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Gallbladder stones--dissolve, blast, or extract? Laparoscopic cholecystectomy versus 'the rest'.

This article reviews selected aspects of the non-surgical/minimally invasive treatments of gallbladder stones (GBS) and discusses briefly the residual role of these treatments in the era of laparoscopic cholecystectomy. In patients with specific, gallstone-related symptoms who wish to retain their 'functioning' gallbladders, there are at least six different management options. They range from rapid but invasive to slow but safe: i) the rotary lithotrite; ii) percutaneous cholecystolithotomy; iii) percutaneous transhepatic or iv) endoscopic retrograde cannulation of the gallbladder followed by instillation (manual or pump-assisted) of contact solvents; v) extracorporeal shock-wave lithotripsy + adjuvant bile acids and; vi) oral bile acids alone. The recommended investigation sequence is i) ultrasound (to diagnose the presence of GBS), followed by ii) oral cholecystography (to assess cystic duct patency, gallbladder anatomy and GBS size, number, lucency, buoyancy, and contour), and iii) regional computed tomography scanning of the gallbladder (to predict stone composition and dissolvability and to plan routes of access to the gallbladder). The decision-making steps are i) choice of some form of active treatment versus no treatment (other than observation); ii) in those with specific symptoms and a patent cystic duct who opt for active treatment, to choose between removing versus retaining the gallbladder; and iii) in those who wish to retain their 'functioning' gallbladder, to offer and select the most appropriate of the alternative options. In conclusion, despite the excellence of laparoscopic cholecystectomy, there remains a place for the non-surgical/minimally invasive approaches in a carefully selected minority of symptomatic GBS patients. Although GBS may recur in approximately 50% of patients, the recurrent stones are often asymptomatic, can be detected 'early' by follow-up ultrasound, and are easily treated. Ultimately, the aim of gallstone research must be to prevent not only recurrent but also primary GBS formation, which would obviate the need for both medical and surgical treatment.

Administration, Oral↗

Mucin and phospholipids determine viscosity of gallbladder bile in patients with gallstones.

AIM: An increased viscosity of gallbladder bile has been considered an important factor in the pathogenesis of gallstone disease. Besides lipids and proteins, mucin has been suggested to affect the viscosity of bile. To further clarify these issues we compared mucin, protein and the lipid componEnts of hepatic and gallbladder bile and its viscosity in patients with gallstones. METHODS: Viscosity of bile (mPa.s) was measured using rotation viscosimetry in regard to the non Newtonian property of bile at low shear rates. RESULTS: Biliary viscosity was markedly higher in gallbladder bile of patients with cholesterol (5.00 +/- 0.60 mPa.s, mean +/- SEM, r= 28) and mixed stones (3.50 +/- 0.68 mPa.s; r= 8) compared to hepatic bile (0.92 +/- 0.06 mPa.s, r= 6). A positive correlation between mucin and viscosity was found in gallbladder biles (r = 0.65; P < 0.001) but not in hepatic biles. The addition of physiologic and supraphysiologic amounts of mucin to gallbladder bile resulted in a dose dependent non linear increase of its viscosity. A positive correlation was determined between phospholipid concentration and viscosity (r = 0.34, P < 0.005) in gallbladder biles. However, no correlation was found between total protein or the other lipid concentrations and viscosity in both gallbladder and hepatic biles. CONCLUSION: The viscosity of gallbladder bile is markedly higher than that of hepatic bile in patients with gallstones. The concentration of mucin is the major determinant of biliary viscosity and may contribute by this mechanism to the role of mucin in the pathogenesis of gallstones.

Adult↗

Preoperative ultrasonographic assessment of the number and size of gallbladder stones: is it a useful predictor of asymptomatic choledochal lithiasis?

OBJECTIVE: To evaluate whether preoperative ultrasonographic assessment of the number and size of gallbladder stones can identify patients at increased risk of having asymptomatic common bile duct stones. METHODS: Ultrasonographic data for 300 consecutive patients undergoing laparoscopic cholecystectomy were analyzed. Patients were divided into a group in which multiple small (< or = 5 mm) or multiple variably sized (both < or = 5 and > 5 mm) gallbladder stones were present ("positive" stones) and a group with multiple large (> 5 mm) or single gallbladder stones, considered "negative." The ultrasonographic description was compared with surgical findings; finally, the prevalence of asymptomatic common bile duct stones in the 2 groups was compared. RESULTS: Ultrasonographic classification of gallbladder stones was confirmed at surgery in 285 cases (95%). Asymptomatic common bile duct stones were diagnosed in 9.5% of patients with an ultrasonographic diagnosis of positive gallbladder stones and in only 2.3% of patients with a diagnosis of negative gallbladder stones (P < .05). CONCLUSIONS: Ultrasonography is able to accurately show gallbladder stones; the appearance of multiple small and variably sized gallbladder stones represent a risk factor for synchronous asymptomatic common bile duct stones.

Cholecystectomy, Laparoscopic↗

Stratification of bile in gallbladder and gallstone formation.

The essential role of the gallbladder in gallstone formation should not be underestimated, as cholesterol stones originate in the gallbladder. The possible significance of stratification of bile in the gallbladder has been studied using recently proposed lithogenic parameters, such as triangular co-ordinates, lithogenic index and cholesterol saturation index. Bile becomes less lithogenic as the concentrating process in the gallbladder progresses. The concentrating activity of the gallbladder seems to differ considerably for each bile constituent. Bile salts are most concentrated in the gallbladder, followed by phospholipids and cholesterol. The presence of a selective absorption process in the gallbladder is suggested. As the gallbladder diminishes the lithogenicity of bile during storage, its role probably lies in its ability to interrupt the enterohepatic circulation leading to the production of lithogenic bile as well as providing a recess to ensure continuous growth of stones.

Bile↗

[Incidence of gallbladder stones in renal transplant recipients].

BACKGROUND/AIMS: Gallbladder stone is one of the major cause of morbidity in adults. Renal transplantation has been found to increase the risk of gallbladder stone formation. The real incidence of gallbladder stones in renal transplant recipients is not exactly known. We performed this study to identify the risk factors for cholecystolithiasis. METHODS: We compared the prevalence of gallbladder stone in 222 renal transplantation patients with that in 222 age and sex matched controls. Patients who had chronic liver disease, renal disease, and diabetes were excluded from the control group. RESULTS: In our study, the incidence of gallbladder stones is 8.6% (19/222 patients) in renal transplantation patients, which was significantly higher than 3.60% (8/222 control) in the control group (p=0.029). In the most of our renal transplantation patients, cholecystolithiasis was asymptomatic. We did not find a difference in age, sex, duration after transplantation, causes of renal failure, resistance index between patients with and without gallbladder stones in renal transplantation patients. CONCLUSIONS: Our results suggest that the incidence of gallbladder stones is higher in renal transplant recipients than non-transplant population in Korea. Further studies will be needed to focus the factors contributing to the gallbladder stone formation after renal transplantation, especially in regard to immunosuppressive drugs.

Adult↗

CCK1 receptor antagonist, dexloxiglumide: effects on human isolated gallbladder. Potential clinical applications.

Cholecystokinin is the main hormonal regulator of gallbladder motility. Dexloxiglumide, the active enantiomer of loxiglumide, interacts competitively with CCK1 receptors as determined in preclinical studies, such as specific radioligand binding assays or functional studies on isolated guinea pig gallbladder, where it inhibited smooth muscle cell contractions induced by cholecystokinin-octapeptide (CCK-8), the most prominent active forms of cholecystokinin. Dexloxiglumide has a potent antagonistic effect, of a competitive nature, on human gallbladder cholecystokinin type 1 receptors. In isolated human gallbladder, dexloxiglumide produced a concentration-dependent rightward shift of the cholecystokinin-octapeptide curve, without affecting its maximal response. Gallbladder motility was evaluated in clinical studies. Dexloxiglumide, orally administered to healthy volunteers at putative therapeutic doses, did not interfere with post-prandial gallbladder kinetics, despite an increase of fasting gallbladder volume. At present, dexloxiglumide is in an advanced stage of clinical research in gastroenterology. Overall, clinical observations suggest that dexloxiglumide may become an effective treatment in several gastrointestinal disorders. Moreover, the beneficial effects can be obtained without increasing the risk of gallstones formation, a potential hazard subsequent to the inhibition of gallbladder contractions and the resulting bile stasis. The potent and selective antagonist dexloxiglumide may offer a possible therapeutic tool for use not only in functional gastrointestinal disorders, such as irritable bowel syndrome, constipation, gastroesophageal reflux disease and functional dyspepsia, but also in other pathologies, such as biliary colics, pancreatic diseases and gastrointestinal tumors.

Journal Article↗

Subtotal cholecystectomy: for the difficult gallbladder in portal hypertension and cholecystitis.

An easy, safe, and definitive operation for the "difficult gallbladder" is described and has been termed subtotal cholecystectomy. Eighteen patients underwent subtotal cholecystectomy during a 30-month period, which constitutes approximately 7% of cholecystectomies performed at our institution. The indications were cholecystitis with severe fibrosis or inflammatory changes that prevented safe dissection in Calot's triangle in 11 patients and portal hypertension in seven patients (liver cirrhosis [two patients] and segmental portal hypertension caused by chronic pancreatitis [five patients]) to prevent massive blood loss from the gallbladder bed. The operation entails leaving the posterior wall of the gallbladder attached to the liver and securing the cystic duct at its origin from within the gallbladder with a purse string technique. The latter obviates the need for dangerous dissection in Calot's triangle. Control of bleeding from the remaining gallbladder edge is greatly facilitated by the use of a running suture after each stage of piecemeal excision of the gallbladder. All patients survived the operation and wound infection occurred in only two patients (11%). One patient required a laparotomy 1 month after surgery for adhesive small bowel obstruction related to the remaining gallbladder wall and site of a liver biopsy. No patients have so far developed postcholecystectomy symptoms (median follow-up 12.2 months; range 3 to 31 months). Subtotal cholecystectomy is a definitive operation that prevents recurrent gallstone formation, as no residual diseased gallbladder mucosa is left in continuity with the biliary system. It provides a simple, safe option in patients in whom cholecystectomy could be hazardous.

Aged↗

Extracorporeal shock-wave lithotripsy of gallbladder stones: an alternative for the selected few.

OBJECTIVE: To define selection criteria for optimal outcome of ESWL with oral litholysis (ursodeoxycholic acid) for gallbladder stones. DESIGN: Prospective study. SETTING: University hospital, Sweden. SUBJECTS: 145 patients with symptomatic gallbladder stones occupying a maximum of half the fasting gallbladder volume and gallbladder opacification at oral cholecystography. MAIN OUTCOME MEASURES: Three-year stone clearance rates in relation to initial stone burden, occurrence of calcified stones, and degree of gallbladder opacification at cholecystography. RESULTS: At all times clearance rates according to life table analysis were significantly higher for patients whose stone volume was < or = 4.2 ml (corresponding to one stone with a diameter of < or = 2.0 cm) (83% at 3 years) than for patients whose stone volume was > 4.2 ml (67% at 3 years), and patients with one stone had significantly higher clearance rates (88% at 3 years) than patients with multiple stones (58% at 3 years). Of all patients treated for gallbladder stones during one year, 25/194 (13%) had a stone volume of < or = 4.2 ml and 16/194 (8%) a solitary stone with volume < or = 4.2 ml. Neither the degree of gallbladder opacification nor the occurrence of calcified stones influenced clearance rates. CONCLUSION: ESWL may be an alternative to surgery in the few patients whose stone volume is roughly 4 ml or less and preferably have only one stone. Gallbladder function and patency of the cystic duct are poorly evaluated by oral cholecystography.

Adult↗

[Occult gallbladder disease or microlithiasis in patients with acute pancreatitis: a frequent clinical event].

BACKGROUND: Patients with acute pancreatitis (AP) and a normal gallbladder by standard echographic evaluation may have "occult" gallbladder disease or microlithiasis with recurrent episodes of AP. AIM: To conduct a prospective evaluation of patients with the diagnosis of non-biliary AP in order to detect "occult" gallbladder disease and to compare its clinical presentation with that of biliary AP. PATIENTS AND METHODS: Patients admitted with the diagnosis of AP to a clinical hospital were included in the study. According to an abdominal ultrasound study, patients were classified as having or not cholelithiasis. A duodenal biliary drainage was performed in 15 patients with AP and without gallbladder stones. RESULTS: Patients without cholelithiasis had recurrent AP more often than patients with biliary AP (53 and 3.3% respectively). Excessive alcohol ingestion did not rule out the possibility of biliary etiology. In 6 patients, the analysis of duodenal bile showed cholesterol crystals, and cholecystectomy confirmed the existence of gallbladder disease in 5. All of them remained asymptomatic during a follow-up period of four years. One patient refused surgery, with subsequent development of gallstones and recurrent episodes of AP. In other 4 patients, gallbladder disease was confirmed by percutaneous gallbladder puncture or during cholecystectomy. No recurrence of AP were observed during the follow-up CONCLUSIONS: Microlithiasis or "occult" gallbladder disease accounts for at least 67% of the original "non-biliary" AP. Duodenal bile analysis is a useful and necessary technique for the evaluation of patients with "non-biliary" acute pancreatitis. Careful clinical and echographic follow-up of this subgroup of patients with AP is mandatory.

Acute Disease↗

Significance of wall thickness in symptomatic gallbladder disease.

One hundred cases of patients who underwent urgent cholecystectomy after presenting with symptoms of acute or subacute gallbladder disease were retrospectively reviewed. Sixty patients had pathologically proved acute cholecystitis, and 40 had chronic cholecystitis alone. One patient had an incidental gallbladder carcinoma, and four had global gangrene of the gallbladder. Focal ischemia, transmural hemorrhage, or focal necrosis (indicating more severe disease) was present in 19 patients. Fifty-four percent of patients had thin-walled gallbladders. Among patients with more severe acute disease, 56% had thin walls. Conversely, 24% of thin-walled gallbladders and 22% of thick-walled gallbladders had evidence of focal necrosis or gangrene. We conclude that gallbladder wall thickness, although demonstrable on preoperative ultrasound examination in all patients, does not correlate directly with severity of disease or pathologic findings.

Acute Disease↗

In vitro and in vivo accuracy of sonographic gallbladder volume determinations.

To assess gallbladder function, sonographic gallbladder volume determinations have been used with increasing frequency. This study presents a modified and automated procedure for gallbladder volume determinations using Simpson's rule of integration, Simpson's method. This method is a standard option in the data systems of many sonographic instruments. Simpson's method was validated in vitro and in vivo, and it was compared with the sum-of-cylinders method for gallbladder volume determinations. In vitro assessment indicated that the two methods were equally accurate, with Simpson's method being more precise. The absolute deviation was independent of the size of the volume and of the shape of the gallbladder. In vivo Simpson's method was validated on 11 patients with cholecystitis. The gallbladder volumes (mean 65 mL; Range 20 mL to 130 mL) measured by sonography differed from the aspirated volumes by 1.5 mL (SD 10.4 mL). Thus Simpson's method is an accurate, precise, and fast method for sonographic gallbladder volume determination.

Animals↗

Micronutrients, antioxidants, and carcinoma of the gallbladder.

OBJECTIVES: Nutrient deficiency in developing countries can be considered a significant contributory factor modifying the multistage process of carcinogenesis. Studies from different parts of the world have shown the deficiency of various micronutrients to be significantly associated with cancer. This study was undertaken to test the above hypothesis in patients with carcinoma of the gallbladder. METHODS: Selenium (Se), zinc (Zn), copper (Cu), manganese (Mn), ascorbic acid (vitamin C), and alpha-tocopherol (vitamin E) were estimated in the serum, bile, and gallbladder tissue of 30 patients each of carcinoma of the gallbladder (group-I), cholelithiasis (group-II), and only in the serum of 30 age- and sex-matched healthy controls (group-III). The minerals were analyzed by atomic absorption spectrophotometer and vitamins by spectrophotometry. RESULTS: The mean serum levels of Se, Zn, Mn, vitamin E, and vitamin C were significantly lower (P < 0.001) in group-I when compared with groups II and III. The mean biliary levels of Se and Zn (0.29, 3.45 mg/L) were reduced significantly (P < 0.001) in group-I when compared with group II (0.51, 5.2 mg/L). Mean tissue levels of Se and Zn were also significantly lower (P < 0.001) in group I (2.75, 43.09 microg/g) compared to group II (3.90, 61.37 microg/g). However, no significant difference was observed in tissue concentration of Mn, vitamin C, and vitamin E. Cu levels and Cu/Zn ratio showed a highly significant (P < 0.001) increase in serum, bile, and gallbladder tissue in carcinoma of the gallbladder compared to the other two groups. CONCLUSIONS: The data supports an association between lower levels of Se, Zn, vitamin E, and risk of carcinoma of the gallbladder and suggest that Cu/Zn ratio could be a useful parameter in evaluating the patients of carcinoma of the gallbladder.

Antioxidants↗

Gallbladder pseudopolyp formation following percutaneous liver biopsy.

Following an unsuccessful liver biopsy in a 16-year-old girl in which only bile was obtained, a sonographic (US) study was performed. The findings were those of free fluid just adjacent to the gallbladder as well as a small intraluminal protrusion of the gallbladder wall. The US features of the gallbladder finding were consistent with a polyp. Gallbladder polyps are very rare in children, however, sporadic case reports do exist. An US study 24 h after the invasive procedure revealed complete regression of the free fluid; the gallbladder wall protrusion has disappeared. We suggest that the tip of the biopsy needle had penetrated the gallbladder wall and caused a bile leak. The needle penetration caused elevation of the inner wall layer at the entrance site, which was indistinguishable from the sonographic findings of a gallbladder polyp [1-4]

Adolescent↗

Gallbladder motility in systemic sclerosis.

In 20 patients with systemic sclerosis (SSc) and 24 healthy controls, gallbladder motility was evaluated by abdominal ultrasonography after stimulation by a standard liquid meal. Results from patients with normal and disturbed oesophageal function were analysed separately in order to investigate the significance of gallbladder motility as a parameter for gastrointestinal involvement in SSc. All patients showed a marked decrease in gallbladder size after stimulation (patients 61 +/- 13%; controls 48 +/- 12%). Patients with oesophageal dysfunction (n = 12) had a slightly lower gallbladder contraction (maximal decrease = 58 +/- 13%) when compared to patients with normal oesophageal function (n = 8; 66 +/- 13%); however, this difference was not statistically significant. Gallbladder motility in patients with SSc was not reduced when compared with healthy controls. SSc-induced oesophageal dysfunction was not associated with impaired gallbladder motility. Thus, measurement of gallbladder emptying is not a helpful tool when looking for gastrointestinal involvement in SSc.

Adolescent↗

Gallbladder motility, gallstones, and the surgeon.

Cholecystectomy is one of the commonest surgical procedures in the Western world, with more than half a million procedures performed annually in the United States alone. In recent years, studies of gallstone pathogenesis and gallbladder disease have increasingly focused on abnormal gallbladder motility in the pathogenesis of some, if not all, gallbladder conditions. The control of gallbladder motility is complex and depends on an intricate interplay of neural and hormonal factors. An understanding of the control of gallbladder motility is crucial to the understanding of the mechanisms of gallstone formation and may help to explain the failure to cure symptoms after cholecystectomy in up to one third of patients. The purpose of this article is to outline mechanisms controlling gallbladder motility, examine recent developments in our understanding of this complex process, and relate changes in motility to common disease conditions of the gallbladder. The role of altered motility in the pathogenesis of gallstones is discussed and the effects of commonly performed surgical procedures such as truncal vagotomy and cholecystectomy on upper gut physiology are reviewed.

Cholecystectomy↗

Floating gallbladder associated with histologically distinct double cancers.

A case of unusually hypermobile floating gallbladder in a 79-year-old woman with histologically distinct double cancers of the gallbladder is described. The patient presented with an abdominal cystic mass, which was palpable with easy mobility from the right lower quadrant practically to the left upper quadrant. Exploratory laparotomy was performed and the cystic mass was found to be a floating gallbladder. The cystic duct was elongated and obstructed, and had a long mesentery. After the operation, latent double cancers of the gallbladder were discovered on histopathological examination. The obstruction of the cystic duct was due to chronic inflammation and had resulted in hydrops of the gallbladder. This was suspected to have played an important role in the carcinogenesis. We believe that this is the first report of a floating gallbladder associated with double gallbladder cancers.

Adenocarcinoma↗

Gallbladder cancer associated with cholesterosis.

We report herein two cases of carcinoma in situ of the gallbladder associated with cholesterosis. The patient in case 1 was an 81-year-old man who underwent a cholecystectomy for cholelithiasis. The resected specimens revealed gallbladder cancer in the fundus which was diagnosed histologically as mucinous carcinoma. Other findings included 13-mm, 12-mm, and 5-mm polypoid lesions in the neck of the gallbladder which macroscopically appeared to be cholesterol polyps, but histologically demonstrated carcinoma in situ with cholesterosis. The patient in case 2 was a 76-year-old man in whom ultrasonography revealed a highly echogenic, elevated lesion in the gallbladder. Cholecystectomy was performed, and a 33 x 28-mm papillary, elevated lesion with cholesterosis was resected from the neck of the gallbladder. Histologically, this was demonstrated to be papillary adenocarcinoma in situ with cholesterosis surrounded by glandular dysplasia. The distribution of the carcinomas and cholesterosis in both of these patients suggests that the adenoma or carcinoma of the gallbladder had occurred first. Then, the tumor epithelium absorbed cholesterol from the bile, and foamy cells were produced. Thus, when treating cholesterol polyps, it should be remembered that it is often difficult to distinguish between cholesterol polyp and gallbladder cancer with cholesterosis.

Adenocarcinoma, Mucinous↗

Telomerase activity and Bcl-2 expression in gallbladders of pancreaticobiliary maljunction patients: a preliminary study.

BACKGROUND: The congenital anomaly pancreaticobiliary maljunction (PBM) is considered to be a precancerous disease. PBM carcinogenesis is believed to be an accumulation of gene abnormalities, but the early events causing PBM carcinogenesis are still unclear. In the present study, telomerase activity and Bcl-2 expression in the gallbladder mucosa of PBM and non-PBM gallbladders were investigated. METHODS: The operative gallbladder materials were from five control cases, two cases of non-PBM gallbladder cancer, three of PBM gallbladder cancer, and three of non-neoplastic PBMs. Multiple sampling was performed from each gallbladder. The studies performed were: (1) immunohistochemistry of p53, Ki-67, and Bcl-2; (2) survey of k-ras point mutations; and (3) measurement of telomerase activity in each sample. RESULTS: In the cases of non-PBM cancer, abnormalities from the above studies were detected only in the cancerous lesions. Normal-appearing mucosa did not show Bcl-2 expression or telomerase activity. However, in the cases of PBM cancer, normal-appearing mucosa showed telomerase activity and Bcl-2 expression, but did not show p53, Ki-67, or k-ras abnormalities. In the non-neoplastic PBM, all samples showed Bcl-2 expression, and many showed telomerase activity. CONCLUSIONS: Bcl-2 expression and activation of telomerase are probably early events causing carcinogenesis of the PBM gallbladder mucosa. They might be important factors causing carcinogenesis associated with chronic inflammation.

Gallbladder↗