Long-term nationwide assessment of polychlorinated dibenzo-p-dioxins/dibenzofurans and dioxin-like polychlorinated biphenyls ambient air concentrations for ten years in South Korea.

In this study, seasonal/regional variations of Polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/DFs) and dioxin like-polychlorinated biphenyls in the ambient air were monitored for ten years (2008-2017) using a high volume air sampler. As a result of strict regulation enforced by Korea Ministry of Environment in 2008, PCDD/DFs concentrations in the ambient air decreased from 0.051 pg I-TEQ Sm-3 in 2009 to 0.014 pg I-TEQ Sm-3 in 2017 which was comparably associated with cut-down of their emission sources from 880.2 g I-TEQ Sm-3 in 2001 to 24.2 g I-TEQ Sm-3 in 2015; revealing that it was only 2.7% against that of 2001. In 2017, mean TEQ concentration level of PCDD/DFs in the air of South Korea was quite low in comparison to its ambient environmental standards of 0.6 pg I-TEQ Sm-3 for PCDD/DFs. Particularly, the sum of PCDD/DFs in the background revealed the lowest level, however, the fraction of octachlorodibenzodioxin among other isomers exposed at the highest level in this study, suggesting that the ambient air quality in the background being studied was severely and persistently impaired by inflowing unknown sources of any possible anthropogenic transboundary migratory air pollutants. Moreover, this study conducted the scientific analysis of the long-term variations in the ambient air and emission sources using principal component analysis. From this of 10 years long-term nationwide assessments for the PCDD/DFs and dl-PCBs in the ambient air, it is possible to prove that South Korean environmental policy to manage POPs has been successfully conducted for the last ten years.

Predictors of Response and Survival in Locally Advanced Adenocarcinoma of the Pancreas Following Neoadjuvant GTX with or Without Radiation Therapy.

LESSONS LEARNED: There is no presenting parameter that predicts the success of neoadjuvant therapy for pancreatic cancer.Despite the images on scans following neoadjuvant therapy, all patients should be evaluated, because inflammation following radiation therapy (RT) may overstate the extent of tumor and vascular involvement. BACKGROUND: In patients presenting with locally advanced pancreatic adenocarcinoma deemed unresectable by two pancreatic cancer surgeons, we analyzed presenting tumor size, extent of vascular involvement, tumor markers, response to neoadjuvant gemcitabine (G), docetaxel (T), and capecitabine (X) with or without additional chemoradiotherapy with GX on R0 resection rates (≥2 mm margins), and survival. METHODS: All patients had baseline magnetic resonance imaging (MRI) and/or computed tomography (CT) scans and endoscopic ultrasound. A baseline positron emission tomography-computed tomography (PET-CT) was performed in 39 patients. The scans were reviewed by two radiologists.GTX (gemcitabine 750 mg/m2 and docetaxel 30 mg/m2 on days 4 and 11 with capecitabine 1,500 mg/m2 days 1-14) was administered on a 3-week schedule for 6 cycles to patients with both arterial and venous-only involvement. Patients in the arterial arm received GX/RT before surgery, and those in the venous arm received GX/RT after R1 resection. Standard-dose RT was delivered by intensity-modulated radiation therapy (IMRT) or conformal fields to 5040 cGy along with capecitabine for 5 days and gemcitabine on day 5 of weeks 1, 2, 4, and 5 of RT, starting with the first full week of RT.A cancer antigen test 19-9 (CA 19-9) was obtained at baseline and days 4 and 11 of each cycle. The rate of change in CA 19-9 was calculated using the formula: (Log10 CA 19-9 time 0) - (Log10 CA 19-9 at 9 weeks)/9 weeks. This was derived based on the observation that the fall in CA 19-9 following effective chemotherapy is a second-order function. RESULTS: Of the 34 patients with arterial involvement and 11 with extensive venous involvement who met the eligibility criteria and began GTX, only 5 patients in the arterial arm did not undergo subsequent resection. The remaining 40 patients were included in this analysis of presenting parameters with respect to R0 resection, disease-free survival (DFS), and overall survival (OS). R0 resection was achieved in 28 of 40 patients (70%), and R1 resection in the remaining 12 (30%). The OS after R0 resection was a median 37 months (95% confidence interval [CI]: 29.3-44.7) compared with 29 months (95% CI: 28.5-41.5) for those with R1 resection.Excluding four postoperative deaths, median DFS for the 25 (71%) with R0 resection was 31 months (95% CI: 11.3-51.1), and the median DFS for R1 resection was only 14 months (95% CI: 11.1-17). Eleven of the twenty-eight (39%) patients achieving R0 resection have not relapsed (median = 45 months, range = 25-71 months). CONCLUSION: R0 resection, the goal of neoadjuvant treatment, can be achieved in 70% of patients presenting with locally advanced pancreatic cancer. The median DFS was 31 months (95% CI: 11. 3-51.1). No relationship was found with tumor size, degree of vascular involvement, carcinoembryonic antigen test (CEA), CA 19-9, degree of tumor regression on scan, fall in CA 19-9, or SUV on PET scan and subsequent survival.

The effect of dexmedetomidine pretreatment on the median effective bolus dose of propofol for facilitating laryngeal mask airway insertion.

BACKGROUND: We designed this study to investigate the effect of dexmedetomidine (1 µg/kg) pretreatment on the median effective dose (ED50) of propofol for facilitating successful laryngeal mask airway (LMA) insertion compared to propofol alone. METHODS: Forty patients were randomized to either the control group (n = 21) or the dexmedetomidine group (n = 19). After infusion of normal saline or dexmedetomidine 1 µg/kg over 10 min, 1 % lidocaine 0.5 mg/kg, followed by propofol 2.5 mg/kg was administered and the laryngeal mask airway was inserted without muscle relaxants. The ED50 of propofol for successful LMA insertion was determined by the modified Dixon's up-and-down method. The ED50 and ED95 were also calculated using an isotonic regression method, based on the pooled adjacent-violators algorithm-adjusted response rate, and the confidential interval (CI) was estimated using a bootstrap approach. RESULTS: The ED50 of propofol for smooth insertion of the LMA was significantly higher in the control group than in the dexmedetomidine group (3.1 ± 0.4 vs 1.9 ± 0.3 mg/kg, P < 0.001). From isotonic regression analysis using a bootstrap approach, the ED50 and ED95 of propofol was 2.9 mg/kg (83 % CI 2.5-3.3 mg/kg) and 3.9 mg/kg (95 % CI 3.5-4.0 mg/kg) in the control group, and 1.8 mg/kg (83 % CI 1.8-2.1 mg/kg) and 2.4 mg/kg (95 % CI 2.0-2.5 mg/kg) in the dexmedetomidine groups, respectively. The apnea time was not significantly different between the two groups. CONCLUSIONS: Pretreatment with dexmedetomidine 1 µg/kg could reduce the propofol requirement by 38 % for facilitating LMA insertion without prolonged respiratory depression and hemodynamic instability.

Pain related to robotic cholecystectomy with lower abdominal ports: effect of the bilateral ultrasound-guided split injection technique of rectus sheath block in female patients: A prospective randomised trial.

BACKGROUND: Robotic cholecystectomy (RC) using port sites in the lower abdominal area (T12-L1) rather than the upper abdomen has recently been introduced as an alternative procedure for laparoscopic cholecystectomy. Therefore, we investigated the time course of different components of pain and the analgesic effect of the bilateral ultrasound-guided split injection technique for rectus sheath block (sRSB) after RC in female patients. METHODS: We randomly assigned 40 patients to undergo ultrasound-guided sRSB (RSB group, n = 20) or to not undergo any block (control group, n = 20). Pain was subdivided into 3 components: superficial wound pain, deep abdominal pain, and referred shoulder pain, which were evaluated with a numeric rating scale (from 0 to 10) at baseline (time of awakening) and at 1, 6, 9, and 24 hours postoperatively. Consumption of fentanyl and general satisfaction were also evaluated 1 hour (before discharge from the postanesthesia care unit) and 24 hours postoperatively (end of study). RESULTS: Superficial wound pain was predominant only at awakening, and after postoperative 1 hour in the control group. Bilateral ultrasound-guided sRSB significantly decreased superficial pain after RC (P < 0.01) and resulted in a better satisfaction score (P < 0.05) 1 hour after RC in the RSB group compared with the control group. The cumulative postoperative consumption of fentanyl at 6, 9, and 24 hours was not significantly different between groups. CONCLUSIONS: After RC with lower abdominal ports, superficial wound pain predominates over deep intra-abdominal pain and shoulder pain only at the time of awakening. Afterwards, superficial and deep pain decreased to insignificant levels in 6 hours. Bilateral ultrasound-guided sRSB was effective only during the first hour. This limited benefit should be balanced against the time and risks entailed in performing RSB.

Neoadjuvant gemcitabine, docetaxel, and capecitabine followed by gemcitabine and capecitabine/radiation therapy and surgery in locally advanced, unresectable pancreatic adenocarcinoma.

BACKGROUND: This prospective study was undertaken to assess toxicity, resectability, and survival in pancreatic adenocarcinoma patients presenting with locally advanced, unresectable disease treated with neoadjuvant gemcitabine, docetaxel, and capecitabine (GTX) and gemcitabine and capecitabine (GX)/radiation therapy (RT). METHODS: All patients presenting to the Pancreas Center were evaluated for eligibility. Forty-five patients (mean age, 64 years; range, 44-83 years)-34 patients deemed unresectable because of arterial involvement and 11 patients deemed unresectable because of extensive venous involvement-were treated with 6 cycles of GTX. Those with arterial involvement were treated with GX/RT after chemotherapy. RESULTS: The GTX and GX/RT treatments were tolerated with the expected drug-related toxicities. There were no bowel perforations, cases of pancreatitis, or delayed strictures. Among those with arterial involvement, 29 underwent subsequent resection, with 20 (69%) achieving R0 resections. All 11 patients with venous-only involvement underwent resection, with 8 achieving R0 resections and 3 achieving complete pathologic responses. For the arterial arm, the 1-year survival rate was 71% (24 of 34 patients), and the median survival was 29 months (95% confidence interval, 21-38 months). Thirteen patients (38%) have not relapsed (range, 5-49+ months). For the venous arm, the median survival has not been reached at more than 42 months. Six patients (55%) in the venous arm did not experience recurrence (range, 6.2-42+ months). CONCLUSIONS: GTX plus GX/RT is an effective neoadjuvant regimen that can be safely administered to patients up to at least the age of 83 years. It is associated with a high response rate, a high rate of R0 resections, and prolonged overall survival.

Effect of particle size on the dissolution behaviors of poorly water-soluble drugs.

This study examined the effects of the particle size of various poorly water-soluble drugs on their dissolution behavior through physicochemical and mathematical analysis. As model drugs, hydrochlorothiazide, aceclofenac, ibuprofen and a discovery candidate were selected. The materials were crystallized using an evaporation method and milled without transformation behavior of crystal forms. The particles were sieved and divided into four size groups (< 45 µm, 45∼150 µm, 150∼250 µm, and 250∼600 µm). The specific surface area with regard to the particle size was measured using a BET surface area measurement. The specific surface area increased with decreasing particle size of the drug, resulting in an increase in dissolution rate. During the initial period of the dissolution study, significant differences in dissolution rate were observed according to the particle size and specific surface areas. On the other hand, in the later stages, the surface-specific dissolution rate was almost consistent regardless of the particle size. These observations were evaluated mathematically and the results suggested that the dissolution rate of poorly soluble drugs is strongly related to the particle size distribution. Moreover, physicochemical analysis helped explain the effect of particle size on the dissolution profiles.

Time-oriented experimental design method to optimize hydrophilic matrix formulations with gelation kinetics and drug release profiles.

A new experimental design methodology was developed by integrating the response surface methodology and the time series modeling. The major purposes were to identify significant factors in determining swelling and release rate from matrix tablets and their relative factor levels for optimizing the experimental responses. Properties of tablet swelling and drug release were assessed with ten factors and two default factors, a hydrophilic model drug (terazosin) and magnesium stearate, and compared with target values. The selected input control factors were arranged in a mixture simplex lattice design with 21 experimental runs. The obtained optimal settings for gelation were PEO, LH-11, Syloid, and Pharmacoat with weight ratios of 215.33 (88.50%), 5.68 (2.33%), 19.27 (7.92%), and 3.04 (1.25%), respectively. The optimal settings for drug release were PEO and citric acid with weight ratios of 191.99 (78.91%) and 51.32 (21.09%), respectively. Based on the results of matrix swelling and drug release, the optimal solutions, target values, and validation experiment results over time were similar and showed consistent patterns with very small biases. The experimental design methodology could be a very promising experimental design method to obtain maximum information with limited time and resources. It could also be very useful in formulation studies by providing a systematic and reliable screening method to characterize significant factors in the sustained release matrix tablet.