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126 results found
Russell TB, Labib PL, Denson J, et al., 2023, Postoperative complications after pancreatoduodenectomy for malignancy: results from the Recurrence After Whipple's (RAW) study, BJS Open, Vol: 7, ISSN: 2474-9842
BACKGROUND: Pancreatoduodenectomy (PD) is associated with significant postoperative morbidity. Surgeons should have a sound understanding of the potential complications for consenting and benchmarking purposes. Furthermore, preoperative identification of high-risk patients can guide patient selection and potentially allow for targeted prehabilitation and/or individualized treatment regimens. Using a large multicentre cohort, this study aimed to calculate the incidence of all PD complications and identify risk factors. METHOD: Data were extracted from the Recurrence After Whipple's (RAW) study, a retrospective cohort study of PD outcomes (29 centres from 8 countries, 2012-2015). The incidence and severity of all complications was recorded and potential risk factors for morbidity, major morbidity (Clavien-Dindo grade > IIIa), postoperative pancreatic fistula (POPF), post-pancreatectomy haemorrhage (PPH) and 90-day mortality were investigated. RESULTS: Among the 1348 included patients, overall morbidity, major morbidity, POPF, PPH and perioperative death affected 53 per cent (n = 720), 17 per cent (n = 228), 8 per cent (n = 108), 6 per cent (n = 84) and 4 per cent (n = 53), respectively. Following multivariable tests, a high BMI (P = 0.007), an ASA grade > II (P < 0.0001) and a classic Whipple approach (P = 0.005) were all associated with increased overall morbidity. In addition, ASA grade > II patients were at increased risk of major morbidity (P < 0.0001), and a raised BMI correlated with a greater risk of POPF (P = 0.001). CONCLUSION: In this multicentre study of PD outcomes, an ASA grade > II was a risk factor for major morbidity and a high BMI was a risk factor for POPF. Patients who are preoperatively identified to be high risk may benefit from targeted prehabilitation or individualized treatment regimens.
Russell TB, Labib PL, Denson J, et al., 2023, Does an extensive diagnostic workup for upfront resectable pancreatic cancer result in a delay which affects survival? Results from an international multicentre study, Annals of Hepato-biliary-pancreatic Surgery, Vol: 27, Pages: 403-414, ISSN: 2508-5778
BACKGROUNDS/AIMS: Pancreatoduodenectomy (PD) is recommended in fit patients with a carcinoma (PDAC) of the pancreatic head, and a delayed resection may affect survival. This study aimed to correlate the time from staging to PD with long-term survival, and study the impact of preoperative investigations (if any) on the timing of surgery. METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study, a multicentre retrospective study of PD outcomes. Only PDAC patients who underwent an upfront resection were included. Patients who received neoadjuvant chemo-/radiotherapy were excluded. Group A (PD within 28 days of most recent preoperative computed tomography [CT]) was compared to group B (> 28 days). RESULTS: A total of 595 patents were included. Compared to group A (median CT-PD time: 12.5 days, interquartile range: 6-21), group B (49 days, 39-64.5) had similar one-year survival (73% vs. 75%, p = 0.6), five-year survival (23% vs. 21%, p = 0.6) and median time-todeath (17 vs. 18 months, p = 0.8). Staging laparoscopy (43 vs. 29.5 days, p = 0.009) and preoperative biliary stenting (39 vs. 20 days, p < 0.001) were associated with a delay to PD, but magnetic resonance imaging (32 vs. 32 days, p = 0.5), positron emission tomography (40 vs. 31 days, p > 0.99) and endoscopic ultrasonography (28 vs. 32 days, p > 0.99) were not. CONCLUSIONS: Although a treatment delay may give rise to patient anxiety, our findings would suggest this does not correlate with worse survival. A delay may be necessary to obtain further information and minimize the number of PD patients diagnosed with early disease recurrence.
Russell TB, Labib PL, Ausania F, et al., 2023, Serious complications of pancreatoduodenectomy correlate with lower rates of adjuvant chemotherapy: Results from the recurrence after Whipple's (RAW) study, EJSO, Vol: 49, ISSN: 0748-7983
Russell TB, Labib PL, Denson J, et al., 2023, Predictors of actual five-year survival and recurrence after pancreatoduodenectomy for ampullary adenocarcinoma: results from an international multicentre retrospective cohort study, HPB, Vol: 25, Pages: 788-797, ISSN: 1365-182X
Soleimani-Nouri P, Entwistle OH, Fehervari M, et al., 2023, A novel framework for surgical reflection, ANNALS OF LAPAROSCOPIC AND ENDOSCOPIC SURGERY, ISSN: 2518-6973
D'Alessio A, Pai M, Spalding D, et al., 2023, Neoadjuvant immunotherapy with ipilimumab plus nivolumab and radiologically and pathologically quantifiable responses through modulation of the tumour microenvironment in resectable hepatocellular carcinoma, Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
Reccia I, Pai M, Kumar J, et al., 2023, Tumour Heterogeneity and the Consequent Practical Challenges in the Management of Gastroenteropancreatic Neuroendocrine Neoplasms, CANCERS, Vol: 15
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Avari P, Eng PC, Hu M, et al., 2023, A novel somatic mutation implicates ATP6V0D1 in proinsulin processing, Journal of the Endocrine Society, Vol: 7, Pages: 1-5, ISSN: 2472-1972
ContextProhormone convertase 1/3 (PC1/3), encoded by protein convertase subtilisin kexin type 1 (PCSK1), converts inactive prohormones into biologically active peptides. Somatic mutations of insulinomas are associated with genetic defects interfering with control of insulin secretion from pancreatic beta cells. However, somatic mutations in proinsulinomas have not been described.ObjectiveWe report a case of a proinsulinoma, with suppressed insulin and C-peptide levels.MethodsA 70-year-old woman presented with a 20-year history of “blackouts.” During a 72-hour fast, blood glucose level dropped to 1.9 mmol/L with suppressed plasma insulin and C-peptide levels, but proinsulin levels were raised at 37 pmol/L (<10 pmol/L).ResultsImaging revealed 3 distinct DOTATATE-avid pancreatic lesions. Laparoscopic spleen-preserving distal pancreatomy was performed. In view of discordant insulin, C-peptide, and proinsulin levels, whole exome sequencing analysis was performed on the tumor. In the somatic exome of the tumor, we found mutations in PCSK expression regulators, as well as a novel truncating somatic mutation in ATP6V0D1, a subunit of the ion pump that acidifies the β-cell compartments where the PCSKs act.ConclusionAppropriately suppressed insulin levels in the context of hypoglycemia do not always indicate the absence of a neuroendocrine islet cell tumor and proinsulin levels may be indicated to solidify the diagnosis. In the context of elevated proinsulin levels, low insulin and C-peptide levels might be explained by somatic mutations that likely implicate proinsulin processing within the tumor. Furthermore, we propose several mechanistic candidates, including ATP6V0D1. Experimental validation using cellular approaches may in future confirm pathomechanisms involved in this rare condition.
Das B, Fehervari M, Hamrang-Yousefi S, et al., 2023, Pancreaticoduodenectomy with right hemicolectomy for advanced malignancy: a single UK hepatopancreaticobiliary centre experience, Colorectal Disease, Vol: 25, Pages: 16-23, ISSN: 1462-8910
AimLocally advanced intestinal neoplasms including colon cancer may require radical en bloc pancreaticoduodenectomy and right hemicolectomy (PD-RC) to achieve curative, margin-negative resection, but the safety and benefit of this uncommon procedure has not been established. The Association of Coloproctology of Great Britain and Ireland IMPACT initiative has also highlighted a lack of awareness about current services available within the UK for patients with advanced colorectal cancer and concerns about low-volume centres managing complex cases. Thus, we aimed to review the feasibility, safety and long-term outcomes of this procedure at a single high-volume hepatopancreaticobiliary surgery unit in the UK.MethodA retrospective cohort study was performed using a database of all consecutive patients with intestinal cancer who had been referred to our regional advanced multidisciplinary team and undergone PD-RC in a 7-year period (2013–2020). Clinico-pathological and outcome data were reviewed.ResultsTen patients (mean age 54 ± 13, 8/10 men) were identified. Final histology revealed the primary tumour sites were colon (n = 7) and duodenum (n = 3). R0 resection was achieved in all cases. The major complication rate (Clavien–Dindo ≥ 3) was 10% (1/10) with no deaths within 90 days of surgery. The Kaplan–Meier estimated 5-year overall survival was 83.3% (95% CI 58.3%–100%). Univariate survival analysis identified perineural invasion and extra-colonic origin as predictors of poor survival (log-rank P < 0.05).ConclusionEn bloc PD-RC for locally advanced intestinal cancer can be performed safely with a high proportion of margin-negative resections and resultant long-term survival in carefully selected patients.
D'Alessio A, Pai M, Spalding D, et al., 2022, PRIME-HCC: phase Ib study of neoadjuvant ipilimumab and nivolumab prior to liver resection for hepatocellular carcinoma, International Liver Congress, Publisher: ELSEVIER, Pages: S108-S109, ISSN: 0168-8278
D'Alessio A, Pai M, Spalding D, et al., 2022, Preliminary results from a phase Ib study of neoadjuvant ipilimumab plus nivolumab prior to liver resection for hepatocellular carcinoma: The PRIME-HCC trial., Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
Alghazawi LOK, Entwistle OH, Fehervari M, et al., 2022, Unusual cause of intraoperative haemorrhage: a lesson for patient counselling, BMJ CASE REPORTS, Vol: 15
Fehervari M, Das B, Soleimani-Nouri P, et al., 2022, Can surgical skills be taught using technological advances online? A comparative study of online and face-to-face surgical skills training, SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, Vol: 36, Pages: 4631-4637, ISSN: 0930-2794
IntroductionOnline teaching has rapidly emerged as a viable alternative to traditional face-to-face education. How to teach surgical skills in the online environment, however, has not yet been fully established nor evaluated.MethodsAn international 1-day online surgical skills course consisting of lectures, pre-recorded virtual workshops, live demonstrations and along with surgical skills teaching in breakout rooms was organised. Based on existing learning theories, new methods were developed to deliver skills teaching online. Simultaneously, traditional in-person surgical skills teaching was also conducted and used as a benchmark. Skills development was assessed by trained demonstrators and self-reported competency scores were compared between the online and face-to-face event.Results553 delegates from 20 different countries attended the online course. Of these, 64 were trained in breakout rooms with a 1:5 demonstrator-to-delegate ratio whilst the remaining 489 delegates participated in didactic skills development sessions. In a separate face-to-face course, 20 delegates were trained with traditional methods. Demonstrators rated the competency of delegates for suturing, tendon repair and vascular anastomosis. There was no significant difference in the competency ratings of delegates receiving online teaching or face-to-face teaching (p = 0.253, p = 0.084, p = 1.00, respectively). The development of the same skills to “articulation” were not different between formats (p = 0.841, p = 0.792, p = 1.00, respectively). Post course self-rated competency scores improved for all technical skills (p < 0.001). Small group sessions, both online and face-to-face, received higher satisfaction ratings compared to large group sessions in terms of clarity of instructions, answers to questions and demonstrator feedback. Overall feedback on teaching quality, however, was e
Kilic Y, Graham A, Tait NP, et al., 2022, Percutaneous biliary stone clearance: is there still a need? A 10-year single-centre experience, CLINICAL RADIOLOGY, Vol: 77, Pages: 130-135, ISSN: 0009-9260
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Tabiri S, Kamarajah SK, Nepogodiev D, et al., 2022, Impact of Bacillus Calmette-Guerin (BCG) vaccination on postoperative mortality in patients with perioperative SARS-CoV-2 infection, BJS Open, Vol: 5, ISSN: 2474-9842
da Costa AC, Spalding D, Cunha-Filho GDA, et al., 2022, HOW TO PERFORM LAPAROSCOPIC DISTAL PANCREATECTOMY USING THE CLOCKWISE TECHNIQUE, ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA-BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY, Vol: 35, ISSN: 0102-6720
McLean KA, Kamarajah SK, Chaudhry D, et al., 2021, Death following pulmonary complications of surgery before and during the SARS-CoV-2 pandemic, BRITISH JOURNAL OF SURGERY, Vol: 108, Pages: 1448-1464, ISSN: 0007-1323
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- Citations: 7
Hashimoto A, Sarker D, Reebye V, et al., 2021, Upregulation of C/EBPα Inhibits Suppressive Activity of Myeloid Cells and Potentiates Antitumor Response in Mice and Patients with Cancer, CLINICAL CANCER RESEARCH, Vol: 27, Pages: 5961-5978, ISSN: 1078-0432
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- Citations: 32
Glasbey J, Ademuyiwa A, Adisa A, et al., 2021, Effect of COVID-19 pandemic lockdowns on planned cancer surgery for 15 tumour types in 61 countries: an international, prospective, cohort study, The Lancet Oncology, Vol: 22, Pages: 1507-1517, ISSN: 1470-2045
BackgroundSurgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction.MethodsThis international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20–60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov, NCT04384926.FindingsOf eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notif
McKay SC, Pathak S, Wilkin RJW, et al., 2021, Impact of SARS-CoV-2 pandemic on pancreatic cancer services and treatment pathways: United Kingdom experience, HPB, Vol: 23, Pages: 1656-1665, ISSN: 1365-182X
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- Citations: 10
Plummer R, Sodergren M, Pinato D, et al., 2021, A PHASE 1 STUDY OF MYELOID MODULATING AGENT MTL-CEBPA IN COMBINATION WITH PEMBROLIZUMAB IN ADULT PATIENTS WITH ADVANCED SOLID TUMOURS, Publisher: BMJ PUBLISHING GROUP, Pages: A545-A545
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- Citations: 2
COVIDSurg Collaborative Co-authors, 2021, Machine learning risk prediction of mortality for patients undergoing surgery with perioperative SARS-CoV-2: the COVIDSurg mortality score, British Journal of Surgery, Vol: 108, Pages: 1274-1292, ISSN: 0007-1323
Since the beginning of the COVID-19 pandemic tens of millions of operations have been cancelled1 as a result of excessive postoperative pulmonary complications (51.2 per cent) and mortality rates (23.8 per cent) in patients with perioperative SARS-CoV-2 infection2. There is an urgent need to restart surgery safely in order to minimize the impact of untreated non-communicable disease.As rates of SARS-CoV-2 infection in elective surgery patients range from 1–9 per cent3–8, vaccination is expected to take years to implement globally9 and preoperative screening is likely to lead to increasing numbers of SARS-CoV-2-positive patients, perioperative SARS-CoV-2 infection will remain a challenge for the foreseeable future.To inform consent and shared decision-making, a robust, globally applicable score is needed to predict individualized mortality risk for patients with perioperative SARS-CoV-2 infection. The authors aimed to develop and validate a machine learning-based risk score to predict postoperative mortality risk in patients with perioperative SARS-CoV-2 infection.
Pinato D, Cortellini A, Sukumaran A, et al., 2021, PRIME-HCC: Phase Ib study of neoadjuvant ipilimumab and nivolumab prior to liver resection for hepatocellular carcinoma, BMC Cancer, Vol: 21, ISSN: 1471-2407
BackgroundAfter liver resection (LR), patients with hepatocellular cancer (HCC) are at high risk of recurrence. There are no approved anti-cancer therapies known to affect such risk, highlighting the acute need for novel systemic therapies to control the probability of disease relapse. Immunotherapy is expanding as a novel treatment option for HCC. Emerging data from cohort 4 of the CA209–040 study, which investigated the safety and preliminary efficacy of nivolumab/ipilimumab co-administration in advanced HCC, suggest that the combination can be delivered safely with an acceptable proportion of reversible grade 3–4 toxicities (27.1%) and a low discontinuation rate (2%) in patients with HCC. Here, we describe the design and rationale of PRIME-HCC, a two-part, multi-centre, phase Ib study to assess safety and bioactivity of the nivolumab/ipilimumab combination prior to LR in early-stage HCC.MethodsThe study involves an initial safety run-in phase (Part 1) to allow for preliminary safety characterisation within the first 6 patients enrolled and a subsequent expansion (Part 2). Ipilimumab will be administered once only on Day 1. Nivolumab will be administered on Day 1 and Day 22 (± 3 days) for a total of two 21-day cycles (i.e. 6 weeks of treatment). The primary objective of the study is to determine the safety and tolerability of the nivolumab/ipilimumab combination prior to LR. The secondary objective is to preliminarily characterize the efficacy of the combination prior to LR, including objective response rate (ORR) and pathologic response rates. Additional exploratory objectives include preliminary evidence of long-term disease control and to identify predictive correlates of response to the nivolumab/ipilimumab combination in HCC.DiscussionThe results of this study will help define the positioning of neoadjuvant nivolumab/ipilimumab combination in the perioperative management of HCC, with potential to improve survival outcom
Glasbey JC, Omar O, Nepogodiev D, et al., 2021, Preoperative nasopharyngeal swab testing and postoperative pulmonary complications in patients undergoing elective surgery during the SARS-CoV-2 pandemic, BRITISH JOURNAL OF SURGERY, Vol: 108, Pages: 88-96, ISSN: 0007-1323
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- Citations: 43
Gavriilidis P, Sutcliffe RP, Roberts KJ, et al., 2020, No difference in mortality among ALPPS, two-staged hepatectomy, and portal vein embolization/ligation: A systematic review by updated traditional and network meta-analyses, HEPATOBILIARY & PANCREATIC DISEASES INTERNATIONAL, Vol: 19, Pages: 411-419, ISSN: 1499-3872
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- Citations: 4
Sarker D, Plummer R, Meyer T, et al., 2020, MTL-CEBPA, a small activating RNA therapeutic upregulating C/EBP-α, in patients with advanced liver cancer: a first-in-human, multicenter, open-label, phase I trial, Clinical Cancer Research, Vol: 26, Pages: 3936-3946, ISSN: 1078-0432
PURPOSE: Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions and multiple oncogenic processes. MTL-CEBPA is a first-in-class small activating RNA oligonucleotide drug that upregulates C/EBP-α. PATIENTS AND METHODS: We conducted a phase I, open-label, dose-escalation trial of MTL-CEBPA in adults with advanced hepatocellular carcinoma (HCC) with cirrhosis, or resulting from nonalcoholic steatohepatitis or with liver metastases. Patients received intravenous MTL-CEBPA once a week for 3 weeks followed by a rest period of 1 week per treatment cycle in the dose-escalation phase (3+3 design). RESULTS: Thirty-eight participants have been treated across six dose levels (28-160 mg/m2) and three dosing schedules. Thirty-four patients were evaluable for safety endpoints at 28 days. MTL-CEBPA treatment-related adverse events were not associated with dose, and no maximum dose was reached across the three schedules evaluated. Grade 3 treatment-related adverse events occurred in nine (24%) patients. In 24 patients with HCC evaluable for efficacy, an objective tumor response was achieved in one patient [4%; partial response (PR) for over 2 years] and stable disease (SD) in 12 (50%). After discontinuation of MTL-CEBPA, seven patients were treated with tyrosine kinase inhibitors (TKIs); three patients had a complete response with one further PR and two with SD. CONCLUSIONS: MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC. These encouraging phase I data validate targeting of C/EBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC.
Noor MS, Dennis J, Al-Hinai K, et al., 2020, Quality Improvement Project: Improving the External Referrals Service of the Hepato-Pancreato-Biliary (HPB) Surgery in a Tertiary Centre, International Surgical Conference of the Association-of-Surgeons-in-Training, Publisher: WILEY, Pages: 187-187, ISSN: 0007-1323
Sarker D, Sodergren M, Plummer ER, et al., 2020, Phase Ib dose escalation and cohort expansion study of the novel myeloid differentiating agent MTL-CEBPA in combination with sorafenib in patients with advanced hepatocellular carcinoma (HCC)., Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
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da Costa AC, Sodergren M, Jayant K, et al., 2020, Radiofrequency combined with immunomodulation for hepatocellular carcinoma: State of the art and innovations, WORLD JOURNAL OF GASTROENTEROLOGY, Vol: 26, Pages: 2040-2048, ISSN: 1007-9327
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- Citations: 10
Sarker D, Sodergren M, Plummer ER, et al., 2020, First-in-human phase I trial of small activating RNA (saRNA) oligonucleotide MTL-CEBPA in combination with sorafenib in patients with advanced hepatocellular carcinoma (HCC), Gastrointestinal Cancers Symposium of the American-Society-of-Clinical-Oncology, Publisher: AMER SOC CLINICAL ONCOLOGY, ISSN: 0732-183X
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