Tumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma.

BACKGROUND: Immune checkpoint inhibitors and targeted therapies have dramatically improved outcomes in patients with advanced melanoma, but approximately half these patients will not have a durable benefit. Phase 1-2 trials of adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) have shown promising responses, but data from phase 3 trials are lacking to determine the role of TILs in treating advanced melanoma. METHODS: In this phase 3, multicenter, open-label trial, we randomly assigned patients with unresectable stage IIIC or IV melanoma in a 1:1 ratio to receive TIL or anti-cytotoxic T-lymphocyte antigen 4 therapy (ipilimumab at 3 mg per kilogram of body weight). Infusion of at least 5×109 TILs was preceded by nonmyeloablative, lymphodepleting chemotherapy (cyclophosphamide plus fludarabine) and followed by high-dose interleukin-2. The primary end point was progression-free survival. RESULTS: A total of 168 patients (86% with disease refractory to anti-programmed death 1 treatment) were assigned to receive TILs (84 patients) or ipilimumab (84 patients). In the intention-to-treat population, median progression-free survival was 7.2 months (95% confidence interval [CI], 4.2 to 13.1) in the TIL group and 3.1 months (95% CI, 3.0 to 4.3) in the ipilimumab group (hazard ratio for progression or death, 0.50; 95% CI, 0.35 to 0.72; P<0.001); 49% (95% CI, 38 to 60) and 21% (95% CI, 13 to 32) of the patients, respectively, had an objective response. Median overall survival was 25.8 months (95% CI, 18.2 to not reached) in the TIL group and 18.9 months (95% CI, 13.8 to 32.6) in the ipilimumab group. Treatment-related adverse events of grade 3 or higher occurred in all patients who received TILs and in 57% of those who received ipilimumab; in the TIL group, these events were mainly chemotherapy-related myelosuppression. CONCLUSIONS: In patients with advanced melanoma, progression-free survival was significantly longer among those who received TIL therapy than among those who received ipilimumab. (Funded by the Dutch Cancer Society and others; ClinicalTrials.gov number, NCT02278887.).

More sentinel lymph node biopsies for thin melanomas after transition to AJCC 8th edition do not increase positivity rate: A Danish population-based study of 7148 patients.

BACKGROUND: We evaluated the outcome of sentinel lymph node biopsies (SLNB) in patients with thin melanoma before and after the implementation of AJCC 8th edition (AJCC8) and identified predictors of positive sentinel lymph nodes (+SLN). METHODS: Patients diagnosed with T1 melanomas (Breslow thickness ≤1 mm) during 2016-2017 as per AJCC 7th edition (AJCC7) (n = 3414) and 2018-2019 as per AJCC8 (n = 3734) were identified in the Danish Melanoma Database. RESULTS: More SLNBs were performed in the AJCC8 cohort compared to the AJCC7 (22.2% vs. 16.2%, p < 0.001), with no significant difference in +SLN rates (4.7% vs. 6.7%, p = 0.118). In the AJCC7 + SLN subgroup, no melanomas were ulcerated, 94.6% had mitotic rate (MR) ≥ 1, 67.6% were ≥0.8 mm and 32.4% would be T1a according to AJCC8. In the AJCC8 + SLN subgroup, 10.3% were ulcerated, 74.4% had MR≥ 1, 97.4% were ≥0.8 mm and 23.1% would be T1a according to AJCC7. On multivariable analysis younger age and MR ≥ 1 were significant predictors of +SLN. CONCLUSION: More SLNBs were performed in T1 melanomas after transition to AJCC8 without an increase in +SLN rate. None of the AJCC8 T1b criteria were significant predictors of +SLN. We suggest that mitosis and younger age should be considered as indications for SLNB in thin melanoma.

Fine needle and core needle ultrasound guided biopsies for assessing suspected melanoma metastasis in lymph nodes and subcutaneous tissue.

BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the diagnostic accuracy of ultrasound guided fine needle aspiration cytology (FNAC) and core needle biopsy (CNB) in different clinical scenarios for melanoma patients with lesions suspected of metastasis. METHODS: We included all patients at our department attending follow-up after surgery for cutaneous melanoma, who had undergone either FNAC or CNB between December 2016 and June 2019. Biopsy results were classified into one of four categories and verified with follow-up including imaging, re-biopsy or histology upon excision. The diagnostic accuracy of FNAC and CNB were calculated overall, and based on location of suspected metastasis, reason for suspicion and stage. RESULTS: We identified 232 biopsies in 164 patients; 109 FNACs and 123 CNBs. For FNAC, overall sensitivity was 83.3% and negative predictive value was 88.4%. For CNB, overall sensitivity was 92.4% and negative predictive value was 88.0%. There were significantly fewer nondiagnostic results using CNB compared to FNAC (χ1 2 = 6.7, p = 0.0095). CONCLUSIONS: There were no significant differences between the diagnostic accuracy of FNAC and CNB in the different clinical scenarios. We found significantly fewer nondiagnostic biopsies when using CNB, although this may reflect the type of lesions selected for each approach.

Factors associated with melanoma-related limb lymphoedema.

BACKGROUND: Melanoma-related limb lymphoedema is a well-known late effect following sentinel node biopsy (SNB), and lymph node dissection (LND) in patients treated of melanoma. However, data on associated risk factors are sparse. This study aimed to investigate factors associated with melanoma-related limb lymphoedema. METHODS: The present cross-sectional single-center clinical study included patients between 18 and 75 years with American Joint Committee on Cancer Stages I-III melanoma treated with wide local excision (WLE) and unilateral axillary or inguinal SNB and/or completion LND (CLND) or therapeutic LND (TLND). The diagnosis of secondary unilateral limb lymphoedema was based on the history, symptoms, and physical examination and staged according to the International Society of Lymphology (ISL). Data on factors associated with lymphoedema were analysed with binary logistic regression models. RESULTS: In total, 642 patients were eligible, of which 435 (68%) patients participated in the study. Among these 431 patients, 109 (25%) had lymphoedema of which 48 (44%), and 61 (56%) were classified with ISL Stages I and II-III, respectively. Multivariate analyses identified primary tumour on the limb (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.17-4.56; p value .017), inguinal surgery (OR, 6.91; 95% CI, 3.49-14.11; p value <.0001), LND (OR, 6.45; 95% CI, 3.18-13.57; p value <.0001), and persistent pain at the site of lymph node surgery as factors associated with lymphoedema (OR, 3.52; 95% CI, 1.54-8.19; p value .003). Multivariable analysis of ISL Stage II-III lymphoedema further identified limb cellulitis to be associated with lymphoedema (OR 5.74; 95% CI, 2.11-15.99; p value .0006). CONCLUSIONS: Melanoma-related limb lymphoedema is associated with inguinal surgery, LND, primary tumour on the limb, persistent pain at the site of lymph node surgery, and cellulitis of the limb. This study highlights the importance of increasing awareness, improving prevention, and treatment of melanoma-related limb lymphoedema.

Effect of increased potassium intake on the renin-angiotensin-aldosterone system and subcutaneous resistance arteries: a randomized crossover study.

BACKGROUND: Increased potassium intake lowers blood pressure (BP) in hypertensive patients. The underlying mechanism is not fully understood but must be complex because increased potassium intake elevates circulating concentrations of the BP-raising hormone aldosterone. METHODS: In a randomized placebo-controlled crossover study in 25 normotensive men, we investigated the effect of 4 weeks of potassium supplement (90 mmol/day) compared with 4 weeks of placebo on the renin-angiotensin-aldosterone system (RAAS), urine composition and 24-h ambulatory BP. Vascular function was also assessed through wire myograph experiments on subcutaneous resistance arteries from gluteal fat biopsies. RESULTS: Higher potassium intake increased urinary potassium excretion (144.7 ± 28.7 versus 67.5 ± 25.5 mmol/24-h; P < 0.0001) and plasma concentrations of potassium (4.3 ± 0.2 versus 4.0 ± 0.2 mmol/L; P = 0.0002), renin {mean 16 [95% confidence interval (CI) 12-23] versus 11 [5-16] mIU/L; P = 0.0047}, angiotensin II [mean 10.0 (95% CI 6.2-13.0) versus 6.1 (4.0-10.0) pmol/L; P = 0.0025] and aldosterone [mean 440 (95% CI 336-521) versus 237 (173-386) pmol/L; P < 0.0001]. Despite RAAS activation, systolic BP (117.6 ± 5.8 versus 118.2 ± 5.2 mmHg; P = 0.48) and diastolic BP (70.8 ± 6.2 versus 70.8 ± 6.3 mmHg; P = 0.97) were unchanged. In the wire myograph experiments, higher potassium intake did not affect endothelial function as assessed by acetylcholine [logarithmically transformed half maximal effective concentration (pEC50): 7.66 ± 0.95 versus 7.59 ± 0.85; P = 0.86] and substance P (pEC50: 8.42 ± 0.77 versus 8.41 ± 0.89; P = 0.97) or vascular smooth muscle cell reactivity as assessed by angiotensin II (pEC50: 9.01 ± 0.86 versus 9.02 ± 0.59; P = 0.93) and sodium nitroprusside (pEC50: 7.85 ± 1.07 versus 8.25 ± 1.32; P = 0.25) but attenuated the vasodilatory response of retigabine (pEC50: 7.47 ± 1.16 versus 8.14 ± 0.90; P = 0.0084), an activator of Kv7 channels. CONCLUSIONS: Four weeks of increased potassium intake activates the RAAS in normotensive men without changing BP and this is not explained by improved vasodilatory responses ex vivo.

Repeatability of Volume and Regional Body Composition Measurements of the Lower Limb Using Dual-energy X-ray Absorptiometry.

Lower limb lymphedema is a dynamic condition in which tissue composition and volume measurements are affected. Various definitions of lower limb lymphedema exist but volume differences between the limbs are widely used. It is therefore necessary to have a readily available noninvasive measurement technique allowing multiple measurements of the lower limbs. This study investigated the repeatability of duplicate volume and regional body composition measurements of the lower limb using the GE Lunar Prodigy dual-energy X-ray absorptiometry (DXA) scanner Prodigy (GE Medical Systems, Madison, WI). Twenty-seven participants (54 limbs), 14 women and 13 men aged 33-71 years with body mass index ranging from 14 to 32 kg/m2 were recruited. Duplicate whole-body DXA scans were performed with repositioning between examinations. Regions of interest were manually drawn for the thigh, lower leg, and foot, and total volume was calculated using the density of bone mineral content, fat, and lean mass. The repeatability of the volume of the lower limb and regional thigh and lower leg tissue composition (bone mineral content, fat, and lean mass) was good with intraclass correlation coefficient values of 0.97 to 0.99, and narrow limits of agreement on the Bland-Altman plots. These results confirm DXA to be a highly repeatable method for volume and tissue composition measurements of the lower limb. In a population at risk of lymphedema, DXA offers a clinically readily available noninvasive method allowing multiple measurements of volume and tissue composition on a routine basis, important for diagnosing, monitoring, managing, and researching lymphedema.

Breast reconstruction with mentor anatomical implants and the risk of implant rotation: A retrospective study of 1134 women.

BACKGROUND: Implant rotation is a known complication to breast reconstruction using anatomical implants. However, there is a lack of large studies investigating the risk of implant rotation and potential predisposing risk factors. METHOD: We reviewed the medical records of all patients who underwent breast reconstruction with Mentor anatomical implants from 2010 to 2021 at two Danish hospitals. We compared the risk of implant rotation between one- and two-stage breast reconstruction using univariate logistic regression. We analyzed the effect of biological mesh, immediate versus delayed reconstruction, and use of a higher final expander volume than the permanent implant volume on the risk of implant rotation. Finally, we analyzed the success rate of revision surgery for implant rotation. RESULTS: In total, 1134 patients were enrolled. Patients who underwent two-stage breast reconstruction (n = 720) had a significantly higher risk of implant rotation than those who underwent one-stage breast reconstruction (n = 426; 11% vs. 5%, p < 0.01). There was no significant association between implant rotation and the use of biological mesh, immediate breast reconstruction, or use of a higher final expander volume than the permanent implant volume. The success rate of revision surgery after implant rotation was 73% (62/85 rotations). CONCLUSIONS: Two-stage breast reconstruction significantly increased the risk of implant rotation compared to one-stage breast reconstruction. The overall risk of implant rotation was low and success rate of revision surgery was high. These findings suggest that anatomical implants are safe to use for breast reconstruction. However, surgeons and patients should be aware of the increased risk of implant rotation after two-stage reconstruction.

Silicone Leakage from Breast Implants Is Determined by Silicone Cohesiveness: A Histological Study of 493 Patients.

BACKGROUND: Silicone leakage from breast implants is a concern with potential implications for patient health. This study aimed to quantify and model silicone leakage from implants to the breast implant capsule and to investigate whether silicone cohesiveness affected the silicone leakage rate. METHODS: Silicone content in the breast implant capsule was quantified histologically by measuring the area of silicone deposits. This was used to model silicone leakage over time based on the time of implantation. The effect of cohesiveness on silicone leakage was investigated across all implant brands with declared cohesiveness and in a subanalysis comparing only Mentor cohesive I implants with cohesive II and III implants. RESULTS: The study included 493 patients with 872 breasts and a median time of implantation of 13.0 years (range 0.4 to 51 years). The modeling of silicone leakage from intact implants showed that leakage and the acceleration of the leakage rate were significantly higher in low-cohesive implants than in highly cohesive implants (p<0.05). This was confirmed when analyzing only Mentor implants (p<0.05) and in the case of implant rupture (p<0.01) where low-cohesive implants also leaked significantly more than highly cohesive implants. CONCLUSIONS: Our results suggest that highly cohesive implants are superior to low-cohesive implants in preventing silicone leakage. Due to the accelerating rate of silicone leakage especially found in low-cohesive implants, we propose that exchange of low-cohesive implants could be discussed with patients 10 to 15 years after implantation to minimize silicone leakage even in the absence of implant rupture.

Breast augmentation under local anesthesia with intercostal blocks and light sedation.

INTRODUCTION: This study of breast augmentations performed under local anesthesia with intercostal blocks and light sedation describes the outcomes and evaluates benefits and complications. METHOD: From December 2005 until August 2019, 335 women consecutively underwent bilateral breast augmentation procedures. The anesthetic protocol consisted of an initial intravenous bolus of 1 mg midazolam and 0.25 mg alfentanil preoperatively. In 2017, this was changed to 2-4 mg midazolam intramuscularly, 1 mg midazolam intravenously, and 2.5 µg sufentanil intravenously. Intercostal blocks were injected at the midaxillary line into the intercostal spaces two to seven. The operating field was infiltrated with tumescent local anesthesia. Retrospective data extraction from patients' medical charts was done, registering demographics, dosage of anesthesia, surgical characteristics, complications, and reoperation rates. RESULTS: Two hundred and eighty-one women underwent primary augmentation and 54 had implant replacement. The most common complications included suboptimal cosmetic results, asymmetry, and healing-related problems. The overall rate of reoperation was 16.1% within an average follow-up period of 2 years, ranging from 0 to 12.5 years. The majority of the reoperations were due to cosmetic reasons. The change in anesthetic regime was associated with a significantly (p < 0.0001) decreased need for supplementary medication with no increased risk of complications. CONCLUSION: Breast augmentations in local anesthesia with intercostal blocks and light sedation can be performed safely and can serve as an alternative to procedures in general anesthesia.

Stage-Specific Risk of Recurrence and Death From Melanoma in Denmark, 2008-2021: A National Observational Cohort Study of 25 720 Patients With Stage IA to IV Melanoma.

Importance: To ensure optimal treatment and surveillance of patients with melanoma, knowledge of the clinical stage-specific risk of recurrence, mortality, and recurrence patterns across the American Joint Committee on Cancer Eighth Edition (AJCC8) substages is needed. Objective: To estimate stage-specific recurrence and melanoma-specific mortality rates, assess absolute stage-specific risks of recurrence and mortality, and describe stage-specific recurrence patterns, including conditional rates. Design: Retrospective cohort study of prospectively collected nationwide population-based registry data. Setting: Nationwide, population-based cohort study. Participants: The 25 720 Danish patients, 18 years or older, diagnosed with first-time stage IA to IV cutaneous melanoma between January 1, 2008, and December 31, 2019, were included and followed up from time of primary treatment until December 31, 2021. Exposures: First diagnosis of stage IA to IV cutaneous melanoma. Main Outcomes: Stage-specific cumulative incidence of recurrence and melanoma-specific mortality, melanoma-specific recurrence-free survival, and assessed absolute stage-specific risks of recurrence and melanoma-specific mortality. Secondary outcomes were stage-specific recurrence patterns, including conditional rates, and melanoma-specific survival. Results: We followed up 25 720 patients for a median of 5.9 years (95% CI, 58.9-59.3 years). Mean age was 59.1 years (95% CI, 58.9-59.3 years). Patients with stage IIB to IIC melanoma were older, had more comorbidities at diagnosis, and had the lowest rate of pathologic staging by sentinel node biopsy (81.6%-87.4%). A total of 10.6% of patients developed recurrence; first recurrence included distant recurrence, alone or with synchronous locoregional recurrence, in 56.6% of patients. We found a comparable risk of recurrence in stages IIIA and IIB (29.7% vs 33.2%) and in stages IIIB and IIC (35.9% vs 36.8%), respectively. Melanoma-specific mortality was comparable between stages IIIA and IIA (13.0% vs 13.6%) and between stages IIIB and IIB (18.4% vs 22.0%), respectively. These risk patterns persisted in cause-specific hazards models. Conclusions and Relevance: This nationwide, population-based cohort study found that the increasing stages of the current AJCC8 staging system do not accurately reflect an increasing risk of recurrence and mortality in melanoma. The high proportion of distant recurrences suggests that hematogenous spread is a more common metastatic pathway than previously assumed, and surveillance with routine functional/cross-sectional imaging should be considered for stages IIB to IV. Future efforts should be put toward developing new tools for risk stratification and determining the survival effect of routine imaging in surveillance.

Antibiotic implant irrigation and deep infection: A retrospective study of 1508 patients undergoing breast reconstruction with implants.

BACKGROUND: Antibiotic implant irrigation is increasingly used to prevent deep infection after implant-based breast reconstruction. However, there is limited evidence of the clinical effect. In this study, we compare the risk of a deep infection in a Danish population of women who either received antibiotic implant irrigation with gentamycin or vancomycin, or no irrigation. METHODS: We retrospectively reviewed consecutive patients undergoing all types of breast reconstruction with implants at Rigshospitalet and Herlev Hospital, Denmark, in 2010-2019. Logistic regression was used to compare the risk of deep infection between no irrigation and irrigation with gentamicin or vancomycin, and to account for the difference in risk between patient subgroups and risk factors. RESULTS: We included 1508 patients who received antibiotic irrigation with gentamicin (500 patients), vancomycin (304 patients) or no irrigation (704 patients). The univariable risk analysis showed a significant decreased risk of deep infection using gentamicin irrigation compared with no irrigation (OR 0.58, p<0.05). However, when adjusting for risk factors for infection, there was no significant decrease in the risk of infection when using gentamicin (OR 0.90, p=0.71) or vancomycin (OR 1.0, p=0.99) compared with the control group. CONCLUSIONS: We found no significant effect of using antibiotic implant irrigation after isolating it from risk factors for deep infection. However, due to the limitations of the study, we cannot conclude that there is no effect of antibiotic implant irrigation. There is a need for a randomized, placebo-controlled trial to investigate the effect, and potential side-effects, of antibiotic implant irrigation.

Socioeconomic position and breast reconstruction in Danish women.

UNLABELLED: Few studies have been conducted on the socioeconomic position of women undergoing breast reconstruction, and none have been conducted in the Danish population. We investigated the association between educational level and breast reconstruction in a nationwide cohort of Danish women with breast cancer. MATERIAL AND METHODS: From nationwide registers, 13 379 women aged 30-80 years who had been treated by mastectomy for breast cancer in Denmark in 1999-2006 were identified and followed up through November 2009. Multivariate logistic regression models were used to investigate the simultaneous influence of educational level on the likelihood of having immediate or delayed (up to three years after mastectomy) breast reconstruction, with adjustment for age, breast cancer characteristics, comorbidity, socioeconomic variables and availability of plastic surgery services at each woman's affiliated hospital. RESULTS: The odds ratios (ORs) for both immediate and delayed breast reconstruction increased significantly with level of education. Being affiliated to a hospital with a plastic surgery department increased the likelihood of both immediate (adjusted OR, 4.02; 95% confidence interval [CI], 2.81-5.75) and delayed breast reconstruction (adjusted OR, 1.41; 95% CI, 1.26-1.66). There was no association between education and breast reconstruction among 30-44 year old women, regardless of type of breast reconstruction; however, medium or higher education was significantly associated with a fourfold increase in the OR for immediate breast reconstruction in women aged 45-59 years and a more than twofold increase in the OR for delayed breast reconstruction in women aged 60-80 years compared to women with short education. CONCLUSION: Increasing education was associated with increasing odds for having immediate or delayed breast reconstruction, but only in the older age groups. The offer of breast reconstruction appears to be unequally distributed in Denmark, and living in an area where the hospital has a plastic surgery department significantly increased the odds for having breast reconstruction.

The clinical course of immediate breast implant reconstruction after breast cancer.

BACKGROUND: The number of women suitable for breast conserving treatment as well as immediate reconstruction after breast cancer has been increasing, and studies of complications hereafter are needed. MATERIAL AND METHODS: The cohort was identified in the prospective database of the Danish Registry for Plastic Surgery of the Breast during the period 1999 to 2006; 167 women with 189 immediate breast reconstructions (40 one-stage and 149 two-stage procedures) after breast cancer without a history of radiation therapy. The women were followed for complications until November 2009. Cumulative incidence risks were computed for infection, hematoma, seroma, severe capsular contracture (modified Baker III and IV), extrusion of the implant, implant rupture, asymmetry/displacement of the implant, any complication, and reoperation. In addition, we compared the postoperative course of immediate two-stage procedures with delayed two-stage procedures. RESULTS: The overall eight-year risk estimates for the immediate procedures were 76.4% for any complication, 5.3% for severe capsular contracture, 29.5% for displacement/asymmetry of the implant and 40.6% for reoperation. Significantly higher risk for reoperation was observed after immediate one-stage than after two-stage procedures. For immediate two-stage procedures acute complications such as infection, seroma and hematoma were higher in the expansion period than after the second planned surgery. Higher risks for acute complications were observed after immediate than after delayed two-stage procedures. CONCLUSION: Immediate breast implant reconstruction was found to have substantial risks of complications in non-radiated women, which should be considered in the guidance of breast cancer patients before choosing reconstructive procedure.

The worse survival outcomes reported for melanoma patients having sentinel node biopsy after lymphoscintigraphy the previous day do not appear to be due to overnight migration of Tc99m-nanocolloid tracer.

INTRODUCTION: It has been reported that the survival of patients having sentinel node (SN) biopsy for melanoma the day after lymphoscintigraphy using Tc99m-nanocolloid is worse than that of patients having lymphoscintigraphy and SN biopsy on the same day [1,2]. A possible explanation suggested is that overnight migration of the tracer from SNs to 2nd-tier nodes occurs, causing failure to remove true SNs. MATERIALS AND METHODS: The possibility of overnight tracer migration leading to errors in SN-identification was investigated in 12 patients scheduled for lymphoscintigraphy the day before surgery by repeating SPECT-CT imaging the next morning, before their SN biopsy. The aim was to check whether onward migration of colloid from previously-identified SNs had occurred. RESULTS: No significant migration of Tc99m-nanocolloid occurred overnight in any patient. All nodes reported to be SNs on day 1 imaging were also present and regarded as SNs on day 2 images. No new foci were visualised on day 2, but some that had been identified on day 1 were not seen on day 2. CONCLUSIONS: Since migration of nanocolloid overnight did not occur, this cannot explain the reported survival disadvantage for patients undergoing SN biopsy the day after lymphoscintigraphy. A likely alternative possibility is that inadequate doses of radioisotope were used for next-day procedures, causing the mistaken removal of 2nd-tier nodes instead of true SNs more frequently. Further research is required to explain the reported reduction in survival of patients having next-day SN biopsy procedures, since the possibility has important clinical implications.

Genetic predisposition to long telomeres is associated with increased mortality after melanoma: A study of 2101 melanoma patients from hospital clinics and the general population.

Whether there is an association between measured and genetically predicted telomere length and melanoma mortality is unclear. We tested the hypothesis that measured and genetically predicted telomere length is associated with mortality after a melanoma diagnosis. We followed 2,101 patients with melanoma from hospital clinics and the general population for risk of death for up to 26 years. All had telomere length measured in DNA from leukocytes, and 2052 of these were genotyped for the three single nucleotide polymorphisms rs7726159 (TERT), rs1317082 (TERC), and rs2487999 (OBFC1); all three genotypes are associated with telomere length and combined into an allele count from 0 to 6. For each telomere-lengthening allele, the hazard ratios (HRs) for mortality in the age-adjusted and multivariable-adjusted Cox analysis were 1.12 (95% confidence interval: 1.02-1.23) and 1.11 (1.01-1.23). However, for each standard deviation increase in measured telomere length, HR for mortality was 0.97 (0.88-1.08). In conclusion, in more than 2000 melanoma patients from hospital clinics and from the general population, genetically predicted long telomeres were associated with increased mortality, but measured leukocyte telomere length was not.

Local complications after cosmetic breast augmentation: results from the Danish Registry for Plastic Surgery of the Breast.

BACKGROUND: Prospective long-term data on the occurrence of complications following breast augmentation are sparse and the reported frequencies differ substantially. METHODS: The Danish Registry for Plastic Surgery of the Breast has prospectively registered preoperative, perioperative, and postoperative data for women undergoing breast augmentation in Denmark since 1999. From the Registry, the authors identified 5373 women with a primary cosmetic breast augmentation between 1999 and 2007. The authors calculated incidence proportions of adverse clinical outcomes within three time intervals (0 to 30 days, 0 to 3 years, and 0 to 5 years) after primary implantation. Outcomes of primary interest were capsular contracture, asymmetry/ displacement of the implant, hematoma, and infection. RESULTS: During the entire follow-up period (mean, 3.8 years; range, 0.1 to 8.7 years), 16.7 percent of the women were registered with an adverse event and 4.8 percent of the women were registered with a surgery-requiring complication. The most common adverse events within 30 days were hematoma (1.1 percent) and infections (1.2 percent), whereas the most common adverse events within 5 years were change of tactile sense (8.7 percent) and asymmetry/ displacement of implant (5.2 percent). Within 5 years, 1.7 percent of the women had a record of severe capsular contracture. Displacement/asymmetry and capsular contracture were the most frequent indications for reoperation with removal or exchange of the implant. CONCLUSIONS: Population-based complication frequencies among women with cosmetic breast augmentation in a Danish nationwide implant registry were generally lower than those reported in other studies, although frequencies of complications increased with length of follow-up.

Management Recommendations for Merkel Cell Carcinoma-A Danish Perspective.

Merkel cell carcinoma (MCC) is a rare malignant neuroendocrine carcinoma of the skin with a poor prognosis and an apparent increase in incidence. Due to its rarity, evidence-based guidelines are limited, and there is a lack of awareness among clinicians. This review constitutes the consensus management recommendations developed by the Danish MCC expert group and is based on a systematic literature search. Patients with localized disease are recommended surgical excision and adjuvant radiotherapy to the primary site; however, this may be omitted in patients with MCC with low risk features. Patients with regional lymph node involvement are recommended complete lymph node removal and adjuvant radiotherapy in case of extracapsular disease. Metastatic disease was traditionally treated with chemotherapy, however, recent clinical trials with immune therapy have been promising. Immune checkpoint inhibitors targeting the programmed cell death protein 1(PD-1)/programmed death-ligand 1(PD-L1) axis should therefore be strongly considered as first-line treatment for fit patients. A 5-year follow-up period is recommended involving clinical exam every 3 months for 2 years and every 6 months for the following 3 years and PET-CT one to two times a year or if clinically indicated. These national recommendations are intended to offer uniform patient treatment and hopefully improve prognosis.

Psychological characteristics of Danish women with cosmetic breast implants.

An excess of suicide among women with cosmetic breast implants compared with controls has consistently been reported in epidemiologic studies. We have evaluated psychological characteristics among 423 Danish women with cosmetic breast implants, compared with 414 controls. Odds ratios (OR) with 95% confidence intervals (CI) for self-reported psychological symptoms were calculated using multiple logistic regression. Substantial excesses of all studied symptoms before implant surgery were reported among women with breast implants compared with women with other cosmetic surgery, whereas ORs for virtually all symptoms occurring after surgery were close to or below 1.0. In particular, ORs for treatment for depression, cognitive/depressive symptoms, and depression/low spirit before surgery were 4.6 (95% CI = 2.1-10.0), 3.9 (95% CI = 1.9-7.8), and 2.5 (95% CI = 1.1-5.5), respectively. In contrast, the corresponding ORs for these 3 psychological symptoms after surgery were 0.9 (95% CI = 0.6-1.4), 1.0 (95% CI = 0.7-1.5), and 1.0 (95% CI = 0.6-1.5), respectively. In conclusion, women with cosmetic breast implants reported preoperative psychological symptoms indicative of depressive disorders substantially more frequently than women with other cosmetic surgery. Future studies using standardized, validated psychiatric assessment tools are needed to determine whether this can explain the higher risk for suicide among a subset of women seeking cosmetic breast implants.