Burden of Keloid Disease: A Cross-sectional Health-related Quality of Life Assessment.

Keloid scars may be painful, itch severely and be cosmetically disturbing. The burden of keloid disease, however, has not yet been determined. This study evaluated the association of keloid disease with health-related quality of life (HRQL) and identified indicators of burden using a cross-sectional survey study, with one disease-specific HRQL measure (Skindex-29) and 2 generic HRQL measures (SF-36 and EQ-5D-5L). A total of 106 keloid patients with no other skin diseases participated in the study. Having keloid disease was associated with a considerable impairment of emotional wellbeing, with most impairment on the emotional and mental HRQL. Pain and itch were the strongest indicators of HRQL impairment in keloid patients. Having painful or itchy keloids was related to low mental and emotional HRQL, implying that patients with keloids require access to effective treatment aimed at alleviating physical symptoms.

The effect of immediate breast reconstruction on the timing of adjuvant chemotherapy: a systematic review.

Adjuvant chemotherapy is often needed to achieve adequate breast cancer control. The increasing popularity of immediate breast reconstruction (IBR) raises concerns that this procedure may delay the time to adjuvant chemotherapy (TTC), which may negatively impact oncological outcome. The current systematic review aims to investigate this effect. During October 2014, a systematic search for clinical studies was performed in six databases with keywords related to breast reconstruction and chemotherapy. Eligible studies met the following inclusion criteria: (1) research population consisted of women receiving therapeutic mastectomy, (2) comparison of IBR with mastectomy only groups, (3) TTC was clearly presented and mentioned as outcome measure, and (4) original studies only (e.g., cohort study, randomized controlled trial, case-control). Fourteen studies were included, representing 5270 patients who had received adjuvant chemotherapy, of whom 1942 had undergone IBR and 3328 mastectomy only. One study found a significantly shorter mean TTC of 12.6 days after IBR, four studies found a significant delay after IBR averaging 6.6-16.8 days, seven studies found no significant difference in TTC between IBR and mastectomy only, and two studies did not perform statistical analyses for comparison. In studies that measured TTC from surgery, mean TTC varied from 29 to 61 days for IBR and from 21 to 60 days for mastectomy only. This systematic review of the current literature showed that IBR does not necessarily delay the start of adjuvant chemotherapy to a clinically relevant extent, suggesting that in general IBR is a valid option for non-metastatic breast cancer patients.

Intralesional 5-fluorouracil in keloid treatment: a systematic review.

In the 1990s, 5-flourouracil (5-FU) was introduced as a treatment for keloids; however, there is still no consensus on its use. In order to guide clinical practice, a systematic review of the clinical evidence on the effectiveness of 5-FU in keloid treatment was carried out. Eight databases were searched on 10 September 2014 using the terms "keloid" and "5-FU", together with all synonyms of these terms. Two reviewers selected original research reports using 5-FU alone or combined with a maximum of 2 other therapies. Eighteen papers were found that reported either on intralesional 5-FU alone, or on 5-FU combined with triamcinolone acetonide (TAC:5-FU) or excision, including 482 patients. 5-FU treatment was effective in 45-96% of patients, but only TAC:5-FU may perform better than TAC alone. Due to a poor level of evidence, further research should establish the superiority of repeated intralesional TAC:5-FU injections over TAC alone with several doses and injection schedules.

Intralesional cryotherapy versus excision with corticosteroid injections or brachytherapy for keloid treatment: Randomised controlled trials.

BACKGROUND: Keloids are a burden for patients due to physical, aesthetic and social consequences. Treatment remains a challenge due to therapy resistance and high recurrence rates. The main goals of treatment are to improve scar appearance and symptoms and patients' quality of life (QoL). METHODS: Two multicentre, randomised controlled open trials that compared 1) intralesional cryotherapy with excision and corticosteroid injections for primary keloids, and 2) intralesional cryotherapy with excision and brachytherapy for therapy resistant keloids. Primary outcome was scar appearance assessed with the Patient and Observer Scar Assessment Scale. Secondary outcomes were patient reported QoL (Skindex-29, SF-36, EQ-5D-5L), recurrence rates and scar volume reduction. For analysis, a linear mixed model was used. Power analysis indicated 33 patients in each group were needed. RESULTS: The trial was prematurely terminated after inclusion of 26 patients due to unexpectedly inferior outcomes after intralesional cryotherapy. For primary keloids no convincing difference between treatments was found, but surgery improved scar appearance while cryotherapy did not. For resistant keloids, excision followed by brachytherapy improved scar appearance (POSAS) and scar symptoms (itch and pain) significantly (p < 0.001, p < 0.001 and p = 0.006 respectively) while cryotherapy did not. Neither of the treatments caused indisputable improvements in QoL. CONCLUSIONS: Intralesional cryotherapy is inferior to keloid excision followed by brachytherapy for resistant keloids. In primary keloids, intralesional cryotherapy reduced keloid volume and, therefore, may be used in these patients and specific cases. Primary keloid group size was too small to draw valid conclusions, further research on the efficacy of intralesional cryotherapy for primary keloids is warranted.

Optimal High-Dose-Rate Brachytherapy Fractionation Scheme After Keloid Excision: A Retrospective Multicenter Comparison of Recurrence Rates and Complications.

PURPOSE: To determine the optimal brachytherapy dose and fractionation scheme for keloid treatment. METHODS AND MATERIALS: Patient cohorts from 3 centers treated with keloid excision followed by 2 × 9 Gy, 3 × 6 Gy, or 2 × 6 Gy high-dose-rate brachytherapy were retrospectively compared regarding recurrence (after at least 12 months' follow-up) and complications (after at least 1 month's follow-up), using logistic regression analyses. RESULTS: A total of 238 keloids were treated. An overall full recurrence rate of 8.3% was found. After correction for confounders (sex, skin color, keloid location, keloid duration) no statistically significant differences in recurrence rates could be discerned between fractionation schemes. There were 12.8% major and 45.6% minor complication rates. Lower radiation dose resulted in significantly fewer complications (odds ratio 0.35, P=.015). CONCLUSIONS: After excision of resistant keloids, high-dose-rate brachytherapy with a biological equivalent dose of approximately 20 Gy is recommended, on the basis of low recurrence and complication rates.

A Systematic Review on the Prevalence, Etiology, and Pathophysiology of Intrinsic Pain in Dermal Scar Tissue.

BACKGROUND: Scars can cause pain, even without symptoms of underlying nerve damage. A lack of knowledge on intrinsic scar pain hampers effective treatment of these complaints. OBJECTIVE: Aggregate current knowledge on the prevalence, etiology, and pathophysiology of intrinsic pain in dermal scars. STUDY DESIGN: Systematic review. SETTING: University Medical Center. METHODS: We searched the Embase, Medline, Cochrane central, CINAHL, Web-of-Science, and Pubmed databases with search terms: scar, skin, pain, and etiology/pathology, adding all synonyms of these terms. Relevant papers were selected and analyzed by 3 reviewers. RESULTS: Intrinsic pain in scars has a low prevalence. However, pathologic scars and burns regularly cause pain of high intensity. The etiology is multifactorial, the extent of trauma was an important predicting factor. Nerve fiber density did not explain the intrinsic pain when pan-neuronal markers were used, while a correlation with an increased number of C-fiber subtypes seems plausible. Nerve growth factor (that stimulate these C-fibers) plays an important role in wound healing. Thereby, it also sensitizes neurons and promotes inflammation, releasing even more neurotrophic factors. Central sensitization causes a long-lasting effect even after wounds are healed. Furthermore, the opioid-system, that influences inflammation and healing and possible systemic sensory alterations after injury, is discussed. LIMITATIONS: Liberal selection criteria challenged the systematic selection of papers. CONCLUSIONS: Burn and pathologic scars often lead to high intensity pain symptoms. This pain has many characteristics of neuropathic pain that could be caused by an imbalance of C-fibers subtypes. The scar tissue itself may alter the nerve fiber distribution; the imbalance results in ongoing neuro-inflammation and pain symptoms. Key words: Systematic review, scar, pain, epidermal innervation, prevalence, neuro inflammatory response, peptidergic fibers.

Intralesional cryotherapy versus excision and corticosteroids or brachytherapy for keloid treatment: study protocol for a randomised controlled trial.

BACKGROUND: Keloids are a burden for patients due to physical, aesthetic and social complaints and treatment remains a challenge because of therapy resistance and high recurrence rates. The main goal of treatment is to improve the quality of life (QoL); this implies that, apart from surgical outcomes, patient-reported outcome measures (PROMs) need to be taken into account. Decision making in keloid treatment is difficult due to heterogeneity of the condition and the lack of comparative studies. METHODS/DESIGN: This is a multicentre, randomised controlled open trial that compares 1) intralesional cryotherapy versus excision and corticosteroids for primary keloids, and 2) intralesional cryotherapy versus excision and brachytherapy for therapy-resistant keloids. The primary outcome is the Patient and Observer Scar Assessment Scale (POSAS), a 12-item scale (with score 12 indicating the best and 120 indicating the worst scar imaginable). A difference of six points on the total score is considered to be of clinical importance. Secondary outcomes are recurrence rates, volume reduction, Skindex-29 scores, SF-36 scores and complication rates. Primary and secondary outcome measurements are taken at baseline, and at 2, 12, 26 and 52 weeks postoperatively. For analysis, a linear mixed model is used. A total of 176 patients will be included over a period of 2.5 years. The protocol is approved by the Medical Ethics Committee of the Erasmus University Medical Centre Rotterdam and follows good clinical practice guidelines. DISCUSSION: The outcomes of this study will improve evidence-based decision making for the treatment of keloids, as well as patient education. TRIAL REGISTRATION: Dutch Trial Register NTR4151.

No disease in the brain of a 115-year-old woman.

Are there limits to the duration of high quality of life? Are there limits to healthy life for a human brain? We have had the opportunity to evaluate the performance of a 112-113-year-old woman and perform full pathological examination of her body immediately after death at the age of 115. The psychological tests revealed that her general performance was above average of healthy adults of 60-75 years. The pathological observations revealed almost no atherosclerotic changes throughout the body. In the brain almost no beta-amyloid plaques or vascular changes were found and only slight accumulation of hyperphosphorylated tau protein with a Braak-stage 2. Counts of the number of locus coeruleus neurons corresponded with the number of neurons found in the brains of healthy people of 60-80 years old. Our observations indicate that the limits of human cognitive function extends far beyond the range that is currently enjoyed by most individuals and that brain disease, even in supercentanarians, is not inevitable.