4. Cellular Aberration


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For MMC-CN Students. Lectured by Prof. Julius Floresta.

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4. Cellular Aberration

  1. 1. 4. CELLULAR ABERRATIONThe Biology of Cancer part 3
  2. 2. CARCINOMA OF THE BREAST Most common non-skin malignancy in women Most important risk factor is gender – only 1% of breast cancer occur in men Incidence rises throughout the woman’s lifetime, peaking at age of 75 to 80 years, and then declining slightly thereafter Women who reach menarche when younger than 11 years of age have 20% increased risk compared with women who are more than 14 years of age at menarche Late menopause also increases risk
  3. 3. CARCINOMA OF THE BREAST Full term pregnancy at ages younger than 20 years have half the risk of nulliparous women or women over age 35 at their first birth Other risk factors: first-degree relatives with breast cancer, atypical hyperplasia, race/ethnicity, estrogen exposure, breast density, radiation exposure Carcinoma of the contralateral breast or endometrium Geographic influence
  4. 4. CARCINOMA OF THE BREAST Diet – caffeine decreases risk and moderate to heavy consumption of alcohol increases risk Obesity Exercise Breastfeeding – the longer you breastfeed, the greater the reduction risk Environmental toxins Tobacco Major risk factors for the development are hormonal and genetic
  5. 5. CARCINOMA OF THE BREAST Carcinoma in-situ or DCIS (ductal carcinoma in- situ) LCIS (lobular carcinoma in-situ) Invasive ductal carcinoma in-situ Invasive lobular carcinoma in-situ Medullary carcinoma Mucinous (colloid) carcinoma Tubular carcinoma Invasive papillary carcinoma Metaplastic carcinoma
  6. 6. CARCINOMA OF THE BREAST Major prognostic factors:1. Invasive carcinoma vs in-situ disease2. Distant metastases3. Lymph node metastases4. Tumor size5. Locally advanced disease6. Inflammatory carcinoma
  7. 7. AJCC StagingStage T: Primary Lymph Node M: distant 5-year survival Cancer (LNs) metastases (%) 0 DCIS or LCIS None Absent 92 I Invasive None Absent 87 carcinoma <2cm II Invasive None Absent 75 carcinoma 1 to 3 positive Absent >2cm LNs <5cm III >5cm 1 to 3 positive Absent 46 Any size >4 positive Absent With skin or 0 to 10 positive Absent chest wall involvement or inflammatory carcinoma IV Any size Negative or Present 13 carcinoma positive LNs
  8. 8. CARCINOMA OF THE BREAST Presence of lump Nipple inversion Breast discharges Changes in the skin – “peau d’orange” Diagnostics: mammography, UTZ, MRI (possibly), biopsy Treatment: surgery, chemotherapy and radiotherapy
  9. 9. FemaleMale
  10. 10. CARCINOMA OF THE BREAST Lumpectomy Partial or Segmental Mastectomy or Quadrantectomy Total Mastectomy Modified Radical Mastectomy Radical Mastectomy (http://www.webmd.com/breast-cancer/breast-cancer-surgery)
  11. 11. LUMPECTOMY This is also referred to as breast-conserving therapy. The surgeon removes the cancerous area and a surrounding margin of normal tissue. A second incision may be made in order to remove the lymph nodes. This treatment aims to maintain a normal breast appearance when the surgery is over.
  12. 12. LUMPECTOMY After the lumpectomy, a five- to eight-week course of radiation therapy is often used to treat the remaining breast tissue. The majority of women who have small, early-stage breast cancers are excellent candidates for this treatment approach.
  13. 13. LUMPECTOMY Women who are not usually eligible for a lumpectomy include:1. those who have already had radiation therapy to the affected breast,2. have two or more areas of cancer in the same breast that are too far apart to be removed through one incision,3. or have cancer that was not completely removed during the lumpectomy surgery
  14. 14. During a partial or segmental mastectomy or quadrantectomy, the surgeonremoves more breast tissue than with a lumpectomy. The cancerous area and asurrounding margin of normal tissue are removed, and radiation therapy is usuallygiven after surgery for six to eight weeks.
  15. 15. With a simple or total mastectomy, the entire breast is removed, but no lymphnodes are removed in this procedure. Simple mastectomy is most frequently usedfor further cancer prevention or when the cancer does not go to the lymph nodes.
  16. 16. The surgeon removes all of the breast tissue along with the nipple in a modifiedradical mastectomy. Lymph nodes in the armpit are also removed. The chestmuscles are left intact. For many patients, mastectomy is accompanied by either animmediate or delayed breast reconstruction. This can be done quite effectively usingeither breast implants or the patients own tissue -- usually from the lower abdomen.
  17. 17. RADICAL MASTECTOMY The surgeon removes all of the breast tissue along with the nipple, lymph nodes in the armpit, and chest wall muscles under the breast. This procedure is rarely performed today because modified radical mastectomy has proved to be as effective, and is less disfiguring.
  18. 18. NURSING INTERVENTIONS1. Monitor for adverse effects of radiation therapy such as fatigue, sore throat, dry cough, nausea, anorexia.2. Monitor for adverse effects of chemotherapy; bone marrow suppression, nausea and vomiting, alopecia, weight gain or loss, fatigue, stomatitis, anxiety, and depression.3. Realize that a diagnosis of breast cancer is a devastating emotional shock to the woman.4. Provide psychological support to the patient throughout the diagnostic and treatment process.5. Involve the patient in planning and treatment.
  19. 19. NURSING INTERVENTIONS6. Describe surgical procedures to alleviate fear.7. Prepare the patient for the effects of chemotherapy, and plan ahead for alopecia, fatigue.8. Administer antiemetics prophylactically, as directed, for patients receiving chemotherapy.9. Administer I.V. fluids and hyperalimentation as indicated.10. Help patient identify and use support persons or family or community.11. Suggest to the patient the psychological interventions may be necessary for anxiety, depression, or sexual problems.12. Teach all women the recommended cancer-screening procedures. (http://nursingcrib.com/nursing-notes-reviewer/breast-cancer/)
  20. 20. CERVICAL CARCINOMA CIN – cervical intraepithelial neoplasia CIN is a precancerous lesion Classified according to degree of dysplasia CIN I – low grade dysplasia, also classified as LSIL or low-grade squamous intraepithelial lesion CIN II and CIN III – both high grade dysplasia, also classified as HSIL or high-grade squamous intraepithelial lesion
  21. 21. CERVICAL CARCINOMA CIN is associated with productive HPV infection (HPV 16) Most LSILs regress spontaneously with only a small percentage progressing to HSIL LSIL does not progress directly to invasive carcinoma
  22. 22. CERVICAL CARCINOMA Squamous cell carcinoma is the most common histologic subtype Accounts for approximately 80% of cases HSIL is an immediate precursor Second most common type is cervical adenocarcinoma (15%) Adenosquamous carcinoma accounts for 5% Peak incidence for invasive cervical carcinoma is 45 years
  23. 23. CERVICAL CARCINOMA Risk factors are related to both host and viral characteristics:1. Multiple sexual partners2. A male partner with multiple previous or current sexual partners3. Young age at first intercourse4. High parity5. Persistent infection with a high oncogenic risk HPV (HPV 16 and 18)6. Immunosuppression7. Certain HLA subtypes8. Use of OCP9. Use of nicotine
  24. 24. CERVICAL CARCINOMA More than half of invasive cervical cancers are detected in women who did not participate in regular screening Cervical cancer screening and prevention1. Pap smear2. Cervical biopsy3. HPV vaccination4. Surgical removal5. Adjunctive radiotherapy and chemotherapy
  25. 25. CERVICAL CARCINOMA Surgery1. Early invasive cancers – cone biopsy2. Highly invasive cancers – hysterectomy with lymph node dissection Prognosis depends on the stage at which the cancer has been detected
  26. 26. ENDOMETRIAL CARCINOMA The most common invasive cancer of the female genital tract Accounts for 7% of all invasive cancer in women Uncommon in women younger than 40 years of age Peak incidence is in 55 to 65 year old women
  27. 27. ENDOMETRIAL CARCINOMA Risk factors:1. Age2. Unopposed estrogen3. Endometrial atrophy4. Obesity as well as thin physique5. Hypertension6. Diabetes
  28. 28. ENDOMETRIAL CARCINOMA No current available screening test May be asymptomatic for a certain period of time Irregular or postmenopausal bleeding with excessive leukorrhea Uterine enlargement may be absent in the early stages Diagnosis is established with biopsy or curettage and histologic examination of the tissue Prognosis depends on the stage and type of carcinoma Treatment consists of surgical removal (TAHBSO with removal of tissues suspected of being involved) alone or in combination with radiotherapy
  29. 29. LEIOMYOSARCOMA Uncommon malignant neoplasm Arise de novo from the myometrium or endometrial stromal precursor cells Equally common before the and after menopause Peak incidence at 40 to 60 years of age Has a striking tendency to recur after removal More than half eventually metastasize through the bloodstream to distant organs (lungs, bone, and brain) 5-year survival rate averages about 40%
  30. 30. OVARIAN CARCINOMAS About 80% of ovarian tumors are benign and mostly occur in young women between the ages of 20 to 45 years old Borderline tumors occur in slightly older ages Malignant tumors are more common in older women Ovarian cancer accounts for 3% of all cancers in females
  31. 31. Choriocarcinoma
  32. 32. PROSTATE CARCINOMA Adenocarcinoma of the prostate is the most common form of cancer in men Accounts for 29% of cancer in the US Typically a disease of men over age 50 Screening is recommended to begin at age 40 Uncommon in Asia Risk factors: genetics, diet and lifestyle (still not clear) Diet: fatty foods has been implicated, those rich in lycopene are suspected of preventing or delaying the development Androgens play an important role in the development
  33. 33. PROSTATE CARCINOMA Most men that underwent TURP have incidental finding of focal cancer, and do not progress when followed up after 10 years Older men are typically followed up Younger men with longer life expectancy may undergo needle biopsy to look for additional cancer Diagnostics include PSA levels (most important test – cutoff point is 4ng/ml), transrectal needle biopsy, imaging studies (to check for metastatic osteoblastic carcinoma to the vertebrae)
  34. 34. PROSTATIC CARCINOMA PSA1. Prostatic Specific Antigen2. 40 to 49 years – 2.5 ng/ml3. 50 to 59 years – 3.5 ng/ml4. 60 to 69 years – 4.5 ng/ml5. 70 to 79 years – 6.5 ng/mlNote:a. numbers 2 to 5 shows the upper age-specific PSA reference rangesb. For the test to be valid, there must be at least three PSA measurements available over a period of 1.5 to 2 yearsc. A man who has a significant rise, even though the latest serum level may be below the normal cutoff (<4ng/ml) should undergo additional work-up
  35. 35. MANAGEMENT Surgery – radical prostatectomy Antibiotic prophylaxis – quinolones and those that cover anaerobic bacteria (during biopsy) Radiation like brachytherapy Cryotherapy Chemotherapy Hormonal therapy http://emedicine.medscape.com/article/379996-followup http://www.medicinenet.com/prostate_cancer/page8.htm#_Toc49845 8220
  36. 36. MANAGEMENT Post-op effects of surgery:1. Risks of anesthesia2. Post-op bleeding3. Impotence – treat with sildenafil (Viagra) tablets, alprostadil (Caverject) injections into the penis, devices like penile prosthesis4. Incontinence http://www.medicinenet.com/prostate_cancer/page8.htm#_Toc49845 8220
  37. 37. PENILE CARCINOMA CIS (carcinoma in-situ) – Bowen disease and bowenoid papulosis Strong association with HPV infection (HPV 16) Bowen disease occurs in the genital region of both men and women, usually over the age of 35 years In men Bowen occur in the skin of the shaft of the penis Bowen disease appears as a solitary, thickened, gray-white, opaque plaque Bowen disease transforms into infiltrating squamous cell carcinoma in approximately 10% of patients
  38. 38. PENILE CARCINOMA Bowenoid papulosis1. Occurs in sexually active adults2. Younger age group3. Presence of multiple (rather than solitary) reddish- brown papules4. Never develops into an invasive carcinoma5. In many cases, spontaneously regresses
  39. 39. PENILE CARCINOMA Invasive carcinoma1. SCC of the penis is an uncommon malignancy2. Circumcision offers protection3. HPV 16 is the most common culprit4. HPV 18 is also implicated5. Cigarette smoking elevates the risk6. Usually found in patients between the ages 40 and 70
  41. 41. ESOPHAGUS Squamous cell carcinoma Adenocarcinoma
  42. 42. ESOPHAGUS Squamous cell carcinomaa. More common worldwideb. Risk factors: alcohol, tobacco use, poverty, caustic esophageal injury, achalasia, Plummer- Vinson syndrome (also known as Paterson-Brown Kelley syndrome; triad of dysphagia, upper esophageal webs and iron deficiency anemia), and frequent consumption of very hot beveragesc. Other risk factors: nutritional deficiencies, polycyclic hydrocarbons, nitrosamines, and other mutagenic compounds such as fungus found on contaminated foods, HPV
  43. 43. ESOPHAGUS Squamous cell carcinomaa. Onset is insidiousb. Ultimately produces dysphagia, odynophagia, and obstructionc. Patients subconsciously adjust to the progressively increasing obstruction by altering their diet from solid to liquid foodsd. Extreme weight loss and debilitatione. Hemorrhage and sepsis may accompany tumor ulcerationf. Occasionally the first symptoms are caused by aspiration of food via a TEF
  44. 44. ESOPHAGUS Adenocarcinomaa. Typically arises in a background of Barrett esophagus and long-standing GERDb. Other risk factors: tobacco use, obesity, prior radiation therapy, diets poor in fresh fruits and vegetablesc. Some H. pylori serotypes are associated with a decreased risk perhaps by causing gastric atrophy and reducing acid reflux
  45. 45. ESOPHAGUS Adenocarcinomaa. Occasionally discovered in evaluation of GERD or surveillance of Barrett esophagusb. Commonly present with pain and difficulty in swallowing, progressive weight loss, hematemesis, chest pain, or vomitingc. By the time symptoms appear, the tumor has usually spread to submucosal lymphatic vesselsd. At the time of diagnosis, it is already at the advanced stagee. Overall 5-year survival is less than 25%
  46. 46. ESOPHAGUS Early stages of esophageal cancer is often treated with surgery However in many instances a combination of chemotherapy and radiotherapy is given prior to surgery to optimize the benefit of surgical therapy In this situation the chemotherapy is usually given at the same time as radiation therapy The most common chemotherapy used for this purpose is a combination of cisplatin and flurouracil (5- FU) After about two months of chemotherapy and radiation patient is evaluated for surgery (http://medicineworld.org/cancer/gi/esophageal/treatment.html)
  47. 47. ESOPHAGUS Surgery for esophageal cancer involves removal of the part of esophagus that is involved with cancer and joining the uninvolved part with stomach. The lymph nodes in the area are also removed. If the cancer is in the upper part of the esophagus the stomach may be pulled up to the chest to compensate for the loss of length in the esophagus.(http://medicineworld.org/cancer/gi/esophageal/treatmen t.html)
  48. 48. ESOPHAGUS If the cancer is in the lower part of the esophagus, surgeon can remove lower part of the esophagus and upper part of the stomach and join the two ends together. Surgery may cure some of the patients with esophageal cancer, however in many patients the cancer may come back after the surgery. (http://medicineworld.org/cancer/gi/esophageal/treatm ent.html)
  49. 49. ESOPHAGUS Treatment of esophageal cancer when the surgery is not an option:a. Because of the high position of the esophageal cancer or due to the poor general condition of the patientb. Such patients are generally treated with a combination of chemotherapy and radiationc. several chemotherapy drugs that are active in esophageal cancer. These include fluorouracil (5-FU), cisplatin, mitomycin, bleomycin, doxorubicin, methotrexate, paclitaxel, vinorelbine, topotecan, and irinotecand. The most commonly used drugs are cisplatin and flurouracil (http://medicineworld.org/cancer/gi/esophageal/treatment.html)
  50. 50. ESOPHAGUS Pallative treatment:a. PDTb. Placement of stentc. Pain control (http://medicineworld.org/cancer/gi/esophageal/treatment.html)
  51. 51. ADENOCARCINOMA OF THE STOMACH The most common malignancy of the stomach Comprises over 90% of all gastric cancers Incidence varies markedly with geography 20-fold higher in Japan, Chile, Costa Rica, and Eastern Europe compared to North America, Northern Europe, Africa and Southeast Asia Factors that decrease risk: intake of green, leafy vegetables, and citrus fruits Factors that increase risk: N-nitroso compounds and smoking used for food preservation
  52. 52. ADENOCARCINOMA OF THE STOMACH Other risk factors:a. Age and gender are risk factors and the disease is more common in men over the age of 55b. Medical conditions that increase the risk for the disease include pernicious anemia (vitamin B-12 deficiency), chronic inflammation of the stomach (atrophic gastritis), and intestinal polyps (noncancerous growths)c. Genetic (hereditary) risk factors include hereditary nonpolyposis colon cancer (HNPCC) syndrome and Li- Fraumeni syndrome (conditions that result in a predisposition to cancer), and a family history of gastrointestinal cancerd. People with type A blood also have an increased risk for stomach cancer. (http://www.oncologychannel.com/gastriccancer/riskfactors.shtml)
  53. 53. ADENOCARCINOMA OF THE STOMACH Abdominal discomfort or pain Blood in stool Bloating (especially after eating) Diarrhea or constipation Fatigue (http://www.oncologychannel.com/gastriccancer/diagnosis.shtml)
  54. 54. ADENOCARCINOMA OF THE STOMACH Fecal occult blood test is used to detect microscopic blood in the stool, which may indicate stomach or other gastrointestinal (GI) cancers (e.g., colorectal cancer). Complete blood count (CBC) is a simple blood test used to measure the concentration of white blood cells, red blood cells, and platelets. In an upper GI series, or barium swallow, the patient drinks a thick, chalky liquid (barium) that coats the esophagus and stomach and makes it easier to detect abnormal areas on x-ray. In double-contrast barium swallow, air is blown into the esophagus and stomach to help the liquid coat the wall of the organs more thoroughly (http://www.oncologychannel.com/gastriccancer/diagnosis.shtml)
  55. 55. GASTROINTESTINAL STROMAL TUMOR GIST most common mesenchymal tumor of the abdomen More than half occur in the stomach Slightly more common in males Peak age of diagnosis in the stomach is approximately 60 years Fewer than 10% occurring in individuals 40 years of age
  56. 56. GASTROINTESTINAL STROMAL TUMOR Symptoms at presentation may be related to mass effects Mucosal ulceration can cause blood loss May be discovered as an incidental finding during radiologic imaging, endoscopy, or abdominal surgery performed for other reasons GIST of the small intestine is more aggressive than those arising in the stomach
  57. 57. GASTROINTESTINAL STROMAL TUMOR Surgery Chemotherapy Radiation therapy Supportive care
  58. 58. HEPATOCELLULAR CARCINOMA HCC There are more than 626,000 new cases per year of primary liver cancer and most of them are HCC About 82% occur in developing countries with high rates of chronic HBV infection, such as in southeast Asia and African countries In the US the incidence increased by 25% between 1993 and 1998, mainly due to HCV and HBV chronic infection Male:Female = 2.4:1
  59. 59. HEPATOCELLULAR CARCINOMA Other risk factors:a. drugs, chemicals and medicationsb. Aflatoxin B1 – from the fungus Aspergillus flavusc. Hemochromatosisd. Cirrhosis http://www.apjohncancerinstitute.org/cancer/liver.htm
  60. 60. HEPATOCELLULAR CARCINOMA In most patients:a. (+) ill-defined upper abdominal painb. Malaisec. Fatigued. Weight losse. Sometimes, awareness of abdominal mass or abdominal fullness
  61. 61. HEPATOCELLULAR CARCINOMA In many cases:a. The enlarged liver can be felt by palpationb. Jaundicec. Feverd. GIT or esophageal variceal bleeding
  62. 62. HEPATOCELLULAR CARCINOMA Labs/Diagnostics:a. Elevated serum alpha-fetoprotein (50%)b. CEAc. Glypican-3 tissue stainingd. Imaging studiese. Biopsy
  63. 63. HEPATOCELLULAR CARCINOMA Management:a. Chemotherapyb. Radiation therapyc. Resectiond. Liver transplantatione. Supportive care: analgesics as needed, measure abdominal girth (ascites), accurate monitoring of intake and output, weight (edema), watch out for bleeding, dietary restrictions, meticulous skin care, neurologic assessment, psychosocial care http://www.apjohncancerinstitute.org/cancer/liver.htm http://findarticles.com/p/articles/mi_qa3689/is_199601/ai_n8743210/