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.

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.

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.

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.).

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.

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.

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.

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.

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.

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.

Shoulder-related donor site morbidity after delayed breast reconstruction with pedicled flaps from the back: An open label randomized controlled clinical trial.

BACKGROUND: This randomized controlled trial (RCT) investigates differences in shoulder-related morbidity after delayed breast reconstruction by either a latissimus dorsi (LD) flap or a thoracodorsal artery perforater (TAP) flap. MATERIAL AND METHODS: In accordance with the CONSORT guidelines, we included women for unilateral delayed breast reconstruction. Patients were randomized to reconstruction by either of the two flaps. Shoulder-function was assessed at baseline and at 3, 6 and 12 months after surgery. The primary endpoint was patient-reported shoulder-related pain. A further objective assessment by the Constant Shoulder Score (CSS) was included as secondary endpoints. RESULTS: A total of 50 women were enrolled over a two-year period and allocated to reconstruction, with 25 patients in each group. Patient-reported shoulder-related pain was significantly lower in the TAP group at 12 months after surgery when adjusting for pain at baseline: OR = 0.05 95%CI(0.005-0.51), p-value = 0.011. The estimated effect on the total CSS at 12 months, when applying the TAP flap instead of the LD flap and adjusting for the baseline score, was 6.2 points with 95%CI(0.5-12.0), p-value 0.033. The TAP flap seems to have a statistically significant positive effect on pain and activity in daily life (ADL), while there were no significant effect on range of motion and strength after one year. CONCLUSION: Patient reconstructed by the TAP flap are less likely to experience shoulder-related pain and have a better shoulder-function one year after the reconstruction. Harvest of the LD flap carries a higher risk of shoulder-function impairment, chronic pain and reduced ADL.

Measured and genetically predicted plasma YKL-40 levels and melanoma mortality.

PURPOSE: High plasma levels of YKL-40 might be associated with mortality in patients with melanoma, and it is unknown if YKL-40 is causally related to mortality. EXPERIMENTAL DESIGN: We studied two cohorts: 2618 patients with melanoma from hospital clinics and 1413 general population patients with melanoma, totalling 4031 patients followed up for mortality end-points for up to 20 years. All were genotyped for CHI3L1 rs4950928, highly predictive of lifelong plasma YKL-40, and plasma YKL-40 levels were measured in 2165 patients. We tested the hypotheses that measured and genetically predicted high plasma YKL-40 are associated with increased mortality in patients with melanoma. RESULTS: For the hospital melanoma cohort, age- and sex-adjusted hazard ratios for death in individuals with measured plasma YKL-40 in the 96-100th percentile versus 1-95th percentile and per 10-percentile increase were 1.52 (95% confidence interval, 1.07-2.16) and 1.07 (1.02-1.11), respectively, most pronounced for patients with localised melanomas. Each C-allele of the CHI3L1 rs4950928 genotype was associated with plasma YKL-40 level increases of 32% in the hospital melanoma cohort (p = 6 × 10-48) and 43% in the general population melanoma cohort (p = 7 × 10-13). Multifactorially adjusted ratios for these increases in the combined cohorts were 1.04 (1.00-1.09) observationally for measured plasma YKL-40 and 0.98 (0.86-1.12) for the genetically predicted plasma YKL-40. CONCLUSION: Measured, but not genetically predicted, increasing plasma YKL-40 was associated with increased mortality in patients with melanoma. Plasma YKL-40 is a marker but less likely to be a cause of increased mortality in patients with melanoma.

Patient-and observer-reported long-term scar quality of wide local excision scars in melanoma patients.

Wide local excision of the primary tumour is the mainstay of treatment for melanoma patients. The aims of this study were to assess the patient- and observer-reported long-term scar quality after surgery using the patient and observer scar assessment scale (POSAS) in melanoma patients, to assess the reliability and validity of POSAS, and to identify factors influencing the scar assessment. This cross-sectional clinical study included 320 melanoma patients with primary tumours on the trunk and limbs. Data regarding patients, treatment, scar characteristics and functional outcomes was analysed. Internal consistency, inter-rater reliability, and convergent validity were examined. Factors influencing the patient- and observer-reported scar quality were tested using regression analyses. Results of the POSAS showed an overall good scar quality. The internal consistency of POSAS was good, and the convergent validity was strong. The inter-rater reliability was only moderate. The patients were influenced by the POSAS sub-items: colour, irregularity, thickness and pain. The observer was influenced by the POSAS sub-items: vascularity, surface area, thickness, relief and pliability. Both patient- and observer-reported scar qualities were influenced by age, location, type of superficial suture, keloids and widened scars. Moreover, the patients were influenced by the scar tightness while the observer was influenced by postoperative complications, hypertrophic scars, suture marks and dog ears. In conclusion POSAS is a reliable and valid scar assessment tool. The factors influencing patient- and observer-reported scar quality differed, and better understanding of this may improve treatment and hence patient-reported scar quality.

Reference Values for Assessment of Unilateral Limb Lymphedema with Dual-Energy X-Ray Absorptiometry.

INTRODUCTION: The clinical assessment of unilateral limb lymphedema is commonly based on measurements of interlimb volume differences. Reference values for interlimb percentage differences of the volume, fat mass, and lean mass measured with dual-energy X-ray absorptiometry (DXA) scan are, however, not established. The aim of the study was to establish and categorize these reference values in normal limbs. METHODS AND RESULTS: DXA scans of the normal arms of 167 and normal legs of 196 melanoma patients (aged 18-75 years, body mass index <40), respectively, were performed. The interlimb percentage difference is calculated as follows: ("Limb-of-interest"-contralateral)/contralateral × 100. The interlimb percentage differences for the limb-of-interest were stratified to upper (according to handedness) and lower limbs and categorized as none/mild, moderate, or severe, respectively, based on whether the value is below, in between, or above the two prediction limits. The prediction limits for interlimb total volume percentage difference were 6% and 10%, 0% and 4%, and 3% and 6% for the dominant arm, nondominant arm, and leg, respectively. Further data are given for interlimb percentage differences of regional (upper arm, lower arm, hand, thigh, lower leg, and foot) and total volume, fat mass, and lean mass, respectively. CONCLUSIONS: The provided clinical reference values allow for identifying and categorizing pathophysiological differences of limbs-of-interest and evaluating tissue composition.

Health-related quality of life in melanoma patients: Impact of melanoma-related limb lymphoedema.

AIM: To explore health-related quality of life (HRQoL) in recurrence-free melanoma patients, with a focus on the association between melanoma-related limb lymphoedema and HRQoL. METHODS: HRQoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), the breast cancer module (EORTC QLQ-BR23) subscales body image and future perspective, the Functional Assessment for Cancer Therapy-General subscale social/family well-being and the Hospital Anxiety and Depression Scale. Data were analysed using linear and ordinal logistic regression adjusting for age and gender. RESULTS: A total of 431 melanoma patients who had undergone wide local excision and axillary or inguinal sentinel lymph node biopsy (SLNB) and/or complete lymph node dissection (CLND) participated. No patients had had recurrence of the disease or had received adjuvant radiotherapy. The HRQoL scores improved with time after surgery. Melanoma-related limb lymphoedema was present in 109 patients (25%). Patients with lymphoedema had significantly worse HRQoL scores in the EORTC QLQ-C30 subscales global health status/quality of life, role and social functioning, fatigue, pain and financial difficulties, as well as in the QLQ-BR23 body image subscale. No associations were found between the limb affected (upper or lower limb), clinical stage of lymphoedema, duration of lymphoedema or type of surgery (SLNB or CLND) and HRQoL. We found an interaction with age and gender in the associations between lymphoedema and HRQoL: younger patients and women with lymphoedema had worse social functioning and women had significantly more impaired body image. CONCLUSIONS: The negative impact of melanoma-related limb lymphoedema on HRQoL emphasises the importance of developing strategies for increasing awareness and improving prevention and treatment of lymphoedema.