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Contains fulltext : 251449.pdf (Publisher’s version ) (Open Access) AIMS: No consensus exists on the clinical value of tumour regression grading (TRG) systems for therapy effects of neoadjuvant chemoradiotherapy (nCRT) in oesophageal adenocarcinoma. Existing TRG systems lack standardization and reproducibility, and do not consider the morphological heterogeneity of tumour response. Therefore, we aim to identify morphological tumour regression patterns of oesophageal adenocarcinoma after nCRT and their association with survival. METHODS AND RESULTS: Patients with oesophageal adenocarcinoma, who underwent nCRT followed by surgery and achieved a partial response to nCRT, were identified from two Dutch upper-gastrointestinal (GI) centres (2005-18; test cohort). Resection specimens were scored for regression patterns by two independent observers according to a pre-defined three-step flowchart. The results were validated in an external cohort (2001-17). In total, 110 patients were included in the test cohort and 115 in the validation cohort. In the test cohort, two major regression patterns were identified: fragmentation (60%) and shrinkage (40%), with an excellent interobserver agreement (κ = 0.87). Here, patients with a fragmented pattern had a significantly higher pathological stage (stages III/IV: 52 versus 16%; P

Comorbidity has large impact on colorectal cancer (CRC) treatment and outcomes and may increase as the population ages. We aimed to evaluate the prevalence and time trends of comorbid diseases in patients with CRC from 1995 to 2010. The Eindhoven Cancer Registry registers comorbidity in all patients with primary CRC in the South of the Netherlands. We analyzed the prevalence of serious comorbid diseases in four time frames from 1995 to 2010. Thereby, we addressed its association with age, gender and socio-economic status (SES). The prevalence of comorbidity was registered in 27,339 patients with primary CRC. During the study period, the prevalence of comorbidity increased from 47% to 62%, multimorbidity increased from 20% to 37%. Hypertension and cardiovascular diseases were most prevalent and increased largely over time (respectively 16-29% and 12-24%). Pulmonary diseases increased in women, but remained stable in men. Average age at diagnosis increased from 68.3 to 69.5 years (p = 0.004). A low SES and male gender were associated with a higher risk of comorbidity (not changing over time). This study indicates that comorbidity among patients with CRC is common, especially in males and patients with a low SES. The prevalence of comorbidity increased from 1995 to 2010, in particular in presumably nutritional diseases. Ageing, increased life expectancy and life style changes may contribute to more comorbid diseases. Also, improved awareness among health care providers on the importance of comorbidity may have resulted in better registration. The increasing burden of comorbidity in patients with CRC emphasizes the need for more focus on individualized medicine.

Contains fulltext : 171846.pdf (Publisher’s version ) (Closed access) BACKGROUND: Local recurrence after rectal cancer treatment occurs in approximately 5% to 10% of patients. Neoadjuvant (chemo)radiotherapy for primary rectal cancer renders treatment of recurrent disease more difficult. OBJECTIVE: The purpose of this study was to review contemporary multimodality therapies, including their outcome, for locally recurrent rectal carcinoma after (chemo)radiotherapy and complete surgical resection of primary rectal cancer. DATA SOURCES: A comprehensive literature search of PubMed and EMBASE was performed. STUDY SELECTION: All English language articles presenting original patient data regarding treatment and the respective outcome of previously irradiated locally recurrent rectal cancer were included. INTERVENTIONS: All of the treatment modalities for locally recurrent rectal cancer were reviewed. MAIN OUTCOME MEASURES: Primary outcome parameters were local control, metastasis-free survival, and overall survival. Secondary outcome parameters were perioperative morbidity and mortality, and prognostic factors for treatment outcome. RESULTS: Of 854 studies, 9 studies and 474 patients with locally recurrent rectal carcinoma were included. Various treatment regimens were used, most with curative intent. Reirradiation was composed of (neo-)adjuvant external beam radiotherapy (with or without concurrent chemotherapy), additional intraoperative radiotherapy, or intraoperative radiotherapy only. Surgical technique highly varied, depending on the extent of the lesion. Radiation toxicity, perioperative morbidity, and mortality were generally acceptable. Outcome was better after curative intent treatment, any surgical resection, and R0 resections in particular. Moreover, reirradiation is associated with increased complete resection rates, which in turn positively affected local control and overall survival. LIMITATIONS: Most studies were retrospectively designed, with highly variable therapies, patient populations, and duration of follow-up. CONCLUSIONS: A complete resection is the most important prognostic factor and should be the goal of treatment in locally recurrent rectal carcinoma. Reirradiation seems safe and of additional value in reaching a complete resection. Considering the available evidence, at present reirradiation should be given on a case-specific basis, with all of the patients entering an international prospective database.

This study aimed to identify risk factors for long-term sexual dysfunction (SD) after rectal cancer treatment. Patients with resectable rectal cancer were randomised to total mesorectal excision with or without preoperative radiotherapy (PRT). Preoperatively and at 3, 6, 12, 18 and 24 months postoperatively, SD scores were filled out in questionnaires. Possible risk factors for postoperative deterioration of sexual functioning, including patients' demographics, tumour-specific factors and treatment-related variables, were investigated with univariate and multivariable regression analyses. Increase in general SD, erectile dysfunction and ejaculatory problems were reported by 76.4, 79.8 and 72.2 percent of the male patients, respectively. Risk factors were nerve damage, blood loss, anastomotic leakage, PRT and the presence of a stoma. In female patients, increase in general SD, dyspareunia and vaginal dryness were reported by 61.5, 59.1 and 56.6 percent, respectively. This was associated with PRT and the presence of a stoma. SD occurs frequently after rectal cancer treatment and is caused by surgical (nerve) damage with an additional effect of PRT. Patients should be informed preoperatively, and education of surgeons in neuroanatomy may provide the key to the improvement of functional outcome.

Contains fulltext : 71387.pdf (Publisher’s version ) (Open Access) BACKGROUND: Not all patients with locally advanced rectal cancer (LARC) respond equally to neo-adjuvant radiochemotherapy (RCT). Patients with highly apoptotic less advanced rectal cancers do not benefit from short-term radiotherapy. This study investigates whether this is also the case in the setting of RCT for LARC. PATIENTS AND METHODS: Tissue microarrays were constructed of biopsy and resection specimens of 201 LARC patients. Apoptosis (M30) and several apoptosis-regulating proteins [p53, Bcl-2, Bax, cyclooxygenase-2 (Cox-2) and mamma serine protease inhibitor (maspin)] were studied with immunohistochemistry. Subsequently, predictive values for local recurrence (LR), overall survival (OS) and histological tumour regression were analysed. RESULTS: Apoptotic levels, quantified as the number of apoptotic cells/mm(2) tumour epithelium, were higher in posttherapy tissues compared with biopsies (P < 0.001). Biopsies from clinical T4 stage tumours demonstrated significantly higher levels of apoptosis than clinical T3 stage tumours (P = 0.020). Therapy-induced apoptosis was higher when the interval between the last day of irradiation and surgery increased (P < 0.001, correlation coefficient = 0.355). Pre- and posttherapy apoptosis, p53, Bcl-2, Bax and Cox-2 were not associated with LR, OS or tumour regression. Intense pretherapy cytoplasmatic staining of maspin indicated a higher risk on LR (P = 0.009) only. CONCLUSION: Combined RCT is also successful in highly apoptotic tumours and is therefore independent of intrinsic apoptosis.

Background Low anterior resection (LAR) may result in faecal incontinence. This study aimed to identify risk factors for long-term faecal incontinence after total mesorectal excision (TME) with or without preoperative radiotherapy (PRT). Methods Between 1996 and 1999, patients with operable rectal cancer were randomized to TME with or without PRT. Eligible patients who underwent LAR were studied retrospectively at 2 years (399 patients) and 5 years (339) after TME. Results At 5 years after surgery faecal incontinence was reported by 61·5 per cent of patients who had PRT and 38·8 per cent of those who did not (P < 0·001). Excessive blood loss and height of the tumour were associated with long-term faecal incontinence, but only in patients treated with PRT. Conclusion Faecal incontinence is likely to occur after PRT and TME, especially when the perineum is irradiated.

The aim of this study was to evaluate nutritional status, food intake, and dysphagia in long-term head and neck cancer survivors.Thirty-two patients with stage III-IV head and neck cancer treated by chemoradiotherapy were invited to evaluate nutritional status (malnutrition, relative weight loss), food intake (food modification; quality), and dysphagia.At a median follow up of 44 months, 6 of 32 patients were at risk for malnutrition. Women (p = .049) and patients with high body mass index before treatment (p = .024) showed more weight loss. None of the 32 patients could eat a "full diet." Six patients used nutritional supplements/tube feeding. Low dysphagia-related quality of life scores were significantly correlated to increased food modification (r = 0.405; p = .024).Nutritional advice in patients with head and neck cancer is still necessary years after chemoradiation and should focus on nutritional status, food modification, and quality, in accord with recommended food groups.

Background The CARTS study is a multicenter feasibility study, investigating the role of rectum saving surgery for distal rectal cancer. Methods/Design Patients with a clinical T1-3 N0 M0 rectal adenocarcinoma below 10 cm from the anal verge will receive neoadjuvant chemoradiation therapy (25 fractions of 2 Gy with concurrent capecitabine). Transanal Endoscopic Microsurgery (TEM) will be performed 8 - 10 weeks after the end of the preoperative treatment depending on the clinical response. Primary objective is to determine the number of patients with a (near) complete pathological response after chemoradiation therapy and TEM. Secondary objectives are the local recurrence rate and quality of life after this combined therapeutic modality. A three-step analysis will be performed after 20, 33 and 55 patients to ensure the feasibility of this treatment protocol. Discussion The CARTS-study is one of the first prospective multicentre trials to investigate the role of a rectum saving treatment modality using chemoradiation therapy and local excision. The CARTS study is registered at clinicaltrials.gov (NCT01273051)

Background Urinary dysfunction (UD) is common after rectal cancer treatment, but the contribution of each treatment component (surgery and radiotherapy) to its development remains unclear. This study aimed to evaluate UD during 5 years after total mesorectal excision (TME) and to investigate the influence of preoperative radiotherapy (PRT) and surgical factors. Methods Patients with operable rectal cancer were randomized to TME with or without PRT. Questionnaires concerning UD were completed by 785 patients before and at several time points after surgery. Possible risk factors, including PRT, demographics, tumour location, and type and extent of resection, were investigated by multivariable regression analysis. Results Long-term incontinence was reported by 38·1 per cent of patients, of whom 72·0 per cent had normal preoperative function. Preoperative incontinence (relative risk (RR) 2·75, P = 0·001) and female sex (RR 2·77, P < 0·001) were independent risk factors. Long-term difficulty in bladder emptying was reported by 30·6 per cent of patients, of whom 65·0 per cent had normal preoperative function. Preoperative difficulty in bladder emptying (RR 2·94, P < 0·001), peroperative blood loss (RR 1·73, P = 0·028) and autonomic nerve damage (RR 2·82, P = 0·024) were independent risk factors. PRT was not associated with UD. Conclusion UD is a significant clinical problem after rectal cancer treatment and is not related to PRT, but rather to surgical nerve damage.