In December 1997, the National Cancer Institute sponsored "The International Workshop on Microsatellite Instability and RER Phenotypes in Cancer Detection and Familial Predisposition," to review and unify the field. The following recommendations were endorsed at the workshop. (a) The form of genomic instability associated with defective DNA mismatch repair in tumors is to be called microsatellite instability (MSI). (b) A panel of five microsatellites has been validated and is recommended as a reference panel for future research in the field. Tumors may be characterized on the basis of: high-frequency MSI (MSI-H), if two or more of the five markers show instability (i.e., have insertion/deletion mutations), and low-frequency MSI (MSI-L), if only one of the five markers shows instability. The distinction between microsatellite stable (MSS) and low frequency MSI (MSI-L) can only be accomplished if a greater number of markers is utilized. (c) A unique clinical and pathological phenotype is identified for the MSI-H tumors, which comprise approximately 15% of colorectal cancers, whereas MSI-L and MSS tumors appear to be phenotypically similar. MSI-H colorectal tumors are found predominantly in the proximal colon, have unique histopathological features, and are associated with a less aggressive clinical course than are stage-matched MSI-L or MSS tumors. Preclinical models suggest the possibility that these tumors may be resistant to the cytotoxicity induced by certain chemotherapeutic agents. The implications for MSI-L are not yet clear. (d) MSI can be measured in fresh or fixed tumor specimens equally well; microdissection of pathological specimens is recommended to enrich for neoplastic tissue; and normal tissue is required to document the presence of MSI. (e) The "Bethesda guidelines," which were developed in 1996 to assist in the selection of tumors for microsatellite analysis, are endorsed. (f) The spectrum of microsatellite alterations in noncolonic tumors was reviewed, and it was concluded that the above recommendations apply only to colorectal neoplasms. (g) A research agenda was recommended.

https://cancerres.aacrjournals.org/content/canres/58/22/5248.full.pdf

A National Cancer Institute Workshop on Microsatellite Instability for Cancer Detection and Familial Predisposition: Development of International Criteria for the Determination of Microsatellite Instability in Colorectal Cancer

https://www.medpagetoday.com/upload/2008/3/6/CRC.pdf

Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology.

The discomfort of internal gastrointestinal examination may soon be a thing of the past. We have developed a new type of endoscopy, which for the first time allows painless endoscopic imaging of the whole of the small bowel. This procedure involves a wireless capsule endoscope and we describe here its successful testing in humans.

Wireless capsule endoscopy

/pdf/pathology-and-genetics-of-tumours-of-the-digestive-system-3xy9cwrc3c.pdf

Pathology and genetics of tumours of the digestive system

Gastroscopy, small bowel endoscopy, and colonoscopy are uncomfortable because they require comparatively large diameter flexible cables to be pushed into the bowel, which carry light by fibreoptic bundles, power, and video signals. Small bowel endoscopy is currently especially limited by problems of discomfort and failure to advance enteroscopes far into the small bowel. There is a clinical need for better methods to examine the small bowel especially in patients with recurrent gastrointestinal bleeding from this site.

https://gut.bmj.com/content/gutjnl/52/suppl_4/iv48.full.pdf

Wireless capsule endoscopy.

https://www.gastrojournal.org/article/S0016-5085(03)01998-X/pdf

Outcome of patients with obscure gastrointestinal bleeding after capsule endoscopy: Report of 100 consecutive cases

Adenomas that contain early invasive carcinoma (ACIC) represent the earliest form of clinically relevant cancer of the colorectum in most patients. In order to assess the incidence of nodal metastases of ACIC, we studied 31 patients in whom the colon was resected after endoscopic polypectomy (EP) done from 1975 to 1987. We also reviewed the pathologic features reported in individual cases and in literature series of ACIC with lymph node metastases published from 1958 to 1986. The lymph node metastatic potential of ACIC is relatively high, ranging from an average value of 8.5% in the literature of to 16.1% in our own study, and is equivalent to the range of 10%-17% that occurs in colorectal carcinomas that invade the submucosa. When an ACIC is seen in an EP specimen in which the polypectomy margin is normal, the decision as to whether the patient should enter a follow-up protocol or have radical surgical resection is determined by the assessment of the probability of the occurrence of nodal metastases. According to several authors, certain histopathologic features make it possible to distinguish between an ACIC with a high-risk of nodal metastases versus those with a low-risk. The most relevant pathologic parameters include the state of the resection margins, the grade of the invasive carcinoma, and the presence or absence of vascular invasion. Of 351 cases of ACIC that were operated on, derived from 16 literature series, 45.6% were high-risk cases and 8.5% had lymph node metastases. In our group of high-risk ACIC that had surgical resection subsequently, the lymph node metastatic rate was 35.7%. Our results help to estimate the nodal metastatic potential of early colorectal carcinomas and stress the importance of adequate pathologic evaluation in order to assess metastatic risk in these patients accurately.

Colorectal adenomas containing invasive carcinoma. Pathologic assessment of lymph node metastatic potential.

A single sigmoidoscopy examination at aroundage 60 years has been proposed as a cost-effective strategy toprevent colorectal cancer. A multicenter randomized con-trolled trial, the SCORE trial, is in progress in Italy to esti-mate the impact of this strategy on colorectal cancer inci-dence and mortality and the duration of the protective effect.We present the baseline screening outcomes.

/pdf/baseline-findings-of-the-italian-multicenter-randomized-1os8a5ehm2.pdf

Baseline findings of the Italian multicenter randomized controlled trial of "once-only sigmoidoscopy"--SCORE

The malignant polyp carries a significant risk of lymphohematic metastasis and mortality. Clinical usefulness of histologic risk factors is still controversial. The study was designed to compute the association between the main histologic risk factors and the occurrence of unfavorable outcomes in patients with malignant polyps. A MEDLINE search regarding malignant polyps was performed. Three histologic risk factors (positive resection margin, poor differentiation of carcinoma, vascular invasion) and five (residual disease, recurrent disease, lymph node metastasis, hematogenous metastasis, mortality) unfavorable clinical outcomes were evaluated. Further analysis was performed by subgrouping polyps in high-risk and low-risk groups. Thirty-one studies enrolling 1,900 patients with malignant polyp were selected. Positivity of resection margin was significantly predictive of the presence of residual disease (odds ratio, 22; P < 0.0001), poorly differentiated carcinoma was associated with an increased mortality (odds ratio, 9.2; P < 0.05), and vascular invasion with a higher lymph node metastasis risk (odds ratio, 7; P < 0.05). Patients with high-risk polyps showed a significantly worse outcome than those with low-risk, especially for mortality (odds ratio, 11; P < 0.05). Surgical-related death was as low as 0.8 percent. All three histologic risk factors are significantly associated with the clinical outcome. Classification in low-risk and high-risk patients may be regarded as a meaningful staging procedure.

Histologic Risk Factors and Clinical Outcome in Colorectal Malignant Polyp: A Pooled-Data Analysis

https://www.gastrojournal.org/article/0016-5085(88)90545-8/pdf

Francesco Paolo Rossini

Papers

Outcome of patients with obscure gastrointestinal bleeding after capsule endoscopy: Report of 100 consecutive cases

Colorectal adenomas containing invasive carcinoma. Pathologic assessment of lymph node metastatic potential.

Baseline findings of the Italian multicenter randomized controlled trial of "once-only sigmoidoscopy"--SCORE

Histologic Risk Factors and Clinical Outcome in Colorectal Malignant Polyp: A Pooled-Data Analysis

Immunohistochemical study of epithelial cell proliferation in hyperplastic polyps, adenomas, and adenocarcinomas of the large bowel