Câncer de colo uterino na gestação / Cervical cancer in pregnancy

PONTOS-CHAVE • A incidência de câncer durante a gestação tem aumentado devido à tendência das mulheres em postergar a gravidez. O câncer de colo de útero é a terceira neoplasia mais comumente diagnosticada durante o período gestacional. • O rastreamento e o diagnóstico devem se dar como nas pacientes não gestantes; a citologia oncótica cervical é o exame obrigatório do pré-natal, e a colposcopia com biópsia pode ser realizada em qualquer período da gestação. • A gestação complicada pelo diagnóstico de um câncer deve sempre ser conduzida em centro de referência e por equipe multidisciplinar. • A interrupção da gestação em situações específicas, para tratamento-padrão, é respaldada por lei. • A quimioterapia neoadjuvante é uma alternativa segura de tratamento durante a gestação, para permitir alcançar a maturidade fetal. Apresenta altas taxas de resposta, sendo relatada progressão neoplásica durante a gestação em apenas 2,9% dos casos. O risco de malformações fetais decorrentes da quimioterapia é semelhante ao da população geral. Contudo, a quimioterapia está associada a restrição de crescimento intraútero, baixo peso ao nascer e mielotoxicidade neonatal. • Na ausência de progressão de doença, deve-se levar a gestação até o termo.

Discussion on how to optimize active surveillance for low-risk papillary thyroid microcarcinoma in China / 中华外科杂志

Active surveillance, as a first-line treatment strategy for low-risk papillary thyroid microcarcinoma, has been recommended by guidelines worldwide. However, active surveillance has not been widely accepted by doctors and patients in China. In view of the huge challenges faced by active surveillance, doctors should improve their understanding of the "low risk" of papillary thyroid micropapillary cancer, identify some intermediate or high-risk cases, be familiar with the criteria and methods of diagnosis for disease progression, and timely turn patients with disease progression into more active treatment strategies. By analyzing the long-term cost-effectiveness of active surveillance, it is clear that medical expense is only one cost form of medical activities, and the health cost (thyroid removal and surgical complications) paid by patients due to"over-diagnosis and over-treatment" is the most important. Moreover, the weakening of the patients' social function caused by surgical procedures is a more hidden and far-reaching cost. The formulation of health economic policies (including medical insurance) should promote the adjustment of diagnosis and treatment behavior to the direction which is conducive to the long-term life and treatment of patients, improving the overall health level of society and reducing the overall cost. At the same time, doctors should stimulate the subjective initiative of patients, help them fully understand the impact of various treatment methods on their psychological and physical status, support patients psychologically, and strengthen their confidence in implementing active surveillance. By strengthening multi-disciplinary treatment team and system support, doctors can achieve risk stratification of papillary thyroid microcarcinoma, accurate judgment of disease progress, timely counseling for psychological problems, and long-term adherence to active surveillance. Improving the treatment level of advanced thyroid cancer is the key point of improve the prognosis. It is important to promote the development of active surveillance for low-risk papillary thyroid microcarcinoma. In the future, it is necessary to carry out multi-center prospective research and accumulate research evidence for promoting the standardization process of active surveillance. Standardized active surveillance will certainly benefit specific papillary thyroid microcarcinoma patients.

Vigilância ativa do câncer de próstata - um conceito em evolução / Active surveillance of prostate cancer - an ongoing concept

A vigilância ativa é a solução encontrada pela urologia para a condução de tumores prostáticos com características de pouca agressividade. Desenvolvida especialmente após as polêmicas que envolveram a validade do rastreamento, essa abordagem vem sendo consolidada como a melhor maneira de se evitar o tratamento desnecessário do câncer de próstata e precisa ser compreendida por todos os médicos que lidam com a saúde do homem.

Active surveillance is the solution found by urology to deal with low-aggressivity prostate tumours. Having been developed following controversies over screening strategies, this has been considered the best approach to avoid unnecessary treatment of prostate cancer and such a concept needs to be well understood by every medical doctor who deals with men's health.

Active surveillance in papillary thyroid carcinoma: not easily accepted but possible in Latin America

ABSTRACT Objectives To determine the percentage of patients with papillary thyroid carcinoma (PTC) who accepted active surveillance as an alternative to surgery in our clinical practice and to describe the clinical characteristics and outcomes of patients with Bethesda category V and VI thyroid nodules who chose active surveillance. Subjects and methods We included 136 PTC patients from the Hospital de Clínicas, University of Buenos Aires without (i) US extrathyroidal extension, (ii) tumors adjacent to the recurrent laryngeal nerve or trachea, and/or (iii) US regional lymph-node metastasis or clinical distant metastasis. PTC progression was defined as the presence of i) a tumor larger than ≥ 3 mm, ii) novel appearance of lymph-node metastasis, and iii) serum thyroglobulin doubling time in less than one year. For patients with these features, surgery was recommended. Results Only 34 (25%) of 136 patients eligible for active surveillance accepted this approach, and around 10% of those who accepted abandoned it due to anxiety. The frequency of patients with tumor enlargement was 17% after a median of 4.6 years of follow-up without any evidence of nodal or distant metastases. Ten patients who underwent surgical treatment after a median time of 4 years of active surveillance (AS) had no evidence of disease after a median of 3.8 years of follow-up after surgery. Conclusion Although not easily accepted in our cohort of patients, AS would be safe and easily applicable in experienced centers.

Clinical and pathologic factors predicting reclassification in active surveillance cohorts

ABSTRACT The incidence of small, lower risk well-differentiated prostate cancer is increasing and almost half of the patients with this diagnosis are candidates for initial conservative management in an attempt to avoid overtreatment and morbidity associated with surgery or radiation. A proportion of patients labeled as low risk, candidates for Active Surveillance (AS), harbor aggressive disease and would benefit from definitive treatment. The focus of this review is to identify clinicopathologic features that may help identify these less optimal AS candidates. A systematic Medline/PubMed Review was performed in January 2017 according to PRISMA guidelines; 83 articles were selected for full text review according to their relevance and after applying limits described. For patients meeting AS criteria including Gleason Score 6, several factors can assist in predicting those patients that are at higher risk for reclassification including higher PSA density, bilateral cancer, African American race, small prostate volume and low testosterone. Nomograms combining these features improve risk stratification. Clinical and pathologic features provide a significant amount of information for risk stratification (>70%) for patients considering active surveillance. Higher risk patient subgroups can benefit from further evaluation or consideration of treatment. Recommendations will continue to evolve as data from longer term AS cohorts matures.

On thin ice: barriers to adoption of surveillance for patients with stage I testicular seminoma. Survey of US radiation oncologists

ABSTRACT Purpose: Most men with stage I testicular seminoma are cured with surgery alone, which is a preferred strategy per national guidelines. The current pattern of practice among US radiation oncologists (ROs) is unknown. Materials and Methods: We surveyed practicing US ROs via an online questionnaire. Respondent's characteristics, self-rated knowledge, perceived patient compliance rates with observation were analyzed for association with treatment recommendations. Results: We received 353 responses from ROs, of whom 23% considered themselves experts. A vast majority (84%) recommend observation as a default strategy, however this rate drops to 3% if the patient is believed to be noncompliant. 33% of respondents believe that survival is jeopardized in case of disease recurrence, and among these respondents only 5% support observation. 22% of respondents over-estimate the likelihood of noncompliance with observation to be in the 50-80% range. Responders with a higher perceived noncompliance rate are more likely to recommend adjuvant therapy (Fisher's exact p<0.01). Only 7% of respondents recommend observation for stage IS seminoma and 45% administer adjuvant RT in patients with elevated pre-orchiectomy alpha-fetal protein levels. Conclusions: Many US ROs over-estimate the likelihood that stage I testicular seminoma patients will be noncompliant with surveillance and incorrectly believe that overall survival is jeopardized if disease recurs on surveillance. Observation is quickly dismissed for patients who are not deemed to be compliant with observation, and is generally not accepted for patients with stage IS disease. There is clearly an opportunity for improved physician education on evidence-based management of stage I testicular seminoma.

En mujeres embarazadas con rotura prematura de membranas y edad gestacional entre 34 y 37 semanas: ¿Es la interrupción del embarazo (manejo activo) mejor que el manejo expectante para reducir la sepsis neonatal? / In pregnant women with premature rupture of membranes and gestational age between 34 and 37 weeks: Is termination of pregnancy (active management) better than expectant management to reduce neonatal sepsis?

INTRODUCCIÓN: La rotura prematura de membranas (RPM) ocurre en un 8 a 10% de las embarazadas, y de ellas, un 20% corresponde a embarazos de pretérmino. El mayor riesgo para el feto luego de una RPM pretérmino son las complicaciones propias de la prematurez. Por debajo de las 34 semanas se favorece el manejo expectante, y el uso de antibióticos y corticoides. Entre las 34 y 37 semanas, sin embargo, las prácticas varían, no habiendo un consenso claro sobre la conducta óptima. OBJETIVO: El objetivo de esta revisión es explorar la evidencia actualmente disponible respecto de la conducta activa versus la expectante en embarazos con RPM entre las 34 y 37 semanas (36 semanas más 6 días). METODOLOGÍA: Se realizó una búsqueda de literatura médica en distintas bases de datos, dentro de las cuales se incluye "PubMed" y "Cochrane", usando los siguientes términos: "Fetal Membranes, Premature Rupture", "Premature Birth", "34 and 37 weeks" y "Clinical Trial". Se limitó la búsqueda a artículos que fueran ensayos clínicos aleatorizados. De un total de 31 trabajos, se seleccionaron 3, a los cuales se les aplicó la pauta de análisis crítico para evaluación de estudios de terapia. RESULTADOS: Se incluyeron 3 estudios que respondían a la pregunta planteada. En el primer estudio se concluyó que en pacientes en que hay interrupción inmediata la incidencia de sepsis neonatal es baja y no es posible demostrar que esta conducta mejore los resultados en comparación con el manejo expectante (2.6% vs. 4.1%). El manejo activo en este estudio se asoció a mayor incidencia de hiperbilirrubinemia, hipoglicemia, y mayor estadía hospitalaria neonatal. En el segundo artículo se planteó que la incidencia de sepsis neonatal sigue siendo baja, lo cual no disminuyó con la inducción del trabajo de parto. Esta tampoco disminuyó el riesgo de otros resultados neonatales o maternos. Finalmente, el tercer estudio concluyó que la interrupción inmediata aumenta las complicaciones neonatales sin disminución de la sepsis neonatal, pero a expensas de mayor frecuencia de fiebre materna y de hemorragia intraparto. CONCLUSIONES: El manejo expectante no es inferior al manejo activo en el contexto de RPM entre las semanas 34 a 37 de edad gestacional.

INTRODUCTION: Premature rupture of membranes (PROM) occur in eight to ten percent of pregnancies, and 20 percent of them occur in preterm pregnancies. Biggest fetal risks after preterm PROM are complications due to prematurity. Before 34 weeks of gestation it is preferred an expectant management, and the use of antibiotics and steroids. Between 34 and 37 weeks, however, practices are variable without a clear consensus about the best management. OBJECTIVE: The objective of this review is to explore the available evidence about active versus expectant management in pregnancies with PROM between 34 and 37 weeks (36 weeks plus 6 days). METHODS: Different databases were searched for medical literature, including 'PubMed' and 'Cochrane', using the following terms: 'Fetal Membranes, Premature Rupture', 'Premature Birth', '34 and 37 weeks' and 'Clinical Trial'. The search was limited to clinical randomized trials. From a total of 31 studies, three were selected, in which critical analysis guidelines for evaluation of therapy studies were applied. RESULTS: Three clinical trials which answered our question were included in this review. The first study concluded that in patients whose pregnancies were interrupted immediately, the incidence of neonatal sepsis was low but is was not able to demonstrate that this action improved outcomes compared to expectant management (2.6% vs 4.1%). Active management in this study was associated to greater incidences of hyperbilirubinemia, hypoglycemia and longer neonatal hospital stay. In the second article the incidence of neonatal sepsis was low and didn't decrease with induction of labor. It also didn't reduce the risk of other maternal nor neonatal outcomes. Finally, the third study concluded that induction of labor increased neonatal complications without reducing neonatal sepsis, but at the expense of increased frequency of intrapartum hemorrhage and maternal fever. CONCLUSION: After analyzing the selected articles, it is possible to conclude that there is enough evidence to say that expectant management is not inferior to active management in relation to PROM between 34 and 37 weeks of gestational age.

Malignant extra-cranial germ cell tumors in children and adolescents: Results following the guidelines of SFOP/SFCE 95 Protocol

Between September 1995 and December 2010, 99 new consecutive assessable patients with extra-cranial MGCT were treated according to SFOP/SFCE TGM95 Protocol. A "watch and wait" strategy for completely resected stage I-II was observed in cases with preoperative high tumor markers levels. Metastatic disease or alpha fetoprotein levels > 15 000 ng/ml cases were treated by VIP chemotherapy (etoposide, ifosfamide and CDDP) 4-6-courses. All other cases were treated by VBP (vinblastine, bleomycin, and CDDP) 3-5 courses. Median age for the whole group was 11.1 (r: 0-17) years. Males: 49, females: 50. Stage I: 19 patients, stage II: 16, stage III: 31 and stage IV: 3. Gonadal disease occurred in 77 cases. Of 21 completely resected stage I-II patients with MGCT who did not receive chemotherapy after surgery, 6 presented disease progression and were successfully treated by chemotherapy and remained disease-free. There were no significant differences in outcome according to age, gender, initial site, staging, and histological variant or high levels of alpha-fetoprotein. Initial non-responsiveness to VIP chemotherapy was the only significant unfavorable prognostic feature. With a median follow-up of 64 (r: 5-204) months, at 10 years EFS and OS estimates for the whole group were 0.82 (SE = 0.05) and 0.90 (SE = 0.03) respectively. Therapy results of MGCT treated with the SFOP/SFCE 95 strategy were excellent. Initial non-response to front line chemotherapy was the only significant adverse prognostic feature. The "watch and wait" strategy for completely resected disease with initial positive markers proved to be safe with optimal outcome.

Entre septiembre de 1995 y diciembre 2010 se registraron 99 nuevos pacientes evaluables consecutivos con tumores germinales malignos (TGM) extra-cerebrales. Los pacientes fueron tratados prospectivamente según los lineamientos del Protocolo SFOP/SFCE TGM95. Se siguió una estrategia de watch and wait para la enfermedad estadio I-II completamente resecada. La enfermedad con metástasis y los casos con niveles de alfa fetoproteína > 15 000 ng/ml fueron tratados con etopósido, ifosfamida y CDDP, 4-6 cursos. El resto fue tratado con vinblastina, bleomicina y CDDP, 3-5 ciclos. La mediana de edad fue de 11.1 (r: 0-17) años. Varones: 49, niñas: 50. Estadio I: 19 casos; II: 16; III: 31y IV: 33. De 21 enfermos con estadios tumorales I y II con resección completa inicial que no tuvieron tratamiento adyuvante, seis progresaron, todos fueron exitosamente tratados con quimioterapia y permanecieron libres de enfermedad. No hubo diferencias significativas en los resultados de supervivencia según edad, género, sitio inicial, estadificación, variante histológica o niveles elevados de alfa-fetoproteína. La resistencia primaria a la quimioterapia VIP fue el único factor pronóstico desfavorable significativo. Con una mediana de seguimiento de 64 (r: 5-204) meses, a 10 años las probabilidades de supervivencia libre de eventos y supervivencia global para todo el grupo fueron respectivamente de 0.82 (EE = 0.05) y 0.90 (EE = 0.03). Los resultados con la estrategia SFOP/SFCE 95 fueron excelentes. La ausencia de respuesta a la quimioterapia de primera línea fue el único factor pronóstico adverso significativo. La estrategia de watch and wait probó ser segura y eficaz.

Long-Term Outcome and Surveillance Colonoscopy after Successful Endoscopic Treatment of Large Sessile Colorectal Polyps

PURPOSE: Although there is a consensus about the need for surveillance colonoscopy after endoscopic resection, the interval remains controversial for large sessile colorectal polyps. The aim of this study was to evaluate the long-term outcome and the adequate surveillance colonoscopy interval required for sessile and flat colorectal polyps larger than 20 mm. MATERIALS AND METHODS: A total of 204 patients with large sessile and flat polyps who received endoscopic treatment from May 2005 to November 2011 in a tertiary referral center were included. RESULTS: The mean age was 65.1 years and 62.7% of the patients were male. The mean follow-up duration was 44.2 months and the median tumor size was 25 mm. One hundred and ten patients (53.9%) received a short interval surveillance colonoscopy (median interval of 6.3 months with range of 1-11 months) and 94 patients (46.1%) received a long interval surveillance colonoscopy (median interval of 13.6 months with range of 12-66 months). There were 14 patients (6.9%) who had local recurrence at the surveillance colonoscopy. Using multivariate regression analysis, a polyp size greater than 40 mm was shown to be independent risk factor for local recurrence. However, piecemeal resection and surveillance colonoscopy interval did not significantly influence local recurrence. CONCLUSION: Endoscopic treatment of large sessile colorectal polyps shows a favorable long-term outcome. Further prospective study is mandatory to define an adequate interval of surveillance colonoscopy.

Response-Guided Therapy for Hepatitis C Virus Recurrence Based on Early Protocol Biopsy after Liver Transplantation

Hepatitis C virus (HCV) recurrence after liver transplantation (LT) is universal and progressive. Here, we report recent results of response-guided therapy for HCV recurrence based on early protocol biopsy after LT. We reviewed patients who underwent LT for HCV related liver disease between 2010 and 2012. Protocol biopsies were performed at 3, 6, and 12 months after LT in HCV recurrence (positive HCV-RNA). For any degree of fibrosis, > or = moderate inflammation on histology or HCV hepatitis accompanying with abnormal liver function, we treated with pegylated interferon and ribavirin. We adjusted treatment period according to individual response to treatment. Among 41 HCV related recipients, 25 (61.0%) who underwent protocol biopsies more than once were enrolled in this study. The mean follow-up time was 43.1 (range, 23-55) months after LT. Genotype 1 and 2 showed in 56.0% and 36.0% patients, respectively. Of the 25 patients, 20 (80.0%) started HCV treatment after LT. Rapid or early virological response was observed in 20 (100%) patients. Fifteen (75.0%) patients finished the treatment with end-of-treatment response. Sustained virological response (SVR) was in 11 (55.0%) patients, including 5 (41.7%) of 12 genotype 1 and 6 (75.0%) of 8 non-genotype 1 (P = 0.197). Only rapid or complete early virological response was a significant predictor for HCV treatment response after LT (100% in SVR group vs. 55.6% in non-SVR group, P = 0.026). Overall 3-yr survival rate was 100%. In conclusion, response-guided therapy for HCV recurrence based on early protocol biopsy after LT shows encouraging results.

Pathological upgrading in prostate cancer patients eligible for active surveillance: Does prostate-specific antigen density matter?

PURPOSE: To evaluate prospectively the role of prostate-specific antigen (PSA) density in predicting Gleason score upgrading in prostate cancer patients eligible for active surveillance (T1/T2, biopsy Gleason score< or =6, PSA< or =10 ng/mL, and < or =2 positive biopsy cores). MATERIALS AND METHODS: Between January 2010 and November 2013, among patients who underwent greater than 10-core transrectal ultrasound-guided biopsy, 60 patients eligible for active surveillance underwent radical prostatectomy. By use of the modified Gleason criteria, the tumor grade of the surgical specimens was examined and compared with the biopsy results. RESULTS: Tumor upgrading occurred in 24 patients (40.0%). Extracapsular disease and positive surgical margins were found in 6 patients (10.0%) and 8 patients (17.30%), respectively. A statistically significant correlation between PSA density and postoperative upgrading was found (p=0.030); this was in contrast with the other studied parameters, which failed to reach significance, including PSA, prostate volume, number of biopsy cores, and number of positive cores. Tumor upgrading was also highly associated with extracapsular cancer extension (p=0.000). The estimated optimal cutoff value of PSA density was 0.13 ng/mL2, obtained by receiver operating characteristic analysis (area under the curve=0.66; p=0.020; 95% confidence interval, 0.53-0.78). CONCLUSIONS: PSA density is a strong predictor of Gleason score upgrading after radical prostatectomy in patients eligible for active surveillance. Because tumor upgrading increases the potential for postoperative pathological adverse findings and prognosis, PSA density should be considered when treating and consulting patients eligible for active surveillance.

Active surveillance of renal masses: an analysis of growth kinetics and clinical outcomes stratified by radiological characteristics at diagnosis

AIMS To determine the growth rate of renal masses (RMs) under active surveillance (AS), and to describe the clinical outcome of AS patients. Materials and Methods We conducted a retrospective review of an AS database to obtain demographics, radiological and pathologic characteristics and RM size of patients. RMs were followed at 6-12 month intervals for ≥1 year with computed tomography (CT), magnetic resonance imaging (MRI), or renal ultrasound. Kaplan-Meier analysis determined the annual likelihood of intervention. RMs were divided into 3 radiographic subcategories (solid, cystic, and angiomyolipoma). A linear regression model determined RM growth rates. Results 131 RMs in 114 patients were included. Median age, Charlson Comorbidity Index score and mean follow-up were 69.1 years, 4.0 and 4.2±2.6 years, respectively. Maximal tumor diameter (MTD) at diagnosis was 2.1±1.3 cm. 49 RMs exhibited negative or zero net growth. Mean MTD growth rate for all RMs was 0.72±3.2 (95% CI: 0.16-1.28) mm/year. When stratified by MTD at diagnosis, mean RM growth rates were 0.84, 0.84, 0.44, 0.74 and 0.71 mm/year for RMs <1 cm, 1-<2cm, 2-<3cm, 3-<4cm and ≥4cm, respectively (p<0.01). The 5 and 10-year freedom from intervention rates were 93.1% and 88.5%, respectively. There was a single case of suspected metastases, but no deaths related to kidney cancer. Conclusions RMs under AS grew slowly, and had a low incidence of requiring surgical intervention and progression. Solid enhancing masses grew slowly, and were more likely to trigger intervention. AS should be considered for selected patients with small RMs. .

Is active surveillance a safe alternative in the management of localized prostate cancer? Pathological features of radical prostatectomy specimens in potential candidates for active surveillance

Introduction and objectiveActive surveillance (AS) has become an accepted alternative for patients with low risk prostate cancer. The purpose of AS is to defer definitive therapy in these patients to avoid treatment-related complications. Our aim was to determine the pathological features of the surgical specimen from potential AS candidates that underwent radical prostatectomy (RP).Materials and MethodsWe retrospectively reviewed a group of patients submitted to RP who met criteria for AS: Gleason score (GS) ≤ 3+3 = 6, PSA ≤ 10ng/mL, T1c - T2a, < 1/3 of positive cores, < 50% of involvement in any core and PSA density < 0.15. We determined the concordance between GS in biopsy and RP specimen (RPS). Other pathological features of the RPS were also analyzed, including surgical margins, extracapsular extension, seminal vesicles and lymph node involvement.ResultsWe identified 167 patients subjected to RP that met the criteria for AS. Fifty two patients (31.1%) had a GS > 6 in the RPS (GS 7 n = 49; GS 8 n = 3). Extracapsular extension, seminal vesicle and lymph node involvement was found in 6.1%, 3.1% and 1.2% of the specimens, respectively.ConclusionIn this study a significant proportion of potential candidates for AS showed features of aggressive and/or high-risk tumors in the RPS. Therefore, before considering a patient for an AS protocol, a proper and strict selection must be performed, and informed consent is crucial for these patients.