CHAPTER 49 Fluid complications Frederic W. Grannis, Jr., MD, Lily Lai, MD, James T. Kakuda, MD, and Carey A. Cullinane, MD MALIGNANT PLEURAL EFFUSION
Pleural effusion is usually caused by a disturbance of the normal Starling forcesregulating reabsorption of fluid in the pleural space, secondary to obstructionof mediastinal lymph nodes draining the parietal pleura. Tumors that metasta-size frequently to these nodes, eg, lung cancer, breast cancer, and lymphoma,cause most malignant effusions. It is, therefore, puzzling that small-cell lungcancer infrequently causes effusions.
Pleural effusion restricts ventilation and causes progressive shortness of breathby compression of lung tissue as well as paradoxical movement of the inverteddiaphragm. Pleural deposits of tumor cause pleuritic pain.
Pleural effusions commonly occur in patients with advanced-stage tumors, whofrequently have metastases at multiple sites (eg, brain, bone, and other organs),physiologic deficits, complications (eg, malnutrition, debilitation), and othercomorbidities. Because of these numerous clinical and pathologic variables, itis difficult to perform meaningful trials in patients with pleural effusions. Forthe same reason, it is often difficult to predict a potential treatment outcomefor the specific patient with multiple interrelated clinical problems. Diagnosis
The new onset of a pleural effusion may herald the presence of a previouslyundiagnosed malignancy or, more typically, complicate the course of a knowntumor. Thoracentesis The first step in management in almost all cases is thoracentesis. An adequate specimen should be obtained and sent for cell count; determina- tion of glucose, protein, lactate dehydrogenase (LDH), and pH; and appropri- ate cultures and cytology. A negative cytology result is not uncommon and does not rule out a malignant etiology.
The Light criteria (LDH > 200 U/L; pleural-serum LDH ratio > 0.6, and pleu-
ral-serum protein ratio > 0.5) help categorize pleural effusions as exudates. The majority of undiagnosed exudates are eventually diagnosed as malignant,whereas < 5% of transudates are shown to be caused by cancer. Pleural biopsy If cytology of an exudative
Image-guided percutaneouscutting-needle biopsy of pleural
effusion is negative and malignant disease is
still suspected (approximately 50% of cases),
blind pleural biopsy has a low diagnostic yield
that can be improved by image guidance.
achieved a positive biopsy in 21 of24 malignant effusions, for an
Thoracoscopy Thoracoscopic examination is
emerging as a reliable diagnostic technique
with a low complication rate. It allows com-
prehensive visualization of one pleural cavity,
coupled with the opportunity to biopsy areas of disease. This method provides adefinitive diagnosis and allows the pathologist to suggest possible sites of pri-mary disease based on the histopathology. Furthermore, this technique permitsthe diagnosis and staging of malignant mesothelioma if it is the cause of theeffusion. Thoracoscopy also offers the opportunity for simultaneous treatment. Bronchoscopy may be helpful when an underlying lung cancer is suspected, especially if there is associated hemoptysis, a lung mass, atelectasis, or a mas- sive effusion. It may also be helpful when there is a cytologically positive effu- sion with no obvious primary tumor. PROGNOSIS
Prognosis with malignant pleural effusion varies by primary tumor. For ex-ample, median survival for lung cancer is 3 months while it is 10 months forbreast cancer. Median survival is also lower in patients with encasement atelecta-sis (3 months). Treatment INITIAL TREATMENT
Because the specific clinical circumstances may vary markedly in different pa-tients, treatment must be individualized to provide the best palliation for eachpatient. In general, malignant pleural effusion should be treated aggressivelyas soon as it is diagnosed. In most cases, effusion will rapidly recur after treat-ment by thoracentesis or tube thoracostomy alone. If the clinician decides toadminister systemic chemotherapy for the underlying primary malignancy, intumors such as breast cancer, lymphoma, and small-cell lung cancer, it isimportant to monitor the patient carefully for recurrent effusion and treatsuch recurrences immediately.
If a malignant pleural effusion is left untreated, the underlying collapsed lungwill become encased by tumor and fibrous tissue in as many as 10%-30% ofcases. Once this encasement atelectasis has occurred, the underlying lung is“trapped” and will no longer reexpand after thoracentesis or tube thoracos-tomy. Characteristically, the chest x-ray in such cases shows resolution of the
pleural effusion after thoracentesis, but the underlying lung remains partially
collapsed. This finding is often misinterpreted by the inexperienced clinicianas evidence of a pneumothorax, and a chest tube is placed. The air space per-
CANCER MANAGEMENT: A MULTIDISCIPLINARY APPROACH
sists and the lung remains unexpanded, even with high suction and pulmonaryphysiotherapy. Allowing the chest tube to remain in place can worsen the situ-ation by causing bronchopleural fistulization and empyema. Physical techniques
To avoid encasement atelectasis, pleural effusion should be treated definitivelyat the time of initial diagnosis. Multiple physical techniques of producing ad-hesions between the parietal and visceral pleura, obliterating the space, andpreventing recurrence have been used. They include open or thoracoscopicpleurectomy, gauze abrasion, or laser pleurodesis. Surgical methods have notbeen demonstrated to have any advantage over simpler chemical pleurodesistechniques in the treatment of malignant effusions but can easily be em-ployed when unresectable tumor with associated effusion is found at thetime of thoracotomy. Chemical agents
Multiple chemical agents have been used. Tetracycline Tetracycline pleurodesis results in a lower incidence of recurrence when compared with tube thoracostomy alone, but often causes severe pain. Doxycyclineand minocycline are probably equivalent in efficacy to tetracycline. Bleomycin Intrapleural bleomycin (Blenoxane), in a dose of 60 U, has been shown to be more effective than tetracycline and is not painful, but it is costly. Absorption of the drug can result in systemic toxicity. Combined use of tetra- cycline and bleomycin has been demonstrated to be more efficacious than the use of either drug singly. Talc pleurodesis was first introduced by Bethune in the 1930s. Talc powder (Sclerosol Intrapleural Aerosol) has demonstrated efficacy in numerous large studies, preventing recurrent effusion in 70%-92% of cases. Talc is less painful than tetracycline. Cost is minimal, but special sterilization techniques must be mastered by the hospital pharmacy.
Talc can be insufflated in a dry state at the time of thoracoscopy or instilled as aslurry through a chest tube. The dose should be restricted to no more than 5 g.
Our group and others have noted problemswith residual multiloculated effusions fol-
lowing talc use. It is important to ensure that
the talc does not solidify and form a concre-
tion in the chest tube, thus preventing the
was unequal and limited and didnot improve in patients who were
reexpansion of the lung following pleurodesis.
Such an event is more likely with the use of
experienced success in manage-ment of pleural effusion (Mager HJ,Pleurodesis technique With any form of Measen B, Verzijlbergen F, et al: Lung
pleurodesis, a 24- to 32-French tube has cus-
tomarily been inserted through a lower intercostal space and placed on un-derwater seal suction drainage until all fluid is drained and the lung has com-pletely reexpanded. Because severe lung damage can be produced by improperchest tube placement, it is imperative to prove the presence of free fluid by apreliminary needle tap and to enter the pleural space gently with a blunt clamptechnique, rather than by blind trocar insertion. If there is any question aboutthe presence of loculated effusion or underlying adhesions, the use of CT orsonography may enhance the safety of the procedure. In the case of large effu-sions, especially those that have been present for some time, the fluid shouldbe drained slowly to avoid reexpansion pulmonary edema.
Significant complications can occur with both thoracentesis and chest tube tho-racostomy. These procedures should not be performed by inexperienced prac-titioners without training and supervision. Premedications If doxycycline or talc is to be used, the patient should be pre-medicated with narcotics. Intrapleural instillation of 20 mL of 1% lidocainebefore administration of the chemical agent may help reduce pain. Following instillation of the chemical agent, the chest tube should remain clampedfor at least 2 hours. If high-volume drainage persists, the treatment can berepeated. The chest tube can be removed after 2 or 3 days if drainage is< 300 mL/day. Follow-up x-rays at monthly intervals assess the
results after the use of thoraco-scopic talc (5 g) pleurodesis under
Alternative approaches Use of small-bore
Chest tube drainage continued for3-5 days postoperatively. The
tubes and outpatient pleurodesis has been ad-
vocated by some investigators and has the po-
tential for reducing hospital stay and treatment
(Cardillo G, Facciolo R, Carbone L, et
cost. Patz performed a prospective, random-
al: Eur J Cardiothorac Surg 21:302-
ized trial of bleomycin vs doxycycline (72%
bleomycin vs 79% doxycycline) pleurodesis
via a 14-French catheter and found no difference in efficacy.
Other approaches that must be considered experimental at this time includesilver nitrate pleurodesis and the use of various biological agents, includingCorynebacterium parvum, OK-432, tumor necrosis factor,interleukin-2(Proleukin), interferon-α (Intron A, Roferon-A), interferon-β (Betaseron), andinterferon-γ (Actimmune). TREATMENT OF ENCASEMENT ATELECTASIS
If encasement atelectasis is found at thoracentesis or thoracoscopy, tube tho-racostomy and pleurodesis are futile and contraindicated. Surgical decortication has been advocated for this problem. This potentially dangerous procedure may result in severe complications, however, such as bronchopleural fistula and empyema.
CANCER MANAGEMENT: A MULTIDISCIPLINARY APPROACH
Pleuroperitoneal shunts The Royal
experience with pleuroperitoneal shunts in
160 patients with malignant pleural effusion
and a trapped lung. Effective palliation was
had lung cancer and 24% hadbreast cancer. There were no
achieved in 95% of patients; 15% of patients
required shunt revisions for complications.
the catheter was placed underthoracoscopic control, 27 of 38
Intermittent thoracentesis, as needed to
relieve symptoms, may be the best option in
patients with a short anticipated survival.
percent had a good result withcontrol of effusion, with subse-
Catheter drainage Another new option is
to insert a tunneled, small-bore, cuffed, sili- intermittent drainage for > 1cone catheter (PleurX Pleural Catheter, Den- month or until death (62%). Fivever Biomaterials, Inc., Denver, Colorado) into percent had major complications,the pleural cavity. The patient or family mem- including empyema and tumor
bers may then drain fluid, using vacuum Chest [abstract 364] [suppl]6:1655,bottles, whenever recurrent effusion causes 2002). symptoms. Putnam prospectively comparedPleurX catheter drainage with doxycycline pleurodesis and found the two tobe equally effective. We have found this device to be useful and well toleratedby patients and caregivers. Pleuroperitoneal shunts and PleurX catheters canhave problems with catheter plugging, infection, and local tumor implants alongthe catheter track. Chemotherapy options depend on the cell type of the tumor and the general condition of the patient. Although intrapleural chemotherapy offers the pos- sibility of high-dose local therapy with minimal systemic effects, only a small number of studies have been performed.
longer mean survival (12 months vs 5 months)
when systemic chemotherapy was given to 71
patients who initially presented with malignant
mg/body) through an implantableaccess system (Infuse-a-Port) in 22
pleural/pericardial effusions. New studies in this
including 17 with non–small-celllung cancer (NSCLC). Median
Radiation therapy may be indicated in some
patients with lymphoma but has limited effec-
tiveness in other tumor types, particularly if
pleural effusion is safe and possiblyeffective (Shoji T, Tanaka F, YanagiharaChylothorax not due to trauma is usually sec- K, et al: Chest 121:821-824, 2002).
ondary to cancer, most frequently lymphoma. An added element of morbidity is conferred
by the loss of protein, calories, and lymphocytes in the draining fluid. Chy-lothorax secondary to lymphoma is usually of low volume and responds totalc pleurodesis in combination with radiotherapy or chemotherapy. PERICARDIAL EFFUSION
Injection of green dye intolymphatics in various areas of the
Pericardial effusion develops in 5%-15% of pa-
pericardium in 12 human cadaversdemonstrated lymphatic channels
tients with cancer and is sometimes the initial
manifestation of malignancy. Most pericardial
effusions in cancer patients result from ob-
struction of the lymphatic drainage of the
(Riquet M, Le Pimpec-Barthes F, Hidden
heart secondary to metastases. The typical pre-
G: Surg Radiol Anat 23:317-319,2001).
sentation is that of a patient with known can-cer who is found to have a large pericardial
effusion without signs of inflammation. Bloody pericardial fluid is not a reli-able sign of malignant effusion.
The most common malignant causes of pericardial effusions are lung and breastcancers, leukemias (specifically acute myelogenous, lymphoblastic, and chronicmyelogenous leukemia [blast crisis]), and lymphomas (approximately 80% ofcases). Pericardial effusions caused by sarcomas, melanomas, thymoma, as wellas GI, ovarian, and cervical cancers are less common.
Not all pericardial effusions associated withcancer are malignant, and cases with negative
cytology may represent as many as half of
the highest value of the upperplethysmographic peak of the
cancer-associated pericardial effusions. Such
effusions are more common in patients with
mediastinal lymphoma, Hodgkin’s disease, or
breast cancer. Other nonmalignant causes in-
clude drug-induced or postirradiation peri-
pericardiocentesis. He concludedthat analysis of pulse-oximetric
carditis, tuberculosis, collagen diseases, ure-
mia, and congestive heart failure. Many effu-
sions that initially have negative cytology will
pulsus paradoxus associated withlarge pericardial effusions
Tamponade occurs when fluid accumulates
faster than the pericardium can stretch. Com-
pression of all four heart chambers ensues,with tachycardia and diminishing cardiac output. Fluid loading can counteractintrapericardial pressure temporarily; reciprocal filling of right- and left-sidedchambers with inspiration and expiration, secondary to paradoxical movementof the ventricular septum, is a final mechanism to maintain blood flow beforedeath. Diagnosis
A high index of suspicion is required to make the diagnosis of pericardialeffusion. Signs and symptoms Dyspnea is the most common symptom. Patients may also complain of chest pain or discomfort, easy fatigability, cough, and ortho- pnea or may be completely asymptomatic. Signs include distant heart sounds and pericardial friction rub. With cardiac tamponade, progressive heart failure
CANCER MANAGEMENT: A MULTIDISCIPLINARY APPROACH
occurs, with increased shortness of breath, cold sweats, confusion, pulsusparadoxus > 13 mm Hg, jugular venous distention, and hypotension. Chest x-ray Chest radiographic evidence of pericardial effusion includes car- diomegaly with a “water bottle” heart, an irregular, nodular contour of the cardiac shadow, and mediastinal widening. ECG The ECG shows nonspecific ST- and T-wave changes, tachycardia, low QRS voltage, electrical alternans, and atrial dysrhythmia. Pericardiocentesis and echocardiography
suspected pericardial effusion but also can
using a new device with a needlecarrier supported by a bracket
document the size of the effusion and its ef-
fect on ventricular function. However, a peri-
cardial tap with cytologic examination (posi-
tive in 50%-85% of cases with associated ma-
(Maggiolini S, Bozzano A, Russo P, et
lignancy) may be necessary to confirm the di-
al: Am J Soc Echocardiogr 14:821-824, 2001).
agnosis of malignant effusion or to differenti-ate it from other causes of pericardial effusion. Serious complications, includ-ing cardiac perforation and death, can occur during pericardiocentesis, evenwhen performed by experienced clinicians. Tumor markers or special staining and cytogenetic techniques may improve the diagnostic yield, but ultimately an open pericardial biopsy may be necessary. CT and MRI as diagnostic adjuncts may provide additional information about the presence and location of loculations or mass lesions within the pericardium and adjacent structures. Cardiac catheterization may occasionally be of value to rule out superior vena caval obstruction, diagnose microvascular tumor spread in the lungs with secondary pulmonary hypertension, and document constrictive pericarditis before surgical intervention. Pericardial fluid has been aspirated in experimen- tal animals by femoral vein catheterization and needle puncture of the right atrial appendage from within. This technique has not been used in humans. Pericardioscopy allows visualization and biopsy at the time of subxiphoid or thoracoscopic pericardiotomy and can improve the diagnostic yield. Prognosis
In general, cancer patients who develop a significant pericardial effusion havea high mortality, with a mean time to death of 2.2-4.7 months. However,about 25% of selected patients treated surgically for cardiac tamponade enjoya 1-year survival. Treatment GENERAL CONCEPTS
As is the case with malignant pleural effusion, it is very difficult to evaluatetreatments for pericardial effusion because of the many variables. Since malig-nant pericardial effusion is less common than malignant pleural effusion, it ismore difficult to collect data in a prospective manner. Certain generalizationscan, however, be derived from available data:
■ All cancer patients with pericardial effusion require a systematic evalu-
ation and should not be dismissed summarily as having an untreatableand/or terminal problem.
■ Ultimately, both the management and natural course of the effusion
depend on: (1) the underlying condition of the patient, (2) the extent ofclinical symptoms associated with the cardiac compression, and (3) thetype and extent of the underlying malignant disease. GENERAL TREATMENT APPROACHES
Asymptomatic, small effusions may be managed with careful follow-up andtreatment directed against the underlying malignancy. On the other hand, car-diac tamponade is a true oncologic emergency. Immediate pericardiocentesis,under echocardiographic guidance, may be performed to relieve the patient’ssymptoms. A high failure rate is anticipated because the effusion rapidly recursunless steps are taken to prevent this. Therefore, a more definitive treatmentplan should be made following the initial diagnostic/therapeutic tap.
In patients with symptomatic, moderate-to-large effusions who do not presentas an emergency, therapy should be aimed at relieving symptoms and pre-venting recurrence of tamponade or constrictive pericardial disease. Patientswith tumors responsive to chemotherapy or radiation therapy may attain longerremissions with appropriate therapy.
There are two theoretical mechanisms for control of pericardial effusion: creationof a persistent defect in the pericardium allowing fluid to drain out and be reab-sorbed by surrounding tissues or injury to the mesothelium resulting in the forma-tion of fibrous adhesions that obliterate the pericardial cavity.
Postmortem studies have demonstrated that both of these mechanisms areoperative. The fact that effusions can recur implies that there is either insuffi-cient damage to the mesothelial layer or that rapid recurrence of effusion pre-vents coaptation of visceral and parietal pericardium and prevents the forma-tion of adhesions. This, in turn, would suggest that early closure of the pericar-dial defect can result in recurrence. TREATMENT METHODS
Various methods can be used to treat malignant pericardial effusion. Observation Observation alone may be reasonable in the presence of small asymptomatic effusions.
CANCER MANAGEMENT: A MULTIDISCIPLINARY APPROACH
Pericardiocentesis is useful in relieving
tamponade and obtaining a diagnosis.
enhances the safety of this procedure. Ninety
percent of pericardial effusions will recur
and pericardial effusion andfollowed their course using serial
within 3 months after pericardiocentesis alone,
recurrence was achieved in 88%. Fifty percent of patients died
Pericardiocentesis and percutaneous tube drainage can now be performed with low risk Chiang F-T, et al: Chest 122:893-899,
groups. Problems that may occur include oc-
clusion or displacement of the small-boretubes, dysrhythmia, recurrent effusion, and infections. The Mayo Clinic grouprecommends initial percutaneous peri-cardiocentesis with extended catheterdrainage as its technique of choice. Intrapericardial sclerotherapy and chemotherapy following percutaneous or open drainage have been reported to be effective treatments by some groups. Problems include pain during sclerosing agent treatments and recurrence of effusions. Good results have been reported with instillation of a number of agents. Agents are selected based on their antitumor or sclerosing effect. Pericardiocentesis and balloon pericardial window After percutaneous
pericardiocentesis, a balloon dilating catheter
can be placed across the pericardium under
fluoroscopic guidance and a window created
pericardial window for manage-ment of pericardial effusion. Subtotal pericardial resection is seldom
thoracoscopically (32) or bysubxiphoid (12) or limited
performed today. Although it is the definitive
treatment, in that there is almost no chance
of recurrence or constriction, higher morbid-
ity and longer recovery time render this op-
eration undesirable in patients who have a
recurrent effusions (4.8%)required reoperations. Eight
short anticipated survival. Its use is restricted
to cancer patients with recurrent effusions
who are in good overall condition and are
expected to survive for up to 1 year.
much lower for patients withNSCLC (2.6 mo) than for patients
Limited pericardial resection (pericardial window) via anterior thoracotomy has a
lower morbidity than less invasive techniques,
Surgical pericardial window is asafe and durable operative
but recovery is delayed. There is a small risk
of recurrence. Cardiac herniation is possible
if the size of the opening in the pericardium
(Cullinane CA, Paz, IB, Grannis FW:Proc Am Soc Clin Oncol [abstract]Subxiphoid pericardial resection can be
performed with the patient under local anes-
thesia and may be combined with tube drainage and/or pericardial sclerosis. Our group and others have noted recurrences following this technique. Subxiphoid pericardioperitoneal window through the fused portion of the diaphragm and pericardium has been developed to allow continued drainage of pericardial fluid into the peritoneum. Experience with the procedure is lim- ited, but recurrences may be less frequent than those associated with subxiphoid drainage alone. Thoracoscopic pericardial resection is our current treatment of choice and has been performed by our group, as well as by others, with low morbidity, mortality, and recurrence rates. General anesthesia with single-lung ventila- tion is required. Technical factors Prior pleurodesis for malignant pleural effusion makes an ipsilateral transpleural operation difficult or impossible. In lung cancer patients, major airway obstruction may preclude single-lung anesthesia and, thus, tho- racoscopic pericardiectomy. Prior median sternotomy may prohibit the use of a subxiphoid approach. Complications A 30-day mortality rate of 10% or higher has been reported for all of these modalities but is related more to the gravity of the underlying tumor and its sequelae. A small percentage of patients will develop severe problems with pulmonary edema or cardiogenic shock following pericardial decompression. The mechanisms of these problems are poorly understood. Late neoplastic pericardial constriction can occur following initially successful partial pericardiectomy. Radiotherapy
External-beam irradiation is utilized infrequently in this clinical setting but maybe an important option in specialized circumstances, especially in patients withradiosensitive tumors who have not received prior radiation therapy. Responsesranging from 66% to 93% have been reported with this form of treatment,depending on the type of associated tumor. Systemic therapy Chemotherapy Systemic chemotherapy is effective in treating pericardial ef- fusions in patients with lymphomas, hematologic malignancies, or breast cancer. Long-term survival can be attained in these patients. If the pericardial effusion is small and/or asymptomatic, invasive treatment may be omitted in some of these cases. Data regarding the effectiveness of systemic chemotherapy or chemotherapy delivered locally in prevention of recurrent pericardial and pleural effusion are quite limited. New studies in this area are badly needed. Biological therapy with various agents is in the early stages of investigation. MALIGNANT ASCITES
Malignant ascites results when there is an imbalance in the secretion of pro-teins and cells into the peritoneal cavity and absorption of fluids via the lym-
CANCER MANAGEMENT: A MULTIDISCIPLINARY APPROACH
phatic system. Greater capillary permeability as a result of the release ofcytokines by malignant cells increases the protein concentration in the perito-neal fluid. Recently, several studies have demonstrated higher levels of VEGF([vascular endothelial growth factor], a cytokine known to cause capillary leak)in the sera and effusions of patients with malignancies. Signs and symptoms
Patients with malignant ascites usually present with anorexia, nausea, respi-ratory compromise, and immobility. Complaints of abdominal bloating, heavi-ness, and ill-fitting clothes are common. Weight gain despite muscle wasting isa prominent sign. Diagnosis
A malignant etiology accounts for only 10% of all cases of ascites. Nonmalig-nant diseases causing ascites include liver failure, congestive heart failure, andocclusion of the inferior vena cava or hepatic vein. About one-third of all pa-tients with malignancies will develop ascites. Malignant ascites has been de-scribed with many tumor types but is most commonly seen with gynecologicneoplasms (~50%), GI malignancies (20%-25%), and breast cancer (10%-18%). In 15%-30% of patients, the ascites is associated with diffuse carcinomatosis ofthe peritoneal cavity. Physical examination does not distinguish whether ascites is due to malig- nant or benign conditions. Patients may have abdominal fullness with fluid wave, anterior distribution of the normal abdominal tympany, and pedal edema. Occasionally, the hepatic metastases or tumor nodules studding the peritoneal surface can be palpated through the abdominal wall, which has been altered by ascitic distention. RADIOLOGIC STUDIES
four different tumor rejectiongenes (BAGE, GAGE, MAGE-1, and
Radiographs Ascites can be inferred from
plain radiographs of the abdomen. Signs in-
clude a ground-glass pattern and centralization
of the intestines and abdominal contents.
patients with non-neoplasticdiseases. The sensitivity and
Ultrasonography Abdominal ultrasonogra-
phy has been shown to be the most sensitive,
ascites using this profile of geneexpression are 94% and 94%,
most specific method for detecting and quan-
tifying ascites. It also permits delineation of
predictive value was 89% (HofmanM, Ruschenburg I: Cancer [CancerCT Abdominal CT is effective in detecting
ascites. In addition, CT scans may demon-strate masses, mesenteric stranding, omental studding, and diffuse carcinoma-tosis. Intravenous and oral contrasts are necessary, thus increasing the degreeof invasiveness of this modality. Paracentesis After the diagnosis of peritoneal ascites has been made on the basis of the physical examination and imaging, paracentesis should be per- formed to characterize the fluid. The color and nature of the fluid often suggest the diagnosis. Malignant ascites can be bloody, opaque, chylous, or serous. Benign ascites is usually serous and clear.
Analysis of the fluid should include cell count, cytology, LDH, proteins, andappropriate evaluation for infectious etiologies. In addition, the fluid can besent for the determination of tumor markers, such as CEA, CA-125, and P-53,and human chorionic gonadotropin-β (hCG-β). The hCG-β level is frequentlyelevated in malignancy-related ascites and has been combined with cytologyto yield an 89.5% efficiency in diagnosis. The use of DNA ploidy indices al-lowed 98.5% sensitivity and 100% sensitivity in the identification of malignantcells within ascitic fluid. Laparoscopy Several studies have utilized minimally invasive laparoscopy as the diagnostic tool of choice. The fluid can be drained under direct visualiza- tion, the peritoneal cavity can be evaluated carefully, and any suspicious masses can be biopsied at the time of the laparoscopy. Prognosis
The presence of ascites in a patient with malignancy often portends end-stagedisease. Median survival after the diagnosis of malignant ascites rangesfrom 7 to 13 weeks. Patients with gynecologic and breast malignancies have abetter overall prognosis than patients with GI malignancies. Treatment
The primary goal of treatment is the palliation of symptoms. Management canbe divided into medical and surgical modalities. Medical therapy
Traditionally, the first line of treatment is medical management. Medical thera-pies include repeated paracentesis, fluid restriction, diuretics, chemotherapy,and intraperitoneal sclerosis. Repeated paracentesis, probably the most frequently employed treatment modality, provides significant symptomatic relief in the majority of cases. The procedure is minimally invasive and can be combined with abdominal ultra- sonography to better localize fluid collections. High-volume paracentesis has been performed without inducing significant hemodynamic instability and with good patient tolerance.
Significant morbidity occurs with repeated taps and becomes more severe witheach tap necessary to alleviate symptoms. Ascitic fluid contains a high concen-tration of proteins. Routine removal of ascites further depletes protein stores. The removal of large volumes of fluid also can result in electrolyte abnormali-ties and hypovolemia. In addition, complications can result from the proce-
CANCER MANAGEMENT: A MULTIDISCIPLINARY APPROACH
dure itself. They include hemorrhage, injury to intra-abdominal structures, peri-tonitis, and bowel obstruction.
With the placement of an intraperitoneal port, used also for the instillation ofintraperitoneal chemotherapy, removal of ascitic fluid is possible without theneed for repeated paracentesis.
Contraindications to repeated paracentesis are viscous loculated fluid and hem-orrhagic fluid. Diuretics, fluid and salt restriction Un-
like ascites from benign causes such as cir-
rhosis and congestive heart failure, malignant
ascites responds poorly to fluid restriction,
and also increases tumor cell lysis. The antibody was injected weekly
decreased salt intake, and diuretic therapy. into the peritoneum of 10 ovarian
The most commonly used diuretics (in pa- cancer patients with malignanttients who may have some response to di- ascites. All 10 responded to theuretic treatment) are spironolactone treatment: 8 patients with(Aldactone) and amiloride (Midamor). Pa- complete resolution of ascites and
tients with massive hepatic metastases are In addition, 8 of the 10 patientsmost likely to benefit from spironolactone.
also had a decreased serum CA-125 level (Marme A, Strauss G,
Starting doses are 100-150 mg tid for spirono- Bastert G, et al: Int J Cancer 101:183-
lactone and 5 mg qd for amiloride. The onset 189, 2002). of action for spironolactone is delayed (3-4days), whereas the effects of amiloride are seen after 24 hours. The most com-mon complications associated with these diuretics are painful gynecomastia,renal tubular acidosis, and hyperkalemia. Chemotherapy, both systemic and intraperitoneal, has had some success in the treatment of malignant ascites. The most commonly used agents are cisplatin (Platinol) and mitomycin (Mutamycin). Intraperitoneal hyperther-
efficacy in GI malignancies to decrease re-
currence of ascites, as well as to prevent the
were studied in a phase II trial inadvanced gastric cancer patients
formation of ascites in patients with perito-
that in 37 patients, 35% had anobjective response with decreased
Sclerotherapy Sclerosing agents include
line), tetracycline (500 mg/50 mL of nor-
mal saline), and talc (5 g/50 mL of normal
saline). Responses are seen in ~30% of pa-
Shimada Y, et al: Proc Am Soc ClinOncol [abstract] 20:132b, 2001).
Theoretically, intraperitoneal chemotherapy
and sclerosis obliterate the peritoneal space and prevent future fluid accumulation. If sclerosis is unsuccessful, it may produce loculations and make subsequentparacentesis difficult. Other systemic therapies There are several reports of the use of gold-198 or phosphorus-32 in patients with peritoneal effusions, with response rates of 30%-
50%. Experimental models and early clinical trials have shown that an intrap-eritoneal bolus of tumor necrosis factor (45-350 µg/m2) given weekly may beeffective in resolving malignant ascites.
Limited surgical options are available to treat patients who have refractoryascites after maximal medical management, demonstrate significant decreasein quality of life as a result of ascites, and have a life expectancy of > 3 months. Peritoneovenous shunts have been used since 1974 for the relief of ascites associated with benign conditions. In the 1980s, shunting was applied to the treatment of malignant ascites.
The LeVeen shunt contains a disc valve in a firm polypropylene casing, whereasthe Denver shunt has a valve that lies within a fluid-filled, compressible sili-cone chamber. Both valves provide a connection between the peritoneal cavityand venous system that permits the free flow of fluid from the peritoneal cavity whena 2- to 4-cm water pressure gradient exists.
Success rates vary with shunting, depending on the nature of the ascites andthe pathology of the primary tumor. Patients with ovarian cancer, for example,do very well, with palliation achieved in ≥ 50% of cases. However, GI malig-nancies are associated with a poorer response rate of 10%-15%. Patient selection Candidates for shunt placement should be carefully selected. Cardiac and respiratory evaluations should be performed prior to the pro-cedure. Shunt placement is contraindicated in the presence of the following:
■ a moribund patient whose death is anticipated within weeks
Complications of shunting Initial concerns about the use of a shunt in the treatment of malignant ascites centered around intravascular propagation of tumor. In practice, there has been little difference in overall mortality in pa- tients with and without shunts. Disseminated intravascular coagulation During the early experience with shunt-ing, particularly in cirrhotic patients, symptomatic clinical disseminated intra-vascular coagulation (DIC) developed rapidly and was a major source of mor-bidity and mortality. However, this complication occurs infrequently in theoncologic population.
The pathophysiology of DIC has been studied extensively and is thought tobe multifactorial. The reinfusion of large volumes of ascitic fluid may cause adeficiency in endogenous circulating coagulation factors by dilution. Second-arily, a fibrinolytic state is initiated by the introduction of soluble collagen(contained within the ascitic fluid) into the bloodstream, leading to a DIC state. Infrequently, full-blown DIC results and requires ligation or shunt removal.
CANCER MANAGEMENT: A MULTIDISCIPLINARY APPROACH
Discarding 50%-70% of the ascitic fluid before establishing the peritoneovenousconnection may prevent this complication.
Commonly, coagulation parameters are abnormal without signs or symptoms. In some institutions, these laboratory values are so consistently abnormal thatthey are used to monitor shunt patency. Abnormalities most commonly seeninclude decreased platelets and fibrinogen and elevated prothrombin time,partial thromboplastin time, and fibrin split products. Other common complications include shunt occlusion (10%-20%), heart failure(6%), ascitic leak from the insertion site (4%), infection (< 5%), and perioperativedeath (10%-20% when all operative candidates are included).
Shunt patency may be associated with the presence of malignant cells. Onestudy found that patients with positive cytology had a 26-day shunt survival, ascompared with 140 days in patients with negative cytology. Other studies havefailed to demonstrate a correlation between ascites with malignant cells anddecreased survival.
Clearly, shunting is not a benign procedure, but in carefully selected patientswho have not responded to other treatment modalities and who are experienc-ing symptoms from ascites, it may provide needed palliation. Because of thelimited effectiveness of peritoneovenous shunts, patients should be carefullyselected prior to placement. Radical peritonectomy Other surgical procedures used to treat malignant ascites have been proposed. They include radical peritonectomy combined with intraperitoneal chemotherapy. This is an extensive operation with signifi- cant morbidity, although initial results appear to demonstrate that it decreases ascites production. To date, no randomized trial has demonstrated that radical peritonectomy increases efficacy or survival. SUGGESTED READING ON MALIGNANT PLEURAL EFFUSION Ang P, Tan H, Leong SS: Primary intrathoracic malignant effusion: A descriptive study. Chest 120:50–54, 2001. Diacon AH, Weiser C, Bollinger CT, et al: Prospective randomized comparison of tho- racoscopic talc poudrage under local anesthesia vs bleomycin instillation for pleurodesis in malignant pleural effusions. Am J Resp Crit Care Med 162:1445–1449, 2000. Fujita A, Takabatake H, Tagaki S, et al: Combination chemotherapy in patients with malignant pleural effusions from non–small-cell lung cancer: Cisplatin, ifosfamide, and irinotecan with recombinant human granulocyte colony factor support. Chest 119:340– 343, 2001. Ichinose Y, Tsuchiya R, Koike T, et al: A prematurely terminated phase III trial of intra- operative intrapleural hypotonic cisplatin treatment in patients with resected non–small- cell lung cancer with positive pleural lavage cytology: The incidence of carcinomatous pleuritis after surgical intervention. J Thorac Cardiovasc Surg 123:695–699, 2002. Ong KC, Indumathi V, Raghuram J, et al: A comparative study of pleurodesis using talc slurry and bleomycin in the management of malignant pleural effusions. Respirology 5:99–103, 2000. Putnam JB, Walsh GL, Swisher SG, et al: Outpatient management of malignant pleu- ral effusion by a chronic indwelling pleural catheter. Ann Thorac Surg 69:369–375, 2000. ON PERICARDIAL EFFUSION Anderson TM, Ray CW, Nwogu CE, et al: Pericardial catheter sclerosis vs surgical pro- cedures for pericardial effusions in cancer patients. J Cardiovasc Surg (Torino) 42:415– 419, 2001. Garcia-Riego A, Cuinas C, Vilanova JJ: Malignant pericardial effusion. Acta Cytol 45:561– 566, 2001. Moriya T, Takiguchi Y, Tabeta H, et al: Controlling malignant pericardial effusion by intrapericardial cisplatin administration in patients with primary non–small-cell lung can- cer. Br J Cancer 83:858–862, 2000. Soler-Soler J, Sagrista-Sauleda J, Permanyer-Miralda G: Management of pericardial effusion. Heart 86:235–240, 2001. Tsang TS, Enrique-Sarano M, Freeman WK, et al: Consecutive 1,127 therapeutic echocardiographically guided pericardiocenteses: Clinical profile, practice patterns, and outcomes spanning 21 years. Mayo Clin Proc 77:429–436, 2002. ON MALIGNANT ASCITES Aslam N, Marino CR: Malignant ascites: New concepts in pathophysiology, diagnosis and management. Arch Intern Med 161:2733–2737, 2001. Bieligk SC, Calvo BF, Coit DG: Peritoneovenous shunting for nongynecologic malig- nant ascites. Cancer 91:1247–1255, 2001. O’Neill MJ, Weissleder R, Gervais DA, et al: Tunneled peritoneal catheter placement under sonographic and fluoroscopic guidance in the palliative treatment of malignant ascites. Am J Roentgenol 177:615–618, 2001. Tamsma JT, Keizer HJ, Meinders AE: Pathogenesis of malignant ascites: Starling’s law of capillary hemodynamics revisited. Ann Oncol 12:1353–1357, 2001.
CANCER MANAGEMENT: A MULTIDISCIPLINARY APPROACH
Preservação da fertilidade: a importância de oferecer esta possibilidade às pacientes com doenças neoplásicas Preservation of fertility: the importance of providing this possibility Segundo o Instituto Nacional do Câncer (INCA)1, as estimativas para o ano de 2010 previam a ocorrência de 500 mil novos casos de câncer no Brasil, sendo que praticamente metade seria em mulheres, das quai
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