5. Cellular Aberration


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Biology of cancer

Prepared by: Sir Flas Julius Floresta

Published in: Health & Medicine

5. Cellular Aberration

  1. 1. 5. CELLULAR ABERRATIONThe Biology of Cancer Part 4
  2. 2. LUNG CARCINOMA Currently the most frequently diagnosed major cancer in the world and the most common cause of cancer mortality worldwide Largely due to carcinogenic effects of cigarette smoke Adenocarcinoma (males 37%, females 47%) Squamous cell carcinoma (males 32%, females 25%) Small cell carcinoma (males 14%, females 18%) Large cell carcinoma (males 18%, females 10%)
  3. 3. LUNG CARCINOMA In the usual case it is discovered in patients in their 50s whose symptoms are several months duration Major presenting complaints:a. Cough (75%)b. Weight loss (40%)c. Chest pain (40%)d. Dyspnea (20%)
  4. 4. LUNG CARCINOMA In general, the adenocarcinoma and squamous cell patterns tend to remain localized longer and have a slightly better prognosis than do the others Paraneoplastic syndromes – clinical manifestations produced by lung tumors that secrete hormones like ADH, ACTH, PTH, calcitonin, gonadotropins, serotonin Lambert-Eaton syndrome – probably due to antibodies produced by certain lung carcinomas
  5. 5. LUNG CARCINOMA Diagnosis1. Chest x-ray2. CT or combined PET–CT3. Cytopathology examination of pleural fluid or sputum4. Usually, bronchoscopy-guided biopsy and fine- needle aspiration5. Sometimes open lung biopsy
  6. 6. LUNG CARCINOMA Management1. Surgery (depending on cell type and stage)2. Chemotherapy3. Radiation therapy4. Nursing care is based on supportive treatment
  7. 7. LUNG CARCINOMA NURSING INTERVENTIONS (http://nursingcrib.com/nursing-notes-reviewer/lung-cancer/)1. Elevate the head of the bed to ease the work of breathing and to prevent fluid collection in upper body (from superior vena cava syndrome).2. Teach breathing retraining exercises to increase diaphragmatic excursion and reduce work of breathing.3. Augment the patient’s ability to cough effectively by splinting the patient’s chest manually.4. Instruct the patient to inspire fully and cough two to three times in one breath.
  8. 8. LUNG CARCINOMA NURSING INTERVENTIONS (http://nursingcrib.com/nursing-notes-reviewer/lung- cancer/)5. Provide humidifier or vaporizer to provide moisture to loosen secretions.6. Teach relaxation techniques to reduce anxiety associated with dyspnea.7. Allow the severely dyspneic patient to sleep in reclining chair. Encourage the patient to conserve energy by decreasing activities.8. Ensure adequate protein intake such as milk, eggs, oral nutritional supplements; and chicken, fowl, and fish if other treatments are not tolerated – to promote healing and prevent edema.
  9. 9. LUNG CARCINOMA NURSING INTERVENTIONS (http://nursingcrib.com/nursing-notes-reviewer/lung- cancer/)9. Advise the patient to eat small amounts of high-calorie and high-protein foods frequently, rather than three daily meals.10. Suggest eating the major meal in the morning if rapid satiety is the problem.11. Change the diet consistency to soft or liquid if patient has esophagitis from radiation therapy.12. Consider alternative pain control methods, such as biofeedback and relaxation methods, to increase the patient’s sense of control.13. Teach the patient to use prescribed medications as needed for pain without being overly concerned about addiction.
  10. 10. THYROID CARCINOMA 1.5% of all cases in the US Female > Male in incidence in those that develop during the early and middle adult years F = M if it develops during childhood and late adult life Papillary carcinoma (>85%) Follicular carcinoma (5% to 15%) Anaplastic (undifferentiated) carcinoma (<5%0 Medullary carcinoma (5%)
  11. 11. THYROID CARCINOMA Papillary carcinoma Follicular carcinomaMost common form 5% to 15% of thyroid malignanciesOccur throughout life, but most often More common in womenbetween the ages of 25 and 50 Present at an older age with a peak incidence between 40 and 60 years of ageAccount for the majority of thyroid More frequent in areas with dietarycarcinomas associated with previous deficiency of iodineexposure to ionizing radiationExcellent prognosis Prognosis is largely dependent on the site of invasion and stageSpread is though the lymphatics Spread is both through the lymphatics and vascular route
  12. 12. THYROID CARCINOMA Neck lump - in the front of the neck near the Adams apple Neck nodule Painless neck lump Neck swelling Hoarseness Difficulty speaking Voice changes Swollen neck lymph nodes Swollen lymph nodes Difficulty swallowing Difficulty breathing Throat pain Neck pain http://www.wrongdiagnosis.com/t/thyroid_cancer/symptoms.htm
  13. 13. THYROID CARCINOMA Physical exam - especially a neck exam. Thyroid blood tests TSH blood test Thyroglobulin blood test Calcium blood test Ultrasonography Radionuclide scanning http://www.wrongdiagnosis.com/t/thyroid_cancer/symptoms.htm
  14. 14. THYROID CARCINOMA Biopsy Fine-needle aspiration Surgical biopsy Pathology analysis Neck ultrasound Neck MRI Neck CT Diagnostic I-131 whole body scan - looks for thyroid cancer cells throughout the body. http://www.wrongdiagnosis.com/t/thyroid_cancer/symptoms.htm
  15. 15. THYROID CARCINOMA Thyroid cancer is most treatable and curable if caught in the earliest stage of the disease. Treatment is individualized to the type and stage of advancement of the disease, a persons age, medical history, coexisting diseases and other factors. Treatment of thyroid cancer may include a combination of surgery, radioactive iodine treatment, chemotherapy, and radiation therapy. Surgery generally includes removing most of the thyroid. Thyroid hormone replacement therapy is prescribed to replace the hormones that were produced by the thyroid. http://www.wrongdiagnosis.com/t/thyroid_cancer/symptoms.htm
  16. 16. PANCREATIC CARCINOMA 4th leading cause of cancer in the US 5-year survival rate is dismal, less than 5% Primarily a disease of the elderly 80% of cases occur between the ages of 60 and 80 Strongest influence is cigarette smoking Other risk factors: fatty diet, chronic pancreatitis, DM, heredity (?)
  17. 17. CLINICAL FEATURES Remain silent until they invade adjacent structures Obstructive jaundice – specially if carcinoma of the pancreatic head Migratory thrombophlebitis (Trousseau sign) – attributable to the elaboration of platelet-aggregating products and procoagulants from the carcinoma or its necrotic products (10% of cases) Course is typically brief and progressive Serum levels of CEA and CA19-9 are often elevated CT-guided biopsy Treatment is surgical (Whipple procedure), chemotherapy and radiotherapy, supportive
  18. 18. WHIPPLE PROCEDURE The Whipple procedure (pancreatoduodenectomy) is the most common operation performed for pancreatic cancer and may be used to treat other cancers such as small bowel cancer. Surgeons remove the head of the pancreas, most of the duodenum (a part of the small intestine), a portion of the bile duct and sometimes a portion of the stomach. After the pancreatoduodenectomy, the surgeon reconstructs the digestive tract.
  19. 19. WHIPPLE PROCEDURE At Mayo Clinic, surgeons perform more than 100 Whipple procedures annually. Patients leave the hospital in an average of 14 days. http://www.mayoclinic.org/pancreatic- cancer/whippleprocedure.html
  20. 20. LEUKEMIA The uncontrolled replication of the hematologic progenitor cells involved in the development of white blood cells, red blood cells, and platelets May originate in any of the blood-forming organs, including the bone marrow, lymphatic system, and spleen A heterogenous disease with various biologic and clinical presentations that influence a person’s response to therapy
  21. 21. LEUKEMIA Classification depends on which progenitor cell it originated (lymphoid or myeloid) and is further classified as being acute or chronic on the basis of clinical presentation and cell maturity In the acute phase, the malignancy occurs during early cell differentiation, resulting in rapid replication with blasts In the chronic phase, unregulated replication of differentiated cells occurs The four major classifications of leukemia:1. Acute lymphocytic leukemia (ALL)2. Chronic lymphocytic leukemia (CLL)3. Acute myelogenous leukemia (AML)4. Chronic myelogenous leukemia (CML)
  22. 22. INCIDENCE 2004 – estimated 33,440 new cases diagnosed 10x likelier to occur on adulthood than in childhood Overall incidence: M>F More often in the older adult, with more than half the cases occurring in the 6th decade Most common leukemias among adults: AML and CML CML: seen more frequently in adults and accounting for a small proportion of the overall leukemias ALL: makes up the smallest proportion of leukemias, and is most frequently seen among pediatric patients
  23. 23. RISK FACTORS Genetics Environmental exposures Viral infections Immunodeficiency Children with Trisomy 21 are approximately 20x likelier to develop leukemia than the general population Children younger than 3 years of age likeliest to develop megakaryoblastic subset of AML Older children are likeliest to develop ALL Siblings are to- to fourfold greater risk of AML High risk among identical twins
  24. 24. RISK FACTORS Diagnostic and ionizing radiation Cigarette smoke Electromagnetic fields or high power lines Alkylating agents is associated with secondary AML Viruses – T and B cell lymphoma Immunodeficiency – high risk for lymphoma
  25. 25. DETECTION – ACUTE LEUKEMIA The patient experiences symptoms within weeks to months of the beginning of the acute malignant process The most common symptoms and physical findings at diagnosisa. Anemiab. Feverc. Thrombocytopeniad. Neutropeniae. Pallorf. Fatigueg. Anorexiah. Petechiaei. Bleedingj. Infection
  26. 26. DETECTION - ACUTE LEUKEMIA In addition, the patient may have extramedullary disease and present with generalized or local lymphadenopathy , bone pain, bone fracture Extramedullary disease:a. CNS involvement – vertigo, nausea, vomiting, papilledema, and blurred visionb. Parotid gland infiltrationc. Testicular infiltrationd. Hepatomegalye. Splenomegaly
  27. 27. DETECTION – CHRONIC LEUKEMIA Clinical manifestations similar to acute leukemia but have an insidious onset Fatigue Exercise Intolerance Night sweats Abnormal fullness secondary to splenomegaly Infection secondary to hypogammaglobulinemia
  28. 28. DIAGNOSIS Complete PE and history CBC with platelets and differential count – peripheral smear Chemistry panel Bone marrow aspirate Morphology/cytochemistry Flow cytometry Immunophenotype Cytogenetic/molecular features LAP (leukocyte alkaline phosphatase) score
  29. 29. Peripheral Smear Normal granulocytesAML
  30. 30. Normal lymphocyte and monocyteCLL
  31. 31. Normal bone marrow aspirateLeukemia - bonemarrow aspirate
  32. 32. Flowcytometry
  33. 33. Immunophenotyping
  34. 34. LAP Score
  35. 35. LEUKEMIAClassification of myeloid malignanciesFABChronic myeloproliferative diseases Myelodysplastic syndromes Acute myeloid leukamiaWHO Chronic myeloproliferative diseases Myelodysplastic/myeloproliferative diseases Myelodysplastic syndromes Acute myeloid leukemiasNote: The WHO classification system puts a few diseases that show characteristics of both myeloproliferative and myelodysplastic conditions into a new, separate group (myeloproliferative/myelodysplastic diseases).(http://xenia.sote.hu/depts/pathophysiology/hematology/e/who- classification.html#myeloid)
  36. 36. CLASSIFICATION OF CHRONICMYELOPROLIFERATIVE DISEASESFAB Chronic myelogenous leukemia (CML) Agnogenic myeloid metaplasia with myelofibrosis (MF) (Idiopathic myelofibrosis) Polycythemia vera (PV) Essential thrombocythemia (ET)
  37. 37. CLASSIFICATION OF CHRONICMYELOPROLIFERATIVE DISEASESWHO CML Ph+: t(9;22)(qq34;q11), BCR/ABL Chronic neutrophilic leukemia Chronic eosinophilic leukemia/hypereosinophilic syndrome Chronic idiopathic myelofibrosis Polycythemia vera Essential thrombocythemia
  38. 38. ACUTE MYELOID LEUKEMIAS (AML)FAB M0: minimally differentiated M1: myeloblastic leukemia without maturation M2: myeloblastic leukemia with maturation M3: hypergranular promyelocytic leukemia M4: myelomonocytic leukemia M4Eo: variant, increase in marrow eosinophils M5: monocytic leukemia M6: erythroleukemia (DiGuglielmos disease) M7: megakaryoblastic leukemia
  39. 39. ACUTE MYELOID LEUKEMIAS (AML)WHO AML with recurrent cytogenetic translocations AML with multilineage dysplasia AML with myelodysplastic syndrome, therapy related AML not otherwise categorizedAML minimally differentiatedAML without maturationAML with maturationAcute myelomonocytic leukemiaAcute monocytic leukemiaAcute erythroid leukemiaAcute megakaryocytic leukemiaAcute basophilic leukemiaAcute panmyelosis with myelofibrosis
  40. 40. LYMPHOMAS WHO classification1. Non-Hodgkin lymphoma B-cell lymphoma T-cell lymphoma2. Hodgkin lymphoma Nodular lymphocyte-predominant Hodgkins disease Classical Hodgkins disease Nodular sclerosis Hodgkins disease Lymphocyte-rich classical Hodgkins disease Mixed-cellularity Hodgkins disease Lymphocyte-depletion Hodgkins disease
  41. 41. TREATMENT Goal1. Eradicate the malignant clone2. Allowing growth of normal hematopoietic cells ALL – treatment is divided into stages1. Induction2. Consolidation3. Maintenance Based on the patient’s prognostic factors, the remission induction chemotherapy program generally includes some if not all of the following drugs:
  42. 42. TREATMENTALL Based on the patient’s prognostic factors, the remission induction chemotherapy program generally includes some if not all of the following drugs:1. Cyclophosphamide2. Vincristine3. Dexamethasone or prednisone4. L-asparaginase5. Doxorubicin
  43. 43. TREATMENTALL Some programs include high doses of methotrexate and cytosine arabinose as part of the induction scheme Others use a drug called etoposide The patient is monitored closely for the disappearance of peripheral blasts and treatment-related side effects At the end of the induction, the marrow is examined for morphologic and molecular presence of disease Many treatment regimens have a month of reintensive induction within the first year of therapy
  44. 44. TREATMENTALL Consolidation is several weeks long and includes courses of methotrexate or cytarabine At the consolidation of treatment, maintenance therapy begins with drugs used in a combination, rotational schedule
  45. 45. TREATMENTALL Maintenance therapy may include:1. Cytarabine2. Thioguanine3. Methotrexate4. Cyclophosphamide5. Vincristine6. Prednisone/dexamethasone7. Doxorubicin8. L-aspariginase9. Mitoxantrone10. 6-mercaptopurine
  46. 46. TREATMENTALL The rotational therapy is administered over a 2- to 3-year course Patients also receive intrathecal chemotherapy with methotrexate or cytarabine for prophylaxis or treatment of CNS involvement If leukemia cells are positive in the spinal fluid, radiation therapy may also be given to the brain Bone marrow/stem cell transplantation may be a treatment option for patients who have an early relapse, have disease that is unresponsive to therapy, or have unfavorable cytogenetics
  47. 47. TREATMENTAML Two phases:1. Induction – cytarabine and daunorubicin or idarubicin; intensive therapy that lasts for 1 week2. Postremission or consolidation to maintain remission – options:a. Several courses of high-dose cytarabine chemotherapyb. Allogenic (donor) stem cell transplantationc. Autologous stem cell transplantation
  48. 48. TREATMENTCML Allogenic bone marrow or stem cell transplantation – the only curative therapy Interferon alfa and imatinib mesylate (Gleevec) – treatment options for ineligible, unwilling, or waiting to undergo transplantation Avoid grapefruit juice when giving Gleevec, because this juice is known to increase the drug’s level
  49. 49. TREATMENTCLL Observation Chemotherapy Monoclonal antibiotics, which target the surface antigen Bone marrow transplantation
  50. 50. REHABILITATION The patient and family must balance the treatment regimen and uncertainty of the future, while attempting to maintain a sense of control and normalcy Fatigue is a common complaint of patients – feelings of sadness, sleepiness, dizziness, nausea, feeling heavy, mentally tired, not one’s self, and feeling sorry for one’s self Patient may not resume their life as it was before leukemia
  51. 51. THE ROLE OF THE NURSE Patient and family education A supportive presence Active monitoring and anticipates events Technically competent Advocacy
  52. 52. LYMPHOMA One of the group of malignancies that originate from the lymphatic system Two groups:1. Hodgkin lymphoma2. Non-Hodgkin lymphoma
  53. 53. HODGKIN LYMPHOMA Age-related bimodal incidence distribution Peaks in mid 20s Declines until mid 40s Increases after age 60 Rare before the age of 10 More common in males One of the most curable malignancies
  54. 54. HODGKIN LYMPHOMA Risk factors1. Etiology is not known2. EBV – has been suggested3. Defects in the immune system function4. Increased incidence among siblings – genetic risk (?)
  55. 55. HODGKIN LYMPHOMA Clinical manifestations1. Often asymptomatic2. Painless lymphadenopathy most commonly found in the supraclavicular, cervical, and mediastinal3. Spleen, liver, and retroperitoneal lymph nodes may be involved4. Unexplained weight loss of more than 10% of body weight in 6 months before diagnosis5. Frequent, drenching night sweats; fever with temperatures above 38C6. Pruritus may be present
  56. 56. HODGKIN LYMPHOMA Diagnosis and Staging1. Thorough history and physical examination2. Hematology3. Chemistry profile4. Histology: Reed-Sternberg cells5. Chest X-ray to demonstrate mediastinal involvement
  57. 57. Ann Arbor Costwold Staging Classification Indicated for Hodgkin and Non-Hodgkin LymphomaClinical StagingStage I Involvement of a single lymph node region. Extension into an extralymphatic organ or site (IE)Stage II Involvement of two or more lymph node regions on the same side of the diaphragm. Extension into an extralymphatic site (IIE)Stage III Involvement of lymph node regions or structures on both sides of the diaphragm. May be divided into disease of the upper (III1) or lower (III2) abdomen, if spleen is involved (IIIS); if extralymphatic extension (IIIE)Stage IV Diffuse involvement of liver, bone marrow, lung, or diffuse extralymphatic diseaseFor all stages A. No symptoms B. Presence of symptoms (fever, sweats, weigh loss of >10% of BW)
  58. 58. HODGKIN LYMPHOMA Treatment1. Radiation therapy – curative in most patients with stage I or II disease2. Chemotherapy – used in most patients with stage III and stage IV disease and in some patients with earlier stage of the disease3. Hematopoietic stem cell transplantation
  59. 59. NON-HODGKIN LYMPHOMA (NHL) Seven times more common than HL Overall 5 years survival rate with optimum treatment for all patients – approximately 50%-60% Males more affected than females Risk factors:a. Congenital or acquired immune deficienciesb. Those undergoing organ transplantationc. Autoimmune disease
  60. 60. ETIOLOGY Malignancy of the B or T lymphocytes Clones of the malignant cells may infiltrate the lymph nodes, bone marrow, peripheral blood, or other organs Pattern of spread is less predictable than in HL Frequently disseminated at the time of diagnosis
  61. 61. CLINICAL MANIFESTATIONS Localized or generalized lymphadenopathy that waxes or wanes over a period of several months Early involvement of the oropharyngeal lymphoid tissue or infiltration of the bone marrow is common Abdominal mass may be detected with GIT involvement Night sweats Fever Weight loss Splenomegaly or hepatomegaly – 1/3 of patients
  62. 62. DIAGNOSIS AND STAGING Careful examination of the all lymph nodes CBC Chemistry Bone marrow and lymph node biopsy Ann Arbor-Costwold Staging Classification – useful but has less value for NHL (does not account for the histology or type of tumor)
  63. 63. TREATMENT Surgery – primary role is to establish diagnosis and to assist with staging, and is rarely needed to prevent bowel obstruction or for splenectomy in patients with hypersplenism Radiation and chemotherapy – NHL is spread via the vascular system (HL is spread contiguously via node extension), so radiotherapy is used as an adjuvant to chemotherapy as opposed to being the primary treatment Immunotherapy/Biotherapy – rituximab (monoclonal antibody) is used for the treatment of relapsed or refractory low-grade or follicular CD20-positive B-cell lymphoma Rituximab is also indicated as a first line treatment with combination chemotherapy for aggressive lymphomas
  64. 64. SYMPTOM MANAGEMENT, LONG-TERMSEQUELAE Education Protection of patients because patients remain neutropenic for a long time Proper referral to the Oncologist Cyclophosphamide is used in chemotherapy – risk of developing secondary malignancies