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A selective approach to histopathology of the gallbladder is justifiable.

BACKGROUND: Recent changes in the NHS have led to a considerably increased workload for histopathologists prompting the publication of guidelines from the Royal College of Pathologists regarding specimen analysis. In most hospitals, cholecystectomy specimens are routinely sent for histology regardless of whether or not there is any visible macroscopic abnormality suggestive of malignancy. Our aim was to assess whether it would be safe to adopt a policy of processing only suspicious gallbladders without compromising patient management and outcome. METHODS: A retrospective analysis of all cholecystectomies performed between 1995 and 1999 was conducted using computerised histopathology records and patient notes. The histopathology department has a standardised procedure for the evaluation of cholecystectomy specimens and all gallbladders had been processed in this manner. RESULTS: 1308 patients had undergone cholecystectomy (mean 262/year). All specimens had been sent for histology: 1249 of the specimens showed chronic cholecystitis, 38 acute cholecystitis or empyema and 16 were removed as part of another procedure. In five gallbladders there was evidence of primary carcinoma. In all cases the gallbladder was opened at the time of surgery (as commented upon in the operation notes) and all showed macroscopic evidence suggestive of carcinoma. Pre-operative ultrasound scanning identified probable carcinoma in three of the five cases. CONCLUSIONS: All cases of gallbladder carcinoma were diagnosed pre-operatively or intra-operatively and a histological diagnosis did not alter the management or outcome of any of these patients. Selective histopathology of the gallbladder is safe and may be a more measured approach saving histolopathology departments time and money.

Aged↗

Factors affecting gallbladder motility: drugs.

Various drugs and medications that inhibit or stimulate gallbladder contraction and basal tone in humans are described. Active gallbladder contraction may be achieved using synthetic hormones such as cholecystokinin, caerulein and motilin, cholinomimetic drugs such as bethanecol, prostigmine, and erythromycin due to its motilin-like effect. Furthermore, cisapride and cholestyramine, may have some excitatory activity on the gallbladder muscle. Intravenous amino acids also induce gallbladder contraction through the release of cholecystokinin. Inhibition of gallbladder contraction induced by a meal, or reduction of the basal fasting tone may be achieved by using atropine and other cholinergics, and by inhibitory hormones such as somatostatin, the nitric acid releaser arginine, the calcium channel antagonist nifedipine, and progesterone. Other drugs such as trimebutine, loperamide and ondansetron may negatively affect gallbladder contraction.

Gallbladder↗

Value of measuring gallbladder motility in clinical practice.

Measurement of gallbladder motility is a powerful research tool, but its value in clinical practice is uncertain. Three main conditions have been investigated for potential clinical application of this measurement. The first potential application is for identification of patients at risk of recurrence following gallstone dissolution with medical therapy. Results in this clinical setting are disappointing due to the low positive predictive value for gallstone recurrence in sluggish gallbladder emptying. The second potential application is for identification of obese patients at risk of gallstone formation during rapid weight loss. In this condition, a high negative predictive value has been reported for a normal gallbladder emptying pattern. The third potential application is for patients with recurrent biliary colic and acalcolous gallbladder disease. The diagnostic value of a provocative test involving intravenous cholecystokinin injection as a method of identifying patients likely to benefit from cholecystectomy is uncertain, partly as a consequence of non-standardized methodology. The balance of evidence reported in this review suggests a low inherent value of measurement of gallbladder motility in clinical practice. Acalcolous gallbladder disease is the clinical setting deserving further investigation on the value of the cholecystokinin provocative test, but this test needs to be standardized.

Acalculous Cholecystitis↗

Electric field stimulation-induced guinea pig gallbladder contractions: role of calcium channels in acetylcholine release.

Gallbladder motility is modulated by intrinsic cholinergic neurons. The aims of this study were to determine: (1) the effect of electric field stimulation (EFS) on guinea pig gallbladder smooth muscle, and (2) the role of calcium channels in mediating neurotransmitter release. Gallbladder muscle strips were studied isometrically in vitro. EFS (1-16 Hz, 100 V, 0.5-msec pulse width, 30-sec train duration) was used to activate the intrinsic nerves. Exogenous acetylcholine was also used to directly stimulate the smooth muscle. EFS produced a frequency-dependent contractile response that was completely abolished by tetrodotoxin. EFS-induced contractions at 16 Hz were suppressed by 84 +/- 4% with atropine, whereas hexamethonium had no effect. The L-type calcium channel blocker, nifedipine, reduced EFS contractions by 51 +/- 4%, whereas it reduced contractions to acetylcholine by only 11 +/- 5%. The N-type calcium channel blocker, omega-conotoxin GVIA, reduced EFS-induced contractions by 22 +/- 9%, but did not affect acetylcholine-induced contractions. EFS-induced contractions of the guinea pig gallbladder are primarily mediated by activation of postganglionic cholinergic neurons. The acetylcholine release from these cholinergic neurons is regulated by L- and N-type calcium channels. The inhibitory effect of calcium channel blockers on the gallbladder seen in vivo may be in part related to inhibition of acetylcholine release from the intrinsic cholinergic nerves of the gallbladder.

Acetylcholine↗

Effect of nitric oxide on gallbladder motility in patients with acalculous biliary pain: a cholescintigraphic study.

The aim of the present study was to evaluate the influence of the exogenous nitric oxide donor glyceryl trinitrate on cerulein-induced gallbladder contraction in patients with acalculous biliary pain. Quantitative hepatobiliary scintigraphy was performed on 33 patients. From the 60th min cerulein (1 ng/kg body wt/min for 10 min intravenous) then from the 90th min the same dose of cerulein plus glyceryl trinitrate (0.5 mg sublingually) (21 patients) or placebo (12 patients) were administered and the gallbladder ejection fraction was measured repeatedly. After the first dose of caerulein, the gallbladder ejection fraction was less than 35% in 23 of 33 patients (nonresponders), while it was more than 35% in the remaining 10 patients (responders). After the second dose of cerulein in 16 nonresponder patients glyceryl trinitrate administration significantly increased the previously impaired gallbladder ejection fraction while in 7 nonresponder patients placebo administration had no effect. In conclusion, normalization of the gallbladder ejection fraction in the majority of patients following glyceryl trinitrate administration suggests that impairment of gallbladder emptying is caused by a functional motility disorder rather than any organic disease.

Biliary Dyskinesia↗

Impaired fatty-meal-stimulated gallbladder contractility in patients with Crohn's disease.

1. The incidence of gallstones in patients with Crohn's disease is increased compared with that in healthy control subjects. This is in part due to reduced terminal ileal bile salt absorption and consequent increased cholesterol saturation in bile. The aim of this study was to evaluate gallbladder contractility, a second important factor in the pathogenesis of gallstones, in Crohn's disease. 2. Thirty patients with Crohn's disease and no known biliary tract disease and nine healthy control subjects were studied. After an overnight fast, gallbladder volume was determined by real-time ultrasonography before and 10, 20, 30, 40, and 50 min after ingestion of a standard liquid fatty meal. 3. Compared with healthy control subjects, patients with Crohn's disease had similar fasting gallbladder volumes (control, 18.7 +/- 2.3 ml; Crohn's disease, 18.2 +/- 2.3 ml). Percentage emptying was significantly impaired at 30, 40 and 50 min in patients with Crohn's disease compared with control subjects. Patients with Crohn's disease limited to the small bowel had gallbladder contractility that was comparable with that of control subjects, whereas in those with large-bowel disease, minimum residual gallbladder volume was significantly smaller than in control subjects. Patients with both large- and small-bowel Crohn's disease demonstrated the most marked abnormalities, with gallbladder volumes significantly larger than those of control subjects at 30, 40 and 50 min. Likewise, patients with Crohn's disease who had undergone previous bowel resection had impaired emptying at 30, 40 and 50 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Sonographic studies of gallbladder kinetics in childhood--a comparison between healthy and mucoviscidosis patients].

In mucoviscidosis, the gallbladder can show signs of disease even in childhood. In 10 of 35 mucoviscidosis patients the authors found thickening of the walls, gallstones and micro-gallbladders on sonographic examination. Compared with healthy children (N = 70), the mucoviscidosis patients showed impairment of the kinetics of the gallbladder to an increasing extent in step with progressing age. X-ray films of the gallbladder were preferably taken while using a preparation containing bile acids for better absorption of the contrast medium. When using this preparation, the gallbladder was found to yield good contrast more frequently than with double-dose cholecystography recommended in literature. However, oral cholecystography yielded additional information in one case only where sonography had failed to produce a clear sonographic image of the gallbladder.

Adolescent↗

Effects of pregnancy and contraceptive steroids on gallbladder function.

We used real-time ultrasonography to study gallbladder kinetics in 11 nonpregnant women, 17 women using steroid contraceptives, and 33 pregnant women. Gallbladder volume was determined after an overnight fast and serially for 90 minutes after a standard liquid meal. After the first trimester of pregnancy, gallbladder volume during fasting and residual volume after contraction were twice as large as in control subjects. The rate of emptying and the percentage emptied were reduced. In early pregnancy the only important abnormality was a 30 per cent decrease in emptying rate. Gallbladder function was not affected by contraceptive steroids. Incomplete empyting of the gallbladder in late pregnancy leaves a large residual volume and may cause retention of cholesterol crystals, a prerequisite for cholesterol-gallstone formation. These findings are consistent with the view that pregnancy increases the risk of cholesterol gallstones. The increased incidence of gallstones associated with contraceptive steroids does not involve abnormal gallbladder kinetics.

Bile↗

Trocar site seeding of inapparent gallbladder carcinoma during laparoscopic cholecystectomy.

There are increasing reports of seeding of tumor at the trocar sites following laparoscopic cholecystectomy in patients with unexpected or inapparent gallbladder carcinoma. A patient is reported here whose primary tumor appeared controlled by surgery and radiation, but who died of the disease after developing implant metastases at three untreated trocar sites. The second case report illustrates the difficulty in identifying gallbladder cancer during laparoscopic cholecystectomy, and the importance of a diligent preoperative effort to establish the diagnosis. Current literature suggests that tumor implantation occurring during laparoscopic cholecystectomy for inapparent carcinoma adversely affects prognosis, and, until the effect of laparoscopy on the spread of this tumor is better understood and controlled, open operation should be performed when carcinoma of the gallbladder is suspected. When laparoscopic cholecystectomy is done for inapparent gallbladder cancer, surgical and adjuvant radiotherapy to the trocar sites appears to improve outcome in association with extended treatment to the gallbladder bed and adjacent areas. Recent reports suggest that progress in diagnostic, surgical, and adjuvant techniques could substantially improve survival in carcinoma of the gallbladder.

Adenocarcinoma↗

Minute squamous cell carcinoma of the gallbladder: a case report.

Following a simple cholecystectomy, a 63-year-old woman with gallstones was histologically diagnosed as having minute squamous cell carcinoma of the gallbladder. A laparotomy revealed a small, firm nodule that appeared to be an adenoma, which was palpated in the fundus of the gallbladder. The resected gallbladder contained 37 small stones and a small and firm mass (0.4 x 0.4 x 0.3 cm in size) on the mucosal side. Histologically, a pure type of well-differentiated squamous cell carcinoma of the gallbladder was diagnosed. To our knowledge, this is the first case of a minute and pure type of squamous cell carcinoma in the gallbladder. This case may have implications for the histogenesis of squamous cell carcinoma of the gallbladder.

Adenoma↗

99mTc-PIPIDA cholescintigraphy in the diagnosis of gallbladder disease.

The efficacy of 99mTc cholescintigraphy in the diagnosis of gallbladder disease was studied in 116 patients. Sixty-one demonstrated gallbladder visualization (normal) and 55 had nonvisualization. In patients with acute abdominal pain, test sensitivity is 100%, specificity is 77%, and accuracy is 83% for the diagnosis of acute cholecystitis; no patient with gallbladder visualization had acute cholecystitis. Test sensitivity for any form of gallbladder disease is 66%, specificity is 82%, and accuracy is 71%; excluding patients with laboratory evidence of hepatobiliary disease, the predictability of acute or chronic cholecystitis increases to 100%. Cholescintigraphy demonstrated common bile duct patency in all eight post-cholecystectomy patients referred for evaluation of possible choledocholithiasis. Thus, gallbladder visualization with 99mTc-PIPIDA virtually excludes the diagnosis of acute cholecystitis, an abnormal test is a good predictor of gallbladder disease because of high specificity, and cholescintigraphy is extremely safe and simple to perform and may be used to demonstrate common bile duct patency.

Acute Disease↗

Cholecystokinin cholecystography in the diagnosis of gallbladder disease.

Twenty-six patients who had typical symptoms of biliary tract disease, e.g. postprandial right upper quadrant pain, nausea and vomiting, fatty food intolerance and flatulence and who had had two or more normal oral cholecystograms were subjected to cholecytokinin cholescystography. Ten patients showed a normal response to the intravenous administration of cholecystokinin, namely prompt and complete emptying of the gallbladder without producing any adverse reaction or symptoms. Sixteen patients demonstrated either no contraction or incomplete contraction of the gallbladder in response to cholecystokinin; several patients had moderate contraction of the gallbladder accompanied by symptoms of biliary colic. This latter group underwent cholecystectomy and operative cholangiography. Fifteen of the 16 patients are asymptomatic or improved, and only one patient continues to have symptoms. All removed gallbladders had histologic evidence of chronic cholecystitis. It is concluded that in some individuals with continuing symptoms suggesting gallbladder disease but normal oral cholecystograms, cholecystokinin cholecystography may be helpful in identifying physiologic dysfunction of the gallbladder.

Adult↗

Computed tomography of the gallbladder: unusual diseases.

Abdominal CT has in many cases become the initial radiographic examination to elucidate the cause of obscure abdominal pain, fever of unknown origin, and other difficult diagnostic abdominal problems. Not infrequently, unsuspected disease involving the gallbladder may be encountered. Computed tomography commonly identifies calcified gallstones, occasionally indicates acute cholecystitis, and clearly determines the extent of gallbladder carcinoma. Other less common entities such as gallbladder perforation, porcelain gallbladder, and milk of calcium bile may be diagnosed if suspicion is high and attention directed to anatomic details of the gallbladder and adjacent organs. A review of abdominal CT performed during a 4.5 year period revealed 20 instances of unusual gallbladder diseases in 16 patients. Most often these were encountered incidentally or during CT evaluation of nonspecific abdominal problems.

Bile↗

Immunohistochemical and genetic analysis of non-small cell and small cell gallbladder carcinoma and their precursor lesions.

Gallbladder carcinomas can be highly lethal neoplasms. Relatively little is known about the genetic abnormalities that underlie these tumors, particularly with respect to their timing in neoplastic progression. The authors evaluated 5 noninvasive dysplasias and 33 invasive gallbladder carcinomas (6 small cell carcinomas, 27 non-small cell carcinomas, of which 16 were accompanied by an in situ carcinoma component) for expression of the protein products of the p16, p53, Dpc4, and pRB tumor suppressor genes by immunohistochemistry. Neoplasms were also evaluated for the presence of activating K-ras oncogene mutations. Seventy-five percent of non-small cell gallbladder carcinomas demonstrated loss of p16 expression, whereas 63% accumulated high levels of p53. Loss of Dpc4 and pRB expression was less frequent, seen in 19% and 4% of the neoplasms, respectively. Thirty percent of neoplasms harbored activating K-ras mutations. In contrast, 100% of the small cell carcinomas of the gallbladder demonstrated inactivation of the pRB/p16 pathway; 67% showed loss of pRB expression, and the other 33% lost p16 expression. Eighty-three percent of small cell carcinomas accumulated high levels of p53, whereas loss of Dpc4 expression and activating K-ras mutations were not found. Among 15 evaluable in situ components, 13 harbored the same alterations found in the invasive component. Inactivation of p16 and p53 occur in the majority of non-small cell gallbladder carcinomas. Dpc4 inactivation and K-ras mutations occur in a significant minority of cases. pRB loss is uncommon in non-small cell gallbladder carcinoma, but virtually all small cell carcinomas inactivate the p16/pRB pathway, usually by retinoblastoma protein loss. It is noteworthy that all of these alterations occur at the level of carcinoma in situ.

Adult↗

Segmentation of the gallbladder: effect on bile entry and exit and its clinical relevance in a patient with abdominal pain.

BACKGROUND: The effects of folds or septa on gallbladder filling and emptying are not known. METHODS: Gallbladder filling and emptying were measured in seven patients with two chambers (segmental) and compared with 10 subjects with a single chamber (control). Percent bile flow into gallbladder, and percent ejection fraction from the proximal and distal segments, and entire gallbladder were measured with cholecystokinin. RESULTS: Bile entry into gallbladder was similar in both groups. In patients with segmentation, overall emptying was low mostly due to poor emptying of the distal segment. CONCLUSION: Segmentation of the gallbladder does not affect bile entry, but acting as a one-way valve, a fold or septum lowers emptying significantly, mostly from the distal segment.

Abdominal Pain↗

Gallbladder carcinoma: radiologic-pathologic correlation.

Primary carcinoma of the gallbladder is an uncommon, aggressive malignancy that affects women more frequently than men. Older age groups are most often affected, and coexisting gallstones are present in the vast majority of cases. The symptoms at presentation are vague and are most often related to adjacent organ invasion. Therefore, despite advances in cross-sectional imaging, early-stage tumors are not often encountered. Imaging studies may reveal a mass replacing the normal gallbladder, diffuse or focal thickening of the gallbladder wall, or a polypoid mass within the gallbladder lumen. Adjacent organ invasion, most commonly involving the liver, is typically present at diagnosis, as is biliary obstruction. Periportal and peripancreatic lymphadenopathy, hematogenous metastases, and peritoneal metastases may also be seen. The vast majority of gallbladder carcinomas are adenocarcinomas. Because most patients present with advanced disease, the prognosis is poor, with a reported 5-year survival rate of less than 5% in most large series. The radiologic differential diagnosis includes the more frequently encountered inflammatory conditions of the gallbladder, xanthogranulomatous cholecystitis, adenomyomatosis, other hepatobiliary malignancies, and metastatic disease.

Diagnosis, Differential↗

Gray-scale ultrasonography as a screening procedure in the detection of gallbladder disease.

The sonographic and surgical findings in 180 patients who underwent cholecystectomy for gallbladder disease were reviewed and correlated. Four abnormal groups were established. In Group I, the gallbladder was visible and contained structures which cast an acoustic shadow. In Group II, there was constant shadowing in the region of the gallbladder fossa, but the gallbladder itself was not visible. In Group III, there was a constant, immobile, echo-dense, nonshadowing area in the gallbladder wall. In Group IV, nonshadowing echoes were seen within the gallbladder lumen. The overall accuracy of ultrasound was 98.9%; the false-negative rate was 2.2%, the false-positive rate 2.8%. 5.6% of Group I patients had normal oral cholecystograms. Because of its high accuracy, minimal preparation, speed of diagnosis, and cost-effectiveness, the authors recommend that ultrasonic cholecystography be considered as a screening method, particularly for small polyps (< 4 mm).

Cholelithiasis↗

Gallbladder disease: appearance of associated transient increased attenuation in the liver at biphasic, contrast-enhanced dynamic CT.

PURPOSE: To evaluate the frequency, location, and appearance of transient increased attenuation in the liver during arterial-phase helical or incremental computed tomography (CT) in patients with gallbladder disease without hepatic extension. MATERIALS AND METHODS: Findings in dynamic CT examinations in 31 patients with surgically proved gallbladder disease not extending into the liver and in 31 control patients without gallbladder disease were retrospectively reviewed and correlated with findings in other imaging examinations. RESULTS: Areas of transient increased hepatic attenuation (n = 27) were identified in 22 of 31 patients with gallbladder disease and in only one of 31 control patients. The difference in these findings was statistically significant (P < .001). In the 27 areas of transient increased hepatic attenuation, these findings were categorized as curvilinear or nodular attenuation adjacent to the gallbladder fossa in 13 (48%), segmental or subsegmental attenuation in segment IV and/or V in seven (26%), lobar attenuation in the left lobe (segments II-IV) in four (15%), and nodular attenuation seen as an early enhancing "pseudolesion" in segment IV in three (11%). Hepatic angiography performed in 10 of the 22 patients showed early depiction of the dilated cystic vein (n = 8) and direct communication with the portal branches (n = 2). CONCLUSION: Transient increased attenuation in the liver had a variable appearance at dynamic arterial-phase CT in most patients with gallbladder disease. This attenuation was most likely due to increased blood flow from the hepatobiliary system.

Adult↗