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This case presents a hyperplastic inflammatory mass at the resection site of a colorectal tubular adenoma. A 65-year-old man with a history of alcohol-associated liver cirrhosis, >10 lifetime polyps, and a CHEK2 mutation underwent hybrid endoscopic submucosal dissection of a 3 cm lateral spreading tumor, nongranular, Paris 0-IIa polyp in the ascending colon. Postresection pathology confirmed tubular adenoma with negative margins (R0). Six-month surveillance colonoscopy in the community identified a mass at the resection site, initially suspected to be local recurrence. Repeat colonoscopy demonstrated a mass which appeared inflammatory, with a Kudo type II hyperplastic pit pattern on narrow-band imaging and near-focus magnification. Biopsies confirmed inflammatory hyperplastic polyp. Three months later, surveillance colonoscopy revealed a shrinking polyp with biopsies consistent with hyperplastic histology. Factors such as portal hypertension, CHEK2 mutation, and concurrent gastric hyperplastic polyps may contribute to this phenomenon., (Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Purpose  To assess how resident and attending ophthalmologists perceive and evaluate ethically controversial scenarios regarding mentorship, authorship, and ethics compliance that may occur during research involving residents. Methods  An online survey was developed and contained 14 controversial vignettes based on common research scenarios that can occur when conducting research with trainees. The scenarios were designed to capture issues regarding three themes: mentorship, authorship, and compliance with ethical guidelines. Resident and attending ophthalmologists at eight military and civilian academic residency programs in the United States were invited to participate. Respondents used a Likert scale to assess the ethicality of the situations in addition to self-reported demographic characteristics. Results  The response rate was 35.6% (77/216), consisting of 37.7% ( n  = 29) residents and 62.3% ( n  = 48) attendings. More attending ophthalmologists responded than residents ( p  = 0.004). Many respondents identified controversies around compliance (67.3%) and authorship (57.1%) as unethical, whereas situations regarding mentorship were largely viewed as neutral to ethical (68.0%). Responses to two scenarios, one regarding mentorship and one regarding authorship, significantly differed between residents and attendings ( p  = 0.001 and p  = 0.022, respectively). Conclusion  Academic ophthalmologists' perceptions of the ethicality of common research scenarios varied. There is a need for more prescriptive guidelines for authorship and mentorship ethics at all training levels to ensure consistency, fairness, and integrity of research., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Secretory carcinoma (SC), also known as mammary analogue secretory carcinoma (MASC), is a rare salivary gland neoplasm with distinctive morphology that harbors a diagnostic ETV6 gene rearrangement. MASC was first described as a type of salivary gland neoplasm in 2010 and resembles breast secretory carcinoma. It is often mistaken for other neoplasms. It usually acts as an indolent tumor but can occasionally behave in an aggressive manner. We present a rare case of a patient with an aggressive SC/MASC of maxillary gingivobuccal sulcus with microcystic, solid and papillary patterns that showed ETV6 gene rearrangement by fluorescence in situ hybridization. Next-generation sequencing revealed t(12;15)(p13;q25) ETV6-NTRK3 translocation. Because SC/MASCs harbor the ETV6-NTRK3 translocation, molecular studies and immunostains are crucial to confirm the diagnosis and direct therapy., (© 2023 by the Association of Clinical Scientists, Inc.)

Introduction: Scalp masses are often the initial presentation of a widely disseminated malignancy. Fine-needle aspiration (FNA) is an optimal method for obtaining an accurate tissue diagnosis, in these patients with initial presentation and those with a known malignancy., Materials and Methods: We reviewed all FNAs of skin and soft tissue lesions from the scalp at our institution over a period of 31 years (1990-2021). Relevant clinical information was obtained from the review of computerized patient record. The histologic type, presentation, previous diagnoses, and survival after the diagnosis were correlated., Results: Thirty patients with scalp masses were identified. All the patients were males with a median age of 61 years (27-81 years). The scalp masses ranged from 0.4 to 6 cm in size. Ten cases (33%) were benign, but the majority of cases (n = 20, 67%) were malignant. Of the malignant lesions sampled, 1 case was a primary squamous-cell carcinoma (SCC), and the remaining 19 cases were metastatic tumors. Of these, 13 cases (68.4%) had a previously diagnosed malignancy. Most of the 19 metastatic lesions were adenocarcinomas or poorly differentiated carcinomas (n = 12, 63.2%), followed by melanoma (n = 4), SCC (n = 1), alveolar soft part sarcoma (n = 1) and large cell lymphoma (n = 1). The most common site of primary was the gastrointestinal tract (6/19, 31.5%) and lung (6/19, 31.5%). The average survival after the diagnosis of these scalp metastases was around 6.3 months, signifying a poor prognosis., Conclusion: In our patient population, most scalp masses were metastatic tumors. Metastasis to the scalp signals advanced disease and is associated with a very poor prognosis. FNA is an easy, safe, rapid, cost effective and precise modality for diagnosing these masses. It can also yield material for molecular testing for newer directed therapies, if needed., (© 2022 Wiley Periodicals LLC.)

Objective: Medical students with a significant other in medical school face challenges when applying for residency as they attempt to match in proximity to their partner. The National Resident Matching Program (NRMP) offers a Couples Match to aid such applicants. This system is not available for ophthalmology and urology because these specialties utilize match systems outside the NRMP and have an early match timeline. The purpose of this study is to analyze usage of the Couples Match and assess ophthalmology and urology applicant viewpoints on the Couples Match system., Design & Setting: First, NRMP data on the Couples Match from 1987 to 2021 was reviewed. Second, an online survey was sent to 559 ophthalmology and 321 urology applicants to The Johns Hopkins University School of Medicine in the 2021 match cycle., Participants: 342 ophthalmology and urology applicants (39% response rate)., Results: There is increased usage of the Couples Match over time. In response to the survey, 89% of participants agreed that a Couples Match should be implemented in their specialty. 107 (31%) had a significant other in medicine. 78% of 68 respondents whose significant other also applied in 2021 reported that they would have used the Couples Match had it been available. 21% of those with a significant other considered not applying to ophthalmology or urology because there was no Couples Match. There are mixed responses regarding whether the early match timeline is beneficial to couples. Female applicants were more likely to report hesitancy about mentioning a significant other during the application process., Conclusions: The Couples Match is highly desired by applicants to ophthalmology and urology, and the lack of such a system is a deterrent to pursuing these fields. Future studies will help elucidate how the match system can be leveraged to aid individuals applying with a significant other., (Copyright © 2022 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and it may present initially with extrahepatic spread in 5%-15% cases. It most commonly metastasizes to lungs, lymph nodes and adrenal glands. Skeletal metastases from HCC are uncommon and carry a very poor prognosis., Methods: We retrospectively reviewed all fine needle aspiration (FNA) specimens of metastatic HCC at our institution from January 1994 to March 2021 using the SNOMED search computer option. Relevant clinical information was obtained from the review of patient's electronic medical records., Results: There were 36 FNAs of metastatic HCC over a period of 27 years. Six patients (16.7%) were found to have skeletal metastases. All six patients were males with a median age of 59 years (54-71 years) and their lesions were osteolytic. The most common site of metastases was vertebra (3/50%). Most patients (67%) had bone metastases as an initial presentation, without prior history of HCC. The mean survival after the diagnosis of skeletal metastases was only 8 months., Conclusion: Detection of extrahepatic HCC to bone is important to avoid any unwanted surgical intervention. In our patient population, the most common site of skeletal metastases from HCC was vertebra, therefore in FNAs of vertebral lytic masses, metastatic HCC should be considered. On FNA, extrahepatic metastases of HCC can mimic other poorly differentiated tumors. They behave in an aggressive fashion, resulting in a grim prognosis. Cytological substrates can be used for future molecular testing, if needed., (© 2022 Wiley Periodicals LLC.)

Objective: Examine trends in the proportion of underrepresented minority (URM) residents from 2011 to 2019 across all specialties and investigate differences between surgical and non-surgical specialties., Design: Cross-sectional study., Setting: N/A., Participants: The authors extracted data on the proportion of URM residents in all specialties from the Accreditation Council for Graduate Medical Education yearly reports., Results: There was a statistically significant decline in the proportion of URM residents in surgical specialties (p < 0.01) from 2011 (9.9%) to 2019 (9.1%) and a significant increase in the proportion of URM residents in non-surgical specialties (p < 0.01) from 2011 (9.6%) to 2019 (10.2%)., Conclusions: This study emphasizes the need to increase recruitment of URMs in medicine, especially in surgical specialties. Findings from this study can inform much-needed initiatives to address barriers to entry for diverse applicants within specialties that lack diversity and have shown minimal improvement over time., (Copyright © 2022 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Importance: The proportion of women in the field of ophthalmology in the US trails the proportion of women in the general population. Sex diversity trends have been studied in other specialties, but there is a dearth of such literature in ophthalmology., Objective: To investigate trends in the proportion of female ophthalmology match applicants, residents, and clinical faculty., Design, Setting, and Participants: This cross-sectional study examined data from the San Francisco Match, the Association of University Professors of Ophthalmology, Accreditation Council for Graduate Medical Education, Association of American Medical Colleges, and American Academy of Ophthalmology (AAO) from January 1, 2011, to December 31, 2019. Data from ophthalmology match applicants, residents, clinical faculty at US medical schools, and AAO members were collected., Main Outcomes and Measures: The proportion of female applicants, residents, and medical school clinical faculty in ophthalmology., Results: Data were obtained from a total of 2807 ophthalmology applicants (35.3% female), 1 004 563 residents (43.8% female), 463 079 clinical faculty members (42.5% female), and 78 968 AAO members (26.1% female). Male ophthalmology residency applicants outnumbered female applicants by a ratio of 1.6:1 from 2016 to 2019. The percentage of female matched applicants in 2016 (41% [168/406]) and 2019 (42% [184/436]) differed by 1% (percent change, 0.99; 95% CI, -1.12 to 3.1; P = .36). There was a 2.3% increase (percent change, 0.34; 95% CI, 0.24-0.43; P < .001) in the percentage of female residents across all surgical specialties from 2011 (39.7% [8710/21 985]) to 2019 (42% [10 951/26 082]) but a 2.5% decrease (percent change, -0.45; 95% CI, -0.84 to -0.06; P = .02) in the percentage of female residents in ophthalmology from 2011 (41.5% [589/1419]) to 2019 (39% [575/1473]). The percentage of female ophthalmology clinical faculty differed by 2% (percent change, 1.02; 95% CI, -0.21 to 2.24; P = .10) from 2017 (38% [1179/3102]) to 2019 (40% [1225/3060]). From 2016 to 2019, male practicing ophthalmologists in the AAO outnumbered female practicing ophthalmologists by a ratio of 3:1., Conclusions and Relevance: This study found that the percentage of women in the field of ophthalmology remains lower than percentages in other specialties, and the percentage of female ophthalmology residents has decreased in recent years. More efforts are needed to improve female representation in ophthalmology.

Background: Inhalation of fungal spores is a strong risk factor for severe asthma and experimentally leads to development of airway mycosis and asthma-like disease in mice. However, in addition to fungal spores, humans are simultaneously exposed to other inflammatory agents such as lipopolysaccharide (LPS), with uncertain relevance to disease expression. To determine how high dose inhalation of LPS influences the expression of allergic airway disease induced by the allergenic mold Aspergillus niger (A. niger)., Methods: C57BL/6J mice were intranasally challenged with the viable spores of A. niger with and without 1 μg of LPS over two weeks. Changes in airway hyperreactivity, airway and lung inflammatory cell recruitment, antigen-specific immunoglobulins, and histopathology were determined., Results: In comparison to mice challenged only with A. niger, addition of LPS (1 μg) to A. niger abrogated airway hyperresponsiveness and strongly attenuated airway eosinophilia, PAS+ goblet cells and T H 2 responses while enhancing T H 1 and T H 17 cell recruitment to lung. Addition of LPS resulted in more severe, diffuse lung inflammation with scattered, loosely-formed parenchymal granulomas, but failed to alter fungus-induced IgE and IgG antibodies., Conclusions: In contrast to the strongly allergic lung phenotype induced by fungal spores alone, addition of a relatively high dose of LPS abrogates asthma-like features, replacing them with a phenotype more consistent with acute hypersensitivity pneumonitis (HP). These findings extend the already established link between airway mycosis and asthma to HP and describe a robust model for further dissecting the pathophysiology of HP., (© 2021. The Author(s).)

Background: Duodenal eosinophilia may play a role in functional dyspepsia (FD), but existing study results are conflicted. We investigated the association between duodenal eosinophils (count and degranulation) and FD symptoms, accounting for atopic conditions, medications, and seasonal variations., Methods: In a cross-sectional study conducted in the Michael E. DeBakey VA Medical Center in Houston, Texas, we analyzed duodenal histopathology of 436 patient samples from a prospective cohort with a validated symptom survey data and chart reviews. FD was defined using Rome II symptom criteria. Eosinophil count was number per 5 high-power fields (HPF), and eosinophil degranulation was eosinophilic granules in the stroma both determined by two independent investigators., Results: The study cohort was predominantly male (87.4%) with a mean age of 59.3 (standard deviation (SD) ± 9.8). Mean and median eosinophil counts were 75.5 (± 47.8) and 63 (IQR: 43, 101) per five HPF, respectively. Duodenal eosinophilia (defined as ≥ 63 per 5 HPF) and eosinophil degranulation were present in 50.5% and 23.1% of patient samples, respectively. FD was observed in 178 patients (41.7%), but neither the mean eosinophil count nor duodenal eosinophilia was associated with FD. Eosinophil degranulation was independently associated with FD overall (OR 1.74; 95% CI 1.08, 2.78; p = 0.02) and early satiety (OR 2.04; 95% CI 1.26, 3.30; p = 0.004)., Conclusions: In this large, ethnically diverse cohort of adult patients, we found no significant association between duodenal eosinophilia and FD. However, the presence of duodenal eosinophilic degranulation, an activated eosinophil marker, was significantly associated with FD, especially early satiety., (© 2020. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: A balance between autonomy and supervision can be difficult to obtain in medical education. In this study, we sought to determine whether the presence and level of supervision of ophthalmology resident outpatient clinic correlates with metrics of resident success, professionalism and stress., Methods: A survey was emailed to all US ophthalmology program directors requesting it be forwarded to PGY4 residents. Questions included whether their program provided a resident-hosted outpatient clinic, and if so, whether residents were mandated to discuss every patient with faculty. Residents were assigned to three categories based on this question (0: no clinic, 1: mandated faculty input, 2: discretionary faculty input). Success metrics included numbers of manuscripts submitted, OKAP scores and success in obtaining fellowships. Professionalism metrics included rating comfort obtaining informed consent, breaking bad news, managing time in clinic, and confidence in providing care in various settings. Residents affirming participation in a continuity clinic also provided perceptions of the level of supervision and how the clinic affected stress., Results: Category 1 residents perceived somewhat too much supervision, while category 2 residents felt that they had somewhat insufficient supervision. The majority of residents in either category did not feel that the continuity clinic affected their overall stress, although those who reported a change in stress usually indicated that the presence of the clinic increased stress. There were no other statistically significant differences between the responses from any category., Conclusions: The presence of a resident-hosted continuity clinic neither adds nor detracts from the success or sense of professionalism of ophthalmology residents. However, when such a clinic is present, the degree of supervision appears to correlate inversely with resident perception of autonomy. These results suggest that the decision of a training program to offer a clinic hosted by residents offering comprehensive continuity care can be informed primarily by faculty and trainee philosophy and personal preferences without comprising education quality, clinical efficiency, residents' perception of stress or their success in fellowship matching.

Purpose: The aims of this study was to compare dental treatment costs for three pharmacologic behavior guidance modalities: (1) dental office-based moderate sedation (SED); (2) hospital-based general anesthesia (GA-H); and (3) dental office-based general anesthesia (GA-OFF). Methods: Data were collected for healthy two- to six-year-olds who had full-mouth rehabilitation using GA-H at the University of North Carolina Children's Hospital, Chapel Hill, N.C., USA. Patients served as their own controls to compare costs across the three modalities. Rendered treatments were quantified using relative value units (RVUs). Costs included opportunity costs and administrative data. We relied upon ordinary least squares analyses to examine the relationship between total costs and RVUs. Results: Of 200 consecutive hospital records, 65 met the inclusion criteria. The mean age was 4.4 years old (range equals two to six years old; 41 ASA I, 24 ASA II). Dental treatment using GA-H averaged 118 minutes (range equals 62 to 256 minutes), with a mean of 12 teeth (range equals six to 20) treated. GA-H costs were 4.1 times greater than GA-OFF costs (range equals 1.1 to 4.9), and 4.5 times greater than SED costs (range equals 0.9 to 7.1); GA-OFF costs were 1.1 times greater than SED costs (range equals 0.7 to 1.6). Conclusions: Treatment completed (measured in relative value units) was correlated highest with costs for dental office-based moderate sedation and least for hospital-based general anesthesia. If more than four SED appointments are needed, GA-OFF may provide cost-savings; however, at no point does GA-H offer cost-savings.

Objective: To develop a probability model of matching into a US ophthalmology residency program using San Francisco Matching Program (SF Match) data., Design: Retrospective data analysis of de-identified application and matching data., Participants: Registrants for the 2013, 2014, and 2015 ophthalmology residency matches conducted by the SF Match., Methods: Descriptive statistics of candidates, comparison of continuous and categorical variables between matched and nonmatched candidates, and linear regression modeling were performed. A recursive partitioning method was used to create a probability of matching algorithm., Main Outcome Measures: Probability of successfully matching based on quantifiable candidate characteristics., Results: Over the 3-year period, 1,959 individuals submitted an average of 64 applications and received a mean of nine interview invitations. The overall match rate was 71%, with 78% matching at one of their top five choices. Successful matches were more likely to occur in US medical school graduates (78% vs 20%, p < 0.001) and applicants on their first attempt (76% vs 29%, p < 0.001). The association between matching and number of programs applied became negative with > 48 applications. Probability of matching was "high" (> 80%) among US graduates with a step 1 United States Medical Licensing Examination (USMLE)score>243(regardless of number of programs applied to), a step 1 USMLE score of 231 to 243 who applied to at least 30 programs, and first-time applicants with a step 1 score >232. No international medical graduates or repeat applicants had a "high" probability of matching., Conclusions: Although advice must be individualized for each candidate, applicants for ophthalmology residency who fall into a "high" probability of matching group are likely to be successful with applications to 45 or fewer programs. Applying to 80 or more programs should be considered for international medical graduates and/or applicants who are previously unmatched. Modification of the match application data form may allow more detailed analysis of variables such as Alpha Omega Alpha or Gold Humanism Honor Society membership, research activity, and composite evaluation on a standardized letter of recommendation., Competing Interests: Conflict of Interest Dr. Feldon reports personal fees from Association of University Professors of Ophthalmology, outside the submitted work, and is Chair of a Department of Ophthalmology that has a residency training program that could be affected by the information in the article. Dr. Stoner reports support for data analysis from the Association of University Professors of Ophthalmology (AUPO), during the conduct of the study. All the other authors report no conflict of interest.

Background: Atypical antipsychotic agents (AAP) alleviate the symptoms of severe mental health disorders, such as schizophrenia, by antagonizing dopamine and serotonin receptors. Recently, AAP have also been shown to exhibit immunomodulatory properties in the central nervous system (CNS)., Objective: Building on research which demonstrated the ability of the AAP risperidone and clozapine to modify the disease course of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), we aimed to more fully investigate the potential of clozapine as a possible treatment for MS., Results: We report that orally administered clozapine significantly reduced the disease severity of EAE in a dose-dependent manner and was effective when administered prophylactically and therapeutically. In comparison to risperidone, quetiapine, and olanzapine, clozapine was the best at reducing disease severity. While clozapine-treated mice had only modest changes to peripheral leukocytes and cytokine responses, these animals had significantly fewer CNS-infiltrating CD4 T cells and myeloid cells. Furthermore, the CNS myeloid cells displayed a less activated phenotype in mice treated with clozapine. Finally, we found that co-administration of clozapine with glatiramer acetate enhanced disease protection compared to either treatment alone., Conclusion: These studies indicate that clozapine is an effective immunomodulatory agent with the potential to treat immune-mediated diseases such as MS.

Rationale: Data about the influence of the type of sedation on yield, complications, and tolerance of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are based mostly on retrospective studies and are largely inconsistent., Objectives: To determine whether the type of sedation influences the diagnostic yield of EBUS-TBNA, its complication rates, and patient tolerance., Methods: Patients referred for EBUS-TBNA were randomized (1:1) to undergo this procedure under general anesthesia (GA) or moderate sedation (MS). Pathologists were blinded to group allocation., Measurements and Main Results: The main outcome was "diagnostic yield," defined as the percentage of patients for whom EBUS-TBNA rendered a specific diagnosis. One hundred and forty-nine patients underwent EBUS-TBNA, 75 under GA and 74 under MS. Demographic and baseline clinical characteristics were well balanced. Two hundred and thirty-six lymph nodes (LNs) and six masses were sampled in the GA group (average, 3.2 ± 1.9 sites/patient), and 200 LNs and six masses in the MS group (average, 2.8 ± 1.5 sites/patient) (P = 0.199). The diagnostic yield was 70.7% (53 of 75) and 68.9% (51 of 74) for the GA group and MS group, respectively (P = 0.816). The sensitivity was 98.2% in the GA group (confidence interval, 97-100%) and 98.1% in the MS group (confidence interval, 97-100%) (P = 0.979). EBUS was completed in all patients in the GA group, and in 69 patients (93.3%) in the MS group (P = 0.028). There were no major complications or escalation of care in either group. Minor complications were more common in the MS group (29.6 vs. 5.3%) (P < 0.001). Most patients stated they "definitely would" undergo this procedure again in both groups (P = 0.355)., Conclusions: EBUS-TBNA performed under MS results in comparable diagnostic yield, rate of major complications, and patient tolerance as under GA. Future prospective multicenter studies are required to corroborate our findings. Clinical trial registered with www.clinicaltrials.gov (NCT 01430962).

Background: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) with bedside cytopathology is the gold standard for assessment of pancreatic, subepithelial, and other lesions in close proximity to the gastrointestinal tract, but it is time-consuming, has certain diagnostic limitations, and bedside cytopathology is not widely available., Aims: The goal of this study is to compare the diagnostic yield of EUS-guided FNA with on-site cytopathology and EUS-guided core biopsy., Methods: Twenty-six patients with gastrointestinal mass lesions requiring biopsy at a tertiary medical center were included in this retrospective analysis of a prospective cohort. Two core biopsies were taken using a 22 gauge needle followed by FNA guided by a bedside cytopathologist at the same endoscopic session. The diagnostic yield and test characteristics of EUS core biopsy and EUS FNA with bedside cytopathology were examined., Results: The mean number of passes was 3.2 for FNA, and the mean procedure time was 39.4 minutes. The final diagnosis was malignant in 92.3 %. Sensitivity and specificity were 83 % and 100 %, respectively, for FNA, and 91.7 % and 100 %, respectively, for core biopsy. Diagnostic accuracy was 92.3 % for FNA and 84.6 % for core biopsy. The two approaches were in agreement in 88.4 % with a kappa statistic of 0.66 (95 % confidence interval 0.33 - 0.99)., Conclusions: An approach using two passes with a core biopsy needle is comparable to the current gold standard of FNA with bedside cytopathology. The performance of two core biopsies is time-efficient and could represent a good alternative to FNA with bedside cytopathology.

Background and Aims: It has been reported that the incidence of intrahepatic cholangiocarcinoma (ICC) has increased in the USA, while extrahepatic cholangiocarcinoma (ECC) has decreased or remained stable. However, neither the recent trends nor the effects of the misclassification of Klatskin tumors are known., Methods: Using the Surveillance, Epidemiology, and End Results program databases, we calculated the average annual age-adjusted incidence rates (AA-IRs) of ICC and ECC in 4-year time periods (1992-1995, 1996-1999, 2000-2003, 2004-2007). These AA-IRs were calculated with misclassified as well as correctly classified Klatskin tumors. AA-IRs were also calculated based on age, sex, and race. Multivariable Poisson regression models were used to evaluate the secular trends of ICC and ECC., Results: The AA-IR of ICC was 0.92 in 1992-1995 and 0.93 in 2004-2007, while the AA-IR of ECC increased from 0.70 in 1992-1995 to 0.95 in 2004-2007. There was no significant trend in AA-IR of ICC (p = 0.07), while there was a significant increase in ECC across the 4-year time periods (p < 0.001). Klatskin tumors comprised 6.7% of CCs with approximately 90 and 45% misclassified as ICC during 1992-2000 and 2001-2007, respectively. Adjusted Poisson models showed no significant differences in the temporal trend of ICC or ECC due to misclassification of Klatskin tumors., Conclusions: The incidence of ICC has remained stable between 1992 and 2007 with only slight fluctuations, while the incidence of ECC has been increasing. Misclassification of Klatskin tumors does not appear to play a significant role in the trends of CCs.

Water-soluble quinone oxidoreductases capable of reducing quinone substrates via a concerted two-electron mechanism have been implicated in bacterial antioxidant defence. Twoelectron transfer avoids formation of dangerously reactive semi-quinone intermediates, moreover previous work in Pseudomonas putida indicated a direct protective effect for the quinols generated by an over-expressed oxidoreductase. Here, the Pseudomonas aeruginosa orthologs of five quinone oxidoreductases--MdaB, ChrR, WrbA, NfsB, and NQO1--were tested for their possible role in defending P. aeruginosa against H2O2 challenge. In in vitro assays, each enzyme was shown to reduce quinone substrates with only minimal semiquinone formation. However, when each was individually over-expressed in P. aeruginosa no overt H2O2-protective phenotype was observed. It was shown that this was due to a masking effect of the P. aeruginosa catalase, KatA; in a katA mutant, H2O2 challenged strains over-expressing the WrbA and MdaB orthologs grew significantly better than the empty plasmid control. A growth advantage was also observed for H2O2 challenged P. putida strains over-expressing P. aeruginosa wrbA, mdaB or katA. Despite not conferring a growth advantage to wild type P. aeruginosa, it is possible that these quinone oxidoreductases defend against H2O2 toxicity at lower concentrations.

Primary angiosarcoma of the spleen is a rare neoplasm arising from endothelial cells. It is an aggressive neoplasm with a poor prognosis. We report a case of 61-year-old Caucasian man who presented with shortness of breath, anemia, leukocytosis, and thrombocytopenia. Ultrasound Sonogram (US) and Computed Tomography (CT) scans revealed a massively enlarged spleen with numerous enhancing hypodense lesions. The spleen was adherent to the omentum, retroperitoneum, and tail of the pancreas. Image-guided Fine Needle Aspiration (FNA) revealed an atypical spindle cell lesion. Resection of the spleen and attached tail of pancreas was performed. Histological examination and immunohistochemical studies revealed a diffuse vascular malignant neoplasm with features of angiosarcoma. The patient appeared disease free after resection. He died within 5 months of unknown etiology.

Objectives: There are no guidelines regarding the best practice for when Barrett's esophagus (BE) is suspected but not confirmed by histology. The aim of this study was to examine the value of endoscopic follow-up for individuals with endoscopic only BE at index endoscopy., Methods: We performed a longitudinal study of patients diagnosed with suspected columnar lined esophagus (CLE) (suspected BE in the absence of histological confirmation of specialized intestinal metaplasia (IM)). We examined three possible outcomes (definite BE defined as CLE plus IM in targeted biopsies, suspected CLE, or no suspected CLE) on repeat endoscopy within 2 years after the index endoscopy and their predictors (clinical, demographic as well as endoscopists' identity)., Results: A total of 107 of 1,844 patients had suspected CLE (101 were <3 cm), and 80 underwent a repeat endoscopy within 2 years. Approximately, 71% (95% confidence interval (CI) 61.1-80.9%) had suspected CLE confirmed at repeat endoscopy and only 29% (95% CI 19.1-38.9%) had IM. The length of CLE on the index esophagogastroduodenoscopies was slightly longer among patients with definite BE on repeat endoscopy than those with suspected CLE and no IM or no CLE (1.6 cm (s.d. 1.3) vs. 1.5 cm (s.d. 1.4), and 1.4 cm (s.d. 1.2), respectively P>0.1). Patient demographics, body mass index, gastro-esophageal reflux disease symptoms, hiatal hernia, and endoscopists' identity were not significantly associated with the outcome on the repeat endoscopy., Conclusions: Most (71%) patients with suspected CLE remain negative for IM in the 2 years following the index endoscopy. The findings support withholding BE diagnosis for individuals with suspected CLE.

We report a case of synchronous primary colonic adenocarcinoma and malignant mesothelioma. A 61-year-old male presented with a six-month history of fatigue and weight loss. An abdominal computed tomography (CT) scan showed a 5.8 cm partially obstructing mass in the cecum with ascites and peritoneal thickening. A biopsy of the large mass showed an adenocarcinoma. Because the patient was clinically thought to be a T4 colon carcinoma with peritoneal metastatic lesions (M1), prior to initiating chemotherapy, a debulking right hemicolectomy was performed. Resection of the colon and ileum revealed a T3N0 colonic mucinous adenocarcinoma and concurrent diffuse malignant peritoneal mesothelioma. Presenting synchronous colonic and peritoneal mesothelial primary malignancies are exceedingly rare but must be considered to prevent incorrect clinical staging.

Bacterial nitroreductase enzymes that can efficiently catalyse the oxygen-independent reduction of prodrugs originally developed to target tumour hypoxia offer great potential for expanding the therapeutic range of these molecules to aerobic tumour regions, via the emerging cancer strategy of gene-directed enzyme prodrug therapy (GDEPT). Two promising hypoxia prodrugs for GDEPT are the dinitrobenzamide mustard PR-104A, and the nitrochloromethylbenzindoline prodrug nitro-CBI-DEI. We describe here use of a nitro-quenched fluorogenic probe to identify MsuE from Pseudomonas aeruginosa as a novel nitroreductase candidate for GDEPT. In SOS and bacteria-delivered enzyme prodrug cytotoxicity assays MsuE was less effective at activating CB1954 (a first-generation GDEPT prodrug) than the "gold standard" nitroreductases NfsA and NfsB from Escherichia coli. However, MsuE exhibited comparable levels of activity with PR-104A and nitro-CBI-DEI, and is the first nitroreductase outside of the NfsA and NfsB enzyme families to do so. These in vitro findings suggest that MsuE is worthy of further evaluation in in vivo models of GDEPT.

Background: The nitro-chloromethylbenzindoline prodrug nitro-CBI-DEI appears a promising candidate for the anti-cancer strategy gene-directed enzyme prodrug therapy, based on its ability to be converted to a highly cytotoxic cell-permeable derivative by the nitroreductase NfsB from Escherichia coli. However, relative to some other nitroaromatic prodrugs, nitro-CBI-DEI is a poor substrate for E. coli NfsB. To address this limitation we evaluated other nitroreductase candidates from E. coli and Pseudomonas aeruginosa., Findings: Initial screens of candidate genes in the E. coli reporter strain SOS-R2 identified two additional nitroreductases, E. coli NfsA and P. aeruginosa NfsB, as being more effective activators of nitro-CBI-DEI than E. coli NfsB. In monolayer cytotoxicity assays, human colon carcinoma (HCT-116) cells transfected with P. aeruginosa NfsB were >4.5-fold more sensitive to nitro-CBI-DEI than cells expressing either E. coli enzyme, and 23.5-fold more sensitive than untransfected HCT-116. In three dimensional mixed cell cultures, not only were the P. aeruginosa NfsB expressing cells 540-fold more sensitive to nitro-CBI-DEI than pure cultures of untransfected HCT-116, the activated drug that they generated also displayed an unprecedented local bystander effect., Conclusion: We posit that the discrepancy in the fold-sensitivity to nitro-CBI-DEI between the two and three dimensional cytotoxicity assays stems from loss of activated drug into the media in the monolayer cultures. This emphasises the importance of evaluating high-bystander GDEPT prodrugs in three dimensional models. The high cytotoxicity and bystander effect exhibited by the NfsB&#95;Pa/nitro-CBI-DEI combination suggest that further preclinical development of this GDEPT pairing is warranted.

H1N1 influenza A virus can trigger fatal hemophagocytic lymphohistiocytosis in immunocompromised patients and in immunocompetent hosts, usually children. We present a case of a 50-year-old man with low-burden chronic lymphocytic leukemia who had sudden reactivation of his leukemia triggered by influenza A (H1N1) infection with hemophagocytic lymphohistiocytosis during the 2009 H1N1 pandemic. His rapid course was complicated by acute respiratory distress syndrome with diffuse alveolar damage, a 6-fold rise in lymphocyte count, disseminated intravascular coagulation, and, ultimately, cardiac arrest. Major findings at autopsy included: bilateral H1N1 pneumonitis with diffuse alveolar damage, intra-alveolar pulmonary hemorrhage, pulmonary microthromboemboli, pulmonary hemorrhagic infarction, hemophagocytic lymphohistiocytosis in multiple locations, and diffuse chronic lymphocytic leukemia. Hemophagocytic lymphohistiocytosis is a serious and often fatal condition, which may be primary or secondary. It may be associated with high-grade lymphoproliferative malignancies, especially in patients with therapy-related leukocytopenia, but only rarely is it seen in uncomplicated chronic lymphocytic leukemia. Hemophagocytic lymphohistiocytosis may be triggered by a variety of infections (viral, fungal, bacterial and parasitic), but H1N1 influenza A-associated hemophagocytic lymphohistiocytosis is often rapidly fatal, especially in children. This adult patient's clinical presentation with low tumor burden and leukocytosis is thus unique. We review the recently published autopsy findings in fatal influenza A (H1N1) infection and the association with resultant secondary hemophagocytic lymphohistiocytosis., (Published by Elsevier Inc.)

Phase I/II cancer gene therapy trials of the Escherichia coli nitroreductase NfsB in partnership with the prodrug CB1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide] have indicated that CB1954 toxicity is dose-limiting at concentrations far below the enzyme K(M). Here we report that the flavin reductase FRase I from Vibrio fischeri is also a CB1954 nitroreductase, which has a substantially lower apparent K(M) than E. coli NfsB. To enhance the activity of FRase I with CB1954 we used targeted mutagenesis and an E. coli SOS reporter strain to engineer single- and multi-residue variants that possess a substantially reduced apparent K(M) and an increased k(cat)/K(M) relative to the wild type enzyme. In a bacteria-delivered model for enzyme prodrug therapy, the engineered FRase I variants were able to kill human colon carcinoma (HCT-116) cells at significantly lower CB1954 concentrations than wild type FRase I or E. coli NfsB., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Anaphylaxis during anaesthesia is a rare event that in ∼60-70% of cases is secondary to neuromuscular blocking agents. It has been suggested previously that the recent introduction of sugammadex may provide a novel therapeutic approach to the management of rocuronium-induced anaphylaxis. We describe the case of a 33-yr-old female who suffered a severe anaphylactic reaction to rocuronium, presenting with cardiovascular collapse on induction of anaesthesia. After 19 min of traditional management, she was given a bolus of sugammadex 500 mg. This was associated with an improvement in the adverse haemodynamic state. The underlying reasons for this are unclear, but sugammadex may potentially be a useful adjunct in the management of rocuronium-induced anaphylaxis.

Background: Clinically overt infections of the epidural catheter skin entry site occur in approximately 1-5% of patients after a few days of catheterization but serious complications such as deep tissue infection or epidural abscess appear rare in the obstetric population. In recent years, sporadic reports and small series suggest that the incidence may be higher than previously estimated., Methods: A retrospective chart review was conducted to identify epidural catheter-related infections occurring between January 2002 and December 2005 in a tertiary referral maternity hospital delivering between 4000 and 6000 women per annum. Cases were identified using International Statistical Classification of Diseases coding., Results: In total 9482 women (52.8%) who delivered had an epidural catheter inserted. There were 258 cases with the relevant code identified and 49 (0.52%, 95% CI 0.37-0.66%) had epidural catheter-related infection. Four women had deep tissue infection (incidence 0.04%, 95% CI 0.01-0.11%; rate 1 in 4741), represented by paraspinous and epidural abscess formation (incidence of both 0.02%, 95% CI 0-0.08%; rate 1 in 2371). Three of the cases are described., Conclusions: Serious epidural catheter-related infection in obstetric patients is rare, but our incidence of serious deep tissue infection was at the upper extreme of figures quoted in other studies., (Crown Copyright 2009. Published by Elsevier Ltd. All rights reserved.)

Primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) overlap syndrome may be found in a significant percentage of patients with either PBC or AIH. However, it is conceivable that most cases of PBC-AIH overlap syndrome are a concurrent manifestation of both diseases which therefore requires treatment of both disease entities. While most cases are found in asymptomatic patients or in patients who have been previously diagnosed with PBC, our patient presented with concurrent PBC and AIH resulting in subfulminant liver failure that responded to treatment with prednisone and ursodeoxycholic acid (UDCA). Extended 4-year follow-up and treatment with UDCA confirmed the diagnosis of PBC and demonstrated serological resolution of AIH.

Background: Transplantable B16 melanoma is widely used as a tumor model to investigate tumor immunity. We wished to characterize the leukocyte populations infiltrating B16 melanoma tumors, and the functional properties of tumor-infiltrating dendritic cells (TIDC)., Materials and Methods: We used the B16 melanoma cell line expressing ovalbumin protein (OVA) to investigate the phenotype and T cell stimulatory capacity of TIDC., Results: The majority of leukocytes in B16 melanoma were macrophages, which colocalized with TIDCs, B and T cells to the peripheral area of the tumor. Both myeloid and plasmacytoid DC populations were present within tumors. Most of these DCs appeared immature, but about a third expressed a mature phenotype. TIDCs did not present tumor-derived antigen, as they were unable to induce the proliferation of tumor-specific CD4+ and CD8+ T cells in vitro unless in the presence of specific peptides. Some presentation of tumor-derived antigen could be demonstrated in the tumor-draining lymph node using in vivo proliferation assays. However, while proliferation of CD8+ T cells was reproducibly demonstrated, no proliferation of CD4+ T cells was observed., Conclusion: In summary, our data suggest that DCs in tumors have limited antigen-presenting function. Inefficient antigen presentation extends to the tumor-draining lymph node, and may affect the generation of antitumor immune responses.

Background: Lagtimes to diagnostic colonoscopy have been used as practice performance measures., Aim: To evaluate the duration, determinants and outcomes of lagtimes between referral for endoscopic evaluation and colorectal cancer (CRC) diagnosis., Methods: We examined the medical records of 289 patients with CRC and evaluated lagtimes, their potential determinants and their association with CRC stage at diagnosis as well as overall survival., Results: Median lag between referral and CRC diagnosis was 41 days (41.5% > 60 days, 30.1% > 90 days). The only significant predictor of lagtime was the initiating event for referral: abnormal symptom, laboratory test or imaging study was associated with shortest and presence of family history was associated with longest lagtimes respectively. Longer lagtimes were associated with lower mortality risk, but this was completely explained by earlier CRC stage. An analysis restricted to 100 patients referred for abnormal CRC screening tests found no association between duration of lag and CRC stage or mortality., Conclusions: There seems to be no meaningful association between mortality in patients with CRC and lagtimes between referral for colonoscopy and CRC diagnosis for periods up to 2-3 months. On the contrary, longer lagtimes were inversely associated with CRC stage at the time of diagnosis.

A role for Langerhans cells (LC) in the induction of immune responses in the skin has yet to be conclusively demonstrated. We used skin immunization with OVA protein to induce immune responses against OVA-expressing melanoma cells. Mice injected with OVA-specific CD8(+) T cells and immunized with OVA onto barrier-disrupted skin had increased numbers of CD8(+) T cells in the blood that produced IFN-gamma and killed target cells. These mice generated accelerated cytotoxic responses after secondary immunization with OVA. Prophylactic or therapeutic immunization with OVA onto barrier-disrupted skin inhibited the growth of B16.OVA tumors. LC played a critical role in the immunization process because depletion of LC at the time of skin immunization dramatically reduced the tumor-protective effect. The topically applied Ag was presented by skin-derived LC in draining lymph nodes to CD8(+) T cells. Thus, targeting of tumor Ags to LC in vivo is an effective strategy for tumor immunotherapy.

Purpose: To report a case of a dendritic epithelial defect with interface inflammation associated with Alternaria sp. after laser in situ keratomileusis (LASIK) surgery., Methods: A case report of a 46-year-old woman who presented with a dendritic epithelial defect and interface inflammation after LASIK surgery., Results: After an apparent post-LASIK herpes simplex keratitis with related interface inflammation failed to respond to medical therapy, cornea culture results were positive for Alternaria fungal sp. 2 weeks and 6 days after presentation. Viral cultures and polymerase chain reaction were negative for herpes simplex virus. Six months after penetrating keratoplasty (and 1 year after LASIK), the patient underwent a cataract extraction OD. Best-corrected visual acuity 18 months after the original LASIK procedure was 20/25 OD., Conclusions: Alternaria keratitis may present with a dendritic epithelial defect with interface inflammation mimicking herpes simplex virus.

Cement-retained, single unit implant supported restorations have become a popular method to treat single tooth edentulous spaces. Occasionally, the clinician is faced with the situation in which the restoration demonstrates mobility. This case report describes the treatment rendered to a patient who presented with a chief complaint of a "loose implant" that had been restored with a cemented PFM crown on a screw retained abutment.

Statement of Problem: Rigidity is a requirement of removable partial denture frameworks. Although commonly used by dentists, the U-shaped (horseshoe) maxillary major connector lacks the rigidity of other maxillary major connector designs., Purpose: The purpose of this study was to determine the effects of changing width, thickness, and shape on the rigidity of U-shaped maxillary major connectors., Material and Methods: Five nickel-chrome alloy frameworks were fabricated from the same master cast for each of 4 different U-shape removable partial denture designs. The designs were an 8-mm wide U-shaped strap with a 6-mm posterior strap (A-P strap), a 13-mm-wide U-shape strap (Wide), an 8-mm-wide U-shape strap that widened to 13 mm at the midline (Notch), and an 8-mm-wide U-shaped strap that was twice the thickness of the other straps (Thick). A fifth group of 5 frameworks was made by removing the posterior strap from the A-P strap frameworks (A strap). Two testing points were marked on each framework corresponding to the first premolar and second molar positions. The frameworks were mounted in a universal testing machine, and vertical (torsional) and horizontal (compressive) loads were applied using a 10-kN load cell at a cross-head speed of 2 mm/min until a deflection of 1 mm occurred. A force-deflection curve was generated for each test, and slope of the curves (N/mm) was compared with analysis of variance and Scheffe's F test (alpha=0.05)., Results: The Thick group was found to be significantly more rigid (P<.05) than the other frameworks when torsional loads were applied to both the premolar (22.42 N/mm) and molar (10.88 N/mm) areas, and when a compressive load was applied to the premolar (232.85 N/mm) area. The A-P strap group was significantly more rigid (P< or =.05) than the other designs when a compressive load was applied to the molar (69.56 N/mm) area. Both the Thick and A-P strap groups were significantly more rigid (P<.05) than the Notch and A strap groups in all tests., Conclusion: Doubling the thickness of the anterior strap of a U-shaped maxillary major connector improved the rigidity of the framework to torsional loads. A posterior strap became more effective in maintaining framework rigidity to compressive forces as the length of the arch increased.

Gastrointestinal stromal tumor (GIST) is a rare, but potentially aggressive tumor. We present an asymptomatic 64-year-old man with an incidental 9-cm GIST that arose in the posterior mediastinum. Wide surgical excision was performed with rotation of an intercostal muscle flap to buttress a surgically created esophageal wall defect. The patient is now free of disease 26 months postoperative. This tumor is defined by the carcinogenic over-expression of KIT-protein, a tyrosine kinase receptor. Accurate diagnosis of gastrointestinal stromal tumor is imperative, as specific medical therapy is now available for potential control of recurrent or metastatic disease.

Previous in vitro data on type I collagen self-assembly into fibrils suggested that the amino acid 776-796 region of the alpha1(I) chain is crucial for fibril formation because it serves as the recognition site for the telopeptide of a docking collagen monomer. We used a natural collagen mutation with a deletion of amino acids 766-801 to confirm the importance of this region for collagen fibril formation. The proband has type III osteogenesis imperfecta and is heterozygous for a COL1A1 IVS 41 A(+4) --> C substitution. The intronic mutation causes splicing of exon 41, confirmed by sequencing of normal and shorter reverse transcriptase-PCR products. Reverse transcriptase-PCR using RNA from proband dermal fibroblasts and clonal cell lines showed the mutant cDNA was about 15% of total alpha1(I) cDNA. The mutant transcript is translated; structurally abnormal alpha chains are demonstrated in the cell layer of proband fibroblasts by SDS-urea-PAGE. The proportion of mutant chains in the secreted procollagen was determined to be 10% by resistance to digestion with MMP-1, since chains lacking exon 41 are missing the vertebral collagenase cleavage site. Secreted proband collagen was used for analysis of kinetics of binding of alpha1(I) C-telopeptide using an optical biosensor. Telopeptide had slower association and faster dissociation from proband than from normal collagen. Purified proband pC-collagen was used to study fibril formation. The presence of the mutant molecules decreases the rate of fibril formation. The fibrils formed in the presence of 10-15% mutant molecules have strikingly increased length compared with normal collagen, but are well organized, as demonstrated by D-periodicity. These results suggest that some collagen molecules containing the mutant chain are incorporated into fibrils and that the absence of the telopeptide binding region from even a small portion of the monomers interferes with fibril growth. Both abnormal fibrils and slower remodeling may contribute to the severe phenotype.in

Objective: To illustrate some of the uncommon cytologic findings of gynecomastia, such as apocrine metaplasia, cellular atypia and foamy macrophages, that can be misinterpreted as evidence of malignancy., Study Design: The clinical data and fine needle aspiration (FNA) cytologic material from 100 men with the diagnosis of gynecomastia were retrospectively reviewed. The excisional biopsy slides were available for 16 cases. For comparison, FNA smears from five men with breast lesions other than gynecomastia were studied., Results: The patients ranged in age from 23 to 91 years. Cytologic findings were as follows: cohesive sheets of cells containing 20-1,000 cells (98%); scattered, single, bipolar cells (78%); spindle cells (68%); ductal epithelial atypia (26%); apocrine metaplasia (8%); and foamy histiocytes (12%). In nine cases the atypia was marked, and in two of them the possibility of malignancy could not be ruled out. Surgical follow-up on 16 patients, including the cases with marked atypia, showed gynecomastia. In one case, gynecomastia was associated with intraductal papilloma. No correlation between the underlying etiology and atypical cytologic features of gynecomastia was identified., Conclusion: Apocrine metaplasia and epithelial atypia are common findings in gynecomastia. Attention to the cell patterns, the presence of sheets of ductal cells and absence of atypical single cells will point to the correct diagnosis.

Lymphoepithelioma-like carcinoma (LELC) is a rare form of lung cancer, usually encountered in Chinese patients. Similar to nasopharyngeal carcinoma, LELC of the lung is strongly associated with Epstein-Barr virus (EBV) infection in Asian patients, but there is controversy over whether an association exists in patients from Western countries. To determine whether such a relationship exists, we retrospectively studied 6 cases of primary LELC of the lung, all of which were in Western patients. There were 4 men and 2 women, ranging in age from 49 to 75 years. The tumors ranged from 1 to 4.5 cm in diameter. Four patients had stage I disease, 1 had stage IIb disease, and 1 had stage IIIa disease. All patients are alive without evidence of disease with a follow-up of 18 to 30 months. Formalin-fixed, paraffin-embedded tissue was stained with hematoxylin-eosin for routine evaluation and immunostained for keratin and leukocyte common antigen (LCA). LCA staining was performed to exclude large-cell lymphoma. Immunoperoxidase staining (1:500 clone CS1-4; Dako, Carpinteria, CA) and in situ hybridization were performed to detect EBV. Tumors consisted of solid nests of undifferentiated tumor cells in a syncytial arrangement surrounded by heavy lymphoplasmacytic infiltrate. Tumor cells stained positively for keratin but negative for LCA. All 6 cases were negative for EBV, suggesting no association between EBV and LELC in the Western population.

Patients with alcoholic liver disease have a high prevalence of hepatitis C virus (HCV) infection. The histological appearances of the liver in patients with alcoholic liver disease and HCV infection are well described. However, liver histology in individuals with dual pathology, both chronic alcohol abuse and HCV infection, is less well understood. The purpose of the present study was to examine this issue and to determine if there is any correlation between specific histological features and the serum biochemical abnormalities seen in these patients. Eighty-six chronic alcoholics, 65 with HCV infection and 21 uninfected subjects, were included in the study. All patients had history of heavy alcohol abuse (consuming 80 g or more of ethanol a day for at least 10 years). The following data were collected on each patient: demographic information (age, gender, race), the amount and duration of alcohol intake, biochemical results, and liver biopsy abnormalities including the histological activity index (HAI) score. HCV-infected alcoholics were younger (P = 0.05) and were more often African American than Caucasian (P < 0.01). Alcohol consumption was significantly greater in uninfected alcoholics compared to those with HCV infection (P < 0.05). Liver histology in subjects with HCV infection showed higher HAI scores for intralobular necrosis (P = 0.008) and periportal inflammation (P = 0.004). Features of "chronic hepatitis" and focal lymphoid aggregates were more frequent in HCV-infected alcoholics (P = 0.001 for each). By contrast, cirrhosis was present in a higher proportion of uninfected alcoholics compared to those with HCV infection (P = 0.05). Histological findings of hepatic fibrosis and total HAI score showed a significant correlation with serum albumin and platelet count in HCV-infected alcoholics. Chronic alcoholics with HCV infection have specific histological appearances that can usually help distinguish these patients from uninfected alcoholics. Correlation analysis indicates that of the various laboratory tests, serum albumin and platelet counts are the best predictors of the severity of liver damage at histology. In chronic alcoholics, the development of cirrhosis is related more to the amount of alcohol consumed than to the presence of HCV infection.