Journal conference

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???????Journal conference

• ????? ??
• ????? ??
• ??2003.9.30

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Malignant Ascites New Concepts in
Pathophysiology, Diagnosis, and
ManagementClinical ObservationAslam, Naeem
MD Marino, Christopher R. MDArch Intern
Med.20011612733-2737
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• Abstract
• Malignant ascites is a manifestation of advanced
  malignant disease that is associated with
  significant morbidity.
• Mainstays of treatment include diuretics and
  recurrent large volume paracentesis.
• Although lymphatic obstruction has been
  considered the major pathophysiologic mechanism
  behind its formation, recent evidence suggests
  that immune modulators, vascular permeability
  factors, and metalloproteinases are contributing
  significantly to the process.
• These new observations offer the opportunity for
  development of new, more targeted therapies for
  the treatment of malignant ascites.
• This article uses a clinical case to highlight
  the problem, then reviews these new concepts in
  the pathophysiology of malignant ascites
  formation.
• The diagnosis and management of this challenging
  medical problem are subsequently discussed, with
  emphasis on how these new pathophysiologic
  insights are being applied to the development of
  novel therapies that may soon change how we
  manage this troubling clinical condition.

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• REPORT OF A CASE
• A 57-year-old white man with a history of
  coronary artery disease, diabetes mellitus,
  hyperlipidemia, and hypertension presented with
  progressive abdominal swelling of 2-week
  duration.
• He reported 1 episode of vomiting (no blood) and
  diffuse abdominal pain that was worsened by
  eating.
• He had chronic intermittent constipation (7-8
  years), but this was unchanged.
• During these 2 weeks, the patient also noted some
  weight gain (several kilograms) and shortness of
  breath when supine.
• He denied paroxysmal nocturnal dyspnea,
  periorbital edema, and ankle swelling and
  reported no history of liver or kidney disease.
• He denied any blood transfusions, but had 1
  tattoo on the right arm. There was a distant
  history of regular alcohol consumption but little
  since 1960.
• He was not aware of any skin lesions.

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• REPORT OF A CASE
• Medical history was significant for myocardial
  infarction, hypertension, and diabetes, which
  were all diagnosed 6 years ago. He had an active
  40 pack-year smoking history and had worked as an
  automobile mechanic most of his life.
• Medications on admission were atenolol,
  nitroglycerin, gemfibrozil, simvastatin,
  pentoxifylline, and glyburide.
• Family history was noncontributory.

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• REPORT OF A CASE
• Results of physical examination showed a
  middle-aged man who was well nourished and in no
  distress. He was oriented to person, place, and
  time. Vital signs included a pulse of 122
  beats/min, blood pressure of 150/102 mm Hg,
  temperature of 36.9C, and respiratory rate of 16
  breaths/min with 98 oxygen saturation on room
  air.
• There were no stigmata of chronic liver disease.
• Results of cardiopulmonary examination disclosed
  no adventitious sounds. No jugular venous
  distension or peripheral edema was found.
• Results of abdominal examination showed a
  protuberant, nontender abdomen with shifting
  dullness. There was no hepatosplenomegaly.
• Results of stool test for occult blood were
  negative.

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• REPORT OF A CASE
• Admission laboratory analyses revealed normal
  results for complete blood cell count, urine
  analysis, electrolyte levels, serum urea
  nitrogen, and creatinine.
• Results of liver function tests included
  bilirubin level of 0.7 mg/dL (12.0 µmol/L),
  alkaline phosphatase level of 94 U/L, aspartate
  aminotransferase level of 15 U/L, alanine
  aminotransferase level of 9 U/L, and
  gamma-glutamyltransferase level of 16 U/L.
  Serum albumin level was 3.0 g/dL.
• Chest radiograph showed a normal heart size and
  increased opacity at the lung bases associated
  with elevated hemidiaphragms.

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• REPORT OF A CASE
• On admission, diagnostic and therapeutic
  paracentesis was performed, with removal of 6 L
  of straw-colored fluid.
• Results of chemical analysis of the fluid
  demonstrated albumin level of 2.5 g/dL
  (serum-ascites albumin gradient of 0.5 g/dL),
  total protein level of 4.5 g/dL, lactate
  dehydrogenase level of 161 U/L, and amylase level
  of 6 U/L. Red blood cell count was 200 cells/mm3
  white blood cell count was 450 cells/mm3
  containing 97 mesothelial cells and 3
  neutrophils. Fluid was sent for cytologic
  analysis.

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• Computed tomography showed thickening and
  enhancement of the omentum and a large amount of
  ascites.
• No mesenteric or periaortic adenopathy.

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• REPORT OF A CASE
• Computed tomography of the abdomen and pelvis
  with intravenous and oral contrast showed
  thickening and enhancement of the omentum and a
  large amount of ascites. No mesenteric or
  periaortic adenopathy was detected. Liver,
  spleen, pancreas, and gallbladder appeared
  normal.
• Results of Doppler ultrasonography were also
  normal.
• During his hospital stay, our patient underwent
  therapeutic paracentesis on 3 occasions.
• Results of cytologic analysis of the ascitic
  fluid subsequently disclosed malignant cells.
• Results of the immunostaining pattern were
  negative for cytokeratin (CAM 5.2),
  carcinoembryonic antigen (CEA), and UCHL-1 and
  positive for S100 protein, most consistent with
  malignant melanoma.

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• REPORT OF A CASE
• On reexamination, a skin lesion was found on the
  patient's scalp, hidden beneath the hair. Results
  of shave biopsy of the scalp lesion were positive
  for malignant melanoma. Results of incisional
  biopsy revealed tumor extension into the
  reticular dermis. The patient was referred to the
  Section of Oncology, Veterans Affairs Medical
  Center, Memphis, Tenn, for further management.
• Visual field defects developed after discharge
  from the hospital, and a computed tomographic
  scan of the head revealed a 5.5-cm tumor
  metastasis in the left occipital lobe. Systemic
  interferon alfa-2a and alfa-2b immunotherapy for
  the primary malignant neoplasm was started.
• Despite aggressive diuresis for his ascites, he
  required another large-volume paracentesis, which
  was complicated by leakage. He died 2 months
  after diagnosis.

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• DIAGNOSIS
• (1) clinical history and examination
• (2) tumour markers
• (3) radiology
• (4) cytology
• (5) biochemical composition of ascites
• (6) laparoscopy

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• DIAGNOSIS
• Serum tumor markers are generally of low
  diagnostic specificity but can assist in
  identifying a potential primary source.
• Ascitic fluid analysis is essential for the
  diagnosis of malignant ascites. Division of
  ascitic fluid into exudate or transudate on the
  basis of total protein content (gt2.5 or lt2.5
  g/dL, respectively) is hampered by a large
  overlap between malignant and nonmalignant
  ascites. Up to 25 of patients with cirrhosis
  (mostly those with cardiac cirrhosis) can have
  high protein levels in ascites, and 18 of
  malignant ascites can be low in protein levels by
  nature.
• Ascitic fluid fibronectin (sensitivity, 100
  specificity, 100) and cholesterol levels have
  been reported to offer an excellent
  discrimination between ascites due to liver
  disease or malignancy. The origin of fibronectin
  in ascitic fluid is unclear. It may be a product
  of malignant cells or of increased turnover of
  connective tissue adjacent to the neoplastic
  implants.

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• DIAGNOSIS
• The detection of tumor cells in ascitic fluid
  remains the gold standard for the diagnosis of
  malignant ascites. Unfortunately, malignancies
  can produce ascites without shedding many
  neoplastic cells into the fluid itself. Even 500
  mL of fluid, which is generally considered
  sufficient for cytologic analysis, has a
  diagnostic sensitivity of only 40 to 60
• Routine blood tests, ultrasound examination, and
  diagnostic paracentesis should be performed on
  all patients. In the presence of malignant
  cytologic findings without a primary tumor
  diagnosis, further investigations of male
  patients may not lead to improved survival, since
  all primary tumor groups are associated with a
  uniformly poor prognosis. Conversely, female
  patients may benefit from further investigation,
  possibly including laparoscopy or even
  laparotomy,

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• Treatments for malignant ascites
• Symptomatic paracentesis
• Diuretic therapy
• Systemic therapy
• Intraperitoneal chemotherapy
• Intraperitoneal radiocolloids
• Peritoneovenous shunt
• Immunotherapy (biological response modifiers)
• Radioimmunotherapy

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• Ending.