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Practical Manual of Tricuspid Valve Diseases

Tricuspid valve (TV) dysfunction can result from morphological alterations in the valve or from functional aberrations of the myocardium. It can be classifed as primary and secondary. Primary TV disease with intrinsic structural abnormality is less common than diseases of the aortic and mitral valves. The slow progression of the disease leads to delayed appearance of symptoms. The physical signs are often less impressive. Hence, it may go undetected until advanced stage results in hepatomegaly, ascites, and leg edema. The secondary form of TV disease is far more common and is often the result of annular dilatation with incomplete valve closure. The functional abnormalities may be in the form of pure or predominant tricuspid stenosis (TS), pure or predominant tricuspid regurgitation (TR), or mixed.

Oral Anticoagulation Therapy

Warfarin and other coumarin derivatives have long been the mainstays of oral anticoagulant therapy. While evidence has proven them effective for treating and decreasing the risk of thromboembolism, these agents also have many burdensome traits for use for both the clinician and patient. As narrow therapeutic index drugs, the therapeutic window between effcacy and toxicity is small with little correlation between dose and therapeutic effect. Genetic factors and other interpatient variability, such as diet and drug-drug interactions, also contribute to the wide dose range and need for frequent monitoring of the international normalized ratio (INR). The alternative therapies to oral anticoagulants used to only include injectable anticoagulants which were often utilized in place of or in addition to warfarin. These injectable agents limitations were mainly in cost and route of administration, and thus lack of patient acceptance. Fortunately, we have entered an era where several viable oral anticoagulant alternatives exist. These direct oral anticoagulants have much more predictable dose-response profles thus eliminating the need for frequent monitoring. In addition, they have few dietary precautions and much less drug-drug interactions. However, these agents are not benign, not interchangeable, and not entirely characterized in regards to drug-drug interactions, reversibility, or use in populations outside of those in the pivotal clinical trials. Dosing, although more predictable in response, does have limitations including various doses and renal doses based on indication. As such, management of all the anticoagulants, whether warfarin, injectable, or the direct oral anticoagulants, is complicated and very patient specifc. A need for extensive education of health care professionals is required.

Molecular Targeted Therapy of Lung Cancer

Classifcation of lung adenocarcinoma was largely revised in the 4th edition of WHO classifcation of tumors of the lung, pleura, thymus, and heart published in 2015. This chapter deals with the major changes in the adenocarcinoma classifcation, briefly describing the defnition, gross and histopathological fndings, genetic profles and clinical features of each subtype, and variants of lung adenocarcinoma. Special reference was also made to the prognostic aspects. The new concepts of adenocarcinoma in situ and minimally invasive adenocarcinoma are especially important from the prognostic point of view because of their virtual connotation as 100% curable cancers if resected completely. Each subtype of invasive adenocarcinoma may be categorized into either good, intermediate, or poor prognostic group. Much progress has been made regarding the genetic profles as well, such as the occurrence of EGFR and KRAS mutations, ALK fusion genes and recently discovered alterations, and NRG1 fusion genes in association with adenocarcinomas with certain characteristics. A brief overview of the major changes in the lung adenocarcinoma classifcation in this chapter will help physicians, radiologists, and pathologists grasp the signifcance and meaning of the histopathological diagnosis according to the new WHO classifcation.

Radiation Therapy for Extranodal Lymphomas

Radiotherapy (RT) after systemic chemotherapy including high-dose (HD) methotrexate is widely accepted as the standard treatment for primary central nervous system lymphoma (PCNSL). Treatment must consider the blood brain barrier as it characterizes the clinical behavior of PCNSL. For consolidation RT in patients with complete remission (CR) after chemotherapy, 23.4–30 Gy of whole-brain radiotherapy (WBRT) is recommended. For salvage RT in patients with non-CR or recurrent disease (RD) after chemotherapy, 36–45 Gy of WBRT or 30 Gy of WBRT followed by 10–20 Gy of boost irradiation is recommended. The reported 5-year survival rate of PCNSL patients is 30–50%; it is worse than for patients with other extranodal lymphomas. Late neurological toxicity is a major problem in long survivors after HD methotrexate and WBRT. Chemotherapy alone may be considered in elderly PCNSL patients who are at high risk for radiation- induced neurocognitive dysfunction.

Radiation Therapy for Liver Tumors

The liver is the central clearing house for most metabolic functions in the body . These functions include lipid, carbohydrate, and protein metabolism; coagulation factor production; albumin production; detoxification of xenobiotics; storage of vitamins and glycogen; and bile processing and secretion. The liver is situated at the receiving end, via the portal circulation, of the intestines, which provide metabolic substrates to the liver. Blood flows out of the liver, carrying away the fruits of its metabolic labor, into the inferior vena cava. Bile flows out of the liver via the bile ducts to aid in digestion and dispose of certain waste products. The liver is for the most part composed of hepatocytes, bile ducts, and blood vessels. Diseases typically target one of these principal components. But, as this is a functional system, injury to one component generally affects other components of the system. The liver has an enormous functional reserve: approximately 80–90% of the liver needs to be destroyed before its essential functions can no longer be adequately performed. Fortunately, the liver is one of the few organs with a high regenerative capacity; this is seen in the ancient Greek story of Prometheus, the giver of fire to humans, who was punished with an endless cycle of having his newly regenerated liver eaten by a bird each day.

Personalized Therapy for Multiple Myeloma

Smoldering multiple myeloma (SMM) is an asymptomatic plasma cell disorder defned in 1980 by Kyle and Greipp on the basis of a series of six patients who met the criteria for multiple myeloma (MM) but whose disease did not have an aggressive course . At the end of 2014, the International Myeloma Working Group (IMWG) updated the defnition, and SMM defned as a plasma cell disorder is now characterized by the presence of ≥3 g/dL serum M-protein and/or 10–60% bone marrow plasma cells (BMPCs), but with no evidence of myeloma-related symptomatology (hypercalcemia, renal insuffciency, anemia, or bone lesions (CRAB)) or any other myelomadefning event (MDE) . According to these recent update criteria, the defnition of SMM excludes asymptomatic patients with BMPCs of 60% or more, serum free light chain (FLC) levels of ≥100, and those with two or more focal lesions in the skeleton as revealed by magnetic resonance imaging (MRI). Kristinsson et al., based on the Swedish Myeloma Registry, has recently reported that 14% of patients diagnosed with myeloma had SMM, and, accordingly, the agestandardized incidence of SMM would be 0.44 cases per 100,000 people.

Acute Side Effects of Radiation Therapy

Cancer is one of the leading causes of death worldwide . Currently, cancer patients survive longer than they did more than two decades ago, and the population living with cancer is increasing. Understanding more about cancer radiobiology and major developments in radiation therapy technology play a critical role in increasing the life expectancy of these patients. Radiation therapies are used with three different concepts in cancer that are defnitive, adjuvant, or palliative. It has been estimated that more than 50% of all cancer patients receive radiation therapy throughout the course of their disease . With new technological advancements in imaging and radiation delivery, radiation therapy has been possible for more complicated cases, increasing the rate of radiation therapy in cancer treatments. In addition to the tumor sterility and tumoricidal effects of radiation therapy ,radiation has the potential to affect normal tissues, which includes tissue damage in radiation therapy felds or systemic side effects (e.g., hematologic side effects,fatigue). Physicians try to lower radiation therapy side effects by defning smaller targets and using more dedicated machines, but side effects continue to occur and their spectrum and severity are changing. As these patients live longer, more attention is directed on their quality of life.

Failed Anti-Reflux Therapy

Initial and scarce attempts to operate the esophagus have been described since the seventeenth century, mostly due to traumatic injury ; however, the real history of esophageal surgery is relatively young compared to other organs. According to Fogelman and Reinmiller , esophageal surgery was both uncommon and poorly performed prior to the nineteenth century. This may be attributed to the fact that the esophagus is a peculiar organ. It has a unique anatomy: (1) important organs surround the esophagus in its entire length; (2) the esophagus crosses the neck, the chest, and the abdomen; (3) it lacks a serosa and its own artery, and (4) the lymphatic drainage is abundant and erratic . This leads to an exclusive surgical anatomy: (1) access routes to the esophagus may be variable and multiple; (2) oncologic margins are elusive; and (3) organs need to be prepared in order to replace it . Also, the esophagus has a distinctive physiology: (1) it is a digestive organ without known absorptive or endocrine functions; (2) it is bounded by two sphincters; and (3) it exhibits a motility pattern only at feed and different from other digestive segments.

Evidence-based Therapy in Vascular Surgery

Recommendations for management of asymptomatic carotid artery disease (European Stroke Organisation et al. 2011): • All patients with asymptomatic carotid artery stenosis should be treated with long-term antiplatelet therapy. (Class-I-recommendation/Level of evidence B) • All patients with asymptomatic carotid artery stenosis should be treated with long-term statin therapy. (Class- I-recommendation/Level of evidence C) • In asymptomatic patients with carotid artery stenosis ≥60%, CEA should be considered as long as the perioperative stroke and death rate for procedures performed by the surgical team is <3% and the patient’s life expectancy exceeds 5 years. (Class-IIa-recommendation/Level of evidence A) • In asymptomatic patients with an indication for carotid revascularization, CAS may be considered as an alternative to CEA in high- volume centres with documented death or stroke rate <3%. (Class-IIb-recommendation/Level of evidence B) Recommendations for management of symptomatic carotid artery disease: • All patients with symptomatic carotid stenosis should receive long-term antiplatelet therapy. (Class-I-recommendation/Level of evidence A) • All patients with symptomatic carotid stenosis should receive long-term statin therapy. (Class-I-recommendation/Level of evidence B) • In patients with symptomatic 70–99% stenosis of the internal carotid artery, CEA is recommended for the prevention of recurrent stroke. (Class- Irecommendation/Level of evidence A).

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