NSAID-induced polyp regression in familial adenomatous polyposis patients

NSAIDs inhibit prostaglandin synthesis. In 1983, Waddell et al first reported that sulindac, a NSAID (Clinoril), caused regression of rectal adenomatous polyps in several patients with familial adenomatous polyposis, an inherited form of colorectal cancer. Subsequently, NSAIDs have been used as chemopreventive agents in animal carcinogenesis models and adenoma regression had been confirmed in human trials with sulindac. This article summarizes these developments and describes possible mechanisms of colorectal neoplasia chemoprevention.     

Prevention of gastrointestinal cancer--the potential role of NSAIDs in colorectal cancer

Gastrointestinal cancers are among the leading sites of cancer and leading causes of cancer-related deaths. Gastrointestinal cancers are often at an advanced stage at the time of diagnosis, and are highly resistant to non-surgical therapy. Thus early diagnosis and prevention are approaches that are under active investigation. Screening and surveillance are considered secondary prevention. Primary prevention is the use of dietary or environmental modification or chemopreventive agents. This written review will emphasize the potential role of acetylsalicylic acid and other non-steroidal anti-inflammatory drugs (NSAIDs) in the prevention of gastrointestinal cancer, and specifically colorectal cancer. Cell culture and animal studies have shown that NSAIDs possess anti-proliferative and anti-neoplastic effects. Recent epidemiologic surveys also suggest that individuals who regularly take NSAIDs, particularly acetylsalicylic acid, have about a 50% decrease in colorectal cancer incidence and mortality. However, in the only interventional trial of aspirin (and beta-carotene), a retrospective analysis had inadequate statistical power to demonstrate any protective effect against colorectal cancer. About a dozen small prospective intervention studies have been done in a total of about a hundred patients with familial adenomatous polyposis to test the efficacy of NSAIDs, particularly sulindac. All human trials have shown substantial partial and some complete regression of colorectal and perhaps also duodenal adenomatous polyps. But virtually all patients had regrowth of adenomatous polyps after sulindac was stopped. In addition, sulindac and other NSAIDs result in occasional adverse events such as gastrointestinal bleeding. Thus sulindac cannot be recommended for routine use outside of a study setting. One valid current approach to the prevention of gastrointestinal cancer, and colorectal cancer in particular, is the adoption of a healthy lifestyle and appropriate screening and surveillance. Screening and surveillance guidelines have been developed by several public agencies and their recommendations should be adopted. In addition, we should adopt a healthy lifestyle and diet, which consists of low fat ( < 30% to total calories), and high fiber (> 3 daily servings of fruits/vegetables), with the avoidance of red meats ( < 3 weekly servings) and alcohol ( < 2 drinks daily), and the absolute avoidance of tobacco smoking.     

Sulindac causes rapid regression of preexisting tumors in Min/+ mice independent of prostaglandin biosynthesis

Several lines of evidence strongly link prostaglandins (PGs) and leukotrienes (LTs) to cancer of the intestine. Several studies have reported a 40-50% reduction in mortality from colorectal cancer in individuals who routinely consume nonsteroidal anti-inflammatory drugs, possibly by inhibiting cyclooxygenase activity. However, the role of eicosanoids in this process is still unclear. The heterozygote Min/+ mouse model, like patients with familial adenomatous polyposis, carries a nonsense mutation in the adenomatous polyposis coli (APC) gene that results in the spontaneous development of intestinal adenomas (100% incidence). This study investigated the association between eicosanoid biosynthesis, intestinal tumor load, and the chemotherapeutic effect of the nonsteroidal anti-inflammatory drug sulindac during early and preexisting phases of tumor growth and development as well as residual effects after drug withdrawal. Administration of sulindac (320 ppm) to Min/+ mice reduced the tumor number by 95% but did not alter the levels of PGE2 and LTB4 in intestinal tissues. Increasing PGE2 and LTB4 levels by 44% with dietary arachidonic acid supplementation had no effect on tumor number or size. When sulindac was added to the arachidonic acid-supplemented diet, tumor number was reduced by 82%, whereas eicosanoid levels remained elevated. In Min/+ mice with established tumors, treatment with sulindac for 4 days reduced tumor number by 75%, and continual administration of sulindac was necessary to maintain a reduced tumor load. In summary, alterations in eicosanoid formation were not correlated with tumor number or size in the Min/+ mouse model; thus, the antitumor effect of sulindac seems to be PG independent.     

Management of desmoid tumors in patients after ileal pouch-anal anastomosis for familial adenomatous polyposis

PURPOSE: The aim of this study was to review the management of desmoid tumors in patients who have undergone ileal pouch-anal anastomosis for familial adenomatous polyposis and their outcome. METHODS: A retrospective review of case notes was undertaken in a series of 196 patients with familial adenomatous polyposis who had had an ileal pouch-anal anastomosis. Eleven patients were identified in whom desmoid tumor had developed (4 male; median age, 30 (range, 16-43) years). RESULTS: Desmoid tumors developed in the abdominal wall alone in 4 of 11 patients. Three enlarging tumors were resected with no subsequent recurrence. No patient received adjuvant treatment and pouch function remained stable at a median follow-up of eight years. Mesenteric desmoid tumors developed in seven patients; the pouch has been excised in two because of ischemia; two other patients have had defunctioning stomas created because of slow progression of their desmoid tumors. One patient had a single-lumen pouch excised and a new S-pouch inserted, with no subsequent recurrence of the desmoid tumor, and in two patients the mesenteric desmoid tumor has remained unchanged. All of these patients received long-term Clinoril (sulindac, Merck & Co., Inc., West Point, PA). Although there has been no significant deterioration in pouch function in patients in whom the pouch remains in situ, the pouch function was significantly worse compared with a control group of patients after ileal pouch-anal anastomosis for familial adenomatous polyposis in whom desmoid tumors did not develop. CONCLUSION: Desmoid tumors developed in 5.6 percent of 196 patients after ileal pouch-anal anastomosis for familial adenomatous polyposis. No patient with abdominal-wall desmoid tumor had a recurrence after local excision. By contrast, mesenteric desmoid tumors eventually resulted in pouch failure in four of seven affected patients.     

Desmoid tumor sensitive to tamoxifen

BACKGROUND: Desmoid tumors are the second leading cause of mortality in patients with familial adenomatous polyposis who have undergone proctocolemy. Both medical and surgical treatment of these non-metastasizing but locally aggressive tumors are difficult. CASE REPORT: A 20-years-old woman consulted 6 years after coloproctectomy for familial adenomatous polyposis. A mesenteric desmoid tumor was found. Resection was not possible. The tumor progressed under sulindac treatment and subocclusion developed. The patient was given tamoxifen, 20 mg/d and the size of the tumor began to regress within a few days together with pain and signs of compression. The treatment was well tolerated for 4.5 years and tumor volume has remained unchanged after a 20-fold reduction compared with the size prior to treatment. The patient has remained symptom-free. DISCUSSION: In this critical clinical situation, tamoxifen provided rapid and prolonged effect and was well tolerated.     

Loss of the PLA2G2A gene in a sporadic colorectal tumor of a patient with a PLA2G2A germline mutation and absence of PLA2G2A germline alterations in patients with FAP

The Min (multiple intestinal neoplasia) mouse with a germline mutation in the adenomatous polyposis coli gene serves as an animal model for familial adenomatous polyposis coli (FAP). The number and age at onset of colorectal adenomas varies in the offspring of Min mice crossed with other strains. The murine gene for the secretory phospholipase A2 (PLA2G2A) was found to be the main candidate for these variations. To test the hypothesis of a correlation between PLA2G2A gene alterations and human tumor development, we screened 14 patients with FAP and 20 patients with sporadic colorectal cancer for germline and somatic PLA2G2A gene mutations. None of the individuals with FAP showed PLA2G2A germline alterations. However, a germline mutation was observed in one patient with an apparently sporadic colorectal tumor; the wildtype allele was somatically lost in the tumor of this patient.     

Inherited colorectal polyposis and cancer risk of the APC I1307K polymorphism

Germ-line and somatic truncating mutations of the APC gene are thought to initiate colorectal tumor formation in familial adenomatous polyposis syndrome and sporadic colorectal carcinogenesis, respectively. Recently, an isoleucine-->lysine polymorphism at codon 1307 (I1307K) of the APC gene has been identified in 6%-7% of the Ashkenazi Jewish population. To assess the risk of this common APC allelic variant in colorectal carcinogenesis, we have analyzed a large cohort of unselected Ashkenazi Jewish subjects with adenomatous polyps and.or colorectal cancer, for the APC I1307K polymorphism. The APC I1307K allele was identified in 48 (10.1%) of 476 patients. Compared with the frequency in two separate population control groups, the APC I1307K allele is associated with an estimated relative risk of 1.5-1.7 for colorectal neoplasia (both P=.01). Furthermore, compared with noncarriers, APC I1307K carriers had increased numbers of adenomas and colorectal cancers per patient (P=.03), as well as a younger age at diagnosis. We conclude that the APC I1307K variant leads to increased adenoma formation and directly contributes to 3%-4% of all Ashkenazi Jewish colorectal cancer. The estimated relative risk for carriers may justify specific clinical screening for the 360,000 Americans expected to harbor this allele, and genetic testing in the setting of long-term-outcome studies may impact significantly on colorectal cancer prevention in this population.     

Molecular biology of colorectal cancer

Colorectal cancer is a significant cause of morbidity and mortality in Western populations. This cancer develops as a result of the pathologic transformation of normal colonic epithelium to an adenomatous polyp and ultimately an invasive cancer. The multistep progression requires years and possibly decades and is accompanied by a number of recently characterized genetic alterations. Mutations in two classes of genes, tumor-suppressor genes and proto-oncogenes, are thought to impart a proliferative advantage to cells and contribute to development of the malignant phenotype. Inactivating mutations of both copies (alleles) of the adenomatous polyposis coli (APC) gene--a tumor-suppressor gene on chromosome 5q--mark one of the earliest events in colorectal carcinogenesis. Germline mutation of the APC gene and subsequent somatic mutation of the second APC allele cause the inherited familial adenomatous polyposis syndrome. This syndrome is characterized by the presence of hundreds to thousands of colonic adenomatous polyps. If these polyps are left untreated, colorectal cancer develops. Mutation leading to dysregulation of the K-ras protooncogene is also thought to be an early event in colon cancer formation. Conversely, loss of heterozygosity on the long arm of chromosome 18 (18q) occurs later in the sequence of development from adenoma to carcinoma, and this mutation may predict poor prognosis. Loss of the 18q region is thought to contribute to inactivation of the DCC tumor-suppressor gene. More recent evidence suggests that other tumor-suppressor genes--DPC4 and MADR2 of the transforming growth factor beta (TGF-beta) pathway--also may be inactivated by allelic loss on chromosome 18q. In addition, mutation of the tumor-suppressor gene p53 on chromosome 17p appears to be a late phenomenon in colorectal carcinogenesis. This mutation may allow the growing tumor with multiple genetic alterations to evade cell cycle arrest and apoptosis. Neoplastic progression is probably accompanied by additional, undiscovered genetic events, which are indicated by allelic loss on chromosomes 1q, 4p, 6p, 8p, 9q, and 22q in 25% to 50% of colorectal cancers. Recently, a third class of genes, DNA repair genes, has been implicated in tumorigenesis of colorectal cancer. Study findings suggest that DNA mismatch repair deficiency, due to germline mutation of the hMSH2, hMLH1, hPMS1, or hPMS2 genes, contributes to development of hereditary nonpolyposis colorectal cancer. The majority of tumors in patients with this disease and 10% to 15% of sporadic colon cancers display microsatellite instability, also know as the replication error positive (RER+) phenotype. This molecular marker of DNA mismatch repair deficiency may predict improved patient survival. Mismatch repair deficiency is thought to lead to mutation and inactivation of the genes for type II TGF-beta receptor and insulin-like growth-factor II receptor. Individuals from families at high risk for colorectal cancer (hereditary nonpolyposis colorectal cancer or familial adenomatous polyposis) should be offered genetic counseling, predictive molecular testing, and when indicated, endoscopic surveillance at appropriate intervals. Recent studies have examined colorectal carcinogenesis in the light of other genetic processes. Telomerase activity is present in almost all cancers, including colorectal cancer, but rarely in benign lesions such as adenomatous polyps or normal tissues. Furthermore, genetic alterations that allow transformed colorectal epithelial cells to escape cell cycle arrest or apoptosis also have been recognized. In addition, hypomethylation or hypermethylation of DNA sequences may alter gene expression without nucleic acid mutation.     

Suppression of human colorectal mucosal prostaglandins: determining the lowest effective aspirin dose

BACKGROUND: A variety of studies have supported the finding that regular intake of aspirin (acetylsalicylic acid) or nonsteroidal anti-inflammatory agents can affect colorectal cancer carcinogenesis. These agents inhibit the synthesis of prostaglandins. High levels of prostaglandins are observed in colon cancer tissues. PURPOSE: Experiments were planned to determine the lowest dose of aspirin that can markedly suppress the levels of mucosal prostaglandins E2 and F(2alpha) in colorectal mucosa and to determine whether a relationship exists between these levels and plasma levels of both acetylsalicylic acid and its metabolite, salicylic acid. METHODS: Healthy men and women aged 18 years or older participated in the study. The participants took a single, daily dose of aspirin (40.5, 81, 162, 324, or 648 mg) or a placebo for 14 days. Colorectal biopsy specimens were taken at baseline, 24 hours after the first dose of aspirin, and 24-30 hours and 72-78 hours after the last, i.e., fourteenth, daily dose of aspirin. The biopsy specimens were assayed for prostaglandins E2 and F(2alpha) by use of a competitive enzyme immunoassay. Plasma concentrations of acetylsalicylic acid and salicylic acid were determined by use of high-performance liquid chromatography. All P values are two-sided. RESULTS: A total of 65 subjects (10 receiving placebo, groups of 10 each receiving 40.5, 81, 162, or 324 mg of aspirin, and a group of 15 receiving 648 mg of aspirin) completed the protocol. One subject reported unacceptable drug-induced toxic effects and did not complete the protocol; other subjects reported acceptable side effects. The lowest dose to significantly suppress colorectal mucosal prostaglandin E2 concentrations from baseline at 24 hours after the first dose (by 22.6%; P = .002) and at 24-30 hours after the last dose (by 14.2%; P = .021) was 162 mg. At 72-78 hours after the last dose, there was significant suppression for subjects receiving 81 mg (by 23.7%; P = .008). The lowest dose to significantly suppress colorectal mucosal prostaglandin F(2alpha) concentrations from baseline at 24 hours after the first dose (by 18.3%; P = .032) was 324 mg. The lowest dose causing a marked reduction in the level of prostaglandin F(2alpha) at 24-30 hours (by 15.1%; P = .003) and 72-78 hours (by 23.0%; P = .0002) after the last dose was 40.5 mg. No detectable amounts of acetylsalicylic acid or salicylic acid were present in the plasma at any of the biopsy time points. CONCLUSIONS: The lowest doses of aspirin taken daily for 14 days to significantly suppress concentrations of colorectal mucosal prostaglandins E2 and F(2alpha) were 81 and 40.5 mg, respectively. The suppression occurred without detectable amounts of aspirin or salicylic acid in the plasma at the time points studied. On the basis of these observations, we recommend a single, daily dose of 81 mg of aspirin in future studies of this drug as a chemopreventive agent for colorectal cancer.     

Colorectal lesions predisposing to cancer

Precursors of colorectal carcinoma are adenomatous polyps, sporadic or arising in familial adenomatous polyposis and Lynch syndrome and chronic inflammatory lesions related to ulcerative colitis and Crohn's disease. The adenoma-carcinoma sequence is well established and early detection and removal of colorectal adenomas is thought to prevent colorectal cancer in high risk asymptomatic persons, i.e. subjects over 45 years, with personal or familial history of adenomas and colorectal cancers. The precancerous potential of adenomatous polyps varies according to tissue type, with increased risk with the extent of the villous component, high grade of dysplasia, large size greater than 1 cm and multiple adenomas. The development of de novo colorectal cancer from normal mucosa with flat adenomas has been recently emphasized. The risk of colonic cancer in patients with ulcerative colitis and Crohn's disease is controversed.     

Enhanced intestinal adenomatous polyp formation in Pms2-/-;Min mice

Analysis of two human familial cancer syndromes, hereditary nonpolyposis colorectal cancer and familial adenomatous polyposis, indicates that mutations in either one of four DNA mismatch repair gene homologues or the adenomatous polyposis coli (APC) gene, respectively, are important for the development of colorectal cancer. To further investigate the role of DNA mismatch repair in intestinal tumorigenesis, we generated mice with mutations in both Apc and the DNA mismatch repair gene, Pms2. Whereas Pms2-deficient mice do not develop intestinal tumors, mice deficient in Pms2 and heterozygous for Min, an allele of Apc, develop approximately three times the number of small intestinal adenomas and four times the number of colon adenomas relative to Min and Pms2+/-;Min mice. Although Pms2 deficiency clearly increases adenoma formation in the Min background, histological analysis indicated no clear evidence for progression to carcinoma.     

Molecular biology of colorectal cancer and clinical consequences for colorectal cancer syndromes

Because of the accomplishments in biotechnical research in the past few decades our knowledge about the molecular mechanisms of carcinogenesis has grown rapidly. Colorectal cancer has been one of the most intensively investigated tumor entities, and it seems to be well established that colorectal tumor growth is associated with an accumulation of acquired somatic mutational events in tumor suppressor genes and oncogenes. Recent progress in our understanding of the molecular basis of the most prevalent colorectal cancer syndromes, such as hereditary nonpolyposis colorectal cancer (HNPCC) and familial adenomatous polyposis (FAP), is reflected by modifications in diagnosis and therapy. Identification and characterization of the causative genes for these colorectal cancer syndromes have enabled precise presymptomatic detection of mutations in individuals who bear an a priori risk of about 50% of developing colorectal cancer. Genotype-phenotype correlations might further increase the clinical management of hereditary colorectal cancer. Even though developments in cancer research are restricted to the minority of individuals with hereditary cancer syndromes, growing knowledge about the effect of low penetrance variations in tumor suppressor genes may affect the diagnosis and therapy of sporadic colorectal cancer.     

Screening for APC mutations based on detection of truncated APC proteins

Mutation of the adenomatous polyposis coli (APC) gene is frequently found in colorectal tumors from both familial adenomatous polyposis (FAP) and non-FAP patients. Analysis of APC mutation is time-consuming and costly due to the large size of the APC gene. As the majority of APC mutations result in the truncation of gene products, the detection of truncated APC proteins may be used as a screening method for APC mutations. The aim of this study is to establish a practical method of detecting truncated APC proteins for the screening of APC mutations. APC proteins in human colorectal cancer cell lines were analyzed by western blotting. Truncated APC proteins were expressed in all of the colorectal cancer cell lines studied. Two species of truncated APC proteins were expressed in two cell lines. Western blotting is a rapid, reliable screening method for APC mutations and provides information on both alleles.     

Incidence of neoplastic polyps in the ileal pouch of patients with familial adenomatous polyposis after restorative proctocolectomy

PURPOSE: Although adenomatous polyps and even adenocarcinomas have been found in the terminal ileum of patients with familial adenomatous polyposis, the prevalence of neoplastic changes in the pouches of patients who have undergone restorative proctocolectomy is unknown. The objective of this study was to determine the frequency of pelvic pouch neoplasia in familial adenomatous polyposis patients after restorative proctocolectomy. METHODS: Patients in a polyposis registry who had undergone restorative proctocolectomy were recruited. Demographic, surgical, pathologic, and endoscopic data were obtained from patient records. Video pouchoscopy was done after two enemas and representative biopsies were taken. RESULTS: Of 102 eligible patients, 26 (17 males and 9 females) participated. Median age at ileal pouch-anal anastomosis was 31 (range, 12-58) years. Median follow-up period was 66 (11-156) months. Adenomas were found in the pouch of 11 (42 percent) patients, in the terminal ileum above the pouch in 1 patient, and in the anal canal of 4 patients. Among patients with pouch polyps, three patients had one lesion, three patients had two lesions, and five patients had more than ten lesions. The incidence of polyps increased steadily with time from restorative proctocolectomy. There was no relation between the incidence of pouch polyposis and the severity of colonic or duodenal disease. CONCLUSIONS: Proctocolectomy and ileal pouch-anal anastomosis is associated with a significant risk of pouch neoplasia in familial adenomatous polyposis patients. The severity of pouch adenomas was not related either to the severity of colonic or duodenal disease. The pelvic pouches of all patients with familial adenomatous polyposis who have undergone restorative proctocolectomy should be examined periodically.     

Fluconazole susceptibility of Candida isolates from oropharyngeal candidosis

New technologies in molecular biology will allow the improvement of screening, diagnosis and prognosis of colorectal cancer patients. For example the determination of germline mutation in APC or in mismatch repair genes in patient with familial adenomatous polyposis or with HNPCC is now possible. The clinical surveillance can be restricted to the patients with these germline defects. More over the knowledge of somatic genetic alterations in colorectal cancer cells seems to be useful in the determination of prognosis of these patients or in order to predict the chemotherapy response.     

Ileal pouch-anal anastomosis as the first choice operation in patients with familial adenomatous polyposis: a ten-year experience

BACKGROUND: The choice between ileal pouch-anal anastomosis (IPAA) and ileorectal anastomosis (IRA) in the treatment of patients with familial adenomatous polyposis remains controversial. The aims of this study were to assess our 10-year experience with proctocolectomy, endoanal mucosectomy, construction of an ileal reservoir pouch, and IPAA in a series of 171 patients with familial adenomatous polyposis and to compare the functional results after IPAA with those after IRA. METHODS: Data from patients treated by IPAA at one institution were prospectively accumulated from October 1983 to October 1993. Medical records of 171 consecutive patients were studied regarding morbidity and functional results. These functional results were compared with those of a series of 23 patients who underwent IRA at the same institution. RESULTS: One patient (0.6%) died after operation. Sixty-two patients (36%) had concomitant colorectal carcinoma, 36 of which tumors were invasive (15 stage A, 13 stage B, and 8 stage C). Forty-six patients (27%) had at least one postoperative complication, with 14 patients requiring reoperation (8%). Twenty-six patients (15%) had obstruction. Seven patients (4%) had pelvic sepsis, and one had transient impotence (0.6%). Only two patients (1%) had a typical episode of pouchitis. The mean follow-up was 29 months (range, 3 to 100 months); 101 patients were monitored for more than 1 year. Little difference was noted between bowel function after IRA and that after IPAA. The mean daytime stool frequency after IPAA was 4.2 with 26% of patients having an average of 1 bowel movement at nighttime, compared with a stool frequency of 3.0 and 13% of patients having night evacuation after IRA. Daytime continence was normal for 98% of patients after IPAA and for all the patients after IRA. Nighttime continence was normal in 96% and 98% of patients, respectively. CONCLUSIONS: Morbidity and functional results after IPAA for familial adenomatous polyposis do not differ from those reported after IRA. For this reason and because of the risk of rectal cancer after ileorectal anastomosis, IPAA with endoanal mucosectomy is our first choice in the treatment of patients with familial adenomatous polyposis.     

Cyclooxygenase-2 inhibitors in tumorigenesis (Part II)

The rate-limiting step in arachidonate metabolism is mediated by enzymes known as cyclooxygenases (COXs). These enzymes catalyze the biosynthesis of prostaglandin H2, the precursor of molecules such as prostaglandins, prostacyclin, and thromboxanes. The COX enzyme family consists of the classical COX-1 enzyme, which is constitutively expressed in many tissues, and a second isozyme, i.e., COX-2, which is induced by various stimuli, such as mitogens and cytokines, and is involved in many inflammatory reactions. Because nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit both COX-1 and COX-2, these drugs also cause unwanted side effects, exemplified by gastrointestinal bleeding. Accumulating evidence indicates that NSAIDs can reduce the incidence of colorectal cancers in human and experimental animals and can reduce the number and size of polyps in patients with familial adenomatous polyposis. This Part II (of a two-part review) focuses on the growing clinical and experimental evidence that NSAIDS and COX-2 inhibitors can influence the risk of colon (and possibly of other) cancers.     

Measurement of histidinohydroxylysinonorleucine and hydroxyproline in skin collagen by reversed-phase high-performance liquid chromatography after 9-fluorenylmethyl chloroformate labeling

The management of intra-abdominal desmoid tumors in patients with familial adenomatous polyposis (FAP) is very difficult. Non-steroidal anti-inflammatory drugs (NSAIDs), anti-estrogenic agents, and steroids are most commonly used, because surgical removal of these tumors may result in severe morbidity, with local recurrence being common. We report a patient with FAP and intra-abdominal desmoid tumors that regressed markedly after prednisolone therapy. The patient, a 38-year-old woman, had undergone total colectomy and ileorectal anastomosis with a diagnosis of FAP with colon cancer. Approximately 17 months after the surgery, she noticed an elastic firm lump in the abdominal wall. She also experienced lower abdominal distension. Computed tomography (CT) of the lower abdomen showed an invasive heterogenous low-density mass occupying the intra-abdominal space. She was treated with sulindac, NSAID, at 300 mg/day, the diagnosis being intra-abdominal desmoid tumors. She exhibited an intestinal obstruction about 9 months after the initiation of sulindac therapy. We changed the treatment and began prednisolone (initial dose, 40 mg/day). This treatment was continued for two years; subsequently, the lesions regressed markedly. She is currently well, more than 3 years after the withdrawal of prednisolone.     

Colorectal adenocarcinoma in patients under 40 years of age

OBJECTIVES: The aim of this study was to assess prognosis and treatment of colorectal cancer in young adults. METHODS: In a retrospective review of 1,917 patients with colorectal cancer, 80 patients were under the age of 40 years (4.2%). RESULTS: The mean follow-up was 5.2 years (range: 0-16 years). There was a family history of colorectal cancer in 20% of the patients, either familial adenomatous polyposis (FAP) or hereditary nonpolyposis colorectal cancer (HNPCC syndrome). Five prognostic factors for the 10 year survival rate were found: stage of tumor in the Astler-Coller classification (A, B1-2, C1-2 and D, 100, 75, 38 and 11% respectively), tumor vascular invasion (16%), poorly differentiated tumors (30%), emergency surgery (21%) and non curative resections (5%). The colon recurrence rate at 8 years was 14% in the case of HNPCC syndrome. The recurrence rate for patients with neither FAP nor HNPCC syndrome was 11.5% at 8 years and for patients alive at 1 year was 16.5%. CONCLUSIONS: In patients under the age of 40 years, a subtotal colectomy, even as a second operation should be considered, if the prognostic factors are favorable. A genetic analysis seems to be essential in the management of these patients.     

Results after restorative proctocolectomy and ileal pouch-anal anastomosis in patients with familial adenomatous polyposis and coexisting colorectal cancer

Although the operation of choice for patients with familial adenomatous polyposis (FAP) is restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA), its place in the management of patients with FAP and cancer has not been defined. The authors have reviewed their experience with these patients to determine the safety of IPAA and its efficacy as a cancer operation. The records of 55 patients with FAP who had undergone IPAA were examined. Follow-up studies included an annual questionnaire and physical examination. Eight patients had FAP with coexisting colorectal cancer. Median age at diagnosis was 25 (range 13-46) years, and at operation 33 (range 22-36) years. Of the eight patients (four men), four had colonic cancer and four had rectal cancer. Synchronous colorectal carcinoma was found in two patients. Staging according to the tumor node metastasis classification showed that five patients had stage 1 tumour, two had stage 2 and one had stage 3. Tumours were well, moderately or poorly differentiated in one, five and two patients respectively. During a median follow-up of 56 (range 14-98) months, metastasis developed in the liver of one patient 66 months after surgery. Two patients suffered complications: one had small bowel obstruction and the other mucosal prolapse. Tubular adenomas were found in the pouch of two patients and in the anal transitional zone of one. Pouch function is good to excellent in all surviving patients. Restorative proctocolectomy for patients with FAP and coexisting colorectal cancer can be undertaken with a favourable prognosis and function. It is compatible with curative intent.