COLECISTITA CRONICA ALITIAZICA

COLECISTITA CRONICA ALITIAZICA

DEFINITION AND CLINICAL FEATURES

Intense epigastric or right upper quadrant pain, starting suddenly, rising in intensity over a 15-minute period, and continuing at a steady plateau for several hours before slowly subsiding is the classic description of biliary pain. Localization of the pain to the right hypochondrium or radiation to the right shoulder is the most specific finding for a biliary tract origin.^[3] The attacks of pain are frequently, but not always, precipitated by a meal and may be accompanied by restlessness and vomiting. Between attacks, the physical findings are usually normal, with the possible exception of residual upper abdominal tenderness.

When a patient presents with such a history and ultrasonography confirms the presence of gallstones, the management is straightforward-namely, elective cholecystectomy (or perhaps an attempt at medical dissolution of the stones)

Acalculous biliary pain is a syndrome in which patients have clinical features identical to those of patients with cholelithiasis and biliary pain but a normal gallbladder on ultrasonography and normal serum levels of liver and pancreatic enzymes. ^{[4] [5]}

EPIDEMIOLOGY AND PATHOPHYSIOLOGY

Acalculous biliary pain is predominantly a disorder of young women.^[6] In one series of more than 100 patients, 83% were female, and the mean age was approximately 30 years.

The cause of the acalculous biliary pain syndrome is not known, but indirect evidence suggests that there may be multiple different etiologies that culminate in the same clinical presentation. Stimulated duodenal bile from patients with acalculous biliary pain is more dilute with respect to both bile acids and phospholipids than bile from patients with gallstones or from control women without biliary symptoms.^[7] The dilute nature of the bile is consistent with other observations showing sluggish and incomplete gallbladder contraction, and the lower molar percentage of phospholipid is consistent with the hypothesis that biliary phospholipids are hydrolyzed to inflammation-producing free fatty acids.

The striking preponderance of young, fertile women in the group of patients with acalculous biliary pain closely parallels the epidemiology of cholelithiasis, an observation suggesting that the two conditions have similar risk factors. Some studies have shown that up to one half of patients with acalculous biliary pain actually have microscopic cholelithiasis in resected gallbladder specimens,^[9] indicating that the original ultrasonogram was falsely negative. Examination of a bile specimen for microlithiasis (Meltzer-Lyon test, discussed later) is helpful in identifying these patients.

Several studies have shown consistently that a subset of patients with acalculous biliary pain have histologic evidence of cholesterolosis in their resected gallbladders. ^{[10] [11] [12]} Although usually thought to be an incidental pathologic finding, cholesterolosis of the gallbladder may, in some patients, disrupt normal gallbladder contraction and result in biliary pain.

Finally, acalculous biliary pain is listed as a functional gastrointestinal disorder by a multinational working committee of gastrointestinal investigators (Rome classification) with the implication that a pathologic lesion is not required for the diagnosis

DIAGNOSIS AND TREATMENT

As described earlier, the clinical features of acalculous biliary pain are identical to those of biliary pain associated with cholelithiasis. A careful review of the patient's complaints should confirm that the symptoms are genuinely suggestive of biliary pain rather than dyspepsia, heartburn, cramping abdominal pain, or flatulence.^[3] If the symptoms suggest biliary pain, a careful review of the ultrasonogram with a radiologist is warranted. Although gallstones larger than 2 mm are unlikely to have been missed (the sensitivity of ultrasonography for detecting stones exceeds 95%), other ultrasonographic evidence of gallbladder disease may have been overlooked if the primary focus was to exclude stones. Patients with adenomyomatosis of the gallbladder or small cholesterol polyps may have biliary pain that is relieved by cholecystectomy.

Examination of the Bile for Cholesterol Crystals (Meltzer-Lyon Test)

If the ultrasonogram is normal, a reasonable approach may be to examine the bile for evidence of cholesterol crystals. Long before the advent of ultrasonography, biliary drainage was used to identify patients who were likely to have gallstones.^[13] The test has been modified so that the bile is now aspirated during an upper endoscopy after stimulation of gallbladder contraction with intravenous cholecystokinin (CCK). The bile should be kept at room temperature and examined immediately (after completion of endoscopy) under the microscope for the presence of characteristic birefringent, notched rhomboid cholesterol crystals or calcium bilirubinate granules.

Limited clinical studies in patients with acalculous biliary pain have shown that approximately one third have crystals in their bile. ^{[10] [11]} If operated on, most of these patients are found to have both microlithiasis and pathologically confirmed cholecystitis and become symptom free after cholecystectomy. The two thirds of patients who do not have crystals in their bile generally experience a benign course and rarely return with evidence of biliary tract disease.

Stimulated Cholescintigraphy

A second approach to selecting patients with acalculous biliary pain who would likely benefit from surgery involves calculation of a gallbladder ejection fraction (GBEF) using cholescintigraphy (An intravenously administered radiolabeled hepatobiliary agent (e.g., ^99mTc-diisopropyl iminodiacetic acid) is concentrated in the gallbladder, and a computer-assisted gamma camera measures activity before and after stimulation of gallbladder contraction with a slow intravenous infusion of CCK over 30 minutes. The GBEF is defined as the change in activity divided by the baseline activity. Studies in healthy volunteers have shown that GBEF averages 75% and virtually always exceeds 35%.

As the test gains clinical acceptance, the predictive value of a positive result is likely to fall. When stimulated cholescintigraphy was first developed, most patients referred for testing had been monitored for years with biliary pain, thereby allowing ample time for other causes of the pain to become manifest. Therefore, the pretest probability of having a primary gallbladder motility derangement was high, and the specificity of the test appeared to be excellent. Now, the test is employed earlier in the evaluation of patients with biliary pain (sometimes immediately after an ultrasonogram that does not demonstrate gallstones), and patients with nonbiliary or self-limiting diseases have not been weeded out. Hence, the earlier cholescintigraphy is employed, the lower the pretest probability of acalculous biliary pain and, unfortunately, the lower the predictive value of a positive result.^[15]

In patients with acalculous biliary pain, much less than one half have a depressed GBEF, but virtually all of those who do have a depressed GBEF continue to have symptoms when followed up for as long as 3 years. If a cholecystectomy is performed in these patients, histologic evidence of chronic cholecystitis is found in approximately 90%, cystic duct narrowing in 80%, and cholesterolosis in 30%.^[12] The long-term outcome, with respect to relief of symptoms, has varied, but two studies have shown that between 67% and 80% of the patients are cured of symptoms after cholecystectomy.

The patients with acalculous biliary pain and a normal GBEF have a variable (but generally benign) course; many are ultimately found to have a nonbiliary cause for the symptoms. Therefore, the combination of an examination of bile for cholesterol crystals and stimulated cholescintigraphy, when applied to patients with classic biliary pain but without ultrasonographically demonstrable gallstones, is a useful means of determining which patients may benefit from empiric cholecystectomy. If the bile contains no crystals and the gallbladder contracts normally, the patient is not likely to benefit from cholecystectomy.

Diagnosticul diferential al CCAL

Colecistita cronica alitiazica trebuie diferentiata de toate celalalte cauze de durere in cadranul abdominal superior.

Celalalte afectiuni ale tractului biliar care sunt excluse imagistic si includ: stricturi ale ductelor biliare, coledocolitiaza, colelitiaza, colangita, cancerul vezicular.

Afectiuni digestive ce pot fi asociate cu durerea la acest nivel si din care fac parte:

-Ulcerul gastroduodenal sugerat de un istoric de dureri epigastrice corelate cu mesele si cu caracterul sezonier. Explorarile necesare sunt endoscopia digestiva superioara sau tranzitul baritat esogastro-duodenal.

-Pancreatita cronica se exclude pe baza anamnezei (consum cronic de etanol), existentei in antecedente a episoadelor de pancreatita acuta si a criteriilor imagistice - dilatatii. Uneori cele doua boli coexista, dar pancreatita nu trebuie acceptata ca diagnostic secundar fara date specifice.

-Durerea severa la nivelul hipocondrului drept asociata cu febra si sensibilitate locala poate sugera perihepatita gonococica ( sindromul Fitz-Hugh-Curtis ). Indicii utili in acest caz sunt reprezentati de sensibilitatea la nivelul anexelor si evidentierea gonococului la microscopia optica, prin coloratia Gram, si culturi celulare din exudatul vaginal. Element sugestiv poate fi si discrepanta intre febra inalta pe care o acuza pacienta si lipsa toxicitatii generale.

-Hepatitele cronice virale sugerate de modificarile evidentiate ecografic, evaluarea testelor functiei hepatice (albumina serica, proteine totale, colesterol, FA, transaminaze, fibrinogen si bilirubina ) si identificarea anticorpilor antivirus hepatitic.

-Sindromul de colon iritabil sugerat de istoricul de durere asociata cu tulburari de tranzit.

La pacientii cu HIV exista unele afectiuni ale tractului biliar ce trebuie diferentiate de colecistita acalculoasa produsa de CMV si anume:

-Colangiopatia in SIDA este un sindrom caracterizat prin anomalii ale ductelor biliare la pacientii cu infectati u HIV. Aceste anomalii includ stenoza papilara, colangita sclerozanta, stricturi extrahepatice si sunt datorate infectiei cu CMV, Microsporia si Criptosporydium. Pacientii prezinta durere in hipocondrul drept si febra sau pot fi asimptomatici, iar anomaliile de laborator consta cresterea FA si a transaminazelor, la care se adauga dilatatia ductala detectata la ultrasonografie.

-Limfomul non-Hodgkin, sarcomul Kaposi pot aparea la nivelul arborelui biliar, dar cazurile sunt extrem de rare.

-Infectiile fungice viscerale care includ si ficatul, cum este histoplasmoza, coccidiomicoza, cryptococoza.

Evolutia si complicatiile CCAL

Colecistia cronica alitiazica poate fi simptomatica ani de zile, poate evolua catre o colecistopatie simptomatica sau catre o colecistita acuta, sau poate prezenta complicatii. Evolutia depinde de extinderea procesului inflamator si de gravitatea infectiei. Respectarea regimului de viata si de alimentatie poate asigura o evolutie favorabila si sa previna complicatiile.