THIS PPT WILL CLEAR YOUR CONCEPTS FOR THE VARIOUS CAUSES OF HYPERCALCEMIA INCLUDING MALIGANCY AND HELP YOU TO FOLLOW SYSTEMATIC APPRAOCH FOR THE DAIGNOSIS AND MANAGEMENT
1) Pineoblastoma and germ cell tumors are rare intracranial tumors, with pineoblastoma occurring most often in young children. Complete surgical resection is difficult due to tumor location.
2) Treatment involves maximal safe surgical resection followed by chemotherapy and craniospinal irradiation. Younger children (<3 years) have a poorer prognosis and require more intensive treatment regimens.
3) Older children (>3 years) have shown improved survival when treated with chemotherapy and craniospinal irradiation after surgery. Younger children have generally not responded well to chemotherapy alone.
Radiotherapy in low grade gliomas benefit with local control advantage
Patients with high risk factors need immediate radiation after surgery
RT dose of 50-54 Gy in 2 Gy/Fr
Fractionated radiosurgery in optic nerve glioma and small volume disease
This document discusses hypercalcemia in malignancy. It begins with an introduction defining hypercalcemia and its prevalence in certain cancers. It then covers normal calcium metabolism regulation involving bone, plasma, vitamin D, and the RANK/RANKL pathway. Etiologies of hypercalcemia in malignancy include PTHrP-mediated humoral hypercalcemia, local osteolytic hypercalcemia, 1,25-dihydroxyvitamin D mediated, and hyperparathyroidism. Clinical presentation involves neurologic, gastrointestinal, cardiovascular, and renal symptoms. Diagnostic evaluation includes calcium levels and approaches based on etiology. Management involves increasing urinary calcium excretion, inhibiting bone resorption with bisphosphonates or den
Breast Cancer - Molecular Basis of HER2+ DiseaseFaryn
This presentation was part of a graduate level advanced molecular cell biology course. It reviews Breast Cancer epidemiology, signs 7 symptoms, diagnosis, genetic testing, hormonal testing and treatment options (briefly), then discusses the specifics of HER2+ cases at the cellular level. It shows how Herceptin and Tykerb work in the cell to block signal cascades, etc.
Low grade gliomas are slow-growing brain tumors that are divided into grades I and II. Grade I tumors have low proliferation and discrete imaging features, while grade II tumors often present with seizures and have nuclear atypia and infiltration on imaging. Molecular markers like IDH1 mutations, 1p19q co-deletions, and MGMT methylation correlate with improved survival. Initial management involves seizure control and surgery if symptomatic, followed by radiotherapy and chemotherapy depending on factors like age, symptoms, and molecular characteristics. Long-term follow up is needed due to the risk of progression to higher grade glioma over time.
DOUBLE HIT AND OTHER MOLECULARLY DEFINED LARGE CELL LYMPHOMASspa718
This document summarizes key information about double hit lymphomas and other molecularly defined large B-cell lymphomas. It discusses how approximately 40% of B-cell lymphomas involve chromosomal translocations involving oncogenes like MYC and BCL2. Double hit lymphomas specifically involve recurrent breakpoints activating both MYC and another oncogene like BCL2. These tumors have a germinal center B-cell phenotype and poor response to standard R-CHOP chemotherapy, with median survival usually less than 1 year. More intensive chemotherapy regimens like dose-adjusted EPOCH show promise for improving outcomes in double hit lymphoma and other MYC-rearranged large B-cell lymphomas.
This document provides information on the management of diffuse gliomas, including:
1. It defines diffuse gliomas and discusses their WHO classification, typically involving infiltration of normal brain tissue without clear borders.
2. Symptoms can include raised intracranial pressure, seizures, focal neurological deficits, and others depending on the tumor location.
3. Managing diffuse gliomas requires a multidisciplinary team including radiologists, neurosurgeons, oncologists and others.
4. Trial evidence is discussed regarding the use of radiotherapy and chemotherapy at different doses and timings for diffuse low-grade gliomas.
1) The document outlines the basic principles of radiation oncology, including the physics of radiation, external beam irradiation, brachytherapy, and radiobiology concepts like the four R's.
2) It discusses treatment planning considerations for factors like tumor size and location as well as combined modality approaches using surgery and radiation.
3) Common acute and late complications of radiation therapy are reviewed, such as mucositis, xerostomia, fibrosis, and central nervous system toxicity.
1) Pineoblastoma and germ cell tumors are rare intracranial tumors, with pineoblastoma occurring most often in young children. Complete surgical resection is difficult due to tumor location.
2) Treatment involves maximal safe surgical resection followed by chemotherapy and craniospinal irradiation. Younger children (<3 years) have a poorer prognosis and require more intensive treatment regimens.
3) Older children (>3 years) have shown improved survival when treated with chemotherapy and craniospinal irradiation after surgery. Younger children have generally not responded well to chemotherapy alone.
Radiotherapy in low grade gliomas benefit with local control advantage
Patients with high risk factors need immediate radiation after surgery
RT dose of 50-54 Gy in 2 Gy/Fr
Fractionated radiosurgery in optic nerve glioma and small volume disease
This document discusses hypercalcemia in malignancy. It begins with an introduction defining hypercalcemia and its prevalence in certain cancers. It then covers normal calcium metabolism regulation involving bone, plasma, vitamin D, and the RANK/RANKL pathway. Etiologies of hypercalcemia in malignancy include PTHrP-mediated humoral hypercalcemia, local osteolytic hypercalcemia, 1,25-dihydroxyvitamin D mediated, and hyperparathyroidism. Clinical presentation involves neurologic, gastrointestinal, cardiovascular, and renal symptoms. Diagnostic evaluation includes calcium levels and approaches based on etiology. Management involves increasing urinary calcium excretion, inhibiting bone resorption with bisphosphonates or den
Breast Cancer - Molecular Basis of HER2+ DiseaseFaryn
This presentation was part of a graduate level advanced molecular cell biology course. It reviews Breast Cancer epidemiology, signs 7 symptoms, diagnosis, genetic testing, hormonal testing and treatment options (briefly), then discusses the specifics of HER2+ cases at the cellular level. It shows how Herceptin and Tykerb work in the cell to block signal cascades, etc.
Low grade gliomas are slow-growing brain tumors that are divided into grades I and II. Grade I tumors have low proliferation and discrete imaging features, while grade II tumors often present with seizures and have nuclear atypia and infiltration on imaging. Molecular markers like IDH1 mutations, 1p19q co-deletions, and MGMT methylation correlate with improved survival. Initial management involves seizure control and surgery if symptomatic, followed by radiotherapy and chemotherapy depending on factors like age, symptoms, and molecular characteristics. Long-term follow up is needed due to the risk of progression to higher grade glioma over time.
DOUBLE HIT AND OTHER MOLECULARLY DEFINED LARGE CELL LYMPHOMASspa718
This document summarizes key information about double hit lymphomas and other molecularly defined large B-cell lymphomas. It discusses how approximately 40% of B-cell lymphomas involve chromosomal translocations involving oncogenes like MYC and BCL2. Double hit lymphomas specifically involve recurrent breakpoints activating both MYC and another oncogene like BCL2. These tumors have a germinal center B-cell phenotype and poor response to standard R-CHOP chemotherapy, with median survival usually less than 1 year. More intensive chemotherapy regimens like dose-adjusted EPOCH show promise for improving outcomes in double hit lymphoma and other MYC-rearranged large B-cell lymphomas.
This document provides information on the management of diffuse gliomas, including:
1. It defines diffuse gliomas and discusses their WHO classification, typically involving infiltration of normal brain tissue without clear borders.
2. Symptoms can include raised intracranial pressure, seizures, focal neurological deficits, and others depending on the tumor location.
3. Managing diffuse gliomas requires a multidisciplinary team including radiologists, neurosurgeons, oncologists and others.
4. Trial evidence is discussed regarding the use of radiotherapy and chemotherapy at different doses and timings for diffuse low-grade gliomas.
1) The document outlines the basic principles of radiation oncology, including the physics of radiation, external beam irradiation, brachytherapy, and radiobiology concepts like the four R's.
2) It discusses treatment planning considerations for factors like tumor size and location as well as combined modality approaches using surgery and radiation.
3) Common acute and late complications of radiation therapy are reviewed, such as mucositis, xerostomia, fibrosis, and central nervous system toxicity.
Ewings sarcoma management Chemotherapy trialsParag Roy
This document provides information on the management of Ewing's Sarcoma, including:
- Ewing's Sarcoma is identified by the translocation t(11;22) in 90-95% of cases.
- Metastases most commonly spread to the lungs, bones, and bone marrow. Nearly all patients have micrometastases at diagnosis.
- Treatment involves induction chemotherapy followed by local control with surgery or radiotherapy and maintenance chemotherapy.
- Several clinical trials have evaluated chemotherapy regimens and dosing schedules, with INT-0099 establishing VDC/IE as the standard of care and AEWS-0031 showing improved outcomes with interval-compressed chemotherapy.
Digital Pathology: Precision Medicine, Deep Learning and Computer Aided Inter...Joel Saltz
In this presentation, I will survey the development of Digital Pathology methodology beginning with the 1997 virtual microscope prototype at Hopkins to current tools, methods and algorithms designed to display, analyze and classify whole slide imaging data. I will describe methods, tools and algorithms to extract information from Pathology images. These tools include ability to traverse whole slide images, segment nuclei, carry out deep learning region classification and characterize relationship between extracted features and morphological structures. I will also describe some of the research efforts that motivate development of these tools, the role Pathomics is playing in precision medicine research as well as the impact of Pathology Informatics on clinical practice and health care quality.
Presentation at the Department of Biomedical Informatics, University Pittsburgh Medical Center, April 27, 2018
Audio and slides for this presentation are also available on YouTube: http://youtu.be/ukXhuy5cXrE
Huma Q. Rana, MD, a cancer geneticist with Dana-Farber Cancer Institute, explains the cancer risk associated with BRCA1 and BRCA2 gene mutations. This presentation was originally given on July 23, 2013 as part of the "What Every Woman Should Know" event put on by Dana-Farber's Susan F. Smith Center for Women's Cancers.
Hypercalcemia of malignancy novel management therapyVishal Ramteke
This document discusses the case of a 56-year-old woman with metastatic breast cancer and hypercalcemia that was refractory to treatment with zoledronic acid and calcitonin. She was started on cinacalcet and dexamethasone, and then administered denosumab injections to further lower her calcium levels. Denosumab binds to RANK ligand to inhibit bone resorption and reduce calcium levels. After receiving denosumab injections on days 1, 8, 15, 29 and 60, the patient's total calcium levels decreased from 13.9 to 7.7 mg/dl. The document discusses how denosumab has been used off-label for persistent hypercalcemia of malignancy.
Central nervous system tumors are the second most common type of cancer in children. 20-25% of childhood cancers are CNS tumors. The most common types are astrocytic tumors such as pilocytic astrocytoma and medulloblastoma. Medulloblastoma is an embryonal tumor that occurs most often in the cerebellum and has a high risk of spreading through the cerebrospinal fluid. Treatment involves maximal surgical resection followed by craniospinal radiation therapy and chemotherapy, with doses and regimens varying based on risk factors like age and extent of resection. Treatment planning for craniospinal irradiation aims to deliver a uniform dose to the entire target volume while minimizing risks of under-
This document discusses advances in oncological PET imaging. It begins by outlining limitations of current PET/CT imaging related to false positives, false negatives, and radiation exposure. It then describes several advances in PET imaging including new radiotracers for tumor characterization, instrumentation improvements, software enhancements to reduce radiation dose, and hybrid PET/MRI imaging. The document provides examples of how various new radiotracers beyond FDG can provide clinical benefits for tumor imaging and characterization.
This document provides an overview of common pediatric brain tumors located in the posterior fossa (infratentorial region). It discusses the most frequently used MRI sequences for evaluating these tumors and provides clinical and imaging features of the most common tumor types, including medulloblastoma, ependymoma, pilocytic astrocytoma, and brainstem glioma. Differential diagnoses are also reviewed. Key sequences discussed are T1WI, T2WI, FLAIR, DWI, and post-contrast T1WI. Common features and imaging findings are highlighted for each tumor type in 1-3 sentences.
The document discusses the importance of nutrition during and after radiation therapy for cancer patients. It notes that malnutrition can result from both the cancer itself and side effects of radiation like mucositis and dysphagia. The European Society on Clinical Nutrition and Metabolism guidelines provide recommendations on energy requirements and interventions. A poem then outlines steps for nutrition management during radiation, including maintaining weight, a high-protein diet, and addressing issues like oral candidiasis and electrolyte imbalances. It emphasizes the importance of nutrition surveillance post-radiation to correct fluid-electrolyte problems and address late effects.
Lecture dedicated to radiogenomics of renal cell carcinoma by Ph.d., MD, Mytsyk Yulian, Department of Urology/Radiology, Lviv National Medical University, presented at IV Ukrainian-Polish Conference on Radiology 2018, Rzeszów
1) The document discusses a study that examined the effects of low dose rate (LDR) radiation exposure versus acute radiation exposure on gene expression in human blood cells. Blood samples from volunteers were exposed to either LDR or acute radiation doses and gene expression was analyzed.
2) The study found that while there were similarities in gene expression responses between LDR and acute exposures, LDR resulted in some distinctive gene expression patterns. In particular, 243 genes showed different expression levels when comparing LDR to acute exposure at 4.45 Gy.
3) The study was able to distinguish LDR exposed samples from acute dose exposures based on their gene expression profiles, identifying candidate genes that could help detect LDR exposures for large
Molecular pathogenesis of CNS tumors lecture covers the following key points in 3 sentences:
The lecture discusses the molecular underpinnings and classification of various CNS tumors including gliomas, medulloblastoma, and meningiomas. It covers important molecular markers and genetic alterations that drive tumor pathogenesis, such as IDH1/2 mutations and 1p/19q codeletion in gliomas, and WNT and Sonic Hedgehog pathways in medulloblastoma classification. The lecture also reviews diagnostic techniques like FISH, IHC, and gene sequencing that are used to detect these molecular alterations and inform tumor grading and targeted therapy approaches.
Personalized medicine in radiation oncology aims to individualize radiotherapy treatment through better imaging, genetics, and biomarkers. Newer radiotherapy techniques like IMRT and IGRT allow for more precise targeting of tumors while minimizing dose to normal tissues. Biomarkers can help characterize tumor hypoxia, proliferation, and a patient's inherent radiosensitivity at the genetic level. Radiogenomics research seeks genetic polymorphisms associated with radiation response and side effects. The goal is to predict treatment outcomes and tailor radiotherapy for each patient's unique biology and genetics.
This document discusses the management of low-grade gliomas. It begins by defining low-grade gliomas as WHO grade I and II primary brain tumors that have a better prognosis than high-grade gliomas but still have the potential to progress into higher grades. The most common symptoms are seizures. Diagnosis is typically made through MRI imaging showing characteristic patterns and biopsy is only recommended if resection is not possible. Treatment options include maximal safe surgical resection followed by observation with serial MRIs, adjuvant radiation therapy, or chemotherapy depending on factors like age, extent of resection, and tumor characteristics. The goal of management is prolonging progression-free survival while minimizing treatment-related morbidity.
The 2021 WHO classification of CNS tumors builds on the 2016 edition by placing greater emphasis on molecular markers for both classification and grading. Some tumors are now entirely classified based on their molecular profile, while others remain primarily histologically assessed. A layered report structure will integrate histological, grading, and molecular information. Notable changes include raising IDH status and 1p19q codeletion to prominence for diffuse gliomas. Grading now occurs within each tumor type rather than equivalently across types. Molecular features can supersede histology in determining grade.
Ewing sarcoma is the second most common bone tumor in children. Radiotherapy plays an important role in the treatment of both localized and metastatic Ewing sarcoma. For localized disease, radiotherapy is recommended for patients who cannot undergo surgery or have unresectable tumors. It is also used post-operatively if there is residual disease. For metastatic disease, radiotherapy can help control the primary tumor and reduce pulmonary metastases when combined with chemotherapy. Advances in radiotherapy planning and techniques have improved outcomes while reducing long-term side effects.
This document discusses targeted cancer therapies and their mechanisms of action. It outlines 10 hallmarks of cancer and describes targeted drugs that inhibit specific proteins and pathways involved in cancer growth. These targeted drugs include small molecule tyrosine kinase inhibitors, monoclonal antibodies, angiogenesis inhibitors, and proteosome inhibitors. Examples are provided of targeted therapies used to treat cancers like chronic myeloid leukemia, lung cancer, breast cancer, and multiple myeloma. Potential side effects of targeted therapies are also mentioned.
Cervical cancer is the second most common cancer affecting women worldwide. It starts in the cells of the cervix and is caused primarily by certain strains of the human papillomavirus (HPV). Other risk factors include smoking, a weakened immune system, multiple pregnancies at a young age, and infections like chlamydia. Screening tests like the Pap smear and HPV test can find pre-cancerous lesions early so they can be treated before they develop into invasive cancer. Prevention strategies include HPV vaccination, routine screening, not smoking, limiting sexual partners, and using condoms.
Radiosensitivity and cell age in the mitotic cycleSneha George
The cell cycle is the ordered process by which a cell grows and divides into two daughter cells. It consists of mitosis (M phase) and interphase (G1, S, and G2 phases). Cell cycle time is measured between successive mitotic divisions. Cell labeling techniques like autoradiography using tritiated thymidine or bromodeoxyuridine are used to identify cells in the DNA synthesis (S) phase. The cell cycle is regulated by cyclin-dependent kinases whose activity drives cell cycle progression. Radiosensitivity varies through the cell cycle, with cells most resistant in late S phase and most sensitive in G1, G2, and M phases. Fractionating radiation doses takes advantage of reassortment
This document discusses calcium homeostasis and hypercalcemia. It notes that calcium is critical for many physiological functions and is mainly stored in bones. Hypercalcemia can be caused by primary hyperparathyroidism, vitamin D excess, certain malignancies, and other conditions. The diagnostic approach involves distinguishing between hyperparathyroidism and hypercalcemia of malignancy based on lab tests. Treatment focuses on rehydration, increasing calciuresis, and decreasing bone resorption or intestinal calcium absorption using medications like calcitonin, bisphosphonates, glucocorticoids, or dialysis depending on the severity of hypercalcemia.
The document discusses diseases of the parathyroid gland. It describes the structure and regulation of parathyroid hormone (PTH) secretion, including how calcium levels control PTH levels. It also discusses hyperparathyroidism, the most common form being primary hyperparathyroidism caused by a single adenoma or hyperplasia of the parathyroid glands leading to elevated PTH levels and hypercalcemia. Signs and symptoms include fatigue, weakness, kidney stones, and bone disease. The genetics and clinical manifestations of primary hyperparathyroidism are also summarized.
Ewings sarcoma management Chemotherapy trialsParag Roy
This document provides information on the management of Ewing's Sarcoma, including:
- Ewing's Sarcoma is identified by the translocation t(11;22) in 90-95% of cases.
- Metastases most commonly spread to the lungs, bones, and bone marrow. Nearly all patients have micrometastases at diagnosis.
- Treatment involves induction chemotherapy followed by local control with surgery or radiotherapy and maintenance chemotherapy.
- Several clinical trials have evaluated chemotherapy regimens and dosing schedules, with INT-0099 establishing VDC/IE as the standard of care and AEWS-0031 showing improved outcomes with interval-compressed chemotherapy.
Digital Pathology: Precision Medicine, Deep Learning and Computer Aided Inter...Joel Saltz
In this presentation, I will survey the development of Digital Pathology methodology beginning with the 1997 virtual microscope prototype at Hopkins to current tools, methods and algorithms designed to display, analyze and classify whole slide imaging data. I will describe methods, tools and algorithms to extract information from Pathology images. These tools include ability to traverse whole slide images, segment nuclei, carry out deep learning region classification and characterize relationship between extracted features and morphological structures. I will also describe some of the research efforts that motivate development of these tools, the role Pathomics is playing in precision medicine research as well as the impact of Pathology Informatics on clinical practice and health care quality.
Presentation at the Department of Biomedical Informatics, University Pittsburgh Medical Center, April 27, 2018
Audio and slides for this presentation are also available on YouTube: http://youtu.be/ukXhuy5cXrE
Huma Q. Rana, MD, a cancer geneticist with Dana-Farber Cancer Institute, explains the cancer risk associated with BRCA1 and BRCA2 gene mutations. This presentation was originally given on July 23, 2013 as part of the "What Every Woman Should Know" event put on by Dana-Farber's Susan F. Smith Center for Women's Cancers.
Hypercalcemia of malignancy novel management therapyVishal Ramteke
This document discusses the case of a 56-year-old woman with metastatic breast cancer and hypercalcemia that was refractory to treatment with zoledronic acid and calcitonin. She was started on cinacalcet and dexamethasone, and then administered denosumab injections to further lower her calcium levels. Denosumab binds to RANK ligand to inhibit bone resorption and reduce calcium levels. After receiving denosumab injections on days 1, 8, 15, 29 and 60, the patient's total calcium levels decreased from 13.9 to 7.7 mg/dl. The document discusses how denosumab has been used off-label for persistent hypercalcemia of malignancy.
Central nervous system tumors are the second most common type of cancer in children. 20-25% of childhood cancers are CNS tumors. The most common types are astrocytic tumors such as pilocytic astrocytoma and medulloblastoma. Medulloblastoma is an embryonal tumor that occurs most often in the cerebellum and has a high risk of spreading through the cerebrospinal fluid. Treatment involves maximal surgical resection followed by craniospinal radiation therapy and chemotherapy, with doses and regimens varying based on risk factors like age and extent of resection. Treatment planning for craniospinal irradiation aims to deliver a uniform dose to the entire target volume while minimizing risks of under-
This document discusses advances in oncological PET imaging. It begins by outlining limitations of current PET/CT imaging related to false positives, false negatives, and radiation exposure. It then describes several advances in PET imaging including new radiotracers for tumor characterization, instrumentation improvements, software enhancements to reduce radiation dose, and hybrid PET/MRI imaging. The document provides examples of how various new radiotracers beyond FDG can provide clinical benefits for tumor imaging and characterization.
This document provides an overview of common pediatric brain tumors located in the posterior fossa (infratentorial region). It discusses the most frequently used MRI sequences for evaluating these tumors and provides clinical and imaging features of the most common tumor types, including medulloblastoma, ependymoma, pilocytic astrocytoma, and brainstem glioma. Differential diagnoses are also reviewed. Key sequences discussed are T1WI, T2WI, FLAIR, DWI, and post-contrast T1WI. Common features and imaging findings are highlighted for each tumor type in 1-3 sentences.
The document discusses the importance of nutrition during and after radiation therapy for cancer patients. It notes that malnutrition can result from both the cancer itself and side effects of radiation like mucositis and dysphagia. The European Society on Clinical Nutrition and Metabolism guidelines provide recommendations on energy requirements and interventions. A poem then outlines steps for nutrition management during radiation, including maintaining weight, a high-protein diet, and addressing issues like oral candidiasis and electrolyte imbalances. It emphasizes the importance of nutrition surveillance post-radiation to correct fluid-electrolyte problems and address late effects.
Lecture dedicated to radiogenomics of renal cell carcinoma by Ph.d., MD, Mytsyk Yulian, Department of Urology/Radiology, Lviv National Medical University, presented at IV Ukrainian-Polish Conference on Radiology 2018, Rzeszów
1) The document discusses a study that examined the effects of low dose rate (LDR) radiation exposure versus acute radiation exposure on gene expression in human blood cells. Blood samples from volunteers were exposed to either LDR or acute radiation doses and gene expression was analyzed.
2) The study found that while there were similarities in gene expression responses between LDR and acute exposures, LDR resulted in some distinctive gene expression patterns. In particular, 243 genes showed different expression levels when comparing LDR to acute exposure at 4.45 Gy.
3) The study was able to distinguish LDR exposed samples from acute dose exposures based on their gene expression profiles, identifying candidate genes that could help detect LDR exposures for large
Molecular pathogenesis of CNS tumors lecture covers the following key points in 3 sentences:
The lecture discusses the molecular underpinnings and classification of various CNS tumors including gliomas, medulloblastoma, and meningiomas. It covers important molecular markers and genetic alterations that drive tumor pathogenesis, such as IDH1/2 mutations and 1p/19q codeletion in gliomas, and WNT and Sonic Hedgehog pathways in medulloblastoma classification. The lecture also reviews diagnostic techniques like FISH, IHC, and gene sequencing that are used to detect these molecular alterations and inform tumor grading and targeted therapy approaches.
Personalized medicine in radiation oncology aims to individualize radiotherapy treatment through better imaging, genetics, and biomarkers. Newer radiotherapy techniques like IMRT and IGRT allow for more precise targeting of tumors while minimizing dose to normal tissues. Biomarkers can help characterize tumor hypoxia, proliferation, and a patient's inherent radiosensitivity at the genetic level. Radiogenomics research seeks genetic polymorphisms associated with radiation response and side effects. The goal is to predict treatment outcomes and tailor radiotherapy for each patient's unique biology and genetics.
This document discusses the management of low-grade gliomas. It begins by defining low-grade gliomas as WHO grade I and II primary brain tumors that have a better prognosis than high-grade gliomas but still have the potential to progress into higher grades. The most common symptoms are seizures. Diagnosis is typically made through MRI imaging showing characteristic patterns and biopsy is only recommended if resection is not possible. Treatment options include maximal safe surgical resection followed by observation with serial MRIs, adjuvant radiation therapy, or chemotherapy depending on factors like age, extent of resection, and tumor characteristics. The goal of management is prolonging progression-free survival while minimizing treatment-related morbidity.
The 2021 WHO classification of CNS tumors builds on the 2016 edition by placing greater emphasis on molecular markers for both classification and grading. Some tumors are now entirely classified based on their molecular profile, while others remain primarily histologically assessed. A layered report structure will integrate histological, grading, and molecular information. Notable changes include raising IDH status and 1p19q codeletion to prominence for diffuse gliomas. Grading now occurs within each tumor type rather than equivalently across types. Molecular features can supersede histology in determining grade.
Ewing sarcoma is the second most common bone tumor in children. Radiotherapy plays an important role in the treatment of both localized and metastatic Ewing sarcoma. For localized disease, radiotherapy is recommended for patients who cannot undergo surgery or have unresectable tumors. It is also used post-operatively if there is residual disease. For metastatic disease, radiotherapy can help control the primary tumor and reduce pulmonary metastases when combined with chemotherapy. Advances in radiotherapy planning and techniques have improved outcomes while reducing long-term side effects.
This document discusses targeted cancer therapies and their mechanisms of action. It outlines 10 hallmarks of cancer and describes targeted drugs that inhibit specific proteins and pathways involved in cancer growth. These targeted drugs include small molecule tyrosine kinase inhibitors, monoclonal antibodies, angiogenesis inhibitors, and proteosome inhibitors. Examples are provided of targeted therapies used to treat cancers like chronic myeloid leukemia, lung cancer, breast cancer, and multiple myeloma. Potential side effects of targeted therapies are also mentioned.
Cervical cancer is the second most common cancer affecting women worldwide. It starts in the cells of the cervix and is caused primarily by certain strains of the human papillomavirus (HPV). Other risk factors include smoking, a weakened immune system, multiple pregnancies at a young age, and infections like chlamydia. Screening tests like the Pap smear and HPV test can find pre-cancerous lesions early so they can be treated before they develop into invasive cancer. Prevention strategies include HPV vaccination, routine screening, not smoking, limiting sexual partners, and using condoms.
Radiosensitivity and cell age in the mitotic cycleSneha George
The cell cycle is the ordered process by which a cell grows and divides into two daughter cells. It consists of mitosis (M phase) and interphase (G1, S, and G2 phases). Cell cycle time is measured between successive mitotic divisions. Cell labeling techniques like autoradiography using tritiated thymidine or bromodeoxyuridine are used to identify cells in the DNA synthesis (S) phase. The cell cycle is regulated by cyclin-dependent kinases whose activity drives cell cycle progression. Radiosensitivity varies through the cell cycle, with cells most resistant in late S phase and most sensitive in G1, G2, and M phases. Fractionating radiation doses takes advantage of reassortment
This document discusses calcium homeostasis and hypercalcemia. It notes that calcium is critical for many physiological functions and is mainly stored in bones. Hypercalcemia can be caused by primary hyperparathyroidism, vitamin D excess, certain malignancies, and other conditions. The diagnostic approach involves distinguishing between hyperparathyroidism and hypercalcemia of malignancy based on lab tests. Treatment focuses on rehydration, increasing calciuresis, and decreasing bone resorption or intestinal calcium absorption using medications like calcitonin, bisphosphonates, glucocorticoids, or dialysis depending on the severity of hypercalcemia.
The document discusses diseases of the parathyroid gland. It describes the structure and regulation of parathyroid hormone (PTH) secretion, including how calcium levels control PTH levels. It also discusses hyperparathyroidism, the most common form being primary hyperparathyroidism caused by a single adenoma or hyperplasia of the parathyroid glands leading to elevated PTH levels and hypercalcemia. Signs and symptoms include fatigue, weakness, kidney stones, and bone disease. The genetics and clinical manifestations of primary hyperparathyroidism are also summarized.
Control of calcium homeostasis involves parathyroid hormone, vitamin D, PTHrP, and calcitonin. Vitamin D is produced in skin and converted to its active form in liver and kidneys to regulate calcium absorption and bone mineralization. Disorders like rickets and osteomalacia can result from vitamin D deficiency. Primary hyperparathyroidism is a common cause of hypercalcemia where an overactive parathyroid gland increases bone resorption and renal calcium reabsorption. Hypocalcemia can occur in chronic kidney disease or hypoparathyroidism and cause neuromuscular symptoms. Multiple endocrine neoplasia type 1 involves tumors of the parathyroid glands, pancreas
The document discusses disorders of the parathyroid glands, which regulate calcium, phosphate, and magnesium levels. It covers primary hyperparathyroidism, caused by excessive PTH from hyperfunctioning parathyroid glands, and secondary hyperparathyroidism, which is an adaptive response to low calcium levels. It also discusses hypoparathyroidism, caused by PTH deficiency, and the resulting hypocalcemia and its neuromuscular symptoms. Diagnosis and treatment options are provided for each disorder.
This document summarizes parathyroid gland anatomy and physiology and various types of hyperparathyroidism. It discusses the role of parathyroid hormone in calcium homeostasis, causes of primary, secondary, and tertiary hyperparathyroidism, associated symptoms and complications, diagnostic testing, treatment options including medication and surgery, and other related conditions like familial benign hypercalcemia and hypercalcemia of malignancy.
The document discusses surgical diseases of the parathyroid glands, including primary hyperparathyroidism, secondary hyperparathyroidism, and tertiary hyperparathyroidism. Primary hyperparathyroidism is caused by an increased production of parathyroid hormone and can be due to a single adenoma, hyperplasia, or carcinoma. It often presents with hypercalcemia, hypophosphatemia, and is typically treated with surgery to remove the affected gland(s). Secondary hyperparathyroidism is caused by chronic kidney disease or other conditions and is treated by addressing the underlying disorder. Tertiary hyperparathyroidism occurs after treatment of chronic kidney disease and may require surgery.
Surgical diseases of the parathyroid gland/reuploadMD Specialclass
- The document discusses surgical diseases of the parathyroid glands, focusing on primary hyperparathyroidism. It describes the anatomy, function, and hormonal regulation of the parathyroid glands.
- Primary hyperparathyroidism is defined as inappropriately increased parathyroid hormone levels and can be caused by a single adenoma, hyperplasia, or carcinoma. The clinical presentation and treatment are discussed.
- Secondary and tertiary hyperparathyroidism, which develop in response to other diseases like chronic kidney failure, are also summarized.
Surgical diseases of the thyroid gland and parathyroid glandMD Specialclass
- The document discusses surgical diseases of the parathyroid glands, including primary hyperparathyroidism which is caused by inappropriately increased amounts of parathyroid hormone relative to calcium levels. The three histologic patterns are single adenoma, hyperplasia, and parathyroid carcinoma.
- Secondary hyperparathyroidism is caused by malfunction of another organ like the kidneys in chronic renal failure patients. Tertiary hyperparathyroidism is persistent hyperparathyroidism after the underlying disorder is resolved, such as after a successful kidney transplant.
- Surgery is the treatment for primary hyperparathyroidism and tertiary hyperparathyroidism, while treatment for secondary hyper
Parathyroid hormone (PTH) regulates calcium homeostasis. Primary hyperparathyroidism is caused by overproduction of PTH by one or more abnormal parathyroid glands. It can cause increased bone resorption and loss of bone mineral density. Surgical removal of the abnormal gland(s) is the only cure. Secondary and tertiary hyperparathyroidism are caused by chronic kidney disease and long-term renal failure which disrupt normal calcium regulation, leading to PTH overproduction. They are treated medically or with subtotal parathyroidectomy. New localization techniques and medications are improving diagnosis and management.
After the class the students will be able
Explain the structures and function of Parathyroid gland.
Explain the age affect on parathyroid gland.
Describe the definition, etiology, risk factors, pathophysiology, medical management, surgical management and Nursing management of Hyperparathyroidism.
Describe the definition, etiology, risk factors, pathophysiology, medical management, surgical management and Nursing management of Hypothyroidism.
List down the health education for Hyperparathyroidism and Hypoparathyroidism.
Disorders of the parathyroid glands can cause significant metabolic disturbances that present challenges for anesthesia and surgery. Parathyroid surgery specifically carries risks related to maintaining normal calcium levels. Pre-op optimization is essential to prevent complications from electrolyte imbalances during and after surgery. Careful monitoring of calcium levels is needed both during and after surgery to address any potential hypocalcemia.
This document summarizes calcium homeostasis and regulation. It discusses that calcium is mostly stored in bones, with small amounts in extracellular and intracellular spaces. Parathyroid hormone (PTH), vitamin D, and calcitonin regulate calcium levels. Primary hyperparathyroidism is usually caused by a single adenoma and results in inappropriate PTH secretion. Malignancy is a common cause of hypercalcemia through humoral factors like PTH-related peptide. Hypocalcemia can result from PTH deficiency, PTH resistance, vitamin D deficiency or resistance, or calcium deposition issues. Treatment involves calcium, vitamin D, magnesium, or addressing the underlying cause.
1) Bone mineral metabolism is tightly regulated by the intestine, kidney, bone, and hormones like PTH, vitamin D, and calcitonin. Calcium levels can be affected by changes in plasma proteins and acid-base balance.
2) Hypercalcemia has various causes like primary hyperparathyroidism and malignancy, and results in symptoms across multiple organ systems. Diagnostic workup to distinguish the causes typically involves testing for PTH and investigating for an underlying malignancy.
3) Hypocalcemia can occur from low or high PTH levels due to conditions like hypoparathyroidism, vitamin D deficiency, or renal failure. It produces neurological symptoms like paresthesias and tet
The document discusses the benefits of exercise for mental health. Regular physical activity can help reduce anxiety and depression and improve mood and cognitive functioning. Exercise causes chemical changes in the brain that may help protect against mental illness and improve symptoms.
This document provides a detailed overview of the history, anatomy, physiology, pathophysiology, clinical presentation, diagnosis, and treatment of primary hyperparathyroidism. It traces the discovery and description of the parathyroid glands from the 19th century through modern understanding. Key points covered include the role of parathyroid hormone in calcium homeostasis, causes of primary hyperparathyroidism including adenomas and hyperplasia, clinical manifestations, use of imaging and intraoperative PTH testing to localize abnormal glands, and surgical treatment approaches.
The document discusses parathyroid glands and parathyroid hormone (PTH). It notes that parathyroid glands secrete PTH, which regulates calcium levels in the blood. PTH acts on bone, kidneys, and stimulates vitamin D production. Secondary hyperparathyroidism occurs in kidney disease and is caused by low calcium and vitamin D levels stimulating increased PTH secretion. Treatment focuses on controlling calcium, phosphate, PTH, and vitamin D levels through diet, binders, analogs, and calcimimetics. For refractory cases, parathyroidectomy may be required.
This document discusses calcium homeostasis and its regulation in the human body. It covers the following key points:
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These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
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3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
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Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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2. INTRODUCTION
Hypercalcemia is a frequent metabolic complication of
both solid and hematological malignancies reported to
occur in up to 30% of patients.
Usually associated with poor prognosis
The most common causes include
1. humoral -mediated by parathyroid hormone–related
peptide (PTHrp),
2. osteolytic cytokine production
3. excess 1,25-dihydroxy vitamin D production.
4. primary hyperparathyroidism or granulomatous diseases.
3. Most common cancers are
lung cancer
multiple myeloma
renal cell carcinoma
breast cancer
colorectal cancers
prostate cancer
4. Calcium is present in the body in two compartments-
Bone and Plasma
In plasma, serum calcium is present in several forms –
Free – 45% of serum calcium
Ionized (active form)- 65% of serum calcium
40% bound to albumin
15% bound to citrate, sulfate and phosphate
Mild
• 10.5-11.9
mg/dl
Moderate
• 12-13.9
mg/dl
Severe
• ≥14
mg/dl
5. Clinical manifestation of
hypercalcemia:-
Mild or indolent hypercalcemia - asymptomatic or
mild non specific symptoms such as constipation,
fatigue, lethargy, musculoskeletal pain and
depression.
Moderate hypercalcemia- polyuria, polydipsia,
dehydration, anorexia, nausea, muscle weakness
and changes in sensorium.
Severe, rapidly progressive hypercalcemia -
significant volume depletion and acute renal
insufficiency, dramatic neurocognitive symptoms
6. Other manifestation of hypercalcemia:-
Renal Polyuria,polydipsia,
nephrolithiasis,
Nephrocalcinosis
Distal renal tubular acidosis
Nephrogenic diabetes insipidus
Acute and chronic renal insufficiency
Gastrointestinal Anorexia, nausea, vomiting
Bowel hypo motility and constipation
Pancreatitis
Peptic ulcer disease
Musculoskeletal Muscle weakness
Bone pain
Osteopenia/osteoporosis
Neurogenic Decreased concentration
Confusion
Fatigue
Stupor, coma
Cardiovascular Shortening of the QT interval
Bradycardia
Hypertension
7. Mechanism of bone
Mineralisation
Hypercalcemia is a result of abnormalities in the normal
bone formation and degradation cycle.
During normal bone turnover, osteoclast activity is
regulated by the binding of RANK surface receptor on
the osteoclast to the receptor activator RANKL on the
osteoblast. This binding of RANK/RANKL regulates
osteoclastogenesis.
Osteoprotegerin is secreted by osteoblasts and
strongly inhibits bone resorption binding to RANKL,
thereby blocking the interaction between
10. Calcium homeostasis is regulated
by following hormones-
parathyroid hormone (PTH)
1,25-dihydroxy vitamin D (1,25[OH]2D)
Calcitonin
serum calcium
serum phosphorus
11. Mechanism of Hypercalcemia
by Paratharmone-
PTH is produced by the parathyroid glands. It
increases serum calcium and decreases serum
phosphorus via direct and indirect stimuli of
osteoclasts. It increases renal calcium absorption and
decreases renal phosphorus absorption.
PTH also stimulates the conversion of 25-hydroxy
vitamin D (25[OH]D) to1,25(OH)2D in the kidneys
through 1-a-hydroxylase, which results in increased
intestinal absorption of both calcium and phosphate.
12. In response to hypercalcemia, calcitonin is secreted
by the parafollicular C cells.
Calcitonin lowers serum calcium by decreasing renal
calcium and phosphorus reabsorption and also by
decreasing bone reabsorption.
13. There have been several proposed
mechanisms for hypercalcemia associated
with malignancies which mainly include:
1. Humoral hypercalcemia of malignancy
2. local osteolytic hypercalcemia
3. excess extrarenal activated vitamin D (1,25[OH]2D)
4. PTH secretion- ectopic or primary
14. Humoral hypercalcemia of
malignancy
It refers specifically to PTHrP- mediated
hypercalcemia. It accounts to almost for 80% of
hypercalcemia in cancer patients.
Most commonly seen in squamous cell carcinomas
such as head and neck, esophageal, cervical, lung
and colon cancers in addition to renal cell, bladder,
breast, endometrial and ovarian cancers and it is
rarely seen in pancreatic neuroendocrine tumors.
15. PTHrP is structurally similar to PTH and like PTH, it
enhances renal tubular reabsorption of calcium while
simultaneously increasing urinary phosphorus excretion.
The result is both hypercalcemia and hypophosphatemia
However, unlike PTH, PTHrP does not increase
1,25(OH)2D and thus does not increase intestinal
absorption of calcium and phosphorus.
PTHrP acts on osteoblasts, leading to enhanced
synthesis of RANKL
17. Local Osteolytic
Hypercalcemia
Local osteolytic hypercalcemia accounts for 20% of
cases and commonly occurs in multiple myeloma and
metastatic breast cancer and less commonly in
leukemia and lymphoma.
Previously, the proposed mechanism was direct
destruction of bone by metastases or malignant cells.
It is now because of the release of local cytokines
from the tumor resulting in excess osteoclast
activation and enhanced bone resorption.
18. Humoral factors associated hypercalcemia include
interleukin 1 (IL-1), IL-3, IL-6, TNF a, TGF a and b,
lymphotoxin and E series prostaglandins.
Macrophage inflammatory protein 1a is associated with
multiple myeloma. It stimulates osteoclastic formation in
human bone marrow cells.
Local cytokines can also be released in metastatic
breast cancer bone lesions such as TGF b, which
stimulate local production of PTHrP.
19. Extra renal production of
1,25(OH)2D
Extra renal production of 1,25(OH)2D by the tumor
accounts for approximately 1% of cases of
hypercalcemia in malignancy.
In normal vitamin D metabolism, stored vitamin D
(25[OH]D) in the liver is converted to 1,25(OH)2D
under the influence of PTH by renal 1-a-hydroxylase
in the kidneys.
1,25(OH)2D causes - increased intestinal absorption
of calcium and enhances osteolytic bone resorption,
resulting in increased serum calcium.
20. Extrarenal production is most commonly seen with
Hodgkin and non-Hodgkin lymphoma and ovarian
dysgerminoma.
Non malignant granulomatous diseases such as
sarcoidosis and other inflammatory conditions can also
produce hypercalcemia as a result of extrarenal
1,25(OH)2D production via autonomous 1-a-hydroxylase
activity in tissue macrophages.
21. Vitamin D intoxication
Excess Vitamin D can result in intoxication and
hypercalcemia.
In vitamin D intoxication, both 25(OH)D and
1,25(OH)2D are elevated with a suppressed PTH
whereas Extra renal production of 1,25(OH)2D can be
seen with low or normal 25(OH)D in addition to high
normal or high 1,25(OH)2D.
22. PTH secretion- ectopic or
primary
Ectopic PTH production by the tumor itself is a rare cause
and occurs in less than 1% of cases.
However, primary hyperparathyroidism as a result of
parathyroid adenoma(s) or hyperplasia can also occur in
patients with malignancy
It is three times more common in women than in men,
especially after the age of 45, with a peak incidence in
the seventh decade
It is also common in those having history of head and
neck irradiation and chronic lithium therapy.
23. It is estimated that 5% to 10% of cases of primary
hyperparathyroidism are the result of hereditary
hyperparathyroid syndromes, including multiple
endocrine neoplasia types 1 and 2. Parathyroid
carcinoma is a rare cause of primary
hyperparathyroidism.
25. Work Up
1. Serum Calcium- Serum calcium is the first step in the work-up
of suspected hypercalcemia.
2. Serum Albumin-Forty percent of calcium in serum is bound to
albumin, and calcium homeostasis is greatly affected by
albumin concentrations. If the albumin is abnormal, the serum
calcium should be corrected for the serum albumin using the
formula-
Serum corrected calcium equation:
0.8 (4.0 - serum albumin) + serum calcium = total estimated
calcium or
Ionized calcium (if total estimated calcium is believed to be
unreliable)
26. 3. pH-In respiratory alkalosis caused by hyperventilation,
the ionized calcium decreases acutely, and reductions in
pH can cause the ionized calcium to rise acutely, both
resulting in relatively rapid shifts.
4. Serum phosphorus - Hypercalcemia can be associated
with both hyper- and hypophosphatemia.
PTH and PTHrP are similar molecules therefore, both are
not concurrently elevated unless there are multiple
etiologies.
27. 5.Vit D
6.Serum Creatinine- A serum creatinine with estimated
glomerular filtration rate (GFR) measurement also has
an effect on the serum PTH level. Renal insufficiency
stimulates PTH production because it inhibits renal 1-a-
hydroxylase.
7. Vitamin A- Rarely, vitamin A toxicity can result in
hypercalcemia.
If the etiology is not clear with the above laboratory
tests then serum and urine protein electrophoresis or
immunofixation along with a skeletal survey is indicated
suspecting Multiple Myeloma
28. 8. 24-hour urine analysis for calcium and creatinine-
24-hour urine calcium clearance to creatinine clearance
ratio can be valuable to differentiate between primary
hyperparathyroidism and familial hypocalciuric
hypercalcemia.
If the urine calcium clearance to creatinine clearance
ratio is low (0.01), then familial hypocalciuric
hypercalcemia should be suspected and definitive
evaluation can include testing for mutations in the
CASR, AP2S1, or GNA11 gene.
29. Laboratory Findings for Specific
Etiologies of Hypercalcemia
Associated With Malignancy
Etiology PTH PTHrP 1,25(OH)D 25(OH)D Phosphorus
PTHrP
mediated
Low High Low or
Normal
Any Value Low
1,25(OH)2D
mediated
Low Low High Low or
Normal
Low
PTH
mediated
High Low High Low or
Normal
Low
Vitamin D
intoxication
Low Low High High Normal/High
30. Treatment
Treatment of the underlying malignancy is always the
primary goal of therapy.
Mild asymptomatic hypercalcemia (calcium, 10.5-11.9
mg/dL) may not need to be treated until after the
work-up has been completed and a diagnosis has
been established.
However, moderate to severe hypercalcemia (calcium
more than 12 mg/dL), especially when associated
with severe renal or neurologic symptoms, requires
prompt, often inpatient management.
31. Medical therapy is aimed at inhibiting bone resorption
and promoting renal calcium excretion.
Reducing intestinal calcium reabsorption is also
important in those with increased extrarenal
1,25(OH)2D production.
33. Promoting Renal Calcium
Excretion
Fluid replacement is first-line therapy for those with
acute renal insufficiency as a result of volume
depletion. Patients often require 1 to 2 L as an initial
bolus and then maintenance fluids of 150 to 300 mL/h
for the next 2 to 3 days or until they are volume
repleted.
34. Furosemide therapy is often used as a means to
provide increased calciuresis. However, it can often
exacerbates dehydration and fluid loss.
Furosemide should be reserved only for patients with
heart failure and those who need diuresis. If
furosemide is used, other electrolytes such as
potassium and phosphorus also need to be monitored
and replaced.
35. Reducing Bone Resorption
Bisphosphonates are first-line therapy and also the mainstay for
long-term therapy. Through direct mechanisms they induce
osteoclast apoptosis, and through indirect mechanisms acting on
the osteoblasts they can reduce osteoclastic bone resorption.
Bisphosphonates affect proliferation and differentiation of
osteoblasts and prevent their apoptosis, and they can also
neutralize the RANKL-mediated stimulation of osteoclasts.
Bisphosphonates should be given within 48 hours of diagnosis,
because it takes approximately 2 to 4 days for them to have
effect.
36. The two available preparations are pamidronate and
zoledronic acid. When compared directly, zoledronic
acid is more potent than pamidronate.
The median response duration is 32 days with
zoledronic acid 4 mg IV while 18 days with
pamidronate 90 mg IV.
Pamidronate is given at 60 to 90 mg IV over 4 to 24
hours. Zoledronic acid is given at 4 mg IV over 15 to
30 minutes.
37. Bisphosphonates unfortunately, have been associated
with nephrotoxicity. Adequate hydration can enhance
renal protection and help preserve renal function.
Dose adjustment- patients with mild to moderate renal
impairment before initiation of therapy (serum creatinine
< 4.5 mg) do not need dose adjustment.
However, it is not recommended in severe renal
impairment (serum creatinine > 4.5 mg/dL).
38. Patients should be adequately hydrated, and a single
dose of 4 mg IV should be given over no less than 15
minutes. Retreatment with zoledronic acid 4 mg may
be considered for persistent hypercalcemia, but no
sooner than 7 days after the initial therapy.
39. Dosing of zoledronic acid for multiple myeloma and
metastatic bone lesions recommends dose
reduction according to creatinine clearance:
GFR DOSE
> 60 ml/min 4 mg
50-60 ml/min 3.5 mg
40-49 ml/min 3.3 mg
30-39 ml/min 3.0 mg
40. Action of Calcitonin
Calcitonin is used to acutely lower calcium levels. When
used with bisphosphonates, it can lower calcium more
rapidly than either agent alone. Unfortunately,
tachyphylaxis can occur within 48 hours as a result of
downregulation of the calcitonin receptors.
Glucocorticoids can be used to enhance the effect of
calcitonin by upregulating the cell-surface calcitonin
receptors and creating new ones on the osteoclast.
Calcitonin is usually dosed at 4 to 8 IU/kg
subcutaneously every 6 to 12 hours.
41. Action of Steroid
Glucocorticoids are also given to treat hypercalcemia
caused by excess extrarenal 1,25(OH)2D and multiple
myeloma. Steroids inhibit osteoclastic bone
resorption by decreasing tumor production of locally
active cytokines, in addition to having direct tumorolytic
effects.
Steroids are usually given as hydrocortisone 200 to
400 mg/d for 3 to 4 days and then prednisone 10 to
20 mg/day for 7 days or prednisone 40 to 60 mg/d
for 10 days. If prednisone is not helpful after 10 days, it
should be discontinued.
42. Denosumab
Denosumab is a human monoclonal antibody to
RANKL. It reduces the osteoclast activity and bone
resorption.
Denosumab is more efficacious than zoledronic acid in
delaying or preventing hypercalcemia of malignancy in
patients with advanced cancer including breast cancer,
other solid tumors, and multiple myeloma.
It is also effective in hypercalcemia refractory to
bisphosphonates.
43. Denosumab is usually given to patients with serum
calcium more than 2.5 mg/dL and who had received
bisphosphonates for more than 7 days and less than 30
days before.
Denosumab is dosed as 120 mg subcutaneously on
days 1, 8, 15, and 29 and every 4 weeks thereafter; it
lowered serum calcium within 10 days.
44. Cinacalcet- It reduces PTH production and is
approved for use in secondary hyperparathyroidism
and refractory parathyroid carcinoma.
It has not been extensively studied in hypercalcemia
of malignancy. It has been approved only for use in
parathyroid carcinoma.
Calcium Chelation- Sodium EDTA and intravenous
phosphate can form complexes with ionized calcium,
after which these are cleared from circulation.
45. Dialysis or continuous renal replacement therapy is
usually reserved for hypercalcemia refractory to all of
the above therapies. It is the ultimate rescue treatment.
It can be considered when hypercalcemia is
accompanied by renal failure.
Editor's Notes
It is four times more common in stage IV cancer and associated with a poor prognosis.
Classification according to conc of calcium
dramatic neurocognitive symptoms ranging from altered mental status to coma.
If the interaction between RANK and RANKL is blocked, then the osteoclasts do not matue and if increased, then there is more osteoclastic expression and more bone resorption.