T cell factor 1 (TCF-1) defines T cell differentiation in colorectal cancer.

The presence of precursor to exhausted (Tpex) CD8+ T cells is important to maintain robust immunity following treatment with immune checkpoint inhibition (ICI). Impressive responses to ICI are emerging in patients with stage II-III mismatch repair (MMR)-deficient (dMMR) colorectal cancer (CRC). We found 64% of dMMR and 15% of mismatch repair-proficient (pMMR) stage III CRCs had a high frequency of tumor infiltrating lymphocytes (TIL-hi). Furthermore, expression of TCF-1 (Tcf7) by CD8+ T cells predicted improved patient prognosis and Tpex cells (CD3+CD8+TCF-1+PD-1+) were abundant within lymphoid aggregates of stage III CRCs. In contrast, CD3+CD8+TCF-1-PD-1+ cells were more abundant at the invasive front and tumor core, while γδ T cells were equally abundant in all tumor areas. Interestingly, no differences in the frequency of Tpex cells were observed between TIL-hi dMMR and TIL-hi pMMR CRCs. Therefore, Tpex cell function and ICI response rates in TIL-hi CRC warrants further investigation.

The effect of an intraoperative patient-specific, surgery-specific haemodynamic algorithm in improving textbook outcomes for hepatobiliary-pancreatic surgery: a multicentre retrospective study.

Background: The concept of a "textbook outcome" is emerging as a metric for ideal surgical outcomes. We aimed to evaluate the impact of an advanced haemodynamic monitoring (AHDM) algorithm on achieving a textbook outcome in patients undergoing hepatobiliary-pancreatic surgery. Methods: This retrospective, multicentre observational study was conducted across private and public teaching sectors in Victoria, Australia. We studied patients managed by a patient-specific, surgery-specific haemodynamic algorithm or via usual care. The primary outcome was the effect of using a patient-specific, surgery-specific AHDM algorithm for achieving a textbook outcome, with adjustment using propensity score matching. The textbook outcome criteria were defined according to the International Expert Delphi Consensus on Defining Textbook Outcome in Liver Surgery and Nationwide Analysis of a Novel Quality Measure in Pancreatic Surgery. Results: Of the 780 weighted cases, 477 (61.2%, 95% CI: 57.7%-64.6%) achieved the textbook outcome. Patients in the AHDM group had a higher rate of textbook outcomes [n = 259 (67.8%)] than those in the Usual care group [n = 218 (54.8%); p < 0.001, estimated odds ratio (95% CI) 1.74 (1.30-2.33)]. The AHDM group had a lower rate of surgery-specific complications, severe complications, and a shorter hospital length of stay (LOS) [OR 2.34 (95% CI: 1.30-4.21), 1.79 (95% CI: 1.12-2.85), and 1.83 (95% CI: 1.35-2.46), respectively]. There was no significant difference between the groups for hospital readmission and mortality. Conclusions: AHDM use was associated with improved outcomes, supporting its integration in hepatobiliary-pancreatic surgery. Prospective trials are warranted to further evaluate the impact of this AHDM algorithm on achieving a textbook impact on long-term outcomes.

Venovenous bypass in adult liver transplant recipients: A single-center observational case series.

BACKGROUND: Very little information is currently available on the use and outcomes of venovenous bypass (VVB) in liver transplantation (LT) in adults in Australia. In this study, we explored the indications, intraoperative course, and postoperative outcomes of patients who underwent VVB in a high-volume LT unit. METHODS: The study was a single-center, retrospective observational case series of adult patients who underwent VVB during LT at Austin Health in Melbourne, Australia between March 2008 and March 2022. Information on baseline preoperative status and intraoperative variables, including specific VVB characteristics as well as postoperative and VVB-related complications was collected. The lengths of intensive care unit and hospital stays as well as intraoperative and in-hospital mortality were recorded. RESULTS: Of the 900 LTs performed at this center during the aforementioned 14-year period, 27 (3%) included a VVB procedure. VVB was performed electively in 16 of these 27 patients (59.3%) and as a rescue technique to control massive bleeding in the other 11 (40.1%). The median (interquartile range [IQR]) age of those who underwent VVB procedures was 48 (39-55) years; the median age was 56 (47-62) years in the non-VVB group (p<0.0001). The median model for end-stage liver disease (MELD) scores were similar between the two patient groups. Complete blood data was available for 622 non-VVB patients. Twenty-six VVB (96.3%) and 603 non-VVB (96.9%) patients required intraoperative blood transfusions. The median (IQR) number of units of packed red blood cells transfused was 7 (4.8-12.5) units in the VVB group compared to 3.0 units (1.0-6.0) in the non-VVB group (p<0.0001). Inpatient mortality was 18.5% and 1.1% for the VVB and non-VVB groups, respectively (p<0.0001). There were no significant differences in length of hospital stay or incidence of acute kidney injury, primary graft dysfunction, or long-term graft failure between the two groups. Patients in the VVB group experienced a higher rate of postoperative non-anastomotic biliary stricture compared to patients in the non-VVB group (33% and 7.9%, respectively; p = 0.0003). CONCLUSIONS: VVB continues to play a vital role in LT. This case series highlights the heightened risk of major complications linked to VVB. However, the global transition to selective use of VVB underscores the urgent need for collaborative multi-center studies designed to address outstanding questions and parameters related to the safe implementation of this procedure.

Renin-Angiotensin Inhibitor, Captopril, Attenuates Growth of Patient-Derived Colorectal Liver Metastasis Organoids.

The recurrence of colorectal liver metastasis (CRLM) following liver resection is common; approximately 40% of patients will experience tumor recurrence post-surgery. Renin-angiotensin inhibitors (RASis) have been shown to attenuate the growth and progression of CRLM in pre-clinical models following liver resection. This study examined the efficacy of the RASi captopril on patient-derived colorectal liver metastasis organoids. Patient-derived organoids (PDOs) were established using fresh samples of colorectal liver metastasis from appropriately consented patients undergoing liver resection. To mimic the regenerating liver post-CRLM liver resection, PDOs were cultured under hepatocyte regeneration conditions in vitro. CRLM PDOs were established from three patients' parent tissue. CRLM PDOs and parent tissue expressed markers of colorectal cancer, CDX2 and CK20, consistently. Furthermore, CRLM PDOs treated with captopril showed a dose dependent reduction in their expansion in vitro. In conclusion, CRLM PDOs recapitulate in vivo disease and displayed a dose-dependent response to treatment with captopril. RASis may be an additional viable treatment for patients with CRLM.

Graft-derived cfDNA Monitoring in Plasma and Bile During Normothermic Machine Perfusion in Liver Transplantation Is Feasible and a Potential Tool for Assessing Graft Viability.

BACKGROUND: Ex vivo normothermic machine perfusion (NMP) is an organ preservation technique that enables an extended assessment of graft suitability before liver transplantation (LT). Established monitoring protocols used during NMP vary significantly in their assessment of transplant suitability when applied to the same grafts. Graft-derived cell-free DNA (gdcfDNA) analysis is an emerging tool for monitoring graft health post-transplantation. We investigated the feasibility of monitoring gdcfDNA during NMP for LT in a proof-of-concept, observational study. METHODS: Serial plasma and bile samples were collected during NMP for 10 consecutive grafts, at 15 min post-machine reperfusion and then 2-h intervals. Digital polymerase chain reaction was used to quantify gdcfDNA at each time point. RESULTS: Five grafts were suitable for LT, there were no cases of primary nonfunction or death in the recipients. gdcfDNA was quantified in all bile and plasma samples (n > 100). In plasma, gdcfDNA concentrations climbed post-machine reperfusion until 4.25 h (median 2.25 h = 15.98 × 10 6 copies/mL, 4.25 h = 40.21 × 10 6 copies/mL). gdcfDNA levels then diverged significantly when comparing the viable and non-viable graft groups (6.25 h, median viable: 117.15 × 10 6 copies/mL versus non-viable: 16.72 × 10 6 copies/mL, P = 0.01). These opposing trends correlated in each graft and in all cases with the viable/non-viable outcome. There was a trend of gradual decline in bile gdcfDNA from viable grafts post-machine reperfusion; discarded grafts showed more variable patterns of release. CONCLUSIONS: gdcfDNA analysis during NMP is a feasible and potential tool to inform viability assessment during NMP for LT. Bile gdcfDNA monitoring offers the prospect of an objective means to assess the degree of biliary injury associated with organ procurement.

A novel two-stage approach to the treatment of renal cell carcinoma with intra-cardiac tumour extension and Budd-Chiari syndrome.

OBJECTIVE: To present the early results of a new technique for the treatment of renal cell carcinoma with intra-cardiac tumour extension and Budd-Chiari syndrome. PATIENTS AND METHODS: The first stage involves transdiaphragmatic debulking of the right heart, inferior vena cava (IVC) and hepatic veins via median sternotomy, followed by a purse-string suture placed in the IVC below the hepatic veins. The second stage is performed separately and involves en bloc resection of the affected kidney, and IVC and vascular reconstruction via an abdominal incision. RESULTS: Three of five patients presented with clinical Budd-Chiari syndrome; two had radiological features only. The median time between surgical procedures was 12 days (IQR 13 days). Four of the five patients had a R0 resection. While all five patients successfully completed both operative stages, one patient died 22 days after the second stage. Of the remaining four, all survive with no disease recurrence. CONCLUSION: While we continue to compile longer-term data for a larger follow-up series, these preliminary findings show the feasibility of this technique and support the development of this programme of surgery.

Evaluating treatment response following locoregional therapy for hepatocellular carcinoma: A review of the available serological and radiological tools for assessment.

Hepatocellular carcinoma (HCC) is an aggressive primary malignancy of the liver and is the third most common cause of cancer-related global mortality. There has been a steady increase in treatment options for HCC in recent years, including innovations in both curative and non-curative therapies. These advances have brought new challenges and necessary improvements in strategies of disease monitoring, to allow early detection of HCC recurrence. Current serological and radiological strategies for post-treatment monitoring and prognostication and their limitations will be discussed and evaluated in this review.

Assessment of Pre-Clinical Liver Models Based on Their Ability to Predict the Liver-Tropism of Adeno-Associated Virus Vectors.

The liver is a prime target for in vivo gene therapies using recombinant adeno-associated viral vectors. Multiple clinical trials have been undertaken for this target in the past 15 years; however, we are still to see market approval of the first liver-targeted adeno-associated virus (AAV)-based gene therapy. Inefficient expression of the therapeutic transgene, vector-induced liver toxicity and capsid, and/or transgene-mediated immune responses reported at high vector doses are the main challenges to date. One of the contributing factors to the insufficient clinical outcomes, despite highly encouraging preclinical data, is the lack of robust, biologically and clinically predictive preclinical models. To this end, this study reports findings of a functional evaluation of 6 AAV vectors in 12 preclinical models of the human liver, with the aim to uncover which combination of models is the most relevant for the identification of AAV capsid variant for safe and efficient transgene delivery to primary human hepatocytes. The results, generated by studies in models ranging from immortalized cells, iPSC-derived and primary hepatocytes, and primary human hepatic organoids to in vivo models, increased our understanding of the strengths and weaknesses of each system. This should allow the development of novel gene therapies targeting the human liver.

External Validation of the United Kingdom Transplant Benefit Score in Australia and New Zealand.

Introduction: In Australia and New Zealand, liver allocation is needs based (based on model for end-stage liver disease score). An alternative allocation system is a transplant benefit-based model. Transplant benefit is quantified by complex waitlist and transplant survival prediction models. Research Questions: To validate the UK transplant benefit score in an Australia and New Zealand population. Design: This study analyzed data on listings and transplants for chronic liver disease between 2009 and 2018, using the Australia and New Zealand Liver and Intestinal Transplant Registry. Excluded were variant syndromes, hepatocellular cancer, urgent listings, pediatric, living donor, and multi-organ listings and transplants. UK transplant benefit waitlist and transplant benefit score were calculated for listings and transplants, respectively. Outcomes were time to waitlist death and time to transplant failure. Calibration and discrimination were assessed with Kaplan-Meier analysis and C-statistics. Results: There were differences in the UK and Australia and New Zealand listing, transplant, and donor populations including older recipient age, higher recipient and donor body mass index, and higher incidence of hepatitis C in the Australia and New Zealand population. Waitlist scores were calculated for 2241 patients and transplant scores were calculated for 1755 patients. The waitlist model C-statistic at 5 years was 0.70 and the transplant model C-statistic was 0.56, with poor calibration of both models. Conclusion: The UK transplant benefit score model performed poorly, suggesting that UK benefit-based allocation would not improve overall outcomes in Australia and New Zealand. Generalizability of survival prediction models was limited by differences in transplant populations and practices.

Endoscopy training in Australia during COVID-19: Efficacy and knowledge assessment of gastroenterology and general surgery trainees.

Background and Aim: During COVID-19, restrictions to elective endoscopy were introduced worldwide. A reduction in procedures may impact trainees' endoscopy learning. This study aims to assess Australian advanced gastroenterology and general surgery trainees' self-perceived efficacy and knowledge in endoscopy during the pandemic. Methods: All Australian gastroenterology and general surgery trainees in their last 2 years of accredited training were invited to participate through email (2020-2021 and 2021-2022 training cycles). The primary outcome was to assess trainees' self-efficacy and knowledge regarding gastrointestinal endoscopy. Secondary outcomes included subgroup analysis between gastroenterology and general surgery trainees. Self-perceived efficacy was assessed with Likert-scale questions on 20 endoscopy procedures and knowledge was assessed through 21 endoscopy-related multiple choice questions. Results: Eighty-one trainees responded to a self-efficacy questionnaire and 77 responded to the knowledge questionnaire. Over 90% of the trainees were confident or extremely confident in diagnostic endoscopy, but only half demonstrated similar efficacy for therapeutic endoscopy. The efficacy for basic endoscopy procedures was higher for gastroenterology trainees (64.0% vs 51.1%, P < 0.001). Last-year trainee achievement of conjoint committee requirements for upper gastrointestinal endoscopy was achieved in 95.8% of gastroenterology trainees versus 22.2% of surgical trainees (P < 0.001). The median score on the knowledge questionnaire was also higher for the gastroenterology subset (90.5% vs 71.4%, P < 0.001). Conclusion: During COVID-19, endoscopy trainees' self-efficacy in endoscopic diagnostic procedures was achieved for most trainees. The differences in self-perceived efficacy and knowledge between gastroenterology and surgical trainees may be reflective of the different opportunities for learning between the two groups.

A systematic review and network meta-analysis of outcomes after open, mini-laparotomy, hybrid, totally laparoscopic, and robotic living donor right hepatectomy.

BACKGROUND: A systematic review and network meta-analysis was performed to compare outcomes after living donor right hepatectomy via the following techniques: conventional open (Open), mini-laparotomy (Minilap), hybrid (Hybrid), totally laparoscopic (Lap), and robotic living donor right hepatectomy (Robotic). METHODS: PubMed, EMBASE, Cochrane, and Scopus were searched from inception to August 2021 for comparative studies of patients who underwent living donor right hepatectomy. RESULTS: Nineteen studies comprising 2,261 patients were included. Operation time was longer in Lap versus Minilap and Open (mean difference 65.09 min, 95% confidence interval 3.40-126.78 and mean difference 34.81 minutes, 95% confidence interval 1.84-67.78), and in Robotic versus Hybrid, Lap, Minilap, and Open (mean difference 144.72 minutes, 95% confidence interval 89.84-199.59, mean difference 113.24 minutes, 95% confidence interval 53.28-173.20, mean difference 178.33 minutes, 95% confidence interval 105.58-251.08 and mean difference 148.05 minutes, 95% confidence interval 97.35-198.74, respectively). Minilap and Open were associated with higher blood loss compared to Lap (mean difference 258.67 mL, 95% confidence interval 107.00-410.33 and mean difference 314.11 mL, 95% confidence interval 143.84-484.37) and Robotic (mean difference 205.60 mL, 95% confidence interval 45.92-365.28 and mean difference 261.04 mL, 95% confidence interval 84.26-437.82). Open was associated with more overall complications compared to Minilap (odds ratio 2.60, 95% confidence interval 1.11-6.08). Recipient biliary complication rate was higher in Minilap and Open versus Hybrid (odds ratio 3.91, 95% confidence interval 1.13-13.55 and odds ratio 11.42, 95% confidence interval 2.27-57.49), and lower in Open versus Minilap (OR 0.07, 95% confidence interval 0.01-0.34). CONCLUSION: Minimally invasive donor right hepatectomy via the various techniques is safe and feasible when performed in high-volume centers, with no major differences in donor complication rates and comparable recipient outcomes once surgeons have mounted the learning curve.

SAR131675, a VEGRF3 Inhibitor, Modulates the Immune Response and Reduces the Growth of Colorectal Cancer Liver Metastasis.

Most patients with colorectal cancer (CRC) develop metastases, predominantly in the liver (CLM). Targeted therapies are being investigated to improve current CLM treatments. This study tested the effectiveness of SAR131675, a selective VEGFR-3 tyrosine kinase inhibitor, to inhibit CLM in a murine model. Following intrasplenic induction of CLM, mice were treated daily with SAR131675. Tumor growth and immune infiltrates into tumor and liver tissues were assessed at 10-, 16- and 22-days post tumor induction by stereology, IHC and flow cytometry. SAR151675 treatment significantly reduced tumor burden and F4/80+ macrophages in the liver tissues. Analysis of immune cell infiltrates in liver showed tissue that at day 22, had the proportion of CD45+ leukocytes significantly reduced, particularly myeloid cells. Analysis of myeloid cells (CD11b+ CD45+) indicated that the proportion of F4/80- Ly6Clow was significantly reduced, including a predominate PD-L1+ subset, while CD3+ T cells increased, particularly CD8+ PD1+, reflected by an increase in the CD8+:CD4+ T cell ratio. In the tumor tissue SAR11675 treatment reduced the predominant population of F4/80+ Ly6Clo and increased CD4+ T cells. These results suggest that SAR131675 alters the immune composition within tumor and the surrounding liver in the later stages of development, resulting in a less immunosuppressive environment. This immunomodulation effect may contribute to the suppression of tumor growth.

The Association of Postoperative Complications and Hospital Costs Following Distal Pancreatectomy.

Background: Understanding the financial implications associated with the complications post-distal pancreatectomy (DP) may be beneficial for the future optimisation of postoperative care pathways and improved cost-efficiency. The primary outcome of this retrospective study was the characterisation of the additional cost associated with postoperative complications following DP. The secondary outcome was the estimation of the prevalence, type and severity of complications post-DP and the determination of which complications were associated with higher costs. Methods: Postoperative complications were retrospectively examined for 62 adult patients undergoing distal pancreatectomy at an Australian university hospital between January 2012 and July 2021. Complications were defined and graded using the Clavien-Dindo (CVD) classification system. In-hospital cost of index admission was calculated using an activity-based costing methodology and was reported in US dollars at 2021 rates. Regression modelling was used to investigate the relationships among selected perioperative variables, complications and costs. Results: 45 patients (72.6%) experienced one or more postoperative complications. The median (IQR) hospital cost in US dollars was 31.6% greater in patients who experienced complications compared to those who experienced no complications ($40,717.8 [27,358.0-59,834.3] vs. $30,946.9 [23,910.8-46,828.1]). Costs for patients with four or more complications were 43.5% higher than for those with three or fewer complications (p = 0.015). Compared to patients with no complications, the median hospital costs increased by 17.1% in patients with minor complications (CVD grade I/II) and by 252% in patients who developed major complication (i.e., CVD grade III/IV) complications. Conclusion: Postoperative complications are a key target for cost-containment strategies. Our findings demonstrate a high prevalence of postoperative complications following distal pancreatectomy with number and severity of postoperative complications being associated with increased hospital costs. (Registered in the Australian New Zealand Clinical Trials Registry [No. ACTRN12622000202763]).

Captopril, a Renin-Angiotensin System Inhibitor, Attenuates Tumour Progression in the Regenerating Liver Following Partial Hepatectomy.

(1) Liver regeneration following partial hepatectomy for colorectal liver metastasis (CRLM) has been linked to tumour recurrence. Inhibition of the renin−angiotensin system (RASi) attenuates CRLM growth in the non-regenerating liver. This study investigates whether RASi exerts an antitumour effect within the regenerating liver following partial hepatectomy for CRLM and examines RASi-induced changes in the tumour immune microenvironment; (2) CRLM in mice was induced via intrasplenic injection of mouse colorectal tumour cells, followed by splenectomy on Day 0. Mice were treated with RASi captopril (250 mg/kg/day), or saline (control) from Day 4 to Day 16 (endpoint) and underwent 70% partial hepatectomy on Day 7. Liver and tumour samples were characterised by flow cytometry and immunofluorescence; (3) captopril treatment reduced tumour burden in mice following partial hepatectomy (p < 0.01). Captopril treatment reduced populations of myeloid-derived suppressor cells (MDSCs) (CD11b+Ly6CHi p < 0.05, CD11b+Ly6CLo p < 0.01) and increased PD-1 expression on infiltrating hepatic tissue-resident memory (TRM)-like CD8+ (p < 0.001) and double-negative (CD4-CD8-; p < 0.001) T cells; (4) RASi reduced CRLM growth in the regenerating liver and altered immune cell composition by reducing populations of immunosuppressive MDSCs and boosting populations of PD-1+ hepatic TRMs. Thus, RASi should be explored as an adjunct therapy for patients undergoing partial hepatectomy for CRLM.

Preliminary experience with continuous right ventricular pressure and transesophageal echocardiography monitoring in orthotopic liver transplantation.

BACKGROUND: Despite increasing attention in the cardiac anesthesiology literature, continuous measurement of right ventricular pressure using a pulmonary artery catheter has not been described in orthotopic liver transplantation, despite similarities in the anesthetic approach to the two populations. We describe our preliminary experience with this technique in orthotopic liver transplantation, and by combining various derived measures with trans-esophageal echocardiography, make some early observations regarding the response of these measures of right ventricular function during the procedure. METHODS: In this case series, ten patients (five men and five women) undergoing orthotopic liver transplantation in our institution had their surgeries performed while monitored with a pulmonary artery catheter with continuous right ventricular port transduction and trans-esophageal echocardiography. We recorded various right ventricular waveform (early-to-end diastolic pressure difference, right ventricular outflow tract gradient, right ventricular dP/dT and right ventricular end-diastolic pressure) and echocardiographic (right ventricular fractional area change, tricuspid annular plane systolic excursion, right ventricular lateral wall strain) and described their change relative to baseline at timepoints five minutes before and after portal vein reperfusion, immediately after hepatic artery reperfusion and on abdominal closure. RESULTS: Except for tricuspid annular plane systolic excursion at five minutes prior to reperfusion (mean -0.8 cm; 95% CI-1.4, -0.3; p = 0.007), no echocardiographic metric was statistically significantly different at any timepoint relative to baseline. In contrast, changes in right ventricular outflow tract gradient and right ventricular dP/dt were highly significant at multiple timepoints, generally peaking immediately before or after reperfusion before reducing, but not returning to baseline in the neohepatic phase. Nine of 10 participants in this series demonstrated a degree of dynamic right ventricular outflow tract obstruction, which met criteria for hemodynamic significance (> 25 mmHg) in two participants. These changes were not materially affected by cardiac index. CONCLUSIONS: Dynamic right ventricular outflow tract obstruction of varying severity appears common in patients undergoing orthotopic liver transplantation. These results are hypothesis generating and will form the basis of future prospective research.

Hepatectomy after bile duct injury: a systematic review.

BACKGROUND: Bile duct injury (BDI) after cholecystectomy can lead to recurrent cholangitis, even after biliary reconstruction. This necessitates hepatectomy in a minority of patients. A systematic review was conducted, summarizing the pattern of biliary injury sustained in this group and their outcomes after hepatectomy. METHODS: A literature search included the MEDLINE, EMBASE, PubMed and Cochrane libraries. Retrospective cohort studies describing outcomes for hepatectomy after BDI, and the nature of the antecedent BDI, published between 1999 and 2019, were selected. RESULTS: Eight articles described a cohort of 2110 patients with BDI. Of these, 84 underwent hepatectomy. Complex vasculo-biliary injuries had been sustained in most cases. The mean time to hepatectomy was between 26 and 224 months after BDI. A right hepatectomy was performed in 67-89% of cases. Post hepatectomy, intra-abdominal infection (range 0-50%) and bile leaks (range 0-45%) occurred variably. Mortality occurred in three series. Nineteen percent of patients (16 of 84) developed recurrent symptoms at follow up. CONCLUSION: Hepatectomy after bile duct injury is an uncommon procedure and represents a salvage strategy when vasculo-biliary injury happens. Liver resection leads to resolution of symptoms in the majority of the cases however postoperative bile leaks and intra-abdominal infection are common.

Reduction in post-operative pancreatic fistula with polyethylene glycol and recombinant human albumin sealant following stapled distal pancreatectomy.

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.

Elevated levels of circulating mitochondrial DNA predict early allograft dysfunction in patients following liver transplantation.

BACKGROUND AND AIM: The role of circulating mitochondrial DNA (cmtDNA) in transplantation remains to be elucidated. cmtDNA may be released into the circulation as a consequence of liver injury; yet recent work also suggests a causative role for cmtDNA leading to hepatocellular injury. We hypothesized that elevated cmtDNA would be associated with adverse events after liver transplantation (LT) and conducted an observational cohort study. METHODS: Twenty-one patients were enrolled prospectively prior to LT. RESULTS: Postoperative complications were observed in 47.6% (n = 10). Seven patients (33.3%) had early allograft dysfunction (EAD), and six patients (28.5%) experienced acute cellular rejection within 6 months of LT. cmtDNA levels were significantly elevated in all recipients after LT compared with healthy controls and preoperative samples (1 361 937 copies/mL [IQR 586 781-3 399 687] after LT; 545 531 copies/mL [IQR 238 562-1 381 015] before LT; and 194 562 copies/mL [IQR 182 359-231 515] in healthy controls) and returned to normal levels by 5 days after transplantation. cmtDNA levels were particularly elevated in those who developed EAD in the early postoperative period (P < 0.001). In all patients, there was initially a strong overall positive correlation between cmtDNA and plasma hepatocellular enzyme levels (P < 0.05). However, the patients with EAD demonstrated a second peak in cmtDNA at postoperative day 7, which did not correlate with liver function tests. CONCLUSIONS: The early release of plasma cmtDNA is strongly associated with hepatocellular damage; however, the late surge in cmtDNA in patients with EAD appeared to be independent of hepatocellular injury as measured by conventional tests.