F ter Borg

Predictors for neoplastic progression in patients with Barrett's Esophagus: a prospective cohort study

OBJECTIVES:Patients with Barretts esophagus (BE) have an increased risk of developing esophageal adenocarcinoma (EAC). As the absolute risk remains low, there is a need for predictors of neoplastic progression to tailor more individualized surveillance programs. The aim of this study was to identify such predictors of progression to high-grade dysplasia (HGD) and EAC in patients with BE after 4 years of surveillance and to develop a prediction model based on these factors.METHODS:We included 713 patients with BE (≥2 cm) with no dysplasia (ND) or low-grade dysplasia (LGD) in a multicenter, prospective cohort study. Data on age, gender, body mass index (BMI), reflux symptoms, tobacco and alcohol use, medication use, upper gastrointestinal (GI) endoscopy findings, and histology were prospectively collected. As part of this study, patients with ND underwent surveillance every 2 years, whereas those with LGD were followed on a yearly basis. Log linear regression analysis was performed to identify risk factors associated with the development of HGD or EAC during surveillance.RESULTS:After 4 years of follow-up, 26/713 (3.4%) patients developed HGD or EAC, with the remaining 687 patients remaining stable with ND or LGD. Multivariable analysis showed that a known duration of BE of ≥10 years (risk ratio (RR) 3.2; 95% confidence interval (CI) 1.3–7.8), length of BE (RR 1.11 per cm increase in length; 95% CI 1.01–1.2), esophagitis (RR 3.5; 95% CI 1.3–9.5), and LGD (RR 9.7; 95% CI 4.4–21.5) were significant predictors of progression to HGD or EAC. In a prediction model, we found that the annual risk of developing HGD or EAC in BE varied between 0.3% and up to 40%. Patients with ND and no other risk factors had the lowest risk of developing HGD or EAC (<1%), whereas those with LGD and at least one other risk factor had the highest risk of neoplastic progression (18–40%).CONCLUSIONS:In patients with BE, the risk of developing HGD or EAC is predominantly determined by the presence of LGD, a known duration of BE of ≥10 years, longer length of BE, and presence of esophagitis. One or combinations of these risk factors are able to identify patients with a low or high risk of neoplastic progression and could therefore be used to individualize surveillance intervals in BE.

Relation between laboratory test results and histological hepatitis activity in individuals positive for hepatitis B surface antigen and antibodies to hepatitis B e antigen

BACKGROUND Hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B e antigen (anti-HBe) commonly coexist, and laboratory tests are often requested to assess histological hepatitis activity. An optimum panel of tests has not been found and the usefulness of hepatitis B virus (HBV) DNA assays in this context has not been established. We assessed various blood tests to find which best predicted hepatitis activity. METHODS Routine plasma biochemical liver tests and serum HBV DNA (hybridisation and PCR assays) were assessed prospectively in 123 patients positive for HBsAg and anti-HBe. We scored histological hepatitis activity (hepatitis activity index) and determined whether chronic active hepatitis (chronic hepatitis with portal and periportal lesions) was present. We analysed the relation between laboratory data and the hepatitis activity index or risk of chronic active hepatitis by multiple regression and multiple logistic regression, respectively. FINDINGS The analyses provided models for predicting either the hepatitis activity index or the risk of chronic active hepatitis. Aspartate aminotransferase was the most important test in the two models. The contribution of HBV DNA and other assays, especially alanine-aminotransferase activity, were of no practical importance. INTERPRETATION Because screening by aspartate-aminotransferase activity could not be improved by the addition of other assays or HBV DNA, patients positive for HBsAg and anti-HBe could be screened for chronic active hepatitis with a single assay and counselling of patients can be improved if proper reference values are used.

A survey of liver pathology in needle biopsies from HBsAg and anti-HBe positive individuals

Aims—To use laboratory data and liver biopsies, prospectively obtained from hepatitis B surface antigen (HBsAg) and anti hepatitis B e antigen (anti-HBe) positive patients, for the assessment of: (1) the relation between biopsy length/number of portal tracts and sampling error; (2) the relation between the severity of piecemeal necrosis and the new grading terminology (minimal, mild, moderate, and severe chronic hepatitis); and (3) liver pathology, which has not been studied in patients with this specific serological profile. Methods—The study group (n = 174) included 104 patients with normal aminotransferase concentrations and no cases with clinically apparent cirrhosis. The specimen length and number of portal tracts were measured at light microscopy examination. Sampling error analysis was related to the discrepancies between aminotransferase concentrations versus histological grade. Detailed histological scorings were undertaken by the reference pathologist and compared with laboratory and hepatitis B virus (HBV) DNA precore sequence data. Results—Sampling error seemed to be a constant feature, even for biopsies ≥ 20 mm, but increased dramatically in biopsies < 5 mm long and/or containing less than four portal tracts. Between 25% and 30% of biopsies, graded as “mild” or “moderate” activity showed features of moderate and severe piecemeal necrosis, respectively. Ten per cent of the patients with normal aminotransferase values had stage III–IV hepatic fibrosis, and 20% had piecemeal necrosis. Only cytoplasmic, not nuclear, core antigen expression was a strong predictor of high hepatitis B viraemia. There was no association between precore stop codon mutations, grade/stage of liver disease, and hepatitis B core antigen (HBcAg) expression. Conclusions—The specimen available for light microscopical examination should be > 5 mm long and should contain more than four portal tracts. In addition, the new grading terminology might give the clinician an inappropriately mild impression of the severity of piecemeal necrosis. Furthermore, even in the presence of normal aminotransferase concentrations, considerable liver pathology can be found in 10–20% of HBsAg and anti-HBe positive individuals; such pathology is not associated with the occurrence of precore stop codon mutations.

Combination therapy with mycophenolate mofetil and ursodeoxycholic acid for primary biliary cirrhosis.

Evidence of autoimmunity in primary biliary cirrhosis (PBC) provides a rationale for treatment with an immunosuppressant. Such a drug should be sufficiently free from serious toxicities to enable patients with asymptomatic, but progressive, disease to be treated longterm. Mycophenolate mofetil (MMF) mediates immunosuppression by selectively and reversibly inhibiting lymphocyte function, and has a more acceptable safety profile than other immunosuppressants that have been used in the treatment of this disease. Two patients, whose response to long-term treatment with ursodeoxycholic acid (UDCA) had been inadequate, were treated with a combination of MMF 2 g daily and UDCA 1 g daily for 12 months. In both patients this regimen was associated with no clinically significant adverse events, a decrease in elevated serum alkaline phosphatase levels to values close to the upper limit of normal, and an almost complete disappearance of the chronic inflammatory cell infiltrate that had been present in pre-combination treatment liver biopsies. MMF may be an appropriate immunosuppressive drug for use in the long-term treatment of patients with PBC, including asymptomatic patients.

Low Morbidity and Mortality after Stenting for Malignant Bowel Obstruction

Background: The difference in mortality between emergency and elective surgery for malignant colonic obstruction is more than 5% in healthy patients below the age of 65 and increases with age to around 20%. Emergency surgery can be avoided by endoscopic placement of a self-expandable metal stent (SEMS). Aim: To evaluate the effectiveness and safety of SEMS as ‘bridge to surgery’. Method: Between January 2001 and July 2008, SEMS were placed for acute malignant colonic obstruction in 45 patients (median age 72 years, range 35–91). Results: The procedure was technically successful in 43 patients (94%) with resolution of obstructive symptoms within 48 h in 87% of the patients. No perforations occurred during the procedure or while awaiting surgery. Two (4%) patients required a second endoscopic procedure. All patients underwent a single-stage surgical procedure. Postoperative mortality was 2.2% (n = 1). Histology showed advanced colorectal cancer (T3–4N1–2M0–1) in 75% of the patients. Conclusion: SEMS placement is a safe and effective procedure as bridge to surgery in patients presenting with colonic obstruction due to colorectal malignancy. This procedure carries a risk of serious complications well below that of the reported difference in mortality between emergency an elective surgery.

Risk for Incomplete Resection after Macroscopic Radical Endoscopic Resection of T1 Colorectal Cancer: A Multicenter Cohort Study

Objectives:The decision to perform secondary surgery after endoscopic resection of T1 colorectal cancer (CRC) depends on the risk of lymph node metastasis and the risk of incomplete resection. We aimed to examine the incidence and risk factors for incomplete endoscopic resection of T1 CRC after a macroscopic radical endoscopic resection.Methods:Data from patients treated between 2000 and 2014 with macroscopic complete endoscopic resection of T1 CRC were collected from 13 hospitals. Incomplete resection was defined as local recurrence at the polypectomy site during follow-up or malignant tissue in the surgically resected specimen in case secondary surgery was performed. Multivariate regression analysis was performed to analyze factors associated with incomplete resection.Results:In total, 877 patients with a median follow-up time of 36.5 months (interquartile range 16.0–68.3) were included, in whom secondary surgery was performed in 358 patients (40.8%). Incomplete resection was observed in 30 patients (3.4%; 95% confidence interval (CI) 2.3–4.6%). Incomplete resection rate was 0.7% (95% CI 0–2.1%) in low-risk T1 CRC vs. 4.4% (95% CI 2.7–6.5%) in high-risk T1 CRC (P=0.04). Overall adverse outcome rate (incomplete resection or metastasis) was 2.1% (95% CI 0–5.0%) in low-risk T1 CRC vs. 11.7% (95% CI 8.8–14.6%) in high-risk T1 CRC (P=0.001). Piecemeal resection (adjusted odds ratio 2.60; 95% CI 1.20–5.61, P=0.02) and non-pedunculated morphology (adjusted odds ratio 2.18; 95% CI 1.01–4.70, P=0.05) were independent risk factors for incomplete resection. Among patients in whom no additional surgery was performed, who developed recurrent cancer, 41.7% (95% CI 20.8–62.5%) died as a result of recurrent cancer.Conclusions:In the absence of histological high-risk factors, a ‘wait-and-see’ policy with limited follow-up is justified. Piecemeal resection and non-pedunculated morphology are independent risk factors for incomplete endoscopic resection of T1 CRC.

Self-expandable metal stent placement versus emergency resection for malignant proximal colon obstructions

BackgroundTraditionally, all patients with a malignant obstruction of the proximal colon (MOPC) are treated with emergency resection. However, recent data suggest that Self-expandable metallic stent (SEMS) placement could lower mortality and morbidity rates. This study therefore aimed to compare SEMS placement with emergency resection as treatment options for MOPC.MethodsAll consecutive patients that underwent SEMS placement for MOPC in the period 2004–2015 at our institution were identified. SEMS placement was the standard of care for colonic obstructions at our institution in that period. All included SEMS patients were matched (1:4) on age (±5 years), gender, ASA-score, tumor location, surgical approach and pTNM-stage with patients treated by emergency resection. Controls were selected from a national database that prospectively registers all patients undergoing surgery for colorectal cancer in the Netherlands.ResultsIn total, 41 patients received SEMS placement for MOPC. In 19 patients SEMS served as a definite palliative measure and in 22 as bridge to surgery. Technical and clinical success rates of SEMS placement were 92.7% and 90.2%, respectively. No significant differences between the SEMS and emergency resection group were found regarding morbidity and mortality rates, the number of radical resections and the number of primary anastomoses. Patients treated with SEMS were, however, less likely to have a temporary stoma constructed (p = 0.04). No SEMS-related complications occurred in patients in whom SEMS was placed as bridge to surgery, whereas one stent-related perforation, three stent migrations, and five stent re-obstructions were observed in the palliative group. Three re-obstructions could be treated with re-stenting, but all other SEMS-related complications required surgical intervention. In the palliative group, SEMS complications necessitating surgery occurred in 31.6% of the patients (6/19).ConclusionSEMS placement for MOPC appears to be a relatively feasible and safe alternative for emergency resection in both the curative and palliative setting.