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M A Rodriguez-Bigas

Publications and source records attributed to M A Rodriguez-Bigas.

At least 37 records · Page 2Linked to original sources
PubMed1999

Clinical implications of multiple colorectal carcinomas in hereditary nonpolyposis colorectal carcinoma.

PURPOSE: An increased incidence of multiple (synchronous and metachronous) colorectal carcinomas has been reported in hereditary nonpolyposis colorectal cancer. This review was undertaken to determine the clinical implications of multiple colorectal carcinomas in hereditary nonpolyposis colorectal cancer. METHODS: A retrospective review of the records of patients in the hereditary nonpolyposis colorectal cancer registry at Roswell Park Cancer Institute who had either synchronous or metachronous colorectal carcinomas was conducted. RESULTS: Twenty-five of 93 patients with documented pathology were found to have multiple colorectal carcinomas. The mean age at diagnosis of the index colorectal carcinoma was 46.7 (range, 28-65) years. There were 7 (7.5 percent) patients with synchronous colorectal carcinomas and 20 (21.5 percent) patients with metachronous colorectal carcinomas. Two of the seven (28.6 percent) patients with synchronous colorectal carcinomas developed a metachronous colorectal carcinoma. In the patients with metachronous colorectal carcinomas, 29 metachronous events were noted: colon (23) and rectum (6). The mean and median time interval for metachronous colorectal carcinomas were 10.9 and 11.8 (range, 1.5-43.8) years, respectively. The mean times to first, second, and third events were 11.7 (range, 1.5-43.5), 7.9 (range, 2.7-18.7), and 12.3 (range, 11.8-12.7) years, respectively. The majority of patients with metachronous colorectal carcinomas did not have stage progression at the diagnosis of the metachronous colorectal carcinomas: 13 patients had lower or same stage at first event, 4 had lower or same stage at second event, and 2 patients had lower stage at third event. Three of 20 patients with metachronous colorectal carcinomas died of their disease. CONCLUSION: Multiple colorectal cancers are common in hereditary nonpolyposis colorectal cancer. Even though stage progression may not be evident at diagnosis of metachronous colorectal cancer, some of these patients will nevertheless die of their disease.

Colorectal Neoplasms↗
PubMed1999

New approach to the substaging of node-positive colorectal adenocarcinoma.

BACKGROUND: Future developments in adjuvant modalities may require substaging of node-positive colorectal adenocarcinoma that is accurately indicative of individual prognoses, upon which therapeutic decisions (e.g., choice of agents and intensity of treatment) may be based. This study compares substaging of node-positive colorectal cancer by venous invasion with substaging by three currently used methods, with respect to the ability of each method to define patient subsets that differ significantly in both disease-free and cancer-related survival rates. METHODS: A total of 171 patients with node-positive colorectal cancer, who had undergone potentially curative resection at least 5 years earlier, were retrospectively substaged by the tumor, node, metastasis (TNM) N1/N2, Astler-Coller C1/C2, Gastrointestinal Tumor Study Group (GITSG) C1/C2, and venous invasion (positive/negative) methods. Disease-free and cancer-related survival curves were calculated (by the Kaplan-Meier method) and compared for statistical significance (using the log-rank test). RESULTS: The separation of disease-free and cancer-related survival curves using the four methods of substaging node-positive colorectal cancer was as follows: TNM, P = .16 (not significant) and P = .12 (not significant); Astler-Coller, P < .01 and P = .006; GITSG, P = .067 (not significant) and P = .03; venous invasion, P = .016 and P = .007, respectively. CONCLUSIONS: Numerical substaging of node-positive colorectal cancer (TNM and GITSG methods) is an inferior predictor of prognosis, compared with substaging by the T value (Astler-Coller) or venous invasion methods. We think that the latter method is the method of choice, because it separates patients who have only lymphatic metastasis from patients who display microscopic hematogenous spread as well. This separation obviously has biological/oncological significance, and it may have practical therapeutic implications in the future.

Adenocarcinoma↗
PubMed1999

Prognostic factors affecting survival in patients with colorectal carcinomatosis.

This study evaluates prognostic factors that may influence survival in patients who present with carcinomatosis from colorectal cancer. Patients may present with carcinomatosis as the pattern of metastases at the initial diagnosis of colorectal cancer. Little is known about the natural history of carcinomatosis and the prognostic factors affecting outcome. All patients treated at Roswell Park Cancer Institute from 1988 to 1994 who presented with carcinomatosis at the initial diagnosis of colorectal cancer were identified. A retrospective review of the medical records for patient and tumor demographics was performed. Estimated survival distributions were calculated by the method of Kaplan and Meier. Tests of significance with respect to survival distribution were based on the log-rank test. Cox proportional hazards model was used for the multivariate analysis. There were 31 males and 38 females. The median age was 61 years (range, 26-80). The primary cancers were in the sigmoid with 24 patients (35%), cecum with 14 patients (20%), and transverse colon with 11 patients (16%). The remainder were distributed throughout the colon and rectum. The most common presentation was large bowel obstruction in 29 patients (42%). T3 and T4 cancers were present in 39 (57%) and 13 patients (19%), respectively. Lymph nodes were positive in 39 patients (57%), and mucin-producing tumors were also present in 39 patients (57%). Twelve patients (17%) had one site of disease, 17 patients (25%) had two sites of disease, and 37 (54%) patients had three or more sites of disease. Ascites was present in 29 patients (42%). Residual disease was present at the completion of surgery in 45 patients, absent in 13 patients, and status unknown in 11. The presence of residual disease (p = 0.0001), presence of ascites (p = 0.02), stage greater than T3 (p = 0.02), and increasing number of carcinomatosis sites (p = 0.006) were found to have a negative impact on survival on univariate analysis. On multivariate analysis, only the presence of residual disease at the completion of surgery was found to be an independent predictor of survival (p = 0.04). Overall median survival was 14 months with a 26% estimated 2-year survival. The presence of gross residual disease at the completion of surgery was shown to be the only independent factor negatively affecting survival. This has potential implications for the operative management of patients presenting with colorectal carcinomatosis.

Adenocarcinoma↗
PubMed1998

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.

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.

Colorectal Neoplasms↗
PubMed1998

Characteristics of small bowel carcinoma in hereditary nonpolyposis colorectal carcinoma. International Collaborative Group on HNPCC.

BACKGROUND: Small bowel carcinoma is uncommon. However, hereditary nonpolyposis colorectal carcinoma (HNPCC) patients are at increased risk of small bowel carcinoma. The purpose of this study was to characterize small bowel tumors in HNPCC patients. METHODS: A questionnaire was mailed to the members of International Collaborative Group on HNPCC (ICG-HNPCC) requesting clinicopathologic data in their registries on HNPCC patients with small bowel carcinoma. Survival was estimated utilizing the Kaplan-Meier method. RESULTS: Forty-two individuals from 40 HNPCC families developed 42 primary and 7 metachronous small bowel tumors. There were 46 adenocarcinomas and 3 carcinoid tumors. The median age at diagnosis of the index small bowel tumor was 49 years. Mismatch repair gene mutations were present in 15 of 42 patients (36%). There were nine hMLH1 and six hMSH2 mutations. The small bowel was the first site of carcinoma in 24 patients (57%). The median survival for the 42 patients was 47 months (range, 0-447 months). The overall 5- and 10-year survival rates were 44% and 33%, respectively. CONCLUSIONS: Small bowel tumors can be the presenting neoplasms in HNPCC patients. Similar to colorectal carcinoma in HNPCC, small bowel adenocarcinomas in HNPCC patients occur at an earlier age and appear to have a better prognosis than those occurring in the general population.

Adenocarcinoma↗
PubMed1998

Colorectal carcinoma survival among hereditary nonpolyposis colorectal carcinoma family members.

BACKGROUND: Patients with hereditary nonpolyposis colorectal carcinoma (HNPCC) reportedly have better prognoses than sporadic colorectal carcinoma (CRC) patients, but it has been unclear whether this could be due to differences in stage at diagnosis. The current study compared stage and survival in a retrospective cohort of HNPCC family members who developed CRC with the same factors in an unselected hospital series of patients with sporadic CRC. METHODS: This retrospective cohort study compared HNPCC cases (274 cases from 98 HNPCC families) with an unselected hospital series comprising 820 consecutive CRC cases. All patients were staged according to the TNM system of the American Joint Committee on Cancer and the International Union Against Cancer. Median follow-up among living patients was > 10 years and 8.5 years, respectively, for the two cohorts. Cox regression was used to compare survival in stage-stratified analyses of time from diagnosis to death. RESULTS: Compared with the unselected series, the HNPCC cases had lower stage disease (P < 0.001), and fewer had distant metastases at diagnosis (P < 0.001 in an analysis stratified by T classification). In stage-stratified survival analysis, the HNPCC cases had a significant overall survival advantage regardless of adjustment for their younger age. A conservative estimate of the hazard ratio (of HNPCC cases to the unselected series) was 0.67 (P < 0.0012). CONCLUSIONS: HNPCC patients had lower stage disease at diagnosis than the unselected CRC cases, mainly due to rarer distant metastases at diagnosis. They survived longer than unselected CRC patients with tumors of the same stage. The estimated death rate for the HNPCC cases, adjusted for stage and age differences, was at most two-thirds of the rate for the hospital series.

Adult↗
PubMed1998

Intraoperative determinants of unresectability for patients with colorectal hepatic metastases.

BACKGROUND: Intrahepatic and extrahepatic factors are utilized by the surgeon in the decision-making process for the performance of hepatic resection for patients with colorectal metastases. Accurate preoperative and intraoperative staging are mandatory to avoid unnecessary surgery. In this report the intraoperative determinants of hepatic unresectability were evaluated. METHODS: This was a retrospective review of medical records from January 1985 to March 1996 of 62 patients with colorectal hepatic metastases who at the time of exploratory laparotomy were deemed to have unresectable disease based on intrahepatic or extrahepatic factors. The stage of the primary tumor, disease free interval, preoperative carcinoembryonic antigen, computed tomography portography, intraoperative ultrasound, and assessment of intrahepatic and extrahepatic tumor extension were evaluated. RESULTS: Intraoperative determination of the extent of required hepatic resection, including trisegmentectomy (9 patients; 15%) and total hepatectomy (10 patients; 16%), accounted for the majority of unresectable patients. Patients with > 4 metastases (8 patients; 13%) and satellitosis (6 patients; 10%) accounted for 23% of unresectable patients. Four patients had extensive nonmalignant hepatic parenchymal disease precluding resection. Thorough abdominal exploration revealed extrahepatic disease in 13 of 62 patients (21%). Routine periportal/celiac lymph node biopsies revealed metastases in an additional 12 patients (19%), 7 of whom (11%) had only periportal/celiac lymph node metastases. CONCLUSIONS: A meticulous abdominal exploration prior to hepatic resection for patients with colorectal metastases is essential to identify those patients with extrahepatic disease. Periportal and celiac lymph nodes commonly are involved by tumor. Therefore, routine periportal/celiac lymph node biopsies should be performed in the absence of other extrahepatic disease.

Aged↗
PubMed1998

Somatic frameshift mutations in DNA mismatch repair and proapoptosis genes in hereditary nonpolyposis colorectal cancer.

An exacerbated genomic instability at simple repeated sequences characterizes cancer of the microsatellite mutator phenotype (MMP). The majority of hereditary nonpolyposis colon cancers (HNPCCs) and about 15% of nonselected ("sporadic") gastrointestinal tumors belong to the MMP pathway of tumorigenesis. Colorectal MMP+ and MMP- tumors exhibit fundamental differences in genotype and phenotype. We have shown previously that "sporadic" MMP+ colon cancers exhibit a paradoxical low incidence of somatic mutations in the p53 tumor suppressor gene and the c-K-ras proto-oncogene. On the other hand, gastrointestinal MMP+ cancers frequently harbor frameshift mutations in genes containing mononucleotide repeats. These include the cell growth regulator gene TGFbetaRII and the proapoptotic gene BAX. We have also recently shown the frequent presence of frameshift mutations in (A)8 and (C)8 tracts within the hMSH3 and hMSH6 DNA mismatch repair genes in sporadic colon cancer of the MMP. Here, we describe the nearly identical incidence of somatic frameshift mutations in these genes in a panel of 27 HNPCC MMP+ cancers: 52% in hMSH3 and BAX and 33% in hMSH6. In contrast, no mutations in any of these genes were found in 10 MMP- cancers of HNPCC patients. These results show that the multistep model for the unfolding of the MMP also applies to HNPCC and further illustrate the importance of the escape from apoptosis in the MMP pathway for gastrointestinal cancer. They also underscore the differences in genotype between tumors with and without enhanced microsatellite instability and the similarities in genotype between tumors of the MMP regardless of their hereditary or sporadic nature.

Adult↗
PubMed1998

Long-term survival in patients with ovarian metastases from colorectal carcinoma.

BACKGROUND: Ovarian metastases (OM) are a relatively uncommon consequence of primary colorectal carcinoma (CRC). The authors present a retrospective review of the impact of elective and therapeutic oophorectomy on the natural history of CRC. METHODS: Patients with primary CRC from January 1964 through March 1996 were reviewed. Survival from the time of OM diagnosis was estimated by the Kaplan-Meier method; differences between groups were based on the log-rank test. RESULTS: A total of 155 patients were studied. Synchronous OM occurred in 90 patients (58.1%); metachronous OM occurred in 65 patients (41.9%). Estimated 5-year survival for patients with synchronous OM was 9%, versus 20% for metachronous OM (P < .0001). Resection of metastatic disease was associated with an improved 5-year survival for synchronous OM (15% vs. 0%, P=.0001) and metachronous OM (24% vs. 0%, P < .0001) if patients were disease-free postoperatively. Other clinical characteristics, including age, menopausal status, stage, and location of primary tumor, had no significant impact on survival. CONCLUSIONS: Ovarian metastases from colorectal carcinoma are associated with a poor outcome. Although there is no survival advantage associated with resection of occult microscopic disease, long-term survival is possible if patients are rendered surgically disease-free.

Adenocarcinoma↗
PubMed1998

Clinicopathologic effects of cryotherapy on hepatic vessels and bile ducts in a porcine model.

BACKGROUND: The proximity of a hepatic tumor to major vessels and bile ducts limits the use of cryotherapy because of the potential damage to these structures. However, the effects of cryotherapy on major hepatic vessels and bile ducts are not well understood. METHODS: Nine pigs underwent laparotomy and intraoperative ultrasound to identify hepatic vessels larger than 5.0 mm. Cryotherapy consisting of two freeze-thaw cycles was performed, incorporating the identified vessel. In four pigs the Pringle maneuver was performed to determine the effects of partial vascular occlusion on the hepatic parenchyma and structures undergoing cryotherapy. The animals were sacrificed 30 days postoperatively, and the livers were processed for histologic examination. RESULTS: Eight of the nine livers had vessels larger than 5.0 mm incorporated into the iceball, with all vessels having evidence of infarction but remaining patent. All the livers had major bile ducts incorporated in the iceball, with eight having evidence of infarction. The Pringle maneuver had no real effect on the degree of vessel and bile duct infarction. There was no incidence of hepatic bleeding, liver fracture, bile leak, or hemobilia. CONCLUSIONS: Cryotherapy results in the infarction of major hepatic vessels and bile ducts but can be safely performed in the porcine model. Proximity of tumors to major vascular and biliary structures may not be a contraindication to the use of cryotherapy. Further studies are necessary to determine whether cryotherapy can be used in humans.

Animals↗
PubMed1998

Mutations in DPC4 (SMAD4) cause juvenile polyposis syndrome, but only account for a minority of cases.

Juvenile polyps are present in a number of Mendelian disorders, sometimes in association only with gastrointestinal cancer [juvenile polyposis syndrome (JPS)] and sometimes as part of known syndromes (Cowden, Gorlin and Banayan-Zonana) in association with developmental abnormalities, dysmorphic features or extra-intestinal tumours. Recently, a gene for JPS was mapped to 18q21.1 and the candidate gene DPC4 (SMAD4) was shown to carry frameshift mutations in some JPS families. We have analysed eight JPS families for linkage to DPC4. Overall, there was no evidence for linkage to DPC4; linkage could be excluded in two of the eight pedigrees and was unlikely in two others. We then tested these eight families and a further 13 familial and sporadic JPS cases for germline mutations in DPC4. Just one germline DPC4 mutation was found (in a familial JPS patient from a pedigree unsuitable for linkage analysis). Like all three previously reported germline mutations, this variant occurred towards the C-terminus of the DPC4 protein. However, our patient's mutation is a missense change (R361C); somatic missense mutations in DPC4 have been reported previously in tumours. We therefore confirm DPC4 as a cause of JPS, but show that there is considerable remaining, uncharacterized genetic heterogeneity in this disease.

DNA-Binding Proteins↗
PubMed1998

Intraoperative endoscopy in the management of patients with colorectal disease.

Preoperative colonoscopy is recommended in the evaluation of patients with lower gastrointestinal malignancies. The purpose of this study was to investigate the indications and impact on patient management in patients undergoing intraoperative endoscopy. This is a retrospective review of patient charts from February 1972 to July 1994 of 69 intraoperative endoscopic procedures performed in 54 patients during 54 operative sessions. The results of intraoperative endoscopy affected patient management in 29 of the 54 operative sessions (54%). This included 9 cases (17%) in which the planned surgical procedure was altered. There were no complications related to the endoscopies and 99% were completed successfully. Intraoperative endoscopy can provide important information that can alter the surgical management of patients with colorectal disease. This technique should be considered when intraoperative palpation fails to identify synchronous lesions identified on preoperative studies or in cases where the preoperative study is suboptimal.

Adult↗
PubMed1997

Complications of absorbable pelvic mesh slings following surgery for rectal carcinoma.

PURPOSE: To evaluate the intraoperative, postoperative, and long-term complications of an absorbable pelvic mesh sling after surgery for rectal carcinoma. METHODS: A retrospective review of medical records from April 8, 1991, through April 8, 1996. RESULTS: Twenty patients with a mean age of 57 (range, 37-79) years underwent pelvic mesh sling placement. The tumor stages were as follows: Stage I, 5; Stage II, 2; Stage III, 11; and Stage IV, 1. A recurrent perianal basal cell carcinoma was not included in the staging group. Surgery consisted of 18 abdominoperineal resections, 1 total proctocolectomy, and one Hartmann's procedure. Mean follow-up was 18 (range, 2-49) months. There were no intraoperative complications related to mesh placement. Twenty-nine complications occurred in 14 patients during the immediate postoperative period. Five were possibly mesh-related and included a pelvic abscess, perineal seroma, toxic perineal wound, pulmonary embolus, and lower extremity deep venous thrombosis, respectively. A mild postoperative ileus developed in 17 patients (85 percent), and a diet was initiated at a mean of seven (range, 4-24) days. Fourteen patients received postoperative radiotherapy with a mean dose of 5,339 (range, 2,500-7,020) cGy delivered in 180-cGy fractions. There were 14 immediate complications caused by radiotherapy in 11 patients, but only two patients required delays in treatment. Two patients had diarrhea alone, six developed perineal dermatitis alone, and three patients had both diarrhea and perineal dermatitis. All patients with diarrhea had received chemoradiation. One patient developed a partial small-bowel obstruction following radiation. CONCLUSIONS: Absorbable pelvic mesh sling placement can be performed with minimum morbidity and is recommended following surgery for rectal cancer when radiation is anticipated as part of multimodality therapy.

Adenocarcinoma↗
PubMed1997

Genomic instability in sporadic colorectal cancer quantitated by inter-simple sequence repeat PCR analysis.

Genomic instability plays a major role in cancer by facilitating tumor progression and tumor heterogeneity. Inter-simple sequence repeat (inter-SSR) PCR has been developed to provide a rapid and reproducible technique for quantitation of the major type of genomic instability observed in sporadic tumors, namely, that manifesting itself as amplifications, deletions, translocations, and insertions. Evaluation of 59 sporadic colorectal cancers by inter-SSR PCR has demonstrated a wide range of instability, independent of tumor stage at diagnosis. Comparison of these data and the results of microsatellite PCR analysis reveals an association of high genomic instability with loss of heterozygosity but no association with the replication error phenomenon arising from defects in mismatch repair.

Adult↗