Incidence and Prediction of Unrelated Mortality After Successful Endoscopic Eradication Therapy for Barrett's Neoplasia

Background &amp; Aims: Follow-up (FU) strategies after endoscopic eradication therapy (EET) for Barrett's neoplasia do not consider the risk of mortality from causes other than esophageal adenocarcinoma (EAC). We aimed to evaluate this risk during long-term FU, and to assess whether the Charlson Comorbidity Index (CCI) can predict mortality. Methods: We included all patients with successful EET from the nationwide Barrett registry in the Netherlands. Data were merged with National Statistics for accurate mortality data. We evaluated annual mortality rates (AMRs, per 1000 person-years) and standardized mortality ratio for other-cause mortality. Performance of the CCI was evaluated by discrimination and calibration. Results: We included 1154 patients with a mean age of 64 years (±9). During median 59 months (p25–p75 37–91; total 6375 person-years), 154 patients (13%) died from other causes than EAC (AMR, 24.1; 95% CI, 20.5–28.2), most commonly non-EAC cancers (n = 58), cardiovascular (n = 31), or pulmonary diseases (n = 26). Four patients died from recurrent EAC (AMR, 0.5; 95% CI, 0.1–1.4). Compared with the general Dutch population, mortality was significantly increased for patients in the lowest 3 age quartiles (ie, age &lt;71 years). Validation of CCI in our population showed good discrimination (Concordance statistic, 0.78; 95% CI, 0.72–0.84) and fair calibration. Conclusion: The other-cause mortality risk after successful EET was more than 40 times higher (48; 95% CI, 15–99) than the risk of EAC-related mortality. Our findings reveal that younger post-EET patients exhibit a significantly reduced life expectancy when compared with the general population. Furthermore, they emphasize the strong predictive ability of CCI for long-term mortality after EET. This straightforward scoring system can inform decisions regarding personalized FU, including appropriate cessation timing.</p

Radiofrequency Ablation vs Endoscopic Surveillance for Patients With Barrett Esophagus and Low-Grade Dysplasia: A Randomized Clinical Trial

Importance Barrett esophagus containing low-grade dysplasia is associated with an increased risk of developing esophageal adenocarcinoma, a cancer with a rapidly increasing incidence in the western world.Objective To investigate whether endoscopic radiofrequency ablation could decrease the rate of neoplastic progression.Design, Setting, and Participants Multicenter randomized clinical trial that enrolled 136 patients with a confirmed diagnosis of Barrett esophagus containing low-grade dysplasia at 9 European sites between June 2007 and June 2011. Patient follow-up ended May 2013.Interventions Eligible patients were randomly assigned in a 1:1 ratio to either endoscopic treatment with radiofrequency ablation (ablation) or endoscopic surveillance (control). Ablation was performed with the balloon device for circumferential ablation of the esophagus or the focal device for targeted ablation, with a maximum of 5 sessions allowed.Main Outcomes and Measures The primary outcome was neoplastic progression to high-grade dysplasia or adenocarcinoma during a 3-year follow-up since randomization. Secondary outcomes were complete eradication of dysplasia and intestinal metaplasia and adverse events.Results Sixty-eight patients were randomized to receive ablation and 68 to receive control. Ablation reduced the risk of progression to high-grade dysplasia or adenocarcinoma by 25.0% (1.5% for ablation vs 26.5% for control; 95% CI, 14.1%-35.9%; P

Pelvic insufficiency fractures and pelvic bone metastases after neoadjuvant (chemo)radiotherapy for rectal cancer

Background: Pelvic insufficiency fractures (PIFs) are a late complication of radiotherapy for pelvic malignancies. We evaluated the incidence, radiologic findings, clinical course, and outcome of PIFs in patients treated with neoadjuvant (chemo)radiotherapy ((C)RT) for rectal cancer. Material and methods: Data of patients diagnosed with rectal cancer from a large teaching hospital treated from 2002 to 2012 were extracted from the Dutch Cancer Registry. All hospital records were reviewed for the diagnosis of PIFs or pelvic bone metastases. An expert radiologist reassessed all imaging procedures of the lower back, abdomen, and pelvis. Results: A total of 513 rectal cancer patients were identified of whom 300 patients (58.5%) were treated with neoadjuvant (C)RT (long- vs. short-course radiotherapy: 91 patients [17.7%] vs. 209 [40.7%], respectively). Twelve PIFs were diagnosed initially according to hospital records and imaging reports of all 513 patients. These 12 patients were treated with neoadjuvant (C)RT. After reassessment of all pelvic imaging procedures done in this patient group (432 patients (84.2%)), 20 additional PIFs were detected in patients treated with neoadjuvant (C)RT, resulting in a 10.7% PIF rate in irradiated patients. One PIF was detected in the group of patients not treated with neoadjuvant (C)RT for rectal cancer. This patient had palliative radiotherapy for prostate cancer and is left out of the analysis. Median follow-up time of 32 PIF patients was 49 months. Median time between start of neoadjuvant (C)RT and diagnosis of PIF was 17 months (IQR 9–28). Overall median survival for patients with PIF was 63.5 months (IQR 44–120). Conclusion: PIFs are a relatively common late complication of neoadjuvant (C)RT for rectal cancer but are often missed or misdiagnosed as pelvic bone metastases. The differentiation of PIFs from pelvic bone metastases is important because of a different treatment and disease outcome.</p

Durability of radiofrequency ablation for treatment of esophageal squamous cell neoplasia : 5-year follow-up of a treated cohort in China

Background and Aims: Radiofrequency ablation (RFA) is an accepted treatment for flat Barrett's neoplasia. Less is known about RFA for esophageal squamous cell neoplasia (ESCN). Our group has reported several prospective studies of RFA for ESCN in China with promising results through 12 months of follow-up. In this cohort study we aimed to evaluate longer term outcomes after RFA for ESCN. Methods: Patients with flat unstained lesions (USLs) on Lugol's endoscopy containing moderate-/high-grade intraepithelial neoplasia (MGIN/HGIN) or mucosal cancer were treated with RFA every 3 months until complete remission (CR; no MGIN or a worse histologic grade). Patients with CR at 12 months (CR12) were included for follow-up and underwent annual Lugol's endoscopy with biopsy sampling and re-RFA for flat USLs. The clinical course of patients with persistent ESCN at 12 months (treatment failures) is also reported. Results: Among the 78 patients in CR12, 67 (86%) had sustained CR during a median of 48 months (interquartile range, 48-48) of follow-up and 5 endoscopies (interquartile range, 4-6). Recurrence occurred in 7 of 78 patients (9%; MGIN, n = 6; HGIN, n = 1); all lesions were managed with RFA. Four other patients (5%) had progression (to HGIN, n = 1; submucosal esophageal squamous cell carcinoma, n = 3). During follow-up protocol violations occurred in 46 of 78 patients (59%). Of the 12 treatment failures, progression occurred in 6. Overall, 2 patients developed subepithelial disease that was not visible after Lugol's endoscopy. Based on post-hoc analysis, the pink-color sign at baseline (a pink color change after Lugol's endoscopy) significantly predicted failure after RFA. Conclusions: RFA is relatively easy to apply and can efficiently treat large areas with ESCN. Despite protocol violations that may have interfered with the efficacy of RFA in 59% of patients, most patients with CR12 had sustained CR during follow-up. However, some patients progressed to advanced disease and 2 developed subepithelial disease, not visible after Lugol's endoscopy. Based on currently available data, we advise the restriction of the use of RFA for flat MGIN and HGIN without the pink-color sign on Lugol's chromoendoscopy. (Clinical trial registration number: NCT02047305.

Pelvic insufficiency fractures and pelvic bone metastases after neoadjuvant (chemo)radiotherapy for rectal cancer

Background: Pelvic insufficiency fractures (PIFs) are a late complication of radiotherapy for pelvic malignancies. We evaluated the incidence, radiologic findings, clinical course, and outcome of PIFs in patients treated with neoadjuvant (chemo)radiotherapy ((C)RT) for rectal cancer. Material and methods: Data of patients diagnosed with rectal cancer from a large teaching hospital treated from 2002 to 2012 were extracted from the Dutch Cancer Registry. All hospital records were reviewed for the diagnosis of PIFs or pelvic bone metastases. An expert radiologist reassessed all imaging procedures of the lower back, abdomen, and pelvis. Results: A total of 513 rectal cancer patients were identified of whom 300 patients (58.5%) were treated with neoadjuvant (C)RT (long- vs. short-course radiotherapy: 91 patients [17.7%] vs. 209 [40.7%], respectively). Twelve PIFs were diagnosed initially according to hospital records and imaging reports of all 513 patients. These 12 patients were treated with neoadjuvant (C)RT. After reassessment of all pelvic imaging procedures done in this patient group (432 patients (84.2%)), 20 additional PIFs were detected in patients treated with neoadjuvant (C)RT, resulting in a 10.7% PIF rate in irradiated patients. One PIF was detected in the group of patients not treated with neoadjuvant (C)RT for rectal cancer. This patient had palliative radiotherapy for prostate cancer and is left out of the analysis. Median follow-up time of 32 PIF patients was 49 months. Median time between start of neoadjuvant (C)RT and diagnosis of PIF was 17 months (IQR 9–28). Overall median survival for patients with PIF was 63.5 months (IQR 44–120). Conclusion: PIFs are a relatively common late complication of neoadjuvant (C)RT for rectal cancer but are often missed or misdiagnosed as pelvic bone metastases. The differentiation of PIFs from pelvic bone metastases is important because of a different treatment and disease outcome.</p

Endoscopic radiofrequency ablation combined with endoscopic resection for early neoplasia in Barrett's esophagus longer than 10 cm

Background: Radiofrequency ablation (RFA) is safe and effective for eradicating Barrett's esophagus (BE) and BE-associated early neoplasia. Most RFA studies have limited the baseline length of BE (<10 cm), and therefore little is known about RFA for longer BE. Objective: To assess the safety and efficacy of RFA with or without prior endoscopic resection (ER) for BE <10 cm containing neoplasia. Design: Prospective trial. Setting: Two tertiary-care centers. Patients This study involved consecutive patients with BE <10 cm with early neoplasia. Intervention Focal ER for visible abnormalities, followed by a maximum of 2 circumferential and 3 focal RFA procedures every 2 to 3 months until complete remission. Main Outcome Measurements: Complete remission, defined as endoscopic resolution of BE and no intestinal metaplasia (CR-IM) or neoplasia (CR-neoplasia) in biopsy specimens. Results Of the 26 patients included, 18 underwent ER for visible abnormalities before RFA. The ER specimens showed early cancer in 11, high-grade intraepithelial neoplasia (HGIN) in 6, and low-grade intraepithelial neoplasia (LGIN) in 1. The worst residual histology, before RFA and after any ER, was HGIN in 16 patients and LGIN in 10 patients. CR-neoplasia and CR-IM were achieved in 83% (95% confidence interval [CI], 63%-95%) and 79% (95% CI, 58%-93%), respectively. None of the patients had fatal or severe complications and 15% (95% CI, 4%-35%) had moderate complications. During a mean (± standard deviation) follow-up of 29 (± 9.1) months, no neoplasia recurred. Limitation:s Tertiary-care center, short follow-up. Conclusion ER for visible abnormalities, followed by RFA of residual BE is a safe and effective treatment for BE <10 cm containing neoplasia, with a low chance of recurrence of neoplasia or BE during follow-up

Prospective study of endoscopic focal cryoballoon ablation for esophageal squamous cell neoplasia in China

Background and Aims: Esophageal squamous cell neoplasia (ESCN) has a significant risk for progression to cancer. Current treatment options, endoscopic mucosal resection (EMR) or submucosal dissection (ESD), have their limitations. The cryoballoon focal ablation system (CbFAS) is a novel endoscopic ablation therapy device. We aimed to assess the safety, tolerability, and efficacy of CbFAS for eradication of ESCN. Methods: In this single-center prospective trial in China, patients with 1 flat unstained lesion (USL) on Lugol chromoendoscopy that contained moderate- or high-grade intraepithelial neoplasia (MGIN or HGIN, respectively) were enrolled. CbFAS was performed using side-by-side applications of 10 seconds, treatment was repeated at 3-month intervals until a complete response (CR) was established. The response at 12 months was the primary trial endpoint. Safety phone calls were performed at 2, 7, and 30 days after the initial CbFAS. Results: We enrolled 80 patients (59 MGIN, 21 HGIN) with a median USL length of 3 cm (interquartile range [IQR], 3-4). Seventy-nine received treatment, with a median of 5 side-by-side applications (IQR, 4-7) per patient over a median of 8 minutes (IQR, 5-10). After a single treatment, 70 of 78 patients (90%) exhibited CR, and 1 was lost to follow-up. The other 8 with persisting USLs were retreated, and all achieved CR after this second treatment. At 12 months after the initial CbFAS, 76 of 78 patients (97%) exhibited CR and 2 (3%) had recurrent MGIN. No strictures or serious adverse events occurred. Four patients developed self-limiting mucosal lacerations on balloon inflation. The postprocedure median pain score was 1 of 10 (IQR, 0-2) at day 2 and 0 (0-0) at days 7 and 30. Conclusions: The results suggest that the CbFAS is safe, well tolerated, and effective in inducing endoscopic and histologic remission in patients with ESCN of limited size. (Clinical trial registration number: NCT02605759.