Postcholecystectomy Syndrome and its Association With

Ampullary Stenosis

James A. Gregg, MD, Boston, Massachusetts

Geoffrey Clark, MD, Dover, New Hampshire

Carey Barr, MD, Natick, Massachusetts

Alan McCartney, MD, Wellesley, Massachusetts

Anthony Milano, MD, Natick, Massachusetts

Charles Volcjak, MD, Fall River, Massachusetts

Cholecystectomy for cholecystitis with or without abdominal pain is an accepted surgical procedure. It is estimated that approximately 400,000 such oper- ations are performed annually in the United States [I]. When cholelithiasis is associated with abdominal pain, it is sometimes difficult to be certain whether the pain is due to the presence of gallstones, associ- ated pancreatitis, ampullary stenosis or a combina- tion of these disorders, since all may produce similar pain patterns. The difficulty in defining these problems preoperatively is undoubtedly the reason for the continuation or recurrence of abdominal pain postoperatively in 10 to 60 percent of patients after cholecystectomy for either cholelithiasis or acalcul- ous cholecystitis, with the highest incidence of un- satisfactory results occurring in patients with acal- culous cholecystitis [Z-13]. Such postoperative symptoms have been labeled the postcholecystec- tomy syndrome or biliary dyskinesia, with neither term defining the actual abnormalities responsible for the patient’s recurrent symptoms. In some studies pancreatitis, retained common duct stones and am- pullary stenosis were found to account for the symptoms, but in many instances no abnormality was demonstrated.

In an effort to more adequately define the cause of persistent or recurrent abdominal pain, we studied 56 consecutive patients who underwent cholecys-

From the Departments of Medicine and Swgery, the Leonard Morse Hospital, Natick, Massachusetts; the Department of Medicine, New England Dea- coness Hospital, Boston, Massachusetts; the Department of Medicine, Wentworth-Douglas Hospital, Dover, New Hampshire; and the Department of Surgery, the Union Hospital, Truesdale Division. Fall River, Massachusetts.

RequeStS for reprints should be addressed to James A. Gregg, MD, 110 Francis Street, Boston, Massachusetts 02215.

tectomy for recurrent upper abdominal pain and returned with similar symptoms postoperatively. The patients were studied with endoscopic retrograde cholangiopancreatography, morphine neostigmine (Prostigmin@) test, gray-scale abdominal ultrasound, upper gastrointestinal series and intravenous chol- angiography when needed. In all but five patients, a definable abnormality was found to account for the patient’s recurrent symptoms.

Material and Methods

Fifty-six patients ranging in age from 22 to 76 years were studied. Fifty-two were women and 4 men. All had undergone cholecystectomy for one or more ep- isodes of upper abdominal pain thought to be sec- ondary to cholecystitis. In all patients the recurrent abdominal pain was in the upper abdomen, usually the right upper quadrant or the epigastrium, and it frequently radiated through to or around to the back. No patient had jaundice. In no patient was there any evidence of pancreatitis preoperatively or at chole- cystectomy. At cholecystectomy, gallstones were found in all but three patients, who had chronic cholecystitis without gallstones. Common duct stones were present in four patients at the time of chole- cystectomy, and each of these patients underwent common duct exploration with choledocholithotomy and t-tube drainage.

Endoscopic retrograde cholangiopancreatography [14] and morphine neostigmine test [15] were per- formed by previously described methods. Abdominal ultrasound was performed using the gray-scale technique. The criteria for ampullary stenosis were

374 The American Journal of Surgery

Postcholecystectomy Syndrome

TABLE I Recurrence of Abdominal Pain After Cholecystectomy

Clinical Condition o-1 l-6 6-12

Months 12m-24 24-60 60-120 >I20

Isolated ampullary stenosis 11 13 3 2 1 1 1

Pancreatitis 5 4 1 2 1 Common duct stone 5 1

Probable common 1 duct stone

Qlsfunctional sphincter 4 or pancreatitis

Total no. of patients* 26 18 4 4 2 1 1

l Total is 57 because 1 patient had ampullary stenosis with a secondary common duct stone

described in an earlier report [15]. Moderate stenosis

was diagnosed when the ampulla was so tight that the cannula could barely be inserted into it. Marked

stenosis was considered present when the orifice was SC) tight that only the tip of the cannula could be impacted in the ampullary orifice. Secretin, 1 unit/kg, was administered intravenously as a bolus to facili- tate cannulation in all patients with moderate to marked stenosis.

Results

The recurrence of abdominal pain after surgery varied but in 44 patients began within 6 months after

cholecystectomy. In three patients, recurrent epi- sodes of abdominal pain began before the patient left t.qe hospital after cholecystectomy. In three patients, injections of morphine for pain intensified or pre- cipitated an attack of abdominal pain identical to

that for which the patient sought help. In many pa- tients the interval between the attacks of pain de- creased after cholecystectomy and the pain became constant, with superimposed episodes of more severe

pain lasting from minutes to days. Table I shows the intervals at which the first postoperative episode of pain occurred. Pancreatitis was ultimately docu-

mented in 13 patients. In 12 it was first found by demonstrating an enlarged pancreas with gray-scale ultrasound or by demonstrating an elevated level of serum amylase (in 8 cases) or lipase (in 4 cases) dur- ing one or more episodes of pain. In one patient pancreat.itis was diagnosed by demonstrating pan- creatic hypersecretion with very high levels of amy- lase and lipase in the pancreatic juice during an in- traductal secretin test [IS] (Gregg JA: unpublished observations).

Forty patients were demonstrated to have mod- erate to marked ampullary stenosis during endo- scopic retrograde cholangiopancreatography. In 32 cases the stenosis was an isolated entity, while in 8 it occurred in association with pancreatitis. The

Volume 139, March 1980

morphine neostigmine test was positive in 20 patients and negative in 8. Twenty of the patients with a positive morphine neostigmine test had moderate to marked ampullary stenosis. Sixteen patients with a

positive morphine neostigmine test had isolated ampullary stenosis, 1 had pancreatitis, 2 had common duct stones, and 1 had a dysfunctional sphincter. Of

the eight patients with a negative morphine neos- tigmine test, seven had pancreatitis and one had

isolated ampullary stenosis.

Abdominal gray-scale ultrasound demonstrated a dilated common bile duct in 5 patients and en- largement of the head of the pancreas (compatible with pancreatic edema) in 5 patients; the results were normal in 45 patients. In four patients in whom

gray-scale ultrasound showed no dilatation of the common duct, the duct was dilated and measured 10 to 16 mm in diameter. The serum alkaline phospha- tase level was elevated in nine patients during an

episode of pain; six of these patients had retained common duct stones.

Endoscopic retrograde cholangiopancreatography was successful in opacifying the pancreatic duct in 45 patients. In two patients with common duct stones on endoscopic retrograde cholangiopancreatography, no attempt was made to opacify the pancreatic duct. Pancreatograms were abnormal in 18 patients, all of

whom demonstrated slight dilatation (4.5 to 7.0 mm) of the main pancreatic duct in the head of the gland. One patient had a small calculus in the main pan- creatic duct. Three patients had irregular margins of the pancreatic duct and two had stenosis of the lower end of the duct. The common duct was opacified in 45 patients and normal in 31. One or more common duct stones were demonstrated in five patients by endoscopic retrograde cholangiopancreatography. A small common duct stone was missed during the procedure in one patient who also had tight ampul- lary stenosis; the stone was subsequently found

during surgery. Endoscopic retrograde cholan- giopancreatography demonstrated dilatation (10 to

375

Gregg et al

22 mm) of the common duct in 12 patients, and in 8 of the 12 the diameter was 12 mm or greater. A di- lated common duct was found in four of the patients with common duct stones. Three patients had ir- regularity of the lower end of the common bile duct, presumably due to pancreatitis.

Comments

The anatomic abnormalities encountered in the present series are similar to those encountered in other series. In almost all cases the cause of recurrent abdominal pain after cholecystectomy was either ampullary stenosis, pancreatitis or retained common duct stone. In only five patients could no definite abnormality be demonstrated as a cause of the pain. Recurrent pancreatitis, ampullary dysfunction or both were thought to account for the recurrent ab- dominal pain in four of these patients, and the fifth probably had passed a common duct stone. Of par- ticular interest was the large number of patients with moderate to marked ampullary stenosis. Langen- buch, as quoted by Grage et al [I 71, first suggested that stenosis of the sphincter of Oddi might represent a cause of biliary-like pain. Trommald and Seabrook [18] provided the first description of ampullary ste- nosis, describing fibrosis of the sphincter in eight patients. Since then, this entity has been increasingly recognized as a cause of upper abdominal pain oc- curring either as an isolated abnormality or in asso- ciation with gallbladder disease, pancreatitis or both [4-13,15,19-361 (Gregg JA: unpublished observa- tions). Hess, as quoted by Classen and Safrany [37], reported that ampullary stenosis was present in 25 percent of patients with gallstones and 50 percent of those with common duct stones. Imamoglu et al [38] found ampulhry stenosis in 58 percent of their pa- tients when routine examination of the ampullary area was performed during cholecystectomy. The clinical course of our patients with ampullary stenosis is similar to that previously reported.

with the postcholecystectomy syndrome using en- doscopic retrograde cholangiopancreatography and demonstrated ampullary stenosis in 5 of 36 patients. Seven were found to have common duct stones and six pancreatitis. Moody et al [30] recently reviewed 28 patients undergoing septectomy, and in some cases sphincteroplasty as well, for the postcholecys- tectomy syndrome, but made no mention of ampul- lary stenosis, even though some of the patients were studied with endoscopic retrograde cholangiopan- creatography. The majority of their patients had retained common duct stones.

The morphine neostigmine test has been helpful in our experience in identifying patients with am- pullary stenosis or ampullary dysfunction. This test was positive in most patients with ampullary stenosis and no pancreatitis. It was positive in only one of eight patients with pancreatitis, even though seven of the eight had associated ampullary stenosis. We believe that the test does not evaluate pancreatic function but rather detects ampullary dysfunction or ampullary stenosis.

A dilated common bile duct was encountered in only 12 patients in this series. As has been true in other studies, dilatation of the common duct is en- countered primarily in patients with common duct stones. Occasionally it is encountered in patients with ampullary stenosis, but usually the common duct is of normal caliber even in the presence of tight ste- nosis. Elevated serum alkaline phosphatase was en- countered principally in patients with common duct stones. In patients in whom the common duct cannot be opacified during endoscopic retrograde cholan- giopancreatography, intravenous cholangiography is indicated. Dilatation of the common duct and de- layed emptying in the absence of common duct stones is presumptive evidence of common duct ob- struction. Abdominal ultrasound may also be very helpful in the detection of a dilated common bile duct, particularly when the caliber of the duct ex- ceeds 15 mm.

Duoclenoscopy with endoscopic retrograde cho- During the last few years we have detected am- langiopancreatography provides an excellent means pullary stenosis preoperatively in many patients with to establish the diagnosis of ampullary stenosis pre- gallstones who were awaiting elective cholecystec- operatively as well as a means of detecting this ab- tomy (Gregg JA: unpublished observations). Dem- normality in patients with previous cholecystectomy onstration of the stenosis preoperatively enabled the who return with abdominal pain. In those patients surgeon to perform sphincteroplasty at the time of in whom a tight sphincter is encountered during cholecystectomy, thus probably saving the patient endoscopy, intravenous administration of secretin a later operative procedure. Ampullary stenosis has will help the endoscopist determine whether the also been detected during surgery, enabling concur- sphincter is closed due to normal sphincter con- rent sphincterotomy or sphincteroplasty. In most traction or whether it is truly stenotic because in instances this was done in conjunction with common patients with tight stenosis, the ampulla either does duct exploration [19-22,26,34]. Some workers have not open or will only barely open after administration found manometry at the time of surgery helpful in of secretin. Deyhle et al [39] also studied patients detecting a dysfunctional or stenotic sphincter [4].

376 The American Journal of Surgery

Pancreatitis was the second most common cause

of the postcholecystectomy syndrome in our series

and has been a major cause in other series also [39]. Teelve of the 13 patients in our series with pan- creatitis also had associated ampullary stenosis. In addition to endoscopic retrograde cholangiopan- creatography, abdominal ultrasound may be helpful in detecting some patients with pancreatitis, but those with chronic pancreatitis or minimal pancreatic

edema may have normal studies [40]. Pancreatic duct abnormalities encountered in our patients during endoscopic retrograde cholangiopancreatography consisted of slight dilatation of the main duct or ir- regular caliber of the duct. An intraductal calculus

was present in only one patient. Retained common duct stones were the least

common cause of the postcholecystectomy syndrome in our series, although in some series they account for the majority of cases [6,26,30]. In our patients with retained common duct stones, recurrent episodes of pain began within the 1st month after cholecystec- tomy in all but one patient; the stones were un- doubtedly overlooked at the time of cholecystectomy. In one patient it appeared that a common duct stone

developed secondary to ampullary stenosis. It has been documented that common duct stones may develop secondary to bile duct obstruction [:!1,26,32,33,38], and we have observed this in other cases as well. The incidence of common duct stones during cholecystectomy ranges from 7 to 15 percent [i ,411, and the incidence of retained common duct stones is about 1 percent [I].

Of the five patients in whom no definite abnor-

mality could be established, four were thought to hsve pancreatitis, a dysfunctional sphincter or both. Dysfunctional sphincters have been noted in other

reports; these patients may have a positive morphine neostigmine test, as did two of ours. In some cases morphine administered parenterally may precipitate

an episode of severe abdominal pain, yet surgical exploration may reveal an entirely normal sphincter [8,42], as it did in one of our cases.

From the results of this study it is apparent that essentially all patients returning after cholecystec- tomy with episodes of pain identical to their preop- erative episodes of biliary-like pain have an organic reason for their symptoms. While pancreatitis and retained common duct stones account for these svmptoms in some patients, ampullary stenosis was dy far the most common cause in our experience.

Whenever possible, an attempt should be made to determine whether associated ampullary stenosis is present in patients undergoing elective cholecys- tectomy for gallstones or acalculous cholecystitis. A rational approach to the problem might be to per-

Volume 139, March 1980

Postcholecystectomy Syndrome

form a morphine neostigmine test in all such pa-

tients. Those with positive results, either with re- production of the patient’s pain or a significant ele-

vation of serum amylase or lipase, should undergo endoscopic retrograde cholangiopancreatography to rule out the presence of associated ampullary ste- nosis. Endoscopic retrograde cholangiopancreatog- raphy might also be beneficial in patients with pain

that is atypical of biliary colic (long episodes of pain or chronic pain of long duration). Such an approach should be helpful in detecting the presence of am-

pullary r;#tenosis preoperatively so that associated sphincteroplasty may be performed during chole- cystectorny, thus saving the patient a later surgical

procedure.

Summary

Fifty-six consecutive patients returning with re- current or persistent upper abdominal pain after cholecystectomy were studied by endoscopic retro- grade cholangiopancreatography, abdominal ultra-

sound and morphine neostigmine test. In 44 patients, pain recurred within 6 months after cholecystectomy.

Forty patients were demonstrated on endoscopic

retrograde cholangiopancreatography to have mod- erate to rnarked ampullary stenosis, which occurred as an isolated abnormality in 32 patients and in as- sociation with pancreatitis in 8. Thirteen patients

were found to have pancreatitis, and 6 had retained common duct stones. In five patients no definite abnormality was demonstrated. The morphine neostigmine test was positive in 16 of 17 patients with isolated ampullary stenosis and in only 1 of 8 with pancreatitis. This test may be helpful in patients who

are to undergo cholecystectomy. In those with posi- tive results, endoscopic retrograde cholangiopan- creatography would help assess the size of the am-

pullary sphincter so that sphincteroplasty could be done at the time of cholecystectomy in appropriate patients.

References

1.

2.

3.

4.

5.

6.

7.

a.

Waye LW. Retained common duct stones. Surg Clin North Am 1973;53:1130.

Meyers SG, Sandweiss DJ, Saltzstein HC. End results after gallbladder operations. Am J Dig Dis 1936;5:667.

Meyers HC. Persistent pain following cholecystectomy. Am Surg 1953;19:412.

Mallet-Guy P, Rose JD. Preoperative manometry and radiology in biliary tract disorders. Br J Surg 1956;44:55.

Berk JE. Postcholecystectomy syndrome. Gastroenterology 1958;34: 1060.

Raymer JB, Tarpanian DA, Meyers SG. Symptoms following cholecystectomy. Am J Dig Dis 1960;5:55.

Burnett W, Shields R. Symptoms after cholecystectomy. Lancet i958;1:923.

Holtzer JD, Hulst SG. Confirmation of postcholecystectomy

Gregg et al

biliary dyskinesia by elevation of serum transaminases (GOT and GPT) after injection of morphine. Acta Med Stand 1973;194:221.

9. Stefanini P, Carbone M, Patrassi N, Loriga P, DeBernardinis G, Negro P. Fattori the influenzano I risultati a distanza della colecistectomia. Recenti Prog Med 1975;58:338.

10. Heinkel Von K, Maurer W, Kimmig JM. Das sogennante postcholezystektomiesyndrom 2. Gastroenterologie 1971;9:3571

11. Troppoli DV, Cella LJ Jr. The postcholecystectomy syndrome. Ann Surg 1953; 137:250.

12. Womack NA. Crider RL. Persistence of symptoms following cholecystectomy. Ann Surg 1947; 126:31.

13. Schein CJ, Beneventano TC. Choledochoduodenal junction stenosis in the postcholecystectomy syndrome. Surgery 1968;64:1039.

14. Gregg JA. Endoscopic cannnulation of the ampulla of Vater. Am J Gastroenterol 1973;60: 142.

15. Gregg JA, Taddeo AE, Milan0 AF, McCartney AJ, Santoro BT, Frager SH, et al. Duodenoscopy and endoscopic pancrea- tography in patients with positive morphine prostigmine tests. Am J Surg 1977;134:318.

16. Gregg JA, Sharma MM. Pancreatic hypersecretion in patients with liver disease. Am J Dig Dis 1978;23:9.

17. Grage TB, Lober PH, lmamoglu K, Wangensteen OH. Stenosis of the sphincter of Dddi. A clinicopathological correlation review of 50 cases. Surgery 1960;48:304.

18. Trommald JP. Seabrook DB. Benign fibrosis of sphincter of Oddi: a report of 8 cases. West J Surg 1950;58:89.

19. Cattell RB, Colcock BF. Fibrosis of the sphincter of Oddi. Ann Surg 1953; 137:797.

20. Riddell DH, Kirtley JA. Stenosis of the sphincter of Oddi. Ann Sura 1959:149:773.

21. CattellEB, Colcock BP, Pollack JL. Stenosis of the sphincter of Dddi. N Enol J Med 1957;256:429.

22. Paulino F, Roseli A. Stenosis of the sphincter of Dddi. Surgery 1963;54:865.

23. Acosta JM, Nardi GL. Papillitis. Arch Surg 1966;92:354. 24. Shingleton WW, Gamburg D. Stenosis of the sphincter of Dddi.

Am J Surg 1970;119:35. 25. Cole WH, Grove WJ. Persistence of symptoms following cho-

lecystectomy with special reference to anomalies of the ampulla of Vater. Ann Surg 1952;136:73.

26. Jones AS, Steedman RA, Keller TB, Smith LL. Transduodenal

sphincteroplasty (not sphincterotomy) for biliary and pan- creatic disease. Indications, contraindications and results. Am J Surg 1969;118:292.

27. Kirtley JA, Youngblood RW. Strictures of the common bile duct and ampulla. Ann Surg 1961;153:725.

28. Partington PF. Sphincterotomy for stenosis of the sphincter of Oddi. Surg Gynecol Obstet 1966;164:282.

29. Trommold JP, Perry JF Jr. Benign fibrosis of the sphincter of Oddi. West J Surg 1950;58:89.

30. Moody FG, Berenson MM, McCloskey D. Transampullary sep- tectomy for post-cholecystectomy pain. Am Surg 1977; 186:415.

31. Taft DA, Wreggit GR. Sphincteroplasty for postcholecystectomy syndrome. Am Surg 1974;40:527.

32. McKittrick LS, Wilson NJ. Indication for and results following exploration of the common bile duct for stones. California Med 1949;7:132.

33. Johnston EV, Waugh JM, Good CA. Residual stones in the common bile duct: the question of operative cholangiograms. Am Surg 1954; 139:293.

34. Paulino F, Cavalcanti A. Anatomy and pathology of the distal common duct: special reference to stenosing Odditis. Am J Dig Dis 1960;5:697.

35. Bartlett MK, Nardi GI. Treatment of pancreatitis by transduodenal sphincterotomy and exploration of the pancreatic duct. N Engl J Med 1960;262:643.

36. Doubilet H, Mulholland JH. Eight year study of pancreatitis and sphincterotomy. JAMA 1956;160:521.

37. Classen MM, Safrany L. Endoscopic papillotomy and removal of gallstones. Br Med J 1975;4:371.

38. lmamoglu K, Perry JF Jr, Wangensteen OH: Experimental production of gallstones by incomplete stricture of the ter- minal common bile duct. Surgery 1957;42:623.

39. Deyhle VP, Ammann R, Nette’L. Wert der endoskopischen retrograde cholangiopankreatographie beim sog. Postcho- lecystectomiesyndrom. Z Gastroenterol 1974; 12:620.

40. Gregg JA, MacDonald DB, Gramm H. Combined endoscopic pancreatography and ultrasonography for the diagnosis of pancreatic disease. Gastroenterology 1975;68:906.

41. Arnold DJ. 28,621 cholecystectomies in Ohio. Am J Surg 1970;119:714.

42. Manier JW, Cohen WN, F’rinten KJ. Dysfunction of the sphincter of Dddi in a postcholecystectomy patient. Am J Gastroenterol 1974;62:148.

378 The American Journal of Surgery