Identificación del fenotipo de inestabilidad microsatelital en carcinoma colorrectal mediante el análisis de la expresión de proteínas reparadoras del ADN: Revisión narrativa / Identification of microsatellite instability phenotype in colorectal carcinoma through expression analysis of DNA mismatch repair proteins: Narrative review

El carcinoma colorrectal (CCR) es de las primeras causas de mortalidad del mundo, presentando Guatemala una incidencia anual de 7.4/millón de habitantes. El síndrome de Lynch se caracteriza clínicamente por un inicio temprano del CCR con lesiones causadas por alteraciones en genes que codifican proteínas reparadoras.Los microsatélites son regiones del ADN con una unidad repetitiva de uno o más nucleótidos y son susceptibles a errores durante la replicación de ADN de los enterocitos. Existe un sistema de reparación que corrige estos errores. Cuando las proteínas reparadoras de este sistema están mutadas o ausentes, dichos errores del ADN persisten. Estas proteínas reparadoras se expresan en el núcleo de las células colónicas normales y son detecta-bles utilizando estudios de inmunohistoquímica (IHQ). Los genes MLH1 y MSH2 pueden encontrarse mutados en el 90% de los casos de cáncer colorrectal y el resto corresponde a MSH6 y PMS2. Esta vía oncogénica se caracteriza por alteración del sistema de reparación de errores durante la replicación del ADN, controlado por los genes MMR (mismatch repair), principalmente MLH1, MSH2, MSH6 y PMS2. Se realizó una revisión extensa de la literatura en PubMed, Springer y JAMA, usando las palabras clave: fenotipo de CCR, Síndrome de Lynch e inestabilidad microsatelital, detectándose 55 artículos. El objetivo de esta revisión es describir la importancia de la identificación del fenotipo del CCR por medios de IHQ y de pruebas moleculares para el eficaz tratamiento con inmunoterapia anti-PD1/PD-L1.

Colorectal cancer (CRC) is one of the leading causes of mortality in the world. In Guatemala it's an important cause of morbidity (7.4 per million inhabitants). Lynch syndrome is clinically characterized by an early onset of nonpolyposis colorectal carcinoma, with multiple lesions and neoplasms. The syndrome is caused by mutations in genes encoding DNA mismatch repair proteins. The microsatellites are regions of the DNA that repeat between one or more nucleotides and are susceptible to errors during replication, these are corrected by a repair system, when genes are mutated, the errors persist. The genes encoding repair proteins are expressed in the nuclei of normal colonic cells which can be observed using immunohistochemical studies. The MLH1, MSH2 genes are found to be mutated in 90% of the cases and the rest corresponds to the MSH6 and PMS2 genes. This oncogenic pathway characteristically consists of an alteration in the DNA repair system that is controlled by mismatch repair genes (MMR). An extensive research was conducted on PubMed, Springer and JAMA, using the keyword: CRC phenotype, Lynch syndrome and microsatellite instability. 55 articles were found. This review«s objective is to understand the mechanisms of nonpolyposis colorectal cancer and the importance of identifying patients with a mutant phenotype as a predictive factor for the efficacy of the anti-PD1/PDL1 immunotherapy and for prognosis.

The relationship between tumor budding and survival in colorectal carcinomas

SUMMARY OBJECTIVE Tumor budding is a parameter that is increasingly understood in colorectal carcinomas. We aimed to investigate the relationship between tumor budding, prognostic factors, and survival METHODS A total of 185 patients who had undergone colorectal surgery were observed. Tumor budding, the tumor budding score, and the relationship between these and prognostic factors, and survival investigated. RESULTS Tumor budding was found in 91 (49.2%) cases. The relationship between the tumor budding score and histological grade, lymphovascular invasion, perineural invasion, pathological lymph node stage, and mortality rates were significant. CONCLUSION In our study, the relationship between tumor budding and survival is very strong. Considering these findings and the literature, the prognostic significance of tumor budding becomes clear and should be stated in pathology reports.

RESUMO OBJETIVO Brotamento de tumor é um parâmetro que é cada vez mais conhecido em carcinomas colorretais. Nosso objetivo foi investigar a relação entre brotamento tumoral e fatores prognósticos e sobrevida. MÉTODOS Um total de 240 pacientes observados, submetidos à cirurgia colorretal. Brotamento de tumor, escore de brotamento tumoral e a relação entre estes e fatores prognósticos, sobrevida investigada. RESULTADOS Brotamento de tumores foi encontrado em 91 (49,2%) casos. A relação entre o escore de brotamento tumoral e o grau histológico, invasão linfovascular, invasão perineural, estadiamento linfonodal patológico e taxas de mortalidade foram significativas. CONCLUSÃO Em nosso estudo, a relação entre brotamento tumoral e sobrevida é muito forte. Em conjunto, todos esses achados e literatura são avaliados simultaneamente, o significado prognóstico da brotação do tumor é claramente visto e deve ser indicado nos relatórios de patologia.

Carcinoma adrenal em crianças: estudo longitudinal em minas gerais, brasil / Adrenal carcinoma in children: longitudinal study in minas gerais, brazil

RESUMO Objetivo: Analisar as características clínicas, laboratoriais e histopatológicas e o percurso até o estabelecimento do diagnóstico e do tratamento de pacientes com carcinoma de suprarrenal (CSR). Métodos: Estudo retrospectivo com 13 pacientes tratados no serviço de oncologia pediátrica do Hospital das Clínicas da Universidade Federal de Minas Gerais (HC-UFMG) entre 2004 e 2015. Resultados: A idade ao diagnóstico variou de 1,0 a 14,8 anos (mediana: 2,0 anos). As manifestações de hipercortisolismo foram identificadas em todos os casos, e as de virilização, em todas as meninas. Todos os pacientes preencheram os critérios de Weiss para diagnóstico histopatológico de CSR. A imuno-histoquímica foi realizada em 61,5% dos casos. A maioria dos pacientes apresentou doença em estádio I (76,9%). Todos foram submetidos à ressecção tumoral total. Dois pacientes (estádios III e IV) receberam quimioterapia associada ao mitotano. O único óbito observado foi do paciente com doença em estádio IV. A probabilidade de sobrevida global para todo o grupo aos 5,0 anos foi de 92,3±7,4%. A mediana de tempo entre o início dos sintomas e o diagnóstico foi de 9,5 meses, e de 6,0 meses entre a primeira consulta e o início do tratamento. Conclusões: A baixa idade ao diagnóstico, o predomínio de casos com doença localizada e a ressecção tumoral completa - com apenas um caso de ruptura de cápsula tumoral - são possivelmente a explicação para a evolução favorável da população estudada. O longo percurso entre o início dos sintomas e o diagnóstico sugere a importância da capacitação dos pediatras para o reconhecimento precoce dos sinais e dos sintomas do CSR.

ABSTRACT Objective: To analyze clinical, laboratory and histopathological features and the path to diagnosis establishment and treatment of patients with adrenal carcinoma (AC). Methods: Retrospective study with 13 patients assisted at the pediatric oncology service of Hospital das Clínicas, Universidade Federal de Minas Gerais, Brazil, between 2004 and 2015. Results: Age at diagnosis ranged from 1.0 to 14.8 years (median: 2.0 years). Manifestations of hypercortisolism were identified in all cases and virilization in all girls. All patients met the Weiss criteria to AC histopathological diagnosis. Immunohistochemistry was performed in 61.5% of the cases. Most patients had stage I disease (76.9%). All subjects were submitted to total tumor resection. Two patients (stages III and IV disease) received chemotherapy associated to mitotane. The only death case was that of a patient with stage IV disease. The probability of overall survival for the entire group up to 5.0 years was 92.3±7.4%. The median time between the onset of symptoms and diagnosis was 9.5 months, and 6.0 months between first visit and start of treatment. Conclusions: Low age at diagnosis, predominance of cases with localized disease and complete tumor resection - with only one case of tumor capsule rupture - can possibly explain the favorable evolution of the studied population. The long period between onset of symptoms and diagnosis highlights the importance of training pediatricians for early recognition of AC signs and symptoms.

Conversion therapy for gastric cancer: expanding the treatment possibilities / Terapia de conversão no câncer gástrico: ampliando as possibilidades de tratamento

ABSTRACT Background: Conversion therapy in gastric cancer (GC) is defined as the use of chemotherapy/radiotherapy followed by surgical resection with curative intent of a tumor that was prior considered unresectable or oncologically incurable. Aim: To evaluate the results of conversion therapy in the treatment of GC. Methods: Retrospective analysis of all GC surgeries between 2009 and 2018. Patients who received any therapy before surgery were further identified to define the conversion group. Results: Out of 1003 surgeries performed for GC, 113 cases underwent neoadjuvant treatment and 16 (1.6%) were considered as conversion therapy. The main indication for treatment was: T4b lesions (n=10), lymph node metastasis (n=4), peritoneal carcinomatosis and hepatic metastasis in one case each. The diagnosis was made by imaging in 14 cases (75%) and during surgical procedure in four (25%). The most commonly used chemotherapy regimens were XP and mFLOX. Major surgical complications occurred in four cases (25%) and one (6.3%) died. After an average follow-up of 20 months, 11 patients (68.7%) had recurrence and nine (56.3%) died. Prolonged recurrence-free survival over 40 months occurred in two cases. Conclusion: Conversion therapy may offer the possibility of prolonged survival for a group of GC patients initially considered beyond therapeutic possibility.

RESUMO Racional : A terapia de conversão no câncer gástrico (CG) é definida como o uso de quimio/radioterapia seguida de ressecção cirúrgica com intenção curativa de um tumor que era considerado irressecável ou oncologicamente incurável. Objetivo : Avaliar os resultados da terapia de conversão no tratamento do CG. Métodos : Análise retrospectiva de todas as operações de CG entre 2009 e 2018. Os pacientes que receberam alguma terapia antes da operação foram também identificados para definir o grupo de conversão. Resultados : Entre 1003 operações realizadas para o CG, 113 foram submetidos ao tratamento neoadjuvante e 16 (1,6%) considerados como terapia de conversão. As principais indicações para o tratamento foram: lesões T4b (n=10), metástase linfonodal (n=4), carcinomatose peritoneal e metástase hepática em 1 caso cada. O diagnóstico foi feito por exame de imagem em 14 casos (75%) e durante o procedimento cirúrgico em 4 casos (25%). Os esquemas quimioterápicos mais utilizados foram XP e mFLOX. Complicações cirúrgicas maiores ocorreram em 4 casos (25%) e 1 (6,3%) foi a óbito. Após seguimento médio de 20 meses, 11 pacientes (68,7%) apresentaram recidiva e 9 (56,3%) morreram. Sobrevida livre de recidiva prolongada acima de 40 meses ocorreu em dois casos. Conclusão : A terapia de conversão pode oferecer possibilidade de sobrevida prolongada para um grupo de pacientes com CG considerados inicialmente fora das possibilidades terapêuticas.

Hormone receptor-negative as a predictive factor for pathologic complete response to neoadjuvant therapy in breast cancer / Receptor hormonal negativo como fator preditivo para resposta patológica completa ao tratamento neoadjuvante de câncer de mama

ABSTRACT Objective To define a predictive factor for pathologic complete response, compare the oncologic outcomes associated with the degree of pathologic response after neoadjuvant chemotherapy, and to analyze pathologic complete response as a prognostic factor for overall survival and progression-free survival. Methods A retrospective study of patients admitted to Hospital Estadual Mário Covas and Hospital Anchieta from 2008 to 2012, with locally advanced breast cancer. Hormone receptor status, HER2 status, histologic and nuclear grade, age upon diagnosis and histological type of the tumor were analyzed. Pathologic evaluation of the tumor was subdivided into pathologic complete response, defined by the absence of tumor; intermediate response, considered as a favorable stage; and poor response, considering low-responder patients. Data obtained were submitted to statistical analysis. Results The study included 243 patients. There was an association of pathologic complete response with HER-2 negative, histological grade 3, stage III, hormone receptor negative, positive lymph node, older age and more advanced tumors. However, after multivariate analysis the only predictor of pathologic complete response was the presence of negative hormone receptor. By analyzing the prognostic factors, hormone receptor negative was considered as an independent risk factor, and pathologic complete response was considered as an independent protective factor. Conclusion Hormone receptor negative is predictive of pathologic complete response and is an isolated risk factor for lower progression-free survival and overall survival. Pathologic complete response is a protective factor for these same survival analyses.

RESUMO Objetivo Definir um fator preditivo para resposta patológica completa, comparar os resultados oncológicos associados com o grau de resposta patológica, após quimioterapia neoadjuvante, e analisar a resposta patológica completa como fator prognóstico para sobrevivência global e livre de progressão de doença. Métodos Estudo retrospectivo de pacientes admitidas no Hospital Estadual Mário Covas e Hospital Anchieta, no período de 2008 a 2012, com câncer de mama localmente avançado. Foram utilizados status dos receptores hormonais, proteína HER2, grau histológico e nuclear, idade do paciente ao diagnóstico e tipo histológico do tumor. A avaliação patológica do tumor foi subdividida em resposta patológica completa, definida com ausência de tumor; resposta intermediária, considerada como um estádio favorável; e resposta ruim, considerando os pacientes pouco respondedores. As informações obtidas foram submetidas à análise estatística. Resultados Foram incluídas 243 pacientes. Verificou-se associação de resposta patológica completa entre HER-2 negativo, grau histológico 3, estadiamento III, receptor hormonal negativo, linfonodo positivo, maior idade e tumores mais avançados. Porém, após análise multivariada, o único fator preditivo de resposta patológica completa foi presença de receptor hormonal negativo. Ao analisar fatores prognósticos, receptor hormonal negativo permaneceu como variável independente de risco, e resposta patológica completa, como variável independente de proteção. Conclusão O receptor hormonal negativo é fator preditivo isolado de resposta patológica completa e fator de risco para menor sobrevida livre de doença e sobrevida global. Já a resposta patológica completa é fator protetor para estas mesmas análises de sobrevivência.

Resultados del tratamiento del cáncer de mama, Programa Nacional de Cáncer del Adulto / Impact of the Chilean Explicit Guaranties Health System (GES) on breast cancer treatment

Background Breast cancer is the most common malignant tumor in women in the world. In 2005, it was incorporated to the Explicit Guaranties Health System (GES) in Chile. Aim To describe the demographic and clinical characteristics of breast cancer patients and to determine the effect of incorporating these women to GES. Material and Methods Medical records of 5,119 women with breast cancer aged 59 ± 14 years, attended at six public hospitals between 2000 and 2010 were reviewed. Median follow up was 87 months (range 1-182). Mortality was assessed using death certificates obtained at the National Identification Registry. Results Sixty six percent of women were in stage I-II, 29% in stage III and 5% in stage IV. Surgery was performed in 4023/5119 cases (79%), adyuvant radiotherapy in 3627/4517 cases (80%), chemotherapy in 3,204/3,424 cases (94%) and hormone therapy in 1,695/2,375 cases (71%). Between 2000 and 2010, there was a significant increase in the proportion of cases in stage I, from 8% to 25%, (p < 0.01). Overall survival (OS) increased 1% per year, since the beginning of GES system (p = 0.024). Five year OS was 75.1%. The figures for Stage I, II, III and IV were 93, 84, 62 and 27% respectively (p < 0.01). Patients without lymph node involvement and who were not triple negative, had a significantly better OS. Conclusions There was a significant increase in stage I cases, and a 1% per year OS improvement after GES system started, compared with the previous period.

Role of regenerating gene IA expression on local invasion and survival in nasopharyngeal carcinoma

BACKGROUND: Regenerating gene IA (REGIA) plays an important role in tissue regeneration and tumors prognosis of epithelium origin. However, the role of REGIA in nasopharyngeal carcinoma (NPC) is unclear. This study aims to investigate the expression and function of REG1A in NPC. RESULTS: We have found that there was 63 patients with REGIA positive expression of 155 patients in this study (40.65%). The positive expression rate of REGIA was 30.50, 44.44 and 47.83% in stage T2, T3 and T4 patients, respectively. The REGIA expression was significantly difference in T2 and T4 stage tumors or T2 and T3-T4 stage. The positive expression rate of REGIA was found to be higher in patients with cervical lymph node persistence than those with cervical lymph node complete regression. Patients with negative REGIA expression had a better overall survival and free survival than those with REGIA positive expression. In addition, according to the univariate and multivariate analysis, the REGIA expression was an independent adverse prognostic factor for NPC patients. CONCLUSION: REGIA expression was a useful biomarker in NPC patients for assessing T stage and survival.

Review of survival rates 20-years after conservative surgery for papillary thyroid carcinoma / Revisão dos resultados de sobrevida a 20 anos da cirurgia conservadora no carcinoma papilífero da tireoide

INTRODUCTION: A less extensive thyroidectomy could be used for patients in the low risk group.OBJECTIVE: To perform a critical follow-up after lobectomy with isthmusectomy for the treatment of papillary thyroid carcinoma in patients with a single nodule limited to the periphery of the lobe.METHODS: Thirty-one patients with thyroid papillary carcinoma operated on till 1993 were selected. They had undergone lobectomy with isthmusectomy. This is a retrospective cohort study in which the oncological outcome (contralateral and regional recurrence) and the reoperation complications (recurrent nerve paralysis/paresis and hypoparathyroidism) were evaluated. Descriptive analysis was employed.RESULTS: In the last decade (2003-2013), 6 (20%) contralateral recurrences were observed in the remaining lobe and in 1 of these cases (3%), contralateral lymph node metastases were noted. A completion thyroidectomy plus lymphadenectomy was performed, without modification of global survival.CONCLUSION: Because of the rate of 20% of contralateral recurrence after a 20-year follow-up, we suggest modification of the surgical paradigm for total thyroidectomy as an initial therapy.

INTRODUÇÃO: Uma cirurgia menos extensa da glândula tireoide poderia ser utilizada em pacientes do grupo de baixo risco.OBJETIVO: Realizar seguimento crítico após hemitireoidectomia para tratamento do carcinoma papilífero de tireoide em casos de nódulo único limitado à periferia do lobo.MÉTODO: Foram selecionados 31 pacientes portadores de carcinoma papilífero de tireoide operados, até 1993, por lobectomia mais istmectomia. Trata-se de um estudo retrospectivo de coorte sendo avaliados o resultado oncológico (recidiva contralateral e regional) e complicações de reoperação (paralisia/paresia de nervo recorrente e hipoparatireoidismo). Utilizou-se análise descritiva.RESULTADOS: Na última década, foram observados 6 (20%) casos de recidivas contralaterais (lobo remanescente) sendo que, em um caso, estava acompanhado de metástases linfonodais contralaterais (3%), sem impacto na sobrevida dos pacientes reoperados.CONCLUSÃO: A ocorrência de 20% de recidiva contralateral após uma média evolutiva de 20 anos sugere revisão do paradigma conservador para a totalização imediata da tireoidectomia.

Serum alkaline phosphatase predicts survival outcomes in patients with skeletal metastatic nasopharyngeal carcinoma

OBJECTIVE: Bone metastasis is frequently associated with nasopharyngeal carcinoma. The diagnosis and follow-up of bone metastatic patients usually relies on skeletal X-ray and bone scintigraphy, which are time-consuming and costly. This study aimed to evaluate whether serum alkaline phosphatase offers clinical value in predicting the clinical response and survival outcome for skeletal metastatic nasopharyngeal carcinoma. METHODS: Serum alkaline phosphatase was measured at baseline and then before each cycle of treatment in 416 nasopharyngeal carcinoma patients with bone metastasis. The correlations between the pre-treatment and post-treatment alkaline phosphatase levels and the treatment efficacy were analyzed using the chi-square test. Survival was analyzed using the Kaplan–Meier method and then compared using the log-rank test. RESULTS: Patients with elevated pre-treatment alkaline phosphatase (>110 IU/L) had significantly worse progression-free survival (P<0.001) and overall survival (P<0.001) than those with a normal level of this marker (≤110 IU/L). Patients with elevated post-treatment alkaline phosphatase had worse progression-free survival (P<0.001) and overall survival (P<0.001) compared with those with a normal level. Patients with normal pre-treatment and post-treatment alkaline phosphatase showed the most favorable prognosis. The Cox multivariate analysis revealed that only the pre-treatment and post-treatment alkaline phosphatase levels were independent prognostic factors for progression-free survival (HR ϝ 1.656, P<0.001; HR ϝ 2.226, P<0.001) and for overall survival (HR ϝ 1.794, P<0.001; HR ϝ 2.657, P<0.001). CONCLUSIONS: Serum alkaline phosphatase appears to be a significant independent prognostic index in patients with skeletal metastatic nasopharyngeal carcinoma, which could reflect the short-term treatment response ...

Preoperative serum albumin as a prognostic factor in patients with upper urinary tract urothelial carcinoma

Purpose The study evaluated whether preoperative measures of the C-reactive protein-based systemic inflammatory response may predict cancer survival independent of tumor stage in patients with upper urinary tract urothelial carcinoma (UTUC). Materials and Methods Between September 1999 and October 2010, 181 patients submitted to radical nephroureterectomy were available for evaluation. Multivariate survival analyses were performed using Cox’s proportional hazards model and the coefficient for each factor was divided by the highest coefficient, multiplied by 4, and rounded to the nearest integer. Results Multivariate analyses showed that tumor location, pathologic T stage, lymphovascular invasion, margin status, and albumin level were independent contributors. The bootstrap-corrected C statistics of the model were 0.813 for disease-specific survival and 0.755 for overall survival, respectively. For time to disease-specific and overall mortality for patients, integrated area under the curve values were 0.792 and 0.739, respectively. When patients were clustered into three groups according to their model-predicted survival, the 5-year disease-specific survival in the low-, intermediate- and high-risk group was 95.4%, 76.2%, and 36.9%, respectively (p<0.001), and were 87.8%, 54.4%, and 31.8%, respectively, for overall survival (p<0.001). Decision curve analysis revealed that the use of model was associated with net benefit gains relative to the treat-all strategy. Conclusions   Pretreatment albumin is a simple biomarker based on routinely available well-standardized measures, and is not an expensive and time-consuming process. Hypoalbuminemia is an independent marker of poor prognosis in patients with upper urinary tract urothelial carcinoma. .

Surgical treatment of clinically early-stage endometrial carcinoma without systematic lymphadenectomy / Tratamento cirúrgico do câncer de endométrio em estágio clínico precoce sem linfadenectomia radical.

Objective: the main aim of this study was to describe the authors’ experience with the surgical treatment of endometrial cancer without systematic lymphadenectomy. Methods: a retrospective cohort study was carried out on a subset of patients suffering of clinically early-stage endometrial carcinoma who underwent hysterectomy and salpingo-oophorectomy without systematic (radical) lymph nodes dissection at our centers from June, 2002, to November, 2011. Descriptive statistics were explored as medians (interquartile range) or frequencies (percentages), as appropriated, and the Kaplan–Meier method was applied for survival estimation. Results: eighty-three patients who underwent surgical treatment with no lymph node dissection (n = 20; 24.1%) or with only a sampling procedure (n=63; 75.98%) were selected for analysis. Among these patients, 27 (32.53%) underwent surgery alone and 56 (67.46%) received some adjuvant treatment. Postoperative complications occurred in five patients (6.02%). Over a median follow-up of 27.4 months (Q25 = 13.7 – Q75 = 46.5), 15 (18.07%) patients suffered from relapses and 11 deaths occurred as result of disease recurrence. Cumulative 1, 2 and 3-year disease- free survivals were 97.32, 91.18 and 78.02%, respectively. Conclusion: on a case-by-case basis, the surgical treatment of clinically early-stage endometrial carcinoma without systematic lymphadenectomy did not seem to decrease survival outcomes and presented low rates of surgical morbidity in our experience, but was also related to a high rate use of adjuvant therapy. .

Objetivo: descrever a experiência dos autores com o tratamento cirúrgico do câncer de endométrio em estádio precoce sem linfadenectomia radical. Métodos: realizou-se estudo de coorte retrospectivo envolvendo um subgrupo de pacientes com câncer de endométrio em estágio clínico precoce tratadas com histerectomia e salpingo-ooforectomia sem linfadenectomia radical, em dois centros pernambucanos, de junho de 2002 a novembro de 2011. As variáveis foram descritas como mediana (intervalo interquartílico) ou frequências (percentuais), utilizando- se o método de Kaplan-Meier para a estimativa das taxas de sobrevivência. Resultados: oitenta e três pacientes submetidas a tratamento cirúrgico sem dissecção linfonodal (n = 20, 24,1%) ou com dissecção apenas por amostragem (n = 63; 75,98%) foram selecionadas para análise. Entre essas pacientes, 27 (32,53%) foram tratadas somente com cirurgia e 56 (67,46%) receberam tratamento adjuvante. Cinco pacientes apresentaram complicações pós-operatórias (6,02%). Durante o acompanhamento mediano de 27,4 meses (Q25 = 13,7 - Q75 = 46,5), 15 (18,07%) pacientes apresentaram recorrência, dentre as quais 11 faleceram em decorrência da recidiva neoplásica. Observou-se sobrevivência cumulativa proporcional livre de doença em um, dois e três anos de 97,32, 91,18 e 78,02%, respectivamente. Conclusão: em um contexto de indicação caso-a-caso, o tratamento cirúrgico do câncer de endométrio em estádio precoce sem linfadenectomia radical parece não ter prejudicado a sobrevivência e apresentou baixas taxas de morbidade cirúrgica em nossa experiência, mas também foi acompanhado de elevada utilização de terapia adjuvante. .

Comparison of Radical Cystectomy with Conservative Treatment in Geriatric ( 80) Patients with Muscle-Invasive Bladder Cancer

Introduction The aim of this study was to compare overall survival in elderly patients (≥ 80 years) with muscle-invasive bladder cancer (MIBC) undergoing either radical cystectomy (RC) or conservative treatment. Material and Methods We performed a retrospective, comparative analysis of overall- and cancer-specific survival in octagenarians with MIBC (≥ pT2) submitted to RC or conservative treatment. Uni- and multivariable Cox regression analysis were performed to assess predictors of overall survival. Cumulative hospital stay was also analyzed for all patients. Results The RC-group consisted of 33 patients with a mean age of 82.3 years (IQR 80.4-85.4 years) and the bladder preservation a cohort of 35 patients aged 83.8 years (IQR 81.8-88.2 years). No difference was detectable for overall survival (15.9 months versus 9.5 months; p = 0.18) and cancer-specific survival (23.5 months versus 19.5 months p = 0.71) or 90-day mortality (6.1% versus 14.3%; p = 0.43) between the two groups. Patients who received conservative treatment had a shorter cumulative length of hospital stay (p = 0.001). Age at the time of transurethral resection of the bladder (TUR-B) was an independent predictor of the overall survival (p = 0.004). Conclusions In this retrospective study, no clear survival benefit was observed for patients ≥ 80 years submitted either to radical cystectomy or conservative treatment. There was however a trend favoring radical cystectomy but this did not approach statistical significance. Octagenarians that underwent RC however spent more of their remaining lifetime in the hospital than those treated conservatively. .

What is the best treatment option in postmenopausal, hormone responsive breast cancer patients with isolated bone metastases.

Background: Bone is the most common metastatic site for breast cancer. Aim: To determine the effectiveness of addition of chemotherapy to hormonal therapy in postmenopausal hormone receptor-positive breast cancer patients with isolated bone metastases. Materials and Methods: Between June 2001 and January 2007, 101 patients were classified into two groups according to initial treatment modalities; patients who received hormonotherapy only (group I) and chemotherapy followed by hormonotherapy (group II). The effect of treatment choice on clinical course, time to progression, and overall survival were evaluated. Results: There were 70 patients in group I and 31 patients in group II. Bone metastases in 27 patients (26.7%) were synchronous and the remainder were metachronous. The median follow-up time was 41 months. The two groups showed similar results when patients' tumor characteristics were compared. However, 81% of synchronous cases had upfront chemotherapy following hormonotherapy, whereas this ratio was only 12% in the metachronous group. All patients received systemic antiresorptive bisphosphonates whereas only 24 patients required palliative radiotherapy at some time during the course of their disease. In groups I and II, the median time to progression was 12 and 16 months (P: 0.96) and median overall survival was 41 and 40 months (P: 0.79), respectively. In HER-2-positive patients, a trend of prolongation of overall survival was observed in group II, but it was not statistically significant (P: 0.12). Conclusions: Anti-hormonal therapy still seems to be considered as the ideal treatment of choice for postmenapousal breast cancer patients with isolated bone metastases.

Neoplasias epiteliales del timo: timoma y carcinoma tímico: caracterización, tratamiento y variables asociadas a supervivencia / Thymic epithelial tumors. Retrospective review of 54 patients

Background: Thymic epithelial tumors are uncommon and can be associated with myasthenia gravis. Aim: To describe variables associated with survival and treatment of thymic epithelial tumors. Material and Methods: Retrospective review of surgical databases of a respiratory diseases hospital, identifying patients operated for a thymic epithelial tumor between 2000 and 2010. Follow up lasted from 12 to 156 months and information was obtained from medical records and death certificates of the Chilean national identification service. Results: Data from 54 patients aged 52.5 +/- 16.4 years (33 women) was retrieved. Forty two patients were symptomatic and 47 were subjected to resective surgery. The pathological diagnosis was thymoma in 46 cases and thymic carcinoma in eight. Fourteen patients had postoperative complications and one died. Mean survival time was 101.8 +/- 10.2 months. One, three and five years survival was 90.7 +/- 3.9, 81.4 +/- 5.7 and 71.8 +/- 8.2 percent, respectively. Preoperative performance status of patients, histological type of the tumor and associated myasthenia gravis were predictors of survival. Conclusions: More commonly, thymic epithelial tumors appear in women, their histological type corresponds to thymomas and their resection is feasible.

Objetivos: Describir características, tratamiento y variables asociadas a supervivencia de neoplasias epiteliales del Timo (NET). Material y Método: Revisión retrospectiva de pacientes con NET. Período: enero de 2000 - agosto de 2010. Se describen características, tratamiento, morbilidad, mortalidad y supervivencia global. Se comparó supervivencias según variables seleccionadas. Se utilizó programa SPSS 15.0. Se consideró significativo p < 0,05. Resultados: 54 pacientes, 33 mujeres, edad promedio 52,5 años. Sintomáticos 42 pacientes. Se realizó cirugía resectiva en 47. Histología: 46 Timomas y 8 Carcinomas Tímicos. Complicaciones en 14 y 1 falleció. Rango seguimiento: 12-156 meses. Tiempo promedio supervivencia 101,8 +/- 10,2 meses. Supervivencia global a 1, 3 y 5 años: 90,7 +/- 3,9 por ciento, 81,4 +/- 5,7 por ciento y 71,8 +/- 8,2 por ciento respectivamente. Se encontraron variables asociadas a supervivencia. Conclusiones: Las NET son más frecuentes en mujeres, la mayoría son sintomáticos e histológicamente son timoma. La cirugía es resectiva en la mayoría. Se identifican variables asociadas a supervivencia.

Clinical and pathological response rates of docetaxel-based neoadjuvant chemotherapy in locally advanced breast cancer and comparison with anthracycline-based chemotherapies: Eight-year experience from single centre.

Introduction: The administration of neoadjuvant chemotherapy (NACT) prior to local therapy is advantageous for women with locally advanced breast cancer (LABC), since it can render inoperable tumors resectable and can increase rates of breast conservative surgeries. Materials and Methods: We retrospectively analyzed LABC patients who received NACT from January 2000 to December 2007. Out of 3000 case records screened, 570 (19%) were LABC and 110/570 (19%) treatment-naïve patients started on NACT were analyzed. Ninety-one (37 docetaxel [D], 54 anthracycline [A]) patients were eligible for response and survival analysis. Pathological complete remission (pCR) was defined as no evidence of malignancy in both breast and axilla. Results: Median age of the whole cohort was 45 years (range 25-68 years). Premenopausal were 42% and estrogen receptor + 49.5%. Most (90%) were T4 tumors and 70% were Stage IIIB. Median numbers of preoperative cycles were six and three in the D and A group respectively. Overall clinical response rates for breast primary were 74.3% and 53.7% (CR 28.6% vs. 16.7%, P=0.58) while for axilla ORR were 75.7% vs. 54.8% (51.4% vs. 40.4% CR, P=0.77) respectively for D and A. Corresponding pCR rates were 19% vs. 13% respectively. There was no significant difference in disease-free (three-year 56.84% vs. 61.16%, P=0.80) and overall survival (three-year 70% vs. 78.5%, P=0.86) between the two groups. Conclusions: Although pCR rates were higher with docetaxel-based NACT, it did not translate into superior disease-free survival / overall survival compared to anthracycline-based chemotherapies.

Invasive bladder cancer in the eighties: transurethral resection or cystectomy?

PURPOSE: Describe morbidity and survival in patients older than 80 years with muscle invasive bladder cancer (MIBC) treated with radical cystectomy (RC) or transurethral resection (TUR) in our institution. MATERIALS AND METHODS: We reviewed our database of all patients older than 80 years treated with RC and TUR for MIBC between 1993 and 2005 in our institution. Twenty-seven patients were submitted to RC, with mean age of 82 years and mean follow-up of 16.4 months. RC was carried out following diagnosis of previous MIBC in 14 cases (51.9 percent). The American Society of Anesthesiology (ASA) score was III or IV in 23 patients (85.1 percent). Seventy-two patients with a mean age of 84 years and mean follow-up of 33 months, diagnosed with MIBC, were managed by means of TUR. The ASA score was III-IV in 64 (88.8 percent) patients. RESULTS: Pathological stage of the RC specimen was pT3 in 18 cases (66.7 percent). Mean hospital stay was 16 days. Early complications were assessed in 8 patients (29.6 percent), with an overall survival (OS) of 42.94 percent, and cancer-specific survival (CSS) of 60.54 percent. In patients submitted to TUR, clinical stage was T2 in 36 cases (50 percent). The mean hospital stay was 7 days, with a readmission rate (RR) of 87.5 percent. OS and CSS was less than 20 percent. CONCLUSIONS: RC in octogenarian patients is a safe procedure, with complication and survival rates comparable to RC series in general population. Transurethral resection (TUR) for patients with MIBC within this age range is a much less morbid procedure, but disease specific survival is lower.

Descripción clínico-morfológica y factores pronósticos en carcinomas de apéndice cecal: estudio de cohorte / Appendiceal malignant tumors: review of 84 cases

Background: Malignant appendiceal tumors account for only 0.5 percent of all gastrointestinal tumors and there are usually diagnosed during the pathological study of excised appendices. Aim: To assess the factors influencing the survival of patients with appendiceal carcinomas. Material and Methods: Retrospective review of records of all primary appendiceal carcinomas diagnosed in the pathology unit of a regional hospital between 1993 and 2008. The surgical procedure, clinical history, morphological features of tumor and survival were recorded. Results: Eighty four patients aged 32 ± 15 years (44 women) with appendiceal carcinoma were identified. In 93 percent of patients, the clinical diagnosis was acute appendicitis. Sixty one patients (73 percent) had a carcinoid tumor, 20 (24 percent) an adenocarcinoma and three (3 percent), an adenocarcinoid tumor. Preoperative suspicion of a malignant tumor, level of tumor infiltration, pathological type, involvement of surgical borders, tumor size over 2 cm in the case of carcinoid tumors and the degree of differentiation of adenocarcinomas, had prognostic value. For adenocarcinomas, performing a right hemicolectomy significantly improved survival. Conclusions: Carcinoid tumors are the most common malignant tumor of the appendix. A right hemicolectomy may improve the survival of patients with appendiceal adenocarcinomas.

Introducción: Los tumores malignos del apéndice cecal representan tan sólo el 0,5 por ciento de todas las neoplasias gastrointestinales. Su diagnóstico generalmente no es sospechado por el clínico, siendo su diagnóstico un hallazgo durante el examen de la pieza operatoria. Algunos de estos tumores presentan buena supervivencia con la sola apendicetomía, aunque en ocasiones es necesario realizar tratamientos complementarios. El objetivo de este estudio es determinar la asociación entre variables clínicas y morfológicas con la supervivencia de pacientes con carcinomas del apéndice cecal y analizar el tratamiento quirúrgico realizado. Material y Método: Cohorte retrospectiva de 84 pacientes con carcinomas apendiculares diagnosticados en el Hospital Hernán Henríquez Aravena de Temuco entre los años 1993-2008. Se estudiaron variables clínico-morfológicas, el tratamiento quirúrgico realizado y la supervivencia para estos pacientes. Se utilizó estadística descriptiva y analítica, aplicando Chi-cuadrado y test exacto de Fisher para variables categóricas y T-Student para variables continuas; y prueba Log-rank (Mantel-Cox) para comparación de curvas de supervivencia con un IC de 95 por ciento. Resultados: Del total de apendicectomías (18.563) se verificaron 84 casos (0,45 por ciento); 48 por ciento hombres y 52 por ciento mujeres con una edad promedio de 31,9 +/- 15 años. En el 93 por ciento de los casos el diagnóstico clínico fue apendicitis aguda. Correspondieron a carcinoide, adenocarcinoma y adenocarcinoide en 61 (73 por ciento), 20 (24 por ciento) y 3 (3 por ciento) casos respectivamente. En el análisis bivariado las siguientes variables mostraron asociación pronóstica estadísticamente significativa: sospecha pre-operatoria (p = 0,009), nivel de infiltración tumoral (p = 0,04), tipo histológico (p = 0,009), compromiso de bordes quirúrgicos (p < 0,001), tamaño tumoral > 2 cm en tumores carcinoides (p = 0,001) y grado de diferenciación en adenocarcinomas...

Survival of a cohort of patients with Intermediate and advanced gall bladder cancer treated with a prospective therapeutic protocol / Sobrevida de uma coorte de pacientes com câncer na vesícula intermédio e avançado tratados com um protocolo terapêutico de natureza prospectiva

PURPOSE: To evaluate the results of a prospective therapeutic protocol with long-term follow up in terms of survival rates in a cohort of patients treated with Intermediate and Advanced GBC (GBC). METHODS: Prospective cohort of patients with intermediate and advanced stages of GBC treated between 1996 and 2006. All cases were treated with a partial hepatic segmentectomy on segments IVb and V and a regional lymph node dissection and six cycles of out-patient chemotherapy (5-FU and leukovorin). With an average follow-up of 31.5 months, the morbidity, operative mortality, hepatic and lymphatic infiltration and actuarial survival were measured. Descriptive statistics were applied as well as bivariate analysis applying Fisher's exact test and non-parametrical tests and Kaplan Meier survival curves. Also logistic regression and proportional risk of Cox were applied. RESULTS: 40 patients were included in this protocol, with an average age of 59.5 years (40-85 years), of which 28 were women (70 percent). Depth of wall infiltration: muscular 8 patients (20 percent), subserosal 12 patients (30 percent), serosal 12 patients (30 percent) and perivesicular adipose tissue 8 patients (20 percent). The series morbidity was 27.5 percent. There was no operative mortality. The chemotherapy was well tolerated. The overall actuarial survival in the series was 50 percent at 60 months. CONCLUSION: Our protocol treatment has morbidity, mortality and survival rates similar to previously reported series.

OBJETIVO: Avaliar os resultados de resultados da aplicação de um protocolo terapêutico de natureza prospectiva, com seguimento em longo prazo nos termos de taxas de sobrevivência em uma coorte de pacientes operados com carcinoma vesícula biliar (CVB) intermédio e avançado. MÉTODOS: A coorte prospectiva de pacientes com estágios intermediários e avançados de CVB tratados entre 1996 e 2006. Todos os casos foram tratados com uma segmentectomia hepática parcial em segmentos IVb e V e uma dissecção linfonodal regional e seis ciclos de quimioterapia de ambulatório (5-FU e leukovorin). Com um tempo de seguimento médio de 31,5 meses, a morbidade, mortalidade operatória, hepático e infiltração linfática e atuarial de sobrevida foram medidas. Estatísticas descritivas foram aplicadas, bem como análise bivariada aplicando o teste exato de Fisher, testes não-paramétricos, curvas de sobrevida Kaplan Meier e técnica de regressão logística e risco proporcional de Cox. RESULTADOS: Foram incluídos 40 pacientes neste protocolo, com uma média de idade de 59,5 anos (40-85 anos), dos quais 28 eram mulheres (70 por cento). Profundidade de infiltração parede: muscular 8 pacientes (20 por cento), subserosal 12 pacientes (30 por cento), serosas 12 pacientes (30 por cento) e perivesicular no tecido adiposo, 8 pacientes (20 por cento). A série morbidade foi de 27,5 por cento. Não houve mortalidade operatória. A quimioterapia foi bem tolerada. A sobrevida global atuarial da série foi de 50 por cento em 60 meses. CONCLUSÃO: Nosso protocolo tem tratamento morbidade, mortalidade e taxas de sobrevivência semelhantes às relatadas anteriormente série.

Carcinoma subseroso de la vesícula biliar (pT2): valor pronóstico de la expresión de los genes supresores de tumores p53 y p27 en matrices de tejidos / p53 and p27 gene expression in subserosal gallbladder carcinoma

Background: Subserosal carcinoma is the stage that presents the greatest difficulty in the diagnosis therapeutic handling and prognosis evaluation. Aim To study the expression of p53 and p27 genes in subserosal gallbladder cancer. Material and methods: One hundred twenty seven tissue samples of subserosal gallbladder cancer (coming from 112 females aged 62 ± 13years and 15 men aged 67 ± 17years) and 50 control samples were selected to construct tissue arrays. p53 andp27genes were determined by immunohistochemistry. Results: Thirty eight percent of tumors were not detected at the macroscopic examination, 52 percent and 17 percent had lymph node and blood vessel involvement, respectively. Fifty six and 46 percent were positive for p53 and p27, respectively. No association between the expression of both genes and gender, degree of differentiation, lymph node or blood vessel involvement, was observed. Overall five years actuarial survival was 32 percent. Patients with positive or negative p53 expression had a 22 percent and 53 percent survival, respectively (p =0.05). No association between survival and p27 expression was observed. Conclusions: p53 gene expression is a prognostic factor for subserosal gallbladder cancer.