Abstract Background Early Barrett cancer can be curatively treated by endoscopic resection. The choice of the resection technique, however—endoscopic mucosal resection (EMR) or submucosal dissection ...(ESD)—largely depends on the assumed infiltration depth as judged by the endoscopist. However, the accuracy of endoscopic diagnosis of the degree of cancer infiltration is not known. Methods Three to four high‐quality images (both in overview and close‐up) from 202 of early Barrett esophagus cancer cases (82% men, mean age 66.9 years) were selected from our endoscopy database (73.3% stage T1a and 26.7% in stage T1b). Images were shown to 9 Barrett esophagus experts, with patients' clinical data (age, sex, Barrett esophagus length) and biopsy results. The experts were asked to predict infiltration depth (T1b vs. T1a), and to suggest the appropriate endoscopic resection technique (EMR or ESD, or surgery). Interobserver variability (kappa values) was also determined for these parameters. Results Overall positive (PPV) and negative predictive values (NPV) to diagnose T1b versus T1a infiltration were 40.7% (95% CI: 36.7, 44.8) and 79.8% (95% CI: 77.5, 81.9), respectively; kappa value was 0.41. Paris classification (kappa 0.51) and suggested treatment also varied between experts. In a post hoc analysis, only the correlation between lesions classified as invisible or flat according to the Paris classification (IIB; 25% of all cases) and the suggested resection technique was better: In this subgroup, EMR was recommended in >80% of cases, with a high complete (basal R0) resection rate (mean of 88.1%). Conclusions Precise endoscopic distinction between mucosal and submucosal involvement of Barrett esophagus cancer by experts as a basis for choosing the resection technique has limited predictive values and high interobserver variability. It seems that mainly invisible/flat lesions may result in good resection outcomes when treated by EMR, but this stratification strategy has to be assessed in further studies.
Colonoscopy is a widely performed procedure with procedural volumes increasing annually throughout the world. Many procedures are now performed as part of colorectal cancer screening programmes. ...Colonoscopy should be of high quality and measures of this quality should be evidence based. New UK key performance indicators and quality assurance standards have been developed by a working group with consensus agreement on each standard reached. This paper reviews the scientific basis for each of the quality measures published in the UK standards.
Background. In May–July 2011, Germany experienced a large food-borne outbreak of Shiga toxin 2—producing Escherichia coli (STEC O104:H4) with 3842 cases, including 855 cases with hemolytic uremic ...syndrome (HUS) and 53 deaths. Methods. A multicenter study was initiated in 5 university hospitals to determine pathogen shedding duration. Diagnostics comprised culture on selective media, toxin enzyme-linked immunosorbent assay, and polymerase chain reaction. Results were correlated with clinical and epidemiologic findings. Testing for pathogen excretion was continued after discharge of the patient. Results. A total of 321 patients (104 male, 217 female) were included (median age, 40 years range, 1–89 days). Median delay from onset of symptoms to hospitalization was 4 days (range, 0–17 days). Two hundred nine patients presented with HUS. The estimate for the median duration of shedding was 17–18 days. Some patients remained STEC O104:H4 positive until the end of the observation time (maximum observed shedding duration: 157 days). There was no significant influence of sex on shedding duration. Patients presenting with HUS had a significantly shortened shedding duration (median, 13–14 days) compared to non-HUS patients (median, 33–34 days). Antimicrobial treatment was also significantly associated with reduced shedding duration. Children (age ≤15 years) had longer shedding durations than adults (median, 35–41 vs 14–15 days). Conclusions. STEC O104:H4 is usually eliminated from the human gut after 1 month, but may sometimes be excreted for several months. Proper follow-up of infected patients is important to avoid further pathogen spread.
An outbreak of Shiga Toxin 2 (Stx-2) producing enterohemorrhagic and enteroaggregative E.coli (EAHEC) O104H4 infection in May 2011 caused enterocolitis and an unprecedented high 22% rate of hemolytic ...uremic syndrome (HUS). The monoclonal anti-C5 antibody Eculizumab (ECU) has been used experimentally in EAHEC patients with HUS but treatment efficacy is uncertain. ECU can effectively prevent hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) caused by a lack of complement-regulating CD55 and CD59 on blood cells. We hypothesized a low expression of CD55 and CD59, as seen in PNH, might correlate with HUS development in EAHEC patients.
76 EAHEC patients (34 only gastrointestinal symptoms GI, 23: HUS, 19: HUS and neurological symptoms HUS/N) and 12 healthy controls (HC) were tested for the expression of CD55 and CD59 on erythrocytes and leukocytes retrospectively. Additionally, the effect of Stx-2 on CD55 and CD59 expression on erythrocytes and leukocytes was studied ex vivo.
CD55 expression on erythrocytes was similar in all patient groups and HC while CD59 showed a significantly higher expression in HUS and HUS/N patients compared to HC and the GI group. CD55 and CD59 expression on leukocytes and their subsets was significantly higher in all patient groups compared to HC regardless of treatment type. However, CD59 expression on erythrocytes was significantly higher in HUS and HUS/N patients treated combined with plasma separation (PS) and ECU compared to HC. Adding Stx-2 ex vivo had no effect on CD55 and CD59 expression on leukocytes from HC or patients.
HUS evolved independently from CD55 and CD59 expression on peripheral blood cells in EAHEC O104:H4 infected patients. Our data do not support a role for CD55 and CD59 in HUS development during EAHEC O104:H4 infection and point to a different mechanism within the complement system for HUS development in EAHEC patients.
The outbreak of Shiga toxin producing E.coli O104:H4 in northern Germany in 2011 was one of the largest worldwide and involved mainly adults. Post-diarrheal hemolytic uremic syndrome (HUS) occurred ...in 22% of STEC positive patients. This study's aim was to assess risk factors for HUS in STEC-infected patients and to develop a score from routine hospital parameters to estimate patient risks for developing HUS. In a cohort analysis, adult patients with STEC infection were included in five participating hospitals in northern Germany between May and July 2011. Clinical data were obtained from questionnaires and medical records, laboratory data were extracted from hospitals' electronic data systems. HUS was defined as thrombocytopenia, hemolytic anemia and acute renal dysfunction. Random forests and multivariate logistic regression were used to identify risk factors for HUS and develop a score using the estimated coefficients as weights. Among 259 adults with STEC infection, vomiting (OR 3.48,95%CI 1.88-6.53), visible blood in stools (OR 3.91,95%CI1.20-16.01), age above 75 years (OR 3.27, 95%CI 1.12-9.70) and elevated leukocyte counts (OR 1.20, 95%CI 1.10-1.31, per 1000 cells/mm(3)) were identified as independent risk factors for HUS. A score using these variables has an area under the ROC curve of 0.74 (95%CI 0.68-0.80). Vomiting, visible blood in stools, higher leukocyte counts, and higher age indicate increased risk for developing HUS. A score using these variables might help to identify high risk patients who potentially benefit from aggressive pre-emptive treatment to prevent or mitigate the devastating consequences of HUS.
Randomized studies have demonstrated that a distal attachment cap with rubber side arms, the Endocuff Vision (ECV; Olympus America, Center Valley, Pa, USA), increased colonoscopic adenoma detection ...rate (ADR) in various mixed patient collectives. This is the first study to evaluate its use in a primary colonoscopic screening program.
Patients over age 55 years undergoing screening colonoscopy in 9 German private offices in Berlin and Hamburg were randomized to either the study group using ECV or the control group using high-definition colonoscopies (standard of care). The main outcome parameter was ADR, whereas secondary outcomes were detection rates of all adenomas per colonoscopy (APCs), of adenoma subgroups, and of hyperplastic polyps.
Of 1416 patients (mean age, 61.1 years; 51.8% women), with a median of 41 examinations per examiner (n = 23; interquartile range, 12-81), 700 were examined with ECV and 716 without. Adjusting for the effects of the colonoscopies, ADR was 39.5% (95% confidence interval CI, 32.6%-46.3%) in the ECV group versus 32.2% (95% CI, 25.9%-38.6%) in the control group, which resulted in an increase of 7.2% (95% CI, 2.3%-12.2%; P = .004). The increase in ADR was mainly because of small polyps, with adjusted ADRs for adenomas <10 mm of 33.3% (95% CI, 26.5%-40.2%) for study patients versus 24.0% (95% CI, 18.2%-29.8%) for control patients (P < .001). APC was also significantly increased (.57 ECV vs .51 control subjects, P = .045).
A distal attachment cap with side arms significantly increased the ADR in patients undergoing primary colonoscopic screening. Because of the correlation of ADR and interval cancer, its use should be encouraged, especially in this setting. (Clinical trial registration number: NCT03442738.)
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Interval cancers occur more frequently in the right colon. One reason could be that right-sided adenomas are frequently missed in colonoscopy examinations. We reanalyzed data from tandem ...colonoscopies to assess adenoma miss rates in relation to location and other factors.
We pooled data from 8 randomized tandem trials comprising 2218 patients who had diagnostic or screening colonoscopies (adenomas detected in 49.8% of patients). We performed a mixed-effects logistic regression with patients as cluster effects with different independent parameters. Factors analyzed included location (left vs right, splenic flexure as cutoff), adenoma size, form, and histologic features. Analyses were controlled for potential confounding factors such as patient sex and age, colonoscopy indication, and bowel cleanliness.
Right-side location was not an independent risk factor for missed adenomas (odds ratio OR compared with the left side, 0.94; 95% CI, 0.75–1.17). However, compared with adenomas ≤5 mm, the OR for missing adenomas of 6–9 mm was 0.62 (95% CI, 0.44–0.87), and the OR for missing adenomas of ≥10 mm was 0.51 (95% CI, 0.33–0.77). Compared with pedunculated adenomas, sessile (OR, 1.82; 95% CI, 1.16–2.85) and flat adenomas (OR, 2.47; 95% CI, 1.49–4.10) were more likely to be missed. Histologic features were not significant risk factors for missed adenomas (OR for adenomas with high-grade intraepithelial neoplasia, 0.68; 95% CI, 0.34–1.37 and OR for sessile serrated adenomas, 0.87; 95% CI, 0.47–1.64 compared with low-grade adenomas). Men had a higher number of adenomas per colonoscopy (1.27; 95% CI, 1.21–1.33) than women (0.86; 95% CI, 0.80–0.93). Men were less likely to have missed adenomas than women (OR for missed adenomas in men, 0.73; 95% CI, 0.57–0.94).
In an analysis of data from 8 randomized trials, we found that right-side location of an adenoma does not increase its odds for being missed during colonoscopy but that adenoma size and histologic features do increase risk. Further studies are needed to determine why adenomas are more frequently missed during colonoscopies in women than men.
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Purpose
The standard of care treatment for patients with advanced pancreatic neuroendocrine tumors (pNET) is a combination of streptozotocin and 5-FU. Although widely used, little is known about the ...best long-term strategy with these substances.
Methods
We here report our experience of 28 patients treated with streptozotocin/5-FU for advanced pNET with special consideration for long-term management using an extended cycle protocol.
Results
Standard 6-weekly Moertel protocol resulted in a median progression-free survival of 21 months (range 3–128) and a median overall survival of 69 months (range 3–157+) in the whole cohort. Thirteen of the 28 patients were switched to an extended 3-month cycle protocol for maintenance therapy. Of these 13 patients, 2 achieved complete remission, 1 partial remission, and 8 stable disease as best response while 2 showed progressive disease following switch to the extended protocol, resulting in an additional median progression-free survival of 23 months. Median overall survival after the start of chemotherapy in this patient group was 69 months (21–157+). Patients benefitted from extended periods free of chemotherapy-associated side effects after switching to the extended cycle protocol.
Conclusions
Switching to an extended cycle protocol of 3 months for maintenance therapy following initial standard cycles may achieve long-term disease stabilization in selected patients with advanced pNET with good patient acceptance.
From May through July 2011 in northern Germany, there was a large outbreak of hemolytic uremic syndrome and bloody diarrhea, which was related to infections from Shiga toxin-producing Escherichia ...coli O104 (STEC). We investigated the depression, posttraumatic symptoms, fatigue, and health-related quality of life among patients within the first 6 months after STEC infection and aimed to identify factors associated with poor outcome.
In a cohort study, we performed baseline assessments of 389 patients (69% female) 3 months after STEC infection (82 ± 36 days) and follow-up assessments of 308 of the patients 6 months afterward (199 ± 17 days). Data were collected at 13 hospitals in northern Germany. Patients completed validated self-report scales and a diagnostic interview.
At baseline, hemolytic uremic syndrome was diagnosed in 31% of the patients. Six months after the infection, mean self-reported severity of depression and posttraumatic symptoms and fatigue were significantly greater than in the general population, and the mean score from the mental component of health-related quality of life survey was significantly lower than average. Posttraumatic stress disorder had recently developed in 3% of patients (95% confidence interval, 1%-5%), and 43% of patients had clinically relevant fatigue (95% confidence interval, 41%-45%). The most important baseline factors associated with poor psychological health 6 months after STEC infection were previous traumatic events, neuroticism, and low social support (all P < .05).
Six months after the major outbreak of STEC infection in northern Germany, a substantial number of patients had poor psychological health, persistent fatigue, and impaired quality of life. For future outbreaks, patients' premorbid risk factors should be considered, which might minimize the long-term effects of infections on mental health.
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