Return of the cold: How hypothermic oxygenated machine perfusion is changing liver transplantation.

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.

Revision Surgery is Possible in Patients With Previous Bovine Pericardium Inferior Vena Cava Reconstruction: A Case Series and Review of Literature.

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.

Pelvic exenteration for chronic fistulating pelvic sepsis after multimodal treatment of pelvic malignancy.

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.

Impact of geographical health disparities on outcomes following pelvic exenteration at a centralised quaternary referral centre.

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.

Normothermic Ex Vivo Machine Perfusion for Liver Transplantation: A Systematic Review of Progress in Humans.

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.

Patterns of DNA mismatch repair protein expression for primary and recurrent colorectal cancer at an advanced surgical unit: A retrospective audit.

AIM: Lynch 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. METHOD: We 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. RESULTS: A 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. CONCLUSION: MMR profiles can change from primary to recurrent CRC and repeat MMR testing for recurrent CRC is completed in only a minority of cases.