Pancreatic Ascites

Etiology

Pancreatic Fistulas

Pancreatic fistulas occur when fluid is continuously leaked from a disrupted pancreatic duct, resulting in an abnormal connection between the duct and another epithelial-lined surface, space, pocket, or lumen.[7] A pancreatic fistula may occur due to iatrogenic or noniatrogenic causes. Noniatrogenic pancreatic fistulas may develop from alcoholic chronic pancreatitis and cholecystitis.[8] 

Iatrogenic causes may include the following:

• Endoscopic retrograde cholangiopancreatography 
• Left renal and or left adrenal surgical procedures 
• Partial and total colectomy with splenic flexure mobilization
• Partial pancreatic resection
• Splenectomy
• Externally drained pancreatic fistulas, typically from pancreatic surgeries
• Anterior pancreatic duct disruptions that lead to peripancreatic fluid collection in the lesser sac
• Posterior pancreatic duct disruptions (resulting in pancreatic-pleural fistula formation and pancreatic pleural effusions) [9][10][11][12]

Noniatrogenic causes may include the following:

• A persistent internal fistula to the peritoneum
• A pseudocyst or walled-off necrosis 
• When inflammatory response does not limit the pancreatic fluid leakage
• Chronic pancreatitis [13][14][15][16]

Pancreatic Pseudocysts

Pancreatic pseudocysts develop when pancreatic duct leakage occurs due to infection, inflammation, trauma, or fistula formation. Complications can occur when the leaking pancreatic fluid is contained, including a pseudocyst, a non-epithelialized wall of granulation, or fibrous tissue containing sterile amylase and pancreatic enzymes. Pseudocysts typically form several weeks after a pancreatitis episode. Pseudocysts may be infected, asymptomatic, or cause abdominal pain, fever, anorexia, or peritoneal signs.

A pseudocyst leak or rupture often leads to pancreatic ascites, reportedly occurring in about 10% (6% to 14%) of patients with pseudocysts. Pancreatic necrosis can cause major pancreatic duct injuries. Pancreatic fluid leakage into the necrosis delays the resorption of the walled-off necrotic material. Dual-modality combined percutaneous and transmural endoscopic stenting is a method that can be used to manage this condition.

Epidemiology

The most common causes of ascites in the United States (US) include cirrhosis (about 85%), peritoneal carcinomatosis (about 7%), and cardiac failure (about 3%). Less common causes include nephrotic syndrome and tuberculosis.[17] Pancreatic ascites is extremely rare, and the epidemiology is not well studied. However, about 3.5% of patients develop chronic pancreatitis, accounting for only about 1% of all abdominal ascites cases.[18][19] Pancreatic ascites tend

to be twice as common in men as in women. The predominant age range is 20 to 50.

However, in the context of pathophysiological association with pancreatic ascites, the following reported incidence rates of pancreatitis may provide some insight and guidance:

• Acute pancreatitis in the US varies from 4.5 to 35 individuals per 100,000 population.
• Chronic pancreatitis was reported in 42 to 73 patients per 100,000 of the adult population in the US.
• The annual incidence rate of chronic pancreatitis in the US ranges between 5 and 8 to 14 individuals per 100,000 adult population.
• The annual occurrence of acute and chronic pancreatitis is 34 and 10 cases per 100,000 adult population, respectively.
• Internal pancreatic fistulae, including pancreatic ascites and pleural effusions, are seen in 7.3% of patients with chronic pancreatitis.
• Both complications are reported simultaneously in 14% of cases, while pancreatic pleural effusion alone is seen in 18%.[20][21][22][23][24][25]   

Pathophysiology

Pancreatic leakage may result from a pseudocyst or walled-off necrosis. Pseudocysts, common in chronic pancreatitis, have a weaker fibrinous wall and are more likely to allow pancreatic secretions to leak into the peritoneum through the disrupted duct.[26] Alternatively, pancreatic duct disruption without a pseudocyst leads to the formation of a fistulous tract. Fluid collections manifest differently depending on the fistula's route.

Fistulas from an anterior pancreatic duct disruption cause secretions to empty directly into the peritoneum, leading to ascites. Posterior pancreatic duct ruptures cause fistula formation through the aortic or esophageal hiatus and, possibly, through the diaphragmatic dome, leading to pleural effusions. Regardless of the route, pancreatic ascites is typically exudative, with high amylase levels.[27] Some have attributed this exudative quality to pancreatic fluid causing a severe inflammatory reaction and increased vasopermeability.

History and Physical

Individuals diagnosed with pancreatic ascites commonly display the demographics associated with chronic pancreatitis, found in about 83% of cases. Patients generally present with a subacute or recent history of progressive abdominal distension or weight loss, with infrequent pain and nausea. Weight loss may occur due to loss of appetite rather than the large amount of fluid retained in the abdomen. Typical symptoms include increasing abdominal girth with mild abdominal discomfort.[28] Nonspecific findings, including tachycardia, ileus, hypotension, and shortness of breath, may result from compromised diaphragmatic motion or related pleural effusions. Protein loss into the abdominal ascites may result in anasarca or pedal edema.

The major determinants of the intensity of the symptoms are the severity of underlying pancreatitis and the degree, location, size, and leakage characteristics of the pancreatic ductal leak. Up to 54% of patients with pancreatic ascites also present with an associated pleural effusion.[29] Patients with such pleural effusions may present with a cough, chest pain, shortness of breath, and increased dyspnea on exertion.[30] A history of chronic pancreatitis is possible due to excessive alcohol intake, where about 3.5% of patients develop pancreatic ascites. A recent history of abdominal trauma or endoscopic ultrasound-guided needle aspiration of the pancreas is common.[31][32][33] The past medical history in many patients is unremarkable for previous episodes of acute pancreatitis, but about one-third will report a recent history of an acute pancreatic attack.[34]  

The physical examination often reveals a large volume of ascites, with marked shifting dullness and fluid waves but little to no abdominal tenderness.[35] Nothing specific about the physical examination identifies the pancreas as the etiology of previously undiagnosed ascites. A careful history and diagnostic paracentesis results determine the next steps.

Evaluation

Assessment for chronic pancreatitis and related complications necessitate diagnostic paracentesis, diagnostic imaging, and laboratory testing. These evaluations help determine the extent of pancreatic damage, identify potential ductal disruptions or fistulas, and guide appropriate treatment strategies.

Diagnostic Paracentesis

The American Association for the Study of Liver Diseases recommends diagnostic paracentesis as the first-line modality for evaluating new-onset abdominal ascites. The procedure is safe, cost-effective, and essential for diagnosis. Diagnostic paracentesis should be performed in all new ascites cases. Amylase level, cell count, culture, Gram stain, cytology, and serum protein are indicated. The results can confirm pancreatic ascites or suggest an alternate diagnosis as follows:

• Total ascitic fluid protein concentration greater than 3 g/dL. A protein level below 15 g/L (1.5 g/dL) suggests possible spontaneous bacterial peritonitis (SBP) or cirrhosis. 
• Ascites fluid amylase level greater than 1000 international units per liter (IU/L) and if levels in the ascitic fluid are substantially higher (3- to 6-fold) than the serum level.
• Serum-ascites albumin gradient (SAAG) is calculated by subtracting the albumin concentration in the ascitic fluid from the serum albumin concentration. Calculated SAAG of less than 1.1 g/dL suggests pancreatic ascites. Ascites secondary to portal hypertension would not have elevated amylase levels and would typically have a protein concentration of less than 1.5 g/dL with SAAG greater than 1.1 g/dL.
• Polymorphonuclear (PMN) lymphocyte counts greater than or equal to 250 cells/mm³ in ascitic fluid and a PMN percentage equal to or greater than 50% are typically found in SBP but may also be seen in patients with pancreatic ascites.  
• Pancreatic ascites results are similar to results found in peritoneal carcinomatosis except for the elevated amylase level.
• Cirrhosis would show a high SAAG exceeding 1.1 g/dL and protein levels below 2.5 g/dL.
• Ascites due to cardiac failure would demonstrate elevated SAAG and ascitic fluid protein levels.[36][37][38][39][40]

Bacterial culture on the ascitic fluid is a diagnostic measure in individuals suspected of SBP, indicated by a PMN count equal to or exceeding 250 cells/mm³ and a positive response to a 48-hour regimen of antibiotics. A bacterial culture is obligatory for patients with ascites scheduled for antibiotic therapy.

Diagnostic Imaging

Imaging techniques are crucial in diagnosing pancreatic ascites and related conditions. These modalities can detect fluid accumulation, identify pancreatic fistulas and pseudocysts, and assess the pancreatic duct's structure and function. However, each technique has limitations and is selected based on the patient's needs and circumstances.

Computed tomography scan

An abdominal CT scan identifies pancreatic pseudocysts and detects small quantities of peritoneal fluid, which tend to accumulate primarily in the Morrison pouch and pelvis. The following findings in the abdominal CT scan suggest pancreatic ascites: 

• Accumulation of intraperitoneal ascitic fluid with over 15 Hounsfield units density, indicating high protein content
• Collapsed or partially collapsed pseudocysts
• Further evidence of chronic pancreatitis, such as diffuse parenchymal glandular atrophy, dilated main pancreatic duct, and pancreatic calcifications [41] 

X-ray and abdominal ultrasound

Plain radiographs and abdominal ultrasound are helpful but of limited diagnostic value in the setting of pancreatic ascites. The following nonspecific features are expected in an abdominal x-ray in a patient with this condition:

• Blurred outline of the soft tissue shadows, such as the liver, spleen, and psoas muscles
• Bulging of the flanks
• Increased interloop spacings of the small bowel
• Medial displacement of the bowel and solid viscera, moving away from the preperitoneal fat stripe
• Presence of fluid in the pelvic peritoneal recess and a positive "dog ear" sign
• Widespread density increases in the abdomen

Abdominal ultrasound findings may indicate intraperitoneal fluid, although no unique or specific characteristics suggest pancreatic ascites. Anechoic ascites is a simple, uncomplicated abdominal fluid collection; floating debris and septations are present in complicated hemorrhagic and loculated ascitic conditions. None of these findings are diagnostic of pancreatic ascites. 

Advanced imaging

Magnetic resonance cholangiopancreatography (MRCP) with secretin stimulation can help visualize the pancreatic duct and any associated leaks or abnormalities.[42] Secretin stimulates pancreatic secretions and improves MRCP's sensitivity by about 50%. Guidelines now recommend this imaging modality as an acceptable diagnostic tool for evaluating the pancreatic duct.[43] MRCP is particularly useful in selected patients who are not good candidates for or wish to avoid endoscopic retrograde cholangiopancreatography (ERCP).[44][45][46] More successful than CT, MRCP visualizes the pancreatic duct and approaches up to 91% correlation with ERCP without endoscopy.[47][48] 

The limitations include ductal disruptions, the need to administer secretin for optimal visualization, and less detection of ductal defect or disconnect if transpapillary stenting is in place and functioning well.[49] Many experts agree that MRCP is a valuable imaging modality for pancreatic ductal anatomy, but the underutilization is probably due to unfamiliarity, cost, logistical obstacles, and limited access or availability of secretin.[50] 

Treatment / Management

Managing pancreatic ascites consists of 3 main interventional pillars: medical, endoscopic, and surgical. A combination of these approaches is often used in a stepwise fashion. Conservative management with medical treatment is usually tried first, followed by endoscopic imaging and stenting. Surgery is performed if this approach fails.

Medical Management

An initial course of medical treatment is proposed for less severe cases since resolution without intervention can occur in approximately one-third of patients. Medical management involves keeping the patient in a nothing-per-orem status and providing nutritional support via total parenteral nutrition (TPN) or total enteral nutrition (TEN).[51][52] TEN is generally preferred, as recent evidence shows it is associated with significantly fewer adverse infectious events.[53][54][55] This trend is likely due to fewer intestinal microbiome and microenvironment alterations than TPN.[56] Electrolyte imbalances should be carefully monitored and managed. (A1)

Somatostatin or octreotide with diuretics decreases pancreatic exocrine function and promotes healing of the disrupted duct.[57] Intermittent therapeutic paracentesis can also help patients with symptomatic ascites.[58][59][60] See our companion StatPearls reference articles on "Octreotide" and "Physiology, Somatostatin.”[61][62] The optimal duration of conservative therapy is unknown, but a 4- to 6-week course is recommended.[63] A triple-drug therapy regimen, including somatostatin analog, gabexate mesylate, and imipenem/cilastatin, is reasonably successful in treating animal models of pancreatic ascites.[64](B3)

Endoscopic Retrograde Cholangiopancreatography and Stenting

ERCP also enables immediate, appropriate endoscopic intervention.[65][66][67] Secretin-augmented MRCP may be recommended, but this modality requires secretin administration for optimal results, and simultaneous endoscopic stenting is difficult. Pancreatic duct disruptions are indicated by contrast extravasation during ERCP injection of the pancreatic duct or secretin-enhanced MRCP.[68][69] 

The mainstay of management following conservative measures remains endoscopic therapy, although a 2-week course of octreotide, a long-acting somatostatin, is suggested first. A transpapillary stent at the pancreatic duct sphincter decreases intraductal pressure and diverts pancreatic secretions to the small bowel, enhancing the healing of the ductal disruption.[70][71] Ideally, the stent should bridge the ductal disruption to optimize the outcome. Duration is typically 4 to 6 weeks, with a longer period associated with improved healing. The stent is removed afterward and may be replaced if any leakage or ductal injury remains.

Stenting generally requires both endoscopic and fluoroscopic guidance, and the usual technique is described as follows: 

• A guidewire is placed endoscopically into the ampulla and pancreatic duct.
• Sphincterotomy or dilation may be needed but is not necessary.
• The guidewire may be advanced carefully to bridge the damaged or disrupted duct area.
• The stent is carefully advanced over the guidewire. The guidewire and stent size should be compatible. The stent must not be extended or pushed completely into the pancreatic duct, as removal is difficult.
• Advancement is facilitated by keeping the guidewire steady and immobile while slowly advancing the stent under an endoscopic view.
• The guidewire is slowly removed when the stent is in an optimal position while the pusher holds the stent in place.
• Fluoroscopic imaging should be used to verify and document the stent's final position.[72]

Stenting through the disrupted or disconnected duct is challenging in large pancreatic necrosis or ductal injuries. In these cases, transpapillary stenting has shown 48% to 100% success in controlling pancreatic ascites and distal segmental atrophy over time. However, stenting is ineffective if the leak results from disconnected duct syndrome, which describes a pancreatic segment separated from the pancreatic head. In such cases, stent placement only across the ampulla is ineffective. Other endoscopic interventions, including transluminal stenting or surgery, are indicated, and an interprofessional approach may be necessary. Following successful transmural stenting procedures, the stents are retained in situ indefinitely.[73]

Endoscopically guided drainage via lumen-apposing covered self-expanding metal stents demonstrates great success rates for draining matured pancreatic fluid collections into the upper gastrointestinal tract. Still, this procedure is considered less valuable in managing pancreatic ascites.[74] These stents should generally be removed after 4 weeks. When used for a disconnected pancreatic duct where longer duration stenting is usually recommended, early replacement with a more standard double pigtail stent was associated with decreased recurrences, fewer failures, and a higher percentage of successful long-term transmural drainage.[75]

Endoscopic ultrasonic imaging is an evolving technology that appears promising. However, the imaging may be limited by access and is operator-dependent.[76][77] Procedural guidelines were recently published in a technical review by the European Society of Gastrointestinal Endoscopy.[78] 

A combined transmural and percutaneous approach has shown promising results in selected cases with walled-off pancreatic necrosis. Other endoscopic interventions include injectable endoscopic glues or fibrinogen injections into the fistula to block further fluid leakage into the peritoneum. However, supporting evidence to recommend use at this time is lacking.[79] Overall, the endoscopic approach has shown promising results without the higher mortality and morbidity associated with a traditional surgical approach.[80][81]

Surgical Intervention

The surgical approach to pancreatic ascites was formerly the standard of care in those failing medical therapy. Now, surgery is reserved for cases where endoscopic intervention has failed or where a complete pancreatic duct disruption is present with no visible opacity proximal to the ductal leak on cholangiography.

Patients on TPN are typically kept at nothing-per-orem for 4 to 6 weeks. Octreotide, diuretics, and intermittent therapeutic paracenteses are used. ERCP and stenting are completed if no improvement is seen after 2 weeks. Formal surgery is recommended if stenting fails due to a disruption or complete disconnect of the ductal system.[82] Distal lesions are amenable to partial pancreatectomy if the remaining pancreatic volume has sufficient endocrine and exocrine function. Proximal lesions of the main pancreatic duct are often treated via pancreaticojejunostomy.

Surgical treatment options for pancreatic duct leaks unresponsive to other therapies include procedures such as the pylorus-preserving pancreaticoduodenectomy and the Beger procedure. These surgeries involve removing the entire pancreatic head and are longer compared to the Frey and Berne procedures, which only require local or partial pancreatic head resection. These procedures successfully restore pancreatic drainage, and the surgeon's choice, experience, local anatomy, and technical considerations at the time of surgery determine the method.[83] In experienced hands, surgical outcomes are generally excellent.[84]

General surgeons must carefully weigh the risks and benefits for each patient considered for surgical intervention. The best outcomes are achieved through close communication and collaboration among pancreatic duct leakage repair and management experts. Referring to a tertiary care facility with greater experience in these complex surgeries may be in the patient's best interests. 

Specific surgical intervention planning and treatment are highly individualized and based on many factors, including: 

• Availability and experience of supportive care
• Endoscopic ultrasound availability and gastroenterologist experience
• Evidence of infection
• Location and severity of the pancreatic duct leak
• Nutritional status
• Outcome of attempted stenting
• Pancreatic duct degree of damage: small leak, partial disruption, or complete disconnection
• Patient comorbidities
• Patient performance status and preferences
• Patient response to conservative treatment
• Technical skills and experience of the interventional gastroenterologist and general surgeon [85][86]

Differential Diagnosis

Pancreatic ascites occurs most often in patients with chronic pancreatitis and usually coincide with a history of excessive alcohol use. In such cases, ascites secondary to increased portal pressure from cirrhosis should be excluded. Other cirrhosis etiologies that may cause ascites in the absence of alcohol use should also be considered. While ascites from cirrhosis usually has a SAAG greater than 1.1 g/dL, an infectious process can affect this value. Other processes with ascites and SAAG greater than 1.1 g/dL are hepatic vein occlusion (Budd-Chiari syndrome), portal vein thrombosis, and right heart failure. Additional causes of ascites include alcoholic hepatitis, constrictive pericarditis, myxedema, portal hypertension, and serositis, as well as the conditions summarized below.

Enteric Duplication Cysts

These cysts are uncommon congenital gastrointestinal anomalies classified by their location and origin within the gastrointestinal tract. Enteric duplication cysts in communication with the pancreas are a rare subset of these congenital anomalies. However, these cysts are considered a differential diagnosis in pediatric patients with recurrent acute and chronic pancreatic attacks. Symptoms and physical examination findings are nonspecific.

Nephrotic Syndrome

The syndrome should be considered in the differential diagnosis for abdominal ascites when the history and physical examination suggest this condition to be the likely diagnosis, with laboratory studies showing a SAAG of less than 1.1 g/dL, a white blood cell count of 500/mm³, and a PMN count of less than 250/mm³. Moreover, a total serum protein of less than 2.5 g/dL with proteinuria of more than 3 g/24 h is diagnostic of nephrotic syndrome and necessitates an evaluation. See our companion StatPearls reference article on "Nephrotic Syndrome." 

Edema is the most significant clinical presentation of nephrotic syndrome. Nephrotic syndrome edema initially starts in the periorbital and leg areas. The edema is gradually generalized, and weight gain, ascites, and pleural effusions are predicted. Hematuria and hypertension may be present, but these conditions occur inconsistently.[88] 

Neoplasms

Malignancy should be considered in new-onset ascites with a SAAG less than 1.1 g/dL, noting that abnormal ascitic fluid cytology is sometimes due to a metaplastic response to the pancreatic fluid leak instead of a malignant process. White blood cell counts greater than 500 cells/mm³ and PMN percentages less than 50% are further clues in a patient with a history of metastatic peritoneal carcinomatosis. Peritoneal metastasis generally presents in the late stage of the disease, typically with symptoms and signs associated with advanced primary cancer. See the companion StatPearls reference article on "Peritoneal Cancer."[89]

Often, peritoneal carcinomatosis is an accidental finding during surgical exploration for primary tumor resection or other elective procedures. The 2 most important clinical findings related to peritoneal carcinomatosis are ascites and bowel obstruction. However, these abnormalities are found in less than 50% of patients.[90] Repeated ascites cytologic analyses can significantly enhance the sensitivity of the peritoneal carcinomatosis diagnosis to 97%.

Peritoneal Tuberculosis

Peritoneal tuberculosis usually occurs with other presentations of abdominal tuberculosis. However, peritoneal tuberculosis may follow the intraperitoneal rupture of necrotic lymph nodes, particularly retroperitoneal and mesenteric lymph nodes. The mentioned lymph nodes may be calcified or have undergone caseating granulomatosis. Tuberculotic ascites is the most common presentation in this scenario but still accounts for only about 2% of all cases of abdominal ascites.[91]

Acid-fast bacilli staining and mycobacterial culture of ascitic fluid have low sensitivity in diagnosing peritoneal tuberculosis. Laparoscopic evaluation, obtaining a peritoneal biopsy, and histological assessment have great value in diagnosis. A low SAAG with lymphocytosis suggests peritoneal tuberculosis.[92][93]

Portal Hypertension

This condition refers to a hepatic venous pressure gradient exceeding 5 mm Hg, increasing plasma volume via the renin-angiotensin-aldosterone pathway. The expanded plasma volume augments cardiac output. Patients with portal hypertension, especially if clinically significant (ie, hepatic venous pressure gradient greater than 10 mm Hg), may present with a decompensated event, including ascites. See the companion StatPearls reference articles on "Hepatic Cirrhosis" and "Portal Hypertension."[94][95]

The following results in the ascites fluid analysis of patients with uncomplicated cirrhosis are as follows:

• White blood cell count of less than 500 cells/mm³
• PMN count of less than 250 cells/mm³
• SAAG of 1.1 g/dL or less
• Total serum protein of less than 2.5 g/dL

Prognosis

The overall prognosis for pancreatic ascites has improved with the availability of endoscopic interventions. A course of conservative medical management leads to recovery in approximately one-third of patients with this condition. Endoscopic placement of a transpapillary stent has a success rate of 82% to 100%. A surgical approach is generally recommended for those in whom medical and endoscopic management fails. The mortality has been reported to be as high as 15% to 25%, but outcomes are positive in experienced hands. Results from recent studies suggest that endoscopic management has reduced mortality, hospital length of stay, and recurrence rates.

Complications

Pancreatic ascites may be managed effectively with conservative measures or endoscopic placement of a transpapillary pancreatic duct stent, mainly when pancreatic duct rupture is evident. ERCP and stent placement increase the risk of acute postprocedural pancreatitis and guidewire complications during the procedure, leading to a possible perforation. Due to inoculation via instrumentation, the procedure also increases the risk of cholangitis or an infected pseudocyst.

The stent can become blocked or infected and migrate to distal portions of the pancreatic duct, making it difficult to retrieve. Prolonged stent placement may lead to pancreatic changes similar to those seen in chronic pancreatitis. Thus, stent retrieval is generally recommended within 4 to 6 weeks. Endoscopic intervention reduces the recurrence of pancreatic ascites compared to conservative medical management, although supporting data is limited.