Relationship between APC genotype, polyp distribution, and oral sulindac treatment in the colon and rectum of patients with familial adenomatous polyposis.

PURPOSE: Familial adenomatous polyposis is an inherited colorectal cancer syndrome characterized by the presence of multiple adenomatous colorectal polyps. Molecular studies have revealed that germline mutations in the APC gene are the underlying cause of the disease. The nonsteroidal anti-inflammatory agent sulindac has been shown to reduce the number of colorectal adenomas. Most sulindac trials in the large bowel have focused on the distal colon and relatively little is known about its effect on the proximal colon. Moreover, it is unknown whether the site of the APC mutation affects the efficacy of sulindac. METHODS: This study investigated whether there were regional differences in the effect of sulindac on the colon and whether response to sulindac was dependent on the site of mutation in the APC gene. In an open prospective study 17 patients with familial adenomatous polyposis were treated with 300 mg oral sulindac daily for four months followed by a washout phase of six months. Ten of the patients had an intact colon and seven had rectal stumps only. The number, size, and the degree of dysplasia of the adenomas were evaluated by colonoscopy at entry, end of treatment and end of the study. RESULTS: Overall, a statistically significant decrease in the number of adenomas was observed (120 +/- 112 to 28 +/- 64, P = 0.007). After cessation of sulindac treatment the number of adenomas increased to 48 +/- 44.5, but remained significantly lower than the values observed at baseline. In the ten patients with intact colons, adenomas decreased by sevenfold in the proximal colon (103 +/- 73 to 15.1 +/- 47.4, P = 0.011) and twofold in the distal colon (80 +/- 52 to 29.6 +/- 37.2, P = 0.005). The size of adenomas and the grade of dysplasia also decreased. No correlation could be seen between the APC mutation site and the response to treatment. CONCLUSION: These data indicate that sulindac reduces the number of adenomas in the entire colon and that the effect seems to be more pronounced in the proximal colon.

[Effect of non-steroidal antirheumatic agents on the gastrointestinal tract: clinical aspects and pathophysiology]. / Wirkung nicht-steroidaler Antirheumatika am Magen-Darm-Trakt: Klinik und Pathophysiologie.

The major gastrointestinal side effects of non-steroidal antiinflammatory drugs (NSAID) mainly occur in the stomach and duodenum. Acute mucosal lesions are almost always seen but only 50% of patients complain of upper abdominal discomfort. NSAIDs elevate the risk of ulcerations of the stomach or duodenum 4 to 5 fold. Side effects in the small bowel are due to elevated intestinal permeability which may lead to inflammatory reactions, chronic blood loss and iron deficiency. Ulceration, perforation and strictures of the small and large bowel may also occur in rare cases.

[Tumor staging and follow-up care in rectosigmoid carcinoma: colonoscopic endosonography compared to CT, MRI and endorectal MRI]. / Tumorstaging und Nachsorge des rektosigmoidalen Karzinoms: die koloskopische Endosonographie im Vergleich mit der CT, MRT und endorektalen MRT.

BACKGROUND AND STUDY AIMS: Endosonography has become the best available method for local staging of primary rectal cancer and diagnosing recurrent local tumor. The aim of this prospective study is to compare the accuracy of endoscopic ultrasound (EUS), using an echo colonoscope (CF-UM 3, CF-UM 20, Olympus optical) to computed tomography (CT), body coil magnetic resonance imaging (MRI) and endorectal coil magnetic resonance imaging (EMRI). PATIENTS AND METHODS: From February 1991 to July 1993 90 patients with primary rectosigmoidal tumors (n = 32: 9 women, 23 men, mean age 68 years [range 37 to 84]) or follow-up examinations for recurrent local cancer (patients: n = 58, examinations: n = 93; 41 women, 52 men, mean age 61 years [range 31 to 84]) were investigated. The results of preoperative examinations were compared to histopathological findings regarding T and N stages. RESULTS: In T staging, accuracy of EUS (78%) was superior to CT (50%) and equivalent to both MRI (75%) and EMRI (80%). The accuracy of EUS (84%) in assessing transmural tumor infiltration was superior to CT, MRT and EMRT (50%, 75% and 80%, resp.); however, CT (77%) and MRI (86%) were more accurate than EUS (64%) and EMRI (33%) in assessing N stages. Recurrent local cancer was found in 22 patients. All but one were detected by EUS. Sensitivity, specificity and accuracy in follow-up examinations for recurrent disease for EUS were 95%, 94% and 95%, for CT 75%, 73% and 74%, for MRI 57%, 100% and 70%, and for EMRI 83%, 100% and 90% resp. CONCLUSIONS: Endoscopic ultrasound proved to be a safe and accurate method of preoperative staging and early diagnosis of recurrent rectal cancer and was superior or at least equivalent to CT, MRI and EMRI.

Anal sphincter defects in fecal incontinence: correlation between endosonography and surgery.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound provides accurate information about the anatomy of the anal sphincter. The purposes of this study were to evaluate the use of flexible echo endoscopes to examine the anal sphincters, to validate the diagnosis of internal and external sphincter defects obtained using echo endoscopes by comparison with surgical findings, and to assess the outcome after surgical sphincter repair. PATIENTS AND METHODS: Twenty-eight patients (13 women, 15 men, median age 50 years, range 30-83) with fecal incontinence--which was of traumatic origin in all but one (childbirth: n = 8; anorectal surgery: n = 17; biopsy of the prostate: n = 2; no trauma: n =1)--were prospectively investigated by endosonography using an echo colonoscope (n = 14) or an echo gastroscope (n = 14) (CF-UM20, GF-UM20, Olympus Optical). The location and extent of the defects of the internal or external sphincters, or both, were compared with the surgical findings in all patients. The surgical outcome was defined as excellent, improved, or unchanged. RESULTS: At surgery, 25 of the 28 patients had an isolated internal sphincter defect (n = 15) or combined sphincter defect (n = 10). Endoscopic ultrasound identified all of the external anal sphincter defects (n = 10), and correctly excluded a defect in 15 of 18 patients (sensitivity, specificity, and accuracy 100%, 83% and 89%, respectively). All of the internal sphincter defects (n = 25) were detected by endosonography. In three patients, a postulated intact internal sphincter was confirmed by surgery (accuracy 100%). In two patients, the extent of the sphincter defect was underestimated. Despite good visualization of the internal and external anal sphincters, as well as of the puborectal muscle in all patients, the shape, diameter, and full radial image sector (360 degrees) of the echo gastroscope made this instrument more practicable than the echo colonoscope. Nineteen of 25 patients who underwent surgery (76%) with proved sphincter defects experienced improvement, the figure reaching 87% (13 of 15) in patients who received isolated internal sphincter defect repair. CONCLUSIONS: Anal endosonography, even using flexible echo endoscopes, is an accurate method for identifying anal sphincter defects, and is the method of choice for preoperative sphincter mapping with special regard to internal sphincter repair, which can be carried out with excellent results.

[Endosonography in diagnosis of insulinoma]. / Die Endosonographie in der Diagnostik des Insulinoms.

AIM: In a prospective study endoscopic ultrasonic localisation of clinically suspected insulinomas was compared with the findings of abdominal ultrasound, computed tomography and magnetic resonance imaging. METHOD: From Dec. 1990 to Jan. 1995 11 patients (8f, 3m, median age 42 [27-79] years) were enrolled in the study. The preoperative endosonographic findings were compared to surgery (n = 7) or clinical follow-up (n = 4). RESULTS: Endoscopic ultrasound identified a solitary tumour (mean size 12.4 mm) in 7 of 11 patients, which was proven at surgery in 5 patients and by transhepatic portal venous sampling after negative partial pancreas resection in 1 patient. One patient is still awaiting surgery. Clinical follow-up (n = 2) and negative intraoperative and histological findings of partial pancreas resection (n = 1) confirmed a true negative examination in 3 patients. One patient with negative endoscopic ultrasound is still under medication for recurrent hypoglyctemia. Abdominal ultrasound (n = 11), computed tomography (n = 11) and magnetic resonance imaging (n = 5) were negative in all investigated patients. CONCLUSION: Endoscopic ultrasound is highly accurate for localisation of insulinomas and should be performed early in the preoperative management of these patients.

Endoscopic ultrasound and endorectal magnetic resonance imaging: a prospective, comparative study for preoperative staging and follow-up of rectal cancer.

BACKGROUND AND STUDY AIMS: Endoscopic ultrasound has become the best available method for local staging of primary rectal cancer and diagnosing recurrent local disease. The aim of this study is to compare the value of endoscopic ultrasound (EUS) to magnetic resonance imaging with an endorectal coil (EMRI). PATIENTS AND METHODS: Twenty-one patients (11 women, 10 men, mean age 63 years, range 31-79) with primary rectal cancer (n = 6) or follow-up examinations for recurrent local disease (n = 15) were investigated by EUS using an echo colonoscope (CF-UM 20, Olympus Optical) and by endorectal coil MRI on a 1.5 tesla MR system (General Electric). T2-weighted and contrast-enhanced T1-weighted images were obtained. The results of preoperative examinations were compared to histopathological findings regarding the T staging, with special focus on the transmural tumor infiltration. RESULTS: EUS identified all tumors, whereas one tumor was missed by EMRI. EUS was superior to EMRI in T staging (accuracy 83%/40%), due to the better differentiation between T1 and T2 tumors, as the endorectal coil could not differentiate between stage T1 and stage T2. The accuracy of EMRI in assessing perirectal infiltration was 80%, compared to EUS with 100%. Local tumor recurrence was found in six of 15 patients, without endoscopic signs of recurrent disease in four of them. All were detected by EUS. Only one recurrence was missed by EMRI. Accuracy and positive and negative predictive values in follow-up examinations for recurrent disease for EUS were 93%, 86%, and 100%, and for both the T2-weighted and T1-weighted contrast-enhanced sequences of endorectal coil MRI, they were 93%, 100%, and 90%, respectively. CONCLUSIONS: Endoscopic ultrasound and endorectal coil MRI are comparable methods in the preoperative staging and early diagnosis of recurrent rectal cancer. The advantages of EUS are the small diameter of the instrument, availability, and lower costs. In contrast, EMRI is operator-independent, and may become important for combined local and distant staging and follow-up examination in rectal cancer, if contrast-enhanced imaging can improve the sensitivity for liver metastases.

Transient pure red cell aplasia caused by antilymphoblast globulin after cadaveric renal transplantation.

Transient pure red cell aplasia (PRCA) in three consecutive patients receiving ATG for management of kidney graft rejection prompted a systematic study of the effects on erythropoiesis of the ATG preparation used at our institution. We found that 90% of patients treated with rabbit anti-T lymphoblast globulin developed reticulocytopenia (less than 17,000 reticulocytes/mm3), with complete disappearance of reticulocytes in 65% of patients and increased requirement for red cell transfusion. PRCA, with selective aplasia of erythroblasts was confirmed by bone marrow aspiration in 4 patients volunteering for aspiration, and by the kinetic of the disappearance of blood reticulocytes in relation to the beginning of ATG treatment. The nadir of thrombocytes and lymphocytes, blood cells directly destroyed by ATG in circulation, followed the start of ATG treatment within 1 to 4 days. In contrast the nadir of reticulocyte counts occurred later, between day 7 and 13 after ATG was begun, reflecting the fact that toxicity was directed against red cell precursors rather than mature circulating cells. In agreement with these clinical findings ALG was found to be cytotoxic in vitro for erythroid precursors. Analogously to autoimmune PRCA caused by autoantibodies to erythroblasts, this type of PRCA could be viewed as "heteroimmune disease."