Publications
334 results found
Jiao LR, Fajardo A, Frampton A, 2016, Gene of the month: HGF, Journal of Clinical Pathology, Vol: 69, Pages: 575-579, ISSN: 0021-9746
Hepatocyte growth factor (HGF) is a multifunctional cytokine with important roles in cell proliferation, survival, motility and morphogenesis. Secreted by cells of mesenchymal origin, HGF is the specific ligand for the tyrosine-kinase receptor c-MET (cellular mesenchymal-epithelial transition), also called MET, which is expressed in different types of epithelial, endothelial and haematopoietic progenitor cells. The HGF/MET axis is involved in several biological processes, such as embryogenesis, organogenesis, adult tissue regeneration (including wound healing and liver regeneration) and carcinogenesis, for both solid and haematological malignancies.1 2 HGF and its particular interaction with the MET receptor have been extensively investigated in the last decades and remain the focus of numerous clinical trials.3–8 This short review focuses on HGF structure and function, as well as its roles in liver regeneration and different types of tumours.
Frampton AE, Krell J, Mato Prado M, et al., 2016, Prospective validation of microRNA signatures for detecting pancreatic malignant transformation in endoscopic-ultrasound guided fine-needle aspiration biopsies, Oncotarget, Vol: 7, ISSN: 1949-2553
Background: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Novel biomarkers are required to aid treatment decisions and improve patient outcomes. MicroRNAs (miRNAs) are potentially ideal diagnostic biomarkers, as they are stable molecules, and tumour and tissue specific. Results: Logistic regression analysis revealed an endoscopic-ultrasound fine-needle aspiration (EUS-FNA) 2-miRNA classifier (miR-21 + miR-155) capable of distinguishing benign from malignant pancreatic lesions with a sensitivity of 81.5% and a specificity of 85.7% (AUC 0.930). Validation FNA cohorts confirmed both miRNAs were overexpressed in malignant disease, while circulating miRNAs performed poorly.Methods: Fifty-five patients with a suspicious pancreatic lesion on cross-sectional imaging were evaluated by EUS-FNA. At echo-endoscopy, the first part of the FNA was sent for cytological assessment and the second part was used for total RNA extraction. Candidate miRNAs were selected after careful review of the literature and expression was quantified by qRT-PCR. Validation was performed on an independent cohort of EUS-FNAs, as well as formalin-fixed paraffin embedded (FFPE) and plasma samples.Conclusions: We provide further evidence for using miRNAs as diagnostic biomarkers for pancreatic malignancy. We demonstrate the feasibility of using fresh EUS-FNAs to establish miRNA-based signatures unique to pancreatic malignant transformation and the potential to enhance risk stratification and selection for surgery.
Yoon S, Huang KW, Reebye V, et al., 2016, Targeted delivery of C/EBPα -saRNA by pancreatic ductal adenocarcinoma-specific RNA aptamers inhibits tumor growth in vivo, Molecular Therapy, Vol: 24, Pages: 1106-1116, ISSN: 1525-0024
The 5-year survival rate for pancreatic ductal adenocarcinoma (PDAC) remains dismal despite current chemotherapeutic agents and inhibitors of molecular targets. As the incidence of PDAC constantly increases, more effective multidrug approaches must be made. Here, we report a novel method of delivering antitumorigenic therapy in PDAC by upregulating the transcriptional factor CCAAT/enhancer-binding protein-α (C/EBPα), recognized for its antiproliferative effects. Small activating RNA (saRNA) duplexes designed to increase C/EBPα expression were linked onto PDAC-specific 2′-Fluropyrimidine RNA aptamers (2′F-RNA) - P19 and P1 for construction of a cell type–specific delivery vehicle. Both P19- and P1-C/EBPα-saRNA conjugates increased expression of C/EBPα and significantly suppressed cell proliferation. Tail vein injection of the saRNA/aptamer conjugates in PANC-1 and in gemcitabine-resistant AsPC-1 mouse-xenografts led to reduced tumor size with no observed toxicity. To exploit the specificity of the P19/P1 aptamers for PDAC cells, we also assessed if conjugation with Cy3 would allow it to be used as a diagnostic tool on archival human pancreatic duodenectomy tissue sections. Scoring pattern from 72 patients suggested a positive correlation between high fluorescent signal in the high mortality patient groups. We propose a novel aptamer-based strategy for delivery of targeted molecular therapy in advanced PDAC where current modalities fail.
Fotopoulou C, Jones BP, Savvatis K, et al., 2016, Maximal effort cytoreductive surgery for disseminated ovarian cancer in a UK setting: challenges and possibilities, Gynecologic Oncology, ISSN: 1095-6859
OBJECTIVE: To assess surgical morbidity and mortality of maximal effort cytoreductive surgery for disseminated epithelial ovarian cancer (EOC) in a UK tertiary center. METHODS/MATERIALS: A monocentric prospective analysis of surgical morbidity and mortality was performed for all consecutive EOC patients who underwent extensive cytoreductive surgery between 01/2013 and 12/2014. Surgical complexity was assessed by the Mayo clinic surgical complexity score (SCS). Only patients with high SCS ≥5 were included in the analysis. RESULTS: We evaluated 118 stage IIIC/IV patients, with a median age of 63 years (range 19-91); 47.5 % had ascites and 29 % a pleural effusion. Median duration of surgery was 247 min (range 100-540 min). Median surgical complexity score was 10 (range 5-15) consisting of bowel resection (71 %), stoma formation (13.6 %), diaphragmatic stripping/resection (67 %), liver/liver capsule resection (39 %), splenectomy (20 %), resection stomach/lesser sac (26.3 %), pleurectomy (17 %), coeliac trunk/subdiaphragmatic lymphadenectomy (8 %). Total macroscopic tumor clearance rate was 89 %. Major surgical complication rate was 18.6 % (n = 22), with a 28-day and 3-month mortality of 1.7 and 3.4 %, respectively. The anastomotic leak rate was 0.8 %; fistula/bowel perforation 3.4 %; thromboembolism 3.4 % and reoperation 4.2 %. Median intensive care unit and hospital stay were 1.7 (range 0-104) and 8 days (range 4-118), respectively. Four patients (3.3 %) failed to receive chemotherapy within the first 8 postoperative weeks. CONCLUSIONS: Maximal effort cytoreductive surgery for EOC is feasible within a UK setting with acceptable morbidity, low intestinal stoma rates and without clinically relevant delays to postoperative chemotherapy. Careful patient selection, and coordinated multidisciplinary effort appear to be the key for good outcome. Future ev
Jawad ZAR, Tsim N, Pai M, et al., 2016, Short and long-term post-operative outcomes of duodenum preserving pancreatic head resection for chronic pancreatitis affecting the head of pancreas: a systematic review and meta-analysis, HPB, Vol: 18, Pages: 121-128, ISSN: 1365-182X
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- Citations: 16
Giglio MC, Spalding DRC, Giakoustidis A, et al., 2016, Meta-analysis of drain amylase content on postoperative day 1 as a predictor of pancreatic fistula following pancreatic resection, British Journal of Surgery, Vol: 103, Pages: 328-336, ISSN: 1365-2168
BackgroundDrain amylase content in the days immediately after major pancreatic resection has been investigated previously as a predictor of postoperative pancreatic fistula (POPF). Its accuracy, however, has not been determined conclusively. The purpose of this study was to evaluate the accuracy of drain amylase content on the first day after major pancreatic resection in predicting the occurrence of POPF.MethodsA literature search of the MEDLINE, Embase and Scopus® databases to 13 May 2015 was performed to identify studies evaluating the accuracy of drain amylase values on day 1 after surgery in predicting the occurrence of POPF. The area under the hierarchical summary receiver operating characteristic (ROC) curve (AUChSROC) was calculated as an index of accuracy, and pooled estimates of accuracy indices (sensitivity and specificity) were calculated at different cut-off levels. Subgroup and meta-regression analyses were performed to test the robustness of the results.ResultsThirteen studies involving 4416 patients were included. The AUChSROC was 0·89 (95 per cent c.i. 0·86 to 0·92) for clinically significant POPF and 0·88 (0·85 to 0·90) for POPF of any grade. Pooled estimates of sensitivity and specificity were calculated for the different cut-offs: 90–100 units/l (0·96 and 0·54 respectively), 350 units/l (0·91 and 0·84) and 5000 units/l (0·59 and 0·91). Accuracy was independent of the type of operation, type of anastomosis performed and octreotide administration.ConclusionEvaluation of drain amylase content on the first day after surgery is highly accurate in predicting POPF following major pancreatic resection. It may allow early drain removal and institution of an enhanced recovery pathway.
Jawad ZA, Kyriakides C, Pai M, et al., 2016, Surgery remains the best option for the management of pain in patients with chronic pancreatitis: a systematic review and meta-analysis, Asian Journal of Surgery, Vol: 40, Pages: 179-185, ISSN: 1015-9584
Controversy related to endoscopic or surgical management of pain in patients with chronic pancreatitis remains. Despite improvement in endoscopic treatments, surgery remains the best option for pain management in these patients.
Edmondson MJ, Sodergren MH, Pucher PH, et al., 2015, Variations and adaptations of associated liver partition and portal vein ligation for staged hepatectomy (ALPPS): Many routes to the summit, Surgery, Vol: 159, Pages: 1058-1072, ISSN: 1532-7361
BackgroundOur aim was to review variations from the originally described associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) procedure and relevant clinical outcomes.MethodsA systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (ie, PRISMA) guidelines. A search of PubMed and Google Scholar was conducted until March 2015. Inclusion criteria were any publications reporting technical variations and descriptions of ALPPS. Exclusion criteria were insufficient technical description, data repeated elsewhere, or data that could not be accessed in English.ResultsInitial search results returned 790 results; 46 studies were included in the final qualitative analysis. There were several alternatives described to the first stage of complete parenchymal split. Variations included partial ALPPS (partial split; hypertrophy of future liver remnant [FLR] 80–90%), radiofrequency-assisted liver partition and portal vein ligation (mean FLR hypertrophy 62%), laparoscopic microwave ablation and portal vein ligation (FLR hypertrophy 78–90%), associating liver tourniquet and portal ligation for staged hepatectomy (median FLR hypertrophy 61%), and sequential associating liver tourniquet and portal ligation for staged hepatectomy (FLR hypertrophy 77%) with a potential decrease in morbidity particularly after stage I. We analyzed several other variations, including considerations for segment IV, operative maneuvers, use of laparoscopy, identification of biliary complications, and liver containment.ConclusionThe current literature demonstrates a large variability in techniques of ALPPS that limits meaningful statistical comparisons of outcomes. Not physically splitting the liver at the first stage may decrease morbidity; however, randomized controlled trials are needed to determine benefits in technical variations.The traditional 2-stage hepatectomy for the treatment of liver tumors h
Jawad Z, Xie F, Jiao LR, 2015, Applications of Nanotechnology in the Management of Cancer Miniature Technology, Great Potential, JAMA SURGERY, Vol: 150, Pages: 1184-1185, ISSN: 2168-6254
Bower G, Toma T, Harling L, et al., 2015, Bariatric Surgery and Non-Alcoholic Fatty Liver Disease: a Systematic Review of Liver Biochemistry and Histology, OBESITY SURGERY, Vol: 25, Pages: 2280-2289, ISSN: 0960-8923
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- Citations: 153
Gall TMH, Tsakok M, Wasan H, et al., 2015, Pancreatic cancer: current management and treatment strategies, POSTGRADUATE MEDICAL JOURNAL, Vol: 91, Pages: 601-607, ISSN: 0032-5473
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- Citations: 23
Gall TMH, Wasan H, Jiao LR, 2015, Pancreatic cancer: current understanding of molecular and genetic aetiologies, POSTGRADUATE MEDICAL JOURNAL, Vol: 91, Pages: 594-600, ISSN: 0032-5473
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- Citations: 3
Frampton AE, Krell J, Gall TMH, et al., 2015, miR-15b and miR-17 Are Tumor-derived Plasma MicroRNAs Dysregulated in Colorectal Neoplasia, Annals of Surgery, Vol: 262, Pages: e61-e61, ISSN: 0003-4932
Sodergren MH, Markar S, Pucher PH, et al., 2015, Safety of transvaginal hybrid NOTES cholecystectomy: a systematic review and meta-analysis, SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, Vol: 29, Pages: 2077-2090, ISSN: 0930-2794
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- Citations: 23
Frampton AE, Krell J, Jamieson NB, et al., 2015, microRNAs with prognostic significance in pancreatic ductal adenocarcinoma: A meta-analysis, European Journal of Cancer, Vol: 51, Pages: 1389-1404, ISSN: 1879-0852
BackgroundReports have described the prognostic relevance of microRNAs (miRNAs) in patients treated for pancreatic ductal adenocarcinoma (PDAC). However, many of these include small numbers of patients. To increase statistical power and improve translation, we performed a systematic review and meta-analysis to determine a pooled conclusion. We examined the impact of miRNAs on overall survival (OS) and disease-free survival (DFS) in PDAC.MethodsEligible studies were identified and quality assessed using multiple search strategies (last search December 2014). Data were collected from studies correlating clinical outcomes with dysregulated tumoural or blood miRNAs. Studies were pooled, and combined hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate strength of the associations.ResultsTwenty studies involving 1525 patients treated for PDAC were included. After correcting for publication bias, OS was significantly shortened in patients with high tumoural miR-21 (adjusted HR = 2.48; 1.96–3.14). This result persisted when only studies adjusting for adjuvant chemotherapy were combined (adjusted HR = 2.72; 1.91–3.89). High miR-21 also predicted reduced DFS (adjusted HR = 3.08; 1.78–5.33). Similarly, we found significant adjusted HRs for poor OS for high miR-155, high miR-203, and low miR-34a; and unadjusted HRs for high miR-222 and high miR-10b. The small number of studies, limited number of miRNAs and paucity of multivariate analyses are the limitations of our study.ConclusionsThis is the first rigorous pooled analysis assessing miRNAs as prognostic biomarkers in PDAC. Tumoural miR-21 overexpression emerged as an important predictor of poor prognosis after PDAC resection independent of other clinicopathologic factors, including adjuvant chemotherapy use.
Sun T, Li X, Zhang P, et al., 2015, Acetylation of Beclin 1 inhibits autophagosome maturation and promotes tumour growth, NATURE COMMUNICATIONS, Vol: 6
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- Citations: 151
Frampton AE, Stebbing J, Gall TMH, et al., 2015, Activating mutations of <i>GNAS</i> and <i>KRAS</i> in cystic fluid can help detect intraductal papillary mucinous neoplasms of the pancreas, EXPERT REVIEW OF MOLECULAR DIAGNOSTICS, Vol: 15, Pages: 325-328, ISSN: 1473-7159
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- Citations: 7
Pai M, Frampton AE, Jiao LR, 2015, Integrating the Evidence for Single-incision Laparoscopic Cholecystectomy: Is It "Looking" Good?, ANNALS OF SURGERY, Vol: 261, Pages: E85-E87, ISSN: 0003-4932
Frampton AE, Castellano L, Colombo T, et al., 2015, Integrated molecular analysis to investigate the role of microRNAs in pancreatic tumour growth and progression, LANCET, Vol: 385, Pages: 37-37, ISSN: 0140-6736
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- Citations: 8
Gall TMH, Sodergren MH, Frampton AE, et al., 2015, Radio-frequency-assisted Liver Partition With Portal Vein Ligation (RALPP) for Liver Regeneration, ANNALS OF SURGERY, Vol: 261, Pages: E45-E46, ISSN: 0003-4932
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- Citations: 64
Gall TMH, Sodergren M, Fan R, et al., 2015, The Hammersmith Laparoscopic Pancreaticogastrostomy: a Novel Laparoscopic Pancreatic Anastomosis During Central Pancreatectomy, International Surgical Congress of the Association-of-Surgeons-of-Great-Britain-and-Ireland (ASGBI), Publisher: WILEY-BLACKWELL, Pages: 266-266, ISSN: 0007-1323
Twaij A, Pucher P, Sodergren M, et al., 2015, Laparoscopic versus Open Approach to Resection of Hepatocellular Carcinoma in Patients with Known Cirrhosis: Systematic Review and Meta-Analysis, International Surgical Congress of the Association-of-Surgeons-of-Great-Britain-and-Ireland (ASGBI), Publisher: WILEY-BLACKWELL, Pages: 269-269, ISSN: 0007-1323
Frampton AE, Krel J, Gall TM, et al., 2015, Prospective Validation of Microrna Signatures for Detecting Pancreatic Malignant Transformation in Endoscopic-Ultrasound Guided Fine-Needle Aspiration Biopsies, International Surgical Congress of the Association-of-Surgeons-of-Great-Britain-and-Ireland (ASGBI), Publisher: WILEY-BLACKWELL, Pages: 7-7, ISSN: 0007-1323
Limongelli P, Vitiello C, Belli A, et al., 2014, Costs of laparoscopic and open liver and pancreatic resection: A systematic review, WORLD JOURNAL OF GASTROENTEROLOGY, Vol: 20, Pages: 17595-17602, ISSN: 1007-9327
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- Citations: 14
Ojha S, Gall T, Sodergren MH, et al., 2014, A case of gossypiboma mimicking intrahepatic cholangiocarcinoma., Ann R Coll Surg Engl, Vol: 96, Pages: e14-e16
INTRODUCTION: A gossypiboma refers to a cotton-based foreign body left inadvertently in the human body following a surgical procedure. Although a rare event, they tend to be found in the abdomen but few are known to be intrahepatic. CASE HISTORY: We report the case of a 44 year-old man who presented with recurrent episodes of jaundice and cholangitis, on a background of a right hepatectomy for hydatid cyst excision 20 years previously. This case was discussed at our hepatobiliary multidisciplinary team meetings on several occasions and a presumed diagnosis of intrahepatic cholangiocarcinoma was made. Biopsies of the mass had purely shown inflammation and remained inconclusive. It was decided that the patient should undergo a complete extended right hepatectomy with resection and reconstruction of the left branch of the portal vein. On attempting to obtain intraoperative frozen section specimens prior to resection, open excision revealed two large swabs encased in a calcified cavity. Removal of the swabs resulted in resolution of the mass and obstructive symptoms. CONCLUSIONS: Gossypiboma should be a rare differential diagnosis in all patients following a laparotomy presenting with obstructive symptoms, particularly in countries where strict surgical protocols may not be in place. This case also highlights the need to perform an intraoperative biopsy in any uncertain case of a liver lesion as we have shown that an extensive operation with its increased morbidity can occasionally be avoided.
Twaij A, Pucher PH, Sodergren MH, et al., 2014, Laparoscopic <i>vs</i> open approach to resection of hepatocellular carcinoma in patients with known cirrhosis: Systematic review and meta-analysis, WORLD JOURNAL OF GASTROENTEROLOGY, Vol: 20, Pages: 8274-8281, ISSN: 1007-9327
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- Citations: 86
Gall TMH, Basyouny M, Frampton AE, et al., 2014, Neoadjuvant chemotherapy and primary-first approach for rectal cancer with synchronous liver metastases, COLORECTAL DISEASE, Vol: 16, Pages: O197-O205, ISSN: 1462-8910
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- Citations: 9
Gall TMH, Jacob J, Frampton AE, et al., 2014, Reduced dissemination of circulating tumor cells with no-touch isolation surgical technique in patients with pancreatic cancer, JAMA Surgery, Vol: 149, Pages: 482-485, ISSN: 2168-6254
Frampton AE, Giovannetti E, Jamieson NB, et al., 2014, A microRNA meta-signature for pancreatic ductal adenocarcinoma, EXPERT REVIEW OF MOLECULAR DIAGNOSTICS, Vol: 14, Pages: 267-271, ISSN: 1473-7159
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- Citations: 25
Gall TMH, Thompson Z, Dinneen EP, et al., 2014, Surgical techniques for improving outcomes in pancreatic ductal adenocarcinoma, EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY, Vol: 8, Pages: 241-246, ISSN: 1747-4124
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- Citations: 6
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