Preoperative low-dose weekly cisplatin and continuous infusion fluorouracil plus hyperfractionated radiotherapy in stage II-III esophageal carcinoma

BACKGROUND: The optimal regimen of preoperative chemoradiotherapy for resectable esophageal cancer has not been established. We evaluated accelerated hyperfractionated radiotherapy (RT) concurrent to low-dose weekly cisplatin and continuous infusion fluorouracil (LDCI-FU) followed by esophagectomy in patients with locally advanced squamous cell carcinoma (SCC) of the esophagus. METHODS: Patients with clinical stage II or III SCC of the esophagus received cisplatin 30 mg/m2/week (days 1, 8, 15), LDCI-FU 300 mg/m2/day (days 1-21), and concomitant RT to a dose of 45 Gy (150 cGy/fraction, 2 fractions/day) on tumor and affected lymph nodes, followed by radical esophagectomy. RESULTS: From 1997 to 2012, 64 patients were treated with this regimen. Twenty-four patients (37 %) had grade 3 esophagitis, 18 (28 %) of whom required hospitalization. The risk of hospitalization was reduced by placement of a jejunostomy tube before starting induction chemoradiotherapy. Six patients (9 %) had grade 3-4 neutropenia. Fifty-three patients (83 %) underwent esophageal resection and complete resection was achieved in 45 (70 %). The overall median survival was 28 months (95 % CI: 20.4-35.6) and 5-year survival was 38 %. In the 18 patients attaining a pathological complete response, median survival was 132 months and 5-year survival was 72 %. Positron emission tomography standardized uptake values (PET SUVmax) post-chemoradiotherapy were associated with pathological response (p = 0.03) and survival (p = 0.04). CONCLUSIONS: Intensive preoperative hyperfractionated RT concomitant to low-dose cisplatin and LDCI-FU is effective in patients with locally advanced SCC of the esophagus, with good pathological response and survival and manageable toxicities. Post-chemoradiotherapy PET SUV max shows promise as a potential prognostic factor

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Preoperative low-dose weekly cisplatin and continuous infusion fluorouracil plus hyperfractionated radiotherapy in stage II-III esophageal carcinoma.

BACKGROUND: The optimal regimen of preoperative chemoradiotherapy for resectable esophageal cancer has not been established. We evaluated accelerated hyperfractionated radiotherapy (RT) concurrent to low-dose weekly cisplatin and continuous infusion fluorouracil (LDCI-FU) followed by esophagectomy in patients with locally advanced squamous cell carcinoma (SCC) of the esophagus. METHODS: Patients with clinical stage II or III SCC of the esophagus received cisplatin 30 mg/m2/week (days 1, 8, 15), LDCI-FU 300 mg/m2/day (days 1-21), and concomitant RT to a dose of 45 Gy (150 cGy/fraction, 2 fractions/day) on tumor and affected lymph nodes, followed by radical esophagectomy. RESULTS: From 1997 to 2012, 64 patients were treated with this regimen. Twenty-four patients (37 %) had grade 3 esophagitis, 18 (28 %) of whom required hospitalization. The risk of hospitalization was reduced by placement of a jejunostomy tube before starting induction chemoradiotherapy. Six patients (9 %) had grade 3-4 neutropenia. Fifty-three patients (83 %) underwent esophageal resection and complete resection was achieved in 45 (70 %). The overall median survival was 28 months (95 % CI: 20.4-35.6) and 5-year survival was 38 %. In the 18 patients attaining a pathological complete response, median survival was 132 months and 5-year survival was 72 %. Positron emission tomography standardized uptake values (PET SUVmax) post-chemoradiotherapy were associated with pathological response (p = 0.03) and survival (p = 0.04). CONCLUSIONS: Intensive preoperative hyperfractionated RT concomitant to low-dose cisplatin and LDCI-FU is effective in patients with locally advanced SCC of the esophagus, with good pathological response and survival and manageable toxicities. Post-chemoradiotherapy PET SUVmax shows promise as a potential prognostic factor.

Análisis de la lipocalina asociada a la gelatinasa de neutrófilos en el paciente crítico / Analysis of neutrophil gelatinase-associated lipocalin in the critical patient

OBJETIVO: Determinar si un valor de NGAL > 150 ng/ml es una buena prueba diagnóstica para detectar precozmente disfunción renal aguda (DRA) en el paciente crítico. DISEÑO: Estudio prospectivo, observacional, de cohorte. Ámbito: Unidad de cuidados intensivos y de cirugía cardíaca del Servicio de Medicina Intensiva del Hospital Germans Trias I Pujol. PARTICIPANTES: Los pacientes ingresados en el Servicio de Medicina Intensiva los días designados en el estudio. INTERVENCIONES: Análisis sanguíneo de la creatinina sérica determinada desde siete días antes del día de inicio del estudio, y diariamente durante cuatro semanas. Determinación de NGAL mediante prueba de orina, en muestra congelada, con el analizador ARCHITECT (Abbott diagnostics)por inmunoanálisis determinado el día de inicio del estudio y dos veces a la semana durante cuatro semanas, análisis de la estancia y mortalidad. RESULTADOS: Se obtuvieron 529 muestras de NGAL de 46 pacientes. El 37% de los pacientes presentaron un valor de NGAL > 150 ng/ml. La sensibilidad de la prueba para diagnosticar DRA fue del 69%, la especificidad fue del 75,7%. Sin embargo, el valor predictivo positivo fue del53%, lo cual significa que el 47% de los pacientes con NGAL alto no desarrollaron DRA. Un NGAL > 150 mg/dL se asoció de manera significativa a un SOFA más alto y a una estancia más larga en UCI. La mortalidad de los pacientes con NGAL elevado fue del 58,8%. CONCLUSIONES: Un NGAL > 150 ng/mL no parece ser una excelente prueba para detectar DRA enel paciente crítico pero si que se asocia con un peor pronóstico

OBJECTIVE: To determine if NGAL value exceeding 150 ng/mL is a good diagnostic test for acuterenal failure in critically ill patients. DESIGN: Prospective, observational cohort. SETTING: Intensive Care Unit and Cardiac Surgery Intensive Care Service at Hospital Germans Trias I Pujol. PARTICIPANTS: Patients admitted to the Intensive Care department the Designated days in the studio. INTERVENTIONS: Analysis of serum creatinine blood given from 7 days prior to the start of the study, and daily during 4 weeks and by determination of NGAL urine test in frozen sample, analyzer ARCHITECT (Abbott Diagnostics) determined by immunoassay the day baseline and 2 times a week for 4 weeks, analysis of the stay and mortality. RESULTS: A total of 529 NGAL samples were obtained from 46 patients. 37% of patients had a value of NGAL > 150 ng/mL. The Sensivity of the test to diagnose acute renal failure was 69%, Specifity was 75,7%. However, the Positive Predictive Test Value was 53%, which means that47% of patients with high NGAL did not develop AKI. A NGAL > 150 mg/dL was associated with a significantly higher SOFA and a longer stay in the ICU. The mortality of patients with elevated NGAL was 58.8%. CONCLUSIONS: A NGAL > 150 ng/mL does not seem to be an excellent test for AKI in critically lll patients but is associated with a worse prognosis

[Analysis of neutrophil gelatinase-associated lipocalin in the critical patient]. / Análisis de la lipocalina asociada a la gelatinasa de neutrófilos en el paciente crítico.

OBJECTIVE: To determine if NGAL value exceeding 150 ng/mL is a good diagnostic test for acute renal failure in critically ill patients. DESIGN: Prospective, observational cohort. SETTING: Intensive Care Unit and Cardiac Surgery Intensive Care Service at Hospital Germans Trias I Pujol. PARTICIPANTS: Patients admitted to the Intensive Care department the Designated days in the studio. INTERVENTIONS: Analysis of serum creatinine blood given from 7 days prior to the start of the study, and daily during 4 weeks and by determination of NGAL urine test in frozen sample, analyzer ARCHITECT (Abbott Diagnostics) determined by immunoassay the day baseline and 2 times a week for 4 weeks, analysis of the stay and mortality. RESULTS: A total of 529 NGAL samples were obtained from 46 patients. 37% of patients had a value of NGAL>150 ng/mL. The Sensivity of the test to diagnose acute renal failure was 69%, Specifity was 75,7%. However, the Positive Predictive Test Value was 53%, which means that 47% of patients with high NGAL did not develop AKI. A NGAL >150 mg/dL was associated with a significantly higher SOFA and a longer stay in the ICU. The mortality of patients with elevated NGAL was 58.8%. CONCLUSIONS: A NGAL>150 ng/mL does not seem to be an excellent test for AKI in critically ill patients but is associated with a worse prognosis.

Weekly docetaxel with concomitant radiotherapy in patients with inoperable oesophageal cancer.

INTRODUCTION: To evaluate the efficacy and tolerability of weekly docetaxel concurrent with radiotherapy in inoperable oesophageal cancer patients. MATERIAL AND METHODS: Thirty-four oesophageal cancer patients with co-morbid medical conditions, locally advanced tumours (T4) or advanced age (older than 75 years) received docetaxel (20 mg/m2 weekly) plus concurrent radiotherapy (2 Gy daily, to a total dose of 66 Gy). Twenty-two patients (64%) were stage III, 19 of whom had T4 tumours. RESULTS: Twenty-seven patients (79%) completed the planned chemoradiotherapy treatment. Nine patients (26%) achieved a complete response and 8 (24%) achieved a partial response, for an overall response rate of 50%. Median survival was 6 months, and 1-year survival was 35%. Patients with T4 tumours had significantly shorter survival than other patients: 5 months for T4 tumours vs. 11 months for T1-3 (p=0.04). Grade 3-4 oesophagitis occurred in 6 patients (17%). There were two treatment-related deaths due to radiation pneumonitis. CONCLUSIONS: Docetaxel plus concurrent radiotherapy is active in poor-prognosis oesophageal cancer patients, with a lower incidence of severe oesophagitis than with cisplatin-based chemoradiotherapy regimens. This schedule can be considered, especially in patients with non-T4 tumours who are not candidates for oesophageal resection.

Weekly docetaxel with concomitant radiotherapy in patients with inoperable oesophageal cancer

INTRODUCTION: To evaluate the efficacy and tolerability of weekly docetaxel concurrent with radiotherapy in inoperable oesophageal cancer patients. MATERIAL AND METHODS: Thirty-four oesophageal cancer patients with co-morbid medical conditions, locally advanced tumours (T4) or advanced age (older than 75 years) received docetaxel (20 mg/m2 weekly) plus concurrent radiotherapy (2 Gy daily, to a total dose of 66 Gy). Twenty-two patients (64%) were stage III, 19 of whom had T4 tumours. RESULTS: Twenty-seven patients (79%) completed the planned chemoradiotherapy treatment. Nine patients (26%) achieved a complete response and 8 (24%) achieved a partial response, for an overall response rate of 50%. Median survival was 6 months, and 1-year survival was 35%. Patients with T4 tumours had significantly shorter survival than other patients: 5 months for T4 tumours vs. 11 months for T1-3 (p=0.04). Grade 3-4 oesophagitis occurred in 6 patients (17%). There were two treatment-related deaths due to radiation pneumonitis. CONCLUSIONS: Docetaxel plus concurrent radiotherapy is active in poor-prognosis oesophageal cancer patients, with a lower incidence of severe oesophagitis than with cisplatin-based chemoradiotherapy regimens. This schedule can be considered, especially in patients with non-T4 tumours who are not candidates for oesophageal resection (AU)

Syngeneic islet transplantation into seminal vesicles of diabetic rats.

Pancreatic islet transplantation has been proposed as an attractive option for the treatment of type I diabetes. Transplantation into different sites has been investigated, among them those that are immuno-logically privileged (e.g., thymus, uterus, brain, anterior eye chamber, and testicle). Because of their characteristics, seminal vesicles could be considered as immunologically privileged organs, but there is no worldwide experience that can confirm it. The purpose of the present study is to assess the viability and functionality of islet transplantation into seminal vesicles of diabetic rats. One hundred ninety inbred adult male syngeneic Lewis rats were used as donors (n = 72), receptors (n = 36), and controls(n = 11). Diabetes was chemically induced through a single intraperitoneal injection of streptozotocin. Groups of 1200 purified islets were introduced in the right seminal vesicle of diabetic rats. Diabetic control rats were sham transplanted. Body weight and glycemia were monitored every 2 d. Of transplanted rats, 16.7% achieved a good function due to islet engraftment, while 30.6% achieved a partially good response, and 52.7% were considered as nonresponding. This is the first report about islet transplantation into seminal vesicles of diabetic animals. Our results indicate that islet transplantation into rat seminal vesicles is technically possible, and that islets can function normally after engraftment into the wall of the seminal vesicle.

Screening for occult cancer in patients with acute deep vein thrombosis or pulmonary embolism.

Patients with acute venous thromboembolism have an increased risk for occult malignancy. Limited screening for these malignancies has become common practice but little is known about its usefulness. This is a prospective cohort follow-up study in consecutive patients with acute venous thromboembolism. All patients underwent a routine clinical evaluation for malignancy, if negative, followed by a limited diagnostic work-up consisting of abdominal and pelvic ultrasound and laboratory markers for malignancy. Clinical follow-up was conducted to detect screening failures. The routine clinical evaluation was performed in 864 patients and revealed malignancy in 34 (3.9%) of them. Among the remaining 830 patients the limited diagnostic work-up revealed 13 further malignancies. During follow-up, cancer became symptomatic in 14 patients who were negative for cancer at screening (sensitivity of limited diagnostic work-up, 48.1%). Malignancies that were identified by the limited diagnostic work-up were early stage in 61% of cases vs. 14% in cases occurring during follow-up. Most patients with occult cancer had idiopathic venous thromboembolism and were older than 70 years. A limited diagnostic work-up for occult cancer in patients with venous thromboembolism has the capacity to identify approximately one-half of the malignancies. Identified malignancies were predominantly in an early stage.

La cirugía del carcinoma de esófago torácico / No disponible

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Evaluating the outcome of severe head injury with transcranial Doppler ultrasonography.

The authors conducted a study to determine the value of transcranial Doppler (TCD) ultrasonography in evaluating the outcome of severely head injured patients and to correlate the TCD values with those obtained from intracranial pressure (ICP) and cerebral perfusion pressure (CPP) monitoring. The authors conducted a prospective study of 125 patients with severe head injury (Glascow Coma Scale scores of less than 9) who underwent TCD ultrasonography according to the standard technique of insonating the middle cerebral artery (MCA) and measuring the mean blood flow velocity and pulsatility index within the first 24 hours of admission. The ICP and CPP values, as well as other clinical, analytical, and neuroimaging data, were also recorded. After 6 months, outcome was evaluated using the Glasgow Outcome Scale. Moderate disability and complete recovery were considered "good" outcome; death, vegetative state, and severe disability were considered "poor." In 67 patients (54%) good outcome was demonstrated whereas in 58 (46%) it was poor. The mean blood flow velocity of the MCA in patients with good outcome was 44 cm/second; in those with poor outcomes it was 36 cm/second (p < 0.003). The mean PI in cases of good outcome was 1 whereas in poor outcome was 1.56 (p < 0.0001). The correlations of ICP and CPP to PI were statistically significant (r2 = 0.6; p < 0.0001). When performed in the first 24 hours of severe head injury, TCD ultrasonography is valid in predicting the patient's outcome at 6 months and correlates significantly with ICP and CPP values.

Platelet count and survival in patients with colorectal cancer--a preliminary study.

In a previous report we found an inverse correlation between pre-operative platelet count (PlC) levels and the risk of post-operative pulmonary embolism in patients undergoing hip surgery. In the present study, we prospectively evaluated the prognostic significance of pre-operative PlC levels on survival in 180 consecutive patients undergoing surgery for colorectal cancer. Other major clinicopathological parameters studied were age, gender, Dukes' stage, duration of surgery, pre-operative haemoglobin levels and transfusion requirements. There were no significant differences in mean pre-operative PlC levels according to tumor stage. Thirty-three patients (18%) died during follow-up (3-23 months, median: 13 months). Univariate analysis (Kaplan-Meier estimates) showed that advanced tumor stage (p < 0.001), duration of surgery (p < 0.05) and a high pre-operative PlC level (p < 0.001) were significantly associated to a poor survival. The multivariate Cox analysis revealed that tumor stage (RR:5.734; 95%C.I.: 2.644-12.44), a high pre-operative PlC level (RR: 2.467; 95%C.I.: 1.117-5.452), and to a lesser extent the patients' age remained independent prognostic variables for mortality. The findings of this preliminary study may be of interest from the point of view of pathogenesis, but also clinically, since they might be used in the decision as to which patients or groups of patients should receive more aggressive therapeutic intervention.

[Primary gastrointestinal lymphomas: response to eradicative therapy and prognostic factors in 52 patients]. / Linfomas gastrointestinales primarios: respuesta al tratamiento erradicativo y factores pronósticos en 52 pacientes.

BACKGROUND: To analyze the response to eradicative therapy and prognostic factors in 52 patients with primary gastrointestinal lymphoma (PGIL) diagnosed at a single institution in a 13 year period. PATIENTS AND METHODS: The main clinical, biological and evolutive data were recorded. Pathologic diagnosis of PGIL was made according to the Working Formulation. Clinical stage was determined by the Ann Arbor system modified by Mushoff. The results of therapy as well as the influence of such characteristics on complete remission (CR), disease-free survival (DFS) and overall survival (OS) were studied. RESULTS: Mean age of the series was 53 years (SD 15). Thirty patients were males. HIV infection preceded PGIL diagnosis in 10 cases. Seventeen had bad performance status (ECOG 2-4) and 30 B symptoms. The PGIL localization was gastric in 31 cases and 29 had a low grade malignant lymphoma. B phenotype was demonstrated in 98% and 22 patients presented advanced stages (IIE2-IV). Treatment was radical surgery followed by intensive chemotherapy in 32 cases, intensive chemotherapy alone in 17, and surgical resection in 3. CR was obtained in 34 patients and 6 of them relapsed. The projected DFS from CR at 9 years was 72% and OS was 26%. CR and survival were not influenced by PGIL localization and treatment type. The main unfavourable prognostic factors were advanced stage (CR and OS), B symptoms (DFS and OS) and advanced ECOG score (CR, DFS and OS). Previous HIV infection had an independent prognostic influence on both CR and OS. CONCLUSIONS: In patients with PGIL, the achievement of CR, DFS and survival have been independent of the type of eradicative treatment used. Performance status, B symptoms and clinical stage have been the main prognostic factors. HIV infection carried an independent prognostic significance.

Endotoxin contamination may be responsible for the unexplained failure of human pancreatic islet transplantation.

Clinical transplantation of human islets has a disappointingly low rate of success. We report here the identification of a possible causative factor: endotoxin present in the collagenase preparations used to disperse the pancreatic tissue before islet purification and transplantation. Supporting evidence includes (1) detection of unexpectedly high levels of endotoxin in most collagenase solutions currently used to digest human pancreases; (2) demonstration that supernatants generated during islet separation are able to induce the inflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in macrophages; and (3) induction of IL-1, IL-6, and TNF-alpha in the islets during the separation procedure. Cytokine expression was assessed by reverse transcription-polymerase chain reaction and, for TNF-alpha, confirmed by enzyme-linked immunoabsorbent assay. It is proposed that endotoxin and locally induced cytokines carried over with the graft activate the endothelium and promote lymphomonocytic infiltration of grafted islets and surrounding liver tissue favoring primary nonfunction and early rejection. These results also have implications for the numerous experimental procedures that use collagenase, and they point to possible ways to improve islet preparation and transplantation protocols.

Band erosion in patients who have undergone vertical banded gastroplasty: incidence and technical solutions.

OBJECTIVES: To study the incidence of band erosion in patients who have undergone vertical banded gastroplasty and to describe the reparative techniques used. DESIGN: A retrospective review case series. SETTING: A university hospital-based tertiary referral center. PATIENTS: Two hundred fifty consecutive morbidly obese patients who underwent vertical banded gastroplasty between 1987 and 1995. MAIN OUTCOME MEASURES: The development of band erosion into the stomach, reparative surgical techniques, and long-term weight loss control. RESULTS: Band erosion developed in 7 (2.8%) of the patients. Two patients had symptoms 1 month after undergoing forced endoscopy. Six patients required reoperation. The operative findings included 2 cases of "external" band erosion through the lesser curvature into the stomach and 4 cases of "internal" band erosion through the circular staple line. The surgical techniques used for repair depended on the radiological and endoscopic data and on the operative findings; the techniques included conversion into a gastric bypass, band replacement after the creation of a new stoma, and gastroplasty plus distal gastric bypass. There were no complications, and adequate long-term weight loss was achieved in all but 1 of the patients who underwent reoperation. CONCLUSION: Band erosion may be corrected using appropriate surgical techniques to allow for adequate long-term weight loss in patients who have undergone vertical banded gastroplasty.