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Introduction Local excision is increasingly used as an alternative treatment for radical surgery in patients with early stage clinical T1 (cT1) rectal cancer. This study provides an overview of incidence, staging accuracy and treatment strategies in patients with cT1 rectal cancer in the Netherlands. Materials and methods Patients with cT1 rectal cancer diagnosed between 2005 and 2018 were included from the Netherlands Cancer Registry. An overview per time period (2005-2009, 2010-2014 and 2015-2018) of the incidence and various treatment strategies used, e.g. local excision (LE) or major resection, with/without neoadjuvant treatment (NAT), were given and trends over time were analysed using the Chi Square for Trend test. In addition, accuracy of tumour staging was described, compared and analysed over time. Results In total, 3033 patients with cT1 rectal cancer were diagnosed. The incidence of cT1 increased from 540 patients in 2005–2009 to 1643 patients in 2015–2018. There was a significant increased use of LE. In cT1N0/X patients, 9.2% received NAT, 25.5% were treated by total mesorectal excision (TME) and 11.4% received a completion TME (cTME) following prior LE. Overall accuracy in tumour staging (cT1 = pT1) was 77.3%, yet significantly worse in cN1/2 patients, as compared to cN0 patients (44.8% vs 77.9%, respectively, p Conclusion Over time, there was an increase in the incidence of cT1 tumours. Both the use of neoadjuvant therapy and TME surgery in clinically node negative patients decreased significantly. Clinical accuracy in T1 tumour staging improved over time, but remained significantly worse in clinical node positive patients.

Background The aim of this nationwide observational study was to evaluate factors associated with multivisceral resection (MVR), margin status and overall survival in locally advanced colorectal cancer (CRC). Material and methods Patients with (y)pT4, cM0 CRC between 2006 and 2017 were selected from the Netherlands Cancer Registry. Cox-proportional hazards modelling was used for survival analysis, stratified for T4a and T4b. Annual hospital volume cut-off was 75 for colon and 40 for rectal resections. Results A total of 11.930 patients were included and 2410 patients (20.2%) underwent MVR. Factors associated with MVR for colon and rectal cancer besides cT4 category were more recent diagnosis (OR 3.61, CI 95% 3.06–4.25 (colon) and OR 2.72, CI 95% 1.82–4.08 (rectum)) and high hospital volume (OR 1.20, CI 95% 1.05–1.38 (colon) and OR 2.17, CI 95% 1.55–3.04 (rectum)). Patients ≥70 year were less likely to undergo MVR for colon cancer (OR 0.80, 95% CI 0.70–0.90). Risk factors for incomplete resection were cT4 (OR 3.08, CI 95% 2.35–4.04 (colon) and OR 1.82, CI 95% 1.13–2.94 (rectum)) and poor/undifferentiated tumors (OR 1.41, CI 95% 1.14–1.72 (colon) and OR 1.69, CI 95% 1.05–2.74 (rectum)). More recent diagnosis was independently associated with less incomplete resections in colon cancer (OR 0.58, CI 95% 0.40–0.76). Independent predictors of survival were age, resection margin, nodal status and adjuvant chemotherapy, but not MVR. Conclusion Treatment of locally advanced CRC with MVR at population level was influenced by year of diagnosis and hospital volume. Margin status in colon cancer improved substantially over time.

Background Bowel dysfunction after rectal cancer surgery is common, with some experiencing low anterior resection syndrome (LARS) is common after rectal cancer surgery. This study examined if transanal total mesorectal excision (TaTME) has a similar risk of LARS and altered quality of life (QoL) as patients who undergo low anterior resection (LAR). Methods Patients who underwent TaTME or traditionally approached total mesorectal excision in a prospective colorectal cancer cohort study (2014–2019) were propensity score matched in a 1 : 1 ratio. LARS and QoL scores were assessed before and after surgery with a primary endpoint of major LARS at 12 months analysed for possible association between factors by logistic regression. Results Of 61 TaTME and 317 LAR patients eligible, 55 from each group were propensity score matched. Higher LARS scores (30.6 versus 25.4, P = 0.010) and more major LARS (65 versus 42 per cent, P = 0.013; OR 2.64, 95 per cent c.i. 1.22 to 5.71) were reported after TaTME. Additionally, QoL score differences (body image, bowel frequency, and embarrassment) were worse in the TaTME group. Conclusions TaTME may be associated with more severe bowel dysfunction than traditional approaches to rectal cancer.

Background Total mesorectal excision (TME) gives excellent oncological results in rectal cancer treatment, but patients may experience functional problems. A novel approach to performing TME is by single‐port transanal minimally invasive surgery. This systematic review evaluated the functional outcomes and quality of life after transanal and laparoscopic TME. Methods A comprehensive search in PubMed, the Cochrane Library, Embase and the trial registers was conducted in May 2019. PRISMA guidelines were used. Data for meta‐analysis were pooled using a random‐effects model. Results A total of 11 660 studies were identified, from which 14 studies and six conference abstracts involving 846 patients (599 transanal TME, 247 laparoscopic TME) were included. A substantial number of patients experienced functional problems consistent with low anterior resection syndrome (LARS). Meta‐analysis found no significant difference in major LARS between the two approaches (risk ratio 1·13, 95 per cent c.i. 0·94 to 1·35; P = 0·18). However, major heterogeneity was present in the studies together with poor reporting of functional baseline assessment. Conclusion No differences in function were observed between transanal and laparoscopic TME., A novel surgical technique for total mesorectal excision (TME) is single‐port transanal minimally invasive surgery. This systematic review aimed to evaluate the functional outcomes and quality of life after transanal total mesorectal excision (TaTME) and compare them with those of laparoscopic TME (LapTME). No differences between TaTME and LapTME were seen in terms of impaired functioning and reduced quality of life after rectal cancer surgery. However, major heterogeneity was present in the studies together with poor reporting of functional baseline assessment. Comparable function

Contains fulltext : 220437.pdf (Publisher’s version ) (Open Access) INTRODUCTION: The aim of this study was to examine the hospital variation in neoadjuvant treatment of rectal cancer according to the different risk groups (low-, intermediate- and high-risk) and evaluate the influence on survival. MATERIALS AND METHODS: Patients with non-metastasized rectal cancer diagnosed between 2009 and 2016 were selected from the Netherlands Cancer Registry. The observed and case-mix adjusted distribution of the different neoadjuvant treatment schemes (none, radiotherapy (RT), chemoradiotherapy (CRT)) by hospital of diagnosis were generated for each risk group in the cohorts before and after the national guideline update of 2014. RESULTS: A total of 25,306 patients were included and after case-mix adjustment, hospital of diagnosis was found to have a significant impact on neoadjuvant treatment administration in each of the three risk groups (p

Background: This study aimed to describe the treatment of metachronous colorectal cancer metastases in a recent population-based cohort. Method: Patients with stage I-III colorectal cancer (CRC), diagnosed between January 1st and June 30th , 2015 who were surgically treated with curative intent were selected from the Netherlands Cancer Registry. Follow-up was at least 3 years after diagnosis of the primary tumour. Treatment of metachronous metastases was categorized into local treatment, systemic treatment, and best supportive care. Overall survival was estimated using Kaplan-Meier method. Results: Out of 5412 patients, 782 (14%) developed metachronous metastases, of whom 393 (50%) underwent local treatment (LT) with or without systemic therapy, 30% of patients underwent only systemic therapy (ST) and 19% only best supportive care (BSC). The most common metastatic site was the liver (51%) followed by lungs (33%) and peritoneum (22%). LT rates were 69%, 66%, and 44% for liver-only, lung-only and, peritoneal-only metastases respectively. Patients receiving LT and ST were significantly younger than patients receiving LT alone, while patients receiving BSC were significantly older than the other groups (p < 0.001). Patients with liver-only or lung-only metastases had a 3-year OS of 50.2% (43.3–56.7 95% CI) and 61.5% (50.7–70.6 95% CI) respectively. Patients with peritoneal-only disease had a lower 3-year OS, 18.1% (10.1–28.0 95% CI). Conclusion: Patients with metastases confined to the liver and lung have the highest rates of local treatment for metachronous metastatic colorectal cancer. The number of patients who underwent local treatment is higher than reported in previous Dutch and international studies.

Background Distant metastatic disease is frequently observed in inflammatory breast cancer (IBC), with a poor prognosis as a consequence. The aim of this study was to analyze the association of hormone receptor (HR) and human epidermal growth factor receptor-2 (HER2) based breast cancer subtypes in stage IV inflammatory breast cancer (IBC) with preferential site of distant metastases and overall survival (OS). Methods For patients with stage IV IBC, diagnosed in the Netherlands between 2005 and 2016, tumors were classified into four breast cancer subtypes: HR+/HER2−, HR+/HER2+, HR−/HER2+, and HR−/HER2−. Patient, tumor, and treatment characteristics and sites of metastases were compared. OS of the subtypes was compared using Kaplan-Meier curves and the log-rank test. Association between subtype and OS was assessed in multivariable models using logistic regression. Results In total, 744 eligible patients were included: 340 (45.7%) tumors were HR+/HER2−, 148 (19.9%) HR−/HER2+, 131 (17.6%) HR+/HER2+, and 125 (16.8%) HR−/HER2−. Bone was the most common metastatic site in all subtypes. A significant predominance of bone metastases was found in HR+/HER2− IBC (71.5%), and liver and lung metastases in the HR−/HER2+ (41.2%) and HR−/HER2− (40.8%) subtypes, respectively. In multivariable analysis, the HR−/HER2− subtype was associated with significantly worse OS as compared to the other subtypes. Conclusion Breast cancer subtypes in stage IV IBC are associated with distinct patterns of metastatic spread and display notable differences in OS. The use of breast cancer subtypes can guide a more patient-tailored staging directed to metastatic site and extend of disease.

Introduction This retrospective study aims to examine the association between body mass index (BMI) and serious postoperative complications, 30-day mortality and overall survival in colorectal cancer (CRC) patients. Materials and methods All CRC patients diagnosed between 2008 and 2013 in the south-eastern part of the Netherlands were included. Patients were categorized into four BMI groups: underweight ( Results A total of 7371 CRC patients were included (underweight 133 (1.8%); normal weight 2054 (41.4%); overweight 2955 (40.1%); obesity 1229 (16.7%)). Underweight patients were more likely to have postoperative complications (18.8% vs. 11.7%, adjusted OR 1.95, 95% CI 1.08–3.49) and had a worse 30-day mortality (9.8% vs. 3.3%, adjusted OR 4.37, 95% CI 2.03–9.42) compared to normal weight patients. After stratification for stage (stage I-III and stage IV), underweight was associated with a worse overall survival in both groups compared to normal weight (stage I-III: HR 2.06, 95%CI 1.51–2.80; stage IV: HR 1.65, 95% CI 1.11–2.45). Overweight was associated with an improved overall survival compared to normal weight in both stage groups. Only in stage IV patients obesity was associated with a significant better overall survival compared to stage IV normal weight patients. Conclusion Underweight CRC patients were more likely to have postoperative complications and a worse 30-day mortality compared to patients in other BMI categories. The underweight population also has a worse long-term survival while overweight CRC patients and obese stage IV CRC patients were associated with an improved survival compared to normal weight patients.

Item does not contain fulltext OBJECTIVE: Palliative pelvic exenteration (PPE) is a technically complex operation with high morbidity and mortality rates, considered in patients with limited life expectancy. There is little evidence to guide practice. We performed a systematic review to evaluate the impact of PPE on symptom relief and quality of life (QoL). METHODS: A systematic review was conducted according to the PRISMA guidelines using Ovid MEDLINE, EMBASe, and PubMed databases for studies reporting on outcomes of PPE for symptom relief or QoL. Descriptive statistics were used on pooled patient cohorts. RESULTS: Twenty-three historical cohorts and case series were included, comprising 509 patients. No comparative studies were found. Most malignancies were of colorectal, gynaecological and urological origin. Common indications for PPE were pain, symptomatic fistula, bleeding, malodour, obstruction and pelvic sepsis. The pooled median postoperative morbidity rate was 53.6% (13-100%), the median in-hospital mortality was 6.3% (0-66.7%), and median OS was 14 months (4-40 months). Some symptom relief was reported in a median of 79% (50-100%) of the patients, although the magnitude of effect was poorly measured. Data for QoL measures were inconclusive. Five studies discouraged performing PPE in any patient, while 18 studies concluded that the procedure can be considered in highly selected patients. CONCLUSION: Available evidence on PPE is of low-quality. Morbidity and mortality rates are high with a short median OS interval. While some symptom relief may be afforded by this procedure, evidence for improvement in QoL is limited. A highly selective individualised approach is required to optimise the risk:benefit equation.

Background: In cancer patients with a poor prognosis, low skeletal muscle radiographic density is associated with higher mortality. Whether this association also holds for early-stage cancer is not very clear. We aimed to study the association between skeletal muscle density and overall mortality among early-stage (stage I–III) colorectal cancer (CRC) patients. Furthermore, we investigated the association between skeletal muscle density and both CRC-specific mortality and disease-free survival in a subset of the study population. Methods: Skeletal muscle density was assessed in 1681 early-stage CRC patients, diagnosed between 2006 and 2015, using pre-operative computed tomography images. Adjusted Cox proportional hazard models were used to evaluate the association between muscle density and overall mortality, CRC-specific mortality and disease-free survival. Results: The median follow-up time was 48 months (range 0–119 months). Low muscle density was detected in 39% of CRC patients. Low muscle density was significantly associated with higher mortality (low vs. normal: adjusted HR 1.91, 95% CI 1.53–2.38). After stratification for comorbidities, the association was highest in patients with ≥ 2 comorbidities (HR 2.11, 95% CI 1.55–2.87). Furthermore, low skeletal muscle density was significantly associated with poorer disease-free survival (HR 1.68, 95% CI 1.14–2.47), but not with CRC-specific mortality (HR 1.68, 95% CI 0.89–3.17) in a subset of the study population. Conclusion: In early-stage CRC patients, low muscle density was significantly associated with higher overall mortality, and worse disease-free survival.

Purpose Persistent fatigue among colorectal cancer (CRC) patients might be associated with unfavorable body composition, but data are sparse and inconsistent. We studied how skeletal muscle index (SMI), skeletal muscle radiodensity (SMR), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) at diagnosis are associated with fatigue up to 24 months post-diagnosis in stage I–III CRC patients. Methods SMI, SMR, VAT, and SAT were assessed among 646 CRC patients using pre-treatment computed tomography images. Fatigue at diagnosis, at 6, and 24 months post-diagnosis was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. The association of SMI, SMR, VAT, and SAT with fatigue (yes/no) was assessed using confounder-adjusted restricted cubic spline analyses. Results Prevalence of fatigue at diagnosis was 18%, at 6 months 25%, and at 24 months 12%. At diagnosis, a significant (p = 0.01) non-linear association of higher levels of SAT with higher prevalence of fatigue was observed. Lower levels of SMR were linearly associated with higher prevalence of fatigue at 6 months post-diagnosis (overall association p = 0.02). None of the body composition parameters were significantly associated with fatigue at 24 months. Conclusion Having more SAT was associated with more fatigue at diagnosis, while low levels of SMR were associated with more fatigue at 6 months post-diagnosis. Implications for Cancer Survivors Our results suggest that it may be interesting to investigate whether interventions that aim to increase SMR around the time of diagnosis may help to lower fatigue. However, more knowledge is needed to understand the mechanisms behind the association of SMR with fatigue.

Introduction Targeted therapy against tumor angiogenesis is widely used in clinical practice for patients with colorectal liver metastases (CRLM). Possible predictive biomarkers for tumor angiogenesis, such as, microvessel density (MVD), hypoxia and cell proliferation, can be determined using immunohistochemical staining. However, patients ineligible for surgical treatment need to undergo invasive diagnostic interventions in order to determine these biomarkers. CT perfusion (CTP) is an emerging functional imaging technique, which can non-invasively determine vascular properties of solid tumors. The purpose of this study was to evaluate CTP with histological biomarkers in CRLM. Material and methods Patients with CRLM underwent CTP one day before liver surgery. CTP analysis was performed on the entire volume of the largest metastases in each patient. Dual-input maximum slope analysis was used and data concerning arterial flow (AF), portal flow (PF) and perfusion index (PI) were recorded. Immunohistochemical staining with CD34, M75/CA-IX and MIB-1 was performed on the rim in the midsection of the tumor to determine respectively MVD, hypoxia and cell proliferation. Results Twenty CRLM in 20 patients were studied. Mean size of the largest CRLM was 37 mm (95% CI 21–54 mm). Mean AF and PF were respectively 64 ml/min/100ml (95% CI 48–79) and 30 ml/min/100ml (95% CI 22–38). Mean PI was 68% (95% CI 62–73). No significant correlation was found between tumor growth patterns and CTP (p = 0.95). MVD did not significantly correlate to AF (r = 0.05; p = 0.84), PF (r = 0.17; p = 0.47) and PI (r = -0.12; p = 0.63). Cell proliferation also did not significantly correlate to AF (r = 0.07; p = 0.78), PF (r = -0.01; p = 0.95) and PI (r = 0.15; p = 0.52). Hypoxia did not significantly correlate to AF (r = -0.05; p = 0.83), however, significantly to PF (r = 0.51; p = 0.02) and a trend to negative correlation with PF (r = -0.43; p = 0.06). However, after controlling the false discovery rate, no significant correlation between CTP and used immunohistochemical biomarkers was found. Conclusion In conclusion, this feasibility study found a trend to negative correlation between PI and hypoxia, CTP might therefore possibly evaluate this prognostic marker in CRLM non-invasively. However, CTP is not an appropriate technique for the assessment of microvessels or cell proliferation in CRLM.

Background This study aimed to examine the sphincter-preservation rate variations in rectal cancer surgery. The influence of hospital volume on sphincter-preservation rates and short-term outcomes (anastomotic leakage (AL), positive circumferential resection margin (CRM), 30- and 90-day mortality rates) were also analysed. Methods Non-metastasized rectal cancer patients treated between 2009 and 2016 were selected from the Netherlands Cancer Registry. Surgical procedures were divided into sphincter-preserving surgery and an end colostomy group. Multivariable logistic regression models were generated to estimate the probability of undergoing sphincter-preserving surgery according to the hospital of surgery and tumour height (low, 5 cm or less, mid, more than 5 cm to 10 cm, and high, more than 10 cm). The influence of annual hospital volume (less than 20, 20–39, more than 40 resections) on sphincter-preservation rate and short-term outcomes was also examined. Results A total of 20 959 patients were included (11 611 sphincter preservation and 8079 end colostomy) and the observed median sphincter-preservation rate in low, mid and high rectal cancer was 29.3, 75.6 and 87.9 per cent respectively. After case-mix adjustment, hospital of surgery was a significant factor for patients’ likelihood for sphincter preservation in all three subgroups (P, This manuscript describes the influence of hospital of surgery on patients’ likelihood of receiving sphincter-preserving surgery in rectal cancer treatment. The authors believe that awareness regarding this subject, and the potential differences between doctors and their preferences regarding choice of surgical treatment, need to be addressed. Besides hospital variation, the influence of annual hospital volume regarding rectal resections on sphincter-preservation rate and short-term outcomes are shown. Most of the previously reported effects of hospital volume on short-term outcomes seem to be resolved, probably due to ongoing clinical auditing and multidisciplinary team meetings.

The tumour microenvironment (TME) forms a major obstacle in effective cancer treatment and for clinical success of immunotherapy. Conventional co-cultures have shed light onto multiple aspects of cancer immunobiology, but they are limited by the lack of physiological complexity. We develop a human organotypic skin melanoma culture (OMC) that allows real-time study of host-malignant cell interactions within a multicellular tissue architecture. By co-culturing decellularized dermis with keratinocytes, fibroblasts and immune cells in the presence of melanoma cells, we generate a reconstructed TME that closely resembles tumour growth as observed in human lesions and supports cell survival and function. We demonstrate that the OMC is suitable and outperforms conventional 2D co-cultures for the study of TME-imprinting mechanisms. Within the OMC, we observe the tumour-driven conversion of cDC2s into CD14+ DCs, characterized by an immunosuppressive phenotype. The OMC provides a valuable approach to study how a TME affects the immune system., Conventional co-culture systems often lack physiological complexity of the tumor microenvironment. Here, the authors report an organotypic skin melanoma culture and use this model to investigate the tumor induced suppression on dendritic cells.

Background The aim of the present study was to evaluate MRI response rate and clinical outcome of short-course radiotherapy (SCRT) on rectal cancer as an alternative to chemoradiotherapy in patients where downstaging is indicated. Methods A retrospective analysis was performed of a patient cohort with rectal carcinoma (cT1-4cN0-2 cM0–1) from a large teaching hospital receiving restaging MRI, deferred surgery or no surgery after SCRT between 2011 and 2017. Patients who received chemotherapy during the interval between SCRT and restaging MRI were excluded. The primary outcome measure was the magnetic resonance tumor regression grade (mrTRG) at restaging MRI after SCRT followed by a long interval. Secondary, pathological tumor stage, complete resection rate and 1-year overall survival were assessed. Results A total of 47 patients (M:F = 27:20, median age 80 (range 53–88) years), were included. In 33 patients MRI was performed for response assessment 10 weeks after SCRT. A moderate or good response (mrTRG≤3) was observed in 24 of 33 patients (73%). While most patients (85%; n = 28) showed cT3 or cT4 stage on baseline MRI, a ypT3 or ypT4 stage was found in only 20 patients (61%) after SCRT (p n = 23 (70%) before SCRT compared to n = 8 (30%) post-treatment (p = 0.03). After SCRT, 39 patients underwent deferred surgery (after a median of 14 weeks after start of SCRT) and a resection with complete margins was achieved in 35 (90%) patients. One-year overall survival after surgery was 82%. Complete pathological response was found in 2 patients (5%). Conclusions The use of SCRT followed by a long interval to restaging showed a moderate to good response in 73% and therefore can be considered as an alternative to chemoradiotherapy in elderly comorbid patients.

Contains fulltext : 220715.pdf (Publisher’s version ) (Closed access) INTRODUCTION: Information regarding the effects of resection of the primary tumor in stage IV inflammatory breast cancer (IBC) is scarce. We analyzed the impact of resection of the primary tumor on overall survival (OS) in a large stage IV IBC population. MATERIALS AND METHODS: Patients diagnosed with stage IV IBC between 2005 and 2016 were selected from the Netherlands Cancer Registry, excluding patients without any treatment. To correct for immortal time bias, we performed a landmark analysis including patients alive at least six months after diagnosis. With propensity score matching, patients undergoing surgery of the primary tumor were matched to patients not receiving surgery. Multivariable Cox proportional hazard analyses were performed to determine the association between treatment strategy and OS in the non-matched and matched cohort. RESULTS: Of the 580 included patients after landmark analysis, 441 patients (76%) received only non-surgical treatments and 139 (24%) underwent surgery (96% mastectomy). Median follow-up was 28.8 and 20.0 months in the surgery and no surgery group, respectively. Surgery in the non-matched cohort was independently associated with better survival (HR0.56[95%CI:0.42-0.75]). In the matched cohort (n = 202), surgically treated patients had improved survival over nonsurgically treated patients (p < 0.005). Multivariable analysis of the matched cohort revealed that surgery was still associated with better survival (HR0.62[95%CI:0.44-0.87]). CONCLUSION: Although residual confounding and confounding by severity cannot be ruled out, this study suggests that surgery of the primary tumor is associated with improved OS and should be considered as part of the treatment strategy in stage IV IBC.

Contains fulltext : 225961.pdf (Publisher’s version ) (Open Access) Follow-up after curative treatment for colorectal cancer (CRC) puts pressure on outpatient services due to the growing number of CRC survivors. The aim of this state-of-the-art review was to evaluate setting, manner and provider of follow-up. Moreover, perceptions of CRC survivors and health care providers regarding standard and alternative follow-up were examined. After a comprehensive literature search of the PubMed database, 69 articles were included reporting on CRC follow-up in the hospital, primary care and home setting. Hospital-based follow-up is most common and has been provided by surgeons, medical oncologists, and gastroenterologists, as well as nurses. Primary care-based follow-up has been provided by general practitioners or nurses. Even though most hospital- or primary care-based follow-up care requires patients to visit the clinic, telephone-based care has proven to be a feasible alternative. Most patients perceived follow-up as positive; valuing screening and detection for disease recurrence and appreciating support for physical and psychosocial symptoms. Hospital-based follow-up performed by the medical specialist or nurse is highly preferred by patients and health care providers. However, willingness of both patients and health care providers for alternative, primary care or remote follow-up exists. Nurse-led and GP-led follow-up have proven to be cost-effective alternatives compared to specialist-led follow-up. If proven safe and acceptable, remote follow-up can become a cost-effective alternative. To decrease the personal and financial burden of follow-up for a growing number of colorectal cancer survivors, a more acceptable, flexible and dynamic care follow-up mode consisting of enhanced communication and role definitions among clinicians is warranted.

Background The precise content and frequency of follow-up of patients with colorectal cancer (CRC) is variable and guideline adherence is low. The aim of this study was to assess the view of colorectal surgeons on their local follow-up schedule and to clarify their opinions about risk-stratification and organ preserving therapies. Equally important, adherence to the Dutch national guidelines was determined. Methods Colorectal surgeons were invited to complete a web-based survey about the importance and interval of clinical follow-up, CEA monitoring and the use of imaging modalities. Furthermore, the opinions regarding physical examination, risk-stratification, organ preserving strategies, and follow-up setting were assessed. Data were analyzed using quantitative and qualitative analysis methods. Results A total of 106 colorectal surgeons from 52 general and 5 university hospitals filled in the survey, yielding a hospital response rate of 74% and a surgeon response rate of 42%. The follow-up of patients with CRC was mainly done by surgeons (71%). The majority of the respondents (68%) did not routinely perform physical examination during follow-up of rectal patients. Abdominal ultrasound was the predominant modality used for detection of liver metastases (77%). Chest X-ray was the main modality for detecting lung metastases (69%). During the first year of follow-up, adherence to the minimal guideline recommendations was high (99–100%). The results demonstrate that, within the framework of the guidelines, some respondents applied a more intensive follow-up and others a less intensive schedule. The majority of the respondents (77%) applied one single follow-up imaging schedule for all patients that underwent treatment with curative intent. Conclusions Dutch colorectal surgeons’ adherence to minimal guideline recommendations was high, but within the guideline framework, opinions differed about the required intensity and content of clinical visits, the interval of CEA monitoring, and the importance and frequency of imaging techniques. This national survey demonstrates current follow-up practice throughout the Netherlands and highlights the follow-up differences of curatively treated patients with CRC.

Contains fulltext : 229816.pdf (Publisher’s version ) (Closed access) INTRODUCTION: In recent decades, the use of pre-operative needle biopsy for breast cancer diagnosis has shifted. There is also an increased demand for availability of predictive factors. This study aims to quantify these changes. MATERIAL AND METHODS: From the Dutch nationwide pathology database (PALGA), all reports on breast cancer for five periods of 3 months between 1996 and 2016 were retrieved. Reports were categorised using automatic recognition of keywords. Classification was checked manually for the first 200 reports per period. The first 100 resected cases in each period underwent detailed investigation. RESULTS: For automatic analysis 34,639 reports were retrieved. Accuracy was 98% compared to manual assessment. Fine needle aspiration cytology (FNAC) decreased from 77% (1996) to 58% (2001), 34% (2006), 25% (2011), and 17% (2016). For detailed assessment, 498 cases were analysed. Diagnostic surgical excision decreased from 24% in 1996 to 3% in 2016, cases with only cytology from 65% to 1%, respectively. Cytology and core needle biopsy (CNB) were combined in 21% of cases in 2016. Pre-operative availability of ER status increased from 3% in 1996 to 36% in 2006 and 78% in 2016 (as compared to 47%, 92%, and 97% for post-operative availability, respectively) and for HER2 status from 0% to 13% and 66% (as compared to 1%, 89%, and 96% for post-operative availability, respectively). CONCLUSION: Results suggest that nationwide, clinics prioritise reliability and availability of ER and HER2 status, replacing FNAC by CNB. However, for optimal treatment planning for all patients, availability of pre-operative receptor status warrants further improvement.

Introduction: Optimized treatment of primary rectal cancer might have influenced treatment characteristics and outcome of locally recurrent rectal cancer (LRRC). Subgroup analysis of the Dutch TME trial showed that preoperative radiotherapy (PRT) for the primary tumour was an independent poor prognostic factor after diagnosis of LRRC. This cross-sectional population study aimed to evaluate treatment and overall survival (OS) of LRRC patients, stratified for prior preoperative radiotherapy (PRT) and intention of treatment of LRRC.Methods: All patients developing LRRC were selected from a collaborative Snapshot study on 2095 surgically treated rectal cancer patients from 71 Dutch hospitals in the year 2011. Cox proportional hazard analysis was performed to determine predictors for OS.Results: A total of 107 LRRC patients (5.1%) were included, of whom 88 (82%) underwent PRT for their primary tumour. LRRC was treated with initial curative intent in 31 patients (29%), with eventual resection in 20 patients (19%). Median OS was 22 and 8 months after curative and palliative intent treatment, respectively (p Conclusions: This cross-sectional study revealed that rectal cancer patients, who underwent curative resection in the Netherlands in 2011 and subsequently developed local recurrence, were amenable for again curative intent treatment in 29%, with a corresponding median survival of 22 months. Prior PRT was not significantly associated with survival after diagnosis of LRRC. (C) 2019 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Contains fulltext : 195651.pdf (Publisher’s version ) (Open Access) BACKGROUND: One of the late complications associated with radiation therapy (RT) is a possible increased risk of second cancer. In this systematic review, we analysed the incidence of rectal cancer following primary pelvic cancer irradiation. METHODS: A literature search was conducted using the PubMed and EMBASE libraries. Original articles that reported on secondary rectal cancer after previous RT for a primary pelvic cancer were included. Sensitivity analyses were performed by correcting for low number of events, high risk of bias, and outlying results. RESULTS: A total of 5171 citations were identified during the literature search, 23 studies were included in the meta-analyses after screening. A pooled analysis, irrespective of primary tumour location, showed an increased risk for rectal cancer following RT (N=403.243) compared with non-irradiated patients (N=615.530) with a relative risk (RR) of 1.43 (95% confidence interval [CI] 1.18-1.72). Organ specific meta-analysis showed an increased risk for rectal cancer after RT for prostate (RR 1.36, 95%CI 1.10-1.67) and cervical cancer (RR 1.61, 95% CI 1.10-2.35). No relation was seen in ovarian cancer patients. The modality of RT did not influence the incidence of rectal cancer. CONCLUSIONS: This review demonstrates an increased risk for second primary rectal cancer in patients who received RT to the pelvic region. This increased risk was modest and could not be confirmed for all primary pelvic cancer sites. The present study does not provide data to change guidelines for surveillance for rectal cancer in previously irradiated patients.

Contains fulltext : 174816pub.pdf (Publisher’s version ) (Closed access) Background: The aim of this study was to analyze the association between radiation therapy (RT) for rectal cancer and the development of second tumors. Patients and methods: Data on all surgically treated non-metastatic primary rectal cancer patients diagnosed between 1989 and 2007 were retrieved from the Netherlands population-based cancer registry. Fine and Gray's competing risk model was used for estimation of the cumulative incidence of second tumors. Multivariable analysis was conducted using Cox regression. Results: The cohort consisted of 29 027 patients of which 15 467 patients had undergone RT. Median follow-up was 7.7 years (range 0-27). Among all 4398 patients who were diagnosed with a second primary tumor, 1030 had one or more pelvic tumors. The standardized incidence risk for any second tumor was 1.16 (95% confidence interval [CI] 1.12-1.19), resulting in 27.7/10 000 excess cancer cases per year in patients treated for rectal cancer compared with the general population. RT reduced the cumulative incidence of second pelvic tumors compared with patients who did not receive RT (subhazard ratio [SHR] 0.77, CI 0.68-0.88). Second prostate tumors were less common in patients who received RT (SHR 0.54, CI 0.46-0.64), gynecological tumors were more frequently observed in patients who received RT (SHR 1.49, CI 1.11-2.00). Conclusions: Patients with previous rectal cancer had a marginally increased risk of a second tumor compared with the general population. Gynecological tumors occurred more often in females who received RT, but this did not result in an overall increased risk for a second cancer. RT even seemed to have a protective effect on the development of other second pelvic tumors, pre-dominantly for prostate cancer. These findings are highly important and can contribute to improved patient counseling.

Background This study assessed trends in the treatment and survival of palliatively treated patients with gastric cancer, with a focus on age-related differences. Methods For this retrospective, population-based, nationwide cohort study, all patients diagnosed between 1989 and 2013 with non-cardia gastric cancer with metastasized disease or invasion into adjacent structures were selected from the Netherlands Cancer Registry. Trends in treatment and 2-year overall survival were analysed and compared between younger (age less than 70 years) and older (aged 70 years or more) patients. Analyses were done for five consecutive periods of 5 years, from 1989–1993 to 2009–2013. Multivariable logistic regression analysis was used to examine the probability of undergoing surgery. Multivariable Cox regression analysis was used to identify independent risk factors for death. Results Palliative resection rates decreased significantly in both younger and older patients, from 24·5 and 26·2 per cent to 3·0 and 5·0 per cent respectively. Compared with patients who received chemotherapy alone, both younger (21·6 versus 6·3 per cent respectively; P < 0·001) and older (14·7 versus 4·6 per cent; P < 0·001) patients who underwent surgery had better 2-year overall survival rates. Multivariable analysis demonstrated that younger and older patients who received chemotherapy alone had worse overall survival than patients who had surgery only (younger: hazard ratio (HR) 1·22, 95 per cent c.i. 1·12 to 1·33; older: HR 1·12, 1·01 to 1·24). After 2003 there was no association between period of diagnosis and overall survival in younger or older patients. Conclusion Despite changes in the use of resection and chemotherapy as palliative treatment, overall survival rates of patients with advanced and metastatic gastric cancer did not improve.

Contains fulltext : 175649.pdf (Publisher’s version ) (Closed access) BACKGROUND: The objective of this study was to map referral patterns in patients with synchronous colorectal liver metastases (SCLM) and to investigate if type, volume and location of the hospital of diagnosis are associated with whether or not patients underwent liver resection. METHODS: This population-based study includes all patients diagnosed with SCLM between 2008 and 2012, based on the Netherlands Cancer Registry. To study inter-hospital variation, the proportion of patients undergoing liver surgery was calculated per hospital of diagnosis. Multivariable multilevel logistic regression analysis was used to investigate the association between hospital characteristics and liver resection. RESULTS: Of 10,520 patients with SCLM, 12% (n = 1259) underwent liver surgery. Of these patients, 58% (n = 733) were referred to another hospital to undergo liver surgery. In 53% of the patients (n = 647), liver resection was performed in a university hospital, in 39% (n = 482) in a dedicated liver centre and in 8% (n = 102) in a general hospital. There was a large inter-hospital variation in the proportion of patients undergoing liver resection (2-26%). In a multilevel logistic regression model, the odds of undergoing liver surgery were higher when patients were diagnosed in hospitals where liver surgery was performed compared with the general hospitals (dedicated liver centre: odds ratio 1.36 [95% confidence intervals 1.08-1.70], university hospital: odds ratio 1.69 [95% confidence intervals 1.22-2.34]). CONCLUSION: There is a large inter-hospital and inter-regional variation in the utilisation of liver resection. Patients diagnosed with SCLM in expert centres had a higher chance of undergoing liver resection.

Contains fulltext : 181925.pdf (Publisher’s version ) (Open Access) INTRODUCTION: This study investigates the treatment and survival of young versus elderly potentially curable gastric cancer patients in the Netherlands. PATIENTS AND METHODS: All noncardia gastric cancer patients with potentially curable gastric cancer according to stage (cTx-3, cNx-3, and cMx-0) diagnosed between 1989 and 2013 were selected from the Netherlands Cancer Registry. Trends in treatment and overall survival were compared between young patients (younger than 70 years) and elderly patients (70 years or older). Multivariable logistic regression analysis was used to examine the probability of patients undergoing surgery and chemotherapy in the most recent period. Multivariable Cox regression analysis was used to identify independent factors associated with survival. RESULTS: In total, 8107 young and 13,814 elderly gastric cancer patients were included. There was a major increase in the proportion of patients treated with resection and chemotherapy after 2004-2008. In young patients the increase was from 2.6% in 1999-2003 to 63% in 2009-2013 (p < 0.01). Also an increase was noticed among elderly patients, from 0.1% to 16% (p < 0.01). Median survival increased from 2004 to 2008 onward particularly in young patients and to a lesser extent in elderly patients (from 28 to 41 months vs from 11 to 13 months). Multivariable Cox regression analyses confirmed that overall survival improved for young and elderly patients. DISCUSSION: Young patients experienced a stronger improvement in survival than elderly patients, resulting in an increasing survival gap. The literature shows this is a problem not only in the Netherlands but also throughout Europe. The dissimilarity in treatment between young and elderly patients could be the reason for this difference.

Background Shoulder complaints are frequently reported after surgical treatment for thyroid carcinoma. However, no specific literature on this topic is available for these patients and, hence, its impact on quality of life (QOL) is unknown and there are no known predictors of shoulder complaints in this specific patient population. Therefore, the purpose of this study was to assess the prevalence of shoulder-related complaints and its relation to QOL and clinical characteristics after thyroid carcinoma surgery by means of a cross-sectional case control study in a tertiary referral center. Methods The prevalence of shoulder complaints and its relation to clinical characteristics and QOL after thyroid carcinoma surgery (n = 109) was compared to a healthy control group (n = 81). Main outcome measures are prevalence of self-reported shoulder complaints, results of the Disabilities of the Arm, Shoulder, and Hand questionnaire (DASH), and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30-questions (EORTC-QLQ-C30). Results Patients with thyroid carcinoma, on average 10.2 years after thyroid surgery, reported a 58.7% prevalence of shoulder-related complaints, which was significantly more than the 13.6% reported by healthy controls (p < .01). Patients with thyroid carcinoma scored worse than healthy controls on most of the different subscales of the DASH and EORTC-QLQ-C30. Bivariate association analysis identified level V neck dissection as being associated with the prevalence of shoulder complaints and the DASH score, and spinal accessory nerve damage and employment status as being associated with the DASH score. Prevalence of shoulder complaints and the DASH scores were significantly correlated to several EORTC-QLQ-C30 scores. Only 11.9% of patients with thyroid carcinoma retrospectively reported having received preoperative information on possible shoulder complaints and only 34.9% of patients with thyroid carcinoma retrospectively reported having received additional care for their shoulder complaints. Conclusion Shoulder complaints represent and underestimated problem and are reported by many patients who had surgery for thyroid carcinoma. Information provision to the patient should be improved, shoulder complaints should be registered, and additional care should be provided after thyroid carcinoma surgery to improve QOL. © 2016 Wiley Periodicals, Inc. Head Neck 39: 260–268, 2017

Contains fulltext : 220489.pdf (Publisher’s version ) (Closed access) Up to 78 % of patients with inflammatory breast cancer (IBC) present with axillary lymph node involvement and up to 40 % with distant metastases. Previous studies indicate that 2-deoxy-2-((18)F)fluoro-d-glucose ([(18)F]FDG) positron emission tomography/computed tomography (PET/CT) might be used for initial staging in patients with inflammatory breast cancer (IBC). In other cancer types, [(18)F]FDG PET/CT has been demonstrated to be a sensitive technique, providing complementary information on locoregional and distant disease to conventional imaging modalities. This systematic review showed that (18)F]FDG PET/CT detects additional locoregional lymph node metastases and distant metastases in 10.3 % of patients, that were not detected with standard staging imaging. Compared with conventional imaging procedures, [(18)F]FDG PET/CT had better diagnostic performance for detection of locoregional and distant metastases and should standardly be used in the diagnostic work-up of IBC patients.

__Background__ Clinically staged T1-3 rectal cancer (cT1-3) is generally treated by total mesorectal excision(TME) with or without neoadjuvant therapy and sometimes requires beyond TME-surgery, whereas cT4 rectal cancer often requires both. This study evaluates the outcome of cT1-3 and cT4 rectal cancer according to hospital volume. __Methods__ Patients undergoing rectal cancer surgery between 2005 and 2013 in the Netherlands were included from the National Cancer Registry. Hospitals were divided into low(1–20), medium(21–50) and high(>50 resections/year) volume for cT1-3 and low(1–4), medium(5–9) and high(≥10 resections/year) volume for cT4 rectal cancer. Cox-proportional hazards model was used for multivariable analysis of overall survival (OS). __Results__ A total of 14.050 confirmed cT1-3 patients and 2.104 cT4 patients underwent surgery. In cT1-3 rectal cancer, there was no significant difference in 5-year OS related to high, medium and low hospital volume (70% vs. 69% vs. 69%). In cT4 rectal cancer, treatment in a high volume cT4 hospital was associated with a survival benefit compared to low volume cT4 hospitals (HR 0.81 95%CI 0.67–0.98) adjusted for non-treatment related confounders, but this was not significant after adjustment for neoadjuvant treatment. Patients with cT4-tumours treated in high volume hospitals had a significantly lower age, more synchronous metastases, more patients treated with neoadjuvant therapy and a higher pT-stage. __Conclusion__ Hospital volume was not associated with survival in cT1-3 rectal cancer. In cT4 rectal cancer, treatment in high volume cT4 hospitals was associated with improved survival compared to low volume cT4 hospitals, although this association lost statistical significance after correction for neoadjuvant treatment.

Seroma is the most frequent complication after mastectomy (ME) and axillary lymph node dissection (ALND). The quilting suture technique, in which skin flaps are sutured to the underlying muscle, was previously investigated and found to reduce seroma incidence after ME and ALND. This study aimed to investigate whether postoperative wound drainage can safely be omitted when quilting sutures are applied. Two groups with a total of 251 consecutive patients who underwent ME, ALND, or both were retrospectively compared. The first group underwent quilting sutures with wound vacuum drainage, and the second group underwent quilting sutures without wound drainage. The primary outcome was the incidence of postoperative clinically significant seroma (CSS). The secondary outcomes were the incidence of postoperative infection, bleeding complications, wound dehiscence, and flap necrosis. The group without a postoperative drain (n = 166) had a significantly lower CSS incidence (8.4%) than the group with a postoperative drain (n = 85, 21.2%) (p

Item does not contain fulltext PURPOSE: The combination of resection and radiofrequency ablation (RFA) may provide an alternative treatment for patients with unresectable colorectal liver metastases (CRLM). Although the results in literature look promising, uncertainty exists with regard to complication risks and survival for this therapy. METHODS: From January 2000 to May 2013, patients were included in a prospective multicenter database when treated for CRLM. Exclusion criteria were: two-staged treatment, synchronous resection of liver metastases and primary tumor, loss to follow-up or extrahepatic metastases. Patients were divided in a resection-only group (ROG) and combination group (CG). Outcome variables were retrospectively analyzed. RESULTS: In CG, 98 patients were included versus 534 patients in ROG. There were no differences in general patient characteristics. Patients in CG had a higher Fong clinical risk score (CRS; P = 0.001), better ASA classification (P = 0.04) and received more neoadjuvant chemotherapy (P = 0.001). There was no difference in postoperative morbidity or 90-day mortality. The 5-year disease-free survival (DFS) for CG and ROG was 25% and 36.1% (P = 0.03), respectively. For the 5-year overall survival (OS) this was respectively 42% and 62.2% (P = 0.001). On multivariate analysis, Fong CRS was a significant predictor for DFS. For OS, Fong CRS, ASA class IV and the combination therapy were significant predictors. CONCLUSION: The combination of hepatic resection and intraoperative RFA is a safe procedure, without increase in postoperative morbidity or mortality. Combining RFA and resection in one session is a valid treatment option for patients who would otherwise be inoperable.

Objective: The study aims to evaluate all patients who underwent liver resection for metastatic disease for demographics, characteristics of the primary tumor and metastasis, volume of liver resection specimens per pathology laboratory and to describe trends in surgical treatment. Methods: Data were prospectively collected using the Dutch nationwide pathology network. All pathology reports containing details on liver resections for metastatic disease between January 2001 and December 2010 were evaluated. Results: A total of 3,916 liver resections were performed in 3,699 patients with a median age of 63 years (range 1-91). The primary tumor was mainly colorectal (n = 3,256; 88.0%). The number of ‘high volume liver centers' increased from 2 to 12 in the study period, whereas the number of ‘low volume centers' decreased. The number of liver resections increased from 224 to 596 per year (p ≤ 0.0001). A significant increase was demonstrated in elderly patients, patients with multiple metastases, liver resections for smaller metastases and minor liver resections. Conclusion: Although the majority of patients were young and had solitary metastasis, indications for liver resection are expanding as indicated by increasing numbers of elderly and patients with multiple liver metastases. Patients with non-colorectal liver metastases were seldom candidates for resection.

Contains fulltext : 152676.pdf (Publisher’s version ) (Open Access) BACKGROUND: Patients with palpable melanoma groin metastases have a poor prognosis. There is debate whether a combined superficial and deep groin dissection (CGD) is necessary or if superficial groin dissection (SGD) alone is sufficient. AIM: The aim of this study was to analyze risk factors for deep pelvic nodal involvement in a retrospective, multicenter cohort of palpable groin melanoma metastases. This could aid in the development of an algorithm for selective surgery in the future. METHODS: This study related to 209 therapeutic CGDs from four tertiary centers in The Netherlands (1992-2013), selected based on complete preoperative imaging and pathology reports. Analyzed risk factors included baseline and primary tumor characteristics, total and positive number of inguinal nodes, inguinal lymph node ratio (LNR) and positive deep pelvic nodes on imaging (computed tomography [CT] +/- positron emission tomography [PET], or PET - low-dose CT). RESULTS: Median age was 57 years, 54 % of patients were female, and median follow-up was 21 months (interquartile range [IQR] 11-46 months). Median Breslow thickness was 2.10 mm (IQR 1.40-3.40 mm), and 26 % of all primary melanomas were ulcerated. Positive deep pelvic nodes occurred in 35 % of CGDs. Significantly fewer inguinal nodes were positive in case of negative deep pelvic nodes (median 1 [IQR 1-2] vs. 3 [IQR 1-4] for positive deep pelvic nodes; p < 0.001), and LNR was significantly lower for negative versus positive deep pelvic nodes [median 0.15 (IQR 0.10-0.25) vs. 0.33 (IQR 0.14-0.54); p < 0.001]. A combination of negative imaging, low LNR, low number of positive inguinal nodes, and no extracapsular extension (ECE) could accurately predict the absence of pelvic nodal involvement in 84 % of patients. CONCLUSIONS: Patients with negative imaging, few positive inguinal nodes, no ECE, and low LNR have a low risk of positive deep pelvic nodes and may safely undergo SGD alone.

Contains fulltext : 193493.pdf (Publisher’s version ) (Closed access) BACKGROUND: In the era of organ preserving strategies in rectal cancer, insight into the efficacy of preoperative therapies is crucial. The goal of the current study was to evaluate and compare tumor response in rectal cancer patients according to their type of preoperative therapy. METHODS: All rectal cancer patients diagnosed between 2005 and 2014, receiving radiation therapy (RT, 5 x 5Gy; N = 764) or chemoradiation therapy (CRT; N = 5070) followed by total mesorectal excision after an interval of 5-15 weeks were retrieved from the nationwide Netherlands Cancer registry. Logistic regression was used for multivariable analysis. RESULTS: Median age of patients treated with RT was 76 years (range 28-92) compared to 64 years (range 21-92) for patients treated with CRT (P < 0.001). Patients treated with RT had a significantly lower clinical stage (P < 0.001). A complete pathologic response (ypT0N0) was found in 9.3% of patients treated with RT, significantly less than in patients treated with CRT (17.5%; odds ratio [OR] 0.37, 95% confidence interval [CI] 0.24-0.57). A good response (ypT0-1N0) was observed in 17.5% of patients treated with RT and in 22.6% of patients treated with CRT (OR 0.70, 95% CI 0.51-0.95). Histological subtype, clinical stage and distance to anus were identified as independent predictors for tumor response. CONCLUSIONS: Despite a more advanced clinical stage, complete pathologic response was more common in patients treated with CRT than in patients treated with RT. Prospective trials are needed to establish the differences in other outcome parameters, including the impact on organ preserving strategies.

Contains fulltext : 153113pub.pdf (Publisher’s version ) (Closed access) INTRODUCTION: New diagnostics, the emergence of total mesorectal excision and neoadjuvant treatments have improved outcome for patients with rectal cancer. Patients with distal rectal cancer undergoing an abdominoperineal excision seem to do worse compared to those treated with sphinctersparing techniques. The aim of this study was to evaluate the quality of care for patients undergoing an abdominoperineal excision for distal rectal cancer during the last 15 years. MATERIALS AND METHODS: All patients with rectal cancer, who underwent an abdominoperineal excision between December 1996 and December 2010 in 5 Dutch hospitals were analysed. Patients were divided into three cohorts; 1996-2001, 2001-2005 and 2006-2010. All data was extracted from medical records. RESULTS: 477 patients were identified. There was no significant difference in sex, age, BMI, prior pelvic surgery and ASA stages between the cohorts. MRI became a standard tool in the work-up, the use increased from 4.5% in the first, to 95.1% in the last cohort (p < 0.0001). Neoadjuvant treatment shifted from predominantly none (64.9% in cohort 1) to short course radiotherapy (66.7% in cohort 2) and chemoradiation therapy (55.7% in cohort 3). There was a trend towards a decreased circumferential resection margin involvement in the cohorts (18.8%, 16.7% and 11.4%; p = 0.142). Accidental bowel perforations have significantly decreased from 28.6%, and 21.7% to 9.2% in cohort 3 (p < 0.0001). CONCLUSION: Significant improvements in work-up, neoadjuvant and surgical treatment have been made for patients with low rectal cancer, undergoing an abdominoperineal excision. These improvements result in improved short term outcome.

Item does not contain fulltext Inflammatory breast cancer (IBC) is the most aggressive entity of breast cancer. Management involves coordination of multidisciplinary management and usually includes neoadjuvant chemotherapy, ablative surgery if a tumor-free resection margin is expected and locoregional radiotherapy. This multimodal therapeutic approach has significantly improved patient survival. However, the median overall survival among women with IBC is still poor. By elucidating the biologic characteristics of IBC, new treatment options may become available. We performed a comprehensive review of the English-language literature on IBC through computerized literature searches. The objective of the current review is to present an overview of the literature related to the biology, imaging and multidisciplinary treatment of inflammatory breast cancer.

Introduction: Centralization of gastric cancer surgery is thought to improve outcome and has been imposed in the Netherlands since 2012. This study analyzes the effect of centralization in terms of treatment outcome and survival in the Eastern part of the Netherlands. Methods: All gastric cancer patients without distant metastases who underwent a gastrectomy in six hospitals in the Eastern part of the Netherlands between 2008 and 2011 (pre-centralization) and 2013–2016 (post-centralization) were selected from the Netherlands Cancer Registry. Patient and tumor characteristics and treatment outcomes (duration of surgery, blood loss, resection margin, lymphadenectomy, chemotherapy, postoperative complications and hospital stay, and overall and disease-free survival) were analyzed and compared between pre- and post-centralization. Results: One hundred forty-four patients were included pre-centralization and 106 patients post-centralization. Patient and tumor characteristics were almost similar in the two periods. After centralization, more patients were treated with perioperative chemotherapy (25 vs. 42% p

Contains fulltext : 174953.pdf (Publisher’s version ) (Open Access) BACKGROUND: Studies showed that axillary lymph node dissection can be safely omitted in presence of positive sentinel lymph node(s) in breast cancer patients treated with breast conserving therapy. Since the outcome of the sentinel lymph node biopsy has no clinical consequence, the value of the procedure itself is being questioned. The aim of the BOOG 2013-08 trial is to investigate whether the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients treated with breast conserving therapy. METHODS: The BOOG 2013-08 is a Dutch prospective non-inferiority randomized multicentre trial. Women with pathologically confirmed clinically node negative T1-2 invasive breast cancer undergoing breast conserving therapy will be randomized for sentinel lymph node biopsy versus no sentinel lymph node biopsy. Endpoints include regional recurrence after 5 (primary endpoint) and 10 years of follow-up, distant-disease free and overall survival, quality of life, morbidity and cost-effectiveness. Previous data indicate a 5-year regional recurrence free survival rate of 99% for the control arm and 96% for the study arm. In combination with a non-inferiority limit of 5% and probability of 0.8, this result in a sample size of 1.644 patients including a lost to follow-up rate of 10%. Primary and secondary endpoints will be reported after 5 and 10 years of follow-up. DISCUSSION: If the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients undergoing breast conserving therapy, this study will cost-effectively lead to a decreased axillary morbidity rate and thereby improved quality of life with non-inferior regional control, distant-disease free survival and overall survival. TRIAL REGISTRATION: The BOOG 2013-08 study is registered in ClinicalTrials.gov since October 20, 2014, Identifier: NCT02271828. https://clinicaltrials.gov/ct2/show/NCT02271828.

Contains fulltext : 137703pub.pdf (Publisher’s version ) (Open Access) Contains fulltext : 137703pos.pdf (Author’s version postprint ) (Open Access) CONTEXT: Patients with thyroid nodules of indeterminate cytology undergo diagnostic surgery according to current guidelines. In 75% of patients, the nodule is benign. In these patients, surgery was unnecessary and unbeneficial because complications may occur. Preoperative fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) was found to have a very high negative predictive value (96%) and might therefore avoid futile surgery, complications, and costs. In the United States, two molecular tests of cytology material are routinely used for this purpose. OBJECTIVE: Five-year cost-effectiveness for routine implementation of FDG-PET/CT was evaluated in adult patients with indeterminate fine-needle aspiration cytology and compared with surgery in all patients and both molecular tests. DESIGN: A Markov decision model was developed to synthesize the evidence on cost-effectiveness about the four alternative strategies. The model was probabilistically analyzed. One-way sensitivity analyses of deterministic input variables likely to influence outcome were performed. SETTING AND SUBJECTS: The model was representative for adult patients with cytologically indeterminate thyroid nodules. MAIN OUTCOME MEASURES: The discounted incremental net monetary benefit (iNMB), the efficiency decision rule containing outcomes as quality-adjusted life-years and (direct) medical cost, of implementation of FDG-PET/CT is displayed. RESULTS: Full implementation of FDG-PET/CT resulted in 40% surgery for benign nodules, compared with 75% in the conventional approach, without a difference in recurrence free and overall survival. The FDG-PET/CT modality is the more efficient technology, with a mean iNMB of euro3684 compared with surgery in all. Also, compared with a gene expression classifier test and a molecular marker panel, the mean iNMB of FDG-PET/CT was euro1030 and euro3851, respectively, and consequently the more efficient alternative. CONCLUSION: Full implementation of preoperative FDG-PET/CT in patients with indeterminate thyroid nodules could prevent up to 47% of current unnecessary surgery leading to lower costs and a modest increase of health-related quality of life. Compared with an approach with diagnostic surgery in all patients and both molecular tests, it is the least expensive alternative with similar effectiveness as the gene-expression classifier.

Item does not contain fulltext PURPOSE: Locally advanced breast cancer (LABC) includes inflammatory breast cancer (IBC) as well as non-inflammatory LABC (NI-LABC). The aim of this population-based study was to compare the tumour characteristics, treatment and relative survival of IBC and NI-LABC patients. METHODS: Patients with either IBC (cT4d) or NI-LABC (cT4a-c) were identified from the nationwide Netherlands Cancer Registry from the period 1989-2015. In each group, patients are divided into three time periods in order to perform a trend analysis: 1989-1997, 1998-2006, and 2007-2015. RESULTS: IBC comprised 1.1% and NI-LABC 4.6% of all diagnosed breast cancer patients. IBC patients showed more nodal metastases (77.8 vs. 69.7%, P < 0.001) and distant metastases (39.7 vs. 34.1%, P < 0.001). IBC tumours were more often triple negative (23.2 vs. 12.8%, P < 0.001) and poorly differentiated (69.8 vs. 53.8%, P < 0.001). Trimodality therapy (neoadjuvant chemotherapy, surgery and adjuvant radiotherapy) was more often applied over time in both groups (IBC: 23.7%-56.0%-68.6%; NI-LABC: 3.7%-25.9%-43.6%; P trend < 0.001). In IBC patients, relative 5-year survival was significantly shorter than in patients with NI-LABC (30.2 vs. 45.1%, P < 0.001). The relative survival significantly improved for IBC from 17.2% (1989-1997) to 30.0 and 38.9% for the last two time periods (1998-2006: P < 0.001; 2007-2015: P < 0.001). In contrast, survival did not significantly improve in NI-LABC breast cancer: from 44.7% (1989-1997) to 44.0 and 48.4% (1998-2006: P = 0.483; 2007-2015: P = 0.091). CONCLUSIONS: IBC has tumour characteristics that determine its aggressive biology compared to NI-LABC. Trimodality therapy was increasingly applied in both groups, but did not improve survival in NI-LABC. Although relative survival in IBC patients has improved during the last decades, it remains a disease with a dismal prognosis.

Contains fulltext : 118739pub.pdf (Publisher’s version ) (Closed access) Contains fulltext : 118739pos.pdf (Author’s version postprint ) (Open Access) As axillary recurrence (AR) after a negative sentinel lymph node biopsy (SLNB) is rare, the prognosis of these patients is unknown. Since treatment paradigms for patients with breast cancer are shifting toward less axillary surgery, the number of ARs might increase. In this study, we evaluated primary and salvage treatment as well as long-term survival of patients diagnosed with an AR. A retrospective analysis of the cancer registry of 16 breast cancer units in the Netherlands was used to identify patients who developed an AR after a negative SLNB performed between 2002 and 2004. Using local hospital records we recorded primary patient-, tumor-, and treatment-characteristics, as well as salvage treatment. We identified 54 patients with an AR, median 30 months (range 3-79) after SLNB. Eighteen patients (33 %) were initially treated with breast conserving therapy, 15 of whom received external beam radiation therapy (EBRT). Thirty-three patients (61 %) did not receive adjuvant systemic treatment. In 45 of the 54 (83 %) patients, a salvage axillary lymph node dissection was performed showing a median of three positive nodes (range 1-24). Nine patients (17 %) were not treated surgically: three were treated with salvage EBRT and six with salvage systemic therapy only. At time of detection of the AR, a total of 7 patients (13 %) had proven distant metastases. After a median follow-up of 47 months (range 3-118), the 5-year "post-recurrence" distant metastasis free survival was 50 % and overall survival was 58 %. Significant negative predictors of survival were negative estrogen receptor (ER) status and receiving adjuvant chemotherapy at initial treatment. AR following a negative SLNB is associated with a 58 % 5-year OS. Prognostic factors are ER- primary tumor and receiving adjuvant chemotherapy as a part of initial treatment, reflecting an aggressive phenotype. Adequate regional and systemic salvage therapy constitute a chance for long-term survival after AR. 01 juli 2013

Background: The aim of this study was to determine whether selection with fluorine-18-deoxyglucose positron emission tomography (FDG-PET) imaging would result in an improved outcome in surgically treated patients with curative resection of colorectal liver metastases (CRLM), stratified by the clinical risk score (CRS) of Fong et al. [Ann Surg 1999;230:309-318]. Patients and Methods: Between January 2000 and December 2009, all patients who underwent resection for CRLM from two different university teaching hospitals in the Netherlands were analysed. Patients were stratified by the CRS. Results: In total 613 patients were eligible for analysis. There was no statistical difference in median disease-free survival (DFS) between patients with and without an FDG-PET scan in both low CRS [17 months (95% CI 12-22) vs. 14 months (95% CI 11-17), p = 0.332] and high CRS [14 months (95% CI 7-21) vs. 9 months (95% CI 8-10), p = 0.073]. There was no statistical difference in median overall survival (OS) between patients with and without an FDG-PET scan in both low CRS [64 months (95% CI 54-74) vs. 54 months (95% CI 42-66), p = 0.663] and high CRS [39 months (95% CI 23-55) vs. 41 months (95% CI 34-48), p = 0.903]. Conclusion: The present study could not demonstrate that patients selected by an FDG-PET scan before liver resection, and stratified by CRS, have an improvement in DFS or OS.

Contains fulltext : 125802pub.pdf (Publisher’s version ) (Closed access) BACKGROUND: Colorectal mucinous adenocarcinoma (MC) has been associated with impaired prognosis compared with nonmucinous adenocarcinoma (NMC). Response to palliative chemotherapy is poor in metastatic disease, but the benefit of adjuvant chemotherapeutic treatment has never been assessed in large patient groups. This study analyses overall survival and efficacy of adjuvant chemotherapy in terms of survival in patients following radical resection for MC. PATIENTS AND METHODS: This population-based study involved 27 251 unselected patients diagnosed with colorectal carcinoma between 1990 and 2010 and recorded in a prospective pathology-based registry. Kaplan-Meier analysis and log-rank testing were used to estimate survival. Cox proportional hazard model was used to calculate multivariate hazard ratios for death. RESULTS: MC was found in 12.3% (N = 3052) of colorectal tumors with a different distribution compared with NMC, with 24.4% located in the rectum and 54.3% in the proximal colon (versus 38.0% and 30.6%), P < 0.0001. NMC was more often classified as stage I disease than MC (20.5% versus 10.9%), P < 0.0001. After adjustments for covariates, MC was associated with a higher risk of death only when located in the rectum [hazard ratio 1.22; 95% confidence interval (CI) 1.11-1.34]. Multivariate regression analysis showed a similar survival after adjuvant chemotherapy for stage III MC and NMC patients. CONCLUSIONS: The poor prognosis for MC is only present in rectal cancer. In the adjuvant setting, there is no difference in the efficacy of chemotherapy between MC and NMC; therefore, current adjuvant treatment recommendations should not take histology into account.

In this study, the reproducibility of T(2) * MR imaging in colorectal liver metastases was assessed and T(2) * values were correlated with the expression of the hypoxia-related markers GLUT-1 and CA-IX as well as the relative vascular area, and the vessel density in resected tumors. The reproducibility of T(2) * was analyzed in 18 patients with in total 22 colorectal liver metastases using the Bland and Altman method for the 16th, 50th, and 84th percentile values. Immunohistochemical staining was performed on 17 resected tumors obtained from 16 patients. The median T(2) * of all liver metastases was 25.0 ± 5.6 ms vs. 23.0 ± 4.1 ms (median ± st.dev.) in normal liver. The coefficient of repeatability was 11.2 ms and the limits of agreement were -13.2 ms and 9.1 ms for median T(2) * values. On average, T(2) * showed fair reproducibility. No correlations between T(2) * values, hypoxia- and vascularity-related markers were observed. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.

Contains fulltext : 172310.pdf (Publisher’s version ) (Open Access) BACKGROUND: Rectal cancer surgery is accompanied with high morbidity and poor long term functional outcome. Screening programs have shown a shift towards more early staged cancers. Patients with early rectal cancer can potentially benefit significantly from rectal preserving therapy. For the earliest stage cancers, local excision is sufficient when the risk of lymph node disease and subsequent recurrence is below 5 %. However, the majority of early cancers are associated with an intermediate risk of lymph node involvement (5-20 %) suggesting that local excision alone is not sufficient, while completion radical surgery, which is currently standard of care, could be a substantial overtreatment for this group of patients. METHODS/STUDY DESIGN: In this multicentre randomised trial, patients with an intermediate risk T1-2 rectal cancer, that has been locally excised using an endoluminal technique, will be randomized between adjuvant chemo-radiotherapylimited to the mesorectum and standard completion total mesorectal excision (TME). To strictly monitor the risk of locoregional recurrence in the experimental arm and enable early salvage surgery, there will be additional follow up with frequent MRI and endoscopy. The primary outcome of the study is three-year local recurrence rate. Secondary outcomes are morbidity, disease free and overall survival, stoma rate, functional outcomes, health related quality of life and costs. The design is a non inferiority study with a total sample size of 302 patients. DISCUSSION: The results of the TESAR trial will potentially demonstrate that adjuvant chemoradiotherapy is an oncological safe treatment option in patients who are confronted with the difficult clinical dilemma of a radically removed intermediate risk early rectal cancer by polypectomy or transanal surgery that is conventionally treated with subsequent radical surgery. Preserving the rectum using adjuvant radiotherapy is expected to significantly improve morbidity, function and quality of life if compared to completion TME surgery. TRIAL REGISTRATION: NCT02371304 , registration date: February 2015.

Contains fulltext : 171283.pdf (Publisher’s version ) (Closed access) PURPOSE: Parastomal hernia (PSH) is a common complication after colostomy formation. Recent studies indicate that mesh implantation during formation of a colostomy might prevent a PSH. To determine if placement of a retromuscular mesh at the colostomy site is a feasible, safe and effective procedure in preventing a parastomal hernia, we performed a multicentre randomized controlled trial in 11 large teaching hospitals and three university centres in The Netherlands. METHODS: Augmentation of the abdominal wall with a retromuscular light-weight polypropylene mesh (Parietene Light, Covidien) around the trephine was compared with traditional colostomy formation. Patients undergoing elective open formation of a permanent end-colostomy were eligible. 150 patients were randomized between 2010 and 2012. Primary endpoint of the PREVENT trial is the incidence of parastomal hernia. Secondary endpoints are morbidity, pain, quality of life, mortality and cost-effectiveness. This article focussed on the early results of the PREVENT trial and, therefore, operation time, postoperative morbidity, pain, and quality of life were measured. RESULTS: Outcomes represent results after 3 months of follow-up. A total of 150 patients were randomized. Mean operation time of the mesh group (N = 72) was significantly longer than in the control group (N = 78) (182.6 vs. 156.8 min; P = 0.018). Four (2.7 %) peristomal infections occurred of which one (1.4 %) in the mesh group. No infection of the mesh occurred. Most of the other infections were infections of the perineal wound, equally distributed over both groups. No statistical differences were discovered in stoma or mesh-related complications, fistula or stricture formation, pain, or quality of life. CONCLUSIONS: During open and elective formation of an end-colostomy, primary placement of a retromuscular light-weight polypropylene mesh for prevention of a parastomal hernia is a safe and feasible procedure. The PREVENT trial is registered at: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2018 .

Background Neoadjuvant chemoradiation therapy (CRT) has been widely implemented in the treatment of rectal cancer patients, but optimal timing of surgery after neoadjuvant therapy is unclear. The purpose of this study was to evaluate the effects of prolonged intervals between long-course CRT and surgery in rectal cancer patients. Methods Data on all rectal cancer patients diagnosed between 2006 and 2011 were retrieved from the population-based Netherlands Cancer Registry; the main outcome parameters were pathologic complete response (pCR) and overall survival (OS). Outcomes were reported separately for patients with early tumors (ETs; N = 217) and locally advanced rectal cancer (LARC; N = 1073). Patients were divided into 2-week interval groups according to treatment interval, ranging from 5–6 to 13–14 weeks. Kaplan–Meier curves, and logistic regression and Cox regression models were used for data analysis. Results No significant difference in pCR rate was observed for ET patients according to treatment interval. Compared with a treatment interval of 7–8 weeks, pCR rates in LARC patients were higher after 9–10 weeks (18.4 %; odds ratio [OR] 1.56, 95 % CI 1.03–2.37) and 11–12 weeks of treatment interval (20.8 %; OR 1.94, 95 % CI 1.15–3.26). Treatment interval did not influence OS in ET or LARC patients. Conclusions Treatment intervals of 9–12 weeks between surgery and CRT seem to improve the chances of pCR in LARC patients, without an effect on OS. The length of treatment interval did not affect outcomes in patients with ET. The ongoing search for minimally invasive surgery drives the need for exploration of factors that improve pathologic response. Electronic supplementary material The online version of this article (doi:10.1245/s10434-016-5294-0) contains supplementary material, which is available to authorized users.

Contains fulltext : 167332pub.pdf (Publisher’s version ) (Closed access) Contains fulltext : 167332pos.pdf (Author’s version postprint ) (Open Access) BACKGROUND: Fine Needle Aspiration Biopsy (FNAB), Core Needle biopsy (CNB) and hybrid techniques including Core Wash Cytology (CWC) are available for same-day diagnosis in breast lesions. In CWC a washing of the biopsy core is processed for a provisional cytological diagnosis, after which the core is processed like a regular CNB. This study focuses on the reliability of CWC in daily practice. METHODS: All consecutive CWC procedures performed in a referral breast centre between May 2009 and May 2012 were reviewed, correlating CWC results with the CNB result, definitive diagnosis after surgical resection and/or follow-up. Symptomatic as well as screen-detected lesions, undergoing CNB were included. RESULTS: 1253 CWC procedures were performed. Definitive histology showed 849 (68%) malignant and 404 (32%) benign lesions. 80% of CWC procedures yielded a conclusive diagnosis: this percentage was higher amongst malignant lesions and lower for benign lesions: 89% and 62% respectively. Sensitivity and specificity of a conclusive CWC result were respectively 98.3% and 90.4%. The eventual incidence of malignancy in the cytological 'atypical' group (5%) was similar to the cytological 'benign' group (6%). CONCLUSION: CWC can be used to make a reliable provisional diagnosis of breast lesions within the hour. The high probability of conclusive results in malignant lesions makes CWC well suited for high risk populations.

Background The use of tumour necrosis factor (TNF) α in isolated limb perfusion (ILP) for in-transit melanoma metastasis is not uniformly accepted. This article reports the long-term results of adding TNF-α to standard melphalan-based ILP (TM-ILP) for treatment of melanoma in-transit metastases. Methods Data for patients treated between 1991 and 2005 were retrieved from a prospectively maintained database. Hyperthermic ILP was performed with 1–4 mg TNF-α. With a median potential follow-up of 13 years, response rates, time to local progression and disease-specific survival were analysed in relation to standard baseline factors. Results Some 118 TM-ILPs were analysed in 105 patients, 54 for stage IIIA, 50 for stage IIIAB and 14 for stage IV disease. The overall response rate was 93·2 per cent; the response was complete in 67·8 per cent and partial in 25·4 per cent. The response rate was significantly influenced by stage of disease (IIIA versus IIIAB; P = 0·006). The complete response was maintained until the end of follow-up in 35 patients (33·3 per cent), and local control was achieved with one additional intervention in 12 others (11·4 per cent). Local progression occurred after 66 ILPs (55·9 per cent). Number of in-transit metastases (P = 0·008) and complete response after ILP (P < 0·001) were strong prognostic factors for time to local progression. The 5-year disease-specific survival rate was 27·3 per cent; survival was positively influenced by age, stage of disease, previous ILP and complete response after ILP. Conclusion ILP with TNF-α may obtain long-term local control in selected patients with in-transit metastases from melanoma.

Item does not contain fulltext BACKGROUND: Management of patients with clinically detectable lymph node metastasis to the groin is by ilioinguinal or combined superficial and deep groin dissection (CGD) according to most literature, but in practice superficial groin dissection (SGD) only is still performed in some centers. The aim of this study is to evaluate the experience in CGD versus SGD patients in our center. METHODS: Between 1991 and 2009, 121 therapeutic CGD and 48 SGD were performed in 169 melanoma patients with palpable groin metastases at our institute. Median follow-up was 20 and, for survivors, 45 months. RESULTS: In this heterogeneous group of patients, overall (OS) and disease-free survival, local control rates, and morbidity rates were not significantly different between CGD and SGD patients. However, CGD patients had a trend towards more chronic lymphedema. Superficial lymph node ratio, the number of positive superficial lymph nodes, and the presence of deep nodes were prognostic factors for survival. CGD patients with involved deep lymph nodes (24.8%) had estimated 5-year OS of 12% compared with 40% with no involved deep lymph nodes (p = 0.001). Preoperative computed tomography (CT) scan had high negative predictive value of 91% for detection of pelvic nodal involvement. CONCLUSIONS: This study demonstrated that survival and local control do not differ for patients with palpable groin metastases treated by CGD or SGD. Patients without pathological iliac nodes on CT might safely undergo SGD, while CGD might be reserved for patients with multiple positive nodes on SGD and/or positive deep nodes on CT scan.