Khalid R Murshid
Department of Surgery, King Khalid University Hospital, Riyadh, Saudi Arabia
Source: http://www.saudijgastro.com/text.asp?1996/2/3/124/34017
Abstract
The objective is to study the Postcholecystectomy Syndrome (PCS); its causes, different methods of diagnosis and different treatment options and their results in order to deduce from the above data the best method of prevention of its occurrence and the best method of treatment once it has occurred. Data sources include a medline search of articles covering this topic in the English literature and the abstracts of non-English articles from 1966-1994. The total number of articles of interest to the study being approximately 120. There are many causes of PCS, some related to improper preoperative diagnosis and some related to avoidable and unavoidable consequences of cholecystectomy. The different diagnostic modalities are dependent on the cause as are the different treatment options. The best treatment of this condition remains prevention whenever possible. Proper diagnosis of those patients who truly require cholecystectomy and care in performing the cholecystectomy will minimize the incidence of this syndrome.
Definition of PCS
This term has been used to signify the heterogeneous group of disorders affecting patients who continue to complain of symptoms after cholecystectomy. It is not really a syndrome and the term is confusing [1] . It was originally defined by Pribram as a pure functional disturbance after cholecystectomy. Today it has become a melting pot of various postoperative syndromes of mostly obscure origin [2] . In about half the cases treated by cholecystectomy, cholecystectomy leaves certain problems of digestive dysfunction (dyspeptic-pain syndrome) unresolved but does not cause new symptoms and therefore there is no justification for the term postcholecystectomy syndrome [3] .
Effect of cholecystectomy
In order to study the causes of the PCS we must know the effects of cholecystectomy and how cholecystectomized patients are different from those with intact gallbladders whether these gallbladders contain gallstones or not. Absence of the gallbladder, on its own, i.e., cholecystectomy per se has not been reported to impair intestinal digestion or absorption [4] . As a matter of fact there is a congenital anomaly known as agenesis of the gallbladder and cystic duct which does occur, although uncommonly [5] , and patients with this anomaly have not been reported to suffer any digestive or absorption problems.
It is a well known fact that the gallbladder acts as a volume reservoir, collecting the bile produced by the liver and releasing it when required, i.e. after a meal. Functional consequences related to this property are rare following cholecystectomy because the loss of the gallbladder is compensated for by the biliary tree [2] which has been shown to be dilated following cholecystectomy (12->13-14 mm) [6],[7] and in one study they were shown on ERCP to have a mean diameter of 18 mm [8] .
This dilatation not only involves the CBD but also the rest of the extrahepatic and intrahepatic bile ducts. These were shown on live biopsies in dogs [9] and in humans [10] following cholecystectomy, and this dilatation is not without consequences. It leads to dilatation, proliferation and formation of anastomoses between the small biliary ducts with evidence of an inflammatory reaction of the connective tissue network of the liver [9] leading to portal and periportal hepatitis, liver fibrosis and cirrhosis [10] .
It is proposed that patients with congenital agenesis of the gallbladder and cystic duct develop symptoms by dyskinetic alteration of the Sphincter of Oddi More Details leading to long-term choledochal distention causing bile stasis and possible infection [5] . This may be an explanation for PCS and also an explanation of the finding of stones many years following cholecystectomy in spite of normal intraoperative cholangiogram [5] . Fifty-six percent of post- cholecystectomy patients undergoing ERCP showed morphological abnormalities in the biliary system (esp. stenosis and stones) [11] .
The gallbladder also acts as a pressure reservoir against a contracted sphincter of Oddi. This has been shown by comparing patients’ manometric CBD pressures following an I.M. injection of 0.2 mg/kg of morphine before and after cholecystectomy. Patients with gallbladders removed showed an increase in CBD pressure. This again may partly explain the development of PCS [12] .
Gallstone patients have a higher tendency to duodenogastric reflux of bile acid. This tendency is further increased by removal of a functioning gallbladder (but not a nonfunctioning gallbladder) [13] . The overall incidence of positive endoscopic and histopathologic changes in the stomach of cholecystectomized patients is 20-30% especially significant is the atrophic type of gastritis [14] . With the passage of time following cholecystectomy, manifestations of chronic duodenal obstruction become advanced. This results in an increase in the incidence, in these patients, of gastroduodenal reflux and decreased acid forming function of the stomach [15] .
In another study, cholecystectomized patients when compared to cholelithiasis patients and healthy patients showed:
1.Much higher duodenogastric reflux
2.Much higher concentrations of bile acid in gastric juice [16] .
There is evidence to suggest that the incidence of colonic tumors is higher in cholecystectomized patients compared to noncholecystectomized patients [17],[18],[19] .
In addition to extrabiliary disorders scar problems were reported by some to be the main organic causes detected in symptomatic cholecystectomized patients [20] . Other acute and nonspecific complications of cholecystectomy (conventional and laparoscopic) include fluid collections, intraperitoneal and CBD stones. Retained intraperitoneal gas and a partial colonic ileus may occur but were found to be usually insignificant [21],[22] .
Does PCS exist
Patients with PCS have higher serum gastrin levels and greater basal acid output (BAO) than asymptomatic cholecystectomized patients [23] . Chronic gastritis occurred in 2.6-4.5% of PCS patients not diagnosed pre-op [24] . The ratio of positive endoscopic and histopathologic changes in the stomach was 14:1 between symptomatic and asymptomatic post-cholecystectomy patients [14] . All of these are objective changes occurring in the symptomatic cholecystectomized patient and prove some basis for the condition.
Incidence of PCS
Only 30% of patients with gallstones come to surgery [1] , which means that asymptomatic gallstones are common. If we study chronic cholecystitis, the commonest indication for cholecystectomy, we will find that the only symptom entirely characteristic of chronic cholecystitis is biliary colic [1] . If all patients with gallstones are operated on, we will surely end up with a high incidence of PCS. Those with no symptoms at all may complain of symptoms related to the operation or its complications and those with symptoms of other systems will continue to complain of their initial symptoms and all will be considered PCS.
The true incidence of PCS depends to a great degree on the indication for cholecystectomy, i.e. a correct diagnosis of chronic cholecystitis, absence of other symptoms related to other systems at the time of surgery and a careful postoperative followup. These factors explain, at least in part, the wide discrepancy in the reported incidence (5-40%) of PCS. [2],[4],[25]
When 100 symptomatic gallstone disease patients, with two or more symptoms, underwent laparoscopic cholecystectomy only 61 showed a complete resolution of symptoms [26] . In another study of 875 patients who had their gallbladders removed, 37.4% were symptomatic [20] . And in a computer analysis of postcholecystectomy biliary tract symptoms on 1,930 patients, only 60% were completely relieved, 35% had symptoms but not severe enough to recommend secondary surgery and about 5% required secondary surgery [27] .
There seems to be a possible predisposition for the development of PCS. When 637 cholelithiasis patients had a liver biopsy performed at the time of cholecystectomy, 373 (58.5%) showed hepatic lesions. PCS was found later in 36 % of those with hepatic lesions compared to only 13% in those with normal liver biopsies [28] . There also appears to be a group of patients which have a higher incidence of PCS, these include:
1.patients followed for 5-9 years vs only two years’ follow up.
2.females in general.
3.younger patients especially females between 40-49 years.
4.those with functioning gallbladders seen on oral cholecystogram.
5.those with a long history of biliary tract symptoms prior to cholecystectomy.
6.those operated on early in the course of an episode of acute cholecystitis [27] .
Causes of PCS
The usual and most common cause of PCS is incorrect preoperative diagnosis. In one study one-third of patients who required secondary surgery after cholecystectomy had abdominal symptoms unrelated to the biliary tract [29] . In general the causes of PCS [Table – 1] can be classified into three groups.
1.The symptoms of the initial presentation, i.e., “cholecystitis” were not related to gallstones.
2.A surgical error, i.e., leaving stones behind, injury to the ducts or any other surgical complications e.g. fluid collection, scar…. etc.
3.A new disease, either of the biliary tract [30] or another system.
An organic cause for the PCS is more likely to be discovered in patients with severe episodic pain and residual biliary disease [1] .
The changes occurring due to the absence of a gallbladder may follow those proposed for congenital agenesis of the gallbladder and cystic duct and may explain the symptoms of PCS [5] . Some believe that delaying the treatment of cholelithiasis is an important factor in the development of PCS, stating that the gallbladder disease has by then become a disease of the biliary tract and consequently the technique of the operation, risks, prognosis, morbidity and mortality have assumed considerably more serious characteristics [31],[32] .
Although there appears to be disagreement as to whether patients presenting with acute cholecystitis should be operated on immediately, or after the acute attack settles (with regards to reducing the incidence of PCS) [33],[27] it appears that other factors may be involved in this issue. Patients operated on during an acute attacks may have a higher incidence of bile duct injury, residual stones, fluid collections, infected wounds and so on while those operated on later may be the victims of repeated attacks and the progression of what was a gallbladder disease to what is a gallbladder and biliary tract disease.
Abdominal organs with disease producing symptoms commonly confused with gallbladder disease are the esophagus, stomach, duodenum, liver, pancreas [32] and the colon. Gallstone patients have a higher tendency to duodenogastric reflux of bile acid. This tendency is further enhanced by removal of a functioning gallbladder. This may explain some of the symptoms in patients with gallstones and also some of the symptoms in patients with PCS [13] . Patients with a functioning gallbladder should be investigated more extensively for other causes of their symptoms before cholecystectomy is performed. [Table – 1]
Atrophic gastritis occurs 14 times more frequently in symptomatic postcholecystectomy patients [14] . Derangement of bile acid metabolism is another factor contributing to the development of PCS [34] . In addition, gastric and duodenal disease were found in 50% of postcholecystectomy patients [35] .
Stones are the most frequent pathology in patients with PCS of biliopancreatic origin [36] . When 5,859 postcholecystectomy patients were studied, obstruction of the CBD was found in 1.8%, of these, 80% were due to stones [29] . The commonest cause of PCS detected by ERCP was retained/recurrent stones in 37/105 patients (35%) [37] .
Intraperitoneally spilt stones are a new complication with the introduction of laparoscopy [21],[38] . A case has been reported by the author as a cause of PCS [39] .
Strictures of the major duodenal papilla or distal CBD were the cause of PCS in 34.6% of cases in one study [40] and 48.7% in another [41] . When there is no morphological evidence of biliary obstruction, one must assume inflammatory changes around the papilla. These are frequent even in normal biliary tracts, and almost always present following cholecystectomy [42] . When 460 PCS patients were analyzed by Gostishchev, V.K. et al. abnormality of the major papilla was found in 32.4% either in the form of papillitis, fibrotic stenosis or the presence of stones. They concluded that papillitis plays a double (cause-effect) role in PCS, i.e., it may cause fibrotic stenosis and it may be the effect of stones or cholangitis [43] . Fibrosis of the papilla may lead to stenosis leading to increased pressure [4] which may explain the pain in PCS [44] . There is increasing evidence to implicate sphincter of Oddi dysmotility as a cause for PCS [1] . It should be considered in the differential diagnosis of any patient with recurrent pain postcholecystectomy [45] , and in up to 30% of cases of PCS, functional disturbances of the sphincter of Oddi are responsible for the clinical picture [46] . Some believe that patients with sphincter of Oddi dysfunction have no greater pressure rise in the CBD after morphine than do asymptomatic cholecystectomized controls. However, a given rise in pressure may lead to pain in a patient with sphincter of Oddi dysfunction but not in a normal control subject and therefore these patients have a greater pain sensitivity to a given increase in CBD pressure [47] .
A suture granuloma has been reported as a cause of PCS [48] but conflicting reports have appeared in the literature regarding amputation neuromas [49],[50],[51],[52] . Some considered them to represent a regular pathomorphologic condition which has no correlation with any postoperative symptoms, and that identical morphologic alterations can also be found on arterial stumps after resection of abdominal organs while others believe greater importance should be attached to them and recommend dividing the cystic duct close to the CBD to deal with neuromas and cystic duct stumps.
Intravenous cholangiograms were performed in 113 patients 2-3 months postlaparoscopic cholecystectomy, the length of the cystic duct stump was found to be up to 1 cm in 34.5%, 1-2 cm in 36.3%, 2-3 cm in 24.8% and > 3 cm in 4.4 % [53] . some report a high incidence of associated pathology in the so called cystic duct stump syndrome [54] . Only 3/40 patients undergoing partial cholecystectomy had ongoing mild dyspeptic symptoms [55] , which means that a long cystic duct stump should not lead to considerable symptoms. A cystic stump with a mean length of 23 mm was found in 56% of 54 patients with PCS but no particular symptom could be restricted to patients with a cystic duct stump [56] . Most authors believe that a cystic duct stump is hardly ever a cause for recurrent symptoms in itself [57],[58] and if symptoms are present that they are due to presence of stones in the cystic duct stump [4] or the CBD. In a study where 1 % of 5,859 postcholecystectomy patients underwent secondary surgery for excision of a long cystic duct stump; in more than 75% of these, the CBD was explored and in nearly half of those explored, stones were recovered. Therefore symptoms are probably due to retained stones and not the cystic duct stump in itself [29] . Some still however recommend its excision when present in cases of persistent pain and dyskinesia [52] .
Intestinal adhesions and scars in the choledochal region are clinically significant and relatively common causes of abdominal complaints following cholecystectomy and should be considered after other causes have been excluded. Particularly significant were adhesions of the distal ileum (P = 0.005) [59] . Scar-related symptoms and extrabiliary disorders were found to be the major organic cause in PCS patients in one study [20] .
The incidence of chronic pancreatitis increases in direct proportion to the duration of stones before cholecystectomy in 318 patients with chronic pancreatitis following cholecystectomy [60] .
There is some evidence to show an increased incidence of colonic tumors in cholecystectomized patients [17],[18],[19] and these may explain some of the symptoms.
Other minor complications of surgery which may be responsible for the PCS are fluid collections [21],[22] seen in 24% of patients 2-4 days post operatively but are rarely significant, intraperitoneal abscess with fistula (mucocutaneous) after residual stones in the peritoneal cavity [61] , choledochoduodenal fistulas (mostly iatrogenic) [62] , intraperitoneal gas and stones [21],[38],[39] , partial colonic ileus [21] , and breaking of a T-tube during removal.
Complications following laparoscopic cholecystectomy in one study involving 29 patients included: 15 bile duct injuries, 7 retained CBD stones, 4 Cystic Duct Stump leaks, 2 bowel perforations, 2 abdominal abscesses, 2 intraperitoneal stones, and 1 unrecognized malignant CBD obstruction [38] . All of these may also occur following conventional cholecystectomy and all may lead to symptoms following cholecystectomy either immediately or late and therefore all qualify as causes for the PCS.
It is worth remembering the study carried out by Tounsi, A. et al, where 637 patients undergoing cholecystectomy also had liver biopsies performed at the same time, 373 of which showed hepatic lesions (58.5%) and the higher incidence of PCS in those with hepatic lesions found 36% vs 13% [28] .
Diagnosis of PCS
There are different methods of diagnosing PCS using different investigative procedures [Table – 2]. A detailed history and examination are vital. The commonest complaint in PCS is jaundice [36] and an organic cause is more likely to be discovered in patients with severe episodic pain and residual biliary disease (1). LFT +/or other noninvasive tests were abnormal in 36/42 patients in one study, but more reliably predicted the presence of specific anatomical type of pancreaticobiliary tract disease [63] . Tests and signs of sphincter of Oddi dysfunction are:
1.A dilated CBD
2.Delayed emptying of contrast from the CBD at ERCP (> 45 min)
3.A transient rise in liver enzymes with pain.
4.Provocative tests (e.g. morphine-prostigmine test)
5.Nuclear scan
6.Fatty meal sonography [45]
But there are many associated problems. They are nonspecific, can be seen in asymptomatic patients, and may be seen with structural lesion of the CBD [45] . About 3-4% of asymptomatic patients have some dilatation of the CBD after cholecystectomy by ultrasonography and therefore if there is no associated rise in bilirubin, or alkaline phosphatase there is no sphincter of Oddi dysfunction [45] .
Ultrasonography is an adequate diagnostic method in nonobstructive PCS [64] . Ultrasonography of the pancreatic duct after secretion stimulation may provide objective criteria to help select patients for sphincteroplasty to treat stenosis of the sphincter of Oddi (or accessory papilla in pancreas divisum) [65] .
Diagnosis of papillary stenosis is not facilitated by ERCP. IV cholangiogram with special regard to bile drainage gives more information [66]
ERCP was useful in revealing stones pre-op in 96% of cases with jaundice and a PCS [67] . ERCP is very useful in diagnosing PCS [68],[69],[70] , and is the investigative procedure of first choice in complex PCS cases in whom IVC fails, gives incomplete information or suggests normality in the face of continuing symptoms or clinical evidence of residual biliary disease [71] . ERCP is essential in the diagnosis and management of PCS and the high yield of abnormal findings amenable to surgical correction in patients with recurrent biliary tract symptoms postcholecystectomy, justifies the use of ERCP in all such patients [63] . ERCP is suggested in unclear abdominal conditions and in PCS after other abdominal diseases have been ruled out and is the principal method of diagnosis in PCS patients with stones or jaundice [36],[72],[73] .
PTC and ERCP in PCS were compared, ERCP was found to be more useful in PCS since it allows observation and biopsy of the duodenum and evaluation of the pancreatic duct [74] . Marotta et al showed the benefits of ERCP by studying 41 patients with recurrent abdominal pain following cholecystectomy. ERCP gave a final diagnosis in 63% of all those studied and in 100% of patients with stones [75] . In 542 postcholecystectomy patients undergoing ERCP, 56% showed morphologic abnormalities in the biliary system (especially stenosis and stones) [11] . And in 42 patients with PCS, ERCP was abnormal in 22 (52%) [63] . However, delayed emptying > 45 mm on ERCP should be read with caution as it may be due to drugs that retard duct emptying [45] .
ERCP is sensitive in demonstrating abnormality of the pancreaticobiliary system, but not very specific as a predictor of good results following transduodenal sphincteroplasty and transampullary septotomy [76] . ERCP was successful in 105 out of 122 patients with PCS (85.3%) and accurately detected abnormality in 67.6%, including:
– 82.6% of patients with biliary symptoms with or without jaundice.
– 34.7% of patients with non biliary symptoms.
– 100 % of patients with biliary symptoms and jaundice.
– 70.4% of patients with biliary symptoms without jaundice.
The commonest abnormality was retained/ recurrent stones 37/105. ERCP detects the anatomical level as well as the nature of the lesion accurately. It is essential and safe in the diagnosis and treatment of patients with PCS [37] .
In PCS due to benign stenosis of the major duodenal papilla, choledohocholithiasis and their combination, ERCP permitted avoidance of repeated operative intervention on 113 patients (89.4%) [77] .
The value of CT and ERCP for examining the bile ducts was studied, it may be concluded that:
•CT on its own lead to a correct diagnosis in 59%.
•CT was valuable for estimating the caliber of the bile ducts, for localizing the level of obstruction, for demonstrating calcified biliary concrements and for showing peribiliary tumors.
•ERCP yielded a correct diagnosis in 67% of cases.
•The value of ERCP lies in the demonstration of poorly calcified and small concrements, strictures, tumors with ductal infiltration and for investigating the PCS.
•Combining CT and ERCP increases the diagnostic accuracy to 82% [78] . Papillitis plays a double (cause-effect) role in PCS [43] . Fibrosis of the papilla from repeated passage of stones may lead to stenosis to a rise in CBD pressure [4] .
There is a recent surge of interest in sphincter of Oddi manometry to diagnose sphincter of Oddi dysfunction but it is not without its problems:
1.Acute pancreatitis occurs in 2% following ERCP alone and in 19% after ERCP manometry.
2.It is difficult to perform.
3.It is invasive.
4.Sedation can only be provided with benzodiazepines in order not to affect the CBD pressure [45].
ERCP manometry is recommended in postcholecystectomy patients with unexplained abdominal pain of pancreaticobiliary origin [79] . Some have shown that patients with PCS have hypertonic dyskinesia of the sphincter of Oddi, i.e. deep and wide waves superimposed on high basal pressures of the sphincter [23] . Endoscopic manometry at the sphincter of Oddi enabled many of the unclarified postcholecystectomy symptoms to be identified. In up to 30% of cases of PCS, functional disturbances of the sphincter are responsible for the clinical picture [46]. While others insist that patients with sphincter of Oddi dysfunction have no greater pressure rise in the CBD after morphine than do asymptomatic cholecystectomized controls and a given rise in pressure might precipitate pain in a patient with sphincter of Oddi dysfunction but not in a normal control subject which means that these patients might have a greater pain sensitivity to a given rise in pressure in the CBD [47] .
The morphine-neostigmine test has been suggested by some as a preoperative test in patients who are to undergo cholecystectomy. In those with positive results ERCP should be done to assess the size of the sphincter of Oddi so that sphincteroplasty could be done at the time of cholecystectomy in appropriate patients [80] .
Morphine-induced bile duct pressure increase, coinciding with pain, is diagnostic of sphincter of Oddi spasm as a cause of postcholecystectomy pain (Nardi test). This test is less specific and less sensitive in diagnosing sphincter of Oddi spasm than manometric studies done in conjunction with the
Nardi test and endoscopic sphincterotomy usually relieves the pain when ampullary stenosis is diagnosed by this combined morphine prostigmine manometry study [47] .
Perfusion manometry in the CBD is thought by some to be a means of objectifying functional disturbances of the bile duct (as pain was reproducible) [81] . However, in another study, reproduction of pain immediately following contrast injection occurred in only 15 out of 224 (6.7%) patients [6] . They believe there is no correlation between pain on injection of contrast and:
1.Increased basal sphincter of Oddi pressure
2.Delayed CBD drainage
3.CBD dilatation
4.Abnormal LFT
and conclude that reproduction of pain (biliary type) associated with contrast injection on ERCP is not a provocative test of sphincter of Oddi dysfunction [6] .
In PCS the triad of raised LFT, dilated CBD, and delayed contrast drainage at ERCP indicates a definite sphincter of Oddi abnormality even if the sphincter of Oddi manometry is normal (35%). Therefore sphincter of Oddi manometry is not only unnecessary but may be misleading [8] . Problems in interpreting sphincter of Oddi manometry include:
1.Determining normal sphincter of Oddi activity and “normal” controls. (Most “normal” controls are patients with unexplained upper abdominal pain with no structural abnormality of the CBD or pancreatic duct on ERCP).
2.Lack of manometric studies of the sphincter of Oddi in patients with other known causes of abdominal pain e.g. peptic ulcer disease and irritable bowel.
3.Differences in basal sphincter of Oddi and CBD pressures due to different catheters, infusion systems and techniques and therefore we can’t compare results from different investigators.
Overall, pressures > 40-45 mm Hg above duodenal pressure (zero) are abnormally high with or without pain [82] .
Isotope studies of the biliary tract have proven to be useful in diagnosing disturbances of bile flow such as dyskinesia or obstruction, and showed significant correlation with symptoms. There was however no correlation between symptoms and serum enzyme levels [83] . PIPIDA nuclear scintigraphy is reliable in diagnosing sphincter of Oddi dysfunction provided, that the patient has normal LFT, and there is prompt appearance of radioisotope in the extrahepatic ducts. These indicate that the patient has no parenchymal liver disease [45] . The single most prevalent pattern in patients with stenosis of the ampulla is diminished washout of radioisotope from the biliary tree when comparing images obtained at one and two hours [82] . In a study on 125 patients with clinical presentation of PCS using scintigraphy, it was found that:
•Normal ducts which emptied within one hour ruled out any significant pathology with a high degree of accuracy 97%.
•Ductal dilatation with functional patency was less reliable in diagnosing normality since 3/20 (15%) with this pattern were proven to have nonobstructing calculi in the CBD.
•Ductal dilatation was a most significant indicator of partial or intermittent ductal obstruction when associated with altered time activity dynamics in the ducts and secondarily delayed biliary to bowel transit time of radiotracer.
•Other very sensitive patterns (Complete CBD obstruction, cystic duct remnant, bile leak [84]
When 30 patients with postcholecystectomy pain were studied using both ERCP and biliary scintigraphy, biliary scintigraphy showed stenosis of the sphincter of Oddi and agreed with ERCP or surgical findings in 9 out of 10 (90%) and biliary
obstruction due to other causes in 8 out of 8 cases (100%). Diagnosis of stenosis of the sphincter of Oddi was made by, the inability to pass a number 3 Bakes’ dilator through the papilla, or a combination of (ductal dilatation, contrast in CBD > 45 min on ERCP, and relief of symptoms after sphincterotomy [23] .
The frequency of dyskinetic disturbances on dynamic hepatobiliary scintigraphy increases with the severity of pathology of cholelithiasis and is most expressed in patients with PCS [85] . Dynamic cholescintigraphy was shown to be an effective method of diagnosis and quantitative estimation of the gastroduodenal reflux in patients with cholelithiasis and postcholecystectomy patients. In patients with PCS the gastroduodenal reflux was detected more frequently and its quantitative indicators were lower than those in patients with cholelithiaisis [86] . Dynamic cholescintigraphy seems to be a reliable noninvasive method for indentification and control of patients with sphincter of Oddi dysfunction suitable for treatment with papillotomy [87] . In cholescintigraphy after food stimulation, biliary- bowel transit time of < 1 hour was considered normal [88] . Dynamic hepatobiliary scintigraphy allowed quantitative estimation of duodenal reflux to be made and the dynamics of excretion of agent before and after cerucal may be an indicator of the functional state of the sphincter of Oddi [89] .
Fifty-three patients with biliary symptoms four-year postcholecystecomy were studied by scan; the findings were as follow:
•A highly significant correlation between symptoms and disturbances of bile flow (e.g. dyskinesia or obstruction).
•No correlation with serum enzymes (LFT).
•The diameter of the CBD provided no evidence of biliary obstructions up to 15 mm but diameters > 10 mm made obstruction likely.
•When there is no morphologic evidence of biliary obstruction, one must assume inflammatory changes around the papilla, these are frequent even in normal biliary tracts and almost always present post cholecystectomy.
•Quantitative hepatobiliary scintigraphy is the most reliable method of objective measurement of disturbances of bile flow and make it possible to avoid the vague diagnosis of PCS [42] .
Fatty meal sonography (cholecystokinin octapeptide sonography) CCK-OP. fatty meals or CCK-OP leads to dilation of an obstructed duct but not an unobstructed duct. The obstruction may be mechanical or functional. ERCP is needed to define the anatomy and exclude a structural lesion after performance of the test. This was found to be as sensitive as (67%) but more specific (100% vs 80%) than biliary scintigraphy in detecting obstruction. A positive fatty meal sonogram always indicates partial CBD obstruction [90] .
Treatment of PCS
The sphincter of Oddi is a complex device relatively independent of the duodenum and has a primarily occluding action [91] . Medical treatment is often successful in PCS of nonobstructive type and ERCP and interventional treatment should be reserved for patients with obstructive symptoms and patients in whom all medical treatment fails [64] . [Table – 3]
Medical treatment
Of the medical forms of treatment for PCS cisapride was used but with poor results [92] . Ursodeoxy cholic acid (UDCA) was used in a double blind therapeutic trial which confirmed its efficacy in the treatment of dyspepsia in cholecystectomized patients i.e. PCS (P=0.03) but showed that it had little influence on the pain factor (P=1.00) [3] .
Bar Meir et al in 1983 reported a case where sublingual nitroglycerin was used and improved the abdominal pain caused by sphincter of Oddi dysfunction and relaxed the sphincter when measured endoscopically [45] . In another study, Guelrud et al stated that nifedipine lowered the sphincter of Oddi pressure in patients with sphincter of Oddi dysfunction (No mention of pain relief) [45] .
The lack of studies of pharmacologic treatment of this problem is suprising for two reasons:
1.The cause of pain is probably due to sphincter spasm and CBD dilatation and therefore smooth muscle relaxants such as nitrates and calcium channel blockers are expected to help.
2.Endoscopic sphincterotomy has a significant morbidity (pancreatitis, cholangitis, duodenal perforation and hemorrhage) and a small mortality 0.4%. This morbidity is even higher when done for sphincter of Oddi dysfunction (9.1%-16%) than when done for gallstone obstruction (6.4%) [45].
Surgical treatment
The mortality for 5,859 cholecystectomized patients was 1.7% while the mortality for a secondary surgery in those patients was 6.7% [29] .
The efficacy of selective vagotomy in persistent spasm of the major duodenal papilla was claimed to be shown in one study [93] . In another, based on the fact that a frequent combination of cholecystitis and reflux esophagitis is noted in between 20-60%, and since reflux esophagitis is usually not diagnosed in cholecystitis patients and is not dealt with during the cholecystectomy, the incidence of PCS patients with reflux will be high. They therefore suggest a Nissen fundoplication to be performed with the cholecystectomy and claim a 30% less frequency of PCS in this group compared to those undergoing cholecystectomy alone [94] .
The bulk of the literature, however, concentrates on the fact that most of the cases of treatable PCS are due to papillary stenosis and patients with organic stenosis of the sphincter of Oddi are cured by treating the stenosis [95] . This treatment is in either of two methods.
1.The simpler endoscopic sphincterotomy, and
2.the more extensive sphincteroplasty or extended sphincteroplasty.
Endoscopic papillotomy is not without its complications. A complication rate of 5.3% and a mortality of 0.8% has been reported for ERCP alone [77] . However, its benefits have been reported in many papers [72] . When 460 patients with PCS were studied and an abnormality of the major duodenal papilla was found in 32.4%. The most common abnormalities were papillitis 59.1%, cicatricial stenosis 56.3% and stones 14.7%. In this study, endoscopic papillotomy was found to be the most effective method of treatment of PCS caused by major duodenal papilla disease and it reduced the number of repeated abdominal operations [43] .
While endoscopic sphincterotomy may be helpful in relieving the pain of sphincter of Oddi dysfunction, to date there is no consensus as to which of several parameters (CBD size, contrast drainage at ERCP or manometrically measured sphincter of Oddi pressures) best predicts the success of sphincterotomy [45] . Silvis comments that on the basis of present knowledge endoscopic sphincterotomy should be done for papillary stenosis only in:
1.Patients with symptoms over a prolonged period
2.Patients who have not responded to symptomatic treatment
3.Patients with severe disability.
4.Patients who have had the surgical treatment alternatives clearly explained to them and understand the risk of both surgery and endoscopy sphincterotomy.
Silvis also states that the greatest danger of endoscopic sphincterotomy for papillary stenosis is indiscriminate use that could subject patients to a risk that is higher than endoscopic sphincterotomy for cholelithiaisis but with less chance of lasting benefit [96].
Forty-five patients with sphincter of Oddi dysfunction were randomized to:
1.Endoscopic sphincterotomy (23 patients).
2.Sham Endoscopic sphincterotomy (24 patients) in a prospective double blind study.
Sixty-eight percent of the sphincterotomy group showed improvement while only 30% of the sham group showed improvement. Data was further analyzed to determine if sphincter of Oddi basal pressure could better predict responders vs non-responders to sphincterotomy. Ninety-one percent of patients with pressures higher than 40 mmHg above duodenal pressure improved after sphincterotomy while only 45% of patients with basal pressures of less than 40 mmHg improved [97] .
Fifty-one patients underwent endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction. In 31 out of 46 (67%) pain was completely abolished and allowed a discontinuation of analgesics. Twenty-four of the 29 patients who were available for follow up and who had presphincterotomy sphincter of Oddi manometry showed no correlation between manometric assessment and outcome of sphincterotomy, but patients with dilated CBD(> 12 mm) and delayed drainage of contrast after ERCP (>45 min) had a more favorable response to sphincterotomy, 77% were asymptomatic at 12 months compared to only 47% in those with normal diameters and normal drainage of contrast. This was significant (P=0.001) [98] . Others have shown no relation between size of CBD, manometry and Nardi test results before sphincterotomy and the outcome of sphincterotomy on pain relief [99] .
ERCP manometry cannot confirm completeness of the sphincterotomy immediately after electrocautery. ERCP manometry 6-8 weeks later could show whether the previous sphincterotomy was complete (i.e. CBD pressure = 0) and assess patient for pain relief related to completeness or otherwise of the sphincterotomy [100] .
There is a high risk repeat papillotomy for papillary stenosis and the risk of such a procedure is higher for papillary stenosis than for CBD stones [101] . Therefore an ERCP manometric study of the pressure at 6-8 weeks for completeness may be wise before re-stenosis occurs at which time repeat and endopapillotomy may be risky.
Ultrasonography of the pancreatic duct after secretion stimulation may provide objective criteria to help select patients for sphincteroplasty to treat stenosis of the sphincter of Oddi (or accessory papilla in pancreas divisum). A positive test was associated with 90% success of sphincteroplasty whereas a negative test was associated with 29% success [65] .
Patients with biliary symptoms related to PCS will benefit significantly from sphincteroplasty whereas patients with pancreatitis will not do as well [76] . Conditions unrelieved by sphincteroplasty include biliary dyskinesia, and relapsing pancreatitis with biliary disease. Transduodenal sphincteroplasty led to satisfactory results in 53 out of 65 patients with benign biliary tract disease. Coincident pancreatic disease was associated with the least satisfactory results [102] . Sphincteroplasty is the best procedure for papillary stenosis (79% of the patients showed good results) [103] .
Moody, F.G. recommends for PCS patients a surgical approach only after persistence of symptoms without apparent cause and a prolonged trial of medical treatment. This surgical approach is in the form of an extended papilloplasty after exploration of the contents of the peritoneal cavity. They claim this will help approximately 75% of patients with chronic postcholecystectomy pain to gain long-term relief of their symptoms [104] .
ERCP is not very specific as a predictor of good results following extended papilloplasty [76] . Patients selected for extended sphincteroplasty (transduodenal sphincteroplasty and transampullary septectomy) were highly suspected of having abnormal papillae by one or more of the following:
1.Symptoms or laboratory findings of hepatobiliary or pancreatic disease.
2.Lack of response to intense medical treatment (43% were addicted to narcotics)
3.Demonstration of an abnormality of the papilla, or dilatation of the bile ducts or pancreatic duct by radio contrast study.
Serious morbidity associated with the procedure includes: 2.2% moderate to severe postoperative pancreatitis, 1.1 % pulmonary embolus.
Results were: No pain in 43%, occasional pain in 33%, and no change in 24%.
Patients with previous sphincteroplasty benefitted the most. Eighty percent had either no pain or occasional pain. Patients who underwent concomitant cholecystectomy and sphincteroplasty responded poorly. Factors associated with failure of the procedure include alcoholism, drug addiction, mental illness, duodenal ulcer disease and papillary cholesterolosis. It is concluded that transduodenal sphincterotomy with transampullary septectomy leads to long-term benefits to carefully selected patients with chronic abdominal pain postcholecystectomy [105] .
Conclusion
In 100 symptomatic gallstone disease patients with two or more symptoms preoperatively, laparoscopic cholecystectomy led to complete absence of symptoms in 61 %. Eighty-four percent considered surgery to be a complete success and only one patient was no better off postoperatively [26] , which proves that cholecystectomy still remains to be the best treatment for symptomatic gallstone disease. On the other hand, when one reviews the multitude of changes occurring after cholecystectomy, one wonders whether one should be performing cholecystectomy for a functioning gallbladder or whether we are performing the wrong operation and only the stones should be removed. PCS can be prevented by more accurate preoperative evaluation and care of the patient prior to and during surgery [1] . The only symptom entirely characteristic of chronic cholecystitis is biliary colic [1] and therefore its presence should be ascertained and other symptoms dealt with prior to cholecystectomy. Not every abdominal pain is biliary colic.
The bulk of the problem lies with asymptomatic gallstones and patients undergoing cholecystectomy for peptic ulcer disorders, hiatus hernia or pancreatitis. Patients should be worked up carefully and their complaints listened to carefully before committing the patient to an operation (and its consequences and sequelae) he did not need in the first place.
There are many diagnostic modalities to diagnose patients with symptoms following cholecystectomy. The simple methods should be performed initially. An ultrasound followed by ERCP in relevant conditions are the best to start off with followed by other investigations depending on the findings. Treatment of PCS is of course dependent on the cause. There remains to be a gap in the trial on medical treatments which need to be worked on. If, however, surgical intervention is required, milder forms such as endoscopic papillotomy should precede the more extensive procedures of sphincteroplasty and extended sphincteroplasty which obviously carry a higher morbidity and mortality.
The PCS is a condition that definitely exists, and another example where prevention is better than cure. Its incidence is by no means expected to drop with the increased popularity of laparoscopy since most complications are shared between conventional and laparoscopic cholecystectomy. In addition, the enthusiasm for and both ease and attractiveness of laparoscopy to both patient and surgeon may sentence more asymptomatic gallstone gallbladders to the guillotine.
PCS need not exist, and indeed most, if not all, of its causes are preventable. A reduction of its incidence should be the target of all surgeons especially if we remember that this condition, when present, will be a major cause of pain in the abdomen (in the case of the patient) and pain in the neck (in the case of his surgeon).
Murshid KR. The postcholecystectomy syndrome: A review. Saudi J Gastroenterol [serial online] 1996 [cited 2014 Sep 7];2:124-37. Available from: http://www.saudijgastro.com/text.asp?1996/2/3/124/34017
References
1. Way L. “Current Surgical Diagnosis and Treatment” Appleton and Lange 10th edition, 1994;557. Back to cited text no. 1
2. Schumpelick V, Truong S, Fass J, Bares R, Geller H. Postcholecystectomy syndrome still a current argument today?). Langenbecks-Arch-Chir-Suppl-II-Verh-Dtsch-Ges Chir 1990:1205-9. Back to cited text no. 2
3. Reggiani P, Anzani A, Erenbourg L, Fontana U, Portaleone B, Vercesi M. Does postcholecystectomy syndrome exist? Epidemiologic features and therapeutic effects of ursodeoxycholic acid. Minerva-Med 1986;77(38):1755-62. Back to cited text no. 3
4. Schoenfield LJ. “Gallstones” Ciba-Geigy Clinical Symposia 1988;40(2):25-7. Back to cited text no. 4
5. Sousa – Escandon A, Rodriquez Garcia J, Sanchez Ibanez J, Gayoso Garcia R, Ghanime Saide G, Rodriquez Perez H. Agenesis of the gallbladder. Statistic review of the Spanish literature and presentation of a new case. Rev Esp Enferm Apar Dig 1989;75(2):135-42. Back to cited text no. 5
6. Schmalz MJ, Geenen JE, Hogan WJ, Dodds WJ, Venu RP, Johnson GK. Pain on common bile duct injection during ERCP: does it indicate sphincter of Oddi dysfunction? Gastrointest Endosc 199036(5):458-61. Back to cited text no. 6
7. Gundel H, Von Fritsch E, Koch H. The significance of endoscopic retrograde cholangiography (ERC) in biliary stasis and the Postcholecystectomy Syndrome. Dtsch Med Wochenschr1975;100(38):1877-81. Back to cited text no. 7
8. Rolny P, Geenen JE, Hogan WJ. Postcholecystectomy patients with “objective signs” of partial bile outflow obstruction: clinical characteristics, sphincter of Oddi manometry findings, and results of therapy. Gastrointest Endosc 1993;39(6):778-81. Back to cited text no. 8
9. Kordzaia DD, Gvazava AV. Characteristics of the reconstruction of bile ducts after cholecystectomy and the postcholecystectomy syndrome. Vestu Khir 1990;145 (10):25-9. Back to cited text no. 9
10. Kartashova O LA, Aseev VP. Morphologic characteristics of the liver in the postcholecystectomy syndrome. Arkh Patol 1986;48(5):25-32. Back to cited text no. 10
11. Tulassy Z, Papp J, Kollin E, Koller O. Postcholecystectomy syndrome: endoscopic and radiological aspects. Wien – Klin – Wochenschr198l;93(2):55-60. Back to cited text no. 11
12. Tanaka M, Ikeda S, Nakayama F. Change in bile duct pressure responses after cholecystectomy: Loss of gallbladder as a pressure reservoir. Gastroenterology 1984;87(5):1154-9. Back to cited text no. 12
13. Svensson JO, Gelin J, Svanvik J. Gallstones, cholecystectomy and duodenogastric reflux of bile acid. Scand J Gastroenterol 1986;21(2):181-7. Back to cited text no. 13
14. Nudo R, Pasta V, Monti M, Vergine M, Picardi N. Correlation between Postcholecystectomy syndrome and biliary reflux gastritis. Endoscopic study. Ann Ital Chir 1989;60(4):291-300;discussion 300-2. Back to cited text no. 14
15. Danilash MM, Lend’el MF, Gaisak MA, Panichkovskii VI, Ligirda AG. Gastric and duodenal functions in patients who have undergone cholecystectomy. Vrach Delo 1991:5:61-3. Back to cited text no. 15
16. Koelsch KA, Kuhne C, Zemlin C. Postcholecystecomy condition: duodenogastric reflux and bile acid concentration in the gastric juice. Z-Gesamte-Inn-Med 1979;34(13):361-4. Back to cited text no. 16
17. Moorehead RJ, Mills JO, Wilson HK, McKelvey ST. Cholecystectomy and the development of colorectal neoplasia: a prospective study. Ann R Coll Surg Engl 1989;71(1):37-9. Back to cited text no. 17
18. Papadimitrion C, Day N, Tzonou A, Gerovassilis F, Manousos 0, Trichopoulos D. Biosocial correlates of colorectal cancer in Greece. Int J Epidemiol 1984;13(2):155-9. Back to cited text no. 18
19. Weitz H, Mayring K, Wiebecke B, Eder M. Cholecystectomy, cholelithiais and cancer of the large intestine. Dtsch Med Wochenschr 1983;108(2):53-7. Back to cited text no. 19
20. Rothenbuhler JM, Chevalley JP, Famos M. Postcholecystectomy syndrome after simple cholecystectomy. Helv Chir Acta 1989;56(1-2):175-8. Back to cited text no. 20
21. Smith R, Kolyn D, Pymar H, Sauerbrei E, Pace RF. Ultrasonographic and radiologic evaluation of patients after cholecystectomy. Can J surg 1992;35(l):55-8. Back to cited text no. 21
22. Elboim CM, Goldman L, Hann L, Palestrant AM, Silen W. Significance of postcholecystectomy subhepatic fluid collections. Ann Surg 1983;198(2):137-41. Back to cited text no. 22
23. Chen XX, Mo JZ, Liu WZ. A study on motility of sphincter of Oddi in post-cholecystectomy syndrome. Chung Hua Nei Ko Tsa Chih 1991;30(6):337-9,381. Back to cited text no. 23
24. Gredzhev AF, Khatsko VV, Minin VV, Vecherko VN, Popov NK, Zorina SV. Chronic gastritis in patients following cholecystectomy. Vrach Delo 1990:29-32. Back to cited text no. 24
25. Bodvall B. The Postcholecystectomy syndrome. Clin Gastroenterol 1973;2:103. Back to cited text no. 25
26. Qureshi MA, Burke PE, Brindley NM, Leahy AL, Osborne DH, Broe PJ, Bouchier Hayes DJ, Grace PA. Postcholecystectomy symptoms after laparoscopic cholecystectomy. Ann R Coll Surg Engl. 1993;75(5):349-53. Back to cited text no. 26
27. Bodvall B, Overgaard B. Computer analysis of postcholecystectomy biliary tract symptoms. Surg Gynecol Obstet 1967;124(4)723-32. Back to cited text no. 27
28. Tounsi A, Chkoff MR, Foucou B, Halhal A, Hamdouch Z, Housni K, Mjahed A, Oudanane M, El-Hachimi. Reflections on the postcholecystectomy syndrome. Ann gastroenterolHepatol Paris 1987;23(2):89-92. Back to cited text no. 28
29. Glenn F, McSherry CK. Secondary abdominal operations for symptoms following biliary tract surgery. Surg Gynae Obs 1965; 122:979. Back to cited text no. 29
30. Henry ML, Carey LC. Complications of cholecystectomy. Surgical Clinics of North America 1983;63:1201-2. Back to cited text no. 30
31. Grill W. The postcholecystectomy syndrome. Prophylaxis and therapy. MMW Munch Med Wochenschr 1977;119(17):569-72. Back to cited text no. 31
32. Kothe W, Mlynek HJ, Schenker U. Results of treatment of cholelithiasis and its consequences; the so-called “Postcholecystectomy Syndrome”. Zentralbl Chir 1976;101 (18):1125-35. Back to cited text no. 32
33. Misra MC, Khanna S, Khosla A, Berry M, Kapur BM. Emergency versus elective cholecystectomy in acute cholecystitis. Jpn J Surg 1988;18(4):384-9. Back to cited text no. 33
34. Iwamura K. Pathologenetic significance of bile acid metabolism in the post-cholecystectomy syndrome. Tokai J Exp Clin Med 1980;5(2):217-32. Back to cited text no. 34
35. Market R. Cause of pain in patients surgically treated for cholelithiasis and postcholecystectomy syndrome. Pol Tyg Lek 1991;46(8-10):151-3. Back to cited text no. 35
36. Useche E, salazar S, Vetencourt R, Castillo J, Guzman S. The effectiveness of endoscopic retrograde cholangiopancreatography in the etiological diagnosis of post cholecystectomy syndrome. GEN 1993;47(3):157-61. Back to cited text no. 36
37. Dilawari JB, Chawla YK, Singhal AK, Kataria S. Postcholecystectomy syndrome in Northern India. Study on the diagnosis and therapeutic role of ERCP. Gastroenterol Jpn 1990;25(3):394-9. Back to cited text no. 37
38. Ward EM, LeRoy AJ, Bender CE, Donohue JH, Hughes RW. Imaging of complications of laparoscopic cholecystectomy. Abdom Imaging 1993;18(2):150-5. Back to cited text no. 38
39. Murshid KR. The postlaparoscopic cholecystectomy syndrome: A case report. Annals of Saudi Med 1995;15 (5):508-11. Back to cited text no. 39
40. Gostishchev, Misnik VI, Kanorskii ID, Megrabian RA, Gu’rev AD, Mallik A, Koshelev IUS. Diagnosis and treatment of postcholecystectomy syndrome. Khirurgiia Mosk 1989;7:8-11. Back to cited text no. 40
41. Aliev MA, Seisembaev MA, Madzhuga VP, Narzhanov BA. Causes, diagnosis and surgical treatment of complications after cholecystectmy. Klin Khir 1991;9:43-5. Back to cited text no. 41
42. Schindler G, Kuper K. Radiological biliary tract diagnosis after cholecystectomy. ROFO Fortschr Geb Rontgenstr NuklearMed 1982:136(1):64-74. Back to cited text no. 42
43. Gostishchev VK, Misnik VI, Kanorskii ID, Megrabian RA, Gur’ev AD, Koshelev IUS. Diseases of the major duodenal papilla as a cause of postcholecystectomy syndrome. Khirurgiia-Mosk 1991;2:3-6. Back to cited text no. 43
44. Weber J, Liebe S, Arendt R. Endoscopic perfusion manometry of the common bile duct in the postcholecystectomy syndrome. Dtsch Z Verdau Stoffwechselkr 1986;46(5):276-81. Back to cited text no. 44
45. Steinberg WM. Spincterof Oddi Dysfunction: A Clinical Controversy. Gastroenterol 1988;95:1409-15. Back to cited text no. 45
46. Brandstatter G, Kratochvill P, Wurzer H. Dysfunction of the sphincter of Oddi as a cause of so-called postcholecystectomy syndrome. Wien Klin Wochenschr 1991;103(19):577-80. Back to cited text no. 46
47. Tanaka M, Ikeda S, Matsumoto S, Yoshimoto H, Nakayama F. Manometric Diagnosis of Sphincter of Oddi Spasm as a Cause of Postcholecystectomy Pain and the Treatment by Endoscopic Sphincterotomy. Ann Surg 1985;202:712-9. Back to cited text no. 47
48. Mager JA, Kovarik V. Suture granuloma as a cause of postcholecystectmy syndrome. Rozhl Chir 1983;62(5):350-2. Back to cited text no. 48
49. Stibenz J, Kretzschmar U, Kunzel W, Dittrich H. Amputation neuroma as a rare cause of so-called postcholecystectomy syndrome. Z Gesamte Inn Med. 1984;39(9):206-8. Back to cited text no. 49
50. Bodner E, Aufschnaiter M, Hager J, Mikuz G. Neuroma of the cystic nerve stump. No explanation for postcholecystectomy pain. Chirurg 1978;49(7):424-7. Back to cited text no. 50
51. Rinella P, Cotroneo O, Vadala G, Polto F. The postcholecystectomy cystic-stump syndrome. Chir Ital 1977;29(3):250-65. Back to cited text no. 51
52. Domeniconi R, Alagni G, Mainenti M. Residual cystic stump. Its significance in postcholecystectomy syndrome. Minerva Chir 1975;30(4):194-200. Back to cited text no. 52
53. Keiler A, Pemegger C, Himof R, Wenl S, Brandtner W. The cystic duct stump after laparoscopic cholecystectomy. Wien Klin Wochenshr 1992;104(12):356-9. Back to cited text no. 53
54. Guerrera C, Rigobello P, De-Anna D, Buccoliero F, Pollinzi V. So-called cystic stump syndrome. Chir Ital 1979;31 (6);1098-110. Back to cited text no. 54
55. Ibrarullah MD, Kacker LK, Sikora SS, Saxena R, Kapoor VK, Kaushik SP. Partial cholecystectomy safe and effective. HPB Surg 1993;7(1):61-5. Back to cited text no. 55
56. Aarimaa M, Makela P. The cystic duct stump and the postcholecystectomy syndrome, an analysis of 54 patients subjected to ERCP. Ann Chir Gynecol 198 1;70(6)297-303. Back to cited text no. 56
57. Hopkins SF, Bivins BA, Griffen WO Jr. The problem of the cystic duct remnant. Surg Gynecol Obstet 1979;148 (4):531-3. Back to cited text no. 57
58. Rogy MA, Fugger R, Herbst F, Schulz F. Re-operation after cholecystectomy. The role of the cystic duct stump. HPB Surg 1991;4(2):129-34. Back to cited text no. 58
59. Hyvarinen H, Sipponen P, Silvennoinen E. Intestinal Adhesions: An overlooked cause of the Postcholecystectomy Syndrome. Hepatogastroenterology 1990;37(Suppl 2):58-61. Back to cited text no. 59
60. Gredzhev AF, Khatsko VV, Zorina SV. Chronic panreatitis in patients with the postcholecystectomy syndrome. Vrach-Delo 1989(4):18-20. Back to cited text no. 60
61. Catarci M, Zaraca F, Scaccia M, Carboni M. Lost intraperitoneal stones after laparoscopic cholecystectomy: harmless sequela or reason for re-operation. Surg Laparosc Endosc 1993;3(4):318-22. Back to cited text no. 61
62. Hunt DR, Blumgart LH. Iatrogenic choledochoduodenal fistula: an unsuspected cause of postcholecystectomy symptoms. Br J Surg 1980;67(1):10-3. Back to cited text no. 62
63. Cooperman M, Ferrara JJ, Carey LC, Thomas FB, Martin EW Jr, Fromkes JJ. Endoscopic retrograde cholangiopancreatography. Its use in the evaluation of non jaundiced patients with the postcholecystectomy syndrome. Arch Surg 1981;116(5):606-9. Back to cited text no. 63
64. Lasson A, Fork FT, Tragardh B, Zederfeldt B. The postcholecystectomy syndrome. bile ducts as pain trigger zone. Scand J Gastroenterol 1988;23(3):265-71. Back to cited text no. 64
65. Warshaw AL, Simeone J, Schapiro RH, Hedberg SE, Mueller PE, Ferrucci JT. Objective Evaluation of Ampullary Stenosis with Ultrasonography and Pancreatic Stimulation. Am J Surg 1985;149:65-72. Back to cited text no. 65
66. Sobbe A, Voigt W. “The endoscopic retrograde cholangiography” Rontgenblatter. 1977;30(10):503-7. Back to cited text no. 66
67. Nechai Al. Sitenlo VM, Zhuk AM, Lisitsyn AS, Lytkina SN. Current problems of diagnosis and treatment of choledocholithiasis. Vestn Khir 1983;130(3):3-11. Back to cited text no. 67
68. Bradstatter G, Kratochvil P, Wiedner F. The diagnosis significance of endoscopic retrograde cholangio-pancreatography in so-called postcholecystectomy syndrome. Wien Klin Wochenschr 1976;8874):806-10. Back to cited text no. 68
69. Braokov N. The so-called postcholecystectomy syndrome in light of the results of endoscopic retrograde cholangiopancreatography. Vutr-Boles 1991;30(2):91-3. Back to cited text no. 69
70. Colquhoun IR, Saywell WR, Dewbury KC. An analysis of referrals for primary diagnostic abdominal ultrasound to a general X-ray department. Br J Radio] 1988;61 (724):297-300. Back to cited text no. 70
71. Blumgart LH, Carachi R, Imrie CW, Benjamin IS, Duncan JG. Diagnosis and management of postcholecystectomy symptoms: the place of endoscopy and retrograde cholangiopancreatography. BrJ Surg 1977;64(11);809-16. Back to cited text no. 71
72. Deyhle P, Stuby K, Jenny S, Nuesch HJ, Kobler E, Ammann R, Sauberli H. The value of endoscopic retrograde cholangiopancreatography in negative or undetermined cholecystocholangiography. Schweiz Med Wochenschr 1976;106(9)314-5. Back to cited text no. 72
73. Ramirez-Degollado J, Avelar Garnica F, Blasco C, Barinagarrementeria R. Endoscopic cholangiography in the postcholecystectomy syndrome. Rev Gastroenterol Mex 1981;46(2):55-8. Back to cited text no. 73
74. Akovbiantz A, Bruhlmann W, Deyhle P. The value of endoscopic retrograde cholangiopancreaticography for the surgery of bile duct and pancreatic diseases. Schewiz Med Wochenschr 1975;105(23):741-5. Back to cited text no. 74
75. Marotta F, Hada R, Morello P, Vitale G, Sasakio M, Ragno F, Ono K. ERCP in the assessment of patients with postcholecystectomy syndrome. Neth J Med 1989;35 (5-6:232-40. Back to cited text no. 75
76. Nussbaum MS, Warner BW, Sax HC, Fischer JE. Transduodenal sphincteroplasty and transampullary septotomy for primary sphincter of Oddi dysfunction. Am J Surg 1989;157(l):38-43. Back to cited text no. 76
77. Bobrov OE, Ogorodnik PV, Loboda DI. Endoscopic papillotomy in patients with postcholecystectomy syndrome. Klin-Khir 1991(3):46-8. Back to cited text no. 77
78. Triller J, Coray T, Kappeler M, Scheurer U. CT and ERCP for the combined study of biliary tract diseases. ROFO Fortschr Geb Rontgenstr NuklearMed 1985;142(2):138-45. Back to cited text no. 78
79. Bar-Meir S, Halpern Z, Bardan E, Gilat T. Frequency of papillary dysfunction among cholecystectomized patients. Hepatology 1984;4(2):328-30. Back to cited text no. 79
80. Gregg JA, Clark G, Ban C, McCartney A, Milano A, Volcjak C. Post-cholecystectomy syndrome and its association with ampullary stenosis. Am J Surg 1980;139 (3):374-8. Back to cited text no. 80
81. Weber J, Liebe S, Arendt R. Endoscopic perfusion manometry of the common bile duct in the postcholecystectomy syndrome. Dtsch Z Verdau Stoffwechselkr 1986;46(5):276-81. Back to cited text no. 81
82. Zeman RK, Burrel MI, Dobbins J, Jaffe MH, Choyke PL. Postcholecystectomy syndrome: Evaluation Using Biliary Scintigraphy and endoscopic retrograde cholangiopancreatography. Radiology 1985; 156:787-92. Back to cited text no. 82
83. Schindler G, Kuper K. Radilogical biliary tract diagnosis after cholecystectomy. ROFO Froschr Geb Rontgenstr Nuklear Med 1982;136(1):64-74. Back to cited text no. 83
84. Weissmann HS, Gliedman ML, Wilk PJ, Sugarman LA, Badia J, Guglielmo K, Freeman LM. Evaluation of the postoperative patient with 99mTc-IDA cholescintigraphy. Semin Nucl Med 1982;12(1):27-52. Back to cited text no. 84
85. Berdov BA, Matveenko EG, Tsypliaev VA, Karakashly DN. The function of the hepatobiliary system in patients with cholelithiasis based on hepatocholescintigraphic data. Med-Radiol-Mosk 1990;35(2):22-5. Back to cited text no. 85
86. Tsypliaev VA, Karakashly DN. Cholescintigraphy in the evaluation of duodenogastric reflux in cholelithiasis. Med Radio Mosk 1990;35(3):36-8. Back to cited text no. 86
87. Farup PG, Tjora S. Sphincter of Oddi dysfunction. Dynamic cholescintigraphy and endoscopic retrograde cholangiopancreatography with papillotomy in diganosis, treatmetn and follow-up study. Scand J Gastroenterol 1989;24(8):956-60. Back to cited text no. 87
88. Hansen HH, Toftgaard C, Rokkjor MJ, Kruse A, Funch Jensen P, Thommesen P. Food stimulated cholescintigraphy as a supplement to ERC in patients with suspected bile flow obstruction. A preliminary study. Rontgenblatter 1990;43 (11):484-6. Back to cited text no. 88
89. Mechtikhanov ZS, Nesterov VG, Astapeva ON. Quantitative hepatobiliary scintigraphy in the diagnosis of duodenogastric reflux and dysfunction of the Oddi’s sphincter in postcholecystectomy syndrome. Vestn Khir Im I I Grek 1991;146(1):25-8. Back to cited text no. 89
90. Darweesh RMA, Dodds WJ, Hogan WJ, Geenen JE, Lawson TL, Stewart ET, Shaker R, Kishk SMA. Fatty-Meal Sonography for evaluating Patients with Suspected Partial Common Duct Obstruction. Am J Roentgenol 1988; 151:63-8. Back to cited text no. 90
91. Torsoli A. Physiology of the human sphincter of Oddi Endoscopy 1988;Suppl 1:166-70. Back to cited text no. 91
92. Farup PG, Tjora S, Tholfsen JK. Effect of cisapride on symptoms and biliary drainage in patients with postcholecystectomy syndrome. Scand J Gastroenterol 1991;26(9):945-50. Back to cited text no. 92
93. Zemskov VS, Radzikhovskii AP, Bobrov OE. Causes, diagnosis and treatment of the postcholecystectomy syndrome. Vestn Khir 1986;137(12):30-4. Back to cited text no. 93
94. Gushcha AL, Baulin SS, Pod’iablonskaia IA. Reflux esophagitis in cholecystitis. Vestn Khir Im I I Grek 1993;150(3-4):21-5. Back to cited text no. 94
95. Vayre P, Jost JL, Hureau J, Roux M. Sclerodystrophy of the sphincter of Oddi. J Chir Paris 1978;115(10):489-96. Back to cited text no. 95
96. Silvis SE. What is the Postcholecystectomy Pain syndrome (editorial) Gastrointest Endosc 1985;31(6):401-2. Back to cited text no. 96
97. Geenen JE, Hogan WJ, Dodds WJ, Toouli J, Venu RP. The efficacy of endoscopic sphincterotomy after cholecystectomy in patients with sphincter of Oddi dysfunction. N Engl J Med 1989;320(2):82-7. Back to cited text no. 97
98. Thatcher BS, Sivak MV, Tedesco FJ, Venues JA, Hutton SW, Achkar EA. Endoscopic Sphincterotomy for Suspected Dysfunction of the Sphincter of Oddi. Gastrointes Endosc 1987;33(2):91-5. Back to cited text no. 98
99. Roberts-Thomson and Toouli. Is endoscopic sphincterotomy for disabling biliary-type pain after cholecystectomy effective?. Gastrointes Endosc 1985;31:370-3. Back to cited text no. 99
100. Staritz M, Ewe K, Meyer-zum-Buschenfelde K. Investigation of the Sphincter of Oddi before, immediately after and six weeks after endoscopic papillotomy. Endoscopy 1986;18(1):14-6. Back to cited text no. 100
101. Richieri JP, Pelisier G. Early papillary stenosis following successful endoscopic sphincterotomy for common bile duct stone. Endoscopy 1984;16(2):77-8. Back to cited text no. 101
102. Kozloff L, Joseph WL. Transduodenal spincteroplasty for biliary tract disease. Am Surg 1975;41(3):125-30. Back to cited text no. 102
103. Partington PF. Twenty-three years of experience with sphincterotomy and sphincteroplasty for stenosis of the sphincter of Oddi. Surg Gynecol Obstet 1977;145(2):161-8. Back to cited text no. 103
104. Moody FG. Postcholecystectomy syndromes. Surg Annu 1987; 19:205-20. Back to cited text no. 104
105. Moody FG, Becker JM, Potts JR. Transduodenal Sphincteroplasty and Transampullary Septectomy for Post-cholecystectomy Pain. Ann Surg 1983;197:627-36. Back to cited text no. 105
