What do women at high risk of breast cancer request of a patient education day? Focus interviews with women before and after deciding about prophylactic interventions.

OBJECTIVE: At a Danish Hospital, we wished to establish a co-designed patient education day about prophylactic interventions for women at high risk of developing breast cancer. However, knowledge is lacking on the women's acceptability and requests for content. The objective of this study is to gain knowledge about the acceptability and requests of the content of a patient education day among women at high risk of breast cancer considering prophylactic mastectomy. METHODS: A user panel consisting of patients and health care professionals developed an interview guide for two focus interviews with two groups of women at high risk of breast cancer; one group had received a prophylactic mastectomy and one group considered it. Thematic analysis was used to explore the participants' acceptability and requests for content. RESULTS: Meaningful content was knowledge about prophylactic interventions, how to share knowledge with partners and children, and talking to equals in a safe forum. Not all participants wished to discuss own surgery in a group setting. CONCLUSION: An education day is an acceptable and supportive format for gaining knowledge about surgery, but since some topics may be vulnerable to discuss in a group setting to some women, we suggest the education day as a valuable supplement to the individual consultations.

FDG-PET/CT in high-risk primary breast cancer-a prospective study of stage migration and clinical impact.

PURPOSE: To investigate the clinical impact of FDG-PET/CT for staging and treatment planning in high-risk primary breast cancer. METHODS: Women with high-risk primary breast cancer were enrolled between September 2017 and August 2019 at Odense University Hospital, Denmark. Conventional mammography with/without MRI was performed before staging by FDG-PET/CT. We studied the accuracy of FDG-PET/CT for the detection of distant metastases, the effect on the change of treatment, and the prevalence of incidental findings. Biopsy and follow-up were used as a reference standard for the accuracy analysis. RESULTS: Of 103 women, 24 (23%) were diagnosed with distant metastases by FDG-PET/CT. Among these, breast surgery was omitted in 18 and could have been spared in six. Another sixteen (16%) patients were upstaged to more advanced loco-regional disease, leading to more extensive radiotherapy. Sensitivity and specificity for diagnosing distant metastases were 1.00 (95% confidence interval: 0.86-1.00) and 0.95 (0.88-0.99), respectively. Twenty-nine incidental findings were detected in 24 women (23%), leading to further examinations in 22 and diagnosis of eight (8/22, 36%) synchronous diseases: cancer (n = 4), thyroiditis (n = 2), aorta aneurysm (n = 1), and meningioma (n = 1). CONCLUSIONS: FDG-PET/CT had a substantial impact on staging and change of treatment in women with high-risk primary breast cancer, and further examination of incidental findings was considered clinically relevant. Our findings suggest that FDG-PET/CT should be considered for primary staging in high-risk primary breast cancer to improve treatment planning.

Adherence to treatment guidelines and survival in older women with early-stage breast cancer in Denmark 2008-2012.

Objectives: The aims of this study were to compare patients 70 years or older with younger patients, to examine whether Danish patients with early-stage breast cancer aged 70 years or more received treatment according to guidelines, the reasons for deviating from the guidelines, and to analyze whether such deviations affected survival.Methods: From the Danish Breast Cancer Cooperative Group (DBCG) database we identified 23,247 women diagnosed with early-stage breast cancer in Denmark from 2008 to 2012. 17,391 were aged less than 70 years and 5856 were 70+ years. We reviewed medical charts of 441 patients aged 70+ years from Funen (a region of Denmark) to ascertain whether treatment was given according to the guidelines of DBCG and if not, the reason for deviating. Overall survival was analyzed by Cox proportional hazards models.Results: Up to age 80 years most women (94%) had surgery according to guidelines, decreasing to 41% in women aged 85+ years, the main reason for omitting surgery being patients' requests. Patients with breast cancer over the age of 80 years did not have an excess mortality compared with the general population in Funen. Compared with women who had surgery according to guidelines, women who did not have surgery had a significantly higher risk of dying with a hazard ratio (HR) of 8.38 (95% Confidence Intervals (CI) 4.46-15.8) if they were less than 80 years and HR = 2.56 (95% CI 1.63-4.01) if they were 80 years or more (p = .003 for interaction).Conclusions: Adherence to treatment according to guidelines decreases with increasing age, mainly for patients aged 80+ years. Our results suggest that surgery is important for the survival of patients aged less than 80 years.

Clinical Evaluation of Scar Quality Following the Use of Prophylactic Negative Pressure Wound Therapy in Obese Women Undergoing Cesarean Delivery: A Trial-Based Scar Evaluation.

OBJECTIVE: To evaluate the cosmetic result of using incisional negative-pressure wound therapy (iNPWT) compared with standard postsurgical dressings in obese women undergoing cesarean delivery (CD). METHODS: Postcesarean scars were objectively evaluated 6 and 12 months postsurgery by a plastic surgeon using the Manchester Scar Scale and the Stony Brook Scar Evaluation Scale. Subjective scar evaluation and health-related quality of life were assessed using the Patient Scar Assessment Scale and the EQ-5D-5L instrument, respectively. Main outcome measures were the cosmetic and functional outcome of treating a standardized surgical wound with iNPWT compared with standard dressings, changes in scar rating over time, and testing different scar scales for cosmetic evaluation. RESULTS: The study found no difference in long-term cosmetic outcomes between iNPWT and standard dressings. The study demonstrated a statistically significant positive change in scar rating from surgery to 12 months postsurgery. A strong association was found between the scar scales with a high correlation between the objective scar scales (R approximately 0.80) and a moderate correlation between the subjective scale and each objective scale (R approximately 0.50). CONCLUSIONS: Prophylactic iNPWT has been found to reduce the risk of surgical site infection following CD. Conversely, this study was not able to detect a difference in the long-term cosmetic result after CD when compared with standard dressings.

The Post-mastectomy Pain Syndrome-A Systematic Review of the Treatment Modalities.

Post-mastectomy pain syndrome (PMPS) is a chronic neuropathic pain condition, affecting many women who have undergone breast cancer surgery. The development of PMPS is complex and the treatment options are limited. In this systematic review, we have analyzed the existing treatment modalities of PMPS. Six studies on five treatments were carefully selected, critically evaluated, and presented. The treatments were: antidepressants, anti-epileptics, topical capsaicin, and autologous fat grafting. Four of these treatments had a significant effect on PMPS. However, most of the studies had several flaws and therefore larger studies of high quality should be performed in the future.

Combined perforator flaps for total breast reconstruction-a narrative review and insights from massive weight loss cases.

Background and Objective: Perforator flaps have revolutionized autologous breast reconstruction, introducing both free and pedicled options as well as the potential for combining flaps. These versatile techniques can be utilized in massive weight loss (MWL) patients, effectively addressing both functional and aesthetic challenges by using their excess skin. This review aims to explore literature on combined pedicled and free perforator flaps for total breast reconstruction, and share our own experience in the field. Methods: A PubMed search up to June 2023 employed Medical Subject Headings (MeSH) terms such as (("combined") OR ("stacked") OR ("conjoined") AND ("perforator flaps")) AND ("breast reconstruction"). Publications in English and Scandinavian languages were manually screened for relevance, and supplemental sources were also reviewed. Key Content and Findings: Limited studies exist on using combined pedicled and free flaps for total breast reconstruction, although combined free flaps are more common. Perforators around the breast base, offer multiple flap options for single or combined use. In our series of 10 women, four underwent total breast reconstruction with a combination of flip-over internal mammary artery perforator (IMAP) flap and thoracodorsal artery perforator (TDAP) flap. Another subset of four, who were MWL patients, received combined TDAP and superior epigastric artery perforator (SEAP) flaps, along with body contouring procedures such as upper body lifts and vertical abdominoplasties, addressing excess skin and improving silhouette. One remaining MWL patient had deflated breasts restored using TDAP and SEAP flaps, along with an upper and lower body lift and vertical abdominoplasty. The last MWL patient underwent a risk-reducing mastectomy, also reconstructed with TDAP and SEAP flaps, and received an upper body lift and vertical abdominoplasty. Conclusions: Combined perforator flap techniques for combined body contouring and breast reconstruction seems safe and especially suitable for MWL patients. They offer a surgical alternative merging body contouring and breast reconstruction in cases where free flap procedures seem less favorable due to skin laxity and deflation of donor sites. However, limited literature on the topic calls for further studies.

Pathology and resection margins following mastectomy prior to immediate breast reconstruction.

Risk of local recurrence (LR) (and even distant disease-free survival) after mastectomy is associated with margin status. Furthermore, the vast majority of LR are located at the anterior (superficial) margin. Margins in mastectomy are considered anatomical borders and not true resection margins; such a conception may erroneously lead to underestimation of the risk of LR after mastectomy. If dissection is accurate along the fascia, only skin, subcutaneous tissue and minimal residual breast gland tissue (rBGT) are expected to remain in the patient. However, the subcutaneous fascia is an inconsistent anatomical structure that may be absent in almost half of patients. Studies and routine clinical practice suggest that resection may frequently, though often focally, be within the breast glandular tissue leaving various amounts of rBGT. Such areas may be nidus for subsequent de novo or recurrent premalignant or malignant disease. There is no consensus on handling of close/positive margins and intervention is extrapolated from studies on breast conserving surgery with subsequent radiotherapy. Handling of a close/positive margin is complicated by poor correlation between the ex vivo findings on the specimen and the attempt to relocate the area of concern in a patient with reconstructed breasts. In this clinical practice review, we strongly advocate for reporting of the lesion-to-margin distance in mastectomies to collect further evidence on the association between LR and margin status.

[Autologous nanofat transplantation for scar treatment].

Damaging the normal skin barrier results in a cascade of reactions resulting in scar formation. Transforming growth factors cause the proliferation of fibroblasts to myofibroblasts, which keep secreting collagen. There are indications, that the proliferation might be inhibited by adipose-derived stem cells (ADSC). Nanofat is a liquid substance containing ADSC. This review is based on five observational human studies, where nanofat was injected into a variant of scars. A significant improvement was demonstrated in all the studies. Scars treated within five years has a better chance of regeneration. Randomized controlled trials are warranted.

Impact of neoadjuvant chemotherapy on surgical complications in breast cancer: A systematic review and meta-analysis.

BACKGROUND: The increased use of neoadjuvant chemotherapy (NACT) facilitates an increase in breast-conserving surgery and immediate breast reconstruction. While NACT is considered to have the same oncological safety as adjuvant chemotherapy, evidence on the impact of NACT on surgical outcomes following breast surgery is unclear and varies across studies. The aim of this systematic review and meta-analysis was to assess the impact of NACT on surgical complications in breast cancer patients undergoing any kind of breast surgery. METHODS: Database searches were conducted (March 26, 2021) to identify studies assessing the impact of NACT on postoperative complications. Studies were included if they compared a group of patients treated with NACT to a control group that was not, and if they reported at least one of our defined outcomes. Primary effect measures were odds ratios (ORs) and mean difference with a 95% confidence interval. Study quality was assessed by the Newcastle-Ottawa Scale. RESULTS: Twenty-six studies comprising 134,191 patients were included. NACT was not associated with an increased complication rate for overall complications (OR: 1.13, 95% CI: 0.86 to 1.47, p = 0.38), individual postoperative complications, nor surgery duration. There was a non-significant trend towards NACT increasing the risk of seroma, wound complications, skin or nipple necrosis, flap ischemia or loss, and implant loss. A significant difference in blood loss was found, favouring NACT (MD = -75.85, 95% CI: -107.47 to -44.23, p < 0.00001). Heterogeneity was significant between the studies (I2>50%). CONCLUSION: Compared to a control group, NACT was not found to affect the surgical complications adversely.

[Alternatives to wire localization of non-palpable breast lesions].

With the introduction of screening mammography, the proportion of smaller, clinically recognised tumors has increased. In cases in which lesions cannot be palpated, a guidewire or a wireless marker is placed. Wire localization is associated with several limitations, despite its status as gold standard. Several wireless methods that meet these limitations have been developed. Methods that increase efficiency and patient satisfaction. This review provides an overview of the existing literature on intra-operative localization methods, and the risk of re-resection associated with excision of non-palpable mammary lesions.

[Suspicion of malignant melanoma in a lymph node caused by tattoo pigment].

This is a case report of a 31-year-old woman going through cancer staging after being diagnosed with breast cancer. During sentinel node dissection, a remarkable dark lymph node was found. Metastatic malignant melanoma was suspected, but with careful histochemical examination the lymph node was confirmed to only contain tattoo pigment. The patient had rather large tattoos on her arms, which was suspected to be the source of the ink in her lymph nodes. Tattoo pigment can complicate cancer staging, and it is important to know this rare effect on lymph nodes when dealing with cancer staging.

Autologous Fat Grafting as Treatment of Postmastectomy Pain Syndrome: A Randomized Controlled Trial.

BACKGROUND: Postmastectomy pain syndrome is a common and disabling side effect of breast cancer treatment. Medical treatment seems to be insufficient for a considerable proportion of patients. Fat grafting has shown promise in relieving pain from postmastectomy pain syndrome, but no randomized clinical trial comparing fat grafting to a sham operation has been performed to date. The authors' objective was to compare the effect of fat grafting compared to a sham operation for treating postmastectomy pain syndrome. METHODS: The authors conducted a single-center, double-blind, randomized clinical trial with two arms between October of 2017 and September of 2020. The authors assessed four patients suffering from postmastectomy pain syndrome for inclusion. The intervention group received scar-releasing rigottomy and fat grafting to the area of pain. The control group received scar-releasing rigottomy and a placebo of saline solution. The primary outcome was the degree of pain measured using the Numerical Rating Scale. The secondary outcomes were the degree and quality of neuropathic pain (Neuropathic Pain Symptom Inventory) and quality of life (36-Item Short-Form Health Survey). Follow-up was 6 months. RESULTS: Thirty-five participants completed follow-up: 18 participants in the intervention group and 17 in the control group. The authors detected no statistically significant changes in average and maximum pain or neuropathic pain. Regarding quality of life, the control group reported a statistically significant improvement in emotional problem parameters, whereas the intervention group reported a deterioration. The authors observed no serious adverse effects. CONCLUSION: The authors did not find evidence to support that fat grafting is superior to a placebo when treating postmastectomy pain syndrome. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Evaluation of Breast Animation Deformity following Pre- and Subpectoral Direct-to-Implant Breast Reconstruction: A Randomized Controlled Trial.

Background The incidence of breast animation deformity (BAD) is reported to be substantial after direct-to-implant breast reconstruction with subpectoral implant placement. It has, however, never been examined if BAD can occur following prepectoral implant placement. Our primary aim was to compare the incidence and degree of BAD after direct-to-implant breast reconstruction using either subpectoral or prepectoral implant placement. Secondary aim of this study was to assess and compare the level of pain between sub- and prepectoral reconstructed women. Methods In this randomized controlled trial, patients were allocated to reconstruction by either subpectoral or prepectoral implant placement in accordance with the CONSORT guidelines. The degree of BAD was assessed by the "Nipple, Surrounding skin, Entire breast (NSE)" grading scale 12 months after surgery. The level of postoperative pain was assessed on a numerical pain rating scale. Results We found a significant difference in the degree of BAD favoring patients in the prepectoral group (23.8 vs. 100%, p < 0.0001; mean NSE grading scale score: 0.4 vs. 3.6, p < 0.0001). The subpectoral reconstructed group reported higher levels of pain on the three subsequent days after surgery. No significant difference in pain levels could be found at 3 months postoperatively. Conclusion The incidence and degree of BAD was significantly lower in women reconstructed by prepectoral direct-to-implant breast reconstruction. Unexpectedly, we found mild degrees of BAD in the prepectoral group. When assessing BAD, distortion can be challenging to discern from rippling.

Prophylactic treatment of breast implants with a solution of gentamicin, vancomycin and cefazolin antibiotics for women undergoing breast reconstructive surgery: protocol for a randomised, double-blind, placebo-controlled trial (The BREAST-AB trial).

INTRODUCTION: Periprosthetic infection is one of the most severe complications following implant-based breast reconstruction affecting 5%-10% of the women. Currently, many surgeons apply antibiotics locally on the breast implant to reduce the risk of postoperative infection, but no randomised, placebo-controlled trials have tested the treatment's efficacy. METHODS AND ANALYSIS: The BREAST-AB trial (BREAST-AntiBiotics) is an investigator-initiated, multicentre, randomised, placebo-controlled, double-blind trial of local treatment with gentamicin, vancomycin and cefazolin on breast implants in women undergoing implant-based breast reconstruction. The trial drug consists of 80 mg gentamicin, 1 g vancomycin and 1 g cefazolin dissolved in 500 mL of isotonic saline. The placebo solution consists of 500 mL isotonic saline. The trial drug is used to wash the dissected tissue pocket and the breast implant prior to insertion. The primary outcome is all-cause explantation of the breast implant within 180 days after the breast reconstruction surgery. This excludes cases where the implant is replaced with a new permanent implant, for example, for cosmetic reasons. Key long-term outcomes include capsular contracture and quality of life. The trial started on 26 January 2021 and is currently recruiting. ETHICS AND DISSEMINATION: The trial was approved by the Regional Ethics Committee of the Capital Region (H-20056592) on 1 January 2021 and the Danish Medicines Agency (2020070016) on 2 August 2020. The main paper will include the primary and secondary outcomes and will be submitted to an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04731025.

Risk of oral clefts in twins.

BACKGROUND: Small studies have indicated that twinning increases the risk of oral cleft. METHODS: We used data from a Danish national population-based cohort study to investigate whether twinning was associated with isolated oral cleft, and to estimate the twin probandwise concordance rate and heritability. Twins (207 affected/130,710) and singletons (7766 affected/4,798,526) born from 1936 through 2004 in Denmark were ascertained by linkage among the Danish Facial Cleft Database, the Danish Twin Registry, and the Civil Registration System. We computed oral cleft prevalence and prevalence proportion ratio for twins versus singletons, stratified for 3 subphenotypes. Probandwise concordance rates and heritability for twins were estimated for 2 phenotypes--cleft lip with or without cleft palate (CL/P) and cleft palate (CP). RESULTS: The prevalence of oral cleft was 15.8 per 10,000 twins and 16.6 per 10,000 singletons (prevalence proportion ratio = 0.95; 95% confidence interval = 0.83-1.1). This prevalence was similar for monozygotic and dizygotic twins. The probandwise concordance rate was higher for CL/P for monozygotic twins than for dizygotic twins (50% vs. 8%, respectively). A similar contrast was present for CP. Recurrence risk for both types of clefts was greater in dizygotic twins than in non-twin siblings. Heritability estimates were above 90% for both CL/P and CP. CONCLUSIONS: No excess risk of oral cleft could be demonstrated for twins compared with singletons. The concordance rates and heritability estimates for both types of clefts show a strong genetic component.

A cohort study of recurrence patterns among more than 54,000 relatives of oral cleft cases in Denmark: support for the multifactorial threshold model of inheritance.

OBJECTIVES: To determine if the anatomical severity of oral clefting affects familial recurrence in a large population based sample. To provide reliable recurrence risk estimates for oral cleft for first, second, and third degree relatives. DESIGN: Population based cohort study. SETTING: Denmark. PARTICIPANTS: 6776 individuals affected with an oral cleft born from 1952 to 2005 and 54 229 relatives. MAIN OUTCOME MEASURES: Recurrence risk estimates for oral cleft for first, second, and third degree relatives and stratification by severity, specificity, parent of origin effect, and family size for first degree relatives. RESULTS: For cleft lip and palate probands we observed recurrence risks for first, second, and third degree relatives of respectively 3.5% (95% CI 3.1% to 4.0%), 0.8% (95% CI 0.6% to 1.0%), and 0.6% (95% CI 0.4% to 0.8%). Individuals affected by the most severe oral cleft had a significantly higher recurrence risk among both offspring and siblings, eg, the recurrence risk for siblings of a proband with isolated bilateral cleft lip with cleft palate was 4.6% (95% CI 3.2 to 6.1) versus 2.5% (95% CI 1.8 to 3.2) for a proband born with a unilateral defect. CONCLUSIONS: Anatomical severity does have an effect on recurrence in first degree relatives and the type of cleft is predictive of the recurrence type. Highly reliable estimates of recurrence have been provided for first cousins in addition to more accurate estimates for first and second degree relatives. These results and the majority of prior data continue to support a multifactorial threshold model of inheritance.

Reproductive patterns among Danish women with oral clefts.

OBJECTIVE: The aim of this study was to compare reproduction patterns among Danish women born with isolated oral clefts versus the Danish background population. DESIGN AND SETTING: A nationwide population-based historic cohort study based on three registers: The Danish Facial Cleft Register, The Danish Civil Registration System, and the Fertility of Women and Couples Dataset. PARTICIPANTS: Through linkages of the registers, the number of children and the exact age at childbirth of all Danish women born with an oral cleft from 1950 through 1988 (N = 1931) were obtained. These data were compared with similar data for the entire Danish female background population (N = 1,184,390). RESULTS AND CONCLUSIONS: This study suggests that childlessness is higher among women born with an oral cleft (55%) than among women in the Danish background population (44%). Excluding women without children, women born with oral cleft had an average of 1.98 children per woman. This did not differ significantly from the background population (2.02 children/woman). Furthermore, the present study found that Danish women born with oral clefts on average were older (27.3 years of age) than the background population (24.7 years of age) when they had their first child (difference = 2.6 years, confidence interval = 2.41 to 2.80). CONCLUSION: Danish women born with an oral cleft more often are childless or have their first child later, but if they have children, they tend to have as many children as other Danish women. Social, psychological, and biological reasons might be responsible for the reduced fertility.

Recurrence risk for offspring of twins discordant for oral cleft: a population-based cohort study of the Danish 1936-2004 cleft twin cohort.

Our objective in this Danish population-based cohort study was to estimate the recurrence risk of isolated oral cleft (OC) for offspring of the unaffected co-twins of OC discordant twin pairs and to compare this risk to the recurrence risk in the offspring of the affected co-twin as well as to the risk in the background population. During 1936-2004, 207 twin pairs were ascertained, among whom at least one twin had an OC. The index persons were twins discordant for OC who had children (N=117), and their offspring (N=239). The participants were ascertained by linkage between The Danish Facial Cleft Database, The Danish Twin Registry and The Danish Civil Registration System. In the study OC recurrence risk for offspring of the affected and unaffected twin and relative risk were compared to the background prevalence. We found that among 110 children of the 54 OC affected twins, two (1.8%) children had OC corresponding to a significantly increased relative risk (RR=10; 95% CI 1.2-35) when compared to the frequency in the background population. Among the 129 children of the 63 unaffected twins, three (2.3%) children were affected, corresponding to a significantly increased relative risk (RR=13; 95% CI 2.6-36) when compared the background prevalence. We concluded that in OC discordant twin pairs similar increased recurrence risks were found among offspring of both OC affected and OC unaffected twins. This provides further evidence for a genetic component in cleft etiology and is useful information for genetic counseling of twin pairs discordant for clefting.

Autoantibodies to folate receptor alpha during early pregnancy and risk of oral clefts in Denmark.

The objective of this study was to determine whether IgG and IgM autoantibodies to folate receptor alpha (FRalpha) in pregnant women are associated with an increased risk of oral cleft-affected offspring. A case-control study nested in the prospective Danish National Birth Cohort (100,418 pregnancies, enrolled during 1997-2003) was done. Hundred eighty-five children were born with an oral cleft. Maternal serum from their mothers (cases) was compared with maternal serum from 779 randomly selected mothers of nonmalformed children (controls). We found that the average level of FRalpha IgG autoantibodies did not differ significantly among cases and controls (p = 0.71). Slightly higher levels of FRalpha IgM autoantibodies were found among controls compared with cases. This was, however, not statistically significant (p = 0.06), except for mothers of children with isolated cleft lip (p = 0.04). Blocking of folate binding to FR was similar among cases and controls (p = 0.54). The results did not change when stratifying into the cleft subgroups, nor when only isolated oral cleft cases were considered. In conclusion, high maternal autoantibody levels and blocking of folate binding to FRalpha in maternal serum during pregnancy are not associated with an increased risk of oral clefts in the offspring in this population-based cohort.