Cost analysis and outcomes of endoscopic, minimal access and open pancreatic necrosectomy.

OBJECTIVES: To assess both individual patient and institutional costs as well as outcomes in patients with pancreatic necrosis who underwent either endoscopic, minimal access or open pancreatic necrosectomy. These data can be used to evaluate clinical effectiveness with a view to informing local health care providers. SUMMARY BACKGROUND DATA: Intervention for infected pancreatic necrosis is associated with a high morbidity, mortality and long hospital stays. Minimal access surgical step-up approaches have been the gold standard of care, however endoscopic approaches are now offered preferentially. METHODS: All patients undergoing endoscopic (EN), minimal access retroperitoneal (MARPN) and open (OPN) necrosectomy at a single institution from April 2015-March 2017 were included. Patients were selected for intervention based on morphology and position of the necrosis and on clinical factors. Patient level costing systems were used to determine inpatient and outpatient costs. RESULTS: 86 patients were included: 38 underwent EN, 35 MARPN and 13 OPN. Pre-operative APACHEII was 6 vs 9 vs 9 (p=0.017) and CRP 107 vs 204 vs 278, (p=0.012), respectively. Post-operative stay was 19 days for EN vs. 41 for MARPN vs. 42 for OPN (p=0.007). Complications occurred in 68.4%, 68.6% and 46.2% (p=0.298) while mortality was 10.5%, 22.9% and 15.4% (p=0.379) respectively. Mean total cost was £31,364 for EN, £52,770 for MARPN (p=0.008) and £60,346 for OPN. Ward and critical care costs for EN were lower than for MARPN (ward: £9,430 vs. £14,033, p=0.024; critical care: £5,317 vs. £16,648, p=0.056).

Outcomes From Minimal Access Retroperitoneal and Open Pancreatic Necrosectomy in 394 Patients With Necrotizing Pancreatitis.

OBJECTIVE: To examine the outcomes from minimal access retroperitoneal pancreatic necrosectomy (MARPN) and open pancreatic necrosectomy (OPN) for severe necrotizing pancreatitis in a single center. BACKGROUND: The optimal management of severe pancreatic necrosis is evolving with a few large center single series. METHODS: Between 1997 and 2013, patients with necrotizing pancreatitis at the Liverpool Pancreas Center were reviewed. Outcome measures were retrospectively analyzed by intention to treat. RESULTS: There were 394 patients who had either MARPN (274, 69.5%) or OPN (120, 30.5%). Complications occurred in 174 MARPN patients (63.5%) and 98 (81.7%) OPN patients (P < 0.001). OPN was associated with increased postoperative multiorgan failure [42 (35%) vs 56 (20.4%), P = 0.001] and median (inter-quartile range) Acute Physiology and Chronic Health Evaluation II score 9 (6-11.5) vs 8 (5-11), P < 0.001] with intensive care required less frequently in MARPN patients [40.9% (112) vs 75% (90), P < 0.001]. The mortality rate was 42 (15.3%) in MARPNs and 28 (23.3%) in OPNs (P = 0.064). Both the mortality and the overall complication rates decreased between 1997-2008 and 2008-2013 [49 (23.8%) vs 21 (11.2%) P = 0.001, respectively; and 151 (73.3%) vs 121 (64.4%), P = 0.080, respectively). Increased mortality was independently associated with age (P < 0.001), preoperative intensive care stay (P = 0.014), and multiple organ failure (P < 0.001); operation before 2008 (P < 0.001) and conversion to OPN (P = 0.035). MARPN independently reduced mortality odds risk (odds ratio = 0.27; 95% confidence interval = 0.12-0.57; P < 0.001). CONCLUSIONS: Increasing experience and advances in perioperative care have led to improvement in outcomes. The role of MARPN in reducing complications and deaths within a multimodality approach remains substantial and should be used initially if feasible.

Incidence of post-ERCP pancreatitis from direct pancreatic juice collection in hereditary pancreatitis and familial pancreatic cancer before and after the introduction of prophylactic pancreatic stents and rectal diclofenac.

OBJECTIVES: Individuals from hereditary pancreatitis (HP) and familial pancreatic cancer (FPC) kindreds are at increased risk of developing pancreatic cancer. Premalignant molecular changes may be detected in pancreatic juice collected by endoscopic retrograde cholangiopancreatography (ERCP). The objective was to determine the risk of post-ERCP pancreatitis (PEP). METHODS: A prospective study (1999-2013) was undertaken of 80 ERCPs (24 in HP and 56 in FPC) from 60 individuals and the impact of PEP prophylaxis using a self-expelling pancreatic stent and 50 mg diclofenac per rectum from 2008. RESULTS: There was no PEP in the HP cohort and 13 (23.2%) PEP from 56 procedures in the FPC cohort (P = 0.0077). Up to 2008 PEP had occurred in 7 (43.8%) of 16 procedures in FPC individuals versus none of 18 procedures in HP individuals (P = 0.0021). After the introduction of prophylaxis, the incidence of PEP fell to 6 (15.0%) of 40 procedures in FPC individuals (P = 0.0347).The odds ratio (95% confidence interval) was 0.23 (0.06-0.84) in favor of prophylaxis (0.035). CONCLUSIONS: Individuals with HP are at minimal risk for PEP. Although the risk of PEP in individuals with FPC can be reduced by using prophylactic self-expelling stents and diclofenac, it remains too high for routine screening.

Endoscopic ultrasound-guided choledoco-duodenostomy as an alternative to percutaneous trans-hepatic cholangiography.

BACKGROUND: Endoscopic ultrasonography (EUS)-guided choledochoduodenostomy (CDS) is an alternative to percutaneous transhepatic cholangiography (PTC) drainage in patients with an obstructed biliary system where conventional endoscopic retrograde biliary drainage (ERBD) has been unsuccessful. METHODS: Five EUS-CDS procedures were reviewed to assess whether successful decompression was achieved and maintained. RESULTS: There was technical success in each instance with no immediate complications. There was a significant fall in the median bilirubin of 164 mmol/l. The median follow-up was 44 days. In one patient the stent migrated with no adverse outcome. CONCLUSION: EUS-CDS is a viable alternative to PTC with fewer complications and comparable success rates. EUS-CDS may offer a future route for novel therapeutic advances.

Preparation, characterization, and scale-up of ketoconazole with enhanced dissolution and bioavailability.

Many new molecular entities targeted for pharmaceutical applications face serious development challenges because of poor water solubility. Although particle engineering technologies such as controlled precipitation have been shown to enhance aqueous dissolution and bioavailability of poorly water soluble active pharmaceutical ingredients, the data available are the results of laboratory-scale experiments. These technologies must be evaluated at larger scale to ensure that the property enhancement is scalable and that the modified drugs can be processed on conventional equipment. In experiments using ketoconazole as the model drug, the controlled precipitation process was shown to produce kg-scale modified drug powder with enhanced dissolution comparable to that of lab-scale powder. Ketoconazole was demonstrated to be stable throughout the controlled precipitation process, with a residual methanol level below the ICH limit. The modified crystalline powder can be formulated, and then compressed using conventional high-speed tableting equipment, and the resulting tablets showed bioavailability more than double that of commercial tablets. When appropriately protected from moisture, both the modified powder and tablets prepared from the modified powder showed no change in dissolution performance for at least 6 months following storage at accelerated conditions and for at least 18 months following storage at room temperature.

In vivo force during arterial interventional radiology needle puncture procedures.

To adequately simulate the forces generated during interventional radiological (IR) procedures, non intrusive in-vivo methods must be used. Using finger tip mounted, non intrusive capacitance force sensor pads (PPS, Los Angeles, California) we have been able to measure the forces involved in interventional radiology without a change in procedure technique. Data acquired during the process of calibration of the capacitance pads in conjunction with extensive in-vitro needle puncture force measurement using a commercially available tensile tester (Nene Industries, UK) are presented here.

Development and characterization of a scalable controlled precipitation process to enhance the dissolution of poorly water-soluble drugs.

PURPOSE: Poorly water-soluble compounds are being found with increasing frequency among pharmacologically active new chemical entities, which is a major concern to the pharmaceutical industry. Some particle engineering technologies have been shown to enhance the dissolution of many promising new compounds that perform poorly in formulation and clinical studies (Rogers et. al., Drug Dev Ind Pharm 27:1003-1015). One novel technology, controlled precipitation, shows significant potential for enhancing the dissolution of poorly soluble compounds. In this study, controlled precipitation is introduced; and process variables, such as mixing zone temperature, are investigated. Finally, scale-up of controlled precipitation from milligram or gram to kilogram quantities is demonstrated. METHODS: Dissolution enhancement capabilities were established using two poorly water-soluble model drugs, danazol and naproxen. Stabilized drug particles from controlled precipitation were compared to milled, physical blend, and bulk drug controls using particle size analysis (Coulter), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), dissolution testing (USP Apparatus 2), and residual solvent analysis. RESULTS: Stabilized nano- and microparticles were produced from controlled precipitation. XRD and SEM analyses confirmed that the drug particles were crystalline. Furthermore, the stabilized particles from controlled precipitation exhibited significantly enhanced dissolution properties. Residual solvent levels were below FDA limits. CONCLUSIONS: Controlled precipitation is a viable and scalable technology that can be used to enhance the dissolution of poorly water-soluble pharmaceutical compounds.