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Grand Rounds

Grand Rounds. SACDALAN, D.B., SALES, M.C., SALONGA, A.E., SALVADOR, D.S., SAQUITAN, A.T., SARANZA, G.R., SEÑA, L.C., SEÑGA, I.R., SERRANO, G.K., SESE, D.G., SIMBULAN, J.C., SOBRIO, M.C., SUAREZ, F.L., SUGUITAN, A., SUMALAPAO, D.E., SY, P.L., SY. S.M., TALADUA, K.M., TAN, C.S. GENERAL DATA. JG

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Grand Rounds

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  1. Grand Rounds SACDALAN, D.B., SALES, M.C., SALONGA, A.E., SALVADOR, D.S., SAQUITAN, A.T., SARANZA, G.R., SEÑA, L.C., SEÑGA, I.R., SERRANO, G.K., SESE, D.G., SIMBULAN, J.C., SOBRIO, M.C., SUAREZ, F.L., SUGUITAN, A., SUMALAPAO, D.E., SY, P.L., SY. S.M., TALADUA, K.M., TAN, C.S.

  2. GENERAL DATA JG 42 years old Female chief complaint : low back pain Previously diagnosed with invasive ductal carcinoma stage 3B

  3. HISTORY OF PRESENT ILLNESS 2 yrs. PTA 6 mo. PTA 5 mo. PTA 1 wk. PTA low back pain -mostly in the evening -temporarily relieved by Mefenamic Acid Pain increased in intensity and was no longer relieved by Mefenamic Acid -prescribed with unrecalled pain medications which offered slight relief Consulted at PGH-OPD and a metastatic work-up (CXR, UTZ and Bone Scan) was done Diagnosed with Invasive Ductal Carcinoma Stage III-B

  4. PATIENT HISTORY PROFILE • Diagnosed with Invasive Ductal Carcinoma Stage III-B 2 years PTC • Underwent MRM, radiation therapy and 6 cycles of chemotherapy • No hormal treatment • (-) HTN, (-)DM, (-)asthma, (-)allergy history of breast cancer: maternal aunt • Nonsmoker • Nonalcoholic • Worked as a bank teller • Menarche at 14 y/o • G2P2 with regular menses Review of Systems (+) weight loss (+) anorexia (+) dyspnea on exertion (-) bowel changes (-) urination changes (-) cough (-) headache (-) seizure (-) headache Past Medical History Family History Personal Social History Obstetrics History

  5. PHYSICAL EXAMINATION

  6. PHYSICAL EXAMINATION

  7. I. Symptom: Low back pain, 42 y/o Consider: • Metabolic x • Infection • Autoimmune/Inflammatory • Neoplasm • Degenerative • Trauma • Congenital x • Vascular x

  8. Infection 1. UTI- ask for other GU symptoms, dysuria, discharge 2. Pelvic Inflammatory Disease- ask for sexual history, other GU symptoms, vaginal discharge 3. Endometriosis - ask for timing of pain, history of heavy menstrual bleeding, other symptoms fatigue, pain with intercourse, diarrhea, constipation, painful bowel movements during the menstrual period, rectal bleeding or blood in urine only during the menstrual period, and irregular bleeding or spotting between periods 4. Osteomyelitis - ask for tenderness, swelling and warmth in the affected area; avoidance of use in the affected part; malaise, loss of appetite, fever, nausea, fatigue, irritability 5. spinal infection- ask for fever, night sweats, and recent weight loss; check for elevated erythrocyte sedimentation rate and, spinous tenderness on percussion.

  9. Degenerative 1. Osteoporosis- patient its over 40 years of age; ask thoroughly focusing on risk factors 2. Lumbar disc herniation- a slowly progressive degenerative process; ask for distribution of pain in the body 3. Acquired spinal stenosis- a consequence of degenerative joint disease that has been present for many years; ask for insidious pain at lower back and buttocks radiating to the legs; burning sensation in the buttocks and posterior thighs; pain typically increases with walking and is relieved by rest. The patient may also feel better when he or she bends at the waist, because the diameter of the spinal canal is increased with flexion and decreased with extension; patient with spinal stenosis feels worse with hyperextension. 4. Spondylolisthesis- ask for progressive neurological deficit, caudaequina syndrome, or unremitting leg pain; affects women more than men

  10. Inflammatory 1. AnkylosingSpondylitis- ask for pattern of pain (usually worse in the morning and improving through the day) and stiffness experienced over 3 months; ask for pain in sacrum, lumbar spine and thoracic spine and other peripheral joints; family history 2. Rheumatoid Arthritis- consider the criteria (presence of four of the following): (1) morning stiffness in and around joints that lasts for longer than one hour (2) arthritis (pain and inflammation) with swelling of three or more joints simultaneously (3) at least one of the joints referred to in (2) must be in the hand (4) symmetric arthritis with simultaneous involvement of the same joint bilaterally (5) rheumatoid nodules over bony prominences or near joints (6) positive serum rheumatoid factor (RF) (7) x-ray changes typical of RA.

  11. Neoplasm 1. spinal tumor (Primary)- severe and progressive pain, which commonly occurs during the night; slow and progressive neurological loss 2. OsteoidOsteoma- back pain that becomes worse at night, but is relieved by taking aspirin; look for visible bone loss on x-ray studies. 3. Metastatic spinal tumors- history of breast ca; unexplained weight loss; ask for other non- spinal symptom; ask for relief of pain: Degenerative Joint Disease is typically relieved by rest while metastatic bone pain is not 4. Multiple Myeloma

  12. Trauma 1. Spinal Fracture- ask for any history of major and minor trauma e.g. falls; ask for neurologic deficits and paralysis 2. CaudaEquina syndrome- ask for bilateral leg pain, numbness, and/or weakness, as well as bowel and bladder incontinence, saddle anesthesia around the anus and buttocks; may be due to spinal stenosis, a spinal cord lesion, a very large posterior disc herniation, an inflammatory reaction, or a combination of all of these pathologies

  13. II. Signs and Symptoms : low back pain mostly in the evening for 6 mos., temporarily relieved by Mefenamic acid; progression of pain slightly relieved by another pain killer (unrecalled); weight loss; previously diagnosed to have Invasive Ductal Carcinoma Stage III-B (-) hx of trauma (-) signs of infection, fever (-) asthma, allergy (-) Cardiorespiratory symptoms except for dyspnea on exertion (-) GU symptoms (-) Abdominal symptoms (-) Neurologic problems

  14. II. Symptoms: low back pain mostly in the evening for 6 mos., temporarily relieved by Mefenamic acid; progression of pain slightly relieved by another pain killer (unrecalled); weight loss; previously diagnosed to have Invasive Ductal Carcinoma Stage III-B Consider: Neoplastic 1. Spinal tumor (Primary)- (+) severe and progressive pain, which commonly occurs during the night; ask if there is slow and progressive neurological loss 2. OsteoidOsteoma- (+) back pain that becomes worse at night, but should be relieved by taking aspirin; look for visible bone loss on x-ray studies. 3. Metastatic spinal tumors- (+) history of breast cancer, weight loss; soft palpable liver, 10 cm liver span which may indicate metastasis to the liver; ask for relief of pain: Degenerative Joint Disease is typically relieved by rest while metastatic bone pain is not

  15. LABORATORY FINDINGS

  16. III. Symptoms: above signs and symptoms plus labs Hypercalcemia- may indicate cancer especially in the ff cases: • Multiple myeloma • Breast cancer • Squamous Cell Lung cancer • Renal cancer These have high propensity to spread to the bones and release calcium into the blood. Some tumors secrete parathyroid-related peptide which acts like PTH.

  17. III. Symptoms, PE + labs Consider: • Neoplasm- Metastatic spinal tumor

  18. Diagnostics

  19. Chest X-ray • Straight PA position with clavicle equidistant with each other. • There is a veil of haziness on the right lower lung with the right lateral sulcus, not defined. • Veil of haziness in the RLL may suggest a pneumonic process with associated pleural effusion. • The right hemi-diaphragm is slightly elevated laterally and the lateral elevation of the right hemi-diaphragm may suggest the presence of a sub-pulmonic effusion. • A right lateral decubitus may be indicated for confirmation. • The delineated osseus structures of the chest appears unremarkable.

  20. Radionuclide Bone Scanning Utilizes a radioactive tracer, a radionuclide to visualize various bone conditions on a scanner Radionuclide emits γ radiation which accumulates at regions called “hot spots” “Hot spots” correspond to areas of interest as these could point towards a tumor or focus of inflammation

  21. Radionuclide Bone Scanning INTERPRETATION • Normal: A scan result isnormal if bone uptake is equal throughout the body that is, there are no “hot” or “cold” spots seen • It is important to note the • symmetric nature of tracer • uptake here

  22. Radionuclide Bone Scanning Abnormal: A scan result is abnormal by virtue of the presence of areas of increased or decreased uptake in the bone imaged. • Increased uptake may indicate inflammation, bone infection, a malignant process, or a metabolic bone dyscrasia such as Paget’s disease • Decreased uptake may indicate bone ischemia/infarction or malignancies such as multiple myeloma

  23. Sample Bone Scan: J.G.

  24. Sample Bone Scan: J.G. Bone scan of J.G. presents hot spots at various sites: ribs, skull, femur, and lumbar spine However taken alone this image is suggestive but not diagnostic of metastasis Sources estimate that bone scanning has an excellent sensitivity of about 95% but a specificity of only 70% for malignancy; and only a 64% positive predictive value for metastasis in patients with a known extra osseous malignancy Good as a screening but not as a diagnostic tool Correlation with clinical findings and other laboratories may be beneficial

  25. Abdominal UTZ • No significant findings

  26. Other Diagnostics • CT Scan • Optimal for the visualization of bone over soft tissue • Higher sensitivity than X-ray • 12000 php (VRPMC) and 9000 (The Medical City) • MRI • Optimal for the visualization of soft tissue pathologies • Some sources note Sensitivity and Specificity to be as high as 95% • Capable of detecting bone marrow involvement which precedes cortical or trabecular bone changes seen in RBS and CT • 17,261 php (St. Luke’s) 19,000 php (The Medical City) • PET Scan • Using a radioactive glucose analog, PET scanning can detect areas of increased metabolic demand such as malignant tumors • Low sensitivity for malignancy, negative result of limited value in work-up • Lower sensitivity and specificity than MRI • 3000-700 USD in the US and 890 USD in S.Kor.

  27. Cancer Staging

  28. PRIMARY TUMOR (T)

  29. REGIONAL LYMPH NODES (N)

  30. DISTANT METASTASIS (M)

  31. STAGE GROUPING

  32. STAGE GROUPING

  33. Epidemiology: Global Burden • Breast cancer is the 3rd most common tumor in the world • Incidence Rates among races: Source: US National Cancer Institute, Surveillance Epidemiology and End Result(SEER, 2009)

  34. Breast CA in the Philippines One of the top 10 leading cancers in both sexes It is also one of the top 10 leading causes of cancer deaths in both sexes #1 site of cancer and cancer deaths in Filipino women

  35. Risk Factors Hormonal • Estrogen exposure Genetic • Tumor suppressor genes • Li-Fraumeni syndrome (p53 mutation) • PTEN gene • DNA Repair genes • BRCA-1 and BRCA-2 genes

  36. HER2 also called HER2/neu, and HER-2 or human epidermal growth factor receptor 2 a gene that sends control signals to cells telling them to grow, divide, and make repairs. A healthy breast cell has 2 copies of the HER2 gene. Breast cancer gets started when a breast cell has more than 2 copies of that gene due to overproduction of HER2 protein. This causes the cells to grow and divide much too quickly. This problem is not genetic but is more likely caused by aging, and wear and tear of the body.

  37. HER2 Breast cancer gets started when a breast cell has more than 2 copies of that gene due to overproduction of HER2 protein. This causes the cells to grow and divide much too quickly. This problem is not genetic but is more likely caused by aging, and wear and tear of the body.

  38. HER2 If breast cancer’s HER2 status is positive then the HER2 genes are over producing and creating the cancer. HER2 positive type of breast cancer is associated with more aggressive disease, greater likelihood of recurrence, poorer prognosis, and decreased survival. If it is negative, HER2 protein is not causing the cancer.

  39. HER2 Immunohistochemistry or IHC measures the production of the HER2 protein by the tumor. Fluorescence In Situ Hybridization or FISH uses fluorescent probes to look at the number of HER2 gene copies in a tumor cell. If there are more than 2 copies of the HER2 gene, then the cancer is HER2 positive.

  40. Other Risk Factors Sex Age Early age at menarche Later age at first full-term pregnancy Late age at Menopause No/short duration of Breastfeeding First-degree relatives w/ breast CA Radiation exposure Endometrial carcinoma Geographic influence Diet

  41. Classification of Breast CA Almost all breast malignancies are adenocarcinomas, with other types (squamous cell, phyloodes, sarcomas, and lymphomas) making up <5% Classified as either carcinoma in situ, or invasive carcinoma

  42. Invasive Ductal Carcinoma Also called invasive carcinoma of no special type (NST) Accounts for about 70-80% of breast CA Carcinomas that cannot be classified as any other subtype Histologically display a wide spectrum of appearances Source: Geneva Foundation for Medical Research and Education

  43. Breast Cancer Metastasis Prognostic Factors

  44. Breast Cancer Metastasis • The most common areas of breast cancer metastasis are: soft tissues, lung/liver and bone (1/3 of cases each) • 5 leading site of metastatic breast CA are: lung, bone, lymph nodes, liver and pleura. • Spread of breast cancer to bone primarily involves the hematogenous route • HPIM • Kang, Y. New tricks agains an old foe: Molecular dissection of metastasis tissue tropism in breast cancer. Breast Disease 26 (2006,2007) 129–138 129.

  45. Why bone? • Seed and Soil Hypothesis • Some proposed mechanisms: • RANK (receptors) are abundant in the breast cancer cells, they preferentially migrate to bone where RANKL (ligand) is abundant • Chemokine receptor CXCR-4 is abundant in breast cancer cells, goes to bone marrow, lungs and liver abundant in SDF-1/CXCL-12, its natural ligand. • Involvement of VEGFR-1+ HPC in areas of metastasis • Breast cancer cell signals, including osteoblast-mediated signals acting on osteoclasts, promote the formation of bone metastases. Hofbauer, LC, Rachner, T, Singh, SK. (2008). Fatal attraction: why breast cancer cells home to bone. Breast Cancer Research 2008, 10:101 Retrieved online at http://breast-cancer-research.com/content/10/1/101 Psailaa, B, Kaplana, RN, Port, ER, Lydena, D. (2006-2007). Priming the ‘soil’ for breast cancer metastasis: The pre-metastatic niche. Breast Disease 26, 65-74, 65. Rose AA, Siegel PM. Breast cancer-derived factors facilitate osteolytic bone metastasis. Bull Cancer. 2006;93:931-943.

  46. Seed and Soil Hypothesis CXCR-4 (receptor) RANK (receptor) SDF-1/CXCL-12(ligand) RANK (ligand) VEGDR-1+HPC Hofbauer, LC, Rachner, T, Singh, SK. (2008). Fatal attraction: why breast cancer cells home to bone. Breast Cancer Research 2008, 10:101 Retrieved online at http://breast-cancer-research.com/content/10/1/101 Psailaa, B, Kaplana, RN, Port, ER, Lydena, D. (2006-2007). Priming the ‘soil’ for breast cancer metastasis: The pre-metastatic niche. Breast Disease 26, 65-74, 65. Rose AA, Siegel PM. Breast cancer-derived factors facilitate osteolytic bone metastasis. Bull Cancer. 2006;93:931-943.

  47. Bone Metastasis • Primary sites: • vertebrae, proximal femur, pelvis, ribs, sternum, proximal humerus, skull • Clinical manifestation: PAIN! • PAIN is the most frequent complaint, it is present over weeks, localized, more severe at night • Other manifestations include swelling, nerve root/ spinal cord compression, pathologic fracture, myelophthisis • Can also be asymptomatic

  48. Bone metastasis • Can be either osteolytic, osteoblastic or both. • In most metastasis, there are stages where osteolytic or osteoblastic tendency predominates.

  49. Osteolytic Bone Metastasis Tumor produces substances that can lead to resorption (ex. Vit D-like steroid, prostaglanding, PTH-related peptide) or the tumor produces cytokines that induce osteoclast formation (ex. IL-1, TNF, receptor activator of NF-êBligand (RANKL) ) Serve as tumor survival factors Bone destruction Release of parathyroid hormone-related peptide, IL-6, TGF Hypercalcemia, excretion of hydroxyprobe-containing peptide HPIM, Hofbauer, LC, Rachner, T, Singh, SK. (2008). Fatal attraction: why breast cancer cells home to bone. Breast Cancer Research 2008, 10:101 Retrieved online at http://breast-cancer-research.com/content/10/1/101

  50. Osteoblastic Bone metastasis Tumor produces cytokines that activate osteoblasts Increased alkaline phosphatase, hypocalcemia

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