December 1978
950
The Journal oj P ED I AT R J C S
Pseudocyst formation In hereditary pancreatitis The previously estimated incidence ofpseudocyst formation in hereditary pancreatitis is approximately
lrRo. Our experience in nine patients with hereditary pancreatitis yielded jive surgically documented pseudocysts and three additional patients with radiographically documented mass effects. Recent studies have shown a 20% spontaneous regression rate for pancreatic pseudocysts (oj all etiologies), when evaluated by B-mode ultrasonography; our experience suggests that the incidence oj pseudocyst formation in hereditary pancreatitis is considerably higher than previously suspected. Ultrasonography is thought to be an excellent method jar diagnosing this entity, of evaluating mass effects identified on radiographic studies, and of providing sequential evaluation of pseudocysts treated surgically or conservatively.
Andrew M. Fried, M.D.,* and Albert C. Selke, M.D., Lexington, Ky.
BEGINNING WITH the original description by Comfort and Steinberg in 1952' only nine pancreatic pseudocysts are documented in conjunction with a family history of hereditary pancreatitis. The incidence of pseudocyst formation in hereditary pancreatitis has been estimated at 10%" compared to an incidence of pancreatic calcifications in the range of 35 to 50%.·' :,In an elegant review and a description of three new kindreds, Kattwinkel et al,! in J973, cited one definite pseudocyst and referred to one other among 30 definite and 51 suspected cases of familial
pancreatitis. Eight members of a single kindred with hereditary pancreatitis have been seen at this institution in the last nine years and a ninth family member (J.e.) was followed at a nearby hospital. Five surgically documented pancreatic pseudocysts have been encountered; an additional three patients presented radiographic evidence of abdominal masses and, although surgical documentation is'lacking, the probability of pseudocyst formation is quite high. Three pseudocysts were diagnosed by ultrasound. In one documented example of pseudocyst. ultrasonography proved to be of great value in detecting spontaneous rupture of the pseudocyst, prompting immediate surgical intervention. Intraperitoneal rupture, the most serious complication of pseudocyst, demands prompt surgical treatment. Our experience suggests that the incidence of From (he Department of Diagnostic Radiology, University of Kentucky Medical Center. "Reprint address: Department of Diagnostic Radiology, University of Kentucky Me~ical Center, Lexington, KY 40506
Vol. 93, No.6, pp. 950-953
pseudocyst formation in hereditary pancreatitis is considerably higher than has been previously reported. CASE REPORTS
Patient D. S. is an 8-year-old white boy with a history of recurrent episodes of abdominal pain, admitted with a palpable left upper quadrant mass. The upper gastrointestinal series confirmed smooth extrinsic compression of the stomach. Ultrasonography outlined a well-circumscribed cystic mass in the left upper quadrant thought to represent a pancreatic pseudocyst (Fig. I). While in the hospital the patient developed varicella and was discharged temporarily. At home, he apparently sustained some trauma to the left upper quadrant and a repeat ultrasonogram (Fig. 2) showed decrease in the size of the pancreatic pseudocyst and clearly demonstrated free intraperitoneal fluid, not previously seen. A diagnosis of rupture of the pseudocyst was made; exploratory laporotomy revealed a pancreatic pseudocyst in the retrogastric area with a small leak in its anterior wall; Roux-en-Y drainage was accomplished without difficulty. His postoperative course was unremarkable and a repeat ultrasonogram was normal. Patient D. R. a l O-year-old white girl, presented with epigastric and left upper quadrant pain. One examiner detected left upper quadrant "fullness" on physical examination; several others did not. Ultrasonography demonstrated a large epigastric and left upper quadrant cystic mass. An upper gastrointestinal series showed extrinsic compression of the stomach by a retrogastric mass. At surgery, about 1,400 rnl of cyst fI uid was evacuated and a cystogastrostomy was performed. Patient 1. C. is a IO-year-old white boy (first cousin of Patients P. R. and D. R.), admitted with abdominal pain and a left upper quadrant mass which, at ultrasound evaluation, was cystic. with gravity-dependent debris. An upper gastrointestinal series was
0022-34761781 120950+04$00.4Q/O 1D 1978 The C. V. Mosby Co,
VoIUI/lf! 93 Number 6
not done. A "grapefruit-sized" mass was identified at operation and cystogastrostomy accomplished. Amylase determination on the cyst fluid yielded a value of 65.000 units. Patient T. S. is a lO-year-old white girl with a history of recurrent pancreatitis beginning at age 3. Her 29-year-old brother has documented pancreatitis as does her father and two paternal uncles. She was admitted with abdominal pain and a pleural effusion of the left side (amylase greater than 200,000 units). An upper gastrointestinal series demonstrated a mass effect thought to represent a pseudocyst. At operation a large pseudocyst was identified arising from the body of the pancreas; drainage by cystogastrostomy was accomplished without difficulty. She was later admitted with an episode of abdominal pain but ultrasound study showed no recurrence of the pseudocyst, and conservative management produced rapid resolution of symptoms. Patient P. R .. a 5-year-old girl, was first seen complaining of left upper quadrant and flank pain. An intravenous pyelogram demonstrated compression of the left collecting system by a left upper quadrant mass without invasion of the collecting system or distortion of the renal outline. This suggested a mass in either the pancreas or retroperitoneal region adjacent to the pancreas. An upper gastrointestinal series was not performed. An-exploratory laporotorny revealed a pseudocyst extending from the tail of the pancreas into the Gerota fascia and the left perirenal space. requiring distal pancreatectomy. splenectomy, and left nephrectomy. Family history includes two paternal first cousins with documented hereditary pancreatitis. The patient is part of the same kindred as Patient T. S.; the link is several generations removed. Patient V. E. is a 14-year-old white girl with a history of recurrent abdominal pain and "stomach problems" since birth. She, too, is a member of the same kindred as Patient D. S. in which the diagnosis of hereditary pancreatitis is well established. On admission no abdominal tenderness or mass was identified. The serum amylase value was 2.272 units and an upper gastrointestinal series demonstrated extrinsic compression on the lesser curvature of the stomach suggesting a pancreatic pseudocyst (Fig. 3). Her response to conservative management was satisfactory. and she was discharged with the diagnosis of hereditary pancreatitis and probable pancreatic pseudocyst. A repeat upper gastrointestinal series revealed considerable diminution in the extrinsic compression of the stomach and the possibility of spontaneous drainage or resorption was entertained. Patient M. R. is a l7-year-old boy with recurrent episodes of abdominal pain diagnosed as pancreatitis. beginning at 8 years of age. His first cousin. Patient P. R. has documented hereditary pancreatitis and both are of the same kindred as Patient T. S. On admission the patient had left upper quadrant tenderness and a serum amylase level of 2,432 units. Conservative management produced a regression of symptoms. An upper gastrointestinal series demonstrated evidence of a mass in the region of the head of the pancreas; no operative intervention was undertaken. Patient M. M. is a 4-year-old boy in the same kindred admitted with a history of inter mitt ant upper abdominal pain since the age of 2. An uncle. 32. has hereditary pancreatitis documented elsewhere. He was treated conservatively with satisfactory regression of his symptoms. An upper gastrointestinal series demon-
Pseudocyst formation in hereditary pancreatitis
951
;'
Fig. 1. Patient D. S. Transverse sonogram at 2 ern below the xiphoid process. Note the large left sided cystic structure ( C) anterior to the left kidney (LK). ML = Midline; L = liver. strated a retroperitoneal mass posterior to the duodenal bulb and proximal C-Ioop. Because of his steady improvement. surgical intervention was not necessary. Patient M. T. R., a 2-year-old white boy is the brother of Patient M. R. He was admitted with a history of recurrent abdominal pain. Serum amylase on admission was 1,360 units and an upper gastrointestinal series was interpreted as normal. The patient improved on conservative management and was discharged without operative intervention. In summary, nine patients, ranging in age from 2 to 17 years, were seen; five were boys. Roentgenographic abnormalities were noted on plain films in live and in six of the seven upper gastrointestinal series performed. Ultrasonography demonstrated abnormalities in all three patients examined. Five patients had surgically documented pancreatic pseudocysts and four children improved on conservative management.
DISCUSSION Hereditary pancreatitis has been defined by Gross' as "inflammation of the pancreas, usually recurrent from childhood, with unusual prevalence among blood-related groups of persons in accordance with mend elian laws (autosomal dominant gene)."
The sex incidence
is
approximately equal and the disease is described exclusively in Caucasians. The clinical features of the disease have been well documented and a variety of complications described. The clinical picture of hereditary pancreatitis follows a relatively predictable pattern with recurrent attacks of severe upper abdominal pain lasting several days. with onset in early childhood." There is disagreement about how often childhood pancreatitis is hereditary in nature;
952
or
Fried and Selke
The Journal Pediatrics December 1978
'x
u
s
Fig. 2. Patient D. S. Repeat ultrasonogram three days later. Longitudinal scan at 7 ern (0 the right of the midline, Note free fluid within the abdomen (arrows) separating liver from diaphragm and collecting in the subhepatic space.
Fig. 3. Patient V. E. Upper gastrointestinal series shows extrinsic compression on the lesser curvature and the antrum of the stomach.
Sibert found only one documented example of hereditary pancreatitis in nine patients reviewed. However, Kattwinkel et al,' in a report encompassing 21 kindreds concluded that the hereditary form was the most common cause of recurrent pancreatitis in childhood. Including both recurrent and single episodes of pancreatitis, the most common
etiologies of pancreatitis in childhood arc traumatic and idiopathic.":" If only patients with recurrent episodes an: considered, it appears that Kuttwinkel's conclusion remains valid. The most common radiographic manifestations encountered in hereditary pancreatitis include pancreatic calcification which is reported present in 33 to 50% of documented examples and, when sought, dilatation of the pancreatic ductal system." t:'·IC, When pathologic or radiographic evaluation of the pancreatic ductal system has been obtained, dilatation of both the main duct and its radicals has been found in every case and appears to be it uniform feature of the disease. In approximately 80% of individuals with pancreatic pseudocyst. displacement of the stomach was noted on upper gastrointestinal series. Pleural effusion of the left side is a frequent finding. Pseudocysts occurring in hereditary pancreatitis are similar to those of other causes. The lesser sac is a frequent location with anterior displacement of the stomach and proximal duodenum!" and occasional inferior displacement of portions of the transverse colon. Rupture of a pancreatic pseudocyst into the Gerota fascia. masquerading as a primary renal neoplasm (Patient P. R.), appears to be unusual. In our kindred of nine patients with documented hereditary pancreatitis, eight had clear radiognLJ?hic manifestations of a mass effect in the upper abdomen and five surgically proven pseudocysts. Regression of a mass effect in one patient is compatible with spontaneous
VO/lIl11e 93 Number 6
regression or internal drainage of a pseudocyst; pancreatic edema or phelgrnon could produce such a picture. Ultrasonography will be of considerable value in distinguishing edema from pseudocyst. In one instance ultrasonography documented a decrease in the size of the pseudocyst due to intraperitoneal rupture. The finding of clearly demonstrable calcification in only one example is unexplained. The relatively recent introduction of ultrasonography as a pivotal diagnostic tool in the identification of pancreatic psuedocysts": I" suggests that the overall incidence of this entity in acute pancreatitis is far greater than originally supposed. In a series of 99 patients, Gonzalez'" found positive ultrasound scans In 52 and noted spontaneous resolution in approximately 20% of demonstrated cystic lesions. A palpable mass was identified in only 38.3% of patients in this series. The apparently constant finding of dilatation of the pancreatic ductal system at radiography 01' pathology in hereditary pancreatitis allows the speculation that the basic pathophysiology involved in this disease entity may predispose to pseudocyst formation. The desire to avoid surgical intervention when possible, the natural history of spontaneous resolution of the disease process in a matter of days, and the established rate of regression of pseudocysts of all etiologies" (about 20
950
The Journal oj P ED I AT R J C S
Pseudocyst formation In hereditary pancreatitis The previously estimated incidence ofpseudocyst formation in hereditary pancreatitis is approximately
lrRo. Our experience in nine patients with hereditary pancreatitis yielded jive surgically documented pseudocysts and three additional patients with radiographically documented mass effects. Recent studies have shown a 20% spontaneous regression rate for pancreatic pseudocysts (oj all etiologies), when evaluated by B-mode ultrasonography; our experience suggests that the incidence oj pseudocyst formation in hereditary pancreatitis is considerably higher than previously suspected. Ultrasonography is thought to be an excellent method jar diagnosing this entity, of evaluating mass effects identified on radiographic studies, and of providing sequential evaluation of pseudocysts treated surgically or conservatively.
Andrew M. Fried, M.D.,* and Albert C. Selke, M.D., Lexington, Ky.
BEGINNING WITH the original description by Comfort and Steinberg in 1952' only nine pancreatic pseudocysts are documented in conjunction with a family history of hereditary pancreatitis. The incidence of pseudocyst formation in hereditary pancreatitis has been estimated at 10%" compared to an incidence of pancreatic calcifications in the range of 35 to 50%.·' :,In an elegant review and a description of three new kindreds, Kattwinkel et al,! in J973, cited one definite pseudocyst and referred to one other among 30 definite and 51 suspected cases of familial
pancreatitis. Eight members of a single kindred with hereditary pancreatitis have been seen at this institution in the last nine years and a ninth family member (J.e.) was followed at a nearby hospital. Five surgically documented pancreatic pseudocysts have been encountered; an additional three patients presented radiographic evidence of abdominal masses and, although surgical documentation is'lacking, the probability of pseudocyst formation is quite high. Three pseudocysts were diagnosed by ultrasound. In one documented example of pseudocyst. ultrasonography proved to be of great value in detecting spontaneous rupture of the pseudocyst, prompting immediate surgical intervention. Intraperitoneal rupture, the most serious complication of pseudocyst, demands prompt surgical treatment. Our experience suggests that the incidence of From (he Department of Diagnostic Radiology, University of Kentucky Medical Center. "Reprint address: Department of Diagnostic Radiology, University of Kentucky Me~ical Center, Lexington, KY 40506
Vol. 93, No.6, pp. 950-953
pseudocyst formation in hereditary pancreatitis is considerably higher than has been previously reported. CASE REPORTS
Patient D. S. is an 8-year-old white boy with a history of recurrent episodes of abdominal pain, admitted with a palpable left upper quadrant mass. The upper gastrointestinal series confirmed smooth extrinsic compression of the stomach. Ultrasonography outlined a well-circumscribed cystic mass in the left upper quadrant thought to represent a pancreatic pseudocyst (Fig. I). While in the hospital the patient developed varicella and was discharged temporarily. At home, he apparently sustained some trauma to the left upper quadrant and a repeat ultrasonogram (Fig. 2) showed decrease in the size of the pancreatic pseudocyst and clearly demonstrated free intraperitoneal fluid, not previously seen. A diagnosis of rupture of the pseudocyst was made; exploratory laporotomy revealed a pancreatic pseudocyst in the retrogastric area with a small leak in its anterior wall; Roux-en-Y drainage was accomplished without difficulty. His postoperative course was unremarkable and a repeat ultrasonogram was normal. Patient D. R. a l O-year-old white girl, presented with epigastric and left upper quadrant pain. One examiner detected left upper quadrant "fullness" on physical examination; several others did not. Ultrasonography demonstrated a large epigastric and left upper quadrant cystic mass. An upper gastrointestinal series showed extrinsic compression of the stomach by a retrogastric mass. At surgery, about 1,400 rnl of cyst fI uid was evacuated and a cystogastrostomy was performed. Patient 1. C. is a IO-year-old white boy (first cousin of Patients P. R. and D. R.), admitted with abdominal pain and a left upper quadrant mass which, at ultrasound evaluation, was cystic. with gravity-dependent debris. An upper gastrointestinal series was
0022-34761781 120950+04$00.4Q/O 1D 1978 The C. V. Mosby Co,
VoIUI/lf! 93 Number 6
not done. A "grapefruit-sized" mass was identified at operation and cystogastrostomy accomplished. Amylase determination on the cyst fluid yielded a value of 65.000 units. Patient T. S. is a lO-year-old white girl with a history of recurrent pancreatitis beginning at age 3. Her 29-year-old brother has documented pancreatitis as does her father and two paternal uncles. She was admitted with abdominal pain and a pleural effusion of the left side (amylase greater than 200,000 units). An upper gastrointestinal series demonstrated a mass effect thought to represent a pseudocyst. At operation a large pseudocyst was identified arising from the body of the pancreas; drainage by cystogastrostomy was accomplished without difficulty. She was later admitted with an episode of abdominal pain but ultrasound study showed no recurrence of the pseudocyst, and conservative management produced rapid resolution of symptoms. Patient P. R .. a 5-year-old girl, was first seen complaining of left upper quadrant and flank pain. An intravenous pyelogram demonstrated compression of the left collecting system by a left upper quadrant mass without invasion of the collecting system or distortion of the renal outline. This suggested a mass in either the pancreas or retroperitoneal region adjacent to the pancreas. An upper gastrointestinal series was not performed. An-exploratory laporotorny revealed a pseudocyst extending from the tail of the pancreas into the Gerota fascia and the left perirenal space. requiring distal pancreatectomy. splenectomy, and left nephrectomy. Family history includes two paternal first cousins with documented hereditary pancreatitis. The patient is part of the same kindred as Patient T. S.; the link is several generations removed. Patient V. E. is a 14-year-old white girl with a history of recurrent abdominal pain and "stomach problems" since birth. She, too, is a member of the same kindred as Patient D. S. in which the diagnosis of hereditary pancreatitis is well established. On admission no abdominal tenderness or mass was identified. The serum amylase value was 2.272 units and an upper gastrointestinal series demonstrated extrinsic compression on the lesser curvature of the stomach suggesting a pancreatic pseudocyst (Fig. 3). Her response to conservative management was satisfactory. and she was discharged with the diagnosis of hereditary pancreatitis and probable pancreatic pseudocyst. A repeat upper gastrointestinal series revealed considerable diminution in the extrinsic compression of the stomach and the possibility of spontaneous drainage or resorption was entertained. Patient M. R. is a l7-year-old boy with recurrent episodes of abdominal pain diagnosed as pancreatitis. beginning at 8 years of age. His first cousin. Patient P. R. has documented hereditary pancreatitis and both are of the same kindred as Patient T. S. On admission the patient had left upper quadrant tenderness and a serum amylase level of 2,432 units. Conservative management produced a regression of symptoms. An upper gastrointestinal series demonstrated evidence of a mass in the region of the head of the pancreas; no operative intervention was undertaken. Patient M. M. is a 4-year-old boy in the same kindred admitted with a history of inter mitt ant upper abdominal pain since the age of 2. An uncle. 32. has hereditary pancreatitis documented elsewhere. He was treated conservatively with satisfactory regression of his symptoms. An upper gastrointestinal series demon-
Pseudocyst formation in hereditary pancreatitis
951
;'
Fig. 1. Patient D. S. Transverse sonogram at 2 ern below the xiphoid process. Note the large left sided cystic structure ( C) anterior to the left kidney (LK). ML = Midline; L = liver. strated a retroperitoneal mass posterior to the duodenal bulb and proximal C-Ioop. Because of his steady improvement. surgical intervention was not necessary. Patient M. T. R., a 2-year-old white boy is the brother of Patient M. R. He was admitted with a history of recurrent abdominal pain. Serum amylase on admission was 1,360 units and an upper gastrointestinal series was interpreted as normal. The patient improved on conservative management and was discharged without operative intervention. In summary, nine patients, ranging in age from 2 to 17 years, were seen; five were boys. Roentgenographic abnormalities were noted on plain films in live and in six of the seven upper gastrointestinal series performed. Ultrasonography demonstrated abnormalities in all three patients examined. Five patients had surgically documented pancreatic pseudocysts and four children improved on conservative management.
DISCUSSION Hereditary pancreatitis has been defined by Gross' as "inflammation of the pancreas, usually recurrent from childhood, with unusual prevalence among blood-related groups of persons in accordance with mend elian laws (autosomal dominant gene)."
The sex incidence
is
approximately equal and the disease is described exclusively in Caucasians. The clinical features of the disease have been well documented and a variety of complications described. The clinical picture of hereditary pancreatitis follows a relatively predictable pattern with recurrent attacks of severe upper abdominal pain lasting several days. with onset in early childhood." There is disagreement about how often childhood pancreatitis is hereditary in nature;
952
or
Fried and Selke
The Journal Pediatrics December 1978
'x
u
s
Fig. 2. Patient D. S. Repeat ultrasonogram three days later. Longitudinal scan at 7 ern (0 the right of the midline, Note free fluid within the abdomen (arrows) separating liver from diaphragm and collecting in the subhepatic space.
Fig. 3. Patient V. E. Upper gastrointestinal series shows extrinsic compression on the lesser curvature and the antrum of the stomach.
Sibert found only one documented example of hereditary pancreatitis in nine patients reviewed. However, Kattwinkel et al,' in a report encompassing 21 kindreds concluded that the hereditary form was the most common cause of recurrent pancreatitis in childhood. Including both recurrent and single episodes of pancreatitis, the most common
etiologies of pancreatitis in childhood arc traumatic and idiopathic.":" If only patients with recurrent episodes an: considered, it appears that Kuttwinkel's conclusion remains valid. The most common radiographic manifestations encountered in hereditary pancreatitis include pancreatic calcification which is reported present in 33 to 50% of documented examples and, when sought, dilatation of the pancreatic ductal system." t:'·IC, When pathologic or radiographic evaluation of the pancreatic ductal system has been obtained, dilatation of both the main duct and its radicals has been found in every case and appears to be it uniform feature of the disease. In approximately 80% of individuals with pancreatic pseudocyst. displacement of the stomach was noted on upper gastrointestinal series. Pleural effusion of the left side is a frequent finding. Pseudocysts occurring in hereditary pancreatitis are similar to those of other causes. The lesser sac is a frequent location with anterior displacement of the stomach and proximal duodenum!" and occasional inferior displacement of portions of the transverse colon. Rupture of a pancreatic pseudocyst into the Gerota fascia. masquerading as a primary renal neoplasm (Patient P. R.), appears to be unusual. In our kindred of nine patients with documented hereditary pancreatitis, eight had clear radiognLJ?hic manifestations of a mass effect in the upper abdomen and five surgically proven pseudocysts. Regression of a mass effect in one patient is compatible with spontaneous
VO/lIl11e 93 Number 6
regression or internal drainage of a pseudocyst; pancreatic edema or phelgrnon could produce such a picture. Ultrasonography will be of considerable value in distinguishing edema from pseudocyst. In one instance ultrasonography documented a decrease in the size of the pseudocyst due to intraperitoneal rupture. The finding of clearly demonstrable calcification in only one example is unexplained. The relatively recent introduction of ultrasonography as a pivotal diagnostic tool in the identification of pancreatic psuedocysts": I" suggests that the overall incidence of this entity in acute pancreatitis is far greater than originally supposed. In a series of 99 patients, Gonzalez'" found positive ultrasound scans In 52 and noted spontaneous resolution in approximately 20% of demonstrated cystic lesions. A palpable mass was identified in only 38.3% of patients in this series. The apparently constant finding of dilatation of the pancreatic ductal system at radiography 01' pathology in hereditary pancreatitis allows the speculation that the basic pathophysiology involved in this disease entity may predispose to pseudocyst formation. The desire to avoid surgical intervention when possible, the natural history of spontaneous resolution of the disease process in a matter of days, and the established rate of regression of pseudocysts of all etiologies" (about 20
