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.

ß-Cell and renal transplantation options for diabetes.

Despite major advances in structured education, insulin delivery and glucose monitoring, diabetes self-management remains an unremitting challenge. Insulin therapy is inextricably linked to risk of dangerous hypoglycaemia and sustained hyperglycaemia remains a leading cause of renal failure. This review sets out to demystify transplantation for diabetes multidisciplinary teams, facilitating consideration and incorporation within holistic overall person-centred management. Deceased and living donor kidney, whole pancreas and isolated islet transplant procedures, indications and potential benefits are described, in addition to outcomes within the integrated UK transplant programme.

Prospective assessment of resection margin status following pancreaticoduodenectomy for pancreatic ductal adenocarcinoma after standardisation of margin definitions.

BACKGROUND: Surgical resection remains the only curative treatment for pancreatic ductal adenocarcinoma (PDAC). The prognostic value of resection margin status following pancreatoduodenectomy (PD) remains controversial. Standardised pathological assessment increases positive margins but limited data is available on the significance of involved margins. We investigated the impact of resection margin status in PDAC on patient outcome. METHOD: We identified all patients with PD for PDAC at one pancreatic cancer centre between August 2008 and December 2014. Demographic, operative, adjuvant therapeutic and survival data was obtained. Pathology data including resection margin status of specific anatomic margins was collected and analysed. RESULTS: 107 patients were included, all pathologically staged as T3 with 102 N1. 87.9% of patients were R1 of which 53.3% showed direct extension to the resection margin. Median survival for R0 patients versus R1<1 mm and R1 = 0 mm was 28.4 versus 15.4 and 25.1 versus 13.4 months. R1 = 0 mm status remained a predictor of poor outcome on multivariate analysis. Evaluation of individual margins (R1<1 mm) showed the SMV and SMA margins were associated with poorer overall survival. Multiple involved margins impacted negatively on outcome. SMA margin patient outcome with R1 = 1-1.9 mm was similar to R1=>2 mm. CONCLUSION: Using an R1 definition of <1 mm and standardised pathology we demonstrate that R1 rates in PDAC can approach 90%. R1 = 0 mm remained an independent prognostic factor for overall survival. Using R1<1 mm we have shown that involvement of medial margins and multiple margins has significant negative impact on overall survival. We conclude that not all margin positivity has the same prognostic significance.

Multicentre observational cohort study of implementation and outcomes of laparoscopic distal pancreatectomy.

BACKGROUND: Laparoscopic distal pancreatectomy (LDP) is increasingly being performed as an alternative to open surgery. Whether the implementation and corresponding learning curve of LDP have an impact on patient outcome is unknown. The aim was to investigate the temporal trends in practice across UK centres. METHODS: This was a retrospective multicentre observational cohort study of LDP in 11 tertiary referral centres in the UK between 2006 and 2016. The learning curve was analysed by pooling data for the first 15 consecutive patients who had LDP and examining trends in surgical outcomes in subsequent patients. RESULTS: In total, 570 patients underwent LDP, whereas 888 underwent open resection. For LDP the median duration of operation was 240 min, with 200 ml blood loss. The conversion rate was 12·1 per cent. Neuroendocrine tumours (26·7 per cent) and mucinous cystic neoplasms (19·7 per cent) were commonest indications. The proportion of LDPs increased from 24·4 per cent in 2006-2009 (P1) to 46·0 per cent in 2014-2016 (P3) (P < 0·001). LDP was increasingly performed for patients aged 70 years or more (16 per cent in P1 versus 34·4 per cent in P3; P = 0·002), pancreatic ductal adenocarcinoma (6 versus 19·1 per cent; P = 0·005) and advanced malignant tumours (27 versus 52 per cent; P = 0·016). With increasing experience, there was a trend for a decrease in blood transfusion rate (14·1 per cent for procedures 1-15 to 3·5 per cent for procedures 46-75; P = 0·008), ICU admissions (32·7 to 19·2 per cent; P = 0·021) and median duration of hospital stay (7 (i.q.r. 5-9) to 6 (4-7) days; P = 0·002). After 30 procedures, a decrease was noted in rates of both overall morbidity (57·7 versus 42·2 per cent for procedures 16-30 versus 46-75 respectively; P = 0·009) and severe morbidity (18·8 versus 9·7 per cent; P = 0·031). CONCLUSION: LDP has increased as a treatment option for lesions of the distal pancreas as indications for the procedure have expanded. Perioperative outcomes improved with the number of procedures performed.

ANTECEDENTES: Cada día se utiliza más la pancreatectomía distal laparoscópica (laparoscopic distal pancreatectomy, LDP) como una alternativa a la cirugía abierta. Se desconoce si la implementación y la correspondiente curva de aprendizaje de la LDP tienen impacto en los resultados. El objetivo fue investigar las tendencias relacionadas con su implementación en los centros del Reino Unido a los largo del tiempo. MÉTODOS: Se realizó el estudio observacional retrospectivo y multicéntrico de una cohorte de LDP en once centros de referencia terciarios del Reino Unido entre 2006-2016. Se analizó la curva de aprendizaje agrupando los 15 primeros pacientes consecutivos de LDP y se compararon los resultados quirúrgicos con los obtenidos en los pacientes subsiguientes. RESULTADOS: En total, se incluyeron 570 pacientes con LDP y 888 con resección abierta. Para el LDP, la mediana de tiempo operatorio fue de 240 minutos con 200 ml de pérdida de sangre. La tasa de conversión fue del 12,2%. Las indicaciones más frecuentes fueron los tumores neuroendocrinos (26,7%) y las neoplasias quísticas mucinosas (19,7%). La proporción de LDP aumentó del 24% al 46% (de 2006-2009 a 2014-2016; P < 0,001). La LDP se realizó cada vez con mayor frecuencia en pacientes de ≥ 70 años (15,8% versus 34,4%, P = 0,002), en pacientes con adenocarcinoma ductal pancreático (6,5% versus 19,1%, P = 0,005) y en pacientes con tumores malignos avanzados (27,3% versus 51,85%, P = 0,016). Con el aumento de la experiencia, disminuyeron las tendencias de la tasa de transfusión sanguínea (14,1% al 3,5%, P = 0,008), los ingresos en la UCI (32,7% a 19,2%, P = 0.021) y la mediana de la duración de la estancia hospitalaria (7 (rango intercuartílico 5-9) a 6 (rango intercuartilico 4-7) días, P = 0,002). Tras 30 procedimientos, disminuyeron tanto la morbilidad global (57,7% versus 42,2%, P = 0,009) como las tasas de morbilidad grave (21,5% versus 14,6%, P = 0,022). CONCLUSIÓN: La pancreatectomía distal laparoscópica se ha incrementado como una opción de tratamiento para las lesiones del páncreas distal a medida que se han ido ampliando las indicaciones del procedimiento. Los resultados perioperatorios mejoran con el número de procedimientos realizados.

De Novo Donor-Specific HLA Antibodies Are Associated With Rapid Loss of Graft Function Following Islet Transplantation in Type 1 Diabetes.

Outcomes after islet transplantation continue to improve but etiology of graft failure remains unclear. De novo donor-specific human leukocyte antigen (HLA) antibodies (DSA) posttransplant are increasingly recognized as a negative prognostic marker. Specific temporal associations between DSA and graft function remain undefined particularly in programs undertaking multiple sequential transplants. Impact of de novo DSA on graft function over 12 months following first islet transplant was determined prospectively in consecutive recipients taking tacrolimus/mycophenolate immunosuppression at a single center. Mixed-meal tolerance test was undertaken in parallel with HLA antibody assessment pretransplant and 1-3 months posttransplant. Sixteen participants received a total of 26 islet transplants. Five (19%) grafts were associated with de novo DSA. Five (31%) recipients were affected: three post-first transplant; two post-second transplant. DSA developed within 4 weeks of all sensitizing grafts and were associated with decreased stimulated C-peptide (median [interquartile range]) at 3 months posttransplant (DSA negative: 613(300-1090); DSA positive 106(34-235) pmol/L [p = 0.004]). De novo DSA directed against most recent islet transplant were absolutely associated with loss of graft function despite maintained immunosuppression at 12 months in the absence of a rescue nonsensitizing transplant. Alemtuzumab induction immunosuppression was associated with reduced incidence of de novo DSA formation (p = 0.03).

Selective internal radiation therapy for liver malignancies.

BACKGROUND: Selective internal radiation therapy (SIRT) is a non-ablative technique for the treatment of liver primaries and metastases, with the intention of reducing tumour bulk. This study aimed to determine optimal patient selection, and elucidate its role as a downsizing modality. METHODS: Data were collected retrospectively on patients who underwent SIRT between 2011 and 2014. The procedure was performed percutaneously by an expert radiologist. Response was analysed in two categories, based on radiological (CT/MRI according to Response Evaluation Criteria In Solid Tumours (RECIST)) and biological (α-fetoprotein, carcinoembryonic antigen, carbohydrate antigen 19-9, chromogranin A) parameters. RESULTS: Forty-four patients were included. Liver metastases from colorectal cancer (22 patients) and hepatocellular carcinoma (HCC) (9) were the most common pathologies. Radiological response data were collected from 31 patients. A reduction in sum of diameters (SOD) was observed in patients with HCC (median -24.1 (95 per cent c.i. -43.4 to -3.8) per cent) and neuroendocrine tumours (-30.0 (-45.6 to -7.7) per cent), whereas a slight increase in SOD was seen in patients with colorectal cancer (4.9 (-10.6 to 55.3) per cent). Biological response was assessed in 17 patients, with a reduction in 12, a mixed response in two and no improvement in three. Six- and 12-month overall survival rates were 71 and 41 per cent respectively. There was no difference in overall survival between the RECIST response groups (median survival 375, 290 and 214 days for patients with a partial response, stable disease and progressive disease respectively; P = 0.130), or according to primary pathology (P = 0.063). Seven patients underwent liver resection with variable responses after SIRT. CONCLUSION: SIRT may be used to downsize tumours and may be used as a bridge to surgery in patients with tumours deemed borderline for resection.

Oncological feasibility of laparoscopic distal pancreatectomy for adenocarcinoma: a single-institution comparative study.

BACKGROUND: Laparoscopic distal pancreatectomy (LDP) is performed increasingly for pancreatic pathology in the body and tail of the pancreas. However, only few reports have compared its oncological efficacy with open distal pancreatectomy (ODP). We compared these two techniques in patients with pancreatic ductal adenocarcinoma. METHODS: From a prospectively maintained database, all patients who underwent either LDP or ODP for adenocarcinoma in the body and tail of the pancreas between January 2008 and December 2011 were compared. Data were analysed using SPSS(®) v19 utilising standard tests. A p value <0.05 was considered significant. RESULTS: Of 101 patients who underwent distal pancreatectomy, 22 had histologically confirmed adenocarcinoma (LDP n = 8, ODP n = 14). Both groups were well matched for age and the size of tumour (22 vs. 32 mm, p = 0.22). Intraoperative blood loss was 306 ml compared with 650 ml for ODP (p = 0.152). A longer operative time was noted for LDP (376 vs. 274 min, p < 0.05). Total length of stay was shorter for LDP compared with ODP (8 vs. 12 days, p = 0.05). The number of postoperative pancreatic fistulas were similar (LDP n = 2 vs. ODP n = 3, p = 0.5). Complete resection (R0) was achieved in 88 % of LDP (n = 7) compared with 86 % of ODP (n = 12). The median number of lymph nodes harvested was 16 for LDP versus 14 for ODP. Overall 3-year survival also was similar: LDP = 82 %, ODP = 74 % (p = 0.89). CONCLUSIONS: From an oncological perspective, LDP is a viable procedure and its results are comparable to ODP for ductal adenocarcinomas arising in the body and tail of the pancreas.

In Situ Production of Zoospores by Five Species of Phytophthora in Aqueous Environments for Use as Inocula.

The goal of this study was to develop a procedure that could be used to evaluate the potential susceptibility of aquatic plants used in constructed wetlands to species of Phytophthora commonly found in nurseries. V8 agar plugs from actively growing cultures of three or four isolates of Phytophthora cinnamomi, P. citrophthora, P. cryptogea, P. nicotianae, and P. palmivora were used to produce inocula. In a laboratory experiment, plugs were placed in plastic cups and covered with 1.5% nonsterile soil extract solution (SES) for 29 days, and zoospore presence and activity in the solution were monitored at 2- or 3-day intervals with a rhododendron leaf disk baiting bioassay. In a greenhouse experiment, plugs of each species of Phytophthora were placed in plastic pots and covered with either SES or Milli-Q water for 13 days during both summer and winter months, and zoospore presence in the solutions were monitored at 3-day intervals with the baiting bioassay and by filtration. Zoospores were present in solutions throughout the 29-day and 13-day experimental periods but consistency of zoospore release varied by species. In the laboratory experiment, colonization of leaf baits decreased over time for some species and often varied among isolates within a species. In the greenhouse experiment, bait colonization decreased over time in both summer and winter, varied among species of Phytophthora in the winter, and was better in Milli-Q water. Zoospore densities in solutions were greater in the summer than in the winter. Decreased zoospore activities for some species of Phytophthora were associated with prolonged temperatures below 13 or above 30°C in the greenhouse. Zoospores from plugs were released consistently in aqueous solutions for at least 13 days. This procedure can be used to provide in situ inocula for the five species of Phytophthora used in this study so that aquatic plant species can be evaluated for potential susceptibility.

The potential contribution of tumour-related factors to the development of FOLFOX-induced sinusoidal obstruction syndrome.

BACKGROUND: Chemotherapy-associated liver injury (CALI) has been linked to increased morbidity and poorer disease-specific outcomes in patients undergoing resection of colorectal liver metastases (CRLM). The aim of this study was to assess the contribution of tumour-related factors to the development of FOLFOX-induced liver injury. METHODS: We assessed the effect of FOLFOX treatment on the murine liver either in the presence or absence of CRLM to evaluate the contribution of both chemotherapy and tumour death to the development of CALI. RESULTS: In the presence of liver metastases, there was increased hepatic expression of plasminogen activator inhibitor-1 (146-fold; P<0.01) and vWF (2.4-fold; P<0.01) transcript as compared with sham-operated controls. In addition, we detected large clusters of megakaryocytes in the spleen of FOLFOX-treated tumour-bearing animals. The livers of FOLFOX-treated animals also showed changes in matrix remodelling genes such as TGFß (P<0.01), MMP2 (P<0.001), TIMP1 (P<0.001) and Pro-Collagen I (P<0.05) which was exacerbated in the presence of tumour. These genes have previously been demonstrated to have a key role in FOLFOX-induced liver injury. CONCLUSION: It appears that the toxicity of FOLFOX chemotherapy is enhanced by tumour-related factors.

Inhibition of CXCR4-CXCL12 chemotaxis in melanoma by AMD11070.

BACKGROUND: Despite intensive research and novel adjuvant therapies, there is currently no cure for metastatic melanoma. The chemokine receptor CXCR4 controls metastasis to sites such as the liver; however, the therapeutic blockade with the existing agents has proven difficult. METHODS: AMD11070, a novel orally bioavailable inhibitor of CXCR4, was tested for its ability to inhibit the migration of melanoma cells compared with the commonly described antagonist AMD3100. RESULTS: AMD11070 abrogated melanoma cell migration and was significantly more effective than AMD3100. Importantly for the clinical context, the expression of B-RAF-V600E did not the affect the sensitivity of AMD11070. CONCLUSION: Liver-resident myofibroblasts excrete CXCL12, which is able to promote the migration of CXCR4-expressing tumour cells from the blood into the liver. Blockade of this axis by AMD11070 thus represents a novel therapeutic strategy for both B-RAF wild-type and mutated melanomas.

Pathogenesis of FOLFOX induced sinusoidal obstruction syndrome in a murine chemotherapy model.

BACKGROUND & AIMS: Sinusoidal obstruction syndrome (SOS) following oxaliplatin based chemotherapy can have a significant impact on post-operative outcome following resection of colorectal liver metastases. To date no relevant experimental models of oxaliplatin induced SOS have been described. The aim of this project was to establish a rodent model which could be utilised to investigate mechanisms underlying SOS to aid the development of therapeutic strategies. METHODS: C57Bl/6 mice, maintained on a purified diet, were treated with intra-peritoneal FOLFOX (n=10), or vehicle (n=10), weekly for five weeks and culled one week following final treatment. Sections of the liver and spleen were fixed in formalin and paraffin embedded for histological analysis. The role of oxidative stress on experimental-induced SOS was determined by dietary supplementation with butylated hydroxyanisole and N-acetylcysteine. RESULTS: FOLFOX treatment was associated with the development of sinusoidal dilatation and hepatocyte atrophy on H&E stained sections of the liver in keeping with SOS. Immunohistochemistry for p21 demonstrated the presence of replicative senescence within the sinusoidal endothelium. FOLFOX induced endothelial damage leads to a pro-thrombotic state within the liver associated with upregulation of PAI-1 (p<0.001), vWF (p<0.01) and Factor X (p<0.001), which may contribute to the propagation of liver injury. Dietary supplementation with the antioxidant BHA prevented the development of significant SOS. CONCLUSIONS: We have developed the first reproducible model of chemotherapy induced SOS that reflects the pathogenesis of this disease in patients. It appears that the use of antioxidants alongside oxaliplatin based chemotherapy may be of value in preventing the development of SOS in patients with colorectal liver metastases.

Liver damage during organ donor procurement in donation after circulatory death compared with donation after brain death.

BACKGROUND: During the past decade the number of livers recovered and transplanted from donation after circulatory death (DCD) donors has increased significantly. As reported previously, injuries are more frequent during kidney procurement from DCD than from donation after brain death (DBD) donors. This aim of this study was to compare outcomes between DCD and DBD with respect to liver injuries. METHODS: Data on liver injuries in organs procured between 2000 and 2010 were obtained from the UK Transplant Registry. RESULTS: A total of 7146 livers were recovered from deceased donors during the study, 628 (8·8 per cent) from DCD donors. Injuries occurred in 1001 procedures (14·0 per cent). There were more arterial (1·6 versus 1·0 per cent), portal (0·5 versus 0·3 per cent) and caval (0·3 versus 0·2 per cent) injuries in the DBD group than in the DCD group, although none of these findings was statistically significant. Capsular injuries occurred more frequently in DCD than DBD (15·6 versus 11·4 per cent; P = 0·002). There was no significant difference between DCD and DBD groups in liver discard rates related to damage. CONCLUSION: There were no differences in terms of vascular injuries between DCD and DBD livers, although capsular injuries occurred more frequently in DCD organs. Continuing the trend for increased frequency of DCD liver recovery, and ensuring that there is an adequately skilled surgical team available for procurement, is vital to improving the utilization of DCD livers.

Methods of haemostasis during liver resection--a UK national survey.

BACKGROUND: Although haemorrhage is a major cause of morbidity and mortality in liver surgery, there is very little available guidance on its management. METHODS: The aim of this study was to identify current practice in the UK in this regard. An online survey was created and hepatobiliary (HPB) specialists who were members of a specialist society and others who were known practitioners were invited by e-mail to complete the survey anonymously. RESULTS: Fifty-one percent responded (n = 36/70), and most of these respondents worked at large HPB centres (>100 liver resections/year; n = 24, 66%). Not all questionnaires were fully completed by the individual surgeons. Thirty-eight percent of the surgeons routinely used Pringle's manoeuvre. Most surgeons used ligation of the inflow vessels (n = 16, 44%) and stapled the outflow vessels (n = 15, 42%). The Cavitron ultrasonic surgical aspirator (CUSA; 54%, 13/24) was preferred for parenchymal transection. The majority routinely used haemostatic adjuncts (n = 22, 62%), whilst 33% (n = 12) used them occasionally. Twenty-three (64%) felt manufactured haemostatic adjuncts played a major role in maintaining haemostasis and 19 preferred fibrin-based products. CONCLUSION: The Pringle manoeuvre is a popular technique amongst specialist UK liver surgeons and the CUSA is used by nearly half of the surgeons. Despite the absence of definitive evidence for their benefit, manufactured haemostatic adjuncts are still widely used, especially the fibrin-based adjuncts.

Prognostic factors and survival after resection of colorectal liver metastasis in the era of preoperative chemotherapy: an 11-year single-centre study.

INTRODUCTION: A variety of factors have been identified in the literature which influence survival following resection of colorectal liver metastases (CRLM). Much of this literature is historical, and its relevance to contemporary practice is not known. The aim of this study was to identify those factors which influence survival during the era of preoperative chemotherapy in patients undergoing resection of CRLM in a UK centre. METHODS: All patients having liver resection for CRLM during an 11-year period up to 2011 were identified from a prospectively maintained database. Prognostic factors analysed included tumour size (≥5 or <5 cm), lymph node status of the primary tumour, margin positivity (R1; <1 mm), neo-adjuvant chemotherapy (for liver), tumour differentiation, number of liver metastases (≥4), preoperative carcinoembryonic antigen (CEA; ≥200 ng/ml) and whether metastases were synchronous (i.e. diagnosed within 12 months of colorectal resection) or metachronous to the primary tumour. Overall survival (OS) was compared using Kaplan-Meier plots and a log rank test for significance. Multivariate analysis was performed using a Cox regression model. Statistical analysis was performed in SPSS v19, and p < 0.05 was considered to be significant. RESULTS: 432 patients underwent resection of CRLM during this period (67% male; mean age 64.5 years), and of these, 54 (13.5%) had re-resections. The overall 5-year survival in this series was 43% with an actuarial 10-year survival of 40%. A preoperative CEA ≥200 ng/ml was present in 10% of patients and was associated with a poorer 5-year OS (24 vs. 45%; p < 0.001). A positive resection margin <1 mm was present in 16% of patients, and this had a negative impact on 5-year OS (15 vs. 47%; p < 0.001). Tumour differentiation, number, biliary or vascular invasion, size, relationship to primary disease, nodal status of the primary disease or the use of neo-adjuvant chemotherapy had no impact on OS. Multivariate analysis identified only the presence of a positive resection margin (OR 1.75; p < 0.05) and a preoperative CEA ≥200 ng/ml (OR 1.88; p < 0.01) as independent predictors of poor OS. CONCLUSION: Despite the wide variety of prognostic factors reported in the literature, this study was only able to identify a preoperative CEA ≥200 ng/ml and the presence of tumour within 1 mm of the resection margin as being of value in predicting survival. These variables are likely to identify patients who may benefit from intensive follow-up to enable early aggressive treatment of recurrent disease.

Kidney damage during organ recovery in donation after circulatory death donors: data from UK National Transplant Database.

During the last 10 years, kidneys recovered/transplanted from donors after circulatory death (DCD) have significantly increased. To optimize their use, there has been an urgent need to minimize both warm and cold ischemia, which often necessitates more rapid removal. To compare the rates of kidney injury during procurement from DCD and donors after brain death (DBD) organ donors. A total of 13 260 kidney procurements were performed in the United Kingdom over a 10-year period (2000-2010). Injuries occurred in 903 procedures (7.1%). Twelve thousand three hundred seventy-two (93.3%) kidneys were recovered from DBD donors and 888 (6.7%) from DCD donors. The rates of kidney injury were significantly higher when recovered from DCD donors (11.4% vs. 6.8%, p < 0.001). Capsular, ureteric and vascular injuries were all significantly more frequent (p = 0.002, p < 0.001 and p = 0.017, respectively). Discard because of injury was more common after DCD donation (p = 0.002). Multivariate analysis demonstrated procurement injuries were significantly associated with DCD donors (p = 0.035) and increased donor age (<0.001) and donor body mass index (BMI; 0.001), donor male gender (p = 0.001) and no liver donation (0.009). We conclude that procurement from DCD donors leads to higher rates of injury to the kidney and are more likely to be discarded.

Effects of low cardiopulmonary reserve on pancreatic leak following pancreaticoduodenectomy.

BACKGROUND: Postoperative complications are increased in patients with reduced cardiopulmonary reserve undergoing major surgery. Pancreatic leak is an important contributor to postoperative complications and death following pancreaticoduodenectomy. The aim of this study was to determine whether reduced cardiopulmonary reserve was a risk factor for pancreatic leak. METHODS: All patients who underwent pancreaticoduodenectomy between January 2006 and July 2010 were identified from a prospectively held database. Data analysis was restricted to those who underwent cardiopulmonary exercise testing during preoperative assessment. Pancreatic leak was defined as grade A, B or C according to the International Study Group on Pancreatic Fistula definition. An anaerobic threshold (AT) cut-off value of 10·1 ml per kg per min was used to identify patients with reduced cardiopulmonary reserve. Univariable and multivariable analyses were performed to identify other risk factors for pancreatic leak. RESULTS: Some 67 men and 57 women with a median age of 66 (range 37-82) years were identified. Low AT was significantly associated with pancreatic leak (45 versus 19·2 per cent in patients with greater cardiopulmonary reserve; P = 0·020), postoperative complications (70 versus 38·5 per cent; P = 0·013) and prolonged hospital stay (29·4 versus 17·5 days; P = 0·001). On multivariable analysis, an AT of 10·1 ml per kg per min or less was the only independent factor associated with pancreatic leak. CONCLUSION: Low cardiopulmonary reserve was associated with pancreatic leak following pancreaticoduodenectomy. AT seems a useful tool for stratifying the risk of postoperative complications.

Intraoperative cholangiography in the laparoscopic cholecystectomy era: why are we still debating?

Laparoscopic cholecystectomy is now one of the most frequently performed abdominal surgical procedures in the world. The most common major complication is bile duct injury, which can have catastrophic repercussions for patients and it has been suggested that intraoperative cholangiography may reduce the rate of bile duct injury. Whether this procedure should be performed routinely is still an active subject of debate. We discuss the available evidence and likely implications for the future.

Robotic versus conventional laparoscopic liver resections: A systematic review and meta-analysis.

BACKGROUND: Theoretical advantages of robotic surgery compared to conventional laparoscopic surgery include improved instrument dexterity, 3D visualization, and better ergonomics. This systematic review and meta-analysis aimed to determine advantages of robotic surgery over laparoscopic surgery in patients undergoing liver resections. METHOD: A systematic literature search was conducted for studies comparing robotic assisted or totally laparoscopic liver resection. Meta-analysis of intraoperative (operative time, blood loss, transfusion rate, conversion rate), oncological (R0 resection rates), and postoperative (bile leak, surgical site infection, pulmonary complications, 30-day and 90-day mortality, length of stay, 90-day readmission and reoperation rates) outcomes was performed using a random effects model. RESULT: Twenty-six non-randomized studies including 2630 patients (950 robotic and 1680 laparoscopic) were included, of which 20% had major robotic liver resection and 14% had major laparoscopic liver resection. Intraoperatively, robotic liver resection was associated with significantly less blood loss (mean: 286 vs 301 mL, p < 0.001) but longer operating time (mean: 281 vs 221 min, p < 0.001). There were no significant differences in conversion rates or transfusion rates between robotic liver resection and laparoscopic liver resection. Postoperatively, there were no significant differences in overall complications, bile leaks, and length of hospital stay between robotic liver resection and laparoscopic liver resection. However, robotic liver resection was associated with significantly lower readmission rates than laparoscopic liver resection (odds ratio: 0.43, p = 0.005). CONCLUSIONS: Robotic liver resection appears to offer some advantages compared to conventional laparoscopic surgery, although both techniques appear equivalent. Importantly, the quality of evidence is generally limited to cohort studies and a high-quality randomized trial comparing both techniques is needed.

Cognitive Motor Dual Task Costs in Older Adults with Motoric Cognitive Risk Syndrome.

The purpose of this study was to characterize Cognitive Motor Dual Task (CMDT) costs for a community-based sample of older adults with Motoric Cognitive Risk Syndrome (MCR), as well as investigate associations between CMDT costs and cognitive performance. Twenty-five community-dwelling older adults (ages 60-89 years) with MCR performed single and dual task complex walking scenarios, as well as a computerized cognitive testing battery. Participants with lower CMDT costs had higher scores on composite measures of Working Memory, Processing Speed, and Shifting, as well as an overall cognitive composite measure. In addition, participants with faster single task gait velocity had higher scores on composite measures of Working Memory, Processing Speed, and overall cognition. Taken together, these results suggest that CMDT paradigms can help to elucidate the interplay between cognitive and motor abilities for older adults with MCR.