Preoperative transhepatic biliary decompression in pancreatic and periampullary cancer

Pancreatic resection for pancreatic and periampullary cancer between 1969 and 1975 at The Ohio State University Hospitals had an associated operative mortality rate of 30% and a morbidity rate of 80%. Transhepatic biliary decompression (THD) has been accepted as a method of preoperative risk reduction in the deeply jaundiced patient and an alternative to surgical biliary decompression. The use of preoperative THD in pancreatic and periampullary cancer was examined. Of 44 patients with bilirubin greater than 10 mg/100 ml, 17 had radical resection (THD=7, no THD=10), and 27 had palliative operation (THD=17, no THD=10). Preoperative serum bilirubin in the THD group was 7.3±1.0 compared to 16.3 ±1.5 in the no THD group (p < 0.05). Operative morbidity rate was: radical surgery: THD (40%), no THD (70%); palliative surgery: THD (18%), no THD (20%). Operative mortality rate was: radical surgery: THD (28%), no THD (60%); palliative surgery: THD (6%), no THD (0%). Catheter-related complications were minimal. Preoperative THD tends to reduce the risk of curative resection for pancreatic and periampullary cancer, but does not alter the outcome of palliative surgery. Long-term THD may be an alternative if palliative surgical biliary decompression either fails or is not technically possible in the patient with unresectable cancer.

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Resumen Se ha agudizado el debate relativo al papel de la resección curativa en el tratamiento del carcinoma pancreático y periampular. Mucha de la discusión se deriva de la excesiva morbilidad y mortalidad de la pancreatoduodenectomía y de la pancreatectomía total. Las cifras sobrepasan el porcentaje de supervivencia a 5 anos en todas las series mayores, y en algunos reportes la mortalidad operatoria es igual o mayor que el porcentaje de pacientes que sobreviven un año.La resección pancreática para cáncer pancreático y periampular entre los años 1969 y 1975 en los Hospitales de la Universidad del Estado de Ohio estuvo asociada con una mortalidad de 30% y una morbilidad de 80%. La descompresión biliar transhepática (DBT) ha sido aceptada como un método de reducción preoperatoria del riesgo quirúrgico en los pacientes intensamente ictéricos y como una alternativa a la descompresión biliar quirúrgica. El uso de la DBT preoperatoria en el cancer pancreático y periampular fué analizado. De 44 pacientes con bilirrubina mayor de 10 mg/100 ml, 17 fueron sometidos a resección radical (DBT = 7, no DBT = 10), y 27 tuvieron una operación paliativa (DBT = 17, no DBT = 10). La bilirrubina sérica en el grupo con DBT fué de 7.3±1.0, comparada con 16.3±1.5 en el grupo sin DBT (p < 0.05). La siguiente fué la morbilidad operatoria: cirugía radical: DBT 40%, no DBT 70%; cirugía paliativa: DBT 18%, no DBT 20%. La siguiente fué la mortalidad operatoria: cirugía radical: DPT 28%, no DPT 60%; cirugía paliativa: DBT 6%, no DBT 0. La DBT preoperatoria tiende a reducir el riesgo de la resección curativa para cáncer pancreático y periampular, pero no modiflca el resultado de la cirugía paliativa. La DBT prolongada puede ser una alternativa si la descompresión biliar quirúrgica falla o no es técnicamente posible en el paciente con cáncer no resecable.

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Résumé La résection pancréatique pour cancer périampullaire ou pour cancer du pancréas entre 1969 et 1975 à Ohio State University Hospital accuse une mortalité opératoire de 30% et une morbidité de 80%. Le drainage biliaire transhépatique (transhepatic biliary decompression: T.H.D.), en présence de ces résultats, a été employé à titre pré-opératoire pour diminuer les risques de l'intervention chez les malades très ictériques et comme alternative au drainage biliaire chirurgical.Chez 44 malades qui présentaient un taux de bilirubine supérieur à 10 mg/dl, 17 ont subi une exérèse (7 après drainage transhépatique, 10 sans drainage transhépatique), 27 ont été traités par une intervention palliative (17 après drainage, 10 sans drainage). Le taux de bilirubine pré-opératoire fut ramené à 7.3±10 chez les malades drainés alors qu'il atteignait 16.3± 1.5 chez les malades qui n'avaient pas subi de drainage préalable.La morbidité opératoire fut en cas de chirurgie radicale de 40% après drainage et de 70% en l'absence de drainage; en cas de chirurgie palliative elle fut de 18% après drainage et de 20% en l'absence de drainage. La mortalité opératoire fut en cas de chirurgie radicale de 28% après drainage et de 60% en l'absence de drainage; en cas de chirurgie palliative elle fut de 6% après drainage et de 0% en l'absence de drainage. Les complications du drainage sont très rares. En un mot le drainage biliaire pré-opératoire réduit les risques de l'exérèse des cancers pancréatiques et des cancers périampullaire mais elle est sans influence en cas d'intervention palliative. Le drainage biliaire transhépatique prolongé offre une alternative au drainage chirurgical lorsque celui-ci échoue ou quand le cancer ne peut être réséqué.

     

Aneurysmal subarachnoid hemorrhage during pregnancy: a comprehensive and systematic review of the literature

Neurosurgical Review - Aneurysmal subarachnoid hemorrhage (aSAH) is an emergent condition requiring rapid intervention and prolonged monitoring. There are few recommendations regarding the...     

Tumor necrosis factor induces apoptosis (programmed cell death) in normal endothelial cells in vitro.

Tumor necrosis factor (TNF) is cytotoxic for many tumoral cell lines, whereas normal cells generally are considered resistant to this action. This study shows that this cytokine causes massive death of bovine endothelial cells in primary culture in a concentration- and time-dependent manner. Dying cells exhibit all the ultrastructural changes and the inter-nucleosome cleavage of DNA associated with apoptosis or 'programmed cell death.' This is the first report clearly showing a direct toxicity of TNF on endothelial cells and demonstrating that this results from the induction of the program of apoptotic death. Our observation raises the possibility that hemorrhagic necrosis in vivo, after treatment with TNF, might involve a direct cytocidal action on endothelial cells of the tumor neovasculature.     

Clinical toxicity associated with tiazofurin

Summary Tiazofurin, an investigational antimetabolite, is undergoing clinical evaluation in leukemia. We analyzed the data base of 198 patients entered in Phase I trials to characterize the incidence and severity of toxicities associated with tiazofurin according to dose and schedule. Severe myelosuppression occurred infrequently, and was not dose-dependent. A five day bolus schedule had a higher incidence of severe or life-threatening neutropenia than other schedules. Tiazofurin produced lymphopenia which was not dose-dependent in the range of 23–36% decrease from baseline, and the effect on lymphocyte count was generally greater than the decline in neutrophil count. Non-hematologic toxicity of a moderate or worse severity ( grade 2) included nausea and vomiting (18% of all courses), serum transaminase elevations (SGOT, 16%; SGPT, 9%), rash (9%), stomatitis (3%), conjunctivitis (3%), headache (10%), other signs of central nervous system toxicity (8%), and cardiac toxicity, primarily pleuropericarditis (4%). Dose-related cutaneous toxicity, headache, and nausea and vomiting were evident in the five day bolus schedule, and myalgia was more frequently reported at higher doses on the single dose schedule. The five day continuous infusion (CI) schedule had a higher incidence of neurotoxicity, cardiac toxicity, SGPT elevations and ocular toxicity than the daily for five days bolus schedule, but none of these differences attained statistical significance. Although the peak plasma concentrations of tiazofurin achieved with the five day bolus schedule were 3-fold higher than the steady-state plasma levels seen with an equal dose given by CI, the area under the concentration-time curve (AUC) was approximately 1.6-fold higher with CI. These observations suggest that both high peak plasma concentrations (above 400 uM) and prolonged exposure to plasma levels exceeding 50 uM may result in a higher incidence of serious non-hematologic toxicity.     

Effect of the peroxisome proliferator perfluorodecanoic acid on growth and lipid metabolism in Sprague Dawley rats fed three dietary levels of selenium

The possible interrelationships between the effects of dietary selenium and perfluorodecanoic acid (PFDA) on growth and lipid metabolism were studied in the male Sprague Dawley rat. Rats were divided into groups and placed on diets containing three levels of selenium (0.04, 0.2, and 1.0 ppm as sodium selenite). Two weeks later, half the rats in each group received a single 35 mg/kg IP injection of PFDA in corn oil, while their pair-fed companion received only vehicle. Rats injected with PFDA stopped gaining weight, and weighed less than pair-fed controls, despite equal food intakes. Two weeks following PFDA administration the rats were killed and plasma cholesterol and triglycerides, and liver peroxisomal enzyme activities were quantified. In contrast to other peroxisome proliferators, PFDA increased plasma triglycerides while decreasing plasma cholesterol. The rate of peroxisomal fatty acid -oxidation was decreased, even though the activity of fatty acyl-CoA oxidase, the first enzyme in the peroxisomal fatty acid -oxidation pathway, was increased. Dietary selenium, other than increasing the liver to body weight ratio, did not alter growth or lipid metabolism. This study demonstrates, for the first time, the existence of a non-hypotriglyceridemic peroxisome proliferator-PFDA.