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Linear IgA bullous dermatosis (LABD) is a rare subepidermal autoimmune blistering disease characterized by linear deposition of IgA along the basement membrane zone. Although most reported cases are idiopathic, there is a subset of patients with drug-induced LABD. Various drugs have been associated with the drug-induced form of the disease. This paper reviews the literature on drugs reported to elicit linear IgA dermatosis and its specific clinical presentation. In addition, a case report of a 77-year-old male patient with linear IgA dermatosis induced by vancomycin is described. The aim of this paper is to emphasize the need to include this differential diagnosis in cases of suspected adverse drug reactions, as well as to highlight the role of drugs in LABD. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses topics concerning adverse drug reactions including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and severe cutaneous adverse reactions (SCAR).

Patients with chronic myeloid leukemia (CML) treated with tyrosine kinase inhibitors (TKIs) often experience cutaneous adverse events, such as rashes and pruritus. In this study, we aimed to compare the risks of cutaneous adverse events between imatinib- and second-generation TKI-treated patients with CML. Paired reviewers independently obtained studies from PubMed, Embase, and Cochrane Library published until 15 March 2022. The following terms were searched: (Leukemia, Myelogenous, Chronic and BCR-ABL Positive), chronic myeloid leukemia, tyrosine kinase inhibitor, TKI, imatinib, dasatinib, nilotinib, bosutinib, and radotinib. Two independent reviewers screened the results and selected articles on cutaneous adverse events. RevMan 5.4 and the Cochrane Collaboration tool were used to perform the meta-analysis and risk of bias assessment. Eleven trials involving 4502 patients were analyzed in this study. Patients treated with second-generation TKIs were significantly more likely to experience cutaneous adverse events than those treated with imatinib with a relative risk (RR) of 1.62 (95% confidence interval [CI], [1.25–2.09]). Except dasatinib (RR [95% CI], 1.39 [0.75–2.56]), the risk of adverse events was more with second-generation TKIs than with imatinib as follows: nilotinib (2.11 [1.53–2.90]), bosutinib (1.41 [1.07–1.86]), and radotinib (1.87 [1.33–2.63]). Rash was the most common cutaneous adverse event that was observed in 21.6% of cases across all grades, followed by pruritus (5.7%) and alopecia (4.3%). In conclusion, our findings suggest that cutaneous adverse events occur more frequently with second-generation TKIs than with imatinib. Therefore, effective management of the cutaneous outcome is necessary to achieve high patient adherence to medication and successful treatment with TKIs. [ABSTRACT FROM AUTHOR]

Malignant tumours are the foremost complications of immunosuppressive treatment. They are a major challenge for organ transplant recipients and their treating physicians. This paper reviews the aetiology and current treatment of an unusual neuroendocrine skin cancer, Merkel cell carcinoma (MCC), caused by a Merkel cell polyomavirus infection. MCC occurs more frequently than expected in immunosuppressed subjects, especially in organ transplant recipients. The current literature comprises reports of 79 organ transplant recipients with MCC. The risk of MCC in organ transplant recipients is increased up to 66-182-fold compared with the general population. In addition to the increased risk of developing MCC, immunosuppressed individuals have poorer MCC-specific survival. The aim of this review article is to familiarize organ transplant doctors with this unique and clinically challenging skin cancer, and to provide recent data on the diagnosis and current treatment recommendations for an immunosuppressed population. [ABSTRACT FROM AUTHOR]

The article focuses on late complications and survival in soft tissue sarcoma (STS) patients who received adjuvant chemotherapy, particularly doxorubicin-based chemotherapy. Topics discussed include the incidence of doxorubicin-induced cardiotoxicity, other treatment-related late-onset adverse events, and survival outcomes in two different treatment groups.

The article reports on research which was conducted as part of a higher educational thesis and investigated the epidemiology, radiology and histology of atypical femoral fractures which were linked to the use of drugs called bisphosphonates. In the article the author offers his opinions on the use of bisphosphonates and on the need for additional research on the treatment of atypical femoral fractures.

Rehabilitation of cancer patients include a broad range of activities aimed at information, counselling, advices on possible change of lifestyle and behaviour, psychological support, social welfare questions, ways of coping with side-effects of the anti-carcinogenic treatment given and additional treatment of numerous clinical problems. The change in the age distribution combined with the growing number of cancer survivors and the scarce economic resources allocated to 'after-treatment' clinical follow-up of cancer patients, even in the Scandinavian countries characterised by their public tax financed health system, emphasize the need for screening of rehabilitation needs among cancer patients. There is a need to identify patients in need for psychological and social intervention. However, this intervention among cancer patients in need has to be based on results achieved in clinical studies. This paper gives a brief introduction to the field of rehabilitation research and indicates a number of areas in which research would be of benefit for the clinical organisation of rehabilitation activities. These areas include the implication of social inequality, a characterisation of cancer patients who rehabilitate successfully, the gender perspective in rehabilitation, the age perspective, how to establish cancer disease specific rehabilitation modules, family and community aspects of rehabilitation, the dilemma between individual responsibility for lifestyle changes and feelings of guilt and the need for models which can determine the best timing of the intervention among cancer patients. [ABSTRACT FROM AUTHOR]

Since they were first administered to patients with anti-body deficiency disorders over 50 years ago, human intravenous immunoglobulin preparations have been used successfully to treat a rapidly increasing number of auto-immune and inflammatory disorders, among which are a series of cutaneous autoimmune and inflammatory diseases. These include dermatomyositis, Kawasaki's disease, a number of autoimmune bullous diseases, severe adverse drug reactions, and other autoimmune and/or allergic conditions, such as atopic dermatitis. Although only a minority of these indications (dermatomyositis, Kawasaki's disease) are officially registered or based on double-blind, placebo-controlled clinical studies, the observed efficacy and safety profile of currently available intravenous immunoglobulin sometimes makes this a treatment of choice for initiation of therapy or for replacement of more toxic alternatives, such as systemic immunosuppressive medications. The increasing use of intravenous immunoglobulin has been associated with further understanding of its mechanism(s) of action, clinical manipulation and associated side-effects, as well as the introduction of improved or new types of intravenous immunoglobulin. This paper reviews the current knowledge of the mode of action of intravenous immunoglobulin, its reported therapeutic effects in cutaneous disease, its mode of administration and safety profile, and compares the currently available intravenous immunoglobulin preparations. [ABSTRACT FROM AUTHOR]

Breast cancer is the most prevalent neoplasm in women in North American and European countries. Data about intensive care unit (ICU) requirements and the related outcomes are scarce. Furthermore, long-term outcome after ICU discharge has not been described. We conducted a retrospective monocenter study including patients with breast cancer requiring unplanned ICU admission over a 14-year period (2007–2020). 177 patients (age = 65[57–75] years) were analyzed. Breast cancer was at a metastatic stage for 122 (68.9%) patients, recently diagnosed in 25 (14.1%) patients or in progression under treatment in 76 (42.9%) patients. Admissions were related to sepsis in 56 (31.6%) patients, to iatrogenic/procedural complication in 19 (10.7%) patients and to specific oncological complications in 47 (26.6%) patients. Seventy-two (40.7%) patients required invasive mechanical ventilation, 57 (32.2%) vasopressors/inotropes, and 26 (14.7%) renal replacement therapy. In-ICU and one-year mortality rates were 20.9% and 57.1%, respectively. Independent factors associated with in-ICU mortality were invasive mechanical ventilation and impaired performance status. One-year mortality in ICU survivors was independently associated with specific complications, triple negative cancer, and impaired performance status. After hospital discharge, most patients (77.4%) were able to continue or initiate antitumoral treatment. ICU admission was linked to the underlying malignancy in one-quarter of breast cancer patients. Despite the low in-ICU mortality rate (20.9%) and thereafter continuation of cancer treatment in most survivors (77.4%), one-year mortality reached 57.1%. Impaired performance status prior to the acute complication was a potent predictor of both short-term and long-term outcomes. [ABSTRACT FROM AUTHOR]

Osimertinib is a recently approved third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR-T790M resistance mutations. The aim of the present meta-analysis was to investigate the efficacy and safety of osimertinib for patients with EGFR-mutated non-small-cell lung cancer (NSCLC). Databases were searched for randomized controlled studies that reported the efficacy and safety of osimertinib versus other treatments (chemotherapy, other EGFR-TKIs, etc.) in treating EGFR-mutated NSCLC. The measured effects included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), central nervous system progression-free survival (CNS-PFS), and overall survival (OS). Additional outcome was the incidence of adverse event. Relative risk (RR) for incidence and hazard ratio (HR) for survival outcomes were pooled. Seven studies containing 3335 participants were finally included. Osimertinib tended to improve ORR and DCR (RRs >1) as compared with other treatments. Osimertinib was also a significant protective factor for PFS, CNS-PFS, and OS (HRs <1 and p <.05). Osimertinib showed similar advantages in improving tumor response and patient survival when used as first-line, second-line, and third-line/adjuvant therapy, respectively, as compared with other treatments (RRs >1 for ORR and DCR; HRs <1 for PFS, CNS-PFS, and OS). Osimertinib also had better therapeutic effects as compared with chemotherapy, other EGFR TKIs, docetaxel + bevacizumab, and placebo, respectively. The five most common adverse events with pooled incidence > 20% were diarrhea, rash, nail effects, dry skin, and stomatitis, yet the pooled incidence of serious adverse events was less than 2%. This meta-analysis suggests that osimertinib has a positive effect in disease control and survival for patients with EGFR-mutated NSCLC with acceptable toxicities. [ABSTRACT FROM AUTHOR]

The article focuses on a case report of complex regional pain syndrome (CRPS) possibly induced by COVID-19 vaccination, with the patient experiencing debilitating foot pain and dermatological manifestations. Topics include the clinical presentation of CRPS, the diagnostic challenges in dermatology, and the potential association between mRNA COVID-19 vaccination and CRPS, emphasizing the need for heightened awareness among dermatologists.

Background and purpose Hip resurfacing (HRS) procedures have gained increasing popularity for younger, higher-demand patients with degenerative hip pathologies. However, with concerns regarding revision rates and possible adverse metal hypersensitivity reactions with metal-on-metal articulations, some authors have questioned the hypothesized superiority of hip resurfacing over total hip arthroplasty (THA). In this meta-analysis, we compared the clinical and radiological outcomes and complication rates of these 2 procedures. Methods A systematic review was undertaken of all published (Medline, CINAHL, AMED, EMBASE) and unpublished or gray literature research databases up to January 2010. Clinical and radiological outcomes as well as complications of HRS were compared to those of THA using risk ratio, mean difference, and standardized mean difference statistics. Studies were critically appraised using the CASP appraisal tool. Results 46 studies were identified from 1,124 citations. These included 3,799 HRSs and 3,282 THAs. On meta-analysis, functional outcomes for subjects following HRS were better than or the same as for subjects with a THA, but there were statistically significantly greater incidences of heterotopic ossification, aseptic loosening, and revision surgery with HRS compared to THA. The evidence base showed a number of methodological inadequacies such as the limited use of power calculations and poor or absent blinding of both patients and assessors, possibly giving rise to assessor bias. Interpretation On the basis of the current evidence base, HRS may have better functional outcomes than THA, but the increased risks of heterotopic ossification, aseptic loosening, and revision surgery following HRS indicate that THA is superior in terms of implant survival. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 47-year-old male patient with advanced synovial sarcoma and was treated with doxorubicin. She was treated with combination chemotherapy consisting of ifosfamide and doxorubicin. The article discusses the use of Pazopanib drug as the only licensed oral tyrosine kinase inhibitor for the treatment of non-adipocytic soft tissue sarcoma.

The article offers information on the Chronic myeloid leukemia (CML), a chronic myeloproliferative disease, consistently associated with the presence of the Philadelphia chromosome coding for the BCR-ABL oncoprotein. It mentions the use of tyrosine kinase inhibitors (TKIs) in CML has highly improved prognosis of CML patients; and also mentions adequate provision of information is an important determinant of both medication adherence in CML and successful management of side effects.

Pruritus is a frequent symptom in medicine. Population-based studies show that every 5th person in the general population has suffered from chronic pruritus at least once in the lifetime with a 12-month incidence of 7%. In patient populations its frequency is much higher depending on the underlying cause, ranging from around 25% in haemodialysis patients to 100% in skin diseases such as urticaria and atopic dermatitis (AD). Pruritus may be the result of a dermatological or non-dermatological disease. Especially in non-diseased skin it may be caused by systemic, neurological or psychiatric diseases, as well as being a side effect of medications. In a number of cases chronic pruritus may be of multifactorial origin. Pruritus needs a precise diagnostic work-up. Management of chronic pruritus comprises treatment of the underlying disease and topical treatment modalities, including symptomatic antipruritic treatment, ultraviolet phototherapy and systemic treatment. Treating chronic pruritus needs to be targeted, multimodal and performed in a step-wise procedure requiring an interdisciplinary approach. We present the updated and consensus based (S2k) European guideline on chronic pruritus by a team of European pruritus experts from different disciplines. This version is an updated version of the guideline that was published in 2012 and updated in 2014 (www.euroderm. org). [ABSTRACT FROM AUTHOR]

A letter to the editor in response to the article "On the origin of cancer cells" in a 1956 issue is presented.

Background:Side effects of chemotherapy may occur at different time-points in the treatment cycle, and the exact assessment time relative to chemotherapy may affect HRQoL scores. The current study examined the variation of HRQoL during chemotherapy cycles, and whether differences in HRQoL scores varied at selected time-points between patients allocated to two different chemotherapy regimens. Material and methods:Patients with stage IIIB or IV non-small-cell lung cancer (NSCLC) were randomly assigned to receive three cycles of carboplatin plus vinorelbine (VC) or gemcitabine (GC) every 3 weeks. HRQoL was reported on the EORTC QLQ-C30 and LC13 on days 1, 4, 8, 11 and 15 of every cycle. Global health status, nausea/vomiting, fatigue and dyspnea (LC13) were defined as the HRQoL scales of primary interest. Results:Fifty-two patients were enrolled. Variation of mean scores of global health status, nausea/vomiting and fatigue showed a consistent pattern during chemotherapy. Day 4 appeared to be the time-point when chemotherapy influenced HRQoL the most. The differences in mean HRQoL scores between the two treatment arms varied at the different time-points, especially for nausea/vomiting. Conclusion:There was a clinically relevant variation of HRQoL during chemotherapy cycles, with increased symptom burden the first week following treatment. Our results suggest that timing of HRQoL assessment can influence the chances of detecting differences between the treatment regimens. [ABSTRACT FROM AUTHOR]

Background:Docetaxel in combination with cisplatin and 5-fluorouracil (5-FU) is one of several standard chemotherapy regimens for patients with advanced gastro-esophageal adenocarcinoma (aGEA) in Europe. To enable outpatient treatment, we evaluated the maximum tolerated dose (MTD), recommended dose (RD), dose limiting toxicity (DLT) and safety of docetaxel in combination with oxaliplatin (O) and S-1 (DOS) in Caucasian patients with aGEA. Methods:We present final results of two parallel phase 1/2a studies (3 + 3 design). Escalating doses of docetaxel and S-1 with fixed dose O were given for 18 weeks every second week (DOS2w) or every third week (DOS3w) followed by S-1 maintenance therapy. Results:Thirty-four patients (18 in DOS2w and 16 in DOS3w) were enrolled between October 2013 and June 2015. Median age was 65 years (range 49–78). DLT was most often febrile neutropenia. Most common severe non-hematological adverse events were diarrhea (9%) and fatigue (6%). The RD of DOS3w was: docetaxel 50 mg/m2, O 100 mg/m2and S-1 25 mg/m2twice daily and of DOS2w was: docetaxel 40 mg/m2, O 70 mg/m2and S-1 35 mg/m2twice daily. Overall, response rate was 56%; median progression-free survival was 9.1 months; and median overall survival was 13.2 months in 34 patients. Conclusions:At the RD, DOS2w and DOS3w showed an acceptable safety profile in patients with aGEA. Clinical trials ID:NCT-01928524 and EudraCT 2012-005187-10 [ABSTRACT FROM PUBLISHER]

Objectives: The primary objective of this study was to investigate the association of systemic diseases, use of medications, allergies and tobacco habits with geographic tongue (GT) and fissured tongue (FT) lesions. The secondary objectives were to evaluate the clinical characteristics of tongue lesions and to compare the overall results for referred and non-referred patients.Methodology: Non-referred patients with GT (GTgp; n = 130) and FT (FTgp; n = 62) were examined by general practitioners (gp) and compared to a control group without oral mucosal lesions (C; n = 1029). Referred patients with GT (GTs; n = 166) and FT (FTs; n = 15) were examined by oral medicine specialists (s) and compared to GTgp and FTgp. Statistical analyses were performed using unpaired t-test or Fisher's exact test. A multiple logistic regression model was developed to control for age and gender as confounders.Results: Compared to the C group, GTgp patients used more anti-hypertensive medications and Swedish snus (p < 0.01). The GTgp group consisted of older males (p < 0.001) compared to C. Compared to the GTgp group, the GTs group was younger, more likely to have symptomatic lesions (p < 0.0001) and comprised of more females. Among the groups examined, FT patients had the highest mean age.Conclusion: This study identified an association between GT and anti-hypertensive medications, as well as the use of Swedish snus. It also found differences in the activities and symptoms of the lesions between referred patients and their counterparts who were seen in general dental practice; these parameters influenced the results when these conditions were taken into account. [ABSTRACT FROM AUTHOR]

Objective. To describe the histological features of bone tissue harvested from patients affected by jaw osteonecrosis associated with bisphoshponates (BONJ) or with radiotherapy (ORN), in undecalcified ground sections. Materials and methods. Sixteen bone tissue samples from 14 patients with BONJ and two patients with ORN were processed in order to obtain both ground, undecalcified sections and decalcified sections. The sections underwent histometric and morphometric analysis. Results. Bone tissue samples obtained from patients with BONJ or ORN of the jaws shared some histological characteristics. Common histological features included the loss of bone architecture, the absence of a proper Haversian system and proper marrow spaces, the presence of necrotic spots of non-mineralized tissue, areas of empty osteocytic lacunae next to areas of hypercellularity, the presence of resorption pits with rare osteoclast-like cells and the presence of bacteria and of an inflammatory infiltrate. A violet rib of tissue characterized by large resorption pits facing was frequently observed between the mineralized bone and the inflammatory infiltrate. Conclusions. The histological features of BONJ and ORN are similar and resemble those of osteomyelitis. Even though it is not clear whether infection is the cause or consequence of bone exposure, inflammatory cells, bacteria or their products may have a massive, direct lytic effect on bone tissue challenged by bisphosphonates. [ABSTRACT FROM AUTHOR]

There is no reliable test to diagnose cephalosporin-induced maculopapular exanthems (MPE). This study aimed to evaluate the role of enzyme-linked immunospot assay in the diagnosis of cephalosporin-induced MPE compared with skin testing. A total of 25 patients with a history of cephalosporin-induced MPE were skin tested and the frequencies of cephalosporin-specific interferon-γ-, interleukin-5-, and interleukin-10-releasing cells/106 peripheral blood mononuclear cells were measured after stimulating with the culprit drug, compared with 20 non-allergic controls. Values greater than means+2 standard deviations of the values in non-allergic controls were considered diagnostic. The study showed that the combination of interferon-γ and interleukin-5 enzyme-linked immunospot assays was more sensitive than skin testing to diagnose cephalosporin allergy (40% vs. 80, p=0.008) and sensitivity increased to 57.1% when the test was performed within 2 years of the drug reaction. Enzyme-linked immunospot assay is a promising tool for confirming the diagnosis of cephalosporin-induced MPE. [ABSTRACT FROM AUTHOR]

Dapsone is widely used in the treatment of leprosy and several chronic inflammatory dermatological conditions. Hypersensitivity reactions to dapsone are potentially fatal adverse drug reactions with unknown prevalence and risk factors. We performed a systematic review covering all reported cases of hypersensitivity reactions, in order to systematically summarize the published evidence on prevalence, clinical course and fatality rate. Articles were identified through standardized search strategies. Included studies were reviewed for hypersensitivity characteristics and odds ratios were calculated in univariate and multivariate regression models to assess the risk factors for fatal outcome. A total of 114 articles (17 epidemiological studies, 97 case reports) totalling 336 patients with hypersensitivity reactions were included for analysis. From the epidemiological studies a total hypersensitivity reaction prevalence rate of 1.4% (95% confidence interval 1.2-1.7%) was determined. Mucosal involvement, hepatitis, higher age and disease occurrence in non-affluent countries were associated with higher risk of fatal outcome. Overall, the fatality rate was 9.9%. [ABSTRACT FROM AUTHOR]

The article discusses research which investigated the use of gefitinib in patients who developed rising prostate specific antigen (PSA) after radical prostatectomy or radiotherapy. Researchers, after evaluating patients who received the drug, found that it was safe and effective, and suggested that further research was needed to investigate how the drug worked.

A letter to the editor is presented which is concerned with the use of 5-Fluorouracil/Leucovorin and arsenic trioxide in patients with refractory/relapsed colorectal carcinoma.

Introduction. The aims of this study were to analyze the systematic and random interfractional set-up errors during Intensity Modulated Radiation Therapy (IMRT) in 20 consecutive nasopharyngeal carcinoma (NPC) patients by means of Electronic Portal Images Device (EPID), to define appropriate Planning Target Volume (PTV) and Planning Risk Volume (PRV) margins, as well as to investigate set-up displacement trend as a function of time during fractionated RT course. Material and methods. Before EPID clinical implementation, an anthropomorphic phantom was shifted intentionally 5 mm to all directions and the EPIs were compared with the digitally reconstructed radiographs (DRRs) to test the system's capability to recognize displacements observed in clinical studies. Then, 578 clinical images were analyzed with a mean of 29 images for each patient. Results. Phantom data showed that the system was able to correct shifts with an accuracy of 1 mm. As regards clinical data, the estimated population systematic errors were 1.3 mm for left-right (L-R), 1 mm for superior-inferior (S-I) and 1.1 mm for anterior-posterior (A-P) directions, respectively. Population random errors were 1.3 mm, 1.5 mm and 1.3 mm for L-R, S-I and A-P directions, respectively. PTV margin was at least 3.4, 3 and 3.2 mm for L-R, S-I and A-P direction, respectively. PRV margins for brainstem and spinal cord were 2.3, 2 and 2.1 mm and 3.8, 3.5 and 3.2 mm for L-R, A-P and S-I directions, respectively. Set-up error displacements showed no significant changes as the therapy progressed (p>0.05), although displacements >3 mm were found more frequently when severe weight loss or tumor nodal shrinkage occurred. Discussion. These results enable us to choose margins that guarantee with sufficient accuracy the coverage of PTVs and organs at risk sparing. Collected data confirmed the need for a strict check of patient position reproducibility in case of anatomical changes. [ABSTRACT FROM AUTHOR]

Background and purpose The current treatment for femoral fractures in children is mostly operative, which contrasts with treatment of other long bone fractures in children. We analyzed treatment injuries in such patients in Finland in order to identify avoidable injuries. Our other aims were to calculate the incidence of these fractures and to describe the treatment method used. Methods The Patient Insurance Centre (PIC) provides financial compensation of patients who have sustained an injury in connection with medical care. We retrospectively analyzed incidence, treatment methods, and all compensation claims concerning treatment of femoral fractures in children who were 0-16 years of age during the 8-year period 1997-2004. Results The incidence of childhood femoral fractures in Finland was 0.27 per 1,000 children aged < 17 years, and two-thirds of the patients were treated operatively during the study period. 30 compensation claims were submitted to PIC during the 8-year study period. The compensation claims mainly concerned pain, insufficient diagnosis or treatment, extra expenses, permanent disability, or inappropriate behavior of medical personnel. Of the claims, 16 of 30 were granted compensation. Compensation was granted for delay in treatment, unnecessary surgery, and for inappropriate surgical technique. The mean amount of compensation was 2,300 euros. Of the injuries that led to compensation, 11 of 16 were regarded as being avoidable in retrospect. Interpretation The calculated risk of a treatment injury in childhood femoral fracture treatment in Finland is approximately 2%, and most of these injuries can be avoided with proper treatment. [ABSTRACT FROM AUTHOR]

We analysed the incidence of second primary intracranial tumours in patients with pituitary adenomas treated with radiotherapy compared to the risk of patients not exposed to irradiation and to the general population. Materials and methods. This retrospective cohort study includes 298 patients with pituitary adenomas that received radiotherapy to the pituitary from 1960 to 2007. The patients were recruited from the Cancer Registry of northern Sweden and the local radiotherapy-registry of the University Hospital in Umeå. Only patients with ≥12 months follow-up after diagnosis of pituitary adenoma were included. A cohort of 131 patients with pituitary adenomas not treated with radiotherapy was used as reference. Standard incidence ratios (SIR) between observed and expected number of second primary intracranial tumours were calculated. Results. The median observation time after diagnosis of pituitary adenoma in 298 patients treated with radiotherapy was 14 years, and the total number of person-years at risk was 4 784. Six (2.0%) of the patients developed second primary intracranial tumours between 7 and 31 years after radiotherapy. Two patients had gliomas and four had meningiomas. The expected number of intracranial tumours was 1.15 giving a SIR of 5.20 (95% CI 1.90-11.31). No significant correlations were found between radiation technique or administered dose and the risk of developing a second primary intracranial tumour. The cumulative risk for second intracranial tumours at 10 and 20 years was 1.3%. Patients not treated with radiotherapy were followed 1 601 years and no second primary intracranial tumour occurred. Discussion. The results indicate an increased risk of second primary intracranial tumours in patients treated with radiotherapy for pituitary adenomas, compared to patients not exposed to irradiation and to the general population. Meningiomas were more frequent than gliomas and the median time interval between radiotherapy and second intracranial tumour was 17 years. [ABSTRACT FROM AUTHOR]

Background and purpose. The rectum is a major dose-limiting organ at risk (OR) in radiotherapy (RT) of prostate cancer. Methods to predict adverse effects in the rectum are therefore important but their precision often limited, not the least by the internal motion of this organ. In this study late rectal morbidity is investigated in relation to the internal motion of the rectum by applying the ‘Planning organ at Risk Volume’ (PRV) concept. Materials and methods: Late rectal morbidity was analysed in 242 prostate cancer patients treated to 70 Gy with conformal RT to either the prostate, the prostate and seminal vesicles or the whole pelvis (initial 50 Gy only). Late rectal morbidity was classified by the late gastro-intestinal (GI) RTOG toxicity scoring system. Cumulative dose-volume histograms (DVHs) were derived for the rectum OR and six rectum PRVs i.e. the OR expanded with six different margins (narrow/intermediate/wide in anterior direction or in both anterior and posterior direction). The difference in rectum dose-volume parameters between patients with Grade 0–1 vs. Grade 2 or higher morbidity was investigated by logistic regression and permutation tests. Results: Late Grade 2 or higher morbidity was observed in 25 of 242 (10%) patients. The logistic regression analysis and the permutation tests reached significance (p ≤ 0.05) for only one dose level of the rectum OR (40 Gy). For the PRVs, several dose levels were found to be significant (p-value range: 0.01–0.046), most pronounced for the PRV with narrow margins of 6 mm anterior and 5 mm posterior with five intermediate (38–42 Gy) and ten high (62–71 Gy) dose levels. Conclusions: The statistical methods applied displayed consistently a small though significant difference in DVH parameters between patients with vs. without Grade 2 or higher late rectal morbidity for intermediate and high dose levels. The difference became most evident when using a PRV with narrow margins. [ABSTRACT FROM AUTHOR]

Purpose. To study the interaction between radiation dose distribution and hypofractionated radiotherapy with respect to the risk of radiation pneumonitis (RP) estimated from normal tissue complication probability (NTCP) models. Material and methods. Eighteen non-small cell lung cancer patients previously treated with helical tomotherapy were selected. For each patient a 3D-conformal plan (3D-CRT) plan was produced in addition to the delivered plan. The standard fractionation schedule was set to 60 Gy in 30 fractions. Iso-efficacy comparisons with hypofractionation were performed by changing the fractionation and the physical prescription dose while keeping the equivalent tumor dose in 2 Gy fractions constant. The risk of developing RP after radiotherapy was estimated using the Mean Equivalent Lung Dose in 2-Gy fractions (MELD2) NTCP model with α/β=4 Gy for the residual lung. Overall treatment time was kept constant. Results. The mean risk of clinical RP after standard fractionation was 7.6% for Tomotherapy (range: 2.8–15.9%) and 9.2% for 3D-CRT (range 3.2–20.2%). Changing to 20 fractions, the Tomotherapy plans became slightly less toxic if the tumor α/β ratio, (α/β)T, was 7 Gy (mean RP risk 7.5%, range 2.8–16%) while the 3D-CRT plans became marginally more toxic (mean RP risk 9.8%, range 3.2–21%). If (α/β)T was 13 Gy, the mean estimated risk of RP is 7.9% for Tomotherapy (range: 2.8–17%) and 10% for 3D-CRT (range 3.2–22%). Conclusion. Modern highly conformal dose distributions are radiobiologically more forgiving with respect to hypofractionation, even for a normal tissue endpoint where α/β is lower than for the tumor in question. [ABSTRACT FROM AUTHOR]

Purpose/background. Validating a predictive model for late rectal bleeding following external beam treatment for prostate cancer would enable safer treatments or dose escalation. We tested the normal tissue complication probability (NTCP) model recommended in the recent QUANTEC review (quantitative analysis of normal tissue effects in the clinic). Material and methods. One hundred and sixty one prostate cancer patients were treated with 3D conformal radiotherapy for prostate cancer at the British Columbia Cancer Agency in a prospective protocol. The total prescription dose for all patients was 74 Gy, delivered in 2 Gy/fraction. 159 3D treatment planning datasets were available for analysis. Rectal dose volume histograms were extracted and fitted to a Lyman-Kutcher-Burman NTCP model. Results. Late rectal bleeding (>grade 2) was observed in 12/159 patients (7.5%). Multivariate logistic regression with dose-volume parameters (V50, V60, V70, etc.) was non-significant. Among clinical variables, only age was significant on a Kaplan-Meier log-rank test (p=0.007, with an optimal cut point of 77 years). Best-fit Lyman-Kutcher-Burman model parameters (with 95% confidence intervals) were: n = 0.068 (0.01, +infinity); m =0.14 (0.0, 0.86); and TD50 = 81 (27, 136) Gy. The peak values fall within the 95% QUANTEC confidence intervals. On this dataset, both models had only modest ability to predict complications: the best-fit model had a Spearman's rank correlation coefficient of rs = 0.099 (p = 0.11) and area under the receiver operating characteristic curve (AUC) of 0.62; the QUANTEC model had rs=0.096 (p= 0.11) and a corresponding AUC of 0.61. Although the QUANTEC model consistently predicted higher NTCP values, it could not be rejected according to the χ2 test (p = 0.44). Conclusions. Observed complications, and best-fit parameter estimates, were consistent with the QUANTEC-preferred NTCP model. However, predictive power was low, at least partly because the rectal dose distribution characteristics do not vary greatly within this patient cohort. [ABSTRACT FROM AUTHOR]

Background. Non-invasive visualization of tumor biological and molecular processes of importance to diagnosis and treatment response is likely to be critical in individualized cancer therapy. Since conventional static 18F-FDG PET with calculation of the semi-quantitative parameter standardized uptake value (SUV) may be subject to many sources of variability, we here present an approach of quantifying the 18F-FDG uptake by analytic two-tissue compartment modeling, extracting kinetic tumor parameters from dynamic 18F-FDG PET. Further, we evaluate the potential of such parameters in radiotherapy response assessment. Material and methods. Male, athymic mice with prostate carcinoma xenografts were subjected to dynamic PET either untreated (n=8) or 24 h post-irradiation (7.5 Gy single dose, n=8). After 10 h of fasting, intravenous bolus injections of 10–15 MBq 18F-FDG were administered and a 1 h dynamic PET scan was performed. 4D emission data were reconstructed using OSEM-MAP, before remote post-processing. Individual arterial input functions were extracted from the image series. Subsequently, tumor 18F-FDG uptake was fitted voxel-by-voxel to a compartment model, producing kinetic parameter maps. Results. The kinetic model separated the 18F-FDG uptake into free and bound tracer and quantified three parameters; forward tracer diffusion ( k1), backward tracer diffusion ( k2), and rate of 18F-FDG phosphorylation, i.e. the glucose metabolism ( k3). The fitted kinetic model gave a goodness of fit ( r2) to the observed data ranging from 0.91 to 0.99, and produced parametrical images of all tumors included in the study. Untreated tumors showed homogeneous intra-group median values of all three parameters ( k1 , k2 and k3), whereas the parameters significantly increased in the tumors irradiated 24 h prior to 18F-FDG PET. Conclusions. This study demonstrates the feasibility of a two-tissue compartment kinetic analysis of dynamic 18F-FDG PET images. If validated, extracted parametrical maps might contribute to tumor biological characterization and radiotherapy response assessment. [ABSTRACT FROM AUTHOR]

There is growing clinical evidence that functional imaging is useful for target volume definition and early assessment of tumour response to external beam radiotherapy. A subject that has perhaps received less attention, but is no less promising, is the application of functional imaging to the prediction or measurement of radiation adverse effects in normal tissues. In this manuscript, we review the current published literature describing the use of positron emission tomography (PET), four-dimensional computed tomography (4D-CT), single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) to study normal tissue function in the context of radiotherapy to the lung, liver and head & neck. Published results to date demonstrate that functional imaging can be used to preferentially avoid normal tissues not easily identifiable on solely anatomical images. It is also a potentially very powerful tool for the early detection of radiotherapy-induced normal tissue adverse effects and could provide valuable data for building predictive models of outcome. However, one of the major challenges to building useful predictive models is that, to date, there are very little data available with combined images of normal function, 3D delivered radiation dose and clinical outcomes. Prospective data collection through well-constructed studies which use established morbidity scores is clearly a priority if significant progress is to be made in this area. [ABSTRACT FROM AUTHOR]

Results of continuous sunitinib, in combination with cetuximab and irinotecan every other week (SIC) for compassionate use in heavily pre-treated patients with mCRC are presented. Patients and methods. Patients with mCRC resistant to oxaliplatin, irinotecan, 5-FU and cetuximab received SIC at two Danish oncologic departments. The regimen consisted of sunitinib given as a continuous-dosing in combination with cetuximab and irinotecan every other week (CetIri). The first six patients started with a daily oral dose of sunitinib of 12.5 mg. Subsequent patients started at a daily dose of 25 mg with the possibility to escalate to 37.5 mg. Results. Twenty-nine patients received SIC. No patient had an objective response, but 13 patients had subjective relief and 42% had stable disease. The median time to progression was 3.2 months and median overall survival was 7.4 months. Fatigue and leukopenia were the most frequently reported severe adverse event (18% grade 3 and 18% grade 3/4, respectively). Discussion. Sunitinib continuous-dosing with 25 mg/day can safely be combined with CetIri administered every other week. [ABSTRACT FROM AUTHOR]

Introduction. The EORTC 22922/10925 trial investigated the potential survival benefit and toxicity of elective irradiation of the internal mammary and medial supraclavicular (IM-MS) nodes Accrual completed in January 2004 and first results are expected in 2012. We present the toxicity reported until year 3 after treatment. Patients and methods. At each visit, toxicity was reported but severity was not graded routinely. Toxicity rates and performance status (PS) changes at three years were compared by χ2 tests and logistic regression models in all the 3 866 of 4 004 patients eligible to the trial who received the allocated treatment. Results. Only lung (fibrosis; dyspnoea; pneumonitis; any lung toxicities) (4.3% vs. 1.3%; p < 0.0001) but not cardiac toxicity (0.3% vs. 0.4%; p = 0.55) significantly increased with IM-MS treatment. No significant worsening of the PS was observed (p = 0.79), suggesting that treatment-related toxicity does not impair patient's daily activities. Conclusions. IM-MS irradiation seems well tolerated and does not significantly impair WHO PS at three years. A follow-up period of at least 10 years is needed to determine whether cardiac toxicity is increased after radiotherapy. [ABSTRACT FROM AUTHOR]

Introduction. Rectal cancer is a common disease in Western populations. Improved treatment modalities have resulted in increased survival and tumour control. With increasing survival there is a growing need for knowledge about the long-term side effects and functional results after the treatment. Aim. To describe the long-term functional outcome in patients treated for rectal cancer through a systematic review of the current literature and to provide an outline of the promising developments within this area. Results. Standard resectional surgery with loss of the rectal reservoir function results in poor functional results in up to 50-60% of the patients. New methods of surgery including the construction of a neoreservoir and improvement of the technique for local excision have been developed to minimize the functional disturbances without compromising the oncological result. The addition of chemo and/or radiotherapy approximately doubles the risk of poor functional results. During the last decades the techniques for chemo/radiotherapy has been markedly improved with a positive impact on functional outcome. New methods for treatment of functional disturbances e.g. bowel irrigation and sacral nerve stimulation are currently under development. Perspectives. To improve the functional outcome in this growing patient population several approaches can be taken. The primary cancer treatment must be improved by minimizing the surgical trauma and optimizing the imaging and radiation techniques. Population screening should be considered in order to find the cancers at an earlier stage, hereby increasing the proportion of patients eligible for local excision without the need for chemo/irradiation. All patients recovering from rectal resection should be examined and registered systematically regarding their functional results and treatment should be offered to the severely affected patients. More studies are still needed to evaluate the efficacy of irrigation and nerve stimulation in this patient group. [ABSTRACT FROM AUTHOR]

Patients with suspected cutaneous adverse drug reactions are often referred to allergy clinics or departments of dermatology for evaluation. These patients are selected compared with patients identified in prospective and cross-sectional studies of hospital populations. This explains the observed variation in prevalence of specific reactions and of eliciting drugs. This study investigated the prevalence of cutaneous adverse drug reactions in a university hospital department of dermatology that is specially focused on allergy. An 8-month survey was carried out during the period April-December 2003. Consecutive patients suspected of having cutaneous adverse drug reactions during this period were examined by dermatologists and investigated. Drug imputability was assessed in the 194 patients included; 33.5% had an exanthema with certain or likely drug imputability. Urticaria and local reactions at injection sites were the most frequent reactions (25% and 18.8%, respectively). β-lactam antibiotics, extracts for desensitization and insulins were the main drug groups involved, and accounted for 22.8%, 17.1% and 14.2%, respectively, of the reactions. Extracts for desensitization and insulins elicited more reactions than expected. This probably reflects the referral pattern to an allergy clinic. [ABSTRACT FROM AUTHOR]

Patients infected with human immunodeficiency virus are highly susceptible to adverse dermatological reactions to specific medications. Severe cutaneous conditions such as Stevens-Johnson syndrome and toxic epidermal necrolysis are associated with high morbidity and, notably for toxic epidermal necrolysis, high mortality. Although overall mortality from human immunodeficiency virus has dramatically declined owing to highly active antiretroviral therapy, these antiretroviral regimens have been associated with a wide spectrum of severe cutaneous reactions. We reviewed case reports and clinical trials in the English literature on Medline® (1966 to 2001) and Aidsline® (1980 to 2000) to determine the prevalence of Stevens-Johnson syndrome and toxic epidermal necrolysis attributable to the current FDA approved antiretroviral medications. We identified a total of approximately 50 patients who had Stevens-Johnson syndrome and/or toxic epidermal necrolysis associated with the use of 5 antiretroviral medications: 2 nucleoside reverse transcriptase inhibitors, zidovudine (2 patients) and didanosine (1 patient); 1 non-nucleoside reverse transcriptase inhibitor, nevirapine (42 patients); and 2 protease inhibitors, indinavir (1 patient) and amprenavir (an unspecified number within the 1% of over 1400 patients experiencing severe life-threatening reactions). Of the reports that specified the onset time of adverse reaction after initiation of treatment, 86% (19/22) of patients experienced reactions within 4 weeks. Ten of the approximately 50 patients were diagnosed with StevensJohnson syndrome or toxic epidermal necrolysis, due to specific antiretroviral medication, or a combination of medications identified by either resolution upon withdrawal, consistent biopsy findings or a positive rechallenge. The remainder of the identified patients were reported in articles lacking data regarding drug administration, reaction history or other details. [ABSTRACT FROM AUTHOR]

Oranges are suspected of inducing adverse skin reactions in patients with atopic eczema. We studied 21 adult patients with atopic eczema and a history of adverse reactions to oranges and 10 patients without. A dietary history, skin tests, serum IgE and oral provocation tests with oranges were obtained. Severity of eczema was monitored by SCORAD, and serum tryptase, eosinophil cationic protein and urinary methylhistamine were measured. No allergic reactions were found to orange in skin prick or patch tests. However, 23 patients (74%) had specific serum IgE to orange. Oral provocation testing resulted in pruritic eczematous or maculopapular skin lesions predominantly at the predilection sites in 16 patients (52%). The SCORAD increased significantly in patients positive to the oral provocation test (p < 0.05). Specific IgE to orange did not correlate with the clinical outcome of the oral provocation test. No significant changes were found in serum mast cell tryptase, eosinophil cationic protein or in urinary methylhistamine excretion. The negative results in the skin tests and a lack of correlation between specific IgE and oral provocation tests indicate that non-IgE-mediated mechanisms are involved in cutaneous adverse reactions to oranges in patients with atopic eczema. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on an anti-body drug conjugate (ADC) called Ado-trastuzamab emtansine (T-DM1) for the treatment of metastatic breast cancer.

In this article, editor of the periodical talks about the value of new knowledge amid the Covid-19 pandemic. It discusses that editors represent different fields in dermato-venereology, along with mentions the work experience of editors including Veli-Matti Kähäri; Maria Palmetun Ekbäck; and the Agneta Andersson.

A letter to the editor is presented which is concerned with toxicity related to the use of the drug erlotinib.

A letter to the editor is presented in response to a research article which was concerned with cardiac toxicity and radiation dose to the heart in definitive non-small lung cancer.

The article presents a letter to the editor about lingual angioedema linked to treatment with everolimus.

The article describes the case of a six-month old boy with iatrogenic Cushing's syndrome after treatment with a topical corticosteroids prescribed for dermatitis. It discusses the symptoms experienced by the patient, results of the patient's physical examination, the patient's medical history and treatment given to the patient.

A letter to the editor is presented which is concerned with pemetrexed induced aseptic meningitis.

The article presents a study of six patients with atopic dermatitis (AD) treated with extracorporeal photopheresis (ECP). Treatment with ECP was tolerated in all patients without any objective or serological clinical adverse reactions. Subjective adverse reactions, primarily in the form of gastrointestinal symptoms, were cited after the oral formulation of 8-methoxypsoralen was given.

Examines the association between acute generalized exanthematous pustulosis and amoxapine. Adverse reaction of amoxapine; Impact of amoxapine on toxic epidermal necrolysis; Cross-reaction between different families of antidepressants.