Charles J. Imber

Advantages of normothermic perfusion over cold storage in liver preservation.

Background. To minimize the ischemia-reperfusion injury that occurs to the liver with the current method of preservation and transplantation, we have used an extracorporeal circuit to preserve the liver with normothermic, oxygenated, sanguineous perfusion. In this study, we directly compared preservation by the standard method of simple cold storage in University of Wisconsin (UW) solution with preservation by perfusion. Methods. Porcine livers were harvested from large white sows weighing between 30 and 50 kg by the standard procedure for human retrieval. The livers were preserved for 24 hr by either cold storage in UW solution (n=5) or by perfusion with oxygenated autologous blood at body temperature (n=5). The extracorporeal circuit used included a centrifugal pump, heat exchanger, and oxygenator. Both groups were then tested on the circuit for a 24 hr reperfusion phase, analyzing synthetic function, metabolic capacity, hemodynamics, markers of hepatocyte and reperfusion injury, and histology. Results. Livers preserved with normothermic perfusion were significantly superior (P =0.05) to cold-stored livers in terms of bile production, factor V production, glucose metabolism, and galactose clearance. Cold-stored livers showed significantly higher levels of hepatocellular enzymes in the perfusate and were found to have significantly more damage by a blinded histological scoring system. Conclusions. Normothermic sanguineous oxygenated perfusion is a superior method of preservation compared with simple cold storage in UW solution. In addition, perfusion allows the possibility to assess viability of the graft before transplantation.

Portal Vein Resection in Borderline Resectable Pancreatic Cancer: A United Kingdom Multicenter Study

BACKGROUNDnUntil recently, in the United Kingdom, borderline resectable pancreatic cancer with invasion into the portomesenteric veins often resulted in surgical bypass because of the presumed high risk for complications and the uncertainty of a survival benefit associated with a vascular resection. Portomesenteric vein resection has therefore remained controversial. We present the second largest published cohort of patients undergoing portal vein resection for borderline resectable (T3) adenocarcinoma of the head of the pancreas.nnnSTUDY DESIGNnThis is a UK multicenter retrospective cohort study comparing pancreaticoduodenectomy with vein resection (PDVR), standard pancreaticoduodenectomy (PD), and surgical bypass (SB). Nine high-volume UK centers contributed. All consecutive patients with T3 (stage IIA to III) adenocarcinoma of the head of the pancreas undergoing surgery between December 1998 and June 2011 were included. The primary outcomes measures are overall survival and in-hospital mortality. Secondary outcomes measure is operative morbidity.nnnRESULTSnOne thousand five hundred and eighty-eight patients underwent surgery for borderline resectable pancreatic cancer; 840 PD, 230 PDVR, and 518 SB. Of 230 PDVR patients, 129 had primary closure (56%), 65 had end to end anastomosis (28%), and 36 had interposition grafts (16%). Both resection groups had greater complication rates than the bypass group, but with no difference between PD and PDVR. In-hospital mortality was similar across all 3 surgical groups. Median survival was 18 months for PD, 18.2 months for PDVR, and 8 months for SB (p = 0.0001).nnnCONCLUSIONSnThis study, the second largest to date on borderline resectable pancreatic cancer, demonstrates no significant difference in perioperative mortality in the 3 groups and a similar overall survival between PD and PDVR; significantly better compared with SB.

A simple scoring system to evaluate the effects of cold ischemia on marginal liver donors

Background. Exactly what constitutes a marginal donor remains ill defined. The authors set out to create a scoring system that objectively classifies a donor as marginal or nonmarginal and to define what the maximum acceptable preservation period is for the marginal liver to minimize early graft dysfunction. Methods. The authors performed an analysis on data collected prospectively of 397 cadaveric liver transplants. Both univariate and multivariate analyses were performed on donor, recipient, and perioperative factors with relation to early allograft dysfunction. A score was developed that classified donors into marginal and nonmarginal populations, and the influence of cold ischemia was determined for each group. Results. Multivariate analysis-determined donor age and steatosis (moderate to severe) were independent predictors of deranged function. This enabled the authors to produce a scoring system to differentiate marginal donors with respect to risk of early allograft dysfunction as follows: Formula=(20.06×steatosis)+ (0.44×donor age), cutoff 23.1. In the marginal group, the cutoff value of cold ischemia time was 12.6 hr. Conclusions. The authors developed a scoring system that classified an organ as marginal or nonmarginal depending on the donor age and degree of steatosis. Marginal livers have a strong risk of developing early allograft dysfunction with increasing cold ischemia times and should be transplanted within 12 hr. Cold ischemia time was not found to be an important factor in the development of early allograft dysfunction in nonmarginal donors.

Optimisation of bile production during normothermic preservation of porcine livers.

Machine perfusion of livers may provide a mechanism for extended preservation of marginal donor organs before transplantation, as well as a method for viability assessment. It has proved possible in a series of experimental porcine liver perfusions to maintain liver viability for up to 72u2003h. However, a reduction in bile production with associated histological evidence of cholestasis was seen after 10u2003h of perfusion, damaging the biliary canaliculi during the preservation period and leaving these organs in an unacceptable condition for transplantation.

A randomized trial of normothermic preservation in liver transplantation

Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time. There was no significant difference in bile duct complications, graft survival or survival of the patient. If translated to clinical practice, these results would have a major impact on liver transplant outcomes and waiting list mortality.Normothermic machine perfusion of the liver improved early graft function, demonstrated by reduced peak serum aspartate transaminase levels and early allograft dysfunction rates, and improved organ utilization and preservation times, although no differences were seen in graft or patient survival.

Hepatic control of perfusate homeostasis during normothermic extrocorporeal preservation.

BACKGROUNDnWe investigated the ability of the isolated porcine liver to maintain acid-base homeostasis in the perfusate and the impact of ischemia-reperfusion injury without or with extracorporeal perfusion.nnnMETHODSnHarvested livers were either stored for 24 hours in cold University of Wisconsin solution or preserved by continuous, normothermic, oxygenated sanguineous perfusion with supplemental nutrition, prostacyclin, and bile salts. After a further 24-hour period of reperfusion of both groups on an extracorporeal circuit, the perfusate was assessed for both biochemical indices of synthetic and metabolic liver function as well as hepatocellular injury and blood gas analysis.nnnRESULTSnLivers injured by cold ischemia during preservation displayed inferior synthetic and metabolic functions. Perfused livers, which displayed minimal ischemic injury, produced more bicarbonate than the cold-stored organs, suggesting autoregulation of pH homeostasis in perfused livers in contrast to progressively worsening acidosis in cold-stored organs.nnnCONCLUSIONSnGiven proper physiologic substrate the porcine liver has the ability to maintain acid-base homeostasis, provided there is not a significant ischemia-reperfusion injury.

Portal Vein Embolization and Ligation for Extended Hepatectomy

Portal vein occlusion through embolization or ligation (PVE, PVL) offers the possibility of increasing the future liver remnant (FLR) and thus reducing the risk of hepatic failure after extended hepatectomy We reviewed the indications, scope and applicability of PVE/PVL in treatment of primary and secondary liver tumours. A thorough PubMED, Embase, Ovid and Cochrane database search was carried out for all original articles with 30 patients or more undergoing either PVE and any patient series with PVL, irrespective of number with outcome measure in at least one of the following parameters: FLR volume change, complications, length of stay, time to surgery, proportion resectable and survival data. PVE can be performed with a technical success in 98.9xa0% (95xa0% confidence interval 97–100) patients, with a mean morbidity of 3.13xa0% (95xa0% CI 1.21–5.04) and a median in-hospital stay of 2.1 (range 1–4) days (very few papers had data on length of stay following PVE). The mean increase in volume of the FLR following PVE was 39.75xa0% (95xa0% CI 30.8–48.6) facilitating extended liver resection after a mean of 37.13xa0days (95xa0% CI 28.51–45.74) with a resectability rate of 76.88xa0% (95xa0% CI 70.91–82.84). Morbidity and mortality following such extended liver resections after PVE is 26.58xa0% (95xa0% CI 19.20–33.95) and 2.59xa0% (95xa0% CI 1.34–3.83) respectively with an in-patient stay of 13.57xa0days (95xa0% CI 9.8–17.37). However following post-PVE liver hypertrophy 6.29xa0% (95xa0% CI 2.24–10.34) patients still have post-resection liver failure and up to 14.2xa0% (95xa0% CI −8.7 to 37) may have positive resection margins. Up to 4.80xa0% (95xa0% CI 2.07–7.52) have failure of hypertrophy after PVE and 17.46xa0% (95xa0% CI 11.89–23.02) may have disease progression during the interim awaiting hypertrophy and subsequent resection. PVL has a greater morbidity and duration of stay of 5.72xa0% (95xa0% CI 0–15.28) and 10.16xa0days (95xa0% CI 6.63–13.69) respectively; as compared to PVE. Duration to surgery following PVL was greater at 53.6xa0days (95xa0% CI 32.14–75.05). PVL induced FLR hypertrophy by a mean of 64.65xa0% (95xa0% CI 0–136.12) giving a resectability rate of 63.68xa0% (95xa0% CI 56.82–70.54). PVL failed to produce enough liver hypertrophy in 7.4xa0% of patients (95xa0% CI 0–16.12). Progression of disease following PVL was 29.29 (95%CI 15.69–42.88). PVE facilitates an extended hepatectomy in patients with limited or inadequate FLR, with good short and long-term outcomes. Patients need to be adequately counselled and consented for PVE and EH in light of these data. PVL would promote hypertrophy as well, but clearly PVE has advantages as compared to PVL on account of its inherent “minimally invasive” nature, fewer complications, length of stay and its feasibility to have shorter times to surgery.

Coil migration – a rare complication of endovascular exclusion of visceral artery pseudoaneurysms and aneurysms

INTRODUCTIONnWe describe a case of metallic, angiographic coil migration, following radiological exclusion of a gastroduodenal artery pseudoaneurysm secondary to chronic pancreatitis.nnnPATIENTS AND METHODSnA 55-year-old man presented to the out-patient clinic with chronic, intermittent, post-prandial, abdominal pain, associated with nausea, vomiting and weight loss. He was known to have chronic pancreatitis and liver disease secondary to alcohol abuse and previously underwent angiographic exclusion of a gastroduodenal artery pseudoaneurysm. During subsequent radiological and endoscopic investigation, an endovascular coil was discovered in the gastric pylorus, associated with ulceration and cavitation. This patient was managed conservatively and enterally fed via naso-jejunal catheter endoscopically placed past the site of the migrated coil. This patient is currently awaiting biliary bypass surgery for chronic pancreatitis, and definitive coil removal will occur concurrently.nnnCONCLUSIONSnLiterature review reveals that this report is only the eighth to describe coil migration following embolisation of a visceral artery pseudoaneurysm or aneurysm. Endovascular embolisation of pseudoaneurysms and aneurysms is generally safe and effective. More common complications of visceral artery embolisation include rebleeding, pseudoaneurysm reformation and pancreatitis.

Outcome after pancreaticoduodenectomy for T3 adenocarcinoma: A multivariable analysis from the UK Vascular Resection for Pancreatic Cancer Study Group

BACKGROUNDnMost resectable pancreatic cancers are classified as T3, including those involving the porto-mesenteric vein. Survival and perioperative morbidity for venous resection have been found to be comparable to standard resection. We investigate factors associated with short and long term outcomes in pancreaticoduodenectomy with (PDVR) and without (PD) venous resection exclusively for T3 adenocarcinoma of the head of the pancreas.nnnMETHODSnThis is a UK multicenter retrospective cohort study assessing outcomes in patients undergoing PD and PDVR. All consecutive patients with T3 only adenocarcinoma of the head of the pancreas undergoing surgery between December 1998 and June 2011 were included. Multivariable logistic and proportional hazards regression analyses were performed to determine the association between the surgical groups and in-hospital mortality (IHM) and overall survival (OS).nnnRESULTSn1070 patients were included of whom 840 (78.5%) had PD and 230 (21.5%) had PDVR. Factors independently associated with IHM were a high creatinine (aHR 1.14, pxa0=xa00.02), post-operative bleeding (aHR 2.86, pxa0=xa00.04) and a re-laparotomy (aHR 8.42, pxa0=xa00.0001). For OS, multivariable analyses identified R1 resection margin status (aHR 1.22, pxa0=xa00.01), N1 nodal status (aHR 1.92, pxa0=xa00.0001), perineural invasion (aHR 1.37, pxa0=xa00.002), tumour size >20mm (aHR 0.63, pxa0=xa00.0001) and a relaparotomy (aHR 1.84, pxa0=xa00.0001) to be independently associated with overall mortality.nnnCONCLUSIONnThis study on T3 adenocarcinoma of the head of the pancreas suggests that IHM is strongly associated with perioperative complications whilst OS is affected by histological parameters. Detailed pre-operative disease evaluation and advances in oncological treatment have the potential to improve OS.

Current status of liver transplantation.

Liver transplantation has become the treatment of choice for a wide range of end-stage liver disease. As outcomes have improved, so the demand for this therapy has increasingly exceeded the availability of donor organs. Access to liver transplantation is controlled such that donor organs are generally allocated to the patients who are likely to benefit most, although if all patients who might benefit were placed on the waiting list, the donor shortage would be greatly increased. Recurrence of the original liver disease is emerging as an important issue. Fewer patients are transplanted for liver tumors, as earlier results showed a very high rate of recurrence. In recent years there has been a change in the underlying conditions of patients on the waiting list, and a preponderance of patients now present with hepatitis C and alcoholic cirrhosis. Increasingly, transplant units are looking to sources of donor organs that would previously have been deemed unsuitable--such marginal donors include non-heart-beating donors (NHBDs). Results from controlled NHBDs--those cases in which cardiac arrest is predicted--suggest that this is a good source of viable organs. Splitting a donor liver to provide two grafts has successfully enabled the transplantation of a child and an adult from one organ. The transplantation of two adults from a single organ remains a greater challenge. Transplantation from living donors has been practiced increasingly over the last decade, although anxieties have been expressed over donor safety. In many countries this now represents a significant contribution to overall liver transplant activity.