Immunohistochemical inflammation in histologically normal gallbladders containing gallstones.

BACKGROUND: The aim of this study was to establish features of inflammation in histologically normal gallbladders with gallstones and compare the expression of inflammatory markers in acutely and chronically inflamed gallbladders. METHODS: Immunohistochemistry was performed on formalin-fixed paraffin-embedded gallbladders for tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-2R, and substance p in three groups: Group I (n = 60) chronic cholecystitis, Group II (n = 57) acute cholecystitis and Group III (n = 45) histologically normal gallbladders with gallstones. Expression was quantified using the H-scoring system. RESULTS: Median, interquartile range expression of mucosal IL-2R in Groups I (2.65, 0.87-7.97) and II (12.30, 6.15-25.55) was significantly increased compared with group III (0.40, 0.10-1.35, p < 0.05). Submucosal IL-2R expression in Groups I (2.0, 1.12-4.95) and II (10.0, 5.95-14.30) was also significantly increased compared with Group III (0.50, 0.15-1.05, p < 0.05). There was no difference in the lymphoid cell IL-6 expression between Groups I (5.95, 1.60-18.15), II (6.10, 1.1-36.15) and III (8.30, 2.60-26.35, p > 0.05). Epithelial IL-6 expression of Group III (8.3, 2.6-26.3) was significantly increased compared with group I (0.5, 0-10.2, p < 0.05) as was epithelial TNF-α expression in Group III (85.0, 70.50-92.0) compared with Groups I (72.50, 45.25.0-85.50, p < 0.05) and II (61.0, 30.0-92.0, p < 0.05). Lymphoid cell Substance P expression in Groups I (1.90, 1.32-2.65) and II (5.62, 2.50-20.8) was significantly increased compared with Group III (1.0,1.0-1.30, p < 0.05). Epithelial cell expression of Substance P in Group III (121.7, 94.6-167.8) was significantly increased compared with Groups I (75.7, 50.6-105.3, p < 0.05) and II (78.9, 43.5-118.5, p < 0.05). CONCLUSION: Histologically normal gallbladders with gallstones exhibited features of inflammation on immunohistochemistry.

Immunohistochemical Inflammation in Histologically Normal Appendices in Patients with Right Iliac Fossa Pain.

BACKGROUND: Histologically normal appendices resected for right iliac fossa pain in children demonstrate immunohistochemical markers of inflammation. We aimed to establish if subclinical inflammation was present in histologically normal appendices resected from adults with right iliac fossa pain. METHODS: Immunohistochemistry was performed on formalin-fixed paraffin-embedded appendices for tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-2R and serotonin in four groups: Group I (n = 120): uncomplicated appendicitis, Group II (n = 118): complicated appendicitis (perforation or gangrene), Group III (n = 104): histologically normal appendices resected for right iliac fossa pain and Group IV (n = 106) appendices resected at elective colectomy. Expression was quantified using the H-scoring system. RESULTS: Median, interquartile range expression of TNF-α was increased in Groups I (5.9, 3.1-9.8), II (6.8, 3.6-12.1) and III (9.8, 6.2-15.2) when compared with Group IV (3.0, 1.4-4.7, p < 0.01). Epithelial expression of IL-6 in Groups II (44.0, 8.0-97.0) and III (71.0, 18.5-130.0) was increased when compared with Group IV (9.5, 1.0-60.2, p < 0.01). Expression of mucosal IL-2R in Groups I (47.4, 34.8-69.0), II (37.8, 25.4-60.4) and III (18.4, 10.1-34.7) was increased when compared with Group IV (2.8, 1.2-5.7, p < 0.01). Serotonin content in Groups I (3.0, 0-30.0) and II (0, 0-8.5) was decreased when compared with Groups III (49.7, 16.7-107.5) and IV (43.5, 9.5-115.8, p < 0.01). CONCLUSION: Histologically normal appendices resected from symptomatic patients exhibited increased proinflammatory cytokine expression on immunohistochemistry suggesting the presence of an inflammatory process not detected on conventional microscopy.

Perioperative Probiotics or Synbiotics in Adults Undergoing Elective Abdominal Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To define the impact of perioperative treatment with probiotics or synbiotics on postoperative outcome in patients undergoing abdominal surgery. BACKGROUND: Postoperative surgical infection accounts for a third of all cases of sepsis, and is a leading cause of morbidity and mortality. Probiotics, prebiotics, and synbiotics (preparations that combine probiotics and prebiotics) are nutritional adjuncts that are emerging as novel therapeutic modalities for preventing surgical infections. However, current evidence on their effects is conflicting. METHODS: A comprehensive search of the PubMed, Embase, and WHO Global Index Medicus electronic databases was performed to identify randomized controlled trials evaluating probiotics or synbiotics in adult patients undergoing elective colorectal, upper gastrointestinal, transplant, or hepatopancreaticobiliary surgery. Bibliographies of studies were also searched. The primary outcome measure was incidence of postoperative infectious complications. Secondary outcomes included incidence of noninfectious complications, mortality, length of hospital stay, and any treatment-related adverse events. Quantitative pooling of the data was undertaken using a random effects model. RESULTS: A total of 34 randomized controlled trials reporting on 2723 participants were included. In the intervention arm, 1354 patients received prebiotic or symbiotic preparations, whereas 1369 patients in the control arm received placebo or standard care. Perioperative administration of either probiotics or synbiotics significantly reduced the risk of infectious complications following abdominal surgery [relative risk (RR) 0.56; 95% confidence interval (CI) 0.46-0.69; P < 0.00001, n = 2723, I = 42%]. Synbiotics showed greater effect on postoperative infections compared with probiotics alone (synbiotics RR: 0.46; 95% CI: 0.33-0.66; P < 0.0001, n = 1399, I = 53% probiotics RR: 0.65; 95% CI: 0.53-0.80; P < 0.0001, n = 1324, I = 18%). Synbiotics but not probiotics also led to a reduction in total length of stay (synbiotics weighted mean difference: -3.89; 95% CI: -6.60 to -1.18 days; P = 0.005, n = 535, I = 91% probiotics RR: -0.65; 95% CI: -2.03-0.72; P = 0.35, n = 294, I = 65%). There were no significant differences in mortality (RR: 0.98; 95% CI: 0.54-1.80; P = 0.96, n = 1729, I = 0%) or noninfectious complications between the intervention and control groups. The preparations were well tolerated with no significant adverse events reported. CONCLUSIONS: Probiotics and synbiotics are safe and effective nutritional adjuncts in reducing postoperative infective complications in elective abdominal surgery. The treatment effects are greatest with synbiotics.

Iron therapy for preoperative anaemia.

BACKGROUND: Preoperative anaemia is common and occurs in 5% to 76% of patients preoperatively. It is associated with an increased risk of perioperative allogeneic blood transfusion, longer hospital stay, and increased morbidity and mortality. Iron deficiency is one of the most common causes of anaemia. Oral and intravenous iron therapy can be used to treat anaemia. Parenteral iron preparations have been shown to be more effective in conditions such as inflammatory bowel disease, chronic heart failure and postpartum haemorrhage due to rapid correction of iron stores. A limited number of studies has investigated iron therapy for the treatment of preoperative anaemia. The aim of this Cochrane Review is to summarise the evidence for iron supplementation, both enteral and parenteral, for the management of preoperative anaemia. OBJECTIVES: To evaluate the effects of preoperative iron therapy (enteral or parenteral) in reducing the need for allogeneic blood transfusions in anaemic patients undergoing surgery. SEARCH METHODS: We ran the search on 30 July 2018. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, the Cochrane Library), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic and Embase (Ovid), CINAHL Plus (EBSCO), PubMed, and clinical trials registries, and we screened reference lists. We ran a top-up search on 28 November 2019; one study is now awaiting classification. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) that compared preoperative iron monotherapy to placebo, no treatment, standard care or another form of iron therapy for anaemic adults undergoing surgery. We defined anaemia as haemoglobin values less than 13 g/dL for males and 12 g/dL for non-pregnant females. DATA COLLECTION AND ANALYSIS: Two review authors collected data and a third review author checked all collected data. Data were collected on the proportion of patients who receive a blood transfusion, the amount of blood transfused per patient (units), quality of life, ferritin levels and haemoglobin levels, measured as continuous variables at the following predetermined time points: pretreatment (baseline), preoperatively but postintervention, and postoperatively. We performed statistical analysis using the Cochrane software, Review Manager 5. We summarised outcome data in tables and forest plots. We used the GRADE approach to describe the quality of the body of evidence. MAIN RESULTS: Six RCTs, with a total of 372 participants, evaluated preoperative iron therapy to correct anaemia before planned surgery. Four studies compared iron therapy (either oral (one study) or intravenous (three studies)) with no treatment, placebo or usual care, and two studies compared intravenous iron therapy with oral iron therapy. Iron therapy was delivered over a range of periods that varied from 48 hours to three weeks prior to surgery. The 372 participants in our analysis fall far short of the 819 required - as calculated by our information size calculation - to detect a 30% reduction in blood transfusions. Five trials, involving 310 people, reported the proportion of participants who received allogeneic blood transfusions. Meta-analysis of iron therapy versus placebo or standard care showed no difference in the proportion of participants who received a blood transfusion (risk ratio (RR) 1.21, 95% confidence interval (CI) 0.87 to 1.70; 4 studies, 200 participants; moderate-quality evidence). Only one study that compared oral versus intravenous iron therapy measured this outcome, and reported no difference in risk of transfusion between groups. There was no difference between the iron therapy and placebo/standard care groups for haemoglobin level preoperatively at the end of the intervention (mean difference (MD) 0.63 g/dL, 95% CI -0.07 to 1.34; 2 studies, 83 participants; low-quality evidence). However, intravenous iron therapy produced an increase in preoperative postintervention haemoglobin levels compared with oral iron (MD 1.23 g/dL, 95% CI 0.80 to 1.65; 2 studies, 172 participants; low-quality evidence). Ferritin levels were increased by intravenous iron, both when compared to standard care ((MD 149.00, 95% CI 25.84 to 272.16; 1 study, 63 participants; low-quality evidence) or to oral iron (MD 395.03 ng/mL, 95% CI 227.72 to 562.35; 2 studies, 151 participants; low-quality evidence). Not all studies measured quality of life, short-term mortality or postoperative morbidity. Some measured the outcomes, but did not report the data, and the studies which did report the data were underpowered. Therefore, uncertainty remains regarding these outcomes. The inclusion of new research in the future is very likely to change these results. AUTHORS' CONCLUSIONS: The use of iron therapy for preoperative anaemia does not show a clinically significant reduction in the proportion of trial participants who received an allogeneic blood transfusion compared to no iron therapy. Results for intravenous iron are consistent with a greater increase in haemoglobin and ferritin when compared to oral iron, but do not provide reliable evidence. These conclusions are drawn from six studies, three of which included very small numbers of participants. Further, well-designed, adequately powered, RCTs are required to determine the true effectiveness of iron therapy for preoperative anaemia. Two studies are currently in progress, and will include 1500 randomised participants.

Antibiotics Versus Appendicectomy for the Treatment of Uncomplicated Acute Appendicitis: An Updated Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: Uncomplicated acute appendicitis has been managed traditionally by early appendicectomy. However, recently, there has been increasing interest in the potential for primary treatment with antibiotics, with studies finding this to be associated with fewer complications than appendicectomy. The aim of this study was to compare outcomes of antibiotic therapy with appendicectomy for uncomplicated acute appendicitis. METHOD: This meta-analysis of randomised controlled trials included adult patients presenting with uncomplicated acute appendicitis treated with antibiotics or appendicectomy. The primary outcome measure was complications. Secondary outcomes included treatment efficacy, hospital length of stay (LOS), readmission rate and incidence of complicated appendicitis. RESULTS: Five randomised controlled trials with a total of 1430 participants (727 undergoing antibiotic therapy and 703 undergoing appendicectomy) were included. There was a 39 % risk reduction in overall complication rates in those treated with antibiotics compared with those undergoing appendicectomy (RR 0.61, 95 % CI 0.44-0.83, p = 0.002). There was no significant difference in hospital LOS (mean difference 0.25 days, 95 % CI -0.05 to 0.56, p = 0.10). In the antibiotic cohort, 123 of 587 patients initially treated successfully with antibiotics were readmitted with symptoms suspicious of recurrent appendicitis. The incidence of complicated appendicitis was not increased in patients who underwent appendicectomy after "failed" antibiotic treatment (10.8 %) versus those who underwent primary appendicectomy (17.9 %). CONCLUSION: Increasing evidence supports the primary treatment of acute uncomplicated appendicitis with antibiotics, in terms of complications, hospital LOS and risk of complicated appendicitis. Antibiotics should be prescribed once a diagnosis of acute appendicitis is made or considered.

Hydration amongst nurses and doctors on-call (the HANDS on prospective cohort study).

BACKGROUND & AIMS: Dehydration of as little 2% of total body weight may impair physical and cognitive performance. The aim of this study was to investigate the prevalence of dehydration at the start and end of shifts in nurses and doctors on-call. The secondary aims were to assess the relation between hydration status and cognitive function. METHODS: This prospective cohort study was conducted on nurses and doctors working on medical and surgical admissions wards at a university teaching hospital. Participants arrived on the ward approximately 20 min before their shift and were asked to provide a urine sample. Height and weight were then measured. A 10 mL blood sample was analysed for full blood count, serum urea and electrolytes, and blood glucose. Cognitive function was assessed using a series of computer-based tests including the Stroop Colour Naming Interference Test and Sternberg Memory Paradigm. Participants then worked normally but were asked to keep a fluid diary for the duration of their shift and fluid balance was estimated. Tests were repeated at the end of the shift. Dehydration was defined as urine osmolality >800 mOsmol/kg and oliguria was defined as urine output <0.5 ml/kg/hour. RESULTS: We recruited 92 nurses and doctors, of whom 88 completed the study, amounting to 130 shifts. 52% participated for one shift, and 48% for two shifts. Thirty-six percent of participants were dehydrated at the start of the shift and 45% were dehydrated at the end of their shift. Mean (SD) urinary osmolality was significantly greater at the end of the shift when compared with the start [720 (282) vs. 622 (297) mOsm/kg, P = 0.031). Moreover, 41% were oliguric at the end of the shift. Single number and five-letter Sternberg short-term memory tests were significantly impaired in dehydrated participants (P < 0.05). CONCLUSIONS: This study highlights that a significant proportion of nurses and doctors were dehydrated at the start and end of medical and surgical shifts. Dehydration was associated with some impairment of cognitive function.

Iron therapy for pre-operative anaemia.

BACKGROUND: Pre-operative anaemia is common and occurs in up to 76% of patients. It is associated with increased peri-operative allogeneic blood transfusions, longer hospital lengths of stay and increased morbidity and mortality. Iron deficiency is one of the most common causes of this anaemia. Oral iron therapy has traditionally been used to treat anaemia but newer, safer parenteral iron preparations have been shown to be more effective in other conditions such as inflammatory bowel disease, chronic heart failure and post-partum haemorrhage. A limited number of studies look at iron therapy for the treatment of pre-operative anaemia. The aim of this Cochrane review is to summarise the evidence for use of iron supplementation, both enteral and parenteral, for the management of pre-operative anaemia. OBJECTIVES: The objective of this review is to evaluate the effects of pre-operative iron therapy (enteral or parenteral) in reducing the need for allogeneic blood transfusions in anaemic patients undergoing surgery. SEARCH METHODS: We ran the search on 25 March 2015. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), EMBASE Classic and EMBASE (Ovid), CINAHL Plus (EBSCO), PubMed, clinical trials registries, conference abstracts, and we screened reference lists. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) which compared pre-operative iron monotherapy to placebo, no treatment, standard of care or another form of iron therapy for anaemic adults undergoing surgery. Anaemia was defined by haemoglobin values less than 13 g/dL for males and 12 g/dL for non-pregnant females. DATA COLLECTION AND ANALYSIS: Data were collected by two authors on the proportion of patients who receive a blood transfusion, amount of blood transfused per patient (units) and haemoglobin measured as continuous variables at pre-determined time-points: pre-treatment, pre-operatively but post-treatment, and post-operatively. Statistical analysis was performed using the Cochrane statistical software, Review Manager 2014. Outcome data were summarised in tables and a forest plot. MAIN RESULTS: Three prospective randomised controlled studies evaluated pre-operative iron therapy to correct anaemia (two in colorectal and one in gynaecological surgery) and included 114 patients in total. One compared oral iron versus standard care (Lidder 2007); one intravenous iron versus control (Edwards 2009); and one study compared oral versus intravenous iron (Kim 2009). Both colorectal trials reported the primary outcome (proportion of patients who received allogeneic blood transfusions) and meta-analysis showed a reduction in blood transfusions with the administration of iron therapy, but the reduction was not statistically significant (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.27 to 1.18). All studies reported haemoglobin change but data for the anaemic patients were only available for two studies (Edwards 2009 and Kim 2009). Edwards 2009 showed no difference in haemoglobin at the end of treatment pre-operatively. The intravenous versus oral iron study showed an increase in haemoglobin with intravenous iron at the end of treatment pre-operatively (MD 1.90 g/dL, 95% CI 1.16 to 2.64; participants = 56), but the results are at high risk of bias because participants with less than 80% compliance with therapy were excluded from the analysis and compliance was lower in the oral iron group due to the side-effects of treatment (Kim 2009).None of the studies reported quality of life, short- or long-term mortality or post-operative morbidity. AUTHORS' CONCLUSIONS: The use of iron therapy for pre-operative anaemia does not show a statistically significant reduction in the proportion of patients who received an allogeneic blood transfusion compared to no iron therapy. However, the 38 patients in our analysis falls far short of the 819 patients our information size calculation recommended to detect a 30% reduction in blood transfusions. Intravenous iron may be more effective than oral iron at increasing haemoglobin. However, all these conclusions are drawn from only three small randomised controlled studies. Further well designed, adequately powered randomised controlled studies are required to determine the true effectiveness of iron therapy for pre-operative anaemia.

Long-Term Worries after Colposcopy: Which Women Are at Increased Risk?

BACKGROUND: A colposcopy examination is the main management option for women with an abnormal cervical screening test result. Although some women experience adverse psychological effects after colposcopy, those at greatest risk are unknown. We investigated predictors of worries about cervical cancer, sex, future fertility and general health during 12 to 30 months after colposcopy. METHODS: We invited 1,515 women, aged 20 to 59 years with low-grade cervical cytology who attended colposcopy to complete questionnaires at recruitment (∼8 weeks after cytology result) and after 12, 18, 24, and 30 months of follow up. Outcomes were worries about having cervical cancer, having sex, future fertility, and general health at any time during follow-up. Factors significantly associated with each outcome were identified using multiple logistic regression. RESULTS: At one or more time points during follow-up, 40% of women reported worries about having cervical cancer, 26% about having sex, 24% about future fertility, and 60% about general health. For all outcomes except sex, worries reported at recruitment were associated with significantly increased risk of worries during follow-up. Significant anxiety at recruitment was associated with all worries during follow-up. Women diagnosed with CIN2+ had significantly higher risks of worries about cervical cancer and future fertility. Management received was associated significantly with worries about cervical cancer and having sex. Younger women significantly more often reported worries about future fertility, whereas women who had children had reduced risk of future fertility worries but increased risk of cervical cancer worries. CONCLUSION: Clinical, sociodemographic, lifestyle, and psychological factors predicted risk of reporting worries after colposcopy.

Identifying and testing candidate genetic polymorphisms in the irritable bowel syndrome (IBS): association with TNFSF15 and TNFα.

OBJECTIVES: The postinfectious irritable bowel syndrome (PI-IBS) suggests that impaired resolution of inflammation could cause IBS symptoms. The authors hypothesised that polymorphisms in genes whose expression were altered by gastroenteritis might be linked to IBS with diarrhoea (IBS-D) which closely resembles PI-IBS. DESIGN: Part 1: 25 healthy volunteers (HVs), 21 patients 6 months after Campylobacter jejuni infection, 37 IBS-D and 19 IBS with constipation (IBS-C) underwent rectal biopsy for gene expression analysis and peripheral blood mononuclear cell cytokine production assessment. Part 2: Polymorphisms in genes whose expression was altered in Part 1 were assessed in 179 HV, 179 IBS-D, 122 IBS-C and 41 PI-IBS. RESULTS: Part 1: Mucosal expression of seven genes was altered in IBS: CCL11, CCL13, Calpain 8 and TNFSF15 increased while NR1D1, GPR161 and GABRE decreased with similar patterns after infection with C jejuni. Part 2: The authors assessed 21 known single nucleotide polymorphisms (SNPs) in these seven genes and one SNP in each of the TNFα and IL-10 genes. Three out of five TNFSF15 SNPs (rs6478108, rs6478109 and rs7848647) showed reduced minor allele frequency (MAF) (0.28, 0.27 and 0.27) in subjects with IBS-D compared with HV (0.38, 0.36 and 0.37; p=0.007, 0.015 and 0.007, respectively) confirming others recent findings. The authors also replicated the previously reported association of the TNFα SNP rs1800629 with PI-IBS which showed an increase in the MAF at 0.30 versus 0.19 for HV (p=0.04). CONCLUSION: IBS-D and PI-IBS patients are associated with TNFSF15 and TNFα genetic polymorphisms which also predispose to Crohn's disease suggesting possible common underlying pathogenesis.

Prognostic value of proliferation assay in the luminal, HER2-positive, and triple-negative biologic classes of breast cancer.

INTRODUCTION: Although the prognostic significance of proliferation in early invasive breast cancer has been recognized for a long time, recent gene-expression profiling studies have reemphasized its biologic and prognostic value and the potential application of its assessment in routine practice, particularly to define prognostic subgroups of luminal/hormone receptor-positive (HR+) tumors. This study aimed to assess the prognostic value of a proliferation assay by using Ki-67 immunohistochemistry as compared with mitotic count scores. METHOD: Proliferation was assessed by using Ki-67 labeling index (Ki-67LI) and mitotic scores in a large (n = 1,550) and well-characterized series of clinically annotated primary operable invasive breast cancer with long-term follow-up. Tumors were phenotyped based on their IHC profiles into luminal/HR+, HER2+, and triple-negative (TN) classes. We used a split-sample development and validation approach to determine the optimal Ki-67LI cut-offs. RESULTS: The optimal cut-points of Ki-67LI were 10% and 50% for the luminal class. Both Ki7LI and MS were able to split luminal tumors into subgroups with significantly variable outcomes, independent of other variables. Neither mitotic count scores nor Ki-67LI was associated with outcome in the HER2+ or the TN classes. CONCLUSIONS: Assessment of proliferation by using Ki-67LI and MS can distinguish subgroups of patients within luminal/hormone receptor-positive breast cancer significantly different in clinical outcomes. Overall, both Ki-67 LI and mitotic-count scores showed comparable results. The method described could provide a cost-effective method for prognostic subclassification of luminal/hormone receptor-positive breast cancer in routine clinical practice.

Portal inflammation is associated with advanced histological changes in alcoholic and non-alcoholic fatty liver disease.

BACKGROUND: Fatty liver disease (FLD), of either alcoholic (AFLD) or non-alcoholic (NAFLD) aetiologies, is characterised histologically by features that are lobulocentric that typically affect zone 3, in contrast with portal-based inflammation characteristics of other forms of chronic liver disease. AIM: The authors aimed to determine the prevalence and significance of portal inflammation in a cohort of adults diagnosed as having AFLD and NAFLD. METHODS: From a histology database, the authors identified 160 patients with biopsy proven AFLD and 214 with NAFLD diagnosed between 1991 and 2001. All liver biopsies were reviewed by one pathologist to evaluate various histological features. RESULTS: More than a mild degree of portal inflammation was found in 47% of AFLD compared with 30% in NAFLD subgroup. A higher degree of portal inflammation in AFLD was associated with a higher mean corpuscular volume, gamma glutamyl transferase (GGT) and alkaline phosphatase, and a lower platelet count and albumin, whereas in NAFLD this was associated with age, presence of diabetes, hypertension, body mass index (BMI), higher fasting blood glucose, cholesterol, alanine transaminase, GGT and ferritin. On regression analysis, portal inflammation was associated with the severity of steatosis (p=0.005), presence of ballooning (p=0.030) in NAFLD and severity of fibrosis in both AFLD and NAFLD (p<0.001). CONCLUSIONS: Portal inflammation is a common component of histological spectrum of both AFLD and NAFLD. In both conditions portal inflammation is associated with clinical and histological features suggestive of advanced disease.

The enhanced recovery after surgery (ERAS) pathway for patients undergoing major elective open colorectal surgery: a meta-analysis of randomized controlled trials.

BACKGROUND & AIMS: The aim of the Enhanced Recovery After Surgery (ERAS) pathway is to attenuate the stress response to surgery and enable rapid recovery. The objective of this meta-analysis was to study the differences in outcomes in patients undergoing major elective open colorectal surgery within an ERAS pathway and those treated with conventional perioperative care. METHODS: Medline, Embase and Cochrane database searches were performed for relevant studies published between January 1966 and November 2009. All randomized controlled trials comparing ERAS with conventional perioperative care were selected. The outcome measures studied were length of hospital stay, complication rates, readmission rates and mortality. RESULTS: Six randomized controlled trials with 452 patients were included. The number of individual ERAS elements used ranged from 4 to 12, with a mean of 9. The length of hospital stay [weighted mean difference (95% confidence interval): -2.55 (-3.24, -1.85)] and complication rates [relative risk (95% confidence interval): 0.53 (0.44, 0.64)] were significantly reduced in the enhanced recovery group. There was no statistically significant difference in readmission and mortality rates. CONCLUSION: ERAS pathways appear to reduce the length of stay and complication rates after major elective open colorectal surgery without compromising patient safety.

Antibiotic therapy versus appendectomy for acute appendicitis: a meta-analysis.

BACKGROUND: Antibiotic treatment has been shown to be effective in treating selected patients with acute appendicitis, and three randomized controlled trials (RCTs) have compared the efficacy of antibiotic therapy alone with that of surgery for acute appendicitis. The purpose of this meta-analysis of RCTs was to assess the outcomes with these two therapeutic modalities. METHODS: All RCTs comparing antibiotic therapy alone with surgery in patients over 18 years of age with suspected acute appendicitis were included. Patients with suspected perforated appendix or peritonitis, and those with an allergy to antibiotics had been excluded in the RCTs. The outcome measures studied were complications, length of hospital stay, and readmissions. RESULTS: Meta-analysis of RCTs of antibiotic therapy versus surgery showed a trend toward a reduced risk of complications in the antibiotic-treated group [RR (95%CI): 0.43 (0.16, 1.18) p = 0.10], without prolonging the length of hospital stay [mean difference (inverse variance, random, 95% CI): 0.11 (-0.22, 0.43) p = 0.53]. Of the 350 patients randomized to the antibiotic group, 238 (68%) were treated successfully with antibiotics alone and 38 (15%) were readmitted. The remaining 112 (32%) patients randomized to antibiotic therapy crossed over to surgery for a variety of reasons. At 1 year, 200 patients in the antibiotic group remained asymptomatic. CONCLUSIONS: This meta-analysis suggests that although antibiotics may be used as primary treatment for selected patients with suspected uncomplicated appendicitis, this is unlikely to supersede appendectomy at present. Selection bias and crossover to surgery in the RCTs suggest that appendectomy is still the gold standard therapy for acute appendicitis.

After-effects reported by women following colposcopy, cervical biopsies and LLETZ: results from the TOMBOLA trial.

OBJECTIVE: Few studies have investigated physical after-effects of colposcopy. We compared post-colposcopy self-reported pain, bleeding, discharge and menstrual changes in women who underwent: colposcopic examination only; cervical punch biopsies; and large loop excision of the transformation zone (LLETZ). DESIGN: Observational study nested within a randomised controlled trial. SETTING: Grampian, Tayside and Nottingham. POPULATION: Nine hundred-and-twenty-nine women, aged 20-59, with low-grade cytology, who had completed their initial colposcopic management. METHODS: Women completed questionnaires on after-effects at approximately 6-weeks, and on menstruation at 4-months, post-colposcopy. MAIN OUTCOME MEASURES: Frequency of pain, bleeding, discharge; changes to first menstrual period post-colposcopy. RESULTS: Seven hundred-and-fifty-one women (80%) completed the 6-week questionnaire. Of women who had only a colposcopic examination, 14-18% reported pain, bleeding or discharge. Around half of women who had biopsies only and two-thirds treated by LLETZ reported pain or discharge (biopsies: 53% pain, 46% discharge; LLETZ: 67% pain, 63% discharge). The frequency of bleeding was similar in the biopsy (79%) and LLETZ groups (87%). Women treated by LLETZ reported bleeding and discharge of significantly longer duration than other women. The duration of pain was similar across management groups. Forty-three percent of women managed by biopsies and 71% managed by LLETZ reported some change to their first period post-colposcopy, as did 29% who only had a colposcopic examination. CONCLUSIONS: Cervical punch biopsies and, especially, LLETZ carry a substantial risk of after-effects. After-effects are also reported by women managed solely by colposcopic examination. Ensuring that women are fully informed about after-effects may help to alleviate anxiety and provide reassurance, thereby minimising the harms of screening.

The pathological response to neoadjuvant chemotherapy with FOLFOX-4 for colorectal liver metastases: a comparative study.

FOLFOX-4 (folinic acid/5-fluorouracil/oxaliplatin) chemotherapy is used to treat patients with colorectal liver metastases. We aimed to assess hepatic histopathological responses to neoadjuvant FOLFOX-4 chemotherapy in patients with colorectal liver metastases. We selected all patients (n = 54) treated with FOLFOX-4 for colorectal liver metastases between June 2002 and June 2005. Only 25 underwent hepatectomy and formed the study group. Histological responses were assessed in the study group and a matched control group (n = 25) that did not receive neoadjuvant chemotherapy. The median (IQR) body mass index in the study and control groups was 24 (22-26) and 24 (23-25) kg/m(2), respectively, (P = NS). Complete histological resolution of tumour occurred in six (24%) patients in the study group. Median residual tumour cellularity was less (35 vs 70%) and fibrosis greater (50 vs 5%) in patients in the study group when compared with controls (P < 0.001). The liver surrounding the tumour was steatotic in 17 (68%) patients in the study group and five (20%) controls (P = 0.001). Hepatic sinusoidal dilatation was more pronounced in patients in the study group than in controls (P < 0.001). The response to FOLFOX-4 was associated with tumour necrosis, fibrosis and inflammation. More than two thirds of patients undergoing hepatectomy after FOLFOX-4 had steatosis despite being non-obese.

The natural history of hepatitis C with severe hepatic fibrosis.

BACKGROUND/AIMS: To examine the morbidity and mortality of patients with severe fibrosis secondary to HCV infection, within a population unbiased by tertiary referral. METHODS: One hundred and fifty HCV infected patients were identified from the Trent HCV study with a liver biopsy taken before 2002 demonstrating severe fibrosis (Ishak stage > or =4). Follow-up data were extracted from the database and hospital records. RESULTS: Median follow-up was 51 months. Of the 131 patients with no prior history of decompensation, 33 (25%) died (n=25) or were transplanted (n=8), after a median interval of 42 months. The probability of survival without liver transplantation was 97%, 88%, and 78% at 1, 3, and 5 years, respectively. Hepatocellular carcinoma and/or decompensation was diagnosed in 33 (25%), after a median interval of 41 months. In multivariate analysis, combination antiviral therapy was associated with improved survival. Prognosis was not affected by the Ishak stage at index biopsy. There was a worse prognosis for the 19 patients with previous decompensation; 17 (89%) having either died (n=15) or been transplanted (n=2). CONCLUSIONS: This study demonstrates that severe liver fibrosis (Ishak stage > or = 4) secondary to hepatitis C is associated with a poor prognosis, that may be improved following combination antiviral treatment.

Excess mortality rates in a cohort of patients infected with the hepatitis C virus: a prospective study.

OBJECTIVE: We analysed the Trent Hepatitis C cohort to determine standardised mortality ratios in patients infected with hepatitis C virus (HCV), and to identify risk factors and associations with all-cause and liver-related mortality. DESIGN: Cohort study. SETTING: Patients with HCV infection attending secondary care within the Trent region of England. PATIENTS: 2285 patients with hepatitis C, followed for 1 year or more. MAIN OUTCOME MEASURES: The death rate in the cohort was compared to that seen in an age- and sex-matched English population. We performed Cox regression analyses to identify factors predictive of all-cause mortality and deaths from liver disease. RESULTS: Standardised mortality ratios in the cohort were three times higher than those expected in the general population of England. The excess deaths were due to liver-related causes and those associated with a drug-using lifestyle. Significant independent predictors of all-cause mortality were age, sex, treatment (protective) and liver biopsy fibrosis. Age, treatment, liver biopsy fibrosis and mean alcohol consumption were predictors of liver-related mortality. HCV was mentioned on 23% of death certificates overall, and on 52% of those of patients dying from a liver-related cause. CONCLUSIONS: Our findings demonstrate that the death rate in patients infected with hepatitis C is three times higher than expected. Severity of disease is associated with a worse prognosis, whilst treatment improves outcome, particularly in those who respond. Use of death certificate data on HCV infection for planning purposes will result in considerable under-estimation of the HCV-related disease burden.

Early postoperative jejunostomy feeding with an immune modulating diet in patients undergoing resectional surgery for upper gastrointestinal cancer: a prospective, randomized, controlled, double-blind study.

BACKGROUND: The provision of perioperative immune modulating enteral feeds after major surgery may result in reduced infective complications, but meta-analyses have not demonstrated a survival advantage. The aim of this study was to determine whether early postoperative immune modulating jejunostomy feeding results in reduced infective complications in patients undergoing resectional surgery for upper gastrointestinal cancer. METHODS: A total of 120 patients undergoing resection for cancers of the pancreas, oesophagus and stomach were randomized in a double-blind manner to receive jejunostomy feeding with an immune modulating diet (Stresson-Group A) or an isonitrogenous, isocaloric feed (1250 Calories and 75 g protein/l--Nutrison High Protein-Group B) for 10-15 days. Feeding was commenced 4h postoperatively and continued for 20 h/day. The target volume (ml/h) was 25 on day 0, 50 on day 1, and 75 thereafter. Outcome measures included complications, hospital stay and mortality. RESULTS: A total of 108 patients (54 in each group) were analysed. Feed delivery, although less than targeted, was similar in both groups. There were 6 (11%) deaths in each group. Median (IQR) postoperative hospital stay was 14.5 (12-23) days in Group A and 17.5 (13-23) days in Group B (P=0.48). A total of 24 (44%) patients in each group had infective complications (P=1.0). A total of 21 (39%) patients in Group A and 28 (52%) in Group B had non-infective complications (P=0.18). Jejunostomy-related complications occurred in 26 (48%) patients in Group A and 30 (56%) in Group B (P=0.3). CONCLUSION: Early postoperative feeding with an immune modulating diet conferred no outcome advantage when compared with a standard feed.

Social behavior and meningococcal carriage in British teenagers.

Understanding predisposing factors for meningococcal carriage may identify targets for public health interventions. Before mass vaccination with meningococcal group C conjugate vaccine began in autumn 1999, we took pharyngeal swabs from approximately 14,000 UK teenagers and collected information on potential risk factors. Neisseria meningitidis was cultured from 2,319 (16.7%) of 13,919 swabs. In multivariable analysis, attendance at pubs/clubs, intimate kissing, and cigarette smoking were each independently and strongly associated with increased risk for meningococcal carriage (p<0.001). Carriage in those with none of these risk factors was 7.8%, compared to 32.8% in those with all 3. Passive smoking was also linked to higher risk for carriage, but age, sex, social deprivation, home crowding, or school characteristics had little or no effect. Social behavior, rather than age or sex, can explain the higher frequency of meningococcal carriage among teenagers. A ban on smoking in public places may reduce risk for transmission.

Estimated progression rates in three United Kingdom hepatitis C cohorts differed according to method of recruitment.

OBJECTIVES: To estimate hepatitis C virus (HCV) progression rates between disease stages prior to cirrhosis, using data from liver biopsies in three observational cohorts. To demonstrate how the method of cohort recruitment can influence the estimation of HCV-progression rates. STUDY DESIGN AND SETTING: Data came from three United Kingdom observational cohorts, assembled from different referral sources. In total, 987 HCV-infected patients with an estimated (or known) date of infection and at least one histologically scored liver biopsy were eligible for inclusion in the analysis. Liver biopsy scores were used to determine the stage of HCV-related liver disease. A three-state continuous time Markov model was used to estimate covariate-specific average probabilities of progression of disease. RESULTS: After adjusting for confounders, considerably different rates of disease progression were estimated in the three cohorts. For a group of patients with the same demographics, the estimated 20-year probability of progression to cirrhosis was 12% (95% confidence interval CI = 6-22) in a hospital-based cohort, 6% (95% CI = 3-13) in a posttransfusion cohort, and 23% (95% CI = 14-37) in a cohort recruited from a tertiary referral center. CONCLUSION: Researchers using estimates of disease progression should be aware that the method of cohort recruitment has considerable influence on the progression rates that are derived.