Papers by James Skipworth
British Journal of Surgery
Background Pathological response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant chemot... more Background Pathological response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant chemotherapy (NAT) can be assessed using grading systems such as the College of American Pathologists (CAP) system, with favourable regression being associated with improved oncological outcomes. The aim of the study was to investigate factors associated with favourable tumour regression in patients undergoing pancreatoduodenectomy (PD) for PDAC. Methods Patients who received NAT before undergoing PDAC resection at two institutions in the United Kingdom between 2013 and 2021 were reviewed. Interactions between chemotherapy regimens, tumour staging, carbohydrate antigen 19-9 (Ca19-9) levels, perioperative factors and tumour regression grading (TRG) were explored. Results 54 patients were identified who were suitable for inclusion. 12 (22%) patients had a favourable response to NAT according to the CAP grading system. A significantly greater reduction in Ca19-9 observed in the favourable TRG gro...
Current Opinion in Critical Care, Apr 1, 2008
To review advances over the last year in the prevention, diagnosis and management of acute pancre... more To review advances over the last year in the prevention, diagnosis and management of acute pancreatitis. Obesity is an independent risk factor for severity in acute pancreatitis, and heavy alcohol consumption for the development of necrosis in severe acute pancreatitis. Biochemical markers have been further tested, including carbohydrate-deficient transferrin for the diagnosis of alcohol-induced acute pancreatitis, urinary trypsinogen-2 as a diagnostic marker for acute pancreatitis, and interleukin-6 and procalcitonin as markers of disease severity. A new, simple stratification system, the 'panc 3 score', has been described. There are conflicting data on the use of antibiotic prophylaxis in acute necrotizing pancreatitis, and on the chemoprevention of postendoscopic retrograde cholangiopancreatography pancreatitis. Enteral feeding is established as standard practice early in the management of acute pancreatitis of all aetiologies; probiotics and other compounds may also play a role. Over the last year, there have been further innovations in the risk stratification and management of acute pancreatitis. Unresolved issues include chemoprevention of endoscopic retrograde cholangiopancreatography-induced acute pancreatitis, the indications for antibiotic prophylaxis in severe acute pancreatitis and nutritional supplementation with probiotics and synbiotics.
Oxford University Press eBooks, Apr 1, 2016
The incidence of acute pancreatitis continues to increase, but the attendant mortality has not de... more The incidence of acute pancreatitis continues to increase, but the attendant mortality has not decreased for >30 years. The pathogenesis remains poorly understood, but the initial mechanism appears to be intracellular activation of pancreatic enzymes, with micro- and macrovascular dysfunction, in conjunction with a systemic inflammatory response acting as a key propagating factor and determinant of severity. A multitude of causes or initiators exist, but there is a common pathophysiological pathway. The use of conventional scoring systems, combined with repeated clinical and laboratory assessment, remain the optimal method of predicting early severity and organ dysfunction. Death occurs in a biphasic pattern with early mortality (<2 weeks) secondary to SIRS and MODS; and late deaths (>2 weeks) due to superinfection of pancreatic necrosis. Assessment of severity should reflect this, with early severity being diagnosed in the presence of organ failure for >48 hours, and late severity defined by the presence of pancreatic and peri-pancreatic complications on CT or other appropriate imaging modalities.
British Journal of Surgery, Dec 1, 2021
patient survival, despite an increased morbidity. Our series reports comparable morbidity and mor... more patient survival, despite an increased morbidity. Our series reports comparable morbidity and mortality to the published literature for DA resected by PD. This study reports a 95% R0 resection rate for DA with a 3-and 5-year survival of 50% and 30% respectively. DFS was found to be significantly higher in patients with no nodal disease, despite predominant T4 disease. This series has identified that lymph node metastasis is one of the most important prognostic determinants of long-term patient survival. Program permission: yes P-P44 Clinical outcomes of consecutive patients undergoing distal pancreatectomy over the last decade at a high volume tertiary pancreatic surgery unit
British Journal of Surgery, Dec 1, 2021
Background: Pseudoaneurysms are recognised to be a serious complication of chronic pancreatitis. ... more Background: Pseudoaneurysms are recognised to be a serious complication of chronic pancreatitis. Visceral artery aneurysms (VAA) can be
Oxford University Press eBooks, Mar 1, 2020
Pancreatic cancer, most commonly in the form of a solid ductal adenocarcinoma, accounts for 3% of... more Pancreatic cancer, most commonly in the form of a solid ductal adenocarcinoma, accounts for 3% of all cancers but ranks in the top five leading causes of cancer deaths in most developed countries, reflecting the fact that it has a very poor prognosis (median survival 6–9 months). It is a disease of older age (85% of patients >65 years), and commoner in smokers. Most patients present with locally advanced or metastatic disease, often with obstructive jaundice. Pain is unusual in early disease, but when present is characteristically described as ‘gnawing’, ever present, and frequently radiating into the back. Weight loss is commonly due to anorexia as a result of jaundice or pain, but can occasionally be the only presenting symptom. Serum biochemistry will typically show elevated bilirubin and a cholestatic picture of liver enzymes, with particular elevation of alkaline phosphatase and γ-glutamyl transferase. Transabdominal ultrasonography is usually the primary investigation in a patient with jaundice and can detect pancreatic tumours greater than 2 cm in size or hepatic metastases with a diagnostic accuracy of 75%, but identifies smaller tumours much less reliably. The essential investigations for the diagnosis and staging of pancreatic cancer are contrast-phased CT scan and occasionally MRI. The only curative treatment for pancreatic cancer is surgical excision. This is technically feasible in up to 20% patients at presentation, but even after careful selection almost 40% of these will have positive microscopic resection margins, and overall postoperative survival is only around 10% at 5 years, the remainder experiencing metastatic disease in the peritoneum, liver, or lungs. Adjuvant chemotherapy with gemcitabine can double the 5-year survival rate. Palliative management may require biliary stenting for jaundice, duodenal stenting (or surgical bypass) for gastric outlet obstruction, pain control, and palliative chemotherapy.
British Journal of Surgery, Jun 22, 2022
Background Data on interventions to reduce postoperative pancreatic fistula (POPF) following panc... more Background Data on interventions to reduce postoperative pancreatic fistula (POPF) following pancreatoduodenectomy (PD) are conflicting. The aim of this study was to assimilate data from RCTs. Methods MEDLINE and Embase databases were searched systematically for RCTs evaluating interventions to reduce all grades of POPF or clinically relevant (CR) POPF after PD. Meta-analysis was undertaken for interventions investigated in multiple studies. A post hoc analysis of negative RCTs assessed whether these had appropriate statistical power. Results Among 22 interventions (7512 patients, 55 studies), 12 were assessed by multiple studies, and subjected to meta-analysis. Of these, external pancreatic duct drainage was the only intervention associated with reduced rates of both CR-POPF (odds ratio (OR) 0.40, 95 per cent c.i. 0.20 to 0.80) and all-POPF (OR 0.42, 0.25 to 0.70). Ulinastatin was associated with reduced rates of CR-POPF (OR 0.24, 0.06 to 0.93). Invagination (versus duct-to-mucosa) pancreatojejunostomy was associated with reduced rates of all-POPF (OR 0.60, 0.40 to 0.90). Most negative RCTs were found to be underpowered, with post hoc power calculations indicating that interventions would need to reduce the POPF rate to 1 per cent or less in order to achieve 80 per cent power in 16 of 34 (all-POPF) and 19 of 25 (CR-POPF) studies respectively. Conclusion This meta-analysis supports a role for several interventions to reduce POPF after PD. RCTs in this field were often relatively small and underpowered, especially those evaluating CR-POPF.
Annals of The Royal College of Surgeons of England, Nov 1, 2007
We present the case of a patient who sustained a blunt head injury resulting in a delayed diagnos... more We present the case of a patient who sustained a blunt head injury resulting in a delayed diagnosis of a carotid-cavernous sinus fistula. Although rare in occurrence, a high index of suspicion is paramount with a history of head injury and developing signs in the eyes and face. Prompt referral to senior ophthalmic and neurosurgical teams is indicated to prevent the possibility of permanent visual loss with this condition.
BMJ Open Respiratory Research, Mar 1, 2017
Introduction: Skeletal muscle impairment is an important feature of chronic obstructive pulmonary... more Introduction: Skeletal muscle impairment is an important feature of chronic obstructive pulmonary disease (COPD). Renin-angiotensin system activity influences muscle phenotype, so we wished to investigate whether it affects the response to pulmonary rehabilitation. Methods: Two studies are described; in the first, the response of 168 COPD patients (mean forced expiratory volume in one second 51.9% predicted) to pulmonary rehabilitation was compared between different ACE insertion/deletion polymorphism genotypes. In a second, independent COPD cohort (n=373), baseline characteristics and response to pulmonary rehabilitation were compared between COPD patients who were or were not taking ACE inhibitors or angiotensin receptor antagonists (ARB). Results: In study 1, the incremental shuttle walk distance improved to a similar extent in all three genotypes; DD/ID/II (n=48/91/29) 69(67)m, 61 (76)m and 78 (78)m, respectively, (p>0.05). In study 2, fat free mass index was higher in those on ACE-I/ARB (n=130) than those who were not (n=243), 17.8 (16.0, 19.8) kg m −2 vs 16.5 (14.9, 18.4) kg/m 2 (p<0.001). However change in fat free mass, walking distance or quality of life in response to pulmonary rehabilitation did not differ between groups. Conclusions: While these data support a positive association of ACE-I/ARB treatment and body composition in COPD, neither treatment to reduce ACE activity nor ACE (I/D) genotype influence response to pulmonary rehabilitation. Chronic obstructive pulmonary disease Contributors NSH, WD-CM, HM, MIP and JM conceived the study. SSCK, CJJ and DS collected data. JRAS and ZP performed genotyping. NSH and SSCK produced the first draft which all authors subsequently contributed to and approved in this final version. NSH is guarantor for the study. Funding Medical Research Council (grant number G0701628) and British Lung Foundation (grant number TC 04/4). Competing interests HM has held a consultancy with ARK therapeutics relating to ACE-I and muscle efficiency. The other authors have no conflicts of interest to declare. Ethics approval Ethics Committee of King's College Hospital (05/Q0703/134).
Expert Opinion on Medical Diagnostics, Aug 23, 2013
Introduction: The worldwide incidence of biliary tract carcinoma (BTC; tumours of the bile ducts ... more Introduction: The worldwide incidence of biliary tract carcinoma (BTC; tumours of the bile ducts and gall-bladder) continues to rise with the only potentially curative treatment remaining surgical resection or transplantation, possible in only a minority of patients. Late presentation and a paucity of effective treatments mandate the development of techniques for early lesion detection. Areas Covered: This article reviews currently available biomarkers for the diagnosis and prognosis of BTC, as well as recently published studies describing novel serum, bile and urinary biomarkers. Expert Opinion: The incorporation of novel analysis techniques, such as digital image analysis and fluorescence in situ hybridization, into existing management algorithms may enhance the accuracy of brush cytology taken at the time of therapeutic endoscopy. However, a key goal is the discovery of reliable non-invasive biomarkers with high sensitivity and specificity. Recent advances in gene sequencing and expression, clonal evolution and tumour heterogeneity in other cancers should advance understanding of BTC tumour biology and facilitate biomarker discovery.
World Journal of Surgery, Jul 15, 2009
Objective A prospective study was undertaken to review the use of combined lumbar spinal and thor... more Objective A prospective study was undertaken to review the use of combined lumbar spinal and thoracic highepidural regional anesthesia in high-risk patients who underwent gastrointestinal/colorectal surgery from 2004 to 2006. Methods Twelve high-risk patients underwent 13 gastrointestinal/colorectal surgical procedures, using a regional anesthetic technique, which consisted of a thoracic epidural and lumbar subarachnoid block. All patients were classified as high risk based on anesthetic assessment (American Society of Anesthesiologists (ASA) score 3 or 4). Results Six (46.2%) of the patients were men, and the overall median age was 86 years. Ten (76.9%) patients presented as emergencies, whereas only three (23.1%) patients underwent elective procedures. All patients subjectively rated their postoperative pain relief as effective. The 30day mortality was 2 (15.4%); however, both of these patients refused initial treatment. Only one (7.7%) patient required delayed ITU admission for respiratory support (CPAP). None of the patients required intubation at any stage. There were two (15.4%) minor and two (15.4%) major early complications and only one (7.7%) delayed complication to date. Median length of stay was 7 days. Two (15.4%) patients had delayed discharge dates, for social reasons. Discussion These patients demonstrated early postoperative recovery, with effective analgesia, no requirements for intubation, and lower morbidity and mortality rates than similar studies of high-risk patients who underwent procedures using general anesthesia. Using this technique, patients were managed appropriately in HDU and the surgical ward, without affecting their overall length of hospital stay. Conclusions This study supports the role of regional anesthetic techniques, combined with targeted, minimally invasive surgery-particularly for the management of highrisk patients presenting in the emergency setting.
PubMed, Nov 9, 2011
Context: Abdominal pain, malabsorption and diabetes all contribute to a negative impact upon nutr... more Context: Abdominal pain, malabsorption and diabetes all contribute to a negative impact upon nutritional status in chronic pancreatitis and no validated standard for the nutritional management of patients exists. Objective: To assess the effect of nasojejunal nutrition in chronic pancreatitis patients. Design: All consecutive chronic pancreatitis patients fed via the nasojejunal route between January 2004 and December 2007 were included in the study. Patients were assessed via retrospective review of case notes. Results: Fifty-eight chronic pancreatitis patients (35 males, 23 females; median age 46 years) were included. Patients were discharged after a median of 14 days and nasojejunal nutrition continued for a median of 47 days. Forty-six patients (79.3%) reported resolution of their abdominal pain and cessation of opioid analgesia intake over the study period and median weight gain at 6 weeks following nutritional cessation was +1 kg (range -24 to +27 kg; P=0.454). Twelve (20.7%) patients reported recurrence of their pain during the follow-up period and complications were both minor and infrequent. Significant improvements were noted in most blood parameters measured, including: sodium (from 134.8 to 138.1 mEq/L; P<0.001); urea (from 3.4 to 5.1 mmol/L; P<0.001); creatinine (from 58.3 to 60.3 µmol/L; P<0.001); corrected calcium (from 2.24 to 2.35 mmol/L; P=0.018); albumin (from 34.5 to 38.7 g/L; P=0.002); CRP (from 73.0 to 25.5 mg/L; P=0.006); and haemoglobin (from 11.8 to 12.4 g/dL; P=0.036). Conclusion: Nasojejunal nutrition, commenced in hospital and continued at home, is safe, efficacious and well tolerated in patients with severe chronic pancreatitis and is effective in helping to relieve pain and diminish analgesic requirements.
Annals of The Royal College of Surgeons of England, Mar 1, 2008
We present a case of massive pneumoperitoneum in association with pneumatosis intestinalis that w... more We present a case of massive pneumoperitoneum in association with pneumatosis intestinalis that was successfully managed without surgery despite a clinical picture of an acute abdomen and biochemical evidence of inflammation and systemic upset. Recognition of non-surgical pneumoperitoneum is important to avoid unnecessary laparotomy, and clinical examination for the presence of peritonitis is the most important determinant of the need for emergency surgery.
International Journal of Cardiology, May 1, 2012
Background: A substantial proportion of patients suffer prolonged length of intensive care unit s... more Background: A substantial proportion of patients suffer prolonged length of intensive care unit stay (PLOS) or prolonged mechanical ventilation (PMV) following coronary artery bypass grafting (CABG). Identifying factors associated with PLOS and PMV would aid in patient risk stratification. We sought to identify the factors associated with PLOS and PMV following CABG. Methods: Participants were patients undergoing first-time elective CABG. All were observed until discharge and clinical data were collected on a standardized proforma. PLOS and PMV were defined a priori as N 2 days and N 12 h respectively, based on centre norms. Results: Of the 439 patients in the study, 105 (23.9%) had PLOS and 111 (25.2%) had PMV. Independent predictors of PMV were age, diabetes, previous myocardial infarction (MI), New York Heart Association (NYHA) class and statin use. The only independent predictor of PLOS was the duration of preceding hypertension. Conclusion: The factors associated with PMV and PLOS in our study are easily attainable, routine clinical details and may be built into bed management algorithms. Confirmation of the association of preceding hypertension and subsequent investigation of the possible mechanism mediating this association, is suggested.
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Papers by James Skipworth