Bile duct regeneration is hypothesized to prevent biliary strictures, a leading cause of morbidity after liver transplantation. Assessing the capacity for biliary regeneration may identify grafts as suitable for transplantation that are currently declined, but this has been unfeasible until now. This study used long-term ex situ normothermic machine perfusion (LT-NMP) to assess biliary regeneration. Human livers that were declined for transplantation were perfused at 36 °C for up to 13.5 days. Bile duct biopsies, bile, and perfusate were collected throughout perfusion, which were examined for features of injury and regeneration. Biliary regeneration was defined as new Ki-67-positive biliary epithelium following severe injury. Ten livers were perfused for a median duration of 7.5 days. Severe bile duct injury occurred in all grafts, and biliary regeneration occurred in 70% of grafts. Traditional biomarkers of biliary viability such as bile glucose improved during perfusion but this was not associated with biliary regeneration (P > .05). In contrast, the maintenance of interleukin-6 and vascular endothelial growth factor-A levels in bile was associated with biliary regeneration (P = .017 for both cytokines). This is the first study to demonstrate biliary regeneration during LT-NMP and identify a cytokine signature in bile as a novel biomarker for biliary regeneration during LT-NMP.

Abstract Background Pelvic exenteration (PE) is a radical procedure involving multi-visceral resection for locally advanced pelvic malignancies. Such radical surgery is associated with prolonged operating theater time and hospital stay, as well as a substantial risk of postoperative complications, and therefore significant financial cost. This study aimed to comprehensively detail the inpatient cost of PE at a specialist center in the Australian public sector. Methods A retrospective costing review of consecutive PE operations at Royal Prince Alfred Hospital in Sydney between March 2014 and June 2022 was performed. Clinical data were extracted from a prospectively maintained database, and in-hospital costing data were provided by the hospital Performance Unit. All statistical analyses were performed using SPSS. Results Pelvic exenteration was performed for 461 patients, of whom 283 (61 %) had primary or recurrent rectal cancer, 160 (35 %) had primary or recurrent non-rectal cancer, and 18 (4 %) had a benign indication. The median admission cost was $108,259.4 ($86,620.8–$144,429.3) (Australian dollars [AUD]), with the highest costs for staffing followed by the operating room. Overall, admission costs were higher for complete PE (p < 0.001), PE combined with cytoreductive surgery (CRS) (p < 0.001), and older patients (p = 0.006). Discussion The total admission cost for patients undergoing PE reflects the complexity of the procedure and the multidisciplinary requirement. Patients of advanced age undergoing complete PE and PE combined with CRS incurred greater costs, but the requirement of a sacrectomy, vertical rectus abdominal flap reconstruction, major nerve or vascular excision, or repair were not associated with higher overall cost in the multivariate analysis.

Hypothermic Oxygenated machine PErfusion (HOPE) has recently emerged as a preservation technique which can reduce ischemic injury and improve clinical outcomes following liver transplantation. First developed with the advent solid organ transplantation techniques, hypothermic machine perfusion largely fell out of favour following the development of preservation solutions which can satisfactorily preserve grafts using the cheap and simple method, static cold storage (SCS). However, with an increasing need to develop techniques to reduce graft injury and better utilise marginal and donation after circulatory death (DCD) grafts, HOPE has emerged as a relatively simple and safe technique to optimise clinical outcomes following liver transplantation. Perfusing the graft with cold, acellular, oxygenated perfusate either via the portal vein (PV) alone, or via both the PV and hepatic artery (HA), HOPE is generally commenced for a period of 1-2 h immediately prior to implantation. The technique has been validated by multiple randomised control trials, and pre-clinical evidence suggests HOPE primarily reduces graft injury by decreasing the accumulation of harmful mitochondrial intermediates, and subsequently, the severity of post-reperfusion injury. HOPE can also facilitate real time graft assessment, most notably via the measurement of flavin mononucleotide (FMN) in the perfusate, allowing transplant teams to make better informed clinical decisions prior to transplantation. HOPE may also provide a platform to administer novel therapeutic agents to ex situ organs without risk of systemic side effects. As such, HOPE is uniquely positioned to revolutionise how liver transplantation is approached and facilitate optimised clinical outcomes for liver transplant recipients.

There is a paucity of research investigating revision surgery for patients with previous inferior vena cava (IVC) reconstruction using bovine pericardium (BP). To the best of our knowledge, no reports of redo procedures have been published in the medical literature. We describe two cases of redo surgery in patients with previous IVC reconstructions using BP following disease recurrence. The first case underwent resection of the BP graft with a second IVC reconstruction using BP, the second case underwent resection of the BP graft without reconstruction due to extensive thromboses. Neither case experienced perioperative complication or morbidity following their redo procedure, and previous IVC reconstruction with BP did not present significant intraoperative technical challenges. One case showed evidence of endothelialisation of the excised BP graft, however, it was not possible to definitively conclude if endothelialisation was present in the second case. Overall, these cases demonstrate that previous IVC reconstruction using BP should not be considered an absolute contraindication for redo surgery in the context of disease recurrence.

BACKGROUND:Pelvic exenteration (PE) is a radical procedure involving multi-visceral resection for locally advanced pelvic malignancies. Such radical surgery is associated with prolonged operating theater time and hospital stay, as well as a substantial risk of postoperative complications, and therefore significant financial cost. This study aimed to comprehensively detail the inpatient cost of PE at a specialist center in the Australian public sector. METHODS:A retrospective costing review of consecutive PE operations at Royal Prince Alfred Hospital in Sydney between March 2014 and June 2022 was performed. Clinical data were extracted from a prospectively maintained database, and in-hospital costing data were provided by the hospital Performance Unit. All statistical analyses were performed using SPSS. RESULTS:Pelvic exenteration was performed for 461 patients, of whom 283 (61 %) had primary or recurrent rectal cancer, 160 (35 %) had primary or recurrent non-rectal cancer, and 18 (4 %) had a benign indication. The median admission cost was $108,259.4 ($86,620.8-$144,429.3) (Australian dollars [AUD]), with the highest costs for staffing followed by the operating room. Overall, admission costs were higher for complete PE (p < 0.001), PE combined with cytoreductive surgery (CRS) (p < 0.001), and older patients (p = 0.006). DISCUSSION:The total admission cost for patients undergoing PE reflects the complexity of the procedure and the multidisciplinary requirement. Patients of advanced age undergoing complete PE and PE combined with CRS incurred greater costs, but the requirement of a sacrectomy, vertical rectus abdominal flap reconstruction, major nerve or vascular excision, or repair were not associated with higher overall cost in the multivariate analysis.

BACKGROUND:Hypothermic Oxygenated machine PErfusion (HOPE) can reduce ischemic reperfusion injury and improve outcomes for liver transplant recipients. However, the effect of HOPE on high-risk extended criteria donor (ECD) and donation after circulatory death determination (DCDD) grafts is incomplete, despite the expectation that this cohort benefit maximally from HOPE. Accordingly, this paper aims to characterize the effect of HOPE on ECD and DCDD grafts. METHODS:This study includes all papers comparing HOPE to static cold storage for high-risk ECD and DCDD grafts. Systematic searches of Medline, Embase, and Scopus were completed using the terms "HOPE" OR "hypothermic oxygenated machine perfusion" AND "liver transplantation". Data were extracted and analyzed using IBM SPSS to perform the meta-analysis. RESULTS:A total of 2286 records were identified, with 10 meeting the inclusion criteria. Overall, the quality of evidence is heterogenous with many papers relying on retrospective controls. However, pooled analysis demonstrates HOPE to significantly reduce the rate of early allograft dysfunction, 12-month graft failure, re-transplantation, total biliary complications, and non-anastomotic strictures for high-risk grafts. CONCLUSIONS:There is good evidence that HOPE improves outcomes following liver transplantation across a number of biochemical and clinical endpoints for high-risk grafts. Of note, the reduction in biliary complications and re-transplantation is particularly significant given the morbidity associated with these endpoints. However, further, high-quality prospective trials with contemporary controls and clinically relevant primary endpoints are needed to better define the impact of HOPE for this cohort of grafts.

AimLynch syndrome is an inherited cancer syndrome associated with an increased lifetime risk of colorectal cancer (CRC) and characterized by germline mutations to one of four DNA mismatch repair (MMR) genes. Immunohistochemical (IHC) testing is used to screen for Lynch syndrome; however, despite routine completion following resection of primary CRC, it is only variably completed following resection of recurrent disease. This may be significant, as MMR protein expression can change from primary to recurrent CRC. The primary aim of this study is to investigate how MMR profiles change from primary to recurrent CRC; the secondary aim is to assess rates of MMR testing of primary and recurrent disease. MethodWe conducted a retrospective analysis of patients undergoing surgery for recurrent CRC from 2018-19 at a high-volume institution. MMR profiles were obtained following both primary and recurrent resection of CRC, and MMR protein expression was evaluated from both time points. ResultsA total of 107 patients met the inclusion criteria and IHC results were obtained for both primary and recurrent resections in 85 cases. MMR profiles changed in nine patients (10.6%), with a loss of staining from primary to recurrent disease in six (7.1%) and a gain of staining in three (3.5%). IHC testing was completed following 88.7% of primary and 39.3% of recurrent resections. ConclusionMMR profiles can change from primary to recurrent CRC and repeat MMR testing for recurrent CRC is completed in only a minority of cases.

Background: Chronic fistulating pelvic sepsis is an uncommon complication of multimodal treatment of visceral pelvic tumours. Radical multi-visceral resection is reserved for patients with persistent, debilitating symptoms despite less invasive treatments and for which there is minimal published data. This study aimed to report the rates of morbidity and long-term sepsis control after pelvic exenteration for chronic fistulating pelvic sepsis.Methods: This retrospective cohort study was conducted at a high-volume pelvic exenteration referral centre. Patients who underwent pelvic exenteration for chronic fistulating pelvic sepsis between September 1994 and January 2023 after previous treatment for pelvic malignancy were included. Data relating to postoperative morbidity, mortality and the rate of recurrent pelvic sepsis or fistulae were retrospectively collected.Results: 19 patients who underwent radical resection for chronic fistulating pelvic sepsis after previous pelvic cancer treatment were included. 11 patients were male (58 %) and median age was 62 years (range 42-79). Previously treated rectal (8 patients, 42 %), prostate (5, 26 %) and cervical cancer (5, 26 %) were most common. 18 patients (95 %) had previously received high-dose pelvic radiotherapy, and 14 (74 %) had required surgical resection. Total pelvic exenteration was performed in 47 % of patients, total cystectomy in 68 % and major pubic bone resection in 37 %. There was no intraoperative or postoperative mortality. Major complication rate was 32 %. 12-month readmission rate was 42 %. At last follow up, 74 % had no signs or symptoms of persisting pelvic sepsis.Conclusions: Pelvic exenteration for refractory pelvic sepsis following treatment of malignancy is safe and effective in selected patients.

Introduction Pelvic exenteration (PE) is an ultra-radical procedure performed for primary or recurrent malignancies confined to the pelvis. Health outcomes for rural Australian populations are generally inferior compared to those from metropolitan centres, however, the effect of geographical location on outcomes following PE is poorly defined. The aim of this study was to investigate how geographical location affects oncological, quality of life (QoL) and survival outcomes following PE. Methods Consecutive patients undergoing PE between 1994 and 2022 at a single centre were included. Patient post codes were linked with the Australian Statistical Geography Standard Remoteness Structure to stratify patients into five groups based on the geographical location of their residence. Primary outcome measures included patient survival, QoL and oncological outcomes. Results A total of 953 patients were included, of which 626 (65.7%) were from major cities, 227 (23.8%) inner regional, 84 (8.8%) outer regional, 9 (0.9%) remote, and 7 (0.7%) very remote areas. Rural patients were more likely to undergo PE for primary rectal cancer (p = 002) and less likely for recurrent, non-rectal carcinoma (p = 0.027). Rural patients less frequently had health insurance (p < 0.001) but were more likely to have undergone neoadjuvant radiotherapy (p = 0.022). No difference in length-of-admission, in-hospital complication rates, QoL at 36 months or survival was observed between groups. Conclusions Despite geographical disparities, rural populations undergoing PE achieved equally favourable outcomes as populations from metropolitan areas. Enhancing access to specialised care may facilitate better outcomes of patients residing in regional and remote areas.

Background: Liver transplantation is a lifesaving procedure for patients with end-stage liver disease (ESLD). However, many patients never receive a transplant due to insufficient donor supply. Historically, organs have been preserved using static cold storage (SCS). However, recently, ex vivo normothermic machine perfusion (NMP) has emerged as an alternative technique. This paper aims to investigate the clinical progress of NMP in humans. Methods: Papers evaluating the clinical outcomes of NMP for liver transplantation in humans were included. Lab-based studies, case reports, and papers utilizing animal models were excluded. Literature searches of MEDLINE and SCOPUS were conducted. The revised Cochrane risk-of-bias tool for randomised trials (RoB 2) and the risk of bias in nonrandomised studies for interventions (ROBINS-I) tools were used. Due to the heterogeneity of the included papers, a meta-analysis was unable to be completed. Results: In total, 606 records were identified, with 25 meeting the inclusion criteria; 16 papers evaluated early allograft dysfunction (EAD) with some evidence for lower rates using NMP compared to SCS; 19 papers evaluated patient or graft survival, with no evidence to suggest superior outcomes with either NMP or SCS; 10 papers evaluated utilization of marginal and donor after circulatory death (DCD) grafts, with good evidence to suggest NMP is superior to SCS. Conclusions: There is good evidence to suggest that NMP is safe and that it likely affords clinical advantages to SCS. The weight of evidence supporting NMP is growing, and this review found the strongest evidence in support of NMP to be its capacity to increase the utilization rates of marginal and DCD allografts.