Thjon J. Tang

Quality evaluation of colonoscopy reporting and colonoscopy performance in daily clinical practice

BACKGROUND Comprehensive monitoring of colonoscopy quality requires complete and accurate colonoscopy reporting. OBJECTIVE This study aimed to assess the compliance with colonoscopy reporting and to assess the quality of colonoscopy performance. DESIGN Consecutive colonoscopy reports were reviewed by hand. Four hundred reports were included from each department. SETTING Daily clinical practice in 12 Dutch endoscopy departments. PATIENTS Consecutive patients undergoing scheduled colonoscopy procedures. MAIN OUTCOME MEASUREMENTS Quality of reporting was assessed by using the American Society for Gastrointestinal Endoscopy criteria for colonoscopy reporting. Quality of colonoscopy performance was evaluated by using the cecal intubation rate and adenoma detection rate (ADR). RESULTS A total of 4800 colonoscopies were performed by 116 endoscopists: 70% by gastroenterologists, 16% by gastroenterology fellows, 10% by internists, 3% by nurse-endoscopists, and 1% by surgeons. The mean age of the patients was 59 years (standard deviation 16), and 47% were male. Reports contained information on indication, sedation practice, and extent of the procedure in more than 90%. Only 62% of the reports mentioned the quality of bowel preparation (range between departments 7%-100%); photographic documentation of the cecal landmarks was present in 71% (range 22%-97%). The adjusted cecal intubation rate was 92% (range 84%-97%). The ADR was 24% (range 13%-32%). LIMITATIONS Dependent on reports, no intervention in endoscopic practice. No analysis for performance per endoscopist. CONCLUSION Colonoscopy reporting varied significantly in clinical practice. Colonoscopy performance met the suggested standards; however, considerable variability between endoscopy departments was found. The results of this study underline the importance of the implementation of quality indicators and guidelines. Moreover, by continuous monitoring of quality parameters, the quality of both colonoscopy reporting and colonoscopy performance can easily be improved.

The prognostic value of histology in the assessment of patients with Budd-Chiari syndrome

BACKGROUND/AIMS It is unclear whether treatment of patients with Budd-Chiari syndrome (BCS) should be based on liver histology, as large histopathological studies have not been performed. We investigated the relationship between the histopathological findings and survival. METHODS We studied the clinical features and findings on biopsy specimens in 45 patients with BCS who were admitted to four tertiary referral medical centers. Histological findings, i.e. congestion, necrosis, inflammation and fibrosis, were graded. Survival was assessed in relation to histological findings and clinical features at the time of diagnosis as well as in relation to subsequent treatment with or without portosystemic shunting. RESULTS Centrilobular congestion, centrilobular necrosis, lobular inflammation and portal inflammation were not significantly related to survival. In addition, there was no association between either pericentral or periportal fibrosis and survival. Univariate analysis revealed that the prothrombin time and Child-Pugh score were significantly related to survival (P = 0.005 and Ptrend = 0.02, respectively). Multivariate analysis yielded the Child-Pugh score, serum alanine aminotransferase (ALT) and treatment with portosystemic shunting as independent prognostic indicators. CONCLUSIONS We found no evidence for a relationship between early liver pathology and survival. Child-Pugh score, serum ALT and portosystemic shunting appeared to be prognostic indicators for patients with BCS.

The role of intrahepatic immune effector cells in inflammatory liver injury and viral control during chronic hepatitis B infection

Summary. Cytotoxic T lymphocytes (CTL) and Kupffer cells play an important role in the immune control of hepatitis B virus (HBV), but may also induce liver injury during infection. We investigated the intrahepatic immune response in liver biopsies of chronic HBV patients in relation to inflammatory liver injury and viral control. Forty‐seven liver biopsies from patients with chronic HBV with varying degrees of inflammation (ALT values) were selected. Acute hepatitis and normal liver specimens served as controls. Immune effector cells, cytotoxic effector molecules and cytokine producing cells were quantified after immunohistochemical staining in lobular and portal areas of the biopsies. The intralobular number of CD8+ T‐lymphocytes was significantly decreased in biopsies of patients with high ALT (r = −0.54; P < 0.001). Higher ALT‐values were correlated with increased numbers of granzyme+ cells in portal areas (r = 0.65; P < 0.001) and higher numbers of intralobular Fas‐L+ cells (r = 0.32; P = 0.05). Fas‐L was expressed on Kupffer and lymphoid cells. More intralobular CD8+ T‐lymphocytes were found in HBeAg− than in HBeAg+ patients (P = 0.002). But IFN‐γ and TNF‐α producing cells were observed sporadically in chronic HBV patients. Hence, in chronic HBV infection, low viral replication and HBeAg negativity is related to increased presence of intralobular CD8+ T‐lymphocytes. Persistence of the virus may be caused by the absence of cells producing anti‐viral cytokines in the liver. Inflammatory liver injury during chronic HBV infection is probably not the result of increased numbers of infiltrating CD8+ T‐lymphocytes, but of Fas‐L expression by Kupffer cells and increased cytolytic activity of cells in portal areas.

Phenotype of inflammatory bowel disease at diagnosis in the Netherlands: a population-based inception cohort study (the Delta Cohort).

Background: To describe the clinical characteristics of inflammatory bowel disease (IBD) at diagnosis in The Netherlands at the population level in the era of biologics. Methods: All patients with newly diagnosed IBD (diagnosis made between January 1, 2006 and January 1, 2007) followed in 9 general hospitals in the southwest of the Netherlands were included in this population-based inception cohort study. Results: A total of 413 patients were enrolled, of which 201 Crohn’s disease (CD) (48.7%), 188 ulcerative colitis (UC) (45.5%), and 24 IBD unclassified (5.8%), with a median age of 38 years (range, 14–95). Seventy-eight patients with CD (38.8%) had ileocolonic disease and 73 patients (36.3%) had pure colonic disease. In 8 patients (4.0%), the upper gastrointestinal tract was involved. Nineteen patients with CD (9.5%) had perianal disease. Thirty-nine patients with CD (19.4%) had stricturing phenotype. Of the patients with UC and IBDU, 39 (18.4%) suffered from pancolitis and 61 (29%) from proctitis. Severe endoscopic lesions at diagnosis were seen in 119 patients (28.8%, 68 CD, 49 UC, and 2 IBDU), whereas 98 patients (23.7%) had severe histological disease activity. Thirteen patients (3.1%, 10 CD and 3 UC) had extraintestinal manifestations at diagnosis. Twenty-three patients (5.6%, 20 CD and 3 UC) had fistula at diagnosis. Conclusions: In this cohort, 31% of the patients with CD had complicated disease at diagnosis, 39% had ileocolonic disease, 9.5% had perianal disease, and in 4% the upper gastrointestinal tract was involved. Most patients with UC suffered from left-sided colitis (51%). Severe endoscopic lesions were reported in 34% of the patients with CD and 26% of the patients with UC. Three percent of the patients with IBD had extraintestinal manifestations.

The intrahepatic immune response during chronic hepatitis B infection can be monitored by the fine-needle aspiration biopsy technique

Frequent analysis of the intrahepatic cellular immune response during chronic hepatitis B infection is not feasible with the liver tissue biopsy technique, due to its risk profile and patient discomfort. We investigated whether the relatively safe and patient-friendly cytological fine-needle aspiration biopsy (FNAB) technique is suited for this purpose. FNABs taken during hepatitis flares in three chronic hepatitis B patients treated with interferon-alpha, showed significant increments of CD8(+)-lymphocytes compared with the FNABs taken before and after the flares. No increments were observed in peripheral blood. The increments of intrahepatic CD8+ lymphocytes detected by the FNAB were related to anti-viral immune reactivity, since they coincided with significant serum hepatitis B virus DNA level reductions and in two of three patients with HBeAg seroconversion. In conclusion, the FNAB technique is suited to investigate the intrahepatic immune response during chronic hepatitis B infection on a frequent basis.

The Incidence of 30-Day Adverse Events After Colonoscopy Among Outpatients in the Netherlands

OBJECTIVES:Colonoscopy is the gold standard for visualization of the colon. It is generally accepted as a safe procedure and major adverse events occur at a low rate. However, few data are available on structured assessment of (minor) post-procedural adverse events.METHODS:Consecutive outpatients undergoing colonoscopy were asked for permission to be called 30 days after their procedure. A standard telephone interview was developed to assess the occurrence of (i) major adverse events (hospital visit required), (ii) minor adverse events, and (iii) days missed from work. Adverse events were further categorized in definite-, possible-, and unrelated adverse events. Patients were contacted between January 2010 and September 2010.RESULTS:Out of a total of 1,528 patients who underwent colonoscopy and gave permission for a telephone call, 1,144 patients were contacted (response: 75%), 49% were male, the mean age was 59 years (s.d.: 14). Thirty-four patients (3%) reported major adverse events. These were definite-related in nine (1%) patients, possible-related in 6 (1%), and unrelated in 19 patients (2%). Minor adverse events were reported by 466 patients (41%). These were definite-related in 336 patients (29%), possible-related in 36 (3%), and unrelated in the remaining 94 patients (8%). Female gender (odds ratio (OR): 1.5), age <50 years (OR: 1.5), colonoscopy for colorectal cancer screening/surveillance (OR: 1.6), and fellow-endoscopy (OR: 1.7) were risk factors for the occurrence of any definite-related adverse event. Patients who reported definite-related adverse events were significantly less often willing to return for colonoscopy (81 vs. 88%, P<0.01) and were less often positive about the entire colonoscopy experience (84 vs. 89%, P=0.04).CONCLUSIONS:Structured assessment of post-colonoscopy adverse events shows that these are more common than generally reported. Close to one-third of patients report definite-related adverse events, which are major in close to 1 in 100 patients. The occurrence of adverse events does have an impact on the willingness to return for colonoscopy.

Monitoring intrahepatic CD8+ T cells by fine-needle aspiration cytology in chronic hepatitis C infection

Summary.  Infection of the liver with hepatitis C virus (HCV) causes compartmentalization of CD8+ cytotoxic T cells to the site of disease. These cells are thought to be involved in viral clearance during interferon therapy. The repetitive analysis of the intrahepatic immune response is hampered by the difficulty to obtain the intrahepatic T cells. The fine‐needle aspiration biopsy (FNAB) technique was evaluated for its use to obtain liver‐derived CD8+ T cells in a minimally invasive way. In 26 chronic HCV patients who were evaluated for Peg‐interferon and ribavirin combination therapy, pre‐treatment FNABs and peripheral blood specimens were obtained simultaneously with liver tissue biopsies, and CD3+ and CD8+ T cells were quantified by immunocytochemistry. The CD8+/CD3+ ratio was significantly higher in the FNABs than in peripheral blood (P < 0.01), and similar to those in portal areas in the tissue biopsies. A significant correlation was observed between numbers of CD3+CD8+ T lymphocytes in the FNABs and the numbers of CD8+ cells in the lobular fields or in the portal tracts of the liver tissue biopsies, but not with CD3+CD8+ T lymphocytes in peripheral blood. Finally, the ratio of CD8+/CD3+ T lymphocytes in FNABs was significantly higher in those patients who responded rapidly to therapy when compared with slow responders at 4 weeks of treatment (P = 0.02). These findings demonstrate that the intrahepatic T‐cell composition is reflected in FNABs, and that the FNAB technique can be used for predicting early virological response to therapy of patients chronically infected with HCV.

Benefit of Earlier Anti-TNF Treatment on IBD Disease Complications?

BACKGROUND Anti-tumour necrosis factor [anti-TNF] treatment was demonstrated to have disease-modifying abilities in inflammatory bowel disease [IBD]. In this study, we aimed to determine the effect of anti-TNF treatment timing on IBD disease complications and mucosal healing [MH]. METHODS The following IBD-related complications were tested in relation to timing of anti-TNF therapy start in newly diagnosed IBD patients [n = 413]: fistula formation, abscess formation, extra-intestinal manifestations [EIM], surgery, referral to academic centre, and MH. RESULTS A total of 85 patients [21%] received anti-TNF (66 Crohns disease [CD], 16 ulcerative colitis [UC], 3 inflammatory bowel disease unclassified [IBDU]) of whom 57% [48 patients] were treated < 16 months after diagnosis. Patients receiving anti-TNF early [< 16 months] did not differ from patients receiving anti-TNF late [> 16 months] regarding gender, age, smoking status, and familial IBD. More importantly, patients receiving anti-TNF early did not suffer less IBD-related complications during follow-up as compared with patients started on anti-TNF late, nor was more MH observed. Similar results were obtained when anti-TNF treated patient were stratified more stringently, ie < 12 months [40 patients] vs >2 4 months [24 patients]. Cox regression analysis showed no beneficial correlations between anti-TNF timing and IBD-related complications. Anti-TNF treated patients achieving MH were 11 times less likely to develop EIMs compared with patients who did not achieved MH while on anti-TNF. CONCLUSIONS This study was unable to confirm a benefit of earlier anti-TNF treatment on IBD disease complications. This could be explained by more aggressive treatment earlier in disease, resulting in fewer IBD complications. However, it seems more likely that inappropriate selection of patients for therapy leads to suboptimal treatment and subsequently suboptimal outcome.

Exploring diagnostic and therapeutic implications of endoscopic mucosal resection in EUS-staged T2 esophageal adenocarcinoma

Background and study aims Treatment strategies for clinical (c)T2N0M0 esophageal adenocarcinoma (EAC) are subject to debate owing to the relative inaccuracy of tumor staging by endoscopic ultrasound (EUS), with profound implications in overstaged patients. We aimed to evaluate the final histological diagnosis of patients initially staged as having a cT2 tumor by EUS, and to assess the value of endoscopic reassessment by an interventional endoscopist, followed by an endoscopic resection when deemed feasible. Patients and methods Two distinct cohorts of patients with cT2 EAC as determined by EUS were included: a retrospective surgical cohort of patients treated by primary esophagectomy, and a prospective cohort of patients who underwent an endoscopic reassessment by an interventional endoscopist. The main outcome measure was the final pathological (p)T stage. Results We identified 134 patients with stage T2 EAC from the surgical cohort. In 72 patients treated by primary esophagectomy, 32/72 (44 %) were downstaged to a pT1 tumor. In 12/72 (17 %), the surgical resection specimen showed tumor characteristics that fulfilled the current criteria for a curative endoscopic resection. In 13 prospectively identified patients with cT2N0M0 EAC, an expert endoscopic reassessment was done. In 11/13 (85 %) the lesion appeared endoscopically resectable and a complete endoscopic resection was performed. Histology revealed a pT1 tumor in all 11 patients, with 5/13 (38 %) fulfilling current criteria for a curative endoscopic resection. Conclusions In this study, 44 % of cT2 EACs were in fact pT1 tumors. Curative treatment by endoscopic resection was achieved in more than a third of these cases. To avoid an unnecessary esophagectomy, an endoscopic reassessment by an interventional endoscopist is recommended for all patients with cT2N0M0 EAC.

Fully vs. partially covered selfexpandable metal stent for palliation of malignant esophageal strictures: a randomized trial (the COPAC study)

BACKGROUND Covered esophageal self-expandable metal stents (SEMSs) are currently used for palliation of malignant dysphagia. The optimal extent of the covering to prevent recurrent obstruction is unknown. Therefore, we aimed to compare fully covered (FC) versus partially covered (PC) SEMSs in patients with incurable malignant esophageal stenosis. METHODS In this multicenter randomized controlled trial, 98 incurable patients with dysphagia caused by a malignant stricture of the esophagus or cardia were randomized 1:1 to an FC-SEMS or PC-SEMS. The primary outcome was recurrent obstruction after endoscopic SEMS placement. Secondary outcomes were technical and clinical success, adverse events, and health-related quality of life (HRQoL). Patients were followed until 6 months after SEMS placement or to SEMS removal, second SEMS insertion, or death, whichever came first. RESULTS Recurrent obstruction after SEMS placement was similar for both types of stents: 19 % for FC-SEMSs and 22 % for PC-SEMSs (P = 0.65). The times to recurrent obstruction did not differ. The frequency of adverse events was similar between the two groups, with major adverse events occurring in 38 % and 47 % of patients for FC-SEMSs and PC-SEMSs, respectively (P = 0.34). No significant differences were seen in technical success, improvement of dysphagia, and HRQoL. Proximal esophageal stenosis and female sex were independently associated with recurrent obstruction and/or major adverse events. CONCLUSIONS Esophageal FC-SEMSs did not reveal a lower recurrent obstruction rate compared with PC-SEMSs in the palliative management of malignant dysphagia.