Atherosclerosis Vindicated: A Case of Chest Pain Due to Capecitabine-Induced Coronary Artery Spasm.

BACKGROUND Capecitabine and other 5-fluorouracil prodrugs are medications widely employed in treating solid tumors, including breast and colorectal cancer. However, they carry a notable risk for cardiotoxicity, including coronary vasospasm, possibly related to their impact on vascular endothelium and smooth muscle. CASE REPORT We present a case of a 45-year-old male with a pancreatic neuroendocrine tumor who developed exertional chest pain after starting capecitabine. Initial evaluations in the emergency department, including a 12-lead electrocardiogram and cardiac enzymes, were normal, but suspicion for coronary vasospasm persisted due to the temporal relationship with drug initiation and symptom characteristics. A graded exercise test reproduced his symptoms, accompanied by hyperacute peaked T waves and subsequent ST segment elevations in the inferior leads. Coronary angiography revealed patent coronary arteries, rendering provocative testing unnecessary due to a high clinical suspicion of capecitabine-induced vasospasm. Discontinuing the patient's medication was a more efficient approach than continuing additional cardiac workup while the drug was still administered. After multidisciplinary discussion, capecitabine was discontinued, leading to symptom resolution and a negative repeat graded exercise test. CONCLUSIONS This case underscores the potential for capecitabine to induce coronary artery vasospasm, emphasizing the importance of prompt medication cessation. Patients receiving capecitabine therapy and experiencing chest pain should undergo an evaluation with consideration of capecitabine-induced vasospasm in the differential diagnosis. Prompt recognition and medication cessation are critical to prevent serious cardiovascular complications including death. In our patient, discontinuing capecitabine resolved his symptoms, emphasizing the significance of discontinuing the causative drug and seeking alternative chemotherapy regimens.

Nonfamilial Bilateral Synchronous Renal Cell Carcinoma with Discordant Histology with Eventual Complete Response to Dual Immunotherapy.

Bilateral synchronous renal cell carcinoma (RCC) is rare, especially in sporadic rather than familial cases. While immunotherapy has improved prognosis, RCC remains a diagnosis with significant morbidity and mortality, particularly pronounced in patients with sarcomatoid RCC (sRCC). We describe a case of a patient with bilateral, synchronous, nonfamilial RCC, with and without sarcomatoid features and differing genetic markers, who demonstrated a pathologic response after neoadjuvant nivolumab and ipilimumab. The patient then had radical left nephrectomy and partial right nephrectomy followed by adjuvant nivolumab and cabozantinib, after which the patient had no evidence of disease. Our patient's illustrative case shows the potential therapeutic value of immunotherapy even in sRCC, the disease's most aggressive clinical subtype.

Expanding TNM for lung cancer through machine learning.

BACKGROUND: Expanding the tumor, lymph node, metastasis (TNM) staging system by accommodating new prognostic and predictive factors for cancer will improve patient stratification and survival prediction. Here, we introduce machine learning for incorporating additional prognostic factors into the conventional TNM for stratifying patients with lung cancer and evaluating survival. METHODS: Data were extracted from SEER. A total of 77 953 patients were analyzed using factors including primary tumor (T), regional lymph node (N), distant metastasis (M), age, and histology type. Ensemble algorithm for clustering cancer data (EACCD) and C-index were applied to generate prognostic groups and expand the current staging system. RESULTS: With T, N, and M, EACCD stratified patients into 11 groups, resulting in a significantly higher accuracy in survival prediction than the 10 AJCC stages (C-index = 0.7346 vs. 0.7247, increase in C-index = 0.0099, 95% CI: 0.0091-0.0106, p-value = 9.2 × 10-147 ). There nevertheless remained a strong association between the EACCD grouping and AJCC staging (rank correlation = 0.9289; p-value = 6.7 × 10-22 ). A further analysis demonstrated that age and histological tumor could be integrated with the TNM. Data were stratified into 12 prognostic groups with an even higher prediction accuracy (C-index = 0.7468 vs. 0.7247, increase in C-index = 0.0221, 95% CI: 0.0212-0.0231, p-value <5 × 10-324 ). CONCLUSIONS: EACCD can be successfully applied to integrate additional factors with T, N, M for lung cancer patients.

Cross-talk between paracrine-acting cytokine and chemokine pathways promotes malignancy in benign human prostatic epithelium.

The present study explores the mechanisms by which human prostatic carcinoma-associated fibroblasts (CAF) induce tumorigenesis in initiated but nonmalignant human prostatic epithelial cells (BPH-1). CAF express elevated levels of both transforming growth factor-beta1 (TGF-beta1) and stromal cell-derived factor-1 (SDF-1/CXCL12). TGF-beta inhibits the growth of BPH-1 cells in vitro, but was found to be necessary for the tumorigenic response to CAF. This counterintuitive result suggested that the TGF-beta signaling system was involved in other processes relating to tumorigenesis. The SDF-1 receptor, CXCR4, is expressed at low levels in benign prostate tissue and in BPH-1 cells in culture. However, CXCR4 levels increase during prostate cancer progression. CXCR4 was found to be induced and localized to the cell membrane in BPH1 cells by CAF-conditioned medium and by CAF cells in tissue recombinants. TGF-beta was both necessary and sufficient to allow the detection of membrane-localized CXCR4 in BPH1 cells. Suppression of epithelial cell CXCR4 expression abrogated the tumorigenic response to CAF. SDF-1, secreted by CAF, acts via the TGF-beta-regulated CXCR4 to activate Akt in the epithelial cells. This mechanism elicits tumorigenesis and obviates the growth-inhibitory effects of TGF-beta. Thus, tumor stroma can contribute to carcinogenesis through synergism between TGF-beta, SDF-1, and CXCR4. These experiments suggest mechanisms by which TGF-beta can shift its role from an inhibitor to a promoter of proliferation during tumor progression. Both the TGF-beta and SDF-1 pathways are targets of drug discovery efforts; these data suggest potential benefits in the cotargeting of these pathways.