Surgery and Peritoneal Tumor Recurrence: pathways studies 'in vitro'

De incidentie van colon carcinomen (kwaadaardige tumoren van de dikke darm) neemt toe in de westerse wereld. In Europa wordt jaarlijks bij 400 000 patiënten dikke darm kanker vastgesteld en overlijden er jaarlijks 200 000 patiënten met deze vorm van kanker. Van alle vormen van kanker staan colon carcinomen met een incidentie van 14% op de derde plaats na long- en prostaatkanker. De overall 5-jaarsoverleving is ongeveer 60-70%, indien er sprake is van lokale uitzaaiing (lokaal recidief) daalt de 5-jaarsoverleving naar 35% en bij uitzaaiingen in andere organen (metastasen) naar 25%. Kwaadaardige tumoren van de alvleesklier (pancreas) hebben een zeer slechte prognose. Na chirurgische resectie zal meer dan 50% van de patiënten een metastase ontwikkelen. Minder dan 15% van de patiënten met een pancreas carcinoom overleeft het eerste jaar en de 5-jaarsoverleving is kleiner dan 5%. De behandeling van keuze bij colon of pancreas carcinomen is chirurgische resectie. Het nadeel van deze chirurgische behandeling is dat tijdens de operatie tumorcellen kunnen los raken door manipulatie van de primaire tumor (‘spilled tumour cells’). Deze tumorcellen kunnen aanhechten op het resetievlak of op een andere plaats in de buik en op deze manier uitgroeien tot een recidief tumor. Bij zowel colon als pancreas carcinomen komt lokaal tumor recidief vaak voor. Daarom is kennis van het ontstaan van lokaal tumor recidief zeer belangrijk. Dit proces kan uitgesplitst worden in tumorcel aanhechting en tumor groei. Het proces van aanhechting van een tumorcel is afhankelijk van een groot aantal factoren. De experimenten beschreven in dit proefschrift bestuderen het proces van aanhechting van de tumorcel en de invloed van factoren, die postoperatief intra-abdominaal (in de buik) worden geproduceerd op deze aanhechting.The general introduction gives an overview of our previous studies, the incidence of gastro-intestinal malignancies and the pathophysiology of local tumour recurrence. This chapter outlines the basics of the peritoneum, infl ammatory reaction, cytokines, adhesion molecules, an

Towards Response ADAptive Radiotherapy for organ preservation for intermediate-risk rectal cancer (preRADAR): protocol of a phase I dose-escalation trial

Introduction Organ preservation is associated with superior functional outcome and quality of life (QoL) compared with total mesorectal excision (TME) for rectal cancer. Only 10% of patients are eligible for organ preservation following short-course radiotherapy (SCRT, 25 Gy in five fractions) and a prolonged interval (4–8 weeks) to response evaluation. The organ preservation rate could potentially be increased by dose-escalated radiotherapy. Online adaptive magnetic resonance-guided radiotherapy (MRgRT) is anticipated to reduce radiation-induced toxicity and enable radiotherapy dose escalation. This trial aims to establish the maximum tolerated dose (MTD) of dose-escalated SCRT using online adaptive MRgRT.Methods and analysis The preRADAR is a multicentre phase I trial with a 6+3 dose-escalation design. Patients with intermediate-risk rectal cancer (cT3c-d(MRF-)N1M0 or cT1-3(MRF-)N1M0) interested in organ preservation are eligible. Patients are treated with a radiotherapy boost of 2×5 Gy (level 0), 3×5 Gy (level 1), 4×5 Gy (level 2) or 5×5 Gy (level 3) on the gross tumour volume in the week following standard SCRT using online adaptive MRgRT. The trial starts on dose level 1. The primary endpoint is the MTD based on the incidence of dose-limiting toxicity (DLT) per dose level. DLT is a composite of maximum one in nine severe radiation-induced toxicities and maximum one in three severe postoperative complications, in patients treated with TME or local excision within 26 weeks following start of treatment. Secondary endpoints include the organ preservation rate, non-DLT, oncological outcomes, patient-reported QoL and functional outcomes up to 2 years following start of treatment. Imaging and laboratory biomarkers are explored for early response prediction.Ethics and dissemination The trial protocol has been approved by the Medical Ethics Committee of the University Medical Centre Utrecht. The primary and secondary trial results will be published in international peer-reviewed journals.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Colonoscopic-Assisted Laparoscopic Wedge Resection for Colonic Lesions A Prospective Multicenter Cohort Study (LIMERIC-Study)

Objective: The aim of this study was to evaluate the safety and efficacy of a modified CAL-WR. Summary Background Data: The use of segmental colectomy in patients with endoscopically unresectable colonic lesions results in significant morbidity and mortality. CAL-WR is an alternative procedure that may reduce morbidity. Methods: This prospective multicenter study was performed in 13 Dutch hospitals between January 2017 and December 2019. Inclusion criteria were (1) colonic lesions inaccessible using current endoscopic resection techniques (judged by an expert panel), (2) non-lifting residual/recurrent adenomatous tissue after previous polypectomy or (3) an undetermined resection margin after endoscopic removal of a low-risk pathological T1 (pT1) colon carcinoma. Thirty-day morbidity, technical success rate and radicality were evaluated. Results: Of the 118 patients included (56% male, mean age 66 years, standard deviation +/- 8 years), 66 (56%) had complex lesions unsuitable for endoscopic removal, 34 (29%) had non-lifting residual/recurrent adenoma after previous polypectomy and 18 (15%) had uncertain resection margins after polypectomy of a pT1 colon carcinoma. CAL-WR was technically successful in 93% and R-0 resection was achieved in 91% of patients. Minor complications (Clavien-Dindo i-ii) were noted in 7 patients (6%) and an additional oncologic segmental resection was performed in 12 cases (11%). Residual tissue at the scar was observed in 5% of patients during endoscopic follow-up. Conclusions: CAL-WR is an effective, organ-preserving approach that results in minor complications and circumvents the need for major surgery. CAL-WR, therefore, deserves consideration when endoscopic excision of circumscribed lesions is impossible or incomplete.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Associations between workability and patient-reported physical, psychological and social outcomes in breast cancer survivors: a cross-sectional study

Purpose: Workability is of increasing importance especially in Asia given the increasing incidence rates and young age of onset of breast cancer. This study explores the determinants of employment and suboptimal workability. And evaluate the association between workability and patient-reported physical, psychological, and social outcomes. Methods: In a hospital-based cross-sectional study, 327 breast cancer survivors, 1 year post-diagnosis were recruited. Employed survivors filled out the workability index, which measures a person’s capacity to meet work demands in relation to current health status. The EORTC-QLQ-C30, EORTC-QLQ-BR23, hospital anxiety and depression scale, multidimensional fatigue inventory, and brief pain index were administered. Fisher’s exact test and Kruskal-Wallis test were used to test for associations of workability and employment status with demographic, clinical characteristics, and patient-reported outcomes. Linear models with standardised scores for patient-reported outcomes were fitted to study the associations of workability with patient-reported outcomes. Results: Of the 327 survivors, < 65 years of age (working age), 140 (43%) were in full-time and 34 (10%) in part-time employment. Employed survivors were younger at time of diagnosis and at time of survey. Employment status was not associated with time since diagnosis, ethnicity, or clinical characteristics. Suboptimal workability was present in 37% of employed survivors of the working age, and more common in jobs that include physical work activities. Higher level of depression, financial difficulty and physical fatigue, more breast symptoms, and poorer global health status were independently associated with poorer workability. Conclusions: Lower employment and reduced workability in breast cancer survivors is common, and reduced workability is associated with higher levels of depression, financial difficulty and physical fatigue, more breast symptoms, and poorer global health status. Longitudinal research on psychosocial support with workability in Asia may find tailored approach to improve or maintain workability in employed breast cancer patients