Significance of predicted future liver remnant volume on liver failure risk after major hepatectomy: a case matched comparative study.

Introduction: Future liver remnant volume (FLRV), a risk factor for liver failure (PHLF) after major hepatectomy (MH), is not routinely measured. This study aimed to evaluate the association between FLRV and PHLF. Patients and methods: All patients undergoing MH (4 + segments) between 2011 and 2018 were identified from a prospectively maintained single-centre database. Perioperative data were collected for patients with PHLF, who were matched (1:2) with non-PHLF controls. FLRV and FLRV% (i.e., % of total liver volume) were calculated retrospectively from preoperative CT scans using Synapse-3D software, and compared between the PHLF and matched control groups. Results: Of 711 patients undergoing MH, PHLF occurred in 27 (3.8%), of whom 24 had preoperative CT scans available. These patients were matched to 48 non-PHLF controls, 98% of whom were classified as being at high risk of PHLF on preoperative risk scoring. FLRV% was significantly lower in the PHLF group, compared to matched controls (median: 28.7 vs. 35.2%, p = 0.010), with FLRV% < 30% in 58% and 29% of patients, respectively. Assessment of the ability of FLRV% to differentiate between PHLF and matched controls returned an area under the ROC curve of 0.69, and an optimal cut-off value of FLRV% < 31.5%, which yielded 79% sensitivity and 67% specificity. Conclusions: FLRV% is significantly predictive of PHLF after MH, with over half of patients with PHLF having FLRV% < 30%. In light of this, we propose that all patients should undergo risk stratification prior to MH, with the high risk patients additionally being assessed with CT volumetry.

Sexual dimorphism and reproductive biology of the Asian bockadam snake (Cerberus schneiderii) in West Java.

Although they are among the most abundant snakes on Earth, and are heavily exploited for their skins and meat, Asian bockadams (or "dog-faced water snakes", Cerberus schneiderii) have attracted relatively little study across their wide geographic range. Based on dissection of 3,382 snakes brought to processing facilities in and around the city of Cirebon in West Java, Indonesia, we document facets of the biology of these mangrove-dwelling aquatic homalopsids. Females attain larger body sizes than do males, and are heavier-bodied (due in part to greater fat reserves) but have shorter tails relative to snout-vent length. Males showed testicular enlargement late in the year (August-November) but both reproductive and non-reproductive females were found year-round. Litters were large (3 to 45 offspring), especially in larger females. The commercial harvest falls mainly on adult snakes of both sexes, with seasonal variation in sex ratios. Life-history traits such as early maturation and frequent production of large litters render this species resilient to commercial harvesting. Future research should explore reasons for strong variation among facilities in the sex ratios of snakes, potentially identifying ways to focus the harvest on the sex (males) whose numbers are less critical for population viability.

Impact of Frailty on Short-Term Outcomes After Laparoscopic and Open Hepatectomy.

BACKGROUND: Although laparoscopic hepatectomy (LH) is associated with improved short-term outcomes compared to open hepatectomy (OH), it is unknown whether frail patients also benefit from LH. The aim of this study was to evaluate the impact of frailty on post-operative outcomes after LH and OH. PATIENTS AND METHODS: Consecutive patients who underwent LH and OH between January 2011 and December 2018 were identified from a prospective database. Frailty was assessed using the modified Frailty Index (mFI), with patients scoring mFI ≥ 1 deemed to be frail. RESULTS: Of 1826 patients, 34.7% (N = 634) were frail and 18.6% (N = 340) were elderly (≥ 75 years). Frail patients had significantly higher 90-day mortality (6.6% vs. 2.9%, p < 0.001) and post-operative complications (36.3% vs. 26.1%, p < 0.001) than those who were not frail, effects that were independent of patient age on multivariate analysis. For those undergoing minor resections, the benefits of LH vs. OH were similar for frail and non-frail patients. Length of hospital stay was 53% longer in OH (vs. LH) in frail patients, compared to 58% longer in the subgroup of non-frail patients. CONCLUSIONS: Frailty is independently associated with inferior post-operative outcomes in patients undergoing hepatectomy. However, the benefits of laparoscopic (compared to open) hepatectomy are similar for frail and non-frail patients. Frailty should not be a contraindication to laparoscopic minor hepatectomy in carefully selected patients.

Outcomes of normothermic machine perfusion of liver grafts in repeat liver transplantation (NAPLES initiative).

BACKGROUND: Retransplantation candidates are disadvantaged owing to lack of good-quality liver grafts. Strategies that can facilitate transplantation of suboptimal grafts into retransplant candidates require investigation. The aim was to determine whether late liver retransplantation can be performed safely with suboptimal grafts, following normothermic machine perfusion. METHODS: A prospectively enrolled group of patients who required liver retransplantation received a suboptimal graft preserved via normothermic machine perfusion. This group was compared with both historical and contemporaneous cohorts of patient who received grafts preserved by cold storage. The primary outcome was 6-month graft and patient survival. RESULTS: The normothermic machine perfusion group comprised 26 patients. The historical (cold storage 1) and contemporaneous (cold storage 2) groups comprised 31 and 25 patients respectively. The 6-month graft survival rate did not differ between groups (cold storage 1, 27 of 31, cold storage 2, 22 of 25; normothermic machine perfusion, 22 of 26; P = 0.934). This was despite the normothermic machine perfusion group having significantly more steatotic grafts (8 of 31, 7 of 25, and 14 of 26 respectively; P = 0.006) and grafts previously declined by at least one other transplant centre (5 of 31, 9 of 25, and 21 of 26; P < 0.001). CONCLUSION: In liver retransplantation, normothermic machine perfusion can safely expand graft options without compromising short-term outcomes.

Liver transplantation is a life-saving procedure for many different diseases. In the UK, one in 10 patients awaiting transplant have had a previous liver transplant. These retransplant operations are complex, and the general belief is that a good-quality donor liver graft is required for best outcomes. However, there is a significant shortage of good-quality organs for liver transplantation, so many patients awaiting retransplantation spend longer on the waiting list. This study investigated whether a new technology, called normothermic machine perfusion, could be used to preserve lower-quality donor livers and have successful outcomes for patients undergoing retransplantation. Traditionally, good-quality livers are preserved in an ice box and the study compared the outcomes of these two different approaches. The aim was to prove that normothermic machine perfusion improves access to transplantation for this group of patients, without compromising outcomes. A group of patients who underwent retransplantation and received a lesser-quality liver preserved with normothermic machine perfusion was compared with two groups of patients who had received a transplant with traditional ice-box preservation. The complications, graft, and patient survival of the former group was compared with those in the latter two groups who underwent liver retransplantation with better-quality liver grafts. The rate of survival and adverse surgical outcomes were comparable between the groups of patients who received a liver preserved via traditional ice-box preservation, and those who received a lesser-quality liver preserved via normothermic machine perfusion. Normothermic machine perfusion can potentially expand the number of suitable donor livers available for retransplant candidates.

The effect of end-ischaemic normothermic machine perfusion on donor hepatic artery endothelial integrity.

BACKGROUND: Ex vivo normothermic machine liver perfusion (NMLP) involves artificial cannulation of vessels and generation of flow pressures. This could lead to shear stress-induced endothelial damage, predisposing to vascular complications, or improved preservation of donor artery quality. This study aims to assess the spatial donor hepatic artery (HA) endothelial quality downstream of the cannulation site after end-ischaemic NMLP. METHODS: Remnant HA segments from the coeliac trunk up to the gastroduodenal artery branching were obtained after NMLP (n = 15) and after static cold storage (SCS) preservation (n = 15). Specimens were fixed in 10% neutral buffered formalin and sectioned at pre-determined anatomical sites downstream of the coeliac trunk. CD31 immunohistostaining was used to assess endothelial integrity by a 5-point ordinal scale (grade 0: intact endothelial lining, grade 5: complete denudation). Endothelial integrity after SCS was used as a control for the state of the endothelium at commencement of NMP. RESULTS: In the SCS specimens, regardless of the anatomical site, near complete endothelial denudation was present throughout the HA (median scores 4.5-5). After NMLP, significantly less endothelial loss in the distal HA was present compared to SCS grafts (NMLP vs. SCS: median grade 3 vs. 4.5; p = 0.042). In NMLP specimens, near complete endothelial denudation was present at the cannulation site in all cases (median grade: 5), with significantly less loss of the endothelial lining the further from the cannulation site (proximal vs. distal, median grade 5 vs. 3; p = 0.005). CONCLUSION: Loss of endothelial lining throughout the HA after SCS and at the cannulation site after NMLP suggests extensive damage related to surgical handling and preservation injury. Gradual improved endothelial lining along more distal sites of the HA after NMLP indicates potential for re-endothelialisation. The regenerative effect of NMLP on artery quality seems to occur to a greater extent further from the cannulation site. Therefore, arterial cannulation for machine perfusion of liver grafts should ideally be as proximal as possible on the coeliac trunk or aortic patch, while the site of anastomosis should preferentially be attempted distal on the common HA.

The COVID-19 Sequelae: A Cross-Sectional Evaluation of Post-recovery Symptoms and the Need for Rehabilitation of COVID-19 Survivors.

Background  As of January 19, 2021, around two million fatalities and 68 million recoveries from coronavirus disease 2019 (COVID-19) have been reported around the globe. The past pandemics of severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) hint toward a risk of occurrence of "Long-COVID" syndrome, i.e., the persistence of post-discharge symptoms among COVID-19 survivors. With the scarcity of literature addressing post-COVID-19 manifestations and little regard for the stigma associated with this disease, survivors' rehabilitation remains widely neglected. The current study aims to assess the prevalence and characteristics of post-COVID-19 manifestations and their effect on the quality of life (QoL) of COVID-19 recovered individuals. We have also analyzed the relationship of time since the recovery of COVID-19 and its severity with the post-discharge symptoms. The stigma affiliated with the infection of SARS coronavirus-2 (SARS-CoV-2) has also been highlighted. Methodology A descriptive, cross-sectional, questionnaire-based study was conducted from September 2020 to December 2020 among 158 COVID-19 recovered patients, whose information was obtained from Dow Diagnostic Laboratory, Ojha Campus, Karachi, Pakistan. The questionnaire consisted of four sections: sociodemographic data, post-COVID-19 manifestations, questions relating to the stigma, and the QoL of the recovered COVID-19 patients. We used the EuroQol five-dimension five-level questionnaire to assess the QoL, while the modified BG Prasad Socioeconomic Classification updated for 2019 was employed to determine the socioeconomic status of the participants. Data were analyzed using SPSS version 24.0 (IBM Corp., Armonk, NY, USA). Data were presented in the form of frequencies and percentages. Results An overwhelming majority (94.9%) experienced at least one post-COVID-19 symptom, with fatigue (82.9%) being the most prevalent post-discharge manifestation. We observed a significant correlation of post-COVID-19 symptoms with gender, age, and time since recovery. COVID-19 severity was found to be significantly related to the five dimensions of the QoL. A significant difference in EuroQol Visual Analog Scale health score was observed between the participants with mild, moderate, and severe COVID-19 infection (p < 0.001). Besides, the associated stigma with SARS-CoV-2 infection was found to be more prevalent in the participants belonging to the upper class as compared to the other classes (p < 0.05). Nonetheless, we also observed a significant association of disease severity with post-COVID-19 manifestations and pre-existing comorbidities. Conclusions The long-COVID syndrome is similar to the post-discharge manifestations of the survivors of prior pandemics of SARS and MERS. Multi-disciplinary rehabilitation teams, healthcare workers, and the general population should recognize the need for systematic assessment of their recovery and further rehabilitation.

Evaluation of the clinical and economic impact of delays to surgery in patients with periampullary cancer.

Background: Early treatment is the only potential cure for periampullary cancer. The pathway to surgery is complex and involves multiple procedures across local and specialist hospitals. The aim of this study was to analyse variability within this pathway, and its impact on cost and outcomes. Methods: Patients undergoing surgery for periampullary cancer (2011-2016) were identified retrospectively and their pathway to surgery was analysed. Patients who had early surgery (shortest quartile, Q1) were compared with those having late surgery (longest quartile, Q4). Results: A total of 483 patients were included in the study, with 121 and 124 patients in Q1 and Q4 respectively. The median time from initial CT to surgery was 21 days for Q1 versus 112 days for Q4 (P < 0·001). Diagnostic delays were common in Q4; these patients required significantly more investigations than those in Q1 (endoscopic ultrasonography (EUS): 74·2 versus 18·2 per cent respectively, P < 0·001; MRI: 33·6 versus 20·6 per cent, P = 0·036). The median time to diagnostic EUS was 13 days in Q1 versus 59 days in Q4 (P < 0·001). Some 42·1 per cent of jaundiced patients in Q1 underwent preoperative biliary drainage, compared with all patients in Q4. There were significantly more unplanned admissions and associated longer duration of hospital stay per patient and costs in Q4 than in Q1 (median: 8 versus 3 days respectively; €5652 versus €2088; both P < 0·001). There was a higher likelihood of potentially curative surgery in Q1 (82·6 per cent versus 66·9 per cent in Q4; P = 0·005). Conclusion: There is wide variation across the entire pathway, suggesting that multiple strategies are required to enable early surgery. Defining an effective pathway by anticipating the need for investigations and avoiding biliary drainage reduces unplanned admissions and costs and increases resection rates.

Propensity-matched analysis of the influence of perioperative statin therapy on outcomes after liver resection.

Background: Perioperative use of statins is reported to improve postoperative outcomes after cardiac and non-cardiovascular surgery. The aim of this study was to investigate the influence of statins on postoperative outcomes including complications of grade IIIa and above, posthepatectomy liver failure (PHLF), and 90-day mortality rates after liver resection. Methods: Patients who underwent hepatectomy between 2013 and 2017 were reviewed to identify statin users and non-users (controls). Propensity matching was conducted for age, BMI, type of surgery and preoperative co-morbidities to compare subgroups. Univariable and multivariable analyses were performed for the following outcomes: 90-day mortality, significant postoperative complications and PHLF. Results: Of 890 patients who had liver resection during the study period, 162 (18·2 per cent) were taking perioperative statins. Propensity analysis selected two matched groups, each comprising 154 patients. Overall, 81 patients (9·1 per cent) developed complications of grade IIIa or above, and the 90-day mortality rate was 3·4 per cent (30 patients), with no statistically significant difference when the groups were compared before and after matching. The rate of PHLF was significantly lower in patients on perioperative statins than in those not taking statins (10·5 versus 17·3 per cent respectively; P = 0·033); similar results were found after propensity matching (10·4 versus 20·8 per cent respectively; P = 0·026). Conclusion: The rate of PHLF was significantly lower in patients taking perioperative statins, but there was no statistically significant difference in severe complications and mortality rates.

Development and multicentre validation of a prognostic model to predict resectability of pancreatic head malignancy.

BACKGROUND: At the time of planned pancreatoduodenectomy patients frequently undergo exploratory laparotomy without resection, leading to delayed systemic therapy. This study aimed to develop and validate a prognostic model for the preoperative prediction of resectability of pancreatic head tumours. METHODS: This was a retrospective study of patients undergoing attempted resection for confirmed malignant tumours of the pancreatic head in a university hospital in Hannover, Germany. The prognostic value of patient and tumour characteristics was investigated in a multivariable logistic regression model. External validation was performed using data from two other centres. RESULTS: Some 109 patients were included in the development cohort, with 51 and 175 patients in the two validation cohorts. Eighty patients (73·4 per cent) in the development cohort underwent resection, and 37 (73 per cent) and 141 (80·6 per cent) in the validation cohorts. The main reasons for performing no resection in the development cohort were: local invasion of vasculature or arterial abutment (15 patients, 52 per cent), and liver (12, 41 per cent), peritoneal (8, 28 per cent) and aortocaval lymph node (6, 21 per cent) metastases. The final model contained the following variables: time to surgery (odds ratio (OR) 0·99, 95 per cent c.i. 0·98 to 0·99), carbohydrate antigen 19-9 concentration (OR 0·99, 0·99 to 0·99), jaundice (OR 4·45, 1·21 to 16·36) and back pain (OR 0·02, 0·00 to 0·22), with an area under the receiver operating characteristic (ROC) curve (AUROC) of 0·918 in the development cohort. AUROC values were 0·813 and 0·761 in the validation cohorts. The positive predictive value of the final model for prediction of resectability was 98·0 per cent in the development cohort, and 91·7 and 94·7 per cent in the two external validation cohorts. [Corrections added on 18 July 2018, after first online publication: The figures for OR of the variables time to surgery and CA19-9 in the abstract and in Table 3 and Table 4 were amended from 1·00 to 0·99]. CONCLUSION: For preoperative prediction of the likelihood of resectability of pancreatic head tumours, this validated model is a valuable addition to CT findings.

Ninety day mortality following pancreatoduodenectomy in England: has the optimum centre volume been identified?

BACKGROUND: Mortality following pancreatoduodenectomy is related to centre volume although the optimal volume is not defined. METHODS: Patients undergoing PD between 2001 and 2016 were identified from UK national databases. The effects of patient variables, centre volume and time period upon 90 day mortality were studied. RESULTS: 90 day mortality (970/14,935, 6.5%) was related to advanced age, comorbidity, diagnosis, ethnicity, deprivation, centre volume and time period. Mortality rates fell markedly from 10.0% in 2001-4 to 4.1% in 2013-16. There was no difference in 90 day mortality between high (36 -60 PD per year) and very high volume (>60) centres. However, patients operated upon at very high volume centres were more elderly (66, 58 -73 vs 65, 56 -72; median, IQR; p = 0.006), deprived (38.7 vs 34.6%; p < 0.001) and co morbid (48.9 vs 46.1%; p = 0.027). CONCLUSION: Although a plateau in the centre volume and mortality relationship appears to have been demonstrated those patients treated at the highest volume centres were at higher risk of mortality. This data suggests therefore that to further understand outcomes from specialist centres characteristics of the patient population should be defined, not just centre volume.

Long-term outcomes of patients with 10 or more colorectal liver metastases.

BACKGROUND: Although the number of colorectal liver metastases (CLM) is decreasingly considered as a contraindication to surgery, patients with 10 CLM or more are often denied liver surgery. This study aimed to evaluate the outcome after liver surgery and to identify prognostic factors of survival in such patients. METHODS: The study population consisted of a multicentre cohort of patients with CLM (N=12 406) operated on, with intention to resect, from January 2005-June 2013 and whose data were prospectively collected in the LiverMetSurvey registry. RESULTS: Overall, the group ⩾10 CLM (N=529, 4.3%) experienced a 5-year overall survival (OS) of 30%. A macroscopically complete (R0/R1) resection (72.8% of patients) was associated with a 3- and 5-year OS of 61% and 39% vs 29% and 5% for R2/no resection patients (P<0.0001). At multivariate analysis, R0/R1 resection emerged as the strongest favourable factor of OS (HR 0.35 (0.26-0.48)). Other independent favourable factors were as follows: maximal tumour size <40 mm (HR 0.67 (0.49-0.92)); age <60 years (HR 0.66 (0.50-0.88)); preoperative MRI (HR 0.65 (0.47-0.89)); and adjuvant chemotherapy (HR 0.73 (0.55-0.98)). The model showed that 5-year OS rates of 30% was possible provided R0/R1 resection associated with at least an additional favourable factor. CONCLUSIONS: Liver resection might provide long-term survival in patients with ⩾10 CLM staged with preoperative MRI, provided R0/R1 resection followed by adjuvant therapy. A validation of these results in another cohort is needed.

A new small bent-toed gecko of the genus Cyrtodactylus (Squamata: Gekkonidae) from the lower slopes of Mount Tambora, Sumbawa Island, Indonesia.

We describe the sixth species of bent-toed gecko from the Lesser Sunda Islands, Indonesia. This species was first collected on the banks of the Oi Marai River on the low northern slopes of Gunung (Mount) Tambora on Sumbawa Island. The new species is differentiated from Greater Sunda Islands (including Sulawesi) and Lesser Sunda Islands congeners by having the following unique combination of characters: (1) two scales between the second pair of postmentals in contact with the first pair; (2) dorsal surface of antebrachium tuberculate; (3) no tubercles on dorsal surface of brachium; (4) dorsal surfaces of thigh and crus tuberculate; (5) 18 irregularly aligned, longitudinal rows of keeled tubercles at midbody; (6) 26-27 paravertebral tubercles; (7) 40 ventral scales between indistinct ventrolateral folds; (8) 16-17 fourth-toe subdigital scales; (9) a continuous enlarged precloacal and femoral scales present, with the enlarged femoral scales arranged in three rows; (10) males with five to six precloacal pores, with four larger pores situated in a short groove; (11) femoral pores absent in both sexes; (12) lack of transversely enlarged subcaudal scales; and (13) 7-9 irregular, paired black blotches on the body.

Management of a pseudo-aneurysm in the hepatic artery after a laparoscopic cholecystectomy.

Introduction Symptomatic hepatic-artery pseudoaneurysm (HAP) after bile-duct injury (BDI) is a rare complication with a varied (but clinically urgent) presentation. Methods A prospectively maintained database of all patients with BDI at laparoscopic cholecystectomy (LC) referred to a tertiary specialist hepatobiliary centre between 1992 and 2011 was searched systematically to identify patients with a symptomatic HAP. Care and outcome of these patients was studied. Results Eight (6 men) of 236 patients with BDI (3.4%) with a median age of 65 (range: 54?6) years presented with symptomatic HAP. Median time of presentation of the HAP from the index LC was 31 (range: 13?16) days. Bleeding was the dominant presentation in 7 patients. One patient presented late (>2 years) with abdominal pain alone. Computed tomography angiography was the most useful investigation. Angioembolisation was successful in 7 patients. One patient died, and another patient developed liver infarction. Three patients (38%) developed biliary strictures after embolisation. Seven patients are alive and well at a median follow-up of 66 months. Conclusions Presentation of HAP is often delayed. A high index of suspicion is necessary for the diagnosis. Computed tomography angiography is the first-line investigation and selective angioembolisation can yield successful outcomes.

Comparison of preoperative CT-based imaging parameters to predict postoperative pancreatic fistula.

AIM: To review all reported methods of preoperative computed tomography (CT) in one patient cohort and to identify which were the strongest to predict postoperative pancreatic fistula (POPF) after pancreatoduodenectomy. MATERIALS AND METHODS: Consecutive patients undergoing pancreatoduodenectomy were included if they had unenhanced CT images for review. Eighteen variables and two scores were tested. Receiver operator characteristics (ROC) were explored. RESULTS: POPF affected 26 of 107 patients (24.3%). Nine variables were significantly related to POPF with pancreatic duct width having the largest area under the ROC curve (AUROC; 0.808, p<0.001). An obese body habitus was associated with POPF with six of nine related variables using data from CT images associated with POPF; of these intra-abdominal wall thickness yielded the largest AUROC (0.713, p=0.001). This corresponded to the finding that body mass index (BMI) was related to POPF (AUROC 0.705, p=0.002). The largest AUROC of all was associated with one of the predictive scores (0.828, p<0.001). Substituting BMI for intra-abdominal wall thickness in this score yielded a non-significant increase to predict POPF (AUROC 0.840, p=0.676). None of the assessments of organ density (in Hounsfield Units) were associated with POPF. CONCLUSION: Data from preoperative CT imaging provides valuable information regarding a patient's risk of POPF. Obesity as assessed by CT images strongly relates to POPF, but the largest single risk factor for POPF is a narrow pancreatic duct.

Transplantation of Declined Liver Allografts Following Normothermic Ex-Situ Evaluation.

The demand for liver transplantation (LT) exceeds supply, with rising waiting list mortality. Utilization of high-risk organs is low and a substantial number of procured livers are discarded. We report the first series of five transplants with rejected livers following viability assessment by normothermic machine perfusion of the liver (NMP-L). The evaluation protocol consisted of perfusate lactate, bile production, vascular flows, and liver appearance. All livers were exposed to a variable period of static cold storage prior to commencing NMP-L. Four organs were recovered from donors after circulatory death and rejected due to prolonged donor warm ischemic times; one liver from a brain-death donor was declined for high liver function tests (LFTs). The median (range) total graft preservation time was 798 (range 724-951) min. The transplant procedure was uneventful in every recipient, with immediate function in all grafts. The median in-hospital stay was 10 (range 6-14) days. At present, all recipients are well, with normalized LFTs at median follow-up of 7 (range 6-19) months. Viability assessment of high-risk grafts using NMP-L provides specific information on liver function and can permit their transplantation while minimizing the recipient risk of primary graft nonfunction. This novel approach may increase organ availability for LT.

Variations in Practice to Therapeutic Monitoring of Tacrolimus following Primary Adult Liver Transplantation.

BACKGROUND: There is limited clinical evidence evaluating the correlation between immunosuppressant monitoring practice and transplant outcomes. OBJECTIVE: To assess current practice of tacrolimus trough monitoring in early post-operative period following liver transplantation (LT), and its impact on outcomes. METHODS: The duration to trough levels (DTT) were calculated in patients undergoing primary LT. The impact of variability in DTT on graft rejection episodes, serum tacrolimus level and renal function was assessed. These results were converted into a drug level estimation tool, which was validated in a prospective cohort of patients. RESULTS: 2946 events in 274 patients were evaluated. The median DTT was 7:19 hrs (range: 27 min to 19:38 hrs). In 72% (2140 events) of the occasions, DTT was <8 hrs. There was a significant (p=0.022) correlation between DTT and tacrolimus level. Despite clinical decisions were taken to modify the dose of tacrolimus based on trough level, neither did DTT affect the average creatinine levels (p=0.923), nor the variability in DTT did affect acute rejection (p=0.914, and 0.712, respectively). A dose estimation tool was developed and applied to validation cohort (n=612), and returned a moderate R(2) value of 0.50. CONCLUSION: There is a significant variation in the "real world" monitoring of tacrolimus with DTT in majority of measurements falling below recommendations; reassuringly, this did not lead to adverse transplant sequelae.

Liver Transplantation Using Grafts From Donors After Circulatory Death: A Propensity Score-Matched Study From a Single Center.

The use of livers from donation after circulatory death (DCD) is increasing, but concerns exist regarding outcomes following use of grafts from "marginal" donors. To compare outcomes in transplants using DCD and donation after brain death (DBD), propensity score matching was performed for 973 patients with chronic liver disease and/or malignancy who underwent primary whole-liver transplant between 2004 and 2014 at University Hospitals Birmingham NHS Foundation Trust. Primary end points were overall graft and patient survival. Secondary end points included postoperative, biliary and vascular complications. Over 10 years, 234 transplants were carried out using DCD grafts. Of the 187 matched DCDs, 82.9% were classified as marginal per British Transplantation Society guidelines. Kaplan-Meier analysis of graft and patient survival found no significant differences for either outcome between the paired DCD and DBD patients (p = 0.162 and p = 0.519, respectively). Aspartate aminotransferase was significantly higher in DCD recipients until 48 h after transplant (p < 0.001). The incidences of acute kidney injury and ischemic cholangiopathy were greater in DCD recipients (32.6% vs. 15% [p < 0.001] and 9.1% vs. 1.1% [p < 0.001], respectively). With appropriate recipient selection, the use of DCDs, including those deemed marginal, can be safe and can produce outcomes comparable to those seen using DBD grafts in similar recipients.

Liver Transplantation After Ex Vivo Normothermic Machine Preservation: A Phase 1 (First-in-Man) Clinical Trial.

The number of donor organs suitable for liver transplantation is restricted by cold preservation and ischemia-reperfusion injury. We present the first patients transplanted using a normothermic machine perfusion (NMP) device that transports and stores an organ in a fully functioning state at 37°C. In this Phase 1 trial, organs were retrieved using standard techniques, attached to the perfusion device at the donor hospital, and transported to the implanting center in a functioning state. NMP livers were matched 1:2 to cold-stored livers. Twenty patients underwent liver transplantation after NMP. Median NMP time was 9.3 (3.5-18.5) h versus median cold ischaemia time of 8.9 (4.2-11.4) h. Thirty-day graft survival was similar (100% NMP vs. 97.5% control, p = 1.00). Median peak aspartate aminotransferase in the first 7 days was significantly lower in the NMP group (417 IU [84-4681]) versus (902 IU [218-8786], p = 0.03). This first report of liver transplantation using NMP-preserved livers demonstrates the safety and feasibility of using this technology from retrieval to transplantation, including transportation. NMP may be valuable in increasing the number of donor livers and improving the function of transplantable organs.

Performance of the revised Atlanta and determinant-based classifications for severity in acute pancreatitis.

BACKGROUND: Severity classification systems aim to stratify patients with acute pancreatitis reliably into coherent risk groups. Recently, the Atlanta 1992 classification has been revised (Atlanta 2012) and a novel determinant-based classification (DBC) system developed. This study assessed the ability of the three systems to stratify disease severity among patients with acute pancreatitis. METHODS: This was an observational cohort study of patients with acute pancreatitis identified from an institutional database. Cohort characteristics, investigations, interventions and outcomes were identified. Systems were compared using receiver operating characteristic (ROC) analysis and Spearman's correlation coefficients. RESULTS: The in-hospital mortality rate was 6·6 per cent (15 of 228 patients). All of the outcomes considered correlated significantly with the three systems, with the exception of the need for surgery in Atlanta 1992. Atlanta 2012 and the DBC had higher area under the curve (AUC) values than Atlanta 1992 for all outcomes. The revised Atlanta and DBC systems both performed similarly with regard to ICU admission (AUC 0·927 and 0·917 respectively; both P < 0·001), need for percutaneous drainage (AUC 0·879 and 0·891; both P < 0·001), need for surgery (AUC 0·827 and 0·845; P = 0·006 and P = 0·004 respectively) and in-hospital mortality (0·955 and 0·931; both P < 0·001). However, the critical category in the DBC system identified patients with the most severe disease; seven of eight patients in this group died in hospital, compared with 15 of 34 with severe pancreatitis according to Atlanta 2012. CONCLUSION: The Atlanta 2012 and DBC perform equally well for classification of disease severity in acute pancreatitis. The addition of a critical category in the DBC identifies patients with the most severe disease.

Maintaining surgical skills for military general surgery: the potential role for multivisceral organ retrieval in military general surgery training and practice.

The closure of the Medical Treatment facility in Camp BASTION and the return to contingency operations presents a new challenge in training and maintaining the skills of military surgeons. Multivisceral organ retrieval presents a unique opportunity to practice some of the more unusual techniques required in military surgery in the National Health Service. This article details the experience that organ retrieval offers and matches this to the needs of military surgeons. National Organ Retrieval Service teams need skilled surgeons, and a mutually beneficial partnership is in prospect.