Prognostic utility of preoperative and postoperative KRAS-mutated circulating tumor DNA (ctDNA) in resected pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease, with surgery being the only possible cure. However, despite surgery, the majority of patients experience recurrence. Recent evidence suggests that perioperative KRAS-mutated circulating tumor DNA (ctDNA) may have prognostic value. Therefore, we conducted a systematic review and meta-analysis to explore the prognostic significance of preoperative and postoperative KRAS-mutated ctDNA testing in resected PDAC. METHODS: We searched PubMed/MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases for studies that reported the effect of preoperative and postoperative KRAS-mutated ctDNA on overall survival (OS) and/or relapse-free survival (RFS) in resected PDAC. We used a random-effects model to determine the pooled OS and RFS hazard ratios (HR) and their corresponding 95 % confidence intervals (CI). RESULTS: We identified 15 studies (868 patients) eligible for analysis. In the preoperative setting, positive ctDNA correlated with worse RFS in 8 studies (HR, 2.067; 95 % CI, 1.346-3.174, P < 0.001) and worse OS in 10 studies (HR, 2.170; 95 % CI, 1.451-3.245, P < 0.001) compared to negative ctDNA. In the postoperative setting, positive ctDNA correlated with worse RFS across 9 studies (HR, 3.32; 95 % CI, 2.19-5.03, P < 0.001) and worse OS in 6 studies (HR, 6.62; 95 % CI, 2.18-20.16, P < 0.001) compared to negative ctDNA. CONCLUSION: Our meta-analysis supports the utility of preoperative and postoperative KRAS-mutated ctDNA testing as a prognostic marker for resected PDAC. Further controlled studies are warranted to confirm these results and to investigate the potential therapeutic implications of positive KRAS-mutated ctDNA.

A Review of Endocrine Therapy in Early-stage Breast Cancer: The Journey From Crudeness to Precision.

Endocrine therapy (ET) is the standard of care for hormone receptor-positive early-stage breast cancer in the adjuvant setting. However, response to ET can vary across patient subgroups. Historically, hormone receptor expression and clinical stage are the main predictors of the benefit of ET. A "window of opportunity" trials has raised significant interest in recent years as a means of assessing the sensitivity of a patient's cancer to short-term neoadjuvant ET, which provides important prognostic information, and helps in decision-making regarding treatment options in a time-efficient and cost-efficient manner. In the era of genomics, molecular profiling has led to the discovery and evaluation of the prognostic and predictive abilities of new molecular profiles. To realize the goal of personalized medicine, we are in urgent need to explore reliable biomarkers or genomic signatures to accurately predict the clinical response and long-term outcomes associated with ET. Validation of these biomarkers as reliable surrogate endpoints can also lead to a revolution in the clinical trial designs, and potentially avoid the need for repeated tissue biopsies in the surveillance of disease response. The clinical potential of tumor genomic profiling marks the beginning of a new era of precision medicine in breast cancer treatment.

Hypercholesterolemia due to lipoprotein-X manifesting as pseudohyponatremia in a patient with cholestasis.

Pseudohyponatremia is an often misdiagnosed condition that needs to be managed by addressing the underlying cause. Treatment of hyponatremic patients with intravenous fluids without ruling out pseudohyponatremia may aggravate a patient's hyponatremia and result in adverse outcomes. In a patient whose sodium is deteriorating, it is critical to diagnose pseudohyponatremia early in the course and acquire necessary consultations, even if the patient is asymptomatic. We discuss a case of a man in his 20s with a history of liver transplantation who presented with unexplained dangerously low sodium while being asymptomatic. The case illustrates an uncommon cause of pseudohyponatremia due to lipoprotein-X hypercholesterolemia in a patient with cholestatic liver disease.

NTRK3 mutation in secretory carcinoma of the parotid gland: A Case report.

Mammary analog secretory carcinoma (MASC) is a newly described carcinoma with a molecular hallmark of ETV6-NTRK3 fusion that promotes oncogenesis. While MASC histopathology was well-studied in the literature, clinical behavior remains unstudied. We present a 22-year-old man with painless parotid mass, which was diagnosed as salivary gland cancer, MASC subtype.

Trastuzumab Deruxtecan-Induced Interstitial Lung Disease/Pneumonitis in ERBB2-Positive Advanced Solid Malignancies: A Systematic Review.

BACKGROUND AND OBJECTIVE: Trastuzumab deruxtecan (T-DXd) is a novel anti-ERBB2 antibody drug conjugate that appears to be associated with an increased risk of lung toxicity. We performed a systematic review to describe the incidence, severity, and management of T-DXd-induced interstitial lung disease (ILD) or pneumonitis. METHODS: We searched PubMed/MEDLINE, Embase, Cochrane, and Web of Sciences through to 1 January, 2022, for human clinical trials that assessed T-DXd in adults with ERBB2-positive advanced solid tumors and described the rate of ILD/pneumonitis. Study screening was performed by two researchers. Data were extracted from the full-text articles. RESULTS: Fourteen studies with a total of 1193 patients with different types of advanced solid malignancies were included in our systematic review. The overall incidence of all-grade ILD/pneumonitis cases that were adjudicated by an independent committee was 11.40% (ILD/pneumonitis cases, n = 136 out of total n = 1193). Grading of the adjudicated T-DXd-induced ILD/pneumonitis was reported in 122 patients with the majority of the cases (78.69%, n = 96) occurring as grade 1 or 2. Death was reported in 13 out of 122 (10.66%) patients. The highest incidence of ILD/pneumonitis was seen in patients with uterine carcinomatosis (26.47%) and non-small cell lung cancer (24.77%). Interstitial lung disease/pneumonitis events were treated with a dose interruption or reduction, treatment discontinuation, corticosteroids, and supportive care. CONCLUSIONS: Interstitial lung disease/pneumonitis is a well-described, serious, and potentially life-threatening adverse event that is associated with T-DXd. Further studies are needed to identify the risk factors and the underlying pathophysiology of T-DXd-induced ILD/pneumonitis to prevent occurrence and to develop effective management strategies.

A comprehensive review on antibody-drug conjugates (ADCs) in the treatment landscape of non-small cell lung cancer (NSCLC).

Even though both targeted and immunotherapy-based therapies have been established as frontline standard-of-care for patients with advanced lung cancer, adverse events, resistance, and disease progression remain unavoidable in most instances. In this scenario, chemotherapy is a popular salvage option, but it has restricted therapeutic index. Antibody-drug conjugates (ADCs) have emerged as a viable option. ADCs combine the specificity of monoclonal antibodies with the cytotoxic effects of chemotherapy to deliver cytotoxic payloads to cancer cells in a direct fashion. Among the promising ADCs used in advanced solid tumors, HER2 targeted ADCs of trastuzumab ematansine and trastuzumab deruxtecan are key drugs in this field.

Anti-PD-1 therapy using cemiplimab for advanced cutaneous squamous cell carcinoma in HIV patient: A case report.

This is a case of a 60-year-old man living with HIV who presented with advanced cutaneous squamous cell carcinoma. After workup, medical and surgical treatment, and disease recurrence, he achieved a complete response with no unexpected toxicities after immunotherapy with cemiplimab.

A Case of a False-Positive Urine Pregnancy Test and Delayed Diagnosis of Obstructive Pyelonephritis.

BACKGROUND Urine pregnancy tests are usually performed by women at home and also by healthcare professionals. However, there are several conditions that may cause a false-positive urine pregnancy test, including trophoblast tumors, malignancy, nephrotic syndrome, adenomyosis, tubo-ovarian abscess, and paraneoplastic syndromes. A case is presented of a false-positive urine pregnancy test in a 28-year-old woman with a history of tubal ligation, who had a delayed diagnosis of obstructive pyelonephritis due to renal calculus. CASE REPORT A 28-year-old woman had previously been sterilized by tubal ligation. She presented with acute pyelonephritis associated with a left staghorn renal calculus and was found to have a false-positive urine pregnancy test, which delayed the diagnosis and management of her acute pyelonephritis. On follow-up, she had a negative serum pregnancy test. Abdominal computed tomography (CT) identified a left-sided staghorn calculus resulting in partial ureteric obstruction and hydronephrosis. She was treated with antibiotics, including cefazoline, and a left nephrostomy tube was sited to treat her hydronephrosis. Her pain was initially managed with acetaminophen and hydrocodone. Four days after her initial hospital admission, the patient was stable enough to go home on oral levofloxacin and pain medication. CONCLUSIONS This case of a false-positive urine pregnancy test in a 28-year-old woman with a history of tubal ligation highlights that this association may result in the delay in the diagnosis and treatment of acute pyelonephritis.

PIK3CA gene aberrancy and role in targeted therapy of solid malignancies.

Phosphoinositide kinases (PIKs) are a group of lipid kinases that are important upstream activators of various signaling pathways that drive oncogenesis. Hyperactivation of the PI3K/AKT/mTOR pathways-either via mutations or genomic amplification-confers key oncogenic activity, essential for the development and progression of several solid tumors. Alterations in the PIK3CA gene are associated with poor prognosis of solid malignancies. Contradictory reports exist in the literature regarding the prognostic value of PIK3CA in aggressive cancers, but most available data highlights an important role of PIK3CA mutation in mediating tumorigenesis via increased signaling of the PI3K/AKT/mTOR survival pathway. Several inhibitors of PI3K/AKT/mTOR pathways have been investigated as potential therapeutic options in solid malignancies. This article reviews the role of PIK3CA mutations and inhibitors of the PI3K/AKT/mTOR pathway in cancer and examines association with the clinico-pathological parameters and prognosis.

Hepatocellular Carcinoma: Molecular Mechanisms and Targeted Therapies.

Hepatocellular carcinoma (HCC) is one of the most common and lethal malignant tumors worldwide. HCC is a complex process that is associated with several etiological factors, which in turn result in aberrant activation of different cellular and molecular pathways and the disruption of balance between activation and inactivation of protooncogenes and tumor suppressor genes, respectively. Since HCC most often occurs in the setting of a diseased or cirrhotic liver and most of the patients are diagnosed at the late stage of disease, prognosis is generally poor. At present, limited treatment options with marginal clinical benefits are available. Systemic therapy, particularly in the form of conventional cytotoxic drugs, are generally ineffective. In recent years, molecular-targeted therapies have been clinically used to treat various cancers, including liver cancer. This approach inhibits the growth of tumor cells by interfering with molecules that are involved in carcinogenesis, which makes it more selective and specific than cytotoxic chemotherapy. Many clinical trials have been carried out while using molecular targeted drugs in advanced HCC with many more in progress. The clinical trials in HCC to date have evaluated a single-targeted therapy alone, or two or more targeted therapies in parallel. The aim of this review is to provide insight of various molecular mechanisms, leading to HCC development and progression, and also the range of experimental therapeutics for patients with advanced HCC. The review will summarize different clinical trials data the successes and failures of these treatments, as well as the most effective and approved drugs designed against HCC.