Immune Checkpoint Inhibitors in Esophageal Carcinoma: Assessment of Efficacy Predictors of Response in Clinical Trials.

Esophageal carcinoma (EC) is among the most common causes of cancer-related deaths worldwide. Even with the improvement of multidisciplinary treatment modalities, advanced unresectable EC patients had limited systemic therapeutic options for an extended period. Recently, immune checkpoint inhibitors (ICIs) have been introduced to advanced EC management in both first-line and second-line options, as well as in postoperative settings in resectable EC after preoperative chemoradiation. Herein, the authors present a comprehensive review of clinical trials on administering ICIs in EC patients while discussing reported clinical, molecular, and immune biomarkers and their predictive value for treatment efficacy.

Who Should Receive Immunotherapy for Advanced Gastroesophageal Cancer?

OPINION STATEMENT: This paper shines a light on the exciting progress being made in using immunotherapy to treat advanced gastroesophageal cancers. The positive results from trials using drugs like Pembrolizumab and Nivolumab are certainly encouraging and open new possibilities for treating this challenging disease. However, it is clear that we still have a lot to learn about how to predict which patients will benefit most from these treatments. The exploration of combining therapies and using machine learning to guide treatment shows promise. Moving forward, it is crucial that researchers and healthcare professionals continue to work together, sharing knowledge and findings to continue the advancements in this important area.

A Comprehensive Review on Cancer Vaccines and Vaccine Strategies in Hepatocellular Carcinoma.

HCC, the most prevalent form of primary liver cancer, presents a substantial global health challenge due to its high mortality and limited therapeutic options. This review delves into the potential of cancer vaccines as a novel therapeutic avenue for HCC. We examine the various categories of cancer vaccines, including peptide-based, dendritic cell-based, viral vector-based, DNA, and mRNA vaccines, and their potential application in HCC management. This review also addresses the inherent challenges in vaccine development, such as tumor heterogeneity and the need for identifying tumor-specific antigens. We underscore the role of cancer vaccines in reshaping the immune environment within HCC, fostering durable immune memory, and their potential in combination therapies. The review also evaluates clinical trials and emphasizes the necessity for more extensive research to optimize vaccine design and patient selection criteria. We conclude with future perspectives, highlighting the significance of personalized therapies, innovative antigen delivery platforms, immune modulatory agents, and predictive biomarkers in revolutionizing HCC treatment. Simple Summary: This review explores the potential of cancer vaccines as a promising therapeutic strategy for hepatocellular carcinoma (HCC), a prevalent and deadly liver cancer. The authors discuss various types of cancer vaccines, their challenges, and their role in modulating the immune response within HCC. They also highlight clinical trials and future perspectives, emphasizing the importance of personalized therapies, novel antigen delivery platforms, and predictive biomarkers. The findings from this research could significantly impact the research community by providing a comprehensive understanding of the current state of cancer vaccines for HCC, thereby guiding future research and potentially transforming HCC treatment strategies.

Cadaveric dissection of connection between accessory hemiazygos vein and left brachiocephalic vein.

PURPOSE: The azygos system of veins has many anatomical variations that can impact mediastinal and vascular interventions. While radiological reports on these are of great clinical value, this study is among the first to present a high-quality cadaveric dissection of a rare anatomical variant to supplement previously published radiologic studies. The azygos venous system consists of the azygos vein (AV), hemiazygos vein (HAV), and the accessory hemiazygos vein (AHAV), which develop from the last portion of the posterior cardinal veins. The normal anatomical configuration includes drainage of the posterior intercostal veins, vertebral vein, esophageal veins, HAV, and AHAV to an unpaired right-side AV at the level of the 8th/9th thoracic vertebra. The reported incidence of AHAV draining directly into the left brachiocephalic vein is 1-2%. METHODS: An adult formalin-fixed 70-year-old female cadaver was dissected as part of a medical gross anatomy elective course. RESULTS: Gross documentation of a direct connection of the HAV to the AHAV with the AHAV draining into the left brachiocephalic vein. CONCLUSION: It is important to note the variations of the azygos system to avoid confusion with a potential pathology such as mediastinal masses. Understanding of the rare variant reported here could be useful in the prevention of iatrogenic bleeding from the misplacement of venous catheters and help facilitate radiological diagnosis in the incidence of venous clot formation.

Leptomeningeal Metastasis from Non-Small Cell Lung Cancer and Current Landscape of Treatments.

Leptomeningeal metastasis (LM), also known as leptomeningeal carcinomatosis (LC), is a devastating complication of metastatic cancer that occurs when neoplastic cells invade the meningeal space. Diagnosis of LM remains challenging given the heterogeneous signs and symptoms at presentation and requires thorough neurological examination, cerebrospinal fluid (CSF) analysis, and MRI of the brain and spine with gadolinium. Detecting neoplastic cells in the CSF is the gold standard for diagnosing leptomeningeal metastases; however, it has low sensitivity and may require multiple CSF samples. New emerging technologies, such as liquid biopsy of CSF, have increased sensitivity and specificity for detecting circulating tumor cells in CSF. The management of LM in patients with NSCLC requires an individualized multidisciplinary approach. Treatment options include surgery for ventricular shunt placement, radiation therapy to bulky or symptomatic disease sites, systemic or intrathecal chemotherapy, molecularly targeted agents, and, more recently, immunotherapy. Targeting actionable mutations in LM from NSCLC, such as EGFR tyrosine kinase inhibitors or anaplastic lymphoma kinase gene rearrangement inhibitors, has shown encouraging results in terms of disease control and survival. Although there are limited data regarding the use of immunotherapy in LM, immunotherapy has produced promising results in several case reports. In this review, we focused on the epidemiology, pathophysiology, clinical presentation, diagnosis, and current treatment strategies, with a special emphasis on novel agents, including targeted therapies and immunotherapy of LM in patients with NSCLC.

Etiology and Management of Dyslipidemia in Patients With Cancer.

Patients with cancer are now living longer than ever before due to the growth and expansion of highly effective antineoplastic therapies. Many of these patients face additional health challenges, of which cardiovascular disease (CVD) is the leading contributor to morbidity and mortality. CVD and cancer share common biological mechanisms and risk factors, including lipid abnormalities. A better understanding of the relationship between lipid metabolism and cancer can reveal strategies for cancer prevention and CVD risk reduction. Several anticancer treatments adversely affect lipid levels, increasing triglycerides and/or LDL-cholesterol. The traditional CVD risk assessment tools do not include cancer-specific parameters and may underestimate the true long-term CVD risk in this patient population. Statins are the mainstay of therapy in both primary and secondary CVD prevention. The role of non-statin therapies, including ezetimibe, PCSK9 inhibitors, bempedoic acid and icosapent ethyl in the management of lipid disorders in patients with cancer remains largely unknown. A contemporary cancer patient needs a personalized comprehensive cardiovascular assessment, management of lipid abnormalities, and prevention of late CVD to achieve optimal overall outcomes.

Etiology and management of hypertension in patients with cancer.

The pathophysiology of hypertension and cancer are intertwined. Hypertension has been associated with an increased likelihood of developing certain cancers and with higher cancer-related mortality. Moreover, various anticancer therapies have been reported to cause new elevated blood pressure or worsening of previously well-controlled hypertension. Hypertension is a well-established risk factor for the development of cardiovascular disease, which is rapidly emerging as one of the leading causes of death and disability in patients with cancer. In this review, we discuss the relationship between hypertension and cancer and the role that hypertension plays in exacerbating the risk for anthracycline- and trastuzumab-induced cardiomyopathy. We then review the common cancer therapies that have been associated with the development of hypertension, including VEGF inhibitors, small molecule tyrosine kinase inhibitors, proteasome inhibitors, alkylating agents, glucocorticoids, and immunosuppressive agents. When available, we present strategies for blood pressure management for each drug class. Finally, we discuss blood pressure goals for patients with cancer and strategies for assessment and management. It is of utmost importance to maintain optimal blood pressure control in the oncologic patient to reduce the risk of chemotherapy-induced cardiotoxicity and to decrease the risk of long-term cardiovascular disease.

A Rare Case of Statin-induced Immune-mediated Necrotizing Myopathy.

Statin-associated myopathy comprises of a spectrum of conditions ranging from benign myalgias to statin-induced immune-mediated necrotizing myopathy. Statin-induced immune-mediated necrotizing myopathy is an autoimmune condition wherein there is a destruction of normal skeletal muscular architecture that can be severely debilitating if not recognized promptly. Given its rarity, management is a challenge. We present one such case that was managed with aggressive immunosuppression.

Talaromycosis in a Patient on Nintedanib for Interstitial Lung Disease.

Talaromycosis is a fungal infection caused by Talaromyces sp. that is predominantly prevalent in patients with acquired immunodeficiency syndrome in the United States. It is also rarely seen in other individuals who are otherwise immunosuppressed. With the advent of immunotherapy and increasing usage of these novel agents in treating several conditions, the prevalence of talaromycosis may increase, especially in people from endemic regions who might harbor a dormant infection. Clinical presentation is non-specific with respiratory symptoms such as shortness of breath, cough, or even fever that can delay the diagnosis. Little is known about the exact pathogenesis of the condition, and management is largely based on anecdotal evidence and small-sized studies. We present the case of an individual on nintedanib, a tyrosine kinase inhibitor that blocks fibroblast growth factor receptor and used for the treatment of interstitial lung disease, who was diagnosed with talaromycosis.

Spontaneous Tumor Lysis Syndrome Due to Endometrial Carcinoma.

Spontaneous tumor lysis syndrome (TLS) is a rare condition in solid tumors, particularly in endometrial carcinoma. Spontaneous TLS occurs without the use of cytotoxic therapy but is observed particularly in hematologic malignancies. Given the high morbidity and mortality associated with spontaneous TLS, it is crucial to identify and treat it promptly. There have been only four cases of spontaneous TLS reported to date in the literature from a uterine source. We present a 59-year-old female with a recently diagnosed endometrial carcinoma with neuroendocrine features by dilation and curettage who presented to the hospital with somnolence, decreased oral intake, and lower abdominal pain of three days duration. She was found to have sepsis secondary to endometritis and spontaneous tumor lysis syndrome by clinical and laboratory definitions (hyperkalemia, hyperphosphatemia, hyperuricemia, and hypocalcemia). Signs of disease progression were found such as worsening retroperitoneal lymphadenopathy that corresponded with the suspected increased tumoral activity. We report the case of a solid tumor (endometrial) presenting with spontaneous TLS, which highlights the importance of the early identification and initiation of treatment.

Bortezomib-induced motor neuropathy: A case report.

INTRODUCTION: Bortezomib is a proteasome inhibitor used in the treatment of multiple myeloma, Waldenström's macroglobulinemia, mantle cell lymphoma. The most reported adverse effects include fatigue, thrombocytopenia, gastrointestinal symptoms, and peripheral neuropathy, which mostly manifests as sensory neuropathic symptoms. We present a case of a patient who experienced motor neuropathy after initiating treatment with bortezomib. CASE REPORT: An 87-year-old male was diagnosed with multiple myeloma and started on treatment with bortezomib, dexamethasone, and lenalidomide (VRd). After five cycles of therapy, he developed lower extremity weakness, which was severely debilitating, affecting his ability to walk, and this prompted his visit to the emergency department. MANAGEMENT AND OUTCOME: The patient was admitted for further workup and underwent electromyography, which was consistent with demyelinating polyneuropathy with active denervation. His symptoms were attributed to bortezomib, and his VRd regimen was held. His symptoms failed to improve despite discontinuation of bortezomib. He then received steroids and intravenous immunoglobulin (IViG) with a gradual resolution of his symptoms. He was thereafter restarted on only lenalidomide and dexamethasone with no recurrence of his neuropathy. DISCUSSION: Clinicians need to be aware of the likely risk for motor neuropathy associated with bortezomib. Risk factors like older age and pre-existing neuropathy can predispose patients to this adverse effect, and clinicians should monitor for this toxicity and facilitate dose reduction or discontinuation of therapy if warranted. Sometimes, patients may also need further treatment with steroids or IVIG.

Reversible Ocular Toxicity of Oxaliplatin: A Case Report.

Oxaliplatin, a platinum-based chemotherapy agent, is commonly used in the treatment of various malignancies. Common adverse effects involve neurological, hematological, gastrointestinal system, and hypersensitivity, and rarely ocular changes have also been reported. We describe the case of a 71-year-old male, who developed reversible ocular toxicity after receiving oxaliplatin for treatment for pancreatic cancer.