Real-World Efficacy and Safety of Multi-Tyrosine Kinase Inhibitors in Radioiodine Refractory Thyroid Cancer.

Background: The management of patients with locally advanced or metastatic differentiated thyroid cancer (DTC) that is refractory to radioiodine (RAI) remains a therapeutic challenge. The multi-tyrosine kinase inhibitors (TKIs) sorafenib and lenvatinib have been approved based on phase 3 clinical trials. Patients and Methods: We aimed at describing the efficacy and safety of TKI treatment of RAI-refractory DTC in a real-world setting at six German referral centers. One hundred and one patients with locally advanced or metastatic RAI-refractory DTC treated with sorafenib, lenvatinib, and/or pazopanib were included. Progression-free survival (PFS) and overall survival (OS) probabilities were estimated by using the Kaplan-Meier method. Results: Ninety-seven of 101 patients had progressive disease before TKI initiation. The median PFS for first-line treatment with sorafenib (n = 33), lenvatinib (n = 53), and pazopanib (n = 15) was 9 (95% confidence interval 5.2-12.8), 12 (4.4-19.6), and 12 months (4.4-19.6), respectively. The median OS for first-line treatment was 37 (10-64) for sorafenib, 47 (15.5-78.5) for lenvatinib, and 34 months (20.2-47.8) for pazopanib. Serious complications (e.g., hemorrhage, acute coronary syndrome, and thrombosis/venous thromboembolism) occurred in 16 out of 75 (21%) patients taking lenvatinib, in 3 out of 42 (7%) patients taking sorafenib, and in 3 out of 24 (13%) patients taking pazopanib. Conclusions: Sorafenib, lenvatinib, and pazopanib are effective treatment options in the majority of patients with RAI-refractory DTC. The PFS and six-month survival rate in patients treated with lenvatinib und pazopanib appear to compare favorably with sorafenib in the first-line treatment setting. However, a more advanced disease stage at treatment initiation in sorafenib- and pazopanib-treated patients in the era before TKI-approval and the retrospective nature of this study precludes a direct comparison of TKIs.

Curcumin attenuates oxidative stress and inflammatory response in the early phase after partial hepatectomy with simultaneous intraabdominal infection in rats.

BACKGROUND: Curcumin is a nontoxic, hepatoprotective antioxidant. It has been shown to efficiently scavenge oxygen free radicals, increase intracellular glutathione concentrations, and prevent lipid peroxidation in rat hepatocytes. Moreover, it has strong anti-inflammatory effects. In the present study we assessed its effect in a model of liver regeneration impaired by bacterial infections. MATERIAL AND METHODS: Male Sprague-Dawley rats underwent sham operation, cecal ligation and puncture (CLP), synchronous partial hepatectomy (PH), and CLP or synchronous PH+CLP with perioperative application of curcumin (100 mg per kg bodyweight per d) 48 h before surgery. Rats were sacrificed 24 h after surgery. Liver function was analyzed by measuring the serum albumin, serum bilirubin, and bile production. The local inflammatory response in the liver tissue was evaluated by quantification of TNF-alpha, IL-6 mRNA, and quantification of IL-1beta by ELISA. In addition, hepatic concentrations of reduced glutathione (GSH) and the oxidized disulfide dimer of glutathione (GSSG) were measured for determination of the redox state. RESULTS: After simultaneous PH+CLP curcumin significantly reduced the expression of TNF-alpha and IL-6 mRNA in the liver tissue. The IL-1beta concentration in the liver was also slightly, but not significantly, lower in the curcumin group. A severe depletion of hepatic glutathione was found in the PH+CLP group. This was reversed by curcumin application, after which the GSH to GSSG ratio increased markedly. The hepatocellular damage, measured by ALT liberation, was significantly lower in the curcumin treated group. The relative liver weight in the curcumin group was significantly higher 24 h after PH+CLP. However, hepatocellular proliferation parameters were not significantly improved by antioxidative treatment with curcumin. Only the Ki-67 index was slightly higher in the curcumin treated PH+CLP group (14+/-3%) than in the untreated PH+CLP group (7%+/-3%). The hepatocyte density was significantly lower in the curcumin group than in the corresponding untreated group. CONCLUSION: In the present model, curcumin revealed significant hepatoprotective effects with stabilization of redox state, reduced liberation of liver enzymes, and attenuated expression of pro-inflammatory cytokines. However, the hepatocellular proliferation was not significantly influenced.

Long-term results of subtotal vs total parathyroidectomy without autotransplantation in kidney transplant recipients.

HYPOTHESIS: Total parathyroidectomy without autotransplantation in kidney transplant recipients leads to reduced recurrence rates and similar improvement of clinical symptoms compared with subtotal parathyroidectomy. DESIGN: A retrospective cohort study. SETTING: University clinic. PATIENTS: Thirty-three patients with functioning renal grafts who underwent primary total (n = 17; group 1) or subtotal (n = 16; group 2) parathyroidectomy for renal hyperparathyroidism. MAIN OUTCOME MEASURES: Long-term levels of intact parathyroid hormone, serum calcium, phosphate, alkaline phosphatase, creatinine, and vitamin D; bone pain; use of medication; and incidence of persistent or recurrent hyperparathyroidism. RESULTS: The mean length of follow-up was 31 months in group 1 and 41 months in group 2. In all patients, postoperative serum calcium and phosphate levels normalized and bone pain markedly decreased. Persistent hypocalcemia was not observed. Serum creatinine levels intermittently increased in both groups but returned to preoperative levels in most of the patients. In group 1, all patients had undetectable intact parathyroid hormone levels throughout the study period. In group 2, 2 patients had persistent and 3 patients developed recurrent hyperparathyroidism (31%) that required therapy with cinacalcet hydrochloride in 3 cases. In 4 of these 5 patients, intact parathyroid hormone levels were greater than 54 ng/L directly after operation. In all, 27 of 33 patients (82%) received cholecalciferol therapy. Additional calcium supplementation was used by 12 group 1 patients (71%) and 3 group 2 patients (19%). CONCLUSIONS: Total parathyroidectomy in kidney transplant recipients appears to be safe and protective against persistent and recurrent disease. If subtotal parathyroidectomy is performed, the remnant should be small.

Probiotic and prebiotic influence beyond the intestinal tract.

Probiotics and prebiotics have long been appreciated for their positive influences on gut health. Research on the mechanisms and effects of these agents shows that their impact reaches beyond the intestine. Effects on the microecology and pathology of the oral cavity, stomach, and vaginal tract have been observed. Likely mediated through immune influences, systemic effects such as reduced severity of colds or other respiratory conditions, impact on allergy incidence and symptoms, and reduced absences from work or daycare have also been noted. These observations, among others, suggest a broader spectrum of influence than commonly considered for these unique substances.

Effect of enteral nutrition and synbiotics on bacterial infection rates after pylorus-preserving pancreatoduodenectomy: a randomized, double-blind trial.

OBJECTIVE: Patients undergoing pancreas resection carry several risk factors for nosocomial bacterial infections. Pre- and probiotics (synbiotics) are potentially useful for prevention of these infections. SUMMARY BACKGROUND DATA: First trials in patients following major abdominal surgery including liver transplantation using one Lactobacillus (LAB) and one fiber showed significant reduction of infection rates and reduced length of antibiotic therapy compared with a control group. The present study was designed to analyze whether a combination of different LAB and fibers would further improve outcome. METHODS: A prospective randomized monocentric double-blind trial was undertaken in 80 patients following pylorus-preserving pancreatoduodenectomy (PPPD). All patients received enteral nutrition immediately postoperatively. One group (A) received a composition of 4 LAB and 4 fibers, and another group (B) received placebo (fibers only) starting the day before surgery and continuing for 8 days. Thirty-day infection rate, length of hospital stay, duration of antibiotic therapy, noninfectious complications, and side effects were recorded. RESULTS: The incidence of postoperative bacterial infections was significantly lower with LAB and fibers (12.5%) than with fibers only (40%). In addition, the duration of antibiotic therapy was significantly shorter in the latter group. Fibers and LAB were well tolerated. CONCLUSION: Early enteral nutrition supplemented with a mixture of LAB and fibers reduces bacterial infection rates and antibiotic therapy following PPPD.