Colorectal cancer

Colorectal cancer is a leading cause of morbidity and mortality with about 300,000 new cases and 200,000 deaths in Europe and the USA each year. Published trials have established a role for chemotherapy in colorectal cancer, in the adjuvant setting for Dukes C colon cancer, with an absolute survival benefit of about 5% and in advanced colorectal cancer, for which it improves quality of life and increases survival by 6-12 months. For rectal cancer, radiotherapy decreases rates of local recurrence and, in locally advanced disease, successfully palliates pain, tenesmus, and bleeding. The evolving understanding of colorectal carcinogenesis, in particular recognition of vital genes that may be mutated or lost during tumour development, has been translated into innovative gene therapy techniques. Finally it is increasingly apparent that surgical site specialisation and a multidisciplinary approach (including surgeons, pathologists, and oncologists) may lead to optimum outcomes for patients with colorectal cancer.     

Colorectal cancer screening

Signals elicited by transforming growth factor-beta (TGF-beta) superfamily ligands are generated following the formation of heteromeric receptor complexes consisting of type I and type II receptors. TAK1, a member of the MAP kinase kinase kinase family, and its activator, TAB1, participate in the bone morphogenetic protein (BMP) signaling pathway involved in mesoderm induction and patterning in early Xenopus embryos. However, the events leading from receptor activation to TAK1 activation remain to be identified. A yeast interaction screen was used to search for proteins that function in the pathway linking the receptors and TAB1-TAK1. The human X-chromosome-linked inhibitor of apoptosis protein (XIAP) was isolated as a TAB1-binding protein. XIAP associated not only with TAB1 but also with the BMP receptors in mammalian cells. Injection of XIAP mRNA into dorsal blastomeres enhanced the ventralization of Xenopus embryos in a TAB1-TAK1-dependent manner. Furthermore, a truncated form of XIAP lacking the TAB1-binding domain partially blocked the expression of ventral mesodermal marker genes induced by a constitutively active BMP type I receptor. These results suggest that XIAP participates in the BMP signaling pathway as a positive regulator linking the BMP receptors and TAB1-TAK1.     

Colorectal cell kinetics

The assessment of cell proliferation in colorectal tissue may provide information with both prognostic and therapeutic implications. A variety of methods are available, including flow cytometric estimations of S phase fraction, immunohistochemical and autoradiographic visualization of exogenous and endogenous proliferation proteins, and morphological and stathmokinetic techniques. There is some correlation between Dukes stage and proliferation state features, and there is increased proliferative activity throughout the adenoma-carcinoma sequence. Data on cell proliferation rates are difficult to obtain. When correctly applied, the metaphase arrest technique remains the 'gold standard' of measuring proliferation, but its usefulness in clinical practice is limited. Recent studies have employed dual measurement flow cytometry and double labelling techniques to produce rate data.     

Colorectal cancer emergencies

From the variety of operative choices for colorectal cancer emergencies, it is difficult to select the best one for the individual patient, who is often old and frail. Appropriate handling of the emergency situation is essential. Treatment of the patient's malignant disease is secondary. The choice of surgical procedure in colorectal cancer emergencies must be based on sound clinical judgement and should be in keeping with the technical skill and experience of the individual surgeon. Surgical failures have major negative consequences not only for the immediate postoperative course, but also for long-term survival and quality of life of these patients.     

Colorectal cancer complicating pregnancy

Colorectal carcinoma complicating pregnancy is rare but associated with a high maternal mortality rate. Stage for stage the survival data are the same for pregnant patients and nonpregnant controls, however diagnosis is often delayed due to pregnancy-associated gastrointestinal symptoms masking cancer symptoms. A high degree of suspicion, especially in high-risk patients, is the key to early detection and improved prognosis. Digital rectal exams, occult fecal blood tests, and flexible sigmoidoscopy or colonoscopy are performed as indicated. Treatment primarily consists of en-bloc resection of the malignancy and regional lymph nodes; timing of colorectal surgery and delivery are based upon clinical presentation, fetal age, and maternal desires.     

Colorectal cancer and hemoccult

Hemoccult slides have been used in an attempt to determine their usefulness as a screening method for the detection of colorectal neoplasia. Two methods have been used. In the first, 300 unprepared patients had an immediate single-stool specimen tested with Hemoccult. Only nine patients were referred for investigation after this single test, and no case of colorectal neoplasia was discovered. In the second method over 2,500 three-stool test kits were distributed to the public, of which 1,160 (46%) have been returned and tested. Positive tests were obtained in 68 patients. Follow-up of 58 of these patients has led to the detection of three cases of carcinoma of the colon and nine cases of benign polyps greater than one centimetre in diameter. The cost of screening patients with a three-stool test has been calculated to be $2.50 per patient.     

Colorectal cancer--an undertreated disease

PURPOSE: Because several macular dystrophies are caused by mutations in the peripherin/RDS gene, we examined autosomal dominant and sporadic cases of central areolar choroidal dystrophy for mutations in the peripherin/RDS gene. METHODS: DNA sequence analysis of the peripherin/RDS gene was performed in four sporadic cases and in ten affected and nine unaffected individuals from seven families with autosomal dominant central areolar choroidal dystrophy. RESULTS: An Arg-142-Trp mutation in the peripherin/RDS gene was found in ten affected family members in seven families. Among these, a 69-year-old man with the Arg-142-Trp mutation, who was unaffected six years before blood sample analysis, showed a parafoveal area of chorioretinal atrophy. The 65-year-old sister of this family had the Arg-142-Trp mutation with no macular abnormalities, but she might still develop central areolar choroidal dystrophy at an older age. No mutation was found in the four sporadic cases. CONCLUSION: Autosomal dominant central areolar choroidal dystrophy, studied in seven families, is caused by an Arg-142-Trp mutation in the peripherin/RDS gene.     

Colorectal lesions predisposing to cancer

Precursors of colorectal carcinoma are adenomatous polyps, sporadic or arising in familial adenomatous polyposis and Lynch syndrome and chronic inflammatory lesions related to ulcerative colitis and Crohn's disease. The adenoma-carcinoma sequence is well established and early detection and removal of colorectal adenomas is thought to prevent colorectal cancer in high risk asymptomatic persons, i.e. subjects over 45 years, with personal or familial history of adenomas and colorectal cancers. The precancerous potential of adenomatous polyps varies according to tissue type, with increased risk with the extent of the villous component, high grade of dysplasia, large size greater than 1 cm and multiple adenomas. The development of de novo colorectal cancer from normal mucosa with flat adenomas has been recently emphasized. The risk of colonic cancer in patients with ulcerative colitis and Crohn's disease is controversed.     

Colorectal manifestations of endocrine disease

PURPOSE: The aim of this review is to alert the colon and rectal surgeon to the colorectal manifestations of endocrine disease. METHODS: This report was obtained by a review of the medical literature. Endocrine disease may initially present as a symptom felt to be referable to colorectal disease. Furthermore symptoms of well-established endocrine disorders may have refractory colorectal symptoms. RESULTS: Constipation is the most common gastrointestinal symptom of diabetics; however, in patients with brittle diabetes, diarrhea may be chronic and intermittent. Unexplained diarrhea, despite an exhaustive work-up for an etiology, should alert the clinician to the possibility of a pancreatic endocrine tumor. Thyroid disorders, depending on activity of the gland, may have refractory constipation, diarrhea, or steatorrhea as the only presenting symptoms. Constipation is a common symptom of hypercalcemia, secondary to hyperparathyroidism. Primary hyperparathyroidism has been associated with increased incidence of malignancies, specifically of colonic origin. In patients with acromegaly a threefold to eightfold increased risk of colon carcinoma or adenomatous polyps is seen. Chronic adrenal insufficiency may present initially as diarrhea and malabsorption. The adrenal gland is a frequent site of metastases from colorectal cancer. Pheochromocytomas may be a cause of occult gastrointestinal bleeding or ischemic colitis. CONCLUSION: Unexplained symptoms referable to the colon and rectum should alert the clinician to the possibility of an underlying endocrine disorder.     

Colorectal cancer detection and screening

Colon cancer is a leading cause of death in the United States and is estimated to cause 56,500 deaths during 1998. Most cancers evolve from adenomatous polyps. Screening asymptomatic average-risk individuals is recommended to reduce colorectal cancer mortality by detection and removal of adenomatous polyps.     

Colorectal cancer in the young patient

Although predominantly a disease of older adults, colorectal cancer affects the younger population with an incidence of two to six per cent. It is thought to carry a less favorable prognosis in the young than in the general population. This may be due to advanced stage of the tumor at diagnosis. This study is composed of 37 patients, aged 40 and younger, treated over a 20-year period for colorectal cancer at Louisiana State University Medical Center-Shreveport and E. A. Conway Hospital. It was performed to investigate the incidence, stage at diagnosis, and prognosis of colorectal cancer in these young patients. The location of the primary tumor was fairly evenly distributed throughout the colon and rectum in this population. Pain, weight loss, rectal bleeding, and nausea and vomiting were the most common presenting symptoms. A family history of colon cancer or premalignant lesions were not risk factors in this study. Seventy per cent of all patients were treated with curative intent, and 42 per cent of these patients developed recurrent disease. The patients in this review presented with a higher incidence of advanced disease. Thirty-seven per cent of the lesions were Duke's C and 22 per cent were Duke's D, with poor 5-year survival (11% and 0%, respectively) when compared with national studies. The absolute 5-year survival for all young patients with colorectal cancer was 26 per cent (5 of 19 patients). It is important for the surgeon to be aware of the potential for colorectal cancer in young patients and to take an aggressive approach to the diagnosis and early treatment of the disease.     

Colorectal surgery using a biofragmentable anastomotic ring

To compare the efficacy of the biofragmentable anastomotic ring (Valtrac-BAR, Davis and Geck, Medical Device Division, Danbury, CT, USA) with conventional anastomotic techniques, 30 patients who underwent colorectal surgery from August 1993 to March 1995 were retrospectively studied. The use of the BAR was also compared with conventional techniques including hand-sewn sutures in 30 patients and an end-to-end anastomosis (EEA) stapler in 24 patients. There were 17 men and 13 women in the BAR group with ages ranging from 37 to 80 years, 18 men and 12 women in the hand-sewn group with ages ranging from 41 to 82 years and 14 men and 10 women in the EEA group with ages ranging from 38 to 72 years. Surgical indications included: 25 colon cancers and five rectal cancers in the BAR group; 27 colon cancers and three rectal cancers in the hand-sewn group; and six colon cancers and 18 rectal cancers in the EEA group. There was no conversion to other anastomotic methods. Most of the patients tolerated a low-residual diet from the fifth post-operative day. No clinical leakage or stricture was noted. Only seven patients were aware of the passage of BAR fragments. The mean hospital stay was 14.1 days. There were no significant differences among these techniques in the return of bowel function, the incidence of surgical complications, including anastomotic leakage, or the length of hospitalization. BAR anastomosis was more time efficient than conventional techniques. Our results confirmed that BAR was an ideal sutureless alternative for anastomosis in colorectal surgery.     

Colorectal stapled anastomoses. Experiences and results

The mechanism whereby passive Rh (D) immunoglobulins suppress the fetomaternal alloimmunization is still unclear. New in vitro tests are needed to better characterize the functional properties of polyclonal anti-Ds. The DAF assay was developed to monitor the antibody-dependent cell-mediated cytotoxicity (ADCC) and the phagocytosis of anti-Rh (D)-sensitized RBCs by effector cells. The principle of this test is based on the oxydization of the 2,7-diaminofluorene (DAF) by the pseudoperoxidase activity of free hemoglobin. The reaction is proportional to the hemoglobin concentration. This test was performed to determine and emphasize the efficacy of different polyclonal anti-D immunoglobulin preparations to mediate lysis and phagocytosis of sensitized RBCs by human peripheral mononuclear cells. The functional properties of different human RhD monoclonal antibodies were also analyzed and compared. The test was found to be convenient to perform and allowed the avoidance of radioactive labelling of RBCs for ADCC studies. It is mainly useful for the direct quantitation of phagocytosis.     

Colorectal schistosomiasis: report of three cases

The facility for mass movement of segments of our world populations creates the need for physicians to recognize and manage diseases not seen in native patients. Such a need has occurred in New York City, where schistosomiasis, with its protean manifestations has been seen with increasing frequency. The cases of three patients who had different clinical manifestations of infestation by S. mansoni are presented. Clinical, radiologic, and pathologic features are discussed. To avoid delay in treatment, physicians must consider the possibility of this disorder in cases of patients from areas of endemic schistosomiasis.     

Colorectal cancer in idiopathic inflammatory bowel disease

The development of colorectal cancer is the most serious long-term problem faced by patients with extensive ulcerative colitis and Crohn's colitis, with an incidence 20-fold higher and an average age of onset 20 years younger than colorectal cancer in the general population. This report summarizes the epidemiology, pathology, and recent advances in the molecular pathogenesis of colorectal cancer in inflammatory bowel disease and of its acknowledged precursor, mucosal dysplasia. It also reviews the rationale behind the use of endoscopic surveillance for dysplasia as a means of reducing cancer mortality, as well as some of the issues involved in its effective implementation.     

Colorectal cancer. Clinical and pathologic features

Despite an improved understanding of the pathogenesis of colorectal cancer and the technical ability to alter its natural history in a large proportion of average and high-risk patients, this cancer remains deadly. There has been no significant change in incidence or survival rates over the past 40 years. This indicates a continued need for earlier detection of polyps and cancers, aggressive surgery for the primary tumor, and improved multimodality treatment for metastatic disease.