[Synchronous multiple carcinomas of the colon].
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The prognostic and biological meaning of the association of colonic cancer with hyperplastic polyps (HP) is not as well known as that with adenomatous polyps (AP). In order to gain some insights into this matter, we have retrospectively studied two hundred and twelve patients with colon-rectal carcinoma in which 64 (30.18%) had synchronous AP, 24 (11.32%) had synchronous HP, 13 (6.13%) had both AP and HP and 111 had no synchronous polyps (52.36%). The 34 cases of synchronous HP, whether or not associated with AP, were located in the same colonic segments of the cancer and were found usually in the sigmoid-rectum. The AP were found throughout the colon-rectum with a similar rate of association with the cancer in each segment. The cancer associated with HP have a higher prevalence in the better prognostic stages of both Dukes and Jass-Morson systems. Conversely both AP and AP+HP associated cancers exhibit prevalences rates higher in the worst prognostic stages. Our observations suggest that separate factors might promote the growth of HP and AP and that a relationship between colonic cancer and synchronous HP might exist and differ from that demonstrated for AP and colonic cancer.
Under examination there were 292 patients. An analysis of results of treatment enabled the authors to conclude that surgical treatment of patients with diffuse polyposis of the colon is the method of choice. The method and volume of operations must be determined according to the involvement of the colon in polyposis, the age and state of the patients. The best method of surgery is a one-step radical operation-subtotal resection of the colon. Polyps concomitant to cancer of the colon should be ablated before the main operation since their histological analysis can change the volume of the planned radical operation. When choosing the method of surgical intervention for patients with primary-multiple cancer against the background of polyps the total portion of the colon with polyps should be ablated.
BACKGROUND: Registries for patients with familial adenomatous polyposis (FAP) can improve patient management. However, in relation to colorectal cancer, a critical review has not previously been undertaken of the effectiveness of screening and surgical protocols within a registry. METHODS: A review was undertaken of 63 gene carriers who received primary treatment for FAP between 1987, when the Northern Region Polyposis Registry was formed, and 1995. RESULTS: In some gene carriers with colorectal cancer, surgery was delayed because of social factors or unpleasant surgical experiences in the family. Colonoscopy failed to detect five colorectal cancers. CONCLUSIONS: Delays in treatment still occur in patients with FAP and colorectal cancer, often because of complex social problems and patients' fear of surgery. If multiple colorectal polyps are present, colonoscopy is not a reliable screening test for malignancy and prophylactic surgery is indicated, preferably before the patient is 20 years old.
The data on 120 cases of primary multiple cancer of the large bowel and 91 cases of diffuse polyposis are discussed. The development, duration and morphological features of metachronous and primary cancer arising after resection of the bowel varying in type and extent were studied. The results pointed to a high risk of cancer in such cases. The study also pointed to disturbances in the enterohepatic system and bile acid circulation as a factor of carcinogenesis in the bowel.
UNLABELLED: The quantitation of DNA and growth fraction in the different step from dysplastic to neoplastic process in large bowel is the aim of this study. 70 colonic polyps were studied. The fresh specimens were processed and DNA analysis was carried out using a Partec CA II flow cytometer and the growth fraction was tested with KI-67 monoclonal antibody. The percentage of S-phase cells has been calculated with the Multicycle program. Our results demonstrated that 7 adenomas were tubulo-villous with mild dysplasia, 39 with mild-moderate dysplasia, 1 with severe dysplasia, 5 were polypoid carcinomas, 2 juvenile polyps, 1 polypoid leiomyoma, 1 inflammatory fibroid polyps. DNA analysis showed a diploid DNA content in non adenomatous polyps, in all adenomas with mild dysplasia, in 37 with mild-moderate dysplasia, in 8 cases with moderate-severe dysplasia and 1 cancer. Aneuploidy was discovered in 2 cases with mild-moderate dysplasia, in 6 cases with moderate-severe dysplasia, in the case of severe dysplasia and in 4 cases of carcinomas. Best indexes of linear correlation (Pearson's r) has been found between S-phase and DNA index (r = .75) and between S-phase and KI-67 (r = .82). IN CONCLUSION: 1) No relationship was found between DNA content and age, sex, size and location of polyps. 2) Aneuploidy is strictly related to moderate-severe grade of dysplasia therefore it is an important element in the development of adenomacarcinoma sequence. 3) DNA-index, S-phase and KI-67 are strictly related.
Telomerase and telomere length are increasingly studied as prognostic markers in malignancy. Telomerase is also known to be expressed in certain nonmalignant cells, although generally at low levels. We investigated telomerase activity and telomere length in premalignant, malignant, inflammatory, and normal colon specimens to determine whether significant differences exist and whether telomerase may serve as a marker for early- or late-stage colorectal cancer. Telomerase activity was evaluated in 130 frozen specimens from human colon cancer (n = 50), adjacent normal colon tissue (n = 50), colon polyps (n = 20), and colitis (n = 10) using a modified telomeric repeat amplification protocol assay, and telomere length was assessed by terminal restriction fragment analysis. High to moderate levels of telomerase activity were detected in 90% of colorectal tumors. Weakly positive activity was detected in 10%. None of the normal tissues exhibited telomerase activity. In polyps and colitis, telomerase activity was found in 60% (12 of 20) and 40% (4 of 10), respectively. Telomerase activity in both nonmalignant lesions was 25- to 54-fold lower than that detected in colon cancer (P < 0.001). We found a positive correlation between tumor cell infiltration determined in cryostat sections and telomerase activity (r = 0.886; P > 0.0001). Late-stage tumors (Dukes C + D) demonstrated increased telomerase activity compared to early-stage tumors (Dukes A + B). Telomere restriction fragments in colon tumors had peak values of 4.8 +/- 1 kbp that were significantly and consistently shorter than those of the adjacent normal tissues (7.54 +/- 1.3 kbp), polyps (7.5 +/- 0.7 kbp), and colitis specimens (7.7 +/- 0.5kbp; P < 0.0001). Telomeres were 0.6 kbp longer in tumors with high telomerase activity and in late-stage cancers (Dukes C + D) compared to those in tumors with low telomerase activity and in early-stage cancers (Dukes A + B). Our data demonstrate that telomerase in colon cancer was commonly acquired, and activity was higher than that in polyps and colitis. However, weak telomerase activity was detected in premalignant and inflammatory lesions. Telomeres in colon cancer were considerably shorter, an indication of extensive cell proliferation and population divisions, whereas adjacent normal colon specimens, polyps, and colitis had comparable telomere lengths. Our results indicate that increased telomerase activity occurs in colon cancer cells that have undergone extensive telomere shortening relative to surrounding normal tissues and in which telomerase-induced stabilization of telomeres may be critical for the continued proliferation of the malignant clone. The link between telomerase activity and stage suggests that telomerase is up-regulated as a function of increased tumor cell invasion, tumor progression, and metastatic potential in colon cancer.
Screening colonoscopy was performed on 119 asymptomatic elderly men with no other risk factors for colonic neoplasms. Ninety adenomas were detected in 49 (41%) subjects. Mean adenoma size was 6.5 mm, with 83 (92%) less than or equal to 10 mm. Forty-nine (54%) adenomas were located proximal to the splenic flexure, and 17 (19%) were classified as tubulovillous or villous. Moderate- to high-grade dysplasia was found in 29 (32%) adenomas and was associated with larger size (p less than 0.0001) and villous architecture (p = 0.0038). Two subjects harbored adenomas with invasive cancer. Seventy-one hyperplastic polyps were found in 40 (34%) subjects. The mean size of hyperplastic polyps was 3.4 mm, and 64 (90%) were located in the left colon. We conclude that, in this population, adenomas are common lesions that are frequently small. However, substantial proportions of these adenomas may be at risk for malignant degeneration due to the presence of villous architecture and higher grades of dysplasia. Because adenomas and hyperplastic polyps are endoscopically indistinguishable, all polyps found at endoscopy should be removed or ablated.
Fourteen cases of vasculitis associated with a neoplasm are reported. The vasculitides were classified as: leukocytolytic vasculitis 7, periarteritis nodosa 4, purpura rheumatica 1, cutaneous granulomatous vasculitis 1, microvasculitis nervosa 1. The neoplasms were diagnosed as: 10 hemopathies (including 4 cases of refractory anemia) and 5 solid tumors (1 patient had 2 tumors). The cutaneous manifestations (purpura, papules, subcutaneous nodules, etc.) and fever were the most common, while joint and neurological involvement were the rarest. The evolution of the vasculitis was usually corticosensitive and independent of the underlying neoplasm. A review of the literature revealed that these vasculitides (primarily leukocytolytic) were frequently associated with dysplastic myelogenous syndromes and hairy cell leukemia, while bronchopulmonary and colonic neoplasms were the most common solid tumors. The mechanisms giving rise to these vasculitides are discussed.
Data of the national cancer registry and the official death statistics are used to analyze the incidence and mortality of malignant neoplasms of the small intestine (ICD 152), the colon (ICD 153) and the rectum (ICD 154) in the German Democratic Republic. An apparent increase of age-adjusted incidence from 1956 to 1975 and of mortality from 1960 to 1970 can be explained by more complete reporting. A further increase of incidence from 1970 on is possible but not proved. There is no conclusive evidence that results of treatment have changed. An international comparison of incidence and mortality is difficult, since sources of information are not as reliable as generally assumed.
Screening for colorectal carcinoma (CRC) was organized for 236 asymptomatic family members in 22 Finnish cancer family syndrome (CFS) kindreds, and 58% (137) of the subjects accepted the invitation. Double-contrast colonography and sigmoidoscopy or colonoscopy were used. In 137 subjects aged 20-65 years, with 3 or more first-degree relatives with CRC, one screening visit showed a colonic neoplasm in 12 (9%) subjects. Two had carcinoma (Dukes A and B), and 10 subjects one or more adenomas. Two of the subjects not attending screening (2%) developed Dukes C colon carcinoma during the study period, and one of them died of cancer. Continued screening of 34 patients with a previously identified CFS showed metachronous colorectal tumours in 12 (35%) cases: 9 operable carcinomas and 9 adenomas within 3 years. The preliminary result of screening on the basis of CFS was encouraging. Effective and continuous screening, however, requires centralized organization. The continued follow-up of identified CFS cases effectively revealed metachronous colorectal tumours at a curable stage, but its benefit was burdened by a high rate of advanced malignancies other than CRC.
Mutation of the APC gene may be a common denominator of all human colon cancer--polypoid and non-polypoid familial cancer as well as sporadic occurrences. Fearon and Vogelstein (1990) have described a series of molecular changes during the progression of human colon cancer, beginning with mutations in APC. Min is a strain of the laboratory mouse carrying a nonsense mutation in Apc, the mouse homologue of APC. The Min strain has been used to test the effect of germline alterations in certain genes identified in the progression pathway of Fearon and Vogelstein. A deficiency in DNA cytosine methylase leads to a reduction in the tumour multiplicity of Min mice contrary to the a priori expectation based on the global hypomethylation of the DNA of early colonic neoplasms. Alterations in Kras had no perceptible effect on the tumour multiplicity of Min mice but may not have been successfully directed to the proliferative cell population. Constitutional mutation of p53 did not influence the multiplicity or histopathology of early Min induced intestinal tumours. The cause and effect analysis of the genetics of colon cancer is clearly in an early phase. An unlinked genetic factor interacting with Min in controlling intestinal tumour multiplicity is Mom1. A central goal for the near future is to identify the Mom1 gene product and to identify other loci that can interact with the Min mutation and affect tumour multiplicity or progression. Mouse chimaeras will permit an analysis of the clonality and cell autonomy of Min induced neoplasms and also of the action of Mom1. The results of these analyses will inform investigators as to what modes of prevention and therapy might be designed for particular tumour types. The Min strain thereby presents an opportunity to discover protective factors against human colon cancer.
A new ultrasound technique for intestinal examination, named "sono-enterocolonography by oral water administration," was devised. The diagnostic usefulness and limitations of this procedure were studied in 56 subjects including 42 normal patients, 10 patients with 13 colonic polyps and 4 patients with colon carcinomas. Except for the rectum, almost all the intestines were clearly visualized by ultra-sonography as tubular structures filled with water. In every case, ileocecal valve movement was clearly observed dynamically. Eight of the 9 elevated polypoid lesions of the bowel, ranging in size from 10 mm to 20 mm, were detected by this method without any special pretreatment. Although this method may not be indicated for the screening of minute lesions, it may possibly be useful as a supportive diagnostic modality for intestinal disorders, especially in the ileocecal region.
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There is some controversy about the indications for surgical resection above the distal rectum following colonoscopic removal of a polyp which proves to be malignant. Sessile, villous adenomas are generally considered to carry greater risk of spreading malignancy than pedunculated, tubular or villous adenomas. Resection is usually recommended in the presence of carcinomatous invasion beyond the muscularis mucosae and/or insufficient tumor-free margin of the stalk if the patient's condition permits.
A total of 175 patients who underwent a curative resection for a colonic (n = 130) or a rectal cancer (n = 45) between 1986 and 1992 were entered into a routine colonoscopy program. Colonoscopies were performed 1 year after the operation, and then at 2-year intervals. The findings at colonoscopy, as well as those of preoperative colonoscopy (when performed), were recorded. Eleven anastomotic recurrences were diagnosed at an asymptomatic stage, at a mean follow-up of 14 months. All of them were identified in patients with a stage B or C primary rectosigmoid cancer. Eight patients underwent another potentially curative re-operation. Only perioperative colonoscopy (preoperative colonoscopy; first postoperative colonoscopy in patients for whom the preoperative procedure was incomplete or not performed) allowed diagnosis of second cancers (n = 7) and adenomatous polyps greater than 10 mm (n = 17). Further colonoscopies detected only polyps less than 10 mm. Positive examination rates for successive follow-up colonoscopies were 15, 20 and 23%, respectively; they were significantly higher in patients who had previously had adenomatous polyps than in patients who had not: 30% versus 6% (P < 0.025), 46% vs 5% (P < 0.005) and 38% vs 11% (P < 0.025), respectively. From these data, the following recommendations are made: (1) All colorectal cancer patients should have a total colonoscopy either before (whenever possible) or soon after operation; (2) Based on results of the perioperative colonoscopy, patients: should undergo their first follow-up colonoscopy only 3 yearly (presence of synchronous adenomatous polyps) or 5 yearly (absence of synchronous adenomatous polyps) after resection; (3) In patients with stage B or C primary rectosigmoid cancer, a surveillance of the suture line by rigid proctosigmoidoscopy should be added during the first 2 postoperative years: 6, 15 and 24 months after the operation.
AIMS: Pseudomyxoma peritonei may have as its primary site a mucinous gastrointestinal adenoma or carcinoma that gains access to the peritoneal cavity. This manuscript describes this disease arising from a benign or malignant colonic polyp. METHODS: From a database of over 1000 pseudomyxoma peritonei patients and colorectal carcinomatosis patients, three cases were identified in which the primary tumor site was a colonic polyp. The clinical history and course of these patients were studied. RESULTS: In a review of the clinical management of these patients, all three had an event whereby neoplastic cells from the surface of the colonic polyp could have gained access to the free peritoneal cavity. The patients developed the characteristic pseudomyxoma peritonei syndrome. All three patients were treated with cytoreductive surgery plus perioperative hyperthermic intraperitoneal chemotherapy. CONCLUSIONS: Colonic polyps can serve as a source of dysplastic cells whereby pseudomyxoma peritonei can result. Caution to prevent seeding to the free peritoneal cavity during surgery for colonic polyps should be observed. If pseudomyxoma peritonei develops, cytoreductive surgery and perioperative intraperitoneal chemotherapy should be considered for treatment.