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Heterotopic gastric mucosa of the rectum. A rare cause of rectal bleeding.

We studied a patient with rectal gastric heterotopia and found nine reported cases of this rare disease in the literature. Symptoms include proctitis and rectal bleeding. Heterotopic gastric epithelium may be developmental or acquired, depending on the type of mucosal epithelium involved. Since this type of lesion can occur anywhere in the alimentary tract and even in multiple sites, long-term follow-up is recommended. The diagnosis is made by biopsy and pathologic examination. The treatment consists of total local excision. Sigmoidoscopy, colonoscopy, and technetium scanning can be used as adjunctive aids in diagnosing secondary sites of gastric heterotopia.

Adolescent↗

Colorectal neodymium-YAG photoablative therapy. Comparing applications and complications on both sides of the peritoneal reflection.

Laser photoablative therapy has seen wide application in the esophagus, stomach, and rectum. Its use in the supraperitoneal colon has been less extensive because of fear of complications. One hundred fifteen patients who presented during a four-year period and underwent neodymium-YAG laser treatment on both sides of the peritoneal reflection (rectum, 47 patients; colon, 68 patients) were reviewed. The various lesions treated with laser therapy included 32 malignant tumors that presented with bleeding or obstruction, 44 large broad-based villous adenomas, six carcinoid tumors, and 33 patients with arteriovenous malformations or radiation proctitis who presented with acute hemorrhage or chronic blood loss. Overall treatment efficiency was 83% in the rectal group vs 87% in the colonic group. There was no significant difference in complication frequency or severity between the two groups, even though 45% of the colonic lesions were located in the thin-walled cecum. There was no laser-related mortality in this series. Laser photoablative therapy is safe and effective treatment for a wide variety of colorectal lesions. In experienced hands, it can be used on either side of the peritoneal reflection with equal efficiency and no increased risk of complications.

Adenoma↗

Definitive nonsurgical therapy of epithelial malignancies of the anal canal. A report of 12 cases.

Twelve patients with epidermoid carcinoma of the anal region ranging in age from 40-89 years were treated with combined chemotherapy (CT) and radiotherapy (RT) in lieu of abdominal-perineal resection. Ten patients received no prior treatment and two patients were treated for local recurrence following limited surgical excision. Two courses of 5-FU infusion and mitomycin C were given 3-4 weeks apart simultaneously with whole pelvis RT to 3000-4140 rad. One patient received an additional tumor volume dose of 3094 rad by interstitial Iridium implant and one patient received an orthovoltage boost of 1000 rad to the anal ring. All patients completed treatment. Complete regression of the anal mass occurred in all patients. Biopsies of the anal region performed after completion of therapy revealed no evidence of residual cancer. Ten of the 12 patients are alive without evidence of disease 4-24 months (median, 14 months) after completion of treatment. Two patients have died seven months after treatment of unrelated causes and were tumor-free at autopsy. All patients developed proctitis, diarrhea, and moist perineal desquamation which resolved by four weeks posttreatment. Based on their experience and that of others recently reported, the authors conclude that the described CT-RT protocol offers a definitive alternative to surgery of epidermoid cancer of the anal region.

Adult↗

Combined preoperative radiation and chemotherapy for squamous cell carcinoma of the anal canal.

Twenty-eight patients with squamous cell carcinoma of the anal canal were treated by preoperative radiation therapy and chemotherapy. The radiation therapy was given for 3000 rad (30 Gy) at 200 rad per day, 5 days a week, to the primary tumor with margin and to the pelvic and inguinal lymph nodes. Chemotherapy was given in the form of 5-fluorouracil infusion 1000 mg/m2 on days 1-4 of the radiation therapy and repeated on days 29-32 of the treatment regimen. Mitomycin C was given in the form of intravenous bolus for 15 mg/m2 on day 1. Surgery was done 4-6 weeks following the last day of radiation treatment. Twelve patients underwent anteroposterior resection, and seven of the 12 had no residual tumor in the surgical specimen, while one patient had microscopic tumor only. An additional 14 patients had complete clinical disappearance of their tumor, and, on excision of the scar, it was found free of microscopic cancer. Two other patients are clinically free of tumor but had no biopsy after therapy. While transient proctitis leukopenia and thrombocytopenia were moderate to severe, no serious complications were observed in these patients. Twenty-two patients are free of tumor and alive one to eight years after treatment. One patient died a cardiac death without tumor four years after surgery. Four patients, all with residual tumor in the specimen, have died of cancer. Their primary lesions were more than 7 cm in maximum diameter at initial examination. One patient died of disseminated disease with no local recurrence after abdominal perineal resection.

Adult↗

Phase II clinical trial using californium 252 fast neutron brachytherapy, external pelvic radiation, and extrafascial hysterectomy in the treatment of bulky, barrel-shaped stage IB cervical cancer.

From June 1977 to June 1983, 32 patients with bulky (greater than 4 cm diameter), barrel-shaped Stage IB cervical cancer were treated at the University of Kentucky Medical Center by a combination of outpatient neutron brachytherapy using californium 252 (252Cf) and external pelvic radiation followed by extrafascial hysterectomy. Nineteen patients had cervical tumors 4 to 6 cm in diameter, and 13 patients had lesions in excess of 6 cm in diameter. A dose of 4500 rad external photon therapy was given from a linear accelerator, and one or two 6-hour 252Cf implants were given during or immediately after external radiation. Extrafascial hysterectomy with bilateral salpingo-oophorectomy was performed 6 weeks after completion of radiation therapy. Complications during and after radiation were minimal and included vaginal stenosis (three) and proctitis (two). Tumor clearance in the hysterectomy specimen was complete in 23 patients (72%) and residual cervical tumor was present in 9 patients (28%). Two patients developed tumor recurrence and died of disease 15 and 27 months after therapy, respectively. Thirty patients remain free of disease 26 to 96 months (median, 52 months) after treatment, and none have been lost to follow-up. The actuarial survival of these patients is 97% at 2 years and 94% at 5 years. Intracavitary neutron therapy is well tolerated and is effective when combined with external radiation and hysterectomy in the treatment of bulky, barrel-shaped Stage IB cervical cancer.

Adult↗

Treatment of advanced bladder carcinoma with irradiation and concomitant 5-fluorouracil infusion.

Nineteen patients with locally advanced bladder cancer were treated with irradiation and concomitant 5-fluorouracil intravenous infusion with or without bolus mitomycin. Eighteen of the 19 patients were evaluated for local response. Eleven of the 18 patients (61%) obtained a complete local response within 3 to 6 months. An additional five patients (28%) showed tumor regression to a superficial state controlled by local transurethral resection and intravesical chemotherapy making the overall local clearance rate 16/18 (89%). The remaining two patients (11%) required salvage cystectomy for persistent disease and presently show no evidence of disease. Nine patients have died. Two patients died of intercurrent disease, six patients died of metastatic disease, and one patient who died from regional disease showed no evidence of local bladder tumor at the time of death. Berkson-Gage life-table analysis yields an adjusted survival of 62.5% at 5 years. Late complications included five patients with hemorrhagic cystitis, two patients with a contracted bladder, and one patient with a hemorrhagic radiation proctitis.

Aged↗

Treatment of stage IIIB cervical cancer with Californium-252 fast-neutron brachytherapy and external photon therapy.

From January 1977 to July 1984, 32 patients with Stage IIIB cervical cancer were treated at the University of Kentucky Medical Center by a combination of outpatient neutron brachytherapy and external pelvic radiation. These patients received 4500 to 5000 rad external photon therapy and two or three outpatient Californium-252 (252Cf) implants, plus sidewall boost irradiation. Treatment results were compared retrospectively to those obtained in a historical control group of patients with Stage IIIB cervical cancer treated with external radiation and conventional photon brachytherapy from 1972 to 1976. Local or regional tumor recurrence developed in 53% of patients treated with neutron therapy and an additional 9% experienced distant metastases. Thirty-eight percent of patients remain free of disease 12 to 96 months (mean, 51 months) after therapy. The 2-year and 5-year survival rates of patients treated with neutron therapy were 53% and 36%, which were not significantly different than those obtained with photon brachytherapy (2-year survival, 61%; 5-year survival, 34%). Complications of neutron therapy were minimal and included proctitis (19%) and vaginal stenosis (9%). There were no cases of enteric fistulae. Outpatient neutron brachytherapy was cost effective and was well tolerated by patients.

Adult↗

Extracolonic malignancies in inflammatory bowel disease.

A population-based cohort with inflammatory bowel disease consisting of 4776 patients (3121 with ulcerative colitis and 1655 with Crohn's disease) was followed for 1 to 50 years for the occurrence of malignant neoplasms. Two hundred eighty-three cancers were observed versus 189.1 expected (standardized incidence ratio [SIR] = 1.5, 95% confidence limits [CL] 1.3 to 1.7). One hundred seventy-eight extracolonic cancers were observed versus 168.8 expected (SIR = 1.1, 95% CL 0.9 to 1.2). In Crohn's disease and extensive ulcerative colitis, observed cases were close to those expected but in ulcerative proctitis, the relative risk of extracolonic cancers was close to significantly increased (SIR = 1.3, 95% CL 1.0 to 1.7). Squamous skin cancers after Crohn's disease (SIR = 5.5, 95% CL 2.0 to 11.9) and connective tissue cancers after ulcerative colitis (SIR = 4.0, 95% CL 1.0 to 10.2) were significantly increased. Those having extensive ulcerative colitis at diagnosis had an increased risk of brain cancers (SIR = 2.4, 95% CL 1.0 to 4.6). Patients with extensive ulcerative colitis had lower than expected risk of breast cancer (SIR = 0.4, 95% CL 0.1 to 1.0).

Brain Neoplasms↗

High-energy proton beam radiation therapy for gynecologic malignancies. Potential of proton beam as an alternative to brachytherapy.

Fifteen patients with advanced gynecologic malignancies were treated with high-energy proton beam radiation therapy (RT) at the Particle Radiation Medical Science Center (PARMS), Tsukuba University, Japan, from 1983 to 1987. The potential of proton beam RT as an alternative to conventional brachytherapy was evaluated. Except for one local recurrence, 14 of 15 patients were locoregionally controlled for 15 to 57 months. Two-year local control rate and 2-year survival rate were 92.3% and 93.3%, respectively. Two cases of transient, radiation-induced proctitis (neither of which required surgical treatment) were the only complications despite a target dose that exceeded 8000 cGy in most cases. The results suggest that sharply localized, high-dose proton beam RT can produce an antitumor effect equivalent to that of conventional brachytherapy.

Aged↗

Radiation therapy in management of carcinoma of the vulva with emphasis on conservation therapy.

BACKGROUND: This report consists of a retrospective analysis of 50 patients with primary invasive and 17 with recurrent histologically confirmed vulvar carcinoma treated with radiation therapy for locoregional disease. METHODS: Of the patients with primary tumors, 13 were treated with wide local excision plus radiation therapy; 13 had radical vulvectomy followed by irradiation to the operative fields and inguinal-femoral/pelvic lymph nodes; 8 received similar postoperative radiation therapy after partial or simple vulvectomy; 16 patients had radiation therapy alone after biopsy; and 17 had recurrent tumors treated with radiation therapy alone. RESULTS: In patients treated with biopsy/local excision, local tumor control was 92-100% in T1-3N0 disease, 40% in similar stages with N1-3, and 27% in recurrent tumors. Among patients treated with partial/radical vulvectomy and radiation therapy, primary tumor control was 90% in those with T1-3 tumors and any nodal stage, 33% in those with any T stage and N3 lymph nodes, and 66% in patients with recurrent tumors. The actuarial 5-year disease-free survival rates were 87% for patients with T1N0 disease, 62% for those with T2-3N0 disease, 30% for those with T1-3N1 disease, and 11% for patients with recurrent tumors; there were no long-term survivors with T4 or N2-3 disease. Four of 17 patients treated for postvulvectomy recurrent disease remain disease-free after local tumor excision and radiation therapy. In patients with T1-2 tumors treated with biopsy/wide tumor excision and radiation therapy with doses less than 50 Gy, the local tumor control was 75% (three of four patients), in contrast to 100% (13 of 13 patients) with 50.01-65 Gy. With T3-4 tumors treated with local excision and radiation therapy, tumor control occurred in none of three patients with doses less than 50 Gy and 66% (six of nine) with 50.01-65 Gy. In patients with T1-2 tumors treated with partial/radical vulvectomy and radiation therapy, local tumor control was 75% (six of eight), regardless of dose level; in T3-4 tumors, it was 67% (four of six patients) with 50-60 Gy and 86% (six of seven) with 65-70 Gy. Differences were not statistically significant. There was no significant dose response for tumor control in the inguinal-femoral lymph nodes, with doses of 50 Gy being adequate for elective treatment of nonpalpable lymph nodes and 60-70 Gy controlling tumor growth in 75-80% of patients with N2-3 nodes when administered postoperatively, after partial or radical lymph node dissection. Significant treatment morbidity included one rectovaginal fistula, one case of proctitis, one rectal stricture, four bone/skin necroses, four vaginal necroses, and one groin abscess. CONCLUSIONS: Wide local tumor excision and radiation therapy or irradiation alone in T1-2 tumors is an alternative treatment to radical vulvectomy in controlling vulvar carcinoma, with significantly less morbidity. In comparison with reported rates for surgery alone, radiation therapy after radical vulvectomy for locally advanced tumors improves tumor control at the primary site and regional lymphatics. Indications and techniques of radiation therapy are discussed.

Adenocarcinoma↗

Hyperbaric oxygen therapy for late radiation tissue injury.

BACKGROUND: Cancer is a significant global health problem. Radiotherapy is a treatment for many cancers and about 50% of patients having radiotherapy with be long-term survivors. Some will experience LRTI developing months or years later. HBOT has been suggested for LRTI based upon the ability to improve the blood supply to these tissues. It is postulated that HBOT may result in both healing of tissues and the prevention of problems following surgery. OBJECTIVES: To assess the benefits and harms of HBOT for treating or preventing LRTI. SEARCH STRATEGY: We searched The Cochrane Central Register of Controlled Trials (CENTRAL) Issue 3, 2004, MEDLINE, EMBASE, CINAHL and DORCTHIM (hyperbaric RCT register) in September 2004. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effect of HBOT versus no HBOT on LRTI prevention or healing. DATA COLLECTION AND ANALYSIS: Three reviewers independently evaluated the quality of the relevant trials using the guidelines of the Cochrane Handbook Clarke 2003) and extracted the data from the included trials. MAIN RESULTS: Six trials contributed to this review (447 participants). For pooled analyses, investigation of heterogeneity suggested important variability between trials. From single studies there was a significantly improved chance of healing following HBOT for radiation proctitis (relative risk (RR) 2.7, 95% confidence Interval (CI) 1.2 to 6.0, P = 0.02, numbers needed to treat (NNT) = 3), and following both surgical flaps (RR 8.7, 95% CI 2.7 to 27.5, P = 0.0002, NNT = 4) and hemimandibulectomy (RR 1.4, 95% CI 1.1 to 1.8, P = 0.001, NNT = 5). There was also a significantly improved probability of healing irradiated tooth sockets following dental extraction (RR 1.4, 95% CI 1.1 to 1.7, P = 0.009, NNT = 4). There was no evidence of benefit in clinical outcomes with established radiation injury to neural tissue, and no data reported on the use of HBOT to treat other manifestations of LRTI. These trials did not report adverse effects. AUTHORS' CONCLUSIONS: These small trials suggest that for people with LRTI affecting tissues of the head, neck, anus and rectum, HBOT is associated with improved outcome. HBOT also appears to reduce the chance of osteoradionecrosis following tooth extraction in an irradiated field. There was no such evidence of any important clinical effect on neurological tissues. The application of HBOT to selected patients and tissues may be justified. Further research is required to establish the optimum patient selection and timing of any therapy. An economic evaluation should be also be undertaken. There is no useful information from this review regarding the efficacy or effectiveness of HBOT for other tissues.

Humans↗

Correlation of clinical and manometric abnormalities of rectal function following chronic radiation injury.

Continuous fluid-inflation proctometrograms were performed in men with the symptoms of chronic radiation proctitis and in age and sex-matched control subjects (n = 10). Rectal volumes and compliance were measured. There was a significant reduction in the rectal volumes at sensory threshold, constant sensation and maximal tolerance and in rectal compliance (P less than 0.01). Comparable pressure measurements did not demonstrate significant differences. The maximum tolerable volume, symptomatic and sigmoidoscopic scoring correlated to rectal compliance (r = 0.77, -0.8, -0.73; P less than 0.01, less than 0.01, less than 0.02, respectively). Reduction in volume and compliance is often not obvious radiologically. Histological evidence suggests that smooth muscle hypertrophy and myenteric plexus damage are contributory.

Aged↗

Results of proctocolectomy for Crohn's disease.

Seventy-four patients have had a one-stage proctocolectomy for the management of Crohn's disease. Indications for operation were: acute colitis 28 per cent, chronic colitis 39 per cent, perianal disease 13 per cent, proctitis and perianal disease 8 per cent, bleeding 5 per cent, coexisting colonic malignancy 7 per cent. There were two hospital deaths (2.7 per cent), both associated with sepsis. Late deaths (n = 13) were most commonly associated with reoperations for recurrent disease (n = 3), cardiovascular disease (n = 4) and colorectal carcinoma (n = 1). Postoperative complications were principally associated with sepsis. Cumulative reoperation rates at 5 and 10 years were 19 and 24 per cent respectively. Recurrence was unrelated to the age of the patients, the duration of disease, or the presence of ileal disease at the time of colectomy.

Adolescent↗

Natural history and treatment of anorectal strictures complicating Crohn's disease.

Forty-four patients seen between 1975 and 1985 with anorectal strictures complicating Crohn's disease have been reviewed to determine the natural history and outcome of surgical treatment. Proctitis was present in 98 per cent, and 93 per cent of patients had sever perianal disease. The site of strictures was rectal in 22, anal in 15 and anorectal in 11 (4 patients had a stricture at 2 sites). Initial treatment was by rectal excision alone in 6, dilatation in 33, and 5 needed no treatment at all. Single dilatation was effective in 15, 8 required two dilatations and in 10 repeated dilatation was necessary. Proctocolectomy was eventually required in 19 patients, 2 have a loop ileostomy and 1 has an ileostomy with a rectal stump in situ. Only 21 remain asymptomatic while 3 continue to need dilatation. Perineal wound healing was delayed in 9 of 19 patients having a proctocolectomy and in 3 the perineal wound has never healed.

Adolescent↗

Changes in clinical characteristics, course, and prognosis of inflammatory bowel disease during the last 5 decades: a population-based study from Copenhagen, Denmark.

BACKGROUND: It remains uncertain whether the increasing incidence of inflammatory bowel disease (IBD) during the last decades has been accompanied by an alteration in the presentation, course, and prognosis of the disease. To answer this question, 3 consecutive population-based IBD cohorts from Copenhagen, Denmark (1962-2005), were assessed and evaluated. METHODS: Phenotype, initial disease course, use of medications, cumulative surgery rate, standardized incidence ratio of colorectal cancer (CRC), and standardized mortality ratio (SMR) were compared in the 3 cohorts, which had a total of 641 patients with Crohn's disease (CD) and 1575 patients with ulcerative colitis (UC). RESULTS: From 1962 to 2005, the proportion of IBD patients suffering from CD increased (P < 0.001), time from onset of symptoms to diagnosis of CD decreased (P = 0.001), and median age at diagnosis of UC increased (P < 0.01). The prevalence of upper gastrointestinal involvement and pure colonic CD varied significantly between cohorts. UC patients diagnosed in the 1990s had a higher prevalence of proctitis, received more medications, and had a milder initial disease course than did previous patients. The surgery rate decreased significantly in CD but not in UC. The risk of CRC in IBD was close to expected over the entire period, whereas the mortality of patients with CD increased (overall SMR, 1.31; 95% CI, 1.07-1.60). CONCLUSIONS: Despite variations in the presentation and initial course of IBD during the last 5 decades, its long-term prognosis remained fairly stable. Treatment of IBD changed recently, and future studies should address the effect of these changes on long-term prognosis.

Adolescent↗

Dose-ranging study of mesalamine (PENTASA) enemas in the treatment of acute ulcerative proctosigmoiditis: results of a multicentered placebo-controlled trial. The U.S. PENTASA Enema Study Group.

The safety and efficacy of mesalamine enemas were determined ina dose-ranging study enrolling 287 patients with ulcerative proctitis and proctosigmoiditis in a double-blind, placebo-controlled, multicenter trial. Patients were randomized to receive placebo, 1, 2, or 4 g in 100 ml mesalamine (PENTASA) enemas h.s. for 8 weeks. Efficacy was assessed by clinical, sigmoidoscopic, and histologic improvement, as well as by induction of remission. Sixty-seven percent, 65%, and 75% of patients receiving 1-, 2-, and 4-g enemas were markedly improved according to the physician's global assessment compared with 27% of patients treated with placebo. The mean improvement in sigmoidoscopic index was 5.8, 5.9, and 6.4 points (on a 15-point scale) for the 1-, 2-, and 4-g enema groups compared with a decrease of 1.8 points for the placebo group. Improvement in biopsy scores was observed in 47, 55, and 59% of 1-, 2-, and 4-g groups contrasted with 27% of the placebo-treated patients. All three doses were significantly more effective than placebo in reducing symptoms and trips to the toilet compared with placebo. No dose-response relation was demonstrated. The safety profile was similar to that of placebo. In conclusion, mesalamine enemas are effective as a single agent in the short-term treatment of distal ulcerative colitis without an apparent dose response between 1 and 4 g nightly.

Acute Disease↗

Cancer in patients with ulcerative colitis.

A cohort of 5,546 ulcerative colitis patients was identified from the Danish Hospital Discharge Register for 1977-1989. Patients not included in the cohort comprised those with proctitis, those treated in outpatient clinics and those for whom follow-up was less than 1 year. The cohort was linked to the Danish Cancer Registry in order to assess the risks for colorectal and other cancers. The linkage revealed a significant increase in the number of colorectal cancers over that in the general population (RR = 1.8; n = 42; 95% CI = 1.3-2.4) with consistent relative risks during early and late follow-up. The relative risk was considerably higher among younger (20-39 years: RR = 22; n = 8; 95% CI = 9.7-44) than older patients (> or = 60 years: RR = 1.3; n = 25; 95% CI = 0.8-1.9), but the risk difference between patients and the general population was approximately constant across all ages. In addition, we observed a significant increase in the relative risk of hepatobiliary cancers (RR = 2.3; n = 9; 95% = 1.0-4.3) and a slight but significant increase in the relative risk of non-melanoma skin cancer (RR = 1.4; n = 37; 95% CI = 1.0-1.9). In summary, our population-based study confirms the increased risk of colorectal cancer among patients with ulcerative colitis and provides new leads suggesting that hepatobiliary cancer and non-melanoma skin cancer should be considered as possible sites for future patient monitoring.

Adult↗

Enteric diseases of homosexual men.

Certain enteric ailments are particularly common among homosexual men. They are primarily infectious diseases and include not only such common venereal diseases as gonorrhea and syphilis but also infections not usually regarded as being sexually transmitted. Among the latter are shigellosis, salmonellosis, giardiasis, and amebiasis. Patients' symptoms are non-specific and seldom helpful in diagnosing particular diseases. The practitioner must be prepared to identify a number of infections with similar presentations that may occur singly or together in gay men. Gonorrhea is probably the most common bacterial infection in gay men. Carriage rates as high as 50% have been reported, and extra-genital carriage is common; this necessitates culturing the urethra, rectum, and pharynx. Procaine penicillin G is the treatment of choice for most patients; spectinomycin is probably the drug of choice in penicillin-sensitive patients. In contrast to other venereal diseases, syphilis may have a characteristic protoscopic presentation. Benzathine penicillin G is the treatment of choice for most patients. Lymphogranuloma venereum causes penile lesions and inguinal lymphadenitis in heterosexual men, whereas homosexual men are more prone to proctitis. The disease may mimic Crohn's disease. Recommended treatment includes tetracycline or sulfamethoxazole-trimethoprim. Shigellosis usually presents as an acute diarrheal illness. Patients generally require only supportive treatment with fluids. Herpes simplex viral infection is difficult to diagnose and has several different presentations, including lumbosacral radiculomyelopathy. Symptomatic treatment with sitz baths, anesthetic ointment, and analgesics is recommended. Venereal warts are believed to be caused by the same virus that causes verrucous warts; they are usually found in the anal canal or around the anal orifice. They are commonly treated with 25% podophyllin solution. Parasitic infections include giardiasis, amebiasis, and pinworm infections. Metronidazole may be used in the treatment of symptomatic giardiasis and amebiasis, but it is not approved for the former indication; quinacrine is approved for giardiasis. Pinworm infestation may be treated with pyrantel pamoate or mebendazole. Cure of enteric diseases in homosexual men must be documented.

Amebiasis↗