Impact of enhanced recovery on oncological outcomes following minimally invasive surgery for rectal cancer.

BACKGROUND: Oncological outcomes of locally advanced rectal cancer depend on the quality of surgical and oncological management. Enhanced recovery pathways (ERPs) have yet to be assessed for their oncological impact when used in combination with minimally invasive surgery. This study assessed outcomes with or without an ERP in patients with rectal cancer. METHODS: This was a retrospective analysis of all consecutive adult patients who underwent elective minimally invasive surgery for primary rectal adenocarcinoma with curative intent between February 2005 and April 2018. Both laparoscopic and robotic procedures were included. Short-term morbidity and overall survival were compared between patients treated according to the institutional ERP and those who received conventional care. RESULTS: A total of 600 patients underwent minimally invasive surgery, of whom 320 (53·3 per cent) were treated according to the ERP and 280 (46·7 per cent) received conventional care. ERP was associated with less overall morbidity (34·7 versus 54·3 per cent; P < 0·001). Patients in the ERP group had improved overall survival on univariable (91·4 versus 81·7 per cent at 5 years; hazard ratio (HR) 0·53, 95 per cent c.i. 0·28 to 0·99) but not multivariable (HR 0·78, 0·41 to 1·50) analysis. Multivariable analysis revealed age (HR 1·46, 1·17 to 1·82), male sex (HR 1·98, 1·05 to 3·70) and complications (HR 2·23, 1·30 to 3·83) as independent risk factors for compromised overall survival. Disease-free survival was comparable for patients who had ERP or conventional treatment (80·5 versus 84·6 per cent at 5 years respectively; P = 0·272). CONCLUSION: Treatment within an ERP was associated with a lower morbidity risk that may have had a subtle impact on overall but not disease-specific survival.

Prognostic value of pathological node status after neoadjuvant radiotherapy for rectal cancer.

BACKGROUND: The prognostic value of pathological lymph node status following neoadjuvant radiotherapy (ypN) remains unclear. This study was designed to determine whether ypN status predicted overall survival. METHODS: Patients with locally advanced rectal adenocarcinoma who underwent neoadjuvant long-course radiation between 2005 and 2014 were identified from the National Cancer Data Base, and divided into ypN0, ypN1 and ypN2 groups. The primary outcome was overall survival. Univariable and multivariable analyses were used to determine factors associated with overall survival. RESULTS: Of 12 271 patients, 3713 (30·3 per cent) were found to have residual nodal positivity. A majority of patients with ypN1 (1663 of 2562) and ypN2 (878 of 1151) disease had suspected lymph node-positive disease before neoadjuvant therapy, compared with 3959 of 8558 with ypN0 tumours (P < 0·001). Moreover, ypN1 and ypN2 were significantly associated with ypT3-4 disease (65·7 and 83·0 per cent respectively versus 39·4 per cent for ypN0; P < 0·001). In unadjusted analyses, survival differed significantly between ypN groups (P < 0·001). Five-year survival rates were 81·6, 71·3 and 55·0 per cent for patients with ypN0, ypN1 and ypN2 disease respectively. After adjustment for confounding variables, ypN1 and ypN2 remained independently associated with overall survival: hazard ratio (HR) 1·61 (95 per cent c.i. 1·46 to 1·77) and 2·63 (2·34 to 2·95) respectively (P < 0·001). Overall survival was significantly longer in patients with ypN1-2 combined with ypT0-2 status than among those with ypT3-4 tumours even with ypN0 status (P = 0·031). Clinical nodal status before neoadjuvant therapy was not significantly associated with overall survival (HR 1·05, 0·97 to 1·13; P = 0·259). CONCLUSION: Both ypT and ypN status is of prognostic significance following neoadjuvant therapy for rectal cancer.

What is the lifetime risk of revision for patients undergoing total hip arthroplasty? a 40-year observational study of patients treated with the Charnley cemented total hip arthroplasty.

AIMS: The purpose of this study was to determine the lifetime risk of revision surgery for patients undergoing Charnley cemented total hip arthroplasty (THA), with 40-year follow up, using death as a competing risk. MATERIALS AND METHODS: We retrospectively reviewed 2000 cemented Charnley THAs, with 51 living hips available at 40 years. RESULTS: The cumulative risk of revision or removal for any reason was 13% (95% confidence interval (CI) 12 to 15). Patients aged under 50 years at the time of surgery had a 35% (95% CI 28 to 42) risk of revision or removal for any reason (Hazard Ratio (HR) 3.6; 95% CI 2.5 to 5.2; p < 0.001), patients 50 to 59 years old had a 20% risk (95% CI 16 to 24) (HR 2.1; 95% CI 1.5 to 2.8; p < 0.0001), patients aged 60 to 69 years had a 9% risk (95% CI 7 to 11) (reference point), and patients ≥ 70 years old had a 5% risk (95% CI 4 to 7) (HR 0.96; 95% CI 0.6 to 1.5; p = 0.86) during their lifetime. Men had a higher risk of revision or removal for any reason (HR 2.1; 95% CI 1.7 to 2.7; p < 0.001). CONCLUSION: With almost all the patients in this series followed up till either death or revision, we have been able to develop a 'rule of thumb' for lifetime likelihood of revision or implant removal for the Charnley THA: one in three for patients < 50 years, one in five for patients 50 to 59 years, one in ten for patients 60 to 69 years, and one in 20 for patients ≥ 70 years. The results provide a benchmark for comparison of outcomes, for the newer designs of THA. Cite this article: Bone Joint J 2016;98-B:1436-40.

Novel partial 5HT3 agonist pumosetrag reduces acid reflux events in uninvestigated GERD patients after a standard refluxogenic meal: a randomized, double-blind, placebo-controlled pharmacodynamic study.

BACKGROUND: Low basal lower esophageal sphincter (LES) pressure and transient LES relaxations are major causes of gastroesophageal reflux disease (GERD). Pumosetrag, a novel selective partial 5HT3 receptor agonist, showed a promising effect on reducing reflux events in health. We aimed to evaluate the effect of pumosetrag on changes in reflux episodes, lower esophageal sphincter pressure (LESP), and specific symptoms in patients with GERD receiving a refluxogenic meal. METHODS: Patients with GERD, who developed heartburn and/or regurgitation after ingestion of a refluxogenic meal, were randomized to 1 of 3 dose levels of pumosetrag (0.2, 0.5, or 0.8 mg) or placebo. Before and after 7 days of treatment, patients underwent manometry, intraesophageal multichannel, intraluminal impedance and pH after a standard refluxogenic meal. KEY RESULTS: A total of 223 patients with GERD [125 (56%) women, mean (SD) age = 36 (12) years] were enrolled. No overall treatment effects were detected for the total number of reflux episodes (acidic and weakly acidic) (p > 0.5); however, significant treatment effects (p < 0.05) on the number of acid reflux episodes were observed with lower values on pumosetrag 0.2 mg (10.8 ± 1.1), 0.5 mg (9.5 ± 1.1), and 0.8 mg (9.9 ± 1.1) compared with placebo (13.3 ± 1.1). Significant treatment effects (p < 0.05) were also observed for the percentage of time pH was <4, with less time for pumosetrag at 0.5 mg (10%) and 0.8 mg (10%) compared with placebo (16%). CONCLUSIONS & INFERENCES: In GERD, the partial 5HT3 agonist pumosetrag significantly reduced the rate of acid reflux events but did not result in a significant change in LESP or symptomatic improvement over a 1-week treatment period.

Clinically important body weight gain following total hip arthroplasty: a cohort study with 5-year follow-up.

OBJECTIVE: Literature examining the effects of total hip arthroplasty (THA) on subsequent body weight gain is inconclusive. Determining the extent to which clinically relevant weight gain occurs following THA has important public health implications. DESIGN: We used multi-variable logistic regression to compare data from one of the largest US-based THA registries to a population-based control sample from the same geographic region. We also identified factors that increased risk of clinically important weight gain specifically among persons undergoing THA. The outcome measure of interest was weight gain of ≥5% of body weight up to 5 years following surgery. RESULTS: The multi-variable adjusted [age, sex, body mass index (BMI), education, comorbidity and pre-surgical weight change] odds ratio for important weight gain was 1.7 [95% confidence interval (CI), 1.06, 2.6] for a person with THA as compared to the control sample. Additional arthroplasty procedures during the 5-year follow-up further increased odds for important weight gain (OR = 2.0, 95% CI, 1.4, 2.7) relative to the control sample. A patient with THA had increased risk of important post-surgical weight gain of 12% (OR = 1.12, 95% CI, 1.08, 1.16) for every kilogram of pre-operative weight loss. CONCLUSIONS: While findings should be interpreted with caution because of missing follow-up weight data, patients with THA appear to be at increased risk of clinically important weight gain following surgery as compared to peers. Patients less than 60 years and who have lost a substantial amount of weight prior to surgery appear to be at particularly high risk of important post-surgical weight gain.

Natalizumab for moderate to severe Crohn's disease in clinical practice: the Mayo Clinic Rochester experience.

BACKGROUND: Not all patients with Crohn's disease (CD) respond or maintain response to anti-tumor necrosis factor (TNF) agents and alternative treatment is necessary. Natalizumab, a monoclonal antibody to alpha-4 integrin approved for CD, has demonstrated efficacy in randomized clinical trials. We describe our experience with natalizumab in clinical practice at Mayo Clinic Rochester. METHODS: Consecutive patients prescribed natalizumab for active CD were invited to participate and were followed prospectively. Incidence of infection, hospitalization, neoplasm, or other adverse events were recorded. Clinical activity was assessed using the Harvey-Bradshaw Index at each 30-day infusion visit. RESULTS: Between April 2008 and September 2010, 36 patients were prescribed natalizumab and 30 (83.3%) agreed to participate. Median disease duration was 9 years (range, 3-43). Twenty-three patients had prior exposure to two anti-TNF agents, seven to one agent. All patients experienced at least one adverse event; none of the 13 patients in whom natalizumab was stopped (43%) discontinued due to adverse events. Five patients had infusions held for infection. No patient developed progressive multifocal leukoencephalopathy (PML). Fourteen patients (46%) had clinical response. The cumulative probability of achieving complete response within 1 year was 56% (28%-73%). Four of seven patients were weaned off corticosteroids. CONCLUSIONS: In our experience with natalizumab in clinical practice, adverse events were manageable and did not result in treatment cessation. No PML cases were seen and clinical response was similar to that in clinical trials. Natalizumab results in clinical benefit in patients who have active disease and have failed anti-TNF therapy.

Case-matched series of enhanced versus standard recovery pathway in minimally invasive colorectal surgery.

BACKGROUND: Accelerated recovery pathways may reduce length of hospital stay after surgery but there are few data on minimally invasive colorectal operations. METHODS: An enhanced recovery pathway (ERP) was instituted, including preoperative analgesia, limited intravenous fluids and opiates, and early feeding. Intrathecal analgesia was administered as needed, but epidural analgesia was not used. The first 66 patients subjected to the ERP were case-matched by surgeon, procedure and age (within 5 years) with patients treated previously in a fast-track pathway (FTP). Short-term and postoperative outcomes to 30 days were compared. RESULTS: Hospital stay was shorter with the ERP than the FTP: median (interquartile range, i.q.r.) 3 (2-3) versus 3 (3-5) days (P < 0·001). A 2-day hospital stay was achieved in 44 and 8 per cent of patients respectively (P < 0·001). Patients in the ERP had a shorter time to recovery of bowel function: median (i.q.r.) 1 (1-2) versus 2 (2-3) days (P < 0·001). Thirty-day complication rates were similar (32 per cent ERP, 27 per cent FTP; P = 0·570). Readmissions within 30 days were more common with ERP, but the difference was not statistically significant (10 versus 5 patients; P = 0·170). Total hospital stay for those readmitted was shorter in the ERP group (18 versus 23 days). CONCLUSION: ERP decreased the length of hospital stay after minimally invasive colorectal surgery.

Clinical predictors of small intestinal bacterial overgrowth by duodenal aspirate culture.

BACKGROUND: There has been increasing interest in small intestinal bacterial overgrowth (SIBO) after reports of a link with irritable bowel syndrome (IBS), yet our understanding of this entity is limited. AIM: Our aim was to estimate the yield of patients undergoing duodenal aspirate culture, and to identify symptoms and features that predict SIBO. METHODS: A medical chart review of patients who had undergone duodenal aspirate culture at an academic medical centre in 2003 was performed to record clinical characteristics and culture results. The associations between aspirate results and symptoms, medical diagnoses and medication use were assessed using logistic regression. RESULTS: A total of 675 patients had available aspirate results. Mean age of the sample was 53 (s.d. 17) and 443 (66%) were female patients. Overall, 8% of aspirates were positive for SIBO; 2% of IBS patients had SIBO. Older age, steatorrhoea and narcotic use were associated with SIBO (P < 0.05). PPI use was not associated with SIBO, but was associated with bacterial growth not meeting criteria for SIBO (P < 0.05). Inflammatory bowel disease (IBD), small bowel diverticula and pancreatitis were positively associated with an abnormal duodenal aspirate (P < 0.05), but other conditions including IBS were not associated with SIBO. CONCLUSION: Older age, steatorrhoea, narcotic use, IBD, small bowel diverticula and pancreatitis were associated with small intestinal bacterial overgrowth based on abnormal duodenal aspirate culture results. However, no clear associations of true small intestinal bacterial overgrowth with IBS or PPI use were detected, in contrast to recent speculation.

Resection of hepatocellular carcinoma in patients without cirrhosis.

BACKGROUND: Outcomes for patients with hepatocellular carcinoma (HCC) without cirrhosis and factors associated with disease progression remain unclear. The goals of this single-institution study were to define the outcomes for such patients, and to determine factors associated with survival and disease progression. METHODS: This was a retrospective review of consecutive patients with HCC without cirrhosis who underwent hepatic resection between 1985 and 2003. Survival was estimated by the Kaplan-Meier method and risk factors were identified by Cox proportional hazards models. RESULTS: A total of 143 patients were enrolled, of whom 29·4 per cent had identifiable risk factors for chronic liver disease. Major resection (at least three segments) was undertaken in 63·6 per cent of patients. The operative mortality rate was 3·5 per cent. Median disease-free survival was 2·4 years. Multivariable analysis revealed presence of multiple tumours as the only independent predictor of tumour recurrence. Median overall survival was 3·3 years. Factors independently associated with decreased overall survival were multiple tumours, high histological grade, perioperative transfusion, male sex and age at least 66 years. CONCLUSION: Patients with HCC but without cirrhosis have acceptable outcomes after resection. Specific risk factors for the development of HCC in these patients have yet to be defined.

Duodenal mastocytosis, eosinophilia and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia.

BACKGROUND: Irritable bowel syndrome (IBS) and functional dyspepsia (FD) are common functional disorders without defined pathology. Mast cells and eosinophils interact with T lymphocytes and may alter enteric nerve and smooth muscle function. AIM: To examine mast cell, eosinophil and intraepithelial lymphocyte populations in duodenal biopsies of subjects with IBS and FD. METHODS: A random sample of an adult Swedish population (n = 1001; mean age 54 years; 51% female) underwent upper endoscopy and biopsy; 51 cases with FD and 41 cases with IBS were compared with 48 randomly selected controls. Eosinophils were identified by light microscopy; mast cells by immunocytochemistry (CD117). Intraepithelial lymphocytes were counted per 100 enterocytes. Cell counts were quantified by counting the number per high power field (HPF) in 5HPFs in the bulb (D1) and second part of duodenum (D2), summed over 5HPFs at each site. RESULTS: Cases and controls showed similar demographics. Compared to controls, IELs in IBS-constipation were significantly increased (P = 0.005). Mast cells were significantly increased in IBS in D2 (P < 0.001), while eosinophils were significantly increased in FD in D1 and D2 (P < 0.001). CONCLUSION: Duodenal mast cell hyperplasia is linked to IBS and eosinophilia to FD, and duodenal biopsy may identify subsets of these disorders.

Irritable bowel syndrome aggregates strongly in families: a family-based case-control study.

Irritable bowel syndrome (IBS) runs in families. Prior family studies surveyed patients inquiring about family history without surveying family members. The stigma associated with IBS may lead relatives to not share information with others,resulting in underestimates of familial aggregation of IBS. The aim of the study was to evaluate the accuracy of patient-report of family history of IBS in cases and controls, and to estimate familial aggregation of IBS using both a case-control and a family-study design. Fifty cases and 53 controls completed symptom questionnaires and provided contact information for first-degree relatives. Questionnaires were mailed to relatives. Relatives were considered to have IBS if they met Rome criteria and did not have an alternate GI diagnosis. Cases and controls identified 573 relatives in their families. A total of 202 (51%) of 396 living relatives participated. The kappa statistics between proband- and relative-reported IBS for case- and control-relatives were 0.27 and 0.04. Cases reported 21%of relatives had IBS; relative-reports showed 37%(P = 0.003). Controls reported 4% of relatives had IBS;relative-reports showed 16% (P = 0.013). Regardless of whether the proband or the relative themselves were the information source, case-relatives were three fold as likely to have IBS than control-relatives (P < 0.05).However, overall rates were higher when data collected from relatives were used. Regardless of approach, strong familial aggregation of IBS was observed. Cases and controls underestimated the frequency of IBS in their relatives and agreement between proband- and relative-report of IBS status was extremely poor, thus emphasizing the need for direct data collection from relatives in IBS family studies.

Age at onset of inflammatory bowel disease and the risk of surgery for non-neoplastic bowel disease.

BACKGROUND: There is conflicting data regarding the response to medical and surgical therapy for inflammatory bowel disease with respect to age at disease onset. AIM: To determine if the age at onset of Crohn's disease and ulcerative colitis is a risk factor for surgery for non-neoplastic bowel disease. METHODS: This was a case-control study of patients evaluated between 1998 and 2001. Cases had undergone an initial operation for bowel disease. Controls were matched 1:1 for gender, disease subtype, date of first visit (+/-2 years), time from diagnosis prior to first visit (+/-3 years) and duration of follow-up. Association with age, disease extent, smoking history, medication use and co-morbidities vs. case/control status was assessed using multiple variable conditional logistic regression to estimate the odds ratio (OR) and 95% confidence intervals (CI) for undergoing surgery. RESULTS: Among 132 Crohn's patients, older patients had lower odds for surgery (OR per 5 years, 0.86; 95% CI: 0.75-0.98). The rate of surgery for non-neoplastic bowel disease was not significantly associated with disease distribution, co-morbidities or cigarette smoking. Among 234 ulcerative colitis patients, the rate of surgery was unrelated to age, disease extent, co-morbidities or cigarette smoking, CONCLUSIONS: For Crohn's disease, but not ulcerative colitis, the risk of surgery for non-neoplastic bowel disease decreases with increasing age at diagnosis, irrespective of disease distribution and history of cigarette smoking.

The changing incidence of oesophageal and gastric adenocarcinoma by anatomic sub-site.

BACKGROUND: The incidence rates of gastric and oesophageal adenocarcinoma are changing significantly, but little is known about specific sub-sites. AIM: To use a population-based approach to describe the trends in the site-specific incidence of oesophageal and gastric adenocarcinoma. METHODS: Using the Rochester Epidemiology Project, all cases of gastric and oesophageal adenocarcinoma among Olmsted County, Minnesota, residents first diagnosed between 1971 and 2000 were identified (n = 186). Complete in-patient and out-patient records were reviewed and site determined from pathological, surgical, endoscopic and radiological reports. RESULTS: Between the decades of 1971-1980 and 1991-2000, the incidence of oesophageal adenocarcinoma increased significantly from 0.4 to 2.5 per 100 000 person-years. The incidence of adenocarcinoma of the oesophagogastric junction also increased from a rate of 0.6 to 2.2 per 100 000 person-years. The incidence rate of cancer involving the gastric cardia was stable but the incidence of adenocarcinoma involving distal gastric sites declined. Combined oesophageal and oesophagogastric junction adenocarcinoma (4.7 per 1 000 000 person-years) was as common as gastric adenocarcinoma (3.4 per 100 000 person-years) in 1991-2000. CONCLUSIONS: The incidence rates of adenocarcinoma involving proximal gastric sub-sites do not appear to be increasing in a manner similar to those involving oesophageal sub-sites.

A double-blind, randomized, placebo-controlled trial of itopride (100 and 200 mg three times daily) on gastric motor and sensory function in healthy volunteers.

Itopride, a dopamine D2 antagonist and acetylcholinesterase inhibitor, significantly improved symptoms in patients with functional dyspepsia in one phase II randomized trial. However, the mechanisms by which itopride may improve symptoms are unknown. We aimed to compare the effects of two doses of itopride and placebo on gastric volumes, gastric emptying, small bowel transit and satiation in female and male healthy volunteers. Randomized, double-blind, placebo-controlled study evaluated gastric function before and after 7 days of itopride 100 mg (n = 16) or 200 mg (n = 15) or placebo (n = 15) t.i.d. Validated methods were used to study gastric accommodation (single photon emission computed tomography), gastric emptying and orocecal transit and satiation postnutrient challenge. The three arms were comparable with regard to age, gender and body mass index. There were no statistically significant effects of itopride on gastric emptying, orocecal transit, fasting gastric volume, maximum tolerated volume or aggregate symptom score with nutrient drink challenge. Postprandial (PP) change in gastric volume differed in the three groups (P = 0.019): 625[+/-28 (SEM)], 555(+/-26) and 512(+/-33) in placebo, itopride 100 and 200 mg groups, respectively. In healthy subjects, itopride reduced total PP gastric volume without accelerating gastric emptying or significantly altering gastric motor and sensory function in healthy individuals.

Quantitative measurement and visual assessment of ileal Crohn's disease activity by computed tomography enterography: correlation with endoscopic severity and C reactive protein.

BACKGROUND: Few studies have correlated computed tomography (CT) enterography findings with endoscopic severity and C reactive protein (CRP) concentrations. AIM: To examine whether small bowel inflammation at CT enterography correlates with endoscopic severity and CRP in patients with Crohn's disease (CD). METHODS: CT enterography datasets from 143 CD patients undergoing ileoscopy were examined for three different CT parameters: CT bowel enhancement, as defined by the ratio of terminal ileal versus control ileal loop attenuation; vascular enlargement of the vasa recta ("the comb sign"); and mesenteric fat density. Correlations between CT scan parameters, endoscopy, and histology severity scores, and CRP were assessed using Spearman's rank correlation and logistic regression. RESULTS: Endoscopic score was significantly correlated with CT bowel enhancement, comb sign, and fat density (Spearman correlation coefficients 0.33-0.39; p<0.001). Correlations with histological inflammation were strongest for bowel enhancement (r = 0.34-0.38; p<0.001). CRP was elevated in patients with increased fat density versus those with increased bowel enhancement only (median 0.96 v 0.23, p = 0.002). CRP did not differ significantly between patients without evidence of active Crohn's and those with bowel enhancement and endoscopic inflammation not involving the perienteric tissues by CT (median 0.24 v 0.36; p = 0.38). CONCLUSION: Quantitative measures of bowel enhancement at CT enterography correlate with endoscopic and histological severity. CRP correlates with radiological findings of perienteric inflammation (increased fat density), but not of inflammation limited to the small bowel wall, underscoring the potential role of perienteric inflammation in CRP response in CD.

Survival and cause specific mortality in patients with inflammatory bowel disease: a long term outcome study in Olmsted County, Minnesota, 1940-2004.

BACKGROUND AND AIMS: We followed a population based cohort of patients with inflammatory bowel disease (IBD) from Olmsted County, Minnesota, in order to analyse long term survival and cause specific mortality. MATERIAL AND METHODS: A total of 692 patients were followed for a median of 14 years. Standardised mortality ratios (SMRs, observed/expected deaths) were calculated for specific causes of death. Cox proportional hazards regression was used to determine if clinical variables were independently associated with mortality. RESULTS: Fifty six of 314 Crohn's disease patients died compared with 46.0 expected (SMR 1.2 (95% confidence interval (CI) 0.9-1.6)), and 62 of 378 ulcerative colitis (UC) patients died compared with 79.2 expected (SMR 0.8 (95% CI 0.6-1.0)). Eighteen patients with Crohn's disease (32%) died from disease related complications, and 12 patients (19%) died from causes related to UC. In Crohn's disease, an increased risk of dying from non-malignant gastrointestinal causes (SMR 6.4 (95% CI 3.2-11.5)), gastrointestinal malignancies (SMR 4.7 (95% CI 1.7-10.2)), and chronic obstructive pulmonary disease (COPD) (SMR 3.5 (95% CI 1.3-7.5)) was observed. In UC, cardiovascular death was reduced (SMR 0.6 (95% CI 0.4-0.9)). Increased age at diagnosis and male sex were associated with mortality in both subtypes. In UC but not Crohn's disease, a diagnosis after 1980 was associated with decreased mortality. CONCLUSIONS: In this population based study of IBD patients from North America, overall survival was similar to that expected in the US White population. Crohn's disease patients were at increased risk of dying from gastrointestinal disease and COPD whereas UC patients had a decreased risk of cardiovascular death.

Comparison of specimen processing and nucleic acid extraction by the swab extraction tube system versus the MagNA Pure LC system for laboratory diagnosis of herpes simplex virus infections by LightCycler PCR.

A total of 563 specimens (234 dermal and 329 genital swabs) from patients suspected of having herpes simplex virus (HSV) infections were processed using two different extraction methods (the MagNA Pure LC system and the swab extraction tube system [SETS]); HSV DNA was amplified by LightCycler PCR. HSV DNA was detected in 157 of 563 specimens (27.9%) processed by the MagNA Pure LC system and in 179 of 563 specimens (31.8%) processed by SETS (P < 0.0001). There was no specimen processed by the MagNA Pure LC extraction method that was positive only for HSV DNA. Of 157 specimens positive by both methods, HSV DNA copy levels were higher (using cycle crossover points [cycle threshold {C(T)}]) with SETS (mean C(T), 25.9 cycles) than with the MagNA Pure LC system (mean C(T), 32.0 cycles) (P < 0.0001). The time to process 32 samples was longer with the MagNA Pure LC extraction system (90 min) than with SETS (35 min). HSV DNA extraction using SETS is faster, less expensive, and more sensitive than the MagNA Pure LC system and could replace the latter for the laboratory diagnosis of HSV infections using LightCycler PCR.

PSC-IBD: a unique form of inflammatory bowel disease associated with primary sclerosing cholangitis.

BACKGROUND: Inflammatory bowel disease associated with primary sclerosing cholangitis (PSC-IBD) may have a high prevalence of rectal sparing, backwash ileitis, and colorectal neoplasia. AIMS: To describe the clinical features and outcomes of PSC-IBD and compare these to a group of chronic ulcerative colitis (CUC) patients. METHODS: The medical records of all patients with PSC-IBD evaluated at the Mayo Clinic Rochester between 1987 and 1992 were abstracted for information on endoscopic and histological features, colorectal neoplasia, surgery, and other clinical outcomes. Patients referred for colorectal neoplasia and those who did not undergo colonoscopy with biopsies were excluded. A control group of CUC patients matched for sex, duration of IBD at first clinic visit, and calendar year of first clinic visit was identified, and similar information was abstracted. RESULTS: Seventy one PSC-IBD patients and 142 CUC patients without PSC were identified. Rectal sparing and backwash ileitis were more common in the PSC-IBD group (52% and 51%, respectively) than in controls (6% and 7%, respectively). Overall, colorectal neoplasia developed in 18 cases and 15 controls, including 11 cancers (seven cases and four controls). An increased risk of colorectal neoplasia or death was not detected in a matched analysis. Although the cumulative incidence of colorectal neoplasia was higher in cases (33%) than in controls (13%) at five years, this was of borderline statistical significance (p=0.054, unmatched log rank test). Overall survival from first clinic visit was significantly worse among cases (79% v 97%) at five years (p<0.001, unmatched log rank test). CONCLUSION: PSC-IBD is frequently characterised by rectal sparing and backwash ileitis. Colorectal neoplasia develops in a substantial fraction and overall survival is worse. PSC-IBD may represent a distinct IBD phenotype.

Optimal testing parameters for blood cultures.

The effects of volume of blood, number of consecutive cultures, and incubation time on pathogen recovery were evaluated for 37,568 blood cultures tested with the automated BACTEC 9240 instrument (Becton Dickinson Diagnostic Instrument Systems) at a tertiary care center over the period of 12 June 1996 through 12 October 1997. When the results for this study were compared with previous data published for manual broth-based blood culture systems and patient samples obtained in the 1970s and 1980s, the following were found: (1) the percentage increase in pathogen recovery per milliliter of blood is less, (2) more consecutive blood culture sets over a 24-h period are required to detect bloodstream pathogens, and (3) a shorter duration of incubation is required to diagnose bloodstream infections. Guidelines developed in the 1970s and 1980s for processing and culturing blood may require revision.

Comparison of the Roche LightCycler vanA/vanB detection assay and culture for detection of vancomycin-resistant enterococci from perianal swabs.

We compared the performance characteristics of a real-time PCR method, the LightCycler vanA/vanB detection assay (Roche Diagnostics Corporation, Indianapolis, Ind.) to that of Enterococcosel agar (BBL, Sparks, Md.) for direct detection of vancomycin-resistant enterococci (VRE) from 894 perianal stool swabs. For 421 of 894 swabs, the result for LightCycler PCR was compared to an Enterococcosel plate containing vancomycin at 6 microg/ml; for the remaining 473 swabs, the result for LightCycler PCR was compared to an Enterococcosel plate containing 8 microg/ml vancomycin. The LightCycler method produced considerably more positive results than either the Enterococcosel plate containing vancomycin at 6 microg/ml (n = 25 versus n = 11; sensitivity, 100%; specificity, 97%; positive predictive value [PPV], 42%; negative predictive value [NPV], 100%) or the Enterococcosel plate containing vancomycin at 8 microg/ml (n = 31 versus n = 10; sensitivity, 100%; specificity, 95%; PPV, 32%; NPV, 100%). When possible, additional testing, including culture, LightCycler PCR, and/or a conventional PCR method (PCR-restriction fragment length polymorphism assay), were performed on either the original specimens or original cultures or subsequent specimens for cases in which the original specimen was positive by LightCycler PCR but the Enterococcosel plate was negative. This additional testing demonstrated positive results for 7 of 14 (50%) evaluable discordant specimens which initially tested as LightCycler PCR positive but culture negative using the Enterococcosel plate containing vancomycin at 6 microg/ml and 12 of 17 (71%) evaluable discordant specimens which initially tested as LightCycler positive but culture negative using the Enterococcosel plate containing vancomycin at (8 microg/ml). These results demonstrate that the LightCycler VRE detection assay is considerably more sensitive than the standard culture method for detecting VRE directly from perianal swab specimens. The LightCycler assay also provides results much faster than culture (approximately 3.5 versus > or =72 h). The use of this test could have important implications for the effective control and prevention of nosocomial outbreaks of VRE.