This document reviews tumor lysis syndrome (TLS), a potentially life-threatening condition caused by the rapid breakdown of tumor cells during chemotherapy or other treatments. It discusses the pathogenesis and risk factors for TLS and provides recommendations for management. TLS is most common in patients with high-proliferating hematological malignancies like acute leukemias and lymphomas. Risk factors include the type and extent of cancer, chemotherapy regimen, age, and preexisting kidney impairment. Management involves aggressive hydration, monitoring and correcting electrolyte abnormalities, controlling uric acid levels, and dialysis for acute kidney injury. TLS requires prompt treatment to prevent complications and interruptions to cancer treatment.
This document outlines a research protocol to study neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) as predictors of systemic inflammation and chronic illness in pre-surgery patients. The study will retrospectively analyze data from 1000 patients who attended a preadmission clinic between January and April 2013. Medical history, exam findings, and blood test results will be collected to calculate NLR and PLR ratios and examine their relationship to inflammation and health conditions. The goal is to determine the prevalence of elevated ratios and their ability to predict surgical risk factors.
This document provides an overview of Hodgkin lymphoma (HL), including:
- HL is a malignancy of mature B lymphocytes that represents 10% of lymphomas diagnosed annually.
- Classical HL has high cure rates of over 85% with radiation and chemotherapy. However, late therapy-related toxicities are a new challenge.
- Staging is important for selecting appropriate therapy intensity, with early stage patients having a better prognosis than advanced stage.
- Treatment depends on stage and risk factors, and may involve chemotherapy alone or with radiation for early stage disease. Advanced stage is treated with chemotherapy only.
- Late effects of therapy include secondary cancers and heart disease, so reducing radiation exposure is a focus of research.
This document discusses current and emerging therapeutic options for adrenocortical carcinoma (ACC). ACC is a rare and aggressive form of endocrine cancer with poor prognosis. Radical surgery is the primary treatment for early-stage ACC but recurrence rates are high. Mitotane is commonly used for advanced ACC but has significant toxicity and low response rates. The document reviews newer targeted therapies and drug combinations that show promise based on the molecular mechanisms driving ACC development and progression. Improved understanding of the genetics and molecular alterations in ACC has contributed to development of new therapeutic strategies needed to effectively treat this cancer.
Please share this webinar with anyone who may be interested!
Watch all our webinars: https://www.youtube.com/playlist?list=PL4dDQscmFYu_ezxuxnAE61hx4JlqAKXpR
In this webinar:
● Signs and symptoms of blood clots, also known as venous thrombosis
● What types of treatments are available
● Why people living with cancer should be aware of the dangers of blood clots and what to do if they occur.
View the video: https://youtu.be/PbZQCHRhoOQ
Follow our social media accounts:
Twitter - https://twitter.com/survivornetca
Facebook - https://www.facebook.com/CanadianSurvivorNet
Pinterest - https://www.pinterest.com/survivornetwork
YouTube - https://www.youtube.com/user/Survivornetca
This document discusses risk factors for hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C virus (HCV) infection. It notes that HCV typically leads to chronic infection in over 60% of patients and cirrhosis may develop over 20 years. The risk of HCC increases with cirrhosis development. Factors like alcohol use, HIV/HBV co-infection, and hepatitis B core antibody positivity can further increase HCC risk. Non-invasive screening tools and risk scores are useful to monitor at-risk patients and prioritize them for HCC surveillance.
Venous Thromboembolism in the Cancer Patientlarriva
Cancer patients are at an increased risk of venous thromboembolism. There have been several guidelines published on the topic from the American College of Chest Physicians (ACCP), the American Society of Clinical Oncology (ASCO), and the National Comprehensive Cancer Network (NCCN). Although they agree on some issues regarding prophylaxis and treatment there are several areas that vary. This presentation covers the varying recommendations and the areas of consensus (yellow boxes) among the guidelines while using a patient case to guide their interpretation.
Chronic kidney disease (CKD) affects 8-16% of the global population and is often underdiagnosed. Defined as a glomerular filtration rate below 60 mL/min/1.73 m2 or markers of kidney damage for over 3 months, CKD is most commonly caused by diabetes and hypertension. Primary care clinicians play an important role in screening for CKD through routine testing of serum creatinine and urine albumin-to-creatinine ratio, diagnosing and staging CKD based on GFR and albuminuria levels, and managing CKD through controlling risk factors, treating complications, and referring high-risk patients to nephrologists. Appropriate screening, diagnosis and management
This document outlines a research protocol to study neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) as predictors of systemic inflammation and chronic illness in pre-surgery patients. The study will retrospectively analyze data from 1000 patients who attended a preadmission clinic between January and April 2013. Medical history, exam findings, and blood test results will be collected to calculate NLR and PLR ratios and examine their relationship to inflammation and health conditions. The goal is to determine the prevalence of elevated ratios and their ability to predict surgical risk factors.
This document provides an overview of Hodgkin lymphoma (HL), including:
- HL is a malignancy of mature B lymphocytes that represents 10% of lymphomas diagnosed annually.
- Classical HL has high cure rates of over 85% with radiation and chemotherapy. However, late therapy-related toxicities are a new challenge.
- Staging is important for selecting appropriate therapy intensity, with early stage patients having a better prognosis than advanced stage.
- Treatment depends on stage and risk factors, and may involve chemotherapy alone or with radiation for early stage disease. Advanced stage is treated with chemotherapy only.
- Late effects of therapy include secondary cancers and heart disease, so reducing radiation exposure is a focus of research.
This document discusses current and emerging therapeutic options for adrenocortical carcinoma (ACC). ACC is a rare and aggressive form of endocrine cancer with poor prognosis. Radical surgery is the primary treatment for early-stage ACC but recurrence rates are high. Mitotane is commonly used for advanced ACC but has significant toxicity and low response rates. The document reviews newer targeted therapies and drug combinations that show promise based on the molecular mechanisms driving ACC development and progression. Improved understanding of the genetics and molecular alterations in ACC has contributed to development of new therapeutic strategies needed to effectively treat this cancer.
Please share this webinar with anyone who may be interested!
Watch all our webinars: https://www.youtube.com/playlist?list=PL4dDQscmFYu_ezxuxnAE61hx4JlqAKXpR
In this webinar:
● Signs and symptoms of blood clots, also known as venous thrombosis
● What types of treatments are available
● Why people living with cancer should be aware of the dangers of blood clots and what to do if they occur.
View the video: https://youtu.be/PbZQCHRhoOQ
Follow our social media accounts:
Twitter - https://twitter.com/survivornetca
Facebook - https://www.facebook.com/CanadianSurvivorNet
Pinterest - https://www.pinterest.com/survivornetwork
YouTube - https://www.youtube.com/user/Survivornetca
This document discusses risk factors for hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C virus (HCV) infection. It notes that HCV typically leads to chronic infection in over 60% of patients and cirrhosis may develop over 20 years. The risk of HCC increases with cirrhosis development. Factors like alcohol use, HIV/HBV co-infection, and hepatitis B core antibody positivity can further increase HCC risk. Non-invasive screening tools and risk scores are useful to monitor at-risk patients and prioritize them for HCC surveillance.
Venous Thromboembolism in the Cancer Patientlarriva
Cancer patients are at an increased risk of venous thromboembolism. There have been several guidelines published on the topic from the American College of Chest Physicians (ACCP), the American Society of Clinical Oncology (ASCO), and the National Comprehensive Cancer Network (NCCN). Although they agree on some issues regarding prophylaxis and treatment there are several areas that vary. This presentation covers the varying recommendations and the areas of consensus (yellow boxes) among the guidelines while using a patient case to guide their interpretation.
Chronic kidney disease (CKD) affects 8-16% of the global population and is often underdiagnosed. Defined as a glomerular filtration rate below 60 mL/min/1.73 m2 or markers of kidney damage for over 3 months, CKD is most commonly caused by diabetes and hypertension. Primary care clinicians play an important role in screening for CKD through routine testing of serum creatinine and urine albumin-to-creatinine ratio, diagnosing and staging CKD based on GFR and albuminuria levels, and managing CKD through controlling risk factors, treating complications, and referring high-risk patients to nephrologists. Appropriate screening, diagnosis and management
This document discusses liver cancers. It covers the anatomy of the liver, epidemiology, etiology, prognostic factors, workup, and staging of liver cancers. Some key points include:
- Liver cancer is the 5th most common cancer in men worldwide and the second leading cause of cancer death. Incidence is highest in East Asia and lowest in Northern Europe.
- Major risk factors for liver cancer include hepatitis B and C infections, alcohol use, and metabolic diseases like hemochromatosis.
- Staging involves radiological imaging like CT scans and tumor markers like AFP. Biopsies may also be used for pathological examination.
- Prognostic factors include tumor size, number, vascular invasion,
This document summarizes several presentations on recent developments in Hodgkin lymphoma. It begins with a discussion of a study comparing the predictive value of interim PET scans done after one or two cycles of therapy. The study found PET scans after one cycle had a higher negative predictive value. Another section summarizes a trial finding patients with low stage disease and a negative PET scan after 3 cycles of ABVD had excellent prognosis without further treatment. Later sections discuss outcomes of combining brentuximab vedotin with standard therapies for relapsed/refractory and advanced stage disease. Results showed improved survival correlated with response to brentuximab vedotin.
Actualización en la etiología, clasificación y manejo de las glomerulopatías.pdfjhinner eloy
This document provides an overview of recent updates in the classification and management of various glomerular diseases. It discusses how new genetic discoveries have led to changes in classifications, such as membranoproliferative glomerulonephritis now being divided into C3 glomerulopathy and immunoglobulin/C3 positive categories. Treatment options for diseases like minimal change disease, membranous nephropathy, and focal segmental glomerulosclerosis have expanded with the use of rituximab and complement inhibitors. Rapidly progressive glomerulonephritis is now classified based on etiology into anti-glomerular basement membrane antibody disease, ANCA-associated vasculitis, and immune complex disorders.
- The document analyzes prognostic factors that influence survival in patients with relapsed follicular lymphoma based on a retrospective study of 151 patients.
- In univariate analysis, factors like older age, higher stage, poorer performance status, shorter duration of response to first-line therapy, and bone marrow involvement were associated with worse survival.
- Multivariate analysis found that duration of response to first-line therapy and performance status at relapse were the most important factors, with 5-year survival ranging from 33-63% based on duration of response.
prevelance of, association with and prognostic role of anemia in HF spectrumSamantaRahman1
This study analyzed 42,985 heart failure patients to examine the prevalence and impact of anemia in those with HFpEF, HFmrEF, and HFrEF. It found that anemia was common in all groups, affecting 41% of HFpEF patients, 35% of HFmrEF patients, and 32% of HFrEF patients. Anemia was associated with higher mortality and hospitalization risk across all groups. While risks differed according to severity and comorbidities, anemia independently predicted worse outcomes regardless of ejection fraction.
Reversal of warfarin associated coagulopathy prothrombin complex concentratesTÀI LIỆU NGÀNH MAY
Để xem full tài liệu Xin vui long liên hệ page để được hỗ trợ
: https://www.facebook.com/thuvienluanvan01
HOẶC
https://www.facebook.com/garmentspace/
https://www.facebook.com/thuvienluanvan01
https://www.facebook.com/thuvienluanvan01
tai lieu tong hop, thu vien luan van, luan van tong hop, do an chuyen nganh
This study assessed the thrombotic risk during oral contraceptive use and pregnancy in 798 female relatives with heterozygous, double heterozygous, or homozygous factor V Leiden or prothrombin mutation from 4 family cohorts. The overall absolute venous thromboembolism (VTE) risk in women with no, single, or combined defects was 0.13, 0.35, and 0.94 per 100 person-years, respectively, while during oral contraceptive use the risks were 0.19, 0.49, and 0.86 per 100 person-years. The risks were highest during pregnancy and postpartum, at 0.73, 1.97, and 7.65 per
Cardiac Troponin Elevation in Patients Without a Specific DiagnosisShadab Ahmad
Measurement of cardiac troponin (cTn) levels is a cornerstone in the assessment of patients with acute chest pain.
An elevation in the cTn level together with a significant change in the setting of coronary ischemia indicates myocardial infarction (MI).
However, even other cardiac and noncardiac conditions may result in acute cTn increases (e.g., arrhythmias, severe hyper- or hypotension, pulmonary embolism, neurologic events, or endurance efforts).
Acute but subtle increases in cTn levels may also be difficult to distinguish from chronic cTn elevation which is a common finding in the elderly, patients with renal failure, or patients with chronic cardiac conditions.
VTE and Cancer Healthcare Professional Educationvtesimplified
Cancer patients are at increased risk of developing blood clots (venous thromboembolism or VTE) due to factors such as tumour infiltration of blood vessels, immobility, and cancer treatments. VTE is a leading cause of death in cancer patients and the risk is highest in the first months after diagnosis. Guidelines recommend thromboprophylaxis for hospitalized cancer patients without bleeding risk, but evidence for routine outpatient prophylaxis is limited to certain high risk groups. Risk assessment tools can help identify those at highest risk who may benefit most from prophylaxis.
This study developed a new prognostic index called MIPI for patients with advanced-stage mantle cell lymphoma based on data from 455 patients treated in 3 clinical trials. The MIPI stratified patients into low-, intermediate-, and high-risk groups based on 4 independent prognostic factors: age, performance status, lactate dehydrogenase level, and leukocyte count. Validation showed the MIPI provided better risk stratification than existing indices and may help guide treatment decisions. Proliferation marker Ki-67 also showed strong additional prognostic relevance when included in the index.
Indications of liver transplantation and scoring syatems.Mayur Rath
Liver transplantation can treat acute liver failure, end-stage liver disease, and some liver cancers. It carries risks of surgery, recurrent disease, and long-term immunosuppression. Acute liver failure is the highest priority for liver transplant (LT), defined as severe liver injury within 26 weeks without preexisting disease. Causes include viruses, drugs, and other factors. Cirrhosis may qualify for LT if complications develop from portal hypertension or liver dysfunction. Scoring systems like MELD and CTP predict disease severity and survival to help determine transplant need. Acute liver failure is further evaluated using criteria from King's College Hospital, Clichy, Japan, and models like MELD and ALFED.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer. It has a high global mortality and incidence rates that vary widely between regions. The highest rates are found in Southeast Asia and Africa, where hepatitis B virus infection is more common. Other major risk factors include hepatitis C virus, alcohol abuse, and cirrhosis. HCC typically presents with nonspecific symptoms in advanced stages. Diagnosis involves imaging tests like ultrasound, CT, and MRI to identify a liver mass, along with blood tests like AFP. Staging considers tumor characteristics and liver function to guide treatment, which may include resection, ablation, transplantation, or other options.
1) This study analyzed prognostic factors that influence survival in patients with relapsed follicular lymphoma by examining clinical data from 151 patients.
2) Univariate analysis found that factors like older age, poorer performance status, advanced stage, short duration of response to initial therapy, and not achieving complete response were associated with worse survival.
3) Multivariate analysis identified that duration of response to initial therapy and performance status at relapse were the most important predictors of long-term survival, with patients having responses lasting 2+ years or good performance status having longer 5-year survival.
Venous thromboembolism (VTE) can be the first sign of an underlying occult or undiagnosed cancer. The risk of occult cancer is higher in patients with unprovoked VTE compared to those with VTE from a provoking factor. Limited screening is recommended for patients over age 40 presenting with unprovoked VTE, including a complete blood count, basic metabolic panel, chest imaging, and consideration of tumor markers based on risk factors. More extensive screening with CT scans is not supported by evidence of improved outcomes and poses risks of unnecessary anticoagulation withdrawal or additional testing. Ongoing surveillance beyond initial screening may be warranted in certain high risk cases such as recurrent unprovoked VTE
Introduction and Aim: Nailfold capillaroscopy is used to assess vascularization in pathologies involving distal blood vessels. This study aims at describing nailfold capillaroscopy fi ndings in a large cohort of Spanish Hereditary Hemorrhagic Telangiectasia (HHT) (Rendu Osler Weber) patients to correlate these fi ndings with the presence of organ involvement.
http://www.scireslit.com/
This document discusses treatment options for Hodgkin lymphoma based on stage. For early stage (I-II) favorable prognosis, ABVD chemotherapy for 3-4 cycles followed by radiation is most commonly used. For early stage unfavorable prognosis, ABVD plus radiation is standard. For advanced stage (III-IV) ABVD is standard but BEACOPP shows improved progression-free survival over ABVD though with greater toxicity. Radiation is often used along with chemotherapy depending on risk factors.
- Several studies have found that older liver transplant recipients (over age 60) have similar short-term outcomes to younger recipients in terms of postoperative morbidity, mortality, and length of hospital stay. However, long-term survival is significantly lower in older recipients, largely due to non-hepatic age-related causes of death.
- While patient survival is lower in older recipients, graft survival is not significantly different between older and younger groups. The increased mortality in older patients is attributed to infections, cardiac events, and neurological causes rather than hepatic causes.
- Careful consideration of medical fitness and life expectancy due to comorbidities is important when evaluating older recipients for liver transplantation. While age alone should not preclude transplantation, risks
This document summarizes key points about HIV-associated lymphoma:
- HIV-associated lymphomas have improved in prognosis due to combination antiretroviral therapy and novel therapies, with many patients now cured.
- Diffuse large B-cell lymphoma and Burkitt lymphoma have excellent outcomes, similar to HIV-negative patients, especially with the addition of rituximab.
- New treatments are still needed to improve outcomes for patients with advanced immunosuppression or adverse tumor subtypes driven by viruses.
Pulmonary embolism update on management and controversies.pdfjosepabloqueroreyes
This document summarizes recent advances in the diagnosis, risk assessment, and management of pulmonary embolism (PE). Key points include:
1) Direct oral anticoagulants (DOACs) such as apixaban, edoxaban, and rivaroxaban are now preferred over warfarin for treating PE due to similar or lower risk of bleeding.
2) Use of clinical probability adjusted or age adjusted D-dimer testing can help reduce unnecessary imaging to diagnose PE.
3) Only a small portion of PE patients have high risk features, but identifying these patients may help determine if additional therapies like thrombolysis are needed.
4) After PE, assessing risk factors can guide duration
Immunosuppressed allograft recipients have three to five folds increase in cancer risk as compared to age matched general population. The most common malignancies encountered are Non Melanotic Skin Cancer, Post Transplant Lymphoproliferative Disorder and Kaposi's Sarcoma. Duration of immunosuppressive therapy and/or type of immunosuppressive agents are important controllable factors which have an impact in the development of tumors. Oncogenic viruses have an important role in the development of these malignancies.
This document discusses liver cancers. It covers the anatomy of the liver, epidemiology, etiology, prognostic factors, workup, and staging of liver cancers. Some key points include:
- Liver cancer is the 5th most common cancer in men worldwide and the second leading cause of cancer death. Incidence is highest in East Asia and lowest in Northern Europe.
- Major risk factors for liver cancer include hepatitis B and C infections, alcohol use, and metabolic diseases like hemochromatosis.
- Staging involves radiological imaging like CT scans and tumor markers like AFP. Biopsies may also be used for pathological examination.
- Prognostic factors include tumor size, number, vascular invasion,
This document summarizes several presentations on recent developments in Hodgkin lymphoma. It begins with a discussion of a study comparing the predictive value of interim PET scans done after one or two cycles of therapy. The study found PET scans after one cycle had a higher negative predictive value. Another section summarizes a trial finding patients with low stage disease and a negative PET scan after 3 cycles of ABVD had excellent prognosis without further treatment. Later sections discuss outcomes of combining brentuximab vedotin with standard therapies for relapsed/refractory and advanced stage disease. Results showed improved survival correlated with response to brentuximab vedotin.
Actualización en la etiología, clasificación y manejo de las glomerulopatías.pdfjhinner eloy
This document provides an overview of recent updates in the classification and management of various glomerular diseases. It discusses how new genetic discoveries have led to changes in classifications, such as membranoproliferative glomerulonephritis now being divided into C3 glomerulopathy and immunoglobulin/C3 positive categories. Treatment options for diseases like minimal change disease, membranous nephropathy, and focal segmental glomerulosclerosis have expanded with the use of rituximab and complement inhibitors. Rapidly progressive glomerulonephritis is now classified based on etiology into anti-glomerular basement membrane antibody disease, ANCA-associated vasculitis, and immune complex disorders.
- The document analyzes prognostic factors that influence survival in patients with relapsed follicular lymphoma based on a retrospective study of 151 patients.
- In univariate analysis, factors like older age, higher stage, poorer performance status, shorter duration of response to first-line therapy, and bone marrow involvement were associated with worse survival.
- Multivariate analysis found that duration of response to first-line therapy and performance status at relapse were the most important factors, with 5-year survival ranging from 33-63% based on duration of response.
prevelance of, association with and prognostic role of anemia in HF spectrumSamantaRahman1
This study analyzed 42,985 heart failure patients to examine the prevalence and impact of anemia in those with HFpEF, HFmrEF, and HFrEF. It found that anemia was common in all groups, affecting 41% of HFpEF patients, 35% of HFmrEF patients, and 32% of HFrEF patients. Anemia was associated with higher mortality and hospitalization risk across all groups. While risks differed according to severity and comorbidities, anemia independently predicted worse outcomes regardless of ejection fraction.
Reversal of warfarin associated coagulopathy prothrombin complex concentratesTÀI LIỆU NGÀNH MAY
Để xem full tài liệu Xin vui long liên hệ page để được hỗ trợ
: https://www.facebook.com/thuvienluanvan01
HOẶC
https://www.facebook.com/garmentspace/
https://www.facebook.com/thuvienluanvan01
https://www.facebook.com/thuvienluanvan01
tai lieu tong hop, thu vien luan van, luan van tong hop, do an chuyen nganh
This study assessed the thrombotic risk during oral contraceptive use and pregnancy in 798 female relatives with heterozygous, double heterozygous, or homozygous factor V Leiden or prothrombin mutation from 4 family cohorts. The overall absolute venous thromboembolism (VTE) risk in women with no, single, or combined defects was 0.13, 0.35, and 0.94 per 100 person-years, respectively, while during oral contraceptive use the risks were 0.19, 0.49, and 0.86 per 100 person-years. The risks were highest during pregnancy and postpartum, at 0.73, 1.97, and 7.65 per
Cardiac Troponin Elevation in Patients Without a Specific DiagnosisShadab Ahmad
Measurement of cardiac troponin (cTn) levels is a cornerstone in the assessment of patients with acute chest pain.
An elevation in the cTn level together with a significant change in the setting of coronary ischemia indicates myocardial infarction (MI).
However, even other cardiac and noncardiac conditions may result in acute cTn increases (e.g., arrhythmias, severe hyper- or hypotension, pulmonary embolism, neurologic events, or endurance efforts).
Acute but subtle increases in cTn levels may also be difficult to distinguish from chronic cTn elevation which is a common finding in the elderly, patients with renal failure, or patients with chronic cardiac conditions.
VTE and Cancer Healthcare Professional Educationvtesimplified
Cancer patients are at increased risk of developing blood clots (venous thromboembolism or VTE) due to factors such as tumour infiltration of blood vessels, immobility, and cancer treatments. VTE is a leading cause of death in cancer patients and the risk is highest in the first months after diagnosis. Guidelines recommend thromboprophylaxis for hospitalized cancer patients without bleeding risk, but evidence for routine outpatient prophylaxis is limited to certain high risk groups. Risk assessment tools can help identify those at highest risk who may benefit most from prophylaxis.
This study developed a new prognostic index called MIPI for patients with advanced-stage mantle cell lymphoma based on data from 455 patients treated in 3 clinical trials. The MIPI stratified patients into low-, intermediate-, and high-risk groups based on 4 independent prognostic factors: age, performance status, lactate dehydrogenase level, and leukocyte count. Validation showed the MIPI provided better risk stratification than existing indices and may help guide treatment decisions. Proliferation marker Ki-67 also showed strong additional prognostic relevance when included in the index.
Indications of liver transplantation and scoring syatems.Mayur Rath
Liver transplantation can treat acute liver failure, end-stage liver disease, and some liver cancers. It carries risks of surgery, recurrent disease, and long-term immunosuppression. Acute liver failure is the highest priority for liver transplant (LT), defined as severe liver injury within 26 weeks without preexisting disease. Causes include viruses, drugs, and other factors. Cirrhosis may qualify for LT if complications develop from portal hypertension or liver dysfunction. Scoring systems like MELD and CTP predict disease severity and survival to help determine transplant need. Acute liver failure is further evaluated using criteria from King's College Hospital, Clichy, Japan, and models like MELD and ALFED.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer. It has a high global mortality and incidence rates that vary widely between regions. The highest rates are found in Southeast Asia and Africa, where hepatitis B virus infection is more common. Other major risk factors include hepatitis C virus, alcohol abuse, and cirrhosis. HCC typically presents with nonspecific symptoms in advanced stages. Diagnosis involves imaging tests like ultrasound, CT, and MRI to identify a liver mass, along with blood tests like AFP. Staging considers tumor characteristics and liver function to guide treatment, which may include resection, ablation, transplantation, or other options.
1) This study analyzed prognostic factors that influence survival in patients with relapsed follicular lymphoma by examining clinical data from 151 patients.
2) Univariate analysis found that factors like older age, poorer performance status, advanced stage, short duration of response to initial therapy, and not achieving complete response were associated with worse survival.
3) Multivariate analysis identified that duration of response to initial therapy and performance status at relapse were the most important predictors of long-term survival, with patients having responses lasting 2+ years or good performance status having longer 5-year survival.
Venous thromboembolism (VTE) can be the first sign of an underlying occult or undiagnosed cancer. The risk of occult cancer is higher in patients with unprovoked VTE compared to those with VTE from a provoking factor. Limited screening is recommended for patients over age 40 presenting with unprovoked VTE, including a complete blood count, basic metabolic panel, chest imaging, and consideration of tumor markers based on risk factors. More extensive screening with CT scans is not supported by evidence of improved outcomes and poses risks of unnecessary anticoagulation withdrawal or additional testing. Ongoing surveillance beyond initial screening may be warranted in certain high risk cases such as recurrent unprovoked VTE
Introduction and Aim: Nailfold capillaroscopy is used to assess vascularization in pathologies involving distal blood vessels. This study aims at describing nailfold capillaroscopy fi ndings in a large cohort of Spanish Hereditary Hemorrhagic Telangiectasia (HHT) (Rendu Osler Weber) patients to correlate these fi ndings with the presence of organ involvement.
http://www.scireslit.com/
This document discusses treatment options for Hodgkin lymphoma based on stage. For early stage (I-II) favorable prognosis, ABVD chemotherapy for 3-4 cycles followed by radiation is most commonly used. For early stage unfavorable prognosis, ABVD plus radiation is standard. For advanced stage (III-IV) ABVD is standard but BEACOPP shows improved progression-free survival over ABVD though with greater toxicity. Radiation is often used along with chemotherapy depending on risk factors.
- Several studies have found that older liver transplant recipients (over age 60) have similar short-term outcomes to younger recipients in terms of postoperative morbidity, mortality, and length of hospital stay. However, long-term survival is significantly lower in older recipients, largely due to non-hepatic age-related causes of death.
- While patient survival is lower in older recipients, graft survival is not significantly different between older and younger groups. The increased mortality in older patients is attributed to infections, cardiac events, and neurological causes rather than hepatic causes.
- Careful consideration of medical fitness and life expectancy due to comorbidities is important when evaluating older recipients for liver transplantation. While age alone should not preclude transplantation, risks
This document summarizes key points about HIV-associated lymphoma:
- HIV-associated lymphomas have improved in prognosis due to combination antiretroviral therapy and novel therapies, with many patients now cured.
- Diffuse large B-cell lymphoma and Burkitt lymphoma have excellent outcomes, similar to HIV-negative patients, especially with the addition of rituximab.
- New treatments are still needed to improve outcomes for patients with advanced immunosuppression or adverse tumor subtypes driven by viruses.
Pulmonary embolism update on management and controversies.pdfjosepabloqueroreyes
This document summarizes recent advances in the diagnosis, risk assessment, and management of pulmonary embolism (PE). Key points include:
1) Direct oral anticoagulants (DOACs) such as apixaban, edoxaban, and rivaroxaban are now preferred over warfarin for treating PE due to similar or lower risk of bleeding.
2) Use of clinical probability adjusted or age adjusted D-dimer testing can help reduce unnecessary imaging to diagnose PE.
3) Only a small portion of PE patients have high risk features, but identifying these patients may help determine if additional therapies like thrombolysis are needed.
4) After PE, assessing risk factors can guide duration
Immunosuppressed allograft recipients have three to five folds increase in cancer risk as compared to age matched general population. The most common malignancies encountered are Non Melanotic Skin Cancer, Post Transplant Lymphoproliferative Disorder and Kaposi's Sarcoma. Duration of immunosuppressive therapy and/or type of immunosuppressive agents are important controllable factors which have an impact in the development of tumors. Oncogenic viruses have an important role in the development of these malignancies.
The document discusses post-transplant malignancies in solid organ transplant recipients. It notes that recipients have a 3-5 fold higher risk of cancer than the general population due to prolonged immunosuppression. The most common post-transplant malignancies are non-melanoma skin cancer, post-transplant lymphoproliferative disorder (PTLD), and Kaposi's sarcoma. PTLD is often associated with Epstein-Barr virus infection and occurs more frequently after transplants of certain organs. Treatment involves reducing immunosuppression when possible and additional therapies depending on the malignancy type and individual case.
This document discusses acquired pure red cell aplasia (PRCA), a disorder characterized by severe anemia and absence of erythroblasts in the bone marrow. It reviews treatments for PRCA, including corticosteroids, cyclosporine A, and other immunosuppressive therapies. Cyclosporine A has proven effective at inducing remission in 65-87% of cases, but concerns remain about sustained remission and relapse rates. The document also discusses the importance of evaluating patients for underlying causes of secondary PRCA such as lymphoproliferative disorder of granular lymphocytes.
One of my best friends (when I was a teenager) died of leukemia. Several advances have been made in the ensuing decades (see attached document). Watch this space for additional notes.
This document discusses lymphoma and its classification. It notes that lymphoma arises from lymphoid tissue and is the most common hematologic malignancy in developed countries. There are two main types, Hodgkin's and non-Hodgkin's lymphoma, with non-Hodgkin's lymphoma accounting for about 85% of cases. The two most common forms of non-Hodgkin's lymphoma are follicular lymphoma and diffuse large B-cell lymphoma. Classification of lymphoma has evolved based on immunophenotypic and genetic features. Many lymphomas express the antigen CD20, which has made it a target for developing monoclonal antibody therapies.
This document provides an introduction to lymphoma and radioimmunotherapy. It discusses that lymphoma originates from lymphoid tissue and is the most common hematologic malignancy. It describes the classification of lymphomas and focuses on two common types - follicular lymphoma and diffuse large B-cell lymphoma. It then introduces radioimmunotherapy as a targeted treatment approach using radiolabeled monoclonal antibodies, with a focus on the anti-CD20 antibody rituximab which is commonly used to treat CD20-positive lymphomas.
Hodgkin's lymphoma accounts for approximately 3% of new cancer cases in the UK each year. It is a cancer of the lymphatic system that is subdivided into Hodgkin's lymphoma and non-Hodgkin's lymphoma. Hodgkin's lymphoma is diagnosed through biopsy of enlarged lymph nodes and characterized by the presence of Reed-Sternberg cells. Treatment depends on the stage of disease and may involve chemotherapy, radiation therapy, or a combination of the two. New targeted therapies are also being developed to treat Hodgkin's lymphoma.
Guidance isth _management_of_coagulopathy_in_covid-19 Dr. Freddy Flores Malpa...Freddy Flores Malpartida
1) This document provides interim guidance from the International Society on Thrombosis and Haemostasis (ISTH) on recognizing and managing coagulopathy in COVID-19.
2) It recommends measuring D-dimers, prothrombin time, and platelet count in all COVID-19 patients to help stratify risk, with increased D-dimers indicating a higher risk of severe illness.
3) For hospitalized COVID-19 patients, the guidance suggests regular monitoring of D-dimers, prothrombin time, platelet count, and fibrinogen to identify worsening coagulopathy, which correlates with poorer outcomes. More aggressive care may be warranted for patients with worsening markers.
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Lysis tumoral syndrome
1. Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=ierr20
Download by: [University of California, San Diego] Date: 08 December 2015, At: 10:13
Expert Review of Hematology
ISSN: 1747-4086 (Print) 1747-4094 (Online) Journal homepage: http://www.tandfonline.com/loi/ierr20
TUMOR LYSIS SYNDROME: REVIEW OF
PATHOGENESIS, RISK FACTORS AND MANAGEMENT
OF A MEDICAL EMERGENCY
M Criscuolo, L Fianchi, G Dragonetti & L Pagano
To cite this article: M Criscuolo, L Fianchi, G Dragonetti & L Pagano (2015): TUMOR LYSIS
SYNDROME: REVIEW OF PATHOGENESIS, RISK FACTORS AND MANAGEMENT OF A MEDICAL
EMERGENCY, Expert Review of Hematology, DOI: 10.1586/17474086.2016.1127156
To link to this article: http://dx.doi.org/10.1586/17474086.2016.1127156
Accepted author version posted online: 02
Dec 2015.
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2. 1
Publisher: Taylor & Francis
Journal: Expert Review of Hematology
DOI: 10.1586/17474086.2016.1127156
TUMOR LYSIS SYNDROME: REVIEW OF PATHOGENESIS, RISK
FACTORS AND MANAGEMENT OF A MEDICAL EMERGENCY
Criscuolo M1
, Fianchi L1
, Dragonetti G1
, Pagano L1
.
1
Hemathology Department, Catholic University of Sacred Heart, Rome Italy
Keywords: tumor lysis syndrome, rasburicase, allopurinol, drug induced
Correspondence to:
Prof. Livio Pagano
lpagano@rm.unicatt.it
Largo A. Gemelli 8 00168
Rome, Italy
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3. 2
ABSTRACT
Tumor lysis syndrome (TLS) is a rare but potentially life-threatening complication of neoplasms,
preferentially hematological malignancies. Well known since at least ninety years ago, this
condition can be misdiagnosed and incorrectly managed due to rapid onset of symptoms,
sometimes overlapping with cancer-derived clinical conditions. Our purpose is to discuss some old
and new issues of this syndrome. Predisposing factors as type of malignancy, chemotherapy
regimen and age are promptly available and useful tools for inducing TLS suspicion. Management
of clinical syndrome requires hydration, fluid balance, electrolytes and hyperuricemia correction,
and ultimately dialysis when acute kidney injury is worsening.
INTRODUCTION
Tumor lysis syndrome (TLS) is a potentially life-threatening medical condition occurring in the early
phase of diagnosis and treatment of high proliferative malignant neoplasms. TLS is characterized
by rapid onset of hyperuricemia, hyperkalemia, hypocalcemia, hyperphosphatemia and renal
impairment following release of intracytoplasmic components during cellular lysis. This condition
has a well-established association with hematological malignancies, particularly acute leukemias
and non-Hodgkin lymphomas1
. The reported incidence of TLS during disease treatment is among
4% and 42%, depending of both pediatric and adult different studies2-7
. The specific incidence of
TLS in leukemias and lymphomas is difficult to address, because of differences in study population
and TLS diagnostic criteria8
: roughly it ranges from 3-7% in acute leukemias and 4-11% in
lymphomas, up to 25% when B lymphoblastic leukemia and Burkitt’s lymphoma are considered
apart3, 4, 6, 7, 9-10
. Although TLS typically occurs early in the course of therapy, spontaneous events
rate has been reported to be 1.08% in a retrospective analysis11
. TLS is less frequent in solid
cancers, and is usually associated with bulky and high chemosensitive diseases; spontaneous
events are restricted to case reports12-16
.
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4. 3
In an effort to prevent clinical symptoms and end organ damage, different risk factors can be
pointed out2, 17, and 18
. First, the type of cancer itself is a strong predictor of spontaneous and
therapy related cell lysis. High proliferative diseases like Burkitt’s lymphoma (BL) or Acute
Lymphoblastic Leukemia (ALL) are often high chemosensitive (Figure 1): after cellular death an
elevated amount of intracellular metabolites is released in the blood stream and rapidly
overcomes kidney clearance function. Nevertheless tumor burden, hyperleukocytosis and
multiorgan spread are other important clinical clues to predict TLS. Further, concomitant patient
conditions like dehydration, underlying kidney impairment and metabolic dysfunction can also
play a role.
TLS management can be challenging for clinicians: mortality rate is reported to be about 15% of
established cases, with a higher percentage of patients affording hemodialysis after acute kidney
injury1
. An incidence of 13% life-threatening complications has been reported for haematological
patients developing TLS2, 16
, and the death rate is one in three among solid cancer patients which
show clinical features of TLS19
. Complications derived from TLS can compromise the administration
of treatment, leading to delaying or interruption of chemotherapy and ultimately worsening
patient’s outcome.
ASSOCIATION WITH TERAPEUTIC AGENTS
The first case of TLS was reported in 1929 in a patient affected by chronic leukemia20
. Since then, a
significant number of drugs and therapeutic intervention has been addressed to be associated
with TLS (Table 1).
Episodic events of TLS during hydroxyurea administration were reported, all in patients whose
primary disease transformed into acute leukemia21-23
. Only five cases of TLS after fludarabine
therapy were detected, and all but one occurred after the first cycle of treatment24-28
.
Some patients with huge splenomegaly or diffuse liver involvement should be carefully monitored
during and after palliative radiotherapy29, 30
or arterial embolization31-32
; a case of post
splenectomy TLS has also been reported33
. Anecdotal reports of TLS in Castleman disease have
also been seen34-35
.
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5. 4
Considering the relevant lymphotoxic activity of steroids, patients undergone high dose
dexamethasone can also develop TLS, especially those affected by either acute or chronic
lymphoid leukemias in which steroids have a well-known therapeutic effect36-44
.
Since the inclusion of Rituximab in the treatment of high grade lymphoproliferative diseases, few
cases of TLS have been reported to be related to its administration: most of patients who
experienced this complication had burden disease and elevated serum LDH level at diagnosis4, 45-51
.
Among nine cases reported in the literature, five patients died after the first course of drug
despite advanced life support intervention, while three were able to tolerate subsequent
Rituximab administrations safely. In the most recent report, TLS occurred in one patient after eight
previous Rituximab courses, during relapse treatment.
In the last years new drugs have been introduced for the treatment of multiple myeloma: in a
reported case series, seven patients with advanced stage multiple myeloma experienced TLS after
treatment with bortezomib; they all had elevated amount of Bence-Jones proteinuria and rapidly
progressing disease. Interestingly, in two patients TLS occurred upon retreatment with bortezomib
in combination with dexamethasone52
.
Even in the era of targeted therapy, event of LTS is reported. Ibrutinib, a Bruton tyrosine kinase
inhibitor, is known to worse lymphocytosis in chronic lymphocytic leukemia (CLL) patients: two
cases of TLS during ibrutinib treatment as single agents are reported53-54
.
Some reports of TLS in CML are also being found, especially in patients transforming to blastic
phase disease55-59
. Two patients with Hodgkin lymphoma were reported to complicate with TLS
after standard chemotherapy: increased release of IL-6 had a role in the latest case60-61
. To date, a
clear relationship between increasing cytokines levels and clinical worsening of TLS has not been
found, even if Nakamura et al. reported four cases of haematological malignancies in which high
serum cytokine levels like IL-6 and TNF-alpha correlate with clinical onset of TLS62
.
In the setting of solid cancers, the first report is about a spontaneous TLS in disseminating
gastrointestinal cancer in 197763
. So far few cases of TLS has been related to previous radiation
therapy in metastatic breast cancer64
or came out after transarterial chemoembolization of
hepatocellular carcinomas65-66
, the majority developing TLS after single agent or combination
therapy67-68
.
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6. 5
In metastatic melanoma, six cases of TLS have been reported: three followed corticosteroids
administration and three arose after conventional chemotherapy associated to biological
treatment69-73
. TLS after hormone therapy is anecdotal74-76
.
Questions arise about the different rates of TLS between hematological malignancies and solid
cancers: these cannot be explained only with different cellular kinetics or treatment response. In
fact, TLS is not reported to be more frequent in germ cells cancer or small cell carcinoma, whose
growth patterns are similar to those of hematological neoplasms, and can be detected even in
tumours not sensitive to chemotherapy67
. Onset time is also different between these two
categories. In haematological malignancies TLS typically arises during the first days of
chemotherapy, while in solid cancers it appears to be delayed to a week or more after treatment:
this is probably attributable to the fact that solid cancer cells are in different cell cycle phases,
while haematological cells are more often synchronous67
.
ELDERLY
Median age of general population is rapidly increasing in the modern era, because of better
management of chronic diseases and improving outcome of different types of cancer. Indeed, they
are expected to experience a wide spread of complications deriving from chemotherapy, and the
low performance status often related to a number of comorbidities put them in higher risk
categories for worse outcome, even if reduced intensity treatments are performed. In this setting,
it is clear that development of TLS can be more frequent and challenging: previous renal
impairment, more pronounced chemosensitivity, less compliance to drugs and pharmacological
interactions may facilitate the onset of this complication. Moreover, the management of this
condition can be more difficult in these patients, because they usually show faster clinical
worsening and have a reduced tolerance to stronger interventions.
Hyperkalemia is the upcoming metabolic alteration, developing between 6 and 72 hours after
chemotherapy: due to the age-related decrease of renin and aldosterone, elderly patients can
have impaired potassium control. If glomerular excretion is also lowered and an acidosis status is
associated, hyperkalemia could be hard to recover. Hyperphosphatemia and associated
hypocalcemia are usually seen between 24 and 48 hours after chemotherapy. Although high level
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7. 6
of serum phosphate is usually attributable to lysis, it could be also be a consequence of metabolic
disorders like hypothyroidism, rhabdomyolysis and laxatives abuse. Hyperphosphatemia and
hypocalcemia are frequently related to chronic renal failure, reduced D vitamin production and
parathyroid hormone resistance. Hyperuricemia usually develops from 24 through 72 hours
following the beginning of treatment, due to augmented DNA and RNA degradation. This may
rapidly overcomes clearance ability of kidneys, leading to urate crystals precipitation in renal
tubules and acute renal impairment, particularly if dehydration and acidosis are present77
.
It’s reasonable to try to prevent TLS in these frail patients, but almost every intervention may
result in overcoming organism homeostatic capacities, leading to worsen clinical conditions.
Elderly people may not be able to tolerate strong hydration because of decreased heart and
vascular reserve, resulting in more frequent fluid overload and edematous state. Heavy diuretic
load should be carefully monitored, particularly if urethral obstruction or benign prostate
hypertrophy coexists, in order to prevent severe hypotension and hyper- or hypotonic state.
Electrolytes derangement correction can take longer to be addressed, especially when kidney
injury is progressing, and hemodialysis may be required. Allopurinol is the cornerstone of TLS
treatment and prevention, but it may interact with a number of drugs through inhibition of
cytochrome P450.
In general, low risk patients only need normal hydration and strict laboratory and clinic monitoring
without prophylaxis for hyperuricemia, except in cases of metabolic alterations, bulky/advanced
disease or high proliferative rate. Patients with intermediate risk of developing TLS should undergo
strong hydration and prophylaxis with allopurinol. In patients with high risk features at
presentation, increased hydration and rasburicase should be administered. If clinical signs of TLS
develop despite prophylaxis with allopurinol, rasburicase should be given and more frequent
monitoring is required to prevent acute kidney injury (AKI).
CLINICAL FEATURES
In the development of acute TLS clinical symptoms usually arise in 12 through 72 hours from the
beginning of chemotherapy. In high proliferating cancers the cytotoxic effects of drugs, hormones,
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8. 7
immunotherapy and radiations lead to massive lysis, electrolytes, nucleic acids and proteins
release in the bloodstream and metabolic derangement.
Catabolism of purine analogues derived from nucleic acids produces high serum uric acid level,
which can be initially controlled by renal clearance. As the production rate overcomes the amount
of 500 mg/day and reaches kidney function limit78, 79
, uric acid levels can increase over the
solubility limit of 15 mg/dl in renal distal tubules and collecting ducts7
, facilitating crystals
formation and deposition. Finally urate precipitation may cause oliguria and acute renal failure.
Intracellular phosphorus concentration can be up to four times higher than normal in tumour cells.
After releasing in the bloodstream, renal phosphorus excretion increases until tubule transport
capacity is saturated: this can be partly worsened by concurrent steroid therapy80
. When
phosphorus-calcium product is more than 70 or calcium-phosphate product is more than 4.6
mmol/l, precipitation of calcium phosphate salts in distal renal tubules may occur more
frequently, especially in the setting of urine alkalinisation, leading to or exacerbate renal failure1,
81
. Hypocalcemia due to the precipitation of calcium phosphate is usually asymptomatic, but it
may elicit neuromuscular irritability and occasionally tetany and seizures. Hyperpotassiemia is
frequently detected as a consequence of cell lysis and/or renal failure and may be seriously life-
threatening causing arrhythmia and sudden death.
TLS features include nausea and vomiting, lethargy, fluid overload, reduced urinary output and
anuria, flank or back pain, muscle cramps, EKG alterations and arrhythmia, tetany, seizures and
even sudden death due to multiorgan failure1
. TLS should be suspected among high risk patients
presenting with these clinical characteristics, even before chemotherapy administration: frequent
laboratory and clinical monitoring and prompt management of complications are the cornerstone
for reducing morbidity and mortality in this category of patients.
RISK EVALUATION
Identification of patients at higher risk of developing TLS is the main step for a correct
management of this potentially life-threatening complication. As previously mentioned, primary
malignancy is the most important factor predicting TLS: in large series studies, evaluating
laboratory and clinical features in adult and pediatric patients, a more elevated incidence of TLS
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9. 8
has been found in BL adult, B-ALL pediatric and Acute Myeloid Leukemia (AML) patients4,7,9,81-83
than in Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin Lymphomas (NHL)27,84-88
. A
correlation with elevated white blood cells (WBC) count at diagnosis and tumour burden has also
been reported89
. TLS is rarely seen in solid tumors66
. On this basis, patients expected to be at low
risk of developing TLS are those with indolent NHL, intermediate risk category includes NHL
patients and high risk patients are those affected by BL, lymphoblastic lymphoma and ALL. AML,
CLL, BL and ALL patients are stratified based on WBC count levels2
.
Rapid proliferation, high tumour burden reflected by elevated serum lactate dehydrogenase (LDH)
level and discrete chemosensitivity suggest more elevated risk diseases, but host conditions as
chronic renal impairment with or without pre-existing electrolytes disturbances, dehydration and
volume depletion also has a predisposing role9, 81, 88-90
. A recent study reported
hyperphosphatemia, together with tumour burden assessed by LDH level and disseminated
intravascular coagulation, as an important factor predicting clinical TLS. Particularly, 1-mmol
increase in blood phosphate level confers a 5-fold increased risk of TLS and AKI in patients with
aggressive haematological diseases91
.
In the last twenty years, few classification systems have been developed in an attempt to facilitate
recognition of rapidly worsening subgroups. In 1993 Hande and Garrow differentiated laboratory
TLS (LTLS) and clinical TLS (CTLS), in order to highlight patients with high risk of complications and
need to tight management4
. Shortcomings of this classification were time-limiting onset of
metabolic alterations within four days from treatment starting and laboratory abnormalities rising
>25% above baseline with no concern about derangement at presentation. In the effort of address
these limitations in the absence of uniformly recognized criteria, Cairo and Bishop developed a
new system in which they consider LTLS as abnormal laboratory findings at presentation and/or
increase >25% above baseline and CLTS as occurrence of renal failure, seizures, cardiac
arrhythmias and/or sudden death79
.
LTSL is defined by the occurrence of two or more of the following alterations arising three days
before through seven days after starting of chemotherapy: increased uric acid >25% from baseline
or values >8 mg/dl (476 μmol/l); increased potassium >25% from baseline or values >6 mEq/l (6
mmol/l); increased phosphorus >25% from baseline or values >4.5 mg/dl (1.45 mmol/l); decreased
calcium >25% from baseline or values <7 mg/dl (1.75 mmol/l). Clinical TLS is defined by the
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10. 9
presence of LTSL associated to at least one among renal failure (creatinine value more than 1.5
times above upper normal limit), cardiac arrhythmia or seizures (Table 2).
Tosi et al. developed a recommendation panel mostly based on the Cairo and Bishop Classification
system, except that they consider creatinine clearance measurement to be a more reliable pattern
of kidney function than serum creatinine level92
.
In 2010 an international experts panel moved to a more complex stratification of patients that
considered histological cancer subtypes, stage and tumour burden, chemotherapeutic agents,
presenting clinical features and previous established chronic diseases, in order to quantify single
patient risk of TLS18
. Based on literature review, they develop a three step model. First evaluation
is about presenting LTLS: it is diagnosed if high level of both potassium and phosphorus occur with
normal uric acid level, or if elevation of one electrolyte level occurs with high uric acid
concentration. Second, patients are stratified according to cancer type. Solid tumours are almost
totally considered low risk disease (LRD), except for those presenting with high burden or known
to be high chemosensitive (germ cells tumour, small-cell lung cancer, neuroblastoma) which are
classified as intermediate risk disease (IRD). Leukemias are differentiated as chronic and acute:
chronic myeloid leukemia (CML) is always LRD and B-ALL is always high risk disease (HRD). CLL is
considered LRD, except when presenting WBC count is high or when targeted and/or biological
therapies are used, that is IRD. AML and ALL can be HRD, IRD, LRD or HRD, IRD respectively based
on WBC count and LDH level. Indolent and Hodgkin lymphomas are classified as LRD; BL is usually
IRD when presenting in early stage and HRD when disseminate. Aggressive lymphomas can be
LRD, IRD or HRD depending on age, LDH, stage and tumour burden; myelomas are always LRD
(Table 3). The third step is about presence or absence of impaired function and cancer
involvement of kidneys: patients classified as low or intermediate risk can be shifted into a more
severe category if clues of renal disease are present. Based on that, the probability of developing
TLS in each category varies from <1% in LRD patients to a >5% risk in HRD patients.
In 2015 some authors evaluated baseline serum uric acid (SUA) as predictor of LTLS in AML
patients: they demonstrated that SUA alone is highly predictive of LTLS development when
compared to more complex models, and correlates to AKI too93
.
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11. 10
MANAGEMENT
The best approach of TLS is prevention: hydration and frequent monitoring of laboratory test in
newly diagnosed patients undergoing chemotherapy is the cornerstone of TLS management.
Hydration +/- diuretics
The first and probably the most important intervention to prevent TLS is hydration, which can be
given virtually to all risk categories. Vigorous fluid administration (3 l/mq/day or 200 ml/kg/day if
body weight <10 kg) reduce waste products concentration, improve renal blood flow and
glomerular filtration rate. Current use of diuretics may be helpful to maintain an urinary output of
100 ml/mq/h (or 6 ml/kg/h if body weight <10 kg), but is contraindicated if hypotension due to
volume depletion or obstructive uropathy occurs. Addition of electrolytes should be avoided, in
order to prevent iatrogenic derangement. Continuous monitoring of fluid balance is strictly
recommended, and blood electrolytes and uric acid concentration tests should be performed at
least every six hours for intermediate risk patients and even more frequently in high risk category.
Hyperuricemia correction
Two drugs are involved so far in the treatment of hyperuricemia. Allopurinol is a structural
analogue of hypoxanthine that competitively inhibits the liver enzyme xanthine-oxidase,
preventing the conversion of hypoxanthine to xanthine and of xanthine to uric acid. It is rapidly
absorbed through gastro-intestinal tract but has a short half-life (60-180 minutes): it is converted
to his active metabolite oxypurinol that has a longer lasting action of 18-30 hours, allowing once
daily administration. Since 1968, an intravenous formulation of allopurinol is available and has
been demonstrated to be not inferior in terms of safety and efficacy to oral compound94
.
Although allopurinol is effective to prevent and treat hyperuricemia89
, there are several limitations
to its use. First, it may cause allergic, even life-threatening adverse reactions like Stevens-Johnson
syndrome95-96
. Second, some important drug interactions are known such as delayed catabolism of
anti-metabolite drugs like 6-mercaptopurin and azathioprine, whose dose should be reduced to
one third or one fourth during allopurinol administration8
. It may also increase bone marrow
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12. 11
toxicity after cyclophosphamide administration and reduce clearance of high dose methotrexate;
attention should be paid with concomitant administration of dicumarol (potential for prolonged
prothrombin time) and chlorpropamide (rise in half life and risk of hypoglycemia in renal impaired
patients)8
.
Allopurinol is administered orally at a dose of 50-100 mg/mq every eight hours (maximum dose:
300 mg/mq/d) or 10 mg/kg divided in three daily doses (maximum dose: 800 mg/d). Because of
renal excretion, dose should be reduced at 50% in the setting of chronic renal failure. Allopurinol
has a slow onset of action of 24-72 hours and does not reduce pre-existing high SUA97
; moreover,
cases of xanthine nephropathy and calculi have been reported89, 98-100
. Treatment should be
started 12 through 24 hours before chemotherapy begins and continued from 3 to 7 days
afterwards or until SUA returns normal or TLS risk lowers2
. Far from being the perfect drug in this
clinical setting, allopurinol still play a major role in the treatment of hyperuricemia.
An alternative approach to hyperuricemia is breaking down uric acid in a more soluble compound.
Humans and primates lack urate-oxidase enzyme, due to two nonsense mutations in the promoter
and coding region of the gene101
: this enzyme is able to convert uric acid in allantoin, which is 5 to
10 times more soluble in urine than uric acid102, 103
. A non-recombinant enzyme called uricozyme
had been initially derived from Aspergillus flavus104
and used in clinical trials with high efficacy105-
108
, but with even life-threatening allergic adverse reactions rate of 5%92,107
. After cloning the
fungal enzyme and expressing it in Saccharomyces cerevisiae strains109
, the recombinant form of
this enzyme has been developed, reducing adverse reaction rate but not efficacy110-112
. This new
drug named rasburicase is well tolerated and highly effective in preventing and reversing TLS
associated hyperuricemia in pediatric and adult patients113
: only 1% allergic adverse events have
been reported. As for uricozyme114
, rasburicase use is contraindicated in glucose 6 phosphate
dehydrogenase deficit patients, because of their inability to break down hydrogen peroxide, a
product of urate oxidase reaction115
. Rasburicase does not need dose adjustment in renal impaired
patients and does not interfere with activity of cytochrome P450.
For an average-weight patient the manufacturer recommends rasburicase to be administered
intravenously at a dose of 0.1-0.2 mg/kg daily from at least 4 hours before chemotherapy up to 5
days; half-life is between 16 and 21 hours for the recommended dose, justifying once daily
administration110
. During rasburicase treatment, importance should be given to sample
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13. 12
management and processing when uric acid levels are checked: recombinant enzyme causes uric
acid degradation in room temperature samples, leading to spurious low serum levels in blood test
results. In order to avoid inaccuracy, blood samples tested for uric acid need to be stored in ice
bath and processed as soon as possible8
.
When considering high-risk patients, rasburicase administration is cost-effective: prevention of
renal failure considerably reduces the total cost of treating patients with haematological
malignancies, mainly due to reduced hospitalisation and lower requirement of renal replacement
therapy9, 116
. Despite effectiveness in treating hyperuricemia and clinical advantages on allopurinol
have been demonstrated, the high cost of rasburicase limits its use in clinical practice only to
patients presenting with the greatest risk of TLS, intolerant to allopurinol or reduced compliance
to oral medications.
Monitoring acid uric level aids to better define the length of treatment duration2, 117
. A number of
studies have been performed, aiming to demonstrate fixed (not weight-based) single dose of
rasburicase to be as effective as scheduled dose in TLS patients. In a randomized study, Vadhan-
Raj et al. demonstrated that a single weight-based rasburicase dose was effective in 100%
potential risk patients and 71.4% high risk patients118
. Some authors compared SUA level
reduction at 24 hours after administration of single fixed dose of rasburicase 3 mg, 6 mg or 7.5 mg:
rasburicase 6 mg administered once was as effective as weight-adjusted dosing in normalizing SUA
level119
. Others reported that fixed dose of rasburicase 3 mg was effective in a large majority of
patients with high risk hematological malignancies, regardless baseline SUA: only 8 out of 42
patients required two or more administrations120
. A single institution series reported a correlation
between fixed single dose rasburicase and baseline SUA level: 6 mg versus 3 mg dosage produced
a median 10 mg/dl versus 5 mg/dl reduction of SUA levels respectively121
. No differences are
reported in reduction of SUA levels after fixed single dose of rasburicase in overweight and obese
compared with normal weight patients121, 122
.
Febuxostat is a xanthine oxidase inhibitor with a non-purine structure which inhibits both the
oxidized and reduced forms of the enzyme, preventing the inhibition of other enzymes involved in
purine and pyrimidine metabolism. Its absorption is not substantially modified by age and gender
and the drug is metabolized in the liver and eliminated by both kidney and liver equally, with no
need for dose adjustment in mild to moderate impaired renal function123
. The recommended dose
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14. 13
for gout and hyperuricemia is 10 mg/day: it is well tolerated, with lower incidence of
hypersensitivity compared to allopurinol, and effective in preventing hyperuricemia associated
with TLS124
. A Japanese group reported that an increased dose of 40 mg/day is not significantly
inferior in TLS prevention compared to allopurinol125
. Recently, in a randomized double-blind
study febuxostat at 120 mg fixed daily dose has been demonstrated to be superior than
allopurinol in preventing TLS, even when different SUA level, TLS risk, creatinine level and
malignancy are analyzed separately126
.
Electrolytes correction
While hypocalcemia is quite always asymptomatic, prompt correction of hyperphosphatemia and
hyperkalemia has to be addressed. Initial treatment of hyperphosphatemia includes intense
hydration regimen like 2-3l/mq/day and oral administration of phosphate binders as aluminium
hydroxide at a dose of 15 ml (50–150 mg/kg/24 h) every six hours; patients should not receive
calcium infusion. Hyperkalemia is frequently asymptomatic and can be corrected by oral or rectal
administration of sodium polystyrene sulphate (1 g/kg with 50% sorbitol every six hours). In
symptomatic patients, more rapid intervention is required, like insulin 0.1 ml/kg and glucose 25%
2 ml/kg infusion. EKG monitoring is needed until potassium has corrected. Hypocalcemia recovery
is not recommended in the setting of hyperphosphatemia because of increased risk of calcium-
phosphate precipitation; if symptoms of hypocalcemia occur, careful infusion of calcium gluconate
50-100 mg/kg may be performed as clinician judgement79
.
Urine alkalinisation
The role of urine alkalinisation is still controversial17, 92, and 97,127-129
. It has been routinely used after
observation of increased solubility of urate products and avoidance of urate crystals deposition130,
131
. The maximum urate solubility occurs at pH 7.5, but in alkaline urine xanthine and
hypoxanthine solubility decreases: this may lead to xanthine crystals precipitation if concurrent
allopurinol is given8, 95,132
. Moreover, alkaline pH may facilitate calcium-phosphorus crystals
formation and increase the risk of symptomatic hypocalcemia. So far urine alkalinisation in not
routinely recommended in TLS management8, 128
, unless required by other clinical conditions92
.
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15. 14
Dialysis
Despite optimal care, some patients can experience acute renal failure, uncontrolled derangement
of electrolytes and fluid overload: they should promptly be evaluated by nephrology specialist and
undergo hemodialysis. Although rasburicase use, renal replacement therapy still ranges between
1.5% for pediatric and 5% for adult patients133
. Although indications for renal replacement are the
same as for other diseases, lower thresholds may be considered in the setting of TLS due to high
rate potassium release and accumulation. Indication for dialysis are hyperkalemia >6 mEq/L,
serum creatinine level >10 mEq/L, hyperphosphatemia >10 mEq/L, SUA >10 mEq/L, symptomatic
hypocalcemia, fluid overload, severe acidosis and uremia79, 134
. In general, standard intermittent
hemodialysis is preferred because of its best clearance of uric acid, even though potassium
rebound limits its efficacy. While phosphorus clearance increases as long as treatment duration
does, continuous renal replacement may be more effective in correcting this alteration135, 136
.
EXPERT COMMENTARY
Clinical TLS is still an emergency that can impair the chance of an effective cytotoxic therapy and
lead to severe morbidity and occasionally deathh. Even in the most recent reports mortality rate is
about 15% of established cases, with a higher percentage of patients facing hemodialysis after
acute kidney injury1
. Prompt recognition of LTLS characteristics and rapid institution of
prophylactic measures usually allow resolution of laboratory derangements and improve clinical
symptoms. Grade of suspicion needs to be kept high: all patients affected by haematological
malignancies undergoing cytotoxic therapy need WBC count, serum electrolytes, LDH, SUA,
albumin and creatinine to be checked. Whenever LTLS is established, vital signs, body weight,
arterial blood analysis, serum electrolytes, SUA and EKG should be strictly monitored, in order to
prevent worsening of renal function, development of clinically significant arrhythmia and
deteriorating general conditions. Uricosuric therapy should also be maximized: patients treated
with allopurinol will benefit from rasburicase shift. In some cases, delay of chemotherapy should
be considered, even though patients typically present with severe disease: initial lower or
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16. 15
fractionated chemotherapy together with strong hydration and rasburicase administration may be
effective in limiting renal toxicity without affecting patients’ outcome.
FIVE-YEAR VIEW
TLS is a well-known complication of chemotherapy treatment; nevertheless morbidity and
mortality still occur in a minority of patients. Since its initial report more than eighty years ago,
clinical skills and therapeutic options have improved and now are currently used in the daily
practice. Among cancer characteristics and pre-existing chronic patients’ diseases, TLS risk factors
have been clearly identified. The most important clues to forecast TSL development are tumor
burden and rate of cell proliferation, both suggestive of high metabolic turnover. Some
chemotherapeutic agents are reported to favor TLS by provoking rapid lysis in chemosensitive
neoplasms, as radiation therapy and local chemoembolization may also do. Cytotoxic, even not
strictly chemotherapeutic, agents like steroids in lymphoproliferative acute and chronic diseases
may also determine TLS. In the era of target therapy, immunotherapy and tyrosine kinase
inhibitors have significantly less hematological toxicity than traditional drugs: nonetheless they
can exacerbate TLS in case of myeloid or lymphoid neoplasms presenting with high WBC count.
Looking at the growing number of targeted drugs whose use will spread in the next future, it is still
of great importance to recognize and treat TLS. Incorrect management of this frequent
chemotherapy complication can lead to suboptimal cancer treatment, end organ damage and
long-lasting sequelae.
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17. 16
KEY ISSUES
TLS is a clinical syndrome that needs a high suspicion to be recognized and correctly managed:
it can lead to severe morbidity and be potentially fatal.
It's important to recognize patients at higher risk of developing this complication, in order to
rapidly institute corrective measures mainly fluid therapy and uricosuric drugs.
Whenever TLS is established, vital signs and laboratory work up should be strictly monitored in
order to identify rapidly worsening patients and maximize intervention.
If acute kidney injury develops, nephrologist evaluation should not be delayed and eventually
hemodialysis should be initiated.
Fixed single dose of rasburicase is not inferior to weight-based dose of rasburicase to control
hyperuricemia, both in normal and in overweight/obese patients. If clinically indicated,
rasburicase can be repeated until SUA normalizes.
In the era of targeted therapy, immunotherapy and tyrosine kinase inhibitors are not free from
metabolic consequences, especially in case of myeloid or lymphoid neoplasms presenting with
high WBC count.
Incorrect management of this frequent chemotherapy complication can lead to suboptimal
cancer treatment, end organ damage and long-lasting sequelae.
In some cases, delay of chemotherapy should be considered: initial lower or fractionated
chemotherapy together with strong hydration and rasburicase administration may be effective
in limiting renal toxicity without affecting patients’ outcome.
Financial and competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a
financial interest in or financial conflict with the subject matter or materials discussed in the manuscript.
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18. 17
This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants
or patents received or pending, or royalties.
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Table 1. Drugs reported to be associated to TLS
Hydroxyurea Fludarabine Steroids Rituximab Bortezomib Ibrutinib
Radiation
therapy
Chen SW. et al
2005
Nakhoul F. et al
1996
Rajagopal S. et al
1992
Hande KR,
Garrow GC
1993
Sezer O. et
al 2006
Byrd JC. et
al 2013
Jain S. et al
2010
Seki JT. et al
2003
Mulligan SP,
Dean MG 1994
Sparano J. et al
1990
Yang H. et al
1999
Kaur V et
al 2014
Schifter T. et
al 1999
Ellis AK, Lee
DH. 2002
List AF. et al
1990
Dhingra K,
Newcom SR 1988
Jensen M. et al
1998
Cheson BD. et al
1998
Tiley C. et al 1992
Abou Mourad
Y. et al 2003
Hussain K. et al
2003
Lerza R. et al
2002
Jabr FI 2005
Coutinho AK. et al
1997
Francescone
SA. et al 2009
Malik IA. et al
1994
Otrock ZK. et
al 2008
Vaisban E. et al
2001
Yang B. et al
2012
Chanimov M. et al
2006
Downloadedby[UniversityofCalifornia,SanDiego]at10:1308December2015
30. 29
Table 2. Diagnostic criteria of LTLS and CLTS (from Cairo&Bishop 2004).
SUA K Ph Ca
LTLS
increase >25% baseline
or >8 mg/dl
increase >25% baseline
or >6 mEq/l
increase >25% baseline
or >4.5 mg/dl
decrease >25% baseline
or <7 mg/dl
CLTS two or more of the above alterations, plus at least one among
Renal failure
Cardiac arrhythmia
Seizures
(SUA: serum uric acid; K: potassium; Ph: phosphorus; Ca: calcium. LTLS: laboratory tumor lysis syndrome; CLTS: clinical
tumor lysis syndrome)
Table 3. Risk criteria for developing TLS (from Cairo&Coiffier 2010).
Low risk disease Intermediate risk disease High risk disease
Type of cancer
germ cells cancer
small-cell lung cancer
neuroblastoma
high burden solid cancer
CML
CLL B-ALL
indolent lymphomas
Hodgkin lymphoma Burkitt lymphoma
multiple myeloma
acute leukemias depending on WBC count and LDH
aggressive lymphomas depending on age, LDH, stage and tumour burden
solid cancer
hematologic neoplasms
solid cancer (all except IRD)
high WBC count CLL
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31. 30
(CML: chronic myeloid leukemia; CLL: chronic lymphocytic leukemia; WBC: white blood cells; B-ALL: B acute
lymphoblastic leukemia).
Figure 1. Percentage of TLS in the hematological neoplasms
(ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; CML: chronic
myeloid leukemia; CLL: chronic lymphocytic leukemia; HL: Hodgkin lymphoneoplasms).
ma; NHL: non-Hodgkin lymphoma; BL: Burkitt lymphoma; MM: multiple myeloma;
MPN: myeloproliferative
11% 4%
11%
18%
4%
31%
2%
15%
4%
ALL
AML
CML
CLL
HL
Aggressive NHL
BL
MM
MPN
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