Peritoneal carcinomatosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]

Synonyms and keywords: Peritoneal metastases; Peritoneal seeding

Overview

Peritoneal carcinomatosis (also known as peritoneal metastases) is defined as a malignant tumor of the peritoneum. Metastases are the most common peritoneal malignancy, commonly metastasize from ovarian cancer, colon cancer, gastric cancer, and pancreatic cancer. Calcified peritoneal carcinomatosis may occur in serous ovarian adenocarcinoma, colon cancer, and gastric cancer. Peritoneal carcinogenesis arises from the celomic epithelium lining of the abdominal cavity (peritoneum) in response to an oncogenic stimulus. Common causes of peritoneal carcinomatosis, include: peritoneal mesothelioma, colon cancer, gastric cancer, and pancreatic cancer. Early clinical features include abdominal pain, abdominal distension, and nausea. If left untreated, the majority of patients with peritoneal carcinomatosis may progress to develop portal hypertension, pulmonary edema, and death. Common complications of peritoneal carcinomatosis include intestinal obstruction and pulmonary thromboembolism. The diagnosis of peritoneal carcinomatosis, include: Imaging findings compatible with peritoneal carcinomatosis, elevated protein concentration (more than 4.0 g/dL) in ascitic fluid, abnormal serum-ascites albumin gradient (less than 1.1 g/dL) in ascitic fluid, and high cell count (lymphocyte predominance). The mainstay medical therapy for peritoneal carcinomatosis is hyperthermic intraperitoneal chemotherapy (HIPEC), followed by cytoreductive surgery, laparotomy in conjunction with cytology testing is the most common approach for the treatment of peritoneal carcinomatosis. Prognosis is generally poor, and the 5-year survival rate of patients with peritoneal carcinomatosis is approximately 20%.

Historical Perspective

• Peritoneal carcinomatosis was first described by Swerdlow in 1959.

Classification

According to the Gilly classification, peritoneal carcinomatosis may be classified according to nodule size and intraperitoneal involvement (localized or diffuse) into 4 categories:

• 0 - No macroscopic disease
• 1 - Malignant granulations less than 5 mm in diameter localized in one part of the abdomen
• 2 - Malignant granulations less than 5 mm in diameter diffuse to the whole abdomen
• 3 - Localized or diffuse malignant granulations 5–20 mm in diameter
• 4 - Localized or diffuse large malignant masses (more than 2 cm in diameter)

Pathophysiology

• The pathogenesis of peritoneal carcinomatosis is characterized by the malignant seeding of a tumor in the peritoneal cavity.
• Peritoneal carcinogenesis arises from the celomic epithelium lining of the abdominal cavity (peritoneum) in response to an oncogenic stimulus.
• The mutation on BRCA1/BRCA2 has been associated with the development of peritoneal carcinomatosis.
• On gross pathology, characteristic findings of peritoneal carcinomatosis, include:
  • Multilocular thin-walled cysts containing serous fluid
  • Occasionally unilocular
  • May be up to 15 cm
  • Adherent to the surface
• On microscopic histopathological analysis, characteristic findings of peritoneal carcinomatosis, include:
  • Thin-walled, irregular-shaped cysts
  • Mesothelial lining
  • Squamous metaplasia
  • Eosinophilic fluid

Causes

Common causes of peritoneal carcinomatosis, include:

• Peritoneal mesothelioma
• Colon cancer
• Gastric cancer
• Pancreatic cancer

Peritoneal carcinomatosis may also be caused by a mutation in the BCRA1 or BCRA2 genes.

Differentiating Peritoneal Carcinomatosis from Other Diseases

Peritoneal carcinomatosis must be differentiated from other diseases that cause abdominal pain, ascites, and weight loss, such as:

• Peritoneal mesothelioma
• Peritoneal tuberculosis
• Pseudomyxoma peritonei
• Spontaneous bacterial peritonitis (SBP)
• Secondary bacterial peritonitis

Differentiating peritoneal carcinomatosis from other diseases

Disease		Prominent clinical findings	Lab tests	Tratment
Primary peritonitis	Spontaneous bacterial peritonitis	Absence of GI perforation, most closely associated with cirrhosis and advanced liver disease. Presents with abrupt onset of fever, abdominal pain, distension, and rebound tenderness.	Most have clinical and biochemical manifestations of advanced cirrhosis or nephrosis like leukocytosis,hypoalbuminemia. Prolonged prothrombin time. SAAG >1.1 g/dL, increased serum lactic acid level, or a decreased ascitic fluid pH (< 7.31) supports the diagnosis. Gram staining reveals bacteria in only 25% of cases. Diagnosed by analysis of the ascitic fluid which reveals WBC > 500/ML, and PMN >250cells/ml. Culture of ascitic fluid inoculated immediately into blood culture media at the bedside usually reveals a single enteric organism, most commonly Escherichia coli, Klebsiella, or streptococci.	Once diagnosed, it is treated with Ceftriaxone.
	Tuberculous peritonitis	Seen in 0.5% of new cases of tuberculosis particularly in young women in endemic areas as a primary infection. Presents with abdominal pain and distension, fever, night sweats, weight loss, and altered bowel habits.	Ascites is present in about half of cases. Abdominal mass may be felt in a third of cases. The peritoneal fluid is characterized by a protein concentration > 3 g/dL with < 1.1 g/dL SAAG and lymphocyte predominance of WBC. Definitive diagnosis in 80% of cases is by culture. Most patients presenting acutely are diagnosed only by laparotomy.	Combination antituberculosis chemotherapy is preferred in chronic cases.
	Continuous Ambulatory Peritoneal Dialysis (CAPD peritonitis)	Peritonitis is one of the major complications of peritoneal dialysis & 72.6% occurred within the first six months of peritoneal dialysis. Historically, coagulase-negative staphylococci were the most common cause of peritonitis in CAPD, presumably due to touch contamination or infection via the pericatheter route. Treatment for peritoneal dialysis-associated peritonitis consists of antimicrobial therapy, in some cases catheter removal is also warranted. Additional therapies for relapsing or recurrent peritonitis may include fibrinolytic agents and peritoneal lavage. Most episodes of peritoneal dialysis-associated peritonitis resolve with outpatient antibiotic treatment.	Majority of peritonitis cases are caused by bacteria (50%-due to gram positive organisms, 15% to gram negative organisms, 20% were culture negative. 2% of cases are caused by fungi, mostly Candida species. Polymicrobial infection in 4%. Exit-site infection was present in 13% and a peritoneal fluid leak in 3 % and M.tuberculosis 0.1%.	Initial empiric antibiotic coverage for peritoneal dialysis-associated peritonitis consists of coverage for gram-positive organisms (by vancomycin or a first-generation cephalosporin) and gram-negative organisms (by a third-generation cephalosporin or an aminoglycoside). Subsequently, the regimen should be adjusted based on culture and sensitivity data. Cure rates are approximately 75%.
Secondary peritonitis	Acute bacterial secondary peritonitis	Occurs after perforating, penetrating, inflammatory, infectious, or ischemic injuries of the GI or GU tracts. Most often follows disruption of a hollow viscera, chemical peritonitis, bacterial peritonitis (polymicrobial, includes aerobic gram negatives {E coli, Klebsiella, Enterobacter, Proteus mirabilis} and gram positives { Enterococcus, Streptococcus} and anaerobes {Bacteroides, clostridia}). Presents with abdominal pain, tenderness, guarding or rigidity, distension, free peritoneal air, and diminished bowel sounds. Signs that reflect irritation of the parietal peritoneum resulting ileus. Systemic findings include fever, chills or rigors, tachycardia, sweating, tachypnea, restlessness, dehydration, oliguria, disorientation, and, ultimately, refractory shock.		Peritoneal lavage, Laparoscopy are the treatment of choice.
	Biliary peritonitis	Most often seen in cases of rupture of pathological gallbladder or bile duct or cholangitic abscess or secondary to obstruction of the biliary tract. Seen in alcoholic patients with ascites.
Tertiary peritonitis		Persistence or recurrence of intraabdominal infection following apparently adequate therapy of primary or secondary peritonitis. Associated with high mortality due to multi organ dysfunction. It presents in a similar way as other peritonitis but is recognized as an adverse outcome with poor prognosis.	Enterococcus, Candida, Staphylococcus epidermidis, and Enterobacter being the most common organisms.	Characterized by lack of response to appropriate surgical and antibiotic therapy due to disturbance in the hosts immune response.
Familial Mediterranean fever (periodic peritonitis, familial paroxysmal polyserositis)		Rare genetic condition which affects individuals of Mediterranean genetic background. Etiology is unclear. Presents with recurrent bouts of abdominal pain and tenderness along with pleuritic or joint pain. Fever and leukocytosis are common.		Colchicine prevents but does not treat acute attacks.
Granulomatous peritonitis		A rare condition caused by disposable surgical fabrics or food particles from a perforated ulcer, eliciting a vigorous granulomatous (delayed hypersensitivity) response in some patients 2-6 weeks after laparotomy. Presents with abdominal pain, fever, nausea and vomiting, ileus, and systemic complaints, mild and diffuse abdominal tenderness.	Diagnosed by the demonstration of diagnostic Maltese cross pattern of starch particles.	The disease is self-limiting. Treated with corticosteroids or anti-inflammatory agents.
Sclerosing encapsulating peritonitis		Seen in conditions associated with long term peritoneal dialysis, shunts like VP shunts, history of abdominal surgeries, liver transplantation. Symptoms include nausea, abdominal pain, diarrhea, anorexia, bloody ascites.
Intraperitoneal abscesses		Most common etiologies being Gastrointestinal perforations, postoperative complications, and penetrating injuries. Signs and symptoms depend on the location of the abscess within the peritoneal cavity and the extent of involvement of the surrounding structures. Diagnosis is suspected in any patient with a predisposing condition. In a third of cases it occurs as a sequela of generalized peritonitis. The pathogenic organisms are similar to those responsible for peritonitis, but anaerobic organisms occupy an important role. The mortality rate of serious intra-abdominal abscesses is about 30%.	Diagnosed best by CT scan of the abdomen.	Treatment consists of prompt and complete CT or US guided drainage of the abscess, control of the primary cause, and adjunctive use of effective antibiotics. Open drainage is reserved for abscesses for which percutaneous drainage is inappropriate or unsuccessful.
Peritoneal mesothelioma		Arises from the mesothelium lining the peritoneal cavity. Its incidence is approximately 300-500 new cases being diagnosed in the United States each year. As with pleural mesothelioma, there is an association with an asbestos exposure. Most commonly affects men at the age of 50-69 years. Patients most often present with abdominal pain and later increased abdominal girth and ascites along with anorexia, weight loss and abdominal pain. Mean time from diagnosis to death is less than 1 year without treatment.	CT with intravenous contrast typically demonstrates the thickening of the peritoneum. Laparoscopy with tissue biopsy or CT guided tissue biopsy with immunohistochemical staining for calretinin, cytokeratin 5/6, mesothelin, and Wilms tumor 1 antigen remain the gold standard for diagnosis.	At laparotomy the goal is cytoreduction with excision. Debulking surgery and intraperitoneal chemotherapy improves survival in some cases.
peritoneal carcinomatosis		Associated with a history of ovarian or GI tract malignancy. Symptoms include ascites, abdominal pain, nausea, vomiting.

Epidemiology and Demographics

• The prevalence of peritoneal carcinomatosis is approximately 0.03 per 100,000 individuals worldwide.

Age

• Peritoneal carcinomatosis is more commonly observed among patients aged 50 - 70 years.
• Peritoneal carcinomatosis is more commonly observed among adults.

Gender

• Females are more commonly affected with peritoneal carcinomatosis than males.

Race

• There is no racial predilection for peritoneal carcinomatosis.

Risk Factors

The most important risk factor in the development of peritoneal carcinomatosis include:

• Ovarian cancer
• Colon cancer
• Gastric cancer
• Pancreatic cancer

Natural History, Complications and Prognosis

• The majority of patients with peritoneal carcinomatosis may be initially asymptomatic.
• Early clinical features include abdominal pain, abdominal distension, and nausea.
• If left untreated, the majority of patients with peritoneal carcinomatosis may progress to develop portal hypertension, pulmonary edema, and death.
• Common complications of peritoneal carcinomatosis include intestinal obstruction and pulmonary thromboembolism.
• Prognosis is generally poor, and the 5 year survival rate of patients with peritoneal carcinomatosis is approximately 20%.

Diagnosis

Diagnostic Criteria

The diagnosis of peritoneal carcinomatosis is made when at least the following diagnostic criteria are met:

• Imaging findings compatible with peritoneal carcinomatosis (see below)
• Elevated protein concentration (more than 4.0 g/dL)
• Abnormal serum-ascites albumin gradient (less than 1.1 g/dL)
• High cell count (lymphocyte predominance)

Symptoms

• Peritoneal carcinomatosis is usually asymptomatic.
• Symptoms of peritoneal carcinomatosis may include the following:

• Abdominal distension
• Nausea
• Bloating
• Intermittent abdominal pain
• Vomiting
• Alternating diarrhea and constipation

Physical Examination

• Patients with peritoneal carcinomatosis usually appear pale and lethargic.
• Physical examination may be remarkable for:

Inspection

• Enlarged abdomen
• Abdominal distension

Palpation

• Bulging of the flanks or shifting dullness
• Fluid thrill or fluid wave

• Other physical examination findings may include:

• Leg swelling
• Bruising
• Gynecomastia

Laboratory Findings

• Laboratory findings consistent with the diagnosis of peritoneal carcinomatosis, include:

• Elevated carcinoembryonic antigen (unspecific)
• Elevated cancer antigen 125 (unspecific)
• Elevated cancer antigen 19-9 (unspecific)

Imaging Findings

• Enhanced CT scan is the imaging modality of choice for peritoneal carcinomatosis.
• On CT, peritoneal carcinomatosis is characterized by the following findings:

• Smooth or nodular peritoneal thickening and enhancement.
• Implants on the liver and the splenic surfaces are frequently seen and result in scalloping of the surface by the masses.
• Sites of tumor implantation are the intersegmental fissure, superior recess of the lesser sac, subphrenic space, and Morison pouch.
• Usually there is large ascites, which is often loculated.

• The images below demonstrate a case of peritoneal carcinomatosis.

Other Diagnostic Studies

• Peritoneal carcinomatosis may also be diagnosed using abdominal paracentesis.
• Findings on paracentesis may include:

• Opalescent appearance
• Elevated protein concentration (more than 4.0 g/dL)
• Abnormal serum-ascites albumin gradient ( less than 1.1 g/dL )

• Other diagnostic studies, include: positron emission tomography (PET)/PET-CT, diagnostic laparoscopy, ultrasonography, magnetic resonance imaging (MRI)

Treatment

Medical Therapy

• The mainstay medical therapy for peritoneal carcinomatosis is hyperthermic intraperitoneal chemotherapy (HIPEC).
• Common chemotherapy agents, include:
  • Mitomycin
  • Cisplatin
  • Oxaliplatin
  • Doxorubicin
  • Mitoxantrone

Surgery

• Cytoreductive surgery is the mainstay of therapy for peritoneal carcinomatosis.
• Laparotomy in conjunction with cytology testing is the most common approach to the treatment of peritoneal carcinomatosis.
• Cytoreductive surgery is composed of three steps: Exploration of the abdominal cavity, debulking and chemoperfusion.

Prevention

• There are no primary preventive measures available for peritoneal carcinomatosis.
• Once diagnosed and successfully treated, patients with peritoneal carcinomatosis are followed-up every 1, 3 or 6 months.
• Follow-up testing includes ultrasound, paracentesis, and abdominal examination.