Genaesthics : Breast Surgery in BRCA1/2 Gene Mutation Carriers

The present thesis focuses on breast surgery in BRCA1/2 gene mutation carriers. The topics that are studied vary broadly, representing the multiple disciplines that are involved in the diagnostic work-up and treatment of BRCA1/2-associated breast cancer. The first part contains studies on molecular and prognostic tumor characteristics in breast cancer. The thesis continues with an anatomical study on safety of prophylactic mastectomy, and finishes with studies on aesthetics and patient reported outcomes of prophylactic breast surgery and breast reconstruction. The title ‘Genaesthics’ is a merger of the two extremities of this spectrum: ‘genetics’ and ‘aesthetics’

Impact of nutritional status and body composition on postoperative outcomes after pelvic exenteration for locally advanced and locally recurrent rectal cancer

BACKGROUND: Pelvic exenteration for locally advanced rectal cancer (LARC) and locally recurrent (LRRC) rectal cancer provides radical resection and local control, but is associated with considerable morbidity. The aim of this study was to determine risk factors, including nutritional status and body composition, for postoperative morbidity and survival after pelvic exenteration in patients with LARC or LRRC. METHODS: Patients with LARC or LRRC who underwent total or posterior pelvic exenteration in a tertiary referral centre from 2003 to 2018 were analysed retrospectively. Nutritional status was assessed using the Malnutrition Universal Screening Tool (MUST). Body composition was estimated using standard-of-care preoperative CT of the abdomen. Logistic regression analyses were performed to identify risk factors for complications with a Clavien-Dindo grade of III or higher. Risk factors for impaired overall survival were calculated using Cox proportional hazards analysis. RESULTS: In total, 227 patients who underwent total (111) or posterior (116) pelvic exenteration were analysed. Major complications (Clavien-Dindo grade at least III) occurred in 82 patients (36.1 per cent). High risk of malnutrition (MUST score 2 or higher) was the only risk factor for major complications (odds ratio 3.99, 95 per cent c.i. 1.76 to 9.02) in multivariable analysis. Mean follow-up was 44.6 months. LRRC (hazard ratio (HR) 1.61, 95 per cent c.i. 1.04 to 2.48) and lymphovascular invasion (HR 2.20, 1.38 to 3.51) were independent risk factors for impaired overall survival. CONCLUSION: A high risk of malnutrition according to the MUST is a strong risk factor for major complications in patients with LARC or LRRC undergoing exenteration surgery

B cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest solid tumors and is resistant to immunotherapy. B cells play an essential role in PDAC progression and immune responses, both locally and systemically. Moreover, increasing evidence suggests that microbial compositions inside the tumor, as well as in the oral cavity and the gut, are important factors in shaping the PDAC immune landscape. However, the gut-associated lymphoid tissue (GALT) has not previously been explored in PDAC patients. In this study, we analyzed healthy vermiform appendix (VA) from 20 patients with PDAC and 32 patients with colon diseases by gene expression immune profiling, flow cytometry analysis, and microbiome sequencing. We show that the VA GALT of PDAC patients exhibits markers of increased inflammation and cytotoxic cell activity. In contrast, B cell function is decreased in PDAC VA GALT based on gene expression profiling; B cells express significantly fewer MHC class II surface receptors, whereas plasma cells express the immune checkpoint molecule HLA-G. Additionally, the vermiform appendix microbiome of PDAC patients is enriched with Klebsiella pneumoniae, Bifidobacterium animalis, and Adlercreutzia equolifaciens, while certain commensals are depleted. Our findings may suggest impaired B cell function within the GALT of PDAC patients, which could potentially be linked to microbial dysbiosis. Additional investigations are imperative to validate our observations and explore these potential targets of future therapies

Patient Satisfaction and Nipple-Areola Sensitivity After Bilateral Prophylactic Mastectomy and Immediate Implant Breast Reconstruction in a High Breast Cancer Risk Population Nipple-Sparing Mastectomy Versus Skin-Sparing Mastectomy

Background: Prophylactic skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) both are associated with major risk reduction in women with high breast cancer risk. Skin-sparing mastectomy followed by nipple-areola complex (NAC) reconstruction is standard of care, but NSM is increasingly being performed. Preservation of the NAC in NSM may increase patient satisfaction. Therefore, we measured NAC sensitivity after NSM and compared patient satisfaction as well as body image after SSM with NSM. Methods: Women who underwent prophylactic bilateral SSM or NSM and immediate implant breast reconstruction between 2002 and 2012 were eligible. Patient satisfaction was assessed using the Breast-Q reconstruction questionnaire, body image using Hopwood's body image scale (BIS), and satisfaction with the (reconstructed) NAC using a study-specific questionnaire. In the NSM group, NAC sensitivity was assessed using Semmes Weinstein monofilaments with a 5-point scale and compared with NAC sensitivity in a nonoperated control group. Results: The SSM group comprised 25 women (50 SSMs) and the NSM group 20 women (39 NSMs). Median follow-up was 65 months in the SSM group compared with 27 months in theNSMgroup (P<0.01). In univariable analyses, Breast-Qscores were favorable in the SSM group compared with theNSMgroup with trends for higher "satisfaction with breasts" (66.2 vs 56.6; P = 0.06) and "satisfaction with outcome" (76.1 vs 61.5; P = 0.09). Mean BIS score of 7.1/30 in the SSM group and 9.3/30 in theNSMgroup(P = 0.35). Adjusted for follow-up, there were no significant differences in Breast-Q scores, nor in BIS scores. Interestingly, satisfaction with the (reconstructed) NAC was similar after SSM and NSM. Nipple-areola complex sensitivity was lower in theNSMgroup(mean score, 1.9; 95% confidence interval, 1.5-2.3) compared with the control group (mean score, 4.7; 95% confidence interval, 4.6-4.9; P < 0.01). Conclusions: Breast-Q scores regarding satisfaction with breasts and overall outcome were in favor of the SSM group. Residual NAC sensitivity after NSM was low. This suggests that SSM followed by NAC reconstruction is a balanced alternative to NSM. We observed no significant differences in body image and NAC specific satisfaction between the NSM and SSM groups