Extrapulmonary sarcoidosis

Sarcoidosis can affect any organ in the body. Frequently extrapulmonary manifestations of the disease are the major cause of morbidity. Treatment of extrapulmonary sarcoidosis often requires consideration of alternative immunosuppressive agents, topical therapy, or therapy that is not specifically directed against the granulomatous inflammation of the disease. This article reviews the clinical presentation and therapy of extrapulmonary sarcoidosis.     

Fine-needle aspiration may miss a third of all malignancy in palpable thyroid nodules: a comprehensive literature review

BACKGROUND: Fine-needle aspiration (FNA) is currently the primary diagnostic procedure in diagnosing thyroid malignancy and guides surgeons on patient selection for thyroidectomy for thyroid nodules. Diagnostic sensitivity is reported to be approximately 80%; however, patients with negative FNA results do not necessarily undergo surgery and are often not considered in statistical analysis. This may lead to bias in previous reported sensitivity of FNA. The aim of this study was to assess the diagnostic performance attributes of FNA based on a comprehensive review and summary of previous literature. METHODS: A comprehensive review of published literature from 1966 to 2005 was performed, using structured selection and appraisal methods to include all studies that have assessed the sensitivity of FNA for detecting thyroid malignancy in palpable thyroid nodules. A statistical modeling study was designed to estimate the possible true sensitivity and specificity of FNA. RESULTS: Twelve studies fulfilled inclusion criteria and were included in the review. Only 1 study had greater than 25% of patients with negative FNA results who proceeded to thyroidectomy. Statistical modeling indicated that the sensitivity of FNA is highly dependent on the risk of malignancy in the patients with negative FNA results who did not undergo thyroidectomy; in the "same risk" scenario, where the risk of malignancy in the whole group with negative FNA result was assumed to be the same as that in patients with negative FNA results who underwent surgical biopsy; sensitivity could be as low as 66% (confidence interval [CI]: 65-68%). CONCLUSION: Based on existing reports, the true diagnostic attributes of FNA for thyroid malignancy in palpable nodules are uncertain and FNA could miss up to a third of all thyroid malignancy. Further research is required to investigate the incidence of malignancy in FNA negative cases and to determine the additive effect of clinical judgment.     

Cognitive function and treatment response in a randomized clinical trial of computer-based training in cognitive-behavioral therapy

Cognitive-behavioral therapy (CBT), because of its comparatively high level of cognitive demand, is likely to be challenging for substance users with limitations in cognitive function. However, it is not known whether computer-assisted versions of CBT will be particularly helpful (e.g., allowing individualized pace and repetition) or difficult (e.g., via complexity of computerized delivery) for such patients. In this secondary analysis of data collected from a randomized clinical trial evaluating computer-assisted CBT, four aspects of cognitive functioning were evaluated among 77 participants. Those with higher levels of risk taking completed fewer sessions and homework assignments and had poorer substance use outcomes.     

Endoscopic sphincterotomy and interval cholecystectomy are reasonable alternatives to index cholecystectomy in severe acute gallstone pancreatitis (GSP)

BACKGROUND: UK guidelines for gallstone pancreatitis (GSP) advocate definitive treatment during the index admission, or within 2 weeks of discharge. However, this target may not always be achievable. This study reviewed current management of GSP in a university hospital and evaluated the risk associated with interval cholecystectomy. METHODS: All patients that presented with GSP over a 4-year period (2002-2005) were stratified for disease severity (APACHE II). Patient demographics, time to definitive therapy [index cholecystectomy; endoscopic sphincterotomy (ES); Interval cholecystectomy], and readmission rates were analysed retrospectively. RESULTS: 100 patients admitted with GSP. Disease severity was mild in 54 patients and severe in 46 patients. Twenty-two patients unsuitable for surgery underwent ES as definitive treatment with no readmissions. Seventy-eight patients underwent cholecystectomy, of which 40 (58%) had an index cholecystectomy, and 38 (42%) an interval cholecystectomy. Only 10 patients with severe GSP had an index cholecystectomy, whilst 30 were readmitted for Interval cholecystectomy (p = 0.04). The median APACHE score was 4 [standard deviation (SD) 3.8] for index cholecystectomy and 8 (SD 2.6) for Interval cholecystectomy (p < 0.05). Median time (range) to surgery was 7.5 (2-30) days for index cholecystectomy and 63 (13-210) days for Interval cholecystectomy. Fifty percent (19/38) of patients with GSP had ES prior to discharge for interval cholecystectomy. Two (5%) patients were readmitted: with acute cholecystitis (n = 1) and acute pancreatitis (n = 1) , whilst awaiting interval cholecystectomy. No mortality was noted in the Index or Interval group. CONCLUSIONS: This study demonstrates that overall 62% (22 endoscopic sphincterotomy and 40 index cholecystectomy) of patients with GSP have definitive therapy during the Index admission. However, surgery was deferred in the majority (n = 30) of patients with severe GSP, and 19/30 underwent ES prior to discharge. ES and interval cholecystectomy in severe GSP is associated with minimal morbidity and readmission rates, and is considered a reasonable alternative to an index cholecystectomy in patients with severe GSP.     

NCCN Task Force report: management of patients with gastrointestinal stromal tumor (GIST)--update of the NCCN clinical practice guidelines

The NCCN Soft Tissue Sarcoma Guidelines include a subsection about treatment recommendations for gastrointestinal stromal tumors (GISTs). The standard of practice rapidly changed after the introduction of effective molecularly targeted therapy (such as imatinib and sunitinib) for GIST. Because of these changes, NCCN organized a multidisciplinary panel composed of experts in the fields of medical oncology, molecular diagnostics, pathology, radiation oncology, and surgery to discuss the optimal approach for the care of patients with GIST at all stages of the disease. The GIST Task Force is composed of NCCN faculty and other key experts from the United States, Europe, and Australia. The Task Force met for the first time in October 2003 and again in December 2006 with the purpose of expanding on the existing NCCN guidelines for gastrointestinal sarcomas and identifying areas of future research to optimize our understanding and treatment of GIST.     

A phase I trial of the selective oral cyclin-dependent kinase inhibitor seliciclib (CYC202; R-Roscovitine), administered twice daily for 7 days every 21 days

Seliciclib (CYC202; R-roscovitine) is the first selective, orally bioavailable inhibitor of cyclin-dependent kinases 1, 2, 7 and 9 to enter clinical trial. Preclinical studies showed antitumour activity in a broad range of human tumour xenografts. A phase I trial was performed with a 7-day b.i.d. p.o. schedule. Twenty-one patients (median age 62 years, range: 39-73 years) were treated with doses of 100, 200 and 800 b.i.d. Dose-limiting toxicities were seen at 800 mg b.i.d.; grade 3 fatigue, grade 3 skin rash, grade 3 hyponatraemia and grade 4 hypokalaemia. Other toxicities included reversible raised creatinine (grade 2), reversible grade 3 abnormal liver function and grade 2 emesis. An 800 mg portion was investigated further in 12 patients, three of whom had MAG3 renograms. One patient with a rapid increase in creatinine on day 3 had a reversible fall in renal perfusion, with full recovery by day 14, and no changes suggestive of renal tubular damage. Further dose escalation was precluded by hypokalaemia. Seliciclib reached peak plasma concentrations between 1 and 4 h and elimination half-life was 2-5 h. Inhibition of retinoblastoma protein phosphorylation was not demonstrated in peripheral blood mononuclear cells. No objective tumour responses were noted, but disease stabilisation was recorded in eight patients; this lasted for a total of six courses (18 weeks) in a patient with ovarian cancer.     

Expression of human neutrophil proteins in acne vulgaris

Background In acne vulgaris patients, the presence of a dysregulation of the production of innate and specific antimicrobial peptides has been postulated. Objective This study aims to determine whether human neutrophil proteins (HNP) 1–3 are expressed in acne patients. Materials and methods HNP 1–3 expression was investigated in 35 acne patients treated with isotretinoin and in 25 healthy subjects. At the beginning of the study, two skin biopsies were taken from acne patients; one biopsy was taken from an established pustule and one from uninvolved skin, and the biopsies were repeated after treatment. Only one biopsy was obtained from controls. Results The statistical analysis showed that pustular lesions of acne patients had significantly higher levels of perivascular and interstitial HNP 1–3 expression when compared with the biopsy of uninvolved skin of these patients (P = 0.003, P = 0.001, respectively) and with that of healthy controls (P = 0.007, P = 0.014, respectively). Isotretinoin treatment achieved a decrease in the perivascular and interstitial HNP 1–3 expression of pustular lesions (P = 0.01, P = 0.001, respectively). Conclusion Our current study demonstrates the novel observation that a recently identified antimicrobial peptide, HNP 1–3, is expressed in neutrophils of acne inflammation but not in uninvolved skin of these patients. These results suggest that HNP 1–3 may contribute to the development of inflammatory lesions of acne.