Randomized clinical trial on enhanced recovery versus standard care following open liver resection.

BACKGROUND: Enhanced recovery programmes (ERPs) have been shown to reduce length of hospital stay (LOS) and complications in colorectal surgery. Whether ERPs have the same benefits in open liver resection surgery is unclear, and randomized clinical trials are lacking. METHODS: Consecutive patients scheduled for open liver resection were randomized to an ERP group or standard care. Primary endpoints were time until medically fit for discharge (MFD) and LOS. Secondary endpoints were postoperative morbidity, pain scores, readmission rate, mortality, quality of life (QoL) and patient satisfaction. ERP elements included greater preoperative education, preoperative oral carbohydrate loading, postoperative goal-directed fluid therapy, early mobilization and physiotherapy. Both groups received standardized anaesthesia with epidural analgesia. RESULTS: The analysis included 46 patients in the ERP group and 45 in the standard care group. Median MFD time was reduced in the ERP group (3 days versus 6 days with standard care; P < 0·001), as was LOS (4 days versus 7 days; P < 0·001). The ERP significantly reduced the rate of medical complications (7 versus 27 per cent; P = 0·020), but not surgical complications (15 versus 11 per cent; P = 0·612), readmissions (4 versus 0 per cent; P = 0·153) or mortality (both 2 per cent; P = 0·987). QoL over 28 days was significantly better in the ERP group (P = 0·002). There was no difference in patient satisfaction. CONCLUSION: ERPs for open liver resection surgery are safe and effective. Patients treated in the ERP recovered faster, were discharged sooner, and had fewer medical-related complications and improved QoL. REGISTRATION NUMBER: ISRCTN03274575 (http://www.controlled-trials.com).

Physical characterization of polyethylene glycols by thermal analytical technique and the effect of humidity and molecular weight.

Polyethylene glycols (PEGs) are well known as excipients in tablet dosage formulations. PEGs are generally known to be inert and have very few interactions with other components in the solid dosage forms. However, the physical nature of PEGs and how they affect the disintegration of tablets is not very well understood for the different molecular weights of PEGs. The knowledge of the effect of molecular weight of PEGs on their physical properties and the effect of humidity on the physical properties of PEGs are important parameters for the choice of a PEG to be acceptable as an excipient in pharmaceutical formulations. This study was done to determine the precision of the DSC physical properties for a wide range of PEGs with varying molecular weights from 194 to 23000 daltons. Nine different molecular weights of PEGs were examined in a DSC controlled Heat-Cool-Heat-Cool-Heat (HCHCH) cycle and the observed reproducible values of melting temperature, heat of fusion, crystallization temperature and the heat of crystallization were compared with values obtained from the literature and the observed percent crystallinity was again cross-checked by X-ray Diffraction (XRD) studies. The comparison values indicated acceptable precision. This study was also done to check the effect of humidity on the DSC physical properties for the entire range of PEGs. The results indicated that humidity probably has a higher effect on the physical properties of the low molecular weight PEGs as compared to the high molecular weight PEGs.

Evaluation of the drug-polymer interaction in calcium alginate beads containing diflunisal.

Calcium alginate gel beads have been developed in recent years as a unique vehicle for oral drug delivery due to their excellent biocompatibility, biodegradability, simple method of preparation, abundant sources, low cost and minimal processing requirements. The objective of this study was to evaluate the drug-polymer interaction in calcium alginate beads containing diflunisal. Diflunisal loaded calcium alginate beads were successfully prepared by ionotropic gelation from solution of sodium alginate and diflunisal into calcium chloride solution. The weight ratio of drug to polymer was selected as 1:1. The calcium alginate beads were characterized by size, Scanning Electron Microscopy (SEM), weight uniformity and drug entrapment efficiency. The existence of a possible interaction between diflunisal and the calcium alginate was investigated by Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD) and Fourier Transform Infra-Red (FTIR) analysis. Drug loaded beads were spherical to oval in shape with low drug entrapment efficiency. The drug was found to be present inside the beads as crystalline to semicrystalline form with no significant physical or chemical interaction between drug and excipients. The results implied that calcium alginate beads can be used as a suitable controlled release carrier for diflunisal.

Centralisation for resection of the pancreatic head: A comparison of operative factors and early outcomes during the evolving unit and tertiary unit phases at a UK institution.

AIMS: To assess impact of centralisation on patients undergoing pancreatic head resections at a tertiary hepatobiliary (HPB) centre in the UK. METHODS: Data were analysed from a prospectively maintained database from 1998 to 2014 on all patients undergoing pancreatic head resections. Two specific time periods were defined; these were the evolving unit phase (EU) from 1998 to 2009 and finally the established tertiary unit phase (TU) from 2010 to 2014. Peri-operative factors and post-operative outcomes were analysed. RESULTS: 395 resections were undertaken during the study period. Following establishment of our tertiary HPB unit, the volume of resections undertaken increased greater than three-fold with an associated increase in case-complexity (p = 0.004). Operating time was found to increase in the TU phase compared with EU phase (p=>0.0005) whilst there was no significant difference in the rate of peri-operative transfusion, or in post-operative morbidity rates. There was a significant reduction in the post-operative length of stay in the TU phase (p = 0.003) with a significantly higher proportion of patients being discharged within 9 days of their procedure (p=<0.0005). There was also a significant reduction in 30-day post-operative mortality in the TU phase (0.5%) compared with the EU phase (3%) (p = 0.029). CONCLUSIONS: Data from our series of 395 cases suggests that centralisation of pancreatic cancer services to a tertiary centre does result in improved patient outcomes. The benefits of a multi-disciplinary and specialist HPB service results in a high volume, high quality unit with improved patient outcomes.

Characterization of polymeric dispersions of dimenhydrinate in ethyl cellulose for controlled release.

Granulations of dimenhydrinate (DMH) were prepared using various concentrations of ethyl cellulose (EC) by the solid dispersion technique. Characterization was done using thermal analysis, powder X-ray diffraction, infrared spectroscopy, optical microscopy and dissolution studies. Humidity studies were performed to investigate the effect of moisture on the drug and solid dispersions. It was seen that the crystalline drug was converted into its amorphous form in all the granulations. There was no chemical interaction between the DMH and EC. The thermal decomposition of drug in the granules was not affected. Dissolution studies revealed that the drug release from the granulations was significantly reduced as compared to the pure drug. As the amount of ethyl cellulose increased, the drug release rate decreased and the drug release kinetics showed a better fit to zero-order kinetics. Humidity studies showed that the drug and granulations remained stable in conditions not exceeding 70%RH. At high humidity of 100%RH, there was formation of the hydrate crystal forms of the drug in the pure drug samples and granules with 1:1 DMH-EC content whereas the granules with higher polymer content did not show any significant changes indicating better drug stability in the granules.

Decolorization kinetics of Procion H-exl dyes from textile dyeing using Fenton-like reactions.

The decolorization kinetics of three commercially used Procion H-exl dyes was studied using a Fenton-like reagent. The effect of the major system parameters (pH, concentration of H(2)O(2) and Fe(3+) and initial dye concentration) on the kinetics was determined. For comparison, the effect of the use of UV irradiated Fenton-like reagent and of Fenton reagent on the kinetics was also examined. In addition, mineralization rates and the biodegradability improvement as well as the effect of the addition of Cl(-), CO(3)(2-) or HCO(3)(-) on the decolorization rates was studied. The reactions were carried out in a 300 ml stirred cylindrical reactor with the capability of UV irradiation. The dye half-life time goes through a minimum with respect to the solution pH between 3 and 4. It also exhibits a broad minimum with respect to Fe(3+) and H(2)O(2) at molar ratios of H(2)O(2)/Fe(3+) from about 100 to 10. The addition of CO(3)(2-) and HCO(3)(-) substantially reduces the decolorization rates, while this effect is significantly less pronounced with Cl(-). At an optimum range of parameters, the mineralization rate (TOC reduction) is very slow for the Fenton-like process (TOC decrease from an initial 49.5 to 41.1 mg/l after 30 min and to only 35.2 mg/l after 600 min), but it increases significantly for the photo-Fenton-like process (to TOC values of 39.7 and 11.4 mg/l, respectively). The biodegradability, as expressed by the BOD/COD ratio, increases significantly from an initial value of 0.11-0.55 for the Fenton-like and to 0.72 for the photo-Fenton-like processes.

Crystal forms of tolbutamide from acetonitrile and 1-octanol: effect of solvent, humidity and compression pressure.

The possibility of obtaining tolbutamide polymorphs was investigated using the solvents acetonitrile and 1-octanol. Tolbutamide is an oral hypoglycemic agent that exists in four polymorphic forms. Characterization of the various polymorphs was carried out by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), infrared spectroscopy (FTIR), optical microscopy and dissolution studies. Form A, crystallized from acetonitrile, resembled the form I polymorph, while form O, crystallized from 1-octanol, resembled the form III polymorph. Tablets of both form A and form O were produced at compression pressures of 2500 lbs and 5000 lbs using cornstarch and talc and were exposed to 40%, 75% and 95% RH conditions. DSC and PXRD studies did not show any significant drug-excipient interaction. Moreover, the change in the crystalline state of either form upon exposure to humidity was not evident. Dissolution studies showed a significantly lower drug release rate from form O tablets compressed at 5000 lbs pressure and exposed to 95% RH. Pressure and humidity had no significant effect on the dissolution profiles on the form A tablets. It was concluded that form A was the robust choice for further formulation development.

Blood donors--Serious adverse reactions (SAR) 2010-2014 EFS Châteauroux, France.

BACKGROUND: In 2013, the national French incidence of serious adverse reactions (SAR) was 155.7 per 100,000 donations and 82% of SAR were grade 2 (French classification of SAR related to blood donors) AIMS: The purpose of our study was to describe the profile of blood donator candidate which had a SAR in our center. METHODS: The study contains all the SAR superior to grade 1 occurred on the site EFS Châteauroux (site and mobile blood collection) from January 2010 to October 31, 2014. We analyzed 37 parameters from the e-fit files (e-site French blood vigilance) and In-log software. RESULTS: We identified 82 SAR for 72,553 blood donations (incidence: 113.02 SAR per 100,000 donations). Forty-one men and 41 women, middle age 39 years (18-66). Average height: 1.68 m (1.49-1.85); average weight: 68 kg (50-98); body mass index (kg/m(2)): 24,13(18.6-31.9). All donors were Caucasian and 30% unemployed. We found 74 vasovagal syncope (VVS), 5 hematomas, 2 arterial injuries and an adverse reaction to citrate. In 90%, the SAR was immediate and of grade 2 in 85% of cases. Thirty-seven percent of SAR were first donation in connection with whole blood in 87% of cases. Regarding the seniority of donors, the number of average donations (whole blood, plasma, platelets) was 16.5. An SAR determined the stop of blood donation in 65% of cases with nearly 80% stoppage if it was a first donation. Seventy-three percent of SAR as a VVS took place during blood collection or within 5 minutes following the end of the donation. Sixty-one percent were men. Forty-four percent of cases were a first donation and 83% occurred in mobile blood collection. Average age was 36 years. The result was a permanent stop of all type of donations in 76% of cases. Twenty-seven percent of SAR as a VVS took place beyond 5 minutes after the end of the donation. Seventy-five percent were women. Thirty percent of cases were a first donation and 95% of SAR occurred in mobile blood collection. Average age was 42 years. The result was a permanent stop of all type of donations in 40% of cases. CONCLUSIONS: When the SAR as a VVS occurs during or within 5 minutes following the end of the donation, it leads to a permanent stop of any type of donation in 76% of cases.

Acute afferent loop syndrome in the early postoperative period following pancreaticoduodenectomy.

INTRODUCTION: Afferent loop syndrome (ALS) is a recognised complication of foregut surgery caused by mechanical obstruction at the gastrojejunostomy anastomosis itself or at a point nearby. Acute ALS has only been reported following pancreaticoduodenectomy (PD) after several years due to recurrence of malignancy at the anastomotic site. We report five cases of acute ALS in the first postoperative week. METHODS: The presentation, clinical findings and successful management of the 5 patients with ALS were obtained from a prospectively collected database of 300 PDs. All five patients with early acute ALS presented with signs and symptoms of a bile leak. Since the fifth patient, the surgical technique has been modified with the creation of a larger window in the transverse mesocolon and a Braun enteroenterostomy. RESULTS: There have been no further incidents of ALS since the adoption of these modifications to the standard technique of PD and there has also been a reduction in postoperative bile leaks (6.4% vs 3.6%, p=0.416). CONCLUSIONS: Acute ALS is a rare but important complication in the immediate postoperative period following PD and causes disruption to adjacent anastomoses, resulting in a bile leak. A prophylactic Braun anastomosis and wide mesocolic window may prevent this complication and subsequent deterioration.

The two-port laparoscopic retroperitoneal approach for minimal access pancreatic necrosectomy.

INTRODUCTION: Despite advances in surgery and critical care, severe pancreatitis continues to be associated with a high rate of mortality, which is increased significantly in the presence of infected pancreatic necrosis. Controversy persists around the optimal treatment for such cases, with specialist units variously advocating open necrosectomy, simple percutaneous drainage or one of several minimal access approaches. We describe our technique and outcomes with a two-port laparoscopic retroperitoneal necrosectomy (2P-LRN). METHODS: Thirteen consecutive patients with proven infected pancreatic necrosis were treated by 2P-LRN over a three-year period in the setting of a specialist hepatopancreatobiliary unit. The median patient age was 46 years (range: 28-87 years) and 10 of the patients were male. RESULTS: The median number of procedures required to clear the necrosis was 2 (range: 1-5), with a median time to discharge following the procedure of 44 days (range: 10-135 days). There was no 90-day mortality and the morbidity rate was 38%, consisting of pancreatic fistula (31%) and bleeding (23%). CONCLUSIONS: Two-port laparoscopic retroperitoneal necrosectomy has been demonstrated to confer similar or better outcomes to other techniques for necrosectomy. It carries the additional advantages of better visualisation, leading to fewer procedures and the opportunity to deploy simple laparoscopic instruments such as diathermy or haemostatic clips.

The effect of human organ preservation and albumin flush solution on in vitro cell metabolic activity.

In liver transplantation, the organ during the recipient's operation is traditionally flushed with 4.5% of human albumin solution to wash away the potassium-rich University of Wisconsin (UW) solution. It has been argued whether albumin could be useful at this stage. We used a new simple non-toxic assay to determine cell viability in vitro. Alamar Blue incorporates a redox indicator which changes colour from blue (oxidised form) to magenta (reduced form) in response to metabolic activity. Cultured human hepatocyte and HUVEC cell lines were exposed for 3, 6, 12 or 24 hours to plain medium, UW solution, human albumin 4.5% solution, UW-containing effluents before and after preservation as well as albumin flushes from different transplantation cases. After addition of Alamar Blue the optical density was measured at 570 nm and the background measured at 600 nm was subtracted. The studies showed a significantly lower metabolic rate of the cells exposed to albumin and albumin-containing flushes at all time periods, even after a short exposure such as 3 hours (p < 0.001). On the other hand, there was no significant difference of growth and metabolic activity rate between cells exposed to UW solution, different UW-containing flushes and medium for up to 12 hours. In conclusion, human albumin is a very poor solution for cell maintenance. In contrast, UW solution has comparable results with the full growth medium for up to 12 hours of exposure.

Formulation development and stabililty testing of extemporaneous suspension prepared from dapsone tablets.

The qualification and quantification of dapsone in suspension were developed and shown to be stability indicating by means of a reverse-phase high-performance liquid chromatographic method. The real solubility of dapsone in water was calculated to be 0.208mg/mL at 25 deg C. The enthalpy of solution and the entropy of solution were calculated to be -175.6 J/g and -43605.7 J/K/M, respectively. An extemporaneous suspension was formulated from commercially available dapsone rablets, and the chemical stability of dapsone in the suspension was determined by means of accelerated stability testing. The 91-day analytical stabilty testing study was conducted at 4, 30, 50, 60, and 70 deg C. The energy of activation for the suspension was determined to be -23288.35 J/K/M. The zero-order rate of degradation for dapsone (k0,25) in suspension at 25 deg C was found to be 0.040845 day -1. The first-order rate of degradation for dapsone in solution was found to be 0.196370 (mg/mL)(day-1). The shelf life for the suspension was calulated to be 31.67 days at 25 deg C and 230.76 days under refrigeration at 4 deg C.