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Background: RECORD-3 compared everolimus and sunitinib as first-line therapy, and the sequence of everolimus followed by sunitinib at progression compared with the opposite (standard) sequence in patients with metastatic renal cell carcinoma (mRCC). This final overall survival (OS) analysis evaluated mature data for secondary end points., Patients and Methods: Patients received either first-line everolimus followed by second-line sunitinib at progression (n = 238) or first-line sunitinib followed by second-line everolimus (n = 233). Secondary end points were combined first- and second-line progression-free survival (PFS), OS, and safety. The impacts of neutrophil lymphocyte ratio (NLR) and baseline levels of soluble biomarkers on OS were explored., Results: At final analysis, median duration of exposure was 5.6 months for everolimus and 8.3 months for sunitinib. Median combined PFS was 21.7 months [95% confidence interval (CI) 15.1-26.7] with everolimus-sunitinib and 22.2 months (95% CI 16.0-29.8) with sunitinib-everolimus [hazard ratio (HR)EVE-SUN/SUN-EVE, 1.2; 95% CI 0.9-1.6]. Median OS was 22.4 months (95% CI 18.6-33.3) for everolimus-sunitinib and 29.5 months (95% CI 22.8-33.1) for sunitinib-everolimus (HREVE-SUN/SUN-EVE, 1.1; 95% CI 0.9-1.4). The rates of grade 3 and 4 adverse events suspected to be related to second-line therapy were 47% with everolimus and 57% with sunitinib. Higher NLR and 12 soluble biomarker levels were identified as prognostic markers for poor OS with the association being largely independent of treatment sequences., Conclusions: Results of this final OS analysis support the sequence of sunitinib followed by everolimus at progression in patients with mRCC. The safety profiles of everolimus and sunitinib were consistent with those previously reported, and there were no unexpected safety signals., Clinical Trials Number: ClinicalTrials.gov identifier, NCT00903175., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.)

Background: This analysis compared the efficacy and safety outcomes by histology of nab-paclitaxel (nab-P) plus carboplatin (C) versus solvent-based paclitaxel (sb-P) plus C in patients with advanced non-small-cell lung cancer (NSCLC) based on preplanned stratification factors specified in the phase III trial protocol., Patients and Methods: Patients with untreated stage III/IV NSCLC received 100 mg/m(2) nab-P weekly and C (area under the curve, AUC = 6) every 3 weeks (q3w) or 200 mg/m(2) sb-P plus C (AUC = 6) q3w. Primary end point was objective overall response rate (ORR)., Results: nab-P/C versus sb-P/C produced a significantly higher ORR (41% versus 24%; response rate ratio [RRR] 1.680; P < 0.001) in patients with squamous cell (SCC) NSCLC. For nab-P/C versus sb-P/C, ORRs were 26% versus 27% (RRR 0.966; P = 0.814) in patients with adenocarcinoma, 33% versus 15% (RRR 2.167; P = 0.323) in patients with large cell carcinoma (LC), and 24% versus 15% (RRR 1.593; P = 0.372) in patients with not otherwise specified histology. Median overall survival for nab-P/C versus sb-P/C in patients with SCC was 10.7 versus 9.5 months (HR 0.890; P = 0.310), and 12.4 versus 10.6 months (HR 1.208; P = 0.721) for patients with LC. nab-P/C produced significantly (P < 0.05) less grade 3/4 neuropathy and arthralgia, whereas sb-P/C produced less thrombocytopenia and anemia., Conclusion(s): First-line nab-P/C demonstrated a favorable risk-benefit profile in patients with NSCLC regardless of histology.

Background: This analysis evaluates safety and efficacy in elderly (≥ 70 years old) versus younger patients enrolled in a phase III advanced non-small-cell lung cancer (NSCLC) trial., Patients and Methods: Untreated stage IIIB/IV patients with PS 0/1 were randomly assigned (1:1) to carboplatin AUC6, day 1 every 3 weeks, and either nab-paclitaxel (Abraxane) 100 mg/m(2) weekly (nab-P/C) or solvent-based paclitaxel (Taxol) 200 mg/m(2) day 1 every 3 weeks (sb-P/C). The primary end-point was overall response rate (ORR)., Results: Fifteen percent of 1052 enrolled patients were elderly: nab-P/C, n = 74; sb-P/C, n = 82. In both age cohorts, the ORR was higher with nab-P/C versus sb-P/C (age ≥ 70: 34% versus 24%, P = 0.196; age <70: 32% versus 25%, P = 0.013). In elderly patients, progression-free survival (PFS) trended in favor of nab-P/C (median 8.0 versus 6.8 months, hazard ratio (HR) 0.687, P = 0.134), and overall survival (OS) was significantly improved (median 19.9 versus 10.4 months, HR 0.583, P = 0.009). In younger patients, PFS (median 6.0 versus 5.8 months, HR 0.903, P = 0.256) and OS (median 11.4 versus 11.3 months, HR 0.999, P = 0.988) were similar in both arms. Adverse events were similar in both age groups, with less neutropenia (P = 0.015), neuropathy (P = 0.001), and arthralgia (P = 0.029), and increased anemia (P = 0.007) with nab-P/C versus sb-P/C., Conclusions: In elderly NSCLC patients, nab-P/C as first-line therapy was well tolerated and improved the ORR and PFS, with substantially longer OS versus sb-PC.

We have compared the effects of sevoflurane and isoflurane on arterial oxygenation, heart rate and mean arterial pressure during one lung anaesthesia in a prospective, crossover study. We studied 28 patients undergoing oesophagogastrectomy, allocated alternatively to one of two groups. Patients in group I/S (n = 14) received 1 MAC (1.1%) of isoflurane in oxygen from induction until the end of 30 min of open chest one lung ventilation (OLV) in the lateral position. This was followed by 1 MAC (2.1%) of sevoflurane in oxygen for the next 30 min of OLV. Patients in group S/I (n = 14) received the two anaesthetic agents in the reverse order. We found no significant difference in arterial oxygenation, heart rate or mean arterial pressure between the two potent inhalation agents. In the subgroup of patients with pulmonary artery catheters (n = 12), we found a significant increase (P < 0.05) in derived shunt during sevoflurane anaesthesia. There was no significant difference in mixed venous saturation and cardiac output. We conclude that during one lung ventilation, the choice between sevoflurane and isoflurane did not significantly influence arterial oxygenation.

Background: Because prolonged survival of heart transplant recipients is expected with the current immunosuppressive treatment, the functional capacity of these long-term survivors is of interest. Previous exercise studies showed no objective improvement in exercise tolerance several years after transplantation, but the extent to which chronotropic incompetence and allograft diastolic dysfunction observed early after transplantation may improve over time has not been defined., Methods: Thirteen untrained heart transplant recipients without symptoms, between 27 and 70 months after transplantation, and 13 age-matched sedentary normal controls underwent maximal upright bicycle exercise testing with simultaneous hemodynamic, radionuclide, and expired gas measurements., Results: Systolic function as measured by ejection fraction was supranormal at rest in the transplant group and normalized with exercise. Despite their maximal exercise effort, transplant recipients had a 60% reduction in their exercise capacity compared with nontransplant recipients. Peak oxygen consumption was similarly reduced by 52%. Cardiac output response to exercise was 43% lower in the transplant group because of a 78% reduction in heart rate reserve and an 18% reduction in maximal stroke volume. Ventricular volumes were similarly reduced after transplantation, but filling pressures remained normal, indicating allograft diastolic dysfunction. Despite the significantly reduced maximal cardiac output, maximal arteriovenous oxygen difference was 25% lower in the transplant recipients, suggesting a peripheral deficit in oxygen handling., Conclusions: Therefore, patients, 2 to 6 years after transplantation, continue to have a significant reduction in exercise tolerance as a result of a combination of severe chronotropic incompetence, limited stroke volume reserve caused by a reduced ventricular size and allograft diastolic dysfunction, and an abnormality in peripheral oxygen delivery or use. Efforts aimed at improving these factors may further enhance the functional capacity of these long-term survivors of heart transplantation.

After heart transplantation, right ventricular failure can occur because of increased afterload. Previous studies have suggested that the maximal pressure the right ventricle can develop is determined primarily by right ventricular perfusion pressure. However, the interaction of the left ventricle and the pericardium as functional co-determinants of maximal right ventricular function is unknown. This study was undertaken to determine the interaction of the pericardium, left ventricular pressure, and right coronary artery perfusion pressure as potential determinants of maximal right ventricular function. In an acute canine preparation, with progressive pulmonary artery constriction, maximal generated right ventricular pressure was determined over a range of left ventricular systolic pressures. Additional groups of dogs were studied with the right coronary artery cannulated and were maintained at constant perfusion pressure. In all preparations, the maximal pressure the right ventricle could generate was linearly related to left ventricular systolic pressure. Having a closed pericardium markedly enhanced this effect; some effect was present with an open pericardium, although the magnitude of the influence of left ventricular pressure on maximal right ventricular pressure was much less. Maintaining constancy of right coronary artery perfusion pressure, either at high or low values, did not alter these findings nor did it alter the influence of the pericardium. These results suggest that right ventricular perfusion may not be the sole determinant of maximal right ventricular function. Furthermore, with the pericardium open, such as in the posttransplantation state, the left ventricular contribution to maximal right ventricular function may be diminished, increasing vulnerability for right ventricular failure caused by increased afterload.

Forty-seven bovine embryos, ranging from the four-cell to expanded blastocyst stage, with grades ranging from excellent to poor, were collected non-surgically from superovulated Holstein heifers. A viability assay based on the measurement of bioluminescent emission from the media surrounding an embryo was tested. This assay measured the activity of the enzyme lactate dehydrogenase (LDH) released into the media by the embryos. Lactate dehydrogenase has been reported to be released into media by nonviable embryos. The assay used is simple, rapid and nonsubjective, requiring approximately 5 min to complete. The LDH assay proved to be a practical method for distinguishing between nonviable and viable embryos. Viability was determined by the observation of embryo development in culture following the LDH assay. The activity of LDH in the media of nonviable embryos was consistently higher than for viable embryos (P<0.001), with no overlap between the two groups. Thus, the LDH assay was shown to be a reliable test of embryo viability.

Esophagogastrectomy is generally considered to be the treatment of choice for resectable tumors of the esophagus. Although many approaches and techniques have been advocated, since April 1983 we have used a left thoracophrenotomy approach for most lesions of the lower two thirds of the esophagus and gastric cardia. Stapling instruments have been used for mobilization of the stomach and fashioning of the esophagogastric anastomosis. One-hundred fifteen patients undergoing resection of malignant tumors with this technique were retrospectively reviewed. Perioperative mortality was 8.7% (10/115). The rate of anastomotic leakage was 1.7% (2/115), and benign narrowing of the anastomosis requiring dilation developed in 16 patients. The rate of recurrent anastomotic tumor was 4.3%. Eighteen patients had complications, and the mean postoperative hospital stay was 13 days. Survival at 3 years was 22.1%. During the period of study, 22 patients underwent esophageal resection by some other approach; the reasons for this are described. The advantages of the left thoracophrenotomy approach are discussed.

One-hundred and twenty excellent morula to blastocyst stage bovine embryos were obtained nonsurgically from superovulated Holstein heifers. Completely portable, nonelectric (manual) liquid nitrogen (LN) freezers combined with simplified freezing curves utilizing self-seeding were compared to a programmable LN freezer (Planner-R204) following the conventional freezing rate for freezing embryos. Seeding was self induced in ampules at -6.8 degrees C and at -5.5 degrees C in straws in the manual freezers. Glycerol was used as the cryoprotectant at 1.5 M concentration. Post-thaw appearance, fluorscein diacetate testing (FDA), and growth after 12 and 24 h incubation were used as indicators of embryo viability. There were no significant differences between embryos frozen in the two types of freezers in terms of the viability tests used. Pregnancy rates resulting from transfer of embryos frozen in the two types of freezers will be determined in subsequent field trials. The manual LN freezers used in this study are capable of successfully freezing bovine embryos. The simplified nature of these freezers and the freezing procedures used with them greatly decreases the complexity and expense of freezing embryos.

The records of 121 patients who underwent surgical thoracoscopy between 1976 and 1987 were reviewed. The indications for thoracoscopy were pleural effusion (88%), pleural thickening (7.4%), and a mass on the chest roentgenogram (15%). All procedures were performed under general anesthesia with a rigid thoracoscope and 91 patients (75%) were diagnosed as having a malignant process. Although thoracotomy was undertaken in 20 patients (16.5%), no patient with benign disease underwent diagnostic thoracotomy. Thoracoscopy had a 98.9% sensitivity and a 93.3% specificity in this series. One patient died of a myocardial infarction after the procedure, and 11 patients (9.1%) had other, predominantly respiratory, complications. We confirm that surgical thoracoscopy is a useful procedure in the diagnosis of pleural processes.

Two hundred forty excellent-quality blastocysts flushed from 53 superovulated Holstein heifers were frozen by 1 of 16 procedures in a 2 x 2 x 2 x 2 factorial design. The main effects included a simple, inexpensive, portable mechanical freezing unit instead of a programmable Liquid Nitrogen (LN) freezer for freezing bovine embryos, cryoprotective agents dimethyl sulfoxide (DMSO) and glycerol, addition rates of the cryoprotectants and freezing rates. Embryo viability was assessed morphologically and by fluorescein diacetate (FDA) evaluation. Neither the type of freezer, the cryoprotectant nor the rate of cryoprotectant addition affected embryo viability. Embryo survival after 12 h of incubation was higher (P < 0.05) using a conventional freezing rate than a two-step method (37.2 vs 16.5%). The correlation coefficient between viability evaluation methods (morphology vs FDA) was influenced by cryoprotectant and embryo processing methods and ranged from -0.13 to +0.70. This study indicates that more simplified embryo freezing equipment and handling procedures may provide protection equal to that of more complicated, expensive equipment and more time-consuming methods. Economical on-farm embryo freezing is feasible.