Truncating NFKB1 variants cause combined NLRP3 inflammasome activation and type I interferon signaling and predispose to necrotizing fasciitis.

In monogenic autoinflammatory diseases, mutations in genes regulating innate immune responses often lead to uncontrolled activation of inflammasome pathways or the type I interferon (IFN-I) response. We describe a mechanism of autoinflammation potentially predisposing patients to life-threatening necrotizing soft tissue inflammation. Six unrelated families are identified in which affected members present with necrotizing fasciitis or severe soft tissue inflammations. Exome sequencing reveals truncating monoallelic loss-of-function variants of nuclear factor κ light-chain enhancer of activated B cells (NFKB1) in affected patients. In patients' macrophages and in NFKB1-variant-bearing THP-1 cells, activation increases both interleukin (IL)-1ß secretion and IFN-I signaling. Truncation of NF-κB1 impairs autophagy, accompanied by the accumulation of reactive oxygen species and reduced degradation of inflammasome receptor nucleotide-binding oligomerization domain, leucine-rich repeat-containing protein 3 (NLRP3), and Toll/IL-1 receptor domain-containing adaptor protein inducing IFN-ß (TRIF), thus leading to combined excessive inflammasome and IFN-I activity. Many of the patients respond to anti-inflammatory treatment, and targeting IL-1ß and/or IFN-I signaling could represent a therapeutic approach for these patients.

Immediate versus delayed breast reconstruction: Long-term follow-up on health-related quality of life and satisfaction with breasts.

INTRODUCTION: Health-related quality of life (HRQL) can be improved by breast reconstruction following mastectomy. The optimal timing of the reconstruction remains unclear. METHODS: A cross-sectional study on 338 women who had undergone immediate or delayed breast reconstruction between 08/2017 and 07/2019 was performed. The postoperative HRQL was assessed using the BREAST-Q Reconstruction Module and the 36-Item Short Form Survey (SF-36). Regression analysis was performed for group-wise comparison. RESULTS: A total of 146 (43%) patients participated. Seventy-seven patients (53%) had undergone immediate, and 69 patients (47%) had delayed reconstruction. The median age was 55 years (interquartile ratio [IQR] 50-62) for the Immeda group te, and 60 years (IQR 54-65) for the delayed reconstruction group. The median follow-up time was 2.3 years (IQR 1.8-2.9). No difference between the groups was detected in satisfaction with breasts (median 61, IQR 53-71 vs. 62, IQR 46-71, p = 0.62), physical well-being of the chest (median 100, IQR 80-100 vs. 100, IQR 80-100, p = 0.95) or psychosocial well-being (median 69, IQR 54-83 vs. 62, IQR 54-74, p = 0.19). No difference was detected in the SF-36 domains either. CONCLUSIONS: The timing of the breast reconstruction does not affect the postoperative HRQL. Patients with both immediate and delayed breast reconstruction reported high satisfaction with the breast and psychosocial well-being.

Hot dots - which nodes should be removed in sentinel lymph node biopsy for melanoma?

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a critical staging tool for melanoma patients. The optimal number of lymph nodes removed in SLNB remains unclear. In this study, we retrospectively analysed and tested different criteria for selecting sentinel lymph nodes (SLNs) by radiotracer uptake and blue dye, and their impact on nodal staging. We also evaluated the association between SLN tumour burden and radiotracer uptake. METHODS: The study population consisted of melanoma patients undergoing SLNB. During the operation all radioactive and blue nodes were removed and sent for histopathological analysis. The ex vivo radioactive count and presence of blue dye of each node were recorded, and these were correlated with presence and size of metastasis in each SLN. RESULTS: Altogether 175 patients with clinically occult metastasis presented with one or more positive, i.e. metastatic, SLNs. The mean number of lymph nodes removed was 4.5, and the mean number of positive lymph nodes was 1.5 per patient. The most radioactive or hottest node was negative in 38 patients (22%). By removing the hottest node and all nodes with radioactivity >10% of the hottest node, 97% of patients would have been staged correctly. In five patients, metastasis was found solely in a SLN with radioactivity <10% of the hottest node. Of all 267 positive nodes removed, 125 (47%) contained blue dye. Patients with a negative hottest node were associated with lower SLN tumour burden. CONCLUSIONS: By removing the hottest node and all nodes with radioactivity >10% of the hottest node, 97% of patients with SLN metastases are correctly staged with or without using blue dye.

"An abdominoplasty modification for post-pregnancy abdomen with rectus diastasis and midline hernia: the technique and results".

SUMMARY: Few women recover from pregnancy abnormally and end up having severe post-pregnancy rectus diastasis (RD) with body control dysfunction, midline hernia or other quality of life impairment. The purpose of this study was to describe the authors' experience using HELP modification of abdominoplasty (Hydrodissection and Epidural anesthesia for Lateral Plication) to restore abdominal wall firmness. 46 consecutive post-pregnancy RD patients were enrolled. The mean intraoperative inter rectus distance was 4.6 cm. RD is not always the only structure that has been elongated. Firmness of the abdominal wall depends also on lateral fascia structures. Our study reports the total plicated distance addressing the lateral laxity in the abdominal wall. In this series total plication was 7.8 cm. In this series 16 patients had a midline hernia. We did not see hernia recurrences, and the rectus bellies were <5mm apart from each other in all participants verified with ultrasound after two years of follow up. Patient perspective of care and surgical outcome were recorded: HRQoL domains were significantly higher postoperatively implicating better health. Lumbar back pain visual analogy scale score was 4.5±2.3 preoperatively and 0.5 ±0.9 postoperatively. The ability to perform sit-ups increased from 0 to 11 suggesting better motor control. Total complication rate was 10.9%. HELP modification seems to offer a reliable and effective treatment method for RD repair with and without a small midline hernia with low complication rate.

Surgery, Limb Edema and Health-related Quality of Life: A Prospective Follow-up Study on Patients With Cutaneous Malignant Melanoma.

BACKGROUND/AIM: The latest developments in oncological therapies for malignant melanoma, and the discovery that complete lymph node dissection offers no survival benefit, are changing the landscape of melanoma surgery. There is a need for more information on health-related quality of life (HRQoL) consequences of melanoma surgery. PATIENTS AND METHODS: This longitudinal cohort study was carried out from 2004 to 2009 in the Helsinki and Uusimaa Hospital District and patients were followed-up at 6, 12 and 24 months. The patients were asked to fill in the generic 15D questionnaire and the cancer-specific European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30). In addition, they were asked selected questions from the EORTC Item Library regarding upper and lower limb edema. RESULTS: A total of 169 (64.5%) patients with local or locally advanced melanoma referred for surgical treatment responded, of whom 161 were included in the final analysis. For the whole patient group, distress, depression and emotional function improved over time. Worse HRQoL in some of the dimensions were associated with female sex, skin transplant versus direct wound closure and complications 30 days or more after surgery, but none was associated with worse overall HRQoL. Postoperative complications, type of wound closure or lymph node surgery had no effect on overall HRQoL. Patient-reported limb edema was associated with worse overall HRQoL at baseline and during follow-up by both instruments. Patients reporting limb edema reported worse mobility and more pain throughout the study. CONCLUSION: Patient-reported limb edema, regardless of the cause, seems to be an important predictor of worse HRQoL among patients with melanoma.

The Cost of Breast Cancer Surgery - Is the Money Spent Reflected on Health-related Quality of Life?

BACKGROUND/AIM: Different treatment options of breast cancer (BC) are dependent on certain cancer- and patient-related features. The cost of treatment varies among patients. This study describes the cost distribution in the treatment of Finnish patients with BC for two years and relates the costs to important outcomes of modern BC treatment. PATIENTS AND METHODS: Health-related quality of life (HRQoL) of 1,065 patients was measured prospectively at baseline, and 3, 6, 12, and 24 months thereafter with a generic (15D) and a disease-specific (EORTC QLQ C-30 BR23) HRQoL-instrument. Clinical data and costs of care were collected from hospital records. Patients were divided into four groups according to the surgical approach: breast-conserving surgery (BCS n=661), mastectomy (n=319), immediate reconstruction (IBR n=51), and delayed reconstruction (DR n=34), and the costs according to the clinic responsible for treatment: oncological-, breast surgery-, and plastic surgery unit. Total costs of care during follow-up are presented groupwise alongside HRQoL results. RESULTS: The mean total cost for BC surgery was 6,015 Euros for BCS, 8,114 euros for mastectomy, 18,217 Euros for IBR, and 19,041 Euros for DR. BCS, IBR, and DR produced good HRQoL. Mastectomy patients had the lowest overall HRQoL and highest cost accumulation at the oncology unit. HRQoL of IBR and DR patients was similar. CONCLUSION: DR produces good HRQoL but generates the highest costs of care. If patients that require reconstruction could be identified earlier and offered IBR instead of mastectomy followed by later DR, the costs of care might be reduced.

Delay in the initiation of adjuvant chemotherapy in patients with breast cancer with mastectomy with or without immediate breast reconstruction.

BACKGROUND: Patients with breast cancer undergoing mastectomy should be offered the option of immediate breast reconstruction (IBR). The aim of this retrospective study was to assess whether there is a delay in the initiation of adjuvant chemotherapy in patients undergoing mastectomy with or without IBR. METHOD: The study included patients aged 70 years or younger with clinically node-negative breast cancer who underwent unilateral mastectomy with IBR (IBR group) or mastectomy alone (no-IBR group) followed by adjuvant chemotherapy at the Helsinki University Hospital between January 2012 to July 2018. RESULTS: A total of 645 patients were included; 186 in the IBR group and 459 in the no-IBR group. Sixty-six (35.5 per cent) patients in the IBR group and 102 (22.2 per cent) patients in the no-IBR group received their first chemotherapy cycle later than 6 weeks after surgery (P < 0.001). The respective numbers for later than 8 weeks were 17 (9.1 per cent) and 14 (3.1 per cent) (P = 0.001). Among all 645 patients, postoperative complications were a significant risk factor for a delay in the initiation of chemotherapy. Sixty-seven (39.9 per cent) patients with and 101 (21.2 per cent) patients without complications had a delay in chemotherapy (P < 0.001). The delay in chemotherapy was due to complications in 39 (59.1 per cent) in the IBR group and in 28 (27.5 per cent) in the no-IBR group (P < 0.001). CONCLUSION: Patients undergoing mastectomy alone were more likely to receive adjuvant chemotherapy within 6 weeks after surgery compared with the IBR patients. IBR significantly increased the risk of postoperative complications in comparison with mastectomy alone. The complications, in turn, were a significant risk factor for delay in adjuvant chemotherapy.

Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma: A Randomized Clinical Trial.

Importance: Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery. Objective: To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases. Design, Setting, and Participants: The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 years with melanoma metastatic to SLN(s). Data were collected from December 2004 to April 2019, and data were analyzed from July 2020 to January 2022. Interventions: Nodal observation with ultrasonography rather than CLND. Main Outcomes and Measures: In-basin nodal recurrence. Results: Of 823 included patients, 479 (58.2%) were male, and the mean (SD) age was 52.8 (13.8) years. Among 855 observed basins, at 10 years, 80.2% (actuarial; 95% CI, 77-83) of basins were free of nodal recurrence. By univariable analysis, freedom from regional nodal recurrence was associated with age younger than 50 years (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70; P < .001), nonulcerated melanoma (HR, 0.36; 95% CI, 0.36-0.49; P < .001), thinner primary melanoma (less than 1.5 mm; HR, 0.46; 95% CI, 0.27-0.78; P = .004), axillary basin (HR, 0.61; 95% CI, 0.44-0.86; P = .005), fewer positive SLNs (1 vs 3 or more; HR, 0.32; 95% CI, 0.14-0.75; P = .008), and SLN tumor burden (measured by diameter less than 1 mm [HR, 0.39; 95% CI, 0.26-0.60; P = .001] or less than 5% area [HR, 0.36; 95% CI, 0.24-0.54; P < .001]). By multivariable analysis, younger age (HR, 0.57; 95% CI, 0.39-0.84; P = .004), thinner primary melanoma (HR, 0.40; 95% CI, 0.22-0.70; P = .002), axillary basin (HR, 0.55; 95% CI, 0.31-0.96; P = .03), SLN metastasis diameter less than 1 mm (HR, 0.52; 95% CI, 0.33-0.81; P = .007), and area less than 5% (HR, 0.58; 95% CI, 0.38-0.88; P = .01) were associated with basin control. When looking at the identified risk factors of age (50 years or older), ulceration, Breslow thickness greater than 3.5 mm, nonaxillary basin, and tumor burden of maximum diameter of 1 mm or greater and/or metastasis area of 5% or greater and excluding missing value cases, basin disease-free rates at 5 years were 96% (95% CI, 88-100) for patients with 0 risk factors, 89% (95% CI, 82-96) for 1 risk factor, 86% (95% CI, 80-93) for 2 risk factors, 80% (95% CI, 71-89) for 3 risk factors, 61% (95% CI, 48-74) for 4 risk factors, and 54% (95% CI, 36-72) for 5 or 6 risk factors. Conclusions and Relevance: This randomized clinical trial was the largest prospective evaluation of long-term regional basin control in patients with melanoma who had nodal observation after removal of a positive SLN. SLN biopsy without CLND cleared disease in the affected nodal basin in most patients, even those with multiple risk factors for in-basin recurrence. In addition to its well-validated value in staging, SLN biopsy may also be regarded as therapeutic in some patients. Trial Registration: ClinicalTrials.gov Identifier: NCT00297895.

Health-Related Quality of Life After Breast Reconstruction: Comparing Outcomes Between Reconstruction Techniques Using the BREAST-Q.

BACKGROUND: Reconstruction of the breast following mastectomy can improve patients' health-related quality of life (HRQL). We aimed to assess HRQL in women after mastectomy and breast reconstruction and to identify differences in HRQL related to the reconstruction method used. METHODS: A cross-sectional study was performed on patients who had undergone breast reconstruction in Helsinki University Hospital between 08/2017 and 7/2019. The postoperative HRQL was assessed using the BREAST-Q (2.0) Reconstruction Module. The results were compared between patients with different reconstruction methods using the Kruskal-Wallis test. RESULTS: A total of 146 patients were identified. Microvascular flaps (n = 77) were the most common method for primary breast reconstruction, followed by latissimus dorsi (LD) flaps (n = 45), fat grafting (n = 18) and implant reconstruction (n = 6). The satisfaction with breasts was high in all groups (median 61, IQR 49-71). The physical well-being of the chest was high regardless of the reconstructive method (median 100, IQR 80-100). However, women with fat grafting reported more adverse effects of radiation (median 17, IQR 14-17 vs. 18, IQR 17-18 for other groups, p = 0.02). Donor site morbidity was low, and patients reported high satisfaction with the back (median 66/100, IQR57-90) and abdomen (median 9/12, IQR 8-10), and physical well-being of the back (median 61/100, IQR 53-70) and abdomen (median 65/100, IQR 60-86). CONCLUSIONS: The patient-reported HRQL after breast reconstruction is high. Most women report being satisfied with the reconstruction, irrespective of the reconstruction method used. The reconstruction method can thus be chosen individually in cooperation between the patient and the surgeon.

Breast Reconstruction-Prospective Follow up on Breast Cancer Patients' Health-Related Quality of Life.

BACKGROUND: Analysing the results of breast reconstruction is important both in terms of oncological safety and health-related quality of life (HRQoL). Immediate breast reconstruction (IBR) is thought to be prone to complications and heavy for patients with no time to adapt to having cancer. Delayed reconstruction (DR) is an option after primary surgery and oncological treatments, but requires patients to go through two recovery periods after surgery. METHODS: A prospective study of 1065 breast cancer patients with repeated measurement of HRQoL with both generic (15D) and disease specific (EORTC QLQ C-30 BR23) measuring tools included 51 IBR patients and 41 DR patients. These patients' HRQoL and reconstruction methods were studied in more detail alongside with clinical data to determine HRQoL levels for patients with IBR and those with mastectomy and DR during a 24-month follow-up. Measuring points were baseline, 3, 6, 12 and 24 months. RESULTS: Most frequent techniques used were abdominal flaps (IBR n = 16, DR n = 14), latissimus dorsi flaps (LD) (IBR n = 19, DR n = 10), implants (IBR n = 12) and fat grafting (DR n = 6). Smaller groups were excluded from group comparisons. Approximately one third of the patients encountered complications. Symptom scores did not differ between reconstruction methods. DR patients had better overall HRQoL at 12 months, but at 24 months the situation had changed in favour of IBR. Both approaches of reconstructive surgery produced good HRQoL with no significant differences between the approaches studied.

Pelvic sentinel lymph nodes have minimal impact on survival in melanoma patients.

BACKGROUND: Lower limb or trunk melanoma often presents with femoral and pelvic sentinel lymph nodes (SLNs). The benefits of harvesting pelvic lymph nodes remain controversial. In this retrospective study, the frequency and predictors of pelvic SLNs (PSLNs), and the impact of PSLNs on survival and staging was investigated. METHODS: Altogether 285 patients with cutaneous melanoma located in the lower limb or trunk underwent sentinel lymph node biopsy of the inguinal/iliac lymph node basin at Helsinki University Hospital from 2009-2013. Patient characteristics, detailed pathology reports and follow-up data were retrieved from hospital files. Subgroups of patients categorized by presence of PSLNs were compared for outcome parameters including progression-free survival, melanoma-specific survival and groin recurrence. RESULTS: Superficial femoral/inguinal SLNs were present in all patients and 199 (69.8 per cent) also had PSLNs removed. Median number of SLNs per patient was five and median number of PSLNs was two. Sixty-three patients (22.1 per cent) had metastases in their SLNs and seven (2.5 per cent) had metastases in PSLNs. A single patient had metastases solely in PSLNs, while superficial SLNs remained negative. Harvesting PSLNs or the number of PSLNs retrieved had no impact on progression-free survival or overall survival. The removal of PSLNs did not affect the risk of postoperative seroma or lymphoedema. The only predictor of positive PSLNs was radioactivity count equal to or more than that of the hottest superficial SLNs. CONCLUSION: Pelvic SLNs have minimal clinical impact on the outcome of melanoma patients especially in cases with negative superficial femoral/inguinal SLNs. Removal of PSLNs should be considered when they are the most radioactive nodes or equal to the hottest superficial femoral/inguinal SLNs in lymphoscintigraphy or during surgery.Preliminary results were presented in part at the International Sentinel Node Society Biennial Meeting, Tokyo, Japan, 11-13 October 2018.

Surgery and health-related quality of life - A prospective follow up study on breast cancer patients in Finland.

INTRODUCTION: The influence of different surgical approaches on breast cancer patients' Health-related Quality of life (HRQoL) is an important determinant when making decisions on the choice of treatment. Knowledge on how patients actually perceive different surgical treatments regarding long-term HRQoL is still scarce. MATERIALS & METHODS: 1065 patients with primary breast cancer operated on from 2008 to 2015 at Helsinki University Hospital, Finland were prospectively followed-up for two years. They filled in two HRQoL questionnaires, the EORTC QLQ C30 - BR 23 and the 15D, at baseline and at 3, 6, 12 and 24 months after surgery. Clinical data on treatments given and the course of recovery were collected from patient records. Patients were divided into four mutually exclusive groups according to surgical method: breast resection (n = 415), oncoplastic resection (n = 248), mastectomy (n = 351) and immediate reconstruction (n = 51). Clinical data were combined with HRQoL scores and analysed as multivariate modelling. RESULTS: All groups experienced initially worsening overall HRQoL after baseline. Oncoplastic resection patients had the best body image and their HRQoL reached the highest level after treatments at 12 months whereas the reconstruction patients reached the highest HRQoL level first at 24 months. Mastectomy patients had the lowest scores throughout the 24-month follow-up. CONCLUSION: Extensive surgery, in terms of immediate reconstruction, led to slower HRQoL recovery than oncoplastic techniques. Mastectomy patients are at risk of having the lowest HRQoL scores throughout their recovery after surgery.

Health-related quality of life in patients having undergone abdominoplasty after massive weight loss.

BACKGROUND: Due to lack of validated body contouring-specific patient-reported outcome (PRO) instruments, the outcomes of abdominoplasty after massive weight loss have been evaluated rather rarely and mainly using generic health-related quality of life (HRQoL) instruments. The aim of the current study was to examine, using body contouring-specific (BODY-Q) and generic (15D) HRQoL instruments, the HRQoL, and key factors related to HRQoL among patients having undergone massive weight loss and abdominoplasty. METHODS: Altogether 52 patients who underwent abdominoplasty due to massive weight loss completed the BODY-Q and the 15D HRQoL instruments. The 15D scores were compared to those of age-, gender-, and BMI-adjusted control sample of the general population. RESULTS: The mean score of the BODY-Q Abdomen scale was 50.7 out of 100 (SD 24.4). The HRQoL of abdominoplasty patients was lower than that of age-, gender-, and BMI-adjusted general population (p = 0.001). Sleeping, discomfort and symptoms, depression, excretion, and sexual activity were the patients' main concerns. Body image and psychological well-being were strongly associated with the perceived HRQoL. The satisfaction with appearance of the abdominal area was not associated with generic HRQoL. CONCLUSIONS: The HRQoL of abdominoplasty patients is lower than that of general population with similar age, gender and BMI. The most important factors associated with the HRQoL of the patients were body image, psychological well-being, and physical function.

Three cases of fulminant cellulitis caused by non-O1, non-O139 Vibrio cholerae in Southern Finland.

Background: Non-O1, non-O139 Vibrio cholerae is endemic in temperate waters. Most often encountered as the pathogen in transient gastroenteritis, it can also cause severe soft tissue infections. While normally a rare pathogen in Finland, we observed seven cases of non-O1, non-O139 V. cholerae infections in Helsinki University Hospital during the hot summer of 2018. Here we present three of these cases with fulminant V. cholerae cellulitis in detail.Methods: Patients with tissue culture positive soft tissue infections between 2017 and 2019 were identified using a local laboratory database. Patients with severe infections requiring surgical revision were included in this series.Results: Three patients with tissue culture positive non-O1, non-O139 V. cholerae cellulitis were identified. All were treated in the summer of 2018 for fulminant lower leg cellulitis. Two patients were febrile and hemodynamically unstable at presentation. One had septicaemia. Surgical revisions were done within the first week of admission, and defects covered with partial-thickness skin grafts several weeks later. Antibiotic treatment varied and continued until the wounds were healed, between one and over two months in total.

Prolyl 4-hydroxylase subunit alpha 1 (P4HA1) is a biomarker of poor prognosis in primary melanomas, and its depletion inhibits melanoma cell invasion and disrupts tumor blood vessel walls.

Melanoma is an unpredictable, highly metastatic malignancy, and treatment of advanced melanoma remains challenging. Novel molecular markers based on the alterations in gene expression and the molecular pathways activated or deactivated during melanoma progression are needed for predicting the course of the disease already in primary tumors and for providing new targets for therapy. Here, we sought to identify genes whose expression in primary melanomas correlate with patient disease-specific survival using global gene expression profiling. Many of the identified potential markers of poor prognosis were associated with the epithelial-mesenchymal transition, extracellular matrix formation, and angiogenesis. We studied further the significance of one of the genes, prolyl 4-hydroxylase subunit alpha 1 (P4HA1), in melanoma progression. P4HA1 depletion in melanoma cells reduced cell adhesion, invasion, and viability in vitro. In melanoma xenograft assays, we found that P4HA1 knockdown reduced melanoma tumor invasion as well as the deposition of collagens, particularly type IV collagen, in the interstitial extracellular matrix and in the basement membranes of tumor blood vessels, leading to vessel wall rupture and hemorrhages. Further, P4HA1 knockdown reduced the secretion of collagen triple helix repeat containing 1 (CTHRC1), an important mediator of melanoma cell migration and invasion, in vitro and its deposition around tumor blood vessels in vivo. Taken together, P4HA1 is an interesting potential prognostic marker and therapeutic target in primary melanomas, influencing many aspects of melanoma tumor progression.

Long-Term Quality of Life of Melanoma Survivors Is Comparable to that of the General Population.

BACKGROUND/AIM: There is a growing need for information regarding the Health-Related Quality of Life (HRQoL) of cancer survivors. This study aimed to assess the HRQoL of patients treated for cutaneous malignant melanoma between 1980 and 2004 in the Helsinki and Uusimaa Hospital district and compare the results to the general population. MATERIALS AND METHODS: HRQoL of 981 cutaneous melanoma patients (aged 13 to 97 years, 56.1% female) was assessed using the generic 15D instrument and compared to the general population. The association between demographic and clinical factors and HRQoL was analyzed using oneway ANOVA, student's t-test and multivariate regression. RESULTS: The mean 15D score of melanoma patients was slightly lower (0.904) than that of the general population (0.911, p=0.027), but the difference was not statistically significant. HRQoL deteriorates with age and metastatic disease and improves with time. CONCLUSION: No evidence was found that long-term HRQoL of melanoma survivors was worse than the general population.

Health-related quality of life in different states of breast cancer - comparing different instruments.

BACKGROUND: The prognosis of breast cancer has improved significantly during the last few decades increasing the interest in health-related quality of life (HRQoL). The aim of this study was to compare the HRQoL scores produced by different instruments and to shed light on their validity in various states of breast cancer by studying the association of cancer-related symptoms with HRQoL. MATERIAL AND METHODS: An observational, cross-sectional study of breast cancer patients treated in the Helsinki and Uusimaa Hospital District from September 2009 to April 2011. A total of 840 patients completed three HRQoL questionnaires: the EQ-5D-3L (including VAS), 15D and EORTC QLQ-30 and a questionnaire concerning sociodemographic factors. Patients were divided into five mutually exclusive groups: primary treatment (n = 118), recovery (6-18 months from diagnosis) (n = 150), remission (>18 months) (n = 382), metastatic disease (n = 176) and palliative care (n = 14). The association of HRQoL with sociodemographic and clinical factors and cancer-related symptoms, screened by the EORTC QLQ-30, was studied by multivariate modeling using stepwise linear regression analysis. RESULTS: HRQoL scores were the best at the time closest to diagnosis and deteriorated with disease progression. The EQ-5D had a pronounced ceiling effect with 40.8% of the respondents scoring 1 (perfect health) compared to 6% for the 15D and 5.6% for VAS. In regression analyses, pain, fatigue and financial difficulties were the most important predictors of lower HRQoL. The 15D showed better discriminatory power and content validity. The EORTC QLQ-C30 functioning deteriorated in advanced states of the disease with physical, social and role functioning being the most affected. Insomnia, fatigue and pain were the most commonly reported symptoms in all groups. CONCLUSIONS: Different HRQoL instruments produce notably different HRQoL scores. The EQ-5D has a pronounced ceiling effect. Pain and fatigue are the most common symptoms associated with poor HRQoL in all disease states.