Effect of a Polyglycolic Acid Mesh Sheet (Neoveil™) in Thyroid Cancer Surgery: A Prospective Randomized Controlled Trial.

Papillary thyroid cancer (PTC) is the most common type of thyroid cancer. Surgery for PTC involves resection of the thyroid gland and central lymph node dissection. Central lymph node dissection is associated with an increased amount of fluid from the dissection area and chyle leakage due to thoracic duct injury. There are few studies that deal with reducing fluid drainage and preventing chyle leakage after thyroid surgery with central lymph node dissection. A polyglycolic acid mesh sheet (Neoveil™) has been demonstrated to prevent postoperative fluid leakage in other surgeries. This study aims to evaluate whether a polyglycolic acid mesh sheet can reduce postoperative drainage and chyle leakage in papillary thyroid cancer surgery, and this study was designed as a prospective, open-label, randomized controlled trial in a single university hospital. The patients were randomly assigned to having only fibrin glue used in the central node dissection area (control group) or to having a polyglycolic acid mesh sheet applied after fibrin glue (treatment group). A total of 330 patients were enrolled, of which 5 patients were excluded. A total of 161 patients were included in the treatment group, and 164 patients were included in the control group. The primary outcome was the drainage amount from the Jackson-Pratt drain, and the secondary outcome was the triglyceride level in the drained fluid on the 1st and 2nd postoperative days. The drainage amount was significantly lower in the treatment group on the 2nd postoperative day (60.9 ± 34.9 mL vs. 72.3 ± 38.0 mL, p = 0.005). The sum of drainage amount during the whole postoperative days (1st and 2nd days) was also significantly lower in the treatment group (142.7 ± 71.0 mL vs. 162.5 ± 71.5 mL, p = 0.013). The postoperative triglyceride levels were lower in the treatment group but were not statistically significant (92.1 ± 60.1 mg/dL vs. 81.3 ± 58.7 mg/dL on postoperative day 1, p = 0.104 and 67.6 ± 99.2 mg/dL vs. 53.6 ± 80.4 mg/dL on postoperative day 2, p = 0.162). No adverse effects were observed in the treatment groups during the postoperative 9-month follow-up. Our study suggests that polyglycolic acid mesh sheets can be safely applied to reduce postoperative drainage amount in thyroidectomy patients who need lymph node dissection.

Causal Relationship between Celiac Stenosis and Pancreaticoduodenal Artery Aneurysm: Interpretation by Simulation Using an Electric Circuit.

Pancreaticoduodenal artery (PDA) aneurysm and celiac artery (CA) stenosis are rare diseases in themselves. Interestingly, however, there are more cases documented in the literature in which these two disease entities occurred together than could be coincidental, and CA stenosis has been suggested as the provocative condition in developing PDA aneurysm. This study is aimed at examining the causal relationship between CA stenosis and PDA aneurysm by simulating the splanchnic circulation with an electric circuit. A patient with multiple PDA aneurysms and collaterals with CA stenosis was treated in our institution using hybrid techniques. The patient's pre- and postoperative status was simulated using an electric circuit, and the two possible scenarios were tested for compatibility: the stenosis-first scenario vs. the aneurysm-first scenario. The simulation was performed in two ways: using Simulink® software (MATLAB® Release 2018b) and actual circuit construction on a breadboard. The stenosis-first scenario showed that as the CA stenosis progresses, the blood flow through PDA increases, favoring the development of an aneurysm and/or collaterals if the artery was already compromised by a weakening condition. On the other hand, the aneurysm-first scenario also showed that if the aneurysm or collaterals developed first, the aneurysm will steal the blood flow through the CA, causing it to collapse if the artery was already compromised by increased wall tension. Contrary to the common belief, this study showed that in patients suffering from concurrent CA stenosis and PDA aneurysm, either condition could develop first and predispose the development of the other. The simulation of splanchnic blood flow with an electric circuit provides a useful tool for analyzing rare vascular diseases that are difficult to provoke in clinical and animal studies.

Changes in Pancreatic Endocrine Function and Morphology After Pancreaticoduodenectomy: A Comparison Between Pancreatic Head Cancer and Other Pathologies.

OBJECTIVES: It is unclear whether the improved glucose metabolism in pancreas head cancer (PHC) patients after pancreaticoduodenectomy is due to the anatomical change or the relief of pancreatic duct obstruction. METHODS: We divided 170 patients into the PHC group (n = 54, 31.8%) and other pathology (non-PHC) group (n = 116, 68.2%). Glucose metabolic function was evaluated using the glucose tolerance index (GTI), and the pancreatic duct obstruction and dilatation was measured using the pancreatic atrophic index (PAI). RESULTS: The preoperative GTI was significantly higher in the PHC group (mean [standard deviation {SD}], 0.84 [1.16]) than in the non-PHC group (0.41 [SD, 0.59], P = 0.000). The postoperative GTI decreased significantly in the PHC group but remained unchanged in the non-PHC group. Similarly, the preoperative PAI was higher in the PHC group (0.32 [SD, 0.19]) than in the non-PHC group (0.13 [SD, 0.09], P = 0.000). The postoperative PAI decreased significantly in the PHC group, but not in the non-PHC group. CONCLUSIONS: The impaired glucose metabolism in PHC can be caused by pancreatic duct obstruction. After pancreaticoduodenectomy, glucose metabolism is improved by the relief of pancreatic duct obstruction, and not by the anatomical change. The patients should be counseled accordingly.

A mixed polymeric micellar formulation of itraconazole: Characteristics, toxicity and pharmacokinetics.

A mixed polymeric micelle formulation of itraconazole (ITZ-PM) was prepared using monomethoxy poly(ethylene glycol)-b-poly(lactic acid) and poly(lactic acid) as drug carrier materials. The ITZ-PM formulation remarkably increased the itraconazole solubility up to 15 mg/mL in aqueous media and provided stable solutions at a wide range of concentrations and pH's. In toxicity studies of single and 28-day repeated administrations to rats and dogs, ITZ-PM was well tolerated at dose levels corresponding to clinical doses. The pharmacokinetic profiles of ITZ-PM for itraconazole and its major metabolite, hydroxy-itraconazole, were comparable to those of the cyclodextrin formulations (Sporanox(R) Injection and Oral Solution) in rats and dogs. These results suggest that ITZ-PM can be an advantageous formulation for both intravenous and oral routes.

Investigation of the release behavior of DEHP from infusion sets by paclitaxel-loaded polymeric micelles.

The current clinical formulation of paclitaxel (Taxol) contains 1:1 blend of Cremophor EL (polyethoxylated castor oil) and dehydrated ethanol. Cremophor EL and dehydrated ethanol are well known to leach di-(2-ethylhexyl) phthalate (DEHP) from polyvinyl chloride (PVC) infusion bags and PVC administration sets. DEHP is a possible hepatotoxin, carcinogen, teratogen and mutagen. Long-term exposure to DEHP may cause health risks. As an alternative formulation for paclitaxel, paclitaxel-loaded polymeric micelles (PLPM), made of monomethoxy poly(ethylene glycol)-block-poly(d,l-lactide) (mPEG-PDLLA) diblock copolymer, has demonstrated clear advantages over Taxol in pharmacokinetics and therapeutic index. Paclitaxel in either PLPM or Taxol formulations, diluted in 0.9% sodium chloride injection, was stable in the PVC infusion bags. The PLPM formulation significantly reduced the amount of DEHP extracted from PVC infusion bags and PVC administration sets. For PLPM diluted in 0.9% sodium chloride injection, the total amount of DEHP delivered over the simulated infusion period was 0.7 mg for 3h and 2.0 mg for 24 h, which was less than 2.9% of the DEHP extracted by Taxol. These results confirmed that there is negligible risk of DEHP exposure from diluted PLPM i.v. infusion using PVC infusion bags and PVC administration sets.

A high-throughput combinatorial approach for the discovery of a cremophor EL-free paclitaxel formulation.

PURPOSE: The purpose of this work was to replace Cremophor-EL in the commercial paclitaxel intravenous formulation, Taxol, using a novel high-throughput combinatorial formulation approach. METHODS: Full factorial combinations of 12 generally regarded as safe excipients at three different concentrations were screened using an automated liquid dispenser. The hit formulations were further optimized to give the final optimized formulation TPI-1. TPI-1 was then tested in rats to compare its pharmacokinetic profile to Taxol. RESULTS: Of the 9,880 combinations tested in the initial screen, 19 were identified as hit combinations. These were further optimized to give the final formulation TPI-1. When tested in rats, TPI-1 was well tolerated at both the low and high doses of 5 mg/kg and 10 mg/kg, whereas Taxol killed all the rats at the high dose. TPI-1 experienced slower elimination compared to Taxol. Similar to Taxol, TPI-1 also exhibited nonlinear pharmacokinetics. CONCLUSIONS: This study demonstrated the power of a high-throughput combinatorial approach for alternative paclitaxel formulations. We believe that this approach can be applied to drug formulation in general and it can improve the speed and efficiency of drug formulation design.