Immune Checkpoint Inhibitor-Associated Optic Neuritis.

Objective Immune checkpoint inhibitors (ICIs) are novel cancer therapies that may be associated with immune-related adverse events (IRAEs) and come to the attention of neuro-ophthalmologists. This systematic review aims to synthesize the reported ICI-associated IRAEs relevant to neuro-ophthalmologists to help in the diagnosis and management of these conditions. Methods A systematic review of the literature indexed by MEDLINE, Embase, CENTRAL, and Web of Science databases was searched from inception to May 2020. Reporting followed the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Primary studies on ICIs and neuro-ophthalmic complications were included. Outcomes included number of cases and incidence of neuro-ophthalmic IRAEs. Results Neuro-ophthalmic complications of ICIs occurred in 0.46% of patients undergoing ICI and may affect the afferent and efferent visual systems. Afferent complications include optic neuritis (12.8%), neuroretinitis (0.9%), and giant cell arteritis (3.7%). Efferent complications include myasthenia gravis (MG) (45.0%), thyroid-like eye disease (11.9%), orbital myositis (13.8%), general myositis with ptosis (7.3%), internuclear ophthalmoplegia (0.9%), opsoclonus-myoclonus-ataxia syndrome (0.9%), and oculomotor nerve palsy (0.9%). Pembrolizumab was the most common causative agent for neuro-ophthalmic complications (32.1%). Mortality was highest for MG (19.8%). Most patients (79.8%) experienced improvement or complete resolution of neuro-ophthalmic symptoms due to cessation of ICI and immunosuppression with systemic corticosteroids. Conclusion While incidence of neuro-ophthalmic IRAEs is low, clinicians involved in the care of cancer patients must be aware of their presentation to facilitate prompt recognition and management. Collaboration between oncology and neuro-ophthalmology teams is required to effectively manage patients and reduce morbidity and mortality.

/pdf/neuro-ophthalmic-complications-of-immune-checkpoint-49tak3hzv7.pdf

Neuro-ophthalmic Complications of Immune Checkpoint Inhibitors: A Systematic Review

Adrenocortical carcinoma (ACC) is a heterogenous group of diseases with different clinical behaviour between adult and paediatric patients. In addition, three histological variants, oncocytic, myxoid and sarcomatoid are noted on the recent World Health Organisation (WHO) classification of ACC. A review of recent literature showed that the different types of ACC have distinctive demographic data, clinical presentation, pathology, biological behaviour, genomic and patients’ prognosis. In addition, recent updates of pathology staging for ACC allow refinement of prognostic grouping for planning treatment of the patients with ACC. These advances in genomic, pathology and staging have driven the development of standardisation of pathology reporting. International standardisation of pathological reporting of adrenocortical carcinoma and adaption to local pathology communities provide universal platforms for clinicians and researchers involved in the management of patients with ACC. To conclude, all these advances in the field of pathology will improve development of management strategies including improvement of clinical care, development of prognostic markers and testing of novel therapeutic approaches for patients with adrenocortical carcinoma.

https://www.mdpi.com/2227-9059/9/2/175/pdf

Adrenocortical Carcinoma: Updates of Clinical and Pathological Features after Renewed World Health Organisation Classification and Pathology Staging.

BackgroundVision loss and other ocular toxicities are rare, but detrimental, side effects of immune checkpoint inhibitors. Herein, we report two patients who developed vision loss while on pembroli...

Vision loss with pembrolizumab treatment: A report of two cases.


 Targeted cancer therapy agents are the latest development in cancer therapeutics. Although the spectrum of their use continues to expand, ocular side effects are frequently encountered with the use of cancer therapeutics. This review describes the ocular side effects of targeted cancer therapy agents.

/pdf/targeted-cancer-therapy-and-its-ophthalmic-side-effects-a-1iy6ba08w7.pdf

Targeted Cancer Therapy and Its Ophthalmic Side Effects: A Review

Pediatric glioblastoma multiforme is an uncommon and highly mortal brain cancer. New therapeutic treatments are being intensively investigated by researchers in order to extend the survival of patients. The immune checkpoint inhibitor nivolumab in the treatment of pediatric glioblastoma multiforme is currently under review; it is a human immunoglobulin G4 monoclonal antibody that works against the programmed cell death protein 1 receptor, designed to enhance an immunologic reaction against cancer cells. Herein, we describe the first report of a bilateral optic neuritis induced by nivolumab in a grade 4 glioblastoma multiforme patient.

Bilateral Optic Neuritis Secondary to Nivolumab Therapy: A Case Report

Most cases of malignancies appear to be sporadic, but some syndromes are associated with malignancies with germline variants. Herein, a child with an unusual association of oncocytic variant adrenocortical carcinoma (ACC) and rhabdomyosarcoma was presented. An 18-month-old-boy was admitted with virilization of the genital area, penis enlargement, and erection which had begun six months ago. Serum total testosterone: 457 ng/dl (<10), androstenedione: 3.35ng/ml (<0.5) and DHEA-SO4: 206 mcg/dl (<35) were measured higher than normal ranges. Right adrenal mass was detected. After adrenalectomy, histopathological examination revealed oncocytic variant ACC. Three-month later from surgery, the child then presented with 6x8 cm sized swelling of the left leg. Histopathological examination revealed embryonal RMS. Testing for tumour protein (TP53) variant by DNA sequence analysis was positive; however; FISH analysis was negative. After chemotherapy and local radiotherapy, the patient is in good condition without tumour recurrence. Only about one-third of these tumours have a variant of TP53. This status also applies to other genetic variants related to cancer. However, a significant association of malignancies strongly suggests a problem in tumour suppressor genes or new variants. Another suppressor gene that is yet unidentified can also be present and effective in this locus. The occurrence of ACC as a part of a syndrome and positive family history of malignancies in patients are clinically important. These patients and their families should be scanned for genetic abnormalities. The patient with ACC should be followed-up carefully for other tumours to detect malignancy early.

/pdf/two-subsequent-metachroneus-solid-tumors-oncocytic-variant-ogrnovzi3v.pdf

Two Subsequent Metachroneus Solid Tumors: Oncocytic Variant Adrenocortical Carcinoma and Rhabdomyosarcoma of Childhood: Case Report and Literature Review

Background: Non-Hodgkin lymphoma (NHL) includes pathologies of different clinical courses, treatments, outcomes. Our study aims to investigate the late effects of NHL survivors (NHLS). Materials and Methods: Among 59 NHL cases, 50 survivors completed their NHL treatment between 2003 and 2019. Out of 59 patients, the cumulative survival rates and event-free survival rates after 10 years since diagnosis were 82.9% ±5.2% and 84.1% ±5.2%, respectively. In addition, we compared the data related to chronic health and psychosocial conditions with their siblings (n = 61). Results: The age and gender ratios were similar in the NHLS (n = 50) and the control group (n = 61). The rate of nephrotoxicity (P = 0.02) and the frequency of admission to the hospital (P < 0.01) were significantly higher in the survivors than in the control group. Cardiotoxicity is detected in 3 (6%) of NHLS with cumulative anthracycline dose <300 mg/m2. The social status (being married [P < 0.01], having children [P = 0.003]) is impaired in NHLS. The alcohol and smoking habits, education status, and health conditions (endocrinologic, cardiac, neurological, and pulmonary) were similar in both groups. One patient had acute myeloid leukemia as a secondary malignancy. Twenty NHLS took rituximab, two of them took brentuximab vedotin plus chemotherapy. NHLS have impairment in health status, social life. Conclusion: Nephrotoxicity is a statistically more common late effect than the others in the survivors. We observe cardiotoxicity in low cumulative doses of anthracycline. A more significant number of patients is required to reveal late side effects on novel drugs.

Late outcomes in children and adolescents with non-Hodgkin lymphoma: A single-center experience

INTRODUCTION The most common causes of cervical lymphadenopathy (LAP) are inflammatory and reactive conditions; only a small proportion have serious pathology, such as malignancy. The objective of this study was to evaluate the relationship between USG findings and histopathological diagnosis of the cervical LAP. POPULATION AND METHODS This retrospective study comprised the cases of cervical LAP in patients aged under 20 years old followed in our center between January 2007 to December 2016. Based on pathology reports, we divided the patients into two groups: benign and malignant. Pathology results and USG findings were compared. RESULTS After the analyze of the histopathological results and USG findings, 107 patients with persistent cervical LAP (44 malignant; 63 benign) were included in the study. Mean age of malignant and benign group were 14 ± 6.1; 11.9 ± 4.8 years, respectively. Hilar vascularity for benign LAP was highly statistically significant (P < 0.0001) and peripheral flow and mixed vascularity for malignant LAP were also statistically significant (p < 0.05). There was not a significant difference in the maximum diameter (27.3 ± 11.1 mm and 29.8 ± 12.3 mm, respectively), however, there was a significant difference in the minimum diameter between benign and malignant groups (13.7 ± 7.3 mm and 18.7 ± 8.8 mm, respectively). CONCLUSIONS The present study suggests that there is a relationship between US and biopsy findings for the differentiation of benign from malignant LAP, especially in terms of nodal hilus and intranodal vascular pattern.

/pdf/differentiation-of-benign-from-malignant-cervical-u7edqq08my.pdf

Differentiation of benign from malignant cervical lymphadenopathy by ultrasonography in children.

Proton MR spectroscopic features of the cisternal segment of the trigeminal nerve in patients with trigeminal neuralgia: A pilot study.

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