Biliary Causes Of The Postcholecystectomy Syndrome And Ways Of Therapeutic Approach

BILIARY CAUSES OF THE POSTCHOLECYSTECTOMY SYNDROME AND WAYS OF THERAPEUTIC APPROACH

Mariana Ungur1, Csiki Zoltan2, Maghiar Adrian3, Feder Bogdan4

1Faculty of Medicine and Pharmacy -Surgery Department, University of Oradea; 2Medical and

Health Science Center, Institute of Medicine, Faculty of Medicine, University of Debrecen; 3Pelican Clinical Hospital Oradea, Faculty of Medicine and Pharmacy-Surgery Department, University of Oradea,4Faculty of Medicine and Pharmacy – Surgery Department, University of Oradea, County Clinical Emergency Hospital Oradea – Surgery I

Mailing address:

Dr. Mariana Ungur- Surgery Department, Faculty of Medicine and Pharmacy, University of Oradea

1 Decembrie Street, 410068, Oradea, Romania

Email: [anonimizat]

Abstract. Postcholecystectomy syndrome is a set of symptoms, particularly in the digestive field that do not disappear after surgical removal of the gallbladder, on the contrary, they worsen the symptoms.

Objectives. The main objective of this paper is to study the biliary causes of the postcholecistectomy syndrome and the ways of therapeutic approach.

Material and method. In the present study there have been used clinical observation sheets of the patients hospitalized in surgical wards, from January 2010 to October 2015 with the diagnosis of postcholecystectomy syndrome.

Results. Between January 2010 and – October 2015 were hospitalized 221 patients, accounting for 67.42% of females. Clinical examinations, and laboratory examinations showed the presence of a postoperative angiocolitis, in a share of 92.30%. Of the 221 cases admitted to surgery with postcholecystectomy syndrome, the biliary causes weight was 14%, in 190 of the cases, the treatment was by drugs 85,97%). In the other 31 cases it was used an endoscopic and/or surgical intervention.

Conclusions. Angiocholitis in postcholecystectomy generate changes in interhepatic and extra hepatic bile ducts which are translated by imaging, by their expansion, with or without parietal modifications, with or without obstruction lesions of the distal bile duct , with a share of 21.26%. The main therapeutic approach in postcholecystectomy syndrome is noninvasive, by drugs, accounting for 85,97%.

Keywords: postcholecystectomy syndrome, angiocholitis, endoscopic sphincterotomy.

Introduction

Postcholecystectomy syndrome is defined like the recurency of the similar symptoms occured before surgery. These symptoms are representing especially by pain localized in the right upper abdominal quadrant, dyspeptic phenomena and presence or absence of jaundice. [1] Frequently, this postcholecystectomy syndrome, occurs when cholecystectomy was performed in the absence of a rigorous indication (i.e. a patient with dyspeptic manifestations in the absence of gallstones). Draws attention to the cholecystectomy indications, in the absence of typical clinical manifestations specific for gallstones and echo argumentation of this gallstones.

The postcholecystectomy syndrome affects approximately 10-15% of the patients with surgical history of cholecystectomy – classical or laparoscopy. It does not reflect objectively the causes of suffering patients with cholecystectomy in history, as cholecystectomy causes some functional disorders of the bile ducts, with a low frequency, 0.21% of the cases. Most of the sufferings for operated bile have another cause.

The postcholecistectomy syndrome is usually a temporary diagnosis. An organic or functional diagnosis is established for most patients after clinical investigations, and rigorous laboratory investigations. A complete preoperative assessment is important to reduce as much as possible, the occurrence of this postcholecistectomy syndrome.[2,3,4]. Furthermore there must be a prior notice of the patients, so to be warned of the possibility of such symptoms for immediate or delayed postoperative period.[2,3,4]

Girls are more likely to develop the postcholecistectomiy syndrome, also, in analogy with the higher incidence and gallstones. The postcholecistectomy syndrome high prevalence for women is caused by the activity of estrogens, especially during childbearing age (young age, pregnancy status, treatment with oral contraceptives). [5]

The objective of this paper is to highlight the biliary pathology of the postcholecistectomy syndrome for cases hospitalized in surgical wards of a county clinical emergency hospital and therapeutic ways of solving the generating cause.

Material and method

In the present study there have been used, as a reference, the hospitalized patients' clinical observation sheets between January 2010- October 2015, with the diagnosis of postcholecistectomy syndrome, in Oradea County Hospital Surgery I and II wards.

The research was conducted using as criteria, the selection of cases by sex, age and the diagnose framing, historical data, methods of clinical investigation, imaging and laboratory methods, association of cholecystectomy with other interventions performed to bile ducts, therapeutic conduct non-invasive versus invasive.

The anamnesis revealed a previous history of cholecystectomy, patients' subjective complaints – the presence of the painful syndrome in the right upper quadrant, of dyspeptic syndrome, of jaundice syndrome.

Useful laboratory examinations for establishing the diagnosis: biliary-retention samples of serum bilirubin, bile pigments in the urine alkaline phosphatase; hepatic cytolysis tests: transaminases, serum iron, lactico dehydrogenises; cellular-albumin hypo function tests, serum pseudo cholinesterase, clotting factors; exploration of hepatic function in lipid metabolism.

Other laboratory tests very helpful for establishing a positive diagnosis were: mesenchymal hyperactivity tests (electrophoresis tests dysproteinemia, immunoelectrophoresis), immunoassay, erythrocyte sedimentation rate, changes in blood counts, blood urea.

Erythrocyte sedimentation rate is higher in jaundice with cholangitis and the neoplasic ones.

Blood count changes; this anemia suggests neoplastic etiology or hemolytic in pre-hepatic jaundice and cirrhosis. Hyperleukocytosis is present in biliary ducts lithiasis in angiocolitis and liver cancer; it is unusual in acute hepatitis.

Blood Urea is important in case of mechanical jaundice; nitrogen retention associated with obstructive jaundice syndrome has a poor prognosis, preceding hepatic-renal failure.

The methods used in the diagnosis of postcholecystectomy syndrome were cholangiography, ultrasonography, computed tomography of the abdomen, colangio RMN, upper gastrointestinal endoscopy, duodenal gastro esophageal barium swallow.

Therapeutic options for postcholecystectomy syndrome consisted of noninvasive medicinal methods and imaging methods or invasive surgical methods.[6]

If the bile sufferings have an organic substrate, then it is performed a surgical intervention (example digestive biliary fistula, long cystic blunt) or endoscopic sphincterotomy (common bile duct lithiasis, stenosis, sclerosis oddities).[6]

Results

Between January 2010 and October 2015 were hospitalized with a diagnosis of postcholecystectomy syndrome in the two surgical clinical sections of the county hospital 221 patients, with a share of females of 149 patients, representing 67.42% and a share of males, of 72 patients representing 32,57%.

Decades of age most frequently used for the diagnosis of postcholecystectomy syndrome in surgical wards were, in descending order by the number of cases: 55-64; 65-74; 75-84 and 45-54 years.

Biliary pathology of postcholecystectomy syndrome.

In 47 cases out of 221 hospitalized cases, the imaging investigations revealed intrahepatic and / or extra hepatic biliary ducts dilatation.

In 31 cases(14%) is highlighted the extra hepatic biliary ducts dilatation, with or without the association of obstructive modifications duct stones calculi or oddian stenoses.

Of the 31 cases with extrahepatic biliary tract dilatation in 15 cases, imaging examination revealed the presence of duct stones lithiasis, as the cause of the postcholecystectomy syndrome.

Of the total hospitalized cases with postcholecystectomy syndrome in 3 cases, the imaging revealed the presence of odditis sclerotic and in other 3 cases, oddian stenosis.

In 4 cases, postcholecystectomy angiocholitis were consecutive to iatrogenic injuries of main bile ducts after laparoscopic cholecystectomy.

It was also reported the presence of postcholeyistectomy angiocolitis after surgery for Klatskin biliary tumor (1 case), ampulla of vater (2 cases) and cholangiocarcinoma of the hepatic hilum (1 case)

In the baseline study, it was reported the presence of angiocholitis after bile digestive anastomoses (anastomoses, coledoco-jejuno anastomosys, duodenal jejunal hepatic, on Y a la Roux) in 10 cases, out of the 221 hospitalized cases with postcholecystectomy syndrome. Also, statistics showed 3 cases of cholangitis after sphincterotomy / transduodenal sphincteroplasty.

There were also hospitalized patients with endoscopic postsphincterotomy cholangitis, a total of 4 cases from the total of 221 patients hospitalized with the postcholecystectomy syndrome.

Table I. Biliary causes in postcholecystectomy syndrome at admitted patients

The treatment of postcholecystectomy syndrome can be done by medication, endoscopic or surgical. Of the 221 cases hospitalized in surgical wards with postcholecystectomy syndrome in 190 cases, the treatment was by medication. In the other 31 cases it was endoscopic and / or surgical.

In eight cases, it was a surgical procedure (table II) and in another 23 cases was performed retrograde endoscopic colecistopancreatography with sphincterotomy and extraction of stones.

In two of the 8 cases after surgery, because of the persistence of biliary cause that generated the postcholecystectomy syndrome, it is performed the endoscopic sphincterotomy; In the first case, for a bile tract fistula, and in the second case for installing a duct stent (lower duct diverticulum)

Table II. Surgical approach – techniques

Discussions

The biliary causes of postcholecystectomy syndrome with the highest representation in the baseline study are: choledocal stones, oddian stenosis and tumor pathology.

In cases with cholangitis postcholecystectomy, the researches conducted to cases hospitalized in surgical wards revealed most commonly an inflammatory syndrome with leukocytosis and neutrophils, and/or bilioexcretory syndrome, and/or hepatocytolisis syndrome, cholestasis; imaging argumentation of the changes of intra and extra hepatic biliary tract is absent most of the times.

Angiocholitis from postcholecystectomy syndrome produce changes to intrahepatic and extra hepatic bile ducts which are translated by imaging, by their expansion, with or without parietal modifications, with or without obstructive lesions of the distal common bile duct, with a share of 21.26%.

The prevalence of postcholecystectomy syndrome due to biliary causes is higher for patients who were associated with primary cholecystectomy surgery and other surgery, biliary-coledocolitotomies, sfincteroplasties, biliary-digestive anastomoses.

The main therapeutic approach for postcholecystectomy syndrome is noninvasive, by drugs, accounting for 90.04%.

Pharmacologic treatment consists of antibiotics, antispasmodics, analgesics, proton pump inhibitors, prokinetics, hepatoprotective, bile acid substituents (ursodeoxycholic acid), pancreatic enzymes (kreon); in oddian dyskinesia – nifedipin, nitroglycerin, amyl nitrite.

The endoscopic retrograde cholangiopancreatography is the modern therapeutic method, that by sphincterotomy / sfincteroplasty allows both removal of common bile duct stones and papillary dyskinesia problems solving; in the reference study, were carried out 23 sphincterotomies / endoscopic sfincteroplasties (10,40%).

Choledocholitotomy associated with duodenal choledo duodenal anastomosis or duodenal Roux-en-Y hepatico-jejunostomy is chosen as a surgical approach when there is a marked dilatation of the main biliary tract, gritted biliary duct stones, stretched stenosis, stenosis of a biliary-digestive anastomosis and oddian restenosis after sphincterotomy.

The statistical data above demonstrates a high prevalence of the postcholecystectomy syndrome to female patients hospitalized in surgical clinical wards (67.42%)

Girls are more likely to develop the postcholecystectomy syndrome, also in analogy with higher incidence and with gallstones. This increased prevalence is due to the estrogen hormone during childbearing age (young age, state of pregnancy, oral contraceptives)

Estrogens increase the cholesterol content in bile and have trigger the cholesterol uptake stimulus by hepatic cells. Consequently it is installed the classic cholestasis "early estrogen." the ratio of cholesterol and phospholipids increases; hepatic bile secretion volume decreases. [5] As an effect occur: increase of the cholesterol synthesis and cholesterin secretion, decrease of the bile acids and cholesterin ratio. Thus, female gender, pregnancy status and oral contraceptives are considered risk factors in the formation of cholesterol gallstones. [5]

Of the 221 cases admitted to surgery, with postcholecystectomy syndrome, in 204 cases(92,30%), clinical and laboratory examinations showed the presence of postoperative angiocolitis. These inflammatory processes produce intrahepatic and extra hepatic changes to bile ducts which are translated by imaging, by their expansion, with or without parietal modifications, with or without obstructive lesions of the distal common bile duct

In 47 cases out of 221 hospitalized cases, imaging investigations conducted revealed dilated biliary tract inter and/or extra hepatic. Small stones can cross the papilla but during bile gorge crossing they can create a barrier with consecutive expansion of main bile ducts; all imaging examination will show a dilated bile but uninhabited (bile passage) This extra hepatic biliary tract swelling may be associated with intrahepatic biliary tract ectasia. Angiocholytis infections may have as an imaging expression, an abnormal highlighting of bile ducts, after the thickening of their walls.[7]

Postcholecystectomy sclerosing angiocholytis have as a consequence, multiple stenoses of bile ducts intra- and/or extra hepatic and usually lead to biliary cirrhosis. In terms of imaging, stenosis may have a multifocal distribution, causing stenosis and consecutive dilations with different intensities, depending on the location in question [7]

In 31 cases, it is highlighted the extra hepatic biliary tract dilatation with or without association of obstructive changes- gallstones or oddian stenosis.

The biliary causes of postcholecystectomy syndrome include: intrahepatic biliary tract lithiasis, choledocal lithiasis, biliary tract tumors and large duodenal papilla tumors, long stump cystic duct stenosis, residual oddian stenosis, large duodenal papilla stenosis, oddian dyskinesia, biliary-digestive anastomosis stenosis (anastomosis coledoco-duodenal and biliary-jejunal inoperable), cystic dilatation of the inter and extra hepatic biliary tract.[8]

Of the 31 cases with extra hepatic biliary tract dilatation, in 15 cases, imaging examination revealed the presence of duct stones, as the cause of the postcholecystectomy syndrome(table I)

Biliary stasis will favor the infection. The inflammatory infiltrate in the common bile duct, will favor inclavated calculus, affecting the functionality of Oddi sphincter. Consequently, oddian stenosis occur.

Of the total hospitalized cases with postcholecystectomy syndrome, in 3 cases, the imaging revealed the presence of sclerotic odditis and in other 3 cases, oddian stenosis.

There are also described the causes related to the surgical act itself, an inadequate surgical technique with extra hepatic biliary tract iatrogenic lesions. In 4 cases, postcholecystectomy angiocholytis were consecutive to iatrogenic injuries of bile tracts after laparoscopic cholecystectomy.

Ampullary enclaved calculi or repeated passage of the micro calculi or achiness by oddian narrow pass cause bouts of acute pancreatitis.[8] In the baseline study were reported frequent cases in which postcholecystectomy cholangitis and choledocal stones were associated with acute pancreatitis. Spasm and posttraumatic edema causes the increased intrapancreatic pressure, on which can be added biliary-pancreatic reflux with potentially infected bile.

Besides the pancreatic activity, the choledocal obstruction will also affect the hepatic activity.

The degree of liver damage depends on the speed of installation, extent, duration of the obstruction and the presence or absence of infection. In obstructive jaundice due to bile duct stones, the liver volume increases, the surface is granular in old obstructions, with the possibility of parenchyma fibrosis.

The research data revealed an association in some cases of angiocholitis and duct stones with satellite hepatitis.

The extra biliary causes of the postcholecystectomy syndrome are: diseases of the liver and pancreas, duodenum disease, reflux esophagitis, peptic ulcer, hiatus hernia, etc..

The prevalence of postcholecystectomy syndrome by biliary causes is higher for patients who were associated with primary cholecystectomy surgery other surgical interventions, on biliary-coledocolitotomies, sfincteroplasty, biliary-digestive anastomoses.

In the reference in the study, it was reported a cholangitis after biliary-digestive anastomosis (coledocojejunoanastomosys duodenal Roux-en-Y hepatico-jejunostomy), in 10 cases out of the 221 hospitalized cases with postcholecystectomy syndrome. Also, statistics showed 3 cases of cholangitis after sphincterotomy / transduodenal sfincteroplasty.

There were also hospitalized patients with cholangitis and post endoscopic sphincterotomy, a number of 4 cases from the total of 221 hospitalized patients with the postcholecystectomy syndrome.

The literature describes a rate of approximately 1% of endoscopic retrograde cholangiopancreatography subsequent to angiocholytes.[9,10,11] In the reference study the prevalence of post ERCP angiocholytis is 1.80%.

The postcholecystectomy syndrome treatment may be performed by medication, surgical or endoscopic procedures.

Of the 221 cases hospitalized in surgical wards with postcholecystectomy syndrome in 190 cases, the treatment was by medication. In the other 31 cases it was endoscopic and/ or surgical.

Endoscopic retrograde cholangiopancreatography, useful diagnostic method is also the therapeutic methods that by sphincterotomy/sfincteroplasty allows both removal of common bile duct stones and the solving of papillary dyskinesia. [12]

The therapeutic approach by endoscopic sphincterotomy is a modern method, which replaced with a very high success rate, the surgery of postcholecystectomy syndrome.[13,14] Endoscopic sphincterotomy is an effective therapeutic method that allows the extraction of residual or recurrent stones in the common bile duct, that do not exceed 1.5 cm in diameter.

The surgical treatment performed for choledocal postcholecystectomy may be represented by choledocolitotomy and Kehr drainage, for residual calculi, with mobile and moderate expansion of bile duct.[11,12]

If the choledocal lithiasis is complicated by the enclavation of calculus in papilla of Vater or by a residual oddian it is performed a choledocolitotomy stenosis and sphincterotomy/oddian sfincteroplasty and external biliary Kehr drainage.

Choledocolithotomy associated with coledoco-duodenal anastomosis or duodenal Roux-en-Y hepatico-jejunostomy is chosen as surgical approach when there is a marked dilatation of the main biliary tract, gritted biliary duct stones, stretched stenosis, stenosis of a biliary-digestive anastomosis and restenosis after oddian sphincterotomy.[11,12]

Intrahepatic biliary tract lithiasis raises difficulties to surgical approach; to eliminate spontaneous the calculi it is necessary to perform a duodenal anastomosis or duodenal Roux-en-Y hepatico-jejunostomy In two of the 8 cases, after the surgery, because of the persistence of biliary cause that generated the postcholecystectomy syndrome, it is performed an endoscopic sphincterotomy; In the first case for a bile fistula and in the second case for installing a duct stent (lower duct diverticulum)

The endoscopic treatment consisted of sphincterotomy by retrograde endoscopic colecistopancreatography, extraction of stones and depending on the case, installing a duct stent.

When the symptoms are the result of Oddi sphincter dyskinesia, initially it is administered a pharmacological treatment represented by nitroglycerin, nifedipine, anticholinergics, amyl nitrite.[15,16,17,18]

This treatment continues for a period of 2-3 months; if there is no obvious clinical improvement it will be performed endoscopic sphincterotomy or surgical sfincteroplasty. Alternatively, it can be used, as symptomatic: antispasmodics or analgesics for the relief of pain complaints.

The dyspeptic symptoms are treated with substituents for billiary acids (ursodeoxycholic acid) or pancreatic enzyme extracts.[19,20] Mild cases of angiocolitis respond well to parenteral administration of ampicillin or cephalosporin in doses of 1 gram every 4-6 hours, or 2 g every 6 hours. It is also considered that last generation penicillins with very broad spectrum of action (mezlocillin, piperacillin) have good biliary excretion, being used frequently.

In severe cases of cholangitis, with an accentuated inflammatory syndrome with hyperleukocytosis it may be initiated a microbial treatment by the combination of several antibiotics like gentamicin, ampicillin, clindamycin, etc..

Conservative drug treatment represents, depending on the symptoms, the generating cause and possibly other associated digestive disorders: proton pump inhibitors, antibiotics, prokinetics, hepatoprotective, antispasmodic, analgesic, ursodeoxycholic acid, kreon, etc..

Pharmacological treatment has increased efficiency for patients who have a non-biliary etiology of postcholecystectomy syndrome.

Outpatient, to avoid repeated postcholecystectomy angiocolitis flashes it is important to initiate an hepatic and gastric sparing regimen, avoiding the consumption of fats, spices, alcohol.

References

Jaunoo S.S, Mohandas S, L.M. Almond LM. Postcholecystectomy syndrome (PCS) . International Journal of Surgery 2010; 8:15–17.

Shaffer EA. Epidemiology and risk factors for gallstone disease: has the paradigm changed in the 21st century? Curr Gastroenterol Rep. 2005;7(2):132-40.

Marschall HU, Einarsson C. Gallstone disease. J Intern Med. 2007 ;261(6):529-42.

Gore RM, Thakrar KH, Newmark GM, Mehta UK, Berlin JW. Gallbladder imaging.Gastroenterol Clin North Am. 2010 ;39(2):265-87.

Ko CW. Risk factors for gallstone-related hospitalization during pregnancy and the postpartum. Am J Gastroenterol. 2006;101(10):2263-8.

Lasson A. The post-cholecystectomy syndrome: diagnostic and therapeutic strategy. Scand J Gastroenterol. 1987;22:897-902.

Braunwald, Fauci, Kasper, Hauser, Longo, Jameson. Harrison’s Principles of Internal Medicine. 15th Edition. McGraw-Hill. 2001.

Kelley's Essentials of Internal Medicine- H. David Humes, Lippincott Williams & Wilkins, 2001

Freeman ML, Nelson DB, Sherman S, et al. Complications of endoscopic biliary sphincterotomy. N Engl J Med 1996;335:909-18.

Masci E, Toti G, Mariani A, et al. Complications of diagnostic and therapeutic ERCP: a prospective multicenter study. Am J Gastroenterol 2001; 96:417-23

Loperfido S, Angelini G, Benedetti G, et al. Major early complications from diagnostic and therapeutic ERCP: a prospective multicenter study. Gastrointest Endosc. 1998;48:1-10

Sivak MV. Endoscopic management of bile duct stones.Am J Surg. 1989;158:228.

Yusuf TE, Mullady DK, Carr-locke DL. Endoscopic retrograde cholangio-pancreatography, endoscopic sphincterotomy and stone removal and endoscopic biliary and pancreatic drainage. In: Textbook of Gastroenterology. 5th ed. USA. Willey Blackwell 2009).

Schofer JM. Biliary causes of postcholecystectomy syndrome. J Emerg Med. 2010 ;

Craig AG, Toouli J. Slow release nifedipine for patients with sphincter of Oddi dyskinesia: results of a pilot study. Intern Med J. 2002; 32:119.

Bar-Meir S, Halpern Z, Bardan E. Nitrate therapy in a patient with papillary dysfunction. Am J Gastroenterol 1983; 78:94.

Rehman, A., Affronti, J., Rao, S. Sphincter of Oddi dysfunction: an evidence-based review. Expert Rev Gastroenterol Hepatol. 2013;7:713–722.

Khuroo MS, Zargar SA, Yattoo GN. Efficacy of nifedipine therapy in patients with sphincter of Oddi dysfunction: a prospective, double-blind, randomized, placebo-controlled, cross over trial. Br J Clin Pharmacol 1992; 33:477.

Okoro N, Patel A, et al. Ursodeoxycholic acid treatment for patients with postcholecystectomy pain and bile microlithiasis. Gastrointest Endosc. 2008;68:69-74.

Bystrovskaia EV. Postcholecystectomy syndrome: pathogenetic and therapeutic clinical aspects of problem. Medical Recommendation. 2012; 2: 83-87.