Hepatic lobectomy in dogs using a stapling device with a vascular cartridge: a retrospective study of 13 cases.

CASE HISTORY: Medical records of two veterinary hospitals in Canada were reviewed to identify cases of dogs that underwent liver lobectomy via open laparotomy using the Endo GIA surgical stapling device with a vascular cartridge (height of open and closed staples: 2.5 and 1.0 mm, respectively) between January 2016 and June 2018. Mean age at the time of surgery of the dogs (n = 13) included in the study was 10.4 (SD 1.5; min 7.9, max 12.8) years and mean body weight was 14 (min 3.9, max 37.8) kg. CLINICAL FINDINGS: Liver masses requiring hepatic lobectomy were identified in 12 dogs by abdominal ultrasound examination. The remaining dog required a lobectomy of the right medial liver lobe to address leakage from the right medial lobe hepatic duct that occurred as a complication of cholecystectomy to treat a ruptured gallbladder mucocoele. TREATMENT AND OUTCOME: Complete liver lobectomy of 14 lobes (11 from the left hepatic division) in 12 dogs and partial lobectomy of one lobe in one dog was performed via open laparotomy using the Endo GIA device. The mean surgical time, including concurrent procedures, was 50 (SD 17; median 45, min 28, max 91) minutes. The most common intra-operative complication was oozing from the transected liver parenchyma in 6/13 dogs, which was mild in all cases. Five dogs experienced minor post-operative complications. No major peri- or post-operative complications occurred, and no patients required surgical re-exploration. All patients survived until discharge and were alive at the 2-week follow-up for suture removal. CLINICAL RELEVANCE: Use of the Endo GIA stapling device with a vascular cartridge is feasible for liver lobectomy of the left hepatic division and in this study had low rates of intra-operative and post-operative complications. The Endo GIA stapling device is a viable option for this type of liver lobectomy in dogs. Though successful, the small number of central (two lobes) and right (one lobe) hepatic division lobectomies in this study precludes us from drawing definitive conclusions about the feasibility of this technique on these divisions.

Retrospective study of 476 tibial plateau levelling osteotomy procedures. Rate of subsequent 'pivot shift', meniscal tear and other complications.

OBJECTIVE: To determine the rate of subsequent 'pivot shift', meniscal tear and risk factors associated with complications of tibial plateau levelling osteotomy (TPLO) and to assess clinical and owner perception outcome. STUDY DESIGN: Retrospective study. SAMPLE POPULATION: Three hundred and forty-eight dogs that had undergone TPLO surgical procedures (n = 476 stifles). METHODS: Medical records were reviewed for the retrieval of information on breed, sex, age, body weight, clinical history, radiograph findings, pre- and postoperative tibial plateau angle, limb alignment, unilateral versus bilateral disease, condition of cranial cruciate ligament (CCL) and menisci, implant material, healing time and complications. Clinical and owner-assessed questionnaire outcomes were also recorded. RESULTS: Forty-six (9.7%) postoperative complications were reported. Twenty (4.2%) were classified as major complications requiring an additional surgical intervention, and 26 (5.5%) as minor complications. No risk factors associated with postoperative complications were identified. Ten (2.1%) subsequent meniscal injuries in the stifles with normal un- altered menisci at time of TPLO were reported with a median postoperative time of 9.5 months. Signs of postoperative 'pivot shift' were reported in 15 (3.1%) stifles. All stifles with a 'pivot shift' had a complete CCL rupture or a debrided partial CCL rupture; a medial menisectomy was identified as a risk factor for a 'pivot shift' (p = 0.02). Dogs with intact medial meniscus had a significantly higher activity level (p <0.0001) and a shorter time to peak function (p = 0.02) than dogs that underwent menisectomy according to an owner questionnaire. CONCLUSIONS: Dogs with TPLO and intact meniscus seemed to have a better and faster recovery than dogs with TPLO and menisectomy based on owner questionnaires. 'Pivot shift' was infrequent after TPLO surgery. All dogs with a 'pivot shift' had a complete CCL rupture or a debrided partial CCL rupture and menisectomy was identified as a risk factor for its occurrence. CLINICAL RELEVANCE: Considering the relatively low rate of subsequent meniscal injury after TPLO, systematic medial meniscal release with TPLO may be unnecessary. The 'pivot shift' deserved further investigation to completely understand its mechanism, to identify its anatomic components and potential consequences on the stifle joint.

Longitudinal tendon tear concurrent with bilateral medial luxation of the superficial digital flexor muscle tendon in a dog.

Luxation of the superficial digital flexor muscle tendon (SDFMT) is a rarely reported condition in dogs, and tendon tear concurrent with SDFMT luxation had never been reported. Abnormal conformation of both calcanei and strenuous activity were suspected as contributing factors in this case. Bilateral medial SDFMT luxation was surgically treated with bursa medial incision release, redundant lateral bursa excision and apposition to the edge of the SDFMT with nonabsorbable sutures. The unilateral longitudinal tendon tear of the SDFMT associated with medial SDFMT luxation was successfully treated with horizontal mattress sutures, and a good outcome was reported for both hindlimbs.

Phase I and pharmacokinetic study of the camptothecin analog DX-8951f administered as a 30-minute infusion every 3 weeks in patients with advanced cancer.

PURPOSE: DX-8951f is a totally synthetic derivative of camptothecin with greater cytotoxicity and more potent topoisomerase I inhibition than SN-38, topotecan, and camptothecin in preclinical studies. This phase I study aimed to describe the toxicity and to determine the maximum-tolerated dose (MTD) and pharmacokinetics of DX-8951f given as a 30-minute intravenous infusion every 3 weeks. PATIENTS AND METHODS: Twelve patients with refractory solid malignancies were treated with DX-8951f at dose levels ranging from 4 to 7.1 mg/m(2). All but one patient had received previous chemotherapy, and eight patients were considered heavily pretreated. Total DX-8951f plasma concentrations were assayed using high-performance liquid chromatography. RESULTS: Thirty-six cycles of DX-8951f were administered. Neutropenia was the dose-limiting toxicity, and it was dose-related, reversible, and noncumulative. Other toxicities included nausea and vomiting, alopecia, asthenia, fever, and anemia. Grade 1 or 2 diarrhea was observed in seven patients but was transient and resolved without requiring treatment. Pharmacokinetic analysis showed that DX-8951f had a half-life of 7.15 hours and a clearance rate of 1.65 L/h.m(2). The DX-8951f area under the plasma-concentration curve increased linearly with the dose. We defined the MTD of DX-8951f administered as a 30-minute intravenous infusion every 3 weeks as 7.1 mg/m(2). CONCLUSION: The dose-limiting toxicity of DX-8951f is neutropenia. The recommended dose for phase II studies is 5.33 mg/m(2) every 3 weeks in patients previously treated with chemotherapy.

A phase I and pharmacokinetic study of the novel aza-anthracenedione compound BBR 2778 in patients with advanced solid malignancies.

BBR 2778 is a novel aza-anthracenedione with no cardiotoxicity in preclinical models. This Phase I dose escalation trial of BBR 2778 was conducted to determine the maximum tolerated dose, the dose-limiting toxicity, and the pharmacokinetic profile of BBR 2778 in patients with advanced solid tumors. BBR 2778 was given in three consecutive weekly 30-min i.v. infusions over a 4-week cycle (cy). Thirty patients (pts) were treated with BBR 2778 at doses ranging from 5 to 150 mg/m2/week. The dose levels 5, 10, 16.5, 25, 37.5, 75, 112.5, and 150 mg/m2/week were investigated in 4 pts (9 cy), 3 pts (3 cy), 3 pts (5 cy), 6 pts (9 cy), 1 pt (1 cy), 4 pts (9 cy), 6 pts (18 cy), and 3 pts (4 cy), respectively. The dose-limiting toxicity was neutropenia, typically occurring at day 14. Other toxicities were mild to moderate and were principally thrombocytopenia, lymphopenia, alopecia, nausea, and vomiting and blue coloration of the skin and urine. No significant cardiac toxicity was observed. The plasma dose concentration curve fitted a biexponential profile, with a rapid distribution phase followed by a prolonged elimination phase (mean t1/2,z, 12 h). BBR 2778 displayed a large volume of distribution (range, 9.7-29.7 l/kg) with a high plasma clearance rate (0.75-1.31 l/h/kg). Less than 10% of the dose was recovered in urine as unchanged drug. The maximum tolerated dose was 150 mg/m2/week for 3 weeks, every 4 weeks. On the basis of this study, the recommended dose for Phase II studies is 112.5 mg/m2/week days 1 and 8 with individual optional administration at day 15, every 4 weeks. Antitumor activity was observed in patients with breast, small cell lung carcinoma, and facial cylindroma. This trial showed that BBR 2778 has a manageable toxicity profile on a weekly schedule. This lead compound of the aza-anthracenedione family shows promising antitumor activity and deserves Phase II investigation in patients with high risk of cumulative cardiotoxicity, such as anthracycline-pretreated breast cancer patients.

Peritoneal carcinomatosis in germ-cell tumor: relations with retroperitoneal lymph node dissection.

Peritoneal carcinomatosis from germ-cell tumor has rarely been described, and thus remains largely unknown. We report here five cases involving this entity. All five patients had embryonal carcinoma in their primary germ-cell tumor. Four of them had undergone retroperitoneal lymph node dissection (RPLND), and viable malignant cells were found. RPLND was performed for relapses (n = 3) and as primary therapy for stage II disease (n = 1). The peritoneum was the only site of relapse in three patients, and was associated with pleural effusion in one. The time to relapse after RPLND ranged from 6 to 14 months. One patient sustained injury to lymph nodes during RPLND, and another patient had a peritoneal xanthelasma. The only three patients already described in the literature underwent RPLND or surgical biopsy. All these observations suggest a striking relation between RPLND and occurrence of subsequent peritoneal carcinomatosis.

[Iatrogenic disorders in the active respiratory systems (respiratory center and its performance]. / Atteintes iatrogènes du système respiratoire actif (commande ventilatoire et ses effecteurs).

Amongst the undesirable effects of medical intervention which touch on the respiratory apparatus one can distinguish schematically those disorders which affect the "passive respiratory system" (lungs, pleura, bronchi and vessels) and those which concern the "active respiratory system (SRA)" (nerve centres, respiratory muscles) which are less often described. After a brief reminder of the principles and limits of the available methods of investigation, this chapter reviews the different iatrogenic disorders of SRA according to their level and their aetiology. Peripheral disorders are touched on such as alterations of phrenic conduction (with particular mention of satellite lesions from cardiac surgery), those of neuromuscular transmission (most often induced by medication) and of intrinsic muscular properties (mainly steroid induced myopathies). Central disorders are described principally as the respiratory effects of neurotropic and non-neurotropic medications and the harmful effects of different substances on the sleep/respiration interaction. The secondary effects of therapy on SRA are all the more marked if there are underlying respiratory or neuromuscular disturbances which allow a large place for preventive measures. The diagnosis is made difficult by the complexity of the structures and functions involved and it is clear that the development of pathophysiological studies, which are still too scarce, should enable better understanding of their clinical significance.

Health promotion research literature in Europe 1995-2005.

BACKGROUND: To undertake an overview of health promotion research in the EEA to inform the collaborative study-SPHERE (Strengthening Public Health Research in Europe). METHODS: A 'filter' (search strategy) was used to search Medline and Embase for a 10-year period from 1995 to 2005. A 32% (6000) sample of the filter output was assessed for proportion constituting health promotion. Output was analysed by country, population, gross domestic product (GDP) and health need (disability-adjusted life years, DALYs). Disease prevention (screening and immunization) and health improvement papers were separately identified. The latter were classified by methodology, level of intervention and topic area. RESULTS: 18,862 papers were identified. One-third was identified as health promotion (2206/6000, 36.7%) equivalent to 6935 (CI 6651-7230). Production varied: Nordic countries were highest producers per million population; the UK the largest net producer. There was a weak relationship between health promotion publication and population size (r(2) = 0.38); a weak inverse relationship with relative health (DALYs per million population) (r(2) = 0.07) and a slightly stronger relationship with GDP (r(2) = 0.45). Twenty-eight percent (626/2206) of the papers identified were disease prevention (screening and immunization). The largest topic areas of the remainder (1580) were diet and exercise, smoking and tobacco, and cardiovascular disease reduction. Accidents and violence, alcohol and mental health each accounted for <5% of total output. Intervention studies were a minority; with less aimed at the regional/national or policy or legal and fiscal levels. CONCLUSION: Health promotion research production varies across Europe. Research commissioning should stress interventional and policy level research.

Cytotoxic chemotherapy: advances in delivery, pharmacology, and testing.

Adjuvant treatment of malignant gliomas, the most common types of primary brain tumors, with intravenous (iv) chemotherapy has not significantly improved survival for patients with these forms of cancer. A major factor in the failure of iv chemotherapy is the blood-brain barrier (BBB), a physiologic impediment to the delivery of cytotoxic chemotherapeutic drugs to the central nervous system (CNS). Intra-arterial and intrathecal infusion, blood-brain barrier disruption, high-dose chemotherapy, intratumoral administration, and convection-enhanced delivery are methods developed to overcome the BBB. Although some of these methods may increase the local concentration-time profile, improvement in clinical outcomes has yet to be definitively established. New methods for assessment of drug delivery to the brain tumor will assume increasing importance in the study of new cytotoxic chemotherapeutic drugs for these types of cancer. Pharmacokinetic studies are critical components of these clinical trials and allow assessment of drug delivery to the CNS and brain tumor. Additionally, pharmacokinetic studies will remain an important component of early clinical trials, particularly for identifying significant drug interactions involving the various supporting medications that are typically used in this patient population.

Normal serum neuron specific enolase (NSE) value after the first cycle of chemotherapy: an early predictor of complete response and survival in patients with small cell lung carcinoma.

BACKGROUND: Serum neuron specific enolase (NSE) is the most sensitive tumor marker of small cell lung carcinoma (SCLC) at diagnosis. Its prognostic value is still debated. Thus, the authors decided to assess the predictive value, in terms of complete response and survival, of serum NSE measured before and after one cycle of chemotherapy in patients with SCLC. METHODS: Sera from 135 patients with histologically proven limited (n = 63) or metastatic (n = 72) SCLC were obtained. Clinical and biologic parameters with a known or suspected prognostic relevance were reviewed. Serum NSE was measured before chemotherapy (D1-NSE) and 28 days after its initiation (D28-NSE). The prognostic value of the parameters under study was evaluated in univariate and multivariate analyses using the Cox proportional hazards model and logistic regression analysis. RESULTS: The level of serum NSE was raised in 120 patients (88%) prior to therapy. The probability of a normal D28-NSE value was not affected by the baseline D1-NSE value. Disease extension (P = 0.0005), performance status (P = 0.0001), D28-NSE (P = 0.003), and carcinoembryonic antigen (CEA) levels (P = 0.008) were found to be predictive for survival, whereas age, gender, plasma sodium, serum protides, and D1-NSE were not. Median survival and 2-year overall survival were 15.3 months and 21% (95% confidence interval [CI], 13-31%) when D28-NSE was normal and 8.1 months and 15% (95% CI, 8-27%) when it was not (P < 0.03). Only performance status (P = 0.001), disease extension (P = 0.002), and D28-NSE (P = 0.02) were found to be independent prognostic parameters for survival in the multivariate analysis. A simple prognostic index was developed using these 3 variables. Limited disease, a normal D28-NSE value, and a normal CEA value prior to therapy were the only parameters predictive for complete response in the univariate analysis, and D28-NSE (P = 0.01) and disease extension (P = 0.0001) were found to be independent variables in multivariate analysis. A complete response to therapy occurred in 62% with a normal D28-NSE value and in only 34% in the opposite case. CONCLUSIONS: Normal serum D28-NSE is a strong, independent early predictor of both complete response to therapy and survival. This simple tool may be proposed for use in the clinic and in research, in association with an assessment of disease extension and performance status, to predict the outcome of patients with SCLC.