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Genetics of rectal cancer.

Two operational subdivisions of hereditary colorectal cancer susceptibility are those with and those without premalignant adenomatous colonic polyp expression. In both of these subdivisions, reliable biomarkers of gene carriage would be of value in patient management as we have previously emphasized. Consideration must also be given to the familial (hereditary) occurrence of inflammatory bowel diseases associating with colorectal cancer susceptibility. The occurrence of rectal cancers should therefore alert the physician to investigate the possibility of a significant family medical history in order to fully elucidate the genetic heterogeneity of susceptibility to this disease. Clinicians should also be alert to the possibility of extracolonic malignancies where probable genetic colorectal cancer susceptibility is evident. Whenever possible, all potential biomarkers should be investigated to aid in definition of genetic heterogeneity.

Colitis↗

Hydrocolonic sonography: a novel screening method for the detection of colon disease?

Hydrocolonic sonography is an easy and harmless technique for the evaluation of the colon wall. In our study, 106 patients were examined by means of hydrocolonic sonography and colonoscopy. The results were compared. Polyps larger than 7 mm were detected, whereas smaller polyps were often missed. Colon cancers were found in 5 patients, and it was possible to stage them. In moderately to severely active forms of inflammatory bowel disease this technique was able to make a differentiation between ulcerative colitis and Crohn's disease. In elderly and very young patients it may well be the primary screening method for evaluating the bowel.

Adult↗

Mucinous cystadenoma of the appendix in a patient with systemic lupus erythematosus.

A 38-year-old female with systemic lupus erythematosus presented with abdominal pain, diarrhea and iron-deficient anemia. Computed tomogram showed a 2 x 4 cm inhomogeneous lesion of the right adnexa. An unusual mass was identified extending from the appendiceal orifice at colonoscopy, and an 8 cm tubular appendix, apparently prolapsed into the cecum, was identified at celiotomy. An appendectomy with cecectomy was performed. On cut section, mucin was extruded from the lumen of the appendix. A mucinous neoplasm of the appendix with mucinous dissection to the serosal surface was reported at the time of frozen section. No gross ovarian pathology or peritoneal implants were noted. Cystadenoma with associated mucocele formation was verified by permanent histology. Mucocele of the vermiform appendix is a rare condition associated with neoplastic transformation in approximately 75% of all cases. Benign mucinous cystadenoma of the appendix should be differentiated from cystadenocarcinoma by frozen section at the time of celiotomy to ensure appropriate treatment. While systemic lupus erythematosus can lead to cutaneous mucinosis, an association with mucinous cystadenoma of the appendix has not been previously reported. Surveillance for metachronous colonic neoplasms is warranted in patients diagnosed with a mucinous neoplasm of the appendix.

Adult↗

Review of recurrent polyps and cancer in 500 patients with initial colonoscopy for polyps.

Five hundred patients with 1240 polyps removed by colonoscopy and polypectomy over a 13-year period are the subject of ongoing follow-up study. Ninety-three percent of the patients have been followed an average of 53 months with a recurrence rate of polypoid disease in 26 percent, of which approximately 7 percent demonstrated malignant changes. This compares to a rate of 7 percent metachronous cancer in patients with a malignancy demonstrated at any time in the past. The highest risk group for recurrence are patients with more than four polyps at initial colonoscopy, with a 59 percent recurrence rate. The following recommendations for follow-up are made: 1) Flexible sigmoidoscopy is adequate yearly follow-up if the original polyps are confined to the rectum and sigmoid. 2) Colonoscopy should be carried out the first year if the original polyps are beyond the rectum and sigmoid, and yearly until the colon is cleared of recurring lesions. 3) Colonoscopy is indicated in patients with cancer before surgery if possible; if not, within six months after resection. 4) Interval six-month examinations are indicated in patients with colon cancer and multiple synchronous polyps until the colon is cleared. 5) Large, sessile polyps resected piecemeal require a three-month follow-up until gone. 6) When the above conditions are met, colonoscopy at three-year intervals is adequate for long-term follow-up of neoplastic polyps to detect and prevent early malignancy.

Adult↗

The significance of diminutive colonic polyps found at flexible sigmoidoscopy.

In order to determine the importance of identification and follow-up of diminutive colonic polyps (DCPs) (i.e., those less than or equal to 5 mm in diameter), we studied 3006 patients undergoing flexible sigmoidoscopy. DCPs were found in 315 patients (10.5%). Biopsy of these lesions showed them to be nonneoplastic in 187 patients (59.4%) and neoplastic in 128 (40.6%). Overall, 35% of all DCPs found were neoplastic. Gross appearance of the lesions was found to be an unreliable means of predicting their histologic makeup. Of the 128 patients with neoplastic DCPs, 73 underwent further examination with barium enema and colonoscopy. Synchronous lesions were found in 57.5%. In 10 patients, synchronous lesions were of significance, including carcinomas, adenomas greater than or equal to 8 mm in diameter, or severely dysplastic adenomas. We conclude that all DCPs discovered at sigmoidoscopy should be biopsied and in patients in whom DCPs are found to be neoplastic, colonoscopy should be undertaken to search for proximal synchronous lesions.

Adenoma↗

Activation of c-Src by receptor tyrosine kinases in human colon cancer cells with high metastatic potential.

Recent data suggest that signal transduction may have a critical role in the development and regulation of the metastatic phenotype. Here, we investigated the role of c-Src activation in the process of human colon cancer metastasis to the liver. Our data, derived from two different sets of human colon cancer cell line metastatic variants, suggest that not only do highly-metastatic cells display constitutively elevated c-Src protein kinase activity when compared to poorly metastatic cells, but also that receptor tyrosine kinases participate in the ligand-activation of c-Src above basal levels. Specifically, the epidermal growth factor receptor (EGFR), p185HER2/Neu and the hepatocyte growth factor receptor (c-Met) appear to be linked to the process because they preferentially activate c-Src in highly-metastatic cells. EGFR was found to associate with c-Src in colon cancer cells and specific inhibitors of the EGFR resulted in a reduction of c-Src activity to basal levels. In addition, c-Src transfectants displayed partially-activated EGFRs, suggesting a feedback role for c-Src in the regulation of the EGFR. p185HER2/Neu was also identified in immunocomplexes of c-Src following ligand activation of the EGFR, but only in highly-metastatic cells. Collectively, these observations suggest a paradigm whereby c-Src interacts with multiple cell-surface growth factors in a catalytic fashion for the development of tumor cells with metastatic potential.

Colonic Neoplasms↗

Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. The National Polyp Study Workgroup.

BACKGROUND: The identification and removal of adenomatous polyps and post-polypectomy surveillance are considered to be important for the control of colorectal cancer. In current practice, the intervals between colonoscopies after polypectomy are variable, often a year long, and not based on data from randomized clinical trials. We sought to determine whether follow-up colonoscopy at three years would detect important colonic lesions as well as follow-up colonoscopy at both one and three years. METHODS: Patients were eligible if they had one or more adenomas, no previous polypectomy, and a complete colonoscopy and all their polyps had been removed. They were randomly assigned to have follow-up colonoscopy at one and three years or at three years only. The two study end points were the detection of any adenoma, and the detection of adenomas with advanced pathological features (defined as those > 1 cm in diameter and those with high-grade dysplasia or invasive cancer). RESULTS: Of 2632 eligible patients, 1418 were randomly assigned to the two follow-up groups, 699 to the two-examination group and 719 to the one-examination group. The percentage of patients with adenomas in the group examined at one and three years was 41.7 percent, as compared with 32.0 percent in the group examined at three years (P = 0.006). The percentage of patients with adenomas with advanced pathological features was the same in both groups (3.3 percent). CONCLUSIONS: Colonoscopy performed three years after colonoscopic removal of adenomatous polyps detects important colonic lesions as effectively as follow-up colonoscopy after both one and three years. An interval of at least three years is recommended before follow-up colonoscopy after both one and three years. An interval of at least three years is recommended before follow-up examination after colonoscopic removal of newly diagnosed adenomatous polyps. Adoption of this recommendation nationally should reduce the cost of post-polypectomy surveillance and screening.

Adenoma↗

Colonic polyps: experience of 236 Indian children.

OBJECTIVES: We studied the clinical spectrum, histology, and malignant potential of colonic polyps in Indian children (< or =12 yr). METHODS: Two hundred thirty-six children with colonic polyps were studied from January 1991 to October 1996. They were evaluated clinically and colonoscopic polypectomy was done. Children with five or more juvenile polyps were labeled as having juvenile polyposis and serial colonoscopic polypectomies were done every 3 wk. Colectomy was performed when there were intractable symptoms or clearing of the polyps by colonoscopy was not possible. Histological examination of the polyps was done. Follow-up colonoscopy was done in children with juvenile polyposis only. RESULTS: The mean age of these children was 6.12 +/- 2.7 yr, with a male preponderance (3.5:1). Rectal bleeding of a mean duration of 14 +/- 16 months was the presenting symptom in 98.7%. Solitary polyps were seen in 76%, multiple polyps in 16.5%, and juvenile polyposis in 7% (n = 17) of the children. A majority (93%) of the polyps were juvenile and 85% were rectosigmoid in location. Adenomatous changes, seen in 11%, were more common in juvenile polyposis (59%) than in juvenile polyps (5%). Among those with juvenile polyposis, colon clearance was achieved in eight, six required colectomy for intractable symptoms, and three were still on the polypectomy program. Polyps recurred in 5% of children with juvenile polyps and 37.5% of those with juvenile polyposis. CONCLUSIONS: Juvenile polyps remain the most common colonic polyps in children. A significant number of cases of polyps are multiple and proximally located, which emphasizes the need for total colonoscopy in all. Juvenile polyps should be removed even if asymptomatic because of their neoplastic potential. Colonoscopic polypectomy is effective even in juvenile polyposis. Surveillance colonoscopy is required in juvenile polyposis only.

Child↗

[Screening study for early detection of intestinal tumors after urinary diversion].

The increased risk of colon carcinoma following urinary diversions via colon makes knowledge about preneoplastic changes necessary. In 30 ureterosigmoidostomy patients with a mean observation period of 16 years flexible sigmoidoscopy with biopsies and nitrosamine analysis of the feces/urine mixture have been performed. In the biopsies we found an increased sialomucin concentration at the ureterocolonic anastomosis in 29.2%--sialomucin is supposed to be a preneoplastic change--with no significant difference to the mucosa periureteral and in the rectum. In 58.3% we found chronic inflammation at the anastomosis, in 29.2% periureteral and 4.2% in the rectum. 2/30 patients developed adenocarcinoma, 1 patient an atypia and 1 patient a juvenile polyp. The nitrosamine excretion of the ureterosigmoidostomy patients were significantly increased compared to 20 healthy controls with no correlation to the histology at the anastomosis or the observation time. Because of the multilocular presence--colon carcinomas develop only at the anastomosis--sialomucin and chronic inflammation seem to be no preneoplastic changes in urinary diversions. The nitrosamine analysis is not suitable for routine follow-up as well.

Adenocarcinoma↗

[Precancerous lesions of the colon and rectum].

We discussed significance of various kinds of precancerous lesions of the colon and rectum. Colonic adenoma was most important as a histogenetic background of colonic carcinoma, as it has been widely accepted. The first malignant transformation of adenoma seemed to occur at the relatively superficial layer of the central portion of adenoma in many cases. Growth rate of adenoma largely depended on cellular atypia. Six of twenty-seven patients with Peutz-Jeghers syndrome had advanced carcinoma and/or carcinoma in Peutz-Jeghers polyp. In general, malignant transformation in the polyp was higher in frequency in polyps more than 3.0 cm in the largest dimension. Significance of precancerous lesions in juvenile polyp, hyperplastic polyp, ulcerative colitis, Crohn's disease and radiation colitis was briefly presented.

Adenoma↗