Establishing an EGFR mutation screening service for non-small cell lung cancer - sample quality criteria and candidate histological predictors.

INTRODUCTION: EGFR screening requires good quality tissue, sensitivity and turn-around time (TAT). We report our experience of routine screening, describing sample type, TAT, specimen quality (cellularity and DNA yield), histopathological description, mutation result and clinical outcome. METHODS: Non-small cell lung cancer (NSCLC) sections were screened for EGFR mutations (M+) in exons 18-21. Clinical, pathological and screening outcome data were collected for year 1 of testing. Screening outcome alone was collected for year 2. RESULTS: In year 1, 152 samples were tested, most (72%) were diagnostic. TAT was 4.9 days (95%confidence interval (CI)=4.5-5.5). EGFR-M+ prevalence was 11% and higher (20%) among never-smoking women with adenocarcinomas (ADCs), but 30% of mutations occurred in current/ex-smoking men. EGFR-M+ tumours were non-mucinous ADCs and 100% thyroid transcription factor (TTF1+). No mutations were detected in poorly differentiated NSCLC-not otherwise specified (NOS). There was a trend for improved overall survival (OS) among EGFR-M+ versus EGFR-M- patients (median OS=78 versus 17 months). In year 1, test failure rate was 19%, and associated with scant cellularity and low DNA concentrations. However 75% of samples with poor cellularity but representative of tumour were informative and mutation prevalence was 9%. In year 2, 755 samples were tested; mutation prevalence was 13% and test failure only 5.4%. Although samples with low DNA concentration (2.2 ng/μL), the mutation rate was 9.2%. CONCLUSION: Routine epidermal growth factor receptor (EGFR) screening using diagnostic samples is fast and feasible even on samples with poor cellularity and DNA content. Mutations tend to occur in better-differentiated non-mucinous TTF1+ ADCs. Whether these histological criteria may be useful to select patients for EGFR testing merits further investigation.

Immediate graft histological assay, post pig's liver transplantation

PURPOSE: To describe the vascular and tissue histopathological changes in seven sequential experimental liver transplantations in pigs. METHODS: Fourteen female pigs, Sus domesticus species, with body mass between 5 and 8 kg were utilized. After the end of all anastomoses of the graft implantation in the receptor, the animal was monitored for 30 minutes, and at its end one of the biopsies was collected for histological analysis. The histological criteria utilized were: lytic hepatocyte necrosis, density of septal and portal inflammatory infiltrated, sinusoidal congestion and hemorrhage. The analysis was performed separately for the portal region in zone 1, 2 and 3. RESULTS: Among the structural changes undergone by the graft, those with greater frequency and intensity were vascular congestion and steatosis, which stood out in transplantations 5, 6 and 7. CONCLUSIONS: The technique demonstrated vascular alterations represented by vasocongestion, edema and minimum inflammatory reaction. In relation to the parenchyma, was observed macrovacuolar pan-acinar steatosis, focal lytic and occasional hemorrhages, beyond the accumulation of hemosiderin in Kuppfer's cells.

A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways

Background: Changing perspectives on the natural history of celiac disease (CD), new serology and genetic tests, and amended histological criteria for diagnosis cast doubt on past prevalence estimates for CD. We set out to establish a more accurate prevalence estimate for CD using a novel serogenetic approach.Methods: The human leukocyte antigen (HLA)-DQ genotype was determined in 356 patients with 'biopsy-confirmed' CD, and in two age-stratified, randomly selected community cohorts of 1,390 women and 1,158 men. Sera were screened for CD-specific serology.Results: Only five 'biopsy-confirmed' patients with CD did not possess the susceptibility alleles HLA-DQ2.5, DQ8, or DQ2.2, and four of these were misdiagnoses. HLA-DQ2.5, DQ8, or DQ2.2 was present in 56% of all women and men in the community cohorts. Transglutaminase (TG)-2 IgA and composite TG2/deamidated gliadin peptide (DGP) IgA/IgG were abnormal in 4.6% and 5.6%, respectively, of the community women and 6.9% and 6.9%, respectively, of the community men, but in the screen-positive group, only 71% and 75%, respectively, of women and 65% and 63%, respectively, of men possessed HLA-DQ2.5, DQ8, or DQ2.2. Medical review was possible for 41% of seropositive women and 50% of seropositive men, and led to biopsy-confirmed CD in 10 women (0.7%) and 6 men (0.5%), but based on relative risk for HLA-DQ2.5, DQ8, or DQ2.2 in all TG2 IgA or TG2/DGP IgA/IgG screen-positive subjects, CD affected 1.3% or 1.9%, respectively, of females and 1.3% or 1.2%, respectively, of men. Serogenetic data from these community cohorts indicated that testing screen positives for HLA-DQ, or carrying out HLA-DQ and further serology, could have reduced unnecessary gastroscopies due to false-positive serology by at least 40% and by over 70%, respectively.Conclusions: Screening with TG2 IgA serology and requiring biopsy confirmation caused the community prevalence of CD to be substantially underestimated. Testing for HLA-DQ genes and confirmatory serology could reduce the numbers of unnecessary gastroscopies. © 2013 Anderson et al.; licensee BioMed Central Ltd.

Individualized immunosuppression after renal transplantation in childhood

Pediatric renal transplantation (TX) has evolved greatly during the past few decades, and today TX is considered the standard care for children with end-stage renal disease. In Finland, 191 children had received renal transplants by October 2007, and 42% of them have already reached adulthood. Improvements in treatment of end-stage renal disease, surgical techniques, intensive care medicine, and in immunosuppressive therapy have paved the way to the current highly successful outcomes of pediatric transplantation. In children, the transplanted graft should last for decades, and normal growth and development should be guaranteed. These objectives set considerable requirements in optimizing and fine-tuning the post-operative therapy. Careful optimization of immunosuppressive therapy is crucial in protecting the graft against rejection, but also in protecting the patient against adverse effects of the medication. In the present study, the results of a retrospective investigation into individualized dosing of immunosuppresive medication, based on pharmacokinetic profiles, therapeutic drug monitoring, graft function and histology studies, and glucocorticoid biological activity determinations, are reported. Subgroups of a total of 178 patients, who received renal transplants in 1988 2006 were included in the study. The mean age at TX was 6.5 years, and approximately 26% of the patients were <2 years of age. The most common diagnosis leading to renal TX was congenital nephrosis of the Finnish type (NPHS1). Pediatric patients in Finland receive standard triple immunosuppression consisting of cyclosporine A (CsA), methylprednisolone (MP) and azathioprine (AZA) after renal TX. Optimal dosing of these agents is important to prevent rejections and preserve graft function in one hand, and to avoid the potentially serious adverse effects on the other hand. CsA has a narrow therapeutic window and individually variable pharmacokinetics. Therapeutic monitoring of CsA is, therefore, mandatory. Traditionally, CsA monitoring has been based on pre-dose trough levels (C0), but recent pharmacokinetic and clinical studies have revealed that the immunosuppressive effect may be related to diurnal CsA exposure and blood CsA concentration 0-4 hours after dosing. The two-hour post-dose concentration (C2) has proved a reliable surrogate marker of CsA exposure. Individual starting doses of CsA were analyzed in 65 patients. A recommended dose based on a pre-TX pharmacokinetic study was calculated for each patient by the pre-TX protocol. The predicted dose was clearly higher in the youngest children than in the older ones (22.9±10.4 and 10.5±5.1 mg/kg/d in patients <2 and >8 years of age, respectively). The actually administered oral doses of CsA were collected for three weeks after TX and compared to the pharmacokinetically predicted dose. After the TX, dosing of CsA was adjusted according to clinical parameters and blood CsA trough concentration. The pharmacokinetically predicted dose and patient age were the two significant parameters explaining post-TX doses of CsA. Accordingly, young children received significantly higher oral doses of CsA than the older ones. The correlation to the actually administered doses after TX was best in those patients, who had a predicted dose clearly higher or lower (> ±25%) than the average in their age-group. Due to the great individual variation in pharmacokinetics standardized dosing of CsA (based on body mass or surface area) may not be adequate. Pre-Tx profiles are helpful in determining suitable initial CsA doses. CsA monitoring based on trough and C2 concentrations was analyzed in 47 patients, who received renal transplants in 2001 2006. C0, C2 and experienced acute rejections were collected during the post-TX hospitalization, and also three months after TX when the first protocol core biopsy was obtained. The patients who remained rejection free had slightly higher C2 concentrations, especially very early after TX. However, after the first two weeks also the trough level was higher in the rejection-free patients than in those with acute rejections. Three months after TX the trough level was higher in patients with normal histology than in those with rejection changes in the routine biopsy. Monitoring of both the trough level and C2 may thus be warranted to guarantee sufficient peak concentration and baseline immunosuppression on one hand and to avoid over-exposure on the other hand. Controlling of rejection in the early months after transplantation is crucial as it may contribute to the development of long-term allograft nephropathy. Recently, it has become evident that immunoactivation fulfilling the histological criteria of acute rejection is possible in a well functioning graft with no clinical sings or laboratory perturbations. The influence of treatment of subclinical rejection, diagnosed in 3-month protocol biopsy, to graft function and histology 18 months after TX was analyzed in 22 patients and compared to 35 historical control patients. The incidence of subclinical rejection at three months was 43%, and the patients received a standard rejection treatment (a course of increased MP) and/or increased baseline immunosuppression, depending on the severity of rejection and graft function. Glomerular filtration rate (GFR) at 18 months was significantly better in the patients who were screened and treated for subclinical rejection in comparison to the historical patients (86.7±22.5 vs. 67.9±31.9 ml/min/1.73m2, respectively). The improvement was most remarkable in the youngest (<2 years) age group (94.1±11.0 vs. 67.9±26.8 ml/min/1.73m2). Histological findings of chronic allograft nephropathy were also more common in the historical patients in the 18-month protocol biopsy. All pediatric renal TX patients receive MP as a part of the baseline immunosuppression. Although the maintenance dose of MP is very low in the majority of the patients, the well-known steroid-related adverse affects are not uncommon. It has been shown in a previous study in Finnish pediatric TX patients that steroid exposure, measured as area under concentration-time curve (AUC), rather than the dose correlates with the adverse effects. In the present study, MP AUC was measured in sixteen stable maintenance patients, and a correlation with excess weight gain during 12 months after TX as well as with height deficit was found. A novel bioassay measuring the activation of glucocorticoid receptor dependent transcription cascade was also employed to assess the biological effect of MP. Glucocorticoid bioactivity was found to be related to the adverse effects, although the relationship was not as apparent as that with serum MP concentration. The findings in this study support individualized monitoring and adjustment of immunosuppression based on pharmacokinetics, graft function and histology. Pharmacokinetic profiles are helpful in estimating drug exposure and thus identifying the patients who might be at risk for excessive or insufficient immunosuppression. Individualized doses and monitoring of blood concentrations should definitely be employed with CsA, but possibly also with steroids. As an alternative to complete steroid withdrawal, individualized dosing based on drug exposure monitoring might help in avoiding the adverse effects. Early screening and treatment of subclinical immunoactivation is beneficial as it improves the prospects of good long-term graft function.

Reproductive biology, spawning season, and growth of female rex sole (Glyptocephalus zachirus) in the Gulf of Alaska

Rex sole (Glyptocephalus zachirus) have a wide distribution throughout the North Pacific, ranging from central Baja California to the western Bering Sea. Although rex sole are an important species in the commercial trawl fisheries off the U.S. West Coast, knowledge of their reproductive biology is limited to one study off the Oregon coast where ovaries were analyzed with gross anatomical methods. This study was initiated to determine reproductive and growth parameters specific to rex sole in the Gulf of Alaska (GOA) stock. Female rex sole (n=594) ranging in total length from 166 to 552 mm were collected opportunistically around Kodiak Island, Alaska, from February 2000 to October 2001. All ovaries were analyzed by using standard histological criteria to determine the maturity stage. Year-round sampling of rex sole ovaries confirmed that rex sole are batch spawners and have a protracted spawning season in the GOA that lasts at least eight months, from October to May; the duration of the spawning season and the months of spawning activity are different from those previously estimated. Female rex sole in the GOA had an estimated length at 50% maturity (ML50) of 352 mm, which is greater than the previously estimated ML50 at southern latitudes. The maximum age of collected female rex sole was 29 years, and the estimated age at 50% maturity (MA50) in the GOA was 5.1 years. The von Bertalanffy growth model for rex sole in the GOA was significantly different from the previously estimated model for rex sole off the Oregon coast. This study indicated that there are higher growth rates for rex sole in the GOA than off the Oregon coast and that there are differences in length at maturity and similarity in age at maturity between the two regions.

Spawning cycles and habitats for ballyhoo (Hemiramphus brasiliensis) and balao (H. balao) in south Florida

Two halfbeak species, ballyhoo (Hemiramphus brasiliensis) and balao (H. balao), are harvested as bait in south Florida waters, and recent changes in fishing effort and regulations prompted this investigation of the overlap of halfbeak fishing grounds and spawning grounds. Halfbeaks were sampled aboard commercial fishing vessels, and during fishery-independent trips, to determine spatial and temporal spawning patterns of both species. Cyclic patterns of gonadosomatic indices (GSIs) indicated that both species spawned during spring and summer months. Histological analysis demonstrated that specific stages of oocyte development can be predicted from GSI values; for example, female ballyhoo with GSIs >6.0 had hydrated oocytes that were 2.0−3.5 mm diameter. Diel changes in oocyte diameters and histological criteria demonstrated that final oocyte maturation occurred over a 30- to 36-hour period and that ballyhoo spawned at dusk. Hydration of oocytes began in the morning, and ovulation occurred at sunset of that same day; therefore females with hydrated oocytes were ready to spawn within hours. We compared maps of all locations where fish were collected to maps of locations where spawning females (i.e. females with GSIs >6.0) were collected to determine the degree of overlap of halfbeak fishing and spawning grounds. We also used geographic information system (GIS) data to describe the depth and bottom type of halfbeak spawning grounds. Ballyhoo spawned all along the coral reef tract of the Atlantic Ocean, inshore of the reef tract, and in association with bank habitats within Florida Bay. In the Atlantic Ocean, balao spawned along the reef tract and in deeper, more offshore waters than did ballyhoo; balao were not found inshore of the coral reef tract or in Florida Bay. Both halfbeak species, considered together, spawned throughout the fishing grounds of south Florida.

Incidence, clinical spectrum, diagnostic features, treatment and predictors of paradoxical reactions during antibiotic treatment of Mycobacterium ulcerans infections

Background: Paradoxical reactions from antibiotic treatment of Mycobacterium ulcerans have recently been recognized. Data is lacking regarding their incidence, clinical and diagnostic features, treatment, outcomes and risk factors in an Australian population.

Methods: Data was collected prospectively on all confirmed cases of M. ulcerans infection managed at Barwon Health Services, Australia, from 1/1/1998-31/12/2011. Paradoxical reactions were defined on clinical and histological criteria and cases were determined by retrospectively reviewing the clinical history and histology of excised lesions. A Poisson regression model was used to examine associations with paradoxical reactions.

Results: Thirty-two of 156 (21%) patients developed paradoxical reactions a median 39 days (IQR 20-73 days) from antibiotic initiation. Forty-two paradoxical episodes occurred with 26 (81%) patients experiencing one and 6 (19%) multiple episodes. Thirty-two (76%) episodes occurred during antibiotic treatment and 10 (24%) episodes occurred a median 37 days after antibiotic treatment. The reaction site involved the original lesion (wound) in 23 (55%), was separate to but within 3 cm of the original lesion (local) in 11 (26%) and was more than 3 cm from the original lesion (distant) in 8 (19%) episodes. Mycobacterial cultures were negative in 33/33 (100%) paradoxical episodes. Post-February 2009 treatment involved more cases with no antibiotic modifications (12/15 compared with 11/27, OR 5.82, 95% CI 1.12-34.07, p = 0.02) and no further surgery (9/15 compared with 2/27, OR 18.75, 95% CI 2.62-172.73, p < 0.001). Six severe cases received prednisone with marked clinical improvement. On multivariable analysis, age ≥ 60 years (RR 2.84, 95% CI 1.12-7.17, p = 0.03), an oedematous lesion (RR 3.44, 95% CI 1.11-10.70, p=0.03) and use of amikacin in the initial antibiotic regimen (RR 6.33, 95% CI 2.09-19.18, p < 0.01) were associated with an increased incidence of paradoxical reactions.

Conclusions: Paradoxical reactions occur frequently during or after antibiotic treatment of M. ulcerans infections in an Australian population and may be increased in older adults, oedematous disease forms, and in those treated with amikacin. Recognition of paradoxical reactions led to changes in management with less surgery, fewer antibiotic modifications and use of prednisolone for severe reactions.

A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways

Background
Changing perspectives on the natural history of celiac disease (CD), new serology and genetic tests, and amended histological criteria for diagnosis cast doubt on past prevalence estimates for CD. We set out to establish a more accurate prevalence estimate for CD using a novel serogenetic approach.

Methods
The human leukocyte antigen (HLA)-DQ genotype was determined in 356 patients with ‘biopsy-confirmed’ CD, and in two age-stratified, randomly selected community cohorts of 1,390 women and 1,158 men. Sera were screened for CD-specific serology.

Results
Only five ‘biopsy-confirmed’ patients with CD did not possess the susceptibility alleles HLA-DQ2.5, DQ8, or DQ2.2, and four of these were misdiagnoses. HLA-DQ2.5, DQ8, or DQ2.2 was present in 56% of all women and men in the community cohorts. Transglutaminase (TG)-2 IgA and composite TG2/deamidated gliadin peptide (DGP) IgA/IgG were abnormal in 4.6% and 5.6%, respectively, of the community women and 6.9% and 6.9%, respectively, of the community men, but in the screen-positive group, only 71% and 75%, respectively, of women and 65% and 63%, respectively, of men possessed HLA-DQ2.5, DQ8, or DQ2.2. Medical review was possible for 41% of seropositive women and 50% of seropositive men, and led to biopsy-confirmed CD in 10 women (0.7%) and 6 men (0.5%), but based on relative risk for HLA-DQ2.5, DQ8, or DQ2.2 in all TG2 IgA or TG2/DGP IgA/IgG screen-positive subjects, CD affected 1.3% or 1.9%, respectively, of females and 1.3% or 1.2%, respectively, of men. Serogenetic data from these community cohorts indicated that testing screen positives for HLA-DQ, or carrying out HLA-DQ and further serology, could have reduced unnecessary gastroscopies due to false-positive serology by at least 40% and by over 70%, respectively.

Conclusions
Screening with TG2 IgA serology and requiring biopsy confirmation caused the community prevalence of CD to be substantially underestimated. Testing for HLA-DQ genes and confirmatory serology could reduce the numbers of unnecessary gastroscopies.

Periacinar Retraction Clefting in Nonneoplastic and Neoplastic Prostatic Glands: Artifact or Molecular Involvement

A space between neoplastic acini and prostatic stroma is not rare and studies have interpreted this as an artifact, considering the absence of endothelial cells indicating vascular invasion. Thus, the aims of this work were to characterize and correlate the occurrence and extent of retraction clefting with the reactivities of alpha and beta dystroglycan (alpha DG, beta DG), laminin, matrix metalloproteinase 2 (MMP-2), p63, insulin-like growth factor 1(IGF-1), vimentin, and fibroblast growth factor 2 (FGF-2). The study was based on nonneoplastic and neoplastic prostatic tissues obtained from necropsies and retropubic radical prostatectomies. The results showed that periacinar retraction clefting was significantly more frequent in prostatic carcinoma samples than in normal prostatic acini. Most of the neoplastic acini (72.0%) showed retraction clefting of more than 50% of circumference, which were significantly more frequent in Gleason score 7 and 6. Decreased collagen and reticular and elastic fibers were verified in the stroma around neoplastic acini. Weak and discontinuous alpha DG, beta DG, and laminin immunoreactivities and intensified MMP-2, vimentin, IGF-1 and FGF-2 immunoreactivities were verified in the neoplastic acini; p63 immunoreactivity was negative in all carcinomas. Thus, these findings showed that the lack of epithelial basal cells, DGs, and laminin and increased MMP-2, IGF-1, and FGF-7 could be considered important pathways in periacinar retraction occurrence. This study demonstrated the origin of and the biological mechanisms responsible for periacinar retraction clefting in prostatic carcinoma.

Comparison of ultrasonography and histopathology for the diagnosis of endometritis in Holstein-Friesian cows

Reproductive diseases are a great barrier to dairy production, as they diminish fertility and cause economic loss. In this context, endometritis plays an important role. Different diagnostic techniques exist for endometritis that vary in sensitivity and specificity. This work aimed to evaluate and compare ultrasonographic and histopathological examinations, and combinations thereof, for the diagnosis of endometritis by determining their sensitivity, specificity, and kappa agreement coefficients using endometrial cytology as the gold standard. We developed an adaptive reading score to perform histological examination of the uterus. In this study, 76 Holstein-Friesian cows, 21 to 47 d postpartum, without vaginal catarrh were submitted to gynecological examinations, including ultrasonographic examination, an endometrial cytology examination, and a uterine biopsy. Our results indicate that ultrasonography is a practical and effective diagnostic method, and a combination of the determination of intrauterine fluid and cervical diameter was the most efficient ultrasonographic method, with 50% sensitivity and 88% specificity. Histopathological examination was a useful diagnostic method that provided rich detail on endometrial inflammation, and allowed evaluation of different components of the tissue such as the epithelium, lamina propria, endometrial glands, and blood vessels; this method had 44% sensitivity and 92% specificity for diagnosis of endometritis.

Fasciola hepatica: Histological changes in the reproductive structures of triclabendazole (TCBZ)-sensitive and TCBZ-resistant flukes after treatment in vivo with TCBZ and the related benzimidazole derivative, Compound Alpha

Twenty-four shed-reared lambs were each infected orally with 250 metacercariae of Fasciola hepatica, using either the triclabendazole (TCBZ)-sensitive Cullompton isolate or the TCBZ-resistant Sligo isolate. Twelve weeks after infection the lambs were treated with TCBZ (10 mg/kg) or with the experimental fasciolicide, Compound Alpha (Cpd alpha), a benzimidazole derivative of TCBZ (15 mg/kg). The lambs were euthanised 48,72 and 96 h after TCBZ treatment, or 24, 48 and 72 h after Cpd a treatment, and flukes were collected from the liver and/or gall bladder of each animal. Untreated animals harbouring 12-week infections were euthanised 24 h after administration of anthelmintic to the treatment groups, and the untreated flukes provided control material. A semi-quantitative assessment of the degree of histological change induced by the two drugs after different times of exposure was achieved by scoring the intensity of three well-defined lesions that developed in the testes and uteri of a representative sample of flukes from each lamb. In general, it was found that in those tissues where active meiosis and/or mitosis occurred (testis, ovary, and vitelline follicles), there was progressive loss of cell content due to apparent failure of cell division to keep pace with expulsion of the mature or effete products. Further, actively dividing cell types tended to become individualised, rounded and condensed, characteristic of apoptotic cell death. Protein synthetic activity was apparently inhibited in the Mehlis' secretory cells. In the uterus, where successful formation of shelled eggs represents the culmination of a complex sequence of cytokinetic, cytological and synthetic activity involving the vitelline follicles, the ovary and the Mehlis' gland, histological evidence indicating failure of ovigenesis was evident from 24 h post-treatment onwards. The development of these lesions may be related to the known antitubulin activity of the benzimidazole class of anthelmintics, to the induction of apoptosis in cells where mitosis or meiosis has aborted due to failure of spindle formation, and to drug-induced inhibition of protein synthesis. The semi-quantitative findings indicated that Cpd a is slightly less efficacious than TCBZ itself in causing histological damage to the reproductive structures of TCBZ-sensitive flukes, and that, like TCBZ, it caused no histological damage in flukes of the TCBZ-resistant isolate. This study illustrates the potential utility of histological techniques for conveniently screening representative samples of flukes in field trials designed to validate instances of drug resistance or to test the efficacy of new products against known drug-resistant and drug-susceptible fluke isolates. It also provides reference criteria for drug-induced histopathological changes in fluke reproductive structures which may aid interpretation of TEM findings. (C) 2009 Elsevier B.V. All rights reserved.

Revised response criteria for polycythemia vera and essential thrombocythemia:an ELN and IWG-MRT consensus project

Standardized response criteria to interpret and compare clinical trials are needed for approval of new therapeutic agents by regulatory agencies. The European LeukemiaNet (ELN) response criteria for essential thrombocythemia (ET) and polycythemia vera (PV) issued in 2009 have been widely adopted as end points in a number of recent clinical trials. However, evidence exists that they do not predict response or provide clinically relevant measures of benefit for the patients. This article presents revised recommendations for assessing response in ET and PV provided by a working group established by ELN and International Working Group-Myeloproliferative Neoplasms Research and Treatment. New definitions of complete and partial remission incorporate clinical, hematological, and histological response assessments that include a standardized symptom assessment form and consider absence of disease progression and vascular events. We anticipate that these criteria will be adopted widely to facilitate the development of new and more effective therapies for ET and PV.

Correlation of clinical, cytological and histological findings in oral squamous cell carcinomas

The present study aimed to investigate the efficiency of exfoliative cytology by correlating the clinical lesions of oral squamous cell carcinoma (OSCC) with exfoliative cytology and histopathological findings. Cases of OSCC diagnosed between 1984 and 2010 were analyzed. The inclusion criteria for the present study were the availability of detailed clinical findings and a diagnosis of the disease through exfoliative cytology and histopathology. The cases were assessed and assigned scores, which were then submitted to modal expression analysis, which considers the higher frequency scores, thus relating the variables. The cytological findings demonstrated that the majority of the cases had malignant potential. Exfoliative cytology should be used as a supplementary tool for the diagnosis of OSCC, as it enables the early detection of these lesions. However, cytology should not be used as a substitute for histopathological examination.

Classificação morfológica e imunostoquímica em microarranjo de tecido (TMA) de linfomas não-Hodgkin em cães conforme os critérios da Histological Classification od Hematopoietic Tumors of Domestic Animals (WHO)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The performance of conventional and fluorescence-based methods for occlusal caries detection: an in vivo study with histological validation

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES