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.

Systemic neutrophil-to-lymphocyte ratio in colorectal cancer: the relationship to patient survival, tumour biology and local lymphocytic response to tumour.

BACKGROUND: Colorectal cancer (CRC) is a major cause of mortality and morbidity. The impact of inflammatory biomarkers (C-reactive protein etc.) on CRC is increasingly studied including systemic neutrophil-to-lymphocyte ratio (NLR) as they seem to predict outcome. METHODS: All patients who underwent curative resection for CRC from 2000 to 2004 at Leeds Teaching Hospitals NHS Trust had pre-operative NLR calculated. Demographic, histopathological and survival data were collected. Tissue microarrays were created and stained to determine the mismatch repair (MMR) protein status of each tumour. Local lymphocytic response to the tumour was assessed and graded. RESULTS: About 358 patients were eligible. Of these 88 had an NLR ⩾5, which predicted lower overall survival and greater disease recurrence. A high NLR is associated with higher pT- and pN-stage and a greater incidence of extramural venous invasion. MMR protein status was not associated with NLR. A pronounced lymphocytic reaction at the invasive margin (IM) indicated a better prognosis and was associated with a lower NLR. CONCLUSION: Neutrophil-to-lymphocyte ratio predicts disease-free and overall survival and is associated with a more aggressive tumour phenotype. The lymphocytic response to tumour at the IM is associated with NLR however dMMR is not. Neutrophil-to-lymphocyte ratio is a cheap, easy-to-access test that predicts outcome in CRC.

Predicting donor asystole following withdrawal of treatment in donation after cardiac death.

Donation after cardiac death donation allows donor pool expansion. The period between withdrawal of treatment and donor a systole is extremely variable; its prolongation often results in unsuccessful organ procurement. We sought to assess a variety of donor variables to determine whether they predicted successful organ retrieval. We included all Donation after Cardiac Death (DCD) retrievals between 2002 and 2009, which were grouped as successful (n = 104) versus unsuccessful (n = 42). Factors that predicted unsuccessful organ procurement included older donor age, donor history of hypertension, higher at withdrawal, and absence of inotropic support. On multivariate analysis, mean arterial pressure retained its significance. Prediction of withdrawal-to-asystole time is complex, but our analysis suggested that donor blood pressure at withdrawal is an important predictor of whether retrieval would be successful.

Comparable outcomes in donation after cardiac death and donation after brainstem death: a matched analysis of renal transplants.

Donation after cardiac death (DCD) donors provide a valuable source of grafts for renal transplantation. They are exposed to an initial warm ischemic insult, which can affect early function. We sought to compare our initial DCD experience in renal transplantation with a case-matched donation after brain death (DBD) cohort from the same period. We included all DCD transplantations in the first 5 years of the program. A control DBD group was matched with a variety of donor and recipient factors. We demonstrated a significantly increased early dysfunction (DGF and primary nonfunction). DCD graft function was poorer than the DBD equivalent at 1- and 3-years. However, medium-term recipient and graft outcomes were comparable. DCD grafts continue to play a vital role in renal transplantation despite evidence of early graft dysfunction.

Impact of cold ischemia on renal transplant outcomes following donation after cardiac death.

Donation after cardiac death (DCD) provides grafts in renal transplantation but is associated with increased early graft dysfunction. Cold ischemia time (CIT) is a factor that is thought to affect outcomes in renal transplantation. We sought to assess the impact of the length of CIT among our DCD cohort of renal transplants performed between April 2002 and December 2009. Since the median CIT was 15.5 hours, we formed two groups CIT < 15.5 (n = 100) and CIT > 15.5 hr (n = 98). We demonstrated an increased incidence of DGF among the extended CIT group, but the long outcomes and the mean graft function were otherwise comparable. In conclusion, CIT affects early graft function; every effort should be made to minimize it in renal transplantation using DCD kidneys.

Impact of age matching of donors to recipients on renal transplant outcomes following donation after cardiac death.

Organ donation after cardiac death (DCD) provides a valuable supply of grafts for renal transplantation. Age matching of donors to recipients is often used. We sought to determine the impact of age matching on the outcomes among our cohort of DCD renal transplant recipients. Using our institutional database, we gathered information on all DCD renal transplants performed between April 2002 and December 2009. We divided the cohort into two groups based upon the donor:recipient age ratio: age-matched (between 25th and 75th percentiles, n = 99) and non-age-matched (<25th percentile and >75th centile, n = 100). We failed to demonstrate any significant difference between the two groups in terms of early complications or long-term outcome or function. Age matching did not appear to affect graft outcomes, particularly for young donors, but may have a role in older donors.

Outcomes following renal transplantation after multiorgan retrieval versus kidney-only retrieval in donation after cardiac death donors.

With the increase of donation after cardiac death (DCD) now including procurements for not only kidney but also liver, pancreas, and lung transplantations, we analyze whether multiorgan DCD retrievals have a negative impact on immediate and short-term renal transplant outcomes due to increased length of time of explantation of the kidney from the donor and the associated risks of re-warming. We performed a retrospective study of all DCD donors from 2002 to 2009 at a single unit. Immediate and short-term outcomes between kidney-only versus multiorgan retrieval were compared. Cold ischaemia was significant between the two groups (P = .04), but all other variables were nonsignificant. The results show that immediate graft function, rates of acute rejection and graft/recipient survival are comparable when DCD allografts are procured from both multiorgan and kidney-only donors. The comparable outcomes from kidney-only and multiorgan donations in this study may be due to by the highly selective use of donors for multiorgan DCD donation. This selectivity may explain the "better" quality of kidney for these cases in which patients were able to tolerate potentially injurious rewarming.

Renal transplantation following donation after cardiac death: impact of duration from withdrawal to asystole.

Donation after cardiac death (DCD) allows for expansion of the donor pool, however, the process for DCD donation can lead to a donor's physiological instability before asystole. This may have a detrimental effect on graft and patient outcomes. We analyzed all 201 DCD donations at our unit from 2002 to 2009 and compared short versus long durations to asystole around the median time (20 min). Delayed graft function was comparable between the groups (P = .13), primary nonfunction was increased in the long duration to asystole group (P < .0001), and acute rejection was increased in the short duration group (P < .001). Five year patient survival was comparable (P = .6). In conclusion, long duration asystole may have an immediate effect on graft survival, but it has no overall detrimental effect on longer-term outcomes. Further studies are required to investigate the acceptable time to wait from withdrawal to asystole.

Sequential transplant of paired kidneys following donation after cardiac death: impact of longer cold ischemia time on the second kidney on graft and patient outcome.

The United Kingdom has no national sharing scheme for kidneys received from donation after cardiac death (DCD). Therefore, both kidneys retrieved by a transplant team are implanted at a single unit, often sequentially. This study analyzes the impact of a prolonged cold ischaemia time on the second transplanted kidney and the effects on short-term and long-term outcomes in all our DCD renal implants from 2002 to 2009. Cold ischaemia time was significantly longer with the second kidney (P = .04) as was delayed graft function (P = .02). Acute rejection was increased in the first transplanted kidney (P < .001). Five-year patient survival was comparable between groups, but 5-year graft survival was higher in the second transplanted group (P = .04). The results confirm that, provided recipient centers are willing to accept higher initial rates of delayed graft function, it is acceptable to transplant DCD grafts sequentially without jeopardizing long-term graft or recipient outcome.

Serum C-reactive protein concentration and the prognosis of ductal adenocarcinoma of the head of pancreas.

BACKGROUND: The prognostic role of serum C-reactive protein in pancreatic cancer has received increasing attention; however the confounding effects of biliary obstruction have not been addressed in previous studies. We sought to determine the prognostic importance of serum CRP prior to biliary intervention in the prognosis of pancreatic adenocarcinoma. METHODS: A retrospective case note review of patients diagnosed with pancreatic cancer between 2001 and 2006. Clinical, radiological and biochemical criteria were correlated with overall survival. Patients were divided into: Group 1 who underwent potentially curative resection, and Group 2 with advanced unresectable disease managed non-surgically. RESULTS: In total, 199 patients were included (58 resected). The proportion of patients with biliary obstruction was equal in both groups. Serum CRP and serum bilirubin concentration at presentation were significantly higher among patients in Group 2 compared to Group 1 (P values). On multivariate analysis, advancing age (P=0.012) and raised serum CRP concentration were independently associated with overall survival only in Group 2 patients (P=0.027, 95% CI 0.31-0.93). This association was independent of biliary tract obstruction. CONCLUSION: Raised serum C-reactive protein concentration at the time of presentation of advanced pancreatic cancer carries a poor prognosis independent of biliary tract obstruction.