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Background: The purpose of this study was to compare 2 weekly docetaxel-based regimens as first-line treatments for advanced gastric cancer and to investigate the expression of secreted protein acidic and rich in cysteine (SPARC) and its abilities to predict treatment-related clinical outcomes., Methods: Patients were randomly selected to receive 3 weekly cycles of docetaxel (35 mg/m(2) on days 1 and 8) plus S-1 (35 mg/m(2) each twice daily on days 1-14) (DS), or docetaxel plus cisplatin (35 mg/m(2) each on days 1 and 8) (DC). Endpoints included overall response rate (primary), survival, toxicity, and quality of life (secondary). SPARC expression in prechemotherapy specimens of primary gastric tumors was evaluated via immunohistochemical analysis., Results: Eighty patients were enrolled in the study. Confirmed overall response rates were 46% (95% confidence interval, 30%-62%) for DS and 24% (95% confidence interval, 11%-38%) for DC via intent-to-treat analysis. Median progression-free survival was 7.3 and 4.9 months and overall survival was 16.0 and 8.3 months for DS and DC, respectively. The most common grade ≥ 3 toxicity was neutropenia. Grade ≥ 3 mucositis (18%) and hand-foot syndrome (8%) were the toxicities most associated with DS, whereas anorexia (20%) and lethargy (20%) were more common with DC. High SPARC expression was related to early progression (hazard ratio, 3.67; P = .042) and poor overall survival (hazard ratio, 2.01; P = .010) in docetaxel chemotherapy on multivariate analysis., Conclusions: The outcomes in this study favored DS over DC for further phase 3 study. The findings suggest that split-dose weekly docetaxel alleviates hematological toxicity without compromising efficacy, and that SPARC expression may help individualize therapy in advanced gastric cancer., (2010 American Cancer Society.)

Background: In colorectal cancer (CRC), DNA methylation anomalies define distinct subgroups termed CpG island methylator phenotype 1 (CIMP1), CIMP2, and CIMP-negative. The role of this classification in predicting recurrence and disease-free survival (DFS) in resected stage III CRC was evaluated., Methods: Sporadic cancers from 161 patients were analyzed. Bisulfite pyrosequencing was used to examine the methylation of 2 global DNA methylation markers (LINE-1, Alu) and 9 loci (MINT1, MINT2, MINT31, P16, hMLH1, P14, SFRP1, SFRP2, and WNT5A). Mutations in BRAF and KRAS were assayed., Results: Gene hypermethylation clustered in discrete groups of patients, indicating the presence of CIMP. K-means clustering analysis identified 3 discrete subgroups: CIMP1 (n = 22, 13.7%), associated with proximal location and BRAF mutations; CIMP2 (n = 40, 24.8%), associated with KRAS mutations; and CIMP-negative (n = 99, 61.5%), associated with distal location. In proximal CRC, CIMP1 was correlated with a higher recurrence rate (53% for CIMP1, 18% for CIMP2, and 26% for CIMP-negative) and a worse DFS (P = .015). Also in proximal CRC, LINE-1 methylation was lower in patients whose cancer recurred compared with those whose cancer did not recur (P = .049). In multivariate analysis, CIMP1 and low LINE1 methylation were independent prognostic factors for DFS in proximal CRC (P = .008 for classification by K-means clustering analysis; P = .040 for LINE-1 methylation status)., Conclusions: DNA methylation is a useful biomarker of recurrence in resected stage III proximal but not distal CRC. However, as the number of CIMP1 cases was small in distal CRC, further study is required to validate our findings., (Copyright © 2010 American Cancer Society.)

Mucinous colorectal carcinoma exhibits distinct clinicopathological features compared to non-mucinous colorectal carcinoma. Previous studies have discovered several molecular genetic features in mucinous colorectal carcinomas, but have limitations as they are confined to a small number of molecules. To understand the mucinous colorectal carcinoma system, this study was designed to identify genes that are differentially expressed in mucinous colorectal carcinoma compared to non-mucinous colorectal carcinoma using cDNA microarrays. cDNA microarray experiments were performed using human cDNA 17k chips with 25 mucinous and 27 non-mucinous cancer tissues. Differentially expressed genes (DEGs) were determined by Welch's t-test and more accurate classifiers were selected from the DEGs using the prediction analysis for microarrays (PAM) software package. Array results were validated using quantitative real-time RT-PCR. The identified gene set was functionally investigated through in silico analysis. Sixty-two DEGs were identified and the 50 highest ranking genes could be used to accurately classify mucinous and non-mucinous colorectal carcinomas. The identified gene set included up-regulated TFF1 (4-fold), AGR2 (3.3-fold), FSCN1 (2.2-fold), CD44 (1.5-fold) and down-regulated SLC26A3 (0.2-fold) in MC. TFF1, AGR2 and SLC26A3 were validated by quantitative real-time RT-PCR. The functions of these DEGs were related to tumorigenesis (14 genes), cell cycle progression (6 genes), invasion (2 genes), anti-apoptosis (7 genes), cell adhesion and proliferation (5 genes) and carbohydrate metabolism (3 genes). We suggest that MC has distinct molecular characteristics from NMC and therefore, that the expression signatures of DEGs may improve the understanding of molecular pathogenesis and clinical behaviors in MC.

Brain metastases from colorectal carcinoma (CRC) are rare. The objectives of this study are to assess the natural history, outcome, and possible prognostic factors in CRC patients with brain metastases. Between 1995 and 2008, 8,732 patients with CRC were treated at Yonsei University Health System. Brain metastases were found in 1.4% of these patients. Retrospective review and statistical analysis of these 126 patients were performed. Median time from diagnosis of metastatic CRC (mCRC) to brain metastases was 9.0 months (range 0-85 months), and 14 patients (11.1%) had brain involvement as their initial presentation. Among the 126 patients, 91.3% had other systemic metastases; the most common extracranial metastatic site was lung (72.2%). Median follow-up duration was 6.1 months (range 0.1-90.3 months), and median survival after diagnosis of brain metastases was 5.4 months [95% confidence interval (CI) 3.9-6.9 months]. Median survival time after diagnosis of brain metastases was 1.5 months for patients who received only steroids (15.9%), 4.0 months for those who received whole-brain radiation therapy (37.5%), 9.5 months for those who received gamma-knife surgery (GKS) (32.5%), and 11.5 months for those who underwent surgery (20%) (P < 0.001). On multivariate analysis, recursive partitioning analysis (RPA) class and amount of chemotherapy before brain metastasis were independent prognostic factors for survival. Overall prognosis of patients with brain metastases from CRC is poor. Nevertheless, patients with low RPA class, or those with previous less chemotherapy showed good prognosis, indicating that proper treatment may result in improved survival time.

We conducted a phase I trial of the antiangiogenic agent 6-O-(4-dimethylaminoethoxy) cinnamoyl fumagillol hemioxalate (CKD-732). Our aims were to determine the maximum tolerated dose (MTD), pharmacokinetics (PK), and safety profiles as well as identify the biologically active dose (BAD) from ex vivo pharmacodynamics (PD) and biomarkers of CKD-732. Using a dose escalation schedule, 19 patients with refractory solid tumors were enrolled at dose levels of CKD-732 ranging from 1 to 15 mg/m(2) given twice weekly for 2 weeks followed by a 1-week rest. No treatment-related deaths occurred in this study. Confusion and insomnia were dose-limiting toxicities (DLTs), and MTD was 15 mg/m(2). The area under the concentration-time curve (AUC) and maximum concentration (Cmax) increased dose dependently with increasing doses. The BAD was 5 mg/m(2) according to ex vivo PD. A decrement in soluble vascular endothelial growth factor receptor-3 (sVEGF-3) level was correlated with a reduction in tumor size (r = 0.54, P = 0.045). The results from this study showed an MTD of 15 mg/m(2) and a BAD of 5 mg/m(2).

Purpose: The benefit of adjuvant radiotherapy in patients with stage IIA (T3N0) rectal cancer following total mesorectal excision (TME) is controversial. We evaluated the effect of adjuvant chemoradiotherapy (CRT) versus chemotherapy (CT) alone on the local recurrence and survival of patients with stage IIA rectal cancer after TME., Methods: Between 1996 and 2004, patients with stage IIA rectal cancer who received adjuvant CT (n = 29) or CRT (n = 122) following TME were enrolled. Oncologic outcomes were compared between groups, and risk factors for local recurrence and overall survival rates were analyzed., Results: The median follow-up period was 78 months. No significant differences were observed in the 5-year local recurrence (3.4% versus 9.0%; P = 0.348) or 5-year overall survival rates (86.2% versus 80.3%; P = 0.924) between CT and CRT. However, involvement of the circumferential resection margin and age >60 years were associated with adverse oncologic outcomes., Conclusions: Additional postoperative radiotherapy did not alter local recurrence or survival after TME in patients with stage IIA rectal cancer. Postoperative radiation may be an overtreatment as an adjuvant therapy in patients with stage IIA rectal cancer if they had no other risk factors. However, randomized controlled trials are warranted to confirm this suggestion.

Background: Simvastatin has demonstrated anti-tumor activity in preclinical studies via tumor cell senescence, anti-angiogenesis, and apoptosis. This phase II trial evaluated the efficacy and toxicity profile of conventional FOLFIRI chemotherapy plus simvastatin in metastatic colorectal cancer patients., Methods: Patients received irinotecan 180 mg/m(2) as a 90-min infusion followed by leucovorin 200 mg/m(2) in a 2-h infusion, and then 5-FU 400 mg/m(2) bolus injection followed by 2,400 mg/m(2) as a 46-h continuous infusion. Treatment cycles were repeated every 2 weeks until documented disease progression, unacceptable toxicity, or patient's refusal. Simvastatin 40 mg tablet was given once daily per oral everyday during the period of chemotherapy without a rest., Results: From October 2005 to June 2006, 49 patients were enrolled. The overall response rate (ORR) was 46.9% (95% CI, 31.0-58.8) by intent-to-treat analysis and 45.8% (95% CI, 33.3-62.8) by per-protocol analysis. There were one complete response (CR) and 22 partial responses (PRs). Both CR and PRs were confirmed at least 4 weeks later. The disease-control rate was 83.7% (95% CI, 73.4-94.0). The median follow-up duration was 25.6 months (range, 20.9-28.8 months). The median survival of all patients was 21.8 months (95% CI, 14.4, 29.2). The median TTP was 9.9 months (95% CI, 6.4, 13.3). No patients experienced additional adverse effect that was definitely caused by simvastatin drug therapy in this trial., Conclusion: The combination of simvastatin plus FOLFIRI was a feasible regimen with promising antitumor activity.

Background: Over the past several years, preoperative chemoradiotherapy (CRT) has contributed remarkably to make more sphincter-preserving procedure (SPP) possible for lower rectal cancer. The aim of this study was to compare the outcomes between abdominoperineal resection (APR) and SPP after preoperative CRT in patients with locally advanced lower rectal cancer., Methods: A retrospective investigation was conducted with a total of 122 patients who underwent radical surgery combined with preoperative CRT for locally advanced lower rectal cancer. Of these, 50 patients underwent APR and 72 received SPP. Surgery was performed 6-8 weeks after completion of preoperative CRT. Oncologic outcomes were compared between the two groups, and the clinicopathologic factors affecting the treatment outcomes were evaluated., Results: Circumferential resection margin (CRM) involvement (P = 0.037) and postoperative complication rate (P = 0.032) were significantly different between APR and SPP. Patients who underwent APR had a higher 5-year local recurrence (22.0% vs. 11.5%, P = 0.028) and lower 5-year cancer-specific survival (52.9% vs. 71.1%, P = 0.03) rate than those who underwent SPP. Pathologic N stage was the most critical predictor for local recurrence and survival., Conclusions: Our study shows that APR following preoperative CRT exhibited more adverse oncologic outcomes compared with SPP. This result may be due to higher rates of CRM involvement in APR even with preoperative CRT. We suggest that sharp perineal dissection and wider cylindrical excision at the level of the anorectal junction are required to avoid CRM involvement and improve oncologic outcomes in patients who undergo APR following preoperative CRT.

The aim of this study was to scrutinize the evidence of adjuvant chemotherapy of gastric cancer by assessing the quality of the medical literature of randomized controlled trials (RCTs). A quality assessment (QA) scoring system was devised with the three parameters-control of bias, quality of report, and quality of design-which consisted 19 items. We searched for all the publications of the RCTs, from 1969 to 2007, with surgery-only arm, and their associated meta-analyses to score. Among the 26 RCTs, quality of three articles were graded as (2+), 10 articles as (1+), and 13 articles as (-). Recently published studies had overall better quality of report, but not necessarily better quality of design. Three studies demonstrating a positive survival benefit of adjuvant chemotherapy had a grade (1+). Hierarchical clustering revealed that the 26 articles were grouped into three major branches associated with study quality and a multi-institutional setting. We also obtained a statistically significant set of ten items (P < 0.001) that could differentiate articles of good (1-2+) and low quality (-) through supervised two-way hierarchical clustering. Finally, the level of recommendation for adjuvant chemotherapy in gastric cancer was to be a "B" according to the Scottish Intercollegiate Guidelines Network (SIGN) System. QA of medical literature should be an essential consideration for medical-related decision-making and the formation of evidence-based guidelines. Multidisciplinary discussion to develop and refine trial design is important for procuring better quality of RCTs of adjuvant chemotherapy of gastric cancer.

Anemia is a unique side effect in Korean gastric cancer patients after S-1 monotherapy. We studied gastric cancer patients from a phase II trial of S-1 monotherapy with a 2-week treatment and 1-week rest schedule. Patients from a phase II trial of S-1 monotherapy with a 4-week treatment and 2-week rest were used as a reference group. The patients were categorized into two groups based on the degree of hemoglobin reduction per cycle of S-1: the mild reduction group (MRG DeltaHb/cycle < or =1.0) or severe reduction group (SRG DeltaHb/cycle >1.0). DeltaHb/cycle was calculated from maximum reduction of hemoglobin per one cycle of the treatment. Microarray-CGH was performed using a 17K cDNA microarray containing 15,723 unique genes. We selected genes with copy number variation defined as amplification (log2R/G >0.68) or deletion (log2R/G <-0.68), and a genetic aberration frequency difference of > or =30% between the MRG and the SRG. There were no differences in clinical factors, S-1 treatment-related factors (dose, dose intensity), toxicity, S-1 metabolism-related gene copy numbers (CYP2A6, DPD), or progression-free survival between the MRG and the SRG. Three genes were selected from microarray-CGH and logistic regression model: logit LN(Z) = (1.321) + (1.038 x PTX1) + (0.211 x MYO5A) + (0.516 x ZNF664). In the SRG, all 3 genes showed a trend of higher copy numbers than the MRG. There were no common anemia-related genes identified from different chemotherapy schedule of S-1 monotherapy. The logistics obtained from 3 genes predicted the hemoglobin reduction with an accuracy of 78%. The AUC was 0.744 for the final regression model. The combined copy number changes of the 3 genes can be developed into a biomarker in predicting S-1 treatment-related anemia.

Mental adjustment and coping affect the physical outcome and survival as well as quality of life in cancer patients. The Mini-Mental Adjustment to Cancer (Mini-MAC) scale is a new refined, economical and reliable self-rating instrument measuring cognitive and behavioral responses to cancer. The aim of this study was to evaluate the psychometric properties of the Mini-MAC in Korean cancer patients. A total of 208 cancer patients recruited from the Yonsei Cancer Center were assessed with the Mini-MAC and the Hospital Anxiety and Depression Scale (HADS). Principal component analysis with varimax rotation for the Korean version of Mini-MAC (K-Mini-MAC) confirmed four factors. Three had psychometric properties similar to Helpless-Hopeless (HH), Anxious Preoccupation (AP) and Cognitive Avoidance (CA) of the original Mini-MAC. A novel factor, named Positive Attitude, included items of both Fatalism (FA) and Fighting Spirit (FS) from the original version. The five subscales from the original version (AP, HH, FS, FA and CA) and Positive Attitude had acceptable internal reliabilities in our sample (Cronbach's alpha coefficient 0.50-0.86; correlation coefficient of test-retest 0.68-0.88). For the validity, significant interscale correlation was observed in the original five subscales and Positive Attitude. Each subscale including Positive Attitude was also significantly related to Depression and Anxiety of HADS. As a whole, the K-Mini-MAC was a reliable, valid and acceptable tool for Korean cancer patients. These findings can provide information about the cross-cultural validity of Mini-MAC scale's factor structure. Cultural differences were also discussed.

Background: The da Vinci system is a newly developed device for colorectal surgery, therefore experience of its use for rectal cancer surgery is limited and there are no reports describing the use of four robotic arms with this system. The aim of this study is to evaluate the safety and feasibility of the four-arm da Vinci system for total mesorectal excision in rectal cancer patients., Methods: Clinicopathologic data were prospectively collected on nine patients who underwent robotic total mesorectal excision using four robotic arms for the treatment of mid or low rectal cancer between November 2006 and Febuary 2007. Patient demographics, perioperative clinical outcomes, and pathology results with macroscopic grading (complete, nearly complete, incomplete) were evaluated., Results: nine patients with mid or low rectal cancer underwent robotic total mesorectal excison using four robotic arms without serious complications. The mean length of hospital stay was 7.4 +/- 1.3 days (range 5.0-10.0 days) and the mean operating time was 220.8 +/- 49.4 min (range 153-315 min). Macroscopic grading of the specimen was complete in eight patients and nearly complete in one patient. There were no cases of conversion., Conclusion: In the present study, we accomplished nine robot-assisted rectal resections safely and effectively.

Purpose: The aim of this study was to evaluate the activity and the safety of a combination regimen of capecitabine and doxorubicin as salvage chemotherapy in advanced gastric cancer patients who had undergone one or two prior chemotherapy regimens., Methods: Patients received capecitabine, 2,500 mg/m(2)/day PO for 14 days (D1-14) and doxorubicin, 30 mg/m(2) IV on day 1 every 3 weeks until disease progression. The response was evaluated according to RECIST criteria, and the toxicity was evaluated by NCI-CTC (version 2.0)., Results: Forty-five patients were enrolled. Twenty-six patients were treated as second-line chemotherapy and the remaining patients as third-line chemotherapy. A total of 152 cycles of chemotherapy (median 2, range 1-12) were administered. Median dose intensities of capecitabine and doxorubicin were 11,326 and 9.6 mg/m(2)/week, respectively. The overall response rate was 6.7% (95% CI, 4.1-12.5%) and the disease control rate was 46.7% (95% CI, 28.6-87.1%) according to an intent-to-treat analysis. The median progression-free survival was 11.3 weeks (95% CI, 5.6-16.7 weeks). The median overall survival was 29.1 weeks (95% CI, 18.3-39.9 weeks) with one-year survival rate of 24%. Severe (grade III/IV) hematologic and non-hematologic toxicity was uncommon and included nausea/vomiting in five (11.1%), neutropenia in two (4.4%), anemia in one (2.2%), and hand-foot syndrome in one patient (2.2%)., Conclusions: The combination of capecitabine and doxorubicin is a feasible salvage regimen in advanced pre-treated gastric cancer.

Until mid-1990s, fluorouracil was the only chemotherapeutic agent available for the treatment of colorectal cancer. The treatment of advanced colorectal cancer has evolved considerably over the last decade. Considerable improvements in survival as well as quality of life have been achieved with the application of oxaliplatin and irinotecan with fluoropyrimidine as a first and subsequent line therapy for colorectal cancer. Development of oral fluoropyrimidines as an alternative to intravenous administration provides an additional option for combination cytotoxic therapy, which is currently being assessed in phase III trials in advanced settings. The appearance of biologic agents in mid-2000s, namely cetuximab and bevacizumab, and their integration with conventional cytotoxic therapy for the treatment of colorectal cancer has additionally expanded the options for the treatment. Their dramatic success has led to further clinical studies of targeted therapy in colorectal cancer, making it one of the most promising areas of cancer research. Although considerable improvement was achieved by incorporating oxaliplatin in adjuvant chemotherapy for the treatment of colon cancer, there has been no phase III trial incorporating new agents in adjuvant setting for rectal cancer. However, many phase II trials on the efficacy of new agents in the setting of concurrent chemoradiation are in progress. Based on their results, randomized phase III clinical trials evaluating new agents in preoperative or postoperative setting will be carried out.

As no standard chemotherapy regimen has been established for advanced gastric cancer, this study sought to evaluate the efficacy and safety of combination chemotherapy that included paclitaxel and leucovorin (LV)-modulated infusional 5-fluorouracil (5-FU) in metastatic gastric cancer. Patients received a three-hour infusion of 175 mg/m2 of paclitaxel on day 1. A bolus of 20 mg/m2 of LV was then administered, followed by a 24-h infusion of 1,000 mg/m2 of 5-FU on days 1 through 3. The treatment cycle was re-peated every 3 weeks until disease progression. Response evaluation was performed according to the RECIST criteria, with toxicity determined by NCI-CTC (version 2.0). A total of 66 patients, including 21 (31.8%) with a history of prior chemotherapy, were enrolled. Fifteen (71.4%) of the 21 patients with prior chemotherapy received prolonged infusional 5-FU. In the 56 evaluable patients (37 in the chemotherapy-naïve group and 19 in the prior chemotherapy group), tumor responses according to prior exposure to chemotherapy were as follows: 17 (45.9%) partial response (PR), 6 (16.2%) stable disease (SD) and 14 (37.8%) progressive disease (PD) in the chemotherapy-naïve group; 1 (7.1%) complete response, 3 (15.8%) PRs, 8 (42.1%) SDs and 7 (36.8%) PDs in the prior chemotherapy group. The overall median response duration was 20 weeks (range, 8-61 weeks), with a median progression-free survival of 20 weeks [95% confidence interval (CI), 13.4-26.6 weeks] and 12 weeks (95% CI, 5.7-18.3 weeks) in the chemotherapy-naïve and prior chemotherapy groups, respectively. The median overall survival was 48 weeks (95% CI, 38-58 weeks) in the chemotherapy-naïve group and 28 weeks (95% CI, 22-34 weeks) in the prior chemotherapy group. The most frequent grade III/IV toxicity was neutro-penia. Non-hematological toxicity of grade III/IV was rare. Paclitaxel in combination with 5-FU/LV is clinically beneficial for patients with advanced gastric cancer and is a feasible salvage regimen for 5-FU-refractory gastric cancer patients.

Surgical resection of colorectal cancer metastasis to the liver results in a 5-year survival rate of around 40%. Liver metastasis from other cancers such as neuroendocrine carcinoma and genitourinary tumors are also treated effectively with combined liver resection. However, hepatic metastasectomy for liver tumor from gastric cancer hasn't been considered as a standard treatment, and the benefit for this treatment has not been established. We report here on two cases of gastrectomy and combined liver resection for synchronous liver metastasis without any evidence of other metastatic lesions, and these two patients have survived for more than 7 years without evidence of disease recurrence. In conclusion, for patients with hepatic metastasis from gastric cancer, combined surgical resection of the liver metastasis should be considered as a treatment option when metastasis to other sites can be excluded.

Percutaneous approaches, such as percutaneous ethanol injection and radiofrequency ablation, have been most widely used for hepatocellular carcinoma patients who were not eligible for surgery. New technologies to improve the efficacy are currently needed. (166)Holmium is a neutron activated radionuclide, and has several beneficial radiophysical characteristics for internal radiation therapy. (166)Holmium-Chitosan complex, in which chitosan is chelated with (166)Holmium, was developed as a radiopharmaceutical for cancer therapy. We have conducted a pilot study to evaluate the clinical efficacy of transarterial administration of (166)Holmium-Chitosan complex in patients with a single and small (< 3 cm) hepatocellular carcinoma. (166)Holmium-Chitosan complex, at a dose of 20 mCi per cm of tumor mass-diameter, was administered through the artery that directly fed the tumor. Twelve patients were treated with a median follow-up duration of 26 (range: 12-61) months. The tumor diameter ranged between 1.5 and 2.5 cm. Ten patients (83%) had complete response and two (17%) had partial response. The median complete response duration was not reached. The median AFP level declined from 83.8 to 8.3 ng/mL within 2 months after treatment. No grade III/IV toxicity was observed. Grade I and II toxicities were observed in four patients (2 abdominal pain, 1 fever, and 1 AST/ALT elevation). No toxic death occurred. This preliminary study shows a promising and durable complete response rate with an acceptable safety profile. Further studies with greater accrual of patients are warranted.

Purpose: To compare the effect of reducing the irradiated small-bowel volume with the use of belly board, bladder distension or both methods combined, in patients with rectal cancer undergoing postoperative pelvic radiotherapy., Patients and Methods: This study enrolled 20 consecutive patients with rectal cancer who were scheduled to receive postoperative pelvic radiotherapy. All patients underwent four sets of CT scans under four different methods as follows: group I: empty bladder without the use of a belly board; group II: empty bladder with the use of a belly board; group III: bladder distension without the use of a belly board; group IV: bladder distension with the use of a belly board. The conventional three-field treatment plan was made using a three-dimensional treatment planning system. The irradiated small-bowel volume was calculated at 10% intervals from 10% to 100% of the prescribed dose., Results: The volume of the irradiated small bowel decreased in the order of group I, group II, group III, and group IV at all dose levels (p < 0.001). In comparison to group I, the mean absolute volume reductions (relative volume reduction) of the irradiated small bowel were 41.5 +/- 20.1 cm(3) (33.9 +/- 12.9%) in group II, 76.6 +/- 30.5 cm(3) (55.1 +/- 17.8%) in group III, and 98.5 +/- 36.7 cm(3) (70.7 +/- 14.5%) in group IV., Conclusion: Bladder distension was a more effective method than the belly board for reducing the irradiated small-bowel volume in postoperative pelvic radiotherapy of rectal cancer patients. The combination of the belly board and bladder distension showed an additive effect and was the most effective method for reducing the irradiated small-bowel volume.

The nature of genetic alterations in bilateral breast cancer (BBC) associated with the distinctive development of a second primary tumor or a metastatic lesion is not clearly established. In this study, patterns of promoter methylation and gene copy number changes were assessed for their utility in the distinction of two types of BBC (synchronous and metachronous). Seven cases of synchronous and five cases of metachronous breast cancer tissues were used in X chromosome inactivation assay to assess the methylation pattern of human androgen receptor gene. X chromosome inactivation assay alone did not provide enough information to distinguish the genetic origins of synchronous and metachronous BBC. When four pairs of paraffin-embedded BBC tissues were used in cDNA array-based CGH with placenta DNA as a reference, higher DNA copy number changes were observed from metachronous pairs (9.0%) than from synchronous pairs (3.1%). From the two cases of metachronous pairs tested, 44 genes were found to be commonly modulated in gene copy numbers in a cancer detected later.