A retrospective multicentre clinical study on management of isolated splenic vein thrombosis: risks and benefits of anticoagulation.

INTRODUCTION: Isolated splenic vein thrombosis (iSVT) is a common complication of pancreatic disease. Whilst patients remain asymptomatic, there is a risk of sinistral portal hypertension and subsequent bleeding from gastric varices if recanalisation does not occur. There is wide variation of iSVT treatment, even within single centres. We report outcomes of iSVT from tertiary referral hepatobiliary and pancreatic (HPB) units including the impact of anticoagulation on recanalisation rates and subsequent variceal bleeding risk. METHODS: A retrospective cohort study including all patients diagnosed with iSVT on contrast-enhanced CT scan abdomen and pelvis between 2011 and 2019 from two institutions. Patients with both SVT and portal vein thrombosis at diagnosis and isolated splenic vein thrombosis secondary to malignancy were excluded. The outcomes of anticoagulation, recanalisation rates, risk of bleeding and progression to portal vein thrombosis were examined using CT scan abdomen and pelvis with contrast. RESULTS: Ninety-eight patients with iSVT were included, of which 39 patients received anticoagulation (40%). The most common cause of iSVT was acute pancreatitis n = 88 (90%). The recanalisation rate in the anticoagulation group was 46% vs 15% in patients receiving no anticoagulation (p = 0.0008, OR = 4.7, 95% CI 1.775 to 11.72). Upper abdominal vascular collaterals (demonstrated on CT scan angiography) were significantly less amongst patients who received anticoagulation treatment (p = 0.03, OR = 0.4, 95% CI 0.1736 to 0.9288). The overall rate of upper GI variceal-related bleeding was 3% (n = 3/98) and it was independent of anticoagulation treatment. Two of the patients received therapeutic anticoagulation. CONCLUSION: The current data supports that therapeutic anticoagulation is associated with a statistically significant increase in recanalisation rates of the splenic vein, with a subsequent reduction in radiological left-sided portal hypertension. However, all patients had a very low risk of variceal bleeding regardless of anticoagulation. The findings from this retrospective study should merit further investigation in large-scale randomised clinical trials.

One-year follow-up of conservative management of appendicitis: results from a single centre during extended lockdown in the COVID-19 pandemic.

INTRODUCTION: Conservative management with antibiotics was recommended by the UK Surgical Royal Colleges early in the COVID-19 pandemic as the first-line treatment for acute uncomplicated appendicitis. METHODS: This is a prospective single-centre cohort study of patients aged 16 years or over, diagnosed clinically and confirmed radiologically with acute appendicitis in a secondary care setting who were initially treated conservatively with antibiotics. The primary outcome was the response to conservative management with antibiotics. Secondary outcomes were: antibiotic duration; operative rates; surgical approach (open, laparoscopic or conversion to open); complication rates; COVID-19 positive rate; rates of readmission within 12 months; and length of hospital stay. RESULTS: A total of 109 patients were included in the study, 67 of whom were male. Median age was 37 (range 17-93) years. A further 28 patients were excluded because of a decision to manage operatively on the index admission or because of other diagnoses. Thirty-three patients (30.3%) had surgery on the index admission after failed conservative management and 15 (13.8%) had surgery on readmission. On histology, 32/48 patients (66.7%) had a diagnosis of complicated appendicitis and 18/48 (37.5%) had a confirmed appendicolith. CONCLUSIONS: There was a high readmission rate (47/109; 43.1%) for surgery, a radiological drain or conservative management within the first year following initial conservative management. There is a significant risk of recurrence of symptoms, particularly in the presence of an appendicolith. Laparoscopic appendicectomy should be the first-line treatment, with conservative management reserved for patients with acute uncomplicated appendicitis who are COVID-19 positive or have comorbidities.

Retrospective observational study of patient outcomes with local wound infusion vs epidural analgesia after open hepato-pancreato-biliary surgery.

BACKGROUND: Epidural analgesia is conventionally used as the mainstay of analgesia in open abdominal surgery but has a small life-changing risk of complications (epidural abscesses or haematomas). Local wound-infusion could be a viable alternative and are associated with fewer adverse effects. METHODS: A retrospective observational analysis of individuals undergoing open hepato-pancreato-biliary surgery over 1 year was undertaken. Patients either received epidural analgesia (EP) or continuous wound infusion (WI) + IV patient controlled anaesthesisa (PCA) with an intraoperative spinal opiate. Outcomes analyzed included length of stay, commencement of oral diet and opioid use. RESULTS: Between Jan 2016- Dec 2016, 110 patients were analyzed (WI n=35, EP n=75). The median length of stay (days) was 8 in both the WI and EP group (p=0.846), the median time to commencing oral diet (days) was 3 in WI group and 2 in EP group (p=0.455). There was no significant difference in the amount of oromorph, codeine or tramadol (mg) between WI and EP groups (p=0.829, p=0.531, p=0.073, respectively). CONCLUSIONS: Continuous wound infusion + IV PCA provided adequate analgesia to patients undergoing open hepato-pancreato-biliary surgery. It was non-inferior to epidural analgesia with respect to hospital stay, commencement of oral diet and opioid use.

Intravenous omega-3 fatty acids are associated with better clinical outcome and less inflammation in patients with predicted severe acute pancreatitis: A randomised double blind controlled trial.

BACKGROUND AND AIMS: Omega-3 fatty acids (FA) can ameliorate the hyper-inflammatory response that occurs in conditions such as severe acute pancreatitis (SAP) and this may improve clinical outcome. We tested the hypothesis that parenteral omega-3 FA from a lipid emulsion that includes fish oil could be beneficial in patients with predicted SAP by reducing C-reactive protein (CRP) concentration (primary outcome), and modulating the inflammatory response and improving clinical outcome (secondary outcomes). METHODS: In a phase II randomized double-blind single-centre controlled trial, patients with predicted SAP were randomised to receive a daily infusion of fish oil containing lipid emulsion (Lipidem® 20%, BBraun) for 7 days (n = 23) or a daily infusion of a lipid emulsion without fish oil (Lipofundin® MCT 20%, BBraun) (n = 22). RESULTS: On admission, both groups had comparable pancreatitis predicted severity and APACHE II scores. Administration of fish oil resulted in lower total blood leukocyte number (P = 0.04), CRP (P = 0.013), interleukin-8 (P = 0.05) and intercellular adhesion molecule 1 (P = 0.01) concentrations, multiple organ dysfunction score, sequential organ failure assessment score (P = 0.004), early warning score (P = 0.01), and systemic inflammatory response syndrome (P = 0.03) compared to the control group. The fish oil group had fewer new organ failures (P = 0.07), lower critical care admission rate (P = 0.06), shorter critical care stay (P = 0.03) and shorter total hospital stay (P = 0.04). CONCLUSIONS: It is concluded that intravenous administration of a fish oil containing lipid emulsion, a source of omega-3 FA, improves clinical outcomes in patients with predicted SAP, benefits that may be linked to reduced inflammation. CLINICALTRIALS. GOV NUMBER: NCT01745861. EU CLINICAL TRIALS REGISTER: EudraCT (2010-018660-16).

Retrospective Analysis of Outcomes Following Percutaneous Cholecystostomy for Acute Cholecystitis.

BACKGROUND: Percutaneous cholecystostomy (PC) is often performed for patients with acute cholecystitis who are too high risk for cholecystectomy. The purpose of this retrospective study was to evaluate the outcomes of this cohort of patients over a 5-year period. METHODS: A retrospective analysis of all patients treated with PC for acute cholecystitis in a tertiary centre teaching hospital was conducted. The study period ranged from January 2010 to December 2015. Clinical data were extracted from the hospitals' electronic database system, as well as reviewing clinical notes and imaging reports. The aims of this study were to detect the reason PC was undertaken as opposed to surgery, the subsequent definitive management of patients initially treated with PC, the incidence of common bile duct stones (CBDS), the complications from PC, and the 30-day mortality. RESULTS: A total of 96 patients were identified. The total number of patients with CBDS was 27 (28.1%). Fourteen (14.6%) patients were shown to have CBDS on initial imaging. CBDS was detected in 12 patients (12.5%) at cholangiogram during their PC procedure. One patient had CBDS detected during a check cholangiogram at 6 weeks, which was not seen on initial imaging. Twenty-eight patients (29.2%) underwent an endoscopic retrograde cholangiopancreatography (ERCP), during their index admission. The main reasons for PC were a high American Society of Anaesthesiologists (ASA) score (49%), sepsis requiring organ support (19.8%), empyema of the gallbladder (29.1%), failed external biliary drainage for biliary obstruction (2.1%), and concomitant palliative malignancy (5.2%). Interval cholecystectomy was performed in 24 patients (25%). The total 30-day in-hospital mortality was 16.7%. CONCLUSION: PC is an effective and safe alternative as salvage therapy in high-risk elderly patients who have multiple comorbidities. It is valuable as a temporising measure before definitive treatment in high-risk patients. A high index of suspicion for CBDS (and further imaging with MRCP or a check cholangiogram) is warranted to detect missed CBDS. This is particularly relevant in this vulnerable group of patients where CBDS may represent a future source of recurrent sepsis.

Cardiopulmonary exercise testing in hepato-biliary & pancreas cancer surgery - A systematic review: Are we any further than walking up a flight of stairs?

INTRODUCTION: Cardiopulmonary exercise testing (CPET) is a reliable, reproducible and non-invasive measure of functional capacity. CPET has been increasingly used to assess pre-operative risk and stratify patients at risk of mortality and morbidity following surgery. CPET parameters that predict outcomes within liver and pancreas cancer surgery still remain to be defined. METHODS: A systematic review to assess CPET use in predicting post-operative outcomes in liver and pancreas cancer surgery was carried out using the following databases AMED, CINAHL, Cochrane Library, EMBASE, Google Scholar and PubMED. RESULTS: Data were extracted from four liver and four pancreas cancer studies. All were single institution, cohort series reporting outcomes with CPET used pre-operatively to assess patient morbidity, length of hospital stay and or mortality. In liver cancer surgery, all four papers reported outcome data on morbidity and patients who were more likely to suffer with complications tended to have an anaerobic threshold (AT) of less than 9.9-11.5 mL min-1.Kg-1. Whilst in pancreas cancer surgery, rates of pancreas fistulae tended to be higher in those patients who had an AT of less than 10 or 10.1 mL min-1.Kg-1. DISCUSSION: The CPET variable most reported and relevant to morbidity in both liver and pancreas cancer surgery appeared to be AT. A pre-operative AT of approximately 10.5 mL min-1.Kg-1 seems to be associated with a worse post-operative convalescence.

Indeterminate Pulmonary Nodules in Resected Liver Metastases from Colorectal Cancer: A Comparison of Patient Outcomes.

AIMS: Hepatic metastasectomy remains the only potentially curative treatment for colorectal liver metastases (CRLM). Some of these patients develop indeterminate pulmonary nodules (IPNs). This study aimed to compare outcomes of patients with and without IPN undergoing resection of CRLM to ascertain whether their presence is clinically significant. METHODS: Cases and controls were identified from a prospectively maintained database of CRLM resections. Patients with staging radiology demonstrating IPNs were included as cases. Controls were matched to the cases by four primary factors: age, type of resection (primary or redo), clinical risk score (CRS) and chemotherapy. RESULTS: The median disease-free survival (DFS) and overall survival (OS) for the cases were 7.0 months (95% CI 4.8-9.2) and 28.6 months (95% CI 21.2-36.0), respectively, and 12.0 months (95% CI 10.7-13.2) and 30.5 months (95% CI 19.4-41.6) for the controls. The 1-, 3- and 5-year survival rates were 92.7, 39.7 and 0.0% for the IPN group, and 92.4, 32.9 and 21.9% for those without. In total, 60.7% of IPN patients progressed to lung metastases, of which 39.3% underwent pulmonary resections. DFS was significantly shorter in the IPN group (p = 0.022), but OS was not significantly different (p = 0.421). The presence of IPN was independently associated with a shortened DFS (p = 0.027), as was a CRS of 3 or greater (p = 0.007). CONCLUSION: This study suggests that IPN does not significantly affect OS, but may predict earlier disease recurrence. IPN presence alone should not preclude radical resection but could be used to prompt more careful post-operative surveillance to detect lung metastases at a potentially operable stage.

Treatment Access and Survival Amongst British Asians with Pancreatic Cancer.

INTRODUCTION: Despite increasingly mixed communities in large cities, there remains a paucity of absolute and comparative data concerning the treatment, access and survival of British Asians with pancreatic cancer. METHODS: A prospective database of 1038 patients with a diagnosis of pancreatic cancer from 2003 to 2012 was analysed. Asian/Asian British was defined as patients identifying themselves as originating from India, Bangladesh or Pakistan. RESULTS: No significant difference was observed in gender split for both Asian/Asian British and White British (AAB and WB). The incidence of pancreas cancer was also equivalent between the two groups at 8.1 versus 8.8 per 100,000 of the population. Age at presentation was significantly younger in AABs when compared to WBs (67 vs. 70 years, p = 0.003). Whilst median maximal tumour diameter, node status and the incidence of metastases were not different between AABs and WBs, the AABs had a significantly greater median T-stage (3.0 versus 2.5, p = 0.0024). The percentage of patients referred for chemotherapy was significantly higher in the AAB group (70.5 vs. 47.7 %, p = 0.0015). Overall survival and survival for patients having palliative treatment were significantly greater in AABs (4.6 vs. 6.1 months and 3.7 vs. 5.1 months). CONCLUSION: This study demonstrates that AAB patients are present with pancreatic cancer at a younger age and that when receiving palliative chemotherapy their survival is significantly better. Further studies and larger data sets over a longer period are required. It is important to examine further the complexity of incidence and survival in ethnic minorities and investigate the underlying reasons when differences are demonstrated.

Medical therapy for polycystic liver disease.

Introduction Somatostatin analogues and rapamycin inhibitors are two classes of drugs available for the management of polycystic liver disease but their overall impact is not clearly established. This article systematically reviews the literature on the medical management of polycystic liver disease. The outcomes assessed include reduction in liver volume and the impact on quality of life. Methods The English language literature published between 1966 and August 2014 was reviewed from a MEDLINE(®), PubMed, Embase™ and Cochrane Library search. Search terms included 'polycystic', 'liver', 'sirolimus', 'everolimus', 'PCLD', 'somatostatin', 'octreotide', 'lanreotide' and 'rapamycin'. Both randomised trials and controlled studies were included. References of the articles retrieved were also searched to identify any further eligible publications. The studies included were appraised using the Jadad score. Results Seven studies were included in the final review. Five studies, of which three were randomised trials, investigated the role of somatostatin analogues and the results showed a mean reduction in liver volume ranging from 2.9% at six months to 4.95 ±6.77% at one year. Only one randomised study examined the influence of rapamycin inhibitors. This trial compared dual therapy with everolimus and octreotide versus octreotide monotherapy. Liver volume reduced by 3.5% and 3.8% in the control and intervention groups respectively but no statistical difference was found between the two groups (p=0.73). Two randomised trials investigating somatostatin analogues assessed quality of life using SF-36(®). Only one subdomain score improved in one of the trials while two subdomain scores improved in the other with somatostatin analogue therapy. Conclusions Somatostatin analogues significantly reduce liver volumes after six months of therapy but have only a modest improvement on quality of life. Rapamycin inhibitors do not confer any additional advantage.

Is Abdominal Fat Distribution Measured by Axial CT Imaging an Indicator of Complications and Mortality in Acute Pancreatitis?

BACKGROUND: Obesity is an important risk-stratifying co-morbidity for many pathological conditions. Controversy exists about its influence in outcomes after acute pancreatitis (AP). This study assessed abdominal fat distribution (subcutaneous, retroperitoneal and intra-abdominal) measured using computer tomography (CT) images and related it to outcomes in patients with AP. METHODS: The case notes of patients admitted with AP were identified from computerised records from 2008 to the 2013. Image analysis software was used to assess the individual abdominal fat distributions from CT images. RESULTS: A total of 79 patients were included. There was no relationship between fat distribution and either severity of, or mortality from, AP. Fat distribution was not found to be an independent risk factor on multivariate analysis. There was, however, a positive correlation between retroperitoneal and intra-abdominal fat with APACHE II scores, Ranson and Glasgow score and Multiple Organ Dysfunction score (MODS) on various days following admission (r = 0.421, p = 0.0008; r = 0.469, p < 0.0001; r = 0.398, p = 0.007; r = 0.336, p = 0.011, respectively). On multiple logistical regression analysis, the only variables associated with mortality were Balthazar Severity Index, MODS and EWS with a p value of <0.0001, 0.0019 and 0.0481, respectively. CONCLUSIONS: Obese patients have worse predicted outcomes as measured by the EWS, MODS and Ranson scores. Abdominal fat distribution, however, was not shown to be directly related to AP severity or mortality. The addition of fat parameters may be of use in prognostic CT severity index models, but from this data, it does not appear to be an independent risk factor of adverse outcome.

Ablation for recurrent hepatocellular carcinoma: a systematic review of clinical efficacy and prognostic factors.

BACKGROUND: Hepatocellular carcinoma (HCC) typically recurs following primary treatment. The primary objective of this systematic review was to evaluate the safety and efficacy of ablative therapies for recurrent HCC. The secondary objective was to identify any factors associated with prognosis following ablation for recurrent disease. METHODS: A systematic search of the literature published between January 2000 and December 2013 was undertaken using the PubMed, Medline and Scopus databases. Reference lists from selected studies were manually searched to ensure complete capture of any relevant data. RESULTS: A total of 19 studies were included in the review. The median age of patients undergoing ablation for recurrent HCC was 58 years (range 52-69 years) and 85 % of patients had cirrhosis (range 56-100 %). HCC recurred as a single nodule in 79 % of those treated with ablation (range 46-100 %). There were few significant complications associated with any form of ablation. Sufficient data were only available to allow analysis of survival outcomes following radiofrequency ablation (RFA). After RFA the median, 1, 3 and 5-year survivals were 84 % (73-99 %), 51 % (42-84 %) and 40 % (28-83 %), respectively. The only factor consistently associated with overall survival following ablation for recurrence was the alpha-fetoprotein (AFP) level. CONCLUSION: Comparable survival figures from previously published systematic reviews suggest that hepatic resection is the most effective treatment for recurrent HCC. However, ablation can be a safe and effective option for the majority of patients with recurrent disease who are unsuitable for surgery. Elevated levels of AFP suggest a poorer prognosis following ablation.

Serology and ultrasound for diagnosis of choledocholithiasis.

INTRODUCTION: Magnetic resonance cholangiopancreatography (MRCP) is not a routine investigation to exclude choledocholithiasis unless there is clinical or biochemical suspicion of common bile duct (CBD) stones. This study attempted to determine which radiological or serological parameters best predicted CBD stones. METHODS: All patients undergoing MRCP from 2005 to 2011 were selected. Patients with pancreatitis were excluded. Liver function tests (LFTs) at admission and prior to MRCP were recorded, as was abdominal ultrasonography and MRCP results. Parameters measured routinely on LFTs included alkaline phosphatase (ALP), alanine transaminase (ALT) and bilirubin. Receiver operating characteristic curve area analysis (area under the curve [AUC]) and chi-squared analysis were undertaken. RESULTS: Overall, 195 patients were identified, 71 of whom had CBD stones on MRCP. Raised ALP levels on admission demonstrated a correlation with CBD stones (AUC: 0.619, odds ratio [OR]: 3.16, p=0.06). At ultrasonography, a dilated CBD (OR: 3.76, p<0.001) and intrahepatic duct dilation (OR: 5.56, p<0.001) were highly significant predictors. However, only 37% of patients had a dilated CBD on ultrasonography. Ongoing elevation of LFT parameters, particularly ALP (AUC: 0.707, OR: 4.64, p<0.001) and ALT (AUC: 0.646, OR: 5.40, p<0.001), displayed a significant correlation with CBD stones. CONCLUSIONS: Ongoing (even if minor) elevations of liver function test parameters should prompt the need to exclude CBD stones even in the presence of a normal CBD diameter on ultrasonography.

Role of preoperative carbohydrate loading: a systematic review.

INTRODUCTION: Surgical stress in the presence of fasting worsens the catabolic state, causes insulin resistance and may delay recovery. Carbohydrate rich drinks given preoperatively may ameliorate these deleterious effects. A systematic review was undertaken to analyse the effect of preoperative carbohydrate loading on insulin resistance, gastric emptying, gastric acidity, patient wellbeing, immunity and nutrition following surgery. METHODS: All studies identified through PubMed until September 2011 were included. References were cross-checked to ensure capture of cited pertinent articles. RESULTS: Overall, 17 randomised controlled trials with a total of 1,445 patients who met the inclusion criteria were identified. Preoperative carbohydrate drinks significantly improved insulin resistance and indices of patient comfort following surgery, especially hunger, thirst, malaise, anxiety and nausea. No definite conclusions could be made regarding preservation of muscle mass. Following ingestion of carbohydrate drinks, no adverse events such as apparent or proven aspiration during or after surgery were reported. CONCLUSIONS: Administration of oral carbohydrate drinks before surgery is probably safe and may have a positive influence on a wide range of perioperative markers of clinical outcome. Further studies are required to determine its cost effectiveness.

The role of magnetic resonance cholangiopancreatography in the management of acute gallstone pancreatitis.

INTRODUCTION: The aim of this study was to identify whether magnetic resonance cholangiopancreatography (MRCP) can be used selectively in patients with acute gallstone pancreatitis to detect choledocholithiasis, based on liver function tests (LFTs) and ultrasonography appearance. METHODS: All patients admitted between January 2008 and January 2011 with gallstone pancreatitis (amylase >300u/l) who underwent MRCP were included in the study. LFTs and radiology reports were obtained from the respective computer systems. RESULTS: Overall, 173 patients with acute gallstone pancreatitis underwent MRCP and 30% (52/173) showed choledocholithiasis. The mean bilirubin level was significantly higher in those with choledocholithiasis (46 ±5µmol/l vs 36 ±3µmol/l, p=0.0388) although there was no significant difference in alkaline phosphatase (276 ±25iu/l vs 229 ±16iu/l, p=0.1154). However, sensitivity of abnormal bilirubin (>21µmol/l) for choledocholithiasis was only 62% and specificity was 41%. Sensitivity of abnormal alkaline phosphatase (>140iu/l) for choledocholithiasis was only 75% and specificity was 37%. There was a significant association between biliary dilatation on ultrasonography and choledocholithiasis on MRCP (p=0.0099) although the sensitivity of biliary dilatation for choledocholithiasis was only 44% and the specificity was 79%. Furthermore, there was no difference in the incidence of choledocholithiasis on MRCP for those patients with persistently deranged LFTs versus those whose LFTs returned to normal (relative risk: 1.07, 95% confidence interval: 0.61-1.89, p=1.00). Overall, 10% of patients with choledocholithiasis on MRCP had entirely normal LFTs on admission and no biliary dilatation or choledocholithiasis on ultrasonography. CONCLUSIONS: All patients with acute gallstone pancreatitis should undergo specific imaging, preferably MRCP, to exclude choledocholithiasis as LFTs and ultrasonography are inaccurate in predicting common bile duct stones.