[Wearing surgical masks in the operation theatre: yes or no?] / Wel of geen mondmaskers dragen op de OK?

OBJECTIVE: In the Netherlands, the surgical mask is part of the standard surgical attire even for the non-sterile personnel in the operation theatre. Solid evidence on the effect on postoperative infection rates is missing. Due to a national scarcity in surgical masks during the first wave of the COVID-19 crisis the usage of these masks was decreased. In our tertiary referral centre for Surgical Oncology, this led to the decision that, for a period of ten weeks, the surgical masks were only being used by the sterile surgical team and not by non-sterile operation theatre personnel. This retrospective study evaluates the influence of this intervention in terms of postoperative wound infection rates. DESIGN: Retrospective cohort study. METHOD: Consecutive patients undergoing surgery during the first COVID-19 wave (2-3-2020 until 11-05-2020) were compared with patients undergoing surgery in the same period a year earlier. Patients undergoing surgery for soft-tissue malignancies were included. Intra-abdominal surgery was excluded. Primary outcome measurement was wound infection rate within 30 days following surgery. Secondary, a cost reduction analysis was made. RESULTS: In the COVID-19 wave, a total of 219 patients underwent surgery for soft-tissue malignancies, compared to 241 a year earlier. The incidence of postoperative wound infection was 58/460 (12.6%) for the total cohort. There was no difference in infection rate between the COVID-19 period and the same period in 2019; 25/219 (11,4%; 95% CI: 7,8-16,4)) vs. 33/241 (13,7%; 95% CI: 9,8-18,6), p = 0,46) respectively. During the COVID-19 wave, a total of 6.400 of surgical masks were used by the personnel in the operation theatre complex, compared to a total of 11.000 in the same period in 2019. This resulted in a reduction of 42% in usage of surgical masks. CONCLUSION: Based on this mono-centric, explorative retrospective cohort study, it seems that omitting the surgical mask for the non-sterile operation theatre personnel does not influence the postoperative wound infection rate. Despite the fact that our sample size is small, the impressive reduction in usage of 42% demands further research initiatives on a larger scale.

Effects of and Lessons Learned from an Internet-Based Physical Activity Support Program (with and without Physiotherapist Telephone Counselling) on Physical Activity Levels of Breast and Prostate Cancer Survivors: The PABLO Randomized Controlled Trial.

BACKGROUND: We developed an Internet-based physical activity (PA) support program (IPAS), which is embedded in a patient portal. We evaluated the effectiveness and costs of IPAS alone (online only) or IPAS combined with physiotherapist telephone counselling (blended care), compared to a control group. METHODS: Breast or prostate cancer survivors, 3-36 months after completing primary treatment, were randomized to 6-months access to online only, blended care, or a control group. At baseline and 6-month post-baseline, minutes of moderate-to-vigorous PA (MVPA) were measured by accelerometers. Secondary outcomes were self-reported PA, fatigue, mood, health-related quality of life, attitude toward PA, and costs. (Generalized) linear models were used to compare the outcomes between groups. RESULTS: We recruited 137 survivors (participation rate 11%). We did not observe any significant between-group differences in MVPA or secondary outcomes. Adherence was rather low and satisfaction scores were low to moderate, with better scores for blended care. Costs for both interventions were low. CONCLUSIONS: Recruitment to the study was challenging and the interventions were less efficacious than anticipated, which led to lessons learned for future trials. Suggestions for future research are as follows: improved accessibility of the support program, increased frequency of support, and use of activity trackers.

(Cost-)effectiveness of an internet-based physical activity support program (with and without physiotherapy counselling) on physical activity levels of breast and prostate cancer survivors: design of the PABLO trial.

BACKGROUND: Higher levels of physical activity (PA) after treatment are associated with beneficial effects on physical and psychosocial functioning of cancer survivors. However, survivors often do not meet the recommended levels of PA. In order to promote PA, we developed a closed internet-based program. The aim of the study is to evaluate the (cost-)effectiveness of an internet-based PA-promotion program, alone or combined with physiotherapy counselling, compared to usual care, on PA-levels of breast or prostate cancer survivors. In this multicenter randomised controlled trial (RCT), breast or prostate cancer survivors who completed their primary treatment 3-12 months earlier, will be randomised to either 6-months access to a fully-automated internet-based intervention alone, an internet-based intervention plus remote support by a physiotherapist, or a control group. The intervention is based on the Transtheoretical Model and includes personalized feedback, information, video's and assignments. Additionally, in a second arm, physiotherapy counselling is provided through monthly scheduled and on-demand telephone calls. The control group will receive usual care and a leaflet with PA guidelines. METHODS: At baseline, 6 and 12 months, the primary outcome (PA) will be measured during 7 consecutive days by accelerometers. Secondary outcomes are self-reported PA, fatigue, mood, health-related quality of life, and costs. The group differences for primary and secondary outcomes will be analyzed using linear mixed models. DISCUSSION: If proven to be (cost)effective, this internet-based intervention, either alone or in combination with telephone support, will be a welcome addition to previous RCT's. TRIAL REGISTRATION: Netherlands trial register (NTR6911), Date of trial registration: December 21, 2017.

Breast conserving surgery for extensive DCIS using multiple radioactive seeds.

BACKGROUND AND OBJECTIVES: Breast conserving surgery (BCS) can be challenging for large regions of ductal carcinoma in situ (DCIS), resulting in high rates of positive resection margins. Radioactive seed localization (RSL) using multiple radioactive iodine (125I) seeds can be used to bracket extensive DCIS (eDCIS). The goal of this study was to retrospectively compare the use of a single or multiple 125I seeds in RSL to enable BCS in patients with eDCIS. METHODS: All patients with eDCIS (area of ≥3.0 cm) who underwent either single or multiple-seed RSL between January 2008 and December 2016 were included. Patient, tumor and surgery characteristics were compared between both groups. Primary outcome measures were positive resection margin and re-operation rates. RESULTS: Respectively 48 and 58 patients with eDCIS underwent single- and multiple-seed RSL and subsequent BCS. The rate of positive resection margin (focal and more than focal) with single-seed RSL was 47.9%, compared to 29.3% with multiple-seed RSL (p = 0.06). The re-operation rate was 39.6% with single-seed RSL and 20.7% in the multiple-seed RSL group (p = 0.05). CONCLUSION: Multiple-seed RSL enables bracketing of large areas of DCIS, with the potential to decrease the high rate of positive resection margins in this patient group.

Employment and social benefits up to 10 years after breast cancer diagnosis: a population-based study.

BACKGROUND: Little is known about employment outcomes after breast cancer (BC) beyond the first years after treatment. METHODS: Employment outcomes were compared with a general population comparison group (N=91 593) up to 10 years after BC for 26 120 patients, diagnosed before age 55 between 2000-2005, with income and social benefits data from Statistics Netherlands. Treatment effects were studied in 14 916 patients, with information on BC recurrences and new cancer events. RESULTS: BC survivors experienced higher risk of losing paid employment (Hazard Ratio (HR): 1.6, 95% Confidence Interval (95% CI) 1.4-1.8) or any work-related event up to 5-7 years (HR 1.5, 95% CI 1.3-1.6) and of receiving disability benefits up to 10 years after diagnosis (HR 2.0, 95% CI 1.6-2.5), with higher risks for younger patients. Axillary lymph node dissection increased risk of disability benefits (HR 1.5, 95% CI 1.4-1.7) or losing paid employment (HR 1.3, 95% CI 1.2-1.5) during the first 5 years of follow-up. Risk of disability benefits was increased among patients receiving mastectomy and radiotherapy (HR 1.2; 95% CI 1.1-1.3) and after chemotherapy (HR 1.7; 95% CI 1.5-1.9) during the first 5 years after diagnosis. CONCLUSIONS: BC treatment at least partly explains the increased risk of adverse employment outcomes up to 10 years after BC.

Simultaneous use of an (125)I-seed to guide tumour excision and (99m)Tc-nanocolloid for sentinel node biopsy in non-palpable breast-conserving surgery.

PURPOSE: In the present study we describe patients with non-palpable breast lesions, in which an Iodine-125 ((125)I)-marker (or "seed") for excision of the primary tumour and Technetium-99m nanocolloid ((99m)Tc-nanocolloid) for sentinel node biopsy (SNB) are used simultaneously. The purpose was to investigate any interference between (125)I-seeds and (99m)Tc-nanocolloid by an in vitro and in vivo analysis. METHODS: Contrast/interference-ratios between (125)I and (99m)Tc count-rates were determined in vitro using a realistic simulation model. Measurements were performed with 3 gamma-probes with different crystal materials. In 25 consecutive patients (99m)Tc-nanocolloid was intratumourally administered at the site of a previously implanted (125)I-seed. Respectively, the (125)I-setting and (99m)Tc-setting of the gamma-probe guided the wide local excision and SNB and maximum counts-per-second (cps) were measured. RESULTS: In vitro the different probes varied in (125)I- and (99m)Tc-sensitivity. The contrast-ratio between (125)I and (99m)Tc in the (125)I-channel was 4.6 for a 3-month-old (125)I-seed using the most appropriate gamma-probe. In vivo the gamma-probe in the (125)I-setting measured a median of 16,300 cps at the tumour site compared to 4820 cps using the (99m)Tc-setting. The (125)I-seed could be well distinguished from the (99m)Tc-nanocolloid in 92% of the patients and 96% required a single operation. The SNB was successful in all patients. CONCLUSIONS: Simultaneous use of (125)I-seeds and (99m)Tc-nanocolloid is possible under well-standardised conditions. Non-palpable breast lesions can be safely excised using the (125)I-seed in combination with a SN procedure. Use of (125)I-seeds is a next step within fine-tuning breast-conserving surgery that should lead to further investigation to confirm its value.

Lymphoscintigraphy and SPECT/CT in multicentric and multifocal breast cancer: does each tumour have a separate drainage pattern? Results of a Dutch multicentre study (MULTISENT).

PURPOSE: To investigate whether lymphoscintigraphy and SPECT/CT after intralesional injection of radiopharmaceutical into each tumour separately in patients with multiple malignancies in one breast yields additional sentinel nodes compared to intralesional injection of the largest tumour only. METHODS: Patients were included prospectively at four centres in The Netherlands. Lymphatic flow was studied using planar lymphoscintigraphy and SPECT/CT until 4 h after administration of (99m)Tc-nanocolloid in the largest tumour. Subsequently, the smaller tumour(s) was injected intratumorally followed by the same imaging sequence. Sentinel nodes were intraoperatively localized using a gamma ray detection probe and vital blue dye. RESULTS: Included in the study were 50 patients. Additional lymphatic drainage was depicted after the second and/or third injection in 32 patients (64%). Comparison of planar images and SPECT/CT images after consecutive injections enabled visualization of the number and location of additional sentinel nodes (32 axillary, 11 internal mammary chain, 2 intramammary, and 1 interpectoral. A sentinel node contained metastases in 17 patients (34%). In five patients with a tumour-positive node in the axilla that was visualized after the first injection, an additional involved axillary node was found after the second injection. In two patients, isolated tumour cells were found in sentinel nodes that were only visualized after the second injection, whilst the sentinel nodes identified after the first injection were tumour-negative. CONCLUSION: Lymphoscintigraphy and SPECT/CT after consecutive intratumoral injections of tracer enable lymphatic mapping of each tumour separately in patients with multiple malignancies within one breast. The high incidence of additional sentinel nodes draining from tumours other than the largest one suggests that separate tumour-related tracer injections may be a more accurate approach to mapping and sampling of sentinel nodes in patients with multicentric or multifocal breast cancer.

Characteristics of breast cancer patients who experience menopausal transition due to treatment.

OBJECTIVE: To identify patient-related and treatment-related factors associated significantly with climacteric symptoms in young patients who experience menopausal transition due to adjuvant treatment for breast cancer. METHODS: This cross-sectional study used questionnaire data collected to screen breast cancer patients for participation in a multicenter trial on the efficacy of supportive interventions for treatment-induced menopausal symptoms. The screening instrument included questions on sociodemographics, menopausal history and current menopausal status and symptoms, treatment history and lifestyle factors. Univariate and multivariate analyses were used to identify factors associated significantly with two major menopausal symptoms, hot flushes/night sweats and vaginal dryness. RESULTS: In total, 435 patients were included in this study. Hot flushes/night sweats exhibited a significant, negative association with education and a significant positive association with alcohol consumption, and having been treated with the combination of chemotherapy and hormonal therapy. Vaginal dryness was positively associated with combined treatment with chemotherapy and hormonal therapy. CONCLUSIONS: Menopausal symptoms among young breast cancer patients who experience menopausal transition due to adjuvant treatment are associated with a number of sociodemographic, lifestyle and treatment-related factors. Carefully designed interventions to prevent or alleviate these symptoms should take these factors into account.

The relevance of breast cancer subtypes in the outcome of neoadjuvant chemotherapy.

BACKGROUND: Breast cancer is increasingly considered a heterogeneous disease. The aim of this study was to assess the differences between histological and receptor-based subtypes in breast-conserving surgery and pathological complete response (pCR) after neoadjuvant chemotherapy. METHOD: A consecutive series of 254 patients with operable breast cancer treated with neoadjuvant chemotherapy was analyzed. Tumors were classified according to their receptor status in estrogen receptor (ER)-positive tumors (HER2-negative), triple-negative tumors, and HER2-positive tumors. The type of surgery feasible prior to neoadjuvant chemotherapy was compared with the actual surgery performed. RESULTS: The overall increase in breast-conserving surgery was 37% (73 of 198). In patients with ductal and lobular carcinomas this increase was 41% (63 of 152, 95% confidence interval [95% CI] 0.34-0.49) and 20% (7 of 35, 95% CI 0.10-0.36), respectively (P = 0.02). Half of the patients with lobular carcinoma had to undergo a secondary mastectomy because of incomplete resection margins. In ER-positive, triple-negative and HER2-positive tumors, the increase in breast-conserving surgery was 39% (42 of 109, 95% CI 0.30-0.48), 24% (11 of 45, 95% CI 0.14-0.38), and 45% (20 of 44, 95% CI 0.32-0.60) (P = 0.11). The pCR rate in ductal and lobular carcinomas was 12% (23 of 195) and 2% (1 of 42), respectively (P = 0.09). In ER-positive, triple-negative and HER2-positive tumors the pCR rates were 2% (3 of 138), 28% (16 of 57), and 18% (10 of 56), respectively. Multivariate analysis showed that the receptor-based subtype was the only significant predictor of pCR (P = 0.004). CONCLUSION: In lobular tumors the benefit with regard to breast-conserving surgery of neoadjuvant chemotherapy is questionable. Although in ER-positive tumors the pCR rate is low, the increase in breast-conserving surgery was remarkable in ductal ER-positive tumors.

Towards rational axillary treatment in relation to neoadjuvant therapy in breast cancer.

AIMS: The purpose of this study is to analyse nodal staging and axillary response in breast cancer patients treated with neoadjuvant chemotherapy (NAC) to explore venues to safely spare patients axillary clearance whenever it could be avoided. METHODS: In 327 patients we determined the nodal status before NAC by ultrasound-guided cytology and if indicated by sentinel node biopsy (SNB). In patients with proven metastasis we analysed the axillary response after NAC. RESULTS: Before NAC, the ultrasound-guided cytology was positive in 252 patients. In the remaining 75 patients SNB was performed prior to NAC. The SNB was negative in 53 patients, thus in these patients axillary clearance could be avoided. All 274 patients with proven axillary metastases at diagnosis underwent axillary clearance after NAC. Twenty percent of the cytology-positive patients (50/252) had an axillary pathological complete remission (pCR) and 68% of the SNB-positive patients (15/22) had no lymph node (LN) metastasis after NAC. Subgroups with a high axillary pCR rate were patients with triple-negative tumours (57%) and human epidermal growth-factor receptor 2 (HER2)-positive tumours (68%) who had a pCR of the primary tumour. CONCLUSIONS: Twenty percent of the patients with proven metastasis by cytology prior to NAC have an axillary pCR. The axillary pCR rate is very high in certain subgroups. Identification of these patients, could result in more axilla-conserving therapies.

[Neoadjuvant systemic therapy in patients with operable primary breast cancer: more benefits than breast-conserving therapy]. / Neoadjuvante systemische therapie bij het primair operabel mammacarcinoom: meer voordelen dan alleen borstsparende behandeling.

OBJECTIVE: To analyse the extent to which primary systemic therapy (PST) achieves the main goals in patients with operable primary breast cancer, these goals being breast-conserving therapy and pathological complete remission (pCR), and to evaluate the response. DESIGN: Retrospective. METHOD: In a retrospective analysis of 254 patients treated with PST in 2000-2007 in the Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, patients with inoperable disease (T4 and/or N3) were excluded. The response was mostly evaluated using contrast-enhanced MRI, whereby the chemotherapy regimen was switched if the reduction in the largest diameter of contrast washout was less than 25%. pCR was defined as no evidence of invasive cancer in the breast and axilla in the resection specimen. RESULTS: In patients with ductal carcinoma and lobular carcinoma an increase in breast-conserving therapy was seen in 32% and 17% of patients respectively. The pCR rate was 12% and 2% respectively. Secondary mastectomy because of irradical resection was required in 3% and 50% respectively. Multivariate analysis indicated that molecular type, defined on the basis of the expression of hormone receptors and human epidermal growth factor receptor 2 (HER2), i.e. luminal (oestrogen receptor-positive), basal (hormone receptor-negative and HER2-negative) and HER2-positive tumours treated with trastuzumab was the only independent predictor of pCR; 2%, 28% and 35% respectively (p=0.004). In 43 patients the chemotherapy regimen was adjusted because the tumour did not respond sufficiently. A favourable clinical response was observed in 72% (31/43) of these patients. CONCLUSION: The observed increase in the number of breast-conserving therapies after PST was clinically relevant. PST may be more effective when contrast-enhanced MRI is used for interim evaluation, based on which the treatment may be switched. There was a clear difference in histological and molecular types of tumour and therefore the choice of treatment may be adjusted accordingly.

Risk of invasion and axillary lymph node metastasis in ductal carcinoma in situ diagnosed by core-needle biopsy.

BACKGROUND: The aim of the study was to assess the risk of invasion and axillary lymph node metastasis in patients with ductal carcinoma in situ (DCIS) diagnosed by preoperative core-needle biopsy. The data were used to select criteria for patients in whom sentinel node (SN) biopsy might be indicated. METHODS: One hundred and seventy-one women with 172 DCIS lesions diagnosed by core-needle biopsy were analysed. Axillary staging was performed by SN biopsy, axillary node sampling, or level 1-2 axillary lymph node dissection. RESULTS: Invasive breast cancer was found in the surgical specimens from 45 tumours (26.2 per cent). Risk factors for invasion were a palpable lesion (odds ratio (OR) 2.95 (95 per cent confidence interval 1.20 to 7.26); P = 0.019), presence of a mass on mammography (OR 3.06 (1.43 to 6.56); P = 0.004), and intermediate (OR 5.81 (1.18 to 28.57); P = 0.030) or poorly differentiated (OR 5.46 (1.17 to 25.64); P = 0.031) tumour grade. Lymph node metastases were found in ten women with DCIS and invasion on final pathology. Factors associated with metastases were age 55 years or less (P = 0.030), invasion of 1.0 cm or more (P < 0.001) and the presence of vascular invasion (P = 0.001). CONCLUSION: SN biopsy should be considered in women with an initial diagnosis of DCIS on core-needle biopsy who are at risk for invasion; this includes women with a palpable lump, a mass on mammography, and intermediate or poor tumour grade.

The sentinel node biopsy in patients with breast cancer; many controversies remain.

The sentinel node procedure has increasingly been used as a diagnostic tool for staging breast cancer. Although many institutes have embraced this procedure, many issues concerning the indications and the technique itself remain unsolved. In this review, several aspects regarding these controversies are discussed from the perspective of The Netherlands Cancer Institute. These include the definitions used to identify the sentinel node, the indications and contraindications for this procedure and the injection site of the tracer and blue dye. What are the clinical implications of a micro-metastasis in the sentinel node? What is the best treatment for patients with an involved axillary node? Should non-axillary sentinel nodes be pursued, and if so, what are the implications for further management of these patients? Finally, the current TNM system is discussed in perspective of the evolving sentinel node procedure. Although many questions remain to be solved, the regional recurrence rates are low when axillary clearance is omitted because of a tumor-free sentinel node.

Changing patterns in diagnosis and treatment of ductal carcinoma in situ of the breast.

BACKGROUND: The increased incidence of ductal carcinoma in situ (DCIS) of the breast and the emergence of new diagnostic and therapeutic tools like mammographic screening, stereotactic core biopsy and reconstructive surgery prompted us to investigate how these developments influenced diagnosis and treatment. METHODS: Clinical and pathological characteristics of 403 patients with DCIS consecutively treated at The Netherlands Cancer Institute between 1986 and 2002 were evaluated and the effect of introduction of mammographic screening, stereotactic core biopsy and reconstruction on diagnosis and treatment was studied. RESULTS: Following the nationwide introduction of mammographic screening the number of non-symptomatic DCIS increased from 47 to 77%. Introduction of stereotactic core biopsy resulted in a rise of one-step procedures from 26 to 52%. Mastectomy rate did not change over time: 59% overall. However, reconstruction rate increased from 17 to 39%. CONCLUSION: This study shows a steep rise in diagnosis of non-symptomatic DCIS after introduction of screening. Further, the introduction of pre-operative diagnosis by stereotactic core biopsy resulted in a decrease of multiple surgical procedures. Mastectomy, with increasing application of breast reconstructions, remains an important treatment modality in the management of DCIS despite advancements in detection and diagnosis.

Aortic aneurysm repair is associated with a lower inflammatory response compared with surgery for inflammatory bowel disease.

BACKGROUND: Since the plasma cytokine profile reflects the body's inflammatory response to injury, this study was designed to prospectively observe the plasma cytokine levels in response to the degree of different sorts of abdominal surgical trauma. METHODS: Plasma levels of TNF-alpha, type I TNF receptor (p55), type II TNF receptor (p75), IL-6, IL-8, IL-10, phospholipase A(2) (PLA(2)), and haptoglobin were measured peri-operatively in patients undergoing bowel resection for inflammatory bowel disease or diverticulitis (IBD) (n = 9), elective repair of abdominal aortic aneurysm (AAA) (n = 9), or laparoscopic cholecystectomy (lap chole) (n = 9). RESULTS: The IBD patients showed a significant (p < 0.05) post-operative elevation in plasma IL-6, p55, p75, and PLA(2) levels, but no significant change in TNF-alpha, IL-8, IL-10 or haptoglobin levels. The AAA patients had a significant post-operative rise in IL-10 levels and a significant decrease in plasma haptoglobin levels, but no significant change of TNF-alpha, IL-6, IL-8, p55, p75, or PLA(2) concentrations. The lap chole patients demonstrated no significant change in any of these parameters. CONCLUSION: These data show that IL-6, IL-10, p55, and p75 are markers to measure the degree of inflammatory stress associated with abdominal operative procedures and demonstrate the relative lack of a cytokine response to laparoscopic cholecystectomy.