This document discusses paraneoplastic syndromes, which are clinical disorders associated with but not directly caused by malignant tumors. It describes several paraneoplastic endocrine, hematologic, neurological, dermatological, and other syndromes, listing their typical clinical presentations, associated laboratory abnormalities and cancers. It discusses evaluation, treatment and prognosis of these syndromes, noting that successful treatment of the primary tumor often leads to resolution of paraneoplastic symptoms.
This document discusses various paraneoplastic syndromes and their treatments according to Harrison's 18th Edition. It addresses endocrine syndromes like humoral hypercalcemia of malignancy, which can be treated by removing excess calcium from the diet and IV bisphosphonates. It also discusses ectopic vasopressin syndrome and its treatment through fluid restriction and vasopressin receptor antagonists. Cushing's syndrome caused by ectopic ACTH production is discussed alongside treatments like adrenalectomy, ketoconazole, and metyrapone. Hematologic syndromes like erythrocytosis, thrombocytosis, eosinophilia and thrombophlebitis are covered as well treatments such as phle
Paraneoplastic syndromes are diseases or symptoms caused by cancer but not by direct local effects of tumors. They are mediated through cross-reacting antibodies, physiologically active factors, or metabolic pathway interference. Syndromes are classified as endocrine, neurological, mucocutaneous, hematological, or other. Common endocrine syndromes include Cushing's syndrome, SIADH, hypoglycemia, and hypercalcemia. Neurological syndromes are often antibody-mediated and include Lambert-Eaton myasthenic syndrome and paraneoplastic cerebellar degeneration. Dermatological manifestations incorporate lesions like acanthosis nigricans. Treatment focuses on managing symptoms and removing the underlying tumor.
This document provides an overview of paraneoplastic syndromes (PNS). Some key points:
1. PNS are clinical disorders associated with malignancies that are not directly caused by the primary tumor or metastases. They are often caused by tumor production of substances that directly or indirectly cause distant symptoms.
2. Endocrine PNS are characterized by excess production and abnormal regulation/peptide processing from atypical tissue sources, often neoplastic cells. Ectopic ACTH syndrome is discussed as an example.
3. Neurological PNS are often mediated by immune responses to onconeuronal antigens, resulting in infiltration of T cells, microglial activation, and neuronal loss. Specific antibodies and their
Management of malignant spinal cord compressionShreya Singh
This document summarizes the management of malignant spinal cord compression. It defines MSCC as cancer growth in or near the spine that presses on the spinal cord. Symptoms include back pain, motor deficits, and sensory deficits. Treatment involves corticosteroids, surgery, and radiotherapy. Surgery plus radiotherapy provides better outcomes than radiotherapy alone for patients with good performance status and at least 3 months life expectancy. Standard radiotherapy is 30 Gy in 10 fractions. Shorter courses are used when survival is poor. Surgery may be indicated for instability, intractable pain, or radioresistant cancers.
This document provides information on febrile neutropenia, including:
- It is a common and serious complication of cancer chemotherapy, especially in those with hematologic malignancies.
- Initial evaluation of febrile neutropenic patients includes assessing infection risk factors and sites, as well as collecting blood and other cultures.
- High-risk patients require intravenous empirical antibiotic therapy in the hospital, while low-risk patients may be treated orally or as outpatients.
- Empirical therapy typically involves a broad-spectrum beta-lactam with coverage against pseudomonas, with vancomycin or other anti-gram positive coverage only added if clinically indicated. Therapy is continued until marrow recovery from neutropenia
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
This document discusses tumor lysis syndrome (TLS), which can occur when tumors undergo rapid cell lysis and release intracellular contents into the bloodstream. TLS can cause electrolyte abnormalities and renal failure. It affects patients with highly proliferative tumors undergoing chemotherapy, radiation or other treatments. The document outlines risk factors, grading criteria, clinical manifestations, prevention strategies including hydration, uric acid reduction and dialysis, as well as treatment of established TLS complications. It also covers hyperleukocytosis, a related condition seen in some leukemia patients.
This document discusses paraneoplastic syndromes, which are clinical disorders associated with but not directly caused by malignant tumors. It describes several paraneoplastic endocrine, hematologic, neurological, dermatological, and other syndromes, listing their typical clinical presentations, associated laboratory abnormalities and cancers. It discusses evaluation, treatment and prognosis of these syndromes, noting that successful treatment of the primary tumor often leads to resolution of paraneoplastic symptoms.
This document discusses various paraneoplastic syndromes and their treatments according to Harrison's 18th Edition. It addresses endocrine syndromes like humoral hypercalcemia of malignancy, which can be treated by removing excess calcium from the diet and IV bisphosphonates. It also discusses ectopic vasopressin syndrome and its treatment through fluid restriction and vasopressin receptor antagonists. Cushing's syndrome caused by ectopic ACTH production is discussed alongside treatments like adrenalectomy, ketoconazole, and metyrapone. Hematologic syndromes like erythrocytosis, thrombocytosis, eosinophilia and thrombophlebitis are covered as well treatments such as phle
Paraneoplastic syndromes are diseases or symptoms caused by cancer but not by direct local effects of tumors. They are mediated through cross-reacting antibodies, physiologically active factors, or metabolic pathway interference. Syndromes are classified as endocrine, neurological, mucocutaneous, hematological, or other. Common endocrine syndromes include Cushing's syndrome, SIADH, hypoglycemia, and hypercalcemia. Neurological syndromes are often antibody-mediated and include Lambert-Eaton myasthenic syndrome and paraneoplastic cerebellar degeneration. Dermatological manifestations incorporate lesions like acanthosis nigricans. Treatment focuses on managing symptoms and removing the underlying tumor.
This document provides an overview of paraneoplastic syndromes (PNS). Some key points:
1. PNS are clinical disorders associated with malignancies that are not directly caused by the primary tumor or metastases. They are often caused by tumor production of substances that directly or indirectly cause distant symptoms.
2. Endocrine PNS are characterized by excess production and abnormal regulation/peptide processing from atypical tissue sources, often neoplastic cells. Ectopic ACTH syndrome is discussed as an example.
3. Neurological PNS are often mediated by immune responses to onconeuronal antigens, resulting in infiltration of T cells, microglial activation, and neuronal loss. Specific antibodies and their
Management of malignant spinal cord compressionShreya Singh
This document summarizes the management of malignant spinal cord compression. It defines MSCC as cancer growth in or near the spine that presses on the spinal cord. Symptoms include back pain, motor deficits, and sensory deficits. Treatment involves corticosteroids, surgery, and radiotherapy. Surgery plus radiotherapy provides better outcomes than radiotherapy alone for patients with good performance status and at least 3 months life expectancy. Standard radiotherapy is 30 Gy in 10 fractions. Shorter courses are used when survival is poor. Surgery may be indicated for instability, intractable pain, or radioresistant cancers.
This document provides information on febrile neutropenia, including:
- It is a common and serious complication of cancer chemotherapy, especially in those with hematologic malignancies.
- Initial evaluation of febrile neutropenic patients includes assessing infection risk factors and sites, as well as collecting blood and other cultures.
- High-risk patients require intravenous empirical antibiotic therapy in the hospital, while low-risk patients may be treated orally or as outpatients.
- Empirical therapy typically involves a broad-spectrum beta-lactam with coverage against pseudomonas, with vancomycin or other anti-gram positive coverage only added if clinically indicated. Therapy is continued until marrow recovery from neutropenia
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
This document discusses tumor lysis syndrome (TLS), which can occur when tumors undergo rapid cell lysis and release intracellular contents into the bloodstream. TLS can cause electrolyte abnormalities and renal failure. It affects patients with highly proliferative tumors undergoing chemotherapy, radiation or other treatments. The document outlines risk factors, grading criteria, clinical manifestations, prevention strategies including hydration, uric acid reduction and dialysis, as well as treatment of established TLS complications. It also covers hyperleukocytosis, a related condition seen in some leukemia patients.
A paraneoplastic syndrome is a disease or symptom that is caused by cancer but is not due to direct involvement of cancer cells. They occur in 10-15% of cancer patients and are typically seen in lung, breast, ovarian, and lymphoma cancers. Paraneoplastic syndromes can be endocrine, neurological, mucocutaneous, or hematological in nature. Common endocrine paraneoplastic syndromes include Cushing syndrome, SIADH, hypercalcemia, hypoglycemia, polycythemia, hyperaldosteronism, and carcinoid syndrome, which result from hormones or cytokines secreted by tumor cells.
The document discusses hepatocellular carcinoma (HCC). It is the most common type of primary liver cancer, accounting for 90% of cases. Risk factors include cirrhosis of the liver caused by hepatitis B, hepatitis C, alcohol use, and non-alcoholic fatty liver disease. Chronic hepatitis B infection significantly increases the risk. The risk of developing HCC is also higher in men than women and increases with age. Precancerous lesions can develop due to chronic liver damage and increase the risk of HCC.
Essential thrombocythemia (2019) by Dr Shami Bhagat SKIMSDr Shami Bhagat
1) Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by overproduction of platelets from a multipotent hematopoietic stem cell. It has a tendency for thrombosis and hemorrhage.
2) The main causes of ET are mutations in JAK2, CALR, and MPL genes which lead to autonomous platelet production.
3) Treatment involves low dose aspirin to prevent thrombosis and cytoreductive agents like hydroxyurea or interferon to reduce platelet counts and prevent complications. Treatment is aimed at symptom control and thrombosis prevention rather than cure.
Bladder cancer is the 7th most common cancer in the US. In 2014, there were 74,690 new cases and 15,580 deaths. Bladder cancer is more common in men than women. Risk factors include smoking, family history, occupational chemical exposure, and bladder infections. Symptoms include blood in the urine, frequent urination, and pain during urination. Diagnosis involves cystoscopy and biopsy. Staging uses CT, MRI, and PET scans to determine if the cancer has invaded the bladder wall or spread. Higher stage and grade cancers have a worse prognosis. Treatment and survival depend on the stage, with 5-year survival rates ranging from 96% for stage 0 to 5.5% for stage IV cancer
Tumour lysis syndrome (TLS) is a metabolic condition caused by the breakdown of malignant cells, characterized by electrolyte abnormalities like hyperuricaemia, hyperphosphataemia, hyperkalaemia and hypocalcaemia. It can occur before, during or after treatment for malignancy. Clinical TLS involves organ failure from electrolyte imbalances. Risk factors include extensive tumour burden and poor renal function. Prevention involves monitoring for symptoms and electrolyte levels before and after therapy. Treatment focuses on correcting electrolyte abnormalities through hydration, diuretics, binders, insulin therapy and dialysis if needed.
This document summarizes information about seminoma, a type of testicular cancer. It discusses the anatomy and epidemiology of testicular tumors. It describes risk factors, pathology, pathways of spread, clinical features, diagnostic workup and staging of seminoma. It provides details about management including surgery, radiation therapy and chemotherapy for different stages. It discusses follow-up protocols and results of therapy.
It describes the prevalence of Breast Cancer among BRCA 1/2 mutations with special consideration to biological background, detection and screening, actions taken upon discovering mutation carriers and whether we have a different therapeutic algorithm than sporadic cases. Special emphasis on the role of PARP inhibitors in the management of metastatic disease.
This document provides an overview of neuroblastoma, including its clinical presentation, pathology, risk grouping, diagnostic workup, prognostic factors, and management. Some key points:
- Neuroblastoma arises from neural crest tissue and is the most common extracranial solid tumor in children. Over 70% present with metastases.
- Risk grouping systems include INSS (International Neuroblastoma Staging System) and more recently INRG (International Neuroblastoma Risk Group) staging.
- Prognostic factors include age, stage, pathology, MYCN status, and other biomarkers.
- Treatment depends on risk but may include surgery, chemotherapy, radiation, stem cell transplant, and immunotherapy. Precise management
This document discusses various targeted cancer therapies including monoclonal antibodies, small molecule inhibitors, and other targeted agents. It describes key targets of these therapies such as protein kinases, growth factor receptors, angiogenesis pathways, and nuclear factors. Specific drugs are discussed that target ABL, EGFR, VEGFR, mTOR, MAPK pathways, and the proteasome. Resistance mechanisms and combination approaches are also mentioned.
Pancoast's tumor, also known as superior sulcus tumor, is a lung cancer that originates in the upper part of the lung near the shoulder blade. It presents with symptoms like arm or shoulder pain, Horner's syndrome, and weakness in hand muscles. Diagnostic imaging includes chest x-rays, CT scans, and MRI to determine the extent of involvement of nearby structures like the brachial plexus and vertebrae. Treatment typically involves chemotherapy, radiation therapy followed by surgical resection to remove the tumor. Prognosis depends on factors like involvement of lymph nodes or vertebrae, with 5-year survival rates ranging from under 10% to 40% depending on these factors.
Colorectal cancer is the third most common cancer in men and women in the US, with odds of around 5% of developing it. Screening colonoscopy is recommended every 10 years starting at age 50. Staging involves determining how deep the cancer has invaded the bowel wall (T stage) and if it has spread to lymph nodes (N stage). Treatment involves surgery with chemotherapy or radiation added for more advanced stages. New drugs have improved survival, which is around 65% at 5 years and varies by stage from 90% for local to 12% for distant disease.
The document discusses the process of tumor invasion and metastasis. It describes how tumor cells must go through a series of steps called the metastatic cascade to break away from the primary tumor and form secondary tumors elsewhere. This involves invasion of the extracellular matrix and vascular dissemination. The key steps of ECM invasion are: 1) changes in cell adhesion, 2) degradation of the ECM, 3) attachment to novel ECM components, and 4) migration of tumor cells through active proteolysis and locomotion. Genetic changes can cause variations in metastatic potential between cancer types by promoting epithelial-to-mesenchymal transition or affecting signaling pathways. Tumors can spread via lymphatics, direct seeding of body cavities,
Follicular lymphoma is the most common indolent non-Hodgkin lymphoma, accounting for about 45% of NHL cases. It involves B cells that are found in the germinal centers of lymph nodes. Key characteristics include a median age of 59 years at presentation, a male to female ratio of 1:1.7, and involvement of lymph nodes in the neck, underarms, or groin. The t(14;18) translocation results in overexpression of the BCL2 gene and inhibition of apoptosis. Treatment depends on the stage and grade of disease, and may include watchful waiting, chemotherapy, radiation therapy, immunotherapy, or stem cell transplantation.
This document summarizes guidelines for the management of febrile neutropenia. It describes definitions of fever and neutropenia and risk factors. Initial evaluation involves blood cultures, site-specific cultures as indicated, and monitoring. Risk is stratified using tools like the MASCC index. Prophylaxis includes hand hygiene, oral care, and sometimes antibiotics or antifungals. Empiric antibiotic therapy is recommended, with modifications based on risk and response. Therapy typically continues until resolution of fever and recovery of neutrophils. Empiric antifungals may be considered for persistent fever.
This document provides an overview of treatment options for advanced or metastatic prostate cancer. It discusses that androgen deprivation therapy (ADT) is usually the first line treatment and can involve medical or surgical castration. For patients where ADT is not suitable or becomes ineffective, there are secondary hormonal treatments and newer agents available, as well as chemotherapy. The document outlines considerations for intermittent versus continuous ADT and treatments after disease becomes castrate-resistant or progresses on docetaxel, including newer agents like abiraterone and enzalutamide. Symptom management is addressed in a separate resource.
Imatinib is the first FDA approved targeted protein kinase inhibitor for chronic myelogenous leukemia and gastrointestinal stromal tumors. It binds to and inactivates the BCR-ABL tyrosine kinase. Dasatinib and nilotinib are also BCR-ABL tyrosine kinase inhibitors approved for CML. Gefitinib, erlotinib and lapatinib inhibit the epidermal growth factor receptor tyrosine kinase and are approved for various cancers. Sunitinib, sorafenib, pazopanib, and vatalanib inhibit vascular endothelial growth factor receptors and are approved for renal cell carcinoma and other cancers. These oral tyrosine kinase inhibitors are important targeted cancer therapies.
Disease of older males.
The Philadelphia chromosome - BCR-ABL gene and it’s Tyrosine kinase protein – central to the pathogenesis.
Occurs in 3 phases
Imatinib has revolutionized the management
This document provides guidelines for the management of febrile neutropenia. It defines neutropenia and its levels of severity. It describes risk factors for infection and common pathogens. It outlines the evaluation, including diagnostic tests and imaging. It provides recommendations for empiric antibiotic therapy based on risk level. It also covers antifungal therapy, management of specific infections like typhlitis, and use of colony-stimulating factors. The goal is to guide clinicians in promptly diagnosing and treating potential infections in immunocompromised patients with febrile neutropenia.
This document discusses cancer and tuberculosis, two ongoing public health challenges. It provides statistics on the global burden of smoking, lung cancer, and tuberculosis. Key risk factors for lung cancer and TB are described, including smoking, genetics, and weakened immune systems. The document then focuses on a retrospective study of 365 tuberculosis patients in Romania, of which 18 also had cancer. Results found the majority were male smokers aged 36-80. Cancers were often late-stage at diagnosis. While TB treatment outcomes were typical, 12 of the 18 cancer patients ultimately died. The association between TB and cancer highlights the need for early cancer screening in high-risk groups.
This document discusses acute kidney injury (AKI), formerly known as acute renal failure. It defines AKI and provides causes and characteristics of pre-renal, renal, and post-renal AKI. Pre-renal AKI is caused by decreased renal perfusion due to issues like volume depletion or heart failure. Renal AKI can be caused by issues affecting the glomeruli, interstitium, or tubules, such as acute tubular necrosis. Post-renal AKI is due to urinary tract obstruction. The document outlines evaluation of AKI including history, exam, urine and serum tests, imaging, and novel biomarkers. It also discusses complications of AKI and general management strategies.
The document discusses acute pancreatitis, including:
1. It provides an overview of the normal anatomy and physiology of the pancreas, as well as the exocrine and endocrine functions.
2. It examines the causes, pathogenesis, clinical presentation, diagnosis, and severity scoring systems used to evaluate acute pancreatitis such as Ranson criteria.
3. It outlines the goals and approaches to treatment for both mild and severe acute pancreatitis, including supportive care, nutritional support, role of ERCP, and antibiotics for infected necrosis.
A paraneoplastic syndrome is a disease or symptom that is caused by cancer but is not due to direct involvement of cancer cells. They occur in 10-15% of cancer patients and are typically seen in lung, breast, ovarian, and lymphoma cancers. Paraneoplastic syndromes can be endocrine, neurological, mucocutaneous, or hematological in nature. Common endocrine paraneoplastic syndromes include Cushing syndrome, SIADH, hypercalcemia, hypoglycemia, polycythemia, hyperaldosteronism, and carcinoid syndrome, which result from hormones or cytokines secreted by tumor cells.
The document discusses hepatocellular carcinoma (HCC). It is the most common type of primary liver cancer, accounting for 90% of cases. Risk factors include cirrhosis of the liver caused by hepatitis B, hepatitis C, alcohol use, and non-alcoholic fatty liver disease. Chronic hepatitis B infection significantly increases the risk. The risk of developing HCC is also higher in men than women and increases with age. Precancerous lesions can develop due to chronic liver damage and increase the risk of HCC.
Essential thrombocythemia (2019) by Dr Shami Bhagat SKIMSDr Shami Bhagat
1) Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by overproduction of platelets from a multipotent hematopoietic stem cell. It has a tendency for thrombosis and hemorrhage.
2) The main causes of ET are mutations in JAK2, CALR, and MPL genes which lead to autonomous platelet production.
3) Treatment involves low dose aspirin to prevent thrombosis and cytoreductive agents like hydroxyurea or interferon to reduce platelet counts and prevent complications. Treatment is aimed at symptom control and thrombosis prevention rather than cure.
Bladder cancer is the 7th most common cancer in the US. In 2014, there were 74,690 new cases and 15,580 deaths. Bladder cancer is more common in men than women. Risk factors include smoking, family history, occupational chemical exposure, and bladder infections. Symptoms include blood in the urine, frequent urination, and pain during urination. Diagnosis involves cystoscopy and biopsy. Staging uses CT, MRI, and PET scans to determine if the cancer has invaded the bladder wall or spread. Higher stage and grade cancers have a worse prognosis. Treatment and survival depend on the stage, with 5-year survival rates ranging from 96% for stage 0 to 5.5% for stage IV cancer
Tumour lysis syndrome (TLS) is a metabolic condition caused by the breakdown of malignant cells, characterized by electrolyte abnormalities like hyperuricaemia, hyperphosphataemia, hyperkalaemia and hypocalcaemia. It can occur before, during or after treatment for malignancy. Clinical TLS involves organ failure from electrolyte imbalances. Risk factors include extensive tumour burden and poor renal function. Prevention involves monitoring for symptoms and electrolyte levels before and after therapy. Treatment focuses on correcting electrolyte abnormalities through hydration, diuretics, binders, insulin therapy and dialysis if needed.
This document summarizes information about seminoma, a type of testicular cancer. It discusses the anatomy and epidemiology of testicular tumors. It describes risk factors, pathology, pathways of spread, clinical features, diagnostic workup and staging of seminoma. It provides details about management including surgery, radiation therapy and chemotherapy for different stages. It discusses follow-up protocols and results of therapy.
It describes the prevalence of Breast Cancer among BRCA 1/2 mutations with special consideration to biological background, detection and screening, actions taken upon discovering mutation carriers and whether we have a different therapeutic algorithm than sporadic cases. Special emphasis on the role of PARP inhibitors in the management of metastatic disease.
This document provides an overview of neuroblastoma, including its clinical presentation, pathology, risk grouping, diagnostic workup, prognostic factors, and management. Some key points:
- Neuroblastoma arises from neural crest tissue and is the most common extracranial solid tumor in children. Over 70% present with metastases.
- Risk grouping systems include INSS (International Neuroblastoma Staging System) and more recently INRG (International Neuroblastoma Risk Group) staging.
- Prognostic factors include age, stage, pathology, MYCN status, and other biomarkers.
- Treatment depends on risk but may include surgery, chemotherapy, radiation, stem cell transplant, and immunotherapy. Precise management
This document discusses various targeted cancer therapies including monoclonal antibodies, small molecule inhibitors, and other targeted agents. It describes key targets of these therapies such as protein kinases, growth factor receptors, angiogenesis pathways, and nuclear factors. Specific drugs are discussed that target ABL, EGFR, VEGFR, mTOR, MAPK pathways, and the proteasome. Resistance mechanisms and combination approaches are also mentioned.
Pancoast's tumor, also known as superior sulcus tumor, is a lung cancer that originates in the upper part of the lung near the shoulder blade. It presents with symptoms like arm or shoulder pain, Horner's syndrome, and weakness in hand muscles. Diagnostic imaging includes chest x-rays, CT scans, and MRI to determine the extent of involvement of nearby structures like the brachial plexus and vertebrae. Treatment typically involves chemotherapy, radiation therapy followed by surgical resection to remove the tumor. Prognosis depends on factors like involvement of lymph nodes or vertebrae, with 5-year survival rates ranging from under 10% to 40% depending on these factors.
Colorectal cancer is the third most common cancer in men and women in the US, with odds of around 5% of developing it. Screening colonoscopy is recommended every 10 years starting at age 50. Staging involves determining how deep the cancer has invaded the bowel wall (T stage) and if it has spread to lymph nodes (N stage). Treatment involves surgery with chemotherapy or radiation added for more advanced stages. New drugs have improved survival, which is around 65% at 5 years and varies by stage from 90% for local to 12% for distant disease.
The document discusses the process of tumor invasion and metastasis. It describes how tumor cells must go through a series of steps called the metastatic cascade to break away from the primary tumor and form secondary tumors elsewhere. This involves invasion of the extracellular matrix and vascular dissemination. The key steps of ECM invasion are: 1) changes in cell adhesion, 2) degradation of the ECM, 3) attachment to novel ECM components, and 4) migration of tumor cells through active proteolysis and locomotion. Genetic changes can cause variations in metastatic potential between cancer types by promoting epithelial-to-mesenchymal transition or affecting signaling pathways. Tumors can spread via lymphatics, direct seeding of body cavities,
Follicular lymphoma is the most common indolent non-Hodgkin lymphoma, accounting for about 45% of NHL cases. It involves B cells that are found in the germinal centers of lymph nodes. Key characteristics include a median age of 59 years at presentation, a male to female ratio of 1:1.7, and involvement of lymph nodes in the neck, underarms, or groin. The t(14;18) translocation results in overexpression of the BCL2 gene and inhibition of apoptosis. Treatment depends on the stage and grade of disease, and may include watchful waiting, chemotherapy, radiation therapy, immunotherapy, or stem cell transplantation.
This document summarizes guidelines for the management of febrile neutropenia. It describes definitions of fever and neutropenia and risk factors. Initial evaluation involves blood cultures, site-specific cultures as indicated, and monitoring. Risk is stratified using tools like the MASCC index. Prophylaxis includes hand hygiene, oral care, and sometimes antibiotics or antifungals. Empiric antibiotic therapy is recommended, with modifications based on risk and response. Therapy typically continues until resolution of fever and recovery of neutrophils. Empiric antifungals may be considered for persistent fever.
This document provides an overview of treatment options for advanced or metastatic prostate cancer. It discusses that androgen deprivation therapy (ADT) is usually the first line treatment and can involve medical or surgical castration. For patients where ADT is not suitable or becomes ineffective, there are secondary hormonal treatments and newer agents available, as well as chemotherapy. The document outlines considerations for intermittent versus continuous ADT and treatments after disease becomes castrate-resistant or progresses on docetaxel, including newer agents like abiraterone and enzalutamide. Symptom management is addressed in a separate resource.
Imatinib is the first FDA approved targeted protein kinase inhibitor for chronic myelogenous leukemia and gastrointestinal stromal tumors. It binds to and inactivates the BCR-ABL tyrosine kinase. Dasatinib and nilotinib are also BCR-ABL tyrosine kinase inhibitors approved for CML. Gefitinib, erlotinib and lapatinib inhibit the epidermal growth factor receptor tyrosine kinase and are approved for various cancers. Sunitinib, sorafenib, pazopanib, and vatalanib inhibit vascular endothelial growth factor receptors and are approved for renal cell carcinoma and other cancers. These oral tyrosine kinase inhibitors are important targeted cancer therapies.
Disease of older males.
The Philadelphia chromosome - BCR-ABL gene and it’s Tyrosine kinase protein – central to the pathogenesis.
Occurs in 3 phases
Imatinib has revolutionized the management
This document provides guidelines for the management of febrile neutropenia. It defines neutropenia and its levels of severity. It describes risk factors for infection and common pathogens. It outlines the evaluation, including diagnostic tests and imaging. It provides recommendations for empiric antibiotic therapy based on risk level. It also covers antifungal therapy, management of specific infections like typhlitis, and use of colony-stimulating factors. The goal is to guide clinicians in promptly diagnosing and treating potential infections in immunocompromised patients with febrile neutropenia.
This document discusses cancer and tuberculosis, two ongoing public health challenges. It provides statistics on the global burden of smoking, lung cancer, and tuberculosis. Key risk factors for lung cancer and TB are described, including smoking, genetics, and weakened immune systems. The document then focuses on a retrospective study of 365 tuberculosis patients in Romania, of which 18 also had cancer. Results found the majority were male smokers aged 36-80. Cancers were often late-stage at diagnosis. While TB treatment outcomes were typical, 12 of the 18 cancer patients ultimately died. The association between TB and cancer highlights the need for early cancer screening in high-risk groups.
This document discusses acute kidney injury (AKI), formerly known as acute renal failure. It defines AKI and provides causes and characteristics of pre-renal, renal, and post-renal AKI. Pre-renal AKI is caused by decreased renal perfusion due to issues like volume depletion or heart failure. Renal AKI can be caused by issues affecting the glomeruli, interstitium, or tubules, such as acute tubular necrosis. Post-renal AKI is due to urinary tract obstruction. The document outlines evaluation of AKI including history, exam, urine and serum tests, imaging, and novel biomarkers. It also discusses complications of AKI and general management strategies.
The document discusses acute pancreatitis, including:
1. It provides an overview of the normal anatomy and physiology of the pancreas, as well as the exocrine and endocrine functions.
2. It examines the causes, pathogenesis, clinical presentation, diagnosis, and severity scoring systems used to evaluate acute pancreatitis such as Ranson criteria.
3. It outlines the goals and approaches to treatment for both mild and severe acute pancreatitis, including supportive care, nutritional support, role of ERCP, and antibiotics for infected necrosis.
Intravenous fluids crystalloids and colloidsomar143
Dr. Omar Kamal Ansari from the department of anaesthesiology discusses intravenous fluid therapy. He describes various types of intravenous fluids including crystalloids like normal saline and Ringer's lactate, colloids like albumin and hetastarch, and discusses their indications, contraindications, and complications. He also discusses fluid requirements, osmolality, electrolyte balances, and principles of intravenous fluid administration.
The document discusses renal system considerations for anesthesia. The kidneys play a vital role in fluid, electrolyte and acid-base balance. Patients with renal failure are at risk of fluid imbalance, electrolyte disturbances and acid-base abnormalities. Anesthesiologists must carefully manage fluids, monitor for hypotension, and use appropriate drugs that are metabolized by the liver rather than the kidneys to avoid further renal injury.
- The document discusses evaluation and management of hypercalcemia. The most common causes are primary hyperparathyroidism and malignancy. Diagnostic workup includes serum calcium, PTH, and history of medications. Hypercalcemic crisis is a medical emergency requiring aggressive intravenous hydration and diuretics, calcitonin, bisphosphonates, or dialysis. Optimal treatment involves identifying and addressing the underlying cause of hypercalcemia.
Diuretics are drugs that promote increased production of urine. The main classes of diuretics are loop diuretics, thiazide diuretics, carbonic anhydrase inhibitors, osmotic diuretics, and aldosterone antagonists. Loop diuretics such as furosemide act on the loop of Henle and are highly effective. Thiazide diuretics such as hydrochlorothiazide are commonly used to treat hypertension and edema. Carbonic anhydrase inhibitors reduce fluid production in various tissues. Osmotic diuretics work by increasing osmotic pressure in the kidney tubules. Aldosterone antagonists such as spironolactone counteract sodium retention caused by
A power point presentation on "Drugs affecting coagulation and anticoagulants" suitable for undergraduate medical students. Also suitable for Post Graduate students of Pharmacology and Pharmaceutical Sciences.
This document discusses adrenal gland disorders. It describes the anatomy and functions of the adrenal cortex and medulla. It then covers various adrenal disorders including adrenal hypofunction (such as Addison's disease), hyperfunction (Cushing's syndrome and hyperaldosteronism), congenital adrenal hyperplasia, and adrenal crisis. It provides details on the causes, clinical presentations, investigations, and management of these various adrenal disorders.
This document provides an overview of endocrine disorders and endocrine system dysfunction. It discusses the roles of various hormones and endocrine glands like the hypothalamus, pituitary gland, thyroid gland, parathyroid glands, adrenal glands, and pancreas. It also summarizes different endocrine diseases, their signs and symptoms, diagnostic tests, and treatment and management approaches.
Acute pancreatitis is an inflammatory process of the pancreas that is usually painful and self-limited. The most common causes are gallstones and alcohol abuse. In mild cases, patients can resume oral intake after symptoms improve. In severe cases, supportive care including fluid resuscitation and nutritional support via enteral feeding is important. Enteral nutrition is preferred over total parenteral nutrition due to lower risks of infection and lower costs with similar or better outcomes. The development of pancreatic necrosis is a marker of severe disease and risk of complications.
This document provides information on acute pancreatitis including its definition, causes, pathogenesis, clinical presentation, diagnosis, severity scoring systems, treatment goals, and approaches to nutrition. The key points are:
1. Acute pancreatitis is an inflammatory process of the pancreas that is usually painful and self-limited, with pancreatic function and morphology returning to normal after attacks. Gallstones and alcohol abuse are the most common causes.
2. The pathogenesis involves premature activation of digestive enzymes within the pancreas, leading to autodigestion and systemic complications in severe cases. Scoring systems like Ranson criteria and CT severity index are used to predict severity and guide management.
3. Treatment goals are to limit systemic
This document provides information on acute pancreatitis including its definition, causes, pathogenesis, clinical presentation, diagnosis, severity scoring systems, treatment goals, and approaches to nutrition. The key points are:
1. Acute pancreatitis is an inflammatory process of the pancreas that is usually painful and self-limited, with pancreatic function and morphology returning to normal after attacks. Gallstones and alcohol abuse are the most common causes.
2. The pathogenesis involves premature activation of digestive enzymes within the pancreas, leading to autodigestion and systemic complications in severe cases. Scoring systems like Ranson criteria and CT severity index are used to predict severity and guide management.
3. Treatment goals are to limit systemic
The document discusses various topics related to nephrology including renal function, acute kidney injury, causes of polyuria, water balance, and fluid resuscitation. It provides definitions, classifications, diagnostic approaches, and management strategies for different kidney conditions.
Hyperkalemia is a life-threatening electrolyte imbalance where potassium levels are elevated. The case discusses a 52-year-old man with diabetes and hypertension who developed quadriparesis due to severe hyperkalemia. His hyperkalemia was caused by multiple factors, including insulin deficiency from uncontrolled diabetes, acidosis, renal dysfunction from medications like an ACE inhibitor and spironolactone, and decreased distal delivery of sodium and water due to his kidney issues. He was treated with dialysis to rapidly lower his potassium level and remove the implicated medications causing his hyperkalemia.
Acute renal failure (ARF), also known as acute kidney injury (AKI), can have various causes including pre-renal, renal, and post-renal factors. The definition includes an abrupt decline in kidney function over 48 hours seen through rises in creatinine or decreases in urine output. Evaluation involves assessing volume status, obtaining urine and blood tests, and ultrasound. Treatment focuses on identifying and treating the underlying cause, providing supportive care like fluid management, and potentially initiating renal replacement therapy for complications such as fluid overload or electrolyte imbalances. Prognosis depends on the severity and underlying etiology of the AKI.
This document discusses hypercalcemia and hypocalcemia in the ICU. It covers the normal levels and functions of calcium, pathophysiology, clinical manifestations, diagnostic evaluation, and treatment options for hypercalcemia and hypocalcemia. The main treatment approaches for hypercalcemia include intravenous fluids, furosemide, bisphosphonates, calcitonin, and steroids. For hypocalcemia, treatment focuses on oral calcium, intravenous calcium, vitamin D, and magnesium supplementation.
Acute Kidney Injury; A case study with detailed etiology and managementkiyingiedison
- A 57-year-old female presented with decreased consciousness, decreased urine output, and vomiting. She was diagnosed with severe malaria and acute kidney injury.
- Laboratory tests showed acute kidney injury with a creatinine of 987umol/L. She received hemodialysis, IV antibiotics, and supportive care.
- Acute kidney injury is defined as an abrupt decrease in kidney function causing retention of waste and electrolyte dysregulation. It involves increased creatinine and decreased urine output. Management focuses on treating the underlying cause, maintaining fluid balance, and correcting biochemical abnormalities.
The document discusses acute kidney injury (AKI), including its definition, causes, evaluation, management, and complications. AKI is defined as an abrupt loss of kidney function leading to accumulation of waste and dysregulation of fluid and electrolytes. It can be caused by prerenal issues like decreased blood flow, intrinsic renal issues like nephrotoxins or glomerular disease, or postrenal issues like urinary obstruction. Evaluation includes labs, imaging, and potentially biopsy. Management focuses on fluid management, electrolyte disturbances, acidosis, nutrition, and dialysis if needed. Complications can include issues like heart problems, infections, bleeding, and mental status changes.
Postpartum blues includes an array of psychiatric manifestations occurring in the period of post-partum, due to hormonal imbalance. Knowing in detail will help for quicker diagnosis and better outcomes.
Prepared in December, 2017.
This is a ppt presentation regarding Acute Hyperglycemic Emergencies we face in routine clinical practices and their management
from Harrison's Principles of Medicine and Paul Marino Emergency Management book
By
Dr.V.B.Kasyapa. J
(MD GM)
This document discusses the approach to anemia. It defines anemia as having insufficient red blood cells or hemoglobin to meet physiological needs. Common symptoms include fatigue, shortness of breath, and palpitations. Clinical evaluation involves assessing symptoms to determine the potential cause, such as blood loss, inflammation, or nutritional deficiencies. Laboratory investigations include complete blood count, iron studies, bone marrow examination, and tests for hemolysis. Anemia is classified as hypo-proliferative, maturation disorders, blood loss, or hemolysis. Treatment depends on the underlying cause and may involve iron supplementation, erythropoietin, vitamin B12/folate, or splenectomy.
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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
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
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. Definition
• Disorders that accompany benign or
malignant tumors, but are not directly related
to mass effects or invasion
• Almost every tumor has the potential
3. Endocrinal PNS
• It may be Eutopic (natural production site)/ Ectopic (atypical production
site)
• Ectopic expression is often a quantitative change rather than an absolute
change in tissue expression
– Abnormal regulation (defective feedback control)
– Abnormal processing (large, unprocessed precursors)
– Abnormal hormone expression (d/t genetic rearrangements)
• If no clinical presentation; it is an epiphenomenon associated with tumor.
4. Examples
Translocation of PTH gene High levels of PTH expression in other
gland
Genetic rearrangements in
Lymphoma/Leukemia
Growth advantage & altered cellular
differentiation & function
Cellular de-differentitation
(partial/selective depression) in SCLC
poor development PTHrP (PTH related
protein) of early development stage
proteins (hCG, alpha PP) are liberated
Epigenetic modifications that alter
transcriptional repression
microRNA expression
5. • In SCLC,
– Neuro endocrine phenotype by
• Basix-helix-loop-helix(bHLH) transcription factor
Human achaetescute homologue 1(hASH-1)
High levels -> Ectopic ACTH
• Hairy enhancer of split 1(HFS-1)
Notch proteins
– Abnormal expression -> Eutopic ↑ ACTH (cell proliferation&
differentiation)
6. Humoral Hypercalcemia of
Malignancy (HHM)
• (MC) in
– Lung, head & neck, skin, esophagus, breast, GUT,
multiple myeloma, lymphomas
• MOA:
– Over production of PTHrP (MC)
– PTHrP from bone mets
– Over production of 1,25-dihydroxy vit D
– Tumor induced production of osteolytic cytokines &
inflammatory mediators & Osteoclastic activation
factors
7. PTHrP
• ParaTHarmone related Protein
• Normally produced during development & cell
renewal
• MOA:
– Binds to PTH receptors -> hyperparathyroidsm like
features
• Actions:
– Skeletal development, regulates cellular proliferation
& differentiation (skin, BM, breast, hair follicles)
8. • PTHrP increased production d/t
– Mutation in oncogenes
– Altered expression of viral/cellular transcription
factors
– Local growth factors
• PTHrP -> pro-survival AKT pathway & Chemokine
receptor CXR4
9. Bone mets TGF-β
Gli transcription
factor & hedgehog
pathways
PTHrPBreast carcinoma
direct local lysis of
bone
PTHrP
Adult T cell
lymphoma (HTLV-
1)
trans activating
Tax protein
PTHrP promotor
activation
PTHrP
12. Diagnosis
• Unlike hyperparathyroidsm
– ↓/Ⓝ 1,25 – dihydroxy vitD
– Decreased PTH
– Loss of normal coupling of bone formation & resorption
• Like Hyperparathyroidsm
– Hypercalemia >3.5 mmol/L (Bone, Groan, Moan, Stone)
– ↑ nephrogenous cAMP excretion
– Metabolic alkalosis
– Hypophoshatemia
– Hyperchloremic metabolic acidosis (less)
13. • Subtle variations are due to
– Receptor activation by PTH/PTHrP
– Other cytokines by Malignant cells
• PTHrP measurement (single/double ab, different epitope)
– Ⓝ people – low
– Preg/lactation/tumor – high
• Symptoms
– Weight loss, Fatigue, Muscle weakness, Unexplained skin rash, Other features of
malignancy/PNS
• BM biopsy in anemia/ abnormal smear
• Bone scan with technetium-labled bisphosphonate for osteolytic mets
(↑sensitivity, ↓specificity)
• Confirm by X-Ray
14. Therapy
• Removal of excess Ca in diet, medication & IV
solutions
• Saline rehydration depending on
comorbidities 200 – 500 ml/hr
• Forced diuresis 20 – 80 mg IV Furosemide
– Add in comorbidities & life threatening conditions
– Always use after complete rehydration
• Oral phosphorus 250 mg Neutro-Phos 3-4/day
– Until S.Phosphorus >1 mmol/L (>3 mg/dl)
15. • Bisphosphonates
– Palmidronate 60 – 90 mg IV
– Zoledronate 4 – 8 mg IV
– Etidronate 7.5 mg/kg/day PO for 3-7 consecutive days
– Useful within 1-2 days & for several weeks
• Dialysis (if bisphosphonates are not enough/
contraindicated/ severe)
• Previously,
– Calcitonin 2 – 8 U/kg SC 6-12 hrly
– Mithramycin
– Now only for rapid corection of severe disease with
unavailable dialysis
16. • Glucocorticoids
– Prednisolone 40 – 100 mg PO in 4 divided doses
– For Lymphomas, Multiple myeloma, Leukemia
• In extensive cases
– Left untreated as it has sedation effect
21. • MOA
– Vasopressin gene activation in tumor cell
– Associated Oxytocin gene expression
– De-repression of locus
– ↑ ADH
• ↓ thirst
• ↑ water retention
– Prolonged ADH action resets osmostats in
hypothalamus, vasopressin secretion
– If additional free water intake/IV fluids increase
causes quick worsening
22. Clinical features
• Symptoms depends on,
– Degree & rapidity of Na levels
– (MC) Chronic
• Mild fatigue, confusion, falls, attention deficit
– Severe hyponatremia <115 mEq/L
– Hypoosmolality odema of brain cells ↓brain
electrolyte content loss of organic solutes such as
creatinine & aminoacids
– Acute Na (<48 hrs)
• Nausea, vomiting, headache, seizures, respiratory arrest,
death
23. Diagnosis
Essential features Remarks
• Plasma osmolality <275
mOsm/kg of water
• Ruleout
• Hyponatremia with Ⓝ/↑ plasma osmolality
• Translocation by ↑ glucose
• Pseudo-hyponatremia by hyperlipidemia/hyperproteinemia
• Urine osmolality
>100mOsm/kg of water with
hypotonicity
• Rule out
• Beer potomania
• Polydipsia
• Clinical euvolemia • Absence of signs of volume depletion by renal/extra-renal
• Dry mucus membranes, tachycardia, orthostasis
• Volume overload by RF, Nephrotic syndrome, cirrhosis, CHF
• Edema, ascites, JVP↑
• Urinary Na >40mmol/L with Ⓝ
dietary intake
• Ⓝ thyroid & adrenal
formation
• No recent use of diuretic
24. Supplementary features
• ↓ serum uric acid < 4 mg/dl
• ↓ BUN < 10 mg/dl
• ↑ fractional excretion of Na > 1%
• ↑ fractional excretion of urea >55%
• Failure to correct hyponatremia with 2L of NS
• Correction of hyponatremia with fluid restriction
• Abnormal result of Water load test
• Inability to excrete 90% of 20mg/kg water load in 4 hrs (or)
• Failure to achieve urine osmolality < 100 mOsm/kg of water
• ↑ serum ADH despite of hypotonicity & clinical euvolemia
25. Management
• Indirect
– Cancer-specific therapy (less useful)
• In non severe
– Fluid restriction < 800 ml/day (< daily insensible
losses + urine ouput)
• Slow improvement, low compliance, insufficient for
symptomatic
– Urea oral administration 30 gm/day
• Osmotic diuresis, ↑ water excretion
• Poor palatability
26. – Demclocycline 300 – 600 mg BD
• Unpredictable onset
• GI intolerance, photosensitivity, azotemia
– Lithium
• Dysregulation of AQP-2
• Interstitial nephritis, ESRD, ↓efficacy of Demeclocycline
– 3% NaCl infusion 8-12 mmol/L correction/24 hrs
Initial infusion rate = Wt(kg) x rate of correction
• Add loop diuretic 20-40 mg in cardiac patients
• Goal: achieve safe serum Na levels
– ≥120 mmol/L (or) correction of 18 mmol/L
27. • Direct – Vasopressin antagonists
– Penetrate deep compared to ADH
– ↓synthesis/ ↓transport of AQP-2 & ↓free water
reabsorption(aquaresis) & ↑urine volume
– Only for Euvolemic/Hypervolemic Hyponatremia
– CI: Hypovolemia
28. – Conivaptan:
• V1a, V2 receptor inhibitor
• IV
• Loading dose: 20 mg over 30 min
• Maintanance dose: 40 mg/day continuous infusion for
4 days
• Erythema, phlebitis, swelling
• Large vein with site change every 24 hrly
• Interactions: with statins, CCBs, BZDs, antifungals,
chemotherapy(vinka alkaloids, etoposide)
29. – Tolvaptan:
• V2 selective, No intrinsic agonistic activity
• 15 mg PO OD 4 days 60 mg PO OD
• Significant ↑in first 4 days & at 30th day
• Increased thirst, dry mouth, increased urination,
polydipsia
• For Mild, Moderate & Severe asymptomatic
hyponatremia
• Not for Symptomatic (only 3% NaCl)
30. Osmotic Demyelination Syndrome
(ODS)
Rapid ↑in S.Na
brain cells reverse it by loss
of solute by ↑ production
of organic osmolytes &
inorganic ions
prevent shift of water to
outside the cell
31. • RF: S.Na ≤105 mmol/L, hypokalemia, alcoholism,
malnutrition, advanced liver disease
• C/F:
– initial symptomatic improvement
– In few days, new/progressive neurologic symptoms
(confusion to spastic quadriplegia, dysarthria, dysphagia)
• MRI: hypodense non-enhancing (T1),hyperdense (T2)
Overwh
elmed
shift
shrinkage
of glial
cells &
cell
damage
due to
burden
disruption
of BBB
inflammato
ry
mediators
damage
oligodendr
ocytes
demyeli
nation
33. • POMC gene codes for ACTH, MSH(Melanocyte
stimulating hormone), β-lipoprotein, etc…
Abundant, aberrant expression
of Internal promotor in tumor
cells (proximal to third exon)
Codes for ↑ACTH production
No signal sequence for protein
processing
Not secreted (or) large,
biologically inactive fragments
secreted
Less abundant,
unregulated expression
of same promotor in
pituitary cells
↑production of Ⓝ
ACTH
35. Ectopic
expression of G-
protein coupled
receptors in
adrenal medulla
GIP related
receptors
Meals induced
GIP production
Activates
receptors in
Adrenal medulla
Adrenal growth
&
↑glucocorticoid
production
36. Clinical features
• Usually less marked compared to other ectopic
ACTH producing causes
– d/t brief exposure periods, cancer cachexia
• Through mineralocorticoid receptors (usually
action is blocked by 11β-Hydroxysteorid
dehydrogenase type II enzyme. But now
overwhelmed)
– Fluid retension, HTN, hypokalemia
• MSH activity
– ↑pigmentation
38. Diagnosis
• If known malignancy easy to find
• Urine free cortisol 2 – 4 x Ⓝ
• Plasma ACTH >22 pmol/L (>100 pg/ml)
– Suppressed in ACTH-independent Cushing’s
• High dose Dexamethasone test 8 mg PO
early morning
– Suppress ACTH (~80%) in pituitary adenomas
– Fail (~90%) in ectopic ACTH
– Can suppress in Bronchial & other carcinoids (by
feedback regulation)
39. • Adrenal blockade with Metyrapone
– Can be done in Carcinoids
• Petrosal sinus catheterisation CRH
stimulation 3:1(petrosal:peripheral) ACTH
pituitary source
• Imaging studies,
– For carcinoids, biopsy
• PET/Octreotide scan,
– For source identification
40. Management
• Treat Underlying tumor: not sufficient
• Adrenalectomy,
– If operating for a tumor
– Otherwise favourable outcome (carcinoids)
– Main tumor unresectable
• Medical blockade (MC)
– Metyrapone 250 – 500 mg PO 6th hrly
– Mitotane 3 – 6 gm PO in 4 divided doses
– Ketoconazole 300 – 600 mg BD PO
– Always combine with glucocorticoid replacement
41. Tumor induced Hypoglycemia
• (MC) with Mesenchymal tumors, hemangio
pericytomas, HCC, Adrenal Ca.
• MOA,
– ↑IGF II secretion
– Large size
• Diagnosis,
– ↓S.Glucose, ↓S.Insulin, Ⓝ/↑S.IGF II(d/t
precursor), Symp. Of Hypoglycemia, ↑IGF II
mRNA expression
42. IGF II gene
(11p15)
Biallelic expression by loss of methylation &
loss of imprinting
Gene induction
↑IGF II production
Supress
GH/Insulin/IGF I
Supress IGF Binding Protein
3(IGFBP3)/ALS(Acid Labile Subunit)
Sequesters IGF II Small circulating complex formation
Greater access to Insulin to target tissues
Circulating binding protein
alterations
↑IGF II bioavailability
Imprinted
43. Treatment
• Avoid hypoglycemia causing drugs
• Treat underlying malignancy (↓ attack rate)
• Frequent meals, IV glucose (during fasting &
sleep)
• Glucagon, glucocorticoids,
– To ↑glucose production
44. Excess Human chorionic gonadotropin
• It has α(MC) & β subunits
• Eutopic
– Trophoblastic tumor
• Ectopic
– Testicular embryonal tumor
– Germ cell tumor
– Extragonadal germinoma
– Lung cancer
– Hepatoma
– Pancreatic isletcell tumor
45. • In men,
– ↑steroidogenesis in Leydig cells & ↑aromatase
activity ↑ estrogen & testosteron
gynaecomastia & precocious puberty
• In women,
– It is asymptomatic
• Serum hCG levels
• Treat underlying cause
47. Phosphatoin
(Fibroblast Growth
Factor-23)
Ternary complex
with klotho protein
& Renal FGF
receptors
↓↓renal
phosphorus
reabsorption
• ↓ conversion of 25-hydroxy vitD 1,25-dihydroxy vitD
• Caused in
• Benign mesenchymal tumors (skeletal extremeties/head)
• Hemangiopericytoma
• Fibroma
• Gaint cell tumors
• Sarcomas
• Prostate & lung Ca.
• Octreotide scan may be useful
• Removal of tumor, reverses the pathlogy
• Supplement phosphates & vit D
• Octrotide: may decrease renal wasting (in pts with Somatostatin receptor
subtype-2)
48. Hematological PNS
• These do not include abnormal cells in
lymphomas or leukemias
• These are PNS caused by solid tumors causing
blood cell abnormalities by humoral
mechanisms
49. Erythrocytosis
tumor
RCC, HCC, Cerebellar hemangioblastoma
EPO↑
Rise in hematocrit
>52% in male
>48% in
Female
Hematocrit Ⓝ
Other tumors
Lymphokines ↑ &
other hormones
50. • Usually asymptomatic
• Sometimes DVT
• In suspected malignancy, with ↑hmt with
↑EPO is confirmative
• Remove underlying cause
• If not operable phlebotomy
51. Granulocytosis
• >8000/µL is seen in tumors
• May be d/t,
– Non PNS (infection, tumor necrosis, steroid
administration, etc…)
– PNS (↑plasma/urinary proteins like G-CSF, GM-CSF &
IL6)
– Idiopathic
• Lung & GI tumors (MC), Breast Ca., Brain &
Ovarian tumors, HL, RCC
53. Thrombocytosis
• >400000/µL
• D/t,
– ↑IL6 ↑production in-vitro & in-vivo
– ↑thrombopoeitin ↑proliferation of megakaryocytes & ↑platelet production
– Idiopathic
• Usually asymptomatic; no direct relation with thrombosis
• Lung & GI tumors (40%), breats, ovarian, endometrial Ca., lumphomas
• Associated with advanced stage & poor prognosis
• No treatment; treat underlying tumor
54. Eosinophilia
• Translocation of 5q ↑IL5 Eosinophilia
• Asymptomatic
• Severe (>5000/µL) – chest tightness, wheeze
• In lymphoma(10%), lung, cervical, GI, renal & breast tumors
• Hemogram & CXR PA (diffuse pulmonary inflitrates)
• Treat underlying tumor
• Oral/inhaled corticosteroids
• IL5 antagonists(under trails)
55. Thrombophlebitis
• (MC) thrombotic conditions in cancer pt
– DVT, Pulmonary Embolism
• Migratory thrombophlebitis in cancer pt
– Trousseau sydrome
– (MC) with Visceral Ca. (pancreatic Ca.)
– Initial symptom
• MOA,
– Immobilisation, post op bed rest, tumor obstruction,
procoagulants & cytokines from tumor, inflammation causing
platelet adhesion & aggregation, endothelial damage d/t
chemotherapy (Bleomycin, L-asparginase, thalidomide
analogues, cisplatin, busulfan, carmustin), association of
primary thrombotic (APS)
56. • C/f:
– Swelling, pain in the leg
– Tenderness, warmth, redness
– Symp.& signs Of pulm embolism (dyspnoea, chest
pain, syncope, tachycardia, cyanosis, hypotension)
– With no H/o cancer
• Will be found in 1 year
• Lung, pancreatic, GI, ovarian, GU, lymphomas
& brain tumors
57. • Diagnosis,
– Impedence plethysmography
– b/l compression USG (noncompressable segment)
– Venography (filling defect)
– Elevation of D-dimer (not reliable much compared to
non-cancerous; ↑ after 65yrs d/t ↑thrombin
deposition & turnover)
– CXR, ECG, ABG, VQ scan
– Pulmonary angiogram (final resort)
– No need to look for cancer in a case of
thrombophlebitis; but look in case of migratory
thrombophlebitis
58. • Treatment,
– UFH/LMWH IV till INR 2-3
• hemorrhagic brain mets, pericardial effusion & proximal DVT
put an IVC filter(greenfield)
– Warfarrin 3 – 6 months
– LMHW 6 months
– Pneumatic boots (can be used for surgery going pt)
– Prophylaxis in,
• Breast Ca. going for chemo, pts with implanted catheters,
hospitalized & receiving thalidomide analogues
• Routine use during chemo is not indicated
• With LMWH/Low dose Aspirin