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Chronic pancreatic ascites and pancreatic pleural effusions
0016~5065/78/0074-0001$02.00/0 GASTROENTEFZOLCGY74134-140, 1978
Vol. 74, No. 1
Copyright 0 1978by the American GastroenterologicalAssociation
CLINICAL
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Printed in U.S A.
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TOPICS
CHRONIC PANCREATIC ASCITES AND PANCREATIC PLEURAL EFFUSIONS JOHN L. CAMERON, M.D., Department
F.A.C.S.
of Surgery, The Johns Hopkins Medical Institutions,
Inflammatory disease of the pancreas is associated with a number of well-documented sequelae. Hypocalcemia, hyperglycemia, abscess, and pseudocyst formation are some of the more common complications seen with acute attacks. Chronic or recurrent inflammatory disease can result in exocrine insufficiency with steatorrhea and endocrine insufficiency, resulting in diabetes. In addition, in the last decade chronic ascites’, 2 and chronic pleural effusion+ 3 have also been recognized as complications of chronic pancreatitis. Despite the marked disparity in clinical presentation and physical findings, the etiologies of pancreatic ascites and pancreatic pleural effisions are identical and not infrequently they are seen together in the same patient. In recent years the pathogenesis of these two entities has been defined, their diagnosis simplified, and guidelines for management established.
Baltimore,
Maryland
The recognition of patients with chronic massive pancreatic pleural effusions has been more recent. In 1973 Anderson et al.” reported 5 patients with this entity and were able to document an additional 11 cases from the literature. In 1976 a series of 34 patients with massive chronic pancreatic ascites and/or effusions from the Johns Hopkins Hospital, 12 (35%) had a pancreatic pleural effusion either alone or in conjunction with ascites. Thus, as awareness of chronic massive pancreatic pleural effusion increases, its recognition can be expected to increase as has that of pancreatic ascites. Pathogenesis
When the first patients with ascites were reported in association with chronic pancreatitis, an obvious explanation was lacking. Blocked intraperitoneal lymphatics secondary to chronic pancreatitis,‘O and subacute periIncidence toneal inflammation from pancreatic enzymes” were The first patients with pancreatic ascites were re- suggested as possibilities. There can be no doubt now, ported in the early 1950’s.4-6Sporadic case reports fol- however, that pancreatic ascites is secondary to a panlowed. In 1967 Cameron et al.’ in a review were able to creatic duct disruption with the leakage of pancreatic document only 13 cases from the literature but estab- secretions directly into the peritoneal cavity. Pancreatic lished simple criteria for its diagnosis. Thereafter, iden- duct disruptions in the face of inflammatory pancreatic tification became more frequent and in 1974 Donowitz disease are common. Often, however, they occur during et al.’ were able to find 80 reported patients with an attack of acute pancreatitis. In this setting the pancreatic ascites, and added 5 of their own. In 1976 inflammatory reaction results in a walling off of the Sankaran and Walt8 reported a series of 26 patients ductal leak by the back wall of the stomach, the with pancreatic ascites seen at Wayne State University transverse colon and mesocolon, and other adjacent over a 17-year period. They stated that 15% of all structures and organs. This walling off results in a patients seen at their institution with pseudocysts had pseudocyst. Occasionally, however, such a duct disrupconcomitant pancreatic ascites.s In 1976 Cameron et tion occurs in the face of chronic inflammatory panal.2 reported a series from the Johns Hopkins Medical creatic disease, in the absence of acute inflammation. Institutions, seen over a lo-year period, of 22 patients In this setting the leak may only be partially walled with pancreatic ascites and 5 additional patients with off, so that a small pseudocyst with a leak results; or both pancreatic ascites and pleural effusions. During the leak is not walled off at all and the ductal hole is in this same interval approximately 40 patients with class- direct communication with the surrounding environical pseudocysts were operated upon at their institution. ment. If the duct disruption is anterior, an internal Thus, as awareness of pancreatic ascites has increased, pancreatic fistula into the peritoneal cavity is formed its recognition has also increased to the point where its and pancreatic secretions flow freely into the abdomen. relative frequency in some series approaches that of Inasmuch as the enzymes are not activated, an acute classical pseudocysts. peritonitis does not occur and painless ascites results. Some peritoneal irritation does occur, however, because large quantities of albumin are found in the ascitic Received May 2, 1977. Accepted July 22, 1977. fluid. Because there is no albumin in pancreatic secreAddress requests for reprints to: John L. Cameron, M.D., Departtions, it has to be from a subacute or chronic peritoneal ment of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland, 21205. exudative reaction. In this same setting, if the duct 134
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disruption is posterior, the pancreatic secretions flow into the retroperitoneum. Once in the retroperitoneum they track along the path of least resistance, which usually is along the esophagus or aorta up into the mediastinum.” In the mediastinum they can be contained and present as a mediastinal pseudocyst,” or more commonly, they can penetrate one or both pleural surfaces and present as unilateral or bilateral pleural effusions. In such instances, the patient has an internal pancreatic fistula between his pancreatic duct and one or both pleural cavities. Although these internal fistulae usually pass through the aortic or esophageal hiatus, instances have been reported in which the fistula passes directly from a pseudocyst up through the dome of the diaphragm into the right or left pleural cavities. l3 These effusions are not to be confused with the small left-sided pleural effusions seen with attacks of acute pancreatitis, which are sympathetic in nature, selflimited, and require no treatment. Chronic pancreatic pleural effusions are the result of an internal pancreatic fistula into the pleural cavity and are massive, recur rapidly if tapped, and require specific therapy (fig. 1). As surgeons have become aware that internal fistulae are the source of pancreatic ascites and pleural effusions, the ductal or pseudocyst leaks have been demonstrated with increasing frequency grossly at the time of surgery or with operative pancreatography.14 In our series of patients with internal pancreatic fistulae at the Johns Hopkins Medical Institutions, 9 patients with pancreatic ascites have undergone pancreatography.” In 8 of the patients the leak was demonstrated; 4 directly from the main pancreatic duct and 4 from pseudocysts. A pseudocyst was demonstrated in the 9th patient but the leak was not found. Three of our patients with pancreatic pleural effusions have undergone pancreatography, and the leak was demonstrated in 2 of them. Furthermore, there are a number of reports of patients with pancreatic ascites in whom a leak from a small pseudocyst or from the main duct was demonstrated with endoscopic retrograde pancreatography before undergoing surgery.“, x, ‘%I7 Finally, drainage of the leak surgically into the stomach or small bowel routinely cures the ascites or effusion.‘” Therefore, the pathogenetic mechanism seems certain. The etiology of the chronic pancreatitis in patients with internal pancreatic fistulas is usually alcohol consumption Twenty-eight (82%) of the 34 patients in our series were alcoholics.2 Two-thirds of the 85 patients with pancreatic ascites in the review of Donowitz et al. were alcoholics.’ How or why the duct disruption that results in an internal pancreatic fistula occurs in these alcoholics in the absence of any clinical symptoms is not known. Trauma is also well documented as a mechanism for pancreatic duct disruption and the formation of an internal pancreatic fistula, and is the most common etiology in children.’ In the past year on two occasions at our institution surgical trauma to the main pancreatic duct has resulted in an internal pancreatic fistula with pancreatic ascites. There have been no definite instances of chronic pancreatic ascites or pleural effusions secondary to biliary tract-induced pan-
FIG. 1. A, chest X-ray of a 36-year-old male with an internal pancreatic fistula into his chest. He was treated nonoperatively initially, but his effusion recurred 2 months later. At surgery a small tract up into his mediastinum along his aorta was identified and divided, and a pseudocyst was drained. His effusion has not recurred. B, chest X-ray of a 32-year-old male with both pancreatic ascites and a pancreatic pleural effusion. Both his ascites and effusion resolved on nonoperative therapy.
creatitis. One patient has been reported with documented pancreatic cancer in association with pancreatic ascites, but this is distinctly unusual.‘” In the vast majority of instances, the etiology will be benign. Presentation The clinical presentation of patients with internal pancreatic fistulae is often deceptive and usually does not suggest chronic inflammatory pancreatic disease. Of the 34 patients reported from Hopkins in 1976,2only 14 had a history of an episode of acute pancreatitis, and in most instances it was months or years before presenting with ascites or a pleural effusion. The remaining 20 patients had no history suggestive of inflammatory disease of the pancreas (table 1). Even though ascites frequently accompanies an attack of acute pancreatitis, it is usually self-limited and resolves as the attack abates. Only rarely after acute pancreatitis will the ascites persist and present the therapeutic problems of
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pancreatic ascites. The age of these 34 patients ranged patients with pancreatic pleural effusions found in the from 4 to 65 years and averaged 40 years. Twenty-nine literature in 1973, 13 presented with primarily pulmoof the patients were male and only 5 were female. nary symptoms.3 The effusion can occur either on the Twenty-six of the patients with internal pancreatic right or on the left, although left-sided effusions seem somewhat more common. Instances of bilateral effufistulae were black and 8 were white. Patients with pancreatic ascites present primarily sions secondary to an internal pancreatic fistula have with a history of a slowly increasing abdominal girth also been reported.3 The effusions are usually massive, (table 2). Because most patients have a significant filling most or all of the pleural cavity. Internal pancreatic fistulae into the peritoneal and history of alcoholic intake, cirrhosis with ascites is often the admitting diagnosis. Tuberculous peritonitis, pleural cavities may be present concomitantly in the constrictive pericarditis, the Budd-Chiari syndrome, same patient. Of the 34 patients we reported in 1976, 5 and intraperitoneal carcinomatosis are other diagnoses (15%) had both ascites and a pleural effusion. Thirtythat can be suggested by the clinical presentation. two per cent of the 26 patients with pancreatic ascites Abdominal pain can be present but usually is not a in Sankaran and Walts’series had concomitant pleural prominent part of the clinical presentation. In only 4 of effusions.8 In 2 patients they were able to demonstrate the 27 patients in the Hopkins series with pancreatic a definite internal fistula between a pseudocyst and the ascites was abdominal pain a component of the present- right pleural cavity. ing complaint. When pain is present, it is often mild. Weight loss, despite the massive ascites, is common.7 Diagnosis On physical examination massive ascites is the most In the past patients with pancreatic ascites presented prominent feature. Abdominal tenderness is usually absent, but if present is mild. Skin lesions which on a difficult clinical diagnostic challenge. In the face of a biopsy have proven to be subcutaneous fat necrosis heavy alcoholic intake, and in most patients in the have been present in 2 of our 34 patients. These skin absence of a history of pancreatitis, cirrhosis with lesions were also present in 9 of the 85 patients reviewed ascites often appeared to be an obvious explanation. by Donowitz et al.’ This incidence of subcutaneous fat When pancreatic ascites occurred in a patient with necrosis, thought secondary to circulating pancreatic concomitant liver disease, which is often the case with enzymes, far exceeds that seen in association with alcohol being the etiological agent for both diseases, acute pancreatitis. undoubtedly the diagnosis was never made. Only when Patients with pancreatic pleural effusions present the entity occurred in the absence of abnormal liver even more of a clinical paradox. Generally their symp- functions was the diagnosis apt to be pursued to the toms are that of dyspnea, chest pain, or a cough, and point of uncovering the pancreatic etiology. Now, howthere is little to suggest abdominal pathology (table 2). ever, data have accumulated so that the differentiation Pulmonary parenchymal or pleural disease is usually of pancreatic ascites from other disease entities with the admitting diagnosis. Among the 7 patients in the ascites can be done quickly and simply. Hopkins series with pancreatic pleural effusion without The amylase in the ascitic fluid of a patient with ascites, only 2 had abdominal complaints. Of the 16 pancreatic ascites is always markedly elevated, often up in the thousands.2*8,l4 In addition, the ascitic fluid albumin is usually elevated to the range of 3 g per dl or TABLE 1. Incidence of acute Dancreatitis in Datients with internal above.za8 In our series of patients with internal pancreatic fistulas, all 27 patients with pancreatic ascites had markedly elevated ascitic fluid amylase values. Of pancreatitis Pleural the 27 patients, 20 had ascitic fluid albumin levels over effusion 3 g per dl. The remaining 7 patients with albumin Current 1 1 0 levels less than 3 g per dl were malnourished and Prior episode 9 2 1 markedly albumimenic. In Sankaran and Walt’s seNone 12 4 4 ries8 all 26 patients had elevated ascitic fluid amylase values, and 26 of the 27 had ascitic fluid albumin levels Total patients 22 7 5 greater than 2.5 g per dl. In cirrhotic ascites the ascitic fluid amylase value is always normal and the albumin level is usually less than 1.5 g per dl. Thus, by simply TABLE 2. Presenting complaint in 34 patients presenting to the Johns Hopkins Hospital with internal pancreatic fistulae determining the amylase and albumin content, what Internal pancreatic fistulae can be a difficult or impossible clinical differentiation, Presenting can be made easily by laboratory data. The ascitic fluid complaint Pleural Ascites Both effusion grossly is usually clear and straw-colored, but can be chylous4 in character or even bloody.6 Erythrocyte and Abdominal swelling 18 4 leukocyte counts are quite variable and do not add any Abdominal pain 3 1 1 Shortness of breath 4 accuracy to the diagnosis. Elevated lipase levels have Cough 2 also been reported in the ascitic fluid,lg but cannot be Weight loss 1 performed as quickly or simply as amylase determinations and do not add anything additional to the diagnoTotal patients 22 7 5 sis or work-up.
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137
Intraabdominal carcinomatosis can also be simulated 10 had elevated serum amylase values, but in 2 patients by a patient with pancreatic ascites who presents with it was normal. Thus, the serum amylase may serve as cachexia, marked weakness, and weight loss. Tosup-a preliminary screen, but a normal value does not rule port this picture further, we have had cytology reports out the entity. The pleural effision in all 12 patients from cell blocks of ascitic fluid come back on 2 patients had a markedly elevated amylase content, usually up with pancreatic ascites as positive for malignant cells. in the thousands. In addition, 10 of the 12 had albumin However, both patients came to surgery and were found levels greater than 3 g per dl. The 2 patients with to have only benign inflammatory pancreatic disease effision albumin levels of less than 3 g per dl were and both patients are long term survivors. Apparently both hypoalbuminemic. Primary or secondary thoracic pancreatic enzymes are capable of inducing metaplasia malignancies can also be associated rarely with effuof serosal cells in pancreatic ascites such that they can sions containing elevated amylase levels, presumably be mistaken for malignant cells. It is worth repeating secondary to blockage of the thoracic duct20 The elevathat there is only 1 patient in the literature with tions are usually minimal to moderate, however, and documented pancreatic malignancy that also had crite- do not approach the elevations into the thousands seen ria for the diagnosis of pancreatic ascites.18The great with internal pancreatic fistulae. As with pancreatic majority of patients with the clinical and laboratory ascites, we have also had a faIsely positive cytology for picture of pancreatic ascites will have benign disease, malignancy in a patient with a chronic pancreatic and even in the face of a positive ascitic fluid cell pleural effusion. Therefore, even in the face of a positive cytology, management should proceed as if the under- cytology, work-up and treatment should be pursued if the laboratory evidence points to a pancreatic pleural lying disease is treatable and curable. The serum amylase is also usually elevated in pan- effusion. Esophageal perforations with effisions high creatic ascites. The serum level is always much lower, in amylase have also been reported, but clinically their however, than the ascitic fluid level.* The serum amy- differentiation usually is not difficult.21 lase elevation is not an indication of active pancreatic Definition of the internal pancreatic fistula preoperainflammatory disease, but probably results from the tively in a patient with a chronic massive pleural passive absorption into the serum of amylase from the effusion by ERP has not yet been reported. However, ascitic fluid. The serum amylase was elevated in 26 of the fistulous tract leading from the pleural cavity to the 27 patients in our series with pancreatic ascites, below the diaphragm has been demonstrated on at but was normal in 1 patient. There are also other case least four occasions by injecting contrast media into the reports of patients with pancreatic ascites with normal pleural effusion. *, 13,** Under fluoroscopic control and serum amylase levels.7 In Sankaran and Walt’s series by changing the position of the patient, the fistulous of 26 patients, 8 the serum amylase was elevated in tract can often be outlined. This information is confirmall. Thus, although the serum amylase value may be a atory anatomical evidence of an internal fistula, but is reasonable screen for pancreatic ascites, a normal se- not quite as valuable as ERP. The primary pancreatic rum value does not rule out the entity and thus the ductal pathology, which will determine the operative ascitic fluid values should be obtained in all patients procedure if the patient comes to surgery, is not defined with ascites. by pleural space injection, but is by ERP. Recently, endoscopic retrograde pancreatography (ERP) has added another dimension to the diagnosis Treatment and work-up of a patient suspected of having pancreatic ascites. There have been at least 8 reported cases of The treatment of internal pancreatic fistulae remains ERP*,8*15-17 successfully demonstrating pancreatic duct somewhat controversial (table 3). Once the diagnosis pathology, and in 4 of the patients the leak into the has been confirmed by ascitic or pleural fluid amylase peritoneal cavity was seen. This clearly gives anatomi- and protein elevations, the treatment can be either cal evidence for the diagnosis and pathogenesis of pan- nonoperative or operative. We have generally followed creatic ascites. More importantly, however, if the pa- a course of treating patients with internal pancreatic tient comes to surgery the operative time will be fistulae initially with a period of nonoperative manageshortened considerably as the pathological anatomy ment. In an attempt to decrease pancreatic secretion to will already be known. Furthermore, it avoids the need a minimum, and thus encourage the sealing of the to open the duodenum for operative pancreatography pancreatic duct or pseudocyst leak, the following regiat the time of surgery, thus decreasing the chance of men has been used: (1) patients have been given nothpostoperative morbidity. Because understanding the ing by mouth, and a nasogastric tube was inserted; (2) pathological anatomy at the time of surgery is the key Diamox and atropine are administered to decrease to designing successfully an adequate resectional or pancreatic secretion further: (3) paracenteses are perdrainage procedure for pancreatic ascites, ERP should formed as needed to keep the peritoneal cavity free be performed in all patients with pancreatic ascites from fluid, and thus encourage the approximation of before surgery. peritoneal surfaces and the sealing of the leak; (4) The diagnostic work-up of a patient with an internal intravenous hyperalimentation has been carried out in pancreatic fistula into a pleural cavity, presenting with recent years because of the poor nutritional status of a chronic massive pleural effusion, should proceed in a most patients with internal pancreatic fistulae, and to fashion identical to that for pancreatic ascites. In our replace the protein lost from the multiple paracenteses. series of 12 patients with pancreatic pleural efTusions,* In the series from the Johns Hopkins Medical Insti-
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tutions, 17 patients with pancreatic ascites were treated initially by the above regimen.* In 8 patients the ascites cleared, several within the first 2 weeks. Seven (41%) have remained permanently free from ascites, 1 patient recurring after a 6-month ascitic-free interval. There were four deaths among these 17 patients undergoing nonoperative therapy. One of the four deaths was secondary to gastrointestinal bleeding; one was from sepsis probably related to hyperalimentation, and the remaining two deaths were sudden and unexplained, presumably either from a myocardial infarction or a pulmonary embolus. This represents a significant mortality in the conservatively treated group, but is more an indication of the state of health of the patients rather than the risks of treatment. Others have noted a high recurrence and low success rate with nonoperative therapy, and are not enthusiastic about its use.8 However, these are patients with a significant operative risk, most of whom would benefit from a course of hyperalimentation before surgery in any event, who have a reasonable chance of success (7 of 17, 41%) with conservative therapy, and we continue to recommend its use (table 4). In the TABLE3. Management of patients with internal pancreatic fistulae Nonoperative treatment Nasogastric tube suction Diamox and atropine Paracenteses Thoracenteses or chest tube Hyperalimentation Operative treatment Direct duct leak Roux en-Y drainage of duct leak Pancreatic resection if leak is distal Roux en-Y drainage of remnant if proximal duct disease present Pseudocyst Roux en-Y drainage of pseudocyst leak Cystogastrostomy if Roux en-Y not possible Resect cyst if small and distal Roux en-Y drainage of remnant if proximal duct disease
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review of Donowitz et al., the mortality rate for 15 patients treated medically was 20%.7 If after a 2- or 3-week period the ascites continues to recur, most patients should be operated upon. There have been five case reports of low dose irradiation to the pancreas in patients with pancreatic ascites with resolution of the ascites in each instance.5*l’* 23-25If a patient were a prohibitive operative risk, this course could be considered. The success of operative management of pancreatic ascites depends upon adequate knowledge of the pathological anatomy. ERP should be attempted preoperatively in all patients being considered for surgery. Multiple case reports document the ability of ERP to define the pathology and at times the site or sites of the ductal leak. If this is successful, operative time will be decreased and the need to open the duodenum for pancreatography at the time of surgery obviated (fig. 2). If ERP is unsuccessful, operative pancreatography should be performed at the time of surgery. This can be done by cannulating the ampulla through a duodenotomy, or by a retrograde technique after amputating the tail of the gland. On occasion the ductal anatomy will be defined adequately by just injecting the pseudocyst with contrast media. This is unusual, however, and pancreatography will be required in most instances. The type of surgical procedure used will depend upon the information gained by pancreatography. If a direct duct leak is demonstrated with no pseudocyst, a direct sinastomosis between the leak and a Roux en-Y jejunal loop will be preferable. If the leak is distal in the tail, a distal pancreatectomy could also be considered. If a small cyst is present in the distal portion of the gland, as is frequently the case with pancreatic ascites, a distal resection removing the tail of the gland and cyst is indicated. If proximal duct disease is present, the pancreatic remnant should be drained with a Roux en-
TABLE4. Results of treatment of 34 patients at the Johns Hopkins Hospital with internal pancreatic fistulae
Results
Internal pancreatic fistulae
-
Ascites
Pleural effusion
Both
Nonoperative Success Failure Deaths
7 6 4
2 1 0
3 2 0
Total patients
17
3
5
Operative Success Failure Deaths
8 0 0
4 1 0
2 0 0
Total patients
8
5
2
FIG. 2. Endoscopic retrograde pancreatography (ERP) of a 32year-old male with pancreatic ascites. The large arrow points to the normal proximal pancreatic duct. The middle-sized arrow points to the distal pseudocyst, and the multiple small arrows point out contrast media leaking freely into the peritoneal cavity.
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Y loop. If the cyst is large, or in a region of the gland not amenable to resection, drainage of the cyst into a Roux en-Y loop or the stomach is preferable. External drainage of the pseodycyst has been accompanied by a very high recurrence rate.*” If these procedures are carried out with a clear understanding of the ductal pathology, there will be few operative recurrences (table 4). Ten patients in our series with pancreatic ascites, and 2 patients with both ascites and pleural effisions were treated surgically. In 10 patients the treatment was successful. One patient subsequently recurred 5 months later and required reoperation, but since then has been as&es-free. There were two deaths among these 12 patients (17%). In the literature review reported by Donowitz et al. in 1974, the operative mortality among 66 patients with pancreatic ascites treated surgically was 15%.’ The need for adequate pancreatography is nicely demonstrated by the series of patients with pancreatic ascites presented by Sankaran and Walt.8 In 7 patients treated surgically with the aid of a pancreatogram, the results were satisfactory in all with no recurrences. In contrast, 19 patients were managed without the aid of a pancreatogram, and the recurrence rate was 53%. The treatment of patients with internal pancreatic fistulae into the chest presenting with chronic massive pleural effusions has been somewhat more successful. Most authors recommend initial nonoperative management, and the success rate has been higher than that for pancreatic ascites. In addition to hyperalimentation, nasogastric suction, and Diamox and atropine administration, patients have been treated with multiple paracenteses or a chest tube. In our series reported in 1976,’ 5 of 8 patients with chronic massive pancreatic pleural effusions, alone or in conjunction with pancreatic ascites, undergoing nonoperative treatment had successful outcomes. Because these patients have a longer fistulous tract than do those with pancreatic ascites, the fistula may be more apt to close without surgical intervention. Six of 7 patients with pancreatic pleural effusions from our institution were managed successfully by surgery (table 4). It is important to remember that the operative management of pancreatic pleural effusions is identical to that of pancreatic ascites. ERP should be attempted before surgery in all patients. If that is unsuccessful, a laparotomy should be performed and operative pancreatography carried out. The appropriate pancreatic drainage or resection should then be performed. Inasmuch as many of these patients present with only chest symptoms, and with no abdominal complaints, a thoracic or thoracoabdominal approach was used in early cases .3,*’It is absolutely unnecessary to enter the chest, and a total abdominal approach should be planned. There were no deaths in the 12 patients with pancreatic pleural effusions in our series. Why these patients with pancreatic pleural effusions should tolerate medical and surgical therapy better than patients with pancreatic ascites is unknown. Perhaps as more patients are recognized and treated, this will become apparent.
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During the last decade the treatment of patients with internal pancreatic fistulae has not been standardized or, for the most part, baaed on adequate anatomical information. In addition, hyperalimentation has not been routinely employed. Today, most patients with internal pancreatic fistulae should be handled successfully, with very low mortality and recurrence rates. A 2- or 3-week period of nonoperative treatment will allow almost one-half of these patients to leave the hospital cured without surgery. The remainder, after adequate pre- or intraoperative pancreatography, should be managed successfully by a drainage or resectional procedure. In the chronically ill patient who has not closed his fistula on conservative management, who represents a high anesthetic risk, a short course of radiotherapy might be considered. With this regimen, most patients with internal pancreatic fistulae should have a successful outcome. Summary Over the past decade ascites and pleural effusions have become recognized as complications of chronic inflammatory disease of the pancreas. In the setting of heavy alcoholic intake, but usually without symptoms, a disruption of the main pancreatic duct can occur, resulting in an internal fistula between the duct and peritoneal cavity, producing massive ascites. If the duct disruption is posterior, pancreatic secretions can track up into the mediastinum and then escape into one or both pleural spaces, resulting in an internal fistula between the pancreatic duct and pleural space, producing a massive effusion. Diagnosis of the internal pancreatic fistula can be made by finding high amylase and albumin levels in the ascitic or pleural fluid. Serum amylase is usually, but not always elevated. Treatment initially should be nonoperative, and should include intravenous hyperalimentation, nasogastric suction, Diamox and atropine administration, and either multiple paracenteses, or multiple thoracenteses, or a chest tube insertion. If medical management is unsuccessful after a 2- or 3-week trial, surgical intervention is indicated. Pancreatography is essential to define the pathological pancreatic duct anatomy. When the duct pathology is determined, and the internal fistula identified, an appropriate drainage or resectional procedure can be chosen. With this regimen, most patients with an internal pancreatic fistula should be managed successfully. REFERENCES 1. Cameron JL, Anderson RP, Zuidema GD: Pancreatic ascites. Surg Gynecol Obstet 125328-332, 1967 2. Cameron JL, Kieffer RS, Anderson WJ, et al: Internal pancreatic fistulas: pancreatic ascites and pleural effisions. Ann Surg 183:587-593, 1976 3. Anderson WJ, Skinner DB, Zuidema GD, et al: Chronic pancreatic pleural effusions. Surg Gynecol Obstet 137:827-830, 1973 4. Crandell WB, Stueck GH Jr, McEvoy CD Jr: Chylous ascites due to a pancreatic pseudocyst. Surgery 34:111-116,1953 5. Davis ML, Kelsey WM: Chronic pancreatitis in childhood. Am J Dis Child 81:687-692, 1951
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6.Smith EB: Hemorrhagic ascites and hemothorax associated with benign pancreatic disease. Arch Surg 67:52-56,1953 7. Donowitz M, Kerstein MD, Spiro HM: Pancreatic ascites. Medicine (Baltimore) 53:183-195, 1974 8. Sankaran S, Walt AJ: Pancreatic ascites: recognition and management. Arch Surg 111:430-434, 1976 9. Sankaran S, Walt AJ: The natural and unnatural history of pancreatic pseudocysts. Br J Surg 62:37-44,1975 10. Schmidt EH, Whitehead RP: Recurrent ascites as an unusual complication of chronic pancreatitis. JAMA 189533-535, 1962 11. Gambill EE, Walters W, Scanlon PW: Chronic relapsing pancreatitis with extensive subacute peritonitis and chronic, recurrent massive “chylous” ascites. Am J Med 28668-670, 1960 12. Jaffe BM, Ferguson TB, Holtz S, et al: Mediastinal pancreatic pseudocysts. Am J Surg 124600-606, 1972 13. Tombroff M, Loicq A, DeKoster JP, et al: Pleural effusion with pancreaticopleural fistula. Br Med J 1:330-331, 1973 14. Cameron JL, Brawley RK, Bender HW, et al: The treatment of pancreatic ascites. Ann Surg 170:668-676, 1969 15. Davis RE, Graham DY: Pancreatic ascites: the role of endoscopic pancreatography. Am J Dig Dis 20:977-980,1975 16. Levine JB, Warshaw AL, Falchuk KR, et al: The value of endoscopic retrograde pancreatography in the management of pancreatic ascites. Surgery 81:360-362,1977 17. Rawlings W, Bynum TE, Pasternak G: Pancreatic ascites: diag-
18. 19. 20. 21.
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24. 25. 26.
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nosis of leakage site by endoscopic pancreatography. Surgery 81:363-365, 1977 Cayten CG, Mullen JL, Rosato EF: Pancreatic ascites with carcinoma of the pancreas. Am J Gastroenterol58:73-76, 1972 Sileo AV, Chawla SK, LoPresti PA: Pancreatic ascites: diagnostic importance of ascitic lipase. Am J Dig Dis 20:1110-1114, 1975 Kaye MD: Pleuropulmonary complications of pancreatitis. Thorax 23:297-306, 1968 Bellman MH, Rajanatnam HN: Perforation of the esophagus with amylase rich pleural effusion. Br J Dis Chest 68:197-201, 1974 Geffroy Y, Boureille J, Morere P, et al: Sem Hop Paris 44:13561368, 1968 Morton RE, Deluca R, Reisman TN, et al: Pancreatic ascites: successful treatment with pancreatic radiation. Am J Dig Dis 21:333-336, 1976 Kavin H, Sobel JD, Dembo AJ: Pancreatic ascites treated by irradiation of pancreas. Br Med J 2:503-504,197l Oeconomopoulos CT, Lee CM Jr: Pseudocysts of the pancreas in infants and young children. Surgery 47:836-845, 1960 Smith RB III, Warren WD, Rivard AA, et al: Pancreatic ascites: diagnosis and management with particular reference to surgical technics. Ann Surg 177:538-546,1973 Mitchell CE: Relapsing pancreatitis with recurrent pericardial and pleural effusions. Ann Intern Med 60:1047-1053, 1964
Vol. 74, No. 1
Copyright 0 1978by the American GastroenterologicalAssociation
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CHRONIC PANCREATIC ASCITES AND PANCREATIC PLEURAL EFFUSIONS JOHN L. CAMERON, M.D., Department
F.A.C.S.
of Surgery, The Johns Hopkins Medical Institutions,
Inflammatory disease of the pancreas is associated with a number of well-documented sequelae. Hypocalcemia, hyperglycemia, abscess, and pseudocyst formation are some of the more common complications seen with acute attacks. Chronic or recurrent inflammatory disease can result in exocrine insufficiency with steatorrhea and endocrine insufficiency, resulting in diabetes. In addition, in the last decade chronic ascites’, 2 and chronic pleural effusion+ 3 have also been recognized as complications of chronic pancreatitis. Despite the marked disparity in clinical presentation and physical findings, the etiologies of pancreatic ascites and pancreatic pleural effisions are identical and not infrequently they are seen together in the same patient. In recent years the pathogenesis of these two entities has been defined, their diagnosis simplified, and guidelines for management established.
Baltimore,
Maryland
The recognition of patients with chronic massive pancreatic pleural effusions has been more recent. In 1973 Anderson et al.” reported 5 patients with this entity and were able to document an additional 11 cases from the literature. In 1976 a series of 34 patients with massive chronic pancreatic ascites and/or effusions from the Johns Hopkins Hospital, 12 (35%) had a pancreatic pleural effusion either alone or in conjunction with ascites. Thus, as awareness of chronic massive pancreatic pleural effusion increases, its recognition can be expected to increase as has that of pancreatic ascites. Pathogenesis
When the first patients with ascites were reported in association with chronic pancreatitis, an obvious explanation was lacking. Blocked intraperitoneal lymphatics secondary to chronic pancreatitis,‘O and subacute periIncidence toneal inflammation from pancreatic enzymes” were The first patients with pancreatic ascites were re- suggested as possibilities. There can be no doubt now, ported in the early 1950’s.4-6Sporadic case reports fol- however, that pancreatic ascites is secondary to a panlowed. In 1967 Cameron et al.’ in a review were able to creatic duct disruption with the leakage of pancreatic document only 13 cases from the literature but estab- secretions directly into the peritoneal cavity. Pancreatic lished simple criteria for its diagnosis. Thereafter, iden- duct disruptions in the face of inflammatory pancreatic tification became more frequent and in 1974 Donowitz disease are common. Often, however, they occur during et al.’ were able to find 80 reported patients with an attack of acute pancreatitis. In this setting the pancreatic ascites, and added 5 of their own. In 1976 inflammatory reaction results in a walling off of the Sankaran and Walt8 reported a series of 26 patients ductal leak by the back wall of the stomach, the with pancreatic ascites seen at Wayne State University transverse colon and mesocolon, and other adjacent over a 17-year period. They stated that 15% of all structures and organs. This walling off results in a patients seen at their institution with pseudocysts had pseudocyst. Occasionally, however, such a duct disrupconcomitant pancreatic ascites.s In 1976 Cameron et tion occurs in the face of chronic inflammatory panal.2 reported a series from the Johns Hopkins Medical creatic disease, in the absence of acute inflammation. Institutions, seen over a lo-year period, of 22 patients In this setting the leak may only be partially walled with pancreatic ascites and 5 additional patients with off, so that a small pseudocyst with a leak results; or both pancreatic ascites and pleural effusions. During the leak is not walled off at all and the ductal hole is in this same interval approximately 40 patients with class- direct communication with the surrounding environical pseudocysts were operated upon at their institution. ment. If the duct disruption is anterior, an internal Thus, as awareness of pancreatic ascites has increased, pancreatic fistula into the peritoneal cavity is formed its recognition has also increased to the point where its and pancreatic secretions flow freely into the abdomen. relative frequency in some series approaches that of Inasmuch as the enzymes are not activated, an acute classical pseudocysts. peritonitis does not occur and painless ascites results. Some peritoneal irritation does occur, however, because large quantities of albumin are found in the ascitic Received May 2, 1977. Accepted July 22, 1977. fluid. Because there is no albumin in pancreatic secreAddress requests for reprints to: John L. Cameron, M.D., Departtions, it has to be from a subacute or chronic peritoneal ment of Surgery, The Johns Hopkins Medical Institutions, Baltimore, Maryland, 21205. exudative reaction. In this same setting, if the duct 134
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disruption is posterior, the pancreatic secretions flow into the retroperitoneum. Once in the retroperitoneum they track along the path of least resistance, which usually is along the esophagus or aorta up into the mediastinum.” In the mediastinum they can be contained and present as a mediastinal pseudocyst,” or more commonly, they can penetrate one or both pleural surfaces and present as unilateral or bilateral pleural effusions. In such instances, the patient has an internal pancreatic fistula between his pancreatic duct and one or both pleural cavities. Although these internal fistulae usually pass through the aortic or esophageal hiatus, instances have been reported in which the fistula passes directly from a pseudocyst up through the dome of the diaphragm into the right or left pleural cavities. l3 These effusions are not to be confused with the small left-sided pleural effusions seen with attacks of acute pancreatitis, which are sympathetic in nature, selflimited, and require no treatment. Chronic pancreatic pleural effusions are the result of an internal pancreatic fistula into the pleural cavity and are massive, recur rapidly if tapped, and require specific therapy (fig. 1). As surgeons have become aware that internal fistulae are the source of pancreatic ascites and pleural effusions, the ductal or pseudocyst leaks have been demonstrated with increasing frequency grossly at the time of surgery or with operative pancreatography.14 In our series of patients with internal pancreatic fistulae at the Johns Hopkins Medical Institutions, 9 patients with pancreatic ascites have undergone pancreatography.” In 8 of the patients the leak was demonstrated; 4 directly from the main pancreatic duct and 4 from pseudocysts. A pseudocyst was demonstrated in the 9th patient but the leak was not found. Three of our patients with pancreatic pleural effusions have undergone pancreatography, and the leak was demonstrated in 2 of them. Furthermore, there are a number of reports of patients with pancreatic ascites in whom a leak from a small pseudocyst or from the main duct was demonstrated with endoscopic retrograde pancreatography before undergoing surgery.“, x, ‘%I7 Finally, drainage of the leak surgically into the stomach or small bowel routinely cures the ascites or effusion.‘” Therefore, the pathogenetic mechanism seems certain. The etiology of the chronic pancreatitis in patients with internal pancreatic fistulas is usually alcohol consumption Twenty-eight (82%) of the 34 patients in our series were alcoholics.2 Two-thirds of the 85 patients with pancreatic ascites in the review of Donowitz et al. were alcoholics.’ How or why the duct disruption that results in an internal pancreatic fistula occurs in these alcoholics in the absence of any clinical symptoms is not known. Trauma is also well documented as a mechanism for pancreatic duct disruption and the formation of an internal pancreatic fistula, and is the most common etiology in children.’ In the past year on two occasions at our institution surgical trauma to the main pancreatic duct has resulted in an internal pancreatic fistula with pancreatic ascites. There have been no definite instances of chronic pancreatic ascites or pleural effusions secondary to biliary tract-induced pan-
FIG. 1. A, chest X-ray of a 36-year-old male with an internal pancreatic fistula into his chest. He was treated nonoperatively initially, but his effusion recurred 2 months later. At surgery a small tract up into his mediastinum along his aorta was identified and divided, and a pseudocyst was drained. His effusion has not recurred. B, chest X-ray of a 32-year-old male with both pancreatic ascites and a pancreatic pleural effusion. Both his ascites and effusion resolved on nonoperative therapy.
creatitis. One patient has been reported with documented pancreatic cancer in association with pancreatic ascites, but this is distinctly unusual.‘” In the vast majority of instances, the etiology will be benign. Presentation The clinical presentation of patients with internal pancreatic fistulae is often deceptive and usually does not suggest chronic inflammatory pancreatic disease. Of the 34 patients reported from Hopkins in 1976,2only 14 had a history of an episode of acute pancreatitis, and in most instances it was months or years before presenting with ascites or a pleural effusion. The remaining 20 patients had no history suggestive of inflammatory disease of the pancreas (table 1). Even though ascites frequently accompanies an attack of acute pancreatitis, it is usually self-limited and resolves as the attack abates. Only rarely after acute pancreatitis will the ascites persist and present the therapeutic problems of
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pancreatic ascites. The age of these 34 patients ranged patients with pancreatic pleural effusions found in the from 4 to 65 years and averaged 40 years. Twenty-nine literature in 1973, 13 presented with primarily pulmoof the patients were male and only 5 were female. nary symptoms.3 The effusion can occur either on the Twenty-six of the patients with internal pancreatic right or on the left, although left-sided effusions seem somewhat more common. Instances of bilateral effufistulae were black and 8 were white. Patients with pancreatic ascites present primarily sions secondary to an internal pancreatic fistula have with a history of a slowly increasing abdominal girth also been reported.3 The effusions are usually massive, (table 2). Because most patients have a significant filling most or all of the pleural cavity. Internal pancreatic fistulae into the peritoneal and history of alcoholic intake, cirrhosis with ascites is often the admitting diagnosis. Tuberculous peritonitis, pleural cavities may be present concomitantly in the constrictive pericarditis, the Budd-Chiari syndrome, same patient. Of the 34 patients we reported in 1976, 5 and intraperitoneal carcinomatosis are other diagnoses (15%) had both ascites and a pleural effusion. Thirtythat can be suggested by the clinical presentation. two per cent of the 26 patients with pancreatic ascites Abdominal pain can be present but usually is not a in Sankaran and Walts’series had concomitant pleural prominent part of the clinical presentation. In only 4 of effusions.8 In 2 patients they were able to demonstrate the 27 patients in the Hopkins series with pancreatic a definite internal fistula between a pseudocyst and the ascites was abdominal pain a component of the present- right pleural cavity. ing complaint. When pain is present, it is often mild. Weight loss, despite the massive ascites, is common.7 Diagnosis On physical examination massive ascites is the most In the past patients with pancreatic ascites presented prominent feature. Abdominal tenderness is usually absent, but if present is mild. Skin lesions which on a difficult clinical diagnostic challenge. In the face of a biopsy have proven to be subcutaneous fat necrosis heavy alcoholic intake, and in most patients in the have been present in 2 of our 34 patients. These skin absence of a history of pancreatitis, cirrhosis with lesions were also present in 9 of the 85 patients reviewed ascites often appeared to be an obvious explanation. by Donowitz et al.’ This incidence of subcutaneous fat When pancreatic ascites occurred in a patient with necrosis, thought secondary to circulating pancreatic concomitant liver disease, which is often the case with enzymes, far exceeds that seen in association with alcohol being the etiological agent for both diseases, acute pancreatitis. undoubtedly the diagnosis was never made. Only when Patients with pancreatic pleural effusions present the entity occurred in the absence of abnormal liver even more of a clinical paradox. Generally their symp- functions was the diagnosis apt to be pursued to the toms are that of dyspnea, chest pain, or a cough, and point of uncovering the pancreatic etiology. Now, howthere is little to suggest abdominal pathology (table 2). ever, data have accumulated so that the differentiation Pulmonary parenchymal or pleural disease is usually of pancreatic ascites from other disease entities with the admitting diagnosis. Among the 7 patients in the ascites can be done quickly and simply. Hopkins series with pancreatic pleural effusion without The amylase in the ascitic fluid of a patient with ascites, only 2 had abdominal complaints. Of the 16 pancreatic ascites is always markedly elevated, often up in the thousands.2*8,l4 In addition, the ascitic fluid albumin is usually elevated to the range of 3 g per dl or TABLE 1. Incidence of acute Dancreatitis in Datients with internal above.za8 In our series of patients with internal pancreatic fistulas, all 27 patients with pancreatic ascites had markedly elevated ascitic fluid amylase values. Of pancreatitis Pleural the 27 patients, 20 had ascitic fluid albumin levels over effusion 3 g per dl. The remaining 7 patients with albumin Current 1 1 0 levels less than 3 g per dl were malnourished and Prior episode 9 2 1 markedly albumimenic. In Sankaran and Walt’s seNone 12 4 4 ries8 all 26 patients had elevated ascitic fluid amylase values, and 26 of the 27 had ascitic fluid albumin levels Total patients 22 7 5 greater than 2.5 g per dl. In cirrhotic ascites the ascitic fluid amylase value is always normal and the albumin level is usually less than 1.5 g per dl. Thus, by simply TABLE 2. Presenting complaint in 34 patients presenting to the Johns Hopkins Hospital with internal pancreatic fistulae determining the amylase and albumin content, what Internal pancreatic fistulae can be a difficult or impossible clinical differentiation, Presenting can be made easily by laboratory data. The ascitic fluid complaint Pleural Ascites Both effusion grossly is usually clear and straw-colored, but can be chylous4 in character or even bloody.6 Erythrocyte and Abdominal swelling 18 4 leukocyte counts are quite variable and do not add any Abdominal pain 3 1 1 Shortness of breath 4 accuracy to the diagnosis. Elevated lipase levels have Cough 2 also been reported in the ascitic fluid,lg but cannot be Weight loss 1 performed as quickly or simply as amylase determinations and do not add anything additional to the diagnoTotal patients 22 7 5 sis or work-up.
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137
Intraabdominal carcinomatosis can also be simulated 10 had elevated serum amylase values, but in 2 patients by a patient with pancreatic ascites who presents with it was normal. Thus, the serum amylase may serve as cachexia, marked weakness, and weight loss. Tosup-a preliminary screen, but a normal value does not rule port this picture further, we have had cytology reports out the entity. The pleural effision in all 12 patients from cell blocks of ascitic fluid come back on 2 patients had a markedly elevated amylase content, usually up with pancreatic ascites as positive for malignant cells. in the thousands. In addition, 10 of the 12 had albumin However, both patients came to surgery and were found levels greater than 3 g per dl. The 2 patients with to have only benign inflammatory pancreatic disease effision albumin levels of less than 3 g per dl were and both patients are long term survivors. Apparently both hypoalbuminemic. Primary or secondary thoracic pancreatic enzymes are capable of inducing metaplasia malignancies can also be associated rarely with effuof serosal cells in pancreatic ascites such that they can sions containing elevated amylase levels, presumably be mistaken for malignant cells. It is worth repeating secondary to blockage of the thoracic duct20 The elevathat there is only 1 patient in the literature with tions are usually minimal to moderate, however, and documented pancreatic malignancy that also had crite- do not approach the elevations into the thousands seen ria for the diagnosis of pancreatic ascites.18The great with internal pancreatic fistulae. As with pancreatic majority of patients with the clinical and laboratory ascites, we have also had a faIsely positive cytology for picture of pancreatic ascites will have benign disease, malignancy in a patient with a chronic pancreatic and even in the face of a positive ascitic fluid cell pleural effusion. Therefore, even in the face of a positive cytology, management should proceed as if the under- cytology, work-up and treatment should be pursued if the laboratory evidence points to a pancreatic pleural lying disease is treatable and curable. The serum amylase is also usually elevated in pan- effusion. Esophageal perforations with effisions high creatic ascites. The serum level is always much lower, in amylase have also been reported, but clinically their however, than the ascitic fluid level.* The serum amy- differentiation usually is not difficult.21 lase elevation is not an indication of active pancreatic Definition of the internal pancreatic fistula preoperainflammatory disease, but probably results from the tively in a patient with a chronic massive pleural passive absorption into the serum of amylase from the effusion by ERP has not yet been reported. However, ascitic fluid. The serum amylase was elevated in 26 of the fistulous tract leading from the pleural cavity to the 27 patients in our series with pancreatic ascites, below the diaphragm has been demonstrated on at but was normal in 1 patient. There are also other case least four occasions by injecting contrast media into the reports of patients with pancreatic ascites with normal pleural effusion. *, 13,** Under fluoroscopic control and serum amylase levels.7 In Sankaran and Walt’s series by changing the position of the patient, the fistulous of 26 patients, 8 the serum amylase was elevated in tract can often be outlined. This information is confirmall. Thus, although the serum amylase value may be a atory anatomical evidence of an internal fistula, but is reasonable screen for pancreatic ascites, a normal se- not quite as valuable as ERP. The primary pancreatic rum value does not rule out the entity and thus the ductal pathology, which will determine the operative ascitic fluid values should be obtained in all patients procedure if the patient comes to surgery, is not defined with ascites. by pleural space injection, but is by ERP. Recently, endoscopic retrograde pancreatography (ERP) has added another dimension to the diagnosis Treatment and work-up of a patient suspected of having pancreatic ascites. There have been at least 8 reported cases of The treatment of internal pancreatic fistulae remains ERP*,8*15-17 successfully demonstrating pancreatic duct somewhat controversial (table 3). Once the diagnosis pathology, and in 4 of the patients the leak into the has been confirmed by ascitic or pleural fluid amylase peritoneal cavity was seen. This clearly gives anatomi- and protein elevations, the treatment can be either cal evidence for the diagnosis and pathogenesis of pan- nonoperative or operative. We have generally followed creatic ascites. More importantly, however, if the pa- a course of treating patients with internal pancreatic tient comes to surgery the operative time will be fistulae initially with a period of nonoperative manageshortened considerably as the pathological anatomy ment. In an attempt to decrease pancreatic secretion to will already be known. Furthermore, it avoids the need a minimum, and thus encourage the sealing of the to open the duodenum for operative pancreatography pancreatic duct or pseudocyst leak, the following regiat the time of surgery, thus decreasing the chance of men has been used: (1) patients have been given nothpostoperative morbidity. Because understanding the ing by mouth, and a nasogastric tube was inserted; (2) pathological anatomy at the time of surgery is the key Diamox and atropine are administered to decrease to designing successfully an adequate resectional or pancreatic secretion further: (3) paracenteses are perdrainage procedure for pancreatic ascites, ERP should formed as needed to keep the peritoneal cavity free be performed in all patients with pancreatic ascites from fluid, and thus encourage the approximation of before surgery. peritoneal surfaces and the sealing of the leak; (4) The diagnostic work-up of a patient with an internal intravenous hyperalimentation has been carried out in pancreatic fistula into a pleural cavity, presenting with recent years because of the poor nutritional status of a chronic massive pleural effusion, should proceed in a most patients with internal pancreatic fistulae, and to fashion identical to that for pancreatic ascites. In our replace the protein lost from the multiple paracenteses. series of 12 patients with pancreatic pleural efTusions,* In the series from the Johns Hopkins Medical Insti-
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tutions, 17 patients with pancreatic ascites were treated initially by the above regimen.* In 8 patients the ascites cleared, several within the first 2 weeks. Seven (41%) have remained permanently free from ascites, 1 patient recurring after a 6-month ascitic-free interval. There were four deaths among these 17 patients undergoing nonoperative therapy. One of the four deaths was secondary to gastrointestinal bleeding; one was from sepsis probably related to hyperalimentation, and the remaining two deaths were sudden and unexplained, presumably either from a myocardial infarction or a pulmonary embolus. This represents a significant mortality in the conservatively treated group, but is more an indication of the state of health of the patients rather than the risks of treatment. Others have noted a high recurrence and low success rate with nonoperative therapy, and are not enthusiastic about its use.8 However, these are patients with a significant operative risk, most of whom would benefit from a course of hyperalimentation before surgery in any event, who have a reasonable chance of success (7 of 17, 41%) with conservative therapy, and we continue to recommend its use (table 4). In the TABLE3. Management of patients with internal pancreatic fistulae Nonoperative treatment Nasogastric tube suction Diamox and atropine Paracenteses Thoracenteses or chest tube Hyperalimentation Operative treatment Direct duct leak Roux en-Y drainage of duct leak Pancreatic resection if leak is distal Roux en-Y drainage of remnant if proximal duct disease present Pseudocyst Roux en-Y drainage of pseudocyst leak Cystogastrostomy if Roux en-Y not possible Resect cyst if small and distal Roux en-Y drainage of remnant if proximal duct disease
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review of Donowitz et al., the mortality rate for 15 patients treated medically was 20%.7 If after a 2- or 3-week period the ascites continues to recur, most patients should be operated upon. There have been five case reports of low dose irradiation to the pancreas in patients with pancreatic ascites with resolution of the ascites in each instance.5*l’* 23-25If a patient were a prohibitive operative risk, this course could be considered. The success of operative management of pancreatic ascites depends upon adequate knowledge of the pathological anatomy. ERP should be attempted preoperatively in all patients being considered for surgery. Multiple case reports document the ability of ERP to define the pathology and at times the site or sites of the ductal leak. If this is successful, operative time will be decreased and the need to open the duodenum for pancreatography at the time of surgery obviated (fig. 2). If ERP is unsuccessful, operative pancreatography should be performed at the time of surgery. This can be done by cannulating the ampulla through a duodenotomy, or by a retrograde technique after amputating the tail of the gland. On occasion the ductal anatomy will be defined adequately by just injecting the pseudocyst with contrast media. This is unusual, however, and pancreatography will be required in most instances. The type of surgical procedure used will depend upon the information gained by pancreatography. If a direct duct leak is demonstrated with no pseudocyst, a direct sinastomosis between the leak and a Roux en-Y jejunal loop will be preferable. If the leak is distal in the tail, a distal pancreatectomy could also be considered. If a small cyst is present in the distal portion of the gland, as is frequently the case with pancreatic ascites, a distal resection removing the tail of the gland and cyst is indicated. If proximal duct disease is present, the pancreatic remnant should be drained with a Roux en-
TABLE4. Results of treatment of 34 patients at the Johns Hopkins Hospital with internal pancreatic fistulae
Results
Internal pancreatic fistulae
-
Ascites
Pleural effusion
Both
Nonoperative Success Failure Deaths
7 6 4
2 1 0
3 2 0
Total patients
17
3
5
Operative Success Failure Deaths
8 0 0
4 1 0
2 0 0
Total patients
8
5
2
FIG. 2. Endoscopic retrograde pancreatography (ERP) of a 32year-old male with pancreatic ascites. The large arrow points to the normal proximal pancreatic duct. The middle-sized arrow points to the distal pseudocyst, and the multiple small arrows point out contrast media leaking freely into the peritoneal cavity.
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Y loop. If the cyst is large, or in a region of the gland not amenable to resection, drainage of the cyst into a Roux en-Y loop or the stomach is preferable. External drainage of the pseodycyst has been accompanied by a very high recurrence rate.*” If these procedures are carried out with a clear understanding of the ductal pathology, there will be few operative recurrences (table 4). Ten patients in our series with pancreatic ascites, and 2 patients with both ascites and pleural effisions were treated surgically. In 10 patients the treatment was successful. One patient subsequently recurred 5 months later and required reoperation, but since then has been as&es-free. There were two deaths among these 12 patients (17%). In the literature review reported by Donowitz et al. in 1974, the operative mortality among 66 patients with pancreatic ascites treated surgically was 15%.’ The need for adequate pancreatography is nicely demonstrated by the series of patients with pancreatic ascites presented by Sankaran and Walt.8 In 7 patients treated surgically with the aid of a pancreatogram, the results were satisfactory in all with no recurrences. In contrast, 19 patients were managed without the aid of a pancreatogram, and the recurrence rate was 53%. The treatment of patients with internal pancreatic fistulae into the chest presenting with chronic massive pleural effusions has been somewhat more successful. Most authors recommend initial nonoperative management, and the success rate has been higher than that for pancreatic ascites. In addition to hyperalimentation, nasogastric suction, and Diamox and atropine administration, patients have been treated with multiple paracenteses or a chest tube. In our series reported in 1976,’ 5 of 8 patients with chronic massive pancreatic pleural effusions, alone or in conjunction with pancreatic ascites, undergoing nonoperative treatment had successful outcomes. Because these patients have a longer fistulous tract than do those with pancreatic ascites, the fistula may be more apt to close without surgical intervention. Six of 7 patients with pancreatic pleural effusions from our institution were managed successfully by surgery (table 4). It is important to remember that the operative management of pancreatic pleural effusions is identical to that of pancreatic ascites. ERP should be attempted before surgery in all patients. If that is unsuccessful, a laparotomy should be performed and operative pancreatography carried out. The appropriate pancreatic drainage or resection should then be performed. Inasmuch as many of these patients present with only chest symptoms, and with no abdominal complaints, a thoracic or thoracoabdominal approach was used in early cases .3,*’It is absolutely unnecessary to enter the chest, and a total abdominal approach should be planned. There were no deaths in the 12 patients with pancreatic pleural effusions in our series. Why these patients with pancreatic pleural effusions should tolerate medical and surgical therapy better than patients with pancreatic ascites is unknown. Perhaps as more patients are recognized and treated, this will become apparent.
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During the last decade the treatment of patients with internal pancreatic fistulae has not been standardized or, for the most part, baaed on adequate anatomical information. In addition, hyperalimentation has not been routinely employed. Today, most patients with internal pancreatic fistulae should be handled successfully, with very low mortality and recurrence rates. A 2- or 3-week period of nonoperative treatment will allow almost one-half of these patients to leave the hospital cured without surgery. The remainder, after adequate pre- or intraoperative pancreatography, should be managed successfully by a drainage or resectional procedure. In the chronically ill patient who has not closed his fistula on conservative management, who represents a high anesthetic risk, a short course of radiotherapy might be considered. With this regimen, most patients with internal pancreatic fistulae should have a successful outcome. Summary Over the past decade ascites and pleural effusions have become recognized as complications of chronic inflammatory disease of the pancreas. In the setting of heavy alcoholic intake, but usually without symptoms, a disruption of the main pancreatic duct can occur, resulting in an internal fistula between the duct and peritoneal cavity, producing massive ascites. If the duct disruption is posterior, pancreatic secretions can track up into the mediastinum and then escape into one or both pleural spaces, resulting in an internal fistula between the pancreatic duct and pleural space, producing a massive effusion. Diagnosis of the internal pancreatic fistula can be made by finding high amylase and albumin levels in the ascitic or pleural fluid. Serum amylase is usually, but not always elevated. Treatment initially should be nonoperative, and should include intravenous hyperalimentation, nasogastric suction, Diamox and atropine administration, and either multiple paracenteses, or multiple thoracenteses, or a chest tube insertion. If medical management is unsuccessful after a 2- or 3-week trial, surgical intervention is indicated. Pancreatography is essential to define the pathological pancreatic duct anatomy. When the duct pathology is determined, and the internal fistula identified, an appropriate drainage or resectional procedure can be chosen. With this regimen, most patients with an internal pancreatic fistula should be managed successfully. REFERENCES 1. Cameron JL, Anderson RP, Zuidema GD: Pancreatic ascites. Surg Gynecol Obstet 125328-332, 1967 2. Cameron JL, Kieffer RS, Anderson WJ, et al: Internal pancreatic fistulas: pancreatic ascites and pleural effisions. Ann Surg 183:587-593, 1976 3. Anderson WJ, Skinner DB, Zuidema GD, et al: Chronic pancreatic pleural effusions. Surg Gynecol Obstet 137:827-830, 1973 4. Crandell WB, Stueck GH Jr, McEvoy CD Jr: Chylous ascites due to a pancreatic pseudocyst. Surgery 34:111-116,1953 5. Davis ML, Kelsey WM: Chronic pancreatitis in childhood. Am J Dis Child 81:687-692, 1951
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6.Smith EB: Hemorrhagic ascites and hemothorax associated with benign pancreatic disease. Arch Surg 67:52-56,1953 7. Donowitz M, Kerstein MD, Spiro HM: Pancreatic ascites. Medicine (Baltimore) 53:183-195, 1974 8. Sankaran S, Walt AJ: Pancreatic ascites: recognition and management. Arch Surg 111:430-434, 1976 9. Sankaran S, Walt AJ: The natural and unnatural history of pancreatic pseudocysts. Br J Surg 62:37-44,1975 10. Schmidt EH, Whitehead RP: Recurrent ascites as an unusual complication of chronic pancreatitis. JAMA 189533-535, 1962 11. Gambill EE, Walters W, Scanlon PW: Chronic relapsing pancreatitis with extensive subacute peritonitis and chronic, recurrent massive “chylous” ascites. Am J Med 28668-670, 1960 12. Jaffe BM, Ferguson TB, Holtz S, et al: Mediastinal pancreatic pseudocysts. Am J Surg 124600-606, 1972 13. Tombroff M, Loicq A, DeKoster JP, et al: Pleural effusion with pancreaticopleural fistula. Br Med J 1:330-331, 1973 14. Cameron JL, Brawley RK, Bender HW, et al: The treatment of pancreatic ascites. Ann Surg 170:668-676, 1969 15. Davis RE, Graham DY: Pancreatic ascites: the role of endoscopic pancreatography. Am J Dig Dis 20:977-980,1975 16. Levine JB, Warshaw AL, Falchuk KR, et al: The value of endoscopic retrograde pancreatography in the management of pancreatic ascites. Surgery 81:360-362,1977 17. Rawlings W, Bynum TE, Pasternak G: Pancreatic ascites: diag-
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nosis of leakage site by endoscopic pancreatography. Surgery 81:363-365, 1977 Cayten CG, Mullen JL, Rosato EF: Pancreatic ascites with carcinoma of the pancreas. Am J Gastroenterol58:73-76, 1972 Sileo AV, Chawla SK, LoPresti PA: Pancreatic ascites: diagnostic importance of ascitic lipase. Am J Dig Dis 20:1110-1114, 1975 Kaye MD: Pleuropulmonary complications of pancreatitis. Thorax 23:297-306, 1968 Bellman MH, Rajanatnam HN: Perforation of the esophagus with amylase rich pleural effusion. Br J Dis Chest 68:197-201, 1974 Geffroy Y, Boureille J, Morere P, et al: Sem Hop Paris 44:13561368, 1968 Morton RE, Deluca R, Reisman TN, et al: Pancreatic ascites: successful treatment with pancreatic radiation. Am J Dig Dis 21:333-336, 1976 Kavin H, Sobel JD, Dembo AJ: Pancreatic ascites treated by irradiation of pancreas. Br Med J 2:503-504,197l Oeconomopoulos CT, Lee CM Jr: Pseudocysts of the pancreas in infants and young children. Surgery 47:836-845, 1960 Smith RB III, Warren WD, Rivard AA, et al: Pancreatic ascites: diagnosis and management with particular reference to surgical technics. Ann Surg 177:538-546,1973 Mitchell CE: Relapsing pancreatitis with recurrent pericardial and pleural effusions. Ann Intern Med 60:1047-1053, 1964