Zin W. Myint

Role of modern immunotherapy in gastrointestinal malignancies: a review of current clinical progress

Gastrointestinal (GI) cancers are a group of highly aggressive malignancies with a huge disease burden worldwide. There is clearly a significant unmet need for new drugs and therapies to further improve the treatment outcomes of GI malignancies. Immunotherapy is a novel treatment strategy that is emerging as an effective and promising treatment option against several types of cancers. CTLA-4 and PD-1 are critical immune checkpoint molecules that negatively regulate T cell activation via distinct mechanisms. Immune checkpoint blockade with antibodies directed against these pathways has already shown clinical efficacy that has led to their FDA approval in the treatment of several solid tumors including melanoma, non-small cell lung cancer, renal cell carcinoma, urothelial carcinoma, and head and neck cancer. This review will summarize the current clinical progress of modern immunotherapy in the field of GI tumors, with a special focus on immune checkpoint blockade.

Sarcoidosis mimicking metastatic thyroid cancer following radioactive iodine therapy

Introduction Sarcoidosis is an inflammatory disease characterized by non-caseating granulomas that can be present in diverse organ systems. Sarcoidosis can be associated with malignancy, presenting either preceding, during, or after chemotherapy. We herewith report a case of sarcoidosis mimicking cancer recurrence that developed after radioactive iodine therapy for papillary thyroid cancer. Background A 68-year-old Caucasian woman was found to have an incidental mediastinal lymph node. She underwent biopsy, which revealed sarcoidosis. There was no further treatment or evidence of recurrence over the ensuing 9 years. She was then diagnosed with low-grade papillary thyroid cancer in the right posterior lobe and treated with total thyroidectomy followed by radioactive iodine therapy. Six months later, she was found to have elevated serum thyroglobulin. Post–remnant ablation scan showed increased tracer uptake in the bed of the thyroid. Though two thyroid ultrasound scans were negative, she was treated with I-131 for possible recurrence. She then developed right hip pain, prompting further investigation. Though a skeletal survey was negative, an 18-fluorodeoxyglucose positron emission tomography (PET) scan study revealed multiple hypermetabolic skeletal lesions in both humeri and the proximal left femur. In addition, hypermetabolic hilar and mediastinal nodes were noted. As widespread cancer metastasis was suspected, bone biopsy was performed, which showed non-caseating granulomas, consistent with recurrence of sarcoidosis. Conclusion Sarcoid lesions may mimic metastatic disease or recurrence in oncologic patients. Biopsy and histopathology examination should be performed to confirm the diagnosis. Recurrence or reactivation of sarcoidosis has been proposed to result from altered immunologic milieu because of the presence of either active cancer or its therapy. Teodorovic and colleagues postulated that the radioactive I-131 therapy leads to reduced secretion of Th2 cytokines such as interleukin (IL)-4, IL-5, and IL-13. Few case reports of sarcoidosis associated with papillary carcinoma have been published; this is the first report of systemic recurrence of sarcoidosis associated with papillary thyroid carcinoma after treatment with radioactive iodine therapy.

Copper deficiency anemia: review article

Copper is a crucial micronutrient needed by animals and humans for proper organ function and metabolic processes such as hemoglobin synthesis, as a neurotransmitter, for iron oxidation, cellular respiration, and antioxidant defense peptide amidation, and in the formation of pigments and connective tissue. Multiple factors, either hereditary or acquired, contribute to the increase in copper deficiency seen clinically over the past decades. The uptake of dietary copper into intestinal cells is via the Ctr1 transporter, located at the apical membrane aspect of intestinal cells and in most tissues. Copper is excreted from enterocytes into the blood via the Cu-ATPase, ATP7A, by trafficking the transporter towards the basolateral membrane. Zinc is another important micronutrient in animals and humans. Although zinc absorption may occur by direct interaction with the Ctr1 transporter, its absorption is slightly different. Copper deficiency affects physiologic systems such as bone marrow hematopoiesis, optic nerve function, and the nervous system in general. Detailed pathophysiology and its related diseases are explained in this manuscript. Diagnosis is made by measuring serum copper, serum ceruloplasmin, and 24-h urine copper levels. Copper deficiency anemia is treated with oral or intravenous copper replacement in the form of copper gluconate, copper sulfate, or copper chloride. Hematological manifestations are fully reversible with copper supplementation over a 4- to 12-week period. However, neurological manifestations are only partially reversible with copper supplementation.

Pernicious Anemia: Fundamental and Practical Aspects in Diagnosis

BACKGROUND Pernicious Anemia (PA), the most common cause of cobalamin deficiency anemia worldwide, is an autoimmune disease of multifactorial etiologies involving complex environmental and immunological factors. Although it was first reported by Addison in 1849 with subsequent advances in understanding of pathogenesis and molecular biology, diagnosis of PA is still challenging for clinicians because of its complexity and diverse clinical presentations. CONCLUSION Herein, we provide an overview of PA, mainly focusing on its scientific and practical aspects in diagnosis. We also discuss the limitations of currently available diagnostic tools for the evaluation of cobalamin deficiency and PA.

Ossifying parosteal lipoma of the thoracic spine: a case report and review of literature

Introduction Lipomas are derived from the mesodermal germ layer and are frequently encountered in adults, and account for almost 50% of all soft tissue tumors. Lipomas are classified based on their component tissues and location. A rare subtype, ossifying parosteal lipoma, accounts for 0.3% of all lipomas and occurs with intimate association with the underlying periosteum of the adjacent bone. Though lipomas are considered to be benign tumors, ossifying parosteal lipomas can manifest symptoms due to their location and relationship to nearby skeletal tissues. We herewith report the first known case of ossifying parosteal lipoma presenting in the region of the thoracic spine. Case presentation An otherwise healthy adolescent boy presented with a 3-year history of a slowly enlarging painless thoracic mass. A general physical examination was normal, aside from a painless 10 cm mobile, hard mass along the posterior spine in the region of T4 through T6. Musculoskeletal and neurovascular examinations were normal. An ultrasound suggested a solid, cylindrically shaped mass with diffuse ossification. The mass was resected, and the pathology revealed ossifying parosteal lipoma without evidence of malignancy. Conclusion Ossifying parosteal lipomas are rare, benign soft tissue tumors that should be added to the differential diagnosis of thoracic masses.

Capecitabine and Temozolomide in Neuroendocrine Tumor of Unknown Primary

Incidence of low grade well-differentiated neuroendocrine tumors (NET) is on the rise. The North American Neuroendocrine Tumor Society estimates that the United States has more than 150,000 gastroenteropancreatic NET patients. About 10% of metastatic NETs can be unknown primary, and due to their rarity, dedicated treatment algorithms and regimens are not defined. Combination of capecitabine and temozolomide (CAPTEM) is one of the systemic treatments used in gastroenteropancreatic NETs. We explored clinical activity of CAPTEM in NET of unknown primary. Methods. Retrospective review of NET of unknown primary managed at the University of Kentucky over the past five years (2012–2016). Result. 56 patients with NET of unknown primary were identified; 12 patients were treated with CAPTEM. Median progression-free survival on CAPTEM in grade II and grade III NET of unknown primary was 10.8 and 7 months, respectively. Six patients showed reduction in metastatic tumor volume at three-month CT scan. Three patients had stable disease and three patients showed disease progression at the first surveillance scan. Common side-effects were as follows: four patients developed grade II thrombocytopenia, three patients developed grade I lymphocytopenia, and two patients developed hand foot syndrome (grades I and III). Six patients developed grade I fatigue. Conclusion. CAPTEM should be considered for grades I and II NET of unknown primary, especially in the case of visceral crisis or bulky disease.

Cancer Associated Thrombosis: Focus on Prevention and Treatment of Venous Thromboembolism

Cancer-associated thrombosis (CAT) accounts for about 20% of all thrombosis worldwide. It is the second leading cause of death in cancer patients. The risk of venous thromboembolism (VTE) is 4 -7 times higher and the risk of recurrent VTE three times higher in the cancer patients, compared to the non-cancer patients. The survival of cancer patients with VTE is lower than that of patients without VTE. In the last two decades, the incidence of CAT has risen in the ambulatory patients than in the inpatient setting. While the role of pharmacologic thromboprophylaxis (PTP) is established in the hospitalized cancer patients, ambulatory PTP is not, except in patients with multiple myeloma and myeloproliferative neoplasms. In the last decade, the low-molecular-weight heparin (LMWH) has emerged as the standard of care for the treatment of acute cancer-associated VTE. Many questions remain unanswered with regards to the optimal duration of LMWH therapy in the CAT, the role of direct oral anticoagulants (DOACs) in CAT, and the optimal anticoagulation management in thrombocytopenic cancer patients. Research trials are necessary to define a subset of ambulatory solid tumor patients who may benefit from PTP and to define the role of DOACs in the prevention and treatment of CAT.

A Case of Post-partum Spontaneous Coronary Artery Dissection with Pulmonary Embolism: Survival with Thrombectomy and Stent Implant.

Spontaneous Coronary Artery Dissection (SCAD) is a rare life-threatening cause of acute coronary syndrome. It can affect young patients without atherosclerotic risk factors, particularly women in the antepartum or early post-partum period, as well as geriatric patients at high risk for atherosclerotic disease. The pathogenesis linking SCAD with pregnancy has not been fully elucidated. The few reported cases of SCAD in the setting of concomitant Pulmonary Embolism (PE) may highlight a potential mechanism in the pregnant or postpartum woman. Heretofore, cases of SCAD with the setting of pulmonary embolism have all been treated conservatively with medical therapy. We herein report a case of SCAD in the left anterior descending artery resulting in Non-ST elevation myocardial infarction and low ejection fraction associated with an acute pulmonary embolism in a young post-partum patient who was treated successfully with thrombectomy followed by stent placement. Her cardiac function returned to normal within six months with no recurrence of symptoms. To our knowledge, this is the first case of SC.