Regression of rectal polyps by indomethacin suppository in familial adenomatous polyposis

PURPOSE: The effect of indomethacin suppository on rectal polyps was evaluated in two patients with familial adenomatous polyposis who had undergone total colectomy and ileoproctostomy. METHODS: Both patients received intrarectal administration of 50 mg of indomethacin suppository once or twice daily to control the rectal remnant polyps. RESULTS: With this treatment, an almost complete regression was achieved within three months, in both patients. Polyps recurred after the interruption of indomethacin treatment in one patient. At the present follow-up of two to three years, no cancer has developed. CONCLUSIONS: Indomethacin suppository treatment was effective in controlling rectal remnant polyps in the two patients with familial adenomatous polyposis. Intraluminal administration of indomethacin in suppository form seems more beneficial since it allows for direct contact of the drug with the lesions and produces a high local concentration of the drug.     

Spontaneous mutation in familial adenomatous polyposis

A retrospective review of the familial adenomatous polyposis registry at the Cleveland Clinic Foundation revealed an incidence of spontaneous mutation in familial adenomatous polyposis (FAP) of 22 percent of family kindreds. These patients were reviewed retrospectively and compared with the total FAP population followed at The Cleveland Clinic Foundation with respect to the onset of disease, the incidence of carcinoma in the resected colon, and incidence of extracolonic manifestations. Review of the characteristics and presentations of these patients suggested that these individuals may harbor a more severe form of FAP. This may be due, in part, to the delay in diagnosis and, therefore, a higher rate of development of colorectal carcinoma and possibly duodenal adenomas. There is also a demonstrable higher rate of extracolonic manifestations of FAP present in this subset of patients. When selecting the initial type of prophylactic colonic resection the surgeon should bear in mind the increased incidence of extracolonic manifestations of the disease in this group of patients and their potential for complications.Read at the meeting of the American Society of Colon and Rectal Surgeons, Anaheim, California, June 12 to 17, 1988.     

Results of ileal J-pouch-anal anastomosis in familial adenomatous polyposis complicated by rectal carcinoma

PURPOSE: Rectal cancer frequently occurs in patients with familial adenomatous polyposis (FAP) and, in some cases, proctocolectomy and ileal pouch-anal anastomosis (IPAA) can be proposed as an alternative to end ileostomy. This study aimed to assess the results of IPAA for familial adenomatous polyposis complicated by rectal carcinoma. PATIENTS AND METHODS: Postoperative morbidity and bowel function following IPAA were assessed in six patients who had a mesorectal excision for rectal cancer. The functional results were compared with those obtained after IPAA in 134 FAP patients without bowel cancer. RESULTS: Carcinomas were located at a mean of 11 cm from the dentate line. There were no postoperative complications. One patient with synchronous hepatic metastases died 6 months after operation and the 5 others were alive without recurrence after a mean follow-up of 29 months. Mean frequency of defecation was 6.5/day (vs. 4.2/day in patients without carcinoma), 86 percent of patients had nocturnal defecation (vs. 50 percent), day and night continence were normal in 66 percent and 33 percent of patients, respectively, compared with 90 percent and 85 percent for IPAA without cancer. Pouch excision was required in one patient for unsatisfactory functional result. CONCLUSION: IPAA can be safely performed for cancer of the upper rectum complicating FAP, but a poor functional outcome related to mesorectal excision has to be expected.     

Serum gastrin values in patients with familial adenomatous polyposis

PURPOSE: An evaluation of the importance of gastrin in the colorectal carcinogenesis in patients with familial adenomatous polyposis was conducted. METHODS: Blood samples from 168 family members of 26 families were investigated for circulating gastrin. Blood was drawn from 65 affected patients, 66 clinically unaffected first-degree relatives, and 37 spouses. RESULTS: We did not find any difference in distribution of serum gastrin among these groups. CONCLUSION: Our results seem to exclude gastrin from being relevant in early carcinogenesis in patients with familial adenomatous polyposis.     

Mortality in patients with familial adenomatous polyposis

The authors identified 132 patients who died with a documented diagnosis of familial adenomatous polyposis (FAP). A review of the medical records, autopsy reports, and in-depth discussion with local physicians and well-informed family members was performed. It was impossible, even after the review, to ascertain the exact cause of death in 22 patients. In the remaining patients, the cause of death was as follows: metastatic colorectal carcinoma, 64 patients (58.2 percent), (colon, 49 [44.5 percent], rectal, 15 [13.6 percent]); desmoid tumors, 12 (10.9 percent); periampullary carcinoma, 9 (8.2 percent); brain tumors, 8 (7.3 percent); perioperative mortalities, 5 (4.5 percent); adrenal carcinoma, 1 (0.9 percent); and abdominal carcinomatosis, 1 (0.9 percent). Ten patients died of causes not related to FAP. The major causes of death in 36 patients who underwent prophylactic colectomy were desmoid tumor and periampullary malignancy. This finding underscores the importance of lifelong surveillance and periodic endoscopic evaluation in patients with FAP.Read at the Tripartite Meeting, Birmingham, United Kingdom, June 19 to 22, 1989.     

Colectomy with ileorectal anastomosis lowers rectal mucosal cell proliferation in familial adenomatous polyposis

Rectal polyp regression has been observed in familial adenomatous polyposis (FAP) after colectomy and ileorectal anastomosis (IRA). In view of the association between risk of neoplasia and epithelial cell turnover rates, a study was conducted to determine the effect of colectomy and IRA on rectal mucosal proliferation in FAP. Endoscopic biopsies of flat rectal mucosa were taken from 12 FAP patients with an established IRA and 10 FAP patients prior to colectomy. Mucosal proliferation was assessed by flash-labeling S-phase cells with bromodeoxyuridine. Labeled cells were visualized on paraffin sections with an immunohistochemical stain using a monoclonal antibody to bromodeoxyuridine. Twenty crypt columns were analyzed. The mean labeling index (percent labeled cells/crypt) of the FAP patients with established IRAs (7.0±1.4 percent) was significantly less than that of the precolectomy patients (12.8±3.0 percent) (Mann-Whitney U test,P =0.0004). Comparison of labeled distribution curves shows a contraction of the crypt proliferative zone in the IRA group. Colectomy with IRA in FAP is associated with a significant reduction in rectal mucosal cell proliferation. These findings support the claim of reduced risk of rectal cancer following this procedure in FAP and are of relevance to the study of environmental vs.genetic control of cell proliferation.Presented at the meeting of the British Society of Gastroenterology, London, September 1991.Dr. Farmer was supported by the St. Mark's Research Foundation.     

Adenocarcinoma of an ileostomy in a patient with familial adenomatous polyposis

A case of adenocarcinoma arising in an ileostomy of 39 years' duration is presented. The patient had undergone proctocolectomy in 1949 for familial adenomatous polyposis, with subsequent ileostomy in 1950, and presented in April 1989 with bleeding and a mass at the stoma site. Biopsy of the mass revealed adenocarcinoma. Adenocarcinoma of an ileostomy is a rare but well-documented complication, with the present patient bringing the total number of reported cases to 18. The literature is reviewed, and surveillance measures are suggested.     

Laparoscopic total abdominal colectomy with ileorectal anastomosis for familial adenomatous polyposis

PURPOSE: This study was undertaken to describe our results in a series of patients undergoing total abdominal colectomy with ileorectal anastomosis (TAC/IRA) using laparoscopic techniques in patients with familial adenomatous polyposis (FAP) and rectal-sparing. Young patients with FAP requiring TAC/IRA may be ideal candidates for minimally invasive surgery, because they are generally thin and have benign disease. They might benefit maximally from the theoretic advantages of these techniques. METHODS: We have performed laparoscopic TAC/IRA in 16 FAP patients (10 females; mean age, 18 years). Procedures were entirely intracorporeal, with a 3-cm to 6-cm specimen extraction incision. RESULTS: Median operative time was 232 (range, 156–285) minutes, and blood loss 175 (range, 50–675) ml. The only intraoperative complication, a twisted ileorectal anastomosis, was noted intraoperatively and revised. There were no conversions to conventional laparotomy. Median postoperative interval to passage of flatus was three days,^1–4 and for bowel movements it was three days.^1–4 Median hospital stay was five days.^3–11 One case of early postoperative small-bowel obstruction was treated nonoperatively, and one case of brachial plexus neuropraxia resolved spontaneously. CONCLUSIONS: Based on this preliminary experience, we believe laparoscopic TAC/ IRA can be a safe and effective treatment for selected patients with FAP. As techniques and instrumentation for laparoscopic colon surgery are perfected, this procedure will likely become an appealing option in the management of patients with FAP. Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996. No reprints are available     

Presymptomatic diagnosis of familial adenomatous polyposis coli

Familial adenomatous polyposis (FAP), an autosomal dominant inherited disease, confers a high risk of colon cancer, and recently the gene responsible for FAP, termed adenomatous polyposis coli (APC) gene, was identified and fully characterized. PURPOSE: For the presymptomatic diagnosis of FAP, we have performed linkage studies using two polymorphic systems close to or at the APC locus; cytosine-adenine dinucleotide repeat length polymorphism and restriction endonuclease RsaI site polymorphism. METHODS and RESULTS: Based on the two polymorphic systems, we have determined the haplotype at the APC locus in 23 individuals of two Korean families with FAP. From these haplotypes of individuals, we could make the diagnosis, whether affected or unaffected, in 74 percent of 31 at-risk persons. To decrease the chance of misdiagnosis caused by recombinant events, the use of haplotypes was better than using one polymorphic system. In addition to polymorphic analysis, we have also searched germline mutations of the APC gene in eight individuals (26 percent of all 31 at risk persons) of another two FAP families which could not be diagnosed definitely by linkage analysis. A 5 base-pairs deletion at codon 1309 was detected in one of the families, and a 5 base-pairs deletion at codon 1185 was also identified in another family by using a ribonuclease protection assay followed by DNA sequencing. From these results, we could diagnose FAP with 100 percent accuracy. CONCLUSION: Linkage studies by the Rsa I site polymorphism and cytosine-adenine repeat length polymorphism as well as the polymerase chain reaction-based sequencing method provide accurate and efficient tools for presymptomatic diagnosis of FAP in their families.Supported in part by a grant from the Seoul National University Hospital Research Fund (04-93-007) and a grant from Korea Science and Engineering Foundation (KOSEF-SRC-56-CRC-8).Read at the meeting of The American Society of Colon and Rectal Surgeons, Chicago, Illinois, May 2 to 7, 1993.     

Gastroduodenal polyps in patients with familial adenomatous polyposis

A review of the endoscopy reports and pathology results from esophagogastroduodenoscopy (EGD) of all patients with familial adenomatous polyposis (FAP) undergoing such an examination was performed. Two hundred fortyseven patients were identified, with an overall prevalence of duodenal adenomas of 66 percent and of fundic gland polyps of 61 percent. Analysis of our more recent experience (1986 to 1990) shows the prevalence to be 88 percent and 84 percent, respectively. A normal-appearing papilla was adenomatous in 50 percent of cases. No case of periampullary carcinoma developed in patients under surveillance. Routine EGD is indicated for patients with FAP. Duodenal adenomas and fundic gland polyps will occur in the majority of patients.Read at the meeting of The American Society of Colon and Rectal Surgeons, Boston, Massachusetts, May 12 to 17, 1991.     

直肠家族性腺瘤性息肉与癌组织中COX—2蛋白表达及意义

用流式细胞仪（FCM）检测19例直肠家族性腺瘤性息肉病（FAP）及39例直肠癌患者癌组织的环氧合酶-2（COX-2）蛋白表达。结果表现，18（94.74%)例息肉组织COX-2蛋白阳性表达，39（100%）例癌组织COX-2蛋白均阳性表达，提示COX-2蛋白表达检测在诊断监测，化学预防息肉癌变过程中可能具有重要意义。     

Noncytotoxic drug therapy for intra-abdominal desmoid tumor in patients with familial adenomatous polyposis

Forty of 416 patients with familial adenomatous polyposis were noted to have intra-abdominal desmoid tumors, and a subgroup of 16 were treated with noncytotoxic drug therapy. Drugs used were sulindac (14 patients), sulindac plus tamoxifen (3 patients), indomethacin (4 patients), tamoxifen (4 patients), progesterone (DEPO-PROVERA^®; Upjohn Co., Kalamazoo, MI) (2 patients), and testolactone (1 patient). Therapy with these drugs for continuous periods of six months or more resulted in three complete and seven partial remissions. When treated patients were compared with untreated patients (n=12), there were significant benefits for the treated group, both in reduction of desmoid size and in improvement of symptoms, despite the inherent selection bias against this. Sulindac was the only drug used in enough patients to permit independent evaluation of its effect, with one complete and seven partial reductions of tumor size. Some patients had a delayed response to sulindac, with tumor shrinkage occurring after an initial period of tumor enlargement. When using sulindac for the treatment of desmoid tumors, this phenomenon should be considered.Read at the meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, April 29 to May 4, 1990.This work was supported by the International Center for Specialty Studies of Cleveland Clinic Foundation.     

Life expectancy after colectomy and ileorectal anastomosis for familial adenomatous polyposis

PURPOSE: Despite the introduction of screening, surveillance, and prophylactic colectomy surgery, patients with familial adenomatous polyposis (FAP) are at risk of dying from other malignancies. METHODS: In order to quantify this risk and identify the causes of mortality, a retrospective life table analysis was performed on 222 patients with familial adenomatous polyposis who had undergone a total colectomy and ileorectal anastomosis between 1948 and 1990. These FAP patients were compared with an age- and sex- matched group of the general population and a relative risk of dying was calculated. RESULTS: Of 222 patients, 53 have died. In a matched group of the general population the expected number of deaths would be 15.8. The relative risk of dying is therefore 3.35. There has been no significant improvement with time and the relative risk is greatest for female patients. CONCLUSION: The three main causes of mortality are upper gastrointestinal malignancy, desmoid disease, and perioperative complications. Further research should therefore be aimed at prevention and improved treatment of these in order to improve survival.This work was performed at St. Mark's Hospital. Ms. K. P. Nugent was funded by the St. Mark's Research Foundation.     

The value of screening and central registration of families with familial adenomatous polyposis

In 1984 a national registry of families with familial adenomatous polyposis was set up in The Netherlands to promote screening in those families. Eighty-two families had been registered by the end of 1988. Analysis of the pedigrees showed that 204 family members at risk had not yet been screened. The diagnosis of familial adenomatous polyposis was histologically confirmed in 230 patients. These patients were subdivided into two groups. Group A comprised patients with familial adenomatous polyposis referred because they were symptomatic, and Group B relatives of these patients who were found by screening to have familial adenomatous polyposis. The authors compared these groups with respect to the occurrence of colorectal carcinoma. Fifty-four patients were found to have a colorectal carcinoma at the time of diagnosis of familial adenomatous polyposis,i.e.,49 of the 104 patients in Group A (47 percent) and five of the 126 patients in Group B (4 percent). The average age at diagnosis of the 104 patients in Group A was 35 years (range, 13 to 66 years) and that of the 126 patients in Group B was 24 years (range, 8 to 59 years). By the age of 40 years, 90 percent of the patients in group B had been diagnosed. Late onset of familial adenomatous polyposis was found in four families. Endoscopy and/or radiography of the upper digestive tract were (was) performed in 44 of the 230 patients. Nineteen patients (43 percent) were found to have polyps in the stomach or duodenum, or both. In our series, only one patient died from cancer of the upper digestive tract (ampullary carcinoma). These results show conclusively that screening leads to the early detection of familial adenomatous polyposis. The value of a national registry is proved by the finding of many at-risk family members who had not previously been screened. Screening should start between the ages of 10 and 12 and should continue up to the age of 50. In the rare cases of families with an apparently late onset of familial adenomatous polyposis, screening should be continued up to age 60. More studies are needed to determine the natural history of polyps in the upper digestive tract.     

Chemotherapy for desmoid tumors in association with familial adenomatous polyposis

PURPOSE: This study was designed to assess the effect of chemotherapy on complex desmoid tumors associated with familial adenomatous polyposis. METHODS: Five patients (3 males, 2 females; age range, 29–45 years) had symptomatic, unresectable intra-abdominal desmoid tumors in association with familial adenomatous polyposis that were unresponsive to conventional medical therapy. Each patient was treated with a cytotoxic chemotherapeutic regimen consisting of doxorubicin and dacarbazine followed by carboplatin and dacarbazine. Response to treatment was assessed by measurement of tumor size using computerized tomography. Follow-up has been for a mean of 22 (range, 10–30) months. RESULTS: One patient has had a complete response, and three patients have had a partial response, with a reduction in tumor volume of at least 50 percent. One patient had a minimum response to treatment and developed a rapid increase in tumor size on cessation of therapy. Complications of treatment included febrile neutropenia, severe epistaxis, and subclavian vein thrombosis. CONCLUSIONS: The cytotoxic chemotherapeutic regimen described is effective in the treatment of selected unresectable desmoid tumors associated with familial adenomatous polyposis and should be considered in symptomatic patients who do not respond to conventional medical therapy.Read at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996. No reprints are available.     

Predictive value of congenital hypertrophy of the retinal pigment epithelium as a clinical marker for familial adenomatous polyposis

One hundred forty-eight members of 53 kindreds with familial adenomatous polyposis (FAP) were examined for congenital hypertrophy of the retinal pigment epithelium (CHRPE) and extracolonic manifestations (ECM) to assess the value of CHRPE as a predictive marker for FAP. Based on eye examination results, the families were divided into 2 groups. In a first group of 34 families, all 61 members diagnosed as having polyps and 13 of the 33 patients at risk had 4 or more lesions distributed in both eyes. By contrast, in a second group of 18 families, all 32 polyposis patients and all 18 members at risk had less than 4 lesions. Extracolonic manifestations were present in 26 of 34 families in the first group and in 11 of 18 families in the second group. Data on one family with ambiguous ancestry were reviewed separately. The existence of 4 or more CHRPE lesions distributed in both eyes seems to be a congenital marker for FAP, present in 65.4 percent of families. When present in a family: 1) it is found in all diagnosed patients in that family, 2) can therefore be considered predictive for the development of polyps in other family members who carry the trait, and 3) if confirmed by longer follow-up, may possibly preclude members without the trait from further evaluation and surveillance.Read at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.     

Results of a thirty-year study of familial adenomatous polyposis coli

PURPOSE: This study was designed to estimate the efficiency of the various methods used to treat familial adenomatous polyposis coli. METHODS: Three hundred ninety patients (219 males) underwent surgery for familial adenomatous polyposis coli; postoperative follow-up was from 1 to 30 years. RESULTS: Coloproctectomy with preservation of the anal sphincter and coloproctectomy with ileoanal pull-through procedures resulted in development of anal canal cancer in 3 (4.1 percent) of 74 patients. Follow-up revealed development of cancer in the large bowel in 26 (10.7 percent) of 242 patients, in whom colectomy with preservation of various colonic segments was performed. CONCLUSIONS: The occurrence rate of cancer is not significantly related to patients' gender, age, length of preserved colonic segment, presence of cancer in the removed colonic segment, or postoperative follow-up period; however, presence of polyps in the colonic segments preserved during surgery significantly increased the risk of development of cancer at a later time.     

Development of invasive adenocarcinoma following colectomy with ileoanal anastomosis for familial polyposis coli

PURPOSE: Proctocolectomy with ileoanal anastomosis has gained increasing acceptance for the prophylactic treatment of patients with familial polyposis coli. Longterm surveillance of the ileal pouch and the pouch-anal anastomosis has not been emphasized despite concern regarding retained rectal mucosa following the procedure. METHODS: A 34-year-old patient with a strong family history of familial polyposis coli was treated at 14 years of age by single-stage proctocolectomy with straight ileoanal anastomosis. Follow-up proctoscopic examinations revealed development of adenomatous changes at the ileoanal anastomosis. RESULTS: This report presents a patient with familial polyposis coli who developed invasive adenocarcinoma at the ileoanal anastomosis 20 years after proctocolectomy with ileoanal anastomosis. CONCLUSIONS: We stress the need for lifelong proctoscopic surveillance in patients with familial polyposis coli treated by proctocolectomy with ileoanal anastomosis.     

Effects of short chain fatty acids on mucosal proliferation and inflammation of ileal pouches in patients with ulcerative colitis and familial polyposis

PURPOSE: To verify whether short chain fatty acids (SCFA) alter the proliferative and endoscopic pattern of the mucosa in ileal pouches of ulcerative colitis (UC) or familial adenomatous polyposis (FAP) patients. METHODS: We studied patients after proctocolectomy carrying a pelvic ileal pouch for FAP or UC (noncanalized pouches in 10 UC and 4 FAP patients and canalized pouches in 6 UC and 5 FAP patients). Patients with noncanalized pouches were treated twice daily for one week with 30 ml of a SCFA solution (60 mM sodium acetate, 30 mM sodium propionate, 40 mM sodium butyrate, and 22 mM sodium chloride, pH 7); patients with canalized pouches were treated with the same solution twice daily for two weeks. Pouch mucosal biopsies were collected before and after SCFA. Mucosal proliferation was assessed by incorporation of [³ H]thymidine in vitro and autoradiography. RESULTS: In UC patients proliferation did not vary in noncanalized pouches but was significantly reduced in canalized pouches after SCFA. In FAP patients SCFA did not alter proliferation. No significant effects of SCFA were observed on daily defecation frequency, endoscopic appearance, or histopathology of the pouches. CONCLUSIONS: SCFA do not control inflammation and clinical functions but reduce cell proliferation in UC patients. On the contrary, FAP patients are refractory to SCFA.Supported by grants of Progetto finalizzato ACRO of CNR, Progetto finalizzato FATMA, of EEC program AIR 2 CT940933, and MURST (40 percent).     

Experience with the use of the circular stapler in rectal surgery

This report provides our personal experience along with a general overview of the use of the circular stapler in rectal surgery. To determine the results of our experience with the use of the circular stapler for construction of anastomoses following resection, a series of 215 anastomoses performed in 214 patients was reviewed. The patients ranged in age from 33 to 88 years. There were 116 men and 98 women. Indications for operation included malignancy, diverticular disease, villous adenoma, Crohn's disease, and rectal procidentia. The types of operation performed included removal of varying portions of the large bowel. The anastomosis was performed in a uniform manner with the EEA ^® (United States Surgical Corp., Norwalk, CT) and more recently the CEEA (United States Surgical Corp., Norwalk, CT). The operative mortality was 0.47 percent, with the death being unrelated to the anastomosis. Intraoperative complications encountered included bleeding, difficult extraction, instrument failure, incomplete doughnuts, deficient anastomoses, and miscellaneous problems. Early postoperative complications included one leak and a number of complications unrelated to the anastomoses. Anastomotic stenosis developed in 27 patients, but only 8 were permanent and only 3 of these were symptomatic. Two of these patients were treated with balloon dilatation. Anastomotic recurrences developed in 131 percent of patients. Our experience gained with the circular stapling device and that reported in the literature have shown it to be a reliable method of performing anastomoses to the rectum in a safe and expeditious manner.This study was conducted with support from The Sir Mortimer B. Davis Jewish General Hospital Foundation and The American Physician Fellowship.