DCIS knowledge of women choosing between active surveillance and surgery for low-risk DCIS.

BACKGROUND: Ductal carcinoma in situ (DCIS) can progress to invasive breast cancer (IBC), but often never will. As we cannot predict accurately which DCIS-lesions will or will not progress to IBC, almost all women with DCIS undergo breast-conserving surgery supplemented with radiotherapy, or even mastectomy. In some countries, endocrine treatment is prescribed as well. This implies many women with non-progressive DCIS undergo overtreatment. To reduce this, the LORD patient preference trial (LORD-PPT) tests whether mammographic active surveillance (AS) is safe by giving women with low-risk DCIS a choice between treatment and AS. For this, sufficient knowledge about DCIS is crucial. Therefore, we assessed women's DCIS knowledge in association with socio-demographic and clinical characteristics. METHODS: LORD-PPT participants (N = 376) completed a questionnaire assessing socio-demographic and clinical characteristics, risk perception, treatment choice and DCIS knowledge after being informed about their diagnosis and treatment options. RESULTS: 66 % of participants had poor knowledge (i.e., answered ≤3 out of 7 knowledge items correctly). Most incorrect answers involved overestimating the safety of AS and misunderstanding of DCIS prognostic risks. Overall, women with higher DCIS knowledge score perceived their risk of developing IBC as being somewhat higher than women with poorer knowledge (p = 0.049). Women with better DCIS knowledge more often chose surgery whilst most women with poorer knowledge chose active surveillance (p = 0.049). DISCUSSION: Our findings show that there is room for improvement of information provision to patients. Decision support tools for patients and clinicians could help to stimulate effective shared decision-making about DCIS management.

Predictive factors for initial treatment response after circumferential radiofrequency ablation for Barrett's esophagus with early neoplasia: a prospective multicenter study.

BACKGROUND AND STUDY AIMS: Radiofrequency ablation (RFA) is safe and effective for the eradication of neoplastic Barrett's esophagus; however, occasionally there is minimal regression after initial circumferential balloon-based RFA (c-RFA). This study aimed to identify predictive factors for a poor response 3 months after c-RFA, and to relate the percentage regression at 3 months to the final treatment outcome. METHODS: We included consecutive patients from 14 centers who underwent c-RFA for high grade dysplasia at worst. Patient and treatment characteristics were registered prospectively. "Poor initial response" was defined as < 50 % regression of the Barrett's esophagus 3 months after c-RFA, graded by two expert endoscopists using endoscopic images. Predictors of initial response were identified through logistic regression analysis. RESULTS: There were 278 patients included (median Barrett's segment C4M6). In poor initial responders (n = 36; 13 %), complete response for neoplasia (CR-neoplasia) was ultimately achieved in 86 % (vs. 98 % in good responders; P < 0.01) and complete response for intestinal metaplasia (CR-IM) in 66 % (vs. 95 %; P < 0.01). Poor responders required 13 months treatment (vs. 7 months; P < 0.01) for a median of four RFA sessions (vs. three; P < 0.01). We identified four independent baseline predictors of poor response: active reflux esophagitis (odds ratio [OR] 37.4; 95 % confidence interval [CI] 3.2 - 433.2); endoscopic resection scar regeneration with Barrett's epithelium (OR 4.7; 95 %CI 1.1 - 20.0); esophageal narrowing pre-RFA (OR 3.9; 95 %CI 1.0 - 15.1); and years of neoplasia pre-RFA (OR 1.2; 95 %CI 1.0 - 1.4). CONCLUSIONS: Patients with a poor initial response to c-RFA have a lower ultimate success rate for CR-neoplasia/CR-IM, require more treatment sessions, and a longer treatment period. A poor initial response to c-RFA occurs more frequently in patients who regenerate their endoscopic resection scar with Barrett's epithelium, and those with ongoing reflux esophagitis, neoplasia in Barrett's esophagus for a longer time, or a narrow esophagus.

Expression pattern of immune suppressive cytokines and growth factors in oesophageal adenocarcinoma reveal a tumour immune escape-promoting microenvironment.

Immunotherapy for solid cancers, such as oesophageal adenocarcinoma (OAC), is generally hampered by an unfavourable immunological tumour microenvironment. This prompted us to investigate the nature of the OAC environment. Biopsies of tumour and normal control tissues were collected from 17 OAC patients, and investigated using fluorescent immunohistochemistry (IHC) for the expression of cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), transforming growth factor-beta, indoleamine 2-3 dioxygenase, CXCL3 and CXCR1, and for measuring a panel of cytokines by cytometric bead array (CBA), and for Granzyme B (GrB), Perforin and PI9 detection by semi-quantitative PCR (QPCR). IHC showed that expression of all the above-mentioned factors is upregulated in 80-93% of the tumours. By QPCR, the cytokine interleukin (IL)-8 was significantly upregulated in tumour samples (P < 0.05). IL-6, IL-10, GrB and Perforin did not show any significant difference between normal and tumour samples, whereas PI9 levels were significantly higher in normal when compared with the tumour samples. CBA confirmed upregulation of IL-8 and show upregulation of IL-1beta in the tumours (P < 0.05). Regarding IL-6 and interferon (IFN)-gamma, no significant differences were observed between normal and tumour tissues. The OAC microenvironment is characterized by a lack of cytokines and factors that normally would enhance anti-cancer responses, such as IFN-gamma and GrB, and by a high expression of several immuno-suppressive factors, such as COX-2, VEGF and IL-8. For future improvement of treatment efficacy of OAC patients, it will be of importance to combine immunotherapy with immune-modulating agents.

Stepwise circumferential and focal ablation of Barrett's esophagus with high-grade dysplasia: results of the first prospective series of 11 patients.

BACKGROUND AND STUDY AIMS: Stepwise circumferential and focal ablation of nondysplastic Barrett's esophagus has proven safe and effective. This study assessed the efficacy and safety of ablation for Barrett's esophagus with high-grade dysplasia (HGD), and residual Barrett's esophagus with dysplasia after prior endoscopic resection for visible lesions. PATIENTS AND METHODS: This was a prospective cohort study. All visible abnormalities were resected prior to ablation. Persistence of dysplasia and absence of invasive cancer was confirmed with biopsies after endoscopic resection. A balloon-based electrode was used for primary circumferential ablation and an endoscope-mounted electrode was used for secondary focal ablation. Eradication of dysplasia and Barrett's esophagus was the main outcome measure. RESULTS: Eleven patients (eight men; median age 60 years) were treated (median Barrett's length 5 cm). Visible abnormalities were removed with endoscopic resection in six patients. The worst pathological grade of residual Barrett's esophagus after endoscopic resection and prior to ablation was LGD (n = 2) and HGD (n = 9). Patients underwent a median of two circumferential and two focal ablation sessions. Complete remission of dysplasia and complete endoscopic and histological removal of Barrett's esophagus was achieved in 11/11 patients (100%). There were no adverse events or strictures, and in none of the 473 biopsies of neo-squamous mucosa was subsquamous Barrett's esophagus ("buried Barrett's") observed. During a median follow-up period of 14 months after the last treatment session and a median number of two follow-up endoscopies, none of the patients showed recurrence of dysplasia or endoscopic signs of recurrent Barrett's mucosa. CONCLUSIONS: Stepwise circumferential and focal ablation appears to be a safe and effective treatment for complete removal of Barrett's esophagus containing HGD, and can be safely performed after prior endoscopic resection for endoscopically visible abnormalities.

Effective treatment of early Barrett's neoplasia with stepwise circumferential and focal ablation using the HALO system.

STUDY AIMS: The aim of the current study was to evaluate the efficacy and safety of stepwise circumferential and focal ablation using the HALO system for Barrett's esophagus containing flat, high-grade dysplasia (HGD) or residual dysplasia after endoscopic resection for HGD or intramucosal cancer (IMC). METHODS: Visible abnormalities were removed with endoscopic resection prior to ablation. Persistence of dysplasia and absence of IMC were confirmed with biopsy after endoscopic resection. A balloon-based electrode was used for primary circumferential ablation and an endoscope-mounted electrode was used for secondary focal ablation. RESULTS: Twelve patients (nine men; median age 70 years) were treated (median Barrett's length 7 cm). Visible abnormalities were removed by endoscopic resection in seven patients. The worst pathological grade of residual Barrett's esophagus after resection and prior to ablation was low-grade dysplasia (LGD) (n = 1) and HGD (n = 11). Patients underwent a median of one circumferential and two focal ablation sessions. Complete remission of dysplasia was achieved in 12/12 patients (100%). Complete endoscopic and histological removal of Barrett's esophagus was achieved in 12/12 patients (100%). There were no ablation-related stenoses, and no subsquamous Barrett's esophagus was observed in 363 biopsies obtained from post-ablation neo-squamous mucosa. Protocolized cleaning of the ablation zone and electrode in between ablations resulted in superior regression of Barrett's esophagus compared with previous studies. During a median follow-up of 14 months no recurrence of dysplasia or Barrett's esophagus was observed. CONCLUSIONS: Stepwise circumferential and focal ablation for Barrett's esophagus with flat HGD or for Barrett's with residual dysplasia after endoscopic resection for HGD/IMC is a safe and effective treatment modality. Its success rate and safety profile compare favorably with alternatives such as esophagectomy, widespread endoscopic resection or photodynamic therapy.