Navigating Complexity: A Case Study on Hemophagocytic Lymphohistiocytosis Diagnosis and Management Challenges.

Hemophagocytic lymphohistiocytosis (HLH) is a severe inflammatory disorder that affects multiple organ systems and carries a high risk of mortality if untreated. Treatment typically involves immune suppression with steroids and cytotoxic drugs. This case report details the evaluation and management of an adult female presenting with atypical symptoms, aims to improve awareness and understanding of HLH in adults, and emphasizes the urgency of timely diagnosis and intervention.

Retrospective Analysis of HER2+ Breast Cancer Outcomes at a County Hospital: Do Published Outcomes Hold up in the Real World?

INTRODUCTION: Landmark trials repeatedly demonstrate that pertuzumab and trastuzumab plus standard chemotherapy have the best outcomes in human epidermal growth factor receptor 2 (HER2) positive breast cancer in the neoadjuvant, adjuvant, and metastatic setting. However, many of these multicenter landmark trials lack diversity and studied largely Caucasian populations. Our goal is to address this under-representation of minorities, and compare pathologic complete response (pCR) rates in our predominantly Hispanic population with HER2 positive breast cancer receiving the same neoadjuvant chemotherapy (NACT) at Olive View-UCLA Medical Center (OVMC) to that of pCR rates observed in the TRYPHAENA trial. METHODS: For this retrospective cohort study, we compiled a list of 53 patients aged 18 and older, 52 female and 1 male, with HER2 positive breast cancer identified by fluorescence in situ hybridization treated at OVMC from December 2015 to May 2018. Our population was 57% Hispanic, 13% white, 13% Filipino, 11% Asian, 2% black, and 4% other. The complete list included patients receiving standard neoadjuvant, adjuvant, and metastatic chemotherapy regimens. We analyzed 23 female patients with HER2 positive breast cancer staged I to IIIC, receiving standard NACT (docetaxel, carboplatin, trastuzumab, and pertuzumab). Metastatic HER2 positive breast cancer patients were excluded. The primary outcome studied was pCR rates after receiving NACT. pCR was defined as the absence of invasive cancer cells from tissue samples removed after surgery. Secondary outcomes measured were side effects of chemotherapy. pCR rates and side effects were compared to TRYPHAENA. Data regarding insurance status, breast cancer detection modality, and time to seek medical attention were recorded. RESULTS: 50% of our patients who received NACT achieved pCR. Our pCR rates mirrored those observed in the TRYPHAENA trial (51.9%). The most common side effect observed in our population was diarrhea. A higher proportion (37.5%) of our patients had liver function test (LFT) elevation compared to the TRYPHAENA trial (3.9%). Baseline LFTs were normal prior to treatment in 96% of patients. In terms of modality of detection, 70% were self-palpated, 26% were detected through routine mammography, and 4% were found incidentally. Average time from mass discovery to seeking medical attention was 3.4 months. Only 26% had medical insurance at diagnosis. Although not included in our study, 28% of our patients were initially diagnosed with stage IV metastatic disease.  Conclusion: Our study found that pCR rates in our primarily Hispanic population compared well to the response rates observed in landmark trials with largely Caucasian populations. Genetic variations in chemo-sensitivity may have a minimal influence on cancer care outcomes in this population.

Targeting the Wnt Pathway in Cancer: A Review of Novel Therapeutics.

Wnt signaling is an evolutionarily conserved pathway that controls cell-to-cell interactions during embryogenesis. In adults, Wnt signaling plays a role in tissue homeostasis in almost every organ system. Aberrations within this pathway are implicated in a spectrum of human diseases. A variety of perturbations have been described in both solid and hematologic malignancies, lending way to Wnt signaling as a target for anti-cancer therapy. Of particular interest is the role of Wnt signaling in the development and maintenance of cancer stem cells, a rare population of cells that are able to maintain a tumor via self-renewal and thought to be more resistant to chemotherapy than bulk tumor cells. The ability to eradicate cancer stem cells may decrease the risk of cancer relapse and metastasis. A number of therapeutic agents specifically targeting the Wnt pathway have entered clinical trials, either as monotherapy or in combination with chemotherapy. We will provide an overview of agents that have been developed to target the Wnt pathways and a summary of pre-clinical and clinical trials.

Cisplatin-Induced Renal Salt Wasting Requiring over 12 Liters of 3% Saline Replacement.

Cisplatin is known to induce Fanconi syndrome and renal salt wasting (RSW). RSW typically only requires transient normal saline (NS) support. We report a severe RSW case that required 12 liters of 3% saline. A 57-year-old woman with limited stage small cell cancer was admitted for cisplatin (80 mg/m2) and etoposide (100 mg/m2) therapy. Patient's serum sodium (SNa) decreased from 138 to 133 and 125 mEq/L within 24 and 48 hours of cisplatin therapy, respectively. A diagnosis of syndrome of inappropriate antidiuretic hormone secretion (SIADH) was initially made. Despite free water restriction, patient's SNa continued to decrease in association with acute onset of headaches, nausea, and dizziness. Three percent saline (3%S) infusion with rates up to 1400 mL/day was required to correct and maintain SNa at 135 mEq/L. Studies to evaluate Fanconi syndrome revealed hypophosphatemia and glucosuria in the absence of serum hyperglycemia. The natriuresis slowed down by 2.5 weeks, but 3%S support was continued for a total volume of 12 liters over 3.5 weeks. Attempts of questionable benefits to slow down glomerular filtration included the administration of ibuprofen and benazepril. To our knowledge, this is the most severe case of RSW ever reported with cisplatin.