MEDICAL MECHANICS-1 by Dr. Sesha sai Chittajallu - HTML preview

o Epithelial carcinomas of the head and neck arise from the mucosal surfaces in the head and neck area and typically are squamous cell in origin. This category includes tumors of the paranasal sinuses, the oral cavity, and the nasopharynx, oropharynx, hypopharynx, and larynx. Tumors of the salivary glands differ from the more common carcinomas of the head and neck

o The term lung cancer is used for tumors arising from the respiratory epithelium (bronchi, bronchioles, and alveoli). Mesotheliomas, lymphomas, and stromal tumors (sarcomas) are distinct from epithelial lung cancers. According to the World Health Organization classification, epithelial lung cancers consist of four major cell types:small cell lung cancer (SCLC) and the so-called non-small cell lung cancer (NSCLC) histologies including adenocarcinoma, squamous cell carcinoma, and large cell carcinoma

o Breast cancer is a malignant proliferation of epithelial cells lining the ducts or lobules of the breast.

o About 10% of esophageal cancers occur in the upper third of the esophagus (cervical esophagus), 35% in the middle third, and 55% in the lower third. Squamous cell carcinomas and adenocarcinomas cannot be distinguished radiographically or endoscopically

o About 85% of stomach cancers are adenocarcinomas, with 15% due to lymphomas and gastrointestinal stromal tumors (GIST) and leiomyosarcomas.

o Most colorectal cancers, regardless of etiology, arise from adenomatous polyps.

o After ampullary carcinomas (many of which arise from biliary or pancreatic ducts), the most frequently occurring small-bowel malignancies are adenocarcinomas, lymphomas, carcinoid tumors, and leiomyosarcomas.

o Preoperative portal vein occlusion can sometimes be performed to cause atrophy of the HCC-involved lobe and compensatory hypertrophy of the noninvolved liver, permitting safer resection.

o Courvoisier’s sign→palpable gall bladder,Virchow’s node→left supra clavicular lymphadenopathy,sister Mary joseph’s nodes→peri umbilical lymphadenopathy

o Several complications of cancer may require  palliative management. These include (1) acute CNS disorders (eg, spinal cord compression and increased intracranial pressure), (2) severe metabolic disorders (eg, hypercalcemia, hypocalcemia, tumor lysis syndrome, hyponatremia, hyperglycemia, hypoglycemia, and hypokalemia with ectopic adrenocorticotropic hormone [ACTH] production), (3) orthopedic disorders (eg, pathologic fracture), (4) urologic disorders (eg, hematuria, hemorrhagic cystitis, and acute obstructive uropathy), (5) general surgical disorders (eg, GI bleeding, bowel perforation, bowel obstruction, extrahepatic biliary obstruction, and intraabdominal abscess formation), (6) malignant effusions (eg, pericardial effusion with cardiac tamponade and pleural effusion with lung compression), (7) complications of chemo- and radiotherapy, and rarely, (8) superior vena cava syndrome.

o The most common primary tumors that cause spinal cord compression are cancers of the lung, breast, and prostate; lymphomas; and multiple myeloma. Cord compression also can be seen in patients with leukemia (chloroma) and a wide range of other solid tumors.Epidural spinal cord compression develops via two mechanisms: (1) by metastatic spread to the vertebral bodies, from where the tumor expands and erodes into the epidural space, and (2) by cancerous involvement of the paravertebral region with extension into the epidural space through the intervertebral foramina. Bone scans and spine x-rays may be normal in the latter cases but usually are abnormal in the former. Vertebral body metastases account for epidural spinal cord compression in approximately 85% of patients with solid tumors and 25% of patients with lymphomas. In the 70% of cancer patients with metastases at death, metastases to the spine are found in 40%. Epidural metastases extend from the paravertebral region in the remainder. In addition to spinal cord compression, sudden irreversible spinal dysfunction may occur from vascular compromise, resulting in spinal cord infarction

o The clinical presentation of epidural spinal cord compression is well known and depends on the level of spinal involvement. Axial pain is the most common presenting symptom (prodromal phase), occurring in 95% of adults and 80% of children with epidural spinal cord compression. Therefore, spinal cord compression should be considered in any patient with cancer and axial pain. The local pain corresponds to the site of the lesions and is described as dull and aching

o Pain may persist for several weeks or months before symptoms of radiculopathy are manifested. Cervical or lumbar disease usually but not always presents as unilateral radiculopathy, whereas thoracic disease produces bilateral symptoms resulting in a bandlike distribution of pain. Radicular pain may be accompanied by sensory or motor loss, as determined by the involved nerve root, and may be easily confused with disk herniation. Pain is usually worse at night and is aggravated by movement, coughing, or the Valsalva maneuver. Because midthoracic back pain is less likely to be due to benign causes, any patient localizing pain and tenderness to this area regardless of a history of malignancy should be evaluated carefully

o Neurologic deficits seen in spinal cord compression usually begin with motor impairment. These are seen more commonly in the distal part of the body or the lower extremities owing to the greater frequency of thoracic and lumbar spine involvement. Anterior spinal cord compression is more common than posterior involvement. Accordingly, patients usu-ally have more motor than sensory disability, at least in the early stages. Sensory impairment follows, parallels the development of motor deficit, and is present in half of patients at the time of diagnosis of spinal cord compression. Autonomic dysfunction occurs later and is present in half of cases

o The neurologic deficit is caused either by mechanical compression by the tumor on the spinal cord or cauda equina or by destruction of a vertebral body sufficient to make it collapse and compress the spinal cord. Once spinal cord compression occurs, progression may be very rapid. Therefore, the presence of myelopathy is a neurologic emergency. Disease presentation and progression depend on the level of spinal involvement. For example, high cervical cord lesions (C3–5) may be lifethreatening because both quadri-plegia and respiratory muscle impairment are common features. Involvement of the thoracic cord typically is characterized by identification of a sensory level on the trunk. In addition, lower extremity weakness and autonomic dysfunction may accompany thoracic cord compression. The specific site of lumbosacral spinal cord compression is less easily determined by physical examination. Patients may present with radiculopathy and loss of associated reflexes or with isolated autonomic dysfunction as seen in the conus syndrome. It is important that each patient have a complete neurologic examination, paying close attention to subtle asymmetries in muscle strength and reflexes. It is important to note that patellar and ankle reflexes provide information only about L4 and S1 nerve roots, respectively. Therefore, normal reflexes of the lower extremity should not be used to exclude the presence of significant myelopathy

o A few drops of cerebrospinal fluid (CSF) should be removed and sent for cytologic examination and protein determination. Additional studies are sent to exclude infection. Lumbar puncture otherwise should be reserved for patients suspected of concomitant leptomeningeal dissemination of tumor. CSF may have elevated protein, normal or low glucose, and a lymphocytic pleocytosis.MRI is the diagnostic study of choice to evaluate spinal cord compression, but plain x-rays of the involved area and planar or CT myelography are potentially useful or necessary. The most important attribute of MRI is its ability to evaluate directly the full length of the cord, thus making it possible for multiple levels of compression to be identified and to determine whether these lesions are related or unrelated to bony erosion or bone destruction by tumor. At least 35% of patients who present with focal symptoms have evidence of subclinical epidural compression at other sites along the spine. MRI also can determine the number of segments and vertebrae involved, the location of a compressive mass, if present (anterior, posterior, or encircling), and perhaps the percentage loss of bone mass. Imaging of the entire spine is usually not done because of the length of time needed (as much as 3 hours), but not taking the time may miss lesions that cause later neurologic compromise. MRI is comparable to myelography and CT scanning with contrast material in detecting leptomeningeal metastasis. However, MRI may be inadequate in patients who may have had previous spinal surgery because metal-induced artifacts may be seen or the patient’s movements cannot be controlled.

o Vertebral metastases can be seen on unenhanced T1-weighted images as foci of low signal intensity (dark) that contrast with the adjacent high signal intensity (bright) of normal adult bone marrow. The administration of gadolinium results in normalization of the tumor, making its appearance similar to that of the marrow. Vertebral metastases rarely cross the disk space, as often seen in infection. However, it sometimes may be difficult to distinguish between malignancy and infection with MRI. Diffuse bone marrow involvement may make interpretation by MRI difficult. This is also true in younger patients with relatively little fatty marrow. MRI is superior to CT scanning with and without intrathecal contrast material (CT myelogram)

o CT myelography remains an important diagnostic method for epidural spinal cord compression, especially when MRI is unavailable. Water-soluble contrast media are preferred. Once a complete block of the spinal canal is demonstrated by a lumbar myelogram, a C1–2 or suboccipital myelogram should be done to define the upper level of block. Myelography may disclose silent epidural metastasis. Lumbar myelography may cause further deterioration of neurologic findings in approximately 14% of patients even with the removal of only a small amount of CSF. Myelography has been associated with complications such as headaches, seizures, allergic reactions, and deterioration of neurologic status

o The differential diagnosis of spinal cord compression includes intervertebral disk herniation, vascular disease (eg, hemorrhage or infarction), infectious processes such as epidural abscess, benign neoplasms (eg, meningioma, neurilemoma, and chordoma), neurologic disorders (eg, multiple sclerosis and amyotrophic lateral sclerosis), transverse myelitis, leptomeningeal carcinomatosis, and paraneoplastic syndromes (eg, necrotizing myelopathy and carcinomatous neuropathy).

o The most commonly used treatment regimen consists of high-dose corticosteroid therapy plus external-beam radiation. Surgery is used selectively either as initial treatment or when specifically indicated.

o To reduce edema of the cord adjacent to the tumor, corticosteroids are used frequently in the treatment of spinal cord compression. These should be started as soon as the diagnosis is suspected. With pain or radiculopathy alone, dexamethasone, 16 mg intravenously, followed by 4–6 mg intravenously or orally every 6 hours, is adequate. Patients with rapidly progressive symptoms or significant myelopathy should be treated with dexamethasone, 100 mg intravenously, followed by 24 mg intravenously every 6 hours. Therapy should be continued until benefit is demonstrated from definitive therapy (ie, radiation or surgery) or neurologic deficits are considered irreversible. Tapering of corticosteroids is accomplished by reducing the dose by about one-third every 3–4 days over a period of 2–3 weeks. Corticosteroids should be reinstituted if neurologic deficits recur. Patients failing to improve after a 7-day trial at 100 mg/day should be rapidly tapered to the lowest dose that will maintain stable neurologic function. Such steroid regimens do not appear to be toxic, although vaginal burning may occur with rapid intravenous administration of dexamethasone. Conversely, corticosteroids may result in serious and fatal complications when used in high doses for more than 40 days or when given to patients with serum albumin concentration of less than 2.5 g/dL

o Radiation therapy alone produces neurologic improvement in 30–50% of patients with epidural spinal cord compression. Pain relief is obtained in the majority of patients with radiation therapy. Radiation-sensitive tumors such as hematologic malignancies and seminomas have the best outcome, breast and prostate cancer have moderately good outcomes, and lung and renal cancer, sarcomas, and melanoma are radioresistant and have the worst outcomes. Radiation therapy and surgical therapy appear to be of equal effectiveness in the treatment of radiosensitive tumors. The usual dose of radiation is 3000–4000 cGy over a period of 3–4 weeks. There are few differences reported between various radiotherapy protocols (ie, dose, number of fractions, and total duration). Complications of radiation therapy include radiation myelopathy and impaired wound healing in patients who undergo subsequent surgery

o Decompressive laminectomy →surgery may be considered (1) when the diagnosis is not known or is in doubt, (2) when there is spinal instability or bone deformity, (3) when there is failure to respond to radiation therapy, (4) when there is a history of previous radiation therapy up to cord tolerance, (5) when there is high cervical spinal cord compression (because of the danger of respiratory failure), (6) in the presence of a radioresistant tumor, especially when the onset of signs is rapid and complete block is present, (7) when atlantoaxial compression is present, (8) when a solitary spinal cord metastasis is present, and (9) as a form of primary treatment before radiation therapy

o Increased ICP can result from primary or metastatic tumors. At least one-fourth of patients dying from malignancy will have brain metastases discovered at autopsy. Hematogenous spread is the most common route of dissemination. Thus most lesions (approximately 80%) are supratentorial. The most common cancers found include lung, renal, breast, and melanoma. Leukemic meningitis and diffuse leukemic infiltration also can cause increased ICP but with-out the focal neurologic or radiographic findings usually seen in primary or metastatic brain tumors.

o Brain edema results from leakage of plasma into the parenchyma through dysfunctional capillaries (ie, vasogenic edema). Studies on the formation, speed, and resolution of brain edema have concluded that increased capillary permeability occurs within the brain tumor itself and not in the surrounding brain tissue. This increased capillary permeability varies depending on the histology of the tumor and its size. Brain edema occurs preferentially in the cerebral white matter. Vascular endothelial growth factors may contribute to dysfunction of tight junctions. It is not clear how brain edema results in neurologic dysfunction, but it is thought to be related to ischemia from a mass effect or from metabolic abnormalities in the surrounding extravascular fluid.

o Headache, nausea, vomiting, mental deterioration, lethargy, somnolence, and confusion are key findings in patients with increased ICP. Flexor or extensor posturing may occur. In addition, decrease in heart rate, increase in blood pressure, and abnormal respiratory pattern (Cushing’s triad) often can be present but are late findings. Cerebellar masses may, however, have a reversed clinical picture. Dilation of one or both pupils suggests rapid and significant increases in ICP. Focal neurologic deficits and abnormal reflexes may be found. Early diagnosis is usually based on the timely observation of subtle alterations in the mental status or state of consciousness of the patient

o Lumbar puncture for diagnosis is to be discouraged because removal of fluid from the intrathecal sac may result in an acute drop in infratentorial pressure, thereby precipitating or worsening herniation. Head CT scan and MRI are the most useful diagnostic tests. The size and location of a tumor mass or masses, the amount of peritumoral edema, shifts in intracranial structures, and ventricular size can be determined easily. No test is completely accurate in predicting risk of herniation. MRI is more sensitive than CT scan for finding tumor, especially when evaluating lesions of the posterior fossa. However, CT scan may better detect bony involvement of the skull. Both noncontrast- and contrast-enhanced CT scans are recommended because the combination not only may detect hemorrhagic lesions (non-contrast-enhanced) but also may allow detection of small lesions (contrast-enhanced).

o The differential diagnosis of increased ICP includes metabolic encephalopathy (eg, hypo- and hypernatremia, hypercalcemia, uremia, hypoxemia, hypoglycemia, and thyroid dys-function), CNS infection, cerebrovascular disease (especially intracranial hemorrhage), drug-induced encephalopathy (eg, sedatives and analgesics), and nutritional deficiencies

o Emergent maneuvers include elective intubation and hyperventilation to maintain PaCO2 between 25 and 30 mm Hg, followed by administration of mannitol, 1–1.5 g/kg intravenously every 6 hours. Some recommend following serum osmolality as a guide to dosing mannitol. Use of mannitol should be avoided when definitive therapy (surgery or radiation) is delayed. In any case, hypotonic fluids may be harmful and should not be given. Early corticosteroid (eg, dexamethasone) administration and fluid restriction appear to be the best means of achieving a decrease in ICP and brain edema.

o Preemptive antiseizure medications are frequently administered, but their value is controversial. Because patients with malignancy have a high risk for venous throm-boembolism, deep venous thrombosis prophylaxis is recommended despite the theoretical risk of hemorrhage from primary or metastatic brain tumor

o Surgery and radiation therapy are important methods of treatment of primary and metastatic brain tumors either as initial or as adjunctive therapy. Candidates for surgical resection should be patients with solitary lesions and limited systemic disease. Radiation therapy usually involves the whole brain and requires an average of 3000 cGy. Most recently, radiosurgery has evolved as a new technique to deliver a single large dose of radiation to a specific target

o Hypercalcemia is the most serious metabolic disorder associated with cancer. Serum calcium is regulated by hormones and locally acting cytokines at three main sites: the gut, the skeletal system, and the kidneys. Parathyroid hormone (PTH) increases the number and function of osteoclasts, inhibits osteoblasts, and increases renal tubular reabsorption of calcium, all of which increase extracellular calcium levels. The hormone also increases production of active vitamin D, which increases the absorption of calcium from the gut

o In all cases of cancer-related hypercalcemia, there is increased calcium resorption from bones relative to bone formation. Increased bone resorption is maintained through the destructive action of tumor cells by increased osteoclast activation mediated through the action of PTH-related polypeptide (PTHrP) and by locally acting cytokines

o PTH and PTHrP are distinguishable by radioassay, and for this reason, it is possible to distinguish humoral hypercalcemia of malignancy from coexisting primary hyperparathy-roidism. Despite a high frequency of bony metastases, prostate, small cell lung cancer, and colorectal carcinoma are rarely associated with hypercalcemia

o In addition to PTHrP, a number of locally active cytokines augment resorption of calcium from bone, including interleukin 1 (IL-1), IL-3, IL-6, IL-8, and IL-11 and tumor necrosis factors (TNF-α and TNF-β),all of which are components of what was formerly called osteoclast-activating factor

o Patients with severe hypercalcemia (serum calcium >14 mg/dL) are usually symptomatic.  Because of the depressive action of hypercalcemia on autonomic nervous tissue, nonspecific symptoms such as anorexia, nausea, and vomiting may occur. These often progress to include abdominal pain, constipation, frank obstipation, increased gastric acid secretion, and acute pancreatitis.

o Hypercalcemia causes a reversible tubular defect in the kidney that limits urinary concentrating ability and promotes dehydration or hypovolemia. If able, patients will admit to polyuria, nocturia, and polydipsia. Metabolic alkalosis is common, and acidosis occurs only when azotemia supervenes. This contrasts with the effects of PTH, in which a mild hyperchloremic acidosis is seen. Hypercalcemia also can lead to precipitation of calcium phosphate crystals in the kidneys and ureters and the formation of renal calculi. Such complications, however, are not commonly associated with hypercalcemia of malignancy, and when they occur, the possibility of coexisting primary hyperparathyroidism should be considered.

o Hypercalcemia may cause electrocardiographic disturbances such as prolongation of the PR and QRS intervals and shortening of the QT interval. With severe hypercalcemia (>16 mg/dL), the T wave widens, increasing the QT interval. At higher serum calcium concentra-tions, bradyarrhythmias and bundle branch block may develop, followed by complete heart block and cardiac arrest in systole.

o Hypercalcemia can result either from humorally mediated bone resorption or from osteolytic metastasis. Pain, fractures, and skeletal deformities can occur. Metastatic calcification occurs in long-standing and very severe hypercalcemia. Extraskeletal deposition of calcium has been observed with hypercalcemia in several organs, including the heart, lungs, kidneys, skin, joints, and conjunctivae.

o Serum calcium, phosphate, and albumin levels should be determined in all patients. This calculation is especially helpful when hypoalbuminemia coexists with hypercalcemia. Hypophosphatemia in the presence of hypercalcemia strongly suggests the presence of PTHrP or primary hyperparathyroidism. Elevated alkaline phosphatase is usually not helpful because it is seen in both primary hyper-parathyroidism and hypercalcemia of malignancy. Direct measurement of PTH and PTHrP may be necessary in some patients.

o Nephrocalcinosis and nephrolithiasis may be present in long-standing hypercalcemia and suggest hyperparathyroidism. Among all patients, the two most common causes of hypercalcemia are malignancy (35%) and primary hyperparathyroidism (54%).

o Moderate hyper-calcemia with minimal symptoms may be managed with administration of intravenous 0.9% NaCl. If the hypercalcemia is more severe and is symptomatic, furosemide and calcitonin may be added. Since the effects of calcitonin are not long-lasting, the use of bisphosphonates early in treatment is indicated. In patients with lymphoma or myeloma and hypercalcemia, corticosteroids are useful because of the significant role of cytokines in the hypercalcemia. Intravenous administration of sodium phosphate can lower the serum calcium level rapidly, but its use is dangerous because calcium phosphate complexes will deposit in blood vessels, lungs, and kidneys with resulting severe organ damage and even fatal hypotension. Therefore, intravenous phos-phates are not recommended. Oral phosphates are of limited value because diarrhea often develops with an intake of more than 2 g/day. Azotemia and hyperphosphatemia are contraindications to phosphate therapy

o Volume and electrolyte repletion are the first priorities. Normal saline (0.9% NaCl), usually containing potassium chloride (10–20 meq/L), is given at a rate of 2–3 L/day. Loop diuretics such as furosemide (40–80 mg intravenously) are used to induce calciuresis and preclude volume overload once fluid deficits are corrected. Calcitonin promotes renal excretion of calcium, inhibits bone resorption, and inhibits gut absorption of calcium. The effects of calcitonin, however, are minor and of short duration. Calcitonin is usually administered over 24 hours as an intravenous infusion in a dose of 3 units/kg or 100–400 units subcutaneously every 8–12 hours

o Corticosteroids decrease intestinal calcium absorption and inhibit bone resorption and in that way act as vitamin D antagonists. Bisphosphonates are used routinely because of their efficacy and low toxicity. They are potent inhibitors of osteoclasts and bind to hydroxyapatite in bone to inhibit dissolution. Hemodialysis is very effective in the treatment of hypercalcemia but is usually reserved for management in the setting of renal failure or life-threatening manifestations. Plicamycin and gallium nitrate decrease bone resorption. Prostaglandin synthetase inhibitors and other investigational drugs such as amifostine (WR-2721) have been used. Amifostine inhibits PTH secretion and bone resorption and facilitates urinary excretion of calcium

o Hypocalcemia is a rare complication of cancer resulting from osteoblastic metastasis secondary either to rapid bone healing  in patients with prostate or breast cancer receiving hormonal therapy or to hyperphosphatemia in patients with tumorlysis syndrome. The most common neoplasm associated with hypocalcemia is prostate cancer, and 31% of patients with prostate cancer and extensive osteoblastic bone metastasis develop hypocalcemia. The skeleton in these patients has been described as a “calcium sink.” Hypocalcemia secondary to tumor lysis syndrome may be severe and appears to result from a rise in the serum calcium × phosphorus product, leading to precipitation of calcium in soft tissues, including the kidneys, and the development of secondary hyperparathyroidism.

o Hypocalcemia also may occur secondarily in patients with low circulating 1,25(OH)2 vitamin D and calcifying chondrosarcoma. Magnesium deficiency results in hypocalcemia in patients with prolonged nasogastric drainage, parenteral hyperalimentation without magnesium supplementation, cisplatin therapy, long-term diuretic therapy, chronic diar-rhea, and chronic alcoholism and does not respond to calcium replacement alone. Treatment of hypercalcemia with plicamycin, bisphosphonates, or intravenous phosphate also may cause hypocalcemia

o The diagnosis of hypocalcemia is made with ease in patients who develop tetany. Paresthesias of the face, hands, and feet associated with muscle cramps, laryngeal spasm, diarrhea, headache, lethargy, irritability, or seizures are the common clinical manifestations. Chvostek’s and Trousseau’s signs are usually present. The ECG usually shows a prolonged QT interval. In long-standing cases, dry skin, papilledema, and cataracts may develop

o The differential diagnosis of hypocalcemia should include severe alkalosis secondary to vomiting, nasogastric suction, or hyperventilation and severe muscle cramps resulting from vincristine or procarbazine therapy

o Treatment of acute severe hypocalcemia (serum calcium < 6 mg/dL) consists of intravenous administration of calcium gluconate or calcium chloride, 1 g every 15–20 minutes until tetany disappears, and magnesium sulfate, 1 g intravenously or intramuscularly every 8–12 hours if the serum magnesium level is less than 1.5 mg/dL or is unknown. In patients with moderate hypocalcemia (serum calcium >7 mg/dL), calcium and magnesium may be replaced more slowly

o When given to a patient with a highly responsive (usually rapidly growing) malignancy, chemotherapy may trigger release of massive amounts of potassium, phosphate, uric acid, and other breakdown products of dying tumor cells into the bloodstream. Hypocalcemia owing to hyperphosphatemia may occur. This syndrome of tumor lysis occurs most commonly in patients with rapidly proliferating and chemotherapy-sensitive malignancies, such as acute leukemia and Burkitt’s lymphoma and, on rare occasions, following treatment of solid tumors and chronic lymphocytic leukemia (CLL). Tumorlysis syndrome has been reported after chemotherapy, radiotherapy, monoclonal antibody treatment, corticosteroids, and rarely spontaneously. Life-threatening complications may occur, including renal failure from hyperuricemia and car