Kentaro Nakao

Quality of Life after Low Anterior Resection and Temporary Loop Ileostomy

PurposeLow anterior resection has become the operation of choice for mid rectal or low rectal cancer. A defunctioning stoma is routinely created at some centers to decrease the risk of leakage requiring surgical intervention. This study was designed to evaluate the quality of life in patients undergoing low anterior resection with a temporary ileostomy.MethodsA prospective longitudinal study was conducted in 22 patients with rectal cancer who underwent low anterior resection with a loop ileostomy. Quality of life was assessed by using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 questionnaires. Twenty-five patients who underwent high anterior resection for rectosigmoid cancer were studied concurrently to evaluate the impact of major colorectal resection without a stoma.ResultsPatients’ scores on the quality of life questionnaires generally improved after high anterior resection; however, for patients who underwent low anterior resection, the scores for physical and role functioning before ileostomy closure were worse than the preoperative values. The scores on the quality of life questionnaires generally improved after ileostomy closure. Ileostomy closure required a short hospital stay and was rarely associated with complications.ConclusionPatients who underwent low anterior resection with ileostomy had significant reductions in physical and role functioning, which apparently improved after ileostomy closure. Similar declines in these quality of life variables were not found in patients who underwent high anterior resection. A temporary ileostomy should be created in selected patients with the highest risk of anastomotic leakage. Increased resources for not only surgical care but also for stoma therapy are necessary for patients who undergo low anterior resection with a temporary ileostomy.

Prospective analysis of quality of life in the first year after colorectal cancer surgery

Little is known of how the quality of life (QOL) of patients with colorectal cancer changes with time following an operation, and whether or not there are predictors of QOL after one year in this population. The European Organization for Research and Treatment of Cancer QLQ-C30 QOL questionnaire was administered to patients before their operation for colorectal cancer, and monthly following the operation for up to one year. Multivariate regression analysis was performed to examine the predictors of QOL one year after the operation. One hundred patients with a mean age of 64 years participated. The scores of five QOL dimensions (physical function, role function, fatigue, pain, and dyspnoea) dropped significantly below the preoperative values at one month following the operation. The scores returned to the preoperative values within three months following the operation. The scores of seven QOL dimensions (global QOL, emotional function, social function, insomnia, appetite loss, diarrhea, and financial difficulties) had improved within three months after the operation. Other scores, including cognitive function, nausea and vomiting, and constipation remained unchanged. Stepwise regression analyses showed that preoperative performance status predicted various QOL scales one year following the operation. The overall QOL of colorectal cancer patients became stabilized about three months after the operation.

Genetic Changes in Primary Colorectal Cancer by Comparative Genomic Hybridization

Comparative genomic hybridization (CGH) is a powerful new technique for the molecular cytogenetic analysis of cancer. In this method, at first the cancer DNA and normal DNA are labeled with biotin and digoxigenin, respectively, and then the labeled DNAs are applied onto normal lymphocyte metaphase preparations in hybridization. After hybridization, they are stained with FITC and rhodamine, respectively, so chromosomal gains and losses in cancer are thus detected by using a green:red ratio. In this study, we analyzed the abnormal chromosomes in nine cases with human primary colon cancer. A gain in chromosomes 11p, 12q, 16p, 20p, and 20q were observed, while a loss of 18q and 22q were discovered. CGH may thus provide us with important information for analyzing the genes in colon cancer.

Fractional Genomic Alteration Detected by Array-Based Comparative Genomic Hybridization Independently Predicts Survival after Hepatic Resection for Metastatic Colorectal Cancer

Purpose: Although liver resection is the primary curative therapy for patients with colorectal hepatic metastases, most patients have a recurrence. Identification of molecular markers that predict patients at highest risk for recurrence may help to target further therapy. Experimental Design: Array-based comparative genomic hybridization was used to investigate the association of DNA copy number alterations with outcome in patients with colorectal liver metastasis resected with curative intent. DNA from 50 liver metastases was labeled and hybridized onto an array consisting of 2,463 bacterial artificial chromosome clones covering the entire genome. The total fraction of genome altered (FGA) in the metastases and the patients clinical risk score (CRS) were calculated to identify independent prognostic factors for survival. Results: An average of 30 ± 14% of the genome was altered in the liver metastases (14% gained and 16% lost). As expected, a lower CRS was an independent predictor of overall survival (P = 0.03). In addition, a high FGA also was an independent predictor of survival (P = 0.01). The median survival time in patients with a low CRS (score 0-2) and a high (≥20%) FGA was 38 months compared with 18 months in patients with a low CRS and a low FGA. Supervised analyses, using Prediction Analysis of Microarrays and Significance Analysis of Microarrays, identified a set of clones, predominantly located on chromosomes 7 and 20, which best predicted survival. Conclusions: Both FGA and CRS are independent predictors of survival in patients with resected hepatic colorectal cancer metastases. The greater the FGA, the more likely the patient is to survive.

Associations of various gene polymorphisms with toxicity in colorectal cancer patients receiving oral uracil and tegafur plus leucovorin: a prospective study

BACKGROUND To assess the predictive value of polymorphism in nine genes, primarily thymidylate synthase (TS) and orotate phosphoribosyltransferase (OPRT), which relates to 5-fluorouracil (5-FU) metabolism, for toxicity in patients treated with oral uracil/tegafur (UFT) plus leucovorin (LV). PATIENTS AND METHODS We treated 99 patients with stage II or III colorectal carcinoma with oral UFT + LV. Germline DNA from patients was genotyped for 5-FU and folate metabolism-relating genes. CYP2A6, tegafur-activating enzyme, and uridine diphosphate-glucuronosyltransferase 1A1 genetic variation were also assessed. Toxicity was graded by the National Cancer Institute Common Toxicity Criteria, version 2.0. RESULTS The multivariate logistic regression revealed that OPRT 638G>C polymorphism was associated with grade 3 diarrhea [odds ratio (OR) 19.84 for patients with the C/C homozygous type compared with patients with wild type, P = 0.014] and polymorphisms of UGT1A1 were associated with hyperbilirubinemia (OR 38.76 for homozygotes and double heterozygotes of *6 or *28 compared with wild type, P = 0.0008). No relationships were observed between TS polymorphisms and any toxicity. CONCLUSIONS OPRT polymorphism predicts toxicity, especially grade 3 or greater diarrhea to oral UFT + LV adjuvant chemotherapy, whereas TS does not, in our study cohort. UGT1A1 polymorphism seems to be a risk factor for hyperbilirubinemia due to UFT+LV.

Gastric and intestinal phenotypic cell marker expressions in gastric differentiated-type carcinomas: association with E-cadherin expression and chromosomal changes

AbstractsGastric and intestinal phenotypic cell markers are widely expressed in gastric carcinomas, irrespective of their histological type. In the present study, the relations between the phenotypic marker expression of the tumour, histological findings, expression of cell adhesion molecules, and the chromosomal changes in gastric differentiated-type carcinomas were examined. The phenotypic marker expression of the tumour was determined by the combination of the expression of the human gastric mucin (HGM), MUC6, MUC2 and CD10, and was evaluated in comparison with the expression of cell adhesion molecules, such as E-cadherin and β-catenin, and chromosomal changes by comparative genomic hybridization (CGH) in 34 gastric differentiated-type carcinomas. Tumours were classified into the gastric- (G-), gastric and intestinal mixed- (GI-), intestinal- (I-), or unclassified- (UC-) phenotype according to the immunopositivity of staining for HGM, MUC6, MUC2, and CD10. G-phenotype tumours were significantly associated with a higher incidence of differentiated-type tumours mixed with undifferentiated-type component, compared with GI- and I-phenotype tumours (88.9 vs 33.3%, P=0.0498 and 88.9 vs 42.9%, P=0.0397; respectively). HGM-positive tumours were significantly associated with a higher incidence of tumours with abnormal expression of E-cadherin, compared with HGM-negative tumours (66.7 vs 21.1%, P=0.0135). GI-phenotype tumours were significantly associated with a higher incidence of tumours with abnormal expression of E-cadherin, compared with I-phenotype tumours (77.8 vs 21.4%, P=0.0131). HGM-negative tumours were significantly associated with higher frequencies of the gains of 19q13.2 and 19q13.3, compared with HGM-positive tumours (57.9 vs 20.0%, P=0.0382 and 63.2 vs 13.3%, P=0.0051; respectively). MUC6-positive tumours were significantly associated with higher frequencies of the gains of 20q13.2, compared with MUC6-negative tumours (71.4 vs 30.0%, P=0.0349). MUC2-positive tumours were significantly associated with the gain of 19p13.3, compared with MUC2-negative tumours (41.2 vs 5.9%, P=0.0391). I-phenotype tumours were significantly associated with higher frequencies of gains of 5p15.2 and 13q33-34, compared with G-phenotype tumours (66.7 vs 0%, P=0.0481, each) and also associated with higher frequencies of gain of 7p21, compared with GI-phenotype tumours (66.7 vs 0%, P=0.0481). Our present results show that gastric differentiated-type carcinomas have different characteristics according to the phenotypic marker expression of the tumour in terms of histological findings, E-cadherin expression and pattern of chromosomal changes.

Randomized clinical trial of the influence of mechanical bowel preparation on faecal microflora in patients undergoing colonic cancer resection

This study investigated the influence of mechanical bowel preparation (MBP) on faecal microflora, using rRNA‐targeted reverse transcription–quantitative polymerase chain reaction in patients undergoing colonic cancer resection.

Prospective randomized trial for determination of optimum size of side limb in low anterior resection with side-to-end anastomosis for rectal carcinoma.

PURPOSE: Functional outcome after low anterior resection with side-to-end anastomosis is comparable with that after a colonic J-pouch construction. The optimum size of the side limb has yet to be determined. This prospective randomized trial compared a 3-cm (short) and 6-cm (long) side limb. METHODS: Forty-four patients with a mid or low rectal cancer undergoing low anterior resection were randomly assigned to each group. Physiologic and clinical assessments were performed preoperatively and at 3, 6, and 12 months after ileostomy closure. Defecography was performed at six months after ileostomy closure. RESULTS: Twenty patients in each group completed the study. Among them, one patient with a short limb and two others with a long limb developed leakage. Sphincter function and reservoir function were similar between the groups. Bowel function or incontinence scoring was similar between the groups. The incidence of incomplete evacuation assessed by defecography in the long limb group was significantly greater than in the short limb group (13/20 long and 5/20 short, P = 0.025). One patient in the long limb group experienced fecal impaction. CONCLUSION: The study showed similar clinical results in patients with either a short limb or a long limb but seemed to be underpowered. A long limb may be associated with fecal impaction in patients undergoing low anterior resection with side-to-end anastomosis.

Health-related quality of life in patients with advanced colorectal cancer: results from a phase II study of S-1 combined with irinotecan (CPT-11)

BackgroundWe carried out this study to examine the health-related quality of life (HRQOL) of patients with advanced colorectal cancer treated with the oral fluoropyrimidine S-1 plus irinotecan (CPT-11).MethodsHRQOL was assessed at baseline (pretreatment) and at 5-week intervals during treatment, using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 questionnaires. The HRQOL data for 12 preselected scales and 21 courses of treatment were then analyzed longitudinally.ResultsThirty-seven patients completed the baseline and post-treatment HRQOL assessments. Statistically significant differences between the baseline and post-treatment HRQOL scores were observed for the global QOL, social function, and pain scales (all QLQ-C30), as well as the body image, future perspective, gastrointestinal tract symptoms, weight loss, and chemotherapy side effects scales (all QLQ-CR38); favorable post-treatment results were observed for all the scales except for body image and chemotherapy side effects, for which post-treatment deteriorations were observed. The changes in body image, future perspective, weight loss, and chemotherapy side effects were each greater than ten points and seemed clinically significant.ConclusionCombined treatment with S-1 plus CPT-11 resulted in an acceptable deterioration in HRQOL functioning and symptoms, compared with baseline levels.

Health-related quality of life of colorectal cancer patients receiving oral UFT plus leucovorin compared with those with surgery alone

BackgroundAdjuvant chemotherapy of oral uracil/ftorafur (UFT) plus leucovorin (LV) has been accepted as the standard of care in the treatment of patients with stage II and III carcinoma of the colon. The objective of the study was to compare HRQOL reported by patients receiving oral UFT plus LV (UFT/LV group) versus no adjuvant treatment (control group) following surgery for colorectal cancer.MethodsNinety nine patients in the UFT/LV group and 83 in the control group participated. HRQOL was assessed with the European Organization for Research and Treatment of Cancer QLQ-C30 and HRQOL data measured longitudinally following surgery were compared between the groups.ResultsEighty-eight percent (87 of 99) received all scheduled doses of UFT plus LV during the first three cycles, and 82 percent (81 of 99) did so for five cycles. The most common type of toxicity in the UFT/LV group was fatigue, which was generally mild. Six patients each had grade 3 diarrhea or anorexia. There were significant differences in the scores for role function, and specific limitations such as fatigue, nausea, and vomiting, dyspnoea, appetite loss, and financial difficulties, which deteriorated in the UFT/LV group.ConclusionsHRQOL in colorectal cancer patients with adjuvant chemotherapy with oral UFT plus LV deteriorated during this phase of treatment compared with those with surgery alone, despite the biased stage of tumor between the groups. Symptom management and social support would improve HRQOL in such a group of patients.