Ferdinando Ficari

What affects continence after anterior resection of the rectum

Functional results after anterior rectal resections are commonly considered satisfactory but variable percentages of postoperative incontinence are often reported. Continence was evaluated after 20 low anterior resections (LAR) and 13 high anterior resections (HAR) by means of clinical assessment, anorectal manometry, and evacuation proctography. Whereas all HAR patients had perfect continence, 10 patients (50 percent of the LAR group had occasional episodes of soiling from liquid feces, 5 patients (25 percent had frequent soiling or occasional incontinence for solid feces, and 1 patient (5 percent had frequent solid stool loss requiring surgical treatment. Anal canal resting pressure at 3 and 4 cm from the anal verge was significantly lower in the LAR group (P<0.02 andP<0.05, respectively) than in the HAR group. However, the maximum voluntary contraction did not differ between the two groups. Rectoanal inhibitory reflex was found to be present in 17 of the 20 patients with LAR and in all patients with HAR. The volume at which the anal sphincter is continuously inhibited was significantly reduced in the LAR group (P<0.001). Also, the conscious rectal sensibility volumes were found to be significantly reduced for threshold, constant, and maximum tolerated volume. Threshold volume for internal sphincter relaxation was lower than the threshold volume for rectal sensation in some patients with LAR. This could allow postoperative fecal soiling. Rectal compliance was decreased (P<0.001) in the LAR group. Evacuation proctography, performed in six LAR patients affected by major soiling or solid stool loss, revealed an abnormal obtuse anorectal angle and pathologic lowering of the perineum at rest and during defecation. The concomitance of internal anal sphincter impairment, reduction in rectal compliance, and previous pelvic floor muscle damage are postulated as cause affecting continence in patients who underwent LAR.

APC gene mutations and colorectal adenomatosis in familial adenomatous polyposis

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 β-catenin binding domain but upstream II β-catenin-binding domain. Mutations between codons 867 and 1114, which affect the I β-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.

Restorative Proctocolectomy or Rectum-Preserving Surgery in Patients with Familial Adenomatous Polyposis: Results of a Prospective Study

Abstract 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.

Treatment of desmoids and mesenteric fibromatosis in familial adenomatous polyposis with raloxifene.

Background Among the great variety of extracolonic manifestations of familial adenomatous polyposis, the most serious are desmoids and fibromatosis of the abdominal cavity. These may be a danger to the patient and a concern to the clinician. Pharmacological management of this relentless problem is favored by surgical intervention. At present, however, beneficial actions of medical therapy are not separable from undesirable side effects. Methods We studied the effects of 120 mg daily of raloxifene, a non-steroidal benzothiophene, on progressive desmoid tumors and mesenteric fibromatosis by evaluation of lesion size and symptoms in 13 patients with familial adenomatous polyposis, selected on the basis of intra-abdominal localization of the lesion, on refractoriness to other medical treatments, and on estrogen receptor-α expression. Results The patients had a significant response to raloxifene therapy, with complete remission in 8 cases and partial response in 5 cases, evaluated by regression of symptoms and tumor size. Serum biochemical parameters did not show any significant changes. Side effects were never observed. Conclusions Although the number of patients included in the study is limited and in spite of some limitations, the available results support that, in the evaluation of response, daily therapy with raloxifene decreases desmoid tumor and mesenteric fibromatosis size and symptoms and does not cause side effects. These findings offer a novel option in the pharmacological treatment of desmoids, leading to medical therapy of these neoplastic lesions in familial adenomatous polyposis patients.

Long-term treatment with sulindac in familial adenomatous polyposis: Is there an actual efficacy in prevention of rectal cancer?

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.

Strictureplasty in Crohn's disease: Surgical option

PURPOSE: The objective of this study was to review early and late results of our personal experience with strictureplasty for patients affected by Crohns 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 Crohns strictures.

CD4+CD161+ T Lymphocytes Infiltrate Crohn’s Disease-Associated Perianal Fistulas and Are Reduced by Anti-TNF-α Local Therapy

Background: Crohn’s disease (CD) is an idiopathic inflammatory bowel disease (IBD) in the pathogenesis of which both Th1 and Th17 lymphocytes have been described as being involved. The NK-associated molecule CD161 has recently been described as a marker of IL-17-producing lymphocytes. In this work we assessed the presence and the functional features of CD161 T helper lymphocytes infiltrating CD-associated perianal fistulas, both before and after inoculation of anti-TNF-α mAbs along the fistula. Methods: In a group of 9 CD patients with fistulizing perianal disease, we evaluated phenotypic and functional features of T cells recovered from the fistula, comparing them with peripheral blood (PB) T lymphocytes. Moreover, the effects anti-TNF-α mAbs injections along the fistula in terms of ability to reduce the inflammatory infiltrate and to determine fistula disappearance were assessed. Results: In CD patients with fistulizing disease there is an accumulation of CD161+ T helper lymphocytes, with higher frequencies of Th1, Th17 and Th17/Th1 cells in the fistula than in PB. Local anti-TNF-α administration is associated with fistula resolution in the majority of patients with disappearance of infiltrating T lymphocytes, without any systemic effect in circulating effector T cells. Conclusions: These findings suggest that CD4+CD161+ T cells with Th17, Th17/Th1 and Th1 phenotype accumulate in CD perianal fistulas, and indicate local anti-TNF-α mAbs administration along the fistula as a promising tool for the treatment of these patients.

Ileal pouch adenomas and carcinomas after restorative proctocolectomy for familial adenomatous polyposis.

BACKGROUND: Restorative proctocolectomy and IPAA has become the treatment of choice in familial adenomatous polyposis. However, several cases of adenomas and carcinomas arising in the ileal pouch were reported. OBJECTIVE: The aim of this study was to evaluate the prevalence and natural history of ileal pouch adenomas and the development of carcinomas in patients with restorative proctocolectomy for familial adenomatous polyposis. DESIGN AND SETTING: We prospectively studied patients who underwent IPAA during the past 20 years at the surgical unit of the University of Florence in Italy. MAIN OUTCOME MEASURES: We investigated the extent of the risk and the factors that are involved in the development of neoplastic changes of the pouch. Furthermore, because it is not entirely clear when and how polyps should be treated, we have revised our modality of treatment for this unusual pathology. PATIENTS: Sixty-nine patients with familial adenomatous polyposis underwent restorative proctocolectomy. In 66 patients, handsewn ileoanal anastomosis with anal canal mucosectomy was performed. After surgery, all patients underwent endoscopic surveillance. RESULTS: After 10 years of follow-up, 1 ileal pouch adenoma was found in 64.9% of restorative proctocolectomy patients, and ileal pouch carcinomas occurred in 2 patients (29 and 59 years old), 3 and 11 years after restorative proctocolectomy. The number of colonic adenomatous polyps influenced the occurrence of pouch adenomas. No patients with <200 colonic adenomas experienced pouch adenomas, but 46% of patients with >1000 colonic polyps had pouch adenomas, and 25% of patients with 200 to 1000 colonic polyps had pouch adenomas at follow-up. No relationship was found between ileal pouch adenomas and pouch shape (J, S, or straight ileoanal anastomosis with multiple myotomies) or the APC mutation. Polyps larger than 5 mm were removed by endoscopy or surgery. CONCLUSIONS: Ileal pouch adenomas were common after restorative proctocolectomy. Patients >50 years of age and patients with >1000 colonic adenomas at the time of colectomy were more prone to ileal pouch adenomas. The development of malignancy in the terminal ileum can present a fast course and does not seem to follow the classic adenoma-carcinoma sequence.

Transcript dosage effect in familial adenomatous polyposis: Model offered by two kindreds with exon 9 APC gene mutations

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. Hum Mutat 11:197–201, 1998.

Pathological features in Crohn's disease determining perforation

Even if Crohns disease (CD) stenoses are related to perforating complications, such as abscess or fistula, it remains unclear why only some stenoses lead to such complications. We have studied the surgical specimens in 94 cases of CD to characterize the anatomical features of stenosis. We found no differences between group A (patients with perforation) and group B (noncomplicated patients) as far as extent of lesion, number of stenoses, and the caliber of the stenotic bowel. In CD of the ileum, the wall thickness of the stenoses was significantly different: 12.0 +/- 3.4 mm in group A and 7.6 +/- 3.1 mm in group B (p less than 0.001). In colonic CD, the length of stenosis was significantly greater in patients with perforation. Duration of symptoms, age at surgery, and sex did not correlate with the increased thickness or with perforating complications. These observations suggest that the fibrotic gastrointestinal tract, poorly distensible, may increase the intraluminal pressure above the stenosis and in this way squeeze bowel content through mucosal fissures of the inflamed bowel. Evaluation and monitoring of wall thickness may help in prompting surgery before the disease is complicated by perforation.