Renal cell carcinoma (RCC) often presents with vague symptoms in its early stages, and patients may remain asymptomatic. As the disease progresses, common clinical features may include:
Hematuria: Blood in the urine is a common sign, often presenting as either visible blood or microscopic hematuria.
Flank Pain: Discomfort or pain in the side or lower back, potentially associated with tumor expansion or pressure on surrounding structures.
Palpable Abdominal Mass: A palpable lump or mass in the abdomen may be felt during a physical examination.
Weight Loss and Fatigue: Advanced stages may lead to unintended weight loss and fatigue.
Paraneoplastic Syndromes: Some RCCs produce hormones or cytokines, leading to paraneoplastic syndromes, such as elevated erythropoietin levels causing polycythemia.
Pathology:
Histological Subtypes: Clear cell, papillary, chromophobe, and other rare subtypes exist. Clear cell is the most common and typically associated with worse prognosis.
Genetic and Molecular Alterations: Mutations in tumor suppressor genes (e.g., VHL, PBRM1, BAP1), chromosomal deletions, and alterations in cellular pathways contribute to RCC development.
Tumor Grading: Fuhrman grade and ISUP grading system assess tumor differentiation, with higher grades indicating a poorer prognosis.
Tumor Necrosis: Histologic coagulative tumor necrosis is an independent predictor of outcome.
Imaging:
CT Scan: High-resolution computed tomography (CT) imaging is the primary modality for RCC diagnosis and staging, providing detailed visualization of the tumor, surrounding structures, and potential metastases.
MRI: Magnetic resonance imaging (MRI) offers additional soft tissue contrast and is particularly useful for characterizing renal masses.
Ultrasound: Ultrasound may be used for initial assessment and is effective in detecting solid masses but may have limitations in characterizing complex lesions.
Nuclear Medicine: Positron emission tomography (PET) scans can be used for staging and detecting distant metastases.
Prognosis:
TNM Staging: The tumor, node, metastasis (TNM) staging system stratifies patients based on the extent of disease.
Anatomic Factors: Invasion into the renal vein or inferior vena cava, perinephric fat extension, and involvement of the urinary collecting system impact prognosis.
Histopathological Factors: Clear cell histology, higher tumor grade, and tumor necrosis are associated with a worse prognosis.
Molecular Markers: Various molecular markers, genetic alterations, and gene expression profiles can provide additional prognostic information.
Survival Rates: Prognosis varies widely, with early-stage disease having better survival rates compared to advanced stages. Advances in targeted therapies and immunotherapy have improved outcomes for some patients with advanced RCC.
Benign Biliary Stricture is a common condition which we encounter during gastro practice. Here we discuss in detail about its diagnosis and management.
Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, presents with various clinical features that can help diagnose and stage the disease. These features, along with imaging studies and laboratory tests, aid in determining the extent and severity of HCC. Here are the key clinical features and staging considerations:
Clinical Features:
Abdominal Pain: HCC can cause pain or discomfort in the upper right abdomen due to liver enlargement or tumor growth.
Jaundice: Yellowing of the skin and eyes (jaundice) may occur when the tumor affects liver function or obstructs the bile ducts.
Weight Loss: Unintentional weight loss may result from factors such as decreased appetite or cancer-related wasting.
Fatigue and Weakness: HCC patients often experience persistent fatigue and generalized weakness.
Loss of Appetite and Nausea: HCC can lead to reduced appetite, resulting in nausea and vomiting.
Abdominal Swelling: Ascites, the accumulation of fluid in the abdomen, may cause abdominal distension and discomfort.
Enlarged Liver: As HCC progresses, the liver may become palpable due to its enlargement and the presence of a tumor.
Staging: HCC staging helps determine the extent and spread of the cancer, guiding treatment decisions. The most commonly used staging system for HCC is the Barcelona
Management of acute lymphoblatic leukemia with light on etiology, clinical features, diagnosis and different aspects of management including chemotherapy and radiation therapy
Euthanasia, derived from Greek words meaning "good death," is a complex and controversial ethical and legal issue revolving around the deliberate ending of a person's life to relieve suffering. It is often a topic of intense debate within medical, legal, religious, and ethical circles.
Types of Euthanasia:
Voluntary Euthanasia: This occurs when a competent person makes a voluntary and informed decision to end their life with the assistance of a medical professional or loved one.
Non-voluntary Euthanasia: In this scenario, the decision to end a person's life is made by someone other than the individual, typically when they are unable to make decisions for themselves due to being in a coma or having advanced dementia.
Involuntary Euthanasia: This is the termination of a person's life against their will or without their consent, often performed in situations where the person's suffering is deemed unbearable or where their quality of life is deemed too low by others.
Assisted Suicide: This involves providing a person with the means or information necessary to end their own life, such as prescribing lethal medication, while the individual ultimately carries out the act themselves.
Ethical Considerations:
Autonomy vs. Sanctity of Life: Supporters of euthanasia argue for individual autonomy and the right to die with dignity, while opponents often cite the sanctity of life and the potential for abuse or slippery slope arguments.
Quality of Life: Discussions often revolve around the subjective nature of suffering and the quality of life, with some arguing that euthanasia can alleviate unnecessary suffering, while others raise concerns about the potential devaluation of certain lives.
Medical Ethics: Euthanasia raises questions about the role of healthcare professionals in end-of-life care, the distinction between killing and allowing to die, and the obligations of physicians to relieve suffering while upholding ethical principles.
Legal Status:
The legality of euthanasia varies greatly around the world. Some countries, such as the Netherlands, Belgium, and Canada, have legalized certain forms of euthanasia under strict conditions, while others, including many U.S. states, maintain its illegality. In some regions, there are ongoing debates and court cases seeking to clarify or change existing laws.
Conclusion:
Euthanasia remains a deeply divisive and emotionally charged issue, touching on fundamental questions about life, death, autonomy, and suffering. As medical technology advances and societal attitudes evolve, discussions surrounding euthanasia are likely to persist, challenging individuals, communities, and policymakers to navigate the complexities of this sensitive topic with compassion and integrity.
Management of locally advanced ovarian, fallopian tube, and peritoneal tumors requires a comprehensive and multidisciplinary approach. Locally advanced tumors are those that have spread beyond the ovaries or fallopian tubes and may involve nearby structures, such as the peritoneum or adjacent organs. Here's a brief overview of the management strategies:
Surgery:
Debulking Surgery: The primary treatment for locally advanced tumors involves cytoreductive or debulking surgery. This aims to remove as much of the tumor as possible. Surgeons may perform a total hysterectomy, bilateral salpingo-oophorectomy, and removal of involved peritoneal tissues.
Lymphadenectomy: Lymph node dissection is often done to assess the extent of the disease spread and to remove involved lymph nodes.
Chemotherapy:
Neoadjuvant Chemotherapy: In some cases, chemotherapy may be administered before surgery to shrink the tumor, making surgery more effective.
Adjuvant Chemotherapy: Following surgery, chemotherapy is typically recommended to target any remaining cancer cells. Platinum-based chemotherapy regimens are commonly used.
Targeted Therapies:
PARP Inhibitors: Poly (ADP-ribose) polymerase inhibitors, such as olaparib and niraparib, have shown efficacy in treating ovarian and related cancers with specific genetic mutations, like BRCA mutations.
Immunotherapy:
Checkpoints Inhibitors: Immune checkpoint inhibitors, like pembrolizumab and nivolumab, may be considered in cases with specific molecular profiles.
Radiation Therapy:
External Beam Radiation: In some situations, radiation therapy may be used to target specific areas affected by the tumor.
Clinical Trials:
Participation in clinical trials may be an option for patients with locally advanced disease, offering access to innovative treatments and therapies.
Follow-up Care:
Regular monitoring and follow-up care are crucial to assess treatment effectiveness and detect any signs of recurrence.
Palliative Care:
Palliative care should be integrated into the management plan to address symptom control, improve quality of life, and provide support for both the patient and their family.
A personalized treatment plan should be developed based on the specific characteristics of the tumor, the patient's overall health, and individual factors. Regular communication among a multidisciplinary team, including surgeons, medical oncologists, radiation oncologists, and other specialists, is essential for optimizing the management of locally advanced ovarian, fallopian tube, and peritoneal tumors.
Benign Biliary Stricture is a common condition which we encounter during gastro practice. Here we discuss in detail about its diagnosis and management.
Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, presents with various clinical features that can help diagnose and stage the disease. These features, along with imaging studies and laboratory tests, aid in determining the extent and severity of HCC. Here are the key clinical features and staging considerations:
Clinical Features:
Abdominal Pain: HCC can cause pain or discomfort in the upper right abdomen due to liver enlargement or tumor growth.
Jaundice: Yellowing of the skin and eyes (jaundice) may occur when the tumor affects liver function or obstructs the bile ducts.
Weight Loss: Unintentional weight loss may result from factors such as decreased appetite or cancer-related wasting.
Fatigue and Weakness: HCC patients often experience persistent fatigue and generalized weakness.
Loss of Appetite and Nausea: HCC can lead to reduced appetite, resulting in nausea and vomiting.
Abdominal Swelling: Ascites, the accumulation of fluid in the abdomen, may cause abdominal distension and discomfort.
Enlarged Liver: As HCC progresses, the liver may become palpable due to its enlargement and the presence of a tumor.
Staging: HCC staging helps determine the extent and spread of the cancer, guiding treatment decisions. The most commonly used staging system for HCC is the Barcelona
Management of acute lymphoblatic leukemia with light on etiology, clinical features, diagnosis and different aspects of management including chemotherapy and radiation therapy
Euthanasia, derived from Greek words meaning "good death," is a complex and controversial ethical and legal issue revolving around the deliberate ending of a person's life to relieve suffering. It is often a topic of intense debate within medical, legal, religious, and ethical circles.
Types of Euthanasia:
Voluntary Euthanasia: This occurs when a competent person makes a voluntary and informed decision to end their life with the assistance of a medical professional or loved one.
Non-voluntary Euthanasia: In this scenario, the decision to end a person's life is made by someone other than the individual, typically when they are unable to make decisions for themselves due to being in a coma or having advanced dementia.
Involuntary Euthanasia: This is the termination of a person's life against their will or without their consent, often performed in situations where the person's suffering is deemed unbearable or where their quality of life is deemed too low by others.
Assisted Suicide: This involves providing a person with the means or information necessary to end their own life, such as prescribing lethal medication, while the individual ultimately carries out the act themselves.
Ethical Considerations:
Autonomy vs. Sanctity of Life: Supporters of euthanasia argue for individual autonomy and the right to die with dignity, while opponents often cite the sanctity of life and the potential for abuse or slippery slope arguments.
Quality of Life: Discussions often revolve around the subjective nature of suffering and the quality of life, with some arguing that euthanasia can alleviate unnecessary suffering, while others raise concerns about the potential devaluation of certain lives.
Medical Ethics: Euthanasia raises questions about the role of healthcare professionals in end-of-life care, the distinction between killing and allowing to die, and the obligations of physicians to relieve suffering while upholding ethical principles.
Legal Status:
The legality of euthanasia varies greatly around the world. Some countries, such as the Netherlands, Belgium, and Canada, have legalized certain forms of euthanasia under strict conditions, while others, including many U.S. states, maintain its illegality. In some regions, there are ongoing debates and court cases seeking to clarify or change existing laws.
Conclusion:
Euthanasia remains a deeply divisive and emotionally charged issue, touching on fundamental questions about life, death, autonomy, and suffering. As medical technology advances and societal attitudes evolve, discussions surrounding euthanasia are likely to persist, challenging individuals, communities, and policymakers to navigate the complexities of this sensitive topic with compassion and integrity.
Management of locally advanced ovarian, fallopian tube, and peritoneal tumors requires a comprehensive and multidisciplinary approach. Locally advanced tumors are those that have spread beyond the ovaries or fallopian tubes and may involve nearby structures, such as the peritoneum or adjacent organs. Here's a brief overview of the management strategies:
Surgery:
Debulking Surgery: The primary treatment for locally advanced tumors involves cytoreductive or debulking surgery. This aims to remove as much of the tumor as possible. Surgeons may perform a total hysterectomy, bilateral salpingo-oophorectomy, and removal of involved peritoneal tissues.
Lymphadenectomy: Lymph node dissection is often done to assess the extent of the disease spread and to remove involved lymph nodes.
Chemotherapy:
Neoadjuvant Chemotherapy: In some cases, chemotherapy may be administered before surgery to shrink the tumor, making surgery more effective.
Adjuvant Chemotherapy: Following surgery, chemotherapy is typically recommended to target any remaining cancer cells. Platinum-based chemotherapy regimens are commonly used.
Targeted Therapies:
PARP Inhibitors: Poly (ADP-ribose) polymerase inhibitors, such as olaparib and niraparib, have shown efficacy in treating ovarian and related cancers with specific genetic mutations, like BRCA mutations.
Immunotherapy:
Checkpoints Inhibitors: Immune checkpoint inhibitors, like pembrolizumab and nivolumab, may be considered in cases with specific molecular profiles.
Radiation Therapy:
External Beam Radiation: In some situations, radiation therapy may be used to target specific areas affected by the tumor.
Clinical Trials:
Participation in clinical trials may be an option for patients with locally advanced disease, offering access to innovative treatments and therapies.
Follow-up Care:
Regular monitoring and follow-up care are crucial to assess treatment effectiveness and detect any signs of recurrence.
Palliative Care:
Palliative care should be integrated into the management plan to address symptom control, improve quality of life, and provide support for both the patient and their family.
A personalized treatment plan should be developed based on the specific characteristics of the tumor, the patient's overall health, and individual factors. Regular communication among a multidisciplinary team, including surgeons, medical oncologists, radiation oncologists, and other specialists, is essential for optimizing the management of locally advanced ovarian, fallopian tube, and peritoneal tumors.
Metastatic breast cancer, specifically HER2-positive subtype, represents an advanced stage of breast cancer characterized by the presence of human epidermal growth factor receptor 2 (HER2) overexpression. HER2-positive breast cancer tends to be more aggressive, but advancements in treatment options have significantly improved outcomes.
Targeted therapies play a crucial role in managing metastatic HER2-positive breast cancer. Trastuzumab (Herceptin) and pertuzumab are monoclonal antibodies that specifically target the HER2 protein, inhibiting its activity and impeding cancer cell growth. These drugs are often used in combination with chemotherapy to enhance their effectiveness.
In addition to trastuzumab and pertuzumab, other HER2-targeted therapies such as ado-trastuzumab emtansine (Kadcyla) and lapatinib may be employed in certain cases. Ado-trastuzumab emtansine is an antibody-drug conjugate that delivers chemotherapy directly to HER2-positive cancer cells, minimizing damage to healthy cells. Lapatinib, on the other hand, is a small molecule inhibitor that blocks HER2 and other related receptors.
Given the chronic nature of metastatic breast cancer, treatment plans are often individualized based on the patient's overall health, specific characteristics of the cancer, and prior treatments. Hormone therapy may also be considered if the cancer is hormone receptor-positive. Clinical trials and ongoing research continue to explore novel treatment options, providing hope for further advancements in managing HER2-positive metastatic breast cancer. Patients are encouraged to work closely with their healthcare team to determine the most appropriate and effective treatment plan tailored to their unique circumstances.
Role of Neoadjuvant Chemotherapy (NACT) in Ovarian Cancer:
Objective: Administer systemic therapy before definitive surgery.
Goal: Reduce perioperative complications, enhance complete resection chances.
Patient Selection:
Offered to clinically apparent, unresectable ovarian cancer cases.
Considered for poor surgical candidates with medical comorbidities.
Diagnostic Laparoscopy: Used in stage III or IV cases to assess resectability.
Chemotherapy Choice: Prefer intravenous platinum-based regimen, e.g., carboplatin plus paclitaxel.
Assessment and Next Steps:
Serial evaluations during NACT, assessing treatment response after three cycles.
Surgical cytoreduction for optimal resection chances.
Consider Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for optimal surgical results if expertise available.
Medical therapy for disease progression or suboptimal response.
Following Surgery:
Recommend adjuvant platinum-based chemotherapy.
Prefer intravenous chemotherapy (carboplatin and paclitaxel for 3-6 cycles) over intraperitoneal therapy.
Non-clear cell renal cell carcinoma (RCC) encompasses diverse subtypes, each requiring tailored therapeutic approaches. Papillary RCC may benefit from immunotherapy or vascular endothelial growth factor receptor (VEGFR) inhibitors. Chromophobe RCC often sees mTOR inhibitors or VEGFR inhibitors as initial treatments. For collecting duct and renal medullary carcinomas, cytotoxic chemotherapy is recommended.
Translocation RCC may respond well to lenvatinib plus pembrolizumab, while unclassified RCC patients might consider immunotherapy-based regimens. Sarcomatoid features in non-clear cell RCC lean towards immunotherapy.
Clinical trials are encouraged due to limited high-quality data, emphasizing the need for personalized strategies based on histologic subtypes. Overall, these recommendations aim to optimize outcomes in the diverse landscape of non-clear cell RCC.
Osteoradionecrosis is a severe complication arising from head and neck radiotherapy. Mainly affecting the posterior mandible, it often manifests in molars and premolars. Common risk factors include high radiation doses, teeth extractions, and smoking. In the context of treatment, ORN can be categorized into four grades (1-4) based on severity.
Key Points:
Incidence: Occurs in approximately 7.5% of cases, with a median onset time of 8 months post-radiotherapy.
Risk Factors:
Higher incidence with elevated mean radiation doses to the mandible.
Smoking and pre-radiotherapy dental extractions significantly increase the risk.
Treatment Approaches:
Conservative management for early stages.
Surgical interventions include sequestrectomy (Stage 2) and, in severe cases, resection (Stage 3, involving mandibulectomy).
Hyperbaric oxygen therapy may aid in non-healing cases.
Prevention:
Precise dose planning tailored to individual patients crucial for minimizing risks.
Consideration of patient-specific factors, such as smoking and dental history, in treatment planning.
ORN underscores the importance of meticulous treatment planning and individualized approaches to minimize this debilitating complication.
Borderline ovarian malignancy, also known as borderline ovarian tumor or ovarian tumors of low malignant potential (LMP), is a distinct category of ovarian tumors that fall between benign and malignant tumors in terms of their behavior and potential for spreading.
Characteristics and Diagnosis:
Histological Features: Borderline ovarian tumors have certain cellular abnormalities that suggest malignancy but lack the invasive qualities seen in fully malignant tumors.
Age Group: They often occur in women of childbearing age, and their incidence tends to be highest in women in their 30s and 40s.
Clinical Presentation: Borderline ovarian tumors may be asymptomatic or present with nonspecific symptoms like abdominal pain, bloating, or changes in urinary habits.
Imaging and Biopsy: Diagnosis typically involves imaging studies, such as ultrasound, and a biopsy or surgical removal of the tumor for a pathological examination to confirm its borderline nature.
Treatment and Prognosis:
Surgical Approach: The primary treatment for borderline ovarian tumors is usually surgery, which involves removing the affected ovary or ovaries. The goal is to perform a comprehensive surgical staging to assess the extent of disease without removing both ovaries unless necessary.
Chemotherapy: Unlike malignant ovarian tumors, borderline tumors are less likely to spread beyond the ovaries. In cases where there is evidence of disease spread or in certain high-risk situations, chemotherapy may be considered.
Prognosis: The overall prognosis for women with borderline ovarian tumors is generally favorable. The majority of patients have an excellent long-term survival rate, especially if the tumor is confined to the ovaries at the time of diagnosis.
Follow-Up and Recurrence:
Regular Monitoring: Given the potential for recurrence, patients with borderline ovarian tumors often undergo regular follow-up examinations, including imaging studies and blood tests (such as CA-125), to monitor for any signs of disease recurrence.
Reproductive Considerations:
Fertility-Sparing Options: For women who wish to preserve fertility, there may be options for fertility-sparing surgery in carefully selected cases where the tumor is unilateral, well-staged, and the patient desires future childbearing.
Conclusion:
Borderline ovarian malignancy represents a unique category in ovarian tumors, requiring a multidisciplinary approach involving gynecologic oncologists, pathologists, and other healthcare professionals. While generally associated with a favorable prognosis, individual cases can vary, and personalized treatment plans are essential for optimal outcomes. Regular follow-up and clear communication between patients and healthcare providers play a crucial role in managing and monitoring borderline ovarian tumors.
Definition: Small cell lung carcinoma (SCLC) is a type of lung cancer that typically starts in the bronchi (large airways) and tends to grow and spread quickly. It accounts for approximately 10-15% of all lung cancers.
Characteristics: SCLC is characterized by small, oat-shaped cancer cells that rapidly divide and form large tumors. It is often associated with a history of smoking and has a strong correlation with tobacco exposure.
Aggressive nature: SCLC is considered highly aggressive, with a tendency to metastasize (spread) early to the lymph nodes and other distant parts of the body, such as the liver, bones, and brain. This rapid spread makes early detection and treatment crucial.
Limited and extensive stage: SCLC is classified into two stages: limited stage and extensive stage. Limited stage means the cancer is confined to one side of the chest and potentially adjacent lymph nodes, whereas extensive stage indicates that the cancer has spread beyond the chest to distant organs.
Treatment approach: The treatment of SCLC typically involves a combination of chemotherapy and radiation therapy. Surgery is generally not recommended for SCLC due to its aggressive nature and tendency to spread early. Chemotherapy, often in combination with immunotherapy, is the mainstay of treatment and can help shrink tumors and control the disease.
Prognosis: The prognosis for SCLC is generally poorer compared to non-small cell lung carcinoma (NSCLC) due to its more aggressive behavior and earlier metastasis. However, treatment advances and research efforts continue to improve outcomes for SCLC patients.
Supportive care: As with any cancer diagnosis, supportive care plays a critical role in managing SCLC. This includes addressing symptoms, managing pain, providing emotional support, and ensuring optimal quality of life for patients.
It's important to consult with healthcare professionals for an accurate diagnosis, personalized treatment plan, and ongoing monitoring for individuals suspected or diagnosed with small cell lung carcinoma.
Definition: Peritoneal mesothelioma is a rare cancer that develops in the lining of the abdomen, known as the peritoneum. It is primarily caused by exposure to asbestos fibers.
Symptoms: Common symptoms include abdominal pain, swelling, changes in bowel habits, unexplained weight loss, and fatigue. However, these symptoms can be nonspecific and resemble other gastrointestinal conditions, which can make diagnosis challenging.
Diagnosis: Diagnosis involves a combination of imaging tests, such as CT scans and MRIs, as well as biopsies to confirm the presence of peritoneal mesothelioma. These tests help determine the extent and stage of the disease.
Treatment options: The management of peritoneal mesothelioma often involves a multimodal approach, tailored to the individual case. Treatment options may include surgery, chemotherapy, and heated intraperitoneal chemotherapy (HIPEC).
Surgical interventions: Cytoreductive surgery aims to remove visible tumors from the abdomen, including affected organs and tissues. It is often performed in combination with HIPEC, a procedure where heated chemotherapy drugs are circulated in the abdominal cavity to target any remaining cancer cells.
Chemotherapy: Systemic chemotherapy, given intravenously or orally, may be used before or after surgery to help shrink tumors, kill cancer cells, and prevent their spread. In some cases, intraperitoneal chemotherapy (IPC) may be used instead of HIPEC.
Palliative care: Palliative care focuses on providing relief from symptoms and improving the quality of life for patients. It may involve pain management, nutritional support, and psychological support for both the patient and their loved ones.
Diagnosis: Prompt and accurate diagnosis is crucial. It involves imaging tests such as X-rays, CT scans, and MRIs, as well as biopsies to confirm the presence of pleural mesothelioma.
Treatment options: The management of pleural mesothelioma typically involves a multidisciplinary approach, which may include surgery, chemotherapy, and radiation therapy. The choice of treatment depends on the stage and extent of the disease, as well as the patient's overall health.
Surgical interventions: Surgical options may include pleurectomy/decortication (removal of the affected tissue lining the lungs) or extrapleural pneumonectomy (removal of the affected lung, lining, and nearby structures). These procedures aim to remove as much of the cancerous tissue as possible.
Chemotherapy: Chemotherapy drugs are often used to kill or slow the growth of cancer cells. They can be administered orally or through intravenous infusions. Sometimes, chemotherapy is given before surgery to shrink tumors and after surgery to target any remaining cancer cells.
Radiation therapy: This treatment involves the use of high-energy X-rays or other radiation sources to target and destroy cancer cells. It can be used before or after surgery, or as a standalone treatment to alleviate symptoms and manage the disease.
Palliative care: Palliative care focuses on improving the quality of life for patients by managing pain, reducing symptoms, and providing emotional and psychological support. It can be integrated into the treatment plan at any stage of the disease.
Systemic treatment in advanced hepatocellular carcinoma (HCC) refers to the use of medications or therapies that are administered throughout the body to target cancer cells beyond the liver. HCC is the most common type of liver cancer and often presents at an advanced stage, making systemic therapies crucial in managing the disease.
One of the main categories of systemic treatment for advanced HCC is targeted therapies. Targeted therapies are designed to selectively inhibit specific molecules or pathways involved in tumor growth, thereby blocking the signals that support cancer cell survival and proliferation. Sorafenib and lenvatinib are examples of targeted therapies that have been approved for the first-line treatment of advanced HCC. They target vascular endothelial growth factor (VEGF) receptors, which play a key role in promoting the growth of new blood vessels necessary for tumor growth. By inhibiting these receptors, these drugs can help slow down tumor growth and improve patient outcomes.
In addition to sorafenib and lenvatinib, other targeted therapies have shown promising results in the treatment of advanced HCC. Regorafenib, for instance, is a multi-kinase inhibitor that targets several pathways involved in tumor angiogenesis, cell proliferation, and survival. Cabozantinib is another multi-kinase inhibitor that has been approved as a second-line treatment option for patients who have progressed on or are intolerant to prior systemic therapy. These targeted therapies have demonstrated efficacy in improving overall survival and delaying disease progression in patients with advanced HCC.
Another significant advancement in systemic treatment for advanced HCC is the use of immune checkpoint inhibitors. Immunotherapy has revolutionized cancer treatment in recent years, including for HCC. Immune checkpoint inhibitors, such as nivolumab and pembrolizumab, work by blocking proteins that act as checkpoints on immune cells, such as programmed cell death protein 1 (PD-1) or its ligand (PD-L1). By doing so, these drugs help restore and enhance the immune system's ability to recognize and eliminate cancer cells. Checkpoint inhibitors have shown promising results, with some patients experiencing durable responses and improved overall survival.
Systemic treatment in advanced hepatocellular carcinoma (HCC) refers to the use of medications or therapies that are administered throughout the body to target cancer cells beyond the liver. HCC is the most common type of liver cancer and often presents at an advanced stage, making systemic therapies crucial in managing the disease.
One of the main categories of systemic treatment for advanced HCC is targeted therapies. Targeted therapies are designed to selectively inhibit specific molecules or pathways involved in tumor growth, thereby blocking the signals that support cancer cell survival and proliferation. Sorafenib and lenvatinib are examples of targeted therapies that have been approved for the first-line treatment of advanced HCC. They target vascular endothelial growth factor (VEGF) receptors, which play a key role in promoting the growth of new blood vessels necessary for tumor growth. By inhibiting these receptors, these drugs can help slow down tumor growth and improve patient outcomes.
In addition to sorafenib and lenvatinib, other targeted therapies have shown promising results in the treatment of advanced HCC. Regorafenib, for instance, is a multi-kinase inhibitor that targets several pathways involved in tumor angiogenesis, cell proliferation, and survival. Cabozantinib is another multi-kinase inhibitor that has been approved as a second-line treatment option for patients who have progressed on or are intolerant to prior systemic therapy. These targeted therapies have demonstrated efficacy in improving overall survival and delaying disease progression in patients with advanced HCC.
Another significant advancement in systemic treatment for advanced HCC is the use of immune checkpoint inhibitors. Immunotherapy has revolutionized cancer treatment in recent years, including for HCC. Immune checkpoint inhibitors, such as nivolumab and pembrolizumab, work by blocking proteins that act as checkpoints on immune cells, such as programmed cell death protein 1 (PD-1) or its ligand (PD-L1). By doing so, these drugs help restore and enhance the immune system's ability to recognize and eliminate cancer cells. Checkpoint inhibitors have shown promising results, with some patients experiencing durable responses and improved overall survival.
CRISPR-Cas9, a revolutionary gene-editing tool, holds immense potential to reshape medicine, agriculture, and our understanding of life. But like any powerful tool, it comes with ethical considerations.
Unveiling CRISPR: This naturally occurring bacterial defense system (crRNA & Cas9 protein) fights viruses. Scientists repurposed it for precise gene editing (correction, deletion, insertion) by targeting specific DNA sequences.
The Promise: CRISPR offers exciting possibilities:
Gene Therapy: Correcting genetic diseases like cystic fibrosis.
Agriculture: Engineering crops resistant to pests and harsh environments.
Research: Studying gene function to unlock new knowledge.
The Peril: Ethical concerns demand attention:
Off-target Effects: Unintended DNA edits can have unforeseen consequences.
Eugenics: Misusing CRISPR for designer babies raises social and ethical questions.
Equity: High costs could limit access to this potentially life-saving technology.
The Path Forward: Responsible development is crucial:
International Collaboration: Clear guidelines are needed for research and human trials.
Public Education: Open discussions ensure informed decisions about CRISPR.
Prioritize Safety and Ethics: Safety and ethical principles must be paramount.
CRISPR offers a powerful tool for a better future, but responsible development and addressing ethical concerns are essential. By prioritizing safety, fostering open dialogue, and ensuring equitable access, we can harness CRISPR's power for the benefit of all. (2998 characters)
Antibiotic Stewardship by Anushri Srivastava.pptxAnushriSrivastav
Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
How many patients does case series should have In comparison to case reports.pdfpubrica101
Pubrica’s team of researchers and writers create scientific and medical research articles, which may be important resources for authors and practitioners. Pubrica medical writers assist you in creating and revising the introduction by alerting the reader to gaps in the chosen study subject. Our professionals understand the order in which the hypothesis topic is followed by the broad subject, the issue, and the backdrop.
https://pubrica.com/academy/case-study-or-series/how-many-patients-does-case-series-should-have-in-comparison-to-case-reports/
Navigating Challenges: Mental Health, Legislation, and the Prison System in B...Guillermo Rivera
This conference will delve into the intricate intersections between mental health, legal frameworks, and the prison system in Bolivia. It aims to provide a comprehensive overview of the current challenges faced by mental health professionals working within the legislative and correctional landscapes. Topics of discussion will include the prevalence and impact of mental health issues among the incarcerated population, the effectiveness of existing mental health policies and legislation, and potential reforms to enhance the mental health support system within prisons.
We understand the unique challenges pickleball players face and are committed to helping you stay healthy and active. In this presentation, we’ll explore the three most common pickleball injuries and provide strategies for prevention and treatment.
R3 Stem Cells and Kidney Repair A New Horizon in Nephrology.pptxR3 Stem Cell
R3 Stem Cells and Kidney Repair: A New Horizon in Nephrology" explores groundbreaking advancements in the use of R3 stem cells for kidney disease treatment. This insightful piece delves into the potential of these cells to regenerate damaged kidney tissue, offering new hope for patients and reshaping the future of nephrology.
The dimensions of healthcare quality refer to various attributes or aspects that define the standard of healthcare services. These dimensions are used to evaluate, measure, and improve the quality of care provided to patients. A comprehensive understanding of these dimensions ensures that healthcare systems can address various aspects of patient care effectively and holistically. Dimensions of Healthcare Quality and Performance of care include the following; Appropriateness, Availability, Competence, Continuity, Effectiveness, Efficiency, Efficacy, Prevention, Respect and Care, Safety as well as Timeliness.
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CHAPTER 1 SEMESTER V - ROLE OF PEADIATRIC NURSE.pdfSachin Sharma
Pediatric nurses play a vital role in the health and well-being of children. Their responsibilities are wide-ranging, and their objectives can be categorized into several key areas:
1. Direct Patient Care:
Objective: Provide comprehensive and compassionate care to infants, children, and adolescents in various healthcare settings (hospitals, clinics, etc.).
This includes tasks like:
Monitoring vital signs and physical condition.
Administering medications and treatments.
Performing procedures as directed by doctors.
Assisting with daily living activities (bathing, feeding).
Providing emotional support and pain management.
2. Health Promotion and Education:
Objective: Promote healthy behaviors and educate children, families, and communities about preventive healthcare.
This includes tasks like:
Administering vaccinations.
Providing education on nutrition, hygiene, and development.
Offering breastfeeding and childbirth support.
Counseling families on safety and injury prevention.
3. Collaboration and Advocacy:
Objective: Collaborate effectively with doctors, social workers, therapists, and other healthcare professionals to ensure coordinated care for children.
Objective: Advocate for the rights and best interests of their patients, especially when children cannot speak for themselves.
This includes tasks like:
Communicating effectively with healthcare teams.
Identifying and addressing potential risks to child welfare.
Educating families about their child's condition and treatment options.
4. Professional Development and Research:
Objective: Stay up-to-date on the latest advancements in pediatric healthcare through continuing education and research.
Objective: Contribute to improving the quality of care for children by participating in research initiatives.
This includes tasks like:
Attending workshops and conferences on pediatric nursing.
Participating in clinical trials related to child health.
Implementing evidence-based practices into their daily routines.
By fulfilling these objectives, pediatric nurses play a crucial role in ensuring the optimal health and well-being of children throughout all stages of their development.
Defecation
Normal defecation begins with movement in the left colon, moving stool toward the anus. When stool reaches the rectum, the distention causes relaxation of the internal sphincter and an awareness of the need to defecate. At the time of defecation, the external sphincter relaxes, and abdominal muscles contract, increasing intrarectal pressure and forcing the stool out
The Valsalva maneuver exerts pressure to expel faeces through a voluntary contraction of the abdominal muscles while maintaining forced expiration against a closed airway. Patients with cardiovascular disease, glaucoma, increased intracranial pressure, or a new surgical wound are at greater risk for cardiac dysrhythmias and elevated blood pressure with the Valsalva maneuver and need to avoid straining to pass the stool.
Normal defecation is painless, resulting in passage of soft, formed stool
CONSTIPATION
Constipation is a symptom, not a disease. Improper diet, reduced fluid intake, lack of exercise, and certain medications can cause constipation. For example, patients receiving opiates for pain after surgery often require a stool softener or laxative to prevent constipation. The signs of constipation include infrequent bowel movements (less than every 3 days), difficulty passing stools, excessive straining, inability to defecate at will, and hard feaces
IMPACTION
Fecal impaction results from unrelieved constipation. It is a collection of hardened feces wedged in the rectum that a person cannot expel. In cases of severe impaction the mass extends up into the sigmoid colon.
DIARRHEA
Diarrhea is an increase in the number of stools and the passage of liquid, unformed feces. It is associated with disorders affecting digestion, absorption, and secretion in the GI tract. Intestinal contents pass through the small and large intestine too quickly to allow for the usual absorption of fluid and nutrients. Irritation within the colon results in increased mucus secretion. As a result, feces become watery, and the patient is unable to control the urge to defecate. Normally an anal bag is safe and effective in long-term treatment of patients with fecal incontinence at home, in hospice, or in the hospital. Fecal incontinence is expensive and a potentially dangerous condition in terms of contamination and risk of skin ulceration
HEMORRHOIDS
Hemorrhoids are dilated, engorged veins in the lining of the rectum. They are either external or internal.
FLATULENCE
As gas accumulates in the lumen of the intestines, the bowel wall stretches and distends (flatulence). It is a common cause of abdominal fullness, pain, and cramping. Normally intestinal gas escapes through the mouth (belching) or the anus (passing of flatus)
FECAL INCONTINENCE
Fecal incontinence is the inability to control passage of feces and gas from the anus. Incontinence harms a patient’s body image
PREPARATION AND GIVING OF LAXATIVESACCORDING TO POTTER AND PERRY,
An enema is the instillation of a solution into the rectum and sig
1. RENAL CELL CARCINOMA: Clinical feature, Pathology,
prognosis
DR. SUMIT KUMAR
Assistant Professor
NEIGRIHMS, Shillong
2. Treatment decisions are tailored to individual cases, taking into account factors such as the patient's overall health
and the specific characteristics of the cancer.
Kidney neoplasms can be primary or secondary. Secondary tumors are often clinically insignificant and discovered
postmortem.
Renal Cell Carcinomas (RCCs): 80-85% of primary renal neoplasms; originate in the renal cortex.
Transitional Cell Carcinomas: Approximately 8%; affect the renal pelvis.
Other Parenchymal Epithelial Tumors: Rare; includes oncocytomas, collecting duct tumors, and renal sarcomas.
Nephroblastoma (Wilms Tumor): Common in children (5-6% of primary renal tumors).
The incidence of RCC varies geographically, with higher rates in developed countries.
Risk factor include smoking, obesity, hypertension, family history of kidney cancer, and certain genetic conditions
like VHL disease.
Surgical removal of the affected kidney (nephrectomy) is often the primary treatment for localized disease.
Advanced cases may require additional approaches, including targeted therapies, immunotherapy, or radiation.
3. • Global Variation: Varies widely globally, with the highest rates in the Czech Republic and North
America.
• INDIA: 21TH rank
• Male Dominance: twofold more common in males than females.
• Age Distribution: Predominantly occurs in the 6th to 8th decade, with a median age at diagnosis
around 64 years.
• Survival Rates: Comparable 5-year survival for African American and White American patients
(over 75%).
• Extent of Disease (SEER Data, 2009-2015):
• Localized Disease: 65 percent.
• Regional Disease: 17 percent.
• Metastatic Disease: 16 percent.
• Unstaged: 3 percent.
• Mortality and Survival Rates:
• Improved Survival: Five-year survival rate doubled from 34 % in 1954 to 75 % from 2009 to
2015.
• Mortality vs. Incidence: Incidence has risen more than threefold higher than the mortality rate.
• Early Detection Impact: Improved survival attributed to earlier detection of smaller tumors (<4
cm) and curative surgical treatment.
4. RISK
FACTOR:
RCC
Smoking
Hyperten
sion
Obesity
Acquired
Cystic
Disease
and CKD
Occupati
onal
Exposure
Analgesic
s
Genetic
Factors
Cytotoxic
Chemoth
erapy
Chronic
Hepatitis
C
Infection
Sickle Cell
Disease
Kidney
Stones
Modifiers
Independent Link: Hypertension
independently predisposes to RCC.
Biological Unknowns: How hypertension
connects to RCC remains unclear
Risk Increase: Cigarette smoking
linked to higher RCC risk.
Severity Impact: More smoking,
more advanced disease at diagnosis.
Diabetes Impact: Modest RCC risk increase in some studies.
Alcohol Effect: Alcohol intake associated with lower RCC risk.
Additional Factors: Diet, reproductive factors, and prior
radiation therapy may modify RCC risk.
Childhood Survivors: Increased RCC risk, especially with prior
kidney-directed radiation or cisplatin exposure
Association: History of kidney stones
tied to higher RCC and transitional cell
carcinoma risk.
Study Limitations: Some study
limitations, including recall bias.
Specific Risk: Sickle cell trait
and disease increase risk for
renal medullary carcinoma
Virus Impact: Chronic infection
significantly increases RCC risK
Childhood Association: Childhood
chemotherapy linked to translocation
RCC later on
Second RCC Risk: Higher risk in those treated
for one renal cancer, especially at a younger
age.
Hereditary Syndromes: Several syndromes
associated with RCC; genetic factors play a role
Chronic Use Risk: Prolonged analgesic
use, especially aspirin, linked to RCC.
Usage Impact: Risk varies with type;
NSAIDs associated with higher risk.
Carcinogen Link: Exposure to
cadmium, asbestos, and petroleum
byproducts increases RCC risk.
Genetic Connection: May be linked to
pathogenic variants, like VHL.
Dialysis Risk: Up to 30x higher RCC risk
in dialysis patients.
Incidence Correlation: Higher risk with
lower eGFR in non-dialysis patients.
Weight Impact: Excess body weight
increases RCC risk.
Better Prognosis: Higher weight
associated with lower stage and grade;
longer survival in metastatic cases.
5. • Many patients remain asymptomatic until
advanced stages.
• Approximately 25% present with distant
metastases or advanced locoregional disease.
• In a series of 701 patients: Incidentally diagnosed
patients had significantly better disease-specific
survival at five years (76% vs. 44% in symptomatic
cases).
• Multivariate analysis attributes the difference to
lower stage and histologic grade at diagnosis.
• In one review of 309 consecutive patients with
RCC, the most common presenting symptoms
were hematuria, abdominal mass, pain, and
weight loss
6. 1.Classic Triad (Present in ≤9%):
• Flank Pain
• Hematuria
• Palpable Abdominal Renal Mass
2.Hematuria:
• Indicates Tumor Invasion of Collecting System
• Severe Cases Cause Clots and Colicky Discomfort
• Clot Presence Significant for Unexplained Hematuria
3.Abdominal/Flank Mass:
• Common with Lower Pole Tumors
• Characteristics: Firm, Homogeneous, Nontender
• Movement with Respiration
4.Scrotal Varicoceles (11% in Males):
• Typically Left-Sided
• Fail to Empty Recumbent: Suspicion of Gonadal Vein Obstruction
5.Inferior Vena Cava Involvement:
• Manifestations: Lower Extremity Edema, Ascites, Hepatic Dysfunction, Pulmonary Emboli
• Possible Budd-Chiari Syndrome
6.Metastatic Disease Symptoms:
• Sites: Lungs, Lymph Nodes, Bone, Liver, Brain
• Diagnosis: Often Through Biopsy of Accessible Metastasis Alongside Abdominal CT-Confirmed Renal Mass.
7. 1. Anemia:
• Precedes RCC Diagnosis in 29-88% of Advanced Cases
• Disproportionately Severe, Normocytic or Microcytic
• Often Associated with Anemia of Chronic Disease
2. Hepatic Dysfunction (Stauffer Syndrome):
• Uncommon, 21% Paraneoplastic Alkaline Phosphatase Elevation
• Associated with Fever, Weight Loss, Fatigue
• May Result from Tumor Cytokine Production (GM-CSF, IL-6)
• Nephrectomy May Improve Hepatic Dysfunction
3. Fever:
• Up to 20% of Patients
• Intermittent, Accompanied by Night Sweats, Anorexia, Weight
Loss, Fatigue
• Unclear Origin
4. Hypercalcemia:
• Occurs in 15% of Advanced RCC
• Mechanisms: Lytic Bone Metastases, PTHrP Overproduction, IL-6
Action
• NSAID (Indomethacin) Administration may be Effective
5.Cachexia:
• Significant Weight Loss and Muscle Atrophy
6.Erythrocytosis:
• 1-5% of Advanced RCC
• Due to Constitutive Erythropoietin Production
• Impaired Regulation of Hypoxia-Inducible Proteins
7.Secondary (AA) Amyloidosis:
• Up to 5% of Patients
• Reflects Chronic Inflammatory Response
• Amyloid Fibrils Composed of Serum Amyloid A Protein
Fragments
8.Thrombocytosis:
• Rare, Poor Prognosis
• Associated with Tumor IL-6 Production
9.Polymyalgia Rheumatica-like Syndrome:
• Resembles Polymyalgia Rheumatica
• Unresponsive to Prednisone, Often Corrected by
Nephrectomy
8. Imaging Modalities:
• Abdominal CT or Ultrasonography: Initial tests for suspected RCC or incidental
findings.
• CT Advantages: High sensitivity; useful for detailed assessment.
• Ultrasonography: Less sensitive but aids in distinguishing simple cysts from tumors.
• MRI: Utilized when CT or ultrasonography is inconclusive or iodinated contrast is
contraindicated.
• MRI Advantages: Assess tumor growth into the collecting system or vessels; helpful in
neoplasm diagnosis.
Criteria for Simple Cyst Differentiation (Ultrasonography):
• Cyst is round, sharply demarcated with smooth walls.
• No echoes within the cyst (anechoic).
• Strong posterior wall echo, indicating good transmission through a cyst.
• If criteria met, no further evaluation needed due to low malignancy likelihood.
CT Findings (Simple Cyst vs. Tumor):
• Simple Cyst: Smooth appearance, no enhancement with intravascular contrast, water-
density.
• Tumor: Thickened irregular walls or septa, enhancement after contrast injection.
MRI with Dynamic Gadolinium Contrast:
• Useful in distinguishing papillary or clear cell RCC from other solid renal neoplasms.
• Does not replace the need for tissue diagnosis.
• Sensitivity for papillary RCC: 86%, Specificity: 92%.
Angiography:
• Indications: Rarely necessary; useful for preoperative vasculature mapping.
• Alternatives: CT or MR angiography preferred for nephron-sparing surgery planning.
9.
10. •Specific CT Findings:
•Enhancement Pattern: Less
intense enhancement
compared to clear cell.
•Cystic Changes: May have
central necrosis or cystic
components.
•Specific CT Findings:
•Intermediate Enhancement:
Between clear cell and papillary
types.
•Distinctive Histology: Pale,
eosinophilic cytoplasm with
perinuclear halos.
•Specific CT Findings:
•Hypervascular Mass:
Enhances intensely in the
arterial phase.
•Clear Cytoplasm: Due to
lipid and glycogen content.
•exophytic appearance
•Characteristics: Solid,
enhancing lesion in the kidney.
•Specific Findings:
•Hypervascularity: Rapid
enhancement during the
arterial phase.
•Washout: Contrast washes
out during the venous and
delayed phases.
Enhancing
Renal Mass:
Clear Cell RCC:
Papillary RCC:
Chromophobe
RCC:
11. •CT Findings:
•Fat Content: Presence of
macroscopic fat (negative
Hounsfield Units) is
characteristic.
•Enhancement: May
enhance with contrast.
•CT Features:
•Enhancement Pattern:
Often shows
homogeneous
enhancement.
•Central Scar: May have a
central stellate scar.
•Simple Renal Cysts:
•CT Appearance: Smooth, thin-walled,
anechoic (no internal echoes).
•Enhancement: No enhancement with
contrast.
•Complex Renal Cysts:
•CT Appearance: Irregular, thickened
walls, internal septations, or solid
components.
•Enhancement: May show variable
enhancement patterns.
•Specific CT Findings:
•Aggressive Features:
Invasion of adjacent
structures,
heterogeneous
enhancement.
•High-Grade Appearance:
Mimics features of a
sarcoma.
Sarcomatoid
RCC:
Cystic Renal
Lesions (Cyst
Differentiation):
Renal
Angiomyolipoma
(AML):
Oncocytoma:
12. • Classification by Cell Type and Growth Pattern:
• RCCs were initially classified based on cell type and growth pattern.
• The classification has evolved to consider morphology, growth pattern, cell of origin,
histochemical, and molecular characteristics.
• Subtypes of RCC:
• Clear Cell (75 to 85 percent): Most common subtype.
• Papillary (10 to 15 percent): Characterized by papillary structures.
• Chromophobe (5 to 10 percent): Distinctive large, polygonal cells.
• Oncocytic (3 to 7 percent): Cells with eosinophilic, granular cytoplasm.
• Collecting Duct (Very Rare): Uncommon subtype.
• Molecularly Defined RCCs (Rare): Subtypes identified based on molecular
characteristics.
• Unclassified (Up to 5 percent): Tumors that do not fit into specific subtypes.
• Prognosis and Unclassified RCCs:
• Up to 5 percent of RCCs are considered unclassified.
• Reports suggest worse prognosis compared to clear cell cancers, but findings are
inconsistent and may depend on clinicopathologic features.
• Sarcomatoid Features:
• RCC with sarcomatoid features is not considered a distinct subtype.
• Sarcomatoid dedifferentiation can occur in any histologic subtype of RCC.
• Small Tumors and Malignancy:
• Tumors smaller than 3 cm were previously thought to be benign adenomas.
• Current understanding recognizes that even small tumors can represent carcinomas,
and size alone may not be sufficient for the malignant-benign distinction.
13. 1.Clear Cell Carcinomas (CCC):
• Origin: Arise from the proximal tubule.
• Macroscopic Appearance: Can be solid or, less
commonly, cystic.
• Association: Specifically associated with von Hippel-
Lindau (VHL) disease.
• Prognosis: Poor prognosis associated with higher
nuclear grade or the presence of a sarcomatoid pattern,
especially in early-stage disease.
• Variants: Multilocular cystic clear cell RCC has a more
favorable prognosis compared to other clear cell
carcinomas.
2.Genomic Alterations:
Chromosome-Level Alterations:
• Loss of 3p (91 to 94 percent): Contains genes
associated with RCC, including VHL, BAP-1, PBRM1,
among others.
• Gain of 5q (67 to 69 percent).
• Monosomy or partial loss of 14q (42 to 45 percent).
• 7q gain (20 percent).
• 8p deletion (32 percent).
14. • Common dedifferentiation in RCC, not a distinct subtype.
• Histology: Presence of sarcoma-like cells, resembling
fibrosarcoma or fibrous histiocytoma.
• Grading: Categorized as grade IV; sarcomatoid component
can range from 1 to 100 percent.
• Prognosis: Higher sarcomatoid proportion may indicate
worse prognosis, but no validated cutoff.
• Aggressive Features: Often accompanied by necrosis
(90%), microvascular invasion (30%), and rhabdoid features
(25%).
• Molecular Insights: Molecular profiles similar to epithelioid
component; specific alterations like NF2, BAP1, CDKN2A,
and EZH2 enrichment.
• Treatment and Prognosis: Rapid disease progression, less
responsive to antiangiogenic therapies; potential robust
response to immune checkpoint inhibitors.
• Immunotherapy Targets: CD274 (PD-L1 gene)
amplifications, higher PD-L1 protein expression, increased
CD8+ T cell infiltration, and upregulation of interferon-gamma
response genes.
• Clinical Implications: Molecular alterations offer potential
h featuring large numbers of discohesive
rhabdoid tumor cells (arrows)
15. • Represents approximately 15% of kidney cancers, originating
from the proximal tubule.
• Classification:
• Historical Types (Type I and Type II): Once classified based on
cytopathologic findings, but this classification is no longer used due to
poor reliability.
• Current Classifications: MET status (MET-driven versus not) and
morphology (biphasic, Warthin-like, solid, papillary renal neoplasm with
reverse polarity).
• Genomic Features:
• Type 1 Papillary RCC:
• Typically presents with stage I or II disease, with a relatively favorable
prognosis.
• Associated with hereditary papillary RCC with activating germline MET
pathogenic variants.
• Somatic MET pathogenic variants identified in 10 to 20% of nonhereditary
cases.
• Altered MET status or increased chromosome 7 copy number identified in 81%
of cases.
• Biomarker-driven classification proposed in advanced papillary RCC based on
MET pathogenic variants.
• Type 2 Papillary RCC:
• Often associated with aggressive disease, advanced stage, and poor
prognosis.
• Many tumors previously categorized as type 2 have been reclassified into
other molecularly defined RCC subtypes.
• Less likely to have alterations in the MET pathway compared to type 1.
Notice the frequent psammomatous
calcifications (arrows) and
macrophages filled with hemosiderin
pigment;
16. Histology:
• Composed of darker cells than clear cell carcinoma.
• Originates from the intercalated cells of the collecting system.
• Lacks abundant lipid and glycogen.
Genetic Characteristics:
• Hypodiploid number of chromosomes.
• Does not delete the 3p chromosomal genetic locus.
• Comparative genomic hybridization studies show a variety of abnormalities, including loss of
chromosomes 1, 2, 6, 10, 13, 17, or 21.
• Upregulation of the KIT oncogene on the cell membranes.
Prognosis:
• Disease Progression: May have a lower risk compared to clear cell carcinomas, potentially
influenced by lower stage at presentation.
• Recurrence and Mortality Rates: Vary; one series with 392 patients showed a 9% recurrence rate
and 6% cancer-related mortality at a median follow-up of 44 months.
• Survival Rates: In one series of 124 patients, the five-year disease-specific survival was initially
better than clear cell carcinoma (78% vs. 60%), but this difference disappeared when corrected for
stage.
TCGA Project Findings:
• Analysis of 66 chromophobe RCCs.
• Mitochondrial DNA and gene expression analysis highlight mitochondrial function as an important
component of disease biology.
• Genomic rearrangements show recurrent structural breakpoints within the TERT promoter region,
correlating with highly elevated TERT expression.
showing the characteristic perinuclear
clearing and distinctive (plant-like) cellular
borders
17. Characteristics:
Uncommon tumors with 3 to 7 percent incidence among renal tumors.
Composed of well-differentiated oncocytes with intensely eosinophilic granular cytoplasm due
to numerous mitochondria.
Typically unilateral and single; multiple and bilateral cases associated with tuberous sclerosis
complex (TSC) and Birt-Hogg-Dubé syndrome.
Histological Challenges:
Distinguishing from RCC can be difficult histologically.
Some solid tumors initially thought to be RCCs may actually be oncocytomas.
Genetic Characteristics:
Chromosomal analyses show heterogeneity, including loss of Y and 1, rearrangements
involving CCND1 at 11q13, involvement of 12q12-13, and loss of 14q.
Cyclin D1 (CCND1) overexpression and rearrangement can help distinguish oncocytoma
from chromophobe RCC.
Behavior and Prognosis:
Behave in a generally benign fashion despite a growth rate similar to RCC.
Well encapsulated, rarely invasive, and rarely associated with metastases.
Coexistence with RCC:
Coexisting RCC identified in 10 to 32 percent, especially in cases of diffuse oncocytic
nodules (renal oncocytosis).
Close monitoring advised, and treatment considered for rapidly growing tumors.
Risk of Metachronous Tumors:
Low risk after resection; retrospective series (median follow-up seven years) showed 4
percent subsequent renal tumors, including oncocytomas and RCCs.
18. Primary tumor (T)
T category T criteria
TX Primary tumor cannot be assessed
T0 No evidence of primary tumor
T1 Tumor <_ 7 cm in greatest dimension, limited to the kidney
T1a Tumor <_4 cm in greastest dimension, limited to the kidney
T1b Tumor >4 cm but < 7 cm in greatest dimension, limited to the kidney
T2 Tumor >7 cm in greatest dimension, limited to the kidney
T2a Tumor >7 cm but < 10 cm in greatest dimension, limited to kidney
T2b Tumor>10 cm , limited to kidney
T3 Tumor extends into major veins or perinephric tissues, but not into the ipsilateral adrenal gland and not beyond Gerota’s fascia
T3a Tumor extends into the renal vein or its segmental branches, or invades the pelvicalyceal system, or invades perinal and/ or renal sinus fat but not
beyond Gerota’s fascia
T3b Tumor extends into the vena cava beloiw the diaphragm
T3c Tumor extends into the vena cava above the diaphragm or invades the wall of the vena cava
T4 Tumor invades beyond Gerota’s fascia ( including contiguous extension into the ipsilateral adrenal gland)
Regional lymph nodes (N)
N category N criteria
NX Regionlal lymph node cannot be assessed
N0 No regional lymph node metastases
N1 Metastasis in regional lymph node(s)
Distant metastasis (M0
Mctegory Mcriteria
M0 No distant metastasis
M1 Distant metastasis
19. Initial evaluation
Evidence of distant metastases on imaging
Yes No
Metastatic disease confirmed by biopsy?
Yes No
1 to 3 metastases with resectable primary? <4cm?
Nephrectomy and
metastasectomy
Candidate for upfront
cytoreductive
nepectomy?
Small renal mass:
Partial nephrectomy
preferred
Is the patient a
candidate for
definitive surgery?
Observation :
systemic therapy
only for recurrence
Cytoreductive
nephrectomy
followed by systemic
therapy
Systemic therapy :possible
cytoreductive neppherectomy if
major response
Choice of
procedure
Radical nephrectomy preffered
Centrally located
Suspected lymph node involvement
Renal vein or IVC involvement
Direct extension into the ipsilateral adrenal gland
Systemic therapy,
palliative care
Partial nephrectomy preffered:
Solitary kidney
Multiple, small, and/or bilateral tumors
With or at risk for chronic renal disease
Yes
No No
Yes
Yes
No Yes No
20. STAGE DISCRIPTION 5- YR SURVIVAL RATE
I Localized tumor, no invasion beyond the kidney >90%
II Localized tumor, some invasion into nearby areas 75-95%
III Tumor extends beyond the kidney and nearby
areas
59-70%
Stage IV:
•Survival Improvement: Overall survival for stage IV RCC has improved in the era of
immunotherapy and targeted therapy.
•In subsequent studies of patients receiving either targeted therapies (such as pazopanib or
sunitinib) or checkpoint inhibitor immunotherapy (with nivolumab plus ipilimumab), median
overall survival was over two years (approximately 28 months)and almost five years (56
months), respectively
21. 1.Urinary Collecting System Invasion:
• Stage III Impact: Significantly worse disease-specific and overall
survival.
• Data: Multivariate analysis in Stage III cases showed 34% vs. 59% and
30% vs. 52% five-year rates.
2.Venous Involvement (T3a, T3b, T3c):
• Impact: Recognized as a prognostic factor in the TNM system.
• Data: Invasion of renal vein, inferior vena cava below diaphragm (T3b),
and wall invasion or extension above diaphragm (T3c) adversely
affects prognosis.
3.Perinephric Fat Extension (T3a):
• Conflicting Data: Inconsistent impact on prognosis.
• Studies: Varied results; two studies found no difference compared to
T1 and T2 tumors, while others identified it as a prognostic factor.
22. 1.Tumor Type:
• Impact: Controversial, with clear cell histology possibly associated with
poorer cancer-specific survival.
• Aggressive Variants: Collecting duct, renal medullary carcinomas, and
histologies with sarcomatoid or rhabdoid features indicate a more aggressive
nature.
2.Tumor Grade:
• Correlation: Higher histologic grade independently correlates with lower
survival.
• Systems: Fuhrman grade and ISUP grading system are commonly used.
• Survival Rates: Grades 1 associated with higher (89%) and grades 3 to 4
with lower (46%) five-year survival rates.
3.Tumor Necrosis:
• Predictor: Histologic coagulative tumor necrosis independently predicts
outcomes, especially in clear cell and chromophobe RCC.
• Integrated Staging: Part of staging systems like SSIGN score
23. • Karnofsky performance status score <80
• Time from original diagnosis to initiation of targeted therapy <1 year
• Hemoglobin less than the lower limit of normal
• Serum calcium greater than the upper limit of normal
• Neutrophil count greater than the upper limit of normal
• Platelet count greater than the upper limit of normal
Favorable risk: None of the above risk factors present.
Intermediate risk: 1 or 2 of the above risk factors present.
Poor risk: 3 or more risk factors present.
24.
25. Renal cell carcinomas (RCCs) are the most common primary tumor arising in the kidney, accounting for approximately 80 to 85
percent of such tumors
Risk factors associated with a significantly increased incidence of RCC include smoking, obesity, hypertension, and others
Abnormalities of the von Hippel- Lindau (VHL) tumor suppressor gene are implicated in most cases of clear cell RCC (both sporadic
and familial).
Abdominal computed tomography (CT) or ultrasound can confirm the presence of a mass, distinguish RCC from a benign cyst, and
assess the extent of disease.
RCC is more frequently being diagnosed incidentally as a consequence of increased use of imaging procedures for other reasons
For patients presenting with localized renal cell carcinoma (RCC), the tumor, node, metastasis (TNM) staging system provides the
primary prognostic information
26. KINDLY COMMENT AND PRESS LIKE
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