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Pancreatic Cysts Simulating Renal Disease1
THE JOURNAL OF UROLOGY
Vol. 62, No. 2, August 1949 Printed in U.S.A.
PANCREATIC CYSTS SIMULATING RENAL DISEASE 1 ERIC P. STONE From the Cushing Veterans Administration Hospital, Framingham, Mass.
Pancreatic cysts so seldom impinge on the field of urology that when one is encountered it presents unusual diagnostic and surgical difficulties. They are most frequently confused with renal tumors and must be considered in the differential diagnosis of the retroperitoneal masses which the urologists are frequently asked to investigate. Cysts of the pancreas are not rarities to the abdominal surgeon. In the available literature several studies of a group of such cases and numerous case reports have been found. In all there has been mention of 821 cases. At the Mayo Clinic the incidence was 1 in 8,000 admissions and 0.3 per cent of all autopsies, although most were small and asymptomatic (Brunschwig). Of the large number of cases to which reference has been found, only 71 were presented in sufficient detail to permit determination of the exact nature and site of the cysts. Of these only 9 cases presented signs or symptoms which implicated the urinary tract and thus presented urological problems. Even to the surgeon the diagnosis of pancreatic cyst presents difficulties as there is nothing pathognomonic about the clinical picture. The symptoms are any combination of the following: abdominal distress varying from vague discomfort to acute pain usually in the epigastrium; anorexia, nausea, vomiting, diarrhea; fever and leukocytosis; and in 61 per cent a palpable mass usually at or above the level of the umbilicus (Brunschwig; Judd, Mattson and Mahorner; Schulte and Emmett). Any one or all of these signs and symptoms may be produced by any of the upper abdominal organs and even by disease above the diaphragm. Diagnosis is further confused by the fact that associated disease of the gallbladder or bile ducts is present in 34 per cent of all cases (Judd, Mattson and Mahorner) not only as an etiological factor in some, but producing symptoms that can also be caused by the cyst. Many of the cysts follow prior attacks of pancreatitis; a certain number occur as the end result of pancreatic hemorrhage due to abdominal trauma and some have been attributed to obstruction of the ampulla of Yater. Therefore, the antecedent history is of considerable importance. In some cases the presence of hypoglycemia is suggestive of the true nature of the illness. If the presence of a pancreatic cyst is suspected, certain laboratory tests may be of aid. There are specific tests of pancreatic function; but too much reliance cannot be placed on them as 1) the physiological reserve of the organ is so great that seven-eighths to nine-tenths of it may be involved before significant variation from normal occur in such analyses (Case) and 2) some of the changes are fleeting. Because of disturbances in digestion, undigested food may be found 1 Published with the permission of the Chief Medical Director, Department of Medicine and Surgery, Veterans Administration, who assumes no responsibility for the opinions expressed or conclusions drawn by the author. 104
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in the feces and there may be steatorrhea. Therefore, examination of the stools is indicated. The most reliable of the functional tests is the cuprous oxide precipitation test for blood amylase (Palowe). This determination was done in 12 of the 71 cases reported in full and showed elevations above normal (80~180) in 8 instances. It is more properly a test for acute pancreatitis, which, although often a precursor of cystic disease, is seldom found by the time the resulting cysts or pseudocysts have formed. It is known that in noncystic disease of the pancreas, the blood amylase rises sharply at the onset of the disturbance but may return to normal within 72 hours. Moreover, it has been found to be elevated in a wide variety of other pathological states as in thrombosis of the mesenteric vessels and portal vein, in penumonia, perforated gastric ulcer in the region of the pancreas, duodenal ulcer and high intestinal obstruction. On the whole, the roentgenologist offers the greatest and most specific aid in the diagnosis of pancreatic cyst. Except for the rare malignant cyst, the condition per se may not cause symptoms. The small and multiple cysts, except when part of a generalized disease such as cystic fibrosis, do not present a diagnostic problem as they cause no dysfunction in the pancreas or neighboring organs. Where large cysts are present, in the majority of the cases, the uninvolved part of the pancreas is functioning normally, so alterations of functional tests do not occur. It is only when the cysts have reached a size to disturb the position and motility of neighboring organs that cysts cause the distress which the patient seeks to have relieved (Brunschwig). By such time, the cysts are large enough to show distortion of major elements of the gastro-intestinal tract in the upper abdomen. Such changes are susceptible to x-ray demonstration and interpretation. Cysts in the head of the pancreas cause a widening of the duodenal loop and may or may not produce a deformity at the distal end of the stomach. Unlike mesenteric or omental cysts which may lie in a similar position, they do not move -with respiration. Cysts of the body are prone to cause a pressure defect of the lesser curvature, while those at the tail produce a smooth, rounded indentation of the greater curvature at or just above its mid-portion. Especially in the last type, which extend posteriorly to the stomach, the lateral views are significant as there is a generalized defect of the posterior wall of the stomach with the organ pushed forward (fig. 1, 1). The duodenal-jejunal junction may be depressed and the splenic flexure may be either indented along its medial aspect or displaced caudally. In the body or tail the cyst, as it increases in size, may project between the stomach and colon instead of rising behind the stomach in which case the stomach is pushed up; the small bowel is depressed and the transverse colon is compressed in the anterior-posterior aspect as it is stretched across the surface of the cyst. Theoretically, splenic enlargement, echinococcus cysts and retroperitoneal tumors could cause similar x-ray findings. The clinical features and blood picture identify the first condition. Skin tests should rule out the second, and the third are extremely rare in the site typically assumed by pancreatic cysts. There is liable to be more confusion where pancreatic cysts arise in heterotopic pan-
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ERIC P. STONE
creatic tissue as no typical gastro-intestinal deformities result. (Bruck; CJ,se; Holt; Young). It is the latter group of cases that have caused the urologist the greatest difficulty as, in the development of the pancreas, foetal intra-abdominal disturbances, presumably fibrosis, may attach the pancreas to a section of the gut. This grows more rapidly than the pancreas and pulls pancreatic cells with it so that ultimately bits of normal pancreatic tissue may be found at any point along the intestinal tract beyond the pancreas. Frequently, they lie at or below the splenic flexure and when such is the case, morbid changes in the heterotopic pancreas may easily simulate a left renal cyst or tumor or perirenal cyst or tumor. The same migratory effect of separate pancreatic tissue may result from adhesion to the mesonephros, resulting in heterotopic pancreas in the renal fossa. Rarely does a cyst in the head of the pancreas become so large and grow in such a direction that it is confused with renal disease (Barbarosa, Dockerty and Waugh).
FIG. 1. 1, Lateral film of abdomen after barium meal, showing deformity of stomach at A.
2, Retrograde pyelogram, showing distortion of splenic flexure at A, and pressure on upper calyx of left kidney at B. 3, Showing distortion of splenic flexure at A, and backward displacement of upper pole of left kidney at B. CASE REPORT
W. N., CVAH No. 6186, a 31 year old single veteran, was admitted to the Neurological Service of Cushing V. A. Hospital on October 9, 1947, complaining of extreme nervousness and phantom limb pain. He had had a previous admission in June 1947 for the same complaints which were relieved until recently, when the pain returned during a period of unusually heavy drinking. Because of his condition, his past history was unreliable but did not include jaundice or any abdominal injury unless such may have occurred when his right arm was shot off during combat; nor could there be elicited the history of attacks which might have represented acute or chronic pancreatitis. For some months he had had vague symptoms of epigastric pain, heartburn, nausea and vomiting which he had attributed to his alcoholic excesses. Two months before admission he had had two episodes of painless bright red hematuria and on admission had diurnal frequency 10-12 times and nocturia 3-4 times for a couple of days. This cleared up spontaneously in 4 days. He had had no chills or fever.
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The initial physical examination showed a thin, pale, restless man. Dur~ng the examination he was constantly sitting up and lying down and picking at the bed clothes. Ansvvers were often irrelevant and there were long pauses while he peered around the room. His facies were anxious; his eyes were injected. There was a heavy odor of alcohol on his breath. Temperature, pulse and respiration were normal. Extra-ocular motions did not coordinate but pupillary reflexes were normal. The heart and lungs were normal and the blood pressure was 110/70. Abdominal examination showed firm musculature and minimal panniculus. There was tenderness in the left costovertebral angle and in the left flank and left upper quadrant with some involuntary spasm in the left upper quadrant. Murphy's sign was positive. A tender mass, oval, firm and non~ movable, was made out in the left upper quadrant to the left of the midline. Its limits -were indefinite but it gave the impression of extending from the left margin of the rectus muscle to the left anterior axillary line and downward to just above the level of the umbilicus. There was dullness to percussion over the mass. It did not pulsate. The remainder of the abdominal examination ,vas negative. There was no change in the mass during the first 10 days of hospitalization. The right arm was missing at the shoulder and there were poorly defined areas of hyperesthesia about the right shoulder and the½ inch stump was tender. Examination of the external genitalia and rectum was negative. The routine urinalysis on admission and three subsequent analyses showei:l·no variation from normal. The leukocyte count varied between 11,500 and 15,500 with about 75 per cent neutrophils throughout. The erythrocyte count decreased steadily from 4.5 million to 3.2 million and there was a corresponding drop in hemoglobin from 11.6 gms to 9.6 gms. On admission the blood nonprotein was 30 mg. per 100 cc; fasting blood sugar, 126 mgm per 100 cc and total protein, 6.2 gm per 100 cc. Blood Kahn was negative and the urine culture was sterile. Examination of the gastro-intestinal tract showed the stomach to be displaced markedly anteriorly and to the right. The first portion of the duodenum was similarly displaced. No intrinsic pathology could be distinguished. Subsequent studies showed displacement of the proximal limb of the splenic flexure anteriorly and to the right. The transverse colon proximal to this was slightly dilated. Serial studies showed slow passage of barium through the narro,-1- distorted limb. The distortion and poor function were considered due to extrinsic pressure. Chest films showed the heart and lung fields to be normal but there was moderate elevation of the left diaphragm. The dorso-lumbar spine showed no abnormality (fig. 1). The patient became rapidly completely disoriented and uncontrollable and was transferred to a closed ward of the Neuro-Psychiatric Service. A urological consultation was requested on the twenty-first day after admission. The patient had recovered from delirium tremens and the phantom limb pain had disappeared. He, however, complained of a steady aching pain in the left kidney region which had become gradually worse over a period of 10 days. There had been increasing leukocytosis to 20,000 and temperature of 101 and 102 F during
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ERIC P. STONE
the past 2 days. Since admission, the mass had increased slightly in size and there was exquisite tenderness anteriorly and posteriorly over the left kidney region, with muscle spasm in these areas. The urine now showed a specific gravity of 1030, 1 plus albumin and 2-4 white blood cells with granular and waxy casts; but no red cells were found. On the basis of the physical examination and the history of hematuria, it was believed that the patient had a renal tumor and he was transferred to the Urological Section. Urological examination (November 1, 1947): The bladder was normal except that in the region of the trigone numerous submucosal black specks were seen which were believed to be remnants of submucosal bleeding. The ureteric orifices were functionally and morphologically normal and clear urine was noted emerging in peristaltic spurts from both orifices. AN o. 6 catheter passed freely to 28 cm. on the left, but due to spasm the right ureter could not be catheterized beyond 2 cm. Clear urine was obtained from the left kidney. After injection of phenolsulphonphthalein the dye appeared on the left in 6 minutes and 4 per cent was collected in 10 minutes. The pelvis accepted 10 cc of 20 per cent diodrast. No urine was obtained from the right ureter at any time due to technical difficulties with the catheter. The left kidney and bladder specimens were sterile and proved negative for tubercle bacilli by stain and culture. Neither specimen showed white or red blood cells. The retrograde pyelograms of the left upper tract (fig. 1, 2 and 3) showed the kidney to be displaced downward and its superior pole displaced posteriorly. There was some depression of the upper calyx and distortion of its infundibulum. There was a suggestion of a soft tissue mass springing from the anterior part of the upper pole. There was kinking at the ureteropelvic junction. The uniformity of the outlines of the depressed upper calyx militated against tumor and the gastro-intestinal studies combined with the pyelograms led to an x-ray and urological diagnosis of cyst of the pancreas; but it was believed that an adrenal cyst had not been ruled out. The next day intravenous pyelograms demonstrated a functionally and morphologically normal right upper genito-urinary tract. Left nephrectomy (Dr. Stone, November 4, 1947): Under continuous spinal anesthesia, a left lumbar oblique incision was made and the lower pole of the kindey was easily exposed. This appeared to be continuous with a large expanding mass which extended up to the diaphragm where it was firmly adherent. There was no line of demaraction between kidney substance and the mass, the renal capsule appearing to be continuous over the surface of kidney and mass. As adhesions between the mass and the muscles of the abdominal wall and the peritoneum were freed, instead of the cystic feel expected, the mass felt firm and solid. It was believed, at this point, that the diagnosis was mistaken and that we were dealing with a renal tumor. Therefore, the renal pedicle was exposed and then the freeing of the mass was continued. This was very difficult because of dense adhesions to all surrounding tissues. At one point while freeing the mass from the diaphragm there was a sudden profuse welling of bright blood from the region of the pedicle, with a concomitant abrupt drop in blood pressure to zero. A clamp was immediately applied to the pedicle and the bleeding promptly
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stopped. The freeing of the upper limits of the mass was continued. Shortly, what proved to have been an extremely thick capsule was broken through and within could be felt a soft walled cyst. Eventually the kidney, thick capsule over the cyst and the cyst were removed in one mass. Inspection of the kidney bed showed good hemostasis of the pedicle but there were several small areas of the slight venous oozing in the renal fossa. A transfusion had been started and at this time the patient's blood pressure was 108/64 and the pulse 110. Pressure for a few moments with hot boric sponges and application of oxycellulose gauze appeared to have controlled the oozing areas. At the end of a routine closure
Fm. 2. Left kidney hemisected at hilus, A, and pancreatic cyst arising from upper pole, B.
around two cigarette drains, the blood pressure was unchanged and he was returned to the recovery room and placed in a shock bed and given supportive treatment; i.e. put in an oxygen tent and given a second transfusion of 500 cc citrated blood. Two hours postoperatively, he had a convulsion and his blood pressure dropped from 108/70 to 90/50 in about 5 minutes. He was pallid, had a cold sweat and was breathing with accessory muscles. Although there was only slight staining of the inner layer of the dressing, it was believed that he was suffering from a primary hemorrhage. Despite further transfusions and intravenous glucose given simultaneously in arm and leg veins and other supportive measures, the patient failed to rally and died 3 hours after the end of the operation. The operative specimen was a kidney (figs. 2 and 3), measuring 12 by 7 by 5
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cm. with an attached cyst containing 390 cc of clear greenish-brown fluid. The cyst was surrounded, except at its abutment on the kidney by a dense gristly fibrous coat, continuous with the renal capsule, 1.8 cm. thick. Within this coat there was a separate cyst wall measuring 0.2 cm. in thickness, although some areas were thinned to 0.1 cm. The cyst wall rested on a depression in the upper pole of the kidney. The internal surface of the cyst wall was chocolate brown in color and showed fine wrinkles. At one point near the apex, there were two
Fm. 3. Operative specimen, cyst and kidney, cyst being opened. A, cyst; B, kidney; C, diverticulum of cyst entering substance of kidney but not communicating with any of renal elements.
diverticulum-like openings measuring 1.0 and 0.3 cm. in diameter. The cyst was freed easily from its bed in the kidney; but at one point there was a prolongation of the cyst into the kidney substance. This was blind and did not communicate with the calyces or pelvis. The kidney itself, except that the capsule was thickened and tenacious, was not remarkable. As the cyst wall was approached, the capsule became much thicker and could not be stripped from the parenchyma. Microscopically the wall of the cyst was composed of dense fibrous tissue in which were scattered large arteries and nerve filaments (fig. 4). In addition islands of pancreatic tissue were visible. Foci of lymphocytes and scattered phagocytes filled with hemosiderin were also seen. A portion of the
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cyst was buried superficially in the kidney. There was fibrosis of the adjacent renal parenchyma with scattered lymphocytes. Parts of the inner surface of the cyst were ragged and lined with granulation tissue. Elsewhere the inner surface was smooth with no cellular elements. Pathological diagnosis: 1) pancreatic cyst; 2) normal kidney. The autopsy showed 1200 cc of bright blood in the peritoneal cavity and 270 cc of clot in the left renal fossa. No tear could be demonstrated in the peritoneum permitting connection between the renal fossa and the peritoneal cavity, but one must have existed. The renal veins and artery were efficiently tied and
Frn. 4. A, photomicrograph of cyst wall, showing fibrous tissue. B, photomicrograph of cyst wall, showing pancreatic tissue, A, imbedded in fibrous tissue, B.
the source of the bleeding could not be found but was presumably from some accessory vessel in the renal fossa. "The intestines were not remarkable except for marked fibrous thickening at the midportion of the transverse colon. Dissection of this region disclosed a sinus running posteriorly to the midportion of the transverse colon and extending upward into the wall both inferiorly and superiorly through two openings. The sinus and its limbs had a diameter of 0.8 cm. and the entire length of the sinus ·which extended down to the site of the removed kidney, although in the renal fossa it was a fibrous cord, was 8 cm. The inner surface of the sinus and its ramifications was lined with greyish-black tissue and was filled v\Tith rather thick greenish fluid. There was a marked fibrous thickening of the pancreas with an ill-defined mass situated below the thickened portion of the transverse colon. This appeared to include the pancreas and
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extended upward toward the stomach. Further examination revealed that in the region of this fibrous thickening there was a cyst 9 cm. in diameter arising in the head of the pancreas. It was firmly adherent to the posterior abdominal wall. The walls consisted of pancreatic tissue except for some portions where they were replaced by fibrous tissue. Small outpocketings of the cyst were noted. One extended toward the duodenum at which point it was adherent and there was here a small sinus extending into the duodenum 3.5 cm. below the pyloric ring. It was 0.4 cm. in diameter. The cyst lumen was crossed by several fibrous trabeculae 2 to 3 cm. in length and 1.5 cm. in thickness. As it passed the cyst wall, the stomach was adherent to it. The cyst contained a very small amount of greenish-black, thick fluid." The left adrenal was present and somewhat edematous. A further small nodule 2 cm. in diameter was found high in the renal bed and contained greenish-black, thick fluid. It appeared to be similar to the other pancreatic cysts. The spleen was enlarged and the artery was involved in some of the fibrous tissue that had surrounded the pancreatic cyst in the renal fossa. The gallbladder and liver were not remarkable. The heart, lungs, brain and remaining genito-urinary organs appeared to be normal. COMMENT
During its development, the dorsal bud of the pancreas undoubtedly became adherent to the mesonephron of the left kidney and as the position of the two changed during their development pancreatic tissue was drawn away from the main body and two bits of pancreatic tissue developed into heterotopic organs within the left kidney fossa. The explanation of cysts occurring simultaneously in all the existing pancreatic tissue in the body is obscure. Pancreatic cysts can follow abdominal injury. A war wound that was severe enough to amputate an arm could have conceivably caused coincidental abdominal trauma sufficient to result in a pancreatic cyst. But it would be difficult to believe that the heterotopic tissue in the renal fossa could have suffered equally. Moreover, traumatic cysts result from walling off of blood and escaped pancreatic fluid by a fibrous tissue reaction, so their walls do not contain pancreatic acini. Therefore, injury as the etiological factor may be ruled out. There were no ducts draining the heterotopic pancreas. That cysts would form in these areas is understandable as the acini functioned until the accumulated fluid inhibited further production of the juice. Then the coincidental obstruction of the ducts of Santorini in the pancreas itself or their invasion by bile or reduction in output of secretin causing inspissation of the pancreatic juice (conventional theories of the formation of pancreatic cysts) might explain the occurrence of the cyst found in the pancreas. However, resort to coincidence seems too easy and facile an explanation of the situation found in this case (Farber). This is especially so in view of recent data concerning the physiology of the pancreas. It is known that pancreatic secretion can be effected by nerve or blood born influences which would be equally active on pancreatic tissue wherever it may be found in the body. Such may be the case in Lindau's disease where
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prenatal disturbances affect the development of the vessels in such a way that angiomata resulting in cysts appear in the pancreas and other organs, spinal cord, kidney and liver (Moore). More cogent are the cysts found in congenital pancreatic steatorrhea in which pancreatic fibrocystic disease is associated with recurrent or chronic respiratory infections and often meconium ileus. Our interest centers around the etiology of the pancreatic phases of this disease as they stress factors extrinsic to the organ. One theory is that the obstruction which causes the cysts is due to obstruction of the smaller ducts by inspissated pancreatic juice. Normally under the influence of secretin there is a flushing of the acini with a thick alkaline fluid which dilutes the pancreatic juice and sweeps it along the ducts. The juice, without this admixed fluid is rich in organic material which is coagulable. The duodenum of children dying of fibrocystic pancreatitis does not contain secretin and it was also found wanting in those cases of intestinal obstruction in which the pancreas shows a similar histological picture (Baggentoss, Power and Grindley; Mallory). Therefore, the basic difficulty lies in the failure of the production of secretin. This may be due to autonomic nerve disturbances which in turn may be due to virus infection, or as some believe, to Vitamin A deficiency. Other possibilities have been suggested: a) autonomic nerve over-stimulation of the pancreas leading to depletion of the zymogen granules resulting in the production of a viscid pancreatic juice; b) dehydration resulting in inspissation of the juice; c) malnutrition resulting in a protein deficiency which prevents the reparative protein synthesis in the cells of the pancreatic acini. No matter which of the above is the true cause of the inspissation of the pancreatic juice with its sequence of obstruction and cyst formation, if the patient survives long enough the small cysts may enlarge and even coalesce to form the type found in this case. In this particular patient, the status of the autonomic nervous system is not known, although his alcoholic history suggests that it might have been seriously disturbed. The possiblity of a virus infection at an earlier date cannot be proved or disproved. But his long alcoholism with its attending gastritis could readily account for vitamin or protein deficiency or both. While any of the above theories could account for similar changes occurring simultaneously in pancreatic tissue in any part of the body, it is obvious that specific application of any one of them to this individual case is highly speculative. The validity of no one of them can be proved postmortem and would have been very difficult to prove even before death. Further comment should be made as to the treatment of the condition found. The treatment of cysts of the pancreas is operative. The vast majority of the cases have been treated by marsupialization of the cyst (Brunschwig; Nygaard and Stacy). The resulting fistulas have usually closed in a period of months, although some have persisted and required closure by jejunal implantation of the proximal end of the fistulous tract (Lahey and Lium). In only 17 was resection of the cyst technically possible although such is the ideal procedure. Twelve were simply drained with eventual recovery in all. One case was aspirated and
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lived for many years with recurrences. Because of the malignanat nature of the cyst found at operation, one case was subjected only to exploration (table 1). In the case reported above, there was one feature that has not been stressed in the literature, and lack of familiarity with it led to an extensive and fatal operation. It was not appreciated that, although many pancreatic cysts are thin walled, a great number, particularly those of long standing or those resulting from an acute attack of pancreatitis, are thick walled. In reviewing the literature, mention of this is found in only one article (Ormond, Wadsworth and Morley). Since performing this operation, a colleague has stated that he was deceived in exactly the same way be a recent case (Austen). When the kidney and the attached cyst were exposed, the pathological mass felt exactly like a stony hard, solid tumor. The renal capsule extended over the mass with no line TABLE
1.
Operations on 80 cases (including one reported in this paper)
OPERATION
NUMBER OP.
DEATH
PERSISTENT FISTULA
END RESULT
--
43
0
2
*40 recovered
1
0
0
1 recovered
Resection
19
2
0
17 recovered
Partial resection and drainage or drainage
14
2
0
1 sinus closed surgically, 1 persistent sinus
Aspiration
1
0
0
1 recurrence
Exploration
1
0
0
*
Marsupialization Marsupialization and instillation of sodium marhuate
* 1 case died later of pancreatic malignancy.
of demarcation being made out. It was believed that the preoperative diagnosis was in error and a difficult nephrectomy was carried out. Had the possibility of such a deceivingly thick walled cyst been realized, aspiration would have revealed the correctness of the preoperative diagnosis and drainage or marsupialization could have been done with little risk to the patient. CASES SIMULATING GENITO-URINARY DISEASE REPORTED IN THE LITERATURE
Nine such cases were found in the articles reviewed. They are summarized in table 2. Including the one here reported, it is seen that a correct diagnosis was made in only 2 of 10 cases. It is noteworthy that blood amylase studies were done preoperatively in only 2 cases and in neither was it of aid. Gastro-intestinal series were done in four and the diagnosis was established in 2 cases by this means. In the urological studies made in 9 of the cases, abnormalities were noted in all.
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PANCREATIC CYSTS SIMULATING RENAL DISEASE
But such changes, while they should be sufficient to rule out renal tumor, do not differentiate between the various types of extrarenal masses that cause pyelographic changes by virtue of external pressure. Seven patients gave a history of attacks of gastro-intestinal symptoms, varying from severe to acute, for some years prior to the onset of the attack which led to the current illness. Four gave TABLE
AUTHOR
Ormond
2.
Panr;reatic cysts affecting the genito-urinary tract
G-U FINDINGS
Rt. kidney lt. of midline.
Lt. pelvis distorted
PREOPERATIVE DIAGNOSIS
OPERATIVE FINDINGS
RESULT
Retro peritoneal tumor
Cyst of head. Mar- Cured supialized. Na. morhuate instilled
Pancreatic cyst
Cyst of tail and body both drained Cyst of tail marsupialized
Cured
Cyst of tail marsupialized
Cured
Mass in lt. kidney region
Cured
Kummer
Lt. upper calyces obliterated
Renal tumor
Ransohoff
Lt. hematuria due to obstruction of renal vein
Sarcoma of kidney Cyst of tail drained
Died
Walters
Displaced It. kidney
Extrarenal tumor
Cyst of tail marsupialized
Cured
Denter
Displaced It. kidney
Found at autopsy
Cyst of tail
Cured
Martin
Mass in It. kidney region
Renal tumor
Cyst of head aspirated
Recovered
Case
Distorted rt. ureter
Renal cyst
Cyst of head marsupialized
Cured
Stone
Compressed upper It. calyces
Pancreatic or adrenal cyst
Cyst, heterotopic, resected
Died
a past history of severe abdominal trauma. In 8 of 10 cases, the urological involvement was on the left side and due to heterotopic cyst or cysts of the tail (Brunschwig). This is understandable as theoretically cysts arising in the head are buffered from the kidney by the duodenum and bile ducts. Disturbances of these structures intervene before the right kidney can be seriously affected, so treatment is instituted before right upper tract symptoms appear. In treatment it is found that the distribution of operative procedures was much the same as that for the whole series. Five were marsupialized, 3 drained, 1 aspirated and 1 resected. The only death resulted from the resection.
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ERIC P. STONE CONCLUSIONS
Masses impinging on the kidneys can readily be demonstrated to be extrinsic by pyelography, but this does not differentiate between the various types of retroperitoneal tumors and cysts which might appear as such masses. To prove or disprove such to be a pancreatic cyst, the following studies may be helpful (in order of importance): a) Gastro-intestinal x-ray. b) Blood amylase determinations. c) Analysis of the past history for prior episodes of biliary attacks, attacks of acute pancreatitis or abdominal trauma. Of the available operative procedures: a) Resection effects a cure without prolonged morbidity from a draining sinus, but this is technically impossible in a majority of the cases. b) Marsupialization, with or without partial resection, eventually effects cure in a large proportion of the cases in which it is carried out. c) Drainage gives about the same results as marsupialization. d) Aspiration is not recommended. It is stressed that a pancreatic cyst may have a thick gristly false capsule which deceives the operator into believing that he is dealing with a solid tumor. If he has expected a cyst and finds a hard mass, attempted aspiration can do no harm if it is a tumor about to be removed and, if fluid is obtained, this may permit a less hazardous procedure than resection. I am indebted to Dr. Robert Fienberg, chief of the Pathology Department and to Dr. Daniel Kornblum, chief of the X-Ray Department of the Cushing V. A Hospital for valuable suggestions and interesting discussions concerning this case. REFERENCES ANDERSON, D. H.: Am. J. Dis. Child., 63: 643, 1942. ANGER, T. AND LEDENTU: Bull. de la Soc. Anatomique de Paris, second series, 10: 197, 1865. AusTEN, GEORGE: Personal communication. BAGGENToss, A.H., POWER, M. H. AND GRINDLEY, J. H.: Am. J. Path., 24: 692, 1948. BARBOSA, J. G., DEC., DOCKERTY, M. B. AND WAUGH, G. B.: Surg., Gynec. & Obst., 82: 527, 1946. BOZEMAN, N.: Med. Record, 21: 46, 1882. BRUCK, S.: Radiology, 25: 303, 1935. BRUNSCHWIG, A.: The Surgery of Pancreatic Tumors. St. Louis: C. V. Mosby Co., 1942, chapts. 7-9. CASE, J. T.: Am. J. Roent. & Radium Therapy, 44: 485, 1940. CONNOLLY, D. I.: Lancet, 1: 803, 1911. ELMAN, R.: Am. J. Dig. Diseases, 6: 237, 1939. FARBER, S.: N. Eng. J. Med., 229: 653 and 682, 1943. HIATT, R. B. AND WILSON, P. E.: Surg., Gynec. & Obst., 87: 317, 1948. HoLT, J. F.: Radiology, 46: 239, 1946. JUDD, E. S.: Minn. Med., 4: 75, 1921. JUDD, E. S., MATTSON, H. AND MAHORNER, H. R.: Arch Surg., 22: 838, 1931. KERR, A. R.: Surg. Gynec. & Obst., 27: 40, 1918. LAHEY, F. H. AND LruM, R.: Surg., Gynec. & Obst., 44: 79, 1930. MAHORNER, H. R.: Proc. Staff Meetings Mayo Clinic; 5: 101, 1930. MALLORY, T. B.: N. Eug. J. Med., 234: 151, 1948. MARTIN, H.B.: Brit. Med. J., 1: 481, 1941. MATTSON, H.: Proc. Staff Meetings, Mayo Clinic, 5: 100, 1930.
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MooRE, R. A.: Textbook of Pathology. Philadelphia: W. B. Saunders Co., 1945, p. 1202. NovAK, E.: Surg., Gynec. & Obst., 45: 586, 1927. NYGAARD, K. K. AND STACY, J.C.: Arch. Surg., 45: 206, 1942. NYGAARD, K. K. AND WALTERS, W.: Ann. Surg., 106: 49, 1937. ORMOND, J. K., WADSWORTH, G. H. AND MORLEY, H. V.: Trans. Am. Assoc. Genito-urin. Surg., 35: 175, 1942. PALOWE, D.: Surg., Gynec. & Obst., 82: 115, 1946. PINKHAM, R. D.: Surg., Gynec. & Obst., 80: 225, 1945. RABINOWITCH, J. AND PINES, B.: Arch. Surg., 45: 727, 1942. RANSOHOFF, J.: Surg., Gynec. & Obst., 22: 275, 1916. SCHULTE, T. L. AND EMMETT, J. L.: J. Urol., 52: 215, 1939. WALTERS, W. AND CLEVELAND, W. H.: Arch. Surg., 47: 819, 1941. WALTERS, W., McCAUGHAN, J.M. AND PuEsTow, C. D.: Cyclopedia of Medicine and Surgery and Specialties. Philadelphia: F. A. Davis Co., Vol. 11, pp. 96--152. WALTERS, W. AND THIESSEN, N. W.: Surg. Olin. N. Am., 15: 1159, 1935. YOUNG, E. L.: N. Eng. J. Med., 216: 334, 1937.
Vol. 62, No. 2, August 1949 Printed in U.S.A.
PANCREATIC CYSTS SIMULATING RENAL DISEASE 1 ERIC P. STONE From the Cushing Veterans Administration Hospital, Framingham, Mass.
Pancreatic cysts so seldom impinge on the field of urology that when one is encountered it presents unusual diagnostic and surgical difficulties. They are most frequently confused with renal tumors and must be considered in the differential diagnosis of the retroperitoneal masses which the urologists are frequently asked to investigate. Cysts of the pancreas are not rarities to the abdominal surgeon. In the available literature several studies of a group of such cases and numerous case reports have been found. In all there has been mention of 821 cases. At the Mayo Clinic the incidence was 1 in 8,000 admissions and 0.3 per cent of all autopsies, although most were small and asymptomatic (Brunschwig). Of the large number of cases to which reference has been found, only 71 were presented in sufficient detail to permit determination of the exact nature and site of the cysts. Of these only 9 cases presented signs or symptoms which implicated the urinary tract and thus presented urological problems. Even to the surgeon the diagnosis of pancreatic cyst presents difficulties as there is nothing pathognomonic about the clinical picture. The symptoms are any combination of the following: abdominal distress varying from vague discomfort to acute pain usually in the epigastrium; anorexia, nausea, vomiting, diarrhea; fever and leukocytosis; and in 61 per cent a palpable mass usually at or above the level of the umbilicus (Brunschwig; Judd, Mattson and Mahorner; Schulte and Emmett). Any one or all of these signs and symptoms may be produced by any of the upper abdominal organs and even by disease above the diaphragm. Diagnosis is further confused by the fact that associated disease of the gallbladder or bile ducts is present in 34 per cent of all cases (Judd, Mattson and Mahorner) not only as an etiological factor in some, but producing symptoms that can also be caused by the cyst. Many of the cysts follow prior attacks of pancreatitis; a certain number occur as the end result of pancreatic hemorrhage due to abdominal trauma and some have been attributed to obstruction of the ampulla of Yater. Therefore, the antecedent history is of considerable importance. In some cases the presence of hypoglycemia is suggestive of the true nature of the illness. If the presence of a pancreatic cyst is suspected, certain laboratory tests may be of aid. There are specific tests of pancreatic function; but too much reliance cannot be placed on them as 1) the physiological reserve of the organ is so great that seven-eighths to nine-tenths of it may be involved before significant variation from normal occur in such analyses (Case) and 2) some of the changes are fleeting. Because of disturbances in digestion, undigested food may be found 1 Published with the permission of the Chief Medical Director, Department of Medicine and Surgery, Veterans Administration, who assumes no responsibility for the opinions expressed or conclusions drawn by the author. 104
PANCREATIC CYSTS SIMULATING RE~AL DISEASE
105
in the feces and there may be steatorrhea. Therefore, examination of the stools is indicated. The most reliable of the functional tests is the cuprous oxide precipitation test for blood amylase (Palowe). This determination was done in 12 of the 71 cases reported in full and showed elevations above normal (80~180) in 8 instances. It is more properly a test for acute pancreatitis, which, although often a precursor of cystic disease, is seldom found by the time the resulting cysts or pseudocysts have formed. It is known that in noncystic disease of the pancreas, the blood amylase rises sharply at the onset of the disturbance but may return to normal within 72 hours. Moreover, it has been found to be elevated in a wide variety of other pathological states as in thrombosis of the mesenteric vessels and portal vein, in penumonia, perforated gastric ulcer in the region of the pancreas, duodenal ulcer and high intestinal obstruction. On the whole, the roentgenologist offers the greatest and most specific aid in the diagnosis of pancreatic cyst. Except for the rare malignant cyst, the condition per se may not cause symptoms. The small and multiple cysts, except when part of a generalized disease such as cystic fibrosis, do not present a diagnostic problem as they cause no dysfunction in the pancreas or neighboring organs. Where large cysts are present, in the majority of the cases, the uninvolved part of the pancreas is functioning normally, so alterations of functional tests do not occur. It is only when the cysts have reached a size to disturb the position and motility of neighboring organs that cysts cause the distress which the patient seeks to have relieved (Brunschwig). By such time, the cysts are large enough to show distortion of major elements of the gastro-intestinal tract in the upper abdomen. Such changes are susceptible to x-ray demonstration and interpretation. Cysts in the head of the pancreas cause a widening of the duodenal loop and may or may not produce a deformity at the distal end of the stomach. Unlike mesenteric or omental cysts which may lie in a similar position, they do not move -with respiration. Cysts of the body are prone to cause a pressure defect of the lesser curvature, while those at the tail produce a smooth, rounded indentation of the greater curvature at or just above its mid-portion. Especially in the last type, which extend posteriorly to the stomach, the lateral views are significant as there is a generalized defect of the posterior wall of the stomach with the organ pushed forward (fig. 1, 1). The duodenal-jejunal junction may be depressed and the splenic flexure may be either indented along its medial aspect or displaced caudally. In the body or tail the cyst, as it increases in size, may project between the stomach and colon instead of rising behind the stomach in which case the stomach is pushed up; the small bowel is depressed and the transverse colon is compressed in the anterior-posterior aspect as it is stretched across the surface of the cyst. Theoretically, splenic enlargement, echinococcus cysts and retroperitoneal tumors could cause similar x-ray findings. The clinical features and blood picture identify the first condition. Skin tests should rule out the second, and the third are extremely rare in the site typically assumed by pancreatic cysts. There is liable to be more confusion where pancreatic cysts arise in heterotopic pan-
106
ERIC P. STONE
creatic tissue as no typical gastro-intestinal deformities result. (Bruck; CJ,se; Holt; Young). It is the latter group of cases that have caused the urologist the greatest difficulty as, in the development of the pancreas, foetal intra-abdominal disturbances, presumably fibrosis, may attach the pancreas to a section of the gut. This grows more rapidly than the pancreas and pulls pancreatic cells with it so that ultimately bits of normal pancreatic tissue may be found at any point along the intestinal tract beyond the pancreas. Frequently, they lie at or below the splenic flexure and when such is the case, morbid changes in the heterotopic pancreas may easily simulate a left renal cyst or tumor or perirenal cyst or tumor. The same migratory effect of separate pancreatic tissue may result from adhesion to the mesonephros, resulting in heterotopic pancreas in the renal fossa. Rarely does a cyst in the head of the pancreas become so large and grow in such a direction that it is confused with renal disease (Barbarosa, Dockerty and Waugh).
FIG. 1. 1, Lateral film of abdomen after barium meal, showing deformity of stomach at A.
2, Retrograde pyelogram, showing distortion of splenic flexure at A, and pressure on upper calyx of left kidney at B. 3, Showing distortion of splenic flexure at A, and backward displacement of upper pole of left kidney at B. CASE REPORT
W. N., CVAH No. 6186, a 31 year old single veteran, was admitted to the Neurological Service of Cushing V. A. Hospital on October 9, 1947, complaining of extreme nervousness and phantom limb pain. He had had a previous admission in June 1947 for the same complaints which were relieved until recently, when the pain returned during a period of unusually heavy drinking. Because of his condition, his past history was unreliable but did not include jaundice or any abdominal injury unless such may have occurred when his right arm was shot off during combat; nor could there be elicited the history of attacks which might have represented acute or chronic pancreatitis. For some months he had had vague symptoms of epigastric pain, heartburn, nausea and vomiting which he had attributed to his alcoholic excesses. Two months before admission he had had two episodes of painless bright red hematuria and on admission had diurnal frequency 10-12 times and nocturia 3-4 times for a couple of days. This cleared up spontaneously in 4 days. He had had no chills or fever.
PANCREATIC CYSTS SIMULATING RENAL DISEASE
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The initial physical examination showed a thin, pale, restless man. Dur~ng the examination he was constantly sitting up and lying down and picking at the bed clothes. Ansvvers were often irrelevant and there were long pauses while he peered around the room. His facies were anxious; his eyes were injected. There was a heavy odor of alcohol on his breath. Temperature, pulse and respiration were normal. Extra-ocular motions did not coordinate but pupillary reflexes were normal. The heart and lungs were normal and the blood pressure was 110/70. Abdominal examination showed firm musculature and minimal panniculus. There was tenderness in the left costovertebral angle and in the left flank and left upper quadrant with some involuntary spasm in the left upper quadrant. Murphy's sign was positive. A tender mass, oval, firm and non~ movable, was made out in the left upper quadrant to the left of the midline. Its limits -were indefinite but it gave the impression of extending from the left margin of the rectus muscle to the left anterior axillary line and downward to just above the level of the umbilicus. There was dullness to percussion over the mass. It did not pulsate. The remainder of the abdominal examination ,vas negative. There was no change in the mass during the first 10 days of hospitalization. The right arm was missing at the shoulder and there were poorly defined areas of hyperesthesia about the right shoulder and the½ inch stump was tender. Examination of the external genitalia and rectum was negative. The routine urinalysis on admission and three subsequent analyses showei:l·no variation from normal. The leukocyte count varied between 11,500 and 15,500 with about 75 per cent neutrophils throughout. The erythrocyte count decreased steadily from 4.5 million to 3.2 million and there was a corresponding drop in hemoglobin from 11.6 gms to 9.6 gms. On admission the blood nonprotein was 30 mg. per 100 cc; fasting blood sugar, 126 mgm per 100 cc and total protein, 6.2 gm per 100 cc. Blood Kahn was negative and the urine culture was sterile. Examination of the gastro-intestinal tract showed the stomach to be displaced markedly anteriorly and to the right. The first portion of the duodenum was similarly displaced. No intrinsic pathology could be distinguished. Subsequent studies showed displacement of the proximal limb of the splenic flexure anteriorly and to the right. The transverse colon proximal to this was slightly dilated. Serial studies showed slow passage of barium through the narro,-1- distorted limb. The distortion and poor function were considered due to extrinsic pressure. Chest films showed the heart and lung fields to be normal but there was moderate elevation of the left diaphragm. The dorso-lumbar spine showed no abnormality (fig. 1). The patient became rapidly completely disoriented and uncontrollable and was transferred to a closed ward of the Neuro-Psychiatric Service. A urological consultation was requested on the twenty-first day after admission. The patient had recovered from delirium tremens and the phantom limb pain had disappeared. He, however, complained of a steady aching pain in the left kidney region which had become gradually worse over a period of 10 days. There had been increasing leukocytosis to 20,000 and temperature of 101 and 102 F during
108
ERIC P. STONE
the past 2 days. Since admission, the mass had increased slightly in size and there was exquisite tenderness anteriorly and posteriorly over the left kidney region, with muscle spasm in these areas. The urine now showed a specific gravity of 1030, 1 plus albumin and 2-4 white blood cells with granular and waxy casts; but no red cells were found. On the basis of the physical examination and the history of hematuria, it was believed that the patient had a renal tumor and he was transferred to the Urological Section. Urological examination (November 1, 1947): The bladder was normal except that in the region of the trigone numerous submucosal black specks were seen which were believed to be remnants of submucosal bleeding. The ureteric orifices were functionally and morphologically normal and clear urine was noted emerging in peristaltic spurts from both orifices. AN o. 6 catheter passed freely to 28 cm. on the left, but due to spasm the right ureter could not be catheterized beyond 2 cm. Clear urine was obtained from the left kidney. After injection of phenolsulphonphthalein the dye appeared on the left in 6 minutes and 4 per cent was collected in 10 minutes. The pelvis accepted 10 cc of 20 per cent diodrast. No urine was obtained from the right ureter at any time due to technical difficulties with the catheter. The left kidney and bladder specimens were sterile and proved negative for tubercle bacilli by stain and culture. Neither specimen showed white or red blood cells. The retrograde pyelograms of the left upper tract (fig. 1, 2 and 3) showed the kidney to be displaced downward and its superior pole displaced posteriorly. There was some depression of the upper calyx and distortion of its infundibulum. There was a suggestion of a soft tissue mass springing from the anterior part of the upper pole. There was kinking at the ureteropelvic junction. The uniformity of the outlines of the depressed upper calyx militated against tumor and the gastro-intestinal studies combined with the pyelograms led to an x-ray and urological diagnosis of cyst of the pancreas; but it was believed that an adrenal cyst had not been ruled out. The next day intravenous pyelograms demonstrated a functionally and morphologically normal right upper genito-urinary tract. Left nephrectomy (Dr. Stone, November 4, 1947): Under continuous spinal anesthesia, a left lumbar oblique incision was made and the lower pole of the kindey was easily exposed. This appeared to be continuous with a large expanding mass which extended up to the diaphragm where it was firmly adherent. There was no line of demaraction between kidney substance and the mass, the renal capsule appearing to be continuous over the surface of kidney and mass. As adhesions between the mass and the muscles of the abdominal wall and the peritoneum were freed, instead of the cystic feel expected, the mass felt firm and solid. It was believed, at this point, that the diagnosis was mistaken and that we were dealing with a renal tumor. Therefore, the renal pedicle was exposed and then the freeing of the mass was continued. This was very difficult because of dense adhesions to all surrounding tissues. At one point while freeing the mass from the diaphragm there was a sudden profuse welling of bright blood from the region of the pedicle, with a concomitant abrupt drop in blood pressure to zero. A clamp was immediately applied to the pedicle and the bleeding promptly
PANCREATIC CYSTS SIMULATING RENAL DISEASE
109
stopped. The freeing of the upper limits of the mass was continued. Shortly, what proved to have been an extremely thick capsule was broken through and within could be felt a soft walled cyst. Eventually the kidney, thick capsule over the cyst and the cyst were removed in one mass. Inspection of the kidney bed showed good hemostasis of the pedicle but there were several small areas of the slight venous oozing in the renal fossa. A transfusion had been started and at this time the patient's blood pressure was 108/64 and the pulse 110. Pressure for a few moments with hot boric sponges and application of oxycellulose gauze appeared to have controlled the oozing areas. At the end of a routine closure
Fm. 2. Left kidney hemisected at hilus, A, and pancreatic cyst arising from upper pole, B.
around two cigarette drains, the blood pressure was unchanged and he was returned to the recovery room and placed in a shock bed and given supportive treatment; i.e. put in an oxygen tent and given a second transfusion of 500 cc citrated blood. Two hours postoperatively, he had a convulsion and his blood pressure dropped from 108/70 to 90/50 in about 5 minutes. He was pallid, had a cold sweat and was breathing with accessory muscles. Although there was only slight staining of the inner layer of the dressing, it was believed that he was suffering from a primary hemorrhage. Despite further transfusions and intravenous glucose given simultaneously in arm and leg veins and other supportive measures, the patient failed to rally and died 3 hours after the end of the operation. The operative specimen was a kidney (figs. 2 and 3), measuring 12 by 7 by 5
110
ERIC P. STONE
cm. with an attached cyst containing 390 cc of clear greenish-brown fluid. The cyst was surrounded, except at its abutment on the kidney by a dense gristly fibrous coat, continuous with the renal capsule, 1.8 cm. thick. Within this coat there was a separate cyst wall measuring 0.2 cm. in thickness, although some areas were thinned to 0.1 cm. The cyst wall rested on a depression in the upper pole of the kidney. The internal surface of the cyst wall was chocolate brown in color and showed fine wrinkles. At one point near the apex, there were two
Fm. 3. Operative specimen, cyst and kidney, cyst being opened. A, cyst; B, kidney; C, diverticulum of cyst entering substance of kidney but not communicating with any of renal elements.
diverticulum-like openings measuring 1.0 and 0.3 cm. in diameter. The cyst was freed easily from its bed in the kidney; but at one point there was a prolongation of the cyst into the kidney substance. This was blind and did not communicate with the calyces or pelvis. The kidney itself, except that the capsule was thickened and tenacious, was not remarkable. As the cyst wall was approached, the capsule became much thicker and could not be stripped from the parenchyma. Microscopically the wall of the cyst was composed of dense fibrous tissue in which were scattered large arteries and nerve filaments (fig. 4). In addition islands of pancreatic tissue were visible. Foci of lymphocytes and scattered phagocytes filled with hemosiderin were also seen. A portion of the
PANCREATIC CYSTS SIMULATING RENAL DISEASE
111
cyst was buried superficially in the kidney. There was fibrosis of the adjacent renal parenchyma with scattered lymphocytes. Parts of the inner surface of the cyst were ragged and lined with granulation tissue. Elsewhere the inner surface was smooth with no cellular elements. Pathological diagnosis: 1) pancreatic cyst; 2) normal kidney. The autopsy showed 1200 cc of bright blood in the peritoneal cavity and 270 cc of clot in the left renal fossa. No tear could be demonstrated in the peritoneum permitting connection between the renal fossa and the peritoneal cavity, but one must have existed. The renal veins and artery were efficiently tied and
Frn. 4. A, photomicrograph of cyst wall, showing fibrous tissue. B, photomicrograph of cyst wall, showing pancreatic tissue, A, imbedded in fibrous tissue, B.
the source of the bleeding could not be found but was presumably from some accessory vessel in the renal fossa. "The intestines were not remarkable except for marked fibrous thickening at the midportion of the transverse colon. Dissection of this region disclosed a sinus running posteriorly to the midportion of the transverse colon and extending upward into the wall both inferiorly and superiorly through two openings. The sinus and its limbs had a diameter of 0.8 cm. and the entire length of the sinus ·which extended down to the site of the removed kidney, although in the renal fossa it was a fibrous cord, was 8 cm. The inner surface of the sinus and its ramifications was lined with greyish-black tissue and was filled v\Tith rather thick greenish fluid. There was a marked fibrous thickening of the pancreas with an ill-defined mass situated below the thickened portion of the transverse colon. This appeared to include the pancreas and
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ERIC P. STONE
extended upward toward the stomach. Further examination revealed that in the region of this fibrous thickening there was a cyst 9 cm. in diameter arising in the head of the pancreas. It was firmly adherent to the posterior abdominal wall. The walls consisted of pancreatic tissue except for some portions where they were replaced by fibrous tissue. Small outpocketings of the cyst were noted. One extended toward the duodenum at which point it was adherent and there was here a small sinus extending into the duodenum 3.5 cm. below the pyloric ring. It was 0.4 cm. in diameter. The cyst lumen was crossed by several fibrous trabeculae 2 to 3 cm. in length and 1.5 cm. in thickness. As it passed the cyst wall, the stomach was adherent to it. The cyst contained a very small amount of greenish-black, thick fluid." The left adrenal was present and somewhat edematous. A further small nodule 2 cm. in diameter was found high in the renal bed and contained greenish-black, thick fluid. It appeared to be similar to the other pancreatic cysts. The spleen was enlarged and the artery was involved in some of the fibrous tissue that had surrounded the pancreatic cyst in the renal fossa. The gallbladder and liver were not remarkable. The heart, lungs, brain and remaining genito-urinary organs appeared to be normal. COMMENT
During its development, the dorsal bud of the pancreas undoubtedly became adherent to the mesonephron of the left kidney and as the position of the two changed during their development pancreatic tissue was drawn away from the main body and two bits of pancreatic tissue developed into heterotopic organs within the left kidney fossa. The explanation of cysts occurring simultaneously in all the existing pancreatic tissue in the body is obscure. Pancreatic cysts can follow abdominal injury. A war wound that was severe enough to amputate an arm could have conceivably caused coincidental abdominal trauma sufficient to result in a pancreatic cyst. But it would be difficult to believe that the heterotopic tissue in the renal fossa could have suffered equally. Moreover, traumatic cysts result from walling off of blood and escaped pancreatic fluid by a fibrous tissue reaction, so their walls do not contain pancreatic acini. Therefore, injury as the etiological factor may be ruled out. There were no ducts draining the heterotopic pancreas. That cysts would form in these areas is understandable as the acini functioned until the accumulated fluid inhibited further production of the juice. Then the coincidental obstruction of the ducts of Santorini in the pancreas itself or their invasion by bile or reduction in output of secretin causing inspissation of the pancreatic juice (conventional theories of the formation of pancreatic cysts) might explain the occurrence of the cyst found in the pancreas. However, resort to coincidence seems too easy and facile an explanation of the situation found in this case (Farber). This is especially so in view of recent data concerning the physiology of the pancreas. It is known that pancreatic secretion can be effected by nerve or blood born influences which would be equally active on pancreatic tissue wherever it may be found in the body. Such may be the case in Lindau's disease where
PANCREATIC CYSTS SIMULATING RENAL DISEASE
113
prenatal disturbances affect the development of the vessels in such a way that angiomata resulting in cysts appear in the pancreas and other organs, spinal cord, kidney and liver (Moore). More cogent are the cysts found in congenital pancreatic steatorrhea in which pancreatic fibrocystic disease is associated with recurrent or chronic respiratory infections and often meconium ileus. Our interest centers around the etiology of the pancreatic phases of this disease as they stress factors extrinsic to the organ. One theory is that the obstruction which causes the cysts is due to obstruction of the smaller ducts by inspissated pancreatic juice. Normally under the influence of secretin there is a flushing of the acini with a thick alkaline fluid which dilutes the pancreatic juice and sweeps it along the ducts. The juice, without this admixed fluid is rich in organic material which is coagulable. The duodenum of children dying of fibrocystic pancreatitis does not contain secretin and it was also found wanting in those cases of intestinal obstruction in which the pancreas shows a similar histological picture (Baggentoss, Power and Grindley; Mallory). Therefore, the basic difficulty lies in the failure of the production of secretin. This may be due to autonomic nerve disturbances which in turn may be due to virus infection, or as some believe, to Vitamin A deficiency. Other possibilities have been suggested: a) autonomic nerve over-stimulation of the pancreas leading to depletion of the zymogen granules resulting in the production of a viscid pancreatic juice; b) dehydration resulting in inspissation of the juice; c) malnutrition resulting in a protein deficiency which prevents the reparative protein synthesis in the cells of the pancreatic acini. No matter which of the above is the true cause of the inspissation of the pancreatic juice with its sequence of obstruction and cyst formation, if the patient survives long enough the small cysts may enlarge and even coalesce to form the type found in this case. In this particular patient, the status of the autonomic nervous system is not known, although his alcoholic history suggests that it might have been seriously disturbed. The possiblity of a virus infection at an earlier date cannot be proved or disproved. But his long alcoholism with its attending gastritis could readily account for vitamin or protein deficiency or both. While any of the above theories could account for similar changes occurring simultaneously in pancreatic tissue in any part of the body, it is obvious that specific application of any one of them to this individual case is highly speculative. The validity of no one of them can be proved postmortem and would have been very difficult to prove even before death. Further comment should be made as to the treatment of the condition found. The treatment of cysts of the pancreas is operative. The vast majority of the cases have been treated by marsupialization of the cyst (Brunschwig; Nygaard and Stacy). The resulting fistulas have usually closed in a period of months, although some have persisted and required closure by jejunal implantation of the proximal end of the fistulous tract (Lahey and Lium). In only 17 was resection of the cyst technically possible although such is the ideal procedure. Twelve were simply drained with eventual recovery in all. One case was aspirated and
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lived for many years with recurrences. Because of the malignanat nature of the cyst found at operation, one case was subjected only to exploration (table 1). In the case reported above, there was one feature that has not been stressed in the literature, and lack of familiarity with it led to an extensive and fatal operation. It was not appreciated that, although many pancreatic cysts are thin walled, a great number, particularly those of long standing or those resulting from an acute attack of pancreatitis, are thick walled. In reviewing the literature, mention of this is found in only one article (Ormond, Wadsworth and Morley). Since performing this operation, a colleague has stated that he was deceived in exactly the same way be a recent case (Austen). When the kidney and the attached cyst were exposed, the pathological mass felt exactly like a stony hard, solid tumor. The renal capsule extended over the mass with no line TABLE
1.
Operations on 80 cases (including one reported in this paper)
OPERATION
NUMBER OP.
DEATH
PERSISTENT FISTULA
END RESULT
--
43
0
2
*40 recovered
1
0
0
1 recovered
Resection
19
2
0
17 recovered
Partial resection and drainage or drainage
14
2
0
1 sinus closed surgically, 1 persistent sinus
Aspiration
1
0
0
1 recurrence
Exploration
1
0
0
*
Marsupialization Marsupialization and instillation of sodium marhuate
* 1 case died later of pancreatic malignancy.
of demarcation being made out. It was believed that the preoperative diagnosis was in error and a difficult nephrectomy was carried out. Had the possibility of such a deceivingly thick walled cyst been realized, aspiration would have revealed the correctness of the preoperative diagnosis and drainage or marsupialization could have been done with little risk to the patient. CASES SIMULATING GENITO-URINARY DISEASE REPORTED IN THE LITERATURE
Nine such cases were found in the articles reviewed. They are summarized in table 2. Including the one here reported, it is seen that a correct diagnosis was made in only 2 of 10 cases. It is noteworthy that blood amylase studies were done preoperatively in only 2 cases and in neither was it of aid. Gastro-intestinal series were done in four and the diagnosis was established in 2 cases by this means. In the urological studies made in 9 of the cases, abnormalities were noted in all.
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PANCREATIC CYSTS SIMULATING RENAL DISEASE
But such changes, while they should be sufficient to rule out renal tumor, do not differentiate between the various types of extrarenal masses that cause pyelographic changes by virtue of external pressure. Seven patients gave a history of attacks of gastro-intestinal symptoms, varying from severe to acute, for some years prior to the onset of the attack which led to the current illness. Four gave TABLE
AUTHOR
Ormond
2.
Panr;reatic cysts affecting the genito-urinary tract
G-U FINDINGS
Rt. kidney lt. of midline.
Lt. pelvis distorted
PREOPERATIVE DIAGNOSIS
OPERATIVE FINDINGS
RESULT
Retro peritoneal tumor
Cyst of head. Mar- Cured supialized. Na. morhuate instilled
Pancreatic cyst
Cyst of tail and body both drained Cyst of tail marsupialized
Cured
Cyst of tail marsupialized
Cured
Mass in lt. kidney region
Cured
Kummer
Lt. upper calyces obliterated
Renal tumor
Ransohoff
Lt. hematuria due to obstruction of renal vein
Sarcoma of kidney Cyst of tail drained
Died
Walters
Displaced It. kidney
Extrarenal tumor
Cyst of tail marsupialized
Cured
Denter
Displaced It. kidney
Found at autopsy
Cyst of tail
Cured
Martin
Mass in It. kidney region
Renal tumor
Cyst of head aspirated
Recovered
Case
Distorted rt. ureter
Renal cyst
Cyst of head marsupialized
Cured
Stone
Compressed upper It. calyces
Pancreatic or adrenal cyst
Cyst, heterotopic, resected
Died
a past history of severe abdominal trauma. In 8 of 10 cases, the urological involvement was on the left side and due to heterotopic cyst or cysts of the tail (Brunschwig). This is understandable as theoretically cysts arising in the head are buffered from the kidney by the duodenum and bile ducts. Disturbances of these structures intervene before the right kidney can be seriously affected, so treatment is instituted before right upper tract symptoms appear. In treatment it is found that the distribution of operative procedures was much the same as that for the whole series. Five were marsupialized, 3 drained, 1 aspirated and 1 resected. The only death resulted from the resection.
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ERIC P. STONE CONCLUSIONS
Masses impinging on the kidneys can readily be demonstrated to be extrinsic by pyelography, but this does not differentiate between the various types of retroperitoneal tumors and cysts which might appear as such masses. To prove or disprove such to be a pancreatic cyst, the following studies may be helpful (in order of importance): a) Gastro-intestinal x-ray. b) Blood amylase determinations. c) Analysis of the past history for prior episodes of biliary attacks, attacks of acute pancreatitis or abdominal trauma. Of the available operative procedures: a) Resection effects a cure without prolonged morbidity from a draining sinus, but this is technically impossible in a majority of the cases. b) Marsupialization, with or without partial resection, eventually effects cure in a large proportion of the cases in which it is carried out. c) Drainage gives about the same results as marsupialization. d) Aspiration is not recommended. It is stressed that a pancreatic cyst may have a thick gristly false capsule which deceives the operator into believing that he is dealing with a solid tumor. If he has expected a cyst and finds a hard mass, attempted aspiration can do no harm if it is a tumor about to be removed and, if fluid is obtained, this may permit a less hazardous procedure than resection. I am indebted to Dr. Robert Fienberg, chief of the Pathology Department and to Dr. Daniel Kornblum, chief of the X-Ray Department of the Cushing V. A Hospital for valuable suggestions and interesting discussions concerning this case. REFERENCES ANDERSON, D. H.: Am. J. Dis. Child., 63: 643, 1942. ANGER, T. AND LEDENTU: Bull. de la Soc. Anatomique de Paris, second series, 10: 197, 1865. AusTEN, GEORGE: Personal communication. BAGGENToss, A.H., POWER, M. H. AND GRINDLEY, J. H.: Am. J. Path., 24: 692, 1948. BARBOSA, J. G., DEC., DOCKERTY, M. B. AND WAUGH, G. B.: Surg., Gynec. & Obst., 82: 527, 1946. BOZEMAN, N.: Med. Record, 21: 46, 1882. BRUCK, S.: Radiology, 25: 303, 1935. BRUNSCHWIG, A.: The Surgery of Pancreatic Tumors. St. Louis: C. V. Mosby Co., 1942, chapts. 7-9. CASE, J. T.: Am. J. Roent. & Radium Therapy, 44: 485, 1940. CONNOLLY, D. I.: Lancet, 1: 803, 1911. ELMAN, R.: Am. J. Dig. Diseases, 6: 237, 1939. FARBER, S.: N. Eng. J. Med., 229: 653 and 682, 1943. HIATT, R. B. AND WILSON, P. E.: Surg., Gynec. & Obst., 87: 317, 1948. HoLT, J. F.: Radiology, 46: 239, 1946. JUDD, E. S.: Minn. Med., 4: 75, 1921. JUDD, E. S., MATTSON, H. AND MAHORNER, H. R.: Arch Surg., 22: 838, 1931. KERR, A. R.: Surg. Gynec. & Obst., 27: 40, 1918. LAHEY, F. H. AND LruM, R.: Surg., Gynec. & Obst., 44: 79, 1930. MAHORNER, H. R.: Proc. Staff Meetings Mayo Clinic; 5: 101, 1930. MALLORY, T. B.: N. Eug. J. Med., 234: 151, 1948. MARTIN, H.B.: Brit. Med. J., 1: 481, 1941. MATTSON, H.: Proc. Staff Meetings, Mayo Clinic, 5: 100, 1930.
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MooRE, R. A.: Textbook of Pathology. Philadelphia: W. B. Saunders Co., 1945, p. 1202. NovAK, E.: Surg., Gynec. & Obst., 45: 586, 1927. NYGAARD, K. K. AND STACY, J.C.: Arch. Surg., 45: 206, 1942. NYGAARD, K. K. AND WALTERS, W.: Ann. Surg., 106: 49, 1937. ORMOND, J. K., WADSWORTH, G. H. AND MORLEY, H. V.: Trans. Am. Assoc. Genito-urin. Surg., 35: 175, 1942. PALOWE, D.: Surg., Gynec. & Obst., 82: 115, 1946. PINKHAM, R. D.: Surg., Gynec. & Obst., 80: 225, 1945. RABINOWITCH, J. AND PINES, B.: Arch. Surg., 45: 727, 1942. RANSOHOFF, J.: Surg., Gynec. & Obst., 22: 275, 1916. SCHULTE, T. L. AND EMMETT, J. L.: J. Urol., 52: 215, 1939. WALTERS, W. AND CLEVELAND, W. H.: Arch. Surg., 47: 819, 1941. WALTERS, W., McCAUGHAN, J.M. AND PuEsTow, C. D.: Cyclopedia of Medicine and Surgery and Specialties. Philadelphia: F. A. Davis Co., Vol. 11, pp. 96--152. WALTERS, W. AND THIESSEN, N. W.: Surg. Olin. N. Am., 15: 1159, 1935. YOUNG, E. L.: N. Eng. J. Med., 216: 334, 1937.