Background: Various descriptive terms are utilised in the radiological reporting of pancreatic tumours and their association with surrounding vasculature which in turn defines tumour resectability. This study aimed to generate and validate a radiological reporting proforma for borderline and locally advanced tumours in an effort to provide standardization, improve the ability to reliably define tumour resectability, and generate consistency when comparing institutional Results. Material and Methods: A group of HPB surgeons and radiologists formed a think tank to identify the key factors that determine tumour resectability, with emphasis on vascular involvement whilst considering current guidelines (MD Anderson and AHPBA/SSAT/SSO/NCCN). The PROTRACT (Pancreatic Tumour Radiological Assessment and Classification) proforma was subsequently generated. A validation analysis assessed concordance between 2 blinded radiologists reporting CT-Pancreas images of borderline and locally advanced tumours. Results: The PROTRACT proforma includes information on all aspects of pancreatic tumours, with a particular emphasis on avoiding descriptive terms of vessel involvement, and rather quantifying this (i.e. length, axial circumferential degree and 'compass position' of involvement, degree of stricturing, presence of occlusion/invasion). The validation study revealed the SMV to be the most commonly involved vessel (72.2%) followed by the PV (50%), with a mean length and degree of involvement across all vessels of 20.5mm and 221degrees. When analyzing concordance between the two reporters, the median concordance rate of vessel involvement, stricturing, occlusion and invasion was 69%, 80%, 100% and 100% respectively. Conclusions: We believe the PROTRACT proforma is a useful tool to improve consistency in the radiological reporting of pancreatic tumours. We hope the current pilot work may be built upon through constructive feedback to optimize the reporting process, and thus improve our ability to compare clinical care and ensure patients are reliably classified into the appropriate tumour category with respect to potential future resection +/- vascular reconstruction.
Neoadjuvante Chemotherapie kann ein borderline resektables (BRPC) oder lokal fortgeschrittenes duktales Adenokarzinom des Pankreas (LAPC) in ein operables Stadium konvertieren. Allerdings existieren nur wenige Studien, die die unterschiedlichen Therapiemöglichkeiten vergleichend untersuchen. In der vorliegenden multizentrischen, retrospektiven Studie wird der prognostische Einfluss verschiedener Chemotherapieregime im neoadjuvanten Setting untersucht.
Aims: Vascular remodelling is a physiological process that is recognised after a number of insults and differs from pathological stenotic disease which can be associated with rejection and donor specific antibodies in transplanted grafts. This study examined the incidence of vascular remodelling following combined kidney and pancreas transplantation. Methods: In 2012 CT angiography became routine for pancreas transplants in the early (<5 days) and late (< 6 months) post-transplant period. This study examined changes in axial/coronal diameters of the arterial conduit, external iliac artery (EIA), internal iliac artery (IIA), superior mesenteric artery (SMA), splenic artery (SA) and renal arteries. Measurements were made by experienced radiologists. Results: 8 transplants were performed with the necessary follow-up scans (6 SPK, 2 PAK). All patients received standard immunosuppression of tacrolimus, MMF +/− prednisolone. Significant uniform luminal narrowing was observed in all vessels except the renal arteries. One episode of pancreatic graft rejection was encountered which resolved with steroids. Two patients developed arterial branch thrombosis (1 early, 1 late) requiring anti-coagulation. Other morbidity included collection (n = 2) and graft pancreatitis (n = 1). All grafts were functioning at a median follow up of 15 months (range 10–21) and all patients were insulin independent. Conclusions: Our data suggests luminal narrowing of all arteries associated with the pancreatic allograft without any corresponding changes in the renal arteries. This does not appear to impact on short term graft function. It is difficult to determine whether this remodelling process directly contributes to the development of vascular pathology. Therefore further studies should be performed to discover whether this phenomenon is detrimental in the long-term, and to determine if therapeutic intervention is required.
Aims: Patients who undergo pancreas transplantation are inherently high-risk candidates due to the comorbidities associated with diabetes and renal failure. Cardiopulmonary exercise testing (CPeT) has been shown to accurately predict the outcome of other major abdominal operations, including liver transplantation. We aimed to establish its validity in predicting the outcome for pancreas transplant patients. Methods: A retrospective review of prospectively captured data was carried out for all consecutive pancreas transplants in a single centre over a 7 year period. CPeT was carried out on all patients prior to placing them on the waiting list. The test was conducted in a consistent environment and reviewed by a trained physician to determine standard objective measures of cardiorespiratory reserve (anaerobic threshold AT, peak oxygen consumption VO2). Results: 68 patients had either pancreas-alone or simultaneous pancreas/ kidney transplants. 17 patients were excluded as they were assessed prior to implementation of the CPeT service. 1 patient didn't reach their AT, so was excluded from the analysis. 50 patients underwent a successful CPeT and were transplanted. Mean donor age was 40.8, median 46. The mean AT for patients with a functioning graft at last follow up was 13.2 (SD 2.8) compared with 11.1 (1.6) for those either deceased or who no longer have a functioning graft (p = 0.006, t-test). There was also a significant difference when comparing the peak VO2 (functioning 16.7 3.9, non-functioning 14.1 2.6, p = 0.015). Conclusions: Preoperative markers of cardiorespiratory reserve determined by CPeT testing can predict graft and patient survival after pancreas transplantation. This may be helpful in improving patient selection for pancreas transplantation.
Aims: 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 aims to identify which patients may benefit most from the procedure, and determine its role as a conversion therapy. Methods: Retrospective data collection on 44 patients. Radiological measurements were made by experienced radiologists to calculate post-SIRT response according to RECIST criteria. Results: Colorectal cancer liver metastases (55%) and hepatocellular carcinoma (17%) were the most common pathologies. Radiological response (RECIST) was assessed in 31 patients. Reduction in SOD (sum of diameters) was most significant in patients with HCC (median -24.1%, CI -43.4 to -3.8) and NET (median -30%, CI -45.6 to -7.7). Biological response was assessed using tumour markers in 17 patients, with a reduction in 12 (70.5%), mixed response in 2 (11.8%) and no improvement in 3 (17.6%). 6 and 12 month OS was 70.5% and 40.9% respectively. There was no difference in OS between the RECIST response groups (p = 0.13), with a more significant impact on OS with respect to primary pathology (p = 0.063). 7 patients (13.8%) underwent liver resection with variable responses post-SIRT. Conclusions: Select patients, most notably those with HCC, either experience a beneficial response or delayed progression; a larger patient cohort with prolonged follow up may translate into a survival benefit. We believe SIRT can be used to downsize tumours as a bridge to surgery in borderline patients, with a potential impact on the future liver remnant. Further studies are required to determine optimal patient selection and compare SIRT with alternative treatment modalities.
Aims: A variety of techniques are used for pancreas transplantation without a clear consensus on the optimal approach. One variation is whether the pancreas graft is placed intra-peritoneally or extraperitoneally. Adequate exposure to iliac vessels can be obtained by either approach, but there are inherent advantages and disadvantages to each. In this study, we aimed to analyse the short and long term differences from either approach. Methods: We performed a retrospective analysis of 50 consecutive pancreas transplants performed in a single centre over a 6-year period. Sufficient data were available on 44 (29 intraperitoneal, 15 extraperitoneal) Data was collected on length of hospital stay, number of returns to theatre due to complications and inflammatory response. Results: The total length of hospital stay was slightly longer in the extra-peritoneal group, but not statistically significant (36.3 vs 46.1 days; t-test, p = 0.5). There was also no significant difference in peak levels of CRP (250.5 vs 256.7, p = 0.88) or number of returns to theatre for complications (0.68 vs 0.8, p = 0.72). However, the peak amylase was significantly higher in the extra-peritoneal group (138.5 vs 263.3, p = 0.02). The long term survival of the grafts was not statistically significant with 17/29 (58.6%) of intraperitoneal grafts including 2 deaths vs 7/15 (46.7%) of extraperitoneal grafts functioning at last follow up. There was no significant difference in donor age (mean intraperitoneal 43.8, extraperitoneal 37.9, p = 0.12). Conclusions: There are no major significant differences in outcome between intra- and extra-peritoneally placed pancreas transplant grafts. There was an increased peak amylase level in the extraperitoneal group which may represent increased localised inflammatory response often observed in extraperitoneal grafts, which may be a reason to favour intraperitoneal placement. However, surgeon and institutional experience remains a factor in choice of technique, as there are no significant differences, this is likely to remain the case.
Aims: The reverse Warburg effect (RWE) is a novel concept supporting a lactate shuttling mechanism between cancer cells (CCs) and stromal cancer associated fibroblasts, which resemble the activated pancreatic stellate cell (PSC) phenotype, which in turn drives anabolic tumour growth. This study aimed to investigate this phenomenon through examination of monocarboxylate transporter (MCT1 & 4) expression, in addition to CD147 (MCT chaperone), caveolin-1 (autophagy marker) and glycolytic enzyme activity. Methods: PSCs were placed in an in vitro transwell co-culture system with MiaPaCa2 cells, an immortalised PDAC line, for 24 and 48 hour time courses, in addition to controls. Protein and RNA was then extracted, and western blot and qPCR analysis subsequently performed. Results: qPCR analysis revealed a significant increase in MCT1 and MCT4 expression in PSCs after co-culture for 24 hours (1810-fold and 77-fold respectively) and 48 hours (4103-fold and 4464-fold respectively) as compared to solo controls. These observations were supported by western blot, with additional CD147 and Cav1 upregulation. CCs also demonstrated an increase in MCT1 and MCT4 expression at 24 hours (9-fold and 1.6-fold respectively) and 48 hours (7-fold and 406-fold respectively). Anti-oxidant (N-acetylcysteine) treatment suggests this upregulation may be ROS-dependent. Glycolytic enzyme expression further supports the RWE theory. Conclusions: The RWE, or an alternative form of metabolic symbiosis involving lactate/pyruvate shuttling, appears to be active between PSCs and CCs. Elaboration of these results may delineate the protumorigenic role of PSCs in lactate metabolism within the tumour environment, and determine the true mode of action and feasibility of MCT inhibition.
A 61-year-old man presented with jaundice, and subsequently underwent an extended left hepatectomy and pancreaticoduodenectomy for a cholangiocarcinoma invading the head of the pancreas. The patient developed sepsis due to a biliary leak at the hepaticojejunostomy. We describe the original use of a biodegradable stent, deployed via percutaneous transhepatic cholangiography into the Roux limb, resulting in good drainage and resolution of sepsis. The chief benefit of this procedure is the lack of need for subsequent removal as well as purported reduced biofilm accumulation. We believe this to be the first reported case of this type and the literature surrounding the subject is also discussed.
Background: Irreversible electroporation (IRE) is a novel procedure to combat pancreatic cancer, whereby high voltage pulses are delivered, resulting in cell death. This represents an ideal alternative to other thermal treatment modalities, as there is no overriding heat effect, therefore reducing the risk, of injury to vessels and ducts.Methods: Multiple databases were searched to January 2014. Primary outcome measures were survival and associated morbidity. 41 articles were initially identified; of these 4 studies met the inclusion criteria, yielding 74 patients in total.Results: 94.5% of patients had locally advanced tumours, the remainder-had metastatic disease. Treated tumour size ranged from 1 to 7 cm. IRE approach included open (70.3%), laparoscopic (2.7%) and percutaneous (27%; ultrasound-guided 30%, CT-guided 70%) Morbidity ranged from 0 to 33%; due to the high number of simultaneous procedures performed (resection/bypass) it was difficult to ascertain IRE-related complications. However no significant bleeding occurred when IRE-alone was performed. Survival statistics suggest a prognostic benefit. Reported survival included: 6 month survival of 40% (n = 5) and 70% (n = 14); PFS and OS 14 and 20 months respectively (n = 54). Results of most interest showed a significant survival benefit in matched IRE vs non-IRE groups (PFS 14 vs 6 mths; p = 0.01, OS 20 vs 11 mths; p = 0.03).Conclusion: Initial evidence suggests IRE incurs a prognostic benefit with minimal morbidity. More high quality research is required to determine the role IRE may play in the multi-modal management of pancreatic cancers. (C) 2014 Elsevier Ltd. All rights reserved.