Pneumonia caused by Streptococcus pneumoniae is a consequence of failure by the host to clear or kill pneumococci inhaled into the lung. The alveolar macrophage is the resident phagocyte of the alveoli of normal human lungs and is responsible for the removal of pathogens that enter gas-exchanging areas. Pathogens can be recognized by a variety of receptors on the surface of the macrophage, including Fc receptors (which recognize the Fc component of cognate immunoglobulin bound to bacteria in immune individuals), complement receptors CR1, CR3, and CR4 (which recognize C3b stabilized on the bacterial surface), and other receptors, including the macrophage scavenger receptor, platelet-activating factor receptor, CD14 (5, 18), and possibly members of the Toll family (29).Following binding to the surface, macrophages will phagocytize both opsonized and unopsonized pathogens, which are internalized and killed in a sequence of discrete stages. Studies with Mycobacterium spp. (6), Leishmania spp. (26), Listeria monocytogenes (24), and Neisseria meningitidis (21) have shown that microorganisms enter phagosomes, which mature into terminal phagolysosomes coincident with acquisition of numerous proteins, including the late endosome/lysosome-associated membrane proteins LAMP-1 and LAMP-2 (3), from the endocytic network.Human alveolar macrophages (HAM) have been demonstrated by radioisotopic methods (16) to phagocytize S. pneumoniae. Capsulate S. pneumoniae organisms have been found to bind poorly to human macrophages (compared to noncapsulate organisms), and therefore their subsequent internalization has been difficult to study. Although opsonization of pathogens markedly increases binding of particles to the surface of macrophages, other organisms, such as Staphylococcus aureus, have been demonstrated to bind to and be phagocytized by HAM in the absence of opsonization (14). We determined the kinetics of internalization and trafficking of a capsulate type 1 S. pneumoniae strain to HAM compartments containing LAMP-1 and measured these kinetics under conditions that might be operating in nonimmune humans. We questioned whether attachment of S. pneumoniae to the surface of HAM in the absence of cognate immunoglobulin or complement results in intracellular trafficking with benign consequences for the pathogen. MATERIALS AND METHODSHarvesting of alveolar macrophages. Healthy volunteers gave informed consent to bronchoscopy and bronchoalveolar lavage (BAL). None had a recent history of viral infection or antibiotic use. Lavage with 200 ml of warm sterile saline was carried out after the bronchoscope was lodged in a middle-lobe subsegmental bronchus under midazolam sedation, and macrophages were derived from BAL fluid using standard methods. This procedure was approved by the South Sheffield Research Ethics Committee (96/270). Briefly, BAL samples were filtered using a coarse porcelain sieve and transferred into 50-ml centrifuge tubes. A pellet was obtained using a short spin (102 ϫ g for 5 min) and was resuspended in serum-free R...

Laparoscopic distal pancreatic resection and enucleation of insulinoma appear to be safe procedures with reduced hospital stay, though morbidity remains significant. The evidence for laparoscopic pancreaticoduodenectomy is in its infancy, but the authors feel it is unlikely that many centers will achieve sufficient case load to make the introduction of minimally invasive resection feasible.

Purpose The objective of this study was to identify variables that predict a difficult laparoscopic cholecystectomy performed in an emergency setting. The secondary aim was to devise a pathway for patients admitted acutely that required a cholecystectomy. Methods Patients admitted to the Emergency General Surgery Department at Nottingham, the United Kingdom that had an emergency cholecystectomy performed during the one-year period from May 2016 to June 2017 were identified. Collected data included patient demographics, clinical presentation, biochemical analysis, radiological findings, subsequent interventions, surgical data, and clinical outcome. A difficult cholecystectomy was defined as operative time >60 minutes, conversion to an open procedure, or sub-total cholecystectomy performed. Results A total of 149 patients were included. Cholecystitis was the most common diagnosis ( n = 86, 57.7%), followed by acute pancreatitis ( n = 36, 24.1%). Fifty-five (36.9%) patients had an elevated C-reactive protein (CRP) >100 mg/dL. One hundred and twenty-one (81.2%) patients who had an emergency cholecystectomy were defined as “difficult”. The overall morbidity rate was 15.4% ( n = 23), and there was no post-operative in-hospital mortality. Univariate analysis showed that age >60 years ( p = 0.012), underlying diagnosis ( p = 0.010), presence of heart rate >90 ( p = 0.027), and an elevated pre-surgery CRP >100 ( p < 0.001) was associated with a difficult emergency cholecystectomy. Multi-variate analysis demonstrated that an elevated pre-surgery CRP >100 was an independent predictor of a difficult emergency cholecystectomy ( p = 0.041). Conclusions An elevated pre-operative CRP is an independent predictor of a technically more difficult cholecystectomy in the emergency setting.

Ann R Coll Surg Engl 2010; 92: [225][226][227][228][229][230] 225 Despite significant advances in cancer treatment over the past decade, colorectal cancer (CRC) remains a major source of cancer-related mortality, being the second commonest malignancy in the UK and accounting for 10% of all cancer-related deaths.1 The majority of these deaths result from the development of metastatic disease. Approximately one-third of patients with CRC present with synchronous liver or lung metastases, with a further 8-25% developing metachronous disease following primary tumour resection.2,3 Changes in surgical and radiological techniques, in addition to new chemotherapeutic regimens, now enable patients with advanced disease, whose only option in the past would have been palliation, to be considered for potentially curative treatment. 4The so-called 'postcode' provision of healthcare services and treatments in the UK has been investigated and highlighted across a range of medical specialities.5-10 However, the majority of these studies have been conducted on a national level, subdividing populations into either strategic health authorities, primary care trusts or medical specialty. 5,6,10 Few investigators have examined the potential inequality of provision at a truly local level within one region. Inequalities in access to healthcare services have previously caused conflict between patients and healthcare HEPATOBILIARY SURGERY Ann R Coll Surg Engl 2010; 92: 225-230

Percutaneous insertion of short metal stents provides a safe and effective alternative to endoscopic stent placement for treating jaundice preoperatively in patients with potentially resectable tumors around the pancreatic head.

Introduction CONTACT is a national multidisciplinary study assessing the impact of the COVID-19 pandemic upon diagnostic and treatment pathways among patients with pancreatic ductal adenocarcinoma (PDAC). Methods The treatment of consecutive patients with newly diagnosed PDAC from a pre-COVID-19 pandemic cohort (07/01/2019-03/03/2019) were compared to a cohort diagnosed during the first wave of the UK pandemic (‘COVID’ cohort, 16/03/2020-10/05/2020), with 12-month follow-up. Results Among 984 patients (pre-COVID: n = 483, COVID: n = 501), the COVID cohort was less likely to receive staging investigations other than CT scanning (29.5% vs. 37.2%, p = 0.010). Among patients treated with curative intent, there was a reduction in the proportion of patients recommended surgery (54.5% vs. 76.6%, p = 0.001) and increase in the proportion recommended upfront chemotherapy (45.5% vs. 23.4%, p = 0.002). Among patients on a non-curative pathway, fewer patients were recommended (47.4% vs. 57.3%, p = 0.004) or received palliative anti-cancer therapy (20.5% vs. 26.5%, p = 0.045). Ultimately, fewer patients in the COVID cohort underwent surgical resection (6.4% vs. 9.3%, p = 0.036), whilst more patients received no anti-cancer treatment (69.3% vs. 59.2% p = 0.009). Despite these differences, there was no difference in median overall survival between the COVID and pre-COVID cohorts, (3.5 (IQR 2.8–4.1) vs. 4.4 (IQR 3.6–5.2) months, p = 0.093). Conclusion Pathways for patients with PDAC were significantly disrupted during the first wave of the COVID-19 pandemic, with fewer patients receiving standard treatments. However, no significant impact on survival was discerned.

Background and aims: Hypertriglyceridaemia is both a primary cause of acute pancreatitis and an epiphenomenon. This study aimed to define the associations between hypertriglyceridaemia and clinical outcomes in patients admitted with acute pancreatitis. Methods: This single-centre prospective observational study included patients with a confirmed clinical, biochemical or radiological diagnosis of acute pancreatitis from August 2017 to September 2018. Baseline demographics, aetiology of pancreatitis, and fasting triglyceride concentrations were recorded and assessed against the surrogate markers of severity: admission to critical care, length of stay (LOS), readmission to hospital, and mortality. Results: In total, 304 patients with a mean ± SD age of 56.1 ± 19.7 years met the inclusion criteria. There were 217 (71.4%) patients with normotriglyceridaemia (<150 mg/dL or <1.7 mmol/L), 47 (15.5%) with mild hypertriglyceridaemia (150e199 mg/dL or 1.7e2.25 mmol/L) and 40 (13.2%) with moderate-tosevere hypertriglyceridaemia (!200 mg/dL or >2.25 mmol/L). The underlying aetiologies of acute pancreatitis were gallstones (55%), alcohol (18%), idiopathic (15%), hypertriglyceridaemia (9%), iatrogenic (2%) and bile duct abnormalities (1%). Patients with hypertriglyceridaemia were younger than those with normotriglyceridaemia (p < 0.05). On multivariate regression, moderate-to-severe hypertriglyceridaemia (OR 5.66, 95% CI: 1.87 to 17.19, p ¼ 0.002) and an elevated C-reactive protein concentration !120 mg/L (OR 1.00, 95% CI: 1.00e1.01, p ¼ 0.040) were associated with admission to critical care. Moderate-tosevere hypertriglyceridaemia was also associated with an increased LOS (p ¼ 0.002) but not readmission (p ¼ 0.752) or mortality (p ¼ 0.069). Conclusion: Moderate-to-severe hypertriglyceridaemia in all aetiological causes of acute pancreatitis was predictive of admission to critical care and prolonged LOS but not readmission or mortality.

Background Recently, statins have been associated with improved survival in certain cancers. The aim of this study was to evaluate the impact of statins on the outcome of patients undergoing surgery for pancreatic cancer. In addition, the effect of statins on the histopathological characteristics of the disease was assessed. Methods A retrospective review of the prospectively maintained hepato‐pancreatico‐biliary database was performed and patients with pancreatic cancer who underwent surgery between January 2014 and December 2017 were included. Statistical analysis was performed to assess the impact of statins on histopathological characteristics and survival outcome. Results A total of 151 patients were included, of whom 71 underwent pancreatic resections and 80 underwent trial dissection and bypass procedures. In the operated group, 20 patients were on statin therapy preoperatively. With respect to disease‐free survival, tumour size (P = 0.023) and lymphatic invasion (P = 0.015) were significant variables on univariate analysis. Gender (P = 0.022), adjuvant chemotherapy (P < 0.001), lymphatic invasion (P = 0.021) and tumour size (P = 0.041) were significant variables on univariate analysis with respect to overall survival. Multivariate analysis identified adjuvant chemotherapy as the only independent predictor of overall survival (P < 0.001). No correlations between the use of statins and the histopathological characteristics were identified. Conclusion Adjuvant chemotherapy is an independent predictor of overall survival in patients undergoing surgery for pancreatic cancer. Statin therapy does not influence survival outcomes and histopathological characteristics following surgery for pancreatic cancer.