Αρχειοθήκη ιστολογίου

Κυριακή 9 Μαΐου 2021

Impact of staging on survival outcomes: a nationwide real-world cohort study of metastatic uveal melanoma

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imageNo data exist regarding whether any first-line treatment for metastatic uveal melanoma provides overall survival (OS) benefit, if staged and compared to best supportive care (BSC). We analyzed OS in a nationwide, consecutive cohort diagnosed with metastatic uveal melanoma between January 1999 and December 2016. The Helsinki University Hospital Working Formulation was used to assign patients to stage IVa, IVb and IVc, corresponding to predicted median OS ≥12,
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Extreme elevation of acute phase reactants and shock secondary to dabrafenib–trametinib

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imageThe emerging role of BRAF and MEK tyrosine-kinase inhibitors has shown new opportunities of treatment for patients with advanced melanoma and BRAF mutations. Its use is associated with some toxicities, as pyrexia, that clinicians may not be familiarized with. We present the case of a patient diagnosed with stage IV melanoma BRAF Val600E mutated who was started on dabrafenib and trametinib and developed three severe episodes of fever, hypotension and acute phase reactants elevation during the first 3 months of therapy, in the absence of microbiological demonstration of infection. The episodes were initia lly managed as a septic shock with broad-spectrum antibiotics and vasoactive drugs, while treatment with dabrafenib and trametinib was withheld. After two subsequent dose reduction of dabrafenib, the patient did not experience new episodes of fever.
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BRAF inhibitor treatment is feasible in the oldest-old advanced melanoma patients

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imageAlthough new compounds have improved the treatment landscape of metastatic melanoma, very limited data exist on the efficacy and safety of treating older patients with novel agents. Here, we provide results of BRAF (BRAFi) ± MEK (MEKi) inhibitor treatment in patients over 75 years (oldest-old patients) with metastatic melanoma. Between 2011 and 2020, 34 consecutive patients with metastatic melanoma over 75 years of age (range 75–89) were treated with BRAFi ± MEKi at the Comprehensive Cancer Center of Helsinki University Hospital. Data on clinical and histopathological features, toxicity, respo nse rate (RR), progression-free survival (PFS) and overall survival (OS) were collected. Patients were treated with BRAFi (n = 22) or BRAFi in combination with MEK inhibitor (MEKi) (n = 12). Grade 1–2 adverse events occurred in 68% of the patients, 32% had grade 3 adverse effects, dose reductions were made for 41% of patients and 29% terminated treatment due to toxicity. Overall, the RR was 62%. Complete responses were achieved in 27% of the patients, and 35% had partial responses. The median PFS was 8 months (range 0–57), and the median OS was 15 months (range 0–71). Tailored BRAFi ± MEKi treatment for older patients is feasible. Adverse effects occur frequently but are manageable by dose adjustment. The occurrence of toxicity of monotherapy was similar to that of combination therapy. The RR and median OS from our retrospective study are comparable with those reported in clinical trials and combination therapy produced somewhat more and longer-lasting respons es. Hence, it seems that older patients may benefit from BRAFi treatment.
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A case of hyperprolactinaemia in a patient with metastatic melanoma

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imageEctopic prolactin production from a malignancy is infrequently reported. We report here a 60-year-old gentleman who presented with hyperprolactinaemia (9100 mIU/L) causing expressible galactorrhoea, decreased libido and fatigue thought to be due to ectopic prolactin secretion from a metastatic melanoma. Upon initiation of pembrolizumab, the patient's symptoms resolved and he became normoprolactinaemic. This corresponded with a partial response on radiological imaging. Although the core biopsy of the metastatic melanoma did not exhibit immunostaining for prolactin, we believe that only a subset of the tumour cells possesses prolactin-secreting capacity. This case illustrates the need to consider ectopic prolactin production for a solid malignant tumour as a rare cause of hyperprolactinaemia in patients with a normal pituitary MRI, in the absence of other causes.
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Prognostic impact of thyroid dysfunctions on progression-free survival in patients with metastatic melanoma treated with anti-PD-1 antibodies

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imageThis study aimed to assess the prognostic value of thyroid dysfunctions in metastatic melanoma patients on anti-programmed death-1 (anti-PD-1). A total of 110 stage IV or inoperable stage III melanoma patients treated with anti-PD-1 alone or in association with anti-CTLA-4 (T-lymphocyte antigen-4) antibody from January 2015 to December 2017 at our institution were enrolled in this retrospective study. Median follow-up was 32.8 months. Transitory thyroid dysfunctions and permanent thyroid dysfunctions were distinguished. The main criterion was progression-free survival. Secondary criteria were best response a nd overall survival. Survival curves were compared with log-rank tests and a cox proportional hazard ratio model was used to adjust patients and melanoma characteristics. Thirty-eight (35%) thyroid dysfunctions were observed during the follow-up, including 25 transitory thyroid dysfunctions (23%) and 13 permanent thyroid dysfunctions (12%). Progression-free survival was longer in patients with thyroid dysfunction (18.1 months) than in patients without thyroid dysfunction (3.9 months, P = 0.0085). In multivariate analysis, thyroid dysfunctions were not an independent predictive factor for progression-free survival. Patients with thyroid dysfunction had a longer overall survival (P = 0.0021), and thyroid dysfunctions were associated with a lower mortality risk (hazard ratio = 0.40; P = 0.005). Best response was positively associated with thyroid dysfunctions (P = 0.048). Thyroid dysfunctions induced by anti-PD-1 were not an independent predictive factor for progression-free survival i n metastatic melanoma patients but seemed associated with a better response and increased overall survival.
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Impact of the development of immune related adverse events in metastatic melanoma treated with PD -1 inhibitors

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imageSome clinical trials have described improved outcomes in patients who develop immune-related adverse events (irAEs) while receiving immune checkpoint inhibitors for advanced melanoma. It is unknown if this effect would be seen in a real-world population. This is a single-center retrospective analysis of all patients receiving single-agent PD-1 inhibitor for unresectable stage III or stage IV melanoma between 2012 and 2018. The majority of patients had cutaneous melanoma and were elderly (put in median and range). Totally 33.3% were BRAF mutated and 66.7% had PD-1 inhibitor as first-line treatment for metastat ic disease. Also, 22% of patients had brain metastases at presentation. Of the 87 patients included in this analysis, 48 (55%) developed at least one irAE. Dermatologic toxicities were the most common irAE. The median time to develop any irAE was 12 weeks. Only one patient died of immune-related toxicity. Overall survival in the population of patients that had an irAE was significantly greater than those that did not have any toxicity (21.1 vs. 7.5 months; P 
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Olfactory Neuroblastoma: A Novel Site of Presentation

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Abstract

Olfactory neuroblastoma (ONB) or esthesioneuroblastoma is a rare malignant intranasal tumor, commonly originated from upper part of nasal cavity. Majority of cases presented with nasal obstruction or epistaxis. ONB is rarely reported in ectopic locations. Here we present the first-ever documented case of an olfactory neuroblastoma situated anterior to body of maxilla, presented as left sided facial swelling. This case report is aimed at achieving the consideration of this rare tumour as a differential diagnosis in the lesions of the anatomical region surrounding the commonly known site of origin i.e. the sinonasal cavity.

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Patient Reported Outcomes of Scalp and Forehead Reconstruction for Defects Following Oncological Resections (North-East Indian Tertiary Cancer Centre Study)

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Abstract

Background Approximately 1–2% of all scalp tumours are malignant, but they comprise up to 13% of all malignant cutaneous neoplasms. The current study presents our experience of reconstruction of scalp and forehead for malignant tumours treated at our centre. Methods This is a single institutional observational study conducted at a tertiary cancer centre in North East India. Post-operative outcomes related to quality of life of patients were measured with help of FACE-Q scales. Face-Q –Satisfaction with outcome and FACE-Q- appearance related psychosocial distress scores were analysed. Histograms were used for descriptive statistics. Data were checked for normality using Kolmogorov–Smirnova and Shapiro–Wilk test. For non-normal data Wilcoxon test was used. A p value less than 0.05 was considered as statistically significant at 5% level of significance. Results Mean age of patients was 57.6 ± 14.2 years. The mean defect size was 89.036 ± 81.77 cm2. The mean satisfaction with outcome scores and distress scores at 3-months was 54.9 ± 8.6 and 34.8 ± 8.5 respectively with a statistically significant p value of 0.001.Mean satisfaction scores and psychological distress scores were better at the end of three months when compared to at the time of discharge with a statistical significant p value of < 0.0001. Conclusion Scalp and forehead reconstructions for defects following oncological resections are technically challenging and if chosen carefully with meticulous planning, both local and free tissue transfers give satisfactory outcome in long term follow up. There are lots of reconstruction options for scalp and forehead defects and knowledge of the basic bio-geometry of the each flap is must.

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Anterior and Central Skull Base Fibrous Dysplasia: A 12 Years’ Experience

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Abstract

Fibrous dysplasia, specially of anterior and central skull base region, is a rare disorder. This article discusses about our experience in this pathology. A tertiary care institute based retrospective type study was conducted over a period of 12 years. Demographics, radiology, intraoperative details, pathology and follow up were taken into consideration and the data was analysed. Sixteen patients with complaints of proptosis, diplopia, nasal obstruction and/or facial deformity, underwent endoscopic sinus surgery. Subtotal resection was done in 5 patients. Ethmoid bone involvement was seen in 12 patients. Post operatively, diplopia persisted in one patient and one patient had epistaxis. All patients were followed up for 2–10 years with no other complications reported. Anterior and central skull base involvement is rare in fibrous dysplasia. However, it can be removed effectively by endoscopic approach. Overall safety of patient has more concern rather than complete removal of disease.

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Partial Middle Turbinectomy Versus Medialization Suturing of Middle Turbinate in the Management of Sinonasal Polyposis: A Comparative Study

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Abstract

The main goals of endoscopic sinus surgery (ESS) is, to enlarge the sinus ostia. Most common cause of failure of ESS is lateralization of the middle turbinate causing recurrent blockade of osteomeatal complex (OMC) and recurrence of disease. Many techniques have been described for preventing lateralization of the middle turbinate. We compared the postoperative outcomes following endoscopic sinus surgery (ESS) for sinonasal polyposis (SNP) with medialization suturing of middle turbinate and partial middle turbinectomy. 60 patients who underwent ESS for SNP were divided into three groups, Group A (Medialization suturing of the middle turbinate with septum), Group B (partial middle turbinectomy) and Group C (control-no middle turbinate intervention). Preoperative Lund Kennedy scoring, Lund McKay scoring, SNOT 22 scoring was done. Post-operatively, Lund Kennedy scoring was done at 1st, 4th, 12th week and SNOT 22 scoring was done at 4th, 12th week. Statistical analysi s and comparison of data between the groups was done. Both the techniques, helped to improve OMC patency, mucosal healing, and to minimize adhesions. Medialization of the middle turbinate helped in improvement of SNOT 22 and Lund Kennedy scores in the postoperative period as compared to the non-interventional group. However, between the two middle turbinate interventional groups there was no statistically significant difference. Achieving middle meatal patency by middle turbinate interventions improves the postoperative outcomes. However, long-term follow-up studies are recommended for evaluation of efficacy of these techniques and to look for recurrence of disease in SNP.

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Studying nerve transfers: Searching for a consensus in nerve axons count

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J Plast Reconstr Aesthet Surg. 2021 Apr 5:S1748-6815(21)00154-6. doi: 10.1016/j.bjps.2021.03.064. Online ahead of print.

ABSTRACT

Axonal count is the base for efficient nerve transfer; despite its capital importance, few studies have been published on human material, most research approaches being performed on experimental animal models of nerve injury. Thus, standard analysis methods are still lacking. Quantitative data obtained have to be reproducible and comparable with published data by other research groups. To share results with the scientific community, the standardization of quantitative analysis is a fundamental step. For this purpose, the experiences of the Italian, Austrian, German, Greek, and Iberian-Latin American groups have been compared with each other and with the existing literature to reach a consensus in the fiber count and draw up a protocol that can make future studies from different centers comparable. The search for a standardization of the methodology was aimed to reduce all the factors that are associated with an increase in the variability of the results. All the preferential methods to be used have been suggested. On the other hand, alternative methods and different methods have been identified to achieve the same goal, which in our experience are completely comparable; therefore, they can be used indifferently by the different centers according to their experience and availability.

PMID:33962889 | DOI:10.1016/j.bjps.2021.03.064

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A review of the impact of hearing interventions on social isolation and loneliness in older people with hearing loss

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Eur Arch Otorhinolaryngol. 2021 May 7. doi: 10.1007/s00405-021-06847-w. Online ahead of print.

ABSTRACT

PURPOSE: Hearing loss affects many older people and is associated with social isolation and loneliness. The impact of hearing interventions however has not been established. The objective of this review is to determine the impact of hearing interventions in older people with hearing loss on social isolation and loneliness.

METHODS: A literature review using PubMed, EMBASE and CINAHL databases was performed. Search terms included older people, elderly, aging, ageing, hearing aid, hearing rehabilitation, social isolation, loneliness and social interaction. English-language studies with participants aged over 60 years diagnosed with hearing loss comparing outcomes pre- and post-hearing interventions were included.

RESULTS: A total of 176 articles were identified of which seven met the inclusion criteria. Five studies examine d the impact of traditional hearing aids whilst two articles examined outcomes after cochlear implantation. Several outcome measures were used. Loneliness outcomes were reported in three studies and social isolation outcomes in four. All studies reported improved social isolation and loneliness scores following hearing intervention.

CONCLUSIONS: Small sample sizes, a lack of high-quality evidence, heterogenicity between studies and the presence of confounding factors limits interpretation of the literature. At present, there is inadequate evidence to support the use of hearing interventions in the treatment of social isolation and loneliness in older people. Given the ageing population, the significance of this health burden cannot be underestimated, emphasising the need for further research.

PMID:33963432 | DOI:10.1007/s00405-021-06847-w

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