Surgery (Austin & Northern Health) - Research Publications
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ItemLung-resident memory B cells established after pulmonary influenza infection display distinct transcriptional and phenotypic profiles(AMER ASSOC ADVANCEMENT SCIENCE, 2022-01)Recent studies have established that memory B cells, largely thought to be circulatory in the blood, can take up long-term residency in inflamed tissues, analogous to widely described tissue-resident T cells. The dynamics of recruitment and retention of memory B cells to tissues and their immunological purpose remains unclear. Here, we characterized tissue-resident memory B cells (BRM) that are stably maintained in the lungs of mice after pulmonary influenza infection. Influenza-specific BRM were localized within inducible bronchus-associated lymphoid tissues (iBALTs) and displayed transcriptional signatures distinct from classical memory B cells in the blood or spleen while showing partial overlap with memory B cells in lung-draining lymph nodes. We identified lung-resident markers, including elevated expression of CXCR3, CCR6, and CD69, on hemagglutinin (HA)- and nucleoprotein (NP)-specific lung BRM. We found that CCR6 facilitates increased recruitment and/or retention of BRM in lungs and differentiation into antibody-secreting cells upon recall. Although expression of CXCR3 and CCR6 was comparable in total and influenza-specific memory B cells isolated across tissues of human donors, CD69 expression was higher in memory B cells from lung and draining lymph nodes of human organ donors relative to splenic and PBMC-derived populations, indicating that mechanisms underpinning BRM localization may be evolutionarily conserved. Last, we demonstrate that human memory B cells in lungs are transcriptionally distinct to populations in lung-draining lymph nodes or PBMCs. These data suggest that BRM may constitute a discrete component of B cell immunity, positioned at the lung mucosa for rapid humoral response against respiratory viral infections.
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ItemAge 80 years and over is not associated with increased morbidity and mortality following pancreaticoduodenectomy(WILEY, 2018-05)BACKGROUND: Pancreaticoduodenectomy (PD) is associated with high morbidity, which is perceived to be increased in the elderly. To our knowledge there have been no Australian series that have compared outcomes of patients over the age of 80 undergoing PD to those who are younger. METHODS: Patients who underwent PD between January 2008 and November 2015 were identified from a prospectively maintained database. RESULTS: A total of 165 patients underwent PD of whom 17 (10.3%) were aged 80 or over. The pre-operative health status, according to American Society of Anesthesiologists class was similar between the groups (P = 0.420). The 90-day mortality rates (5.9% in the elderly and 2% in the younger group; P = 0.355) and the post-operative complication rates (64.7% in the elderly versus 62.8% in the younger group; P = 0.88) were similar. Overall median length of hospital stay was also similar between the groups, but older patients were far more likely to be discharged to a rehabilitation facility than younger patients (47.1 versus 12.8%; P < 0.0001). Older patients with pancreatic adenocarcinoma (n = 10) had significantly lower median survival than the younger group (n = 69) (16.6 versus 22.5 months; P = 0.048). CONCLUSION: No significant differences were seen in the rate of complications following PD in patients aged 80 or over compared to younger patients, although there appears to be a shorter survival in the elderly patients treated for pancreatic cancer. Careful selection of elderly patients and optimal peri-operative care, rather than age should be used to determine whether surgical intervention is indicated in this patient group.
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ItemEmergency presentations of acute biliary pain: changing patterns of management in a tertiary institute(WILEY, 2018-12)BACKGROUND: Acute biliary pain is the most common presentation of gallstone disease. Untreated patients risk recurrent pain, cholecystitis, obstructive jaundice, pancreatitis and multiple hospital presentations. We examine the outcome of implementing a policy to offer laparoscopic cholecystectomy on index presentation to patients with biliary colic in a tertiary hospital in Australia. METHODS: This is a retrospective cohort study of adult patients presenting to the emergency department (ED) with biliary pain during three 12-month periods. Outcomes in Group A, 3 years prior to policy implementation, were compared with groups 2 and 7 years post implementation (Groups B and C). Primary outcomes were representations to ED, admission rate and time to cholecystectomy. RESULTS: A total of 584 patients presented with biliary colic during the three study periods. Of these, 391 underwent cholecystectomy with three Strasberg Type A bile leaks and no bile duct injuries. The policy increased admission rates (A = 15.8%, B = 62.9%, C = 29.5%, P < 0.001) and surgery on index presentation (A = 12.0%, B = 60.7%, C = 27.4%, P < 0.001). There was a decline in time to cholecystectomy (days) (A = 143, B = 15, C = 31, P < 0.001), post-operative length of stay (days) (A = 3.6, B = 3.2, C = 2.0, P < 0.05) and representation rates to ED (A = 42.1%, B = 7.1%, C = 19.9%, P < 0.001). There was a decline in policy adherence in the later cohort. CONCLUSION: Index hospital admission and cholecystectomy for biliary colic decrease patient representations, time to surgery, post-operative stay and complications of gallstone disease. This study demonstrates the impact of the policy with initial improvement, the dangers of policy attrition and the need for continued reinforcement.
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ItemOutcomes for children after second liver transplantations are similar to those after first transplantations: a binational registry analysis(WILEY, 2020-11)Objective To assess long term graft and patient survival after donor liver retransplantation in children in Australia and New Zealand during 1986–2017; to determine the factors that influence survival. Design Retrospective cohort analysis (registry data). Setting, participants Australia and New Zealand Liver Transplant Registry data for all liver retransplantations in children (under 18 years of age), 1986–2017, in all four paediatric and six adult liver transplantation centres in the two countries. Main outcome measures Graft and patient survival at one, 5, 10 and 15 years. Results 142 liver retransplantations were undertaken in children (59 during 1986–2000, 83 during 2001–2017). Kaplan–Meier survival analysis indicated that survival was significantly greater during 2001–2017 than 1986–2000 (P < 0.001). During 2001–2017, graft survival one year after retransplantation was 84%, at 5 years 75%, at 10 years 70%, and at 15 years 54%; patient survival was 89% at one year, 87% at 5 years, 87% at 10 years, and 71% at 15 years. Median time between transplantations was 0.2 years (IQR, 0.03–1.4 years) during 1986–2000, and 1.8 years (IQR, 0.1–6.8 years) during 2001–2017 (P = 0.002). The proportion of graft failures that involved split grafts was larger during 2001–2017 (35 of 83, 42%) than 1986–2000 (10 of 59, 17%). Graft type, cause of graft failure, and number of transplants did not influence survival following retransplantation. Conclusion Survival for children following retransplantation is excellent. Graft survival is similar for split and whole grafts. Children on the liver waiting list requiring retransplantation should have the same access to donor grafts as children requiring a first transplant.
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ItemAdaptive immunity to human coronaviruses is widespread but low in magnitude(WILEY, 2021)OBJECTIVES: Endemic human coronaviruses (hCoVs) circulate worldwide but cause minimal mortality. Although seroconversion to hCoV is near ubiquitous during childhood, little is known about hCoV-specific T-cell memory in adults. METHODS: We quantified CD4 T-cell and antibody responses to hCoV spike antigens in 42 SARS-CoV-2-uninfected individuals. Antigen-specific memory T cells and circulating T follicular helper (cTFH) cells were identified using an activation-induced marker assay and characterised for memory phenotype and chemokine receptor expression. RESULTS: T-cell responses were widespread within conventional memory and cTFH compartments but did not correlate with IgG titres. SARS-CoV-2 cross-reactive T cells were observed in 48% of participants and correlated with HKU1 memory. hCoV-specific T cells exhibited a CCR6+ central memory phenotype in the blood, but were enriched for frequency and CXCR3 expression in human lung-draining lymph nodes. CONCLUSION: Overall, hCoV-specific humoral and cellular memory are independently maintained, with a shared phenotype existing among coronavirus-specific CD4 T cells. This understanding of endemic coronavirus immunity provides insight into the homeostatic maintenance of immune responses that are likely to be critical components of protection against SARS-CoV-2.
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ItemEpidemiology and outcomes of acute liver failure in Australia(BAISHIDENG PUBLISHING GROUP INC, 2019-07-27)BACKGROUND: Acute liver failure (ALF) is a life-threatening syndrome with varying aetiologies requiring complex care and multidisciplinary management. Its changing incidence, aetiology and outcomes over the last 16 years in the Australian context remain uncertain. AIM: To describe the changing incidence, aetiology and outcomes of ALF in South Eastern Australia. METHODS: The database of the Victorian Liver Transplant Unit was interrogated to identify all cases of ALF in adults (> 16 years) in adults hospitalised between January 2002 and December 2017. Overall, 169 patients meeting criteria for ALF were identified. Demographics, aetiology of ALF, rates of transplantation and outcomes were collected for all patients. Transplant free survival and overall survival (OS) were assessed based on survival to discharge from hospital. Results were compared to data from a historical cohort from the same unit from 1988-2001. RESULTS: Paracetamol was the most common aetiology of acute liver failure, accounting for 50% of cases, with an increased incidence compared with the historical cohort (P = 0.046). Viral hepatitis and non-paracetamol drug or toxin induced liver injury accounted for 15% and 10% of cases respectively. Transplant free survival (TFS) improved significantly compared to the historical cohort (52% vs 38%, P = 0.032). TFS was highest in paracetamol toxicity with spontaneous recovery in 72% of cases compared to 31% of non-paracetamol ALF (P < 0.001). Fifty-nine patients were waitlisted for emergency liver transplantation. Nine of these died while waiting for an organ to become available. Forty-two patients (25%) underwent emergency liver transplantation with a 1, 3 and 5 year survival of 81%, 78% and 72% respectively. CONCLUSION: Paracetamol toxicity is the most common aetiology of ALF in South-Eastern Australia with a rising incidence over 30 years. TFS has improved, however it remains low in non-paracetamol ALF.
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ItemReduction in post-operative pancreatic fistula with polyethylene glycol and recombinant human albumin sealant following stapled distal pancreatectomy(WILEY, 2021-11)BACKGROUND: Postoperative pancreatic fistula (POPF) remains a significant cause of morbidity in patients undergoing distal pancreatectomy (DP). The use of polyethylene glycol (PEG) and recombinant human albumin sealant gel applied to the transected pancreatic margin in DP may reduce POPF rates and was assessed. METHODS: A retrospective single centre cohort study of patient undergoing DP at an Australian high volume tertiary institution between January 2015 and January 2021. Rates of POPF in patients undergoing stapled pancreatic transection with PEG sealant were compared to other methods. RESULTS: A total of 54 cases were identified for analysis, with 16 undergoing stapled DP combined with staple line application of PEG (PEG group). Most patients in the control group had stapled DP 92% (35 of 38), with 47% (18 of 38) combined with a reinforcing buttress, with or without the use other glue types. Overall, 28 of 54 (52%) developed a POPF, with a significantly lower rate in the PEG group (3 of 16 vs. 25 of 38 in the Control group; p = 0.003). Clinically significant Grade B/C POPF was lower in the PEG group (0 of 16 vs. 9 of 28 in the Control group; p = 0.045), and patients in the PEG group had a shorter median (range) length of hospital stay (6 [4-14] days vs. 10 [6-41] days p = 0.04). CONCLUSION: Stapled DP with the application of PEG and recombinant human albumin sealant to the transection line appears to be associated with a lower rate of clinically significant POPF.
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ItemBiliary stenting versus surgical bypass for palliation of periampullary malignancy(SPRINGER INDIA, 2013-03)BACKGROUND: Patients with periampullary cancers may not be suitable for curative resection due to locally advanced disease, metastases, or poor health. Biliary stenting and surgical bypass are utilized for symptom control, but the true benefit of one technique over the other is not clear. METHODS: A retrospective analysis of case records was undertaken of patients with periampullary (pancreatic head/uncinate process, distal bile duct, and ampulla of Vater and surrounding duodenum) malignancy treated between June 2004 and June 2010 in a tertiary center by palliative biliary stenting or palliative surgical bypass. RESULTS: Of the 69 patients included in the analysis, combined biliary and gastric bypass was performed on 28, while 41 underwent biliary stent (metallic, n = 39) insertion. Patients undergoing stenting were significantly older and less likely to be offered chemotherapy than those from the surgical bypass group. Overall, there were significantly more complications in the stent insertion group (85 %) than the surgical bypass group (36 %) (p = 0.003). The stent group required significantly more subsequent procedures than the surgical bypass group. Metal stent obstruction occurred in 16 of 39 (41 %) patients, with a median stent patency of 224 days. The overall median survival of patients in this study was 7 months with no significant difference between the groups (p = 0.992). The presence of metastases at presentation was the only independent factor associated with decreased survival. CONCLUSION: There was no survival difference between stenting vs. surgical bypass for palliation of periampullary cancer. There was, however, a high rate of stent occlusion and need for repeat procedures in patients treated by metal stenting, suggesting that stenting may be best suited to patients predicted as having the shortest survival.
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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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ItemNo Preview AvailableOutcomes of contemporary management of gangrenous and non-gangrenous acute cholecystitis(WILEY-BLACKWELL, 2011-08)BACKGROUND: Gangrenous cholecystitis (GC) is considered a more severe form of acute cholecystitis. The risk factors associated with this condition and its impact on morbidity and mortality compared with those of non-gangrenous acute cholecystitis (NGAC) are poorly defined and based largely on findings from older studies. METHODS: Patients with histologically confirmed acute cholecystitis treated in specialized units in a tertiary hospital between 2005 and 2010 were identified from a prospectively maintained database. Data were reviewed retrospectively and patients with GC were compared with those with NGAC. RESULTS: A total of 184 patients with NGAC and 106 with GC were identified. The risk factors associated with GC included older age (69 years vs. 57 years; P= 0.001), diabetes (19% vs. 10%; P= 0.049), temperature of >38 °C (36% vs. 16%; P < 0.001), tachycardia (31% vs. 15%; P= 0.002), detection of muscle rigidity on examination (27% vs. 12%; P= 0.01) and greater elevations in white cell count (WCC) (13.4 × 10⁹/l vs. 10.7 × 10⁹/l; P < 0.001), C-reactive protein (CRP) (94 mg/l vs. 17 mg/l; P= 0.001), bilirubin (19 µmol/l vs. 17 µmol/l; P= 0.029), urea (5.3 mmol/l vs. 4.7 mmol/l; P= 0.016) and creatinine (82 µmol/l vs. 74 µmol/l; P= 0.001). The time from admission to operation in days was greater in the GC group (median = 1 day, range: 0-14 days vs. median = 1 day, range: 0-10 days; P= 0.029). There was no overall difference in complication rates between the GC and NGAC groups (22% vs. 14%; P= 0.102). There was a lower incidence of common bile duct stones in the GC group (5% vs. 13%; P= 0.017). Gangrenous cholecystitis was associated with increased mortality (4% vs. 0%; P= 0.017), but this was not an independent risk factor on multivariate analysis. CONCLUSIONS: Gangrenous cholecystitis has certain clinical features and associated laboratory findings that may help to differentiate it from NGAC. It is not associated with an overall increase in complications when treated in a specialized unit.