Metastatic Small-Cell Lung Cancer Presenting as Primary Adrenal Insufficiency.

A 40-year-old male smoker with HIV was admitted for cough, hypotension, and abdominal pain for 5 days. Chest radiography showed a right lower lobe consolidation. CT of the chest, abdomen, and pelvis revealed paratracheal adenopathy, a 5.8 × 4.5 cm mass invading the right bronchus intermedius, and dense bilateral adrenal masses, measuring 5.4 × 4.0 cm on the right and 4.8 × 2.0 cm on the left. Laboratory studies showed white blood cell count of 18.5 K/mm3, sodium of 131 mmol/L, creatinine of 1.6 mg/dL, and CD4 count of 567 cells/mm3. The random morning cortisol level was 7.0 µg/dL, the ACTH stimulation test yielded inappropriate response, and a random serum ACTH was elevated at 83.4 pg/mL. MRI brain revealed no pituitary adenoma confirming primary adrenal insufficiency. The adrenal CT washout study was consistent with solid mass content, concerning for metastasis. Bronchoscopy with endobronchial mass and paratracheal lymph node biopsy confirmed small-cell lung cancer (SCLC). Intravenous steroids, 100 mg hydrocortisone every 8 hours, improved his hypotension and abdominal pain. PET scan revealed metabolically active right paratracheal mass, right hilar mass, and bilateral adrenal masses. Treatment included palliative chemotherapy consisting of carboplatin/etoposide/atezolizumab and chest radiation. We present this novel case to demonstrate SCLC's ability to cause primary adrenal insufficiency, as well as evaluate clinical response to chemotherapeutics.

Retrospective Analysis of Cisplatin Nephrotoxicity in Patients With Head and Neck Cancer Receiving Outpatient Treatment With Concurrent High-dose Cisplatin and Radiotherapy.

OBJECTIVES: Cisplatin remains the pivotal chemotherapy in squamous cell carcinoma of the head and neck (SCCHN), with nephrotoxicity considered the dose-limiting toxicity. The purpose of our study was to propose an outpatient high-dose cisplatin protocol aimed at preventing nephrotoxicity and to analyze the results of its utilization in patients with SCCHN treated with concurrent radiotherapy. MATERIALS AND METHODS: We retrospectively evaluated 82 SCCHN patients treated with outpatient high-dose cisplatin concurrent with radiotherapy at our institution. Acute kidney injury (AKI) and chronic kidney disease were defined by Kidney Disease Improving Global Outcomes criteria. Associated factors were identified using analysis of covariance models for categorical variables and adjusted Pearson correlations for continuous variables. RESULTS: The incidence of AKI during treatment was 34.2%. With a median follow-up of 25.7 months, the average decrease in estimated glomerular filtration rate was 12.57 mL/min/1.73 m (SD=18.58). At 1 year and at last follow-up, 5.4% and 4.4% of patients had estimated glomerular filtration rate <60 mL/min/1.73 m. Predictors associated with AKI and chronic kidney disease were: lower baseline weight and creatinine, higher baseline creatinine clearance, smoking, female sex, African American race, hypertension, and increased hydration and magnesium replacement requirements. CONCLUSIONS: We encountered limited early and late nephrotoxicity. Importantly, nephrotoxicity was not the main dose-limiting toxicity. Our results emphasize the importance of close monitoring and additional replacement of water and electrolytes as needed. A consistent method of measuring and reporting chemotherapy-induced nephrotoxicity would be a valuable contribution to the literature.

Treatment of brain metastases of lung cancer in the era of precision medicine.

Common and deadly complications of non-small cell lung cancer (NSCLC) are brain metastases (BM). BM portends a poorer prognosis with limited effective treatment options and current management strategies present several challenges from iatrogenic complications of supportive medications, optimal delivery of drug across the blood-brain barrier, and preservation of neurocognitive function. Long term side effects and survivorship issues have become more evident in the era of targeted therapy where a systemic disease is much better controlled. Targeted therapies and immunotherapy are beginning to provide improvements in responses and survival rates. With further advancements and experience, our knowledge in this era of precision medicine will likely lead to strides in improving the quality of life and overall survival of patients with BM from NSCLC. In this review, we present the most recent updates in treatment of BM in NSCLC in regards to targeted and immunotherapy.

Heat suppresses activation of an auxin-responsive promoter in cultured guard cell protoplasts of tree tobacco.

Cultured guard cell protoplasts (GCP) of tree tobacco (Nicotiana glauca) comprise a novel system for investigating the cell signaling mechanisms that lead to acquired thermotolerance and thermoinhibition. At 32 degrees C in a medium containing an auxin (1-naphthaleneacetic acid [NAA]) and a cytokinin (6-benzylaminopurine), GCP expand, regenerate cell walls, dedifferentiate, and divide. At 38 degrees C, GCP acquire thermotolerance within 24 h, but their expansion is limited and they neither regenerate walls nor reenter the cell cycle. These putative indicators of auxin insensitivity led us to hypothesize that heat suppresses induction of auxin-regulated genes in GCP. Protoplasts were transformed with BA-mgfp5-ER, in which the BA auxin-responsive promoter regulates transcription of mgfp5-ER encoding thermostable green fluorescent protein (GFP) or with a similar 35S-cauliflower mosaic virus constitutive promoter construct. Heat suppressed NAA-mediated activation of BA. After 21 h at 32 degrees C in media with NAA, 49.0% +/- 3.9% of BA-mgfp5-ER transformants strongly expressed GFP; expression percentages were similar to those of 35S-mgfp5-ER transformants at 32 degrees C or 38 degrees C. After 21 h at 38 degrees C in media with NAA, 7.9% +/- 1.6% of BA-mgfp5-ER transformants weakly expressed GFP, similar to GCP cultured at 32 degrees C in media lacking NAA. Expression at 38 degrees C was not increased by incubating for 48 h or increasing NAA concentrations 20-fold. After 9 to 12 h at 38 degrees C, BA was no longer activated when cells were transferred to 32 degrees C. Heat-stressed cells accumulate reactive oxygen species, and hydrogen peroxide (H(2)O(2)) suppresses auxin-responsive promoter activation in Arabidopsis (Arabidopsis thaliana) mesophyll protoplasts. H(2)O(2) did not suppress BA activation at 32 degrees C, nor did superoxide and H(2)O(2) scavengers prevent BA suppression at 38 degrees C.