Assessment of the reporting of quality and outcome measures in hepatic resections: a call for 90-day reporting in all hepatectomy series

BackgroundThe aim of this paper is to assess the current state of quality and outcomes measures being reported for hepatic resections in the recent literature.MethodsMedline and PubMed databases were searched for English language articles published between 1 January 2002 and 30 April 2013. Two examiners reviewed each article and relevant citations for appropriateness of inclusion, which excluded papers of liver donor hepatic resections, repeat hepatectomies or meta-analyses. Data were extracted and summarized by two examiners for analysis.ResultsFifty-five studies were identified with suitable reporting to assess peri-operative mortality in hepatic resections. In only 35% (19/55) of the studies was the follow-up time explicitly stated, and in 47% (26/55) of studies peri-operative mortality was limited to in-hospital or 30 days. The time period in which complications were captured was not explicitly stated in 19 out of 28 studies. The remaining studies only captured complications within 30 days of the index operation (8/28). There was a paucity of quality literature addressing truly patient-centred outcomes.ConclusionQuality outcomes after a hepatic resection are inconsistently reported in the literature. Quality outcome studies for a hepatectomy should report mortality and morbidity at a minimum of 90 days after surgery.     

Epidermal growth factor suppresses renal tubular apoptosis following ureteral obstruction

Objectives. Acute unilateral ureteral obstruction (UUO) results in ipsilateral hydronephrosis characterized by a decrease in epidermal growth factor (EGF) mRNA expression and EGF protein levels in the distal renal tubules. UUO results in programmed cell death with increases in the characteristic markers of apoptosis. To suppress the apoptotic response during UUO, recombinant EGF was administered during renal obstruction and the ensuing molecular and histologic changes were studied.Methods. Mature Sprague-Dawley rats underwent left ureteral obstruction and the kidneys were harvested at 24, 48, and 72 hours. Markers of apoptosis included DNA laddering pattern on agarose gel electrophoresis, in situ gap labeling of fragmented DNA for quantitative apoptotic body determination, polyadenylated mRNA expression of SGP-2, and in situ hybridization for sulfated glycoprotein-2 (SGP-2) mRNA. Studies were repeated in rats following administration of 10, 20, and 40 μg of subcutaneous recombinant EGF on a daily basis after UUO.Results. Subcutaneous injection of EGF into unilaterally obstructed rats promotes renal tubular epithelial cell regeneration, as demonstrated by increased cortical mitotic activity. Systemic EGF supplementation in these unilaterally obstructed rats also resulted in a decrease in the intensity of the DNA laddering pattern associated with renal tubular apoptosis. An in situ labeling procedure to identify apoptotic nuclei in the ureterally obstructed kidneys revealed a 50% reduction in apoptosis after EGF administration. Northern blot analysis and in situ hybridization for SGP-2 mRNA or clusterin gene product also revealed a decreased expression in the obstructed and EGF-treated renal parenchyma.Conclusions. These data suggest that EGF, apart from its known role as a mitogenic substance for renal tubular epithelial cells, is also a critical in vivo renal cell survival factor for the developmentally mature kidney.     

Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies

Summary Cytosine arabinsodie (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m² as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9–12 and 21–24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m²×2 doses of ara-C and 50 mg/m² of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.Supported in part by grants from the National Cancer Institute (CA-12197 and CA-09422) and the American Cancer Society CF-85-182     

Tuberculosis of the upper limb joints

Summary Seventy-four cases of tuberculosis of the upper limb joints (sterno-clavicular 1; shoulder 12; elbow 42; wrist 10 and fingers 9), treated by two of the authors, were reviewed. Eighty-seven percent presented at an advanced stage of destruction. The diagnosis was proved in 71 out of 74 cases. In most, the treatment was 6–12 months of chemotherapy, plaster immobilization (in order to prevent or correct deformity) and functional rehabilitation whenever possible. The sterno-clavicular and finger joints were not immobilized. Response to chemotherapy was favourable in 66 of the patients followed up. One relapse occurred at the 18th month.The affected shoulder joints healed with loss of movement, but were not painful. At the elbow, ten patients developed spontaneous bony fusion in the right-angle position, 27 had a useful range of motion and 19 had more than 70° of flexion-extension movement. One patient had an arthrodesis. At the wrist, two patients healed with painful stiffness and an arthrodesis was performed. All the finger lesions healed with painless stiffness which did not interfere much with function because rehabilitation had been started early. The authors believe that conservative management usually gives better results than arthrodesis or excision of the joint.

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Résumé Les auteurs rapportent les résultats de leur expérience dans 74 cas d'ostéo-arthrite tuberculeuse du membre supérieur: 1 sterno-claviculaire, 12 scapulo-humérales, 42 coudes, 10 poignets et 9 articulations des doigts, toutes traitées personnellement par les deux auteurs principaux. Sur le plan diagnostique, 87% des patients se présentaient à un stade de destruction avancée. Le diagnostic de certitude fut obtenu dans 71 cas sur 74. Dans la majorité des cas, le traitement a été standardisé: chimiothérapie de 6 à 12 mois, immobilisation plâtrée pour prévenir ou corriger les déformations, suivie de reéducation chaque fois que possible. Les lésions de la sterno-claviculaire et des doigts ne furent pas immobilisées. Les résultats ont été bons en ce qui concerne la chimiothérapie: 66 réponses favorables chez 66 patients suivis. Il y a eu une rechute au 18éme mois. Du point de vue orthopédique, les lésions scapulo-humérales ont guéri avec une raideur de l'épaule toujours importante mais indolore. Au niveau du coude, 10 patients évoluèrent vers la fusion osseuse précoce spontanée, qui se fit à 90° de flexion grâce à l'immobilisation plâtrée; 27 guérirent avec une conservation variable des mouvements du coude dans un secteur fonctionnel et 19 d'entre eux présentaient plus de 70° d'étendue de flexion; 1 patient fut arthrodésé. Au niveau du poignet, 2 patients guérirent avec une raideur douloureuse qui nécessita une arthrodèse. Les lésions des doigts guérirent avec une raideur plus ou moins marquée, bien compensée par la mobilité des autres articulations, conservée intacte par la reéducation. Les auteurs concluent à la meilleure qualité des résultats du traitement conservateur que des classiques interventions d'arthrodèse ou de résection articulaire.

     

Inhibition and reversal of platelet-rich arterial thrombus in vivo: direct vs. indirect factor Xa inhibition

BACKGROUND/OBJECTIVE: The efficacy of a direct factor (F)Xa inhibitor, ZK-807834, was compared with indirect inhibition by enoxaparin for inhibition and deaggregation of acute platelet-rich thrombi in a well-characterized porcine carotid injury model. METHODS: A crush injury was performed on a randomly chosen carotid artery and the thrombus allowed to propagate for 30 min. Pigs then received intravenous drug for 35 min: ZK-807834-Dose 1 (40 microg kg(-1) bolus + 1.5 microg kg(-1) min(-1) infusion, n=6); ZK-807834-Dose 2 (20 microg kg(-1) bolus + 0.75 microg kg(-1) min(-1) infusion; n=6); enoxaparin (1 mg kg(-1) bolus; n=6); or saline (n=6). Five minutes after drug initiation, the contralateral artery was injured. Thrombus size was monitored by scintillation detection of autologous 111In-platelets. RESULTS: The prothrombin time ratio was 2.2 +/- 0.1; 1.4 +/- 0.3; 1.2 +/- 0.9 and 1.1 +/- 0.2, respectively. ZK-807834-Dose 1 significantly inhibited carotid platelet deposition (525 +/- 226 x 10(6) cm(-2); P = 0.008), whereas ZK-807834-Dose 2 (2325 +/- 768) and enoxaparin (1236 +/- 383) were not different from saline (2776 +/- 642). Thrombus deaggregation was greatest for animals receiving ZK-807834-Dose 1 (473 +/- 185). Neither ZK-807834-Dose 2 (1588 +/- 480) nor enoxaparin (1618 +/- 686) was different from saline control (2222 +/- 598). CONCLUSIONS: Direct FXa inhibition with ZK-807834, at a prothrombin time ratio of 2.2, effectively inhibits thrombosis and promptly deaggregates thrombi induced by arterial injury. In contrast, indirect FXa inhibition with enoxaparin was ineffective.     

New potent verapamil derivatives that reverse multidrug resistance in human renal carcinoma cells and in transgenic mice expressing the human MDR1 gene.

Multidrug resistance in human renal cell carcinoma is mainly caused by expression of the MDR1 gene and is characterized by a broad spectrum cross resistance to many natural product chemotherapeutic agents. This resistance can be overcome by applying chemosensitizers which inhibit the function of the MDR1 gene product P-glycoprotein. The development of new reversing agents with fewer side effects and a higher potency in modifying resistance is a high priority of research on drug resistance. We have evaluated four new verapamil derivatives on 21 primary human renal cell carcinomas in vitro, and also tested them in an MDR-transgenic mice model. These mice express the human MDR1 gene in their bone marrow cells and measurement of their white blood counts provides a simple, rapid and reliable system to screen for the potency of MDR-reversing agents in vivo. We demonstrate here that all four drugs are effective in reversing multidrug resistance in primary cultures of human renal cell carcinomas when used in combination with vinblastine chemotherapy, and to a lesser extent with doxorubicin or daunomycin chemotherapy. Our in vivo data indicate that two of these reversing agents display low toxicity at high concentrations and are more effective at low, clinically achievable concentrations, than the other two drugs and R-verapamil. These results make the two new drugs attractive candidates to be taken into clinical trials.