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A bstract 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.

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.

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.

Introduction Complete resection is the most important prognostic factor in surgery for pelvic tumors. In locally advanced and recurrent pelvic malignancies, radical margins are sometimes difficult to obtain because of close relation to or growth in adjacent organs/structures. Total pelvic exenteration (TPE) is an exenterative operation for these advanced tumors and involves en bloc resection of the rectum, bladder, and internal genital organs (prostate/seminal vesicles or uterus, ovaries and/or vagina). Methods Between 1994 and 2008, a TPE was performed in 69 patients with pelvic cancer; 48 with rectal cancer (32 primary and 16 recurrent), 14 with cervical cancer (1 primary and 13 recurrent), 5 with sarcoma (3 primary and 2 recurrent), 1 with primary vaginal, and 1 with recurrent endometrial carcinoma. Ten patients were treated with neoadjuvant chemotherapy and 66 patients with preoperative radiotherapy to induce down-staging. Eighteen patients received IORT because of an incomplete or marginal complete resection. Results The median follow-up was 43 (range, 1–196) months. Median duration of surgery was 448 (range, 300–670) minutes, median blood loss was 6,300 (range, 750–21,000) ml, and hospitalization was 17 (range, 4–65) days. Overall major and minor complication rates were 34% and 57%, respectively. The in-hospital mortality rate was 1%. A complete resection was possible in 75% of all patients, a microscopically incomplete resection (R1) in 16%, and a macroscopically incomplete resection (R2) in 9%. Five-year local control for primary locally advanced rectal cancer, recurrent rectal cancer, and cervical cancer was 89%, 38%, and 64%, respectively. Overall survival after 5 years for primary locally advanced rectal cancer, recurrent rectal cancer, and cervical cancer was 66%, 8%, and 45%. Conclusions Total pelvic exenteration is accompanied with considerable morbidity, but good local control and acceptable overall survival justifies the use of this extensive surgical technique in most patients, especially patients with primary locally advanced rectal cancer and recurrent cervical cancer.

Background Trials failed to demonstrate additional value of completion axillary lymph node dissection in case of limited sentinel lymph node metastases in breast cancer patients undergoing breast conserving therapy. It has been suggested that the low regional recurrence rates in these trials might partially be ascribed to accidental irradiation of part of the axilla by whole breast radiation therapy, which precludes extrapolation of results to mastectomy patients. The aim of the randomized controlled BOOG 2013–07 trial is therefore to investigate whether completion axillary treatment can be safely omitted in sentinel lymph node positive breast cancer patients treated with mastectomy. Design This study is designed as a non-inferiority randomized controlled multicentre trial. Women aged 18 years or older diagnosed with unilateral invasive clinically T1-2 N0 breast cancer who are treated with mastectomy, and who have a maximum of three axillary sentinel lymph nodes containing micro- and/or macrometastases, will be randomized for completion axillary treatment versus no completion axillary treatment. Completion axillary treatment can consist of completion axillary lymph node dissection or axillary radiation therapy. Primary endpoint is regional recurrence rate at 5 years. Based on a 5-year regional recurrence free survival rate of 98 % among controls and 96 % for study subjects, the sample size amounts 439 per arm (including 10 % lost to follow-up), to be able to reject the null hypothesis that the rate for study and control subjects is inferior by at least 5 % with a probability of 0.8. Results will be reported after 5 and 10 years of follow-up. Discussion We hypothesize that completion axillary treatment can be safely omitted in sentinel node positive breast cancer patients undergoing mastectomy. If confirmed, this study will significantly decrease the number of breast cancer patients receiving extensive treatment of the axilla, thereby diminishing the risk of morbidity and improving quality of life, while maintaining excellent regional control and without affecting survival. Trial registration The BOOG 2013–07 study is registered in the register of ClinicalTrials.gov since April 10, 2014, Identifier: NCT02112682 .

Background Approximately one third of the colorectal cancer survivors (CRCS) experience high levels of psychological distress. Common concerns experienced by CRCS include distress related to physical problems, anxiety, fear of cancer recurrence (FCR) and depressive symptoms. However, psychological interventions for distressed CRCS are scarce. Therefore, a blended therapy was developed, combining face-to-face cognitive behavioral therapy (CBT) with online self-management activities and telephone consultations. The aim of the study is to evaluate the efficacy and cost-effectiveness of this blended therapy in reducing psychological distress in CRCS. Methods/design The CORRECT study is a two-arm multicenter randomized controlled trial (RCT). A sample of 160 highly distressed CRCS (a score on the Distress Thermometer of 5 or higher) will be recruited from several hospitals in the Netherlands. CRCS will be randomized to either the intervention condition (blended CBT) or the control condition (care as usual). The blended therapy covers approximately 14 weeks and combines five face-to-face sessions and three telephone consultations with a psychologist, with access to an interactive self-management website. It includes three modules which are individually-tailored to patient concerns and aimed at decreasing: 1) distress caused by physical consequences of CRC, 2) anxiety and FCR, 3) depressive symptoms. Patients can choose between the optional modules. The primary outcome is general distress (Brief Symptom Inventory-18). Secondary outcomes are quality of life and general psychological wellbeing. Assessments will take place at baseline prior to randomization, after 4 and 7 months. Discussion Blended CBT is an innovative and promising approach for providing tailored supportive care to reduce high distress in CRCS. If the intervention proves to be effective, an evidence-based intervention will become available for implementation in clinical practice. Trial registration This trial is registered in the Netherlands Trial Register ( NTR6025 ) on August 3, 2016.

Purpose An overall trend is observed towards de-escalation of axillary surgery in patients with breast cancer. The objective of this study was to evaluate this trend in patients treated with neoadjuvant systemic therapy (NST). Methods Patients with cT1-4N0-3 breast cancer treated with NST (2006–2016) were selected from the Netherlands Cancer Registry. Patients were classified by clinical node status (cN) and type of axillary surgery. Uni- and multivariable logistic regression analyses were performed to determine the clinicopathological factors associated with performing ALND in cN+ patients. Results A total of 12,461 patients treated with NST were identified [5830 cN0 patients (46.8%), 6631 cN+ patients (53.2%)]. In cN0 patients, an overall increase in sentinel lymph node biopsy (SLNB) only (not followed by ALND) was seen from 11% in 2006 to 94% in 2016 ( p  < 0.001). SLNB performed post-NST increased from 33 to 62% ( p  < 0.001). In cN+ patients, an overall decrease in ALND was seen from 99% in 2006 to 53% in 2016 ( p  < 0.001). Age (OR 1.01, CI 1.00–1.02), year of diagnosis (OR 0.47, CI 0.44–0.50), HER2-positive disease (OR 0.62, CI 0.52–0.75), clinical tumor stage (T2 vs. T1 OR 1.32, CI 1.06–1.65, T3 vs. T1 OR 2.04, CI 1.58–2.63, T4 vs. T1 OR 6.37, CI 4.26–9.50), and clinical nodal stage (N3 vs. N1 OR 1.65, CI 1.28–2.12) were correlated with performing ALND in cN+ patients. Conclusions ALND decreased substantially over the past decade in patients treated with NST. Assessment of long-term prognosis of patients in whom ALND is omitted after NST is urgently needed.

Purpose Both “high tie” (HT) and “low tie” (LT) are well-known strategies in rectal surgery. The aim of this study was to compare colonic perfusion after HT to colonic perfusion after LT. Methods Patients undergoing rectal resection for malignancy were included. Colonic perfusion was measured with laser Doppler flowmetry, immediately after laparotomy on the antimesenterial side of the colon segment that was to become the afferent loop (measurement A). This measurement was repeated after rectal resection (measurement B). The blood flow ratios (B/A) were compared between the HT group and the LT group. Results Blood flow was measured in 33 patients, 16 undergoing HT and 17 undergoing LT. Colonic blood flow slightly decreased in the HT group whereas the flow increased in the LT group. The blood flow ratio was significantly higher in the LT group (1.48 vs. 0.91; p  = 0.04), independent of the blood pressure. Conclusion This study shows the blood flow ratio to be higher in the LT group. This suggests that anastomoses may benefit from better perfusion when LT is performed.

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.

Background Seroma is the most common complication following breast cancer surgery, with reported incidence up to 90%. Seroma causes patient discomfort, is associated with surgical site infections (SSI), often requires treatment and increases healthcare consumption. The quilting suture technique, in which the skin flaps are sutured to the pectoralis muscle, leads to a significant reduction of seroma with a decrease in the number of aspirations and surgical site infections. However, implementation is lagging due to unknown side effects, increase in operation time and cost effectiveness. Main objective of this study is to assess the impact of large scale implementation of the quilting suture technique in patients undergoing mastectomy and/or axillary lymph node dissection (ALND). Methods The QUILT study is a stepped wedge design study performed among nine teaching hospitals in the Netherlands. The study consists of nine steps, with each step one hospital will implement the quilting suture technique. Allocation of the order of implementation will be randomization-based. Primary outcome is ‘textbook outcome’, i.e.no wound complications, no re-admission, re-operation or unscheduled visit to the outpatient clinic and no increased use of postoperative analgesics. A total of 113 patients is required based on a sample size calculation. Secondary outcomes are shoulder function, cosmetic outcome, satisfaction with thoracic wall and health care consumption. Follow-up lasts for 6 months. Discussion This will be one of the first multicentre prospective studies in which quilting without postoperative wound drain is compared with conventional wound closure. We hypothesize that quilting is a simple technique to increase textbook outcome, enhance patient comfort and reduce health care consumption.