Identification and characterisation of a rare MTTP variant underlying hereditary non-alcoholic fatty liver disease.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is a complex trait with an estimated prevalence of 25% globally. We aimed to identify the genetic variant underlying a four-generation family with progressive NAFLD leading to cirrhosis, decompensation, and development of hepatocellular carcinoma in the absence of common risk factors such as obesity and type 2 diabetes. Methods: Exome sequencing and genome comparisons were used to identify the likely causal variant. We extensively characterised the clinical phenotype and post-prandial metabolic responses of family members with the identified novel variant in comparison with healthy non-carriers and wild-type patients with NAFLD. Variant-expressing hepatocyte-like cells (HLCs) were derived from human-induced pluripotent stem cells generated from homozygous donor skin fibroblasts and restored to wild-type using CRISPR-Cas9. The phenotype was assessed using imaging, targeted RNA analysis, and molecular expression arrays. Results: We identified a rare causal variant c.1691T>C p.I564T (rs745447480) in MTTP, encoding microsomal triglyceride transfer protein (MTP), associated with progressive NAFLD, unrelated to metabolic syndrome and without characteristic features of abetalipoproteinaemia. HLCs derived from a homozygote donor had significantly lower MTP activity and lower lipoprotein ApoB secretion than wild-type cells, while having similar levels of MTP mRNA and protein. Cytoplasmic triglyceride accumulation in HLCs triggered endoplasmic reticulum stress, secretion of pro-inflammatory mediators, and production of reactive oxygen species. Conclusions: We have identified and characterised a rare causal variant in MTTP, and homozygosity for MTTP p.I564T is associated with progressive NAFLD without any other manifestations of abetalipoproteinaemia. Our findings provide insights into mechanisms driving progressive NAFLD. Impact and Implications: A rare genetic variant in the gene MTTP has been identified as responsible for the development of severe non-alcoholic fatty liver disease in a four-generation family with no typical disease risk factors. A cell line culture created harbouring this variant gene was characterised to understand how this genetic variation leads to a defect in liver cells, which results in accumulation of fat and processes that promote disease. This is now a useful model for studying the disease pathways and to discover new ways to treat common types of fatty liver disease.

ZEB1 and IL-6/11-STAT3 signalling cooperate to define invasive potential of pancreatic cancer cells via differential regulation of the expression of S100 proteins.

BACKGROUND: S100 proteins have been implicated in various aspects of cancer, including epithelial-mesenchymal transitions (EMT), invasion and metastasis, and also in inflammatory disorders. Here we examined the impact of individual members of this family on the invasion of pancreatic ductal adenocarcinoma (PDAC) cells, and their regulation by EMT and inflammation. METHODS: Invasion of PDAC cells was analysed in zebrafish embryo xenografts and in transwell invasion assays. Expression and regulation of S100 proteins was studied in vitro by immunoblotting, quantitative PCR and immunofluorescence, and in pancreatic lesions by immunohistochemistry. RESULTS: Whereas the expression of most S100 proteins is characteristic for epithelial PDAC cell lines, S100A4 and S100A6 are strongly expressed in mesenchymal cells and upregulated by ZEB1. S100A4/A6 and epithelial protein S100A14 respectively promote and represses cell invasion. IL-6/11-STAT3 pathway stimulates expression of most S100 proteins. ZEB1 synergises with IL-6/11-STAT3 to upregulate S100A4/A6, but nullifies the effect of inflammation on S100A14 expression. CONCLUSION: EMT/ZEB1 and IL-6/11-STAT3 signalling act independently and congregate to establish the expression pattern of S100 proteins, which drives invasion. Although ZEB1 regulates expression of S100 family members, these effects are masked by IL-6/11-STAT3 signalling, and S100 proteins cannot be considered as bona fide EMT markers in PDAC.

Clinical risk scores in the current era of neoadjuvant chemotherapy for colorectal liver metastases.

BACKGROUND: Clinical risk scores (CRS) within the context of neoadjuvant chemotherapy for colorectal liver metastases (CRLM) has not been validated. The predictive value of clinical risk scoring in patients administered neoadjuvant chemotherapy prior to liver surgery for CRLM is evaluated. METHODS: A prospective database over a 15-year period (April 1999 to March 2014) was analysed. We identified two groups: A, neoadjuvant chemotherapy prior to CRLM surgery; and B, no neoadjuvant chemotherapy. RESULTS: Overall median survival in groups A and B were 36 (2-137) months and 33 (2-137) months. In group A, nodal status, size, number of metastases and carcinoembryonic antigen levels were not found to be independent predictors of overall survival (OS). However, patients with a shorter disease-free interval of less than 12 months had an increased OS (P = 0.0001). Multivariate analysis of high- and low-risk scores compared against survival in group B (P < 0.05) confirms the applicability of the scoring system in traditional settings. CONCLUSION: Traditional CRS are not a prognostic predictive tool when applied to patients receiving neoadjuvant chemotherapy for CRLM. Disease-free interval may be one independent variable for use in future risk score systems specifically developed for the neoadjuvant chemotherapy era.

Profiling tumour heterogeneity through circulating tumour DNA in patients with pancreatic cancer.

The majority of pancreatic ductal adenocarcinomas (PDAC) are diagnosed late so that surgery is rarely curative. Earlier detection could significantly increase the likelihood of successful treatment and improve survival. The aim of the study was to provide proof of principle that point mutations in key cancer genes can be identified by sequencing circulating free DNA (cfDNA) and that this could be used to detect early PDACs and potentially, premalignant lesions, to help target early effective treatment. Targeted next generation sequencing (tNGS) analysis of mutation hotspots in 50 cancer genes was conducted in 26 patients with PDAC, 14 patients with chronic pancreatitis (CP) and 12 healthy controls with KRAS status validated by digital droplet PCR. A higher median level of total cfDNA was observed in patients with PDAC (585 ng/ml) compared to either patients with CP (300 ng/ml) or healthy controls (175 ng/ml). PDAC tissue showed wide mutational heterogeneity, whereas KRAS was the most commonly mutated gene in cfDNA of patients with PDAC and was significantly associated with a poor disease specific survival (p=0.018). This study demonstrates that tNGS of cfDNA is feasible to characterise the circulating genomic profile in PDAC and that driver mutations in KRAS have prognostic value but cannot currently be used to detect early emergence of disease. Importantly, monitoring total cfDNA levels may have utility in individuals "at risk" and warrants further investigation.

Early warning score independently predicts adverse outcome and mortality in patients with acute pancreatitis.

PURPOSE: The aim of this study was to compare the prognostic value of established scoring systems with early warning scores in a large cohort of patients with acute pancreatitis. METHODS: In patients presenting with acute pancreatitis, age, sex, American Society of Anaesthesiologists (ASA) grade, Modified Glasgow Score, Ranson criteria, APACHE II scores and early warning score (EWS) were recorded for the first 72 h following admission. These variables were compared between survivors and non-survivors, between patients with mild/moderate and severe pancreatitis (based on the 2012 Atlanta Classification) and between patients with a favourable or adverse outcome. RESULTS: A total of 629 patients were identified. EWS was the best predictor of adverse outcome amongst all of the assessed variables (area under curve (AUC) values 0.81, 0.84 and 0.83 for days 1, 2 and 3, respectively) and was the most accurate predictor of mortality on both days 2 and 3 (AUC values of 0.88 and 0.89, respectively). Multivariable analysis revealed that an EWS ≥2 was independently associated with severity of pancreatitis, adverse outcome and mortality. CONCLUSION: This study confirms the usefulness of EWS in predicting the outcome of acute pancreatitis. It should become the mainstay of risk stratification in patients with acute pancreatitis.

Repeat hepatectomy is independently associated with favorable long-term outcome in patients with colorectal liver metastases.

Up to three-quarters of patients undergoing liver resection for colorectal liver metastases (CRLM) develop intrahepatic recurrence. Repeat hepatic resection appears to provide the optimal chance of cure for these patients. The aim of this study was to analyze short- and long-term outcomes following index and repeat hepatectomy for CRLM. Clinicopathological data were obtained from a prospectively maintained database. Perioperative variables and outcomes were compared using the Chi-squared test. Variables associated with long-term survival following index and second hepatectomy were identified by Cox regression analyses. Over the study period, 488 patients underwent hepatic resection for CRLM, with 71 patients undergoing repeat hepatectomy. There was no significant difference in rates of morbidity (P = 0.135), major morbidity (P = 0.638), or mortality (P = 0.623) when index and second hepatectomy were compared. Performance of repeat hepatectomy was independently associated with increased overall and cancer-specific survival following index hepatectomy. Short disease-free interval between index and second hepatectomy, number of liver metastases >1, and resection of extrahepatic disease were independently associated with shortened survival following repeat resection. Repeat hepatectomy for recurrent CRLM offers short-term outcomes equivalent to those of patients undergoing index hepatectomy, while being independently associated with improved long-term patient survival.

The impact of an omega-3 fatty acid rich lipid emulsion on fatty acid profiles in critically ill septic patients.

BACKGROUND: Death from sepsis in the intensive therapy unit (ITU) is frequently preceded by the development of multiple organ failure as a result of uncontrolled inflammation. Treatment with omega-3 (n-3) fatty acids (FAs), principally eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has been demonstrated to attenuate the effects of uncontrolled inflammation and may be clinically beneficial in reducing mortality from organ dysfunction. Fish oil (FO) is a source of EPA and DHA. METHODS: A randomized trial investigating the effects of parenteral (intravenous) nutrition providing FO (0.092g EPA+DHA/kg body weight/day) was conducted. Sixty consecutive ITU patients diagnosed with sepsis were randomised to receive either once daily parenteral FO and standard medical care or standard medical care only. RESULTS: Forty one patients (21 received fish oil; 20 controls) consented to blood sampling and blood was taken on days 0, 1, 2, 3, 5, 7, 10 and 13; because of deaths, patient discharge and withdrawal of consent, the number of blood samples available for analysis diminished with time. FA composition of plasma phosphatidylcholine (PC), plasma non-esterified FAs (NEFAs) and peripheral blood mononuclear cells (PBMCs) was determined by gas chromatography. EPA and DHA were rapidly incorporated into all 3 lipid pools investigated. There was a reduction in the arachidonic acid (AA) to EPA+DHA ratio in plasma PC and NEFAs. Fewer patients died in the FO group (13.3% (n=4)) compared with the control group (26.7% (n=8)) but this difference was not significant. A reduction in the AA/(EPA+DHA) ratio in PBMCs and plasma PC was associated with significantly improved survival. Plasma PC, plasma NEFA and PBMC FA profiles are rapidly altered by FO infusion in critically ill septic patients. CONCLUSION: The provision of high dose n-3 FAs resulted in a rapid and significant increase in EPA and DHA and a reduction in AA/(EPA+DHA) ratio. This latter reduction is associated with improved survival.

Prognostic performance of inflammation-based prognostic indices in patients with resectable colorectal liver metastases.

A range of prognostic cellular indices of the systemic inflammatory response, namely the neutrophil-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), combination of platelet count and neutrophil-lymphocyte ratio (COP-NLR) and prognostic nutritional index (PNI), have been developed and found to have prognostic utility across varied malignancies. The current study is the first to examine the prognostic value of these six inflammatory scores in patients with resectable colorectal liver metastases (CRLM). Data from 302 consecutive patients undergoing surgery for resectable CRLM were evaluated. The prognostic influence of clinicopathological variables and the inflammatory scores NLR, dNLR, PLR, LMR, COP-NLR and PNI upon overall survival (OS) and cancer-specific survival (CSS) were determined by log-rank analysis and univariate and multivariate Cox regression analyses. High preoperative NLR was the only inflammatory variable independently associated with shortened OS (HR 1.769, 95 % CI 1.302-2.403, P < 0.001) or CSS (HR 1.927, 95 % CI 1.398-2.655, P < 0.001) following metastasectomy. When NLR was replaced by dNLR in analyses, high dNLR was independently associated with shortened OS (HR 1.932, 95 % CI 1.356-2.754, P < 0.001) and CSS (HR 1.807, 95 % CI 1.209-2.702, P = 0.004). The inflammatory scores PLR, LMR, COP-NLR and PNI demonstrated no independent association with either overall or cancer-specific survival in the study population. Our findings support high preoperative NLR and dNLR as independent prognostic factors for poor outcome in patients undergoing CRLM resection, with prognostic value superior to other cellular-based systemic inflammatory scores.

A randomized controlled trial investigating the effects of parenteral fish oil on survival outcomes in critically ill patients with sepsis: a pilot study.

INTRODUCTION: Death from sepsis in the intensive care unit (ITU) is frequently preceded by the development of multiple organ failure as a result of uncontrolled inflammation. Treatment with ω-3 has been demonstrated to attenuate the effects of uncontrolled inflammation and may be clinically beneficial. METHOD: A randomized control trial investigating the effects of parenteral ω-3 was carried out. Consecutive patients diagnosed with sepsis were entered into the study and randomized to receive either parenteral ω-3 or standard medical care only. The primary outcome measure was a reduction in organ dysfunction using the Sequential Organ Failure Assessment (SOFA) score as a surrogate marker. The secondary outcome measures were mortality, length of stay, mean C-reactive protein (CRP), and days free of organ dysfunction/failure. RESULTS: Sixty patients were included in the study. The baseline demographics were matched for the two cohorts. Patients treated with parenteral ω-3 were associated with a significant reduction in new organ dysfunction (Δ-SOFA 2.2 ± 2.2 vs. 1.0 ± 1.5, P = .005 and maximum-SOFA 10.1 ± 4.2 vs. 8.1 ± 3.2, P = .041) and maximum CRP (186.7 ± 78 vs. 141.5 ± 62.6, P = .019). There was no significant reduction in the length of stay between cohorts. Patients treated with ω-3 in the strata of less severe sepsis had a significant reduction in mortality (P = .042). CONCLUSION: The treatment of critically ill septic patients with parenteral ω-3 is safe. It is associated with a significant reduction in organ dysfunction. It may be associated with a reduction in mortality in patients with less severe sepsis.

Biliary stenting for benign and malignant obstructive jaundice: safe use of extended stent-change intervals.

PURPOSE: This study compared 2 methods of palliative stent placement, 6-monthly interval stent changes (RS), or a single-stent policy with no planned stent change (SS). RESULTS: A total of 460 patients were identified. There were no significant differences in the proportion of patients requiring unplanned stent changes in the RS or SS group (22.3% vs. 22.8%). Median survival was not significantly different between the RS and SS groups, for both benign disease (96 vs. 92 mo) and malignant disease (9 vs. 6 mo). Patients undergoing unplanned stent changes had the poorest survival and the highest stent change-related complication rate. Patients with a blocked stent episode were more likely to develop further problems with stent patency, within a median interval of 2.5 months. CONCLUSIONS: In carefully selected patients, a single stent may be adequate with no planned change of stent. There appears to be a clearly defined subgroup of patients who have recurrent problems with stent patency; these should have their interval exchange brought forward on a 3-monthly basis, or a self-expanding metal stent should be used.

Overexpression of the Nek2 kinase in colorectal cancer correlates with beta-catenin relocalization and shortened cancer-specific survival.

The serine/threonine kinase Nek2 (NIMA-related kinase 2) regulates centrosome separation and mitotic progression, with overexpression causing induction of aneuploidy in vitro. Overexpression may also enable tumour progression through effects upon Akt signalling, cell adhesion markers and the Wnt pathway. The objective of this study was to examine Nek2 protein expression in colorectal cancer (CRC). Nek2 protein expression was examined in a panel of CRC cell lines using Western blotting and immunofluorescence microscopy. Nek2 and beta-catenin expression were examined by immunohistochemistry in a series of resected CRC, as well as their matched lymph node and liver metastases, and correlated with clinicopathological characteristics. Nek2 protein expression in all CRC lines examined was higher than in the immortalised colonocyte line HCEC. Nek2 overexpression was present in 86.4% of resected CRC and was significantly associated with advancing AJCC tumour stage and shortened cancer-specific survival. Elevated Nek2 expression was maintained within all matched metastases from overexpressing primary tumours. Nek2 overexpression was significantly associated with lower tumour membranous beta-catenin expression and higher cytoplasmic and nuclear beta-catenin accumulation. These data support a role for Nek2 in CRC progression and confirm potential for Nek2 inhibition as a therapeutic avenue in CRC.

Spontaneous discharge of 'spilled gallstone' with complete resolution of retroperitoneal abscess in a patient treated for putative tuberculosis.

A 76-year-old man presented 5 months following an open cholecystectomy with a complicated retroperitoneal abscess secondary to a retained gallstone, which was misdiagnosed as a tuberculous abscess. Subsequently, the stone was eventually spontaneously discharged with complete resolution of the associated collection.

Notch3 and HEY-1 as prognostic biomarkers in pancreatic adenocarcinoma.

In order to achieve a better outcome for pancreatic cancer patients, reliable biomarkers are required which allow for improved diagnosis. These may emanate from a more detailed molecular understanding of the aggressive nature of this disease. Having previously reported that Notch3 activation appeared to be associated with more aggressive disease, we have now examined components of this pathway (Notch1, Notch3, Notch4, HES-1, HEY-1) in more detail in resectable (n = 42) and non-resectable (n = 50) tumours compared to uninvolved pancreas. All three Notch family members were significantly elevated in tumour tissue, compared to uninvolved pancreas, with expression maintained within matched lymph node metastases. Furthermore, significantly higher nuclear expression of Notch1, -3 and -4, HES-1, and HEY-1 (all p ≤ 0.001) was noted in locally advanced and metastatic tumours compared to resectable cancers. In survival analyses, nuclear Notch3 and HEY-1 expression were significantly associated with reduced overall and disease-free survival following tumour resection with curative intent, with nuclear HEY-1 maintaining independent prognostic significance for both outcomes on multivariate analysis. These data further support a central role for Notch signalling in pancreatic cancer and suggest that nuclear expression of Notch3 and its target gene, HEY-1, merit validation in biomarker panels for diagnosis, prognosis and treatment efficacy. A peptide fragment of Notch3 was detected in plasma from patients with inoperable pancreatic cancer, but due to wide inter-individual variation, mean levels were not significantly different compared to age-matched controls.

Influence of hepatic parenchymal histology on outcome following right hepatic trisectionectomy.

BACKGROUND: Histological abnormalities in the non-tumour-bearing liver (NTBL) may influence outcome following hepatectomy. Effects will be most pertinent following right trisectionectomy but have yet to be specifically examined in this context. This study aimed to investigate the influence of perioperative factors, including NTBL histology, on outcome following right trisectionectomy. METHODS: Pathological review of the NTBL of 103 consecutive patients undergoing right trisectionectomy between January 2003 and December 2009 was performed using established criteria for steatosis, non-alcoholic steatohepatitis (NASH), sinusoidal injury (SI), fibrosis and cholestasis. Perioperative and pathological factors were correlated with post-operative outcome (morbidity, major morbidity, hepatic insufficiency and mortality). RESULTS: Morbidity, hepatic insufficiency and major morbidity occurred in 37.9 %, 14.6 % and 22.3 % of cases, respectively. Ninety-day mortality rate was 5.8 %. NASH (P = 0.007) and perioperative blood transfusion (P = 0.001) were independently associated with hepatic insufficiency following trisectionectomy. NASH (P = 0.028), perioperative transfusion (P = 0.016), diabetes mellitus (P = 0.047) and coronary artery disease (P = 0.036) were independently associated with major morbidity. Steatosis, SI, fibrosis and cholestasis in the NTBL demonstrated no association with any adverse outcome. CONCLUSION: NASH, but not steatosis or SI, is associated with adverse outcome following right trisectionectomy and caution must be exerted when considering major hepatectomy in patients with NASH.

Risk and Cost-effectiveness of Surveillance Followed by Cholecystectomy for Gallbladder Polyps.

OBJECTIVE To ascertain the best management options for patients presenting with gallbladder polyps. DESIGN Retrospective case-note analysis. SETTING Tertiary referral teaching hospital practice. PATIENTS Patients with ultrasonography-detected gallbladder polyps. INTERVENTIONS Ultrasonography surveillance or surgery. MAIN OUTCOME MEASURES Demographic data and size and number of polyps were recorded as well as size increase and histological findings. Detection rates for potentially neoplastic and frankly neoplastic polyps were recorded and compared with complication rates from cholecystectomy. Cost-effectiveness of ultrasonography surveillance was examined. RESULTS Nine hundred eighty-six patients were identified and 467 patients underwent further follow-up. Only 6.6% of polyps exhibited an increase in size over the surveillance period. Polyps that subsequently progressed in size on surveillance had a significantly greater diameter at first presentation than those polyps that remained static (7 mm vs 5 mm, respectively) (P < .05). Only 3.7% of resected polyps had malignant or potentially malignant histology. Size greater than 10 mm and increase in size during surveillance predicted neoplastic potential. CONCLUSIONS A surveillance with or without selective surgery policy could potentially detect and prevent 5.4 gallbladder cancers per 1000 individuals per year with a cost saving of more than £130 000 (US $201 676) per year. Cancer prevention benefits would exceed the risk ratios from cholecystectomy complications. Polyps greater than 10 mm should be resected; those between 5 and 10 mm should be under ultrasonography surveillance.

Results from a consecutive series of laparoscopic incisional and ventral hernia repairs.

INTRODUCTION: Incisional hernia is a problematic complication of abdominal surgery and both late and early outcomes can be unsatisfactory. Laparoscopic repair has been gaining popularity for both incisional and ventral herniae. However, the perceived benefits have not been convincingly demonstrated by randomized-controlled studies or meta-analyses. METHODS: Case notes from 54 patients undergoing consecutive laparoscopic repairs of the abdominal wall hernia at a single center were reviewed. Demographic data, postoperative complications, length of stay, and recurrence rates were all recorded. RESULTS: The majority of the patients had incisional hernia, with de novo ventral hernia comprising 7.4% of the total. Forty percent of patients had undergone at least 1 previous repair of their incisional hernia. The median recorded diameter of the hernia defect was 5 cm. No recurrences were recorded over a median follow-up of 26 months. Complications were all minor and included seroma formation, hematoma, and wound infection (n=5 patients). Median operative duration was 45 minutes and median length of stay postoperatively was 1 day. CONCLUSIONS: The results compare well with those in the published literature and would support the continued use of laparoscopic incisional/ventral hernia repair. Any benefits from this approach, however, are likely to be operator dependent. As a result, all units undertaking such repairs should regularly review their results and compare them with the reported standard.

Improving the diagnostic yield from staging laparoscopy for periampullary malignancies: the value of preoperative inflammatory markers and radiological tumor size.

OBJECTIVES: The role of laparoscopy in staging periampullary malignancies is to detect small-volume metastatic disease not visible on preoperative imaging. Owing to improvements in preoperative imaging, some centers no longer undertake routine laparoscopic staging, whereas others still find it a useful pre-exploration tool. METHODS: This study investigated the diagnostic yield of staging laparoscopies in 137 consecutive potentially resectable patients with periampullary malignancies. Serology on presentation, tumor size on computed tomography and proinflammatory markers such as C-reactive protein, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and Glasgow Prognostic Score were also examined to see if they were able to identify patients more likely to benefit from staging laparoscopy. RESULTS: Laparoscopy identified occult disease in 16.1% of the patients. Only tumor diameter on cross-sectional imaging was related to an increase in diagnostic yield on staging laparoscopy. Area-under-curve values for tumor size and occult disease at laparoscopy were 0.8, with P = 0.0001. CONCLUSION: Staging laparoscopy is a useful adjunct to computed tomography in staging periampullary cancers. Tumor size (especially >45 mm) is the only preoperative marker predictive of unexpected occult disease and may be used to select high-risk patients for laparoscopic staging.

Evaluation of nurse-led discharge following laparoscopic surgery.

INTRODUCTION: The United Kingdom's Department of Health has identified reducing delays in patient discharge as a key aim for Health Service development. Laparoscopic cholecystectomy and laparoscopic inguinal hernia repair may be safely performed on a short stay basis, but day case rates remain low, with delays in discharge identified as a major contributing factor. Nurse-led discharge has been widely advocated to speed patient discharge across varied specialities, but objective evidence to support its use is lacking. This study aimed to assess the effectiveness of nurse-led discharge following laparoscopic surgery. METHODS: A retrospective comparison of doctor-led and nurse-led discharge following laparoscopic surgery was performed by analysis of two consecutive 4-month periods, prior to and following the introduction of nurse-led discharge by a laparoscopic nurse specialist. Outcomes assessed included time to discharge, reasons for delayed discharge, hospital readmissions and primary care episodes following discharge. RESULTS: A total of 128 patients were included in the study, with each discharge group containing 64 patients. Patients in the nurse-led discharge group were significantly more likely to be discharged on the day of surgery than patients in the doctor-led discharge group (17.2% vs. 4.7%; P = 0.023), with a highly significant difference in same day discharge rates noted among patients operated on during morning theatre lists (44.0% vs. 10.7%; P = 0.006). There was no significant difference between the discharge groups in readmission rates or in the number of patients seeking primary care attention following discharge. CONCLUSIONS: Nurse-led discharge may speed discharge following laparoscopic surgery with no apparent detriment to patient care.

Bilirubin levels predict malignancy in patients with obstructive jaundice.

BACKGROUND: Differentiating between benign and malignant causes of obstructive jaundice can be challenging, even with the advanced imaging and endoscopic techniques currently available. In patients with obstructive jaundice, the predictive accuracy of bilirubin levels at presentation was examined in order to determine whether such data could be used to differentiate between malignant and benign disease. METHODS: A total of 1,026 patients with obstructive jaundice were identified. Patients were divided into benign and malignant groups. The benign patients were subgrouped into those with choledocholithiasis and those with inflammatory strictures of the biliary tree. Bilirubin levels at presentation and other demographic data were obtained from case records. RESULTS: Area under the curve (AUC) values for bilirubin as a predictor of malignancy were highly significant for all benign presentations and for those with benign biliary strictures (AUC: 0.8 for both groups; P < 0.001). A bilirubin level > 100 µmol/l was determined to provide the optimum sensitivity and specificity for malignancy in all patients and in those without choledocholithiasis (71.9% and 86.9%, 71.9% and 88.0%, respectively). The application of a bilirubin level > 250 µmol/l achieved specificities of 97.1% and 98.0% in each subgroup of patients, respectively. CONCLUSIONS: In patients with obstructive jaundice, bilirubin levels in isolation represent an important tool for discriminating between benign and malignant underlying causes.