The epidemiology of acute pancreatitis in tasmania over a 12-year period: Is this a disease of disadvantage?

BACKGROUND: The global incidence of acute pancreatitis (AP) is increasing, but little information exists about trends in Australia. This study aimed to describe incidence trends, along with clinical and socio-demographic associations, in the state of Tasmania over a recent 12-year period. METHODS: The study cohort was obtained by linking clinical and administrative datasets encompassing the whole Tasmanian population between 2007 and 2018, inclusive. Pancreatitis case definition was based on relevant ICD-10 hospitalization codes, or elevated serum lipase or amylase in pathology data. Age-standardised incidence rates were estimated, overall and stratified by sex, aetiology, and Index of Relative Socio-economic Disadvantage (IRSD). RESULTS: In the study period, 4905 public hospital AP episodes were identified in 3503 people. The age-standardised person-based incidence rate across the entire period was 54 per 100,000 per year. Incidence was inversely related to IRSD score; 71 per 100,000 per year in the most disadvantaged quartile compared to 32 in the least disadvantaged. Biliary AP incidence was higher than that of alcohol-related AP, although the greatest incidence was in "unspecified" cases. There was an increase in incidence for the whole cohort (average annual percent change 3.23 %), largely driven by the two most disadvantaged IRSD quartiles; the least disadvantaged quartile saw a slight overall decrease. CONCLUSION: This is the first Australian study providing robust evidence that AP incidence is increasing and is at the upper limit of population-based studies worldwide. This increased incidence is greatest in socio-economically disadvantaged areas, meriting further research to develop targeted, holistic management strategies.

Systematic Review of Preoperative Prognostic Biomarkers in Perihilar Cholangiocarcinoma.

Perihilar cholangiocarcinoma (pCCA) is an uncommon malignancy with generally poor prognosis. Surgery is the primary curative treatment; however, the perioperative mortality and morbidity rates are high, with a low 5-year survival rate. Use of preoperative prognostic biomarkers to predict survival outcomes after surgery for pCCA are not well-established currently. This systematic review aimed to identify and summarise preoperative biomarkers associated with survival in pCCA, thereby potentially improving treatment decision-making. The Embase, Medline, and Cochrane databases were searched, and a systematic review was performed using the PRISMA guidelines. English-language studies examining the association between serum and/or tissue-derived biomarkers in pCCA and overall and/or disease-free survival were included. Our systematic review identified 64 biomarkers across 48 relevant studies. Raised serum CA19-9, bilirubin, CEA, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and tumour MMP9, and low serum albumin were most associated with poorer survival; however, the cutoff values used widely varied. Several promising molecular markers with prognostic significance were also identified, including tumour HMGA2, MUC5AC/6, IDH1, PIWIL2, and DNA index. In conclusion, several biomarkers have been identified in serum and tumour specimens that prognosticate overall and disease-free survival after pCCA resection. These, however, require external validation in large cohort studies and/or in preoperatively obtained specimens, especially tissue biopsy, to recommend their use.

Hepatic artery pseudoaneurysm rupture: A case report.

Hepatic artery pseudoaneurysms are an uncommon complication of blunt hepatic trauma typically presenting in a delayed fashion. A 40-year-old male presented to a trauma centre after a 6-metre fall from a construction site with multiple injuries including a grade IV liver laceration centred around the porta hepatis. This liver injury was managed non-operatively. On day sixteen of admission, he had a sudden cardiac arrest from haemorrhagic shock with a subsequent CT demonstrating a ruptured extrahepatic proper hepatic artery pseudoaneurysm. Despite laparotomy and vessel repair, he died from pulmonary complications of aspiration pneumonia and acute lung injury associated with massive transfusion. The literature demonstrates conflicting views regarding the utility of repeat CT to detect a pseudoaneurysm in asymptomatic, non-operatively managed patients with blunt hepatic trauma. In particular, the literature does not distinguish the utility of repeat routine CT for intrahepatic and extrahepatic hepatic artery pseudoaneurysm, the latter if which is rarer. Current guidelines recommend against it, but there are observational studies suggesting utility, particularly in high grade (≥IV) liver injury. In patients with a high-grade injury extending to the porta hepatis, repeat imaging should be considered to detect possible pseudoaneurysm.

Evolution of laparoscopic pancreaticoduodenectomy at Westmead Hospital.

BACKGROUND: Despite its proposed benefits, laparoscopic pancreaticoduodenectomy (LPD) has not been widely adopted due to its technical complexity and steep learning curve. The aim of this study was to report a single surgeon's experience in the stepwise implementation of LPD and evolution of technique over a nine-year period in a moderate-high volume unit. METHODS: Carefully selected patients underwent LPD initially by hybrid approach (laparoscopic resection and open reconstruction), which evolved into a total LPD (laparoscopic resection and reconstruction). Data was prospectively collected to include patient characteristics, intraoperative data, evolution of technique and postoperative outcomes. RESULTS: A total of 25 patients underwent hybrid LPD (HLPD) and 20 patients underwent total LPD (TLPD). There was no 90-day mortality. Three patients developed a postoperative pancreatic fistula (POPF), all of which occurred in patients undergoing HLPD. There was no POPF in 20 consecutive TLPD. There was no evidence of anastomotic strictures in the hepaticojejunostomy in patients undergoing TLPD at long term follow up. CONCLUSION: A gradual and cautious progression from HLPD to TLPD is essential to ensure safe implementation into a unit. LPD should only be considered in carefully selected patients, with outcomes subjected to regular and rigorous independent audit.

Outcomes of endovascular, open surgical and autotransplantation techniques for renal artery aneurysm repair: a systematic review and meta-analysis.

BACKGROUND: Renal artery aneurysms (RAA) can be repaired with endovascular exclusion (EVR), open repair (OR), or ex-vivo repair with renal autotransplantation (ERAT). This systematic review compares repair indications, aneurysm characteristics, and complications following these interventions. METHODS: A systematic review of databases including MEDLINE, PUBMED, and EMBASE by two independent reviewers for studies from January 2000-November 2022. All studies evaluating repair indications, RAA morphology, morbidity and mortality following EVR, OR, and ERAT were included. RESULTS: A total of 38 studies were included with 1540 EVR, 2377 OR and 109 ERAT subjects. Increasing aneurysm size, or diameters >20 mm, were the most common repair indications across EVR and OR (n = 537; 48%), and ERAT (n = 23; 52%). All ERAT repairs were at or distal to renal artery bifurcations (n = 46). Meta-analyses demonstrated significantly shorter length of stay (LOS) with EVR compared to OR (mean difference -4.06, 95% confidence interval (CI) -5.69 to -2.43, P < 0.001). No significant differences were found in mean aneurysm diameter (P = 0.23), total complications (P = 0.17), and mortality (P = 0.85). Major complications (Clavien-Dindo ≥III) across studies most commonly included acute renal failure (EVR 4.9% vs. OR 7.0%). Nephrectomy was the most common major complication in ERAT (5.5%). CONCLUSIONS: Outcomes following EVR and OR of RAAs are comparable. EVR offers a shorter LOS, with no difference in morbidity or mortality. ERAT is currently only utilized for distal RAAs, however carries higher risk of infarction and nephrectomy necessitating specialized expertise or algorithms to assist appropriate selection of repair methods.

HGF/c-Met pathway inhibition combined with chemotherapy increases cytotoxic T-cell infiltration and inhibits pancreatic tumour growth and metastasis.

Pancreatic cancer (PC) is a deadly cancer with a high mortality rate. The unique characteristics of PC, including desmoplasia and immunosuppression, have made it difficult to develop effective treatment strategies. Pancreatic stellate cells (PSCs) play a crucial role in the progression of the disease by interacting with cancer cells. One of the key mediators of PSC - cancer cell interactions is the hepatocyte growth factor (HGF)/c-MET pathway. Using an immunocompetent in vivo model of PC as well as in vitro experiments, this study has shown that a combined approach using HGF/c-MET inhibitors to target stromal-tumour interactions and chemotherapy (gemcitabine) to target cancer cells effectively decreases tumour volume, EMT, and stemness, and importantly, eliminates metastasis. Notably, HGF/c-MET inhibition decreases TGF-ß secretion by cancer cells, resulting in an increase in cytotoxic T-cell infiltration, thus contributing to cancer cell death in tumours. HGF/c-MET inhibition + chemotherapy was also found to normalise the gut microbiome and improve gut microbial diversity. These findings provide a strong platform for assessment of this triple therapy (HGF/c-MET inhibition + chemotherapy) approach in the clinical setting.

Improving Quality Metrics with a Day-only Skin Abscess Protocol: Experience from Australia.

BACKGROUND: Skin abscesses are a common emergency presentation often requiring incision and drainage; however, issues with theatre access lead to delays in management and high costs. The long-term impact in a tertiary centre of a standardised day-only protocol is unknown. The aim was to evaluate the impact of day-only skin abscess protocol (DOSAP) for emergency surgery of skin abscesses in a tertiary institution in Australia and to provide a blueprint for other institutions. METHODS: A retrospective cohort study analysed several time periods: Period A (July 2014 to 2015, n = 201) pre-DOSAP implementation, Period B (July 2016 to 2017, n = 259) post-DOSAP, and Period C (July 2018 to 2022, n = 1,625) prospectively analysed four 12-month periods to assess long-term utilisation of DOSAP. Primary outcomes were length of stay and delay to theatre. Secondary outcome measures included theatre start time, representation rates and total costs. Statistical analysis using nonparametric methods was used to analyse the data. RESULTS: There was a significant decrease in ward length of stay (1.25 days vs. 0.65 days, P < 0.0001), delay to theatre (0.81 days vs. 0.44 days, P < 0.0001) and theatre start time before 10AM (44 cases vs. 96 cases, P < 0.0001) after implementation of DOSAP. There was a significant decrease in median cost of admission of $711.74 after accounting for inflation. Period C reported 1,006 abscess presentations successfully managed by DOSAP over the four-year period. CONCLUSION: Our study demonstrates the successful implementation of DOSAP in an Australian tertiary centre. The ongoing utilisation of the protocol demonstrates the ease of applicability.

Insulating jackets thermally protect kidneys in an ex vivo model of second warm ischemia.

BACKGROUND: Kidney transplantation is the current optimal treatment for suitable patients with end-stage renal disease. The second warm ischemic time (SWIT) is known to negatively impact delayed graft function, and long-term graft survival, and methods are required to ameliorate the impacts of SWIT on transplantation outcomes. MATERIALS AND METHODS: This study primarily focused on determining the effect of a novel thermally insulating jacket on the thermal profile of the human kidney and quantifying the reduction in thermal energy experienced using this device (KPJ™). An ex vivo simulated transplantation model was developed to determine the thermal profiles of non-utilized human kidneys with and without KPJ™ (n = 5). Control kidney temperature profiles were validated against the temperature profiles of n = 10 kidneys during clinical kidney transplantation. RESULTS: Using the ex-vivo water bath model, the thermally insulated human kidney reached the 15°C metabolic threshold temperature at 44.5 ± 1.9 min (vs control: 17.3 ± 1.8 min (p = 0.00172)) and remained within the 18°C threshold until 53.3 ± 1.3 min (vs control: 20.9 ± 2.0 min (p = 0.002)). The specific heat capacity of KPJ™ protected kidney was four-fold compared to the control kidney. The clinical temperature audit, closely correlated with the water bath model, hence validating this ex-vivo human kidney transplant model. CONCLUSION: Intraoperative thermal protection is a simple and viable method of reducing the thermal injury that occurs during the SWIT and increasing the specific heat capacity of the system. Such technology could easily be translated into clinical kidney transplant practice.

Reducing unplanned general surgical readmissions: a review of the Australian and New Zealand National Surgical Quality Improvement Program Database.

BACKGROUND: Unplanned surgical readmissions are an important indicator of quality care and are a key focus of improvement programs. The aims of this study were to evaluate the factors that lead to unplanned hospital readmissions in patients undergoing general surgical procedures and to identify preventable readmissions. METHODS: A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program database from 2016 to 2020 at a tertiary hospital was conducted to identify patients undergoing a general surgical procedure. Various perioperative parameters were studied to identify risk factors and reasons for unplanned readmission. Preventable readmissions were identified. RESULTS: A total of 3069 patients underwent a general surgical procedure. Of these, the overall unplanned readmission rate was 8.8% (n = 247). The most common reason for readmission was associated with surgical site infections (n = 112, 44.3%) followed by pain (n = 50, 20.2%), with over 45% deemed as preventable readmissions. Factors associated with increased risk of readmission included older age, longer index length of stay, prolonged operative time, elective procedures, higher ASA score and contaminated procedures. CONCLUSION: Unplanned readmissions are more likely to occur in patients who develop postoperative complications. Understanding factors associated with readmissions may facilitate targeted quality improvement projects that reduce hospital readmission after surgery.

Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio use in detecting bowel ischaemia in adhesional small bowel obstruction.

BACKGROUND: Bowel ischaemia significantly increases morbidity and mortality from adhesional small bowel obstruction. Current biomarkers and clinical parameters have poor predictive value for ischaemia. Our study investigated whether neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) could be used to predict bowel ischaemia in adhesional small bowel obstruction. METHODS: This single-centre retrospective study collected clinical, biochemical and radiological data from patients with adhesional small bowel obstruction between 2017 and 2020 who underwent operative management. The presence or absence of bowel ischaemia/infarction was used to distinguish two populations. Biochemical markers on admission and immediately prior to operation were collected to give platelet-lymphocyte ratio (PLR0 and PLRPRE-OP , respectively) and neutrophil-lymphocyte ratio (NLR0 and NLRPRE-OP , respectively). SAS 9.4 (SAS Institute Inc., Cary, NC) software was used for data analysis with Mann-Whitney U testing for continuous variables and Pearson Chi-square test for categorical variables. Sensitivity and specificity for PLR and NLR were calculated by means of receiver operating characteristic (ROC) curve analysis. RESULTS: Twenty-seven patients had intra-operative bowel ischaemia whilst the remaining 73 had no evidence of bowel ischaemia. Both median PLRPRE-OP and NLRPRE-OP were significantly higher in patients with bowel ischaemia compared to those without (PLRPRE-OP 272 [IQR 224-433] and 231 [IQR 146-295] respectively, P = 0.027; NLRPRE-OP 12.5 [IQR 8.6-21.3] v. 5.5 [IQR 3.5-10.2] respectively, P ≤ 0.001). Area under the receiver operator characteristic curve (AUC) was 0.762 for NLRPRE-OP , with a sensitivity of 85.1% and specificity of 63% for NLR 7.4. CONCLUSION: Raised NLR is predictive of bowel ischaemia in patients with adhesional small bowel obstruction.

Early routine (erCT) versus selective computed tomography (sCT) for acute abdominal pain: A systematic review and meta-analysis of randomised trials.

BACKGROUND: There are ongoing controversies about the routine use of computed tomography (CT) in the evaluation of acute abdominal pain (AAP), our study was designed to evaluate the impacts of early routine use CT (erCT) and selective CT (sCT) on clinical outcomes. METHODS: We conducted a meta-analysis of randomized trials. We included non-quadrant and non-region-specific studies only. The primary outcomes were the number of correct diagnoses at 24 h, mortality, and length of stay (LOS). The secondary outcomes were the number of corrected diagnoses from an initial misdiagnosis, major changes in management, and non-specific abdominal pain (NSAP). RESULTS: 6 Studies from 3 RCTs were included, enrolling 570 patients. erCT showed a higher number of correct diagnoses and corrected diagnoses at 24 h, [risk ratio (RR) 1.13, 95% confidence interval (CI) 1.01-1.26, P = 0.03] and [RR 1.36, 95% CI 1.01-1.85, P = 0.04] respectively, and a lower mortality at 6 months [RR 0.36, 95% CI 0.15-0.87, P = 0.02]. However, no differences were shown in LOS [mean difference (MD) -0.65, 95% CI -2.88 - 1.58, P = 0.57], major changes in management [RR 1.45, 95% CI 0.94-2.22, P = 0.09] and NSAP [RR 0.92, 95% CI 0.57-1.50, P = 0.74]. CONCLUSION: erCT has demonstrated both diagnostic and survival benefits by having more correct diagnoses at 24 h and lower mortality at 6 months. Further study should focus on determining the subpopulation that would most benefit from the potentially differential effects of erCT.

Does Sentinel Lymph Node Biopsy Accurately Stage the Clinically Negative Neck in Early Oral Cavity Squamous Cell Carcinoma?

PURPOSE: Sentinel lymph node biopsy (SLNB) is being increasingly used worldwide as a minimally invasive option to stage the clinically node-negative neck (N0) in patients with early oral cavity squamous cell carcinomas (OCSCC). We performed this trial to assess the reliability and validity of the technique. METHODS: We did this prospective interventional nonrandomized study in patients with early (cT1-T2 OCSCC) and with negative neck. All patients underwent preoperative lymphoscintigraphy; SLNB was followed immediately by completion neck dissection (CND), thus each patient serving as their own control. The primary outcomes evaluated are sentinel lymph node (SLN) detection rate, SLN retrieval rate, and SLN status (positive or negative) compared with pathology of CND specimen to detect any false negatives. The secondary outcomes included SLN analyses (tumor burden, location in different levels of the neck, laterality, extracapsular spread, and total nodes positive) and overall survival. RESULTS: Of 60 patients, 59 (98%) had successful SLN detection with the lymphoscintigram failing to localize in 1 patient. Of the remaining 59 patients, 58 (96%) had all the SLNs retrieved, resulting in 96.4% sentinel node retrieval rate. In total, 24 (41%) SLNs were positive with 1 false negative. Using a combination of SLN and CND findings as the gold standard for lymph node involvement status, SLNB had a sensitivity of 96% (95% confidence interval [CI]: 80-100%), a specificity of 100% (95% CI: 90-100%), and negative predictive value of 97% (95% CI: 85-100%). CONCLUSION: The results of this study suggest that SLNB is an accurate technique to assess the nodal status in patients with cT1-T2 N0 OCSCC and should be considered for eligible patients.

"The armor phenomenon" in obese patients with penetrating thoracoabdominal injuries: A systematic review and meta-analysis.

BACKGROUND: Obesity represents a growing global health threat, which generally portends increased morbidity and mortality in the context of traumatic injuries. We hypothesized that there may exist a protective effect related to increased weight and truncal girth provided for obese patients in penetrating torso injuries, although this may not exert a significant positive impact overall upon clinical outcomes. METHODS: A comprehensive review of the literature was conducted across five databases up to March 2021 (Medline, Pubmed, Embase, Web of Science and the Cochrane library) to examine the effect of obesity on penetrating thoracoabdominal injuries. The primary outcome was to determine the rate of nonsignificant injury and injury patterns. Secondary outcomes examined were lengths of stay, complications, and mortality. Comparisons were drawn by meta-analysis. The study protocol was registered with PROSPERO under CRD42020216277. RESULTS: There were 2,952 publications assessed with 12 meeting the inclusion criteria for review. Nine studies were included for quantitative analysis, including 5,013 patients sustaining penetrating thoracoabdominal injuries, of which 29.6% were obese. Obese patients that sustained stab injuries underwent more nontherapeutic operations. Obese patients that sustained gunshot injuries had longer intensive care and total hospital length of stay. Obese patients suffered more respiratory complications and were at an increased risk of death during their admission. CONCLUSION: The "armor phenomenon" does not truly protect obese patients, a population that experiences increased morbidity and mortality following penetrating thoracoabdominal injuries. LEVEL OF EVIDENCE: Systematic Review and Meta-Analysis; Level IV.

Metastatic phenotype and immunosuppressive tumour microenvironment in pancreatic ductal adenocarcinoma: Key role of the urokinase plasminogen activator (PLAU).

Background: Previous studies have revealed the role of dysregulated urokinase plasminogen activator (encoded by PLAU) expression and activity in several pathways associated with cancer progression. However, systematic investigation into the association of PLAU expression with factors that modulate PDAC (pancreatic ductal adenocarcinoma) progression is lacking, such as those affecting stromal (pancreatic stellate cell, PSC)-cancer cell interactions, tumour immunity, PDAC subtypes and clinical outcomes from potential PLAU inhibition. Methods: This study used an integrated bioinformatics approach to identify prognostic markers correlated with PLAU expression using different transcriptomics, proteomics, and clinical data sets. We then determined the association of dysregulated PLAU and correlated signatures with oncogenic pathways, metastatic phenotypes, stroma, immunosuppressive tumour microenvironment (TME) and clinical outcome. Finally, using an in vivo orthotopic model of pancreatic cancer, we confirmed the predicted effect of inhibiting PLAU on tumour growth and metastasis. Results: Our analyses revealed that PLAU upregulation is not only associated with numerous other prognostic markers but also associated with the activation of various oncogenic signalling pathways, aggressive phenotypes relevant to PDAC growth and metastasis, such as proliferation, epithelial-mesenchymal transition (EMT), stemness, hypoxia, extracellular cell matrix (ECM) degradation, upregulation of stromal signatures, and immune suppression in the tumour microenvironment (TME). Moreover, the upregulation of PLAU was directly connected with signalling pathways known to mediate PSC-cancer cell interactions. Furthermore, PLAU upregulation was associated with the aggressive basal/squamous phenotype of PDAC and significantly reduced overall survival, indicating that this subset of patients may benefit from therapeutic interventions to inhibit PLAU activity. Our studies with a clinically relevant orthotopic pancreatic model showed that even short-term PLAU inhibition is sufficient to significantly halt tumour growth and, importantly, eliminate visible metastasis. Conclusion: Elevated PLAU correlates with increased aggressive phenotypes, stromal score, and immune suppression in PDAC. PLAU upregulation is also closely associated with the basal subtype type of PDAC; patients with this subtype are at high risk of mortality from the disease and may benefit from therapeutic targeting of PLAU.

The Role of Targeted Versus Standard Antibiotic Prophylaxis in Pancreatoduodenectomy in Reducing Postoperative Infectious Complications: A Systematic Review and Meta-analysis.

INTRODUCTION: Infectious complications are common after pancreatoduodenectomy, which in turn are associated with preoperative biliary drainage. Current guidelines recommend a first-generation cephalosporin as perioperative antibiotic prophylaxis. However, some studies support the use of targeted antibiotics. The aim of this systematic review and meta-analysis is to evaluate the role of prophylactic targeted antibiotics compared to standard antibiotics in reducing postoperative infections after pancreatoduodenectomy. METHODS: A search from MEDLINE, EMBASE, and Cochrane library from 1946 to July 2020 was conducted. Studies were included if they compared targeted antibiotics with standard perioperative antibiotics while including outcome data on surgical site infections (SSI). Targeted therapy was defined as perioperative antibiotics targeting organisms prevalent in bile instrumentation or by culture data obtained from the patient or institution. Outcomes assessed were the rate of SSIs and their microbiology profile. Analyses included demographic data, perioperative antibiotics, postoperative outcomes including microbiology data, and meta-analysis was performed where applicable. RESULTS: Seven studies were included, with a total of 849 patients undergoing pancreatoduodenectomy. Targeted antibiotics were associated with a significantly lower rate of postoperative SSI compared to standard antibiotic therapy [21.1% vs 41.9%; risk ratios (RR) 0.55, 95% confidence interval 0.37-0.81]. Wound/incisional site infections and organ space infections were lower in patients receiving targeted antibiotic prophylaxis (RR 0.33, P = 0.0002 and RR 0.54, P = 0.0004, respectively). Enterococcus species were the most common bacteria reported. CONCLUSION: There was a significant reduction in overall SSI rates when targeted antibiotics was used. Current standard antibiotic prophylaxis is inadequate in covering microbes prevalent in postoperative infections developing after pancreatoduodenectomy.

Pharmacological prevention of post-operative pancreatitis: systematic review and meta-analysis of randomized controlled trials on animal studies.

BACKGROUND: Postoperative pancreatic fistula (POPF) remains a significant complication of pancreatic resection with recent evidence showing a strong association between post-operative pancreatitis and subsequent development of POPF. Incidence and severity of pancreatitis following endoscopic therapy has been effectively reduced with indomethacin prophylaxis, however further agents require evaluation. We present a systematic literature review and meta-analysis of the prophylactic treatment with corticosteroids or n-acetyl cysteine (NAC) of induced pancreatitis in rodent models. METHODS: A systematic literature search was conducted using Pubmed, Medline, Embase and Cochrane library to identify eligible randomized control trials (RCT) involving animal models that examined NAC or corticosteroids. The primary outcome was the subsequent effect on serum amylase and IL-6 and the histopathological markers of severity such as pancreatic oedema and necrosis. RESULTS: Four RCTs (n = 178) met inclusion criteria examining NAC and eight RCTs (n = 546) examining corticosteroid agents (dexamethasone, hydrocortisone, methylprednisolone). Prophylactic administration of all corticosteroid agents showed a net effect in favour of reducing markers of severity of pancreatitis. NAC showed a significant reduction in severity of amylase and necrosis. CONCLUSION: The RCTs examined suggest that prophylactic administration of corticosteroid agents and NAC can reduce the severity of pancreatitis as indicated by histopathologic markers, serum amylase and IL-6 levels.

HGF/c-Met Inhibition as Adjuvant Therapy Improves Outcomes in an Orthotopic Mouse Model of Pancreatic Cancer.

BACKGROUND: Inhibition of hepatocyte growth factor (HGF)/c-MET pathway, a major mediator of pancreatic stellate cell (PSC)-PC cell interactions, retards local and distant cancer progression. This study examines the use of this treatment in preventing PC progression after resection. We further investigate the postulated existence of circulating PSCs (cPSCs) as a mediator of metastatic PC. METHODS: Two orthotopic PC mouse models, produced by implantation of a mixture of luciferase-tagged human pancreatic cancer cells (AsPC-1), and human PSCs were used. Model 1 mice underwent distal pancreatectomy 3-weeks post-implantation (n = 62). One-week post-resection, mice were randomised to four treatments of 8 weeks: (i) IgG, (ii) gemcitabine (G), (iii) HGF/c-MET inhibition (HiCi) and (iv) HiCi + G. Tumour burden was assessed longitudinally by bioluminescence. Circulating tumour cells and cPSCs were enriched by filtration. Tumours of Model 2 mice progressed for 8 weeks prior to the collection of primary tumour, metastases and blood for single-cell RNA-sequencing (scRNA-seq). RESULTS: HiCi treatments: (1) reduced both the risk and rate of disease progression after resection; (2) demonstrated an anti-angiogenic effect on immunohistochemistry; (3) reduced cPSC counts. cPSCs were identified using immunocytochemistry (α-smooth muscle actin+, pan-cytokeratin-, CD45-), and by specific PSC markers. scRNA-seq confirmed the existence of cPSCs and identified potential genes associated with development into cPSCs. CONCLUSIONS: This study is the first to demonstrate the efficacy of adjuvant HGF/c-Met inhibition for PC and provides the first confirmation of the existence of circulating PSCs.

Consistency of global recommendations regarding open versus laparoscopic surgery during the COVID-19 pandemic: a systematic review.

BACKGROUND: Throughout the COVID-19 pandemic, there has been worldwide debate regarding whether open surgery should be performed in preference to laparoscopic surgery due to the theoretical higher risk of viral aerosolization by the release of pneumoperitoneum. We aimed to assess the consistency of national and international surgical society recommendations regarding the choice of surgical approach; assess the quality of evidence of viral emission in surgical aerosol; and assess the quality of evidence comparing aerosol generation by different surgical energy devices. METHODS: A systematic review of PubMed, Medline, Embase and Cochrane databases was performed. Three search strategies were employed. Twenty-eight studies were included in the final analysis and quality appraised. Confidence in review findings was assessed using the GRADE-CERQual (Confidence in Evidence from Reviews of Qualitative research) tool. RESULTS: Worldwide recommendations regarding open versus laparoscopic surgery are consistent, with a majority recommending that surgical approach is decided on a case-by-case, risk minimization approach. There is limited, low-quality evidence that viral particles can be emitted in surgical aerosol. There is a paucity of literature on the quantity of aerosol produced by different surgical energy devices, and no evidence to support the use of certain surgical instruments to minimize aerosol production. CONCLUSIONS: There is considerable consistency among worldwide recommendations regarding the choice of surgical approach, although the evidence base is lacking. To inform clinical recommendations, further research examining viral emission, transmission, infectivity and amount of surgical aerosol produced is required.

Protection From the Second Warm Ischemic Injury in Kidney Transplantation Using an Ex Vivo Porcine Model and Thermally Insulating Jackets.

BACKGROUND: Kidney transplantation is the optimum treatment for kidney failure in carefully selected patients. Technical surgical complications and second warm ischemic time (SWIT) increase the risk of delayed graft function (DGF) and subsequent short- and long-term graft outcomes including the need for post-transplant dialysis and graft failure. Intraoperative organ thermal regulation could reduce SWIT, minimizing surgical complications due to time pressure, and limiting graft ischemia-reperfusion injury. METHODS: A novel ischemic-injury thermal protection jacket (iiPJ) was designed and fabricated in silicone composite and polyurethane (PU) elastomer prototypes. Both were compared with no thermal insulation as controls. Time to reach ischemic threshold (15°C) and thermal energy transfer were compared. A water bath model was used to examine the thermal protective properties of porcine kidneys, as a feasibility study prior to in vivo translation. RESULTS: In both iterations of the iiPJ, the time taken to reach the warm ischemia threshold was 35.2 ± 1.4 minutes (silicone) and 38.4 ± 3.1 minutes (PU), compared with 17.2 ± 1.5 minutes for controls (n = 5, P < .001 for both comparisons). Thermal energy transfer was also found to be significantly less for both iiPJ variants compared with controls. There was no significant difference between the thermal performance of the 2 iiPJ variants. CONCLUSION: Protection from SWIT by using a protective insulation jacket is feasible. With clinical translation, this novel strategy could facilitate more optimal surgical performance and reduce transplanted organ ischemia-reperfusion injury, in particular the SWIT, potentially affecting delayed graft function and long-term outcomes.