Post-cholecystektomický syndrom

Epidemiology

• 5-30% of patients
• 10-15% being the most reasonable range [1]

• 65% of patients had no symptoms
• 28% had mild symptoms
• 5% had moderate symptoms
• 2% had severe symptoms [1]

Rizikové fkatory

• Urgent operation - higher risk for developing PCS

Stones

• Performed for stones
• 10-25% develop PCS
• no stones
• 29% develop PCS [1]

Duration of symptoms before surgery

• Less than 1 year
• 15.4% develop PCS
• 1-5 years
• 21% develop PCS
• 6-10 years
• 31% develop PCS
• More than 10 years
• 34% develop PCS [1]

Choledochotomy

• Performed
• 23% of patients develop PCS
• Not performed
• 19% develop PCS [1]

typical or atypical preoperative symptoms

• no difference in the incidence of PCS [1]

Previous surgery

• Bile spill
• Stone spill
• no difference in the incidence of PCS [1]

Age

• 20-29 years
• Incidence of 43%
• 30-39 years
• 27%
• 40-49 years
• 21%
• 50-59 years
• 26%
• 60-69 years
• 31%
• Older than 70 years
• Did not develop PCS [1]

Sex

• Females
• 28% incidence of PCS
• Males
• 15% incidence [1]

Psychosocial status

• Clear association between the Prevalence of functional gastrointestinal diseases and some psychiatric disorders
• Psychosocial problems
• Anxiety syndrome
• Panic disorder
• Sexual victimization
• Altered pain perception
• Increased pain sensitivity [4]

Patofyziologie PCS

Continuously increased bile flow

• Into the upper gastrointestinal (GI) tract may contribute to
• Esophagitis
• Gastritis [1]
• Fasting gastric bile acid concentration
• Increased after cholecystectomy
• Increase was greater in patients with PCS [1]
• Lower GIT
• Diarrhea
• Colicky lower abdominal pain [1]

Gallbladder remnant and cystic duct

• Residual or reformed gallbladder
• Stump cholelithiasis
• Neuroma [1]

Pain associated with PCS

• Sphincter of Oddi dysfunction
• Post-surgical adhesions
• Biliary microlithiasis

• Cca 50% of cases are due
• Biliary causes
• Remaining stone
• Biliary injury
• Dysmotility
• Choledococyst

• Remaining 50% due to non-biliary causes
• Upper abdominal pain and gallstones
• Both common
• Not always related

Functional Extrabiliary Causes

• Altered antroduodenal motility
• Antroduodenal dyscoordination
• Duodenal wall spasm [5]
• Synchronization between the SO motility and the fasting phases of the duodenal motor activity
• Malfunction of the duodenal pace- maker may be one possible pathophysiological factor
• Pathologically increased amount of duodenogastric bile reflux
• Also in association with PCS

Irritable bowel syndrome (IBS)

• May occur after cholecystectomy
• Dyspeptic symptoms
• By altered gut motility
• Strong correlation between the presence of IBS and SO motility disorders [5]
• RUQ pain can be also evoked by balloon distension
• In the upper gut
• In the right-sided colon [5]

Antral gastritis after cholecystectomy

• Significantly increased
• Probably caused by bile acids
• Coexistent Helicobacter pylori infection is uncertain

Gastroesophageal reflux

• May also be exacerbated in patients with PCS
• Associated with a significant fall in the lower oesophageal sphincter pressure
• Higher rate of bile reflux into the esophagus

Enhanced colon motility

• After administration of exogenous CCK in patients with IBS
• Might be responsible for some abdominal complaints after feeding
• bile acids may induce an exaggerated motility

Chronic minimal inflammatory response of the colon

• Ude to bile acids

Functional Biliary Causes

Sphincter of Oddi dysfunction (SOD)

• Uncommon clinical entity
• 1.5 - 3% of PCS patients
• Episodes of moderate to severe steady pain
• Located in the epigastrium
• Or the RUQ
• Recurring more than three months
• RUQ pain may radiate to the epigastrium or the back
• Starts 15-30 min after a meal
• Lasts more than 60 minutes
• Evoked by fatty food
• Transient elevations of liver enzymes (AST/ALT/AP)
• Dilated common bile or pancreatic duct
• In an absence of an obvious structural cause [4]

SO stenosis

• Inflammation
• Fibrosis
• Smooth muscle hypertrophy

SO dyskinesia

• Functional motility disorder of the SO
• Neuromuscular incoordination [4]

• ERCP - diagnostic evaluation
• Dilated common bile duct (> 12 mm)
• Delayed contrast drainage time (> 45 min)
• Without stone or obvious organic cause
• More prevalent in patients with SO stenosis than in SO dyskinesia

SOD group I

• Abdominal pain
• Abnormally elevated liver or pancreatic enzymes
• Dilated common bile or main pancreatic duct
• Delayed contrast drainage time

SOD group II

• Abdominal pain
• One more above mentioned criteria

SOD group III

• Only abdominal pain
• None of the other criteria

Diagnostic

• Risk of post- ERCP pancreatitis
• Relatively high in patients having SOD
• Non-invasive classification of SOD is better
• Abdominal ultrasound
• Endoscopic ultrasonography
• MRCP (common bile duct anatomy and diameter)
• Hepatobiliary scintigraphy (delayed isotope contrast drainage time)
• May be useful before the clinical decision of further invasive diagnostic investigations
• Endoscopic SO manometry
• Increased baseline pressure
• Proved to be the most important diagnostic finding [4]
• Increased the amplitude of phasic contractions
• Increased number of retrograde contractions
• Increased frequency of phasic contractions
• Increased the pressure of the common bile duct
• Paradoxical response to cholecystokinin administration

Cholecystokinin (CCK)

• Potent inhibitor of SO basal and phasic activity
• The release of CCK after food intake
• Most important factor in the inhibition of the SO during the postprandial period
• Allowing the movement of an increased bile flow across the SO with decreased resistance !!!
• After i.v. administration of CCK
• Inhibitory effect lasts 2-6 minutes
• Afterward the SO activity returns to normal
• Appears to be via stimulation of
• nitric oxide
• Vasoactive intestinal polypeptide
• Mediated non-adrenergic-noncholinergic (NANC) inhibitory neurons
• Overriding the direct smooth muscle stimulatory effect of CCK

Denervation pattern od Oddi Sfincter

• Imbalance between the dominant inhibitory effect and the direct smooth muscle excitatory action of CCK on the SO
• May lead to
• Inappropriate spasm
• Paradoxical response of the SO after CCK administration
• Lack of inhibitory action of the CCK on the SO can be the consequence of denervation of the SO
• Cholecystectomy might be responsible for this
• In a few patients with PCS reproduction of biliary pain
• Observed at the time of paradoxical SO spasm during CCK administration
• Experimental distension of the common bile duct
• Induces localized RUQ or epigastrial pain
• Accompanied by nausea and vomiting
• Pain during ERCP can be regarded as a good indicator of an oversensitive biliary tract
• Low compliance to volume changes
• Might act as a pain trigger zone

Pohotovost Oddyho svěrače ke spasmu

• Presence of opioid receptors in the SO area
• Morphine sulfate (MS) has a stimulatory effect on the human SO
• Very small doses of MS (2.5 ug/kg) increases the frequency and the amplitude of phasic contractions
• Larger doses can cause SO spasm with a substantial elevation of the SO basal pressure
• Can be antagonized by naloxone, but not by atropine
• Direct smooth muscle stimulatory effect of MS
• By facilitating the Ca++ influx through the voltage dependent or receptor operated calcium channels
• There is a subgroup of patients with PCS, who have exaggerated SO contractile response after MS administration
• Factors influencing motor responses to morphine provocation tests
• Not related either to those which determine the basal SO motility or the responses to intravenous CCK [4]

Symptoms after cholecystectomy

• Abu Farsakh et al found gastritis to be more frequent postoperatively (30% vs 50%) [1]

• Dyspepsia, nausea, and vomiting [3]
• GER and gastritis
• Flatulence, bloating, and diarrhea [3]
• Persistent pain in the upper right abdomen [3]

Dif. dg. etiologie symptomů

• Effective communication between patients and their physicians is necessary !!!
• In 20% organ other than hepatobiliary or pancreatic

PCS was caused by

• Functional disorders in 26% of patients
• Peptic disease in 4%
• Wound pain in 2.4%
• Stones in 1%
• Subhepatic fluid in 0.8%
• Incisional hernia in 0.4% [1]

Psychiatric disorder

• 50% of patients with a preoperative psychiatric disorder have an organic cause of PCS !!! [1]
• 23% of patients without a psychiatric disorder have an organic cause

Liver

• Fatty infiltration of liver
• Hepatitis
• Hydrohepatosis
• Cirrhosis
• Chronic idiopathic jaundice
• Gilbert disease
• Dubin-Johnson syndrome
• Hepatolithiasis
• Sclerosing cholangitis
• Cyst

Biliary tract

• Cholangitis
• Adhesions
• Strictures
• Trauma
• Cyst
• Malignancy and cholangiocarcinoma
• Obstruction
• Choledocholithiasis
• Dilation without obstruction
• Hypertension or nonspecific dilation
• Dyskinesia
• Fistula

Periampullary

• Sphincter of Oddi dyskinesia, spasm, or hypertrophy
• Sphincter of Oddi stricture
• Papilloma
• Cancer

Pancreas

• Pancreatitis
• Pancreatic stone
• Pancreatic cancer
• Pancreatic cysts
• Benign tumors

Esophagus

• Aerophagia
• Diaphragmatic hernia
• Hiatal hernia
• Achalasia

Stomach

• Bile gastritis
• Peptic ulcer disease
• Gastric cancer

Duodenum

• Adhesions
• Duodenal diverticula
• Irritable bowel disease

Small bowel

• Adhesions
• Incisional hernia
• Irritable bowel disease

Colon

• Constipation
• Diarrhea
• Incisional hernia
• Irritable bowel disease

Vascular

• Intestinal angina
• Coronary angina

Nerve

• Neuroma
• Intercostal neuralgia
• Spinal nerve lesions
• Sympathetic imbalance
• Neurosis
• Psychic tension or anxiety

Bone

• Arthritis

Other

• Adrenal cancer
• Thyrotoxicosis
• Foreign bodies
• Gallstones
• Surgical clips

Organic Extrabiliary DiseasesDifferential diagnosis can be difficult since symptoms similar to PCS may originate from other organic diseases of the esophagus, stomach, small and large bowel or the pancreas. Careful case history, physical examination, laboratory studies, abdominal ultrasound, abdominal computer tomography and gastrointestinal endoscopy may be useful to identify an underlying organic disorder. Disease of the dorsal spine may manifest in a disabling, chronic abdominal pain and represent an important and treatable cause of PCS, which is unfortunately infrequently diagnosed [10]. The pain originated from the vertebral column can be discogenic and zygapophysial- joint (facet) mediated or it can be a result of spinal root compression [11]. The early phase of herpes zoster may also induce neuropathy and radiating burning pain a few days before the typical skin rash appears. Upper abdominal pain, which can be reproduced by pressure on the lower costal margin, may be caused by costochondritis or lesions of the intercostal nerves [12]. Regardless of the exact pathomechanism, the diagnosis requires clinical suspicion. Complete neurological and rheumatological examination should be always performed in these patients.Organic Biliary DiseasesResidual or de novo formed common bile duct stones are the most common organic biliary causes of PCS. After cholecystectomy bile duct stones can occur in 5-15% of the patients depending on the population studied, whether operative or preoperative cholangiography was applied and the period of the follow-up [13]. Although retained bile duct stones are far more frequent, some stones are clearly formed (de novo) in the common bile duct [14]. Pathological elevation of liver enzymes (bilirubin and alkaline phosphatase) and a dilated common bile duct (CBD) can predict the presence of stones in the majority of cholecystectomized patients. In contrast, the absence of these clinical manifestations has a 95% negative predictive value for choledocholithiasis [15]. Magnetic resonance cholangiopancreatography (MRCP) is the first choice of diagnostic method to demonstrate CBD stones in these patients. In contrast, ERCP enables therapeutic intervention, such as endoscopic sphincterotomy and immediate stone extraction at the time of diagnosis [15]. Benign postoperative bile duct strictures are infrequent causes of PCS, and the majority of such strictures are initiated by accidental surgical trauma during cholecystectomy. While the incidence of duct injuries during open cholecystectomy was around 0.1%, recent reports suggested that the laparoscopic approach increases the frequency by ten times [16]. Commonly observed symptoms caused by bile duct strictures are fever, chills, and jaundice that are the characteristic signs of recurrent cholangitis [24]. ERCP and endoscopic biliary multiple plastic stenting after balloon dilatation can provide good and long-term biliary drainage in the majority of patients [17]. Benign or malignant tumors of the Vater papilla and the periampullary area can mimic symptoms related to a PCS, such as biliary colic and jaundice. The villous adenoma and the adenocarcinoma of the Vater papilla are represented in 5% and 0.2% of all gastrointestinal tumors [18]. ERCP is the most accurate diagnostic test since it provides direct visualization of the papilla of Vater with an access for biopsy and endoscopic papillectomy [19]. Choledochal cyst is a cystic dilatation of the common bile duct and is a rather rare condition. It can be classified into three types: (I) the segmental cystic dilatation of the common bile duct, (II) the solitary common bile duct diverticulum arising laterally, (III) the dilatation of the intra-duodenal portion of the common bile duct (choledochocele). It can be associated with the anomalous connection of the pancreatic and biliary duct (ACPBD), which may be demonstrated by ERCP, MRCP or by endoscopic ultrasonography. ACPBD can be visualized as a long common channel and a high connection between the pancreas and bile duct outside of the sphincter zone. The majority of patients with choledochal cysts are asymptomatic, but they may be presented with abdominal pain, nausea, vomiting, biliary colic, and jaundice. Gallstones and pancreatitis have been associated with this entity in 25 and 30% of the cases. There is an increased risk of development of cholangiocarcinoma within the cyst and also for gallbladder carcinoma due to pancreaticobiliary reflux of the pancreatic juice that must be taken into consideration during the follow-up. ERCP and endoscopic manometry seem to be useful in clarifying the pathophysiology of symptomatic choledochocele and ACPBD [20-23]. Several reports suggested that juxtapapillary diverticulum (JPD) might cause symptoms or diseases of the biliary and pancreatic duct. It has been proved, that the incidence of cholangitis and common bile duct stones were increased in patients with JPD, but there was no similar relationship between the gallbladder stones and JPD [24]. Common bile duct stones associated with JPD are usually pigment stones, which are thought to be associated with infections and stasis. In patients with JPD endoscopic manometry usually demonstrated decreased SO baseline pressure, which may be responsible for the increased risk of ascending cholangitis, but the compression of the distal bile duct by the distended diverticulum may cause obstructive symptoms as well [25]. Several authors have suggested that the cystic duct stump or gallbladder remnant left behind after cholecystectomy; so-called cystic duct stump may be responsible for PCS. Cystic duct syndrome (CDS) described in 1950 by Garlock in cholecystectomized patients with recurrent cholangitis [26]. Since the majority of their patients had common bile duct stones, they were convinced that the cystic duct remnant can form calculi, which are responsible for the symptoms. Ten years later, Glenn F. suggested, that’s a long cystic duct remnant can be a sole cause of postcholecystectomy pain, and indicated a satisfactory outcome after the operative removal of the cystic duct stump [27]. Unfortunately, in controlled studies no significant difference was found between symptomatic and asymptomatic cholecystectomized subjects in the frequency of cystic duct remnant [28]. Therefore, CDS should not be considered as a reliable cause of PCS.

Diagnostics

• Ultrasound of the abdominal cavity.
• General and biochemical blood.
• Intravenous cholangiography.
• Esophagogastroduodenoscopy
• Examination of the stomach, duodenum
• Area major duodenal papilla.
• Retrograde cholangiopancreatography.
• Analysis of biliary sludge
• Obtained through endoscopic retrograde cholangiopancreatography (ERCP)
• SeHCAT
• Or other test for bile acid diarrhea [3]

Laboratorní testy

Postcholecystectomy pain - suggests biliary colic ?

• Alkaline phosphatase
• bilirubin
• ALT
• Amylase
• Lipase
• ERCP with biliary manometry
• Or biliary nuclear scanning [4]

• Elevated liver enzymes
• Suggest sphincter of Oddi dysfunction [4]
• Elevated amylase and lipase
• Suggest dysfunction of the sphincter’s pancreatic portion [4]

Progonoza

• Transient
• Persistent
• Lifelong
• Chronic condition
• Cca in 10% of postcholecystectomy cases

Pain

• 75% good-to-fair relief of pain on long-term follow-up [1]

Short-term complications

• Common (5-40%) [1]

Hyperamylasemia

• Most common complication
• Usually resolves by postoperative day 10 [1]

Pancreatitis

• Expected in 5% of cases [1]

Death

• In 1% [1]

Terapie

• Dle příčiny
• Pharmacologic
• Surgical approaches [1]

Irritable bowel syndrome

Bulking agents

Antispasmodics

Sedatives

Irritable sphincter

High-dose calcium channel blockers

Nitrates

• Available evidence is not yet convincing [1]

Chronic diarrhea in PCS

• Type of bile acid diarrhea
• Treated with a bile acid sequestrant
• Cholestyramine
• Colestipol
• Colesevelam
• May be better tolerated [3]
• Nízkotučná strava

Gastroesophageal reflux disease (GERD) or gastritis symptoms

• Correlated with gastric bile salt concentration [2]
• Occasionally provide relief [1]

Antacids

Histamine 2 (H2) blockers

• Tohle se asi vyplatí mít doma pro případ aktuního pálení žáhy a neváhat to použít

Proton pump inhibitors (PPIs)

Lovastatin

• Might provide at least some relief in as many as 67% of patients [1]

Pain caused by biliary microlithiasis

• Oral ursodeoxycholic acid
• Can alleviate the condition [3]

Surgical Intervention

• At the specific diagnosis
• Complete evaluation (including ERCP with sphincterotomy)
• Can be both diagnostic and therapeutic
• Exploratory surgery
• Last resort in the patient who lacks a diagnosis and whose condition proves refractory to medical therapy
• Resection of
• Scar and nerve tissue around the cystic duct stump
• Neuroma
• Cystic duct remnant
• Sphincter dilation
• Sphincterotomy
• Sphincteroplasty
• Biliary bypass
• Common bile duct (CBD) exploration
• Stone removal
• Sphincteroplasty
• Including the bile and pancreatic ducts [2]

• Patient continues to experience debilitating, intermittent right-upper-quadrant pain
• no diagnosis is found
• The procedure of choice after a normal exploratory laparotomy is transduodenal sphincteroplasty [2]

• Remnant cystic duct lithiasis - RCDL
• Gallstones within the cystic duct after cholecystectomy
• Endoscopic therapy may suffice
• Surgical excision of the RCDL may be necessary in some cases [2]

Strava - diet modification

• Absence of gallbladder
• Bile enters the intestine constantly
• But in small quantities

Bile insufficiency

• Not enough for digestion of fatty foods

Reduced fat diet

Enzyme preparations

Cholagogue

Constatn bile secretion and GIT irritation

Antispasmodics

Bile acid sequestrant

Literatura:

[1] emedicine.medscape.com/article/192761-overview
[2] emedicine.medscape.com/article/192761-treatment#d8
[3] en.wikipedia.org/wiki/Postcholecystectomy_syndrome
[4] www.msdmanuals.com/professional/hepatic-and-biliary-disorders/gallbladder-and-bile-duct-disorders/postcholecystectomy-syndrome
[5] www.omicsgroup.org/journals/postcholecystectomy-syndrome-from-pathophysiology-to-differentialdiagnosis--a-critical-review-2165-7092-1000162.php?aid=63731
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