Restorative proctocolectomy impairs fertility and pregnancy outcomes in women with ulcerative colitis.

AIM: The effect of restorative proctocolectomy (RPC) on fertility and pregnancy in women with ulcerative colitis (UC) was evaluated. METHOD: Post-RPC female patients with UC who were attempting to become pregnant filled out questionnaires on fertility and pregnancy. Demographic and pouch data of pregnancies ending with delivery were collected from a prospective database. RESULTS: Forty-one women, 44 ± 10 years of age, completed the questionnaires. The median follow-up period post-RPC was 167 (range, 20-352) months. Before RPC, 26 women had 70 pregnancies and 62 deliveries. After RPC, 17 women had 32 pregnancies and 26 deliveries (P = 0.0035). Post-RPC, 10 (37%) of 27 patients failed to conceive compared with 26/26 successful attempts before RPC (P = 0.0006). The number of offspring per patient was 2.38 ± 1.27 before, and 0.68 ± 0.93 after, RPC (P < 0.0001). A higher number of spontaneous pregnancies occurred before (56/62; 90%) than after (15/25; 60%) RPC (P = 0.0004). The time to conception was longer (5.0 ± 11.6 vs 16.3 ± 25.1 months; P = 0.039) and there were more in-vitro fertilization procedures (three vs six) post-RPC. The gestation period was similar, but after RPC more deliveries were by Caesarean section (12.9% vs 46.2%; P = 0.0007). Babies born before RPC weighed more than those born after RPC (3.16 ± 0.61 kg vs 2.79 ± 0.68 kg, respectively; P = 0.0327). CONCLUSION: RPC is associated with an increased risk of infertility, similar duration of gestation and lower birthweight. Female candidates for RPC who have not finished family planning should be counselled accordingly.

Risk factors for chronic pouchitis after ileal pouch-anal anastomosis: a prospective cohort study.

AIM: The association between various demographic, clinical and pathological parameters and the evolution of chronic pouchitis was evaluated. METHOD: All ulcerative colitis patients who underwent ileal pouch anal anastomosis (1981-2009) were followed prospectively in a comprehensive pouch clinic. We examined risk factors including the presence of appendiceal inflammation and backwash ileitis in the colonic specimen, gender, ethnicity, age at disease onset, disease duration, extent of colitis, presence of extraintestinal manifestations (e.g. primary sclerosing cholangitis), family history of inflammatory bowel disease, indication for surgery, medical treatment, age at operation, staged procedure, diverting ileostomy and length of follow-up. Univariate analysis was performed on all risk factors followed by logistic regression analysis. RESULTS: The 201 enrolled patients (106 women, age at surgery 35 ± 15 years) were followed for a mean of 108 months. One hundred and thirty-eight (69%) had either a normal pouch or episodes of acute pouchitis and 63 (31%) developed chronic pouchitis. On univariate analysis the presence of an ileostomy (P = 0.017), pancolitis (P = 0.008), shorter disease duration (P = 0.04) and longer follow-up (P = 0.01) were identified as risk factors for chronic pouchitis. Multivariate analysis showed that patients with pancolitis (OR 3.26, 95% CI 1.20-8.85) and longer follow-up (OR 1.09, 95% CI 1.01-1.18) were more likely to develop chronic pouchitis. There was also an association to disease duration but this did not reach a level of significance. CONCLUSIONS: Pancolitis and longer follow-up are directly related to the development of chronic pouchitis.

Compression anastomoses in colorectal surgery: a review.

The main serious risks of anastomotic construction in the colon and rectum include dehiscence and stricture formation. There is a resurgence of interest in sutureless anastomoses formed by compression elements since the introduction of shape memory alloy (SMA) systems, which evoke minimal early inflammatory response whilst maintaining anastomotic integrity. Currently, the most commonly used SMA is the nickel-titanium (NiTi) alloy that is highly biocompatible, returning to its pre-deformed stable (austenite) shape under different mechanical and thermal loads for use in humans. Pre-clinical data for shape memory alloy systems in colorectal anastomoses are limited, but it appears to be safe in porcine and canine models with limited leakage and reduced stricture formation. There does not appear to be any difference in tissue biochemistry of inflammatory markers when compared with conventional stapled techniques, although the few studies available show a markedly reduced early inflammatory response at the anastomotic site with the NiTi device. The majority of the clinical data concerning compression anastomoses are derived from the biofragmentable anastomotic ring device. This device has fallen out of use because of reported leaks, instrumental failure and problems with device expulsion. A novel SMA device, the NiTi anastomotic ring, permits construction of a low rectal anastomosis construction during open or laparoscopic procedures. The preliminary data demonstrate a safety comparable to conventional staple technology. This device also provides the potential of benefit of reduced anastomotic inflammation, because the compression ring results in direct serosa-to-serosa (or alternatively serosa-to-muscularis propria) apposition without the persistence of residual foreign material. This type of construction could lead to a reduced incidence of early anastomotic leakage and/or the development of anastomotic stenosis. Randomized clinical trials employing a NiTi arm for elective, emergency and high-risk colorectal anastomoses are required to determine its indications and clinical profile as well as to assess whether such technology may selectively obviate the need for proximal diversion in low colorectal anastomoses.

The effect of neoadjuvant Imatinib therapy on outcome and survival after rectal gastrointestinal stromal tumour.

AIM: The study aimed to characterize the pathological and clinical response of rectal gastrointestinal stromal tumours (GISTs) to neoadjuvant Imatinib. METHOD: The medical records of patients with rectal GISTs who were diagnosed and treated in five medical centres in Israel between January 2002 and January 2009 were retrospectively examined. Twelve patients who fulfilled the inclusion criteria of nonmetastatic rectal GIST for which preoperative neoadjuvant treatment with Imatinib was considered were suitable for enrollment. RESULTS: Of the 12 patients, nine received neoadjuvant treatment with Imatinib. The three patients who had immediate surgery were excluded. There were five men and four women with a median age of 63 years and a median follow up of 32 months. All tumours were located in the lower two-thirds of the rectum. One patient had a complete clinical response, six had a partial response and two had stable disease. Seven patients subsequently underwent surgery; six had an R0 resection and one had an R1 resection. Three patients had recurrence. There was no disease-related mortality. The reduction in both tumour size and mitotic activity during preoperative Imatinib therapy was significant. CONCLUSION: Preoperative Imatinib therapy can shrink large rectal GISTs, improving the chances of successful radical surgery and decreasing the risk of considerable morbidity.

Colorectal carcinoma in inflammatory bowel disease: a comparison between Crohn's and ulcerative colitis.

AIM: The study assessed the clinicopathological features and survival rates of inflammatory bowel disease (IBD) patients with colorectal carcinoma (CRC), which accounts for ∼ 15% of all IBD associated death. METHOD: The medical records of patients operated on for CRC in three institutions between 1992 and 2009 were reviewed, and those with Crohn's colitis (CC) and ulcerative colitis (UC) were identified. Data on age, gender, disease duration, colitis severity, surgical procedure, tumour stage and survival were retrieved. RESULTS: Fifty-three patients (40 UC and 13 CC, 27 men, mean age at operation 54 years) were found. All parameters were comparable between the groups. Mean disease duration before CRC was 22.7 years for UC and 16.6 years for CC patients (P = 0.04). CRC was diagnosed preoperatively in 43 (81%) patients. Twenty-eight patients had colon cancer, 23 had rectal cancer and two patients had more than one cancer. All malignancies were located in segments with colitis. Over one-half were diagnosed at an advanced stage (36% stage III; 17% stage IV). At a mean follow up of 56 ± 65 months, 60% were alive (54% disease free) and 40% were dead from cancer-related causes. The 5-year survival rate was 61% for the UC and 37% for the CC patients (P = NS). CONCLUSION: CRC in IBD patients is frequently diagnosed at an advanced stage, a factor that contributes to poor prognosis. The risk of CRC in CC patients is comparable to those with UC. Long-term surveillance is recommended for patients with long-standing CC and UC.

Long-term outcome of loose seton for complex anal fistula: a two-centre study of patients with and without Crohn's disease.

OBJECTIVE: Complex anal fistulas traverse a significant portion of the external sphincter muscle, making their treatment a surgical challenge. Several surgical options are used with conflicting results. The aim of this study was to analyse the results of permanent loose seton in the management of high anal fistulas in Crohn's disease (CD) patients and two-stage seton fistulotomy in patients without CD. METHOD: We retrospectively reviewed the clinical records of 77 patients with complex anal fistula treated by loose seton over a 4-year period, in two medical centres. Recorded parameters included demographics, medical history, type of fistula, disease duration, previous surgery, morbidity, recurrence and mortality. RESULTS: Sixty patients without CD underwent 107 fistula-related surgical procedures, and 17 CD patients underwent 29 procedures. Early postoperative complications were recorded in eight (10%) patients. Perioperative complications, mainly local sepsis or bleeding, were recorded in eight (10%) patients. Long-term complications were observed in nine non-CD and four CD patients. During a median follow-up period of 24 months, the recurrence rate was 40% in CD patients and 47% in patients without CD. Five patients (four non-CD patients and one CD patient) developed some degree of faecal incontinence. CONCLUSION: The fistula recurrence rate following two-stage seton fistulotomy in non-CD patients was high. In CD patients the use of permanent loose seton is effective in controlling local sepsis in about half of patients and has low rates of subsequent incontinence.

Is stapled ileal pouch anal anastomosis a safe option in ulcerative colitis patients with dysplasia or cancer?

PURPOSE: The purpose of this study was to investigate the oncological and clinical outcome of ulcerative colitis (UC) patients with coexisting colorectal cancer/dysplasia following stapled ileal pouch-anal anastomosis (IPAA). MATERIALS AND METHODS: One hundred eighty-five UC patients who underwent stapled IPAA were followed prospectively in a comprehensive pouch clinic. They were divided into three groups: colorectal cancer, dysplasia, and no cancer/dysplasia. Demographic parameters, clinical data, and oncological and functional outcome of the three groups were compared. RESULTS: Sixteen patients had cancer and 14 had dysplasia. Two of the three cancer patients who developed metastatic disease died. One patient who had rectal cancer was found to have cancer cells in the rectal cuff 10 years after IPAA. All other cancer/dysplasia patients were disease-free at 62 months (median). The 5-year survival rate was 87.5% for the cancer group and 100% for the others (p < 0.0001). Chemotherapy (nine patients) did not affect pouch function. Two rectal cancer patients who received radiotherapy did not maintain a functioning pouch. Overall pouch failure rates were 19%, 7%, and 6% for cancer, dysplasia, and no-cancer/dysplasia patients, respectively (p = 0.13). The mean frequency of bowel movements in 24 h was similar between the groups. CONCLUSIONS: Stapled IPAA is a reasonable option for UC patients with cancer/dysplasia. Chemotherapy is safe, but the effect of radiation on pouch outcome is worrisome. Close long-term follow-up for UC patients with cancer/dysplasia is recommended for early detection of possible recurrence.

Familial adenomatous polyposis at the Tel Aviv Medical Center: demographic and clinical features.

UNLABELLED: Familial adenomatous polyposis (FAP) is an uncommon, but widespread genetic disorder that develops multiple colonic adenomatous polyps and, if untreated, can lead to large bowel cancer. Little is known about its occurrence and characteristics in the Israeli population. AIMS: To evaluate FAP prevalence, phenotypic manifestations and compliance for diagnosis and follow-up in our registry. METHODS: Since 1993 approximately one-half of FAP patients in Israel have been seen and followed-up by us before and/or after colectomy. They and their families were encouraged to have mutation analysis, genetic and/or endoscopic screening. RESULTS: 37 pedigrees were identified, including 2 non-Jewish. The Jewish ethnic distribution was similar to that of the general population and the point prevalence rate estimated as 28.4/one million Jewish inhabitants. There were 461 first-degree relatives at-risk for FAP. Genetic screening was completed and successful in 28 pedigrees (87.5%), and 73 FAP patients entered the registry. Marked intra- familial phenotypic variations with minimal disease manifestation were noted in 11 patients belonging to 4 pedigrees. Cancer occurred in 15.1% (11 patients), in 10 before FAP diagnosis or during follow- up elsewhere, but one non-compliant patient developed duodenal cancer. One other patient died from a massive, neglected, intra- abdominal desmoid. Compliance for evaluation and follow-up of pedigree members and individual FAP patients was inadequate in 29% and 27%, respectively. CONCLUSIONS: FAP occurs in the Israeli Jewish population at the expected rate, but is inadequately recognized in non-Jews. The inadequate compliance for screening and post-surgical follow-up needs to be addressed by educating the public, health care workers and Health Insurers.

Crohn's disease isolated to the appendix: truths and fallacies.

Twenty-five cases of Crohn's disease confined to the appendix were reported in eight hospitals in Israel during a 15-year period. Review of the histologic slides confirmed the diagnosis in 22 cases. Re-evaluation of these 22 patients included physical examination and radiologic studies of the small and large bowel. Rectosigmoidoscopy was performed in 16 patients. Signs and symptoms of Crohn's disease at other sites in the gastrointestinal tract did not occur during follow-up periods of two to 15 years (mean, 6.4 years) after appendectomy. This study and a review of the literature indicate that in most cases (93 per cent) Crohn's disease initially limited to the appendix is not a predictor of subsequent involvement of another portion of the bowel. It is concluded that the so-called Crohn's disease isolated to the appendix is a form of chronic granulomatous and follicular appendicitis of unknown etiology that is unrelated nosologically in the majority of the cases to Crohn's disease proper.

Polarization microscopy of picrosirius red stained sections: a useful method for qualitative evaluation of intestinal wall collagen.

Collagen pattern in healing anastomosis of intestinal wall was compared with its normal pattern in the submucosal layer. Polarization colours were recorded for thin (0.8 micron or less) and thick (1.6-2.4 micron) collagen fibres. The polarization colours of thick collagen fibres in the anastomotic site were more greenish-yellow and yellow than those in normal intestine which were more yellowish-orange and orange. These findings indicate that the collagen in the anastomotic site 4 days after operation is less packed than the collagen of normal rat intestine. Examination of the polarization colours of Picrosirius red-stained sections is a useful procedure to follow healing of anastomotic sites or diagnosis of collagen pathology in different pathologic conditions in the intestinal wall.

Intra-rectal injection of tumour cells: a novel animal model of rectal cancer.

The purpose of this study was to develop an animal model of rectal cancer. Three murine-derived cell lines, B16 melanoma, CT26 and MCA38 colon carcinoma, as well as the human colon cancer cell line LS174T were injected into the submucosa of the mouse rectum. Subcutaneous CT26 anbd B16 tumours and intra-caecal CT26 tumours served as controls for tumourigenicity of the cell lines. B16 melanoma produced a locally aggressive rectal tumour as well as skin and para-aortic lymph node metastases. CT26 produced local tumour when injected intra-rectally and colon tumours and liver metastases when injected into the caecum. MCA38 and LS174T intra-rectal injections resulted in large rectal carcinomas without metastases. We believe that growth of a colon cancer cell line in the rectum approximates the human disease more closely than other models of colorectal cancer. We would expect that the model could similarly be utilized to assess the effects of novel adjuvant treatments for rectal cancer as well as in the study of the tumour biology of rectal cancer.

Effect of photodynamic therapy on normal fibroblasts and colon anastomotic healing in mice.

Photodynamic therapy as an adjuvant modality to surgical resection of colon cancer is feasible provided that it does not affect healing of the anastomosis. The aim of this study was to evaluate the effects of photodynamic therapy on the viability of normal fibroblasts and on the healing process of colonic anastomosis in mice. Both in vitro and in vivo methods were employed. For in vitro study, 2 x 10(to the fifth power); human fibroblasts were incubated in triplicate with 5-aminolevulinic acid (2.5 microg/well) for 48 hours. Cells then underwent photoradiation at light doses of 50, 100, and 200 joules/cm(2) using a nonlaser light source. Viability was assessed by methylene blue dye exclusion. For in vivo studies, 60 mice were randomized into study and control groups and underwent laparotomy involving colonic anastomosis. The anastomosis underwent photodynamic therapy using 5-aminolevulinic acid (60 mg/kg) as a photosensitizer and a nonlaser light (40 joules/cm(2)). On postoperative days 1, 4, 7, 14, and 21, six mice were killed and subjected to bursting pressure and histologic examinations. Results of in vitro study showed pretreatment cell viability to be 96% to 99% in both groups. Photodynamic therapy caused no significant change in fibroblast viability at all light doses. Results of in vivo studies showed that the mean bursting pressure of both groups dropped to a low peak on day 4. Subsequently there was a gradual increase in bursting pressure along the examined time points (P <0. 001). There was no difference in bursting pressure between the two groups for all time points examined. It was concluded that photodynamic therapy has no effect on viability of normal human fibroblasts and no adverse effects on healing of colonic anastomosis.

Reduction of surgery-induced peritoneal adhesions by methylene blue.

BACKGROUND: The possible involvement of inflammatory mediators such as nitric oxide (NO), and reports of protective effects of antioxidants, led us to test the effectiveness of methylene blue and NO synthesis inhibitor in reducing adhesion formation. METHODS: Generation of adhesions in rats, by scraping the anterior uterine horn wall, was followed by intraperitoneal administration of saline methylene blue, or N alpha-t-BOC-omega-nitro-L-arginine. Additional rats received identical treatments, but without the serosal damage. Two weeks later, formation of adhesions was quantitatively graded. RESULTS: Adhesions were found in <5% of the rats with the sham surgery, regardless of treatment. In the experimental group, >95% of the rats treated with saline or NO synthetase inhibitor had severe adhesions, in contrast to 5% of the methylene blue treated rats. Severity of adhesion was lower in the methylene blue group (P <0.001). CONCLUSIONS: Methylene blue was very effective in preventing formation of peritoneal adhesions. Its activity is probably through inhibition of free-radical generation and not of nitric oxide action.

Carcinoid tumor of the coccyx: case report and review of the literature.

STUDY DESIGN: Report of a patient with a carcinoid tumor of the coccyx. OBJECTIVES: To describe the clinical presentation, diagnosis, and treatment of a patient with a carcinoid tumor of the coccyx and to review the relevant medical literature in English. SUMMARY OF BACKGROUND DATA: No reports of a carcinoid tumor of the coccyx were found in the literature. Seven reports of carcinoid of the sacrum are described. METHODS: Clinical history, magnetic resonance imaging studies, and light and electronic microscope micrographs are reviewed. RESULTS: A coccygeal mass was detected during evaluation of coccygodynia in a 40-year-old woman. Four years after extended coccygectomy, there are no signs of local tumor recurrence. CONCLUSIONS: Carcinoid tumor of the coccyx is extremely rare. An extended coccygectomy may lead to a cure or at least to a prolonged disease-free interval.

Carcinoma of the breast in women 30 years of age or younger.

Between 1960 and 1975, 20 women aged 30 years or younger and with carcinoma of the breast were treated at the Chaim Sheba Medical Center. Eight are alive four to 12 years after the primary operative treatment, and 12 have died. The most important factor affecting the ultimate prognosis was the presence of metastasis in axillary nodes, which was found in 70 per cent of the women at surgery. On the other hand, slowly progressing circumscribed tumors of the medullary and intraductal types were more frequently found, occurring in six of the patients. This fact seems to improve the prognosis. Hence, the overall survival rate of women who are 30 years old or younger with carcinoma of the breast is comparable to that of women in other age groups with the same disease.

Scintigraphic demonstration of acute gastrointestinal bleeding caused by gallbladder carcinoma eroding the colon.

Massive lower gastrointestinal (GI) bleeding caused by gallbladder carcinoma eroding into the colonic wall was demonstrated accurately by Tc-99m RBCs. In addition, retrograde bleeding into the gallbladder was also identified while arteriography did not show contrast extravasation. This case supports the use of Tc-99m RBCs over Tc-99m sulfur colloid for more accurate localization of lower GI bleeding.

The importance of early surgery in children with ulcerative colitis.

BACKGROUND: Ulcerative colitis begins in early childhood in 4% of cases. Medical therapy is non-specific, and as many as 70% of children will ultimately require surgery. The dynamic growth, physical and psychological changes that characterize childhood are severely compromised by the complications of ulcerative colitis and its therapy. OBJECTIVE: To review the outcome of children undergoing early surgery for ulcerative colitis at a tertiary medical center in Israel. METHODS: A retrospective review was conducted of all children operated on following failure of medical therapy for ulcerative colitis during a 5 year period. RESULTS: Eleven children underwent a J-pouch procedure with ileo-anal anastomosis in one to three stages. Postoperative complications included recurrent pouchitis in 5 patients, intestinal obstruction in 3, fistula with incontinence in one, stricture in one, and wound infection in 4. Follow-up revealed that most of the patients have three to four soft bowel movements daily. All currently enjoy normal physical activities and a rich social life. CONCLUSIONS: The quality of life in children with ulcerative colitis was markedly improved following J-pouch surgery. This procedure was not associated with major complications. We recommend early surgery as an alternative to aggressive medical therapy in children with this disease.

[Transanal endoscopic microsurgery for local excision of rectal neoplasms].

We removed 30 benign, sessile, rectal polyps by the transanal approach between January 1990 and April 1994. In 16 patients we used transanal endoscopic microsurgery (TEM), while in 14 the adenoma was removed by submucosal excision (SE). There were 3 local recurrences in the SE group, but none as yet in the TEM group. There was no operative mortality. Early complications included myocardial infarction in 1 patient and persistent postoperative fever which responded to antibiotic treatment in another. Late complications included temporary, anal mucous leakage in 10% and 5% of the TEM and SE groups, respectively. TEM was found to be efficient for the removal of polyps in the upper and middle thirds of the rectum, and SE for those in the lower third. This enables safe removal of rectal polyps, avoiding the need for complex operations involving greater risks.

[Restorative proctocolectomy for ulcerative colitis and familial polyposis].

From 1987-1994 we performed 35 proctocolectomies with ileal pouch anal anastomosis. The indication for operation was ulcerative colitis in 29 and familial polyposis in 6. The mean ages at operation were 35 and 25 years, respectively. The most common postoperative complication was small bowel obstruction in 25% of the patients, requiring re-operation in half of them. The incidence of this complication may be reduced by operating in only 1 stage when possible, without creating a protective ileostomy. The second serious complication was pouchitis, in 17%, which was controlled by antibiotics. There has been no mortality. All patients, except for 2 with an S-shaped pouch, evacuate spontaneously a mean of 5 bowel movements a day. Continence was mildly impaired (usually night-staining of a pad) in 30% of patients in whom the pouch-anal anastomosis was performed after stripping the mucosa of the rectal remnant. In those in whom the pouch-anal anastomosis was performed by means of the double stapling technique, continence was almost completely preserved. We therefore recommend that proctocolectomy with ileal pouch-anal anastomosis be performed in 1 stage when possible, using the double stapling technique. Staged operation should be reserved for severely ill patients, or when stripping of the rectal mucosa is performed for familial polyposis and ulcerative colitis with severe dysplasia.

[Anterior resection with colo-anal anastomosis for low rectal cancer].

Between May 1989 and April 1993 we treated 108 patients, aged 44-82 years, for rectal cancer. Of them, 7 men and 2 women underwent anterior resection with colo-anal anastomosis. In this group the average distance of the tumor from the anal verge was 6 cm. Follow-up ranged from 12-48 months. There was no operative mortality. Perioperative morbidity included wound infection in 1 patient and pelvic sepsis in another; temporary disturbances in micturition occurred in 4; 1 developed an anastomotic stricture and another intestinal obstruction; 1 died of systemic spread; another was reoperated and salvaged, but had a local recurrence 3 years after the first operation. Continence was achieved in 6, while 3 had minor impairment of control. Frank incontinence did not occur. We believe that anterior resection with colo-anal anastomosis in low rectal cancer avoids a permanent colostomy, while meeting oncological and functional criteria. We advocate this procedure in selected patients with low rectal cancer.