Macrofollicular variant of follicular thyroid carcinoma: a clinical,cytologic, morphologic,and image analysis study of a unique case

Thyroid lesions composed of large follicles that contain abundant colloid are usually regarded as benign hyperplastic or adenomatous nodules both by fine-needle aspiration cytology and histology. In such cases, the pathologist is less likely to request a complete inclusion of the capsule into paraffin block and to look for vascular and/or capsular invasion, the only criteria that permit the differential diagnosis between a benign nodule and a follicular carcinoma. We report the first case of a follicular thyroid carcinoma composed predominantly (>90%) of macrofollicles with a surface area that was up to 5 times larger than the surface area of normal follicles, as calculated with an image analysis system. Capsular invasion was detected in 2 separate foci. The tumor was classified as a minimally invasive follicular carcinoma, macrofollicular variant. This case is detailed to highlight the potential pitfall that may arise from an incomplete histological analysis of a macrofollicular lesion, with particular attention paid to the differential diagnoses.     

Calcium channel blocker prevents T helper type 2 cell-mediated airway inflammation

RATIONALE: Ca(2+) signaling controls the production of T helper (Th) type 2 cytokines known to be deleterious in asthma. Recently, we showed that Ca(2+) signaling was dihydropyridine (DHP)-sensitive in Th2 lymphocytes and that the DHP derivate, nicardipine, used in the treatment of cardiovascular pathologies, prevents Th2-dependent B cell polyclonal activation. OBJECTIVES: We tested the effect of nicardipine in experimental allergic asthma. METHODS: BALB/c mice immunized with ovalbumin (OVA) in alum and challenged with intranasal OVA were treated with nicardipine once the Th2 response, or even airway inflammation, was induced. We also tested the effect of nicardipine in asthma induced by transferring OVA-specific Th2 cells in BALB/c mice exposed to intranasal OVA. We checked the impact of nicardipine on T-cell responses and airway inflammation. MEASUREMENTS AND MAIN RESULTS: Nicardipine inhibited in vitro Ca(2+) response in Th2 cells. In vivo, it impeded the development of Th2-mediated airway inflammation and reduced the capacity of lymphocytes from lung-draining lymph nodes to secrete Th2, but not Th1, cytokines. Nicardipine did not affect antigen presentation to CD4(+) T lymphocytes, nor the initial localization of Th2 cells into the lungs of mice exposed to intranasal OVA; however, it reduced the production of type 2 cytokines and the amplification of the Th2 response in mice with asthma. Conversely, nicardipine had no effect on Th1-mediated airway inflammation. CONCLUSIONS: Nicardipine improves experimental asthma by impairing Th2-dependent inflammation. This study could provide a rationale for developing drugs selectively targeting DHP receptors of Th2 lymphocytes, potentially beneficial in the treatment of asthma.     

A prospective long-term study of 220 patients with a retrievable vena cava filter for secondary prevention of venous thromboembolism

BACKGROUND: The immediate and long-term clinical events associated with the placement and removal of a retrievable filter (ALN filter; ALN Implants Chirurgicaux; Ghisonaccia, France) remain largely unknown. METHODS: This was a prospective cohort study with an 18-month follow-up. All consecutive patients scheduled for placement of an ALN filter between April 1999 and June 2005 in the Radiology Department of our hospital were included. RESULTS: During the study period, placement of an ALN filter was indicated in 220 patients (mean age, 70.8 years), who were followed up for a median duration of 338.5 days (range, 1 to 561 days); 148 patients (67.3%) completed the 18-month follow-up. No patients were unavailable for follow-up. All patients had an acute or past venous thromboembolism. Main indications were recurrent venous thromboembolism despite adequate anticoagulation therapy (10.9%), transient bleeding event (21.8%), definitive contraindication for anticoagulant therapy (26.8%), or obligation to stop anticoagulant therapy due to major surgery, major trauma, or invasive procedure (37.7%). Filter insertion was successful in 98.6% of patients and resulted in an immediate complication in 11.8%. The median duration of filter implantation was 166 days (first to third quartiles, 34 to 478 days). Meanwhile, 17.0% (37 of 217 patients) had at least one venous thromboembolic event. Filter retrieval was attempted in 25.3% of patients after a median of 51 days (range, 6 to 352 days); removal was successful at the first attempt in 92.7% of patients. CONCLUSIONS: The filter could be easily inserted and successfully removed up to 1 year after insertion. Its safety and efficacy in preventing pulmonary embolism should be properly assessed in a randomized study.     

Acinar cell carcinoma of the pancreas with predominant intraductal growth: report of a case

Acinar cell carcinoma (ACC) of the pancreas accounts for approximately 1% of all exocrine pancreatic tumours. We report a rare form of ACC in a 66-year-old man. This tumour was revealed by epigastric pain and weight loss. Abdominal computed tomography showed a hypodense, well-demarcated, heterogeneous lesion, in the head of the pancreas, measuring 4.2 cm in diameter. There was a marked dilatation of the main pancreatic duct upstream, with tumour spreading within this duct. The diagnosis of ACC was made on the fine needle aspiration cytology performed during endoscopic ultrasound examination. On the pancreaticoduodenectomy specimen, the dilated main pancreatic duct (2.5 cm in diameter) was filled by an exophytic tumour. Histological examination showed an ACC, with predominant intraductal growth (main and accessory pancreatic ducts), with pancreatic parenchymal and duodenal invasion. Neuroendocrine markers were negative. To our knowledge, this is the second report of an ACC with predominant intraductal spread. These rare forms of ACC can be confused with intraductal papillary-mucinous neoplasms. In our report, fine needle aspiration cytology performed during endoscopic ultrasound examination was a valuable tool in the diagnostic assessment.     

DNA polymerase θ up-regulation is associated with poor survival in breast cancer,perturbs DNA replication,and promotes genetic instability

“Replicative stress” is one of the main factors underlying neoplasia from its early stages. Genes involved in DNA synthesis may therefore represent an underexplored source of potential prognostic markers for cancer. To this aim, we generated gene expression profiles from two independent cohorts (France, n = 206; United Kingdom, n = 117) of patients with previously untreated primary breast cancers. We report here that among the 13 human nuclear DNA polymerase genes, DNA Polymerase θ (POLQ) is the only one significantly up-regulated in breast cancer compared with normal breast tissues. Importantly, POLQ up-regulation significantly correlates with poor clinical outcome (4.3-fold increased risk of death in patients with high POLQ expression), and this correlation is independent of Cyclin E expression or the number of positive nodes, which are currently considered as markers for poor outcome. POLQ expression provides thus an additional indicator for the survival outcome of patients with high Cyclin E tumor expression or high number of positive lymph nodes. Furthermore, to decipher the molecular consequences of POLQ up-regulation in breast cancer, we generated human MRC5-SV cell lines that stably overexpress POLQ. Strong POLQ expression was directly associated with defective DNA replication fork progression and chromosomal damage. Therefore, POLQ overexpression may be a promising genetic instability and prognostic marker for breast cancer.     

Peripheral neural lesion-induced stress urinary incontinence in anaesthetized female cats

OBJECTIVES

To characterize the effect of acute unilateral and bilateral lesion of the pelvic and pudendal nerves, and nerves innervating the iliococcygeous and pubococcygeous muscles during sneezing in anaesthetized female cats, on intravesical pressure (IVP), urethral pressure (UPs) and external urethral sphincter (EUS) activity.

MATERIALS AND METHODS

In seven anaesthetized female cats UPs along the urethra (UPs1–4) and IVPs were recorded in the emptied bladder during sneezing before and after unilateral and then bilateral peripheral neural lesions. UPs were measured using microtip transducer catheters with UP4 positioned in the distal urethra where the EUS is located. Urine leakage was also noted, after urethral catheter removal and bladder filling.

RESULTS

During sneezing, in intact cats, the magnitude of UP4 was larger than those of IVP and UPs1–3. The area under the curve of both anal sphincter and EUS electromyography was increased. There was no urine leakage. After unilateral neural lesions, the mean magnitude of response was similar all along the urethra and in the bladder. The distal UP response was significantly lower than that recorded in intact cats. In addition, there was urine leakage in six of the seven cats. Bilateral neural lesions caused permanent urine leakage and significant decreases in all the UP responses.

CONCLUSION

In female cats, during sneezing, neurally driven reflex contractions of EUS leading to an increase in distal UP contribute to active urethral closure mechanisms and ensure urinary continence.     

Consumption of herbal remedies and dietary supplements amongst patients hospitalized in medical wards

AIMS: Herbal remedies may have adverse effects and potentially serious interactions with some commonly prescribed conventional medications. Little is known about consumption of herbal remedies and dietary supplements by hospitalized patients. The aim was to evaluate the rate of consumption and characterize the patients hospitalized in internal medicine departments who consume herbal remedies and dietary supplements. Also, to assess the medical teams' awareness and assess the percentage of patients with possible drug-herb interactions. METHODS: Patients hospitalized in the medical wards of two hospitals in Israel were interviewed about their use of herbal remedies or dietary supplements. The medical records were searched for evidence that the medical team had knowledge of the use of herbal remedies or dietary supplements. RESULTS: Two hundred and ninety-nine hospitalized medical patients were interviewed. Of the participants, 26.8% were herbal or dietary supplement consumers (HC). On multivariate analysis the only variates associated with herbal or dietary supplement consumption were the hospital [odds ratio (OR) 2.97, 95% confidence interval (CI) 1.29, 6.52], income (OR 0.39, 95% CI 0.15, 1.05), smoking habits (OR 0.17, 95% CI 0.05, 0.55) and benign prostatic hypertrophy (OR 4.64, 95% CI 1.3, 16.5). Ninety-four percent of the patients had not been asked specifically of herbal consumption by the medical team. Only 23% of the hospital's medical files of the HC patients had any record of the use of herbal or dietary supplements. Seven possible drug-herbal interactions were encountered (7.1%). The most serious was an interaction between camomile tea and ciclosporin. CONCLUSIONS: Herbal remedy consumption is common amongst patients hospitalized in internal medicine wards and is often overlooked by the medical team. Patients and doctors should be more aware of the possible adverse effects and of the potential of herb-drug interactions.