Bleeding from the pancreatic cut surface post pancreaticoduodenectomy: a review of a tertiary referral centre.

BACKGROUND: Haemorrhage from the pancreatic cut surface after pancreaticoduodenectomy is uncommon. The optimal treatment for post-pancreatectomy haemorrhage (PPH) from the pancreatic cut surface remains controversial. METHODS: We performed a retrospective analysis including all patients who underwent a pancreatiocoduodenectomy between 2008 and 2018 at a single tertiary institution in Melbourne, Australia, to analyse the incidence, potential risk factors, treatment and outcomes of cut surface PPH. RESULTS: A total of 168 pancreaticoduodenectomies were performed during the study period with pancreaticogastrostomy being the most common method of reconstruction at our institution (84.5%). There were 12 instances of cut surface PPH (7.1%). The majority of cases of cut surface PPH occurred within 48 h following pancreaticoduodenectomy (67%) with 41.7% occurring in the first 24 h. All but one patient required surgical intervention but length of stay did not appear to be increased compared to those without cut surface PPH. There was a trend towards patients with cut surface PPH being more likely to have a non-dilated pancreatic duct (75% versus 49%; P = 0.079). No significant differences were noted between patient with and without cut surface PPH with regards to abnormalities in platelet counts (3.2% versus 0%; P = 0.529), international normalized ratio (4.5% versus 8.3%; P = 0.694) and prophylactic anticoagulant administration or continuing antiplatelet use (28.2 versus 16.7%; P = 0.630). CONCLUSION: We believe that an unobstructed pancreas, in combination with the acidic environment associated with a dunking pancreaticogastrostomy anastomosis, may predispose to bleeding from the cut surface of the pancreas.

The Role of Laparoscopic Cholecystectomy After Severe and/or Necrotic Pancreatitis in the Setting of Modern Minimally Invasive Management of Pancreatic Necrosis.

OBJECTIVES: The trend toward minimally invasive procedures (MIP) in necrotizing pancreatitis is increasing. The optimal timing and technique of cholecystectomy in severe/necrotizing pancreatitis is unclear. This study aims to determine the role of laparoscopic cholecystectomy after severe/necrotizing pancreatitis in the context of MIP. METHODS: Retrospective analysis of a prospective database was performed for consecutive patients after cholecystectomy for gallstone pancreatitis between January 2011 and January 2018 at Monash Health, Melbourne, Australia. RESULTS: Three hundred fifty-five patients with gallstone pancreatitis underwent laparoscopic cholecystectomy with 2 conversions. Patients with severe pancreatitis were older (P = 0.002), with a more even sex distribution when compared with mild pancreatitis. Females predominated in the mild pancreatitis group.Patients with moderate/severe pancreatitis (P = 0.002) and necrosis (P > 0.001) were more likely to have delayed cholecystectomy compared with mild pancreatitis. There was no increase in biliary presentations while awaiting cholecystectomy. Length of stay for patients with severe/necrotizing pancreatitis (P = 0.001) was increased, surgical complications appeared similar. CONCLUSIONS: Laparoscopic cholecystectomy can be performed safely and effectively for pancreatitis, irrespective of severity. The paradigm shift in the management of severe necrotizing pancreatitis away from open necrosectomy toward MIP can be extended to encompass laparoscopic cholecystectomy.

Interventional management of necrotizing pancreatitis: an Australian experience.

BACKGROUND: The interventional management of necrotizing pancreatitis has evolved from early open surgery to delayed endoscopic or percutaneous intervention. However, few studies have directly compared the three treatment modalities. We aim to compare the outcomes of patients who had endoscopic, percutaneous or surgical interventions for necrotizing pancreatitis at our institution. METHODS: This is a retrospective cohort study of patients who had interventions for necrotizing pancreatitis at our institution from 2005 to 2014. Primary outcome was length of stay (LOS); secondary outcomes were complication rate and number of procedures required for resolution of necrosis. RESULTS: Thirty patients were included. Mortality rate was 13% (four patients). Median LOS and time to intervention was 88 and 28 days, respectively. There were no significant differences in the computed tomography severity indices and 48-h C-reactive protein levels among the three groups. Initial endoscopic intervention was associated with a median LOS of 62 days compared with 101 days in the percutaneous group and 91 days in the surgical group (P = 0.04). There were higher rates of pancreatic fistulae (40%) (P = 0.012) and new onset diabetes (30%) (P = 0.046) in the surgical group. Median number of procedures was similar among the three groups. Median LOS for patients with delayed intervention (fourth to sixth week of pancreatitis) was 66 days, compared with 137 days in patients with early intervention (first to third week) and 104 days in patients with late intervention (seventh week onwards) (P ≤ 0.001). CONCLUSION: A delayed, endoscopy first approach appears to be a reasonable strategy as it is associated with decreased LOS and low complication rate.

Usefulness of early post-operative liver function test monitoring after laparoscopic common bile duct exploration.

BACKGROUND: This study examines the usefulness of early post-operative liver function test (LFT) monitoring in predicting retained choledocholithiasis after laparoscopic common bile duct exploration (LCBDE). METHODS: Data on patients who had LCBDE over a 3-year period were collected retrospectively. Patients who had ongoing choledocholithiasis after unsuccessful LCBDE were considered for the test group and patients who had successful LCBDE were considered for the control group. Preoperative, day 1 post-operative and day 2 post-operative alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), alanine transaminase (ALT) and bilirubin levels were recorded. Proportions of patients who had worsening LFTs were analysed in each group. RESULTS: Proportions of patient who had worsening LFTs on day 1 were not statistically different between two groups and they were statistically equal on equivalence testing (two one-sided tests). On day 2, proportions of patient were again not statistically different. Bilirubin and ALT were statistically equivalent (P = 0.022 and P = 0.025 respectively) but GGT and ALP failed to achieve statistical equivalence (P = 0.062 and P = 0.138 respectively) on day 2. Twelve patients with normal appearing final intraoperative cholangiogram needed reintervention due to retained choledocholithiasis diagnosed subsequently. LFTs progressively improved despite presence of choledocholithiasis in eight of these 12 patients (75%) and only four were diagnosed by worsening post-operative LFTs during index admission. CONCLUSION: LFTs in the early post-operative period are not useful in determining which patients require biliary imaging or intervention after an apparently successful LCBDE.

Management of CBD stones in patients having laparoscopic cholecystectomy in a private setting in Australia.

INTRODUCTION: Laparoscopic bile duct exploration at the time of laparoscopic cholecystectomy has been promoted as being equally successful as endoscopic bile duct clearance. Further, if successful it offers the possibility of reducing the number of interventions required and therefore reducing overall costs. However, there is little in the literature that describe current treatment patterns in the Australian environment. METHODS: Medicare data were obtained for the number of patients undergoing laparoscopic cholecystectomy, intraoperative cholangiography, laparoscopic transcystic bile duct exploration, laparoscopic choledochotomy and bile duct exploration, endoscopic retrograde cholangiopancreatography (ERCP), sphincterotomy and endoscopic biliary stent insertion. RESULTS: Although there was significant state-to-state variation in the prevalence of laparoscopic bile duct exploration (0.6-3.7%), ERCP remained the predominant method of bile duct clearance in the setting of laparoscopic cholecystectomy (5.4%). Transcystic bile duct exploration is far more common than laparoscopic choledochotomy, which is a rare procedure. This suggests that patients with a dilated common bile duct and large or multiple stones are typically undergoing ERCP rather than laparoscopic bile duct clearance. CONCLUSION: Despite the apparent attractiveness of laparoscopic bile duct exploration at the time of cholecystectomy, ERCP remains the most common method of dealing with choledocholithiasis in the setting of an intact gallbladder in Australia.

KRAS mutation is associated with lung metastasis in patients with curatively resected colorectal cancer.

PURPOSE: Oncogene mutations contribute to colorectal cancer development. We searched for differences in oncogene mutation profiles between colorectal cancer metastases from different sites and evaluated these as markers for site of relapse. EXPERIMENTAL DESIGN: One hundred colorectal cancer metastases were screened for mutations in 19 oncogenes, and further 61 metastases and 87 matched primary cancers were analyzed for genes with identified mutations. Mutation prevalence was compared between (a) metastases from liver (n = 65), lung (n = 50), and brain (n = 46), (b) metastases and matched primary cancers, and (c) metastases and an independent cohort of primary cancers (n = 604). Mutations differing between metastasis sites were evaluated as markers for site of relapse in 859 patients from the VICTOR trial. RESULTS: In colorectal cancer metastases, mutations were detected in 4 of 19 oncogenes: BRAF (3.1%), KRAS (48.4%), NRAS (6.2%), and PIK3CA (16.1%). KRAS mutation prevalence was significantly higher in lung (62.0%) and brain (56.5%) than in liver metastases (32.3%; P = 0.003). Mutation status was highly concordant between primary cancer and metastasis from the same individual. Compared with independent primary cancers, KRAS mutations were more common in lung and brain metastases (P < 0.005), but similar in liver metastases. Correspondingly, KRAS mutation was associated with lung relapse (HR = 2.1; 95% CI, 1.2 to 3.5, P = 0.007) but not liver relapse in patients from the VICTOR trial. CONCLUSIONS: KRAS mutation seems to be associated with metastasis in specific sites, lung and brain, in colorectal cancer patients. Our data highlight the potential of somatic mutations for informing surveillance strategies.

Differential distribution and regulation of mouse cardiac Na+/K+-ATPase alpha1 and alpha2 subunits in T-tubule and surface sarcolemmal membranes.

OBJECTIVES: Two Na+/K+-ATPase (NKA) alpha-subunit isoforms, alpha1 and alpha2, are expressed in the adult mouse heart. The subcellular distribution of these isoforms in T-tubule and surface sarcolemmal (SSL) membranes and their regulation by cAMP-dependent protein kinase (PKA) is unclear. METHODS: We used formamide-induced detubulation of mouse ventricular myocytes to investigate differential functional distribution and regulation by PKA of alpha1 and alpha2 in T-tubule versus SSL membranes by measuring NKA current (I(pump)) and NKA-mediated Na+ efflux (-d[Na](i)/dt). RESULTS: I(pump) is composed of 88% alpha(1)-mediated I(pump) (Ialpha1) and 12% alpha2-mediated I(pump) (Ialpha2). alpha1 and alpha2 subunits demonstrate distinct ouabain affinities (105+/-6 and 0.3+/-0.1 micromol/L respectively) but similar affinity for intracellular Na+ (K(1/2)Na+ of 16.6+/-0.8 and 16.7+/-2.6 mmol/L respectively). Detubulation reduced (i) I(pump) density (1.42+/-0.1 to 1.20+/-0.04 pA/pF), (ii) cell capacitance (181+/-12 to 127+/-17 pF), and (iii) Ialpha2 contribution (12 to 6%). Total I(pump) density was approximately 60% higher in T-tubule (1.94 pA/pF, derived) vs. SSL membranes. Although T-tubule membranes represent only 30% of total surface area, they generate approximately 70% of Ialpha2 and approximately 37% of Ialpha1. Ialpha1 density was substantially higher than Ialpha2 in SSL (Ialpha1:Ialpha2 = 16:1) but this was markedly reduced in T-tubules (4:1). In addition to differential localisation, isoprenaline (ISO, 1 micromol/L) significantly increased alpha1-mediated NKA Na+ affinity (from 16.6+/-0.8 to 13.3+/-1.4 mmol/L) and caused a small increase in maximal NKA Na+ efflux rate. ISO had no effect on alpha2-mediated NKA activity. CONCLUSION: These data suggest that NKA alpha1 and alpha2 subunits are differentially localised and regulated by PKA in T-tubule and SSL membranes and may have distinct regulatory roles in cardiac excitation-contraction coupling.

FCCP is cardioprotective at concentrations that cause mitochondrial oxidation without detectable depolarisation.

OBJECTIVE: The role of mitochondria and in particular of mitochondrial uncoupling in the mechanism of cardioprotection is not defined. In the accompanying paper we have shown that pretreatment of isolated rat hearts with a low concentration (100 nM) of FCCP, prior to global ischaemia, is cardioprotective, while 300 nM FCCP exacerbates injury. Here we define the mitochondrial responses to increasing concentrations of FCCP and also to explore the equivalence of the cardioprotective doses of diazoxide. METHODS: Changes in mitochondrial respiration in response to FCCP and diazoxide were determined in isolated rat ventricular myocytes. In addition, mitochondrial state was monitored using confocal microscopy to record mitochondrial potential (TMRM) and redox state (NADH) during FCCP and diazoxide treatment. Myocytes were also voltage-clamped and whole cell currents recorded in response to 100 nM FCCP. RESULTS: FCCP (10-1000 nM) caused significant dose-dependent increase in oxygen consumption. Diazoxide (30 microM) failed to cause any measurable change in mitochondrial function. FCCP at 100 nM caused mitochondrial oxidation, but no change in mitochondrial membrane potential or (sarc)K(ATP) channel current, while at 300 nM, FCCP caused significant mitochondrial depolarisation. Diazoxide failed to induce any mitochondrial oxidation or depolarisation. CONCLUSIONS: Concentrations of FCCP that cause mitochondrial oxidation without depolarisation are cardioprotective. Higher FCCP concentrations dissipate mitochondrial membrane potential and exacerbate injury. This establishes the principle that mild mitochondrial uncoupling activates a protective mechanism. Diazoxide did not cause mitochondrial oxidation or mitochondrial depolarisation, suggesting it induces protection via another mechanism.