What is the Operative Cost of Managing Acute Appendicitis in the NHS: The Impact of Stump Technique and Perioperative Imaging.

BACKGROUND: Acute appendicitis is a common surgical emergency that is typically managed with laparoscopic appendicectomy in UK centres. A number of variables influence the cost of managing this condition. Our aim was to identify the major influencing factors in our centre by performing a cumulative cost analysis. METHODS: We retrospectively analysed the costs associated with 99 cases of acute appendicitis managed with laparoscopic appendicectomy at Ninewells Hospital, Dundee, from January 2014 to February 2016. Costs were categorised according to blood tests, imaging, medications, operative costs and length of stay. RESULTS: Our cohort included 66 males, 33 females and 28 paediatric cases. The total cost was £220030.52 with a mean of £2222.53 per patient. The factor with the greatest influence on overall cost was operative time (53.2%) followed by length of stay (39.2%). There was no cost difference between adults and children (p = 0.24) or males and females (p = 0.38). Mean cost in adults ≥50 years was greater than those <50 years (£2899.32 vs £2152.97, p = 0.008) and greater in those who underwent imaging as opposed to no imaging (£2789.53 vs £2010.65, p = 0.0001). For appendiceal stump technique, polymer clips were cheaper (£1844.70) than ligatures (£2380.11, p = 0.006). CONCLUSIONS: Operative time (53.2%) and length of stay (39.2%) had the greatest impact on the cost in our cohort. Older patients have a greater overall cost, and this is associated with increased utilisation of imaging. Further studies assessing the safety and feasibility of methods to reduce operative time and to investigate the safety of reducing length of stay are required.

Histology of portal vascular changes associated with idiopathic non-cirrhotic portal hypertension: nomenclature and definition.

Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare vascular liver disease that has attracted new interest in recent years. It is characterised by clinical signs of portal hypertension in the absence of cirrhosis or severe fibrosis and any known cause of portal hypertension. As much uncertainty exists about INCPH pathophysiology, and no definite diagnostic tests are available, liver biopsy is an essential tool for achieving a definite diagnosis. Unfortunately, the histological diagnosis of INCPH is not always straightforward, as the characteristic lesions are unevenly distributed, vary greatly in their severity, are often very subtle, and are not all necessarily present in a single case. Furthermore, specifically for the characteristic portal vessel changes observed in INCPH, the terminology and definition are ambiguous, which adds complexity to the already complex clinicopathological scenario. An international study group of liver pathologists and hepatologists pursued a consensus on nomenclature for the portal vascular lesions of INCPH. Such standardisation may assist pathologists in the recognition of such lesions, and will possibly facilitate further advancement in this field.

MicroRNA-mediated regulation of immune responses to intestinal helminth infections.

Intestinal helminth infections are highly prevalent in the developing world, often resulting in chronic infection and inflicting high host morbidity. With the emergence of drug-resistant parasites, a limited number of chemotherapeutic drugs available and stalling vaccine efforts, an increased understanding of antihelminth immunity is essential to provide new avenues to therapeutic intervention. MicroRNAs are a class of small, nonprotein coding RNAs which negatively regulate mRNA translation, thus providing finite control over gene expression in a plethora of biological settings. The miRNA-mediated coordinated control of gene expression has been shown to be essential in infection and immunity, in promoting and fine-tuning the appropriate immune response. This review gathers together and discusses observations of miRNA-mediated effects on the immune system and the subsequent impact on our understanding of antihelminth immunity.

Role of aetiology in the progression, regression, and parenchymal remodelling of liver disease: implications for liver biopsy interpretation.

Clinicopathological concepts on acute and chronic liver disease have evolved rapidly during the last few years, with advances in general and specific treatment options and improved patient outcomes. The old paradigm of 'irreversibility' of cirrhosis had been challenged in major ways, and the validity of the usage of the term 'cirrhosis' has come into question. This paper addresses aetiology-based clinicopathological concepts and features that may deserve attention because they may determine disease outcome and, specifically, patterns of regression and remodelling. A variety of therapeutic interventions may influence remaining disease features after elimination of damaging agents (virus, alcohol, etc.), and determine the final clinical outcome including the risk of hepatocellular carcinoma (HCC). New concepts create new responsibilities and opportunities for the pathologist to contribute to the understanding of liver pathology and communicate this with clinical colleagues and researchers.

Documentation of Pregnancy Status, Gynaecological History, Date of Last Menstrual Period and Contraception Use in Emergency Surgical Admissions: Time for a Change in Practice?

OBJECTIVE: To determine whether pregnancy status, gynaecological history, date of last menstrual period and contraceptive use are documented in emergency female admissions of reproductive age admitted to general surgery. DESIGN: This is a retrospective study. SETTING: This study was conducted in the United Kingdom. POPULATION: Females of reproductive age (12-50 years) admitted as an emergency to general surgery with abdominal pain were considered in this study. METHODS: Retrospective analysis of medical notes of emergency female admissions with abdominal pain between January and September 2012. We recorded whether a pregnancy test result was documented (cycle 1). Results were analysed and a prompt added to the medical clerk-in document. We re-audited (cycle 2) between January and June 2013 looking for improvement. MAIN OUTCOME MEASURES: Documented pregnancy status within 24 h of admission and prior to any surgical intervention. RESULTS: 100 case notes were reviewed in stage 1. 30 patients (30 %) had a documented pregnancy status. 32 (32 %), 25 (25 %) and 29 (29 %) had a documented gynaecology history, contraceptive use and date of last menstrual period (LMP), respectively. 24 patients underwent emergency surgery, 6 (25 %) had a documented pregnancy status prior to surgery. Of 50 patients reviewed in stage 2, 37 (75.0 %) had a documented pregnancy status (p < 0.001), with 41 (82 %) having both gynaecological history (p < 0.0001) and contraceptive use (p < 0.0001) documented. 40 patients (80 % had a documented LMP (p < 0.0001). 7 patients required surgery, of whom 6 (85.7 %) had a documented pregnancy test prior to surgery (p = 0.001). All pregnancy tests were negative. CONCLUSIONS: A simple prompt in the surgical admission document has significantly improved the documentation of pregnancy status and gynaecological history in our female patients, particularly in those who require surgical intervention. A number of patient safety concerns were addressed locally, but require a coordinated, interdisciplinary discussion and a national guideline. A minimum standard of care, in females of reproductive age, should include mandatory objective documentation of pregnancy status, whether or not they require surgical intervention.

Xanthogranulomatous inflammation of terminal ileum: report of a case with small bowel involvement.

Xanthogranulomatous inflammation is a rare pathological condition most frequently detected in the kidney and gallbladder. Reported herein is a case of xanthogranulomatous inflammation in a 51-year-old male presenting as a mass-forming lesion in the terminal ileum with mucosal ulceration. Diagnostic laparoscopy followed by ileocecectomy was performed due to intra-operative suspicion of carcinoma of appendix. This is a report of the condition involving the terminal ileum with mucosal ulceration and full-thickness involvement of bowel wall which are uncommon features of xanthogranulomatous inflammation in previously reported lower gastro-intestinal tract lesions.

Classification of and cytoreductive surgery for low-grade appendiceal mucinous neoplasms.

BACKGROUND: Low-grade appendiceal mucinous neoplasm (LAMN) is a precursor lesion for pseudomyxoma peritonei (PMP), which, if treated suboptimally, may later disseminate throughout the abdominal cavity. The role of cytoreductive surgery for these relatively early lesions is unclear. METHODS: Clinicopathological details and treatment outcomes of patients with a LAMN and disease limited to the appendix or immediate periappendiceal tissues, referred to a national treatment centre between 2002 and 2009, were evaluated prospectively. RESULTS: Of 379 patients with a diagnosis of PMP, 43 (median age 49 years) had LAMNs localized to the appendix and periappendiceal tissue. Thirty-two patients initially presented with symptoms of acute appendicitis or right iliac fossa pain. Two distinct lesions were identified: type I (disease confined to the appendiceal lumen) and type II (mucin and/or neoplastic epithelium in the appendiceal submucosa, wall and/or periappendiceal tissue, with or without perforation). Type I lesions were managed by a watch-and-wait surveillance policy with serial measurement of tumour markers and computed tomography in 14 of 16 patients. Seventeen of 27 patients with type II lesions underwent risk-reducing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with low morbidity. After a median follow-up of 40 months, there was no disease progression in either treatment pathway. CONCLUSION: This study identified two LAMN subtypes. Type II lesions have pathological features of increased risk for dissemination and should be considered for risk-reducing cytoreductive surgery.

A modified Delphi process to establish research priorities in hernia surgery.

BACKGROUND: Abdominal wall hernia repair is one of the most commonly performed surgical procedures worldwide, yet despite this, there remains a lack of high-quality evidence to support best management. The aim of the study was to use a modified Delphi process to determine future research priorities in this field. METHODS: Stakeholders were invited by email, using British Hernia Society membership details or Twitter, to submit individual research questions via an online survey. In addition, questions obtained from a patient focus group (PFG) were collated to form Phase I. Two rounds of prioritization by stakeholders (phases II and III) were then completed to determine a final list of research questions. All questions were analyzed on an anonymized basis. RESULTS: A total of 266 questions, 19 from the PFG, were submitted by 113 stakeholders in Phase I. Of these, 64 questions were taken forward for prioritization in Phase II, which was completed by 107 stakeholders. Following Phase II analysis, 97 stakeholders prioritized 36 questions in Phase III. This resulted in a final list of 14 research questions, 3 of which were from the PFG. Stakeholders included patients and healthcare professionals (consultant surgeons, trainee surgeons and other multidisciplinary members) from over 27 countries during the 3 phases. CONCLUSION: The study has identified 14 key research priorities pertaining to abdominal wall hernia surgery. Uniquely, these priorities have been determined from participation by both healthcare professionals and patients. These priorities should now be addressed by well-designed, high-quality international collaborative research.

Primary hepatolithiasis, recurrent pyogenic cholangitis, and oriental cholangiohepatitis: a tale of 3 countries.

Primary hepatolithiasis (HL), recurrent pyogenic cholangitis, and oriental cholangiohepatitis are terms commonly used in Japan, Hong Kong, and Korea respectively, and describing the different aspects of the same disease, with "HL" indicating the pathologic changes, "recurrent pyogenic cholangitis" emphasizing the clinical presentation and suppurative inflammation, and "oriental cholangiohepatitis" highlighting its ethnic preference and mysterious nature. HL is predominantly a disease of the far east and shows great regional differences in the incidence and the type of intrahepatic stones. Pathologically, it is characterized by pigmented calcium bilirubinate stones within dilated intrahepatic bile ducts featuring chronic inflammation, mural fibrosis, and proliferation of peribiliary glands, without extrahepatic biliary obstruction. Episodes of suppurative inflammation cumulate in sclerosing cholangitis in peripheral ducts and parenchymal fibrosis from scarring and collapse. Mass-forming inflammatory pseudotumor and neoplasms-like intraductal papillary neoplasms and cholangiocarcinoma are increasingly recognized complications. Bacterial infection and dietary factors are believed to be important in the formation of pigment stones within intrahepatic bile ducts, whereas parasitic infestation is likely coincidental. With improvement of environmental conditions and westernization of diet, the incidence of pigment stones has decreased. At the same time, cholesterol stones with milder clinical manifestations and pathologic changes are increasingly recognized, and for which stone dissolution therapy can be considered. Understanding the underlying pathology avoids confusion with other diseases more prevalent in the western world, and allows correct selection of the appropriate treatment.

Blind outcome assessment: the development and use of procedures to maintain and describe blinding in a pragmatic physiotherapy rehabilitation trial.

OBJECTIVES: (1) To develop trial protocols which promote the achievement of blind outcome assessment. (2) To report outcome assessor beliefs regarding group allocation at follow-up assessments. (3) To document and describe instances of unblinding occurring during the trial to assist and inform rehabilitation researchers and clinicians. DESIGN: Prospective longitudinal observational study. SETTING: An NHS Hospital Trust specializing in orthopaedic surgery. SUBJECTS: One hundred and seven patients participating in a prospective pragmatic randomized controlled trial investigating physiotherapy rehabilitation following total knee arthroplasty, plus three outcome assessors. INTERVENTIONS: A protocol was developed using available research and designed to minimize instances of unblinding during a physiotherapy rehabilitation trial. Administrative, office, patient and research staff procedures were included. MAIN MEASURES: Trial questionnaires measured blind outcome assessment responses at 3 and 12 months post surgery. The outcome assessor kept a field diary recording the events surrounding instances of unblinding. Data underwent descriptive and content analysis. RESULTS: Blind outcome assessment was believed successful for n = 74 (81.32%) assessments at 3-month follow-up, and n = 83 (91.21%) at 12 months. Forty instances (n = 28 participants) of unblinding were described in the field diary. While the main cause of unblinding was participants telling the outcome assessor, in 12.5% of events the assessor drew the wrong conclusion regarding group allocation. Not all unblinding events were remembered at subsequent assessments, even in this relatively small trial. CONCLUSIONS: Blind outcome assessment was considered achievable in this trial. Specific trial protocols enabled blinding beliefs to be reported and instances of unblinding to be described.

"What if I'm not trans enough? What if I'm not man enough?": Transgender young adults' experiences of gender-affirming healthcare readiness assessments in Aotearoa New Zealand.

Background: A growing body of transgender health research reports that transgender people often feel pressure to conform to a dominant narrative during gender-affirming readiness assessments. In New Zealand, however, no study to date has specifically examined transgender people's experiences of readiness assessments for gender-affirming healthcare. Aims: This study aimed to explore the experiences of transgender young adults (aged 16-30) during gender-affirming readiness assessments in New Zealand. We also sought participants' views on improving transgender healthcare provision. Methods: Thirteen transgender young adults took part in individual interviews or focus groups. Participants were asked to describe how they felt about the questions asked during readiness assessments and how the readiness assessment process could be improved. We used thematic analysis to identify patterns of meaning across the dataset. Results: We identified two themes. Firstly, proving gender explores participants' views of readiness assessments as designed to establish whether they were "trans enough" or "truly" transgender, and why readiness assessments are conducted in this manner. Secondly, the trans narrative describes the pressure participants felt to adhere to a dominant transgender narrative in order to gain access to the healthcare they needed. Discussion: Our findings call attention to the importance of a trans-affirmative approach and the need to clarify the purpose of gender-affirming healthcare readiness assessments in New Zealand.

Long-term outcomes for patients with peritoneal acellular mucinosis secondary to low grade appendiceal mucinous neoplasms.

INTRODUCTION: Low grade appendiceal mucinous neoplasms (LAMN) are known to metastasise to the peritoneum resulting in pseudomyxoma peritonei (PMP). Literature suggests that the long-term outcome is dependent on the cellular grade of the peritoneal histology, less is known about the risk to patients with acellular mucinosis (AM) alone. This study aims to review long-term outcomes in patients with PMP treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC), whose peritoneal histology was AM secondary to LAMN. METHODS: Pathological and treatment outcomes were collected from a prospectively maintained database between 2005 and 2019. Data was collected on patients with LAMN and AM diagnosed following CRS/HIPEC. A single institution performed the surgery and pathology reporting, samples reported by three different pathologists. RESULTS: Of the 2079 patients with any appendiceal neoplasm referred between 2005 and 2019, 809 underwent CRS/HIPEC, 67 (8%) of those had PMP with purely AM secondary to a LAMN. In the AM group the median age was 59, 37 (55%) were female, follow up was for a median 39 (2-145) months. Inpatient mortality occurred in 1 patient (1.5%), disease specific mortality in 2 (3%), recurrence in 2 (3%) and disease progression in 1 (1.5%). CONCLUSION: This study has identified AM secondary to LAMN as a low risk group for recurrence following CRS/HIPEC compared with epithelial pathology. Given such a low rate of recurrence we would recommend low intensity surveillance post CRS/HIPEC. Agreed standardised pathological assessment is required to exclude cellular material in specimens and diagnose AM.

Indications and outcomes for repeat cytoreductive surgery and heated intra-peritoneal chemotherapy in peritoneal surface malignancy.

INTRODUCTION: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is offered in specialist centres as a treatment for peritoneal surface tumours. Despite its demonstrated efficacy, intra-abdominal recurrence occurs in 31-57% of patients. The aim of this study is to review the early and long-term outcomes in patients who undergo repeat CRS/HIPEC. MATERIALS AND METHODS: A retrospective review of a prospectively maintained database of patients who had undergone repeat CRS/HIPEC for appendiceal neoplasms and colorectal peritoneal metastases (CRPM) from 2003 to 2019 was performed at a single specialist centre. Data pertaining to both short term outcomes and survival were evaluated. RESULTS: Of 1259 patients who had undergone CRS/HIPEC, 84(6.7%) underwent repeat surgery: 45(53.6%) had pseudomyxoma peritonei (PMP) secondary to low grade appendiceal mucinous neoplasms (LAMN), 21(25.0%) had appendix carcinoma and 18(21.4%) had CRPM. Demographics, intra-operative findings and short-term outcomes were comparable across tumour types and between procedures. Median (95% CI) interval between procedures was 22.7(18.9-26.6) months and was comparable between tumour types. Median (95%CI) overall survival was not reached for the cohort overall or for those with PMP, but was 61.0(32.6-89.4) months for those with appendix cancer and 76.9(47.4-106.4) months for CRPM (p=<0.001). Survival was favourable in the PMP group (HR [95%CI] 0.044 [0.008-0.262]; p = 0.000) and unfavourable in the CC2-3 at index CRS procedure group (HR [95%CI] 25.612 [2.703-242.703]; p = 0.005). CONCLUSION: Our findings demonstrate that repeat cytoredutive surgery with HIPEC can result in favourable survival, especially for patients with PMP when complete cytoreduction is achieved at index operation. We recommend that detailed patient assessment is performed through an expert multidisciplinary team meeting (MDT).

ERp57 is up-regulated in free fatty acids-induced steatotic L-02 cells and human nonalcoholic fatty livers.

Pathogenesis of nonalcoholic fatty liver disease (NAFLD) is not clear. In this study we aimed to identify proteins involved in NAFLD development in free fatty acids (FFA)-induced hepatosteatotic cells and in human liver biopsies. Steatosis was induced by incubating a normal human hepatocyte-derived cell line L-02 with FFA. Differentially expressed proteins in the steatotic cells were analyzed by two-dimensional gel electrophoresis-based proteomics. Involvement of one of the up-regulated proteins in steatosis was characterized using the RNA interference approach with the steatotic cells. Protein expression levels in liver biopsies of patients with NAFLD were assessed by immunohistochemistry. Proteomic analysis of L-02 steatotic cells revealed the up-regulation of ERp57, a condition not previously implicated in NAFLD. Knockdown of ERp57 expression with siRNA significantly reduced fat accumulation in the steatotic cells. ERp57 expression was detected in 16 out of 17 patient biopsies and correlated with inflammation grades or fibrosis stages, while in 5 normal biopsies ERp57 expression was not detectable in hepatocytes. In conclusion, ERp57 was up-regulated in FFA-induced steatotic hepatic cells and in NAFLD patient livers and demonstrated steatotic properties in cultured cells. Further investigations are warranted to verify the involvement of ERp57 in NAFLD development.

Closure of the appendiceal stump in laparoscopic appendectomy: A systematic review of the literature.

BACKGROUND: Closure of the appendiceal stump is a key step performed during laparoscopic appendicectomy. Inadequate management of the appendiceal stump has the potential to cause significant morbidity. Several methods of stump closure have been described, however high-level evidence is limited. We performed a systematic review evaluating clinical outcomes and quality of the evidence for the methods of appendiceal stump closure. METHODS: A systematic literature search was performed using Medline, Embase, Cochrane Database and Google Scholar to identify studies comparing appendiceal stump closure methods in laparoscopic appendectomy for acute appendicitis from inception to October 2019. Data regarding operative duration, peri-operative complications, length of stay and costs were collated from all included studies. RESULTS: From 160 identified studies, 19 met the inclusion criteria. Endoloops and endoclips provide equivalent clinical outcomes at lower cost, while operative duration was shortest with endoclip closure. Endostapler devices have the lowest rate of peri-operative complications (3.56%), however their cost limits their regular use in many healthcare environments. Post-operative complication rate and length of stay were similar for all stump closure methods. Conclusion: Although there are no significant differences in method of stump closure in laparoscopic appendectomy, closure with endoclips provides the shortest operative duration. There is a need for robust and standardized reporting of cost data when comparing stump closure methods, together with higher level evidence in the form of multi-centre randomized controlled trials before firm conclusions can be drawn regarding the optimal method of stump closure.

Treatments and outcomes of peritoneal surface tumors through a centralized national service (United kingdom).

PURPOSE: Treatment of peritoneal surface malignancies with combined cytoreductive surgery and heated intraperitoneal chemotherapy may improve oncologic outcome. To better define treatment pathways, five-year results in patients referred to one of two centralized national treatment centers in the United Kingdom were analyzed. METHODS: A prospective database of patients referred to the Manchester Peritoneal Tumor Service, established in 2002, was analyzed. Outcomes were evaluated using Kaplan-Meier life tables and Cox models. RESULTS: Two hundred seventy-eight patients (median age, 56.9 (range, 16-86) years) were considered by a dedicated multidisciplinary team and tracked on seven clinical pathways. Among the 118 surgically treated, the most common diagnosis was pseudomyxoma peritonei (101 patients, 86%). Major complications occurred in 11 patients (9%); there was no 30-day mortality. Where complete cytoreduction was achieved, three-year and five-year tumor-related survival rates were 94% and 86%, respectively. In the Cox model, incompleteness of cytoreduction (P = 0.001) and high-grade tumor (P < 0.0001) were independent prognosticators of poor outcome. CONCLUSION: The establishment of a national treatment center has allowed refinement of techniques to achieve internationally recognized results. Having achieved low levels of morbidity and mortality in the treatment of mainly pseudomyxoma peritonei of appendiceal origin, the technique of cytoreductive surgery and heated intraperitoneal chemotherapy may be considered for peritoneal carcinomatosis of colorectal origin.

A phase II study evaluating the use of concurrent mitomycin C and capecitabine in patients with advanced unresectable pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is a rare neoplastic process characterised by progressive intra-abdominal dissemination of mucinous tumour, and generally considered resistant to systemic chemotherapy. A phase II study in patients with advanced unresectable PMP was undertaken to evaluate the combination of systemic concurrent mitomycin C (7 mg m(-2) i.v. on day 1) and capecitabine (1250 mg m(-2) b.d. on days 1-14) in a 3-weekly cycle (MCap). Response was determined by semiquantitative assessment of disease volume on serial computed tomographic (CT) scans and serum tumour marker (CEA, CA125, CA19-9) changes at 12 weeks. Between 2003 and 2006, 40 patients were recruited through a national centre for the treatment of peritoneal surface tumours. At baseline, 23 patients had progressive disease and 17 had stable disease. Of 39 assessable patients, 15 (38%, 95% confidence intervals (CIs): 25, 54%) benefited from chemotherapy in the form of either reductions in mucinous deposition or stabilisation of progressive pretreatment disease determined on CT scan. Notably, two patients, originally considered unresectable, following MCap and re-staging underwent potentially curative cytoreductive surgery. Grade 3/4 toxicity rates were low (6%, 95% CIs: 4, 9%). Twenty out of 29 assessed patients (69%, 95% CIs: 51, 83%) felt that their Global Health Status improved during chemotherapy. This is the first trial to demonstrate an apparent benefit of systemic chemotherapy in patients with advanced unresectable PMP.

Acute-on-chronic liver failure 2018: a need for (urgent) liver biopsy?

INTRODUCTION: 'Acute-on-Chronic-Liver Failure (ACLF)' entered hepatology practice by the end of the 20th century. Although we lack precise and universally agreed definitions, acute decompensation of chronic liver disease with jaundice and deranged clotting, multi-organ failure and high, short-term mortality are hallmarks of the syndrome. Timely recognition and and treatment, including urgent liver transplantation, may save the life of certain patients. The diagnosis and management are mostly based on clinical features, but some have suggested to incorporate histopathology (liver biopsy). This may add to the differentiation between acute and chronic disease, primary and concomitant etiologies, and identify prognostic determinants. Areas covered: A review of the literature on ACLF and the outcome of the discussions at a topical international meeting on specific histopathological aspects of diagnosis and prognosis of the syndrome. Expert commentary: There is a lack of standardized descriptions of histopathological features and there is limited prospective experience with the role of pathology of ACLF. It is important for the clinical hepatologist to understand the potential and limitations of (transjugular) liver biopsy in ACLF and for the pathologist to help address the clinical question and recognise the histopathological features that help to characterize ACLF, both in terms of diagnosis and prognosis.

Hepatic origin of cholesteryl oleate in coronary artery atherosclerosis in African green monkeys. Enrichment by dietary monounsaturated fat.

Relationships among plasma lipoprotein cholesterol, cholesterol secretion by the isolated, perfused liver, and coronary artery atherosclerosis were examined in African green monkeys fed diets containing cholesterol and 35% of calories as fat enriched in polyunsaturated, monounsaturated, or saturated fatty acids. The livers of animals fed monounsaturated fat had significantly higher cholesteryl ester concentrations (8.5 mg/g wet wt) than the livers of the other diet groups (3.65 and 3.37 mg/g wet wt for saturated and polyunsaturated fat groups, respectively) and this concentration was highly correlated with plasma cholesterol and apoB concentrations in each diet group. Cholesteryl oleate was 58 and 74. 5% of the liver cholesteryl ester in the saturated and monounsaturated fat groups. In each diet group, perfusate cholesteryl ester accumulation rate was highly correlated to liver and plasma cholesterol concentrations, and to plasma LDL cholesteryl ester content. Cholesteryl oleate was 48 and 67% of the cholesteryl esters that accumulated in perfusate in the saturated and monounsaturated fat animals, and this percentage was very highly correlated (r = -0.9) with plasma apoB concentration. Finally, in these two diet groups, liver perfusate cholesteryl ester accumulation rate was well correlated (r >/= 0.8) to coronary artery cholesteryl ester concentration, a measure of the extent of coronary artery atherosclerosis that occurred over the five years of diet induction in these animals. These data define an important role for the liver in the cholesteryl oleate enrichment of the plasma lipoproteins in the saturated and monounsaturated fat groups, and demonstrate strong relationships among hepatic cholesteryl ester concentration, cholesteryl ester secretion, and LDL particle cholesteryl ester content. The high correlation between liver cholesteryl ester secretion and coronary artery atherosclerosis provides the first direct demonstration of the high degree of importance of hepatic cholesteryl ester secretion in the development of this disease process. The remarkable degree of enrichment of cholesteryl oleate in plasma cholesteryl esters of the monounsaturated fat group may account for the relatively high amount of coronary artery atherosclerosis in this group.