New insights in optimizing treatment and the role of cancer stem cells in esophageal cancer

De incidentie van het slokdarmcarcinoom is stijgende en de 5-jaars overleving op het moment van diagnose is tussen de 15 en 20%. Een beter inzicht in de oncogenese van het slokdarmcarcinoom en de moleculaire mechanismen die verantwoordelijk zijn voor ziekte progressie is belangrijk om onze huidige therapie te verbeteren en om nieuwe therapeutische strategieën te ontwikkelen. In dit proefschrift liet optimalisatie van de huidige behandeling een verbetering zien in de prognose en uitkomst van slokdarmkanker patiënten. Een optimaal bepaalde circumferentieël snijvlak heeft een significante invloed op de prognose. Daarnaast bleek carboplatin/paclitaxel, als definitief chemoradiotherapie schema een beter tolereerbaar schema met vergelijkbare overleving vergeleken met cisplatinum/ 5-FU. Het kankerstamcel model kan mogelijk een bijdrage leveren aan betere inzichten in de oncogenese van het slokdarmcarcinoom, en daarmee lijden tot verbetering van de huidige therapie en nieuwe prognostische factoren. In dit proefschrift had het OE19 sferoïde gekweekte cellijn model enkele kankerstamcel eigenschappen en verdere validatie van dit model is interessant. Verder bleek verlies van de markers CD44 and SOX2, markers geassocieerd met kankerstamcellen, prognostisch voor overleving. Identificatie en het bepalen van de rol van kankerstamcellen in slokdarmkanker kan een mogelijke nieuwe strategie zijn om de overleving van slokdarmkanker patiënten te verbeteren

Endoscopic resection for residual oesophageal neoplasia after definitive chemoradiotherapy

Definitive chemoradiation is the recommended treatment for locally advanced, irresectable oesophageal cancer and a valid alternative to neoadjuvant chemoradiotherapy (CRT) with surgery in oesophageal squamous cell cancer (OSCC) patients. In case of locoregional recurrence, salvage treatment can be considered in fit and resectable patients. Salvage surgery is a valid option but associated with significant morbidity. Therefore, for tumors confined to the mucosa or submucosal layers endoscopic resection is a good and less-invasive alternative. Over the last decade several case-series have demonstrated a high technical success rate of endoscopic treatment after definitive CRT. In this review we summarize the clinical outcomes and challenges of endoscopic treatment of early recurrence after definitive CRT in oesophageal cancer.</p

Endoscopic resection for residual oesophageal neoplasia after definitive chemoradiotherapy

Definitive chemoradiation is the recommended treatment for locally advanced, irresectable oesophageal cancer and a valid alternative to neoadjuvant chemoradiotherapy (CRT) with surgery in oesophageal squamous cell cancer (OSCC) patients. In case of locoregional recurrence, salvage treatment can be considered in fit and resectable patients. Salvage surgery is a valid option but associated with significant morbidity. Therefore, for tumors confined to the mucosa or submucosal layers endoscopic resection is a good and less-invasive alternative. Over the last decade several case-series have demonstrated a high technical success rate of endoscopic treatment after definitive CRT. In this review we summarize the clinical outcomes and challenges of endoscopic treatment of early recurrence after definitive CRT in oesophageal cancer.</p

A Critical Appraisal of Circumferential Resection Margins in Esophageal Carcinoma

In esophageal cancer, circumferential resection margins (CRMs) are considered to be of relevant prognostic value, but a reliable definition of tumor-free CRM is still unclear. The aim of this study was to appraise the clinical prognostic value of microscopic CRM involvement and to determine the optimal limit of CRM.To define the optimal tumor-free CRM we included 98 consecutive patients who underwent extended esophagectomy with microscopic tumor-free resection margins (R0) between 1997 and 2006. CRMs were measured in tenths of millimeters with inked lateral margins. Outcome of patients with CRM involvement was compared with a statistically comparable control group of 21 patients with microscopic positive resection margins (R1).A cutoff point of CRM at a parts per thousand currency sign1.0 mm and &gt; 1.0 mm appeared to be an adequate marker for survival and prognosis (both P &lt;0.001). The outcome in patients with CRMs a parts per thousand currency sign1.0 and &gt; 0 mm was equal to that in patients with CRM of 0 mm (P = 0.43). CRM involvement was an independent prognostic factor for both recurrent disease (P = 0.001) and survival (P &lt;0.001). Survival of patients with positive CRMs (a parts per thousand currency sign1 mm) did not significantly differ from patients with an R1 resection (P = 0.12).Involvement of the circumferential resection margins is an independent prognostic factor for recurrent disease and survival in esophageal cancer. The optimal limit for a positive CRM is a parts per thousand currency sign1 mm and for a free CRM is &gt; 1.0 mm. Patients with unfavorable CRM should be approached as patients with R1 resection with corresponding outcome.</p

Adequacy of endoscopic recognition and surveillance of gastric intestinal metaplasia and atrophic gastritis: A multicentre retrospective study in low incidence countries

BACKGROUND: Gastric atrophy (GA) and gastric intestinal metaplasia (GIM) are precursor conditions to gastric adenocarcinoma (GAC) and should be monitored endoscopically in selected individuals. However, little is known about adherence to recommendations in clinical practice in low-risk countries. OBJECTIVE: The aim of this study was to evaluate endoscopic recognition and adequacy of surveillance for GA and GIM in countries with low GAC prevalence. METHODS: We retrospectively analysed patients diagnosed with GIM or GA in three centers in The Netherlands and UK between 2012 and 2019. Cases with GIM and/or GA diagnosis at index endoscopy were retrieved through systematic search of pathology databases using 'gastric' and 'intestinal metaplasia' or 'atrophy' keywords. Endoscopy reports were analysed to ascertain accuracy of endoscopic diagnoses. Adequacy of surveillance was assessed following histological diagnosis at the index endoscopy based on ESGE guidelines published in 2012. RESULTS: We included 396 patients with a median follow-up of 57.2 months. Mean age was 66 years and the rates of antrum-predominant versus extensive GIM were comparable (37% vs 38%). Endoscopic recognition rates were 48.5% for GA and 16.3% for GIM. Surveillance was adequately carried out in 215 of 396 patients (54.3%). CONCLUSION: In countries with a low incidence of GAC, the rate of endoscopic recognition of gastric pre-cancerous lesions and adherence to surveillance recommendation are low. Substantial improvement is required in endoscopic training and awareness of guidelines recommendation in order to optimise detection and management of pre-malignant gastric conditions

Categorizing Risks within Barrett's Esophagus To Guide Surveillance and Interception; Suggesting a New Framework.

Barrett's esophagus is a precancerous condition that can progress in a stepwise manner to dysplasia and eventually esophageal adenocarcinoma (EAC). Once diagnosed, patients with Barrett's esophagus are kept on surveillance to detect progression so that timely intervention can occur with endoscopic therapy. Several demographic and clinical risk factors are known to increase progression toward EAC, such as longer Barrett's segments, and these patients are kept on tighter surveillance. While p53 IHC has been advocated as an adjunct to histopathologic diagnosis, use of this biomarker is variable, and no other molecular factors are currently applied. Given the new evidence available, it is time to consider whether other risk factors or tools could be applied in clinical practice to decide on closer or attenuated surveillance. In this commentary, we summarize the most relevant risk factors for Barrett's esophagus progression, highlight the most promising novel risk stratification tools-including nonendoscopic triage and commercial biomarker panels, and propose a new framework suggesting how to incorporate risk stratification into clinical practice

Informal interprofessional learning: Visualizing the clinical workplace

Daily collaboration of senior doctors, residents and nurses involves a major potential for sharing knowledge between professionals. Therefore, more attention needs to be paid to informal learning to create strategies and appropriate conditions for enhancing and effectuating informal learning in the workplace. The aim of this study is to visualize and describe patterns of informal interprofessional learning relations among staff in complex care. Questionnaires with four network questions recognized as indicators of informal learning in the clinical workplace were handed out to intensive and medium care unit (ICU/MCU) staff members (N = 108), of which 77% were completed and returned. Data were analyzed using social network analysis and Mokken scale analysis. Densities, tie strength and reciprocity of the four networks created show MCU and ICU nurses as subgroups within the ward and reveal central but relatively one-sided relations of senior doctors with nurses and residents. Based on the analyses, we formulated a scale of intensity of informal learning relations that can be used to understand and stimulate informal interprofessional learning. © 2012 Informa UK, Ltd