FREQUENCY AND CLINICO-PATHOLOGICAL ASSOCIATIONS OF RAS MUTATIONS IN COLORECTAL CANCER IN THE VICTORIAN POPULATION

Background : Mutations in the oncogene ras occur in 20–50% of colorectal cancers. The presence of these mutations allows screening tests to be developed based on the identification of mutant DNA in cells derived from cancers. A study of the prevalence and clinicopathological associations of ras mutations was undertaken. Methods : The frequency of mutations in codons 12 and 13 of the K-ras gene was investigated in 103 colorectal carcinomas using restriction fragment length polymorphism. Results : Mutations were detected in 32% (33/103) of the tumours, predominantly in codon 12 (25/33). No mutations were detected in normal-appearing mucosa from the same patients. Conclusions : Analysis of the frequency of ras mutations compared with various independent clinical variables revealed a sex-linked relationship between the presence of a ras mutation and nodal status but no correlation with any other clinical parameter was found. The findings suggest that screening tests based on ras mutation detection may lack sensitivity because of the presence of mutations in only 32% of tumours.     

TREATMENT PRINCIPLES IN ADVANCED COLORECTAL CANCER

Background: Colorectal cancer is an important disease in the Australian community. Whilst there has been much discussion about the appropriate management of local disease, particularly with respect to the issue of adjuvant therapy, there has been relatively little local discussion of treatment options in metastatic colorectal cancer. Methods: The critical principles underlying treatment in this setting are briefly outlined in the present article, indicating wherever possible what options could be considered standard, and based on the available literature, which approaches must still be considered experimental at this time. Results: Overall, the results of treatment in this group of patients remain poor. Conclusion: Further clinical trials are required to address the issues affecting patients with metastatic colorectal cancer.     

THE INFLUENCE OF OTHER DISEASES UPON THE OUTCOME OF COLORECTAL CANCER PATIENTS

Little attention may be paid during follow up of colorectal cancer patients to other medical problems because the follow up is normally focused upon the diagnosis of recurrence and the detection of metachronous neoplasms. Attention directed at improving the medical condition of patients would be justified if it were shown that other diseases had a significant effect upon survival. Review of a selected consecutive series of 207 patients included collection of data about variables relating to demography, pathology, presentation, smoking, present and past health, performance, surgery, complications, length of stay, mortality, follow up and cause of death. Significance of relationships between medical and surgical problems and the outcome was determined by analyses of variation. Medical problems were present in 79% of patients; correlated with advancing age. Medical problems were not associated with complications, or with inpatient death. Previous cerebrovascular accident. dementia, limited mobility and increasing numbers of problems were associated with prolonged stay. Prolongation of stay, however, was related mainly to surgical complications. Smoking, which was present in 50% of patients, did not alter performance status, stage or substage, stay or survival significantly. Smoking and respiratory complications were associated significantly. Patients with heart or peripheral vascular disease had significantly poorer survival (P= 0.07) than those without those problems. Survival was reduced significantly for patients known to have diabetes, cardiovascular and cerebrovascular disease and limited mobility. Other malignant neoplasms were responsible for 18% of deaths which were unrelated to colorectal cancer. Residual or recurrent colorectal cancer had a more rapid adverse influence upon outcome than did medical problems. Attention to preventative therapy of cardiovascular disease during follow up might improve survival of patients who have resections for colorectal carcinomata.     

大肠癌肝转移的诊断与治疗

目的：总结大肠癌肝转移的治疗经验。方法：回顾126例大肠癌肝转移患者的临床资料。比较分析了肝转移灶切除与综合治疗两组病人的治疗效果。结果：手术切除组1，3，5年生存率分别为81.6%(31/38),44.4%(8/18）和20％（2／10），而综合治疗组分别为44.3%,21.6%和5.8%。结论：手术中B超检查对肝转移灶的定位诊断最有价值。对肝转移灶应尽可能手术切除，术后辅助化疗等综合治疗，可延长患者生存期。     

IL—2术前皮下免疫治疗对晚期结肠癌病人免疫功能及生存期的影响

目的：观察术前IL－2皮下注射治疗对晚期实施姑息性手术的结肠癌病人免疫功能及生存期的影响。方法：共收集可供分析的50例Dukes分期为D的结肠癌病人,将其分为术前IL－2治疗组和非IL－2治疗组。术后两组病人给予相同的化疗。疗程结束后检测外周血T淋巴细胞亚群、NK细胞杀伤活性、可溶性IL－2受体（sIL-2R）,观察两组免疫功能的变化,对两组病人同时进行2年的随访,观察生存期。结果：术前IL－2治疗组外周血T淋巴细胞亚群CD3^＋、CD4^＋水平及CD4^＋／CD8^＋比值,NK细胞杀伤活性明显高于不用IL－2组;可溶性IL－2受体（sIL-2R）水平在使用IL－2组明显低于未用组。1年生存率用IL－2组也显著高于未用组。结论：术前IL－2皮下注射治疗可以提高晚期结肠癌病人的免疫功能,中和外科手术诱发的免疫抑制,延长患者的生存期.     

INVESTIGATION,FOLLOW-UP AND RECURRENCE AFTER RESECTION OF COLORECTAL CANCER

A study was undertaken to determine the patterns of management in the 2 years following resection of colorectal cancer by Victorian surgeons. Patients were identified by the Victorian Cancer Register as having colorectal cancer diagnosed between 1 July and 31 December 1987. The surgeon of each of the 947 eligible patients who underwent surgery was sent a questionnaire seeking information about the pre-operative investigation. type of surgery and subsequent line of referral. Only 16% of colonic cancers and 39% of rectal cancers were biopsied pre-operatively and colonoscopy was undertaken in one-half and one-third respectively. Of the 737 responses, 555 patients were considered to have had curative surgery, and details of their follow-up during the four 6-month periods following surgery was analysed; this includes the effect of tumour stage and surgeon activity on the use and frequency of each test. Most patients had a clinical examination in each of the 6 month periods, but almost half did not have a colonoscopy and two-thirds did not have the serum CEA level measured at all. Only one in eight had a chest X-ray and fewer had the liver scanned during this 2 year period. Eighty-two patients (20% of those satisfactorily followed) suffered a recurrence during this period. Twenty-six were asymptomatic at the time of recurrence and were diagnosed by a routine test and of these, eight were diagnosed by tests used infrequently. Sixteen (20%) were considered surgically curable.     

大肠癌术后围手术期死亡11例原因分析

1991年始手术治疗大肠癌612例，术后围手术期死亡11例，死亡率1.8%，手术期死亡与肿瘤、手术、患者等因素有密切关系，提出早期发现梗阻性大肠癌；合理选择高龄高危晚期大肠癌的手术方式、提高手术质量；加强围手术期的处理以降低死亡率。     

PREVIOUS INTRAVENOUS CHEMOTHERAPY DOES NOT ALTER RESPONSE RATE OR SURVIVAL TIME OF PATIENTS WITH HEPATIC METASTASES FROM COLORECTAL CANCER TREATED BY HEPATIC ARTERY CHEMOTHERAPY

Background : The present paper addressed the issue of whether pretreatment with intravenous (IV) chemotherapy affects response rate or survival in patients receiving hepatic artery chemotherapy (HAC). Methods : Case note reviews of 164 patients treated in a teaching hospital from June 1990 to July 1996 were carried out. Results : The response rate and carcino-embryonic antigen (CEA) fall in the two groups was almost identical. There was a nonsignificant survival advantage in the non-pretreatment group. Conclusions : Previous administration of IV chemotherapy did not affect the CEA response of patients receiving HAC.     

老年人大肠癌患者内镜与临床分析

目的：探讨老年大肠癌患者的特点。方法：分析120例老年大肠癌的结肠镜检查结果、临床表现及手术治疗情况。结果：（1）老年大肠癌患者以黏液血便为主，占85％。（2）左半结肠多见，以直肠癌检出率最高；（3）直肠癌肛诊阳性率为86％，结肠癌诊断大肠癌的准确率为99％。（4）BorrmannⅠ、Ⅱ、Ⅲ型大肠癌手术根治率分别为83％，82％及53％。结论：老年患者大肠癌发生率较高，以左半结肠多见，病程长，分化好。结肠镜检查可判断大肠癌的部位、范围和程度，但只能为选择手术方式提供参考。     

PERITONECTOMY AND INTRAPERITONEAL CHEMOTHERAPY IN APPENDICEAL AND COLORECTAL CANCER

Background : Peritoneal spread of gastrointestinal malignancies has been regarded as an incurable disease, and treatment has been aimed at short-term palliation. The use of cytoreductive surgery, including peritonectomy procedures and intraperitoneal chemotherapy, has been proposed with the intention of prolonging survival, and perhaps curing patients with peritoneal carcinomatosis from appendiceal and possibly colon cancers. A series of eight patients who have undergone this procedure at St George Hospital is presented, and the results obtained by other groups are reviewed. Method : Eight patients fitted the criteria for peritoneal carcinomatosis between January 1996 and November 1998. In seven patients this was secondary to appendiceal or colon cancer, and one patient had signet ring cancer of the uterus. The surgical treatment involved removing all macroscopic evidence of disease, and this was followed by early postoperative intraperitoneal chemotherapy. Results : The eight patients (seven female, one male) ranged in age from 25 to 67 years. There were seven complications, including two patients with pelvic abscesses, and one patient who developed Tenchkoff catheter occlusion. There were three deaths, one due to pelvic sepsis after 30 days, and the other two were due to metastatic disease. Of the remaining five patients, two have developed recurrence and three remain disease-free. Conclusion : The results of peritonectomy and intraperitoneal chemotherapy for appendiceal tumours are encouraging. The role in colorectal cancer is less clear, although there are some reports that suggest a benefit.     

K-RAS MUTATION AND LOSS OF HETEROZYGOSITY OF CHROMOSOME 17P AND SURVIVAL IN COLORECTAL CANCER

Background : The development of colorectal cancer (CRC) is thought to be a multistage process involving alterations to several types of genes, including oncogenes and tumour suppressor genes. This study examined the associations between allelic deletions of chromosome 17p in the region of the p53 gene and K-ras gene mutation and survival among CRC patients. Methods : Resected specimens from 233 patients were examined. Point mutation of codon 12 of K-ras was assessed using a modified polymerase chain reaction method. Allelic deletion of 17p was demonstrated by loss of heterozygosity (LOH) with the marker Mfd144. Results : Fifty-seven tumours (24%) showed somatic point mutation of codon 12 of K-ras and 86 tumours (37%) showed LOH of Mfd144. There were 107 tumours (46%) with either K-ras mutation or LOH and 18 tumours (8%) with both. Compared with patients with neither alteration, significantly poorer survival was experienced only by those with both alterations (P= 0.015). However, when this variable was introduced into a multivariate analysis controlling for the patient's age and tumour stage, it failed to show a statistically significant independent effect on survival. Conclusions : Point mutation of K-ras and LOH of Mfd144 in CRC does not add to the prognostic information already available from clinicopathological staging.     

COMMUNITY (MIS)UNDERSTANDING OF COLORECTAL CANCER TREATMENT

Background: A study was undertaken to assess community understanding of colorectal cancer symptoms and colorectal cancer treatment. Methods: A computer-assisted telephone survey was undertaken to interview 1000 men and women aged 40–60 years. Results: Overall there was a considerable lack of information in the community about colorectal cancer symptoms and treatment. Men were less knowledgeable than women, and 28% of men were unable to name any symptoms of bowel cancer. Although surgery was mentioned by 53% of the sample, a third could not name any treatments. Most responses to questions about the effects of treatment related to chemotherapy-related disturbances and the possibility of having a colostomy bag postoperatively. Conclusions: There is inaccurate information in the community about colorectal cancer symptoms and treatment. This may inhibit involvement in screening programmes or delay presentation for therapy, as a result of undue concern about the prospects of treatment.     

INTRA-OPERATIVE ULTRASOUND FOR THE DETECTION OF HEPATIC METASTASES FROM COLORECTAL CANCER

The aim of this study was to compare the accuracy of intra-operative ultrasound (IOUS) with other imaging modalities and with surgical palpation in detecting liver metastases from colorectal cancer (CRC). Intra-operative ultrasound was performed in 100 patients undergoing surgery for CRC. All patients had pre-operative liver function tests, transcutaneous ultrasound and computerized tomography (CT) scan of the liver. The liver was palpated intra-operatively by a surgeon who was unaware of the pre-operative findings. The liver was then assessed by IOUS. Intra-operative ultrasound detected more patients with metastases than either CT scan, transcutaneous ultrasound or surgical palpation. It also detected a greater number of smaller metastases in these patients and allowed better anatomical definition compared with pre-operative investigations.     

MORBIDITY AND MORTALITY AFTER SINGLE- AND DOUBLE-STAPLED COLORECTAL ANASTOMOSES IN PATIENTS WITH CARCINOMA OF THE RECTUM

Background : The optimal method of restoring intestinal continuity after rectal resection has been controversial. This study aims to compare the morbidity, mortality and survival of patients having either single-stapled (SS) or double-stapled (DS) colorectal anastomoses following resection of the rectum for cancer. Methods : Peri-operative and long-term follow-up data were prospectively documented in all patients undergoing rectal resection for carcinoma with a stapled anastomosis at our institution over a 14-year period. Patients were stratified by anastomotic technique (SS or DS). Peri-operative mortality, complications potentially related to anastomotic technique and cancer-related outcome were compared. Results : Two hundred and thirty-five patients had SS and 65 patients had DS anastomoses. The groups were well matched for age, sex, and tumour stage. Double-stapled anastomoses were used more frequently in the distal third of the rectum (P < 0.001). The distal margin of resection was not influenced by anastomotic technique. Major anastomotic leakage in 2.9% of SS cases was not significantly different from 6.1% of DS cases, and leakage was not influenced by anastomotic technique at any given level of the rectum. Two-year local recurrence rates were not significantly different between groups (SS 3.5%: DS 5.9%). Conclusions : These results suggest that the double-stapling technique is as safe as the single-stapling technique for constructing an anastomosis after excision of the rectum for cancer, in terms of the risk of leakage, the development of an anastomotic stricture. or local recurrence.     

A SURVIVAL REGRESSION ANALYSIS OF PROGNOSTIC FACTORS IN COLORECTAL CANCER

Background: Many prognostic factors of colorectal cancer are known but their actual clinical validity is still uncertain. The aim of the present study was to verify, on the basis of our experience, the prognostic validy of variables for survival by using survival regression analysis. Methods: From January 1978 to December 1986 the prognostic factors for 192 patients were analysed. These patients had undergone surgical resection for colorectal cancer. The follow up was completed in every patient by the end of December 1992. with a median follow up of 10 years (range 6–14 years). The prognostic factors considered in the statistical analysis were age. sex, size of tumour, site, grade, direct spread, node involvement and stage (according to Astler-Coller and pTNM). Results: Of the prognostic factors, sex was the only one not to show any prognostic significance. In the survival regression analysis we have used an accelerated failure time model (equivalent to the Cox proportional hazard model); age. grade and stage were significant covariables. Conclusions: Although clinical pathological staging (pTNM) appears as a pre-eminent prognostic factor, and as our analysis shows. it needs a further variable (grading), which has been shown to affect the prognosis in a significant way.     

THE MANAGEMENT OF COLORECTAL PERFORATION AND PERITONITIS

Background : Surgical outcomes in patients presenting with colonic perforation or peritonitis tend to be poor. This study was undertaken to determine outcomes in such patients at a time before multiple re-laparotomies were performed. Methods : Retrospective analysis of computer records of all patients presenting acutely to the University Surgical Unit (Wellington School of Medicine) with colonic perforation or peritonitis over a 15-year period. Results : Seventy-three patients, 33 males and 40 females were admitted with either perforation or localized peritonitis of colorectal origin. Of these, 78% were managed as emergencies, but six were admitted electively and found incidentally. Consultant surgeons performed surgery slightly more frequently than registrars. Two patients were managed non-operatively. Forty-one percent received peri-operative blood transfusion and 22% peri-operative total parenteral nutrition. The majority of patients presented with either peritonitis or free perforation in association with diverticular disease. The site of perforation was either ileocolic or sigmoid colonic in the majority of patients. Hartmann'operation was the most commonly performed resection. Respiratory, urinary and wound infections were the most commonly observed postoperative complications. Two patients developed anastomotic leaks (6.3%). The overall persistent intra-abdominal infection rate was 5.5%. Seven patients died following surgery. Conclusions : Resection of the perforated bowel is mandatory and this should be followed by anastomoses in the case of right-sided lesions and a Hartmann'operation or resection, colostomy and mucous fistula in distally situated lesions.     

结直肠癌根治术后短期内再手术的原因和预后

报告结直肠癌根治术后两周内因并发症再手术的46例,约占全部根治术的2.9%.再手术原因包括:肠硬阻30例、吻合口瘘8例、腹部切口裂开6例、腹内疝5例、人工肛回缩及坏死各1例.再手术患者5年、10年生存率均明显低于同一资料中总的结直肠癌根治术后患者的5年、10年生存率.     

结直肠癌同时肝转移的手术疗效分析

目的分析结直肠癌同时肝转移的手术疗效。方法回顾性分析自1996年1月至2004年4月东方肝胆外科医院手术治疗的74例结直肠癌同时肝转移患者,其中同时手术组47例,异时手术组27例。结果无手术后1月内死亡病例,总的术后1、3、5年累积生存率分别为81．1％、41．2％和14．8％;同时手术组术后1、3、5年累积生存率分别为82．9％、40．5％和11．8％;异时手术组术后1、3、5年累积生存率分别为77．8％、42．2％和19．7％,两组比较差异无统计学意义（log-rank,P〉0．05）。两组手术并发症发生率同时组为19．1％,而异时组为11．1％（Х^2,P〉0．05）。原发肿瘤位于直肠共21例,12例行同时手术,9例行异时手术,两组术后生存率比较无明显差异（log-rank,P〉0．05）。结论结直肠癌同时肝转移患者同时手术和异时手术疗效相似,手术并发症无明显增加,同时手术是安全可行的;原发肿瘤位于直肠不能作为选择同时手术的禁忌症。     

A COMMUNITY-BASED HOSPITAL EXPERIENCE WITH COLORECTAL CANCER

Background : Survival figures for patients with colorectal cancer are often based on data from tertiary referral centres for colorectal surgery. The relevance of such data to community-based hospitals is questionable. The aim of the present study was to determine the long-term survival in patients presenting with colorectal cancer to a large community-based teaching hospital. Methods : A search was conducted on the hospital computerized database to determine those patients who were admitted with a diagnosis of colorectal cancer between 1989 and 1994. These records were linked to the Deaths Registry to determine long-term survival. Results : A total of 477 patients were managed at Fremantle Hospital over the 5-year period. Nearly half of these patients (47.6%) presented via the hospital emergency centre. At diagnosis, 57.8% of patients had advanced cancers with either nodal or distant metastases. Surgery was undertaken on 455 patients, with a postoperative mortality of 4.5%. The corrected 5-year survival rate for patients undergoing curative resections (i.e. complete local excision and no evidence of metastases) was 62.9% for colon cancers and 48.2% for rectal cancers. Local recurrence developed in 21.4% of patients with rectal cancers. Conclusions : A majority of patients with colorectal cancers are continuing to present with advanced disease. Earlier diagnosis of these cancers through community-based screening programmes could well serve as an achievable solution to this problem.