Management of Brain Metastases: A Review of Novel Therapies.

Brain metastases (BMs) represent the most common intracranial tumors in adults, and most commonly originate from lung, followed by breast, melanoma, kidney, and colorectal cancer. Management of BM is individualized based on the size and number of brain metastases, the extent of extracranial disease, the primary tumor subtype, neurological symptoms, and prior lines of therapy. Until recently, treatment strategies were limited to local therapies, like surgical resection and radiotherapy, the latter in the form of whole-brain radiotherapy or stereotactic radiosurgery. The next generation of local strategies includes laser interstitial thermal therapy, magnetic hyperthermic therapy, post-resection brachytherapy, and focused ultrasound. New targeted therapies and immunotherapies with documented intracranial activity have transformed clinical outcomes. Novel systemic therapies with intracranial utility include new anaplastic lymphoma kinase inhibitors like brigatinib and ensartinib; selective "rearranged during transfection" inhibitors like selpercatinib and pralsetinib; B-raf proto-oncogene inhibitors like encorafenib and vemurafenib; Kirsten rat sarcoma viral oncogene inhibitors like sotorasib and adagrasib; ROS1 gene rearrangement (ROS1) inhibitors, anti-neurotrophic tyrosine receptor kinase agents like larotrectinib and entrectinib; anti-human epidermal growth factor receptor 2/epidermal growth factor receptor exon 20 agent like poziotinib; and antibody-drug conjugates like trastuzumab-emtansine and trastuzumab-deruxtecan. This review highlights the modern multidisciplinary management of BM, emphasizing the integration of systemic and local therapies.

Tracheal Duplication Cyst Presenting as Chest Pain.

Tracheal duplication cysts (TDCs) are congenital malformations that are rarely diagnosed in adulthood. The authors present a case of a 43-year-old female with no known comorbidities with a two-year history of chest and upper abdominal pain. Her previous imaging on an outpatient basis was suggestive of an esophageal duplication cyst, and she was lost to follow-up until the current admission. She gave a past surgical history of video-assisted thoracoscopic surgery for a "cyst" excision, with the relevant details unavailable. On examination, the findings were unremarkable. Repeat imaging was suggestive of an esophageal duplication cyst with no change in dimensions. She underwent a right-sided elective thoracotomy and cyst excision. Intraoperatively, a smooth globular mass was visualized next to the esophagus below the level of the carina. The biopsy revealed a TDC. The patient had an uneventful postoperative period and was asymptomatic on follow-up after three months. TDCs pose a diagnostic challenge as they can only be diagnosed by imaging and histopathology. However, when the imaging is atypical, histopathology clinches the diagnosis. Complete surgical excision is recommended for symptomatic patients after ruling out malignancy. Recurrence of the lesion must be considered in patients such as ours. Our case emphasizes the consideration of TDCs in the differential diagnosis and advocates the importance of complete surgical resection to prevent a recurrence.

Giant lung tumor in hereditary spherocytosis: inflammatory myofibroblastic tumor.

Inflammatory myofibroblastic tumors are a rare subset of lung lesions in the adult age group. They pose a diagnostic challenge as they present with non-specific findings. We report a 27-year-old female with an inflammatory myofibroblastic tumor on a background of hereditary spherocytosis.

Idiopathic Extremity Arteriovenous Fistula: A Rare Etiology of Cardiac Failure.

Idiopathic extremity arteriovenous fistulas are rare, abnormal connections between arteries and veins commonly occurring between iliac vessels. We present the case of a 42-year-old female who was referred to our center for a mitral valve replacement with a one-year history of breathlessness and a six-month history of progressive abdominal distension. Physical examination revealed a pansystolic murmur in the mitral area, basal crepitations, and a non-tender pulsatile swelling in the right iliac fossa. Imaging showed severe mitral regurgitation in heart failure along with a large arteriovenous fistula between the common femoral vessels which suggested that the arteriovenous fistula was the etiology of heart failure. Postoperatively, the patient showed significant improvement in symptoms with imaging. On follow-up, the patient reported no progression of symptoms. Our case demonstrated an idiopathic extremity arteriovenous fistula in an unusual location, unexpectedly causing heart failure despite a significant valvular disease. Therefore, arteriovenous fistulas warrant inclusion in the differential of heart failure despite a valvular lesion and absence of classical signs of high output heart failure, as in our case.

Prevalence and Predictors of Restless Leg Syndrome in Adolescents and Young Adults of Bengaluru City, India: A Cross-Sectional Study.

INTRODUCTION: Restless leg syndrome (RLS) is a sensorimotor disease characterized by an urge to move the legs, often caused by uncomfortable and unpleasant sensations in the legs. It affects the quality of sleep which in turn affects scholastic performance in children and predisposes them to cardiovascular diseases in the long run. Hence, the primary aim of this study was to assess the prevalence and predictors of RLS, poor sleep quality, and excessive daytime sleepiness (EDS). METHODS: This was a cross-sectional observational study conducted between September 2017 and March 2020 in Bengaluru, India, including all consenting PreUniversity College, Degree College, and Higher Secondary school students. After parental consent and assent (if applicable) was obtained, a semi-structured standardized pilot-tested questionnaire consisting of the RLS diagnostic criteria, Pittsburgh Sleep Quality Index (PSQI), Epworth sleepiness scale, and questions on sleep hygiene was administered. The prevalence was expressed as proportions and 95% confidence intervals (95% CI). Regression analysis was done to determine the predictors. RESULTS: The overall prevalence (95% CI; frequency) of students with RLS, poor sleep quality, and EDS in our study population was 8.36% (7.54, 9.24; n = 1,544/4,211), 36.67% (35.21, 38.14; n = 1,544/4,211), and 39.87% (38.39, 41.37; n = 1,679/4,211), respectively. PSQI and Epworth score were the significant predictors of RLS. Age, Epworth score, knowledge score, and the number of unacceptable sleep habits were the significant predictors of sleep quality. Female gender, PSQI, RLS, knowledge score, and the number of unacceptable sleep habits were the significant predictors of EDS. CONCLUSIONS: The prevalence of RLS, those with poor sleep quality and EDS among adolescents and young adults was higher when compared to the historical data of general population in the same city.

Absent Testis With a Mediastinal Germ Cell Tumor.

Primary mediastinal mixed germ cell tumors (PMMGCTs) are rare, aggressive tumors that, at diagnosis, are typically metastatic. A 22-year-old male with a three-month history of cough, chest pain, and fever presented to our outpatient department. Clinical examination showed reduced left-sided air entry in the left hemithorax, with a non-palpable left testis. Imaging suggested a large anterior mediastinal mass and an absent left testis. Multiple biopsies revealed only necrotic tissue, and laboratory investigations showed elevated alpha-fetoprotein levels. A provisional diagnosis of mediastinal germ tumor was made, and surgical excision was planned given absent nodal or distant metastasis. Intraoperatively, a densely adherent bosselated mass was found. A biopsy revealed a mixed germ cell tumor with a predominant seminoma component and chemotherapy with cisplatin and ifosfamide was advised. However, the patient was lost to follow-up after one cycle. PMMGCTs possibly occur due to reverse migration. These tumors warrant an early diagnosis due to their highly aggressive nature. A multimodal approach with chemotherapy with surgical resection is recommended. Our case sheds light on the possible mechanism and emphasizes the impact of early diagnosis.

Primary Malignant Synovial Tumor in the Mediastinum.

Primary mediastinal synovial sarcomas constitute a rare subset of mediastinal tumors. The diagnosis is often delayed at the time of presentation impacting the five-year survival rate due to its highly aggressive natural history. We report a 22-year old female with a monophasic variant of the primary mediastinal synovial sarcoma. A 22-year-old female, with a two-month history of productive cough, fever, breathlessness, was referred to our center in view of persistent right-sided hydropneumothorax despite multiple thoracocenteses. Examination revealed reduced right-sided air entry with a succussion splash. Imaging suggested a well-defined cystic lesion with fluid, air foci, and multiple septations. A provisional diagnosis of a ruptured hydatid cyst was made and exploratory thoracotomy was planned. Intraoperatively, a well-defined cystic lesion with 350 mL of hemorrhagic fluid, densely adherent to the lung and diaphragm, was found. The biopsy revealed a monophasic spindle cell variant of the primary synovial sarcoma. Follow-up positron emission tomography (PET) on postoperative day 20 showed no residual disease and evidence of metastasis. However, the patient was lost to follow up following one cycle of chemotherapy with ifosfamide. Primary mediastinal synovial sarcomas are aggressive tumors that warrant an early diagnosis for prompt treatment. They usually present with non-specific respiratory symptoms. The gold standard of diagnostic modalities is a molecular panel looking for the translocation - t(X;18)(p11;q11). However, in low-middle income countries, a biopsy may be more practical, as they are cost-effective. The treatment is surgical resection, with combined chemotherapy and radiotherapy if metastases are present. Our case emphasizes the early detection of this lesion, its mimicry with other lesions, and the impact of early diagnosis.