Surgery (Austin & Northern Health) - Research Publications
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ItemThe impact of fluid intervention on complications and length of hospital stay after pancreaticoduodenectomy (Whipple's procedure)(BIOMED CENTRAL LTD, 2014-05-14)BACKGROUND: There is limited information on the impact on perioperative fluid intervention on complications and length of hospital stay following pancreaticoduodenectomy. Therefore, we conducted a detailed analysis of fluid intervention in patients undergoing pancreaticoduodenectomy at a university teaching hospital to test the hypothesis that a restrictive intravenous fluid regime and/or a neutral or negative cumulative fluid balance, would impact on perioperative complications and length of hospital stay. METHODS: We retrospectively obtained demographic, operative details, detailed fluid prescription, complications and outcomes data for 150 consecutive patients undergoing pancreaticoduodenectomy in a university teaching hospital. Prognostic predictors for length of hospital stay and complications were determined. RESULTS: One hundred and fifty consecutive patients undergoing pancreaticoduodenectomy were evaluated between 2006 and 2012. The majority of patients were, middle-aged, overweight and ASA class III. Postoperative complications were frequent and occurred in 86 patients (57%). The majority of complications were graded as Clavien-Dindo Class 2 and 3. Postoperative pancreatic fistula occurred in 13 patients (9%), and delayed gastric emptying occurred in 25 patients (17%). Other postoperative surgical complications included sepsis (22%), bile leak (4%), and postoperative bleeding (2%). Serious medical complications included pulmonary edema (6%), myocardial infarction (8%), cardiac arrhythmias (13%), respiratory failure (8%), and renal failure (7%). Patients with complications received a higher median volume of intravenous therapy and had higher cumulative positive fluid balances. Postoperative length of stay was significantly longer in patients with complications (median 25 days vs. 10 days; p < 0.001). After adjustment for covariates, a fluid balance of less than 1 litre on postoperative day 1 and surgeon caseloads were associated with the development of complications. CONCLUSIONS: In the context of pancreaticoduodenectomy, restrictive perioperative fluid intervention and negative cumulative fluid balance were associated with fewer complications and shorter length of hospital stay. These findings provide good opportunities to evaluate strategies aimed at improving perioperative care.
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ItemPressurized Pulse Irrigation with Saline Reduces Surgical-site Infections following Major Hepatobiliary and Pancreatic Surgery: Randomized Controlled Trial(SPRINGER, 2014-02)BACKGROUND: Surgical site infections (SSI) are a significant cause of postoperative morbidity. Pressurized pulse irrigation of subcutaneous tissues may lower infection rates by aiding in the debridement of necrotic tissue and reducing bacterial counts compared to simply pouring saline into the wound. METHODS: A total of 128 patients undergoing laparotomy extending beyond 2 h were randomized to treatment of wounds by pressurized pulse lavage irrigation (<15 psi) with 2 L normal saline (pulse irrigation group), or to standard irrigation with 2 L normal saline poured into the wound, immediately prior to skin closure (standard group). Only elective cases were included, and all cases were performed within a specialized hepatobiliary and pancreatic surgery unit. RESULTS: There were 62 patients managed by standard irrigation and 68 were managed by pulse irrigation. The groups were comparable in most aspects. Overall there were 16 (13 %) SSI. Significantly fewer SSI occurred in the pulse irrigation group [4 (6 %) vs. 12 (19 %); p = 0.032]. On multivariate analysis, the use of pulse irrigation was the only factor associated with a reduction in SSI with an odds ratio (OR) of 0.3 [95 % confidence interval (95 % CI) 0.1-0.8; p = 0.031]. In contrast, hospital length of stay of greater than 14 days was associated with increased infections with an OR of 7.6 (95 % CI 2.4-24.9; p = 0.001). CONCLUSIONS: Pulse irrigation of laparotomy wounds in operations exceeding 2 h duration reduced SSI after major hepatobiliary pancreatic surgery. (Australian New Zealand Clinical Trials Registry, ACTRN12612000170820).
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ItemGlucagon-like peptide 1 and peptide YY are in separate storage organelles in enteroendocrine cells(SPRINGER, 2014-07)A sub-group of enteroendocrine cells (L cells) release gastrointestinal hormones, GLP-1 and PYY, which have different but overlapping physiological effects, in response to intraluminal nutrients. Whilst their release profiles are not identical, how the plasma levels of these two hormones are differentially regulated is not well understood. We investigate the possibility that GLP-1 and PYY are in separate storage vesicles. In this study, the subcellular location of GLP-1 and PYY storage organelles is investigated using double-labelling immunohistochemistry, super resolution microscopy and high-resolution confocal microscopy. In all species tested, human, pig, rat and mouse, most cytoplasmic stores that exhibited GLP-1 or PYY immunofluorescence were distinct from each other. The volume occupancy, determined by 3D analysis, overlapped by only about 10∼20 %. At the lower resolution achieved by conventional confocal microscopy, there was also evidence of GLP-1 and PYY being in separate storage compartments but, in subcellular regions where there were many storage vesicles, separate storage could not be resolved. The results indicate that different storage vesicles in L cells contain predominantly GLP-1 or predominantly PYY. Whether GLP-1 and PYY storage vesicles are selectively mobilised and their products are selectively released needs to be determined.
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ItemFluid prescription practices of anesthesiologists managing patients undergoing elective colonoscopy: an observational study.(Springer Science and Business Media LLC, 2014-06-10)BACKGROUND: Routine fluid prescription is common practice amongst anesthesiologists caring for patients undergoing colonoscopy. However there is limited information about routine procedural fluid prescription practices of anesthesiologists in this setting. Routine fluid administration may also have important pharmaco-economic implications for the health care budget. Therefore we performed a prospective observational study assessing the fluid prescription practices of anesthesiologists caring for patients undergoing elective colonoscopy. METHODS: With Institutional Review Board approval, adult patients receiving procedural fluid intervention during elective colonoscopy were included. DATA COLLECTED: size of intravenous cannula inserted, volumes of fluid administered, adverse events, procedure duration, and pharmaco-economic costs associated with fluid prescription. Anesthesiologists and gastroenterologists were blinded to the study. RESULTS: We collected data on 289 patients who received fluid prescription by their attending anesthesiologist. Median patient age: 48 yrs (range 18-83), gender: 174 (60%) female; median duration of procedure: 24 minutes (range 12-48). Cannula size: 181 (63%) patients received a 22G cannula or smaller. Median volume of fluid administered during the colonoscopy was 325 ml (range 0 to 1000 ml). Median duration of the procedure: 25 minutes (range 12 to 48 minutes). Median volume of fluid administered in the post anaesthesia recovery unit: 450 ml (range 0 to 1000 ml). Fifteen patients (5%) became hypotensive during the procedure and two patients (<1%) developed hypotension in the PACU. There was no difference in the median fluid requirements between patients with hypotension and those without. Fluid volumes were strongly associated with increasing cannula diameter (p = 0.0001), however there was no association between fluid volumes administered and vasopressor use, peri-procedural adverse events, or procedure duration. At our institution fluid therapy currently cost about AUD$4.90 per patient: 1 L crystalloid $1.18 and fluid delivery set $3.77 Our institution performs over 9000 endoscopic procedures annually with fluid therapy costing about $45,000/year. CONCLUSIONS: Routine fluid prescription by anesthesiologists managing patients undergoing colonoscopy was ineffective with low actual fluid volumes delivered during the procedure. There was no association between volumes of fluid delivered and procedural hypotension, adverse events, or procedure duration. Anesthesiologists should question the clinical and pharmaco-economic value of routine fluid administration for patients undergoing elective endoscopy.
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ItemGlaucarubinone and gemcitabine synergistically reduce pancreatic cancer growth via down-regulation of P21-activated kinases(ELSEVIER IRELAND LTD, 2014-05-01)Pancreatic cancer is one of the most lethal of human malignancies. Nearly 100% cases of pancreatic cancer carry mutations in KRas. P-21-activated kinases (PAKs) are activated by and act downstream of KRas. Glaucarubinone, a natural product first isolated from the seeds of the tree Simarouba glauca, was originally developed as an antimalarial drug, and has more recently been recognised as an anticancer agent. The aims of this study were to determine whether glaucarubinone, alone or in combination with the front-line chemotherapeutic agent gemcitabine, would inhibit the growth of pancreatic cancer cells in vitro or in vivo and the mechanism involved. Growth of the human pancreatic cancer cell lines PANC-1 and MiaPaCa-2 was measured by (3)H-thymidine incorporation in vitro, and by volume as xenografts in SCID mice. The expression and activities of the two serine/threonine kinases PAK1 and PAK4, which are key regulators of cancer progression, were measured by Western blotting. Here we report that glaucarubinone decreased proliferation and migration of pancreatic cancer cells in vitro, and reduced their growth as xenografts in vivo. Treatment with glaucarubinone and gemcitabine reduced proliferation in vitro and tumor growth in vivo more than treatment with either glaucarubinone or gemcitabine alone. Treatment with glaucarubinone reduced PAK1 and PAK4 activities, which were further decreased by the combination of glaucarubinone and gemcitabine. These results indicate that glaucarubinone reduced pancreatic cancer cell growth at least in part via inhibition of pathways involving PAK1 and PAK4. The synergistic inhibition by glaucarubinone and gemcitabine observed both in vitro and in vivo suggests that glaucarubinone may be a useful adjunct to current regimes of chemotherapy.