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M (Distant metastases)

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Bacillus Calmette-Guerin (BCG), which is an attenuated strain of Mycobacterium bovis that has a stimulatory effect on immune responses (probably the most effective agent for preventing a recurrence or for treating carcinoma in situ)

α-Interferon , an immune modulator

Carcinoma in situ (Tis). Intravesical BCG is the most effective agent. It is usually given in six weekly instillations, with a repeat course if a complete response (normal follow-up cystoscopy, biopsies, and cytology) is not attained.

Muscle-invasive localized disease (T2, T3, T4). The 5-year survival for organ-confined lesions is 70%–75%.

Radiation therapy is relatively ineffective, with a 20% long-term survival. Newer investigational uses of radiation therapy involve attempts at bladder preservation through combination protocols using systemic chemotherapy plus radiation therapy. Radiation therapy prior to radical cystectomy has not improved survival or decreased the incidence of local recurrence.

Radical cystectomy

In men, pelvic lymphadenectomy with cystoprostatectomy is performed. Urethrectomy is performed if there is tumor involvement of the prostatic urethra.

In women, anterior pelvic exenteration is performed, in which the bladder, urethra, uterus, fallopian tubes, ovaries, and anterior vaginal wall are removed.

Chemotherapy prior to cystectomy is a newer combination approach with debatable improvements in survival.

Urinary diversion

Conduits can be created using ileum or transverse colon. These allow urine to traverse into an external collection device on the abdominal wall.

Continent diversion involves the creation of an intra -abdominal reservoir for urine, which is drained by passing a catheter through a stoma on the abdominal wall.

Neobladder formation using the small bowel (ileum) or colon allows men to void via

FIGURE 25-3 A retrograde pyelogram reveals a large radiolucent irregular filling defect in the distal ureter with proximal hydroureteronephrosis. Ureteroscopy with biopsy confirmed a transitional cell carcinoma.

FIGURE 25-4 Left: A retrograde pyelogram reveals a large radiolucent filling defect that involves most of the renal pelvis. A computed tomography (CT) scan (right) shows this mass to be soft tissue density (not a calculus). Ureteroscopy and biopsy confirmed a transitional cell carcinoma.

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Conservative excision may be appropriate for low -grade, low -stage ureteral tumors. This involves tumor excision with primary ureteroureterostomy or ureteral reimplantation (into the bladder) for distal ureteral lesions.

Endoscopic treatment. Newer equipment has allowed for endoscopic ureteral resection of low -grade and low -stage tumors. The role is still evolving but is currently reserved for patients with low -grade, papillary tumors in solitary renal units or for patients whose health precludes major surgical intervention.

D Renal cell carcinoma

Epidemiology. There are approximately 30,000 new cases of renal cell carcinoma per year. The disease is more common in men than in women and has a peak incidence in the fifth to seventh decades of life. Renal cell carcinoma is associated with von Hippel–Lindau disease (VHL).

Etiology. There is no known specific causative agent, but smoking may be a risk factor. Cytogenetic studies most commonly show defects in chromosome 3, the locus of the VHL gene, a tumor suppressor gene.

Clinical presentation. Renal cell carcinoma is commonly discovered during radiographic studies for other complaints (incidental). The classic triad of pain, hematuria, and flank mass is very uncommon.

Paraneoplastic syndromes are uncommon but include:

Stouffer's syndrome (nonmetastatic hepatic dysfunction), which is a poor prognostic sign

Hypercalcemia, which has an unclear etiology

Hypertension, due to a local vascular phenomenon or renin secretion

Erythrocytosis , due to erythropoietin production

Endogenous pyrogen production and fevers , the cause of which are unknown

Diagnosis

Excretory urography with nephrotomography allows abnormal renal contours or extrinsic compression of the renal collecting system to be seen.

Ultrasonography is useful for differentiating a simple renal cyst from a complex or solid lesion. Criteria for a simple cyst are absence of internal echoes; a smooth, thin wall; and an acoustic shadow arising from the edges of the cyst. Any lesion that is not a simple cyst on ultrasound requires a CT evaluation.

CT scan with intravenous and oral contrast is the most cost -effective diagnostic and staging modality. It evaluates local tumor, venous extension, regional lymph nodes, and liver metastases.

MRI may be better at defining venous extension than CT scan. Its cost -effectiveness is not clear.

Renal arteriography is rarely used, being reserved for renal-sparing surgery (i.e., partial nephrectomy). Its diagnostic role has been replaced by the CT scan.

Venacavography is used for delineating the renal vein or caval tumor thrombus but has been replaced by MRI.

Percutaneous aspiration and biopsy is usually unnecessary. Biopsy is a reasonable method of diagnosis for patients with metastatic disease for tissue confirmation.

Solid renal tumor. The differential diagnosis for a solid renal tumor includes:

Renal cell carcinoma

Renal oncocytoma, which comprises approximately 3%–5% of solid renal tumors and has a benign natural history

Renal angiomyolipoma, which is a benign tumor that contains smooth muscle, blood vessels, and adipocytes. A CT scan can distinguish this tumor based on the presence of fat. This type of tumor is associated with tuberous sclerosis.

Fibroma, lipoma (rare)

Renal adenoma, which is thought historically to be benign. It is often found at autopsy and is less than 3 cm in size. Histologically, it is identical to renal cell carcinoma. It is now considered to be a small renal cell carcinoma.

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TABLE 25-4 TNM Staging Classification of Renal Cell Carcinoma

T (Primary tumor)

M (Distant metastases)

M0 No distant metastases

M1 Distant metastases present

Reprinted with permission from Lawrence PF, Bell RM, Dayton MT. Essentials of Surgical Specialties, 2nd ed. Baltimore: Williams & Wilkins; 1993:393.

Staging and prognosis

Staging classification (Table 25 -4)

Prognosis

Patients with lymph node metastases have a 5-year survival rate between 10% and 50%.

Patients with stage I lesions have a 5-year survival rate of approximately 75%.

Patients with stage II or IIIa lesions have a 5-year survival rate of approximately 50%.

Treatment

Stage I and stage II lesions

Radical nephrectomy (open or laparoscopic) is surgical removal of the ipsilateral adrenal gland, kidney, and investing adipose tissue and fascia. Regional lymphadenectomy may also performed.

Lymphadenectomy. For left -sided lesions, the para -aortic nodes are removed. For right -sided lesions, paracaval are removed.

Stages IlIa and IV. Treatment involves the concomitant excision of the renal vein or caval thrombus. The surgical approach is based on the extent of caval disease.

Stage IIIb

Minimal disease. Complete excision may be warranted, but the prognosis is poor.

Bulky disease or stage IV lesions may require nephrectomy for palliation of symptoms or for research and study purposes.

Metastatic renal cell carcinoma

Chemotherapy is essentially ineffective, possibly because of the frequent expression of the multidrug resistance (MDR) gene or P -glycoprotein.

Hormonal therapy is ineffective.

Immunotherapy. Ongoing investigations using interferon, interleukin, lymphokine-activated killer (LAK) cells, and tumor-infiltrating lymphocytes (TIL) have shown objective responses in 15%–30% of patients. Interferon plus nephrectomy has a median survival of less than 12

months.

E Testicular tumors

Pathology

The major germ cell tumors of the testis are seminomatous and nonseminomatous tumors. Nonseminomatous germ cell tumors (NSGCT) include embryonal carcinoma, teratoma,

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choriocarcinoma, and yolk sac tumors, alone or in combination. Secondary tumors include lymphomas.

Cryptorchidism (undescended testis) increases the risk of testicular malignancy.

Epidemiology

Although testis tumors are generally uncommon, they are the most common malignancy in men between the ages of 20 and 34 years.

Age. The tumor type is age dependent: Yolk sac tumors and teratomas are common in infants. All cell types may be seen in young adults: Seminoma is more common in men between the ages of 35 and 60 years, and lymphomas predominate in men older than 60 years.

Race. Testicular cancer occurs infrequently in blacks compared with whites.

Clinical presentation. Despite efforts to educate physicians and patients about routine testicular selfexamination, a significant delay is common before diagnosis. Approximately 33%–50% of patients have identifiable metastatic disease at initial presentation.

Local signs and symptoms

Painless swelling or enlargement of the testicle occurs in 65% of patients. Pain (13%–49%) suggests hemorrhage or infarction and may be confused with epididymitis.

“Heaviness” may be experienced on the affected side.

Failure of epididymitis to resolve as expected with appropriate antimicrobial agents should alert the physician to the possibility of occult malignancy.

Excessive pain or injury from minimal testicular trauma may indicate an underlying malignancy.

Signs and symptoms of metastatic disease prompt evaluation in 10% of patients and may include abdominal or back pain, nausea, anorexia, weight loss, gynecomastia, abdominal mass, cough, dyspnea, and hemoptysis.

Diagnosis

Physical examination may reveal a firm, nontender, or mildly tender distinct mass or diffuse testicular swelling.

A reactive hydrocele occurs in 5%–10% of cases.

Findings of gynecomastia or an abdominal mass suggest an advanced testicular malignancy.