in exon 19 (DEL) and a point mutation in exon 21 (L858R), predict gefitinib sensitivity in patients with non–small cell lung cancer (NSCLC). In this study, we verified the accuracy of EGFR mutation analysis in small samples by high-resolution melting analysis (HRMA), which is a rapid method using PCR amplification with a dye to analyze the melting curves in NSCLC. Experimental Design: We designed a prospective study to compare the sensitivity and specificity of HRMA and DNA sequencing with laser capture microdissection. Eligible patients with lung lesions were screened by bronchoscopy or percutaneous needle biopsy to histologically confirm the diagnosis, followed by surgical resection of the NSCLC. Small diagnostic specimens were analyzed for EGFR mutations by HRMA, and the surgically resected specimens were examined for mutations by HRMA and DNA sequencing. Results: The analyses for EGFR mutations were conducted in 52 eligible cases of the 92 enrolled patients. EGFR mutations were detected in 18 (34.6%) patients. The results of HRMA from surgically resected specimens as well as DNA sequencing revealed 100% sensitivity and specificity. On the other hand, the sensitivity and specificity of HRMA from the small diagnostic specimens were 83.3% and 100%, respectively. Conclusions: In this study, we showed that HRMA is a highly accurate method for detecting DEL and L858R mutations in patients with NSCLC, although it is necessary to consider the identification of patients with a false-negative result when the analysis is conducted using small samples.

Recently reported randomized controlled trials demonstrated that laparoscopic surgery (LS) was comparable or superior to open surgery with regard to the long-term outcome for colon and rectosigmoidal carcinoma; however, controversy persists with regard to the appropriateness of LS for patients with rectal carcinoma. To examine the technical and oncological feasibility of LS for rectal carcinoma, a phase II trial was started in patients with a preoperative diagnosis of Stage 0/I rectal carcinoma, under the direction of the Japan Society of Laparoscopic Colorectal Surgery. Surgeons in 39 specialized institutions will recruit 350 patients. The primary end-point in the first stage is the anastomotic leakage rate by double-stapling technique and that in the second stage is overall survival. Secondary end-points are relapse-free survival, short-term clinical outcome, adverse events, the rate of histologically curative operation, the proportion of completion of LS and the conversion rate.

Objective: As prognosis of advanced gastric cancer is still poor, a standard regimen after firstline fluorouracil (FU)-based chemotherapy has not yet been established. Therefore, we conducted a phase II study to evaluate the efficacy and toxicity of sequential treatment with methotrexate (MTX) and also 5-FU as second-line chemotherapy in patients with advanced gastric cancer. Methods: Treatment consisted of weekly doses of MTX (100 mg/m 2 , i.v. bolus), followed by 5-FU (600 mg/m 2 , i.v. bolus) 3 h after MTX administration. Leucovorin rescue therapy (six doses of 10 mg/m 2 , given at 6-h intervals) was commenced 24 h after a treatment with MTX. The primary endpoint was the response rate. Results: Between December 1992 and June 1995, 56 patients were registered in this study and one was ineligible. All registered patients were included in all analyses. The median age of the patients was 60 years (20‐75 years). Most patients (75%) had a performance status of 0 or 1, and 51 (90%) received 5-FU-based chemotherapy as first-line treatment. The major adverse events were myelosuppression and gastrointestinal toxicity. Grade 4 neutropenia occurred in 6.3% of the patients. The overall objective response rate was 9.0% [five partial responses among 56 patients, 95% confidence interval (CI): 3.0‐20%]. The median overall survival time was 237 days, and the 1-year survival proportion was 21.4%. Conclusions: Sequential MTX/5-FU therapy provides good survival outcomes with tolerable toxicity despite a limited response in patients with previously treated advanced gastric cancer. This regimen is now being evaluated in a randomized study in patients with pretreated advanced gastric cancer, by the Japan Clinical Oncology Group.

Establishment of a sensitive, reliable and non-invasive method for the diagnosis of early-stage colorectal cancer is necessary, because colorectal cancer can be cured surgically if diagnosed early. The aim of the present study was to evaluate the feasibility of using PCR-SSCP (polymerase chain reaction-single strand conformation polymorphism) analysis of the DNA extracted from the colonocytes isolated from naturally evacuated feces, in order to detect colorectal cancer.Colonocytes exfoliated into feces, retrieved from 33 patients with colorectal cancer and 63 healthy volunteers, were analyzed for the presence of mutations in their DNA. The DNA extracted from the colonocytes was examined for mutations of the APC, K-ras and p53 genes using direct sequence analysis, and also subjected to PCR-SSCP analysis.Genetic alterations were detected in the colonocytes isolated from the feces of 12 out of 33 patients with colorectal cancer (36.4%) by direct sequence analysis. PCR-SSCP analysis using the same DNA samples revealed abnormal signals in 18 of the 33 patients (54.5%). However, 3 and 7 among the 63 healthy volunteers were also found to have abnormal genetic alterations by direct sequence and PCR-SSCP analysis, respectively.The present study indicated the feasibility of using PCR-SSCP analysis for the detection of mutations in the DNA extracted from colonocytes isolated from naturally evacuated fecal samples.

PurposeBecause they have large variations in consumption, Asian countries are suitable settings for studies of the effect of relatively high-dose isoflavone intake on breast cancer risk. Nevertheless, no prospective study from Asia has assessed blood or urine levels as biomarkers of isoflavone intake.Patients and MethodsA total of 24,226 women ages 40 to 69 years in the Japan Public Health Center–based prospective study who responded to the baseline questionnaire and provided blood in 1990 to 1995 were observed to December 2002. During a mean 10.6 years of follow-up, 144 patients newly diagnosed with breast cancer were identified. Two matched controls for each patient were selected from the cohort. Isoflavone levels were assessed by plasma level and food frequency questionnaire, and the odds ratio of breast cancer according to isoflavone level was estimated using a conditional logistic regression model.ResultsWe found a statistically significant inverse association between plasma genistein and risk of breast cancer, but no association for plasma daidzein. Adjusted odds ratios for the highest versus lowest quartile of plasma level were 0.34 for genistein (95% CI, 0.16 to 0.74; P for trend, .02) and 0.71 for daidzein (95% CI, 0.35 to 1.44; P for trend, .54). Median plasma genistein values in the control group were 31.9 ng/mL for the lowest and 353.9 ng/mL for the highest quartile groups. Regarding dietary intake of isoflavones, nonsignificant inverse associations were observed for both genistein and daidzein.ConclusionThis nested case-control study found an inverse association between plasma genistein and the risk of breast cancer in Japan.

The pulmonary adenoma susceptibility 1 (Pas1) gene affects susceptibility to the development of lung adenomas in mice with a subset of the adenomas progressing to adenocarcinoma (ADC). In this study, genotype distributions for 10 polymorphisms in the human counterparts for three mouse candidate Pas1 genes, KRAS, CASC1/LAS1 and LRMP, were examined in a hospital-based case-control study consisting of 364 lung ADC cases and 253 controls. All the ADC cases were subjected to lobectomy and subsequent pathological investigation of atypical adenomatous hyperplasia (AAH), a putative precursor for peripheral lung ADC, including bronchioloalveolar carcinoma, in the resected lobes. Eighty-one (22%) of the ADC cases carried at least one AAH lesion in addition to the primary ADC and 34 (9%) of them carried multiple AAH lesions. None of the 10 polymorphisms examined showed significant associations with overall lung ADC risk (P > 0.05). However, minor allele carriers for two polymorphisms in the KRAS gene, KRAS-1 and -6, showed significantly increased odds ratios (ORs) for ADC accompanied by multiple AAHs [OR = 3.0; 95% confidence interval (CI) = 1.4-6.2, P = 0.004 and OR = 2.4; 95% CI = 1.1-4.7, P = 0.02, respectively]. Minor haplotypes including the minor allele for the KRAS-6 polymorphism showed increased ORs for ADC accompanied by multiple AAHs, and KRAS transcripts from the minor allele for this polymorphism were more abundantly detected in lung tissues than those from the major allele. Thus, KRAS polymorphisms were indicated to be involved in risk for the development of AAHs that progress to ADC by causing differential KRAS oncogene expression in the lungs.

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. Financial Disclosure(s) The authors have no proprietary or commercial interest in any materials discussed in this article.

CD10 mRNA expression in colorectal cancer and its relationship with cancer progression and prognosis were investigated.CD10 mRNA was quantified in 167 colorectal cancer and matched normal tissue samples using real-time polymerase chain reaction (RT-PCR). The tumor to normal tissue (TIN) CD10 mRNA ratio was compared with clinicopathological factors and prognosis.CD10 mRNA was overexpressed in 138 of the 167 tumors in comparison with the matched normal tissues. TIN was higher in colon, pN1/pN2, stage III and IV, and well- or moderately-differentiated adenocarcinoma than in rectum, pNO, stage I and II, and poorly-differentiated or mucinous adenocarcinoma, respectively. However, these differences were not significant. TIN was not associated with prognosis.CD10 mRNA showed significantly higher expression in tumor tissues than in matched normal tissues. Although CD10 mRNA was associated with invasion depth, lymph node status and TNM stage, it was not associated with prognosis.

Background: No risk factor has been confirmed for para-aortic lymph node (PAN) metastasis from gastric cancer. To identify the risk factors and the most frequent route of metastasis to PAN, we analyzed the prospective data from a phase III trial. Methods: In JCOG9501 comparing D2 and D2 þ PAN dissection, 260 patients with T2(SS)T4 gastric cancer underwent radical gastrectomy with PAN dissection. The association between various clinicopathological factors and PAN metastasis was examined. Results: Macroscopic N stage and tumor size � 5 cm were significant risk factors for PAN metastasis after adjusting for other factors. The proportion of PAN metastasis was clearly different between the N0‐1 group and the N2‐4 group (2.8% versus 20.5%). In the additional multivariate analysis including 17 regional lymph node stations, station No. 7 was the only station with statistical significance (P ¼ 0.002, odds ratio ¼ 41.0). Conclusion: Macroscopic N stage and tumor size were associated with PAN metastasis, and the lymphatics along the left gastric artery seemed to be the most frequent route to the nodes surrounding the aorta. These findings may be useful in predicting PAN metastasis.

The aim of this study was to investigate whether the wound infection (WI) rate in laparoscopic surgery (LS) for colorectal cancer is lower than that in open surgery (OS), and to evaluate the influence of perioperative intravenous antibiotic prophylaxis on the development of WI in LS.We performed a meta-analysis study comparing the WI rate in patients who underwent either OS or LS in randomized controlled trials (RCTs), with a relatively large number of registered patients. Moreover, a subgroup analysis of recently reported RCTs from Japan was performed, and 290 consecutive patients who underwent LS for colorectal cancer at our institution were evaluated for the influence of perioperative intravenous antibiotic prophylaxis on the development of WI.The WI rate of the LS group was significantly lower than that of the OS group in a meta-analysis; however, no positive effect of the intra-and postoperative antibiotic prophylaxis on the development of WI was demonstrated.Laparoscopic surgery for colorectal cancer is considered a surgical technique that has a lower incidence of WI in comparison to OS. Well-designed prospective, randomized controlled trials should therefore be conducted to evaluate whether intraoperative repeated dosing or postoperative repeated dosing is effective in reducing WI in LS.

To evaluate the hypothesis that, in terms of all-cause death, drinking alcohol 1-4 days per week is less harmful than daily (5-7 days/week) drinking of the same quantity of alcohol, a prospective cohort study using a self-administered questionnaire was conducted in Japan between 1990 and 2003 of 88,746 subjects (41,702 men and 47,044 women) aged 40-69 years at baseline. Among male regular drinkers consuming alcohol more than 1 day per week, light drinkers (300 g/week) showed no increase in all-cause mortality irrespective of frequency of alcohol intake. Heavy drinkers (or = 300 g/week), however, showed an increased risk of all-cause mortality among those who consumed alcohol 5-7 days per week, while no obvious increase was observed among those who consumed alcohol less than 4 days per week. Hazard ratios for drinkers who consumed alcohol 5-7 days per week were 1.29 (95% confidence interval: 1.12, 1.50) for 300-449 g per week and 1.55 (95% confidence interval: 1.32, 1.81) foror = 450 g per week when compared with those for occasional drinkers who consumed alcohol 1-3 days per month. These findings support the Japanese social belief that "liver holidays," abstaining from alcohol for more than 2 days per week, are important for heavy drinkers.

We report a rare case of colon cancer in which a depressed-type tumor only 5 mm in diameter invaded the submucosal layer and produced intermediate lymph node metastasis. A 47-year-old male received a total colonoscopy for a depressed-type lesion with marginal elevation in the sigmoid colon. The lesion measured 5 mm in diameter. On chromoendoscopic examination, the depression was clearly demarcated and an irregular pit pattern was identified in the demarcated area by magnification suggesting invasion of the submucosal layer requiring surgery. Laparoscopic-assisted sigmoidectomy was performed and the resected specimen demonstrated well-differentiated adenocarcinoma. The depth of invasion was only 900 microm. There was no lymphovascular invasion although not only paracolic, but also intermediate lymph node metastasis was detected. There have been some reports about small depressed-type colorectal cancer invading the submucosal layer; however, intermediate LN metastasis is very rare in submucosal colorectal cancer. In this case, there were two noteworthy points: 1) despite the small size, submucosal invasion could be estimated preoperatively, therefore, a successful lymph node dissection was performed by laparoscopic surgery; and 2) although this depressed-type cancer invaded the submucosal layer only 900 microm and there was no lymphovascular invasion, intermediate lymph node metastasis was detected.

Purpose: Several models of cancer progression, including clonal evolution, parallel evolution, and same-gene models, have been proposed to date. The purpose of this study is to investigate the authenticity of these models by comparison of accumulated genetic alterations between primary and corresponding metastatic lung cancers. Experimental Design: A whole-genome allelic imbalance scanning using a high-resolution single nucleotide polymorphism array and mutational analysis of the p53, EGFR, and KRAS genes were done on eight sets of primary and metastatic lung cancers. Based on the genotype data, the natural history of each case was deduced, and candidate metastasis suppressor loci were determined. Results: Five to 20 chromosomal regions showed allelic imbalance in each tumor. Accumulated genetic alterations were similar between primary and corresponding metastatic tumors, and the majority(>67%) of genetic alterations detected in metastatic tumors was also detected in the corresponding primary tumors. On the other hand, in seven of the eight cases, there were genetic alterations accumulated only in metastatic tumors. Among these alterations, allelic imbalances at chromosome 11p15 and 11p11-p13 regions were the most frequent ones (4 of 8, 50%). Likewise, four cases showed genetic alterations detected only in primary tumors. Conclusions: The natural history of each case indicated that the process of metastasis varies among cases, and that all three models are applicable to lung cancer progression. According to the clonal and parallel evolution models, it is possible that a metastasis suppressor gene(s) for lung cancer is present on chromosome 11p.

11102 Background: Obesity is reported to be associated with worse prognosis in early breast cancer. As obesity is rare and low BMI is relatively common in Japanese population compared to Caucasians...

Background: Helicobacter pylori infection potently induces methylation of CpG islands in gastric mucosae, which is considered to decrease to a certain level after active H. pylori infection discontinues. Noncancerous gastric mucosae of H. pylori–negative cases with a gastric cancer had higher methylation levels than those of H. pylori–negative healthy individuals. Here, using cases with multiple gastric cancers, we analyzed whether the higher methylation levels correlated with the higher risk of gastric cancers. Methods: Twenty-six healthy volunteers (HV), 30 cases with a single well-differentiated gastric cancer (S cases), and 32 cases with multiple well-differentiated gastric cancers (M cases) were recruited. H. pylori infection status was analyzed by the culture method. Methylation levels were quantified by real-time methylation-specific PCR of seven CpG islands. Results: In H. pylori–negative individuals, significant increasing trends were present in the order of HV, S cases, and M cases for FLNc and HAND1 methylation levels (P < 0.01, Spearman's rank-order test). Furthermore, the FLNc methylation level of M cases was significantly higher than that of S cases (P < 0.01, t test). Even adjusted by the extent of gastric atrophy, the FLNc methylation level retained a significant increasing trend (P = 0.03). In contrast, methylation levels in H. pylori–positive individuals were increased to various degrees in all the three groups. Conclusions: In H. pylori–negative individuals, methylation levels in gastric mucosae significantly increased in cases with a single gastric cancer and more in cases with multiple gastric cancers. Quantitative analysis of methylation levels is a promising risk marker for gastric cancers. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2317–21)

With advances in diagnostic techniques and treatment modalities, the number of patients identified with colorectal carcinoma who develop multiple primary malignancy during long-term follow-up has been increasing. We investigated multiple primary malignancies occurring in a large number of colorectal carcinoma patients who had undergone surgery in the 1980s at our institution. A total of 1,304 Japanese patients with colorectal carcinoma treated between January 1980 and December 1989 were prospectively followed to investigate the situations in which multiple primary malignancies occurred. To determine whether the incidence of multiple primary malignancies in this series was higher than expected, we calculated the expected numbers of carcinoma occurrences and evaluated these findings by exact binomial test. The median follow-up period was 95 months. The incidence of multiple primary malignancy was 18.7 percent (143/765) among males and 14.7 percent (79/539) among females. The most common site of multiple primary malignancy among males was the stomach, followed by the lung, prostate, larynx, liver, esophagus, and urinary bladder. The most common site among females was the uterus, followed by the stomach, breast, and liver. The sites that showed a higher incidence of multiple primary malignancy than the expected value were: the prostate, larynx, urinary bladder, oral cavity/pharynx and thyroid among males, and the uterus and oral cavity/pharynx among females. Fifteen to 20 percent of Japanese colorectal carcinoma patients experienced multiple primary malignancies. Postoperative long-term screening methods should be established considering the actual occurrence numbers and risk rate of multiple primary malignancies in addition to metachronous colorectal carcinoma.

Background/Aims: This study investigated appropriate level of upward lymph node (LN) dissection in advanced lower rectal carcinoma. Methods: A total of 285 consecutive patients with stage II/III lower rectal carcinoma were analyzed. LN dissection was classified as follows: division of the root of the superior rectal artery (UD2), division of the root of the inferior mesenteric artery (UD3) and UD3 with para-aortic LN dissection (UD4). Results: LN metastases at the root of the inferior mesenteric artery were found in 4 patients. Their prognoses were worse than those of the other stage III patients (p = 0.011). On the other hand, LN metastases along the superior rectal artery were discovered in 14 patients, whose 5-year overall survival rate was 61.2%. By removing the LNs either UD2 or UD3/4, a similar survival rate was achieved in stage III patients with LN metastases along the superior rectal artery. Conclusion: Survival of a minority with metastatic LNs at the root of the inferior mesenteric artery was poor. Additionally, survival is no worse in patients with positive LN along the superior rectal artery as long as these positive nodes are resected by either UD2 or UD3/4. Low ligation is adequate for advanced lower rectal carcinoma.

Primary mesenteric liposarcoma is a rare entity that has been reported only 14 times in English literature. The treatment strategy for mesenteric liposarcoma is, if no distant metastases are detected, surgical resection with a wide surgical margin, often followed by radiation and/or adjuvant chemotherapy for high-risk patients. However, the efficacy of pre-operative chemotherapy is unknown. If the tumor is shrunk by pre-operative chemotherapy, we could achieve complete surgical resection, which is difficult when the tumor is too large or is invading neighboring organs. We herein describe a case of huge mesenteric liposarcoma that showed significant tumor shrinkage by pre-operative chemotherapy using doxorubicin, cisplatin and ifosfamide, allowing a margin-negative operation.

The present study evaluated the short- and middle-term surgical outcomes of laparoscopic surgery (LS) for rectal carcinoma in comparison with a case-control series of open surgery (OS).Between February 1998 and December 2004, 47 patients with rectal carcinoma underwent LS. These patients were compared with a conventional OS group matched for age, gender, location of tumor, surgical procedure, extent of resection and pathological stage.The median follow-up period for the LS group and the OS group was 25 and 49 months, respectively. In the LS group, median operative time was significantly longer but median blood loss was lower than those in the OS group. There was one requiring conversion to OS. Postoperative intervals until liquid and solid intakes, and hospital stay were significantly shorter in the LS group. Postoperative complications rates are similar and anastomotic leakage occurred in one patient in each group. In the LS group, the levels of white blood cell count on postoperative day 1 and C-reactive protein on postoperative days 1 and 2 were significantly lower than those in the OS group.LS for rectal carcinoma provides benefits during the early postoperative period without increase in morbidity or mortality.

To determine whether the allelic status of chromosomes is clinically useful in colorectal cancer, the allelic losses at chromosomes 17p, 18q, 22q and 3p and their relationships with the clinicopathological features in colorectal cancer (CRC) patients, who had undergone curative surgery without adjuvant chemotherapy, were examined.The allelic status at 17p, 18q, 22q and 3p was analyzed by PCR-SSCP (polymerase chain reaction single-strand conformation polymorphism) in 139 CRC from patients who had undergone curative surgery between October 1994 and June 1996. The relationships between these allelic losses and the clinicopathological features were investigated.The lymph node status was significantly associated with the allelic status of 17p, 18q and 22q. The tumor site and tumor differentiation were significantly associated with the allelic status of 18q. When patients with more than two allelic losses were defined as the high allelic loss group and those with no, or only one allelic loss were defined as the low allelic loss group, it was found that the lymph node involvement was significantly higher in the high than in the low allelic loss group. Only three out of 25 patients in the low allelic loss group had lymph node metastasis, and 15 patients in this group without lymphatic invasion had no lymph node metastasis. There was no relationship between the allelic status and survival at any stage.The allelic status was significantly associated with lymph node metastasis. A combination of allelic status and lymphatic invasion assessment can predict the lymph node status before radical surgery.

Summary Background Because of the inaccessibility of mediastinal nodal metastases, the left thoracoabdominal approach (LTA) has often been used to treat gastric cancer of the cardia or subcardia. In a randomised phase III study, we aimed to compare LTA with the abdominal-transhiatal approach (TH) in the treatment of these tumours. Methods Between July, 1995, and December, 2003, 167 patients were enrolled from 27 Japanese hospitals and randomly assigned to TH (n=82) or LTA (n=85). The primary endpoint was overall survival, and secondary endpoints were disease-free survival, postoperative morbidity and hospital mortality, and postoperative symptoms and change of respiratory function. The projected sample size was 302. After the first interim analysis, the predicted probability of LTA having a significantly better overall survival than TH at the final analysis was only 3·65%, and the trial was closed immediately. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00149266. Findings 5-year overall survival was 52·3% (95% CI 40·4–64·1) in the TH group and 37·9% (26·1–49·6) in the LTA group. The hazard ratio of death for LTA compared with TH was 1·36 (0·89–2·08, p=0·92). Three patients died in hospital after LTA but none after TH. Morbidity was worse after LTA than after TH. Interpretation Because LTA does not improve survival after TH and leads to increased morbidity in patients with cancer of the cardia or subcardia, LTA cannot be justified to treat these tumours.

The impact of overweight on the outcome of gastrectomy with lymphadenectomy is controversial, and data from a well-controlled, randomized study are needed to identify a possible relationship. We used data from 523 patients registered for a prospective randomized trial comparing D2 and extended para-aortic D3 lymphadenectomy to compare the effects of body mass index (BMI) and the extent of lymphadenectomy for the development of general or major surgical complications (anastomotic leakage, abdominal abscess, and pancreatic fistula). Seventy-seven patients were classified as overweight with BMI ≥ 25, and 38 and 39 of these patients underwent a D2 or D3 lymphadenectomy, respectively. Among the 446 patients classified as nonoverweight with BMI < 25, 225 received D2 and 221 received D3 lymphadenectomy. Surgical complications, operation time, and blood loss were statistically significantly associated with BMI, and logistic regression analysis revealed that overweight directly affected the occurrence of surgical complications even after considering operation time and blood loss as intermediate factors instead of outcome variables. Among patients undergoing D2 lymphadenectomy, being overweight increased the risk for surgical complications and blood loss, whereas overweight was associated with only blood loss and operation time among patients receiving D3 lymphadenectomy. Overweight increased the risk of surgical complications in patients undergoing gastrectomy both directly and indirectly through operation time and blood loss. The impact of overweight on surgical complications was more evident in patients undergoing a D2 dissection.