Rectus muscle flap for repair of refractory bladder fistula following renal transplantation: a case report

We report a case of refractory bladder fistula in a diabetic renal allograft recipient that recurred shortly after conventional operative repair without any detectable external cause. After reoperation and use of a vascularized rectus muscle flap the fistula closed and the patient has retained excellent graft function. It is suggested that this technique should be considered as the primary repair modality for bladder fistulas in diabetic recipients, when wound healing is impaired seriously as a consequence of the combined effects of diabetic microangiopathy and steroid therapy.     

Screening assays for immunologic infertility: a comparison study.

Because the immunobead antisperm antibody test (IBT) is difficult to learn and results are heavily operator-dependent, we compared findings on IBT with those of SpermMAR and SpermCheck in 58 patients to determine whether the latter two tests could demonstrate improved screening ability. Assays performed on both sperm and serum (i.e., direct and indirect) yielded 100% positive predictive values when IBT was used as the standard. Both SpermCheck and SpermMAR are easier to perform, and, as the former has a slightly greater sensitivity, we recommend SpermCheck for the detection of immunologic infertility.     

Immunotherapy of mammary adenocarcinoma metastases in C3H/HeN mice with chronic administration of cyclo-oxygenase inhibitors alone or in combination with IL-2

In this study the efficacy of treatment of two cyclo-oxygenase inhibitors, ibuprofen (Ibu) and indomethacin (Indo), are compared in the immunotherapy of metastasis designed to reverse prostaglandin E₂ (PGE₂)mediated inactivation of interleukin-2 (IL-2)-dependent host killer cell lineages. These agents were tested either alone for the prevention of metastasis or in combination with IL-2 for the eradication of established metastasis. C3H/HeN mice were placed on chronic oral Ibu (CIbT; 200 and 600 ,g/ml of water) or Indo (CIT; 10 g/ml) 5 days after s.c. transplantation of 5 × 10⁵ metastatic C3L5 mammary carcinoma for the prevention of spontaneous lung metastases. They showed intolerance to Indo at a dosage of 14 g/ml, which was well tolerated by other mouse strains in previous studies, but tolerated the Ibu dosages used. Control and treated mice were killed on day 30 to score metastatic lung colonies, to evaluate killer activity in splenocytes against natural killer (NK)-sensitive YAC-1 lymphoma or NK-resistant C3L5 adenocarcinoma and 8911 lymphoma targets, and to phenotype the surface markers of killer cells. CIbT and CIT alone at the above dosage significantly reduced the number of lung colonies, retarded local tumor growth and restored NK activity of splenic killer cells expressing AGM-1⁺, Thy-1^–, Lyt-2^– phenotype. To treat established lung metastasis, mice bearing 15-day C3L5 transplants were given CIbT or CIT alone or in combination with two 4-day rounds (days 20–23, 31–34) of IL-2 (15 000 Cetus units, i.p. every 8 h) and were killed on day 35 to score lung colonies and characterize splenic killer cells. CIbT or CIT alone reduced the number of spontaneous lung metastases and restored anti-YAC-1 killer function of splenocytes with NK-like phenotype (AGM-1⁺, Thy-1^–, Lyt-2^–); some anti-C3L5 killer function was also generated in the high dose Ibu group and the killer cell showed AGM-1⁺, Thy-1⁺ and Lyt-2⁺ phenotype. Combined therapies with CIbT or CIT plus IL-2 were more effective in reducing metastases and promoting killer cell function, the best results being achieved with high dose Ibu + IL-2. All killer cells expressed AGM-1 and Thy-1. In addition, C3L5 killer cells also expressed Lyt-2, suggesting T-cell stimulation. PGE₂ synthesis in the host was inhibited by at least 50% in mice subjected to CIbT or CIT. Thus, Ibu proved to be an excellent substitute for Indo in preventing metastasis and NK cell activation when given alone, and also in ameliorating established metastasis and activating lymphokine-activated killer cells when combined with IL-2.     

The epidemiology of atopic dermatitis at a tertiary referral skin center in Singapore

Atopic dermatitis is a common chronic, relapsing, pruritic ecematous skin condition with a predilection for the flexural areas and occurs in patients with a personal or family history of atopy. The aim of this study is to describe the profile of atopic dermatitis seen at the National Skin Centre in Singapore. A retrospective chart review was conducted of all the patients with atopic dermatitis seen during the first six months of 1994. There were 492 patients whose ages ranged from one month to 74 years with an equal sex ratio. The prevalence was 2%. The onset of the disease occurred before the age of 10 years in 61.2% of patients. In 13.6% of the patients, the onset was after the age of 21 years. Two hundred and fifty-four patients (52%) had "pure" atopic dermatitis without concomitant respiratory allergies. Two hundred and thirty-eight patients (48%) suffered from a "mixed" type, with 23% having allergic rhinitis, 12% having asthma and 13% having both asthma and allergic rhinitis. Two hundred and thirty-one patients (47%) had at least one first-degree family member with atropy: atopic dermatitis (17%), asthma (15%) and allergic rhinitis (15%). Most of the patients, 416 (84.5%), had subacute eczema at presentation. Ichthyosis vulgaris was present in 38 patients (8%) and pityriasis alba in 13 patients (3%). The most common infective complication was bacterial infection (impetiginized eczema, folliculitis, cellullitis) present in 95 patients (19%) followed by viral infections (eczema herpeticum, viral warts and molluscum contagiosum) in 17 patients (3%). Allergies were noted in 43 patients (9%) based on the history given. The most common was drug allergies (penicillin and co-trimoxazole) in 28 patients followed by food allergies in 11 patients. Common aggravating factors reported include heat, sweating, stress, thick clothing and grass intolerance. Most patients could be controlled with a fairly simple regimen of moisturizers, topical steroids and antibiotics for acute flares. Short courses of systemic steroids were used in 78 patients (16%). Three patients were treated with phototherapy, Two on UVAB and one on PUVA. The pattern of atopic dermatitis in Singapore is similar to that reported in the Western literature except for a lower prevalence and a significant proportion of adult onset atopic dermatitis.     

Replicative MCM7 protein as a proliferation marker in endometrial carcinoma: a tissue microarray and clinicopathological analysis

AIMS: To assess, in tissue microarray (TMA), the proliferative activity of endometrial carcinoma using one of the minichromosome maintenance (MCM) proteins (MCM7), and to explore its potential value for prognosis. MCM proteins are essential for eukaryotic DNA replication and have recently been used to define the proliferative compartments in human tissues. METHODS AND RESULTS: Immunohistochemistry for MCM7 and Ki67 was performed on TMAs constructed from 212 cases of endometrial carcinoma. MCM7 and Ki67 expression was quantified according to the extent of nuclear staining. An analysis was carried out of the association between MCM7 expression and that of Ki67 and the clinicopathological characteristics of endometrial carcinoma. MCM7 and Ki67 immunoreactivity was clearly evident in the nuclei of tumour cells. MCM7 and Ki67 labelling indices in endometrial carcinomas correlated with each other (P < 0.001). A significant correlation existed between the MCM7 labelling index and histological grade (P = 0.008) and patients' age at diagnosis (P < 0.001). Well-differentiated carcinomas and younger patients had a lower MCM7 index. Poor survival was observed in patients with endometrial carcinoma with a high MCM7 index (P = 0.03) and MCM7 was found to be an independent prognostic factor by multivariate analysis (P = 0.04). The Ki67 labelling index correlated with histological grade (P = 0.01) but had no significant prognostic impact (P = 0.50). CONCLUSIONS: In this TMA study on endometrial carcinoma, MCM7 was found to be a more reliable and useful marker than Ki67 in assessing tumour proliferation and in the prognosis of patients.     

Micropapillary variant of urothelial carcinoma of the urinary bladder; a clinicopathological and immunohistochemical study

AIMS: To investigate whether prognosis in micropapillary urothelial carcinoma is related to the proportion of the micropapillary component (MPC), and to identify the immunohistochemical features of MPC. METHODS AND RESULTS: This study presents a clinicopathological analysis of 20 patients with micropapillary urothelial carcinoma of the bladder with cystectomy specimens for evaluation. Tumours were stratified on the extent of MPC: focal, <10%; moderate, 10-50%; extensive, >50%; and this was correlated with tumour stage and prognosis. Sixteen males and four females were aged 56-81 years (mean 69 years). All cases had high-grade morphology in the micropapillary carcinoma and typical urothelial carcinoma. All cases with extensive MPC (n = 4) were of a high pathological stage (pT3 or pT4) and died of disease (DOD) or other causes. Eighty percent with moderate MPC (eight of 10 cases) were pT3 or pT4 and 50% DOD or are alive with disease. Eighty-four percent with focal MPC (five of six cases) were pT1 or pTa. In high-stage cases, the most invasive component was MPC. High-stage cases had an 85% risk of being advanced at presentation with micropapillary carcinoma. All pT2 or lower stage cases had micropapillary carcinoma on prior transurethral resections of bladder tumour (TURB). High-stage carcinomas had 30% and 54%, respectively, of surface MPC and urothelial carcinoma in situ, in comparison with 85% and 28% in lower stage carcinomas. Immunohistochemical staining was similarly positive in MPC and typical urothelial carcinoma with cytokeratin (CK)7, CK20, epithelial membrane antigen, carcinoembryonic antigen and cytokeratin 34betaE12. CA125 staining was seen only in MPC in 43% of cases. CONCLUSIONS: Micropapillary urothelial carcinoma is a high-grade carcinoma in which the prognosis is related to the proportion and location of the MPC. Cases with moderate or extensive MPC are at high risk of being advanced at presentation. Cases with <10% MPC and surface MPC have a high chance of detection at an early stage. The morphology and immunohistochemical profile of the MPC suggest that it is a form of glandular differentiation in urothelial carcinoma.     

Effects of dietary fatty acids on the early stages of neoplastic induction in the rat pancreas. Changes in fatty acid composition and development of atypical acinar cell nodules.

Diets enriched with fat, especially unsaturated fat, promote experimental pancreatic carcinogenesis, but little is known of the effects of individual fatty acids. The effect of stearic and oleic acid on pancreatic fatty acids and atypical acinar cell nodules (preneoplastic lesions) was studied in 14-day-old weanling male Leeds strain rats (n = 60) given the carcinogen azaserine. Rats were allocated to one of six groups: untreated controls (n = 10), 20% stearic acid diet (n = 10), 20% oleic acid diet (n = 10), carcinogen alone (n = 10), carcinogen plus 20% stearic acid diet (n = 10) or carcinogen plus 20% oleic acid diet (n = 10). Azaserine was administered by intraperitoneal injection in a dose of 30 mg/kg at 2, 3 and 4 weeks of age. When total lipid extracts of pancreas were examined, there was an increase in stearic acid in the stearic acid fed group and an increase in oleic acid in the oleic acid fed group, irrespective of carcinogen treatment. The relative content of all other pancreatic fatty acids was suppressed by feeding oleic acid. At 26 weeks, the number and volumetric indices of pancreatic atypical acinar cell nodules was increased only in rats given azaserine and oleic acid. The enhancing effect of oleic acid on pancreatic carcinogenesis may be associated with pancreatic fatty acid changes.     

p21WAF1/CIP1 expression in gestational trophoblastic disease: correlation with clinicopathological parameters, and Ki67 and p53 gene expression.

BACKGROUND: The p21WAF1/CIP1 gene mediates growth arrest by inhibiting G1 cyclin dependent kinases and has been considered as a downstream effector of the tumour suppressor gene p53. AIM: To analyse the role of p21WAF1/CIP1 in gestational trophoblastic disease. METHODS: The immunohistochemical expression of p21WAF1/CIP1 gene was measured in 33 placentas, 28 partial hydatidiform moles, 54 complete hydatidiform moles, and 13 choriocarcinomas in paraffin wax embedded tissue. The results were correlated with p53 (DO7) and Ki67 (MIB1) immunoreactivity as well as clinical progress. RESULTS: p21WAF1/CIP1 immunoreactivity was found predominantly in the nuclei of the syncytiotrophoblasts. p21WAF1/CIP1 protein expression correlated with gestational age in normal placentas (p = 0.0001) but not in hydatidiform moles (p = 0.89). Complete hydatidiform moles and choriocarcinomas had a significantly higher p21WAF1/CIP1 expression compared with normal placentas and partial hydatidiform moles (p < 0.001); there was no difference between placentas and partial hydatidiform moles. No correlation between p21WAF1/CIP1 expression and either the proliferation (Ki67) index (p = 0.34) or p53 protein accumulation (p = 0.68) was demonstrated. There was no significant difference (p > 0.05) in p21WAF1/CIP1 expression between the 17 patients who developed persistent gestational trophoblastic disease and those who did not. CONCLUSIONS: This study suggests that p21WAF1/CIP1 expression in trophoblastic disease may be induced by a p53 independent pathway. The proliferative activity of gestational trophoblastic diseases might not be determined solely by the control of the cell cycle operated by p21WAF1/CIP1. p21WAF1/CIP1 expression is not an accurate prognostic indicator of gestational trophoblastic disease.