Preliminary experience with a new robotic technique to facilitate distal pancreatectomy with spleen preservation: left lateral approach in right lateral decubitus position.

Spleen-preserving distal pancreatectomy (SP-DP), for patients with benign or small low-grade malignant tumors of the body or tail of the pancreas, is the ideal procedure although it is technically demanding. The robotic da Vinci system has been introduced to overcome these technical challenges and reduce operative risks. We report our experience of a new variation in surgical technique: the left lateral approach robotic spleen-preserving distal pancreatectomy (RSP-DP) in right lateral decubitus position. We performed this new variant of SP-DP, in five patients, using the da Vinci Xi system. Technical and clinical feasibility are described. The mean age and body mass index were 53.4 years and 31.4 kg/m2, respectively. The mean total operative time was 323 min. The estimated mean blood loss was 240 ml. In all patients, the spleen could be preserved. In four patients, the splenic vessels were also preserved. One patient required a Warshaw technique due to significant fibrosis attached to the splenic vein. The postoperative period of all patients was uneventful except the presence of biochemical leak (BL) in two patients that only required maintenance of the drainage at home. The mean length of hospital stay was 6 days after surgery. The left lateral approach robotic SP-DP in right lateral decubitus position is a feasible and safe procedure for distal benign or small low-grade malignant tumors of the left pancreas. The right lateral decubitus position associated to robotic surgery can facilitate this complex procedure, especially when splenic vessels preservation is indicated, with a lower risk of conversion and shortening of the learning curve.

Alteration in Levels of Specific miRNAs and Their Potential Protein Targets between Human Pancreatic Cancer Samples, Adjacent Normal Tissue, and Xenografts Derived from These Tumors.

Herein, we describe the global comparison of miRNAs in human pancreatic cancer tumors, adjacent normal tissue, and matched patient-derived xenograft models using microarray screening. RNA was extracted from seven tumor, five adjacent normal, and eight FI PDX tumor samples and analyzed by Affymetrix GeneChip miRNA 4.0 array. A transcriptome analysis console (TAC) was used to generate comparative lists of up- and downregulated miRNAs for the comparisons, tumor vs. normal and F1 PDX vs. tumor. Particular attention was paid to miRNAs that were changed in the same direction in both comparisons. We identified the involvement in pancreatic tumor tissue of several miRNAs, including miR4534, miR3154, and miR4742, not previously highlighted as being involved in this type of cancer. Investigation in the parallel mRNA and protein lists from the same samples allowed the elimination of proteins where altered expression correlated with corresponding mRNA levels and was thus less likely to be miRNA regulated. Using the remaining differential expression protein lists for proteins predicted to be targeted for differentially expressed miRNA on our list, we were able to tentatively ascribe specific protein changes to individual miRNA. Particularly interesting target proteins for miRs 615-3p, 2467-3p, 4742-5p, 509-5p, and 605-3p were identified. Prominent among the protein targets are enzymes involved in aldehyde metabolism and membrane transport and trafficking. These results may help to uncover vulnerabilities that could enable novel approaches to treating pancreatic cancer.

Impact of neoadjuvant chemotherapy on post-hepatectomy regeneration for patients with colorectal cancer liver metastasis - Systematic review and meta-analysis.

BACKGROUND: Today, there is still debate on the impact of neoadjuvant chemotherapy (NeoChem) on liver regeneration (LivReg). The objectives of this study were to assess the impact of NeoChem and its characteristics (addition of bevacizumab, number of cycles and time from end of NeoChem) on post-hepatectomy LivReg. MATERIAL & METHODS: Studies reporting LivReg in patients submitted to liver resection were included. Pubmed, Scopus, Web of Science, Embase, and Cochrane databases were searched. Only studies comparing NeoChem vs no chemotherapy or comparing chemotherapy characteristics from 1990 to present were included. Two researchers individually screened the identified records registered in a predesigned database. Primary outcome was future liver remnant regeneration rate (FLR3). Bias of the studies was evaluated with the ROBINS-I tool, and quality of evidence with the GRADE system. Data was presented as mean difference or standard mean difference. RESULTS: Eight studies with a total of 681 patients were selected. Seven were retrospective and one prospective comparative cohort studies. In patients submitted to major hepatectomy, NeoChem did not have an impact on LivReg (MD 3.12, 95% CI -2,12-8.36, p 0,24). Adding bevacizumab to standard NeoChem was associated with better FLR3 (SMD 0.45, 95% CI 0.19-0.71, p 0.0006). DISCUSSION: The main drawback of this review is the retrospective nature of the available studies. NeoChem does not have a negative impact on postoperative LivReg in patients submitted to liver resection. Regimens with bevacizumab seem to be associated with better postoperative LivReg rates when compared to standard NeoChem.

The Impact of Molecular Biology in the Seeding, Treatment Choices and Follow-Up of Colorectal Cancer Liver Metastases-A Narrative Review.

There is a clear association between the molecular profile of colorectal cancer liver metastases (CRCLM) and the degree to which aggressive progression of the disease impacts patient survival. However, much of our knowledge of the molecular behaviour of colorectal cancer cells comes from experimental studies with, as yet, limited application in clinical practice. In this article, we review the current advances in the understanding of the molecular behaviour of CRCLM and present possible future therapeutic applications. This review focuses on three important steps in CRCLM development, progression and treatment: (1) the dissemination of malignant cells from primary tumours and the seeding to metastatic sites; (2) the response to modern regimens of chemotherapy; and (3) the possibility of predicting early progression and recurrence patterns by molecular analysis in liquid biopsy.

Short notice cancellations - an insight into Irish surgical waiting lists.

BACKGROUND: The reasons underlying prolonged waiting lists for surgery in Ireland are multifactorial. Patient-related factors including non-attendances contribute in part to the current waiting times. AIMS: To determine the rate of short notice cancellation for day case surgery in a model 2 HSE hospital over a 1-month period and to implement an intervention to try and reduce the rate of cancellation. METHODS: The cancellation rate was documented over a 1-month period in the hospital. An intervention was then implemented, involving a phone call to the patient from a member of the surgical team to attempt to reduce the cancellation rate. Cancellations were re-audited after the implementation of the phone intervention. RESULTS: The initial audit revealed a cancellation rate of 39.7% during the first month prior to implementation of the phone intervention. A phone call intervention from a member of the surgical team was associated with a decrease in cancellations from 39.7 to 14.6% (p < 0.01). CONCLUSIONS: While cancellations remained high even after our intervention, a simple phone call was effective and more than halved our cancellation rate. Future efforts need to focus on increasing awareness of patient responsibility for attending scheduled appointments and procedures.

Obesity in Adults: A 2022 Adapted Clinical Practice Guideline for Ireland.

BACKGROUND: This Clinical Practice Guideline (CPG) for the management of obesity in adults in Ireland, adapted from the Canadian CPG, defines obesity as a complex chronic disease characterised by excess or dysfunctional adiposity that impairs health. The guideline reflects substantial advances in the understanding of the determinants, pathophysiology, assessment, and treatment of obesity. SUMMARY: It shifts the focus of obesity management toward improving patient-centred health outcomes, functional outcomes, and social and economic participation, rather than weight loss alone. It gives recommendations for care that are underpinned by evidence-based principles of chronic disease management; validate patients' lived experiences; move beyond simplistic approaches of "eat less, move more" and address the root drivers of obesity. KEY MESSAGES: People living with obesity face substantial bias and stigma, which contribute to increased morbidity and mortality independent of body weight. Education is needed for all healthcare professionals in Ireland to address the gap in skills, increase knowledge of evidence-based practice, and eliminate bias and stigma in healthcare settings. We call for people living with obesity in Ireland to have access to evidence-informed care, including medical, medical nutrition therapy, physical activity and physical rehabilitation interventions, psychological interventions, pharmacotherapy, and bariatric surgery. This can be best achieved by resourcing and fully implementing the Model of Care for the Management of Adult Overweight and Obesity. To address health inequalities, we also call for the inclusion of obesity in the Structured Chronic Disease Management Programme and for pharmacotherapy reimbursement, to ensure equal access to treatment based on health-need rather than ability to pay.

Measurement of Body Composition in Pancreatic Cancer: A Systematic Review, Meta-Analysis, and Recommendations for Future Study Design.

BACKGROUND/OBJECTIVES: Sarcopenia in pancreatic cancer may increase the risk of chemotherapy-related toxicity and post-operative morbidity. This systematic review and meta-analysis aimed to quantify the prevalence of sarcopenia in early stage pancreatic cancer. METHODS: Relevant studies were identified using Ovid Medline and Elsevier Embase. Pooled estimates of prevalence rates (percentages) and corresponding 95% confidence interval (CI) were computed using a random-effects model to allow for heterogeneity between studies. RESULTS: The majority of the 33 studies (n = 5,593 patients) included in this meta-analysis utilized computed tomography (CT)-derived measures for body composition assessment in patients undergoing pancreatic resection. Reported prevalence of sarcopenia varied between 14 and 74%, and the pooled prevalence was 39% (95% CI: 38-40%) Heterogeneity was considerable, however, (I2 = 93%) and did not improve significantly when controlling for assessment method, and use of pre-defined cut-offs for sarcopenia, limiting potential to evaluate the true impact of sarcopenia. CONCLUSION: The ready availability of sequential CT offers a valuable opportunity for body composition assessment, but the quality of assessment and interpretation must improve before the impact of body composition on treatment-related outcomes and survival can be assessed. We suggest recommendations for the assessment of body composition for the design of future studies.

Hepatic resection for breast cancer related liver metastases: A single institution experience.

BACKGROUND & OBJECTIVE: Liver resection for breast cancer liver metastases is becoming a more widely accepted therapeutic option for selected groups of patients. The aim of this study was to describe the outcomes of patients undergoing liver resection for breast cancer-related liver metastases and identify any variables associated with recurrence or survival. METHODS: A retrospective review of a prospectively maintained database was undertaken for the 12 year period between 2009 and 2021. Clinicopathological, treatment, intraoperative, recurrence, survival and follow-up data were collected on all patients. Kaplan-Meier methods, the log-rank test and Cox proportional hazards regression analysis were used to identify variables that were associated with recurrence and survival. RESULTS: A total of 20 patients underwent 21 liver resections over the 12-year period. There were no deaths within 30 days of surgery and an operative morbidity occurred in 23.8% of cases. The median local recurrence free survival and disease free survival times were both 50 months, while the 5 year overall survival rate was 65%. The presence of extrahepatic metastases were associated with a decreased time to local recurrence (p < 0.01) and worse overall survival (p = 0.02). CONCLUSIONS: This study has demonstrated that liver resection for breast cancer-related liver metastases is feasible, safe and associated with prolonged disease free and overall survival in selected patients. It is likely that this option will be offered to more patients going forward, however, the difficulty lies in selecting out those who will benefit from liver resection particularly given the increasing number of systemic treatments and local ablative methods available that offer good long-term results.

Shifting concepts in the management of colorectal liver metastases.

Management of patients with colorectal liver metastases has evolved considerably due to a better understanding of the biology of the disease with concurrent improvements in surgical techniques, oncological strategies and radiological interventions. This review article examines the factors that have contributed to this radical change. Management will be discussed in relation to chemotherapy, surgery and interventional radiology. The addition of chemotherapy and biological agents has greatly extended the reach and scope of surgery. Parenchymal sparing resections, repeat resections, two stage hepatectomy and Associating Liver Partition and Portal Vein ligation are all available to the hepatobiliary surgeon who deals with colorectal liver metastases. Interventional radiology techniques like liver venous deprivation may also replace established surgical practice. Whilst traditionally it was thought that only a few liver metastases could be treated effectively, nowadays tumour number is no longer a limiting factor provided enough functioning liver can be spared and the patient can tolerate the operation.

Early infection is an independent risk factor for increased mortality in patients with culture-confirmed infected pancreatic necrosis.

BACKGROUND: Mortality in infected pancreatic necrosis (IPN) is dynamic over the course of the disease, with type and timing of interventions as well as persistent organ failure being key determinants. The timing of infection onset and how it pertains to mortality is not well defined. OBJECTIVES: To determine the association between mortality and the development of early IPN. METHODS: International multicenter retrospective cohort study of patients with IPN, confirmed by a positive microbial culture from (peri) pancreatic collections. The association between timing of infection onset, timing of interventions and mortality were assessed using Cox regression analyses. RESULTS: A total of 743 patients from 19 centers across 3 continents with culture-confirmed IPN from 2000 to 2016 were evaluated, mortality rate was 20.9% (155/734). Early infection was associated with a higher mortality, when early infection occurred within the first 4 weeks from presentation with acute pancreatitis. After adjusting for comorbidity, advanced age, organ failure, enteral nutrition and parenteral nutrition, early infection (≤4 weeks) and early open surgery (≤4 weeks) were associated with increased mortality [HR: 2.45 (95% CI: 1.63-3.67), p < 0.001 and HR: 4.88 (95% CI: 1.70-13.98), p = 0.003, respectively]. There was no association between late open surgery, early or late minimally invasive surgery, early or late percutaneous drainage with mortality (p > 0.05). CONCLUSION: Early infection was associated with increased mortality, independent of interventions. Early surgery remains a strong predictor of excess mortality.

Selective Resection of Type 1 Gastric Neuroendocrine Neoplasms and the Risk of Progression in an Endoscopic Surveillance Programme.

BACKGROUND: Current guidance for type 1 gastric neuroendocrine neoplasms (gNENs) recommends either resection of all visible lesions or selective resection of gNENs >10 mm. We adopt a selective strategy targeting lesions approaching 10 mm for endoscopic mucosal resection (EMR) and provide surveillance for smaller lesions. OBJECTIVES: This study aimed to describe the incidence of type 1 gNENs requiring endoscopic/surgical resection and the risk of disease progression (both considered significant disease) on endoscopic surveillance. The secondary objective was to assess the risk factors for disease progression during surveillance and the incidence of gastric dysplasia/adenoma/adenocarcinoma. METHODS: We collected consecutive patients with type 1 gNENs and obtained demographic and clinical data through the electronic patient record. RESULTS: In our cohort of 57 patients, 12 patients had EMR at index gastroscopy; 7 patients had surgery (4: large/multiple gNENs and 3: nodal metastases) (5.2% [3/57] risk of nodal metastases); and a patient with nodal and liver metastases (1.8% [1/57] risk of distant metastases). The prevalence of gastric adenocarcinoma in our study was 3.5% with an incidence rate of 9.59 per 1,000 persons per year. For patients undergoing surveillance, 29.5% (13/44) of patients progressed requiring resection. Serum gastrin was significantly higher in patients who progressed to resection (p value = 0.023). CONCLUSION: We concluded that up to a third of patients with type 1 gNENs have significant disease requiring resection. Hence, endoscopic surveillance and resect strategy would benefit patients.

The effect of preoperative chemotherapy on liver regeneration after portal vein embolization/ligation or liver resection in patients with colorectal liver metastasis: a systematic review protocol.

INTRODUCTION: Liver resection (LR) in patients with liver metastasis from colorectal cancer remains the only curative treatment. Perioperative chemotherapy improves prognosis of these patients. However, there are concerns regarding the effect of preoperative chemotherapy on liver regeneration, which is a key event in avoiding liver failure after LR. The primary objective of this systematic review is to assess the effect of neoadjuvant chemotherapy on liver regeneration after (LR) or portal vein embolization (PVE) in patients with liver metastasis from colorectal cancer. The secondary objectives are to evaluate the impact of the type of chemotherapy, number of cycles, and time between end of treatment and procedure (LR or PVE) and to investigate whether there is an association between degree of hypertrophy and postoperative liver failure. METHODS: This meta-analysis will include studies reporting liver regeneration rates in patients submitted to LR or PVE. Pubmed, Scopus, Web of Science, Embase, and Cochrane databases will be searched. Only studies comparing neoadjuvant vs no chemotherapy, or comparing chemotherapy characteristics (bevacizumab administration, number of cycles, and time from finishing chemotherapy until intervention), will be included. We will select studies from 1990 to present. Two researchers will individually screen the identified records, according to a list of inclusion and exclusion criteria. Primary outcome will be future liver remnant regeneration rate. Bias of the studies will be evaluated with the ROBINS-I tool, and quality of evidence for all outcomes will be determined with the GRADE system. The data will be registered in a predesigned database. If selected studies are sufficiently homogeneous, we will perform a meta-analysis of reported results. In the event of a substantial heterogeneity, a qualitative systematic review will be performed. DISCUSSION: The results of this systematic review may help to better identify the patients affected by liver metastasis that could present low regeneration rates after neoadjuvant chemotherapy. These patients are at risk to develop liver failure after extended hepatectomies and therefore are not good candidates for such aggressive procedures. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42020178481 (July 5, 2020).

Proteomic Analysis of Cell Lines and Primary Tumors in Pancreatic Cancer Identifies Proteins Expressed Only In Vitro and Only In Vivo.

OBJECTIVES: A limited repertoire of good pancreatic ductal adenocarcinoma (PDAC) models is one of the main barriers in developing effective new PDAC treatments. We aimed to characterize 6 commonly used PDAC cell lines and compare them with PDAC patient tumor samples using proteomics. METHODS: Proteomic methods were used to generate an extensive catalog of proteins from 10 PDAC surgical specimens, 9 biopsies of adjacent normal tissue, and 6 PDAC cell lines. Protein lists were interrogated to determine what extent the proteome of the cell lines reflects the proteome of primary pancreatic tumors. RESULTS: We identified 7973 proteins from the cell lines, 5680 proteins from the tumor tissues, and 4943 proteins from the adjacent normal tissues. We identified 324 proteins unique to the cell lines, some of which may play a role in survival of cells in culture. Conversely, a list of 63 proteins expressed only in the patient samples, whose expression is lost in culture, may place limitations on the degree to which these model systems reflect tumor biology in vivo. CONCLUSIONS: Our work offers a catalog of proteins detected in each of the PDAC cell lines, providing a useful guide for researchers seeking model systems for PDAC functional studies.

Metastatic uveal melanoma: A valid indication for liver resection.

PURPOSE: Owing to its relative resistance to chemotherapeutics, prognosis following the diagnosis of metastatic uveal melanoma has remained disappointing. On this basis, liver resection in cases of isolated hepatic metastases has been postulated as a viable treatment option. Herein we performed an analysis of patients who underwent hepatic metastatectomy for uveal melanoma and compared their outcomes to those undergoing resection for colorectal cancer liver metastases (CRLM) in the same time period. METHODS: From 2008 to 2018, all patients referred to our unit with hepatic metastases were included for analysis. Performing a 3:1 matched cohort analysis, patients with metastatic uveal melanoma were matched for age, sex, operative approach, tumour number and size to those undergoing resection for CRLM. Clinicopathological data was sought from a prospectively maintained database and reviewed along with 30-day post-operative morbidity and mortality. RESULTS: Fifteen patients underwent hepatic metastasectomy for primary uveal melanoma. A further 45 patients undergoing hepatectomy for metastatic colorectal cancer acted as the control group. No in-hospital mortality was noted with four patients (26.6%) developing post-operative morbidity. The median follow-up period following melanoma resection was 27 months (range 5-211) with 1-, 3- and 5- year overall survival for this cohort of 86.6%, 53.3% and 40%, respectively. There was no difference in overall survival between the melanoma and CRLM group (p =0.80). CONCLUSION: In patients presenting with hepatic metastases from uveal melanoma, this present study supports the rationale to proceed to surgery with acceptable morbidity and mortality.

Rehabilitation strategies following oesophagogastric and Hepatopancreaticobiliary cancer (ReStOre II): a protocol for a randomized controlled trial.

BACKGROUND: Curative treatment for upper gastrointestinal (UGI) and hepatopancreaticobiliary (HPB) cancers, involves complex surgical resection often in combination with neoadjuvant/adjuvant chemo/chemoradiotherapy. With advancing survival rates, there is an emergent cohort of UGI and HPB cancer survivors with physical and nutritional deficits, resultant from both the cancer and its treatments. Therefore, rehabilitation to counteract these impairments is required to maximise health related quality of life (HRQOL) in survivorship. The initial feasibility of a multidisciplinary rehabilitation programme for UGI survivors was established in the Rehabilitation Strategies following Oesophago-gastric Cancer (ReStOre) feasibility study and pilot randomised controlled trial (RCT). ReStOre II will now further investigate the efficacy of that programme as it applies to a wider cohort of UGI and HPB cancer survivors, namely survivors of cancer of the oesophagus, stomach, pancreas, and liver. METHODS: The ReStOre II RCT will compare a 12-week multidisciplinary rehabilitation programme of supervised and self-managed exercise, dietary counselling, and education to standard survivorship care in a cohort of UGI and HPB cancer survivors who are > 3-months post-oesophagectomy/ gastrectomy/ pancreaticoduodenectomy, or major liver resection. One hundred twenty participants (60 per study arm) will be recruited to establish a mean increase in the primary outcome (cardiorespiratory fitness) of 3.5 ml/min/kg with 90% power, 5% significance allowing for 20% drop out. Study outcomes of physical function, body composition, nutritional status, HRQOL, and fatigue will be measured at baseline (T0), post-intervention (T1), and 3-months follow-up (T2). At 1-year follow-up (T3), HRQOL alone will be measured. The impact of ReStOre II on well-being will be examined qualitatively with focus groups/interviews (T1, T2). Bio-samples will be collected from T0-T2 to establish a national UGI and HPB cancer survivorship biobank. The cost effectiveness of ReStOre II will also be analysed. DISCUSSION: This RCT will investigate the efficacy of a 12-week multidisciplinary rehabilitation programme for survivors of UGI and HPB cancer compared to standard survivorship care. If effective, ReStOre II will provide an exemplar model of rehabilitation for UGI and HPB cancer survivors. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov, registration number: NCT03958019, date registered: 21/05/2019.

Physical function in patients with resectable cancer of the pancreas and liver-a systematic review.

PURPOSE: Surgery is the only potentially curative treatment for pancreatic and liver cancer. However, even in high-volume centres, surgical resection is associated with significant morbidity with resultant physical decline. This systematic review explored physical function and its' implications in the management of resectable cancer of the pancreas and liver. METHODS: EMBASE, Medline OVID, CINAHL, Cochrane Library and Web of Science were searched up to June 2019 using a predefined search strategy. Screening of titles, abstracts, and full texts, data extraction, and risk of bias assessment was performed independently by two reviewers. A third reviewer resolved disagreements by consensus. RESULTS: Sixteen studies with a total of 1224 participants were included. Heterogeneity of the literature prevented a meta-analysis. Physical function across the pancreatic/liver cancer trajectory has been under investigated. The relationship between physical function and pancreatic/liver cancer resection outcome remains unclear, although anaerobic threshold appears the strongest predictor of postoperative outcomes. Conclusions regarding the impact of rehabilitative interventions on physical function were limited due to risk of bias concerns. CONCLUSIONS: High-quality evidence regarding the implications of physical function in resectable pancreatic and liver cancers is lacking. Well-designed trials are required to examine physical function across the pancreatic/liver cancer continuum and to measure the impact of rehabilitation on physical function. IMPLICATIONS FOR CANCER SURVIVORS: As survival rates for pancreatic and liver cancer slowly improve a greater understanding of the impact of these cancers and their treatments on physical function, and the potential impact of rehabilitative interventions for survivors is required.

Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients.

Pancreatic cancer remains among the most lethal cancers worldwide, with poor early detection rates and poor survival rates. Patient-derived xenograft (PDX) models have increasingly been used in preclinical and clinical research of solid cancers to fulfil unmet need. Fresh tumour samples from human pancreatic adenocarcinoma patients were implanted in severe combined immunodeficiency (SCID) mice. Samples from 78% of treatment-naïve pancreatic ductal adenocarcinoma patients grew as PDX tumours and were confirmed by histopathology. Frozen samples from F1 PDX tumours could be later successfully passaged in SCID mice to F2 PDX tumours. The human origin of the PDX was confirmed using human-specific antibodies; however, the stromal component was replaced by murine cells. Cell lines were successfully developed from three PDX tumours. RNA was extracted from eight PDX tumours and where possible, corresponding primary tumour (T) and adjacent normal tissues (N). mRNA profiles of tumour vs. F1 PDX and normal vs. tumour were compared by Affymetrix microarray analysis. Differential gene expression showed over 5000 genes changed across the N vs. T and T vs. PDX samples. Gene ontology analysis of a subset of genes demonstrated genes upregulated in normal vs. tumour vs. PDX were linked with cell cycle, cycles cell process and mitotic cell cycle. Amongst the mRNA candidates elevated in the PDX and tumour vs. normal were SERPINB5, FERMT1, AGR2, SLC6A14 and TOP2A. These genes have been associated with growth, proliferation, invasion and metastasis in pancreatic cancer previously. Cumulatively, this demonstrates the applicability of PDX models and transcriptomic array to identify genes associated with growth and proliferation of pancreatic cancer.

Neoadjuvant Chemoradiotherapy and Liver Transplantation for Unresectable Hilar Cholangiocarcinoma: The Irish Experience of the Mayo Protocol.

BACKGROUND: Pioneered by the Mayo Clinic, multimodal therapy with neoadjuvant chemoradiotherapy and orthotopic liver transplant has emerged as a promising option for unresectable hilar cholangiocarcinoma (hCCA). This study reports the experience of the Irish National Liver Transplant Programme with the Mayo Protocol. METHODS: All patients diagnosed with unresectable hCCA between 2004 and 2016, who were eligible for the treatment protocol, were prospectively studied. RESULTS: Thirty-seven patients commenced chemoradiotherapy. Of those, 11 were excluded due to disease progression and 26 proceeded to liver transplantation. There were 24 males, the median age was 49, and 88% had underlying primary sclerosing cholangitis. R0 and pathologic complete response rates were 96% and 62%, respectively. Overall median survival was 53 months and 1-, 3-, and 5-year survival was 81%, 69%, and 55%, respectively. The median survival of patients achieving a pathologic complete response was 83.8 months compared with 20.9 months in the group with residual disease (P = 0.036). Six patients (23%) developed disease recurrence. Among the patients who developed metastatic disease during neoadjuvant treatment, median survival was 10.5 months compared with 53 months in patients who proceeded to transplant (P < 0.001). CONCLUSIONS: Neoadjuvant chemoradiotherapy followed by liver transplantation substantially increases the survival of patients with unresectable hCCA. Achieving a pathologic complete response confers a significant survival benefit.

Chemotherapy and repeat resection abrogate the prognostic value of neutrophil lymphocyte ratio in colorectal liver metastases.

BACKGROUND: Evolution in surgical and oncological management of CRLM has called into question the utility of clinical risk scores. We sought to establish if neutrophil lymphocyte ratio (NLR) has a prognostic role in this patient cohort. METHODS: From 2005 to 2015,379 hepatectomies were performed for CRLM, 322 underwent index hepatectomy, 57 s hepatectomies were performed. Clinicopathological data were obtained from a prospectively maintained database. Variables associated with longterm survival following index and second hepatectomy were identified by Cox regression analyses and reviewed along with 30-day post-operative morbidity and mortality. RESULTS: Following index hepatectomy 1-,3-and 5-year survival was 90.7%, 68.1% and 48.6%. Major resection, positive margins and >5 tumours were negatively associated with survival. Those with elevated NLR(>5) had a median survival of 55 months, compared to 70 months with lower NLR(p = 0.027). Following neoadjuvant chemotherapy, no association between NLR and survival was demonstrated (p = 0.93). Furthermore, NLR >5 had no impact on prognosis following repeat hepatectomy. Tumour diameter >5 cm (p = 0.04) was the sole predictor of poorer survival (p = 0.049). CONCLUSION: Despite elevated NLR correlating with shorter survival following index hepatectomy, this effect is negated by neoadjuvant chemotherapy and second hepatectomy for recurrent disease. This data would not support the use of NLR in the preoperative decision algorithm for patients with CRLM.

Characterising the impact of body composition change during neoadjuvant chemotherapy for pancreatic cancer.

BACKGROUND: Pancreatic Cancer remains a lethal disease for the majority of patients. New chemotherapy agents such as Folfirinox offer therapeutic potential for patients who present with Borderline Resectable disease (BRPC). However, results to date are inconsistent, with factors such as malnutrition limiting successful drug delivery. We sought to determine the prevalence of sarcopenia in BRPC patients at diagnosis, and to quantify body composition change during chemotherapy. METHODS: The diagnostic/restaging CT scans of BRPC patients were analysed. Body composition was measured at L3 using Tomovision Slice-O-Matic™. Total muscle and adipose tissue mass were estimated using validated regression equations. Sarcopenia was defined as per gender- and body mass index (BMI)-specific lumbar skeletal muscle index (LSMI) and muscle attenuation reference values. RESULTS: Seventy-eight patients received neo-adjuvant chemotherapy, and 67 patients underwent restaging CT, at which point a third were deemed resectable. Half were sarcopenic at diagnosis, and sarcopenia was equally prevalent across all BMI categories.. Skeletal muscle and adipose tissue (intra-muscular, visceral and sub-cutaneous) area decreased during chemotherapy (p < 0.0001). Low muscle attenuation was observed in half of patients at diagnosis, and was associated with increased mortality risk. Loss of lean tissue parameters during chemotherapy was associated with an increased mortality risk; specifically fat-free mass, HR 1.1 (95% CI 1.03-1.17, p = 0.003) and skeletal muscle mass, HR 1.21 (95%CI 1.08-1.35, p = 0.001). CONCLUSIONS: Sarcopenia was prevalent in half of patients at the time of diagnosis with BRPC. Low muscle attenuation at diagnosis, coupled with lean tissue loss during chemotherapy, independently increased mortality risk.