Oncologic Emergencies

Sarah Adams and Stephen C. Rubin

The American Cancer Society reports that approximately 78,500 new invasive cancers of the female reproductive tract were diagnosed in the United States in 2008 (1).

VAGINAL BLEEDING

Endometrial cancer and cervical cancer, as well as less common malignancies such as sarcomas, gestational trophoblastic disease, and advanced vulvar can­cer, may present with vaginal bleeding (3). As with any patient, initial evaluation of a woman presenting with vaginal bleeding should determine whether she is hemodynamically stable based on blood pressure and pulse, and patients who appear syncopal should be resuscitated appropriately. As part of this initial eval­uation, a pregnancy test should be performed for all women of reproductive age. Once the patient is stable, the cause of vaginal bleeding can be determined by its pattern and findings on physical examination.

Cervical cancer

Vaginal bleeding caused by cervical cancer is usually painless and often occurs between menses or postcoitally. Given the success of cervical cancer screening in the United States, most patients presenting with advanced cervical cancer may have a history ofpoor health maintenance without regular Pap smears or a history of abnor­mal Pap smears or other pelvic infections.

On physical examination, it is important to visualize the cervix with a spec­ulum prior to performing a bimanual examination so that any bleeding resulting from manipulation of the cervix will not compromise the speculum examina­tion. After gently inserting the speculum, any clots in the vaginal vault can be evacuated and the source of bleeding can be determined. Advanced cervical cancer may present with a large fungating tumor or with ulceration of the cervix or the upper vagina. Biopsy of the cervix to confirm the diagnosis may be per­formed at this time or deferred until a planned examination under anesthesia to avoid causing further bleeding. Small areas of bleeding may be treated with Monsel solution or silver nitrite. Brisk bleeding may require tamponade with vaginal packing and admission to a gynecologic oncology service. If the bleeding is unremitting, the patient may need hypogastric artery ligation, embolization, or high-dose radiation therapy (4). Following the speculum examination, a bimanual examination will reveal the size and the extent of the disease, including the presence of parametrial spread, or the involvement of the rectum or the blad­der. Laboratory studies should include a pregnancy test and a complete blood count as well as a chemistry panel to check for evidence of renal dysfunction which might suggest obstruction of the distal collecting system. If the bleeding is not severe, the patient can be discharged once appropriate referral and prompt follow-up by a qualified gynecologic oncologist has been arranged.

Endometrial Cancer

Vaginal bleeding caused by endometrial or other corpus cancers is usually not as severe as that caused by cervical cancer. The majority of patients with endome­trial cancer are postmenopausal, with a mean age of 60 years (3).

In most cases, it will not be possible to make a definitive diagnosis of endo­metrial cancer during an emergency department visit, although postmenopausal women presenting with vaginal bleeding are considered to have endometrial cancer until proven otherwise. The differential diagnosis is much broader in a premenopausal woman and may include such benign causes as anovulatory bleeding, fibroids, complications from pregnancy, and infection.

On speculum examination, the bleeding will be from the cervical os. A pel­vic examination will determine whether the uterus is enlarged and whether there is any extrauterine spread of the tumor. The bleeding is seldom life threatening, and most patients can be discharged from the emergency department as long as adequate provisions are made for prompt referral to a qualified gynecologist.

Gestational Trophoblastic Disease

Women with gestational trophoblastic neoplasia most commonly present with vaginal bleeding (5). This disease is seen at early or late reproductive ages and affects 1 in 1,200 pregnancies in the United States. Patients may report recurrent vaginal bleeding and an absence of fetal movements.

On examination, the uterine size is often greater than expected for gesta­tional age. Bleeding will be seen from the cervical os on speculum examination, and occasionally, vesicular material also may be seen extruding through the os (3). The definitive diagnosis is made by ultrasonography, which shows a distinctive multiechogenic pattern.

Vulvar Cancer

Bleeding caused by vulvar cancer is rare (6). Women presenting with bleeding usually have an advanced vulvar lesion. Patients with advanced diseases and bleeding should be admitted to initiate treatment.

THROMBOEMBOLISM

Patients with gynecologic malignancy have a high risk of thromboembolic dis­ease due to an acquired coagulopathy due to the cancer combined with com­pression and venous stasis caused by large pelvic tumors (7). This risk is increased in the postoperative period and should be considered for women presenting with asymmetric edema or shortness of breath. Women with deep venous thrombosis usually present with unilateral lower extremity edema, which may be difficult to differentiate from lymphedema resulting from lymphadenectomy. Venous Doppler ultrasound is required to identify clots, and evaluation should include the upper thigh if possible.

Pulmonary embolus is a dangerous complication of pelvic surgery and malignancy and should be suspected in patients reporting shortness of breath or pleuritic chest pain. Conversely, patients presenting with a pulmo­nary embolus should undergo evaluation for malignancy as a possible etiol­ogy of their coagulopathy. Women with pulmonary clots are likely to be tachycardic and hypoxic. Lung examination is often unremarkable, but decreased breath sounds or dullness to percussion may be evident if the thrombus is accompanied by pleural effusion. Lab values such as d-dimer may assist with the diagnosis, but a helical CT will be most sensitive in con­firming the present of a clot. If the patient cannot tolerate IV dye for the CT scan, a ventilation-perfusion study can be performed. Patients with new venous thrombosis or pulmonary embolism are usually admitted to initiate anticoagulation.

POSTOPERATIVE WOUND COMPLICATIONS

Wound Infections

Common postoperative infections include superficial wound cellulitis, infected hematomas, abscesses, and infections of the vaginal cuff after hysterectomy.

Wound Dehiscence

Wound dehiscence usually occurs 5 to 7 days after surgery but may present after staple removal 10 days to 2 weeks postoperatively. If the wound is healthy, without discharge or signs of infection, and if the defect is small, the patient can be managed with debridement and dressing changes. Larger defects may benefit from a wound vac or closed suction system. In either case, the patient’s surgeon should be consulted.

Evisceration

Evisceration, with fascial separation, may present as an incisional mass or bulge with valsalva, and patients may report pain or nausea which can be sudden in onset or related to exertion or coughing. Risk factors for evisceration include a history of prior hernia, steroid use, immunosuppression, poorly controlled dia­betes, obesity, infection, chronic cough, and tobacco use (9). Evaluation of the wound will reveal a fascial defect and sometimes bowel herniation. If the bowel is exposed, the wound should be covered with sterile, moist towels, and arrange­ments made for the patient to be taken to the operating room for fascial closure.

Vaginal Cuff Cellulitis

The other common postoperative infections in patients with gynecologic malignancies are vaginal cuff cellulitis and cuff abscess. Vaginal cuff cellulitis occurs in 8% of those who receive antibiotic prophylaxis before a hysterectomy (8). The most common cause is a mixed infection of anaerobes endogenous to the vagina and Gram-negative aerobic bacteria. Women with cuff cellulitis may present with purulent discharge, persistent vaginal bleeding, and fever. On examination, the cuff will be erythematous and friable. Most patients are treated with oral antibiotics, but women who are acutely febrile or who have evidence of an abscess should be admitted for treatment and possible drainage of the pelvic collection in the operating room.

Vaginal Cuff Dehiscence

Vaginal cuff dehiscence is a rare complication following hysterectomy that requires prompt medical attention. Risk factors include early resumption of intercourse postoperatively, increased intra-abdominal pressure, smoking, history of prior surgery or radiation, connective tissue disease, and steroid use (10). Patients may present with vaginal pain or pressure or with protru­sion of bowel into the vaginal vault. The diagnosis can be confirmed with a sterile speculum examination and requires an immediate gynecologic con­sult for surgical management.

GASTROINTESTINAL COMPLICATIONS

Bowel Obstruction

Because ovarian cancer metastasizes to the serosal surfaces of the bowel, bowel obstruction is a common problem for patients with advanced or recurrent disease and is the presenting symptom for approximately 5% of patients (11). Bowel obstruction may also occur postoperatively as a consequence of adhesion forma­tion or bowel stricture. Women with bowel obstruction present with persistent nausea and vomiting or anorexia, often have abdominal pain and distention, and may report an absence of flatus or bowel movements. They are typically dehydrated and may be tachycardic or mildly hypotensive as a result. Tympany, distention, and tenderness may be evident on abdominal examination, and radio­graphic studies will show air-fluid levels and bowel distention. It is critical to note overdistention of the large bowel as a diameter >10 cm is associated with a high risk of perforation and requires prompt surgical decompression (12). Women with a bowel obstruction usually require admission for hydration and bowel rest or sur­gery. Placement of a nasogastric tube to drain the stomach and decompress the bowel will alleviate some of their symptoms and may hasten recovery.

Bowel Perforation

Less commonly, patients may present with bowel perforation resulting from obstruction or from tumor infiltration of the bowel wall. In addition to women with massive dilation of the bowel, patients with recurrent cancer and a history of prior obstruction or those treated with anti-angiogenic chemotherapies, such as bevacizumab, are at increased risk of bowel perforation. In some cases, the symptoms may be unexpectedly subtle, but most patients with bowel injury will have abdominal pain that can be severe. This may be accompanied by fever, tachycardia, and abdominal rigidity resulting from acute peritonitis. A CT scan with gastrografin may be helpful to confirm the diagnosis but should not delay surgical intervention. These patients should be resuscitated with IV fluid and given broad-spectrum antibiotics. Consultation with a gynecologic oncologist or surgeon should be obtained immediately.

Gastrointestinal Fistulas

Women with gynecologic malignancies may develop gastrointestinal fistulas as a consequence of tumor infiltration of the bowel or as a complication of surgery or treatment with radiation or chemotherapy. Fistulas developing in the postop­erative period can result from an unrecognized enterotomy at the time of surgery, from erosion of a foreign body such as an intraperitoneal drain or from infection and wound breakdown. In patients treated with radiation or antian- giogenic chemothearpy, fistulas result from devascularization and breakdown of the affected tissue. Patients with enterocutaneous fistulas may present with discharge from a prior incision site from surgery or a percutaneous drain site. Subcutaneous fluid collections may yield feculent material, and local necrosis or an overlying cellulitis with erythema, warmth, or tenderness may be evident. Enterovaginal or rectovaginal communications cause persistent vaginal dis­charge which can be caustic small bowel contents or feculent material if the dis­tal intestinal tract is involved. It is often difficult to localize the fistulous tract due to patient discomfort, especially in patients who have vaginal stenosis from prior irradiation, but a gentle speculum examination may be helpful to confirm the diagnosis. CT fistulograms can also be performed to document the location of the fistulous tract for treatment planning. Women with a new fistula, or with evidence of infection from a chronic fistula, should be admitted for workup and management.

Bowel Prolapse

Many women with ovarian cancer or other gynecologic malignancies require colostomy or ileostomy to achieve optimal surgical results or to manage a bowel obstruction from recurrent disease. Colostomy complications, including stenosis of the stoma, peristomal hernia, wound infection, and prolapse, occur in approxi­mately 30% of patients (13). Women may present with complaints of a mass at the site of the stoma or prolapse of the bowel through the stoma which can be associ­ated with bleeding or tenderness. Peristomal herniation of bowel requires admis­sion for prompt surgical correction. Mucosal prolapse of the stoma can be reduced by gentle digital pressure, but it should be done expeditiously to prevent infection or edema. In either case, consultation should be requested from a gynecologic oncolo­gist or a surgeon for management, and the exposed bowel should be kept moist and protected with gauze.

UROLOGIC COMPLICATIONS

Ureteral Obstruction

Ureteral obstruction can be caused by compression from a large pelvic tumor or by stricture from radiation treatment or postoperative adhesions, or it may result directly from an intraoperative injury. Women with ureteral obstruction often present with nonspecific flank pain, occasionally radiating to the pelvis and the groin. The onset may be gradual and is often associated with concurrent urinary infection or even urosepsis. In cases of bilateral obstruction, anemia and azotemia may result. The diagnosis can be made using intravenous pyelogra­phy, computed tomography, renal nuclear scanning, or renal ultrasonography showing hydronephrosis. Management depends on the severity of the obstruc­tion, but antibiotics should be administered after specimens for blood and urine cultures have been obtained. Postoperative patients should be admitted for surgical consultation and repair, and women with renal compromise or urosep­sis will also require hospitalization for treatment. Stable patients with insidious signs of ureteral obstruction may be discharged once arrangements are made for follow-up care.

Urologic Fistulas

Urinary fistulas may develop following radical surgery or radiation or as a result of extensive tumor involvement of the lower pelvis, most commonly in patients with cervical or vaginal cancer. Postoperative fistulas occur from 7 to 21 days after surgery and are most common in patients undergoing radical hysterectomy requiring extensive ureterolysis and pelvic dissection (14). The incidence of fis­tula formation after radical hysterectomy is approximately 1%, but this rate is three times higher in patients treated with adjuvant radiation therapy (14). Ureteral fistulas caused by radiation therapy typically develop 6 to 12 months after completion of treatment. In patients with advanced cervical or vaginal tumors, large fistulas may develop from erosion of the tumor into the base of the bladder or the urethra.

Symptoms of ureteral fi stulas include urinary incontinence, frequency, dysuria, hematuria, and watery vaginal discharge. Fistulas can be diagnosed either by directly observing urine in the vagina or by injecting indigo carmine intravenously and placing a tampon in the vagina. Most do not require emergent hospital admission, but patients should be referred to a gynecologic oncologist for management and repair.

Urinary Conduit Complications

Urinary conduits may be constructed using a segment of ileum or colon as a reservoir and conduit. Complications include blockage of the ureteroconduit anas­tomotic site, with ureteral obstruction and possibly urosepsis; conduit necrosis; stomal necrosis; and electrolyte imbalance owing to absorption of chloride in an overly long conduit, resulting in hyperchloremic acidosis (15,16). Management in the emergency department is supportive. Admission considerations depend on the patient’s overall electrolyte balance, the presence of urinary obstruction, and the patient’s ability to return for follow-up care. Intravenous pyelography or ultra­sonography usually defines the problem. If urinary obstruction has resulted in uro­sepsis, emergency percutaneous nephrostomy may be necessary (17). Appropriate consultation with the gynecologic oncologist should be obtained.

Neurologic deficits

The differential diagnosis for patients presenting with a change in mental status is broad and in patients with a history of malignancy, includes infection, cere­brovascular accident, and metastatic disease. The most common etiology is infection, particularly in elderly patients, which requires a thorough workup including imaging studies and cultures of blood, urine, and possibly spinal fluid. Patients undergoing chemothearpy may be neutropenic and unable to mount an inflammatory response with fever or leukocytosis. In patients in whom infection is suspected, admission and empiric treatment with broad-spectrum antibiotics is advised.

As discussed above, patients with gynecologic malignancies are also coag- ulopathic and, consequently, are at risk for both hemorrhagic and embolic strokes. Women presenting with neurologic deficits and a history of prior clot or patients who are currently anticoagulated with warfarin or heparin should have imaging studies performed to rule out an intracranial bleed.

Although relatively uncommon except in very advanced disease, metasta­sis to the brain is possible in women with ovarian, endometrial, uterine, or cervi­cal cancers. Depending on the location of the lesion, patients with intracranial masses may present with headache, changes in mental status, vertigo, seizure, or neurologic deficits. CT or MRI scans may show a distinct mass, or lumbar puncture may reveal evidence of meningeal carcinomatosis with high opening pressure, elevated protein or white blood cell count, low glucose, and positive cytology. Patients with acute neurologic changes, or evidence of spinal cord com­pression, should have a neurosurgery consultation for operative decompression or steroid treatment to decrease swelling and inflammation.

COMPLICATIONS OF RADIATION THERAPY

Radiation Enteritis

Radiation therapy is used for the primary treatment of advanced cervical cancer, as well as uterine cancers, vulvar cancer, and locally recurrent ovarian cancer. An early complication during or immediately following treatment with radiothearpy is radiation proctitis or enteritis with diarrhea (18). Patients with severe diarrhea may become dehydrated and present to the emergency department for evaluation and resuscitation. These women can usually be treated with diphenoxylate (Lomotil) and fluid resuscitation, without admission. In some cases, rectal bleed­ing may result from radiation proctitis. Cort enemas (hydrocortisone) and a low- residue diet can be recommended for mild bleeding, but bleeding heavy enough to require fluid resuscitation or transfusion also requires consultation to a gyneco­logic or surgical service. In severe cases that do not respond to medical manage­ment, angiographic embolization or colostomy may be required.

Hemorrhagic Cystitis

Hemorrhagic cystitis can be caused by radiation therapy or some types of chemo­therapy. Bleeding can be managed in the emergency department with bladder irrigation using a three-way catheter. If the bleeding is not severe once any clots are removed from the bladder, the patient may be discharged with follow-up care. In severe hemorrhage, the patient will need to be admitted for more aggressive management and both urologic and gynecologic consultations are necessary.

COMPLICATIONS OF CHEMOTHERAPY

Nausea and Vomiting

The most commonly used drugs in gynecologic oncology are cisplatin, carbo- platin, and paclitaxel. Complications caused by cisplatin and carboplatin, which are administered as a bolus, include nausea and vomiting, which may be unremitting despite the use of prophylactic antiemetics (19). Symptoms are most severe on the day of treatment and, occasionally, may require emergent medical attention in the days following instillation. Once fluid and electrolyte sta­tuses are assured, the patient can often be managed with additional antiemetic medications and rarely will need to be admitted for hydration.

Hypersensitivity Reactions

Paclitaxel (Taxol) is used for induction chemotherapy for women with ovarian cancer and uterine cancers. The most severe toxicity associated with taxol is an immediate hypersensitivity reaction, which can require transfer to the emer­gency room during infusion. Patients may become acutely hypertensive or hypotensive and flushed. They may experience shortness of breath or chest pain and can become hypoxic. Taxol can also cause cardiac toxicity manifested by sinus bradycardia (30%), bradyarrhythmia with AV blockade, and short-lived ventricular tachycardia (20). Although most of these side effects are noted while the patient is receiving chemotherapy, they can occasionally occur after dis­charge, particularly if the patient is given a 3-hour taxol infusion. Most patients recover quickly following treatment with steroids, antihistamines, fluids, and supportive care, but severe cases may require respiratory support.

Bone Marrow Suppression

Many chemotherapeutic drugs, including taxol and platinum compounds, can cause bone marrow suppression with neutropenia, anemia, and thrombocytopenia. It is unusual for these patients to be seen in the emergency department; however, women presenting with fever or evidence of infection and an absolute neutrophil counts <500 should be admitted for empiric broad-spectrum antibiotic therapy. Rarely, patients with anemia or severe thrombocytopenia will require admission for transfusion of platelets and packed red cells.

SUMMARY

Women with gynecologic cancers are susceptible to medical complications from their tumor burden as well as from surgery, chemotherapy, or radiation therapy that may require emergent medical attention. It is important to consider effects and toxicities of these interventions when evaluating patients with a history of malignancy in the emergency department and to consult with a gynecologic oncol­ogist to assist with diagnosis and management to ensure that these women receive the care they need.

COMMON PITFALLS

■ In the presence of vaginal bleeding in a patient of reproductive age, pregnancy should be ruled out.

■ If the cecum is dilated to 10 cm from large bowel obstruction, prompt decompression is mandatory.

■ Necrotizing fasciitis requires prompt surgical debridement and admission.

■ If any amount of ureteral obstruction is diagnosed, urosepsis must be ruled out before the patient is discharged from the ED.

■ Febrile neutropenic patients must be admitted.

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