Successful desensitization to oxaliplatin after a single initial dose of omalizumab in a patient with elevated IgE levels

No disponible

Intensified neoadjuvant multimodal approach in synchronous liver metastases from gastric cancer: a single institutional experience

Background. Synchronous liver metastases (LM) from gastric (GC) or esophagogastric junction (EGJ) adenocarcinoma are a rare events. Several trials have evaluated the role of liver surgery in this setting, but the impact of preoperative therapy remains undetermined. Methods. Patients with synchronous LM from GC/EGJ adenocarcinoma who achieved disease control after induction chemotherapy (ICT) and were subsequently scheduled to chemoradiotherapy (CRT) to the primary tumor and surgery assessment were retrospectively analyzed. Pathological response, patterns of relapse, progression-free survival (PFS), and overall survival (OS) were calculated. From July 2002 to September 2012, 16 patients fulfilling the inclusion criteria were identified. Results. Primary tumor site was GC (nine patients) or EGJ (seven patients). LM were considered technically unresectable in nine patients. Radiological response to the whole neoadjuvant program was achieved in 13 patients. Eight patients underwent surgical resection of the primary tumor; in five of these LM were resected. A complete pathological response in the primary or in the LM was found in four and three patients, respectively. The most frequent site of relapse/progression was systemic (eight patients). Local and liver-only relapses were observed in two patients each. After a median follow-up of 91 months, the median OS and PFS were 23.0 (95% CI 13.2-32.8) and 17.0 months (95% CI 11.7-22.3). 5-year actuarial PFS is 17.6%. Conclusion. Our results suggest that an intensified approach using ICT followed by CRT in synchronous LM from GC/EGJ adenocarcinoma is feasible and may translate into prolonged survival times in selected patients

No disponible

Intensified neoadjuvant multimodal approach in synchronous liver metastases from gastric cancer: a single institutional experience.

BACKGROUND: Synchronous liver metastases (LM) from gastric (GC) or esophagogastric junction (EGJ) adenocarcinoma are a rare events. Several trials have evaluated the role of liver surgery in this setting, but the impact of preoperative therapy remains undetermined. METHODS: Patients with synchronous LM from GC/EGJ adenocarcinoma who achieved disease control after induction chemotherapy (ICT) and were subsequently scheduled to chemoradiotherapy (CRT) to the primary tumor and surgery assessment were retrospectively analyzed. Pathological response, patterns of relapse, progression-free survival (PFS), and overall survival (OS) were calculated. From July 2002 to September 2012, 16 patients fulfilling the inclusion criteria were identified. RESULTS: Primary tumor site was GC (nine patients) or EGJ (seven patients). LM were considered technically unresectable in nine patients. Radiological response to the whole neoadjuvant program was achieved in 13 patients. Eight patients underwent surgical resection of the primary tumor; in five of these LM were resected. A complete pathological response in the primary or in the LM was found in four and three patients, respectively. The most frequent site of relapse/progression was systemic (eight patients). Local and liver-only relapses were observed in two patients each. After a median follow-up of 91 months, the median OS and PFS were 23.0 (95% CI 13.2-32.8) and 17.0 months (95% CI 11.7-22.3). 5-year actuarial PFS is 17.6%. CONCLUSION: Our results suggest that an intensified approach using ICT followed by CRT in synchronous LM from GC/EGJ adenocarcinoma is feasible and may translate into prolonged survival times in selected patients.

Mid-term oncologic outcome of a novel approach for locally advanced colon cancer with neoadjuvant chemotherapy and surgery

Purpose. Neoadjuvant chemotherapy is being actively tested as an emerging alternative for the treatment of locally advanced colon cancer (LACC) patients, resembling its use in other gastrointestinal tumors. This study assesses the mid-term oncologic outcome of LACC patients treated with oxaliplatin and fluoropyrimidines-based preoperative chemotherapy followed by surgery. Methods and patients. Patients with radiologically resectable LACC treated with neoadjuvant therapy between 2009 and 2014 were retrospectively analyzed. Radiological, metabolic, and pathological tumor response was assessed. Both postoperative complications, relapse-free survival (RFS), and overall survival (OS) were studied. Results. Sixty-five LACC patients who received treatment were included. Planned treatment was completed by 93.8 % of patients. All patients underwent surgery without delay. The median time between the start of chemotherapy and surgery was 71 days (65-82). No progressive disease was observed during preoperative treatment. A statistically significant tumor volume reduction of 62.5 % was achieved by CT scan (39.8-79.8) (p < 0.001). It was also observed a median reduction of 40.5 % (24.2-63.7 %) (p < 0.005) of SUVmax (Standard Uptake Value) by PET-CT scan. Complete pathologic response was achieved in 4.6 % of patients. Postoperative complications were observed in 15.4 % of patients, with no cases of mortality. After a median follow-up of 40.1 months, (p25-p75: 27.3-57.8) 3-5 year actuarial RFS was 88.9-85.6 %, respectively. Five-year actuarial OS was 95.3 %. Conclusion. Preoperative chemotherapy in LACC patients is safe and able to induce major tumor regression. Survival times are encouraging, and further research seems warranted (AU)

No disponible

Mid-term oncologic outcome of a novel approach for locally advanced colon cancer with neoadjuvant chemotherapy and surgery.

PURPOSE: Neoadjuvant chemotherapy is being actively tested as an emerging alternative for the treatment of locally advanced colon cancer (LACC) patients, resembling its use in other gastrointestinal tumors. This study assesses the mid-term oncologic outcome of LACC patients treated with oxaliplatin and fluoropyrimidines-based preoperative chemotherapy followed by surgery. METHODS AND PATIENTS: Patients with radiologically resectable LACC treated with neoadjuvant therapy between 2009 and 2014 were retrospectively analyzed. Radiological, metabolic, and pathological tumor response was assessed. Both postoperative complications, relapse-free survival (RFS), and overall survival (OS) were studied. RESULTS: Sixty-five LACC patients who received treatment were included. Planned treatment was completed by 93.8 % of patients. All patients underwent surgery without delay. The median time between the start of chemotherapy and surgery was 71 days (65-82). No progressive disease was observed during preoperative treatment. A statistically significant tumor volume reduction of 62.5 % was achieved by CT scan (39.8-79.8) (p < 0.001). It was also observed a median reduction of 40.5 % (24.2-63.7 %) (p < 0.005) of SUVmax (Standard Uptake Value) by PET-CT scan. Complete pathologic response was achieved in 4.6 % of patients. Postoperative complications were observed in 15.4 % of patients, with no cases of mortality. After a median follow-up of 40.1 months, (p 25-p 75: 27.3-57.8) 3-5 year actuarial RFS was 88.9-85.6 %, respectively. Five-year actuarial OS was 95.3 %. CONCLUSION: Preoperative chemotherapy in LACC patients is safe and able to induce major tumor regression. Survival times are encouraging, and further research seems warranted.

Development of the National Kidney Transplantation Program in Uruguay.

The first kidney transplantation (KT) in Uruguay was performed in 1969. We report the rates of KT and survival of patients and grafts up to December 2014. The country has a surface of 176,215 km(2) and a population of 3,286,314 inhabitants (18.6 inhabitants per km(2)). Till December 31, 2014, 1,940 KT have been performed in Uruguay (41.8 pmp that year); 90.4% of them were from cadaveric donors (CD). Median age of recipients (R) was 44 ± 14 years; R older than 55 years increased from 0 to 27% during the period. Our pre-emptive KT program started in 2007. Optimal donors (D) decreased from 65.2% to 35.5%, and D older than 45 years old increased from 9% to 37%. Trauma as cause of death decreased from 49% to 32% and stroke as cause of death increased from 25% to 39%. Patient survival rates at 1, 5, and 8 years were 93%, 87%, and 78%, respectively for KT performed between 1980 and 1989; they were 98%, 93%, and 89%, respectively, for KT performed between 1990 and1999; they were 97%, 91%, and 90%, respectively, for KT performed between 2000 and 2010. In December 2013, there were 1098 patients pmp in renal replacement therapy, 758 pmp in dialysis, and 340 pmp (30.9%) with a functioning graft. Our national KT program is mainly based (90.6%) on cadaveric donation. Epidemiological changes in the characteristics of R and D followed the changes in aging that occurred in the general population and the dialysis population. The survival rates from patients and kidneys are similar to those reported by the European and the American registries.

Preliminary outcome of a treatment strategy based on perioperative chemotherapy and surgery in patients with locally advanced colon cancer.

AIM: Preoperative chemotherapy followed by radical surgery is an attractive treatment for locally advanced colon cancer (LACC) given the promising results of this approach in other locally advanced tumours. The study evaluates the outcome and treatment-related complications of perioperative oxaliplatin- and capecitabine-based chemotherapy and surgery for clinical Stage III colon cancer. METHOD: Twenty-two consecutive patients with a CT-staged LACC were included. All were staged at baseline and before surgery. Surgery-related complications and oncological outcome were determined. RESULTS: Toxicity was manageable, with 19/22 patients completing the planned chemotherapy protocol. The median time from initial diagnosis to surgery was 65.5 days. The median time from the end of chemotherapy to surgery was 22 days. After neoadjuvant treatment, tumour reduction of 69.5% was observed by CT scan and a 59.9% decrease of SUVmax (standard uptake value) was achieved on positron emission tomography/CT. No progressive disease was reported during preoperative chemotherapy and surgery was performed in all 22 patients. Four patients developed postoperative complications. After a median postoperative follow-up of 14.4 months, the actuarial overall and disease-free survival rates were 100 and 90%. CONCLUSION: Neoadjuvant chemotherapy followed by surgery and chemotherapy for LACC is safe without apparent increase of early and medium-term complications.

Association of RRM1 -37A>C polymorphism with clinical outcome in colorectal cancer patients treated with gemcitabine-based chemotherapy.

BACKGROUND: To investigate whether single nucleotide polymorphisms (SNPs) in gemcitabine (GMB) metabolism genes were associated with clinical outcome in pre-treated metastatic colorectal cancer (mCRC) patients. PATIENTS AND METHODS: SNPs of hCNT1, hENT1, CDA, dCTD and RRM1 genes were evaluated in 95 mCRC patients and detected using TaqMan genotyping assays. Association of genotypes with overall response rate (ORR), time to progression (TTP) and overall survival (OS) was tested by univariate and multivariate analysis. RRM1 -37A>C polymorphism was correlated with GMB IC50 value and with the RRM1 gene expression level in CRC cell lines. RESULTS: The ORR was 38.9%. The median TTP and OS were 4 and 14.3 months, respectively. By multivariate analysis, patients carrying the RRM1 -37CC genotype or the CDA A-76 C-containing allele had a significantly higher likelihood of achieving a tumour response. RRM1 -37A>C polymorphism remained associated with clinical efficacy (TTP). In vitro experiments, in CRC cell lines, showed that the RRM1 A-37C genotype was associated with the levels of RRM1 expression and with GMB IC50 values. Finally, the down-regulation of RRM1 with a specific siRNA strongly influenced GMB sensitivity. CONCLUSION: RRM1 -37A>C polymorphism may represent a useful biomarker to select mCRC patients most likely to benefit from GMB-based salvage therapy.

La coordinación de esfuerzos en casos clínicos complejos: un valor añadido de cuidados paliativos en un hospital universitario / Coordinating efforts in complex clinical cases: added value of palliative care at a university teaching hospitalpcuth

Los cuidados paliativos se entienden generalmente en el contexto de la atención a pacientes terminales ingresados en hospitales o en unidades de hospitales de larga estancia. Sin embargo, cada vez son más frecuentes estas unidades en hospitales de alto nivel de desarrollo. Presentamos el caso de una paciente de especial complejidad, diagnosticada de carcinoma de recto en la que confluían cuatro problemas de difícil abordaje: dolor neuropático descontrolado a pesar de opioides, infección con repercusión sistémica, herida quirúrgica abierta y desánimo completo. Mostramos las medidas que se adoptaron y cómo una excelente colaboración inter-departamental, bajo la coordinación del equipo de medicina paliativa, sirvió para solucionar una situación que en un punto llegó aparecer insostenible (AU)

Palliative care is generally understood on caring for terminal patients in chronic settings but more recently these units are developing also in acute caresettings or university hospitals as consultants teams. We report the case of a complex patient with rectal adenocarcinoma and four problems of difficult approach: uncontrolled neuropathic pain despite opioids treatment, systemic infection, depression with intense demoralisation and open surgery wound. We show the measures adopted and how an excellent inter-departmental collaboration under the co-ordination of palliative medicine consultant team helped to resolve the untenable situation (AU)

Dose-finding study and pharmacogenomic analysis of fixed-rate infusion of gemcitabine, irinotecan and bevacizumab in pretreated metastatic colorectal cancer patients.

BACKGROUND: To determine the dose-limiting toxicity (DLT), maximum tolerated dose, recommended dose (RD) and preliminary evidence of activity of escalating doses of irinotecan (CPT-11) fixed-dose-rate infusional gemcitabine (FDR-GMB) and bevacizumab in pretreated metastatic colorectal cancer (mCRC) patients. Pharmacogenomic analysis was performed to investigate the association between VEGF single-nucleotide polymorphisms and clinical outcome. PATIENTS AND METHODS: A total of 89 mCRC patients were recruited in a two-step study design; 28 were included in the dose-finding study and 59 in the pharmacogenomic analysis. The FDR-GMB of 1000 mg m⁻², bevacizumab 5 mg kg⁻¹ and CPT-11 doses ranging from 100 to 160 mg m⁻² were explored. The VEGF protein serum levels were quantified by EIA. Allelic discrimination was performed to genotype polymorphisms in the VEGF gene. RESULTS: CPT-11 RD was 150 mg m⁻². Diarrhoea and neutropenia were the DLT. After a median follow-up of 42 months, the median time to progression (TTP) and overall survival were 5.2 and 19.9 months, respectively. VEGF levels were significantly correlated with VEGF-2578AA and VEGF-460CC genotypes, and a trend was observed with VEGF+405GG genotype. The presence of any of these genotypes correlated with a longer median TTP (8.8 vs 4.5 months, P=0.04). CONCLUSION: The triplet combination tested in this study is effective and well tolerated. A possible predictive role for VEGF gene polymorphisms and baseline VEGF circulating levels is suggested.

Oxaliplatin, irinotecan and capecitabine as first-line therapy in metastatic colorectal cancer (mCRC): a dose-finding study and pharmacogenomic analysis.

BACKGROUND: A dose-finding study was performed to evaluate the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD) and the recommended dose (RD) of escalating the doses of capecitabine and fixed doses of irinotecan and oxaliplatin on a biweekly schedule for metastatic colorectal cancer patients (mCRC). A pharmacogenomic analysis was performed to investigate the association between SNPs and treatment outcome. METHODS: Eighty-seven chemotherapy-naïve mCRC patients were recruited through a two-step study design; 27 were included in the dose-finding study and 60 in the pharmacogenomic analysis. Oxaliplatin (85 mg m(-2)) and CPT-11 (150 mg m(-2)), both on day 1, and capecitabine doses ranging from 850 to 1500 mg m(-2) bid on days 1-7 were explored. Peripheral blood samples were used to genotype 13 SNPs in 10 genes related to drug metabolism or efficacy. Univariate and multivariate Cox analysis was performed to examine associations between SNPs, ORR and PFS. RESULTS: The capecitabine RD was 1000 mg m(-2) bid. Diarrhoea and neutropenia were the DLTs. After a median follow-up of 52.5 months, the median PFS and OS were 12 (95% CI; 10.6-13.4) and 27 months (95% CI; 17.2-36.8), respectively.The GSTP1-G genotype, the Köhne low-risk category and use of a consolidation approach strongly correlated with decreased risk of progression. Patients with all favourable variables showed a median PFS of 42 months vs 3.4 months in the group with all adverse factors. A superior clinical response was obtained in patients with one GSTP1-G allele as compared with GSTP1-AA carriers (P=0.004). CONCLUSION: First-line therapy with oxaliplatin, irinotecan and capecitabine is efficient and well-tolerated. The GSTP1 polymorphism A>G status was significantly associated with ORR and PFS in mCRC treated with this triplet therapy.

[Coordinating efforts in complex clinical cases: added value of palliative care at a university teaching hospital]. / La coordinación de esfuerzos en casos clínicos complejos: un valor añadido de cuidados paliativos en un hospital universitario.

Palliative care is generally understood on caring for terminal patients in chronic settings but more recently these units are developing also in acute care settings or university hospitals as consultants teams. We report the case of a complex patient with rectal adenocarcinoma and four problems of difficult approach: uncontrolled neuropathic pain despite opioids treatment, systemic infection, depression with intense demoralisation and open surgery wound. We show the measures adopted and how an excellent inter-departmental collaboration under the co-ordination of palliative medicine consultant team helped to resolve the untenable situation.

Preliminary results of the combination of bevacizumab and weekly Paclitaxel in advanced melanoma.

BACKGROUND: Pretreated advanced melanoma is a poor prognosis scenario with few, if any, active therapeutic options. The antibody against vascular endothelial growth factor, bevacizumab, has demonstrated increased activity in combination with chemotherapy in many tumors. We intended to evaluate the activity of the combination of weekly paclitaxel and bevacizumab in previously treated metastatic melanoma. PATIENTS AND METHODS: Patients with previously treated metastatic melanoma received paclitaxel 70 mg/m(2) weekly and bevacizumab 10 mg/kg biweekly for 5 consecutive weeks every 6 weeks. RESULTS: Twelve patients were treated. Two patients (16.6%) achieved a partial response and 7 patients (58.3%) stable disease. Responses were seen in soft tissue, lung and brain metastases. Median disease-free and overall survival times were 3.7 and 7.8 months, respectively. Treatment was well tolerated. Main toxicities were grade 3 asymptomatic lymphopenia in 6 patients, grade 3 leucopenia in 2 patients, and grade 3 thrombocytopenia in 1 patient. CONCLUSIONS: Our preliminary results suggest that the combination of bevacizumab and weekly paclitaxel is active and safe in patients with metastatic melanoma, warranting further investigation.

Combining chemotherapy and targeted therapies in metastatic colorectal cancer.

Colorectal cancer remains one of the major causes of cancer death worldwide. During the past years, the development of new effective treatment options has led to a considerable improvement in the outcome of this disease. The advent of agents such as capecitabine, irinotecan, oxaliplatin, erbitux and bevacizumab has translated into median survival times in the range of 2 years. Intense efforts have focused on identifying novel agents targeting specific growth factor receptors, critical signal transduction pathways or mediators of angiogenesis. In addition, several clinical trials have suggested that some of these molecularly targeted drugs can be safely and effectively used in combination with conventional chemotherapy. In this article we review various treatment options combining cytotoxic and targeted therapies currently available for patients with metastatic colorectal cancer.

Epidermal growth factor receptor inhibitors in colorectal cancer treatment: what's new?

Colorectal cancer constitutes one of the most common malignancies and the second leading cause of death from cancer in the western world representing one million new cases and half a million deaths annually worldwide. The treatment of patients with metastatic colon cancer comprises different regimens of chemotherapeutic compounds (fluoropyrimidines, irinotecan and oxaliplatin) and new targeted therapies. Interestingly, most recent trials that attempt to expose patients to all five-drug classes (fluoropyrimidines, irinotecan, oxaliplatin, bevacizumab and cetuximab) achieve an overall survival well over 2 years. In this review we will focus on the main epidermal growth factor receptor inhibitors demonstrating clinical benefit for colorectal cancer mainly cetuximab, panitumumab, erlotinib and gefitinib. We will also describe briefly the molecular steps that lie beneath them and the different clinical or molecular mechanisms that are reported for resistance and response.

Ileal carcinoid tumor with liver metastases and cardiac involvement treated with intraarterial liposomal doxorubicin and valve replacement.

Unless carcinoid are in general slow-growing tumors, some cases could be frankly malignant. The commonest cause of death in patients suffering a carcinoid tumor is liver failure due to tumor progression. When tumors have a fast evolution a multidisciplinary approach must be perform. This case report is an example of this specific situation.

Algunos instrumentos de evaluación utilizados en Cuidados Paliativos (II): el Cuestionario Breve de Dolor (Brief Pain Inventory, BPI) / No disponible

El Cuestionario Breve de Dolor (Brief Pain Inventory, BPI) es un cuestionario autoadministrado y de fácil comprensión. Fue desarrollado por Daut en 1983 y la versión española fue validada por Badia y cols. en pacientes oncológicos en 2002. El BPI es un instrumento multidimensional de valoración del dolor que proporciona información sobre la intensidad del dolor y su interferencia en las actividades diarias de los pacientes.Valora también la descripción, la localización del dolor y el nivel de alivio que proporciona el tratamiento. Existe una versión abreviada de sólo 11 ítems que puede ser más adecuada para pacientes de cuidados paliativos.En la práctica clínica diaria muchas veces basta una evaluación rápida y unidimensional del dolor. Sin embargo, cuando el dolor sea el problema principal del paciente y por tanto, la evaluación multidimensional imprescindible, el BPI puede ser el instrumento adecuado a utilizar. Además, en las situaciones complejas, el BPI permite presentar resultados de un modo científicamente aceptado (AU)

The Brief Pain Inventory (BPI) is an autoevaluated questionnaire easy to understand. Daut developed it in 1983, Badía and collaborators validated the Spanish version in 2002. The BPI is a multidimensional tool for pain evaluation. Pain intensity and interference with daily living activities are the main domains evaluated by the questionnaire. Also the questionnaire explore location and qualitative aspects of pain and the level of relief with treatment. A short version with only 11 items, more adequate for palliative care patients, is available. Usually, in clinical daily activity a quick and unidimensional pain evaluation could be enough. But when the pain is the main problem for a single patient, the multidimensional evaluation of pain is mandatory and then, the BPI can be the appropriate instrument for that propose. Furthermore, the BPI questionnaire is a scientific and universally acceptable way to refer complex situations (AU)