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1.
G Chir ; 40(4Supp.): 1-40, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32003714

RESUMO

Enhanced Recovery After Surgery (ERAS) pathway is a multi-disciplinary, patient-centered protocol relying on the implementation of the best evidence-based perioperative practice. In the field of colorectal surgery, the application of ERAS programs is associated with up to 50% reduction of morbidity rates and up to 2.5 days reduction of postoperative hospital stay. However, widespread adoption of ERAS pathways is still yet to come, mainly because of the lack of proper information and communication. Purpose of this paper is to support the diffusion of ERAS pathways through a critical review of the existing evidence by members of the two national societies dealing with ERAS pathways in Italy, the PeriOperative Italian Society (POIS) and the Associazione Italiana Chirurghi Ospedalieri (ACOI), showing the results of a consensus development conference held at Matera, Italy, during the national ACOI Congress on June 10, 2019.


Assuntos
Cirurgia Colorretal , Consenso , Recuperação Pós-Cirúrgica Melhorada/normas , Sociedades Médicas , Comorbidade , Aconselhamento , Humanos , Itália , Cuidados Pré-Operatórios/métodos
3.
Suppl Tumori ; 4(3): S31, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16437885

RESUMO

This paper reports six patients with perianal Crohn's disease (CD), who developed anal cancer in chronic anal fistulas. Tumors have been often diagnosed at an advanced stage and had a worse prognosis than cancers arising in the general population as tumor symptoms may mimic symptoms of CD, resulting in delay in diagnosis. Patients with perianal CD should undergo a careful surveillance program for ano-rectal carcinoma, including routine biopsy of any suspected lesion. When malignancy is found, an aggressive surgical approach and complementary therapy are mandatory.


Assuntos
Neoplasias do Ânus/etiologia , Doença de Crohn/complicações , Fístula Retal/complicações , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
4.
J Chemother ; 14(4): 366-72, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12420854

RESUMO

Amoxicillin/clavulanic acid (amoxicillin 2 g/clavulanic acid 200 mg) has been administered in comparison to cefotaxime (2 g) for antimicrobial prophylaxis in 476 evaluable patients undergoing abdominal surgery at high risk of septic complications. Both antibiotics were administered as a single infusion. 205 evaluable patients (110 in amoxicillin/clavulanic acid group and 95 in cefotaxime group) underwent upper gastrointestinal surgery (including gastroduodenal and biliary surgery). The wound infection rate was 4.5% for amoxicillin/clavulanic acid and 7.4% for cefotaxime, with no significant differences. Intra-abdominal abscesses were observed in 3 patients in the amoxicillin/clavulanic acid group and in 1 patient in the cefotaxime group. 271 evaluable patients (135 in amoxicillin/clavulanic acid group and 136 in cefotaxime group) underwent lower gastrointestinal surgery (including colorectal surgery). The wound infection rate was 11% for amoxicillin/clavulanic acid and 13% for cefotaxime, with no significant differences. A purulent discharge was present in 3 patients in both groups. Intra-abdominal abscesses were observed in 3 patients in the amoxicillin/clavulanic acid group and in 4 patients in the cefotaxime group. No serious adverse events and no cases of diarrhea were observed. In conclusion, in our experience amoxicillin/clavulanic acid proved to be as effective as cefotaxime in protecting patients from surgical infections in abdominal surgery. Its use in surgical prophylaxis may help decrease the cost of treatment and reduce the risk of resistance to antibiotics and superinfections.


Assuntos
Abdome/cirurgia , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Cefotaxima/uso terapêutico , Ácido Clavulânico/uso terapêutico , Quimioterapia Combinada/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Infecção da Ferida Cirúrgica/prevenção & controle
5.
Dis Colon Rectum ; 43(7): 920-6, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10910236

RESUMO

PURPOSE: The objective of this study was to review early and late results of our personal experience with strictureplasty for patients affected by Crohn's disease. METHOD: During a 16-year period, 44 of 383 patients underwent strictureplasty. Of the 269 strictures present at surgery, 174 were treated by performing strictureplasties (156 were closed transversely according to the Heineke-Mikulicz technique, 16 were done side-to-side in the Finney manner, and 2 were done according to Jaboulay technique), and 88 were treated with a synchronous resection. An individualized technique was used for seven other strictures, with side-to-side ileocolic (5 strictures in 3 patients) or ileoileal anastomosis (2 strictures in one patient). RESULTS: No operative mortality was recorded, nor were septic complications caused by anastomotic leakage observed. The mean follow-up period was 47.8 +/- 42.4 (range, 3-132) months. After a median follow-up period of 50 (range, 18-89) months, a second operation for symptomatic recurrence was performed on ten patients, and two of them developed new symptomatic strictures after 3 and 36 months, requiring a third operation. Symptomatic restrictures of previous strictureplasty sites requiring surgery occurred in 8.8 percent of cases. Furthermore, no statistically significant difference (Kaplan-Meier) was observed in the reoperation rate among the patients with skip lesions or closed strictures or among patients treated by strictureplasty alone or with associated resection. CONCLUSION: We conclude that strictureplasty is a valuable adjunct or alternative to resection in the treatment of Crohn's strictures.


Assuntos
Doença de Crohn/cirurgia , Intestino Delgado/cirurgia , Adolescente , Adulto , Constrição Patológica , Doença de Crohn/patologia , Feminino , Humanos , Obstrução Intestinal/cirurgia , Intestino Delgado/patologia , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos
6.
J Surg Oncol ; 74(1): 15-20, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10861602

RESUMO

BACKGROUND AND OBJECTIVES: Ileorectal anastomosis (IRA) is still used in the treatment of familial adenomatous polyposis (FAP). Sulindac appears to induce regression of colorectal adenomas; however, its effects in long-term therapy and in preventing carcinoma remain unclear. METHODS: Fifteen FAP patients treated by IRA received sulindac (200 mg/day) for a mean period of 48.6 +/- 28.7 (range 12-124) months. Number, size, and type of rectal polyps were assessed by endoscopic and histological evaluation every 6 months. RESULTS: Significant regression of polyps was observed in all patients after 6 months (P < 0.02). However, after a mean of 48.6 +/- 28.7 months, both number and size of polyps increased again, showing no statistical difference with baseline values. Minute polyps appeared reddish, while the largest lesions were flat or slightly elevated. Endoscopic polypectomy was necessary in 9 patients and transanal surgical excision in 3. Two patients were submitted to restorative proctectomy because of a large polyp with severe dysplasia and a rectal cancer, respectively. CONCLUSIONS: Sulindac appears to influence the morphological appearance of polyps in FAP patients, inducing apparent regression. However, at a dose of 200 mg, it does not influence the progression of polyps toward a malignant pattern.


Assuntos
Polipose Adenomatosa do Colo/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Neoplasias Retais/prevenção & controle , Sulindaco/uso terapêutico , Polipose Adenomatosa do Colo/patologia , Polipose Adenomatosa do Colo/cirurgia , Adolescente , Adulto , Neoplasias Colorretais/patologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Proctocolectomia Restauradora , Neoplasias Retais/patologia
7.
Br J Cancer ; 82(2): 348-53, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10646887

RESUMO

Correlations between germline APC mutation sites and colorectal pathophenotypes, as evaluated by the direct count of adenomas at colectomy, were investigated analysing colectomy specimens from 29 FAP patients carrying one mis-sense (codon 208) and 14 frame-shift or non-sense APC mutations (codons 232, 367, 437, 623, 876, 995, 1061, 1068, 1075, 1112, 1114, 1309, 1324, 1556). The mis-sense mutation at codon 208 was associated with a relatively mild colorectal pathophenotype. The mutation at codon 367, subject to alternative splicing, was associated with attenuated FAP. The mutation at codon 1309 was associated with the profuse colorectal adenomatosis. For 13 mutations, predicted to result in null alleles or truncated APC proteins, we correlated density and distribution of colorectal adenomas with the predicted functional effects of the mutation. The most severe colorectal pathophenotype was significantly associated with the truncating mutation at codon 1309, which is located downstream to the I beta-catenin binding domain but upstream II beta-catenin-binding domain. Mutations between codons 867 and 1114, which affect the I beta-catenin binding domain, as well as mutations occurring in exons 6 and 9, predicted to result in null alleles, were associated with a less severe colorectal pathophenotype. Overall, the highest number of adenomas was detected in the right colon, followed by the left colon, transverse colon sigma and rectum. However, the highest density of adenomas was observed in the left colon, followed by the right colon, sigma, transverse colon and rectum. Colorectal carcinomas, observed in only five patients, were all in the left colon.


Assuntos
Adenoma/genética , Polipose Adenomatosa do Colo/genética , Neoplasias Colorretais/genética , Genes APC/genética , Mutação em Linhagem Germinativa/genética , Adenoma/etiologia , Adenoma/patologia , Polipose Adenomatosa do Colo/patologia , Adolescente , Adulto , Criança , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo
8.
Cancer Res ; 59(15): 3570-5, 1999 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-10446963

RESUMO

We analyzed the hMLH1 and hMSH2 genes in 30 unrelated hereditary nonpolyposis colorectal cancer (HNPCC) patients using mutational and immunohistochemical analyses combined whenever possible with primer extension assays, designed to estimate hMLH1 and hMSH2 transcript expression in peripheral blood lymphocytes. Single-strand conformational polymorphism screening and PCR-direct sequencing revealed seven hMLH1 and five hMSH2 sequence variants in 14 unrelated HNPCC patients, including three definite pathogenic mutations, four amino acid substitutions of uncertain pathogenic significance, and five polymorphisms. Immunohistochemistry indicated the lack of either hMLH1 or hMSH2 protein expression in tumors from 13 patients, and the absence of both hMLH1 and hMSH2 immunostaining was observed in the tumor from one additional case. The lack of hMLH1 or hMSH2 immunostaining was associated with the presence of microsatellite instability in the corresponding tumor and was also observed in tumors from patients negative for pathogenic mutations by mutational screening. There was a marked unbalance in the allelic expression of either hMLH1 or hMSH2 transcripts in three of eight unrelated HNPCC patients that could be analyzed, although a less marked unbalance was detected in two additional patients. Tumors from patients with germ-line unbalance in hMLH1 or hMSH2 transcript expression did not express the corresponding mismatch repair protein and displayed microsatellite instability. Our results indicate that constitutional alterations in hMLH1 and hMSH2 transcript expression may represent genetic markers for HNPCC carrier status also in cases in which mutational analysis did not detect a definite pathogenic variant. This suggests that transcript deregulation may represent a relevant mode of germ-line inactivation for mismatch repair genes.


Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo do DNA/genética , Proteínas de Ligação a DNA , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/biossíntese , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Adaptadoras de Transdução de Sinal , Alelos , Proteínas de Transporte , Neoplasias Colorretais Hereditárias sem Polipose/metabolismo , Análise Mutacional de DNA , Heterogeneidade Genética , Marcadores Genéticos , Predisposição Genética para Doença , Humanos , Linfócitos/metabolismo , Repetições de Microssatélites , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS , Proteínas de Neoplasias/genética , Proteínas Nucleares , Mutação Puntual , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Deleção de Sequência , Transcrição Gênica
9.
Oncol Res ; 11(9): 437-45, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10821538

RESUMO

Patients with advanced colorectal cancer are currently being treated with 5-fluorouracil (5-FU)-based chemotherapy. A growing number of patients with resectable disease receive adjuvant therapy with 5-FU/levamisole (LEV) or 5-FU/folinic acid (LV). However, many patients still fail on these treatments, due to occurrence of natural or acquired tumor resistance. Among clinically relevant mechanisms of resistance to fluoropyrimidines, increased expression of thymidylate synthase (TS) has been emphasized. Another potentially relevant mechanism involves a decrease in folylpolyglutamate synthetase (FPGS) expression. To establish the value of these genes as prognostic factors and predictors of the outcome of 5-FU-based chemotherapy in colorectal cancer, we measured their expression in colorectal tumors from patients undergoing surgery and postoperative chemotherapy and compared it with that in normal colonic mucosa. This was done by a semi quantitative, nonradioisotopic polymerase chain reaction (PCR) method using beta-actin as an internal standard and expressed as a TS/beta-actin or a FPGS/beta-actin mRNA ratio. In tumor samples from 21 colorectal cancer patients, TS gene expression varied 118-fold. The median TS/beta-actin ratio was, in fact, 41.36 x 10(-3) (range 2.49 x 10(-3) to 294.54 x 10(-3)). Little variation in TS gene expression was observed in corresponding normal colic mucosa; the TS/beta-actin gene ratio was lower (median 26.16 x 10(-3); range 8.49 x 10(-3) to 69.49 x 10(-3)). Among tumor explants from 20 patients, FPGS expression varied over 161-fold. A similar marked variation was also observed in normal colonic mucosal samples (over 185-fold). Overall and disease-free survival data suggest an inverse association between the level of tumor TS and FPGS expression and clinical prognosis. The availability of this sensitive and accurate assay for gene expression should now make it possible to extend these laboratory/clinical correlations to larger populations.


Assuntos
Neoplasias Colorretais/enzimologia , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Peptídeo Sintases/genética , Timidilato Sintase/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa
10.
Hum Mutat ; 11(3): 197-201, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9521420

RESUMO

Analysis of genotype-phenotype correlations in familial adenomatous polyposis (FAP) patients demonstrated that the phenotypic heterogeneity of FAP is partly related to the mutation site. We investigated the molecular basis for the difference in severity of colorectal disease observed comparing FAP patients from two kindreds with neighbouring germline mutations in exon 9 of the APC gene. Patients from one kindred presented with a attenuated form of FAP, characterized by a low number of colorectal adenomas (up to 22). In FAP patients from this kindred, the APC gene mutation was localized at codon 367, in the portion of exon 9 that is alternately spliced. This is expected to result in the splicing-out of the mutation site in a fraction of mRNA molecules and in the residual production of wild-type transcripts from the mutant APC allele. Patients from the other kindred manifested a FAP phenotype characterized by hundreds of colorectal adenomas (320 to > 500). In these patients, the APC gene mutation abolished the donor site of exon 9a, used in both alternately spliced isoforms of the exon. The analysis of the relative levels of mutant and wild-type transcripts in unaffected colonic mucosa demonstrated that the mutant allele was not expressed. The model offered by our FAP patients with neighbouring exon 9 APC mutations supports the view that in addition to the mutation site, the type of mutation and transcript dosage effects contribute to the heterogeneity of disease phenotypes.


Assuntos
Polipose Adenomatosa do Colo/genética , Éxons/genética , Genes APC/genética , Mutação/genética , RNA Mensageiro/genética , Adolescente , Adulto , Processamento Alternativo , Criança , Análise Mutacional de DNA , Heterogeneidade Genética , Humanos , Mucosa Intestinal/química , Itália , Pessoa de Meia-Idade , Linhagem , Fenótipo , Polimorfismo Conformacional de Fita Simples , RNA Mensageiro/análise
11.
World J Surg ; 21(6): 653-8; discussion 659, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9230666

RESUMO

Surgical treatment of familial adenomatous polyposis (FAP) is still controversial. From 1984 we carried out a prospective evaluation of total colectomy with ileorectal anastomosis (IRA) and restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) to determine differences in postoperative complications, functional results, occurrence of desmoids, and recurrence of polyps in the rectal stump. IRA was performed below the peritoneal reflection and was indicated in the absence of rectal cancer and in the presence of fewer than 10 polyps or minute polyposis in the last 10 cm of the rectal mucosa. IRA patients underwent a regular endoscopic follow-up and prolonged sulindac administration (100 mg twice daily). When criteria for IRA were absent, IPAA was performed adopting a manual anastomosis at the pectinate line. Fourteen patients were operated with IRA and 24 with IPAA. There was no difference in sex and age between the two groups of patients. The number of rectal polyps was significantly different in the two groups. Immediate postoperative complications were observed in only five IPAA patients, three of whom (12%) required reoperation. Late postoperative complications occurred more frequently in IRA patients (14%) than in IPAA patients (4%). Desmoids developed in both groups (five in the IRA group and four in IPAA group). The number of bowel movements was similar in both groups, but 25% of IPAA patients complained of nocturnal fecal soiling. Fulguration or polypectomy for recurrent polyps was necessary in all but two IRA patients at follow-up. The rectal stump was easily eradicated by polyps in all but four patients with minute polyps at surgery. In the latter patients a diffuse or carpeting rectal polyposis occurred. IPAA can give optimum control of colorectal polyposis in FAP patients with an acceptable incidence of postoperative complications and satisfactory functional results. This type of surgical procedure is indicated in most FAP patients, and IRA should be reserved for patients without polyps or with fewer than 10 polyps in the rectal stump; otherwise growth of polyps cannot be adequately controlled.


Assuntos
Polipose Adenomatosa do Colo/cirurgia , Proctocolectomia Restauradora , Reto/cirurgia , Adolescente , Adulto , Anastomose Cirúrgica , Criança , Colectomia , Feminino , Humanos , Íleo/cirurgia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Prospectivos
12.
Anticancer Res ; 17(3C): 2099-104, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9216671

RESUMO

BACKGROUND: Clinical and experimental evidence suggest that estrogen has a role in the natural history of desmoid tumor (DT) and colorectal carcinoma. METHODS: The biological effects of LY117018, a nonsteroidal antiestrogen benzothiophene derivative, were assessed on a human adenocarcinoma cell line (HCT8 cells), and on DT cells and colorectal cancer derived fibroblasts in primary culture. RESULTS: LY117018 inhibited cell proliferation and collagen type I synthesis in DT cells. The compound also reduced cell growth in HCT8 cells and colorectal cancer fibroblasts. Binding experiments revealed the presence of estrogen binding sites in DT cells and frozen tissues but LY117018 did not displace [3H]17 beta E2 binding to DT cells. CONCLUSIONS: Present results demonstrate that LY117018 inhibits epithelial and fibroblastic colon cancer cells proliferation and proliferation and differentiation of desmoid cells in vitro. The lack of displacement of [3H]17 beta E2 binding to desmoid cells by LY117018 suggests the existence of distinct LY117018 binding sites.


Assuntos
Colágeno/biossíntese , Antagonistas de Estrogênios/toxicidade , Pirrolidinas/toxicidade , Tiofenos/toxicidade , Adenocarcinoma , Sítios de Ligação , Ligação Competitiva , Divisão Celular/efeitos dos fármacos , Neoplasias do Colo , Neoplasias Colorretais , Dexametasona/farmacologia , Estradiol/metabolismo , Fibroblastos , Fibromatose Agressiva , Humanos , Cinética , Progesterona/farmacologia , Tamoxifeno/farmacologia , Testosterona/farmacologia , Células Tumorais Cultivadas
13.
Int J Colorectal Dis ; 12(5): 261-6, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9401838

RESUMO

UNLABELLED: An alternative technique of restorative proctocolectomy, by means of straight ileoanal anastomosis with multiple myotomies (SIAM) of the terminal ileum in 15 patients, nine with familial adenomatous polyposis (FAP) and six with ulcerative colitis (UC) is reported. SURGICAL TECHNIQUE: Eight to ten longitudinal myotomies (3-4 cm long, on three different circumferential sites) were performed on the terminal ileum for a total length of 12-14 cm. CLINICAL RESULTS: At a mean follow up of 44 months (range 3-84 months) from the closure of the ileostomy, daytime continence was achieved in all the patients; stool frequency per 24 hours (+/- SD) was 4.1 +/- 1.8 for FAP patients and 5.8 +/- 1.7 for UC patients; nocturnal defecation was 1.0 +/- 0.5 and 1.2 +/- 0.8 for FAP and UC patients respectively; frequent nocturnal soiling was present in 2/5 of UC patients, and in 3/9 of FAP patients. SIAM failed in one UC patient that was converted to an ileoanal reservoir because of poor functional result. Signs of ileal mucosal inflammation were never observed at endoscopic examination. Histopathological assessment showed no evidence of acute terminal ileitis. MANOMETRIC FINDINGS: A significant postoperative reduction in anal resting pressure was observed after SIAM. Neither the absence of anal inhibitory reflex nor the presence of high pressure waves generated in the terminal ileum during air insufflation were related to the presence of soiling. The closure of the loop ileostomy was followed by an increased capacity and distensibility of the terminal ileum. Values of neorectal compliance were similar in FAP and UC patients although FAP patients were able to reach higher values of maximum tolerated volume and pressure. CONCLUSIONS: 1) SIAM can be an alternative to pelvic pouch in patients who have undergone restorative proctocolectomy when the construction of the pouch is not feasible. 2) The functional result observed after SIAM has been shown to be similar to that observed after pouch construction.


Assuntos
Pólipos Adenomatosos/cirurgia , Canal Anal/cirurgia , Colite Ulcerativa/cirurgia , Íleo/cirurgia , Músculo Liso/cirurgia , Proctocolectomia Restauradora/métodos , Adolescente , Adulto , Canal Anal/fisiologia , Anastomose Cirúrgica/métodos , Criança , Feminino , Seguimentos , Humanos , Íleo/fisiologia , Masculino , Manometria , Pessoa de Meia-Idade , Músculo Liso/fisiologia
14.
Cancer ; 78(11): 2400-10, 1996 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-8941012

RESUMO

BACKGROUND: Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is the most common extracolonic manifestation of familial adenomatous polyposis (FAP) and is an early clinical marker of the disease. It seems to be correlated with the position of constitutional mutations of the adenomatous polyposis coli (APC) gene. METHODS: The authors investigated the expression of CHRPE and its correlation with the position of the APC gene in FAP patients and in "at risk" relatives from 31 FAP kindreds. To obtain comparable data on CHRPE expression, the authors developed a novel scoring system based on morphologic and dimensional criteria. RESULTS: A positive CHRPE score was obtained in 29 of 39 FAP patients (74%) and in 16 of 53 relatives who showed no clinical evidence of FAP (30%). Colonoscopy revealed polyps in 20 of the 47 relatives who could be examined. The cumulative sensitivity and specificity of CHRPE were 72.88% and 96.29%, respectively. APC gene mutations were characterized in 34 subjects from 17 kindreds. In 28 of the subjects, mutations were detected in exon 15, between codons 876 and 1324. Mutations were found in exon 9 in 6 subjects. In 3 of the 6 subjects, they were found at the site where both forms of alternative splicing of the exon occur (codon 437). In the other 3 subjects (another kindred), mutations were found in the portion of exon 9 in which alternative splicing occurs (codon 367). Only 1 of the 6 subjects (16.6%) with mutations in exon 9 had a positive CHRPE score, compared with 28 of 28 subjects (100%) with mutations in exon 15. None of the 3 subjects with mutations in codon 437 had a positive CHRPE score. The CHRPE scores of exon 15 mutation carriers varied markedly both within and among kindreds, irrespective of the mutation site. CONCLUSIONS: The results of this study indicate that the site of APC gene mutation influences CHRPE expression but is not the only factor responsible for the presence and level of retinal lesions in FAP patients.


Assuntos
Polipose Adenomatosa do Colo/genética , Deleção de Genes , Genes APC/genética , Mutação em Linhagem Germinativa , Epitélio Pigmentado Ocular/patologia , Polipose Adenomatosa do Colo/diagnóstico , Adolescente , Adulto , Criança , Pré-Escolar , Éxons/genética , Feminino , Humanos , Hipertrofia/congênito , Hipertrofia/diagnóstico , Hipertrofia/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Sensibilidade e Especificidade
15.
Radiother Oncol ; 40(2): 127-35, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8884966

RESUMO

BACKGROUND AND PURPOSE: To analyse the outcome, the treatment related side effects, the prognostic significance of clinical parameters in a group of patients with rectal cancer receiving postoperative radiotherapy after radical resection. MATERIALS AND METHODS: From 1980 to 1990 148 consecutive patients with rectal carcinoma stage B2-B3 or C1-C2-C3 were treated with postoperative radiotherapy after radical surgery. All patients received 50 Gy in 25 sessions in 5 weeks. In 42 a "flash' dose of 5 Gy was also given within 24 h before surgery. Median follow up was 8.1 years. RESULTS: At 5 years the overall survival was 54%, the determined (cancer specific) survival 61%, the local recurrence-free survival 88%. The influence of stage, histotype, distance from anal margin, type of surgery, number of involved nodes and flash dose were analysed. Overall and determined survival and distant metastasis rate were significantly influenced (P < 0.005) by the pathological stage. Patients with more than 3 involved nodes presented a significantly lower determined survival (P < 0.001) and a higher distant relapse rate (P < 0.005) than those with 3 or less involved nodes. A higher determined survival (P < 0.01) was also found in patients receiving the preoperative "flash'; this group was however unbalanced in respect to the relative number of cases with 3 or less involved nodes. The incidence of major side effects requiring surgery or hospitalization for medical treatment was 35% before 1985 and 12% thereafter. The systematic use of small bowel visualization during simulation and the discontinuation of the flash dose were the main modifications introduced in the second period. As a consequence of the small bowel visualization the size of lateral fields was slightly reduced and some patients were excluded from the treatment. CONCLUSIONS: Value of postoperative radiotherapy to decrease the incidence of local recurrence was confirmed in this retrospective study; the incidence of side effects was however considerable and did not support the addition of chemotherapy as advised by the NIH consensus meeting. Our policy was therefore moved to preoperative irradiation whose combination with chemotherapy was recently reported to be better tolerated and highly effective.


Assuntos
Neoplasias Retais/radioterapia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Cuidados Pós-Operatórios , Complicações Pós-Operatórias , Radioterapia Adjuvante , Neoplasias Retais/mortalidade , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Análise de Sobrevida
17.
Radiol Med ; 90(4): 431-7, 1995 Oct.
Artigo em Italiano | MEDLINE | ID: mdl-8552820

RESUMO

The accurate locoregional staging of rectal cancer is important in choosing and planning therapy. The diagnostic contribution of endorectal ultrasonography and of Computed Tomography is well known because both methods have been widely used in the last ten years. More recently, Magnetic Resonance Imaging (MRI) has been introduced in the preoperative staging of rectal cancer: most interestingly, in the last three years endorectal surface coils have become available as a clinical device. February through November, 1994, twenty patients affected with rectal carcinoma were examined with endorectal MRI. In order to assess their accuracy, MR staging results were compared with pathologic findings. MRI was performed with an 0.5 T system equipped with an endorectal surface coil. In all cases T2-weighted turbo spin-echo sequences were performed on axial and sagittal or coronal planes. Rectal wall layers were reliably demonstrated in all patients. The comparison with pathologic findings showed 78.9% MR accuracy in assessing tumor infiltration depth. In addition, the study of perirectal lymph nodes showed 83.2% MR sensitivity and 53.8% MR specificity. The high resolution images obtained using endorectal surface coils and the well-known panoramic capabilities of this method reveal MR potentials in rectal carcinoma staging.


Assuntos
Adenocarcinoma/diagnóstico , Imageamento por Ressonância Magnética/instrumentação , Neoplasias Retais/diagnóstico , Adenocarcinoma/patologia , Adulto , Idoso , Biópsia , Feminino , Humanos , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Reto/patologia , Sensibilidade e Especificidade
18.
Anticancer Res ; 15(5B): 2247-53, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8572632

RESUMO

The aim of this study was to evaluate the relationship between DNA ploidy, proliferative activity and other prognostic factors and the survival of patients with colorectal cancer. 45 patients were prospectively investigated for 6 years. Fresh multiple samples for flow cytometric analysis of DNA content were collected during surgical resection of primary tumor. A 42% frequency of aneuploidy was observed with a median DNA index value of 1.54. The proliferative activity (%S+G2M cells) was higher in the aneuploid cell sub-population (28.6%) compared to the diploid counterpart (22.7%)(p = 0.05). No significant relationship between DNA ploidy and tumor site, Dukes' stage, histological type, grading age or sex was observed. No correlation between DNA ploidy and survival was demonstrated, including in the analysis of patient subsets according to stage. No additive prognostic information was obtained from a breakdown analysis as a function of DI values, percentages of aneuploid cells and proliferative activity. This study suggests that flow cytometric content analysis lacks prognostic value in colorectal carcinoma.


Assuntos
Neoplasias Colorretais/patologia , DNA de Neoplasias/análise , Citometria de Fluxo , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneuploidia , Divisão Celular , Neoplasias Colorretais/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico
19.
Hum Mutat ; 5(2): 144-52, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-7749413

RESUMO

Germline mutations of the adenomatous polyposis coli (APC) gene tend to cluster in discrete regions. Some of these mutations occur frequently in familial adenomatous polyposis coli (FAP) patients, and strategies for genetic diagnosis of the disease should include simple methods for their detection. We studied a total of 48 FAP-affected or "at-risk" members from 31 unrelated FAP pedigrees. Unrelated patients were analyzed using heteroduplex analysis on agarose minigels (HAAM) and multiplex allele-specific PCR. This novel strategy readily and reliably detected the three frequently occurring APC deletions at codons 1061, 1068, and 1309, allowing identification of mutant alleles in nine unrelated patients. A targeted mutational analysis, based on HAAM and amplification refractory mutation system (ARMS), allowed the rapid identification of 11 additional subjects with germline deletions, among relatives of the patients in whom mutations had been detected by multiplex PCR and HAAM. The use of two independent PCR-based tests, employing distinct sets of primers, reduces the possibility that artifacts occurring during DNA amplification may interfere with the diagnostic evaluation. The analysis of genotype-phenotype correlations provided evidence for heterogeneity with regard to the extent of colonic and extracolonic manifestations of the disease in subjects bearing identical mutations. However, the consistent association of the deletion at codon 1309 with more severe colonic disease than that observed in patients with mutations at codons 1061 and 1068, supports a correlation between mutation site and penetrance of FAP.


Assuntos
Polipose Adenomatosa do Colo/diagnóstico , Polipose Adenomatosa do Colo/genética , Genes APC , Mutação , Reação em Cadeia da Polimerase/métodos , Adolescente , Adulto , Alelos , Sequência de Bases , Criança , Pré-Escolar , Análise Mutacional de DNA , Saúde da Família , Feminino , Géis , Genótipo , Humanos , Masculino , Dados de Sequência Molecular , Ácidos Nucleicos Heteroduplexes/química , Ácidos Nucleicos Heteroduplexes/genética , Linhagem , Fenótipo , Sefarose
20.
Chir Ital ; 47(5): 15-23, 1995.
Artigo em Italiano | MEDLINE | ID: mdl-9162600

RESUMO

Strictureplasty has become one of the surgical options available for skip-lesions and for duodenal, multiple small bowel or anastomotic strictures caused by Crohn's disease. Over a sixteen-year period, 44 patients underwent strictureplasty for 269 symptomatic strictures associated with Crohn's disease. After a median follow-up of 50 months (range 18-89) a second additional operation for symptomatic recurrence was performed in 10 patients, two of whom developed new symptomatic strictures after 3 and 36 months, requiring a third operation. Of all the strictures present at surgery, 174 were treated performing strictureplasties (156 were closed transversely using Heineke-Mickulicz, 16 in a side-to-side Finney fashion and 2 in the manner of Jabolay) and 88 with synchronous resection. Furthermore, 7 other strictures were treated with a side-to-side ileocolic (5 strictures in 3 patients) or ileoileal (2 strictures in one patient) anastomosis. No operative mortality was recorded and there were no septic complications due to anastomotic leak. The mean follow-up period was 47.8 +/- 42.4 months (range 3-132). Symptomatic restrictures of previous strictureplasty sites requiring surgery occurred in 8.8% of cases. Furthermore, no statistically significant difference (Kaplan-Meier) was observed in the reoperation rate among patients affected respectively by skip lesions or multiple strictures or among patients treated only by strictureplasty or with an associated resection. We concluded that strictureplasty is a valuable adjunct to resection in the treatment of Crohn's strictures.


Assuntos
Colo/cirurgia , Doença de Crohn/complicações , Doença de Crohn/cirurgia , Intestino Delgado/cirurgia , Adolescente , Adulto , Anastomose Cirúrgica , Colo/patologia , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Feminino , Humanos , Intestino Delgado/patologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
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