Adjuvant Iodine 131

Background. Survival after liver resection for HCC is compromised by a high rate of intrahepatic recurrence. Adjuvant treatment with a single, postoperative dose of intra-arterial I131 lipiodol has shown promise, as a means of prolonging disease-free survival (DFS). Methodology. DFS and overall survival (OS) after a single dose of postoperative I131 lipiodol were compared to liver resection alone, for treatment of hepatocellular carcinoma (HCC). Data were collected retrospectively for patients who had a curative resection for HCC between December 1993 and September 2011. Seventy-two patients were given I131 lipiodol after surgery and 70 patients had surgery alone. Results. The DFS at 1, 3, and 5 years was 72%, 43%, and 26% in the surgery group and 70%, 39%, and 29% in the adjuvant I131 lipiodol group (p=0.75). The 1-, 3-, and 5-year OS was 83%, 64%, and 52% in the surgery group and 96%, 72%, and 61% in the adjuvant I131 lipiodol group (p=0.16). Conclusion. This retrospective study has found no significant benefit to survival, after adjuvant treatment with I131 lipiodol

Improving psychosocial outcomes for caregivers of people with poor prognosis gastrointestinal cancers: a randomized controlled trial (Family Connect)

Abstract Purpose This study investigated the effectiveness of a structured telephone intervention for caregivers of people diagnosed with poor prognosis gastrointestinal cancer to improve psychosocial outcomes for both caregivers and patients. Methods Caregivers of patients starting treatment for upper gastrointestinal or Dukes D colorectal cancer were randomly assigned (1:1) to the Family Connect telephone intervention or usual care. Caregivers in the intervention group received four standardized telephone calls in the 10 weeks following patient hospital discharge. Caregivers' quality of life (QOL), caregiver burden, unmet supportive care needs and distress were assessed at 3 and 6 months. Patients' QOL, unmet supportive care needs, distress and health service utilization were also assessed at these time points. Results Caregivers (128) were randomized to intervention or usual care groups. At 3 months, caregiver QOL scores and other caregiver-reported outcomes were similar in both groups. Intervention group participants experienced a greater sense of social support (p=.049) and reduced worry about finances (p=.014). Patients whose caregiver was randomized to the intervention also had fewer emergency department presentations and unplanned hospital readmissions at 3 months post-discharge (total 17 vs. 5, p=.01). Conclusions This standardized intervention did not demonstrate any significant improvements in caregiver well-being but did result in a decrease in patient emergency department presentations and unplanned hospital readmissions in the immediate post-discharge period. The trend towards improvements in a number of caregiver outcomes and the improvement in health service utilization support further development of telephone-based caregiver-focused supportive care interventions

PRehabIlitatiOn with pReoperatIve exercise and educaTion for patients undergoing major abdominal cancer surgerY: protocol for a multicentre randomised controlled TRIAL (PRIORITY TRIAL)

Background Radical surgery is the mainstream treatment for patients presenting with advanced primary or recurrent gastrointestinal cancers; however, the rate of postoperative complications is exceptionally high. The current evidence suggests that improving patients’ fitness during the preoperative period may enhance postoperative recovery. Thus, the primary aim of this study is to establish the effectiveness of prehabilitation with a progressive, individualised, preoperative exercise and education program compared to usual care alone in reducing the proportion of patients with postoperative in-hospital complications. The secondary aims are to investigate the effectiveness of the preoperative intervention on reducing the length of intensive care unit and hospital stay, improving quality of life and morbidity, and reducing costs. Methods This is a multi-centre, assessor-blinded, pragmatic, comparative, randomised controlled trial. A total of 172 patients undergoing pelvic exenteration, cytoreductive surgery, oesophagectomy, hepatectomy, gastrectomy or pancreatectomy will be recruited. Participants will be randomly allocated to prehabilitation with a preoperative exercise and education program (intervention group), delivered over 4 to 8 weeks before surgery by community physiotherapists/exercise physiologists, or usual care alone (control group). The intervention will comprise 12 to 24 individualised, progressive exercise sessions (including aerobic/anaerobic, resistance, and respiratory exercises), recommendations of home exercises (16 to 32 sessions), and daily incidental physical activity advice. Outcome measures will be collected at baseline, the week prior to surgery, during the hospital stay, and on the day of discharge from hospital, and 1 month and 1 months postoperatively. The primary outcome will be the development of in-hospital complications. Secondary outcomes include the length of intensive care unit and hospital stay, quality of life, postoperative morbidity and costs. Discussion The successful completion of this trial will provide robust and high-quality evidence on the efficacy of a preoperative community- and home-based exercise and education intervention on important postoperative outcomes of patients undergoing major gastrointestinal cancer surgery

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association

Here we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs

Vascular biliopathy as a cause of common bile duct obstruction successfully treated by mesocaval shunt and endoscopic retrograde cholangiopancreatography biliary stent placement

Common bile duct stenosis owing to extrahepatic portal varices is termed "portal hypertensive biliopathy" (PHB) and is a rare occurrence. We report a case of PHB owing to portal vein thrombosis with cavernous transformation successfully managed by mesocaval shunt and endoscopic retrograde cholangiopancreatography (ERCP) biliary stent placement. A 44-year-old male, who presented with hematemesis, melena, jaundice, and abdominal pain, underwent gastroscopy, which revealed bleeding gastric varices. Computed tomography with arterial and venous imaging demonstrated portal vein thrombosis with cavernous transformation and extensive extrahepatic varices within the porta hepatis causing common bile duct obstruction from extrinsic compression. Biliary decompression was achieved with ERCP, and a small common bile duct stone was retrieved. A mesocaval shunt with a 16 mm Dacron graft successfully treated the portal hypertension. PHB is rare. We report a case successfully treated by mesocaval shunt and ERCP.3 page(s

Dissecting Pseudoaneurysm of the Proper Hepatic Artery Repaired by Primary Anastomosis: A Case Report

Background. Although rare, visceral artery pseudoaneurysms often present as surgical emergencies with a specific mortality rate as high as 35% related to aneurysmal rupture. Risk factors for the development of iatrogenic pseudoaneurysms include anticoagulation, female gender, obesity, and vessel calcification. Case Report. We present a case of an elderly female who developed a dissecting pseudoaneurysm of the proper hepatic artery after undergoing routine surgery to resect a large duodenal adenoma. Surgical repair comprised of resection and primary anastomosis was employed resulting in a favourable outcome. Discussion/Conclusion. Surgical management reduces the risk of hepatic ischemia, biliary complications, and abscess formation. Although stenting, coil embolization, and thrombin injection are all plausible options for management, we propose that surgical reconstruction be considered seriously as a treatment for such spontaneous pseudoaneurysms