DIAGNOSIS & TREATMENT - PART 6 potx

Carcinoma of the Prostate■ Essentials of Diagnosis • More common and seemingly more aggressive in blacks • Exact role of screening uncertain; may prove to be more useful inmiddle-aged me

Thyroid Cancer

■ Essentials of Diagnosis

• History of irradiation to neck in some patients

• Often hard, painless nodule; dysphagia or hoarseness occasionally

• Cervical lymphadenopathy when local metastases present

• Thyroid function tests normal; nodule is characteristically pled with calcium on x-ray, cold by radioiodine scan, and solid byultrasound; does not regress with thyroid hormone administration

stip-■ Differential Diagnosis

• Thyroiditis

• Other neck masses and other causes of lymphadenopathy

• Thyroglossal duct cyst

• Benign thyroid nodules

postoper-• Prognosis related to cell type and histology; papillary carcinomaoffers excellent outlook, anaplastic the worst

• Medullary thyroid cancer is typically refractory to chemotherapyand radiation; diagnosable by calcitonin elevation in MEN syn-dromes

■ Pearl

In patients who had thymus radiation during childhood—a common practice in past years—a thyroid nodule is malignant until proved other- wise.

Reference

Rossi RL et al: Thyroid cancer Surg Clin North Am 2000;80:571 [PMID:10836007]

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Carcinoma of the Prostate

■ Essentials of Diagnosis

• More common and seemingly more aggressive in blacks

• Exact role of screening uncertain; may prove to be more useful inmiddle-aged men, especially blacks

• Symptoms of prostatism more often absent than present; bonepain (especially back) if metastases present; asymptomatic inmany, however

• Stony, hard, irregular prostate palpable, usually lateral part ofgland

• Osteoblastic osseous metastases visible by plain radiograph

• Prostate-specific antigen (PSA) is age-dependent and is elevated

in older patients with benign prostatic hyperplasia and also acuteprostatitis; reliably predicts extent of neoplastic disease andrecurrence after prostatectomy

■ Differential Diagnosis

• Benign prostatic hyperplasia (may be associated)

• Scarring secondary due to tuberculosis or calculi

combina-• Radiation or surgical therapy for local nodal metastases in selectedpatients after prostatectomy

• Androgen ablation (chemical or surgical) for metastatic disease,though exact timing of initiation of therapy (at diagnosis or atonset of symptoms) is unclear

• Combination chemotherapy may benefit selected patients withhormone-refractory metastatic disease

Tumors of the Testis

■ Essentials of Diagnosis

• Painless testicular nodule; peak incidence at age 20–35

• Testis does not transilluminate

• Gynecomastia, premature virilization in occasional patients

• Tumor markers (AFP, LDH, hCG) useful in diagnosis, ing response to therapy, and surveillance for relapse

monitor-• Pure seminoma produces hCG only, while nonseminomatousgerm cell tumors may produce hCG and AFP

• Postsurgical radiation therapy also useful for other malignant celltypes

• Platinum-based chemotherapy curative in appreciable majority ofpatients with advanced or metastatic disease

Carcinoma of the Bladder (Transitional Cell Carcinoma)

■ Essentials of Diagnosis

• More common in men over 40 years of age; predisposing factors

include smoking and alcohol as well as chronic Schistosoma haematobium infection, exposure to certain industrial toxins, or

previous cyclophosphamide therapy

• Microscopic or gross hematuria with no other symptoms is themost common presentation

• Suprapubic pain, urgency, and frequency when concurrent tion present

infec-• Occasional uremia if both ureterovesical orifices obstructed

• Tumor visible by cystoscopy

• Radical cystectomy standard with muscle-invasive tumors, thoughless morbid procedures with intensive follow-up may provide sim-ilar outcomes

• Role of adjuvant chemotherapy or radiation for completely sected patients unclear, but generally offered to those at high risk

Adenocarcinoma of the Kidney (Renal Cell Carcinoma; Hypernephroma)

• Flank or abdominal mass may be palpable

• When flank pain, hematuria, and palpable mass— the “too-latetriad”—are present, only 15% are curable

• Anemia in 30%, erythrocytosis in 3%; hypercalcemia, glycemia sometimes seen

hypo-• Frequent tumor or tumor thrombus invasion of renal vein andascending inferior vena cava, on occasion causing superior venacava syndrome

• Renal ultrasound, CT, or MRI reveals characteristic lesion

■ Differential Diagnosis

• Simple cyst

• Polycystic kidney disease

• Single complex renal cyst; but 70% of these are malignant

• Nephrectomy curative for patients with early stage lesions

• Poor response to chemotherapy or radiation in metastatic disease

• Small response rate to combination bio-chemotherapy leukin 2 plus cytotoxic agents), though very toxic

(inter-• Resection of primary lesion has been documented to result inregression of metastases on rare occasions

• Nonmyeloablating allogeneic bone marrow transplantation hassignificant response rate in highly selected patients

■ Pearl

A small proportion of patients have a nonmetastatic hepatopathy, with elevation of alkaline phosphatase; this abnormality does not imply in- operability and disappears with resection of the tumor.

Reference

Motzer RJ et al: Renal-cell carcinoma N Engl J Med 1996;335:865 [PMID:8778606]

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Malignant Tumors of the Esophagus

• Staging of disease aided by endoscopic ultrasound

• Squamous histology more common, though incidence of carcinoma increasing rapidly in Western countries for unclearreasons

adeno-■ Differential Diagnosis

• Benign tumors of the esophagus

• Benign esophageal stricture or achalasia

Carcinoma of the Stomach

■ Essentials of Diagnosis

• Few early symptoms, but abdominal pain not unusual; late plaints include dyspepsia, anorexia, nausea, early satiety, weightloss

com-• Palpable abdominal mass (late)

• Iron deficiency anemia, fecal occult blood positive; achlorhydriapresent in minority of patients

• Mass or ulcer visualized radiographically; endoscopic biopsy andcytologic examination diagnostic

• Associated with atrophic gastritis, Helicobacter pylori; role of

diet, previous partial gastrectomy controversial

■ Differential Diagnosis

• Benign gastric ulcer

• Gastritis

• Functional or irritable bowel syndrome

• Other gastric tumors, eg, leiomyosarcoma, lymphoma

• Pyogenic lung abscess

• Metastasis from extrapulmonary primary tumor

• Benign lung tumor, eg, hamartoma

• Noninfectious granulomatous disease

Reference

Hoffman PC et al: Lung cancer Lancet 2000;355:479 [PMID: 10841143]

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Pleural Mesothelioma

■ Essentials of Diagnosis

• Insidious dyspnea, nonpleuritic chest pain, weight loss

• Dullness to percussion, diminished breath sounds, pleural frictionrub, clubbing

• Nodular or irregular unilateral pleural thickening, often with fusion by chest radiograph; CT scan often helpful

ef-• Pleural biopsy usually necessary for diagnosis, though malignantnature of tumor only confirmed by natural history; pleural fluidexudative and usually hemorrhagic

• Strong association with asbestos exposure, with usual latencyfrom time of exposure 20 years or more

inves-• One-year mortality rate > 75%

Primary Intracranial Tumors

• Radiation post surgery is mainstay of therapy

• Herniation treated with intravenous corticosteroids, mannitol,and surgical decompression if possible

• Prophylactic anticonvulsants are also commonly given

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Fluid, Acid-Base,

& Electrolyte Disorders

Dehydration (Simple & Uncomplicated)

■ Differential Diagnosis

• Hemorrhage

• Sepsis

• Gastrointestinal fluid losses

• Skin sodium losses associated with burns or sweating

• Renal sodium loss

• Adrenal insufficiency

• Nonketotic hyperosmolar state in type 2 diabetics

■ Treatment

• Identify source of volume loss if present

• Replete with normal saline, blood, or colloid as indicated

• Half-normal saline may be substituted when blood pressure malizes

■ Essentials of Diagnosis

• History of hemorrhage, myocardial infarction, sepsis, trauma, oranaphylaxis

• Tachycardia, hypotension, hypothermia, tachypnea

• Cool, sweaty skin with pallor; may be warm or flushed, however,with early sepsis; clouded sensorium, altered level of conscious-ness, seizures

• Oliguria, increased urinary osmolality and specific gravity, mia, disseminated intravascular coagulation, metabolic acidosismay complicate

ane-• Hemodynamic measurements depend upon underlying cause

• Empiric broad-spectrum antibiotics often necessary

• Restore hemodynamics with fluids; vasopressor medications may

be required

• Maintain urine output

• Treat contributing disease (eg, diabetes mellitus)

■ Essentials of Diagnosis

• Usually severe thirst unless mentation altered; oliguria

• If hypovolemic, loose skin with poor turgor, tachycardia, tension

hypo-• Serum sodium > 145 meq/L, serum osmolality > 300 meq/Lcaused by free water loss

• Affected patients usually include the very old, very young, cally ill, or neurologically impaired

■ Differential Diagnosis

• Hypovolemic causes (thiazide diuretics, osmotic diuresis, adrenalinsufficiency, vomiting, diarrhea, fluid sequestration or third-spacing)

• Hypervolemic causes (congestive heart failure, cirrhosis, tic syndrome, renal failure, pregnancy)

nephro-• Euvolemic causes (hypothyroidism, SIADH, adrenocortical ficiency, reset osmostat, primary polydipsia)

insuf-• Hypertonic or isotonic hyponatremia (hyperglycemia, intravenousmannitol)

• Pseudohyponatremia (hypertriglyceridemia, paraproteinemia):laboratory artifact

■ Treatment

• Treat underlying disorder

• Corticosteroids empirically if adrenal insufficiency suspected

• Gradual correction (24 –48 hours) of sodium unless severe centralnervous system signs present (beware of central pontine myeli-nolysis)

• If hypovolemic, use saline

• If hypervolemic, use water restriction, diuretics, and normal salinevolume replacement of urine output

• Demeclocycline in selected patients with SIADH

■ Pearl

A sodium less than 130 mg/dL, BUN less than 10 mg/dL, and uricemia in a patient without liver, heart, or kidney disease is virtually diagnostic of SIADH.

hypo-Reference

Adrogue HJ et al: Hyponatremia N Engl J Med 2000;342:1581 [PMID:10824078]

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■ Essentials of Diagnosis

• Weakness or flaccid paralysis, abdominal distention, diarrhea

• Serum potassium > 5 meq/L

• Electrocardiographic changes: peaked T waves, loss of P wavewith sinoventricular rhythm, QRS widening, ventricular asystole,cardiac arrest

■ Differential Diagnosis

• Renal failure with oliguria

• Hypoaldosteronism (hyporeninism, potassium-sparing diuretics,ACE inhibitors, adrenal disease, interstitial renal disease)

• Dietary potassium restriction and sodium polystyrene sulfonate

or diuretic to lower body potassium subacutely

• Dialysis if oliguric renal failure or severe acidosis complicates

■ Pearl

A “junctional” rhythm in a patient with marked renal insufficiency is

in all likelihood sinus rhythm with failure of atrial depolarization.

Reference

Halperin ML et al: Potassium Lancet 1998;352:135 [PMID: 98336038]

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depres-• Serum potassium < 3.5 meq/L; metabolic alkalosis sometimesconcurrent

• Renal tubular acidosis (types I, II)

• Bartter’s, Gitelman’s, and Liddle’s syndromes

• Familial hypokalemic periodic paralysis

• Severe dietary potassium restriction

■ Treatment

• Identify and treat underlying cause

• Oral or intravenous potassium supplementation

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■ Essentials of Diagnosis

• Polyuria and constipation; abdominal pain in some

• Thirst and dehydration

• Mild hypertension

• Altered mentation, hyporeflexia, stupor, coma

• Serum calcium > 10.2 mg/dL (corrected with concurrent serumalbumin)

• Renal insufficiency or azotemia, isosthenuria

• Shortened QT interval due to short ST segment, ventricular systoles

• Vitamin D intoxication

• Milk-alkali syndrome

• Sarcoidosis

• Tuberculosis

• Paget’s disease of bone, especially with immobilization

• Familial hypocalciuric hypercalcemia

■ Treatment

• Identify and treat underlying disorder

• Volume expansion, loop diuretics (once euvolemic)

• Glucocorticoids, calcitonin, bisphosphonates, and dialysis all ful in certain instances

use-• Resection of parathyroid adenoma, if present

■ Essentials of Diagnosis

• Abdominal and muscle cramps, stridor; tetany and seizures

• Diplopia, facial paresthesias

• Positive Chvostek and Trousseau signs

• Cataracts if chronic, likewise basal ganglion calcifications

• Serum calcium < 8.5 mg/dL (corrected with concurrent serumalbumin); phosphate usually elevated; hypomagnesemia maycause or complicate

• Electrocardiographic changes: prolonged QT interval; lar arrhythmias, including ventricular tachycardia

• Identify and treat underlying disorder

• For tetany, seizures, or arrhythmias, give calcium gluconateintravenously

• Magnesium replacement if indicated

• Oral calcium and vitamin D supplements

• Phosphate-binding antacids if phosphate elevated

■ Essentials of Diagnosis

• Few distinct symptoms

• Cataracts, basal ganglion calcifications in hypoparathyroidism

• Serum phosphate > 5 mg/dL; renal failure, hypocalcemia sionally seen

occa-■ Differential Diagnosis

• Renal failure

• Hypoparathyroidism

• Excess phosphate intake, vitamin D toxicity

• Phosphate-containing laxative use

• Cell destruction, rhabdomyolysis, respiratory or metabolic dosis

aci-• Multiple myeloma

■ Treatment

• Treat underlying disease when possible

• Oral calcium carbonate to reduce phosphate absorption

■ Essentials of Diagnosis

• Seldom an isolated abnormality

• Anorexia, myopathy, arthralgias

• Irritability, confusion, seizures, coma

• Intravenous phosphate replacement when severe

• Oral phosphate supplements (unless hypercalcemic); be cautiousabout overshooting

• Correct magnesium deficit, if present

■ Essentials of Diagnosis

• Weakness, hyporeflexia, respiratory muscle paralysis

• Confusion, altered mentation

• Serum magnesium > 3 mg/dL; renal insufficiency common; creased uric acid, phosphate, potassium, and decreased calciummay be seen

in-• Increased PR interval → heart block → cardiac arrest

• Correct renal insufficiency, if possible (volume expansion)

• Intravenous calcium chloride for severe manifestations (eg, cardiographic changes, respiratory arrest)

electro-• Dialysis

■ Pearl

Be cautious about magnesium-containing antacids—available OTC—

in patients with renal insufficiency.

Reference

Weisinger JR et al: Magnesium and phosphorus Lancet 1998;352:391 [PMID:9717944]

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• Identify and treat underlying cause

• Intravenous magnesium replacement followed by oral nance

mainte-• Calcium and potassium supplements if needed

Respiratory Acidosis

■ Essentials of Diagnosis

• Central to all is alveolar hypoventilation

• Confusion, altered mentation, somnolence

• Dyspnea, respiratory distress, pulmonary abnormalities with orwithout cyanosis and asterixis

• Arterial PCO2increased; arterial pH decreased

• Lung disease may be acute (pneumonia, asthma) or chronic(COPD)

• May occur in the absence of lung disease

■ Differential Diagnosis

• Chronic obstructive lung disease or airway obstruction

• Central nervous system depressants

• Structural disorders of the thorax

• Myxedema

• Neurologic disorders, eg, Guillain-Barré syndrome

■ Treatment

• Address underlying cause

• Artificial ventilation if necessary to oxygenate, invasive or invasive

non-■ Pearl

Hypoxemia must be corrected before ascribing mental status changes

to an elevated P CO 2 ; it’s the case in most hypercapnic patients.

Reference

Adrogue HJ et al: Management of life-threatening acid-base disorders First oftwo parts N Engl J Med 1998;338:26 [PMID: 9414329]

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• Restrictive lung disease or hypoxia

• Central nervous system lesion

• Correct hypoxia or underlying ventilatory stimulant

• Increase ventilatory dead space (eg, breathe into paper bag, butonly in anxiety-induced hyperventilation)

■ Pearl

A lowered P CO 2 is a dependable early sign of bacteremia and sepsis syndrome.

Reference

Adrogue HJ et al: Management of life-threatening acid-base disorders Second

of two parts N Engl J Med 1998;338:107 [PMID: 9420343]

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Metabolic Acidosis

■ Essentials of Diagnosis

• Dyspnea, hyperventilation, respiratory fatigue

• Tachycardia, hypotension, shock (depending on cause)

• Acetone breath (in ketoacidosis)

• Arterial pH < 7.35, serum bicarbonate decreased; anion gap may

be normal or high; ketonuria

• Identify and treat underlying cause

• Correct volume, electrolyte status

• Bicarbonate therapy indicated in ethylene glycol or methanol icity, renal tubular acidosis, debated for other causes

tox-• Hemodialysis, mechanical ventilation if necessary

Metabolic Alkalosis

■ Essentials of Diagnosis

• Weakness, malaise, lethargy; other symptoms depend on cause

• Hyporeflexia, tetany, ileus, muscle weakness

• Arterial pH > 7.45, PCO2up to 45 mm Hg, and serum bicarbonate

> 30 meq/L; serum potassium and chloride usually low; ventilation is seldom prominent irrespective of pH

hypo-■ Differential Diagnosis

• Loss of acid (vomiting or nasogastric aspiration)

• Diuretic overuse or any volume contraction

• Exogenous bicarbonate or base load

• Primary hyperaldosteronism states (hyperreninemia, ingestion ofsome types of licorice, adrenal tumor or hyperplasia, Bartter’s orGitelman’s syndrome)

■ Treatment

• Identify and correct underlying cause

• Replenish volume and electrolytes (use 0.9% sodium chloride)

• Hydrochloric acid rarely if ever needed

• Symptoms or signs of urinary tract infection may be present

• Nodular, indurated epididymis, testes, or prostate

• Sterile pyuria or hematuria without bacteriuria; white blood cellcasts can be seen with renal parenchymal involvement

• Positive culture of morning urine on one of three consecutivesamples

• Plain radiographs may show renal and lower tract calcifications

• Excretory urogram reveals “moth-eaten” calices, papillary sis, and beading of ureters

necro-• Occasionally, ulcers or granulomas of bladder wall at cystoscopy

■ Differential Diagnosis

• Other causes of chronic urinary tract infections

• Interstitial nephritis, especially drug-induced

• Standard combination antituberculosis therapy

• Surgical procedures for obstruction and severe hemorrhage

• Nephrectomy for extensive destruction of the kidney