Is there a place for gastroenterostomy in patients with advanced cancer of the head of the pancreas?

There remains doubt about the need for gastroenterostomy in patients with advanced cancer of the pancreatic head, performed either prophylactically or when passage of food becomes impossible. The records of 142 patients admitted for advanced pancreatic cancer to the Erasmus University Hospital over a period of 11 years were reviewed. We concentrated especially on the pre- and postoperative intake of food in cases involving gastroenterostomy and the morbidity and mortality associated with abdominal surgery in these patients. Of 129 patients without symptoms of gastric outlet obstruction at the time of diagnosis, 31 underwent prophylactic gastroenterostomy. The procedure did not prevent gastric outlet obstruction in 4 patients. Of the remaining 98 patients, 15 developed gastric outlet obstruction. Cox proportional hazards analysis showed no significant difference in the interval to the occurrence of a symptomatic obstruction between these two groups, taking into account other covariables. Postoperative complications and mortality regarding a gastroenterostomy were high, ranging from 9% to 41% and 11% to 33%, respectively. Our results do not indicate that prophylactic gastroenterostomy may significantly prevent future gastric outlet obstruction; therefore, as it also increases morbidity, it should not be performed. A gastroenterostomy to relieve symptoms should be considered carefully, as the success rate is low and is accompanied by a considerable incidence of morbidity and mortality.

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Resumen Persiste la duda sobre la necesidad de practicar gastroenterostomía en pacientes con cáncer avanzado de la cabeza del páncreas, así sea profiláctica o en presencia de obstrucción al paso de los alimentos. Se revisaron las historias de 142 pacientes con cáncer avanzado de la cabeza del páncreas en el Hospital de la Universidad de Erasmo observados en un periodo de 11 años. El estudio se concentré especialmente sobre la ingesta pre y postoperatoria de alimentos en los pacientos con gastroenterostomía y en la morbilidad y mortalidad asociada con la cirugía abdominal. De 129 pacientes libres de síntomas de obstrucción en el momento del diagnóstico, 31 fueron sometidos a gastroenterostomía profiláctica; el procedimiento no logró prevenir la obstrucción gástrica en 4 casos. De los 98 pacientes restantes, 15 desarrollaron obstrucción gástrico. El análisis proporcional de Cox no demostró diferencia significativa en el intervalo transcurrido hasta la aparición de los sintomas entre los dos grupos, tomando en consideración diversas variables. Las tasas de complicaciones y de mortalidad postoperatoria en relación con la gastroenterostomía fueron elevadas, 9–41% y 11–33%, respectivamente. Nuestros resultados no indican que la gastroenterostomía profiláctica pueda prevenir la obstrucción gástrica y, por cuanto incrementa la morbilidad, no debe ser realizada. La gastroenterostomía por razones de sintomatologia debe ser cuidadosamente considerada, puesto que la tasa de éxito es baja y se acompana de considerable morbilidad y mortalidad.

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Résumé Réaliser une gastroentérostomie de faÇon prophylactique ou seulement lorsque l'alimentation devient impossible chez un patient ayant un cancer de la tÊte du pancréas reste une question sans réponse. Les dossiers de 142 patients ayant un cancer avancé de la tÊte du pancréas, observés à l'HÔpital Universitaire Erasmus en l'espace de 11 ans, ont été revus. Nous avons noté la possibilité d'alimentation en périodes préet postopératoire ainsi que la morbidité et mortalité en rapport avec la chirurgie chez ces patients. Des 129 patients n'ayant pas de symptÔmes d'obstruction postpylorique au moment du diagnostic, 31 ont eu une gastroentérostomie à titre prophylactique. Cette intervention n'a pu prévenir l'obstruction chez 4 de ces patients. Des 98 autres patients, 15 ont développé une obstruction postpylorique. Une analyse multifactorielle selon le modèle de Cox n'a pu démontrer de différence significative entre les deux groupes pour l'intervalle entre le moment du diagnostic et la survenue de l'obstruction. Le taux de complications et de décès postopératoires après gastroentérostomie était élevée, variant respectivement entre 9% et 41% et 11% et 33%. Nos résultats indiquent que la gastroentérostomie à titre prophylactique ne prévient pas la survenue d'une obstruction postpylorique mais qu'elle accroÎt la morbidité. Dans ces conditions, la gastroentérostomie ne devrait Être réalisée qu'en cas d'obstruction symptomatique, mais en sachant qu'elle n'est pas toujours couronnée de succès et que les taux de mortalité et de morbidité ne sont pas nuls.

     

Four cycles of BEP versus an alternating regime of PVB and BEP in patients with poor-prognosis metastatic testicular non-seminoma; a randomised study of the EORTC Genitourinary Tract Cancer Cooperative Group.

We have investigated whether an alternating induction chemotherapy regimen of PVB/BEP is superior to BEP in patients with poor-prognosis testicular non-seminoma. A total of 234 eligible patients were randomised to receive an alternating schedule of PVB/BEP for a total of four cycles or four cycles of BEP. Poor prognosis was defined as any of the following: lymph node metastases larger than 5 cm, lung metastases more than four in number or larger than 2 cm, haematogenic spread outside the lungs, such as in liver and bone, human chorionic gonadotrophin > 10,000 IU l-1 or alphafetoprotein > 1000 IU l-1. The complete response (CR) rates to PVB/BEP and BEP were similar, 76% and 72% respectively (P = 0.58). In addition, there was no significant difference in relapse rate, disease-free and overall survival at an average follow-up of 6 years. The 5-year progression-free and survival rates in both treatment groups were approximately 80%. The PVB/BEP regime was more toxic with regard to bone marrow function; the frequencies of leucocytes below 1000 microliters-1, leucocytopenic fever and platelets below 25,000 microliters-1, throughout four cycles were 28% vs 5% (P < 0.001), 16% vs 5% (P = 0.006), and 10% vs 1% (P = 0.001) respectively. Neuropathy also occurred more often in the PVB/BEP arm: 47% vs 25% (P = 0.001). This study shows that an alternating regimen of PVB/BEP is not superior to BEP and that it is more myelo- and neurotoxic.     

Plasma metallothionein concentration in patients with liver disorders: special emphasis on the relation with primary biliary cirrhosis

The plasma metallothionein concentration was evaluated in healthy subjects and in patients with several types of liver disorders. Plasma metallothionein concentrations in controls varied between 2.4 and 4.8 ng/ml. Patients with disorders associated with increased liver copper concentrations (i.e., primary biliary cirrhosis and primary sclerosing cholangitis) had significantly (both p less than 0.002) elevated plasma metallothionein concentrations (range = 1.8 to 52.2 ng/ml), and a considerable number of these were above the maximum control level (21 of 41 patients). In contrast, patients with liver disorders not associated with increased liver copper concentrations (alcoholic and cryptogenic cirrhosis, and acute viral and chronic active hepatitis) generally had normal plasma metallothionein concentrations and only a few were above the maximum control level (11 of 64 patients, maximum = 8.8 ng/ml). The metallothionein concentrations in plasma samples from patients in stage I or II primary biliary cirrhosis were within or slightly above the control range, whereas most patients in stage III had elevated levels (p less than 0.002), and almost all patients in stage IV had clearly elevated (p less than 0.0001) concentrations. In primary biliary cirrhosis the plasma metallothionein concentration tended to increase during the evolution of the disorder, and the concentration correlated significantly with the serum total bilirubin concentration. In conclusion, the plasma metallothionein concentration is significantly elevated in patients with primary biliary cirrhosis and in patients with primary sclerosing cholangitis. Although related to the histological stage of primary biliary cirrhosis, the measurement of plasma metallothionein concentrations contributes little to the diagnosis or the evaluation of the severity of these disorders.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phase IB study of doxorubicin in combination with the multidrug resistance reversing agent S9788 in advanced colorectal and renal cell cancer.

S9788 is a new triazineaminopiperidine derivate capable of reversing multidrug resistance (MDR) in cells resistant to chemotherapeutic agents such as doxorubicin. It does not belong to a known class of MDR revertants, but its action involves the binding of P-glycoprotein. Thirty-eight evaluable patients with advanced colorectal or renal cell cancer were treated with doxorubicin alone (16 patients) followed after disease progression with combination treatment of doxorubicin plus S9788 (12 patients) or upfront with the combination of doxorubicin plus S9788 (22 patients). S9788 was given i.v. as a loading dose of 56 mg m-2 over 30 min followed by doxorubicin given at 50 mg m-2 as a bolus infusion. Thereafter, a 2-h infusion of S9788 was administered at escalating doses ranging from 24 to 120 mg m-2 in subsequent cohorts of 4-10 patients. Pharmacokinetic analysis demonstrated that concentrations of S9788 that are known to reverse MDR in vitro were achieved in patients at non-toxic doses. Compared with treatment with doxorubicin alone, treatment with the combination of doxorubicin and S9788 produced a significant increase in the occurrence of WHO grade 3-4 granulocytopenia. Treatment with S9788 was cardiotoxic as it caused a dose-dependent and reversible increase in corrected QT intervals as well as clinically non-significant arrhythmias on 24- or 48-h Holter recordings. Although clinically relevant cardiac toxicities did not occur, the study was terminated as higher doses of S9788 may increase the risk of severe cardiac arrhythmias. Twenty-nine patients treated with S9788 plus doxorubicin were evaluable for response, and one patient, who progressed after treatment with doxorubicin alone, achieved a partial response. We conclude that S9788 administered at the doses and schedule used in this study results in relevant plasma concentrations in humans and can safely be administered in combination with doxorubicin.     

Elevated levels of acute phase plasma proteins in major depression.

Levels of acute phase and other plasma proteins were measured in 21 men with major depression, 28 men with alcohol dependence, and 12 men who acted as controls. The depressed men had significantly elevated levels of the acute phase proteins, haptoglobin and alpha-1-antichymotrypsin, and of immunoglobulin G. The elevations in haptoglobin and alpha-1-antichymotrypsin were highly correlated with each other, and were correlated with the severity of depression and negatively correlated with the thyroid stimulating hormone response to thyrotropin. The alcoholic men had elevated haptoglobin levels, but significantly decreased levels of immunoglobulin G. These findings provide further evidence for an inflammatory response during depression.     

Noninvasive in vivo 13C-NMR spectroscopy in the rat to study the pharmacokinetics of 13C-labeled xenobiotics.

Noninvasive NMR methodology has been developed to enable monitoring of 13C-labeled xenobiotics in the rat in vivo. 2,2-Dichloro-1-(2-chlorophenyl)-1-(4-chlorophenyl)-[3-13C]-propane can be detected in the liver of intact rats by in vivo 13C surface coil NMR spectroscopy after ip administration of the compound. The experiments were performed at 1.9 and 9.4 Tesla. The intrahepatic changes of the signal intensity of the labeled compound were followed as a function of time. In the days following administration, the concentration decreased and dropped to values below the detection limit after 12 days. The study demonstrates the feasibility of studies on pharmacokinetics of 13C-labeled compounds in the rat using noninvasive, in vivo surface coil NMR spectroscopy in animals. The sensitivity allows the detection of a single dose of the drug of 200 mg/kg, but can be improved.     

Reflex sympathetic dystrophy of the left hand and motor impairments of the unaffected right hand: impaired central motor processing?

OBJECTIVE: To test whether central motor processing can be impaired in chronic reflex sympathetic dystrophy (RSD). DESIGN: Experimental 2-group analysis. SETTING: Tertiary care center in the Netherlands. PARTICIPANTS: Five patients with stage 3 RSD of the left forearm, free of symptoms and complaints in the right forearm; and 10 healthy control subjects. INTERVENTION: On a digitizer, RSD patients and controls had to draw 3 sequences of graphemes of different complexity with their (unaffected) dominant right hand. The drawing tracks were segmented in time periods between points of velocity minima of the pen tip. MAIN OUTCOME MEASURES: Mean velocity, coefficients of variation of both length and movement time per segment, and mean intersegmental pausing time were calculated for each sequence. RESULTS: A repeated-measures analysis of variance by using the multivariate method yielded a 35% lower mean velocity (F(1,13) = 5.83, P =.031), a 110% larger segment length variability (F(1,13) = 9.72, P =.008) and a 60% larger variability of movement time per segment (F(1,13) = 5.78, P =.032) in RSD patients. No group difference was found for intersegmental pausing time or any interaction effect with the type of task. CONCLUSION: Patients with chronic RSD have a normal ability to preprogram sequential movements of their unaffected hand; but with impaired temporospatial coding and movement execution. We concluded that cortical mechanisms may be involved in motor impairments in patients with chronic RSD.     

Perforation Rates for Nonsterile Examination Gloves in Routine Dermatologic Procedures

BACKGROUND: Low cost, nonsterile examination gloves are used routinely to perform various dermatologic procedures. OBJECTIVE: To evaluate the perforation rate of nonsterile examination gloves in routine dermatologic procedures. METHODS: Three hundred fifty nonsterile latex examination gloves used to perform shave biopsies were evaluated for perforations using an air inflation/water submersion method. Ninety gloves, which were intentionally perforated with a 30-gauge needle, were used as controls to assess our evaluation method. RESULTS: Eight of the 350 gloves were found to have a perforation, which corresponds to a 2.3% perforation rate. Seven of the eight perforations were found in the web space between the second and third finger sleeves, with one being an obvious manufacturing error. All 90 perforations of the control group were correctly identified. CONCLUSION: There appears to be a very low risk of glove perforation when nonsterile examination gloves are used in routine dermatologic procedures.