Immunohistologic parameters in minimal morphologic change duodenal biopsies from patients with clinically suspected gluten-sensitive enteropathy.

Subclinical or latent cases of gluten-sensitive enteropathy (GSE) are difficult to diagnose, and serology-positive, histology-negative (minimal morphologic change) and serology-negative, histology-positive patients have been identified. Both, particularly the histology-negative group, require the correct diagnosis for proper management, especially because the concept of minimal histologic change GSE has escaped attention in standard textbooks. We assessed the numbers and distribution of intraepithelial T cells and their subsets with CD3, CD8, and CD4 immunostaining and examined for crypt hyperplasia with mitotic and Ki-67 proliferative indices with the aim of refining the criteria for the diagnosis of minimal change GSE. Duodenal biopsies from 46 clinically suspected cases of GSE tested for antigliadin, antiendomysium, and antitissue transglutaminase antibodies were divided into four groups: serology-positive, histology-positive (S+H+, n = 20); serology-positive, histology-negative (S+H-, n = 22), representing the minimal morphologic change group; serology-negative, histology-positive (S-H+, n = 4); and serology-negative, histology-negative (S-H-, n = 28), controls with histologically normal duodenal biopsies obtained for unrelated reasons. The numbers of CD3+ and CD8+ intraepithelial T cells (IETCs) were significantly higher in histology-positive biopsies with (mean, 40.3/100 and 39.3/100 enterocytes, respectively) and without positive serology (mean, 33.3/100 and 35/100 enterocytes, respectively) compared with all other groups (S+H-, mean, 26.5/100 and 24.3/100 enterocytes, respectively; S-H-, mean, 23.3/100 and 17.9/100 enterocytes, respectively). Values for Ki-67 index in crypt enterocytes were also significantly different between histology-positive and histology-negative groups (P = 0.000). The distribution of CD3+ and CD8+ IETCs was mostly even along the surface enterocytes in histology-positive cases compared with the controls, which showed an uneven distribution. The 2 parameters that significantly discriminated between minimal morphologic change GSE (S+H-) and controls (S-H-) were Ki-67 index (P = 0.007) and the distribution pattern of CD8+ IETCs (P = 0.049). CD4 IETC counts were generally low, with no significant difference between all groups. The few S-H+ cases seen most likely represented false-negative serology, because the assessed parameters of this group and S+H+ cases were indistinguishable.     

HPV genotyping in cervical cancer in Northern Thailand: adapting the linear array HPV assay for use on paraffin-embedded tissue

ObjectiveThe objective of this study was to review our experience with abdominal radical trachelectomy in patients with early-stage cervical cancer.MethodsWe performed a retrospective review of all patients who underwent an abdominal radical trachelectomy at the Instituto de Cancerologia—Clinica las Americas in Medellin, Colombia, between April 2002 and January 2008. Data collected included age, stage, histopathologic subtype, tumor size, evidence of lymph-vascular space invasion, estimated blood loss, number of perioperative blood transfusions, number and disease status of lymph nodes removed, disease status of surgical specimen, length of hospital stay, intraoperative and postoperative complications, follow-up time, and fertility outcomes.ResultsFifteen patients underwent an abdominal radical trachelectomy during the study period. The median patient age was 30 years (range, 25–38). Three patients had stage IA2 and 12 had stage IB1 cervical cancer. Eleven patients had squamous cell carcinoma and 4 had adenocarcinoma. Thirteen patients were diagnosed by cervical conization and 2 by colposcopically directed biopsy. All patients had tumors smaller than 2 cm. The median estimated blood loss was 400 ml (range, 200–1000). The median surgical time was 265 min (range, 210–330). The median number of units of packed red blood cells transfused per patient was 2. The median number of lymph nodes removed was 26 (range, 11–48). The median length of hospitalization was 3 days (range, 2–7). The median follow-up time was 32 months (range, 5–32). There was 1 intraoperative complication and 6 postoperative complications in 4 patients. No patient has had a recurrence. Three patients were able to conceive spontaneously; 1 delivered at 31 weeks' gestation, and 2 delivered at term.ConclusionAbdominal radical trachelectomy is feasible and can be performed safely in a developing country in well-selected patients with early cervical cancer who wish to preserve their fertility.     

Cardiac mortality is associated with low levels of omega-3 and omega-6 fatty acids in the heart of cadavers with a history of coronary heart disease

The benefits of omega-3 (ie, eicosapentaenoic acid and docosahexaenoic acid [DHA]) and omega-6 (ie, linoleic acid and arachidonic acid [AA]) fatty acids on reducing cardiac mortality are still debated. In this study, we tested the hypothesis that high levels of omega-3 and omega-6 fatty acids in heart tissues are associated with low cardiac mortality in Thai cadavers. One hundred fresh cadavers were examined in this study. The cause of death, history of coronary heart disease (CHD), and fish consumption habits were obtained from death certificates, cadaver medical record profiles, and a questionnaire to a person who lived with the subject before death. In each cadaver, biopsies of cardiac tissues were taken from the interventricular septum for measurement of fatty acid. Of the 100 cadavers (average age, 69 ± 13 years), 60 were men. The frequency of fish consumption was directly associated with omega-3 and omega-6 fatty acids in heart tissues (P < .01). History of CHD and cause of death (cardiac vs noncardiac) were not significantly associated with levels of omega-3 or omega-6 fatty acids. However, in cadavers with a history of CHD, high levels of omega-3 and omega-6, particularly DHA and AA, were associated with low cardiac mortality (P < .05). Fish consumption is associated with levels of omega-3 and omega-6 fatty acids in heart tissues. Although omega-3 and omega-6 fatty acids are not associated with cardiac mortality in the overall studied population, their low levels (especially DHA and AA) in heart tissues are associated with high cardiac mortality in cadavers with a history of CHD.     

Lymphadenopathy due to Penicillium marneffei infection: diagnosis by fine needle aspiration cytology.

Penicillium marneffei is an opportunistic fungal infection that usually causes disseminated disease, mainly in immunocompromised individuals, especially those with HIV infection. Untreated cases are usually fatal. Diagnosis is traditionally made by biopsy and/or culture; successful diagnosis by fine needle aspiration (FNA) has only been reported once. We present eight cases of HIV-infected patients with lymphadenopathy caused by P. marneffei infection, in which the diagnosis was made by FNA. In all cases, intracellular and extracellular yeast forms were visualized, and the characteristic cross-septation of P. marneffei was highlighted by GMS staining. All diagnoses were confirmed by culture. Anti-fungal treatment for P. marneffei was initiated, resulting in marked clinical improvement. We conclude that a diagnosis of lymphadenopathy caused by P. marneffei can reliably be made by FNA. The diagnosis is more rapid than biopsy or culture, allowing rapid institution of therapy, particularly important in immunocompromised patients. In all our cases, not only were lymphoma and other causes of lymphadenopathy ruled out, but also the necessity for an open surgical biopsy was obviated. This can be especially beneficial to patients (e.g., three in our study) in which lymphadenopathy is confined to deep intra-abdominal nodes.     

T-type calcium channel as a portal of iron uptake into cardiomyocytes of beta-thalassemic mice

Objectives: Iron‐overload condition can be found in β‐thalassemic patients with regular blood transfusion, leading to iron deposition in various organs including the heart. Elevated cardiac iron causes iron‐overload cardiomyopathy, a condition that provokes mortality because of heart failure in patients with thalassemia. Previous studies demonstrated that myocardial iron uptake may occur via L‐type calcium channels (LTCCs). However, direct evidence regarding the claimed pathway in thalassemic cardiomyocytes has never been investigated. Methods: Hearts from genetic‐altered β‐thalassemic mice and adult wild‐type mice were used for cultured ventricular cardiomyocytes. Blockers for LTCC, T‐type calcium channel (TTCC), transferrin receptor1 (TfR1), and divalent metal transporter1 (DMT1) were used, and quantification of cellular iron uptake under various iron loading conditions was performed by Calcein‐AM fluorescence assay. Microarray analysis was performed to investigate gene expressions in the hearts of these mice. Results: This study demonstrated that iron uptake under iron‐overload conditions in the cultured ventricular myocytes of thalassemic mice was greater than that of wild‐type cells (P < 0.01). TTCC blocker, efonidipine, and an iron chelator, deferoxamine, could prevent iron uptake into cultured cardiomyocytes, whereas blockers of TfR1, DMT1, and LTCC could not. Microarray analysis from thalassemic hearts demonstrated highly up‐regulated genes of TTCC, zinc transporter, and transferrin receptor2. Conclusions: Our findings indicated that iron uptake mechanisms in cultured thalassemic cardiomyocytes are mainly mediated by TTCC, suggesting that TTCC is the important pathway for iron uptake in this cultured thalassemic cardiomyocyte model.     

Primary and metastatic mucinous adenocarcinomas of the ovary: Evaluation of the diagnostic approach using tumor size and laterality

OBJECTIVE: To evaluate the usefulness of the recently proposed algorithm (Seidman JD, Kurman RJ, Ronnett BM. Primary and metastatic mucinous adenocarcinomas in the ovaries: incidence in routine practice with a new approach to improve intraoperative diagnosis. Am J Surg Pathol 2003; 27: 985-93 [5]) that classifies mucinous adenocarcinomas of the ovary as primary when they were unilateral > or =10 cm and as metastatic when they were unilateral <10 cm or bilateral. METHODS: Malignant ovarian neoplasms, which were resected in Chiang Mai University Hospital between 1992 and 2003, were histologically reviewed. Mucinous adenocarcinomas involving the ovary were identified. The medical records and radiologic materials were reviewed in correlation with the pathologic features to identify the primary site. RESULTS: There were 74 cases of mucinous adenocarcinomas; 16 were primary ovarian; 52, metastatic; and 6 of indeterminate primary site (primary versus metastatic). Primary mucinous adenocarcinomas had a mean size of 16.4 cm and bilateral involvement in 13%. Metastatic mucinous adenocarcinomas had a mean size of 11.7 cm and bilateral involvement in 77%. Excluding the 6 tumors of indeterminate primary site, the proposed algorithm correctly classified primary and metastatic tumors in 84% of 68 cases. Of 21 unilateral mucinous adenocarcinomas > or =10 cm, 62% were primary ovarian. Of 5 unilateral tumors <10 cm, 80% were metastatic. Of 42 bilateral mucinous adenocarcinomas, 95% were metastatic. CONCLUSION: The algorithm provided high accuracy in the overall prediction of primary and metastatic mucinous adenocarcinomas of the ovary, with major strength in the identification of metastatic tumors by bilaterality or size <10 cm. However, the prediction of primary mucinous adenocarcinomas by unilaterality and size > or =10 cm was less reliable than previously reported. Due to the overlapping features between primary and metastatic tumors and the higher frequency of the latter, the possibility of metastases should always be borne in mind in the evaluation of mucinous adenocarcinomas of the ovary.     

Interobserver Reproducibility with LiquiPrepTM Liquid-based Cervical Cytology Screening in a Developing Country.

Objective: A modified liquid-based techniques known as the “LiquiPrepTM (LP) system” requires neitherexpensive equipment nor complicated specimen preparation. The aim of this study was to assess the applicabilityof the LP for use in a developing country. Methods: Cervical cytology specimens were collected from 777 women,using the Cervex-BrushTM. The brush was first smeared on a glass side for conventional Papanicolaou (CP)stain, and then immersed in preservation fluid for LP preparation. Cytologic interpretations were classified intofour categories: 1) no atypical cells, 2) atypical squamous epithelial cells (ASC), 3) definite epithelial cellabnormality, and 4) unsatisfactory specimen. Interobserver variability was tested using weighted kappa statistics.Results: An LP specimen cost $9 per case compared to $3 per case for a conventional Pap smear. The time tolearn the technique was only a few days. Forty six (5.92%) specimens by LP were unsatisfactory. The overallagreement between cytopathologists was 96.7% (weighted κ=0.62), with 95.6% (weighted κ=0.44) for the casesenrolled earlier, increasing to 97.9% (weighted κ=0.78) for the cases enrolled later. Conclusions: In summary,after a short learning curve, interobserver reproducibility of LP smear was near perfect. This feature of the LP,together with the relatively low cost and simple protocol, makes it quite suitable for cervical cytology screeningin developing countries. Moreover, with this technique, some of each sample can be reserved for additionalstudies such as HPV detection and subtyping.     

Prognostic Value of p53 Expression in Early Stage Cervical Carcinoma Treated by Surgery.

Objective: To evaluate the prognostic significance of p53 protein expression in patients with early stage cervical carcinoma treated by surgery alone in a well-controlled study. Methods: A matched case-control study was performed in patients with stage Ib-IIa cervical carcinoma who underwent radical hysterectomy with pelvic lymphadenectomy. Patients had neither lymph node metastasis nor involvement of the parametrium and surgical margins, and did not receive any adjuvant treatment. Cases included 30 patients who had tumor recurrence within 5 years after surgery; controls included 60 patients who were disease-free for at least 5 years after surgery. Cases and controls were within 10 years of age, had the same stage and tumor type, and underwent surgery on as close to the same date as possible. The tumor sizes of cases and controls were within 1 cm of each other. Expression of p53 protein was studied by immunohistochemistry. Expression was considered positive when at least 10% of tumor cells showed nuclear staining. Results: No significant difference of p53 expression was observed between the case group and the control group (33% versus 40%). High histologic grade of tumors and lymphovascular space invasion were significantly associated with tumor recurrence in multivariable analysis (p=0.012 and 0.014, respectively). Conclusion: In this study, expression of p53 did not correlate with tumor recurrence. Immunohistochemistry for p53 protein appears to provide no prognostic information in the patients with early stage cervical cancer treated by surgery.