Waiting times for surgical and diagnostic procedures in public hospitals in Mexico / Tiempos de espera para procedimientos quirúrgicos y diagnósticos en hospitales públicos de México

Objective. A retrospective evaluation of waiting times for elective procedures was conducted in a sample of Mexican public hospitals from the following institutions: the Mexican Institute for Social Security (IMSS), the Institute for Social Security and Social Services for Civil Servants (ISSSTE) and the Ministry of Health (MoH). Our aim was to describe current waiting times and identify opportunities to redistribute service demand among public institutions. Materials and methods. We examined current waiting times and productivity for seven elective surgical and four diagnostic imaging procedures, selected on the basis of their relative frequency and comparability with other national health systems. Results. Mean waiting time for the seven surgical procedures in the three institutions was 14 weeks. IMSS and ISSSTE hospitals showed better performance (12 and 13 weeks) than the MoH hospitals (15 weeks). Mean waiting time for the four diagnostic procedures was 11 weeks. IMSS hospitals (10 weeks) showed better average waiting times than ISSSTE (12 weeks) and MoH hospitals (11 weeks). Conclusion. Substantial variations were revealed, not only among institutions but also within the same institution. These variations need to be addressed in order to improve patient satisfaction.

Objetivo. Se llevó a cabo una evaluación retrospectiva de los tiempos de espera para procedimientos electivos en una muestra de hospitales públicos en México de las siguientes instituciones: Instituto Mexicano del Seguro Social (IMSS), Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE) y Secretaría de Salud (SS). El propósito era describir la situación actual en materia de tiempos de espera e identificar oportunidades de redistribución de la demanda de servicios entre instituciones públicas. Material y métodos. Se analizaron los tiempos de espera y la productividad para siete procedimientos quirúrgicos y cuatro procedimientos diagnósticos seleccionados sobre la base de su frecuencia relativa y comparabilidad con otros sistemas de salud nacionales. Resultados. El tiempo de espera promedio para los siete procedimientos quirúrgicos en las tres instituciones fue de 14 semanas. Los hospitales del IMSS y el ISSSTE mostraron un mejor desempeño (12 y 13 semanas) frente a los hospitales de la SS (15 semanas). El tiempo de espera promedio para los cuatro procedimientos diagnósticos fue de 11 semanas. Los hospitales del IMSS mostraron un tiempo de espera promedio mejor (10 semanas) que los hospitales del ISSSTE (12 semanas) y la SS (11 semanas). Conclusión. Se identificaron variaciones importantes no sólo entre instituciones sino también al interior de cada una de ellas. Estas variaciones deben atenderse para así mejorar la satisfacción de los usuarios de los servicios.

ATP-Based Chemotherapy Response Assay in Primary or Recurrent Ovarian and Peritoneal Cancer

PURPOSE: To investigate chemosensitivity with an adenosine triphosphate-based chemotherapy response assay in patients with epithelial ovarian or peritoneal cancer according to tumor histology, grade, and disease status. MATERIALS AND METHODS: One hundred specimens were collected during primary or secondary debulking from 67 patients with primary ovarian cancer, 24 patients with recurrent ovarian cancer, 5 patients with primary peritoneal cancer, and 4 patients with recurrent peritoneal cancer; samples were collected between August 2006 and June 2009. Tumor cells were isolated and cultured for 48 hours in media containing chemotherapy. The chemosensitivity index (CI) was calculated as 300 minus the sum of the cell death rate at 0.2x, 1x, and 5x drug concentrations, and the CI values were compared. RESULTS: CI values were obtained from 93 of 100 patients. The most active agents against primary disease were ifosfamide and paclitaxel. For primary serous adenocarcinoma, paclitaxel and irinotecan were the most active, followed by ifosfamide. For clear cell carcinoma, ifosfamide was the most active, followed by paclitaxel and irinotecan. Although not statistically significant, the CIs of cisplatin, carboplatin, paclitaxel, and docetaxel decreased as tumor grade increased. In 14 cases of recurrent disease, paclitaxel was the most active, followed by ifosfamide and cisplatin. CONCLUSION: Ifosfamide and paclitaxel were the most active drugs for primary and recurrent disease. Therefore, we recommend further clinical studies to confirm the efficacy of paclitaxel, ifosfamide, and cisplatin combination chemotherapy for recurrent and primary ovarian cancer.

FOLFIRI as Second-line Chemotherapy after Failure of FOLFOX4 in Advanced Colorectal Cancer: A Korean Single-center Experience / 대한소화기학회지

BACKGROUND/AIMS: The incidence of colorectal cancer has been increasing every year in Korea. Irinotecan- or oxaliplatin-based regimens including biologic agents are known to be effective in patients with advanced colorectal cancer. But in practice, FOLFOX (combination of oxaliplatin, 5-fluorouracil, and leucovorin) or FOLFIRI (combination of irinotecan, 5-fluorouracil, and leucovorin) regimens without biologic agents are more commonly used in Korea due to of the high costs of biologic agents. The aim of this study was to evaluate the efficacy and toxicity of FOLFIRI following FOLFOX4 in patients with advanced colorectal cancer. METHODS: A total of 54 patients with advanced colorectal cancer who were treated between May 2005 and May 2013 with FOLFOX4 as first-line chemotherapy and with FOLFIRI as second-line chemotherapy at Kosin University Gospel Hospital (Busan, Korea) were reviewed retrospectively. RESULTS: A total of 54 patients received second-line FOLFIRI chemotherapy. Five patients (9.3%) had a partial response, 29 patients (53.7%) had a stable disease. The median overall survival was 8.90 months and the median time to progression was 4.33 months. Toxicities were tolerable. CONCLUSIONS: In a Korean population, FOLFIRI as second-line chemotherapy is effective and well tolerated in patients with advanced colorectal cancer after failure of FOLFOX4. Although the efficacy of FOLFIRI in this study was lower than that of second-line FOLFIRI with biologic agents, these results can help in the formulation of a treatment strategy for financially troubled patients.

Alternativas terapéuticas actuales de las metástasis hepáticas: [revisión] / Current therapeutic options for liver metastasis: [review]

The liver is a common site of hematogenous metastasis, especially from gastrointestinal malignancies. Liver metastasis are generally classified as stage IV disease. Previously treatment in such patients was met with great skeptiscism. However, advances in surgical and medical therapies during the last two decades have provided effective therapeutic options for selected patients. Since major hepatic resections are now performed with acceptable morbidity and a mortality rate <3 percent, colorectal cancer metastasis to the liver are associated with 5-year survival rates of 30 percent or more. Meanwhile, a variety of new therapies have been developed, including hepatic artery infusion of chemotherapy; alcoholic, crio and radiofrequency ablation and novel strategies of systemic chemotherapy with the development of molecular targeted new products. These new therapeutic armamentarium have been used mostly in liver metastasis from colorectal cancer patients. However, liver metastasis of neuroendocrine tumors and selected cases of non colorectal cancer liver metastasis are benefited from the same strategies. This report summarizes the different therapeutic tools, their advantages and results mainly on colorectal cancer liver metastasis. These results are expected to improve even further with multimodality approaches.

Phase II study of cisplatin combined to irinotecan administered alternatingly with docetaxel in advanced non-small cell lung cancer.

OBJECTIVE: To assess the activity and toxicity of cisplatin and irinotecan alternating with docetaxel in patients with advanced non-small cell lung cancer (NSCLC). MATERIAL AND METHOD: Eligibility included chemo-naïve stage IIIB with malignant effusion and stage IV NSCLC patients with measurable disease and a good performance status. Twenty-four patients were enrolled into the present study. There were 19 males and 5 females with a median age of 58.5 years and the median performance status was 1. Ninety-six percent had stage IV disease. These patients received cisplatin at 80 mg/ m2 and irinotecan at 200 mg/m2 on day 1, followed by docetaxel at 75 mg/m2 on day 22, in 6-week cycle for a maximum of 3 cycles. RESULTS: Eight out of twenty-two evaluable patients obtained a partial response (36%). The median time to tumor progression was 6 months. The median survival time and 1-year survival rate were 10.4 months and 45% respectively. The most frequent severe toxicities were neutropenia, anemia, and diarrhea. Febrile neutropenia occurred in four patients (16%), and was the cause of treatment-related deaths in two (8%). Other nonhematologic toxicities were mild including nausea, vomiting, and skin rash. CONCLUSION: Alternating cisplatin and irinotecan with docetaxel, as used in the present study was feasible and demonstrated encouraging efficacy in patients with non-small cell lung cancer However, this approach appears to be more toxic, especially in myelosuppression, than in previous reports of the sequential use of the similar agents.

Safety and efficacy of cetuximab-chemotherapy combination in Saudi patients with metastatic colorectal cancer.

BACKGROUND: Cetuximab-based combination chemotherapy (CBCC) proved safe and effective as second-line strategy for metastatic colorectal cancer (mCRC). This prospective phase-II study was designed to assess the efficacy and safety of CBCC as first-, second- or third-line among Saudi patients with mCRC. MATERIALS AND METHODS: Patients with mCRC were offered CBCC to assess time-to-disease progression (TTP), response rate and duration, overall survival (OS) and safety. RESULTS: Nineteen patients were eligible and their median age was 51 years. Seven patients received CBCC as first-line and 12 as second- or third-line. Responses: 11 (58%) partial responses, 5 (26%) stable disease and 3 (16%) disease progressions. The median response duration was 4.3 months [95% confidence interval (CI): 3.4-5.2 months]. The median TTP was 6.8 months (95% CI: 2-13.9 months) for all 19 patients compared to 9.3 months (95% CI: 3.9-14.6 months) for the seven patients who received CBCC as first-line. The median OS for the entire population was 12.3 months (95% CI could not be determined). On the other hand, while the median OS for those who received CBCC as first-line have not been reached, the median OS for those who received CBCC after failure of other salvage therapies was 12.3 months (95% CI: 3.2-21.4 months). CBCC was generally tolerable. One patient had a severe hypersensitivity reaction and another fatal cardiac arrest. CONCLUSION: CBCC is active with an acceptable safety profile. Until results from phase-III clinical trials are available, using CBCC as first-line is probably justified.

Una variedad genética de la UDP-glucuronosil transferasa asociada a toxicidad gastrointestinal por irinotecan / A prevalent genetic variety of UDP-glycuronosyl transferase predicts high risk of irinotecan toxicity

Los avances en genética y biología molecular han impulsado la aparición de nuevas áreas de estudio en la medicina, como la farmacogenómica, la cual intenta predecir la respuesta y toxicidad a drogas en función de la variabilidad genética de cada individuo, constituyendo los llamados síndromes fármacogenómicos. La oncología podría beneficiarse debido a la gran toxicidad de sus fármacos. Hay varios loci genéticos que se están analizando por su potencial valor predictivo y hasta ahora sólo tres de ellos demostraron cierto grado de utilidad clínica. En especial, el estudio del número de repeticiones del dinucleótido timina-adenina (TA) en el promotor de la enzima UDP-glucuronosil-transferasa (UGT) mostró ser capaz de predecir neutropenia severa en pacientes expuestos a dosis intermedias y altas de irinotecan. Comunicamos el caso de una paciente con cáncer de pulmón de células pequeñas que padeció toxicidad hematológica y gastrointestinal grave tras haber sido tratada con dosis relativamente bajas (65 mg/m2) de irinotecan, y en quien un análisis del ADN leucocitario mostró la presencia de homocigosis para siete repeticiones de TA. Este caso es un ejemplo de aplicabilidad clínica del test, se discute su utilidad como predictor de toxicidad y la conducta a tomar frente a pacientes con estas características.

The advances in genetics and molecular biology have raised new areas in medicine, such as pharmacogenomics, which tries to predict drug responses and toxicities based on the individual genetic variability, describing the so called: pharmacogenomic syndromes. Oncology would find this development extremely useful because of the severe toxicity of chemotherapy. There are a lot of genetic loci under investigation for their potential in predicting drug toxicity, but only three of them have showed clinical usefulness up to now. In particular, quantification of the number of thymine-adenine (TA) dinucleotics in the promoter region of the UDP-glucuronosyl-transferase 1A1 enzime (TA indel) proved to be capable of predicting severe neutropenia in patients exposed to intermediate or high doses of irinotecan. Herein we report a case of a patient with small cell lung cancer who suffered severe hematological and gastrointestinal toxicity after being treated with relatively low doses (65 mg/m2) of irinotecan and whose leucocyte DNA analysis showed the presence of seven TA repetitions in both alleles. This case is an example of the clinical applicability and the utility of the test as a toxicity predictor. We also discuss the clinical decisions that may be taken with these patients.

A Phase II Study of Cetuximab (Erbitux(R)) plus FOLFIRI for Irinotecan and Oxaliplatin-refractory Metastatic Colorectal Cancer

We have evaluated the efficacy and safety of cetuximab plus FOLFIRI for irinotecan and oxaliplatin-refractory colorectal cancers. From September 2004 to February 2006, 31 patients with metastatic colorectal cancer were treated with cetuximab (400 mg/m2 intravenously [IV] over 2 hr on day 1 followed by weekly 1-hr infusions of 250 mg/m2) plus bi-weekly FOLFIRI (irinotecan 150 mg/m2 IV over 90 min, and leucovorin 100 mg/m2 IV over 2 hr, followed by 5-FU 400 mg/m2 IV bolus on day 1, and followed by 5-FU 2,400 mg/m2 by continuous IV over 46 hrs). Patients received a median of four cycles (range: 1-23). Eight (25.8%) patients had confirmed partial responses and 10 (32.2%) had stable disease. After a median follow-up of 13.2 months for surviving patients, the median time to progression was 2.9 months, the median duration of response was 5.4 months, and the median overall survival was 10.9 months. Skin toxicity was observed in 25 patients (80.4%) including grade 3 in 6 patients (19.4%). Other common non-hematologic toxicities of all grades were mucositis (32.3%), asthenia (22.6%), diarrhea (12.9%), and paronychial cracking (12.9%). The combination of cetuximab with FOLFIRI was effective and tolerable in colorectal cancer patients heavily pretreated with a number of chemotherapy regimens.

Biweekly Irinotecan and Cisplatin as Second-line Chemotherapy in Pretreated Patients with Advanced Gastric Cancer: A Multicenter Phase II Study

The current phase II study was conducted to evaluate the response rate and safety of a combination regimen of biweekly irinotecan plus cisplatin in pretreated patients with advanced gastric cancer. Patients with previously treated metastatic or recurrent gastric cancer received intravenous irinotecan 70 mg/m2 and cisplatin 30 mg/m2 on day 1 and 15 every 4-week cycle. Thirty-two patients were enrolled in the current study. Of these, 31 patients were assessable for efficacy and all for toxicity. No complete response and 5 partial responses were confirmed, giving an overall response rate of 15.6% (95% CI; 2.3-28.9%). The median time to progression and median overall survival for all patients was 113 days and 184 days, respectively. Grade 3/4 neutropenia occurred in 6 patients (18.8%), yet no febrile neutropenia was observed. In addition, grade 3 anorexia was observed in 4 patients (12.5%) and grade 3 diarrhea occurred in 2 patients (6.2%). The combination chemotherapy of biweekly irinotecan and cisplatin was found to be moderately effective and well tolerated in pretreated patients with advanced gastric cancer. Accordingly, this regimen can be regarded as an important second-line treatment option for advanced gastric cancer.

Irinotecan, Continuous 5-Fluorouracil, and Low dose of Leucovorin (modified FOLFIRI) as First Line of Therapy in Recurrent or Metastatic Colorectal Cancer

BACKGROUND: Irinotecan, in combination with 5-fluorouracil (5-FU) and a high dose of leucovorin (LV), known as FOLFIRI regimen, has shown activity in recurrent or metastatic colorectal cancer. Therefore, we evaluated the efficacy and safety of irinotecan, 5-FU and a low dose of LV (modified FOLFIRI) as a first line of therapy for patients with relapsed or metastatic colorectal cancer. METHODS: Between January 2002 and October 2004, 44 patients with histologically confirmed recurrent or metastatic colorectal cancer were enrolled. The chemotherapy regimen schedule consisted of 180 mg/m2 of irinotecan being administered intravenously (i.v) on Day 1, 400 mg/m2 of 5-FU via i.v bolus with 600 mg/m2 of continuous infusion for 22 hrs on both Day 1 and 2, and 20 mg/m2 of leucovorin on both Day 1 and 2, repeated every two weeks. RESULTS: The overall response rate was 47.8%. Of the 40 evaluated patients, one had CR (2.3%) and 20 had PR (46.5%). Toxicities were mild and easily manageable. Three patients experienced 23 episodes of Grade 3/4 leukopenia., Only one patient developed Grade 3/4 diarrhea. None experienced Grade 3/4 thrombocytopenia. CONCLUSION: Modified FOLFIRI with a low dose of LV is an effective and tolerable regimen for patients with recurrent or metastatic colorectal cancer.

Current treatment and future directions in neuroblastoma.

OBJECTIVE: The International Neuroblastoma Staging System (INSS) and Pathology Classification (INPC) were applied to analyze the results of treatment of 644 patients with neuroblastoma treated in Japan during the years from 1995 to 1999, and it was found that the pathology classification (INPC) showed the strongest relevance to prognosis compared to other factors such as stage, MYNC amplification, DNA ploidy and 1p-deletion. Current results of treatment for advanced neuroblastoma are still not satisfactory, so innovative therapeutic methods have been sought during the past 10 years. METHODS: Prospects for irinotecan and recombinant human endostatin (rhEndostatin) were studied expertimentally and clinically. RESULTS: Irinotecan is a water-soluble derivative of camptothecin, which is isolated from a Chinese tree, Camptotheca acuminata; Its effectiveness against neuroblastoma was confirmed by in vivo preclinical studies, and phase I clinical trials in Japan concluded the maximum tolerated dose of this agent is 160-180 mg/m2/day for 3 consecutive days, repeated after 25 days off. Phase II trials with this dose began, and we could obtain some encouraging results with the clinical use of irinotecan. rhEndostatin has been studied in in vivo experimental models. The action of rhEndostatin was quite different from those of other cytotoxic chemotherapeutic agents, and continuous administration of this substance showed a more marked anti-effect than its intermittent use. CONCLUSION: Irinotecan appears to be promising when it is given to the patients neuroblastoma, whereas rhEndostatin needs to have more preclinical studies before it is used in patients.

Clinical activity and benefit of irinotecan (CPT-11) in patients with metastatic colorectal carcinoma pre-treated with fluorouracil-based chemotherapy.

The purpose of this prospective study was to assess the efficacy, clinical benefit and safety of irinotecan (CPT-11) in patients with 5-fluorouracil-resistant metastatic colorectal cancer (CRC). Sixteen patients with World Health Organization (WHO) performance status < or = 2 were treated with CPT-11 350 mg/m2 every 3 weeks. The observed partial response (PR) rate was 6.3 per cent with a high rate of stable disease (SD) (43.7%) which was of long duration (21.1 weeks for the best response; 1PR, 7SD). The median survival time for the 16 patients entered into this study was 69.6 weeks. There was no toxic death. The most frequent adverse events were neutropenia (31% grade 3/4) and delayed diarrhea (9.7%). CPT-11 has definite activity in the treatment of progressive metastatic CRC truly resistant to 5-FU which translated into clinical survival benefit. Median survival from first administration of CPT-11 was 78.6 weeks for patients with best response (PR + SD) compared with 28.1 weeks for patients with progressive disease (PD) (P = 0.01). With the appearance of new active drugs in this highly chemotherapy-resistant disease, the definition of response should be reassessed in CRC.