Malignant colonic polyps: is polypectomy adequate treatment?

The management of patients with endoscopically removed malignant intestinal polyps is controversial. The risk of residual disease should be assessed against the risk of a surgical operation. The authors report 35 cases of malignant polyps (5.5% of 641 colonoscopically removed adenomas). Sixteen patients had carcinoma in situ and received no further treatment and 19 had invasive carcinoma (sessile in 6, pedunculated in 13). Of these 19, 7 did not undergo surgery--because of old age in 2, minimal invasion in 3, a low rectal location in 1 and refusal in 1. Twelve patients (3 with sessile, 9 with pedunculated polyps) underwent a surgical resection, and residual disease was present in 3 (25%), 1 with positive nodes. Reported criteria of increased risk of residual disease--cancer in lymphatics or veins, incomplete excision, tumour at resection margin, sessile and villous tumours--were present in nine. All three patients with residual disease had microscopically involved margins of resection. The authors believe that the increased risk of recurrence justifies the risk associated with subsequent surgical resection unless the patient is otherwise a poor operative risk.     

Transjugular intrahepatic portosystemic shunt before abdominal surgery in cirrhotic patients: a retrospective, comparative study.

Surgery in cirrhotic patients is associated with high morbidity and mortality related to portal hypertension and liver insufficiency. Therefore, preoperative portal decompression is a logical approach to facilitate abdominal surgery and hopefully to improve postoperative survival. The present study evaluated the clinical outcomes of 18 patients (mean age 58 years) with cirrhosis (seven alcoholics and 11 nonalcoholics) who underwent transjugular intrahepatic portosystemic shunt (TIPS) placement before antrectomy (n=5), colectomy (n=10), small-bowel resection (n=1), pancreatectomy (n=1) and nephrectomy (n=1). TIPS was performed a mean (+/-SD) of 72+/-21 days before surgery and induced a marked mean decrease in portohepatic gradient from 21.4+/-3.9 mmHg to 8.4+/-3.4 mmHg. Cirrhotic patients (n=17) who underwent elective abdominal surgery without preoperative TIPS placement were used as the control group. Both groups were matched for age, etiology of cirrhosis, indications for surgery, type of surgery and coagulation parameters. The mean Pugh score was significantly higher in the TIPS group (7.7 versus 6.2). No significant differences were observed for operative blood loss, postoperative complications, duration of hospitalization and one-month (83% versus 88%) or one-year (54% versus 63%) cumulative survival rate. Analysis using the Cox proportional hazards model showed that neither TIPS placement nor preoperative Pugh score were independent predictors for survival. The present study suggests that preoperative TIPS placement does not improve postoperative evolution after abdominal surgery in cirrhotic patients with good or moderately impaired liver function.     

Neuron-specific enolase and malignant lymphomas (23 cases)

Summary The immunoreactivity of polyclonal antiserum to neuron-specific enolase (NSE) has been investigated. Twenty-three cases of malignant lymphoma (ML) were studied and compared with previously published reports. In our study 11 out of 23 cases showed strong or weak NSE positivity; any type of ML could be positive or negative even among B or T cell ML. This study indicated that polyclonal NSE is not a specific marker; it might be an inconstant marker of ML with no apparent correlation between reactivity and morphology or phenotype.     

Hydrosalpinges adversely affect markers of endometrial receptivity

While in-vitro fertilization (IVF) was initially developed in women with tubal factor infertility, recent clinical studies have suggested that the presence of hydrosalpinges lowers implantation and pregnancy rates. We postulated that these hydrosalpinges cause impaired endometrial receptivity. A total of 103 women with hydrosalpinges were prospectively evaluated, and compared with 55 infertile and 44 fertile controls. All women had endometrial biopsies during the window of implantation, analysed by conventional histological criteria, and also stained for three integrin markers of endometrial receptivity (alpha1beta1, alpha4beta1 and alpha vbeta3). Women with hydrosalpinges (cases) expressed significantly less of the alpha vbeta3 integrin compared with controls. There was no difference in expression of alpha1beta1 or alpha4beta1 among groups. A significantly greater number of cases had out of phase histology and missing alpha vbeta3 (type I defects) and absent integrin expression despite normal histological maturation (type II) defects, compared with controls. Of 20 women with impaired endometrial receptivity who were also biopsied after hydrosalpinx surgery, 70% demonstrated increased alpha vbeta3 expression. Seventy-seven percent of type I and 57% of type II defects were corrected postoperatively. Using markers of endometrial receptivity, this study demonstrates that inflammatory hydrosalpinges have an adverse effect on endometrial receptivity, which in some cases may be overcome by surgical treatment of the hydrosalpinx.      

bcl-2 transgene expression promotes survival and reduces proliferation of CD3-CD4-CD8- T cell progenitors

Proliferative expansion and apoptotic cell death play prominent roles in T cell development. The molecular control of cell cycle progression and apoptosis appear to be inter-connected since the Bcl-2 protein can inhibit apoptosis and slow cell cycle progression in cortical thymocytes and mature T cells, particularly during the transition from the quiescent state into the cell cycle. Here the impact of bcl-2 transgene expression on CD3-CD4-CD8- T cell progenitors was assessed. Bcl-2 enhanced the survival of these progenitors at all of the four major differentiation stages, CD25- CD44+ (pro-T1), CD25 + CD44+ (pro- T2), CD25 + CD44- (pro-T3) and CD25-CD44- (pro-T4). However, it reduced cell cycling and slowed turnover only in the pro-T4 subset. From an analysis of bcl-2 transgenic mice expressing a TCR transgene or bearing a mutation in the scid or rag-1 gene we conclude that Bcl-2 inhibits proliferation only of T cell progenitors that are activated via the pre- TCR, not those stimulated via c-Kit and the IL-7 receptor.      

Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism

Parathyroid hormone secretion is negatively regulated by a 7- transmembrane domain, G-protein coupled Ca(2+)-sensing receptor. We hypothesized that activating mutations in this receptor might cause autosomal dominant hypoparathyroidism (ADHP). Consistent with this hypothesis, we identified, in two families with ADHP, heterozygous missense mutations in the Ca(2+)-sensing receptor gene that cosegregated with the disorder. None of 50 normal controls had either mutation. We also identified a de novo, missense Ca(2+)-sensing receptor mutation in a child with severe sporadic hypoparathyroidism. The amino acid substitution in one ADHP family affected the N-terminal, extracellular domain of the receptor. The other mutations involved the transmembrane region. Unlike patients with acquired hypoparathyroidism, patients with these mutations had hypercalciuria even at low serum calcium concentrations. Their greater hypercalciuria presumably reflected activation of Ca(2+)-sensing receptors in kidney cells, where the receptor negatively regulates calcium reabsorption. This augmented hypercalciuria increases the risk of renal complications and thus has implications for the choice of therapy.      

Symptomatic peripheral arterial disease: the value of a validated questionnaire and a clinical decision rule

BACKGROUND: If a validated questionnaire, when applied to patients reporting with symptoms of intermittent claudication, could adequately discriminate between those with and without peripheral arterial disease, GPs could avoid the diagnostic measurement of the ankle brachial index. AIM: To investigate the Edinburgh Claudication Questionnaire (ECQ) in general practice and to develop a clinical decision rule based on risk factors to enable GPs to easily assess the likelihood of peripheral arterial disease. DESIGN OF STUDY: An observational study. SETTING: General practice in The Netherlands. METHOD: This observational study included patients of > or =55 years visiting their GP for symptoms suggestive of intermittent claudication or with one risk factor. The ECQ and the ankle brachial index were performed. The prevalence of peripheral arterial disease, defined as an ankle brachial index <0.9, was related to risk factors using logistic regression analyses, on which a clinical decision rule was developed and related to the presence of peripheral arterial disease. RESULTS: Of the 4790 included patients visiting their GP with symptoms suggestive of intermittent claudication, 4527 were eligible for analyses. The prevalence of peripheral arterial disease in this group was 48.3%. The sensitivity of the ECQ was only 56.2%. The prevalence of peripheral arterial disease in a clinical decision rule that included age, male sex, smoking, hypertension, hypercholesterolemia, and a positive ECQ, increased from 14% in the lowest to 76% in the highest category. CONCLUSION: This study indicates that the ECQ alone has an inadequate diagnostic value in detecting patients with peripheral arterial disease. The ankle brachial index should be performed to diagnose peripheral arterial disease in patients with complaints suggestive of intermittent claudication, although our clinical decision rule could help to differentiate between extremely high and lower prevalence of peripheral arterial disease.     

Ultrastructure of the Kidney in Acute Interstitial Nephritis

Fifteen percutaneous renal biopsies from patients with acute renal failure due to acute interstitial nephritis (AIN), in almost all cases due to drugs, were studied by electron microscopy. Differential counting of interstitial cells showed an average of 69% lymphocytes (small and large) and 11 % macrophages. Plasma cells and eosinophils were comparatively rare. The infiltrate resembled that of acute rejection, suggesting a cellular hypersensitivity reaction. Proximal and distal tubules were severely affected focally. Migration of lymphocytes through the tubular basement membrane of otherwise well-preserved tubules was considered to be the first phase. Other tubules showed extreme thinning of the tubular basement membrane, with still intact cellular walls. Rupture of the tubular basement membrane and necrotic disintegration of tubular epithelial cells are probably late phenomena. The non-necrotic tubules displayed severe reduction of proximal brush border and proximal as well as distal tubular basolateral infoldings. Focal tubular disintegration leading to tubular block and/or backleak as well as decrease of proximal tubular sodium resorption leading to a decreased glomerular filtration (a mechanism probably also acting in ischemic acute renal failure) may all be factors responsible for the acute renal failure in AIN.