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.

Gemcitabine-based adjuvant chemotherapy in subtypes of ampullary adenocarcinoma: international propensity score-matched cohort study.

BACKGROUND: Whether patients who undergo resection of ampullary adenocarcinoma have a survival benefit from adjuvant chemotherapy is currently unknown. The aim of this study was to compare survival between patients with and without adjuvant chemotherapy after resection of ampullary adenocarcinoma in a propensity score-matched analysis. METHODS: An international multicentre cohort study was conducted, including patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma between 2006 and 2017, in 13 centres in six countries. Propensity scores were used to match patients who received adjuvant chemotherapy with those who did not, in the entire cohort and in two subgroups (pancreatobiliary/mixed and intestinal subtypes). Survival was assessed using the Kaplan-Meier method and Cox regression analyses. RESULTS: Overall, 1163 patients underwent pancreatoduodenectomy for ampullary adenocarcinoma. After excluding 187 patients, median survival in the remaining 976 patients was 67 (95 per cent c.i. 56 to 78) months. A total of 520 patients (53·3 per cent) received adjuvant chemotherapy. In a propensity score-matched cohort (194 patients in each group), survival was better among patients who received adjuvant chemotherapy than in those who did not (median survival not reached versus 60 months respectively; P = 0·051). A survival benefit was seen in patients with the pancreatobiliary/mixed subtype; median survival was not reached in patients receiving adjuvant chemotherapy and 32 months in the group without chemotherapy (P = 0·020). Patients with the intestinal subtype did not show any survival benefit from adjuvant chemotherapy. CONCLUSION: Patients with resected ampullary adenocarcinoma may benefit from gemcitabine-based adjuvant chemotherapy, but this effect may be reserved for those with the pancreatobiliary and/or mixed subtype.

ANTECEDENTES: Actualmente se desconoce si la quimioterapia adyuvante ofrece un beneficio en la supervivencia de los pacientes que se someten a resección de un adenocarcinoma ampular. El objetivo de este estudio fue comparar la supervivencia mediante la concordancia estimada por emparejamiento por puntaje de propensión, entre pacientes con y sin quimioterapia adyuvante después de la resección de un adenocarcinoma ampular. MÉTODOS: Se realizó un estudio internacional de cohortes multicéntrico, que incluyó a los pacientes que se sometieron a una duodenopancreatectomía por adenocarcinoma ampular (2006-2017) en 13 centros de seis países. Los puntajes de propensión se usaron para emparejar a los pacientes que recibieron quimioterapia adyuvante con los que no; tanto en la cohorte completa como en dos subgrupos (subtipo pancreaticobiliar / mixto e intestinal). La supervivencia se evaluó utilizando el método de Kaplan-Meier y las regresiones de Cox. RESULTADOS: En total, 1.163 pacientes fueron sometidos a una duodenopancreatectomía por adenocarcinoma ampular. Después de excluir a 179 pacientes, la mediana de supervivencia de los 976 pacientes restantes fue de 67 meses (i.c. del 95%, 56-78), de los cuales un total de 520 pacientes (53%) recibieron quimioterapia adyuvante. En una cohorte de emparejamiento por puntaje de propensión (194 versus 194 pacientes), la mediana de supervivencia fue mejor en los pacientes tratados con quimioterapia adyuvante en comparación con aquellos sin quimioterapia adyuvante (no se alcanzó la mediana de supervivencia versus 60 meses, respectivamente; P = 0,051). En el subtipo pancreaticobiliar/mixto se observó un beneficio en la supervivencia; no se alcanzó la mediana de supervivencia en pacientes que recibieron quimioterapia adyuvante versus 32 meses en el grupo sin quimioterapia, P = 0,020. El subtipo intestinal no mostró beneficio en la supervivencia de la quimioterapia adyuvante. CONCLUSIÓN: Los pacientes con adenocarcinoma ampular resecado pueden beneficiarse de la quimioterapia adyuvante basada en gemcitabina, pero este efecto podría reservarse para aquellos pacientes con subtipo de tumor pancreaticobiliar y/o mixto.

Enzyme replacement improves survival among patients with pancreatic cancer: Results of a population based study.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) and malnutrition are prevalent among patients with pancreatic adenocarcinoma. Pancreatic enzyme replacement therapy (PERT) can correct PEI but its use among patients with pancreatic cancer is unclear as are effects upon survival. This population-based study sought to address these issues METHODS: Subjects with pancreatic adenocarcinoma were identified from the UK Clinical Practice Research Datalink (CPRD). Propensity score matching generated matched pairs of subjects who did and did not receive PERT. Progression to all-cause mortality was compared using parametric survival models that included a range of relevant co-variables RESULTS: PERT use among the whole cohort (987/4554) was 21.7%. Some 1614 subjects generated 807 matched pairs. This resulted in a total, censored follow-up period of 1643 years. There were 1403 deaths in total, representing unadjusted mortality rates of 748 and 994 deaths per 1000 person-years for PERT-treated cases and their matched non-PERT-treated controls, respectively. With reference to the observed survival in pancreatic adenocarcinoma patients, adjusted median survival time was 262% greater in PERT-treated cases (survival time ratio (STR) = 2.62, 95% CI 2.27-3.02) when compared with matched, non-PERT-treated controls. Survival remained significantly greater among subjects receiving PERT regardless of the studied subgroup with respect to use of surgery or chemotherapy CONCLUSIONS: This population based study observes that the majority of patients with pancreatic adenocarcinoma do not receive PERT. PERT is associated with increased survival among patients with pancreatic adenocarcinoma suggesting a lack of clinical awareness and potential benefit of addressing malnutrition among these patients.

Examination of inequivalent wetting on the crystal habit surfaces of RS-ibuprofen using grid-based molecular modelling.

Synthonic engineering tools, including grid-based searching molecular modelling, are applied to investigate the wetting interactions of the solute and four crystallisation solvents (ethanol, ethyl acetate, acetonitrile and toluene) with the {100}, {001} and {011} forms of RS-ibuprofen. The grid-based methods, in particular the construction of a crystal slab parallel to a given plane in a coordinate system with one axis perpendicular to the surface, are defined in detail. The interaction strengths and nature (dispersive, hydrogen bonding (H-bonding) or coulombic forces) are related to the crystal growth rates and morphologies. The solute is found to interact strongest with the capping {011}, then the side {001} and weakest with the top {100} habit surfaces. The solute interactions with the {100} and {001} surfaces are found to be almost solely dominated by dispersive force contributions, whilst the same with the {011} surfaces are found to have a greater contribution from H-bonding and coulombic forces. The increased surface rugosity, at the molecular level of the {011} surfaces, results in a favourable docking site in a surface 'valley', not present in the {100} and {001} surfaces. The H-bonding solvents ethanol, acetonitrile and ethyl acetate are found to strongly interact with the {011} surfaces and weakly with the {001} surfaces, with the {011} interactions having a much greater contribution from H-bonding and coulombic forces. The interaction energies of the apolar and aprotic solvent toluene, with the {011} and {001} surfaces, are found to be very close. Toluene is found having slightly stronger interactions with the {001} than the {011} surfaces, which are all dominated by dispersive interactions. The ratio of the average energy of the top 100 solvent interactions with the {001} surface divided by the average energy of the top 100 interactions with the {011} surface is compared to the ratio of the experimentally measured growth rates of the same forms. In general, the interaction energy ratio is found to have an inverse ratio with the growth rates, implying that the solvents which are calculated to interact strongly with a particular surface are impeding the growth of that surface and reducing the growth rate, in turn impacting upon the final morphology of the material.

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.

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.

Do not forget the boys - gender differences in children living in high HIV-affected communities in South Africa and Malawi in a longitudinal, community-based study.

Gender is an important factor in child development. Especially in sub-Saharan Africa, girls have often been shown to be less likely to access education compared to boys. The consequence of this has been that that programmes addressing child development are often aimed at girls in order to redress gender imbalances. This study examines the effect of gender on the development of children attending community-based organisations in high HIV-affected areas, and explores whether community-based organisation attendance was associated with any changes in gender differences over time. Baseline data from 989 children and 12-15 month follow from 854 (86% response rate) were used to examine gender differences in children from Malawi and South Africa. At baseline, where there were differences by gender, these tended to disadvantage boys. It was found that boys were significantly more often found to be subjected to violence. Boys showed worse performance at school and more behavioural problems than girls. These gender differences persisted from baseline to follow-up. At follow-up, boys self-reported significantly worse average quality of life than girls. Only harsh discipline differed by gender in progression over time: boys experienced a stronger reduction in harsh physical discipline than girls from baseline to follow-up. Since harsh discipline was associated with boys' worse educational outcomes and behavioural problems, our data cautiously suggests that gender differences could be reduced over time. In conclusion, our data suggests that, perhaps due to the narrow equity approach focusing on provision for girls, boys may be overlooked. As a result, there are some specific experiences where boys are generally worse off. These differences have distinct ramifications for the educational and emotional development of boys. A broader equity approach to child development might be warranted to ensure that the needs of both girls and boys are considered, and that boys are not overlooked.

The influence of solution environment on the nucleation kinetics and crystallisability of para-aminobenzoic acid.

The influence of solvent type on the solution thermodynamics, nucleation-kinetics and crystal growth of alpha para-aminobenzoic acid (PABA) crystallising from supersaturated ethanol, acetonitrile and water solutions, is examined using poly-thermal analysis of the metastable zone width. Application of a recently proposed model for analysis of crystallisation kinetics (J. Cryst. Growth, 2010, 312, 698-704) indicates a solvent and concentration dependence of the nucleation mechanism and key nucleation parameters for the alpha form of PABA. The mechanism of nucleation is found to change from instantaneous to progressive with decreasing concentration and also when changing the solvent from ethanol to acetonitrile to water. The dependence of the nucleation mechanism is correlated to the kinetic component of the nucleation rate through calculated values of instantaneously nucleated crystallites, which increase from 1.40 × 109 m-3 in ethanol to 1.08 × 1010 m-3 in acetonitrile to 2.58 × 1010 m-3 in water. This in combination with low calculated number concentrations of interfacial tension between 1.13 and 2.71 mJ m-2, supports the conclusion that the kinetic component of the nucleation rate is more limiting when crystallising PABA from ethanol solutions in comparison to water solutions. This finding is further supported by molecular dynamics simulations of the solvation free energy of PABA, which is found to be greatest in water, -42.4 kJ mol-1 and lowest in ethanol, -58.5 kJ mol-1.

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.

Cost-utility analysis of operative versus non-operative treatment for colorectal liver metastases.

BACKGROUND: Surgical resection of colorectal liver metastases (CRLMs) is the standard of care when possible, although this strategy has not been compared with non-operative interventions in controlled trials. Although survival outcomes are clear, the cost-effectiveness of surgery is not. This study aimed to estimate the cost-effectiveness of resection for CRLMs compared with non-operative treatment (palliative care including chemotherapy). METHODS: Operative and non-operative cohorts were identified from a prospectively maintained database. Patients in the operative cohort had a minimum of 10 years of follow-up. A model-based cost-utility analysis was conducted to quantify the mean cost and quality-adjusted life-years (QALYs) over a lifetime time horizon. The analysis was conducted from a healthcare provider perspective (UK National Health Service) in a secondary care (hospital) setting. RESULTS: Median survival was 41 and 21 months in the operative and non-operative cohorts respectively (P < 0·001). The operative strategy dominated non-operative treatments, being less costly (€22,200 versus €32,800) and more effective (4·017 versus 1·111 QALYs gained). The results of extensive sensitivity analysis showed that the operative strategy dominated non-operative treatment in every scenario. CONCLUSION: Operative treatment of CRLMs yields greater survival than non-operative treatment, and is both more effective and less costly.

Towards an understanding of the nucleation of alpha-para amino benzoic acid from ethanolic solutions: a multi-scale approach.

The molecular assembly and subsequent nucleation of para-amino benzoic acid (PABA) from ethanolic solutions is probed using a multi-scale and multi-technique approach. This is applied by examining and interrelating information regarding the molecular, solution-state, cluster, solid-state and surface structures to understand why the alpha form of PABA is crystallised in preference to its low temperature beta form. Calculations suggest that conformational changes within the solute molecule play little or no role in directing the nucleation of either the alpha or beta crystal forms. Combined ab initio and molecular dynamics calculations of the stability of small clusters in solution suggests that the hydrogen-bonded carboxylic acid dimers, present in the alpha structure, are the most stable in solution and play a major role in the self-assembly and polymorphic expression of the alpha form in ethanol in preference to the beta form. These calculations are in good agreement with X-ray small-angle scattering analysis which reveals the presence of PABA clusters in ethanol which are consistent with the size and shape of a carboxylic acid dimer. SAXS studies also reveal the presence of larger cluster structures in a size range 10-40 nm which appear to grow, perhaps reflecting a change in the balance between monomers and dimers within the solution during the nucleation process. The results of crystallisation-kinetics experiments indicate an instantaneous nucleation mechanism where the number of instantaneously nucleated crystallites is calculated to be 1360-660 nuclei per ml and the subsequent growth is found to be only rate limited by diffusion of the growth unit to the crystallite surface. A linear dependence of growth rate with respect to supersaturation is observed for the (0 1 -1) capping face, which is associated with strong π-π stacking interactions. This is consistent with a solid-on-solid mechanism associated with surface roughened growth and concomitant poor lattice-perfection. Conversely, the side (1 0 -1) surface has a growth mechanism consistent with a 2D nucleation birth and spread mechanism. Hence, these mechanisms result in very fast growth along the b-axis and the needle-like morphology that is observed for alpha-PABA.

Emergency treatment of haemorrhaging coeliac or mesenteric artery aneurysms and pseudoaneurysms in the era of endovascular management.

OBJECTIVES: Patients requiring emergency treatment of visceral artery aneurysms (VAAs) can be treated by endovascular or surgical techniques. Outcomes after failed attempts at endovascular control are unclear as is the present role of surgery. This study reviewed treatment and outcomes of a contemporary cohort of patients with symptomatic VAAs at a tertiary referral centre. METHODS: Patients undergoing emergency treatment of a VAA of the coeliac, mesenteric arteries, or their branches were identified over a 5-year period. Patient variables, treatments, and outcomes were assessed. RESULTS: Forty-eight patients underwent 65 radiological and two surgical procedures. Pseuodaneuryms were present in 45 (94%) of patients. Interventional radiology procedures were the initial treatment in every patient. The initial success was 40 out of 48 (83%). Patients requiring more than one procedure were all successfully treated. Regarding initial failures, if the VAA sac could not be accessed at angiography an alternative procedure to control the VAA was required in every case. If initial endovascular treatment failed, repeating the same procedure was successful in half of the patients. Ultrasound-guided percutaneous VAA embolisation was used in four patients. The 30-day mortality was eight out of 48 (17%). There were four recorded complications including one death directly attributable to VAA treatment. CONCLUSIONS: Patients needing emergency treatment of a VAA could be well served by non-surgical management. When the initial attempt at control of bleeding is unsuccessful it is important to consider non-conventional means of accessing these arteries. The need for surgery, in selected centres, may exist for a small group of patients after initial failed radiological treatment only.

Performance of prognostic scores in predicting long-term outcome following resection of colorectal liver metastases.

BACKGROUND: Ten-year survival appears to define cure following resection of colorectal liver metastases (CRLMs). Various scores exist to predict outcome at 5 years. This study applied several scores to a patient cohort with 10 years of actual follow-up to assess their performance beyond 5 years. METHODS: The study included consecutive patients who underwent liver resection at a single institution between 1992 and 2001. The ability of eight prognostic scoring systems to predict disease-free (DFS) and disease-specific (DSS) survival was analysed using the C-statistic. RESULTS: Among 286 patients, the 1-, 3-, 5- and 10-year actual DSS rates were 86.6, 58.3, 39.5 and 24.5 per cent respectively. Seventy patients underwent 105 further resections for recurrent disease, of which 84.8 per cent were within 5 years of follow-up. Analysis of C-statistics showed only one score--the Rees postoperative index--to be a significant predictor of DFS and DSS at all time points. The remaining scores performed less well, and regularly showed no significant improvement in predictive accuracy over what would be expected by chance alone. No score yielded a C-statistic in excess of 0.8 at any time point. CONCLUSION: Although available risk scores can predict DFS and DSS, none does so with sufficient discriminatory accuracy to identify all episodes of recurrent disease. A non-negligible proportion of patients develop recurrent disease beyond 5 years of follow-up and so surveillance beyond this point may be advantageous.

Recurrent disease detection after resection of pancreatic ductal adenocarcinoma using a recurrence-focused surveillance strategy (RADAR-PANC): protocol of an international randomized controlled trial according to the Trials within Cohorts design.

BACKGROUND: Disease recurrence remains one of the biggest concerns in patients after resection of pancreatic ductal adenocarcinoma (PDAC). Despite (neo)adjuvant systemic therapy, most patients experience local and/or distant PDAC recurrence within 2 years. High-level evidence regarding the benefits of recurrence-focused surveillance after PDAC resection is missing, and the impact of early detection and treatment of recurrence on survival and quality of life is unknown. In most European countries, recurrence-focused follow-up after surgery for PDAC is currently lacking. Consequently, guidelines regarding postoperative surveillance are based on expert opinion and other low-level evidence. The recent emergence of more potent local and systemic treatment options for PDAC recurrence has increased interest in early diagnosis. To determine whether early detection and treatment of recurrence can lead to improved survival and quality of life, we designed an international randomized trial. METHODS: This randomized controlled trial is nested within an existing prospective cohort in pancreatic cancer centers in the Netherlands (Dutch Pancreatic Cancer Project; PACAP) and the United Kingdom (UK) (Pancreas Cancer: Observations of Practice and survival; PACOPS) according to the "Trials within Cohorts" (TwiCs) design. All PACAP/PACOPS participants with a macroscopically radical resection (R0-R1) of histologically confirmed PDAC, who provided informed consent for TwiCs and participation in quality of life questionnaires, are included. Participants randomized to the intervention arm are offered recurrence-focused surveillance, existing of clinical evaluation, serum cancer antigen (CA) 19-9 testing, and contrast-enhanced computed tomography (CT) of chest and abdomen every three months during the first 2 years after surgery. Participants in the control arm of the study will undergo non-standardized clinical follow-up, generally consisting of clinical follow-up with imaging and serum tumor marker testing only in case of onset of symptoms, according to local practice in the participating hospital. The primary endpoint is overall survival. Secondary endpoints include quality of life, patterns of recurrence, compliance to and costs of recurrence-focused follow-up, and the impact on recurrence-focused treatment. DISCUSSION: The RADAR-PANC trial will be the first randomized controlled trial to generate high level evidence for the current clinical equipoise regarding the value of recurrence-focused postoperative surveillance with serial tumor marker testing and routine imaging in patients after PDAC resection. The Trials within Cohort design allows us to study the acceptability of recurrence-focused surveillance among cohort participants and increases the generalizability of findings to the general population. While it is strongly encouraged to offer all trial participants treatment at time of recurrence diagnosis, type and timing of treatment will be determined through shared decision-making. This might reduce the potential survival benefits of recurrence-focused surveillance, although insights into the impact on patients' quality of life will be obtained. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04875325 . Registered on May 6, 2021.

Efficacy of intraperitoneal local anaesthetic techniques during laparoscopic cholecystectomy.

BACKGROUND: Pain following laparoscopic cholecystectomy (LC) is a barrier to early discharge. Some studies have demonstrated that local anaesthetic (LA) washed over the liver and gallbladder decreases postoperative pain. In many patients pain is partially of diaphragmatic origin which may not be treated effectively by topical wash. This study assesses the efficacy of LA injected to the peritoneum of the right hemidiaphragm or topical wash with a control group. METHODS: We performed a double-blind randomized sham controlled trial of 128 consecutive subjects who underwent elective LC. Patients received subcutaneous bupivacaine, a diaphragmatic injection of bupivacaine or sham, and topical wash over the liver/gallbladder with bupivacaine or sham depending upon allocation. The primary outcome was VAS pain scores on the ward. Secondary outcomes included VRS pain scores in theatre recovery, analgesic use, physiological observations, time to eating and ambulation, and successful day-case surgery. RESULTS: Pain scores were significantly lower in both LA groups versus control in theatre recovery but only in the subperitoneal diaphragm injection group when the patients returned to the ward. Subperitoneal diaphragm injection was associated with a reduced time in theatre recovery (p = 0.04). CONCLUSIONS: Intraperitoneal techniques of LA during LC decrease postoperative pain and shorten time in theatre recovery. Injection of LA to the right hemidiaphragm is associated with lower pain scores for a longer period following LC than a previously validated wash technique.

Long-term symptomatic relief following surgical sphincteroplasty for sphincter of Oddi dysfunction.

INTRODUCTION: Surgical sphincteroplasty (SS) for sphincter of Oddi dysfunction (SOD) can be performed primarily or following failed endoscopic therapy. The role of SS in an era of endoscopic management is unclear. This study presents long-term follow-up of patients who had undergone SS at a tertiary referral unit. METHODS: Patients were identified from a departmental database and sent post-operative questionnaires to review pain scores and satisfaction with the procedure. Indications, pre-operative interventions and complications were recorded. RESULTS: Seventeen patients underwent SS over 13 years. Thirteen patients had objective features of biliary obstruction (delayed excretion of isotope or elevated sphincter pressures). The positive predictive value, sensitivity and specificity of morphine 99mTc-TBIDA in this series was 100, 100 and 92%, respectively. There were 12 responders of whom all but one had symptomatic improvement. Median follow-up was 5.1 years. Pain was significantly lower following SS (16 ± 9 vs. 67 ± 11; p = 0.003) and median satisfaction with the procedure was high (95%). CONCLUSIONS: Excellent symptomatic pain relief following SS can be achieved in carefully selected patients. Manometry does not appear to be essential for diagnosing SOD and morphine provocation hepatic scintigraphy was used to reliably identify patients who would benefit from SS.

Should non-anaesthetists perform pre-hospital rapid sequence induction? an observational study.

INTRODUCTION: The use of rapid sequence induction and tracheal intubation (RSI) in the pre-hospital environment is controversial. Currently, it is felt that competence to perform RSI should be defined by skills in anaesthesia not by the primary speciality of a practitioner. This aim of the study was to evaluate the tracheal intubation success rate of doctors drawn from different clinical specialities performing RSI in the pre-hospital environment. METHOD: Retrospective review of all RSI performed by doctors operating on the Warwickshire and Northamptonshire Air Ambulance over a 5-year period. Tracheal intubation failure rates were calculated and analysed for proportional differences between groups by χ(2) and, where appropriate, Fisher's exact test. RESULTS: 4362 active missions were flown. RSI was performed in 200 cases (4.6%, 3.1/month). Successful intubation occurred in 194 cases, giving a failure rate of 3% (6 cases, 95% CI 0.6 to 5.3%). While no difference in failure rate was observed between emergency department (ED) staff and anaesthetists (2.73% (3/110, 95% CI 0 to 5.7%) vs 0% (0/55, 95% CI 0 to 0%); p=0.55), a significant difference was found when non-ED, non-anaesthetic staff (GP and surgical) were compared to anaesthetists (10.34% (3/29, 95% CI 0 to 21.4%) vs 0%; p=0.04). There was no significant difference associated with seniority of practitioner (p=0.65). CONCLUSIONS: Non-anaesthetic practitioners have a higher tracheal intubation failure rate during pre-hospital RSI. This likely reflects a lack of training opportunities and infrequency of clinical experience. Strategies to improve pre-hospital airway management are required.

Chest decompression during the resuscitation of patients in prehospital traumatic cardiac arrest.

BACKGROUND: Tension and bilateral pneumothorax can cause or contribute to death following trauma. A surgical incision (thoracostomy) or needle decompression through the chest wall rapidly treats these conditions. Resuscitation of patients in traumatic cardiac arrest focuses on treating common and reversible life-threatening conditions. A study was undertaken to observe the practice, findings and outcome of chest decompression when performed as part of the resuscitation strategy of these patients by air ambulance crews. METHODS: Patients in prehospital traumatic cardiac arrest were identified over a 39-month period from an air ambulance database. The use of thoracostomy or needle decompression was identified together with indications, findings and outcome. Primary outcome was return of cardiac output by arrival at hospital. RESULTS: 18 of 37 cases underwent chest decompression (17 thoracostomy, 1 needle decompression). Four patients had a return of cardiac output (3 tension pneumothorax, 1 bilateral pneumothorax). Six further cases were positive for intrathoracic injury. In 2 cases the injuries identified were incompatible with life and resuscitation efforts were consequently ceased. CONCLUSIONS: Chest decompression in traumatic cardiac arrest identifies and treats a high proportion of potentially life-ending injuries and should be considered as part of the resuscitation effort of patients in traumatic cardiac arrest. In a proportion of patients, non-survivable injuries are identified which guide resuscitation efforts.