Prognostic Factors of Long-term Survival Following Radical Resection for Ampullary Carcinoma.

BACKGROUND: The incidence of adenocarcinoma of the ampulla of Vater has been increasing over the past years. Nevertheless, it is still a rare disease and the prognostic factors predicting long-term survival are not sufficiently clarified. This study aims to evaluate the association between histopathological characteristics and long-term survival of patients with ampullary cancer after curative resection, as well as the efficiency of immunohistochemical expression of CK7, CK20, and CDX2 to distinguish the histopathological (intestinal or pancreaticobiliary) patterns. METHODS: Demographic, histopathological data, pTNM stage, and immunohistochemical expression patterns were collected from 65 patients with adenocarcinoma of the ampulla of Vater. Five and 10-year overall and disease-free survival rates after curative resection were determined. RESULTS: Of the 65 patients with ampullary carcinoma, 47 (72%) underwent radical resection. The 5- and 10-year overall survival rate was 46% and 37%, respectively. Our results demonstrate that the main prognostic factors were the presence and number of lymph node metastases, lymph node ratio (LNR), differentiation grade, and lymphovascular invasion. After multivariate analysis, only lymph node ratio ≥ 20% remained an independent prognostic factor of survival (HR: 2.63 95% CI: 1.05-6.61; p = 0.039). CONCLUSION: Here, we demonstrated more evidence that the lymph node metastases are associated with poor prognosis in ampullary carcinoma. Particularly, the relation between the number of metastatic lymph nodes and the number of harvested lymph node (LNR) should be considered a major prognostic factor.

Histopathological grading of breast ductal carcinoma in situ: validation of a web-based survey through intra-observer reproducibility analysis.

BACKGROUND: Histopathological grading diagnosis of ductal carcinoma in situ (DCIS) of the breast may be very difficult even for experts, and it is important for therapeutic decisions. The challenge may be due to the inaccurate and/or subjective application of the diagnosis criteria. The aim of this study was to investigate the intra-observer agreement between a traditional method and a developed web-based questionnaire for scoring breast DCIS. METHODS: A cross-sectional study was carried out to evaluate the diagnostic agreement of an electronic questionnaire and its point scoring system with the subjective reading of digital images for 3 different DCIS grading systems: Holland, Van Nuys and modified Black nuclear grade system. Three pathologists analyzed the same set of digitized images from 43 DCIS cases using two different web-based programs. In the first phase, they accessed a website with a newly created questionnaire and scoring system developed to allow the determination of the histological grade of the cases. After at least 6 months, the pathologists read again the same images, but without the help of the questionnaire, indicating subjectively the diagnoses. The intra-observer agreement analysis was employed to validate this innovative web-based survey. RESULTS: Overall, diagnostic reproducibility was similar for all histologic grading classification systems, with kappa values of 0.57 ± 0.10, 0.67 ± 0.09 and 0.67 ± 0.09 for Holland, Van Nuys classification and modified Black nuclear grade system respectively. Only two 2-step diagnostic disagreements were found, one for Holland and another for Van Nuys. Both cases were superestimated by the web-based survey. CONCLUSION: The diagnostic agreement between the web-based questionnaire and a traditional method, both using digital images, is moderate to good for Holland, Van Nuys and modified Black nuclear grade system. The use of a scoring point system does not appear to pose a major risk of presenting large (2-step) diagnostic disagreements. These findings indicate that the use of this point scoring system in this web-based survey to grade objectively DCIS lesions is a useful diagnostic tool.

NTPDase3 and ecto-5'-nucleotidase/CD73 are differentially expressed during mouse bladder cancer progression.

According to the World Health Organization, bladder cancer is the seventh most common cancer among men in the world. The current treatments for this malignancy are not efficient to prevent the recurrence and progression of tumors. Then, researches continue looking for better therapeutic targets which can end up in new and more efficient treatments. One of the recent findings was the identification that the purinergic system was involved in bladder tumorigenesis. The ectonucleotidases, mainly ecto-5'-nucleotidase/CD73 have been revealed as new players in cancer progression and malignity. In this work, we investigated the NTPDase3 and ecto-5'-nucleotidase/CD73 expression in cancer progression in vivo. Bladder tumor was induced in mice by the addition of 0.05 % of N-butyl-N-(hydroxybutyl)-nitrosamine (BBN) in the drinking water for 4, 8, 12, 18, and 24 weeks. After this period, mice bladders were removed for histopathology analysis and immunofluorescence assays. The bladder of animals which has received BBN had alterations, mainly inflammation, in initial times of tumor induction. After 18 weeks, mice's bladder has developed histological alterations similar to human transitional cell carcinoma. The cancerous urothelium, from mice that received BBN for 18 and 24 weeks, presented a weak immunostaining to NTPDase3, in contrast to an increased expression of ecto-5'-nucleotidase/CD73. The altered expression of NTPDase3 and ecto-5'-nucleotidase/CD73 presented herein adds further evidence to support the idea that alterations in ectonucleotidases are involved in bladder tumorigenesis and reinforce the ecto-5'-nucleotidase/CD73 as a future biomarker and/or a target for pharmacological therapy of bladder cancer.

Ectonucleotidases in tumor cells and tumor-associated immune cells: an overview.

Increasing evidence points out that genetic alteration does not guarantee the development of a tumor and indicates that complex interactions of tumor cells with the microenvironment are fundamental to tumorigenesis. Among the pathological alterations that give tumor cells invasive potential, disruption of inflammatory response and the purinergic signaling are emerging as an important component of cancer progression. Nucleotide/nucleoside receptor-mediated cell communication is orchestrated by ectonucleotidases, which efficiently hydrolyze ATP, ADP, and AMP to adenosine. ATP can act as danger signaling whereas adenosine, acts as a negative feedback mechanism to limit inflammation. Many tumors exhibit alterations in ATP-metabolizing enzymes, which may contribute to the pathological events observed in solid cancer. In this paper, the main changes occurring in the expression and activity of ectonucleotidases in tumor cells as well as in tumor-associated immune cells are discussed. Furthermore, we focus on the understanding of the purinergic signaling primarily as exemplified by research done by the group on gliomas.

Assessment of the Fournier(®) cervical specimen self-sampling device using the Papanicolaou method.

INTRODUCTION: Communities of socially excluded immigrant women, especially Muslim, Asian, Aboriginal and Maroon, are among the groups of women with low rates of cervical screening. Exclusion of the pelvic examination could result in a higher acceptance of the cervical screening among these communities and an increase in screening coverage. AIM: To assess the performance of the Fournier(®) cervical specimen self-sampling device for the cytological diagnosis of precursor or neoplastic lesions in the uterine cervix using the Papanicolaou method. METHODS: A case-control study was conducted at the Cervical Pathology Outpatient Clinic. Liquid-based cytology slides were obtained by the Fournier device and stained using the Papanicolaou method. The slides were analyzed by two pathologists, blinded for the colposcopic and histological results and compared to Papanicolaou smears that were obtained using the traditional method of speculum examination. RESULTS: There were 68 patients who were considered free from precursor or neoplastic cervical lesions. There were 35 cases of low-grade lesions, 13 cases of high-grade lesions and 3 cases of squamous-cell carcinoma. According to the first and second pathologists, the sensitivities of the device for identifying precursor or neoplastic cervical lesions were 50.0 and 60.0%, and the specificities of the method were 81.8 and 73.8%. According to the first and second pathologists, the positive predictive values of the diagnostic test were 0.67 and 0.63, and the negative predictive values were 0.68 and 0.71, respectively. CONCLUSION: Sensitivity and specificity of the Fournier device test was comparable to Papanicolaou smears tests obtained using the traditional method with speculum examination.

Avaliação da expressão imunoistoquímica da proteína p16INK4a no adenocarcinoma de esôfago / Protein p16INK4a immunohistochemical expression in adenocarcinoma of the esophagus

INTRODUÇÃO: O adenocarcinoma de esôfago apresenta aumento de frequência nas últimas décadas, particularmente em países desenvolvidos. O esôfago de Barrett é reconhecido como a principal lesão precursora e o estudo da sequência metaplasia-displasia-adenocarcinoma mostra a ocorrência de alterações genéticas desde suas fases mais incipientes. As alterações no p16INK4a são relatadas como frequentes no esôfago de Barrett e no carcinoma de esôfago. OBJETIVO: Verificar a prevalência da expressão imunoistoquímica da proteína p16INK4a em exames anatomopatológicos de pacientes com adenocarcinoma de esôfago. MÉTODO: A população do estudo foi constituída de 37 pacientes com adenocarcinoma de esôfago. A expressão da proteína p16 foi detectada por meio de análise imunoistoquímica, com anticorpo primário p16INK4aAb-7, clone 16P07, NeoMarkers e avaliada de acordo com o Sistema de Escore de Imunorreatividade (Immunoreactive scoring system - IRS) modificado. RESULTADOS: No grupo houve predominância de pacientes do sexo masculino (86,5 por cento) e a maioria dos casos correspondia a estádios avançados (III e IV = 67,5 por cento). Em 12 casos (32,4 por cento) foi identificada expressão imunoistoquímica da proteína p16INK4a. Não foi observada relação significativa entre a perda da expressão da proteína p16INK4a e o grau de diferenciação histológica (p=0,81) nem com o estadiamento da doença (p=0,485). CONCLUSÃO: Ocorre perda da expressão imunoistoquímica da proteína p16INK4a, corroborando as informações de que a inativação do gene p16 é um evento frequente e que pode exercer papel importante na carcinogênese do adenocarcinoma de esôfago.

BACKGROUND: The esophageal adenocarcinoma shows an increasing frequence in the last decades, specially in the developed countries. The Barrett´s esophagus is accepted as the major premalignant lesion and the metaplasia-dysplasia-adenocarcinoma sequence presents a lot of genetic changes since its early events. The alterations in p16INK4a are frequent in Barrett´s esophagus and esophageal carcinoma. AIM: To verify the prevalence of the immunohistochemical expression of the p16INK4a protein in patients with esophageal adenocarcinoma. METHODS: The study population consisted of 37 patients with resected esophageal adenocarcinoma. The p16INK4a protein expression was determined by immunohistochemistry using primary antibody p16INK4aAb-7, clone 16P07 NeoMarkers and assessed according to the Immunoreactive scoring system (IRS). RESULTS: Of 37 analyzed patients, the most were male (86,5 percent) and the advanced disease was predominant (stages III and IV = 67,5 percent). In 12 (32,4 percent) the immunohistochemistry was positive for p16INK4a.There was no significative relation between the protein expression and the degrees of histological differentiation of the biopsies and surgical especimens (p=0,81) neither with the staging (p=0,485). CONCLUSION: The lost of the immunohistochemical expression of the p16INK4a protein in this study suggests that p16 is enroled in the carcinogenesis of the adenocarcinoma of esophagus.

Clinical and pathological correlations of C4d immunostaining and its influence on the outcome of kidney transplant recipients.

INTRODUCTION: C4d is a marker of antibody-mediated rejection (ABMR) in kidney allografts, although cellular rejection also have C4d deposits. OBJECTIVE: To correlate C4d expression with clinico-pathological parameters and graft outcomes at three years. METHODS: One hundred forty six renal transplantation recipients with graft biopsies by indication were included. C4d staining was performed by paraffin-immunohistochemistry. Graft function and survival were measured, and predictive variables of the outcome were determined by multivariate Cox regression. RESULTS: C4d staining was detected in 48 (31%) biopsies, of which 23 (14.7%) had diffuse and 25 (16%) focal distribution. Pre-transplantation panel reactive antibodies (%PRA) class I and II were significantly higher in C4d positive patients as compared to those C4d negative. Both glomerulitis and pericapillaritis were associated to C4d (p = 0.002 and p < 0.001, respectively). The presence of C4d in biopsies diagnosed as no rejection (NR), acute cellular rejection (ACR) or interstitial fibrosis/ tubular atrophy (IF/TA) did not impact graft function or survival. Compared to NR, ACR and IF/TA C4d⁻, patients with ABMR C4d⁺ had the worst graft survival over 3 years (p = 0.034), but there was no difference between ABMR versus NR, ACR and IF/TA that were C4d positive (p = 0.10). In Cox regression, graft function at biopsy and high %PRA levels were predictors of graft loss. CONCLUSIONS: This study confirmed that C4d staining in kidney graft biopsies is a clinically useful marker of ABMR, with well defined clinical and pathological correlations. The impact of C4d deposition in other histologic diagnoses deserves further investigation.

Clinical and pathological correlations of C4d immunostaining and its infl uence on the outcome of kidney transplant recipients / Correlações clinico-patológicas da marcação de C4d e sua influência na evolução de receptores de transplante renal

INTRODUCTION: C4d is a marker of antibody-mediated rejection (ABMR) in kidney allografts, although cellular rejection also have C4d deposits. OBJECTIVE: To correlate C4d expression with clinico-pathological parameters and graft outcomes at three years. METHODS: One hundred forty six renal transplantation recipients with graft biopsies by indication were included. C4d staining was performed by paraffin-immunohistochemistry. Graft function and survival were measured, and predictive variables of the outcome were determined by multivariate Cox regression. RESULTS: C4d staining was detected in 48 (31 percent) biopsies, of which 23 (14.7 percent) had diffuse and 25 (16 percent) focal distribution. Pre-transplantation panel reactive antibodies ( percentPRA) class I and II were significantly higher in C4d positive patients as compared to those C4d negative. Both glomerulitis and pericapillaritis were associated to C4d (p = 0.002 and p < 0.001, respectively). The presence of C4d in biopsies diagnosed as no rejection (NR), acute cellular rejection (ACR) or interstitial fibrosis/ tubular atrophy (IF/TA) did not impact graft function or survival. Compared to NR, ACR and IF/TA C4d-, patients with ABMR C4d+ had the worst graft survival over 3 years (p = 0.034), but there was no difference between ABMR versus NR, ACR and IF/TA that were C4d positive (p = 0.10). In Cox regression, graft function at biopsy and high percentPRA levels were predictors of graft loss. CONCLUSIONS: This study confirmed that C4d staining in kidney graft biopsies is a clinically useful marker of ABMR, with well defined clinical and pathological correlations. The impact of C4d deposition in other histologic diagnoses deserves further investigation.

INTRODUÇÃO: A fração do complemento C4d é um marcador de rejeição mediada por anticorpos (RMA) em aloenxertos renais, embora na rejeição celular também se observem depósitos de C4d. OBJETIVOS: Correlacionar a expressão de C4d com parâmetros clínicopatológicos e a evolução do enxerto renal em três anos. MÉTODOS: Foram incluídos 146 receptores de transplante renal com biópsias por indicação. A marcação de C4d foi feita por imuno-histoquímica em parafina. Foram medidas a função e a sobrevida do enxerto e determinadas as variáveis preditivas de sua evolução por meio de modelo de regressão de Cox. RESULTADOS: A marcação positiva para C4d foi detectada em 48 (31 por cento) biópsias, das quais 23 (14,7 por cento) tinham marcação difusa e 25 (16 por cento), focal. A reatividade contra painel ( por centoPRA) de classe I e II pré-transplante foi significativamente maior nos pacientes C4d+ quando comparada aos C4d-. Tanto glomerulite quanto pericapilarite foram associadas com C4d (p = 0,002 e p < 0,001, respectivamente). A presença de C4d em biópsias sem rejeição (SR), rejeição celular aguda (RCA) ou fibrose intersticial/atrofia tubular (FI/AT) não teve impacto na função ou na sobrevida do enxerto. Comparados a indivíduos com SR, RCA e FI/AT C4d-, pacientes com RMA C4d+ tiveram pior sobrevida do enxerto em 3 anos (p = 0,034), mas não houve diferença entre RMA versus SR, RCA e FI/AT C4d+ (p = 0,10). Na regressão de Cox, função do enxerto no momento da biópsia e por centoPRA alto foram preditores de perda do enxerto. CONCLUSÕES: A pesquisa de C4d em biópsias do enxerto renal é útil para identificar RMA, com correlações clínicopatológicas bem definidas. O impacto do C4d em outros diagnósticos histológicos necessita de investigação adicional.

Adipocyte morphometric evaluation and angiogenesis in the omentum transposed to the breast: a preliminary study.

OBJECTIVE: The purpose of this study was to describe the probable mechanism of the volume increase of laparoscopically harvested omentum flaps used to treat breast deformities. METHODS: A histological analysis of omentum samples was performed to study the volume increase of laparoscopically harvested omentum flaps. Samples were harvested immediately after the transposition of the omentum from the abdominal cavity to the breast region and during the second surgical procedure for breast symmetrization of eight patients submitted to the transposition of the omentum flap. Changes in the morphometric measurements of the adipocytes (perimeter, diameter, and area), microvascular density (as measured by the CD31 endothelial marker), and immunohistochemical expression of VEGF were documented. RESULTS: The increases in adipocyte size and microvascular density were statistically significant (P < 0.012). The expression levels of VEGF were lower in the second set of samples when compared to the first set, but the differences were not statistically significant (P < 0.093). CONCLUSION: These results demonstrate an increase in cellular volume as measured by adipocyte perimeter, diameter, and area. Moreover, the increase in the number of vessels in the second set of samples suggests that neoangiogenesis was stimulated by the initial increase in VEGF expression levels observed in the first set of samples. The increase in VEGF expression in the flap may have been caused by adipocyte hypertrophy resulting from neoangiogenesis.

Chlamydia trachomatis and human papillomavirus coinfection: association with p16INK4a and Ki67 expression in biopsies of patients with pre-neoplastic and neoplastic lesions.

The objective of this study was to identify the frequency of coinfection by human papillomavirus (HPV) and Chlamydia trachomatis (CT) in cervical lesions and relate it with immunohistochemical expression of p16INK4a and Ki67, both oncogenicity markers. A cross-sectional study with 86 women from primary care units in southern Brazil was conducted. Cervical swabs were collected for HPV-DNA and CT-DNA detection, through the polymerase chain reaction technique (PCR). The immunohistochemical analysis was performed on biopsy cervical tissue material to identify the expression of p16INK4a and Ki67 cell cycle markers. About 83 % were positive for HPV-DNA and 19% had coinfection with CT-DNA. Among coinfected women, 56% expressed p16INK4a. There was a statistically significant association between the histological grade of the lesion and Ki67 expression. All high-grade lesions, 50% of low-grade lesions and 31% of negative biopsies expressed Ki67 (p = 0.004). A total of 37% of coinfected women expressed both markers. In conclusion, although more than half of the coinfected patients have expressed p16INK4a and more than one third have expressed both markers, these results suggest no association between those variables. However, other studies involving larger samples are necessary to corroborate such findings.

Chlamydia trachomatis and human papillomavirus coinfection: association with p16INK4a and Ki67 expression in biopsies of patients with pre-neoplastic and neoplastic lesions

The objective of this study was to identify the frequency of coinfection by human papillomavirus (HPV) and Chlamydia trachomatis (CT) in cervical lesions and relate it with immunohistochemical expression of p16INK4a and Ki67, both oncogenicity markers. A cross-sectional study with 86 women from primary care units in southern Brazil was conducted. Cervical swabs were collected for HPV-DNA and CT-DNA detection, through the polymerase chain reaction technique (PCR). The immunohistochemical analysis was performed on biopsy cervical tissue material to identify the expression of p16INK4a and Ki67 cell cycle markers. About 83 percent were positive for HPV-DNA and 19 percent had coinfection with CT-DNA. Among coinfected women, 56 percent expressed p16INK4a. There was a statistically significant association between the histological grade of the lesion and Ki67 expression. All high-grade lesions, 50 percent of low-grade lesions and 31 percent of negative biopsies expressed Ki67 (p = 0.004). A total of 37 percent of coinfected women expressed both markers. In conclusion, although more than half of the coinfected patients have expressed p16INK4a and more than one third have expressed both markers, these results suggest no association between those variables. However, other studies involving larger samples are necessary to corroborate such findings.

Adipocyte morphometric evaluation and angiogenesis in the omentum transposed to the breast: a preliminary study

OBJECTIVE: The purpose of this study was to describe the probable mechanism of the volume increase of laparoscopically harvested omentum flaps used to treat breast deformities. METHODS: A histological analysis of omentum samples was performed to study the volume increase of laparoscopically harvested omentum flaps. Samples were harvested immediately after the transposition of the omentum from the abdominal cavity to the breast region and during the second surgical procedure for breast symmetrization of eight patients submitted to the transposition of the omentum flap. Changes in the morphometric measurements of the adipocytes (perimeter, diameter, and area), microvascular density (as measured by the CD31 endothelial marker), and immunohistochemical expression of VEGF were documented. RESULTS: The increases in adipocyte size and microvascular density were statistically significant (P < 0.012). The expression levels of VEGF were lower in the second set of samples when compared to the first set, but the differences were not statistically significant (P < 0.093). CONCLUSION: These results demonstrate an increase in cellular volume as measured by adipocyte perimeter, diameter, and area. Moreover, the increase in the number of vessels in the second set of samples suggests that neoangiogenesis was stimulated by the initial increase in VEGF expression levels observed in the first set of samples. The increase in VEGF expression in the flap may have been caused by adipocyte hypertrophy resulting from neoangiogenesis.

[Effects of gadolinium chloride on sodium taurocholate-induced pancreatitis in rats]. / Efeitos do cloreto de gadolínio na pancreatite induzida por tauracolato de sódio em ratos.

OBJECTIVE: To evaluate the effects of the use of gadolinium chloride before and after induction of acute pancreatitis with sodium taurocholate 3% in rats. METHODS: Wistar rats were divided into five groups: SF--control with saline intra-ductal and IV; GD control with saline intra-ductal and gadolinium chloride IV; TS--with AP control induced by sodium taurocholate 3% and saline IV; GDTS--pre-treatment with GD (24 hours before the induction of AP) and TSGD--treatment with GD (1 hour after the induction of AP). Analysis was made in serum amylase, transaminases and TNF-α; determination of the MPO activity in lung tissue, lung and pancreatic histology. RESULTS: The number of dead animals before the end of the experiment was significantly higher in TSGD (P = 0.046). The scores of pancreatitis and lung damage were higher in the groups that used sodium taurocholate compared to groups with intra-ductal infusion of saline solution. There were no differences in other variables studied when comparing TS, GDTS and TSGD groups. CONCLUSION: The benefits with the use of gadolinium chloride as a prophylactic and therapeutic drug were not demonstrated.

Efeitos do cloreto de gadolínio na pancreatite induzida por tauracolato de sódio em ratos / Effects of gadolinium chloride on sodium taurocholate-induced pancreatitis in rats

OBJETIVO: Avaliar os efeitos do uso de cloreto de gadolínio como pré-tratamento e tratamento em um modelo experimental de pancreatite em ratos induzida por tauracolato de sódio a 3 por cento. MÉTODOS: Ratos Wistar foram divididos em cinco grupos: grupo SF - controle com solução fisiológica intra-ductal e IV; grupo TS - controle com PA induzida por tauracolato de sódio a 3 por cento e solução fisiológica a 0,9 por cento IV; grupo GD - controle com SF intra-ductal e cloreto de gadolínio IV; grupo GDTS - pré-tratamento com GD (24h antes da indução da PA) e grupo TSGD - tratamento com GD (1h após a indução da PA). Foi realizado dosagem sérica de amilase, transaminases e TNF-á; determinação da atividade da MPO no tecido pulmonar; histologia pancreática e pulmonar. RESULTADOS: O número de animais mortos antes do término previsto do experimento foi significativamente maior no grupo TSGD (p=0,046). Os escores de pancreatite e de dano pulmonar foram mais elevados nos grupos que utilizaram tauracolato em comparação aos grupos com infusão intra-ductal de solução salina. Não houve diferenças nas demais variáveis estudadas na comparação entre os grupos TS; GDTS e TSGD. CONCLUSÃO: Não foram demonstrados benefícios com o uso de cloreto de gadolínio de forma profilática e terapêutica.

OBJECTIVE: To evaluate the effects of the use of gadolinium chloride before and after induction of acute pancreatitis with sodium taurocholate 3 percent in rats. METHODS: Wistar rats were divided into five groups: SF - control with saline intra-ductal and IV; GD control with saline intra-ductal and gadolinium chloride IV; TS - with AP control induced by sodium taurocholate 3 percent and saline IV; GDTS - pre-treatment with GD (24 hours before the induction of AP) and TSGD - treatment with GD (1 hour after the induction of AP). Analysis was made in serum amylase, transaminases and TNF-á; determination of the MPO activity in lung tissue, lung and pancreatic histology. RESULTS: The number of dead animals before the end of the experiment was significantly higher in TSGD (P = 0.046). The scores of pancreatitis and lung damage were higher in the groups that used sodium taurocholate compared to groups with intra-ductal infusion of saline solution. There were no differences in other variables studied when comparing TS, GDTS and TSGD groups. CONCLUSION: The benefits with the use of gadolinium chloride as a prophylactic and therapeutic drug were not demonstrated.

Reproducibility of three classification systems of ductal carcinoma in situ of the breast using a web-based survey.

This study assessed the degree of diagnostic agreement among pathologists between three classification systems of ductal carcinoma in situ of the breast (DCIS). Thirteen pathologists received the same set of digitized images of microscopy of 43 DCIS cases and answered a questionnaire containing the criteria to compose the three classification systems studied: Holland, modified Lagios, and Van Nuys. A computer program was created, which organizes the information collected from each pathologist, supplying the histological grading of the cases within the three classification systems. The results were analyzed using percental agreement and the Kappa test. Diagnostic agreement for the three DCIS of the breast classification systems presented K values that varied from 0.27 to 0.37. Among the three classifications used, most agreement was for Van Nuys, showing a Kappa index of 0.37. These results matched the interobserver agreements, with Kappa indices varying from 0.13 to 0.64 for the Holland classification; 0.23 to 0.61 for the modified Lagios classification; and 0.23 to 0.74 for the Van Nuys classification. Pathologists specialized in breast pathology showed greater reproducibility for all the criteria evaluated. Comparing the three classification systems, diagnostic agreement and accuracy were rated higher for the classification of Van Nuys compared to modified Lagios and Holland.

Laparoscopic treatment of Poland's syndrome using the omentum flap technique.

OBJECTIVE: For patients with Poland's syndrome, a transverse skin fold in the anterior axillary pillar, infra-clavicular depression and an anomalous breast contour are the most uncomfortable disfigurements. This study aims to demonstrate that superior aesthetic results can be achieved by using a laparoscopically harvested omentum flap to treat this condition. METHODS: From a prospectively maintained clinical database of patients undergoing a laparoscopic omentum flap procedure for breast reconstruction, all of the patients with Poland's syndrome were identified and their outcomes were studied. RESULTS: Thirteen consecutive patients with Poland's syndrome were treated and evaluated regarding breast contour, reconstruction of the anterior axillary pillar and filling of the infra-clavicular depression. Implants were employed beneath the flap in 76% of cases to improve symmetry. In 23% of cases, a contra-lateral mastopexy was performed, and in 15% of cases, a breast implant was used. The consistency of the flap is similar to natural breast tissue and only a small incision in the breast fold is needed. The majority of patients (85%) were female, with a mean age of 26 (18-53). The flap is extremely malleable, adapts to irregular surfaces, and has a long vascular pedicle. Additionally, its removal does not leave a scar at the donor site as the removal of muscular flaps does. For example, the removal of the latissimus dorsi flap causes a deformity in the dorsal contour. The mean operative time was 201 minutes (80-350) and the mean hospital stay was 2.3 days (1-5). CONCLUSIONS: The outcomes of these patients revealed that the omentum flap technique provided superior amelioration of the deformities caused by Poland's syndrome when compared with other reconstructive options.

Aesthetic improvements in Poland's syndrome treatment with omentum flap.

BACKGROUND: There are many techniques that can be used to reconstruct anomalous breast volume in Poland's syndrome, but repair of the stigmatizing deformities such as the transverse skin fold in the anterior axillary pillar, infraclavicular depression, and anomalous breast contours continues to be a challenge. This study aimed to demonstrate the superior results of laparoscopically harvested omentum flap to achieve these aesthetic improvements. METHODS: Patients with Poland's syndrome from a clinical database were identified and their outcomes were studied. RESULTS: In 15 consecutive patients with Poland's syndrome, the breast contour, the anterior axillary pillar, and the infraclavicular depression were treated with omentum flap and evaluated. Silicone implants were used beneath the flap in 80% of cases to improve symmetry. Flap consistency was similar to that of the natural breast and only a small incision in the breast fold was needed. The flap is extremely malleable, adapts to irregular surfaces, and has a long vascular pedicle. It does not leave a scar at the donor site as muscular flaps do. The omentum can repair small irregularities in breast contour, achieving a natural result different from all other flaps. Due to its malleability, it is possible to reconstruct even the extension to the axillary pillar, which is impossible with all other techniques. CONCLUSIONS: The omentum flap technique is a means of repairing the deformities caused by Poland's syndrome and improves the aesthetic result with outcomes that seem superior to any other reconstructive option.

A proteína p16 e o melanoma cutâneo / P16 protein and cutaneous malignant melanoma

Nas últimas décadas, é intensa a procura de uma explicação genética sobre a origem, o crescimento e a progressão do melanoma cutâneo. A tentativa de encontrar uma ligação direta entre as mutações gênicas e a origem da doença tem sido o objetivo dos pesquisadores dedicados ao estudo dessa neoplasia. Diversos métodos são utilizados na busca de uma avaliação prognóstica para a progressão do melanoma, citando-se, entre eles, a pesquisa do linfonodo sentinela, a imuno-histoquímica, as técnicas moleculares e a técnica de microarray. A necessidade de estabelecer um método, com excelente sensibilidade e especificidade, tem levado os pesquisadores a buscarem melhores evidências. É importante para esses estudos a obtenção de dados confiáveis sobre as técnicas, progressão e sobrevida livre de doença. Por meio da imuno-histoquímica, técnica relativamente simples e de baixo custo, a expressão da proteína p16 pode ser analisada e correlacionada com o prognóstico da doença. No melanoma cutâneo, a expressão da proteína diminui, à medida que aumenta sua agressividade, ou seja, é forte nos nevos e melanomas in situ e fraca ou ausente nos melanomas metastáticos. Em alguns estudos, a comparação com outros marcadores é analisada. A finalidade deste estudo é fazer uma revisão da literatura internacional sobre o uso da proteína p16 como fator prognóstico para o melanoma, bem como avaliar a importância das alterações do gene p16INK4a, corresponsáveis pela gênese e evolução do melanoma

In the last decades there has been an intense search for a genetic explanation of the origin, growth and progression of cutaneous melanoma. The attempt to find a direct link between gene mutations and the root of the disorder has been the aim of researchers devoted to the study of this neoplasia. Many are the methods used in the search of a prognostic evaluation for the progression of melanoma, e.g. research on the sentinel lymph node, immunohistochemistry, molecular techniques and the microarray technique. The need for a method with optimal sensitivity and specificity has led researchers to search for better evidence. For these studies it is important to obtain reliable data on the techniques, progression and survival free of disease. By means of immunohistochemistry, which is a relatively simple, low cost technique, the p16 protein expression can be assessed and correlated with disease prognosis. In cutaneous melanoma, p16 expression decreases as its aggressiveness increases, i.e. it is strong in the nevi and melanomas in situ and weak or absent in the metastatic melanomas. Other studies have analyzed how it compares with other markers. The purpose of this study is to make a review of the international literature on the use of p16 protein as a prognostic factor for melanoma, as well as to evaluate the importance of alterations in the p16INK4a gene, co-responsible for the genesis and progress of melanoma

Laparoscopic treatment of Poland's syndrome using the omentum flap technique

OBJECTIVE: For patients with Poland's syndrome, a transverse skin fold in the anterior axillary pillar, infra-clavicular depression and an anomalous breast contour are the most uncomfortable disfigurements. This study aims to demonstrate that superior aesthetic results can be achieved by using a laparoscopically harvested omentum flap to treat this condition. METHODS: From a prospectively maintained clinical database of patients undergoing a laparoscopic omentum flap procedure for breast reconstruction, all of the patients with Poland's syndrome were identified and their outcomes were studied. RESULTS: Thirteen consecutive patients with Poland's syndrome were treated and evaluated regarding breast contour, reconstruction of the anterior axillary pillar and filling of the infra-clavicular depression. Implants were employed beneath the flap in 76 percent of cases to improve symmetry. In 23 percent of cases, a contra-lateral mastopexy was performed, and in 15 percent of cases, a breast implant was used. The consistency of the flap is similar to natural breast tissue and only a small incision in the breast fold is needed. The majority of patients (85 percent) were female, with a mean age of 26 (18-53). The flap is extremely malleable, adapts to irregular surfaces, and has a long vascular pedicle. Additionally, its removal does not leave a scar at the donor site as the removal of muscular flaps does. For example, the removal of the latissimus dorsi flap causes a deformity in the dorsal contour. The mean operative time was 201 minutes (80-350) and the mean hospital stay was 2.3 days (1-5). CONCLUSIONS: The outcomes of these patients revealed that the omentum flap technique provided superior amelioration of the deformities caused by Poland's syndrome when compared with other reconstructive options.

Immunohistochemical evaluation for P53 and VEGF (Vascular Endothelial Growth Factor) is not prognostic for long term survival in end stage esophageal adenocarcinoma / Avaliação imunoistoquímica do P53 e VEGF (Fator de Crescimetno Endotelial Vascular) não representa fator prognóstico para sobrevida a longo prazo na fase terminal do adenocarcinoma do esôfago

OBJECTIVES: To correlate the expression of p53 protein and VEGF with the prognosis of patients submitted to curative resection to treat esophageal adenocarcinoma. METHODS: Forty-six patients with esophageal adenocarcinoma, submitted to curative resection, were studied. The expressions of p53 protein and VEGF were assessed by immunohistochemistry in 52.2 percent and 47.8 percent of tumors, respectively. RESULTS: P53 protein and VEGF expressions coincided in 26 percent of the cases, and no correlation between these expressions was observed. None of the clinicopathological factors showed a significant correlation with p53 protein or VEGF expressions. There was no significant association between p53 protein and VEGF expressions and long-term survival. CONCLUSION: The expression of p53 protein and VEGF did not correlate with prognosis in esophageal adenocarcinoma patients submitted to curative resection.

OBJETIVO: Correlacionar a expressão do p53 e VEGF com o prognóstico de pacientes submetidos à operação curativa para tratar adenocarcinoma do esôfago. MÉTODO: Foram estudados 46 pacientes com adenocarcinoma de esôfago, submetidos à ressecções curativas. As expressões do p53 e VEGF foram assessadas por imunoistoquímica em 52.2 por cento e 47.8 por cento dos tumors, respectivamente . RESULTADOS: As expressões de ambos coincidiram em 26 por cento dos casos sem correlação entre elas. Os fatores clinicopatológicos estudados não mostraram correlação significante. Não houve associação significante entre as expresses do p53 e VEGF na sobrevida a longo prazo. CONCLUSÃO: As expressões do p53 e VEGF não se correlacionaram com o prognóstico do adenocarcinoma do esôfago nos pacientes operados com ressecções curativas.