Should obesity be associated with worse urinary continence outcomes after robotic-assisted radical prostatectomy? a propensity score matching analysis.

PURPOSE: To analyze the association between obesity and urinary incontinence rate in men submitted to robot-assisted radical prostatectomy (RARP) in a high-volume cancer center. MATERIALS AND METHODS: We reported 1.077 men who underwent RARP as the primary treatment for localized prostate cancer from 2013 to 2017. Patients were classified as non-obese (normal BMI or overweight) or obese men (BMI ≥30kg/m2). They were grouped according to the age, PSA level, D'Amico risk group, Gleason score, ASA classification, pathological stage, prostate volume, salvage/adjuvant radiotherapy, perioperative complications, and follow-up time. Urinary continence was defined as the use of no pads. For the analysis of long-term urinary continence recovery, we conducted a 1:1 propensity-score matching to control confounders. RESULTS: Among the obese patients, mean BMI was 32.8kg/m2, ranging 30 - 45.7kg/m2. Only 2% was morbidly obese. Obese presented more comorbidities and larger prostates. Median follow-up time was 15 months for the obese. Complications classified as Clavien ≥3 were reported in 5.6% of the obese and in 4.4% of the non-obese men (p=0.423). Median time for continence recovery was 4 months in both groups. In this analysis, HR was 0.989 for urinary continence recovery in obese (95%CI=0.789 - 1.240; p=0.927). CONCLUSIONS: Obese can safely undergo RARP with similar continence outcomes comparing to the non-obese men when performed by surgeons with a standardized operative technique. Future studies should perform a subgroup analysis regarding the association of obesity with other comorbidities, intending to optimize patient counseling.

Prostate Cancer Screening in Brazil: a single center experience in the public health system.

PURPOSE: Incidence and mortality of prostate cancer (PCa) are still increasing in developing countries. Limited access to the health system or more aggressive disease are potential reasons for this. Ethnic and social differences in developed countries seem to make inappropriate to extrapolate data from other centers. We aim to report the epidemiological profile of a PSA-screened population from a cancer center in Brazil. MATERIALS AND METHODS: We retrospectively selected 9.692 men enrolled in a PCa prevention program, comprising total PSA level and digital rectal examination at the first appointment, associated with complementary tests when necessary. Men aged over 40 years-old were included after shared decision-making process. Prostate biopsy (TRUS) was performed when clinically suspected for PCa. After the diagnosis, patients underwent appropriate treatment. RESULTS: TRUS was performed in 5.5% of men and PCa incidence was 2.6%. Overall ratio between number of patients who needed to be screened in order to diagnose one cancer was 38.9 patients, with 2.1 biopsies performed to diagnose a cancer. Positive predictive value (PPV) of TRUS biopsy in this strategy was 47.2%, varying from 38.5% (<50 years-old) to 60% (>80 years-old). We evidenced 70 patients (27.9%) classified as low risk tumors, 74 (29.5%) as intermediate risk, and 107 (42.6%) as high-risk disease. CONCLUSIONS: PSA-screening remains controversial in literature. In front of a huge miscegenated people and considering the big proportion of high-risk PCa, even in young men diagnosed with the disease, it is imperative to inform patients and health providers about these data particularities in Brazil.

Does histologic type correlate to outcome after pelvic exenteration for cervical and vaginal cancer?

BACKGROUND: Adenocarcinoma (AC) of the cervix comprises 15-20 % of all cervical carcinomas, and data regarding the prognostic value of histologic type after pelvic exenteration (PE) are lacking. Our aim was to analyze the prognostic value of histologic type in overall survival (OS) and disease-specific survival (DSS) after PE and correlate it to clinical and pathologic variables. METHODS: We reviewed a series of 77 individuals who underwent PE for cervical or vaginal cancer from January 1980 to December 2010. RESULTS: Mean age was 54.5 years. Fifty-three patients (68.9 %) had cervical and 24 (31.1 %) vaginal cancer. Fifty-six (72.7 %) were squamous cell carcinoma (SCC) and 21 (27.3 %) ACs. We performed 42 (54.5 %) total, 18 anterior, 8 posterior, and 9 lateral extended PE. Median tumor size was 5 cm. Surgical margins were negative in 91.7 % of cases. Median operative time, length of hospital stay, and blood transfusion volume were, respectively, 420 (range 180-720) mins, 13.5 (range 4-79) days, and 900 (range 300-3900) ml. Median follow-up was 13.7 (range 1.09-114.3) months. SCC statistically correlated with presence of perineural invasion (p = 0.004). Five-year OS and DSS were, respectively, 24.4 and 37.1 %. SCC (p = 0.003) and grade 3 (p = 0.001) negatively affected OS in univariate analysis. SCC (p = 0.006), grade 3 (p = 0.003), perineural invasion (p = 0.03), lymph node metastasis (p = 0.02), and positive margins (p = 0.04) negatively affected DSS in univariate analysis. SCC and grade 3 retained the higher risk of death (OS and DSS) in multivariate analysis. CONCLUSIONS: AC histology in cervical and vaginal cancer is associated with better outcome after PE compared to SCC.

Intraoperative ultrasound for benign cystic teratoma. Report of two cases.

PURPOSE: Teratoma is one of the most common ovarian neoplasms and frequently leads to laparoscopic surgical procedure. When this tumor is small and the ovarian surface seems regular during the surgery, it is difficult to localize the tumor. METHODS: We used a standard transvaginal ultrasound probe during the procedure and filled the pelvic cavity with saline solution of 0.9% in order to create an interface between the saline solution and the surgical instruments. RESULTS: We could localize the teratoma with confidence and precision, allowing to perform a sparing surgery. CONCLUSION: This is a simple, secure and efficient technique that can be performed in most of the institutions.

Conservative management of extramammary paget disease with imiquimod.

OBJECTIVE: Extramammary Paget disease is a rare cutaneous neoplasm that most frequently affects the vulva. Surgery remains the preferred treatment, despite its association with high recurrence rates. Few reports have described conservative treatments for vulvar Paget disease. Our aim was to evaluate the efficacy of conservative treatment with imiquimod. MATERIALS AND METHODS: We performed a retrospective analysis of 4 patients who were treated with topical imiquimod 5% cream. RESULTS: One patient underwent vulvectomy after imiquimod therapy, and 3 patients experienced extensive recurrent disease that was unsuitable for surgical resection and were treated successfully with imiquimod. CONCLUSIONS: Imiquimod is an effective therapeutic agent for the conservative treatment of vulvar Paget disease.

Epidemiology of Urological Cancers in Brazil: Trends in Mortality Rates Over More Than Two Decades.

BACKGROUND: Considering the socioeconomic disparities and inequalities observed in the healthcare resources among the Brazilian regions, we aimed to analyze the mortality trends of urological cancers in Brazil to identify areas with differential risks. METHODS: Deaths related to prostate (PCa), bladder (BCa), kidney (KC), penile (PeC), and testis (TCa) cancers from 1996 to 2019 were retrieved from the Mortality Information System database (Brazil). Geographic and temporal patterns were analyzed using age-standardized mortality rates (ASMRs). A joinpoint regression model was used to identify changes in the trends and calculate the average annual percentage change (AAPC) for each region. RESULTS: In Brazil, the ASMRs (per 100,000 persons/year) were 11.76 for PCa; 1.37, BCa; 1.13, KC; 0.33, and PeC; 0.26, TCa over the period. Increasing mortality trends were registered for BCa (AAPC = 0.45 in men; 0.57 in women), KC (AAPC = 2.03 in men), PeC (AAPC = 1.01), and TCa (AAPC = 2.06). The PCa mortality presented a significant reduction after 2006. The Northeast and North regions showed the highest increases in the PCa mortality. The South registered the highest ASMRs for BCa and KC, but the highest increasing trends occurred in the men from the Northeast. The North presented the highest ASMR for PeC, while the South registered the highest ASMR for TCa. CONCLUSION: Differences among regions may be partly explained by disparities in the healthcare systems. Over the study period, the North and Northeast regions presented more discrepant mortality rates. Efforts should be made to ensure access to the healthcare resources for people at risk, particularly in these regions.

Surgical implications of mesenteric lymph node metastasis from advanced ovarian cancer after bowel resection.

BACKGROUND: Studies addressing mesenteric and mesocolic lymph node metastasis in patients with advanced ovarian cancer that have undergone bowel resection are lacking. METHODS: A retrospective analysis was performed in a series of 50 individuals who underwent surgical cytoreduction for epithelial ovarian cancer that included bowel resection from April 2004 to September 2010. RESULTS: Forty-one patients had bowel resection with mesenteric lymph nodes that were suitable for analysis. Twenty-four (58.5%) patients underwent retosigmoidectomies, 14 (34.1%) received other types of colectomies, and three (7.3%) underwent small bowel resection. There was serosal involvement in 14 cases (34.1%), muscularis propria invasion in 13 cases (31.7%), submucosa invasion in six cases (14.6%), and mucosa in eight cases (19.5%). Lymphatic invasion was observed in 24 patients (58.5%). A median of 14 mesenteric lymph nodes were analyzed. Metastatic lymph nodes were observed in 29 (70.7%) cases. Invasion into the muscularis propria (P = 0.036), lymphatic invasion (P = 0.045), and retroperitoneal lymph node metastasis (P = 0.002) correlated significantly with mesenteric lymph node involvement. CONCLUSIONS: Resection of regional lymph nodes of affected organs that is similar to surgical procedures that are performed for colorectal carcinoma is an appropriate, optimal debulking surgery for patients with ovarian carcinoma.

Pelvic Pseudoaneurysm as a Cause of Severe Hematuria After Robotic-assisted Radical Prostatectomy.

OBJECTIVE: To alert the medical society regarding that hematuria after radical prostatectomy can be caused by pelvic pseudoaneurysm. METHODS: Case report of a 61-year-old male underwent extraperitoneal robotic-assisted radical prostatectomy. He was readmitted on the 15th POD due to gross hematuria with resolution after bladder irrigation. It returned on the 21st POD. RESULTS: The CT angiography evidenced the pseudoaneurysm of the left internal iliac artery. Selective embolization was effectively performed, with no additional bleeding or pelvic ischemia. Endovascular therapy is the preferred method of treatment. CONCLUSION: The pelvic pseudoaneurysm is a rare, but serious complication that can cause severe bleeding. In our experience, we had 3 cases of persistent hematuria caused by pelvic pseudoaneurysm after 1810 robotic-assisted radical prostatectomy.

Cost-effectiveness analysis of robotic-assisted versus retropubic radical prostatectomy: a single cancer center experience.

Prostate cancer (PCa) treatment has been greatly impacted by the robotic surgery. The economics literature about PCa is scarce. We aim to carry-out cost-effectiveness and cost-utility analyses of the robotic-assisted radical prostatectomy (RALP) using the "time-driven activity-based cost" methodology. Patients who underwent radical prostatectomy in 2013 were retrospectively analyzed in a cancer center over a 5-year period. Fifty-six patients underwent RALP and 149 patients underwent retropubic radical prostatectomy (RRP). The amounts were subject to a 5% discount as correction of monetary value considering time elapsed. Calculation of the Incremental Cost-Effectiveness Ratios (ICER) related to events avoided and the Incremental Cost-Utility Ratio (ICUR) related to "QALY saved" were performed. QALY was performed using values of utility and "disutility" weights from the "Cost-Effectiveness Analysis Registry". Hypothetical cohorts were simulated with 1000 patients in each group, based on the treatment outcomes. Total and average costs were R$1,903,671.93, and R$12,776.32 for the RRP group, and R$1,373,987.26, and R$24,535.49 for the RALP group, respectively. The costs to treat the hypothetical cohorts were R$10,010,582.35 for RRP, and R$19,224,195.90 for RALP. ICER calculation evidenced R$9,213,613.55 of difference between groups. ICUR was R$ 22,690.83 per QALY saved. Limitations were the lack of cost-effectiveness analyses related to re-hospitalization rates and complications, single center perspective, and currency-translation differences. Medical fees were not included. RALP showed advantages in cost-effectiveness and cost-utility over RRP in the long term. Despite the increased costs to the introduction of robotic technology, its adoption should be encouraged due to the gains.

Cost-Effectiveness Analysis of Prostate Cancer Screening in Brazil.

INTRODUCTION: Prostate cancer is one of the most common malignancies among men worldwide. Prostate-specific antigen (PSA) screening shows uncertain benefits and harms from clinical and economic perspectives, resulting in an important impact on healthcare systems. Because of nonstandardized studies and substantial differences among populations, data are still inconclusive. OBJECTIVE: The objective of this study was to carry out long-term cost-effectiveness and cost-utility analysis on the PSA-screened population from the service provider's perspective in the Brazilian population. METHODS: We performed a cost-effectiveness and cost-utility analysis using clinical outcomes obtained from 9692 men enrolled in the PSA screening program. Prostate cancer treatments, 5-year follow-up outcomes, and all related costs were examined. Data were compared with a nonscreened prostate cancer population to calculate incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR). ICER and ICUR were compared with the Brazilian-established willingness-to-pay (WTP) threshold (WTP = R$ 114 026.55). RESULTS: A total of 251 of 9692 men had a diagnosis of prostate cancer (2.6%), of which 90% had localized disease. Two hundred and five patients were treated as follows: surgery (45.37%); radiation therapy (11.22%); radiation plus androgen deprivation therapy (21.95%); active surveillance (13.17%); exclusive androgen deprivation therapy (7.32%); and watchful waiting (0.98%). Two simulated cohorts were compared based on screening and nonscreening groups. Values obtained were-ICER of R$ 44 491.39 per life saved and ICUR of R$ 10 851.56 per quality-adjusted life year (QALY) gained-below the Brazilian WTP threshold and showed cost-effectiveness and cost-utility advantages. CONCLUSION: According to the Brazilian WTP, PSA screening is a cost-effective policy from a hospital and long-term perspective and should have more standardized studies developed in different populations and economies.

Comparative Analysis of Functional Outcomes Between Two Different Techniques After 1088 Robotic-Assisted Radical Prostatectomies in a High-Volume Cancer Center: A Clipless Approach.

Introduction: Robotic-Assisted Radical Prostatectomy (RARP) has largely replaced the open technique worldwide as the first surgical modality for prostate cancer. We aim at describing the experience of RARP at a high-volume single cancer center, proposing a modified technique of nerve-sparing prostatectomy and comparing functional outcomes throughout our experience. Materials and Methods: We retrospectively reviewed 1088 patients divided into group 1 (operated from May 2013 to November 2014), submitted to the standard transperitoneal robotic technique, and group 2 (operated from December 2014 to December 2017), submitted to extraperitoneal RARP with complete anterior peri-prostatic preservation technique and a clipless approach (no use of clips and cautious use of bipolar energy). We constructed a retrospective 1:2 matched-pair analysis considering age, body mass index, D'Amico risk classification, and American Society of Anesthesiologists classification as matching criteria. Univariate and multivariate Cox logistic regression analysis were used to identify predictors related to recovery of continence and erectile function. Results: Groups were comparable by clinical and demographic variables. There was no significant difference in overall continence rate. Mean time for continence recovery was 6.6 months in group 1 and 5.8 months in group 2. Erectile function recovery, with or without drugs, in 12 months was described in 53.5% in group 1 and 75% in group 2. Potency recovery was significantly earlier in group 2. Conclusions: In our experience, extraperitoneal RARP with complete anterior peri-prostatic preservation and a clipless approach is a feasible and reproducible technique. It demonstrated improved erectile function recovery and similar continence results. Prospective multicenter studies are needed to validate these results.

Should obesity be associated with worse urinary continence outcomes after robotic-assisted radical prostatectomy? a propensity score matching analysis

ABSTRACT Purpose: To analyze the association between obesity and urinary incontinence rate in men submitted to robot-assisted radical prostatectomy (RARP) in a high-volume cancer center. Materials and Methods: We reported 1.077 men who underwent RARP as the primary treatment for localized prostate cancer from 2013 to 2017. Patients were classified as non-obese (normal BMI or overweight) or obese men (BMI ≥30kg/m2). They were grouped according to the age, PSA level, D'Amico risk group, Gleason score, ASA classification, pathological stage, prostate volume, salvage/adjuvant radiotherapy, perioperative complications, and follow-up time. Urinary continence was defined as the use of no pads. For the analysis of long-term urinary continence recovery, we conducted a 1:1 propensity-score matching to control confounders. Results: Among the obese patients, mean BMI was 32.8kg/m2, ranging 30 - 45.7kg/m2. Only 2% was morbidly obese. Obese presented more comorbidities and larger prostates. Median follow-up time was 15 months for the obese. Complications classified as Clavien ≥3 were reported in 5.6% of the obese and in 4.4% of the non-obese men (p=0.423). Median time for continence recovery was 4 months in both groups. In this analysis, HR was 0.989 for urinary continence recovery in obese (95%CI=0.789 - 1.240; p=0.927). Conclusions: Obese can safely undergo RARP with similar continence outcomes comparing to the non-obese men when performed by surgeons with a standardized operative technique. Future studies should perform a subgroup analysis regarding the association of obesity with other comorbidities, intending to optimize patient counseling.

Prostate Cancer Screening in Brazil: a single center experience in the public health system

ABSTRACT Purpose: Incidence and mortality of prostate cancer (PCa) are still increasing in developing countries. Limited access to the health system or more aggressive disease are potential reasons for this. Ethnic and social differences in developed countries seem to make inappropriate to extrapolate data from other centers. We aim to report the epidemiological profile of a PSA-screened population from a cancer center in Brazil. Materials and Methods: We retrospectively selected 9.692 men enrolled in a PCa prevention program, comprising total PSA level and digital rectal examination at the first appointment, associated with complementary tests when necessary. Men aged over 40 years-old were included after shared decision-making process. Prostate biopsy (TRUS) was performed when clinically suspected for PCa. After the diagnosis, patients underwent appropriate treatment. Results: TRUS was performed in 5.5% of men and PCa incidence was 2.6%. Overall ratio between number of patients who needed to be screened in order to diagnose one cancer was 38.9 patients, with 2.1 biopsies performed to diagnose a cancer. Positive predictive value (PPV) of TRUS biopsy in this strategy was 47.2%, varying from 38.5% (<50 years-old) to 60% (>80 years-old). We evidenced 70 patients (27.9%) classified as low risk tumors, 74 (29.5%) as intermediate risk, and 107 (42.6%) as high-risk disease. Conclusions: PSA-screening remains controversial in literature. In front of a huge miscegenated people and considering the big proportion of high-risk PCa, even in young men diagnosed with the disease, it is imperative to inform patients and health providers about these data particularities in Brazil.

Prognostic value of nuclear factor κ B expression in patients with advanced cervical cancer undergoing radiation therapy followed by hysterectomy.

AIMS: The nuclear factor κ B (NF-κB) family comprises transcription factors that promote the development and progression of cancer. The NF-κB pathway is induced by radiation therapy and may be related to tumour radioresistance. The aim of this study was to evaluate the expression of NF-κB as a predictor of the response to radiotherapy and its value as a prognostic marker. METHODS: A retrospective analysis was performed in a series of 32 individuals with stage IB2 and IIB cervical cancer who underwent radiotherapy, followed by radical hysterectomy, from January 1992 to June 2001. NF-κB-p65 and NF-κB-p50 expression was examined by immunohistochemistry in biopsies from all patients before radiotherapy and in 12 patients with residual tumours after radiotherapy. RESULTS: 16 (50%) patients had residual disease after radical hysterectomy. The median follow-up time was 73.5 months, and the 5-year overall survival was 66.5%. Before radiotherapy, cytoplasmic expression of NF-κB-p65 and NF-κB-p50 was noted in 91% and 97% of cases, respectively, versus 59% of cases with nuclear expression of these subunits. Cytoplasmic expression of NF-κB-p65 and NF-κB-p50 in the residual tumours after radiotherapy was observed in 50% of cases; 75% of cases with residual tumours had nuclear expression of NF-κB-p50 versus none with NF-κB-p65. NF-κB-p65 and NF-κB-p50 did not correlate with the risk of residual tumours after radiotherapy or recurrence or death. CONCLUSIONS: These data suggest that NF-κB does not predict the response to radiotherapy and does not correlate with poor outcomes in advanced cervical cancer.

Análise da custo-efetividade do rastreamento e das modalidades terapêuticas do câncer de próstata / Cost-effectiveness analysis of prostate cancer screening and therapeutic modalities

O câncer de próstata é a segunda neoplasia maligna mais comum no mundo. Apesar do emprego do rastreamento populacional com o uso do PSA (Prostate specific antigen) ter proporcionado diminuição na mortalidade pela doença, sua validade tem sido questionada em alguns grandes estudos. A da falta de políticas de prevenção efetivas e de dados brasileiros sobre o comportamento do câncer de próstata desfavorecem a análise sobre a realidade dessa população. As opções terapêuticas curativas para o câncer de próstata em seus estágios iniciais incluem a prostatectomia radical, radioterapia, ablação prostática com ultrassom de alta frequência (HIFU), todas elas relacionadas a complicações e sequelas funcionais, as quais podem ser diminuídas com o uso de técnicas minimamente invasivas, porém acarretando impacto no aumento de custos das fontes pagadoras. O presente estudo analisa a relação custoefetividade de um programa de rastreamento populacional de câncer de próstata na cidade de São Paulo (SP ­ Brasil), bem como custo-efetividade das cirurgias (aberta e robótica); a relação de custo minimização entre radioterapia e terapia ablativa (HIFU), e os custos de hormonioterapia, quimioterapia e outras terapias sistêmicas paliativas realizadas no A.C.Camargo Cancer Center entre os anos de 2013 e 2018. A análise dos resultados demonstrou que o rastreamento populacional e a prostatectomia radical robótica são custo-efetivas em relação ao não rastreamento e à prostatectomia aberta, segundo os padrões de cálculo estabelecidos pela OMS (AU)

Prostate cancer is the second most common malignancy in the world. Despite of prostate specific antigen (PSA) based population screening had shown mortality reduction, its validity has been questioned in some large studies. The lack of effective Brazilian prevention policies and data on prostate cancer behavior undermine a population's reality analysis. Curative treatment options for initial prostate cancer include radical prostatectomy, radiotherapy and high frequency ultrasound prostate ablation (HIFU), all of them related to complications and functional sequelae, which can be diminished by using minimally invasive techniques, however, affecting the rising costs of paying sources. This study analyzes the cost-effectiveness of a prostate cancer population screening program in the city of São Paulo (SP - Brazil), as well as the cost-effectiveness of surgeries (open and robotic approaches); a minimized-cost relationship between radiotherapy and ablative therapy (HIFU), and general costs of hormone therapy, chemotherapy and other palliative systemic therapies performed at the A.C.Camargo Cancer Center between 2013 and 2018. Results demonstrated that PSA based population screening and Robotic radical prostatectomy are cost-effective compared to not-screening population and open prostatectomy, according to WHO calculation standards (AU)

Análise imunoistoquímica das vias Notch, WNT e NF-KB em carcinoma epidermóide e lesões precursoras do colo uterino / Immunohistochemical analysis of Notch, WNT and NF-KB pathways in squamous cell carcinoma and precursor lesions of the cervix

O câncer do colo do útero é um importante problema de saúde em todo o mundo, principalmente nos países em desenvolvimento. A análise dos mecanismos das múltiplas etapas da carcinogênese do colo do útero propiciou melhor compreensão das vias de sinalização intracelulares alteradas na evolução das lesões intraepiteliais (LIEs) para o carcinoma invasivo. A interação das proteínas E6 e E7 do HPV de alto risco com vias de sinalização do NOTCH, NF-kB e WNT parece constituir uma importante via carcinogênica no colo do útero. Estudos recentes demonstram interação entre tais vias no desenvolvimento de neoplasias malignas de outros órgãos. No entanto poucos estudos analisaram conjuntamente a expressão dessas proteínas na transição das LIEs de baixo e alto graus (LIEBG e LIEAG) para o carcinoma invasor em amostras de tecido. Para analisar a expressão destas proteínas durante as etapas da progressão do carcinoma epidermóide do colo do útero, foram selecionadas amostras de 84 pacientes com diagnósticos de neoplasias intraepiteliais e carcinomas invasores do colo uterino, contendo 15 casos de LIEBG, 30 casos de LIEAG e 39 casos de carcinoma epidermóide (CEC) do arquivo de Anatomia Patológica do A.C. Camargo Cancer Center. Foram avaliadas, através da imunoistoquímica, as expressões das proteínas das vias NOTCH, WNT E NF-kB nas lesões intraepiteliais de baixo e alto graus e em carcinomas invasores do colo do útero estádio clínico I da FIGO, verificando suas relações com a sua evolução patológica sequencial. As expressões imunoistoquímicas das proteínas Notch 1 e NFkB p105 se correlacionaram com a progressão das LIEs para o carcinoma invasor com p < 0,0001 e 0,005 respectivamente. O presente estudo demonstra que essas vias intracelulares podem estar envolvidas na progressão do câncer de colo uterino.

Cervical cancer is a major health problem worldwide, especially in developing countries. The analysis of the mechanisms of multistep carcinogenesis of cervical cancer provided better understanding of altered intracellular signaling pathways during the development of squamous intraepithelial lesions (IELs) to invasive carcinoma. The high-risk HPV proteins E6 and E7 interaction with NOTCH, NF - kB and WNT signaling appears to be an important carcinogenic pathway in cervical cancer. Recent studies have shown interaction between these pathways in development of malignant neoplasms of other organs. However, few studies analyzed the expression of these proteins together in the transition from low and high-grade (LSIL and HSIL) to invasive carcinoma in tissue samples. To analyze the expression of these proteins during the progression stages of squamous cell carcinoma of the cervix, samples from 84 patients were selected with diagnoses of intraepithelial neoplasia and invasive carcinoma of the cervix, whereas 15 cases of LSIL, 30 cases of HSIL and 39 cases of squamous cell carcinoma (SCC) from the Pathology's Department files, in A.C.Camargo Cancer Center. The protein's expressions of NOTCH, WNT and NF - kB pathways were evaluated by immunohistochemical staining in LSIL, HSIL and FIGO's stage I invasive carcinoma of the cervix, correlating with the pathological sequential of progression. The immunohistochemical expression of Notch 1 and NF - kB p105 proteins correlated with the progression of IELs for invasive carcinoma with p <0.0001 and 0.005 respectively. The present study demonstrates that these intracellular pathways may play a role in the progression of cervical cancer.

Análise imunoistoquímica das vias Notch, WNT e NF-KB em carcinoma epidermóide e lesões precursoras do colo uterino

O câncer do colo do útero é um importante problema de saúde em todo o mundo, principalmente nos países em desenvolvimento. A análise dos mecanismos das múltiplas etapas da carcinogênese do colo do útero propiciou melhor compreensão das vias de sinalização intracelulares alteradas na evolução das lesões intraepiteliais(LIEs) para o carcinoma invasivo. A interação das proteínas E6 e E7 do HPV de alto risco com vias de sinalização do NOTCH, NF-kB e WNT parece constituir uma importante via carcinogênica no colo do útero. Estudos recentes demonstraminteração entre tais vias no desenvolvimento de neoplasias malignas de outros órgãos. No entanto poucos estudos analisaram conjuntamente a expressão dessas proteínas na transição das LIEs de baixo e alto graus (LIEBG e LIEAG) para o carcinoma invasor em amostras de tecido. Para analisar a expressão destas proteínas durante as etapas da progressão do carcinoma epidermóide do colo do útero, foramselecionadas amostras de 84 pacientes com diagnósticos de neoplasias intraepiteliais e carcinomas invasores do colo uterino, contendo 15 casos de LIEBG, 30 casos de LIEAG e 39 casos de carcinoma epidermóide (CEC) do arquivo de Anatomia Patológica do AC Camargo Cancer Center. Foram avaliadas, através da imunoistoquímica, as expressões das proteínas das vias NOTCH, WNT E NF-kB nas lesões intraepiteliais de baixo e alto graus e em carcinomas invasores do colo do útero estádio clínico I da FIGO, verificando suas relações com a sua evolução patológica sequencial. As expressões imunoistoquímicas das proteínas Notch 1 e NFkB p105 se correlacionaram com a progressão das LIEs para o carcinoma invasor com p<0,0001 e 0,005 respectivamente. O presente estudo demonstra que essas viasintracelulares podem estar envolvidas na progressão do câncer de colo uterino(au)

Cervical cancer is a major health problem worldwide, especially in developingcountries. The analysis of the mechanisms of multistep carcinogenesis of cervicalcancer provided better understanding of altered intracellular signaling pathwaysduring the development of squamous intraepithelial lesions (IELs) to invasivecarcinoma. The high-risk HPV proteins E6 and E7 interaction with NOTCH, NF - kBand WNT signaling appears to be an important carcinogenic pathway in cervicalcancer. Recent studies have shown interaction between these pathways indevelopment of malignant neoplasms of other organs. However, few studiesanalyzed the expression of these proteins together in the transition from low andhigh-grade (LSIL and HSIL) to invasive carcinoma in tissue samples. To analyze the expression of these proteins during the progression stages of squamous cellcarcinoma of the cervix, samples from 84 patients were selected with diagnoses ofintraepithelial neoplasia and invasive carcinoma of the cervix, whereas 15 cases of LSIL, 30 cases of HSIL and 39 cases of squamous cell carcinoma (SCC) from the Pathology’s Department files, in A.C.Camargo Cancer Center. The protein’sexpressions of NOTCH, WNT and NF - kB pathways were evaluated by immunohistochemical staining in LSIL, HSIL and FIGO’s stage I invasivecarcinoma of the cervix, correlating with the pathological sequential of progression.The immunohistochemical expression of Notch 1 and NF - kB p105 proteinscorrelated with the progression of IELs for invasive carcinoma with p <0.0001 and 0.005 respectively. The present study demonstrates that these intracellular pathways may play a role in the progression of cervical cancer