Novel role for PINX1 as a coregulator of nuclear hormone receptors.

Estrogen receptor alpha (ERα) has an established role in breast cancer biology. Transcriptional activation by ERα is a multistep process influenced by coactivator and corepressor proteins. This work shows that Pin2 interacting protein 1 (PINX1) interacts with the N-terminal domain of ERα and functions as a corepressor of ERα. Furthermore, it represses both AF-1 and AF-2 transcriptional activities. Chromatin immunoprecipitation assays verified that the interaction between ERα and PINX1 occurs on E2 regulated promoters and enhanced expression of PINX1 deregulates the expression of a number of genes that have a role in cell growth and proliferation in breast cancer. PINX1 overexpression decreases estrogen mediated proliferation of breast cancer cell lines, while its depletion shows the opposite effect. Taken together, these data show a novel molecular mechanism for PINX1 as an attenuator of estrogen receptor activity in breast cancer cell lines, furthering its role as a tumor suppressor gene in breast cancer.

[Third National Ovarian Consensus. 2011. Grupo de Investigación en Cáncer de Ovario y Tumores Ginecológicos de México "GICOM"]. / Tercer Consenso Nacional de Cáncer de Ovario 2011. Grupo de Investigación en Cáncer de Ovario y Tumores Ginecológicos de México "GICOM".

INTRODUCTION: Ovarian cancer (OC) is the third most common gynecologic malignancy worldwide. Most of cases it is of epithelial origin. At the present time there is not a standardized screening method, which makes difficult the early diagnosis. The 5-year survival is 90% for early stages, however most cases present at advanced stages, which have a 5-year survival of only 5-20%. GICOM collaborative group, under the auspice of different institutions, have made the following consensus in order to make recommendations for the diagnosis and management regarding to this neoplasia. MATERIAL AND METHODS: The following recommendations were made by independent professionals in the field of Gynecologic Oncology, questions and statements were based on a comprehensive and systematic review of literature. It took place in the context of a meeting of two days in which a debate was held. These statements are the conclusions reached by agreement of the participant members. RESULTS: No screening method is recommended at the time for the detection of early lesions of ovarian cancer in general population. Staging is surgical, according to FIGO. In regards to the pre-surgery evaluation of the patient, it is recommended to perform chest radiography and CT scan of abdomen and pelvis with IV contrast. According to the histopathology of the tumor, in order to consider it as borderline, the minimum percentage of proliferative component must be 10% of tumor's surface. The recommended standardized treatment includes primary surgery for diagnosis, staging and cytoreduction, followed by adjuvant chemotherapy Surgery must be performed by an Oncologist Gynecologist or an Oncologist Surgeon because inadequate surgery performed by another specialist has been reported in 75% of cases. In regards to surgery it is recommended to perform total omentectomy since subclinic metastasis have been documented in 10-30% of all cases, and systematic limphadenectomy, necessary to be able to obtain an adequate surgical staging. Fertility-sparing surgery will be performed in certain cases, the procedure should include a detailed inspection of the contralateral ovary and also negative for malignancy omentum and ovary biopsy. Until now, laparoscopy for diagnostic-staging surgery is not well known as a recommended method. The recommended chemotherapy is based on platin and taxanes for 6 cycles, except in Stage IA, IB and grade 1, which have a good prognosis. In advanced stages, primary cytoreduction is recommended as initial treatment. Minimal invasion surgery is not a recommended procedure for the treatment of advanced ovarian cancer. Radiotherapy can be used to palliate symptoms. Follow up of the patients every 2-4 months for 2 years, every 3-6 months for 3 years and anually after the 5th year is recommended. Evaluation of quality of life of the patient must be done periodically. CONCLUSIONS: In the present, there is not a standardized screening method. Diagnosis in early stages means a better survival. Standardized treatment includes primary surgery with the objective to perform an optimal cytoreduction followed by chemotherapy Treatment must be individualized according to each patient. Radiotherapy can be indicated to palliate symptoms.

[Psychosocial adjustment in colorectal cancer patients undergoing chemotherapy or chemoradiotherapy].

BACKGROUND: Psychosocial adaptation is a measurement that represents the patient's adjustment to those changes involved in their illness. We undertook this study to search for individual characteristics and clinical aspects associated with successful psychosocial adjustment in patients with colorectal cancer (CRC) undergoing (CT) chemotherapy or chemoradiotherapy (CRT). METHODS: Seventy-five patients with CRC treated with CT or CRT in a cancer center were included. Psychosocial Adjustment to Illness Scale Self-Reporting (PAIS-SR) questionnaire was used as a measurement of psychosocial adjustment. RESULTS: Psychosocial adaptation was successful in 18 patients (24%) and unsuccessful in 57 patients (76%). Young patients, married patients and males showed lower psychosocial adaptation to disease. This is associated with the decrease in sexual relations, economic resources and psychological symptoms. Patients complained that they were unsatisfied due to the lack of disease and treatment information offered by the heath care team. CONCLUSIONS: In the process of adaptation, clinical features such as tumor location and treatment scheme are considered basic, as well as age, education, marital status. Areas such as sexuality, interpersonal and family relationships, economic status and emotional state of patients affected by the disease and treatments provide a deep complexity in the study of the psychosocial adaptation process in patients with CRC.

Multimodal treatment of locally advanced cervical cancer.

BACKGROUND: Radiation therapy with concomitant chemotherapy is the standard treatment for locally advanced cervical cancer. In Mexico, most patients are still treated with radiation therapy alone. The aim of this work was to demonstrate that results obtained with combined treatments in the Mexican population are similar to those reported in the literature. METHODS: Survival was analyzed in three sequential phase II studies of combined treatment: neoadjuvant chemotherapy followed by surgery (NEOCT+Sx) -February to July 1999; concomitant chemoradiotherapy (CT/RT) -August to December 1999; and neoadjuvant chemotherapy followed by surgery plus adjuvant chemoradiotherapy (NEOCT+Sx+CT/RT) -December 2000 to June 2001. These results were compared with a historical control group treated with radiation therapy alone between September and December 1998. The Kaplan-Meier product-limit method, log-rank test and Cox proportional hazards model were used for analysis. RESULTS: Results showed that the three combined modalities significantly reduced the risk of death. Treatment with NEOCT+Sx reduced the risk to 0.452 (95% CI 0.246-0.830), p=0.010. The risk reduction with CT/RT was 0.408 (95% CI 0.218-0.762), p=0.005, and for the group of patients receiving NEOCT+Sx+CT/RT risk was reduced to 0.365 (95% CI 0.169-0.787), p=0.010. The corresponding absolute survival benefit was 14% for patients in stages IB2-IIA, 24% for IIB, and 21% for stage IIIB. CONCLUSIONS: Within the limitations of a non-randomized study, our results are in agreement with those obtained from published randomized phase III trials which state that radiation therapy alone is a suboptimal treatment for locally advanced cervical cancer; hence, patients should receive cisplatin-based chemoradiotherapy as a standard treatment.

A retrospective analysis of patients with gallbladder cancer treated with radical resection versus cholecystectomy plus external radiotherapy.

BACKGROUND/AIMS: To compare patients with gallbladder cancer treated with radical resection and regional lymphadenectomy (RR-RL) versus simple cholecystectomy and adjuvant external radiotherapy (SC-ERT) and determine outcome. METHODOLOGY: Presentation, operative data, complications and survival were examined in 137 patients. In particular, the 45 patients treated with RR-RL or SC-ERT. RESULTS: Twenty-five had SC-ERT and 20 had a RR-RL. There were no epidemiological differences between groups. Resection of segments IV-b and V and en bloc dissection of regional lymph nodes was the most frequently used procedure (75%). The morbidity and mortality of the radical procedure were 25% and 10%. The morbidity of SC-ERT was 16%. All patients with Nevin I are alive. For lesions Nevin II and Nevin III RR-RL offered a 100% 5-year survival rate and SC-ERT had a 62% and 39% 5-year survival rate respectively. For lesions Nevin IV and V there was no difference in long-term survival. CONCLUSIONS: RR-RL is better than SC-ERT in patients with Nevin II and III lesions because it improves survival rate. SC-ERT can be recommended as an alternative treatment. For more advanced lesions further trials are needed.

[The role of minimal invasion surgery in the management of patients with gastric carcinoma]. / El papel de la cirugía de invasión mínima en el manejo de pacientes con carcinoma gástrico.

In the last decade, minimal invasion surgery (MIS) has been used in a great variety of diseases and clinical situations. In gastric carcinoma (GC), specific indications in various circumstances have been described. MIS is used to make a diagnosis, for clinical stage classification, and for respectability evaluation, allowing to design a suitable therapy for each patient, because effective neoadjuvant treatments (chemotherapy and radiochemotherapy) are available. MIS has also been used for surgical resection of gastric neoplasia, including endoscopic mucosal resection, wedge resection of gastric wall, subtotal gastrectomy, total gastrectomy or even lymphadenectomy. MIS is used for perform palliative gastrojejunostomy in patients with distal GC, as well as for gastrostomy or jejunostomy for enteral nutrition in specific situations. MIS is still in experimental phase in GC, except in the case of preoperative staging laparoscopy.

Long-term results of paclitaxel in FIGO stage III ovarian carcinoma.

The combination of platinum and paclitaxel is the standard treatment of advanced ovarian carcinoma; however, recent studies have questioned the actual role of the combination as compared to either of the two agents alone. We report an open-label, two-center, phase II study of upfront paclitaxel for patients with histological diagnosis of stage III ovarian carcinoma. Treatment consisted of paclitaxel at 175 mg/m2 administered in a 3-h infusion every 21 days. Response was evaluated after the third course by either laparoscopy or exploratory laparotomy. Patients with stable or progressive disease discontinued treatment, whereas responding patients continued treatment until a maximum of six courses. Response, toxicity, time to progression (TTP) and survival were evaluated. From November 1993 to December 1995, 30 patients were accrued. All patients underwent primary cytoreduction; 17 (57%) and 13 (43%) patients had residual tumors <2 and >2 cm, respectively. Of 27 patients evaluable, objective responses were seen in 18 (66.4%) (95% CI 49.5-83.2)--12 complete (45%) and six partial (22%). Four patients had stable disease (15%) and five (18%) patients progressed. A total of 149 courses were administered to 30 patients, median 4 (range 1-6). Grade 3/4 neutropenia was seen in 13% of courses, peripheral neuropathy, myalgia and arthralgia were frequent, but transitory and relieved with analgesics. At a median follow-up time of 44.5 months (0-99) the TTP and median survival were 16.6 and 43.1 months, respectively. We conclude that single-agent paclitaxel is an effective and well-tolerated first-line treatment for advanced ovarian carcinoma.

[Rectal cancer and pregnancy]. / Cáncer de recto y embarazo.

OBJECTIVE: To present Instituto Nacional de Cancerología de México, Gastroenterology Service management of rectal cancer in pregnant patients in a retrospective case study. CASE REPORT: Two patients were found, 25 an 34 years of age; both adenocarcinomas presented in Dukes D stage and manifested in third trimester of pregnancy. Main clinical manifestations were pelvic pain, hematochezia, and weight loss. Both patients died due to disease progression. CONCLUSIONS: Rectal cancer in pregnant patients is generally an advanced disease at diagnosis.

Cirugía en tumores hepáticos benignos / Surgery in bening liver tumors

Objetivo: evaluar las indicaciones y los resultados de la cirugía en los tumores hepáticos benignos (THB). La resección continúa siendo la mejor forma de manejo para los THB sintomáticas, en los últimos años los resultados operatorios han mejorado en centros de gran experiencia.Pacientes y método: se revisaron los expedientes clínicos de pacientes con THB operados durante el periodo de mayo de 1995 a diciembre de 1999.Resultados: se operaron 17 pacientes, 15 fueron mujeres y dos hombres. La edad promedio fue de 45 años (margen 32-68 años). Fueron 11 hemangiomas cavernosos, dos adenomas hepáticos, dos hiperplasias nodulares focales, un angiomiolipoma hepático y un adenofibroma biliar. Presentaban síntomas doce pacientes (70 por ciento), tres fueron operados con imágenes sospechosas de malignidad, uno por crecimiento acelerado y otro por su estirpe histológica. El tamaño promedio de la lesión fue de 7 cm (margen 3-19 cm). Se realizaron siete resecciones mayores que incluyeron cinco hepatectomías derechas y una izquierda, así como una trisegmentectomía izquierda. Diez resecciones menores (cinco resecciones del segmento lateral izquierdo, tres enucleaciones, dos segmentectomías). La hemorragia intraoperatoria promedio fue de 1,200 mL (margen de 100 a 3,000 mL). Dos pacientes (11.7 por ciento) presentaron complicaciones y no se presentó mortalidad operatoria. El seguimiento promedio fue de 26 meses (margen de 2 a 52 meses) y todos se encuentran asintomáticos al momento de la publicación. Se concluye que la selección cuidadosa de los casos permite realizar la resección de estas lesiones, con adecuados márgenes de seguridad, que permiten eliminar la sintomatología.

Hepatectomía parcial por laparoscopia. Informe del primer caso en México / Laparoscopic partial hepatectomy. Report of the first case in Mexico

Se presenta el caso clínico de una mujer de 47 años de edad que fue referida con dolor abdominal y una lesión focal en el segmento lateral izquierdo del hígado. Después de realizar estudios de extensión tumoral se practicó segmentectomía lateral izquierda por abordaje laparoscópico. Su evolución no presentó complicaciones y fue egresada en el segundo día postoperatorio. El reporte histopatológico fue de hiperplasia nodular focal. Hasta donde conocemos, éste es el primer caso operado con este abordaje en México.

Indicaciones y resultados de la resección hepática en tumores benignos y malignos / Indications for and results of the hepatic resection in malignant and benignant tumors

Objetivo: evaluar las indicaciones y los resultados obtenidos en 75 resecciones hepáticas. Introducción: en los últimos años la morbilidad y la mortalidad de este procedimiento en centros especializados, ha disminuido en parte por menor hemorragia intraoperatoria y por mejor manejo perioperatorio. Material y método: se revisaron los expedientes clínicos de 72 pacientes quienes fueron sometidos a 75 resecciones hepáticas en un periodo de 4 años. Resultados: 52 realizadas a mujeres y 23 a hombres. El margen de edad varió de 15 a 88 años (x :50 + 22 años). Las indicaciones de cirugía fueron metástasis hepáticas en 28, carcinoma de vesícula y/o vía biliar en 17, tumores hepáticos benignos en 16, y tumores primarios malignos en 14. Se realizaron 47 resecciones mayores que incluyeron 25 hepatectomías derechas, 13 hepatectomías izquierdas, 5 trisegmentectomías derechas y 4 trisegmentectomías izquierdas. Veintiocho resecciones menores que incluyeron 12 resecciones del segmento lateral izquierdo, 9 bisegmentectomías, 5 segmentectomías y 2 resecciones del lóbulo caudado. El tiempo de cirugía varió de 60-540 min (x :260 + 97min), el promedio de hemorragia intraoperatoria fue de 1439 + 660 mL (margen 20-5000 mL). En 63 pacientes se utilizó la maniobra de Pringle y el tiempo promedio de isquemia fue de 42 + 25 minutos (margen 20-100 minutos). Presentaron complicaciones 25 pacientes (33 por ciento), 3 intraoperatorias y 22 posoperatorias, siendo las más frecuentes: la insuficiencia hepática, la hemorragia intraabdominal, la ascitis y las colecciones biliares. La mortalidad operatoria (< 30 días) fue de 8 por ciento. Cuatro pacientes fallecieron por insuficiencia hepática y falla orgánica múltiple, uno por neumonía e infarto del miocardio y uno por sepsis. Conclusiones: la resección hepática es una excelente alternativa terapéutica en pacientes con lesiones hepáticas focales benignas y malignas.

Carcinoma hepatocelular. Experiencia en el Instituto Nacional de Cancerología / Hepatocellular carcinoma. Experience at the Instituto Nacional de Cancerología

Antecedentes. El carcinoma hepatocelular (CHC) es un tumor poco común en México, corresponde al 14 por ciento de todas las neoplasias malignas, en contraste con otros países como los del sureste de Asia, Japón y los localizados al sur del Sahara, en donde su incidencia es sumamente elevada. Frecuentemente es diagnósticado en etapas clínicas avanzadas impidiendo así una cirugía curativa. Objetivo. Analizar las características generales de pacientes con CHC, así como su manejo. Métodos. Se realizó un estudio observacional, retrospectivo, transversal de 63 casos documentados por histología de CHC. Resultados. Treinta y dos pacientes fueron del sexo masculino (50.7 por ciento), 31 del femenino, la edad promedio fue de 56 años, 18 tenían historia de alcoholismo. La hepatomegalia, el dolor abdominal y la pérdida de peso fueron los datos predominantes. El alfa-fetoproteína (AFP) fue positiva en el 55 por ciento de los casos, el ultrasonido y la tomografía computada de abdomen fueron los estudios de mayor utilidad. El 56 por ciento tenía asociación a hepatopatía crónica, 51 por ciento a cirrosis alcohólica, 43 por ciento a cirrosis por otra causa no determinada y 6 por ciento a hepatitis crónica. Setenta por ciento se diagnosticó en etapa clínica II, 17 por ciento en etapa III. Sólo un 31 por ciento fue llevado a cirugía, de los cuales en el 70 por ciento se efectuó únicamente laparotomía y biopsia, 15 por ciento resección hepática y 15 por ciento desarterialización, 54 por ciento no recibió ningún tratamiento. Las complicaciones postoperatorias fueron del 25 por ciento y la mortalidad del 20 por ciento con supervivencia promedio de 10 meses. Conclusiones. El CHC es un tumor raro en nuestro medio. La mayoría de los casos se diagnosticaron en etapas avanzadas. La relación hombre mujer fue similar, contrario a lo reportado en la literatura. El porcentaje de AFP elevada fue bajo (55 por ciento). Por lo avanzado de la enfermedad y/o las malas condiciones de los pacientes, la mayoría se consideraron irresecables por lo que es necesario evaluar otras formas de tratamiento. Es recomendable identificar a pacientes con alto riesgo de desarrollar CHC para realizar detección y tratamiento oportuno