The clinical application and cost analysis of fine-needle aspiration biopsy in the diagnosis of mass lesions in sarcoidosis

BACKGROUND: Sarcoidosis is a prevalent disease of unknown cause characterized by granulomatous inflammation that often creates deep and/or superficial mass lesions. Tissue samples are considered the "gold standard" in diagnosis; however, it is a medically treated disease. We analyzed the utility and relative cost-effectiveness of fine-needle aspiration biopsy (FNAB) in the clinical investigation of patients with both suspected and unsuspected sarcoidosis. METHODS: All FNAB cases with sarcoidosis either as the cytologic diagnosis or mentioned as part of the differential diagnosis were retrospectively reviewed for clinical history, follow-up, cytologic features, and surgical pathology findings. Comparative analysis of cost of FNAB and excisional biopsy were also made. RESULTS: Thirty-two FNABs in 28 patients included 17 women and 11 men. Anatomic sites included lymph node (n = 17), lung (n = 5), salivary gland (n = 8), and liver (n = 2). Sarcoidosis had already been diagnosed or was a clinical consideration prior to FNAB in 14 cases. Chest radiograph showed abnormal findings in 19 cases. Angiotensin-converting enzyme (ACE) was measured in seven patients and was elevated in four. All aspirates showed granulomatous inflammation; in 22 patients, special stains or cultures for microorganisms were negative. Simultaneous or subsequent excisional biopsies confirmed the FNAB findings in 17 patients. Institutional ratios of excisional biopsy to FNAB in the diagnosis of sarcoidosis ranged from 4 to 19:1. The cost of FNAB was only 12.5 to 50% that of tissue biopsy. CONCLUSIONS: FNAB appears to be underutilized in the diagnosis of sarcoidosis. When used in conjunction with radiologic and laboratory data, FNAB may be a reliable and cost-effective method of diagnosis, especially in patients with an established diagnosis of sarcoidosis.     

A randomised trial of radiotherapy compared with cisplatin chemo-radiotherapy in patients with unresectable squamous cell cancer of the esophagus.

BACKGROUND AND PURPOSE: Following our phase II experience, a randomised trial was undertaken to evaluate the efficacy of adding chemotherapy to radiotherapy in patients with unresectable squamous cell cancer of the esophagus. PATIENTS AND METHODS: Patients randomised to the RT group received 50 Gy/25 fx/5 weeks of teletherapy followed 1-2 weeks later with 12 Gy/2 fx of high-dose-rate intra-lumenal brachytherapy spaced a week apart. Following the first 3 years of recruitment, due to unexpected late morbidity, brachytherapy was excluded and the protocol modified to 66 Gy/33 fx/6.5 weeks. The CRT group received identical radiotherapy with concurrent weekly cisplatin at 35 mg/m(2) for 6-7 cycles. RESULTS: Between April 1999 and December 2005, 125 patients were randomised to a RT (n=60) or CRT group (n=65). Radiotherapy treatment was completed in 78% (47/60) of the RT group and 89% (58/65) of the CRT group (P=0.10). Six or more cycles of cisplatin could be delivered in 63% (41/65), which resulted in RTOG grade 3 neutropenia of 3%. Late morbidity in the form of ulcers (5% vs. 15% odds ratio 0.29, 95% CI 0.08-1.11, P=0.08) and strictures (13% vs. 28%, odds ratio 0.40, 95% CI 0.16-1.01, P=0.05) was observed in the RT and CRT groups, respectively. At a median follow up of 23 months of all patients alive (range 6-82 months) and with 95/125 events, the median, 1, 2 and 5 year projected survival was 7.1 months, 32.3%, 22.8% and 13.7% vs. 13.4 months, 57.6%, 38.9% and 24.8% for the RT and CRT groups, respectively (hazard ratio 0.65, 95% CI 0.44-0.98, P=0.038). CONCLUSIONS: The addition of concurrent cisplatin to radiotherapy resulted in a modest improvement in survival and was associated with manageable additional acute and late morbidity.     

Lithocholylcholine,a bile acid/acetylcholine hybrid,is a muscarinic receptor antagonist

Previous work from our laboratory indicates that bile acids, specifically lithocholic acid conjugates, interact with muscarinic receptors on gastric chief cells. Structural similarities between acetylcholine and lithocholyltaurine suggest a potential molecular basis for their interaction with the same receptor. We synthesized a hybrid molecule consisting of the steroid nucleus of lithocholyltaurine and the choline moiety of acetylcholine. The new molecule, lithocholylcholine, is hydrolyzed by acetyl-cholinesterase. Lithocholylcholine inhibited binding of a cholinergic radioligand to Chinese hamster ovary cells expressing each of the five muscarinic receptor subtypes. The binding affinities (K(i); micromolar) of lithocholylcholine for these receptors were: M3 (1.0) > M1 (2.7) > M2 (4.1) = M4 (4.9) > M5 (6.2). Lithocholylcholine inhibited intracellular signaling pathways mediated by interaction with M1, M2, and M3 muscarinic receptors. Regarding M3 receptors, lithocholylcholine was 10-fold more potent than lithocholyltaurine in terms of binding affinity and inhibition of acetylcholine-induced increases in inositol phosphate formation and mitogen-activated protein kinase phosphorylation. In a functional assay, lithocholylcholine inhibited acetylcholine-induced relaxation of rat aortic rings. These observations indicate that lithocholylcholine is a muscarinic receptor antagonist and provide further evidence that bile acids may have gastrointestinal signaling functions that extend beyond their effects on sterol metabolism, lipid absorption, and cholesterol elimination. Hybrid molecules created from bile acids and acetylcholine may be used to develop selective muscarinic receptor ligands.     

Glutathione S-transferase: a potential new marker of intestinal ischemia

Background/Purpose: The accurate and early diagnosis of intestinal ischemia remains difficult chiefly because of a lack of a suitable marker that is noninvasive and easy to use. The glutathione S-transferases (GST) are a family of cytosolic enzymes involved in detoxification and released from a variety of cells when the cell membrane is damaged. The enzymes are distributed widely in the intestine and show isoform specificity in their distribution throughout the intestinal tract. Several previous reports have shown the utility of these enzymes in the diagnosis of liver and renal graft damage during and after organ transplantation. The object of this study was to determine if GST levels correlated with histologic changes of intestinal ischemia in a controlled animal model of mesenteric intestinal ischemia.Methods: Control and experimental male Sprague-Dawley rats underwent laparotomy and ligation of the Superior Mesenteric Artery (SMA) and both control and experimental animals were studied at 30, 60, 90, 120, and 240 minutes. Blood taken from the Inferior Vena Cava (IVC) and Portal Vein (PV) and jejunal and ileal perfusates were assayed for [alpha ] and [mu ] isoforms of GST using a commercially available enzyme immunoassay. In addition, jejunal and ileal segments were sampled and reviewed by a histopathologist blinded to the group being studied.Results: A reproducible pattern of intestinal ischemia was noted with worsening grades of injury observed with greater ligation times. Luminal [alpha ] and [mu ] GST release (as measured by the appearance in luminal perfusate) increased with increasing ischemia times. Increased ischemia times resulted in increased levels of [alpha ] and [mu ] GST in both portal and systemic venous samples but lagged behind the appearance of raised luminal GST values.Conclusions: The results suggest that GST may be an interesting and useful marker in the early detection of intestinal ischemia. Its detection in peripheral blood has implications for a more detailed study design to determine the sensitivity and specificity of this marker in more diverse clinical conditions such as necrotizing enterocolitis and superior mesenteric artery occlusion.     

Patch testing in discoid eczema

Fifty patients of both sexes with clinically suspected discoid eczema were patch tested with the Indian Standard Patch Test Battery approved by the Contact and Occupational Dermatosis Forum of India (CODFI). Most of these patients were young adults between 20 and 39 years old, with a mean age of 36 years. The mean duration of symptoms was 21/2 years. The occupational profiles of the patients included farmers (24%), housewives (18%), students (14%), housewives engaged in farming (12%), shopkeepers (10%), and laborers (8%). The miscellaneous group, including technicians, drivers, cable operators, office workers, and computer operators, accounted for the remaining 14%. The common clinical patterns of presentation of discoid eczema included hands and feet (44%), hands and forearms' (30%), legs and feet (12%) and trunk and limbs (12%). Patch test analysis of these patients revealed that, out of the 50 subjects tested, 28 (56%) reacted to one or more allergens. Potassium dichromate was the most common allergen (20%), followed by nickel (16%), cobalt chloride, and fragrance (12% each) in decreasing order of frequency. Hence, it may be concluded that patch testing should be considered for all patients with severe or persistent discoid eczema because allergic contact dermatitis may be relatively common in such patients and the avoidance of offending allergens may be of substantial benefit to the patients.     

Singing paraplegia: a distinctive manifestation of a spinal dural arteriovenous fistula

The unique case of a baritone with a spinal dural arteriovenous fistula (SDAVF) causing recurrent, acute paraplegia during singing is described. This case underscores the presence of impaired venous drainage in these lesions and the high level of clinical suspicion required for their diagnosis in patients with any myelopathy.     

A case of emotional facial palsy with ipsilateral anterior inferior cerebellar artery territory infarction

Emotional facial palsy (EFP) commonly results from anterolateral thalamic or striatocapsular infarcts. Its occurrence in brainstem lesions is uncommon, with previously reported cases being restricted to superior cerebellar artery infarction (3 cases). We report an unusual case of EFP ipsilateral to an anterior inferior cerebellar artery infarction, which opens new insights into the facial corticobulbar tract pathway.