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While mild to moderate elevation of liver transaminases is common with anorexia nervosa, acute hepatic injury with severe elevation of transaminases and coagulopathy is rare . We report a 24-year male with anorexia nervosa who was presented with acute liver injury. Alanine transferase and aspartate transferase peaked at 2033 IU/ml and 1410 IU/ml respectively. More common causes of acute liver injury were ruled out. Liver biopsy did not show centrilobular necrosis or congestion which are the hallmarks of ischemic liver injury. The patient has improved on re-institution of proper nutrition. In conclusion, acute liver injury can occasionally be caused by anorexia nervosa. The pathophysiologic mechanism involved, on contrary to what previously reported, is unlikely tissue hypoperfusion.

We retrospectively studied the use of endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) as a tool for the diagnosis of deep-seated lymphoma. An on-site assessment at the time of EUS-FNAB was performed by a cytopathologist using Diff-Quik (American Scientific Products, McGraw Park, IL) stain. In addition, Papanicolaou stains were performed on EUS-FNAB smears, immunohistochemical stains were performed on cell blocks, and additional samples were sent for flow cytometric analysis. Final cytologic diagnosis was correlated with surgical pathology and/or clinical follow-up. We evaluated EUS-FNAB specimens of deep-seated lymph nodes, spleen, stomach, and pancreas, and 1 EUS-guided needle core biopsy specimen of a lymph node. Thirteen cases of deep-seated lymphoma were diagnosed, including non-Hodgkin lymphomas and Hodgkin lymphoma. One case of hairy cell leukemia was diagnosed. EUS-FNAB is a minimally invasive, cost-effective, and useful tool for the primary diagnosis or staging of deep-seated lymphomas.

BACKGROUND Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsy allows the detailed imaging and FNA not only of both intramural and extramural structures and lesions of the gastrointestinal (GI) tract but also of various intraabdominal organs. Thus, EUS-FNA biopsy offers a novel opportunity to evaluate and obtain cytology samples from adrenal gland lesions. The objective of the current study was to determine the utility of EUS-FNA in the diagnosis of adrenal lesions. METHODS The authors conducted a prospective evaluation of 24 consecutive EUS-FNA biopsy specimens obtained from patients with adrenal lesions. An attending cytopathologist was present on site to assess specimen adequacy and to provide rapid interpretation of air-dried material that had been stained with Diff-Quik (Baxter Scientific Products, McGraw Park, IL). Additional samples were obtained for ThinPrep (Cytyc Corporation, Boxborough, MA) preparation, and cell blocks subsequently were prepared. Appropriate immunohistochemical staining was performed as indicated. The cytologic diagnosis was then analyzed for correlations with the final diagnosis, which was based on relevant correlative cytologic or histologic examination of biopsied/resected pathology materials and/or final clinical follow-up. RESULTS In total, 24 EUS-FNA biopsy specimens (from 18 males and 6 females) were obtained from adrenal glands. The mean patient age was 62.2 years (range, 48–81 years). Adequate cellularity was noted in all 24 samples. Seven of 24 samples (29%) were reported to be positive for carcinoma. All samples that were diagnosed as metastatic carcinoma were confirmed on subsequent follow-up. EUS-FNA performed simultaneously with adrenal gland aspiration either from the primary site (n = 1) or from metastases to lymph nodes (n = 3) supported diagnoses of metastatic carcinoma. Six of seven samples were metastatic from the lung, and one specimen was a direct extension of a transitional renal cell carcinoma. EUS-FNA biopsy of the right adrenal gland in one patient revealed myelolipoma. In 16 patients, benign adrenal gland cells were noted on EUS-FNA biopsy specimens from enlarged adrenal glands. In 5 samples (31%), signs of adenoma were evident. Morphology alone could not distinguish between adrenal adenoma and adrenal hyperplasia. No significant complications were reported after EUS-FNA biopsy of adrenal glands. CONCLUSIONS EUS-FNA biopsy is a highly specific and safe technique for confirming the diagnosis of carcinoma metastatic to the adrenal glands. Along with cytologic evaluation, EUS imaging is needed to support the diagnosis of adrenal adenoma. Cancer (Cancer Cytopathol) 2004. © 2004 American Cancer Society.

Malignant neoplasia in 4 alpacas was characterized by acute onset of clinical signs and rapidly deteriorating condition. Postmortem examination revealed metastatic or multicentric neoplasia in the abdominal organs of alpacas 1, 3, and 4 and an extensive thoracic mass in alpaca 2. Immunohistochemical stains supported a diagnosis of B-cell lymphosarcoma in alpacas 1–3 and a neuroendocrine neoplasm in alpaca 4.

Sarcoma represents less than 2% of all neoplasms diagnosed or recognized in effusions. Epithelioid peripheral nerve sheath tumor is a rare tumor that is difficult to differentiate from other epithelioid tumors without the use of ancillary studies. A 39-year-old paraplegic man presented with hematuria and a bladder mass that extended to involve the pelvic peritoneum. Light microscopy using hematoxylin-eosin, Papanicolaou, and immunohistochemical stains as well as transmission electron microscopy showed features of epithelioid malignant peripheral nerve sheath tumor with rhabdoid features and an accompanying eosinophilic infiltrate. Cytologic smears confirmed the similarities between the primary tumor in the bladder and the cells in the pelvic fluid and excluded the possibility of reactive changes related to postsurgical radiation. Ancillary studies were critical in narrowing the differential diagnoses and reaching the final conclusion.

Evaluation of anal intraepithelial neoplasia (AIN) is subjective. Previous studies have shown p16 and Ki-67 expressions to correlate with AIN grade. Biomarkers like p16 and Ki-67 may improve interobserver agreement. The objectives were (1) to determine the extent of interobserver agreement in evaluating AIN on routine hematoxylin and eosin (HE) sections and (2) to test whether p16 and/or Ki-67 staining improve interobserver diagnostic agreement.Seventy-seven anal specimens were retrieved. Sections were stained with monoclonal antibodies against p16 and Ki-67. Blind to the original diagnoses, 4 pathologists assessed HE alone, p16 alone, Ki-67 alone, and all 3 simultaneously. Diagnoses were normal/reactive, AIN I/HPV, AIN II, and AIN III. Agreement was calculated using kappa and S statistics.Pathologists were board certified and had 2 to 25 years (mean = 13.6 years) of experience. Fair agreement was observed using HE diagnosis alone (kappa = 0.38, S = 0.56). The p16 diagnostic evaluation demonstrated the highest agreement (kappa = 0.57, S = 0.73). Interobserver agreement for Ki-67 alone and for HE/p16/Ki-67 combined were comparable to that of HE alone (kappa = 0.4, S = 0.54 and kappa = 0.44, S = 0.62, respectively). When the pathologists' diagnoses for all diagnostic evaluations were compared with consensus diagnoses, the lowest average magnitude of disagreement was seen with Ki-67 alone, followed by p16 alone, HE/p16/Ki-67 combined, and HE alone.Interobserver agreement for diagnosis of AIN was fair when based solely on HE preparation. p16 alone improved interobserver agreement and demonstrated superior agreement when compared with HE, Ki-67, and HE/p16/Ki-67 combined.

Ischemia/reperfusion (IR) injury in transplanted livers contributes to organ dysfunction and failure and is characterized in part by loss of NO bioavailability. Inhalation of NO is nontoxic and at high concentrations (80 ppm) inhibits IR injury in extrapulmonary tissues. In this prospective, blinded, placebo-controlled study, we evaluated the hypothesis that administration of inhaled NO (iNO; 80 ppm) to patients undergoing orthotopic liver transplantation inhibits hepatic IR injury, resulting in improved liver function. Patients were randomized to receive either placebo or iNO (n = 10 per group) during the operative period only. When results were adjusted for cold ischemia time and sex, iNO significantly decreased hospital length of stay, and evaluation of serum transaminases (alanine transaminase, aspartate aminotransferase) and coagulation times (prothrombin time, partial thromboplastin time) indicated that iNO improved the rate at which liver function was restored after transplantation. iNO did not significantly affect changes in inflammatory markers in liver tissue 1 hour after reperfusion but significantly lowered hepatocyte apoptosis. Evaluation of circulating NO metabolites indicated that the most likely candidate transducer of extrapulmonary effects of iNO was nitrite. In summary, this study supports the clinical use of iNO as an extrapulmonary therapeutic to improve organ function following transplantation.

BACKGROUND. The objective of this study was to assess the rate and possible reasons for false-negative (FN) reflex human papillomavirus (HPV)-DNA tests. METHODS. The authors reviewed all ThinPrep cervical specimens that were submitted for reflex HPV-DNA testing using the Digene Hybrid Capture II (HC2) method from January 2002 to January 2004. Follow-up biopsies were reviewed. The results were considered HPV-FN if the HPV-DNA test was negative and the biopsy was positive for grade ≥2 cervical intraepithelial neoplasia (CIN2+), and the results were considered true positive (HPV-TP) if the HPV-DNA test was positive and the biopsy showed CIN2+. HPV-FN cases were compared with HPV-TP cases regarding the grade and extent of CIN, the number of abnormal cells on the original ThinPrep slide, and the presence of amplifiable, viral DNA on biopsy. RESULTS. In total, 1520 (66%) of 2309 patients who had diagnoses of atypical squamous cells of undetermined significance (ASCUS) were negative for HPV DNA and 789 patients of 2309 patients (34%) were positive for HPV DNA. Three hundred sixteen women (40%) who had a positive HPV-DNA test underwent a biopsy. Of those, 36 biopsies (11%) showed CIN2+ (HPV-TP), and 154 biopsies (66%) showed CIN1. Cervical tissue was available for review from 82 women who had negative HPV-DNA tests; of these, 6 tissue samples (7%) showed CIN2+ (HPV-FN), and 13 tissue samples (16%) showed CIN1. Therefore, in the total ASCUS population that was triaged with reflex HPV testing, there were at least 42 women who were diagnosed with CIN2+, for an estimated CIN2+ FN fraction of 14% (6 of 42 women). HPV-FN lesions were smaller (but the difference was not statistically significant) and shed significantly fewer abnormal cells than HPV-TP cases. Polymerase chain reaction testing for viral DNA in the biopsy was detected in 3 of 6 women who had HPV-FN results; none of those positive results demonstrated a viral type that was not included in the Digene probes. CONCLUSIONS. Although the rate of FN high-grade lesions was significantly higher than that reported in the ASCUS/Low-grade Squamous Intraepithelial Lesion Triage trial, most missed lesions were small and shed few abnormal cells. It was assumed that those lesions were either in early stages or in regressing stages, which made their clinical significance uncertain. Cancer (Cancer Cytopathol) 2007. © 2007 American Cancer Society.

The practice of onsite cytology interpretation varies across endoscopic ultrasound (EUS) programs in the United States and Europe. The value, reliability, and agreement of rapid onsite evaluation (ROSE) compared with final interpretation and its impact on patient management remain largely unknown. We compared agreement between ROSE of EUS-FNA (endoscopic ultrasound-guided fine needle aspiration) specimens with final cytology interpretation and their respective operating characteristics.We prospectively evaluated consecutive EUS-FNA specimens obtained by a single endosonographer in the presence of an attending cytopathologist (July 2000-November 2002). The "agreement" between ROSE and final cytology interpretation was assessed by the "kappa" statistic. The frequency and possible reasons for discrepancy between ROSE and final cytologic interpretation were determined.A total of 540 patients (median age 63 yr, 77% white) underwent EUS-FNAs of 656 lesions. These included lymph nodes (LNs, N = 248), solid pancreatic masses (SPMs, N = 229), cystic pancreatic masses (CPM, N = 57), mural lesions (41), bile duct/gallbladder (N = 28), liver (N = 17), mediastinum/lung (N = 17), adrenal (N = 15), spleen (N = 3), and kidney (N = 1). Data were available for onsite evaluation in 607 lesions. Initial cytology was benign (N = 243), atypical (N = 23), suspicious (24), malignant (300), and indeterminate (N = 17). Out of the 243 benign lesions interpreted by onsite evaluation, five lesions (2.1%) were upgraded to be malignant or suspicious for malignancy on final cytology report. Of the 300 lesions initially reported malignant on ROSE, 294 (98%) remained malignant on the final cytology. There was an excellent agreement between ROSE and final cytologic evaluation (kappa = 84.0%, 95% CI 80.2-87.7), Compared with the true final status, accuracy for final interpretation was slightly higher than for ROSE but was not statistically significant (95.8%vs 93.9%). Scant cellularity remained the most frequent reason for discrepancy, accounting for 21 of 51 discrepancies (41%). Other reasons for discrepancy included: cases requiring an intradepartmental consultation (22%), cases requiring ancillary studies (12%), intra-observer variability (10%), and challenging diagnosis (10%). In three cases, (6%) we were unable to determine the possible reason for discrepancy.ROSE of EUS-FNA specimens is highly accurate compared with final cytologic evaluation. Because the diagnosis of malignancy rarely changes, informing our patients and their families and our referring physicians of a cancer diagnosis significantly reduces physician work load and expedites patient management. The majority of discrepancies are related to the nature of the lesion either because it sheds few cells, has challenging morphology, and/or requires additional ancillary studies.

BACKGROUND Computerized tomographic (CT)-guided fine-needle aspiration (FNA) cytology is a well-established tool in the diagnosis of hepatic lesions. Endoscopic ultrasound-guided FNA (EUS-FNA), developed recently and used predominantly in evaluating mediastinal and pancreatic lesions, provides access to a significant portion of the liver and to perihepatic structures not readily accessible by a percutaneous approach. METHODS A recent experience (1997-2002) with CT-guided FNA of liver lesions at the University of Alabama Birmingham (UAB) was compared with the first 2.5 years of EUS-FNA experience (2000-2002). Cases were identified using a SNOMED search and all reports and cytologic slides were retrieved for review. RESULTS In 6 years, 34 percutaneous CT-FNA liver biopsies were performed at UAB; in approximately 2.5 years, 16 EUS-FNA liver biopsies were done. In both groups the primary clinical indication was suspected metastatic carcinoma (CT, 41% of cases vs. EUS, 56%). The 2 techniques yielded a similar range of benign, atypical, and malignant diagnoses (CT: 26%, 18%, and 56% vs. EUS: 19%, 25%, and 56%). Because of the clinical setting in which EUS-FNA is usually performed, a much narrower range of neoplasms was sampled by EUS-FNA. Benign gastrointestinal epithelial cells were identified in 60% of the EUS-FNA specimens. CONCLUSIONS Early experience suggests EUS-FNA is comparable to CT-FNA in terms of diagnostic utility for hepatic lesions. Anatomy limits EUS-FNA to only a fraction of the hepatic parenchyma, but that fraction includes the hilum and left lobe of the liver and the proximal biliary tract. The gallbladder, extrahepatic biliary system, and perihilar lymph nodes are readily accessible. Proximate high-resolution ultrasound imaging and cytopathologist involvement in the EUS-FNA process are further advantages. Awareness of artifacts inherent in EUS-FNA sampling (i.e., gut epithelial cells) can minimize a potential diagnostic pitfall. Cancer (Cancer Cytopathol) 2006. © 2006 American Cancer Society.

Decreases in endothelial nitric oxide synthase derived nitric oxide (NO) production during liver transplantation promotes injury. We hypothesized that preemptive inhaled NO (iNO) would improve allograft function (primary) and reduce complications post-transplantation (secondary). Patients at two university centers (Center A and B) were randomized to receive placebo (n = 20/center) or iNO (80 ppm, n = 20/center) during the operative phase of liver transplantation. Data were analyzed at set intervals for up to 9-months post-transplantation and compared between groups. Patient characteristics and outcomes were examined with the Mann-Whitney U test, Student t-test, logistic regression, repeated measures ANOVA, and Cox proportional hazards models. Combined and site stratified analyses were performed. MELD scores were significantly higher at Center B (22.5 vs. 19.5, p