Expression of KATP channels in human cervical cancer: Potential tools for diagnosis and therapy.

Various ion channels, including ATP-sensitive potassium (KATP) channels, are expressed in cancer and have been suggested as potential tumor markers and therapeutic targets. KATP channels are composed of at least two types of subunit, an inwardly rectifying K+ channel (Kir6.x) and a sulfonylurea receptor (SUR). However, the association between KATP channels and cervical cancer remains elusive. The present study determined that the Kir6.2, SUR1 and SUR2 subunits are expressed in cervical cancer cell lines and/or human biopsies. The potential association of subunit expression with tumor differentiation and invasion was analyzed. The effect of the KATP channel blocker glibenclamide on the proliferation of cervical cancer cell lines was also studied. Five cervical cancer cell lines, two primary cultures of cervical cancer cells, one normal keratinocyte cell line and 74 human biopsies were used in the experiments. The mRNA and protein levels of the Kir6.2 subunit were assessed by reverse transcription-polymerase chain reaction and immunochemistry, respectively. Cell proliferation was evaluated by MTT assay. Kir6.2 subunit overexpression compared with control, was observed in some cervical cancer cell lines and cervical tumor tissues. Additionally, increased KATP channel expression was observed in high-grade, poorly differentiated and invasive human cervical cancer biopsies. Kir6.2 subunit expression was not observed in the majority of the non-cancerous cervical tissues. The effect of the KATP channel blocker glibenclamide on the proliferation of five different cervical cancer cell lines was studied, revealing that as Kir6.2 mRNA expression increased, the inhibitory effect of glibenclamide also increased. The results of the present study suggest, for the first time to the best of our knowledge, that the KATP channel subunits, Kir6.2 and SUR2, could potentially represent tools for diagnosing and treating cervical cancer.

Vólvulo primario de íleon: una rara forma de obstrucción intestinal en el adulto: reporte de caso y revisión de la literatura / Primary volvulus of ileum: A rare form of intestinal obstruction in the adult: case report and literature review

Resumen Antecedentes El vólvulo de intestino delgado se produce por el giro anormal del intestino delgado alrededor del eje de su propio mesenterio, lo cual puede generar obstrucción intestinal, isquemia, infarto o perforación. Caso clínico Paciente masculino de 71 años que cursó con abdomen agudo. Sospechando cuadro de oclusión intestinal, se realizó exploración quirúrgica en la que se encontró como hallazgos vólvulo de intestino delgado en la válvula ileocecal, con isquemia y necrosis de 280 cm de intestino delgado, por lo cual se realizó resección intestinal e ileostomía terminal, preservando 320 cm de intestino delgado viable desde ángulo duodeno-yeyunal. Cursó con una evolución satisfactoria. Discusión El vólvulo de intestino delgado es una entidad infrecuente y una urgencia quirúrgica que amenaza la vida. Se debe sospechar en todos los pacientes que presenten dolor abdominal abrupto y signos de obstrucción intestinal, sin cirugía abdominal previa ni otras causas obvias. El diagnóstico precoz y la intervención quirúrgica inmediata son factores clave asociados con un mejor pronóstico para este grupo de pacientes.

Background The small bowel volvulus is caused by the abnormal rotation of the small intestine around the axis of its own mesentery. This can lead to intestinal obstruction, ischemia, infarction or perforation. Clinical case A 71-year-old male patient with an acute abdominal pain, suspicious for a bowel occlusion, performed a surgical exploration, finding small bowel volvulus at the ileocecal valve level, with necrosis and ischemia of 280 cm of the small intestine, resulting in intestinal resection and terminal ileostomy. Still preserving 320 cm of viable small intestine from the duodenojejunal angle, with a satisfactory evolution. Discussion Small bowel volvulus is an uncommon entity, and a life-threatening surgical emergency, that should be suspected in all patients with abrupt abdominal pain and signs of bowel obstruction, without previous abdominal surgery or other obvious causes. Early diagnosis and immediate surgical intervention are key factors associated with a better prognosis for this group of patients.

Pre-exenterative chemotherapy, a novel therapeutic approach for patients with persistent or recurrent cervical cancer.

BACKGROUND: Most cervical cancer patients with pelvic recurrent or persistent disease are not candidates for exenteration, therefore, they only receive palliative chemotherapy. Here we report the results of a novel treatment modality for these patients pre-exenterative chemotherapy- under the rational that the shrinking of the pelvic tumor would allow its resection. METHODS: Patients with recurrent or persistent disease and no evidence of systemic disease, considered not be candidates for pelvic exenteration because of the extent of pelvic tumor, received 3-courses of platinum-based chemotherapy. Response was evaluated by CT scan and bimanual pelvic examination; however the decision to perform exenteration relied on the physical findings. Toxicity to chemotherapy was evaluated with standard criteria. Survival was analyzed with the Kaplan-Meier method. RESULTS: Seventeen patients were studied. The median number of chemotherapy courses was 4. There were 9 patients who responded to chemotherapy, evaluated by bimanual examination and underwent pelvic exenteration. Four of them had pathological complete response. Eight patients did not respond and were not subjected to surgery. One patient died due to exenteration complications. At a median follow-up of 11 months, the median survival for the whole group was 11 months, 3 months in the non-operated and 32 months in those subjected to exenteration. CONCLUSION: Pre-exenterative chemotherapy is an alternative for cervical cancer patients that are no candidates for exenteration because of the extent of the pelvic disease. Its place in the management of recurrent disease needs to be investigated in randomized studies, however, its value for offering long-term survival in some of these patients with no other option than palliative care must be stressed.

Induction chemotherapy with gemcitabine and oxaliplatin for locally advanced cervical carcinoma.

Induction chemotherapy followed by surgery, particularly with newer agents or combinations, remains to be explored in locally advanced cervical cancer. Gemcitabine cisplatin is a very active combination for this tumor, therefore we explored the activity of gemcitabine in combination with oxaliplatin. Ten untreated patients with histologic diagnosis of cervical carcinoma and staged as IB2 to IIIB were treated with 3 21-day courses of oxaliplatin 130 mg/m day 1 and gemcitabine 1,250 mg/m days 1 and 8 followed by locoregional treatment with either surgery or concomitant chemoradiation. Response and toxicity were evaluated at the end of chemotherapy. All patients were evaluable. The overall clinical response rate was 80%, being complete in 3 patients (30%) and partial in 5 (50%). Seven (70%) patients underwent surgery, and three (30%) had chemoradiation as definitive treatment. Hematologic toxicity was moderate, with leukopenia grades III-IV in 17 and 0%; granulocytopenia grades III-IV in 23 and 3%, respectively. Eight patients had grade I oropharyngeal toxicity. At a median follow-up of 11 months (range: 10-12), all patients are disease free. Gemcitabine oxaliplatin is a very active and well-tolerated combination for locally advanced cervical cancer.

Quimiterapia neoadyuvante en pacientes con carcinoma epidermoide de cérvix estadio IB2 y IIA: resultados preliminares de un estudio aleatorizado / Neoadyuvant chemotherapy in patients with cervical carcinoma stages IB2 and IIA: preliminary results in aletorized study

Antecedentes. El cáncer de cérvix es el tumor maligno más frecuente en México. Estudios fase II de quimioterapia neoadyuvante seguida de cirugía en pacientes con estadios clínicos IB2 y IIA sugieren un beneficio en cuanto a control local y supervivencia en comparación con radioterapia sola. Objetivo. Determinar si la quimioterapia neoadyuvante seguida de cirugía mejora la supervivencia en comparación a radioterapia en pacientes con cáncer epidermoide de cérvix estadios IB2 y IIA. Pacientes y métodos. Pacientes en estadios IB2 y IIA de acuerdo a la clasificación de la Federación Internacional de Ginecología y Obstetricia (FIGO) fueron asignadas de manera aleatoria para recibir quimioterapia neoadyuvante con el siguiente esquema: cisplatino 50 mg/m2 d1, vincristina 1.5 mg/m2 d1 y bleomicina 20 mg/m2 d1, d2 y d3 (PVB) en infusión intravenosa continua. Los ciclos se administraron cada 10 días por tres veces. Después de la quimioterapia, las pacientes fueron sometidas a histerectomía radical y linfadenectomía pélvica bilateral. Se administró radioterapia adyuvante en caso de ganglios pélvicos positivos; afección parametrial; margen quirúrgico positivo e invasión estromal mayor de dos tercios del espesor cervical. Las pacientes del brazo de radioterapia recibieron una combinación de teleterapia y braquiterapia a una dosis de 8,500 y 5,500 cGy a los puntos A y B, respectivamente. Resultados. El estudio fue planeado para incluir 80 pacientes por brazo, pero se terminó de manera prematura por lo que sólo se incluyeron 20 enfermas (10 por brazo). La respuesta global a la quimioterapia fue del 90 por ciento y nueve de ellas fueron sometidas a cirugía. Nueve de las diez pacientes asignadas a radiación que completaron el tratamiento obtuvieron respuesta completa. El tratamiento fue bien tolerado en ambos grupos de mujeres. A un seguimiento máximo de 14 meses, una paciente en cada brazo ha recaído. Conclusión. Los resultados preliminares de este estudio sugieren que la quimioterapia neoadyuvante con PVB es factible, produce alto índice de respuestas y parece disminuir la presencia de factores patológicos de alto riesgo para recurrencia.