Summary
Background
Azathioprine (AZA) and mercaptopurine (MP) are the cornerstone of steroid‐sparing strategies in autoimmune hepatitis (AIH). Up to 20% of patients do not tolerate or respond to ...these regimens.
Aim
To evaluate retrospectively the tolerability and efficacy of tioguanine (thioguanine) (TG) therapy in selected patients with AIH and AIH variant syndromes.
Methods
Records of 52 patients who received TG therapy were retrieved from nine hospitals in the Netherlands. Indications for TG treatment were intolerable side effects on AZA or MP (n = 38), insufficient response (n = 11) or first‐line treatment (n = 3). Treatment efficacy was defined as normalisation of serum aminotransferases and serum immunoglobulin G.
Results
No serious adverse events occurred in patients treated with TG during a median follow‐up of 18 months (range 1‐194). Treatment was well tolerated in 41 patients (79%), whereas four had tolerable (8%) and seven (13%) intolerable side effects. Thirty‐eight patients were treated with TG after intolerable side effects on AZA or MP; 29 patients continued TG therapy of whom 24 (83%) achieved complete biochemical remission, four (14%) had incomplete and one (3%) had no response; nine discontinued treatment. Seven of 11 patients with insufficient response to AZA or MP were responsive to TG, three with complete and four with incomplete biochemical remission; four discontinued due to intolerance (n = 2) and non‐response (n = 2). TG was effective in all AIH patients as first‐line maintenance treatment.
Conclusion
In our retrospective review of TG therapy in selected patients with AIH or AIH variants who previously failed on AZA or MP, TG appeared tolerable with biochemical efficacy.
Background The OLGA (operative link on gastritis assessment) staging system is based on severity of atrophic gastritis (AG). AG remains a difficult histopathologic diagnosis with low interobserver ...agreement, whereas intestinal metaplasia (IM) is associated with high interobserver agreement. Objective The aim of this study was to evaluate whether a staging system based on IM is preferable to estimate gastric cancer risk. Design and Setting Prospective multicenter study. Patients A total of 125 patients previously diagnosed with gastric IM or dysplasia. Interventions Surveillance endoscopy with extensive biopsy sampling. Main Outcome Measurements Three pathologists graded biopsy specimens according to the Sydney classification. Interobserver agreement was analyzed by kappa statistics. In the OLGA, AG was replaced by IM, creating the OLGIM. Results Interobserver agreement was fair for dysplasia (κ = 0.4), substantial for AG (κ = 0.6), almost perfect for IM (κ = 0.9), and improved for all stages of OLGIM compared with OLGA. Overall, 84 (67%) and 79 (63%) patients were classified as stage I-IV according to OLGA and OLGIM, respectively. Of the dysplasia patients, 5 (71%) and 6 (86%) clustered in stage III-IV of OLGA and OLGIM, respectively. Limitation Prospective studies should confirm the correlation between gastric cancer risk and OLGIM stages. Conclusion Replacement of AG by IM in the staging of gastritis considerably increases interobserver agreement. The correlation with the severity of gastritis remains at least as strong. Therefore, the OLGIM may be preferred over the OLGA for the prediction of gastric cancer risk in patients with premalignant lesions.
Local full-thickness resections of the scar (FTRS) after local excision of a T1 colorectal cancer (CRC) with uncertain resection margins is proposed as an alternative strategy to completion surgery ...(CS), provided that no local intramural residual cancer (LIRC) is found. However, a comparison on long-term oncological outcome between both strategies is missing.
A large cohort of patients with consecutive T1 CRC between 2000 and 2017 was used. Patients were selected if they underwent a macroscopically complete local excision of a T1 CRC but positive or unassessable (R1/Rx) resection margins at histology and without lymphovascular invasion or poor differentiation. Patients treated with CS or FTRS were compared on the presence of CRC recurrence, a 5-year overall survival, disease-free survival, and metastasis-free survival.
Of 3,697 patients with a T1 CRC, 434 met the inclusion criteria (mean age 66 years, 61% men). Three hundred thirty-four patients underwent CS, and 100 patients underwent FTRS. The median follow-up period was 64 months. CRC recurrence was seen in 7 patients who underwent CS (2.2%, 95% CI 0.9%-4.6%) and in 8 patients who underwent FTRS (9.0%, 95% CI 3.9%-17.7%). Disease-free survival was lower in FTRS strategy (96.8% vs 89.9%, P = 0.019), but 5 of the 8 FTRS recurrences could be treated with salvage surgery. The metastasis-free survival (CS 96.8% vs FTRS 92.1%, P = 0.10) and overall survival (CS 95.6% vs FTRS 94.4%, P = 0.55) did not differ significantly between both strategies.
FTRS after local excision of a T1 CRC with R1/Rx resection margins as a sole risk factor, followed by surveillance and salvage surgery in case of CRC recurrence, could be a valid alternative strategy to CS.
Advanced colorectal cancer (CRC) consensus molecular subtype 4 (CMS4) or CRC with a low immunoscore is associated with shorter survival times. Non-metastatic CRC with microsatellite instability (MSI) ...is associated with a lower risk of recurrence. We evaluated outcome (lymph node metastases LNM or cancer recurrence) in these tumor subtypes in patients with surgically-removed non-pedunculated T1 CRC by performing a multicenter case-cohort study. We included all patients in 13 hospitals in the Netherlands from 2000–2014 (n = 651). We randomly selected a subgroup of patients (n = 223) and all patients with LNM or recurrence (n = 63), and median follow-up of 44 months. We centrally reviewed tumor-slides, and constructed and immunostained tissue microarrays determining MSI, CMS (MSI/CMS1, CMS2/3, or CMS4), and immunoscore (I-low/I-high). We used weighted Cox proportional hazard models to evaluate the association of MSI, CMS, and immunoscore with LNM or recurrence, adjusting for conventional histologic risk factors. In the randomly selected subgroup of patients, 7.1% of tumors were MSI/CMS1, 91.0% CMS2/3, 1.8% CMS4, and 25% I-low. In the case-cohort, patients with CMS4 tumors had an increased risk for LNM or recurrence compared with patients with tumors of other CMSs (adjusted hazard ratio HR, 3.97; 95% CI, 1.12–14.06; P = 0.03). Albeit not significant, tumors with MSI had a lower risk for LNM or recurrence than other tumor subtypes (adjusted HR, 0.52; 95% CI, 0.12–2.30; P = 0.39), whereas tumors with a low immunoscore had an increased risk for LNM or recurrence (adjusted HR, 1.30; 95% CI, 0.68–2.48; P = 0.43). In conclusion, in a case-cohort study of patients with non-pedunculated T1 CRC, MSI, and immunoscore were not significantly associated with adverse outcome after surgery. CMS4 substantially increased the risk of adverse outcome. However, CMS4 is rare in T1 CRCs, limiting its value for determining the risk in patients.
This study evaluated the preresection accuracy of optical diagnosis of T1 colorectal cancer (CRC) in large non-pedunculated colorectal polyps (LNPCPs).
In this multicentre prospective study, ...endoscopists predicted the histology during colonoscopy in consecutive patients with LNPCPs using a standardised procedure for optical assessment. The presence of morphological features assessed with white light, and vascular and surface pattern with narrow-band imaging (NBI) were recorded, together with the optical diagnosis, the confidence level of prediction and the recommended treatment. A risk score chart was developed and validated using a multivariable mixed effects binary logistic least absolute shrinkage and selection (LASSO) model.
Among 343 LNPCPs, 47 cancers were found (36 T1 CRCs and 11 ≥T2 CRCs), of which 11 T1 CRCs were superficial invasive T1 CRCs (23.4% of all malignant polyps). Sensitivity and specificity for optical diagnosis of T1 CRC were 78.7% (95% CI 64.3 to 89.3) and 94.2% (95% CI 90.9 to 96.6), and 63.3% (95% CI 43.9 to 80.1) and 99.0% (95% CI 97.1 to 100.0) for optical diagnosis of endoscopically unresectable lesions (ie, ≥T1 CRC with deep invasion), respectively. A LASSO-derived model using white light and NBI features discriminated T1 CRCs from non-invasive polyps with a cross-validation area under the curve (AUC) of 0.85 (95% CI 0.80 to 0.90). This model was validated in a temporal validation set of 100 LNPCPs (AUC of 0.81; 95% CI 0.66 to 0.96).
Our study provides insights in the preresection accuracy of optical diagnosis of T1 CRC. Sensitivity is still limited, so further studies will show how the risk score chart could be improved and finally used for clinical decision making with regard to the type of endoresection to be used and whether to proceed to surgery instead of endoscopy.
NTR5561.
•Long-term oncologic outcomes seem similar when emergency surgery is compared to stent placement.•Permanent stoma rate is lower when patients are initially treated with SEMS as bridge to ...surgery.•Sensitivity analysis shows opposite outcomes, with a trend towards worse survival in the SEMS group when only RCTs are taken into account.•Adequate experience with SEMS placement seems of importance for long-term oncologic outcomes.
This meta-analysis aims to determine the long-term oncological outcomes of SEMS as bridge to surgery (BTS) versus emergency surgery (ES). A systematic search without restrictions was conducted, and all studies comparing SEMS with ES reporting on long-term outcomes were included. Methodological quality was assessed using the appropriate tools. Twenty-one comparative studies were selected, reporting on 1919 patients. Meta-analysis showed no significant difference regarding three- and five-year overall survival (OR = 0·85 (0·68-1·08) and OR = 1·04 (0·68-1·57), respectively), disease-free survival (OR = 0·96 (0·73-1·26) and OR = 0·86 (0·54-1·36), respectively) and local recurrence rate (OR = 1·32 (0·78-2·23)). Permanent stomas were significantly lower in the SEMS group (OR 0·49 (0·32-0·74)). Sensitivity analysis on three-year survival showed opposite outcomes, with a trend towards worse survival in the SEMS group when only RCTs are taken into account. In conclusion, when in experienced hands, SEMS placement as BTS seems oncologically safe.
Introduction
Guidelines recommend endoscopy with biopsies to stratify patients with gastric premalignant lesions (GPL) to high and low progression risk. High-risk patients are recommended to undergo ...surveillance. We aimed to assess the accuracy of guideline recommendations to identify low-risk patients, who can safely be discharged from surveillance.
Methods
This study includes patients with GPL. Patients underwent at least two endoscopies with an interval of 1–6 years. Patients were defined ‘low risk’ if they fulfilled requirements for discharge, and ‘high risk’ if they fulfilled requirements for surveillance, according to European guidelines (MAPS-2012, updated MAPS-2019, BSG). Patients defined ‘low risk’ with progression of disease during follow-up (FU) were considered ‘misclassified’ as low risk.
Results
334 patients (median age 60 years IQR11; 48.7% male) were included and followed for a median of 48 months. At baseline, 181/334 (54%) patients were defined low risk. Of these, 32.6% were ‘misclassified’, showing progression of disease during FU. If MAPS-2019 were followed, 169/334 (51%) patients were defined low risk, of which 32.5% were ‘misclassified’. If BSG were followed, 174/334 (51%) patients were defined low risk, of which 32.2% were ‘misclassified’. Seven patients developed gastric cancer (GC) or dysplasia, four patients were ‘misclassified’ based on MAPS-2012 and three on MAPS-2019 and BSG. By performing one additional endoscopy 72.9% (95% CI 62.4–83.3) of high-risk patients and all patients who developed GC or dysplasia were identified.
Conclusion
One-third of patients that would have been discharged from GC surveillance, appeared to be ‘misclassified’ as low risk. One additional endoscopy will reduce this risk by 70%.
IMPORTANCE: Bridge to elective surgery using self-expandable metal stent (SEMS) placement is a debated alternative to emergency resection for patients with left-sided obstructive colon cancer because ...of oncologic concerns. A decompressing stoma (DS) might be a valid alternative, but relevant studies are scarce. OBJECTIVE: To compare DS with SEMS as a bridge to surgery for nonlocally advanced left-sided obstructive colon cancer using propensity score matching. DESIGN, SETTING, AND PARTICIPANTS: This national, population-based cohort study was performed at 75 of 77 hospitals in the Netherlands. A total of 4216 patients with left-sided obstructive colon cancer treated from January 1, 2009, to December 31, 2016, were identified from the Dutch Colorectal Audit and 3153 patients were studied. Additional procedural and intermediate-term outcome data were retrospectively collected from individual patient files, resulting in a median follow-up of 32 months (interquartile range, 15-57 months). Data were analyzed from April 7 to October 28, 2019. EXPOSURES: Decompressing stoma vs SEMS as a bridge to surgery. MAIN OUTCOMES AND MEASURES: Primary anastomosis rate, postresection presence of a stoma, complications, additional interventions, permanent stoma, locoregional recurrence, disease-free survival, and overall survival. Propensity score matching was performed according to age, sex, body mass index, American Society of Anesthesiologists score, prior abdominal surgery, tumor location, pN stage, cM stage, length of stenosis, and year of resection. RESULTS: A total of 3153 of the eligible 4216 patients were included in the study (mean SD age, 69.7 11.8 years; 1741 55.2% male); after exclusions, 443 patients underwent bridge to surgery (240 undergoing DS and 203 undergoing SEMS). Propensity score matching led to 2 groups of 121 patients each. Patients undergoing SEMS had more primary anastomoses (104 of 121 86.0% vs 90 of 120 75.0%, P = .02), more postresection stomas (81 of 121 66.9% vs 34 of 117 29.1%, P < .001), fewer major complications (7 of 121 5.8% vs 18 of 118 15.3%, P = .02), and more subsequent interventions, including stoma reversal (65 of 113 57.5% vs 33 of 117 28.2%, P < .001). After DS and SEMS, the 3-year locoregional recurrence rates were 11.7% for DS and 18.8% for SEMS (hazard ratio HR, 0.62; 95% CI, 0.30-1.28; P = .20), the 3-year disease-free survival rates were 64.0% for DS and 56.9% for SEMS (HR, 0.90; 95% CI, 0.61-1.33; P = .60), and the 3-year overall survival rates were 78.0% for DS and 71.8% for SEMS (HR, 0.77; 95% CI, 0.48-1.22; P = .26). CONCLUSIONS AND RELEVANCE: The findings suggest that DS as bridge to resection of left-sided obstructive colon cancer is associated with advantages and disadvantages compared with SEMS, with similar intermediate-term oncologic outcomes. The existing equipoise indicates the need for a randomized clinical trial that compares the 2 bridging techniques.
Recommendations in Barrett’s esophagus (BE) guidelines are mainly based on male patients. We aimed to evaluate sex differences in BE patients in (1) probability of and (2) time to neoplastic ...progression, and (3) differences in the stage distribution of neoplasia. We conducted a multicenter prospective cohort study including 868 BE patients. Cox regression modeling and accelerated failure time modeling were used to estimate the sex differences. Neoplastic progression was defined as high-grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC). Among the 639 (74%) males and 229 females that were included (median follow-up 7.1 years), 61 (7.0%) developed HGD/EAC. Neoplastic progression risk was estimated to be twice as high among males (HR 2.26, 95% CI 1.11–4.62) than females. The risk of HGD was found to be higher in males (HR 3.76, 95% CI 1.33–10.6). Time to HGD/EAC (AR 0.52, 95% CI 0.29–0.95) and HGD (AR 0.40, 95% CI 0.19–0.86) was shorter in males. Females had proportionally more EAC than HGD and tended to have higher stages of neoplasia at diagnosis. In conclusion, both the risk of and time to neoplastic progression were higher in males. However, females were proportionally more often diagnosed with (advanced) EAC. We should strive for improved neoplastic risk stratification per individual BE patient, incorporating sex disparities into new prediction models.
In contrast to the adverse event (AE) risk of endoscopic resection (ER) of adenomas, the intra- and postprocedural AE risks of ER of T1 colorectal cancer (CRC) are scarcely reported in the ...literature. It is unclear whether ER of early CRCs, which grow into the submucosal layer and sometimes show incomplete lifting, is associated with an increased AE risk. We aimed to identify the AE rate after ER of T1 CRCs and to identify the risk factors associated with these AEs.
Medical records of patients with T1 CRCs diagnosed between 2000 and 2014 in 15 hospitals in the Netherlands were reviewed. Patients who underwent primary ER were selected. The primary outcome was the occurrence of endoscopy-related AEs. The secondary outcome was the identification of risk factors. Multivariate logistic regression was performed.
Endoscopic AEs occurred in 59 of 1069 (5.5%) patients, among which 37.3% were classified as mild, 59.3% as moderate, and 3.4% as severe. AEs were postprocedural bleeding (n = 40, 3.7%), perforation (n = 13, 1.2%), and postpolypectomy electrocoagulation syndrome (n = 6, 0.6%). No fatal AEs were observed. Independent predictors for AEs were age >70 years (odds ratio, 2.11; 95% confidence interval, 1.12-3.96) and tumor size >20 mm (odds ratio, 2.22; 95% confidence interval, 1.05-4.69).
In this large multicenter retrospective cohort study, AE rates of ER of T1 CRC (5.5%) are comparable with reported AE rates for adenomas. Larger tumor size and age >70 years are independent predictors for AEs. This study suggests that endoscopic treatment of T1 CRCs is not associated with an increased periprocedural AE risk.
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