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L Bertario

Publications and source records attributed to L Bertario.

At least 37 records · Page 2Linked to original sources
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

The familial adenomatous polyposis region exhibits many different haplotypes.

In the present study, we used five different polymorphic markers to construct the haplotype at the adenomatous polyposis coli (APC) locus in families with familial adenomatous polyposis (FAP) and in the normal Italian population. Non-ambiguous haplotypes were reconstructed from 246 normal chromosomes and 65 FAP chromosomes. In the control population, the four polymorphisms intragenic to APC gave rise to 16 haplotypes, the most common of which (II and XV) accounted for over 50% of all chromosomes. In FAP patients, 13 haplotypes were found but their distribution was not statistically different from normal subjects. Eighty complete chromosomal haplotypes (many fewer than the theoretical maximum of 208) for the five polymorphic sites assayed were observed in the control population, 35 being found in the FAP patients. We compared the distribution of these haplotypes within the two groups; no statistically significant differences between normal and FAP chromosomes were found. The elevated heterogeneity of FAP chromosomes was clearly confirmed by the observation that 19 patients who carried one or other of the two most common APC mutations (nt 3183 and nt 3927) showed 18 different haplotypes. On the basis of these results, we were not able to identify a founder FAP chromosome. Various mechanisms are presented to explain this observation.

Adenomatous Polyposis Coli↗
PubMed1998

Mutations of adenomatous polyposis coli (APC) gene are uncommon in sporadic desmoid tumours.

Desmoids are locally aggressive, non-metastasizing soft-tissue tumours, whose aetiology is still unclear. In patients affected with familial adenomatous polyposis (FAP), the incidence of desmoids is much higher than in the general population. The APC gene, which is responsible for FAP, is involved in the development of desmoids associated with this syndrome. In this study 16 sporadic and four FAP-related desmoids were analysed in order to investigate the possible involvement of APC in non-syndromic cases also. The 5' end (exons 1-11) and the coding portion of exon 15 of APC were screened using the in vitro synthesized-protein assay (IVSP). Exons 5, 6, 8-14, and a region of exon 15 spanning codons 1036-1634 were investigated by single-strand conformation polymorphism (SSCP) analysis. APC germline mutations were identified in all FAP patients, but not in sporadic cases. Somatic mutations were found in three FAP-associated desmoids (75%) and two sporadic tumours (12.5%). In one of the latter cases, both alleles were affected. These findings indicate a limited role of the gene in the development of desmoid tumours outside FAP.

Adenomatous Polyposis Coli↗
PubMed1998

Rapid assessment of replication error phenotype in gastric cancer.

Forty gastric tumors were investigated for microsatellite instability at the D2S119 and L-myc loci. These tumors and 143 other gastrointestinal cancers were previously analyzed for instability at several different microsatellites. By evaluating previous and present results, repeated sequences were selected that frequently underwent replication errors (RERs). To coamplify these sequences, the following multiplex polymerase chain reactions (PCRs) were performed: 1) D2S119/L-myc/D18S59; 2) D2S119/L-myc/D3S1076; and 3) D2S177/L-myc/BAT-RII. Therefore, the 40 gastric tumors in the present survey were rescreened using multiplex PCRs. Each multiplex allowed detection of nearly all RER+ tumors (80% for multiplex 3 and 87% for multiplexes 1 and 2) that had been previously identified by amplifying 9 different loci with independent reactions. Moreover, for multiplexes 1 and 2, the size differences between normal and RER alleles were sufficient to be detected by electrophoresis on conventional polyacrylamide gels after DNA staining with ethidium bromide. This approach allows a rapid and easy assessment of RER phenotype in gastric tumors.

Chromosomes, Human, Pair 2↗
PubMed1998

Chain-terminating mutations in the APC gene lead to alterations in APC RNA and protein concentration.

APC mutations introduce premature stop codons into the open reading frame of the gene, leading to the formation of truncated tumor suppressor proteins. Both RNA and protein levels are likely to be profoundly altered by such nonsense mutations. To test this hypothesis, Western blotting and RT-PCR strategies were used to characterize mutant and normal APC protein and APC RNA concentrations in lymphoblastoid cell lines from 22 unrelated polyposis patients carrying different APC mutations. Variable levels of truncated APC peptides were observed in 14 of 14 cell lines with APC mutations within exon 15. No truncated APC protein was detected in six of eight cell lines with APC mutations located 5' of exon 15. Mutations located in exon 15 showed mutant RNA underrepresentation in four of eight cell lines, whereas mutations located 5' of exon 15 showed RNA reduction in five of six cell lines. These findings indicate that a two- to threefold decrease in RNA concentration is common when APC alleles carry chain-terminating mutations. They also suggest that the severe decrease of truncated APC protein observed in some cell lines is due to mechanisms acting at the protein level.

Adenomatous Polyposis Coli Protein↗
PubMed1997

Surgical treatment of locally recurrent rectal carcinoma.

PURPOSE: This study was performed to analyze the outcomes of patients with local (pelvic) recurrence (following radical surgery for rectal cancer) who subsequently underwent a new operation. METHODS: Forty-five patients (19 percent of 213 local recurrences) were explored surgically because the disease was deemed to be confined to the pelvis with a limited extension and, therefore, amenable to surgical cure. RESULTS: Only 21 of the 45 patients who underwent surgical exploration had an oncologically radical operation (R0). In the remaining 24 patients, either a simple exploration or palliation or a nonradical procedure (R1-R2) was performed. In the R0 group, there was a 19 percent five-year survival rate vs. a 0 percent rate in the R1-R2 group (median survival, 4 months). Site of recurrence (anastomosis vs. other sites) was statistically associated with a higher chance of long-term survival for those who underwent an R0 operation. CONCLUSIONS: The prognosis of locally recurrent rectal cancer is dismal; less than 10 percent of all patients who underwent surgical treatment benefit from reoperation with an overall survival for five years. On the basis of these results, we no longer consider the surgical approach as the primary option for treating locally recurrent rectal cancer.

Adenocarcinoma↗
PubMed1997

Rectal cancer risk in hereditary nonpolyposis colorectal cancer after abdominal colectomy. International Collaborative Group on HNPCC.

OBJECTIVE: The authors analyzed the incidence of rectal cancer in patients with hereditary nonpolyposis colorectal cancer (HNPCC) after an abdominal colectomy. SUMMARY BACKGROUND DATA: The treatment of choice for a newly diagnosed patient with HNPCC with colon cancer is an abdominal colectomy. The incidence of rectal cancer after abdominal colectomy in HNPCC is not known. MATERIALS AND METHODS: A questionnaire was mailed to all International Collaborative Group on HNPCC members to identify patients in whom rectal cancer developed after total, subtotal or completion colectomy. Statistics were performed using the log-rank test, Kaplan-Meier method, and Cox's proportional hazards model. RESULTS: Rectal cancer developed in 8 (11%) of 71 patients a median of 158 months (range, 38-282 months) from their primary procedure. Of these eight patients, adenomas in the rectal mucosa developed in five at risk either before (4) or synchronous (1) with the diagnosis of rectal cancer. At the time of diagnosis of rectal cancer, six of eight patients were being observed. Age at first procedure and whether the patient was under surveillance were the only significant variables (p < 0.05) in the multivariate analysis in terms of rectal cancer risk. The risk of developing rectal cancer was estimated to be 3% every 3 years after abdominal colectomy for the first 12 years. CONCLUSIONS: The risk of rectal cancer in patients with HNPCC after an abdominal colectomy is approximately 12% at 12 years. Age at first surgical procedure and surveillance correlated with rectal cancer risk. Aggressive endoscopic surveillance of the rectum should be performed after abdominal colectomy.

Abdomen↗
PubMed1997

Primary anorectal melanomas: an istitutional experience.

Primary melanomas (M) of the rectum and anal canal are a rare pathological event, constituting approximately 1% of all invasive tumors in this site. From January 1973 to December 1990 at the Istituto Nazionale per lo Studio e 1a Cura dei Tumori of Milan, 11 patients were treated for M (5 males and 6 females), with a mean age of 60 years (range 40-80). The site of origin of the M was rectal in four patients, anal in five patients and in the anorectal joint in two patients. The lesion was prevalently polypoid and the average size was 4 cm (1-7.5 cm). Symptoms referred by the patients were rectal bleeding and tenesmus. In one patient the diagnosis was made after biopsy of an inguinal metastatic lymphnode. Of the 11 patients, six underwent curative resection (four Miles' resections and two local excisions). One patient is still alive with no evidence of disease after 120 months. The remaining five patients were submitted to palliative treatment, due to the presence of metastases in four of them and to age and general conditions in one. All of these patients died at 1, 2, 4, 5, and 6 months (median: 4 months). Overall median survival was eight months: 20 months in the radically treated group and four months in the palliatively treated group. Our data are in agreement with those reported in literature and confirm the prognostic severity of anorectal M due both to late diagnosis and the biological aggressiveness of the neoplasm.

Adult↗
PubMed1997

Mean age of tumor onset in hereditary nonpolyposis colorectal cancer (HNPCC) families correlates with the presence of mutations in DNA mismatch repair genes.

Fourteen Italian families affected with hereditary nonpolyposis colorectal cancer (HNPCC) were screened for germline mutations at three DNA mismatch repair (MMR) genes, MSH2, MLHI, and GTBP, by using a combination of different methods that included an in vitro synthesized protein assay, single-strand conformation polymorphism analysis, and direct sequencing. DNA alterations were observed in six instances, including a single base deletion in MSH2 exon 14, an A-to-G transition in the splice donor site of MLHI exon 6, and two missense mutations in MLHI exons 5 and 9. A previously reported common mutation affecting the splice donor site of MSH2 exon 5 was identified in two families. No mutations were detected in the GTBP gene. In total, eight of 16 Italian HNPCC families (50%), including two previously reported kindreds, were found to carry a mutation in MMR genes. We compared the mean age of colorectal cancer onset in the index cases (three patients for each family) between the two groups of kindreds, those with identified mutation vs. those without, and found that the first had a significantly lower value (43.0 vs. 53.7 years, P = 0.014). This finding suggests that HNPCC families with a more advanced age of tumor onset are less likely to be associated with known MMR genes.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Preoperative radiotherapy for resectable cancer of the middle-distal rectum: its effect on the primary lesion as determined by endorectal ultrasound using flexible echo colonoscope.

20 patients with rectal cancer within 8 cm of the anal verge were studied. Endoscopic endosonography was carried out before and after pre-operative radiotherapy (45 Gy over three weeks). The local extent (tumour stage and diameter) was compared with the results of histopathological examination of the resected specimen after anterior resection or total rectal excision. The Tumour Regression Grade (TRG) and lymph node status were also estimated. Two patients were not evaluated endosonographically. Two (11%) of the remaining 18 patients showed ultrasound evidence of down staging (14/18 uT3/4 pre-radiotherapy: 12/18 uT3/4 after) and tumour diameter was significantly reduced. Tumour Regression Grade estimation showed evidence of response to treatment, showing regression of more than 50% in 13 (65%) of cases. Involved nodes were less than 5 mm in diameter in 45% of cases. Histopathological evidence of nodal metastatic regression was seen in 13 (28%) of all involved nodes found. The ultrasonically determined response to radiotherapy may offer useful information in predicting outcome and possibly in selecting surgery.

Adenocarcinoma↗
PubMed1996

Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis.

BACKGROUND & AIMS: Hereditary nonpolyposis colorectal cancer is characterized by early-onset colorectal cancer and the occurrence of various other cancers. The recent isolation of four mismatch repair genes responsible for hereditary nonpolyposis colorectal cancer allows for the identification of carriers within affected families. The purpose of this study was to assess the age-specific cancer risk in a large series of gene carriers. METHODS: Thirty-four families were studied by mutation analysis. In 19 of these families, pathogenic mutations were found at hMSH2 or hMLH1. Of 382 relatives, 124 had a mutation in hMLH1 and 86 in hMSH2. RESULTS: The lifetime risk of colorectal cancer was the same in both groups of gene carriers (80%). The risk of endometrial cancer was greater in hMSH2 gene carriers compared with hMLH1 gene carriers (61% vs. 42%), but the difference was not statistically significant. A very high relative risk of cancer of the small bowel (relative risk of >100) was observed in carriers of either gene. Only the carriers of hMSH2 mutations had a significantly increased relative risk of cancer of the urinary tract (kidney and ureter) (relative risk of 75.3), stomach (relative risk of 19.3), and ovaries (relative risk of 8.0). CONCLUSIONS: This study provides estimates of cancer risk that may contribute to the appropriate management of gene carriers within families with hereditary nonpolyposis colorectal cancer.

Adolescent↗
PubMed1996

Molecular screening of families affected by familial adenomatous polyposis (FAP).

OBJECTIVES: To assess the risk of developing familial adenomatous polyposis (FAP) in presymptomatic individuals using APC gene flanking and intragenic polymorphic markers. SETTING: Twenty families enrolled in the Italian Registry of Polyposis comprising a total of 217 individuals, including 53 (24%) presymptomatic subjects with a 50% a priori risk of FAP, were analysed. Direct analysis techniques had previously failed to identify the FAP mutation in these families. METHODS: DNA isolated from peripheral mononuclear blood cells and tissue sections was analysed by the polymerase chain reaction and a panel of seven highly polymorphic markers--YN5.64, CB83, CB26, LNS, APC1458.5, MBC, 37AB. Amplification products were separated by a modified denaturing gel electrophoresis method. RESULTS: The haplotype associated with the disease was identified in 18 families (90%). The segregation of the FAP haplotype in these kindreds showed that 10 presymptomatic individuals had inherited the FAP mutation and carried a high risk of developing the disease. The remaining two families were not informative because of the lack of a sufficient number of probands or biological specimens. CONCLUSIONS: These data indicate that indirect analysis with linked DNA markers has a high rate of success in defining the risk of FAP of presymptomatic subjects, provided that a sufficient number of probands or samples is available. Uninformative families accounted for 10% of the total, indicating that linkage analysis may still have higher sensitivity than direct mutation analysis techniques. The combined use of both approaches should be implemented, however, to enhance further the application of molecular genetics to the screening of families with FAP.

Adenomatous Polyposis Coli↗
PubMed1996

Majority of hMLH1 mutations responsible for hereditary nonpolyposis colorectal cancer cluster at the exonic region 15-16.

Hereditary nonpolyposis colorectal cancer (HNPCC) is a common autosomal dominant cancer susceptibility condition. Inherited mutations in at least four DNA mismatch repair genes, hMSH2, hMLH1, hPMS1, and hPMS2, are known to cause HNPCC. In this study we used denaturing gradient gel electrophoresis (DGGE) to screen for hMLH1 mutations in 34 unrelated HNPCC families (30 Dutch, 3 Italian, and 1 Danish). Ten novel pathogenic germ-line mutations (seven affecting splice sites, two frameshifts, and one in-frame deletion of a single amino acid) have been identified in 12 (35%) of these families. In a previous study, hMSH2 mutations were found in 21% of the same families. While the spectrum of mutations at the hMSH2 gene among HNPCC patients appears heterogeneous, a cluster of hMLH1 mutations has been found in the region encompassing exons 15 and 16, which accounts for 50% of all the independent hMLH1 mutations described to date and for > 20% of the unrelated HNPCC kindreds here analyzed. This unexpected finding has a great practical value in the clinical scenario of genetic services.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Comparative analysis of results of guaiac and immunochemical tests for faecal occult blood in colorectal cancer screening in two oncological institutions.

The performances of three faecal occult blood tests, rehydrated Hemoccult (HOR), Hemoccult sensa (HOS) and Hemeselect (HSEL) on 3 days were compared in 1,725 subjects consecutively recruited in two oncological institutions in Milan and Florence. Significant differences between the results were evident as far as HOR positivity rates (7.5% vs 4.0%, respectively) and specificity (94.3% vs 97.5%, respectively) are concerned. Overall positivity rates of HOR, HOS and HSEL were 5.9%, 5.4% and 12%, respectively; significant differences were evident between HSEL and each of the two guaiac tests. Cancer was detected in eight subjects, adenoma/s in 47. Specificity estimates were 95.8%, 90.2% and 90.5% for HOR, HOS and HSEL, respectively; significant differences were evident between HSEL and the other two tests. No significant difference between tests was evident for sensitivity or positive predictive values for cancer or adenomas. In the CSPO (Florence) population (1,223 subjects; five with cancer, 16 with adenoma/s) the performances of 1-day HSEL testing were determined on the basis of the first faecal sample only and compared with 3-day HOR, HOS and HSEL testing. The positivity rates of 1-day HSEL, 3-day HOR, HOS and HSEL testing were 7.0%, 5.0%, 5.5% and 12.9%, respectively. Only 3-day HSEL positivity rate was significantly higher than 1-day HSEL. One-day HSEL specificity (94.9%) was significantly higher than 3-day HSEL (90.0%), whereas no significant difference was seen between 1-day HSEL, HOR (96.5%), and HOS (96.1%) specificity. No significant difference between tests is evident in the CSPO population as far as positive predictive values and sensitivity for cancer and adenomas are concerned.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenoma↗
PubMed1994

Age of onset in familial adenomatous polyposis: heterogeneity within families and among APC mutations.

Heterogeneity among and within FAP pedigrees for the age of symptom onset and the age at death from colorectal cancer was studied in a sample of 583 patients of the Italian Polyposis Registry. The among pedigree variation was largely explained by clustering of families in two groups, 'early FAP' (most colorectal cancer deaths below 45 years of age) and 'late FAP' families (most deaths above age 45). The within-family variation was explained by a marked phenomenon of anticipation (15 years per generation, on the average), possibly not due to ascertainment bias. We then considered the pedigrees with identified mutation in the APC gene. Six families shared a common deletion at codon 1309 and showed the early FAP phenotype. Two families shared a mutation at codon 1061 and revealed the late FAP phenotype. Another two families (codons 453 and 302) clustered with the late FAP group, whereas a family with mutation at codon 835 clustered with the early FAP group. We suggest that there are at least two classes of mutations in the APC gene with different consequences at the phenotypic level. It seems that there are several critical points within the APC protein sequence at which truncation causes a more aggressive disease than truncation at other points.

Adenomatous Polyposis Coli↗