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Real-time sonography for screening of gallbladder dysfunction in children with type 1 diabetes mellitus.

The aim of this study was to evaluate the occurrence of gallbladder dysfunction in children with type 1 diabetes mellitus using real-time ultrasonography. The study population consisted of 20 diabetic children (11 male, 9 female; age 11.7+/-2.8 years; diabetes duration 0.5-7 years) with clinically negative neuropathy findings and 15 healthy controls (11 male, 4 female; age 10.5+/-3.7 years). Three-dimensional measurements of the gallbladder were made before and 15, 30, 45, 60 min after intake of diet chocolate. Gallbladder volumes were calculated by the ellipsoid formula. Fasting gallbladder volume of diabetic children (16.9+/-9.5 ml) was significantly greater than that of the controls (10.6+/-5.3 ml; p=0.017). Ejection fraction and maximal contraction showed no significant difference between the two groups. Diabetic patients with multiple microvascular complications had diminished gallbladder motility. There was a negative correlation between BMI and maximal contraction (p<0.05). Nerve conduction velocity was diminished in 45% of the diabetic patients. In conclusion, gallbladder function is preserved in pediatric type 1 diabetic patients with a disease duration less then 10 years, but dilated gallbladder at rest may be an early sign of gastrointestinal autonomic neuropathy and a risk factor for gallstone formation.

Adolescent↗

Gallbladder contractility and volume characteristics in gallstone dyspepsia.

AIM: It is difficult to differentiate gallstone dyspepsia and functional dyspepsia by clinical symptoms and signs. We hypothesized that gallstone dyspepsia was related to abnormal gallbladder motility. We aimed to differentiate gallstone dyspepsia from functional dyspepsia by measuring gallbladder motility. METHODS: We measured gallbladder volume changes in response to gastric distension (saline 500 mL) and fatty meal in 10 normal volunteers (controls) and 62 patients with gallstones and dyspepsia before cholecystectomy. Forty cholecystectomized patients were symptom free or had improvement (group I), while the remaining 22 patients had persistent dyspepsia (group II). Gallbladder volume change and ejection fraction were analyzed and compared among the three groups. RESULTS: In group I, there were significant decreases in gallbladder volumes 5-25 min after gastric distension, compared to fasting volumes. Compared to normal volunteers and group II, group I had significantly decreased gallbladder volumes 10-20 min after drinking 500 mL of normal saline and 10 to 50 min after eating fatty meal. CONCLUSION: Our results support the hypothesis that increased gallbladder contraction after gastric distension or fatty meal may be related to dyspeptic symptoms in uncomplicated gallstone disease. These findings may be useful in differentiating functional dyspepsia from gallstone dyspepsia, patients with the latter disease may benefit from laparoscopic cholecystectomy.

Adult↗

Diagnosis and treatment of gallbladder perforation.

AIM: To present our clinical experience with gallbladder perforation cases. METHODS: Records of 332 patients who received medical and/or surgical treatment with the diagnosis of acute cholecystitis in our clinic between 1997 and 2006 were reviewed retrospectively. Sixteen (4.8%) of those patients had gallbladder perforation. The parameters including age, gender, time from the onset of symptoms to the time of surgery, diagnostic procedures, surgical treatment, morbidity, and mortality were evaluated. RESULTS: Seven patients had type I gallbladder perforation, 7 type II gallbladder perforation, and 2 type III gallbladder perforation according to Niemeier's classification. The patients underwent surgery after administration of intravenous electrolyte solutions, and were treated with analgesics and antibiotics within the first 36 h (mean 9 h) after admission. Two patients died of sepsis and multiple organ failure in the early postoperative period. Subhepatic abscess, pelvic abscess, pneumonia, pancreatitis, and acute renal failure were found in 6 patients. CONCLUSION: Early diagnosis and emergency surgical treatment of gallbladder perforation are of crucial importance. Upper abdominal computerized tomography for acute cholecystitis patients may contribute to the preoperative diagnosis of gallbladder perforation.

Aged↗

Gallbladder cancer in a high risk area: morphological features and spread patterns.

BACKGROUND/AIMS: Gallbladder carcinoma is one of the most frequent malignant tumors in Chile. The aim of this paper is to show our experiences in gallbladder carcinoma. METHODOLOGY: Six-hundred-sixty-nine cases of gallbladder carcinoma were included in this prospective study; 557 females (83.5%) and 112 males (16.5%). In 466 cases (70%), diagnosis was carried out in the cholecystectomy sample, 45 cases were partial cholecystectomies and 158 cases were metastases of gallbladder carcinoma. RESULTS: Ninety-eight per cent of the cases were adenocarcinomas, and in 85% of the cases gallstones were observed. Thirty-seven per cent of the primary tumors were macroscopically inapparent. One-hundred-thirty-one cases (29%) were early carcinomas and 323 cases (71%) were advanced carcinomas. A relationship between differentiation grade and infiltration level (p=0.0001) was observed. Lymph-node metastasis was found in 18.5%, 4.5% and 3.3% in the first, second and third lymph-node barriers respectively. Muscular tumors presented no lymph-node metastasis, while in serosal tumors lymph node metastasis reached 62% (p=0.04). Hepatic tumor infiltration was observed in 11%, 19% and 38% of muscular, subserosal and serosal tumors. CONCLUSIONS: The high frequency of inapparent carcinomas, gallstones and inflammatory changes of the vesicular wall are elements that make the pre-operative diagnosis of gallbladder carcinoma difficult. Differentiation grade and infiltration level are the most reliable prognostic factors in gallbladder carcinoma. Lymph-node metastasis or liver tumor infiltration are infrequent in early gallbladder carcinoma.

Adenocarcinoma↗

Expression of the GLUT1 glucose transporter in gallbladder carcinomas.

BACKGROUND/AIMS: It has previously been shown that glucose uptake and use is more prevalent in carcinomas than in normal cells and tissues. We hypothesized that human erythrocyte glucose transporter-1 expression is increased in gallbladder carcinoma and might be correlated with prognostic significance. METHODOLOGY: A total of 71 cases of gallbladder carcinomas, 2 cases of gallbladder dysplasia and 20 cases of gallbladder adenomas were examined immunohistochemically to evaluate the expression of glucose transporter-1 protein in the light of their relationship with various prognostic factors. RESULTS: Glucose transporter-1 was stained in the cell membrane of the cancer cells. Adjacent normal mucosa was negative for glucose transporter-1 staining. Thirty-seven gallbladder carcinomas (52.1%) showed positive staining for glucose transporter-1, however only one of the adenomas (5.0%) and none of the dysplasias were positive (P < 0.05). There was significant correlation between glucose transporter-1 expression and histologic tumor type, and tumor stage. In the multivariate analysis, tumor stage was statistically significant (P = 0.05), but glucose transporter-1 expression was not significant (P = 0.07). The mean survival periods of the glucose transporter-1 positive and negative groups were 24 months and 58 months, respectively (P = 0.003). CONCLUSIONS: Our results suggest that glucose transporter-1 protein expression is strongly associated with neoplastic progression in gallbladder carcinomas, and that glucose transporter-1 expression identifies with a worse prognosis in the patients with gallbladder carcinomas.

Adenocarcinoma↗

Gallbladder polyps, cholesterolosis, adenomyomatosis, and acute acalculous cholecystitis.

Acute acalculous cholecystitis is characterized by acute inflammation of the gallbladder in the absence of stones, usually occurring in elderly and critically ill patients with atherosclerosis, recent surgery or trauma, or hemodynamic instability. Patients may present with only unexplained fever, leukocytosis, and hyperamylasemia without right upper quadrant tenderness. If untreated, rapid progression to gangrene and perforation occurs. Surgical cholecystectomy and cholecystostomy provide the most definitive treatment although recent studies indicate success with percutaneous or endoscopic cholecystostomy. Cholesterolosis and adenomyomatosis of the gallbladder are usually clinically silent and incidental findings at the time of cholecystectomy. Cholesterolosis is characterized by mucosal villous hyperplasia with excessive accumulation of cholesterol esters within epithelial macrophages. Usually clinically silent, the condition rarely is associated with biliary symptoms or idiopathic pancreatitis and cannot reliably be detected by ultrasonography. Adenomyomatosis describes an acquired, hyperplastic lesion of the gallbladder characterized by excessive proliferation of surface epithelium with invaginations into a thickened muscularis propria. Ultrasonography may reveal a thickened gallbladder wall with intramural diverticula. Adenomyomatosis may portend a higher risk of gallbladder malignancy. Most cases of cholesterolosis and adenomyomatosis identified by imaging require no specific treatment. Gallbladder polyps include all mucosal projections into the gallbladder lumen and include cholesterol polyps, adenomyomas, inflammatory polyps, adenomas, and other miscellaneous polyps. Most polyps are nonneoplastic and rarely cause symptoms. Cholecystectomy is advocated for polyps greater than 10 mm in size because of increased risk of adenomatous or carcinomatous features.

Acalculous Cholecystitis↗

[A study of the dynamics of gallbladder contraction in irritable bowel syndrome].

We examined gallbladder motility function after intramuscular injection of caerulein (0.2 micrograms/kg) to the cases of irritable bowel syndrome (IBS) by using ultrasonography. We measured gallbladder area pre and after caerulein injection (0' 5' 10' 15' 20' 25' 30' 40' 50' 60') and calculated contraction rate of gallbladder in each time. We applied one way analysis of variance among the four groups [diarrhea group (N = 9), alternative group (N = 8), constipation group (N = 8), control group (N = 15)]. Gallbladder contraction rate was low in diarrhea group and high in constipation group (p less than 0.05). And then we classified gallbladder contraction pattern to three groups (hyperkinetic, intermediate, hypokinetic). These three groups correlated bowel habits and biliary knocked pain. Therefore, constipation group showed hyperkinetic tendency and diarrhea group showed hypokinetic tendency (chi 2 analysis: p = 0.004 CMH analysis: p = 0.001). And biliary knocked pain significantly appeared in constipation group and hyperkinetic type of gallbladder (chi 2 analysis: p = 0.026, CMH analysis: p = 0.019). Consequently, it was suggested that bowel habits concerned with abnormality of gallbladder motility function in IBS.

Adolescent↗

Congenital duplication of the gallbladder.

Duplication of the gallbladder is a rare congenital anomaly of the biliary system. In this article, two cases of gallbladder duplication are presented. The first case is a patient with double gallbladder and concomitant choledocholithiasis. The probable diagnosis of double gallbladder was made preoperatively by computed tomography. The patient underwent a successful open cholecystectomy and common bile duct exploration. In the second case, two cystic formations in the place of gallbladder are demonstrated with ultrasound scan in a woman with acute cholecystitis. At surgery, two gallbladders were found. A brief review of epidemiology and anatomy of double gallbladder is included, along with a discussion of the difficulties in diagnosis and treatment of this condition.

Aged↗

Ultrasonography of the gallbladder in patients with a clinical suspicion of acute cholecystitis.

The prevalence of ultrasonographic (US) signs described in the literature in cases of acute cholecystitis (wall thickening, increased volume, roundness and local tenderness of the gallbladder, an anechoic layer in the gallbladder wall and cholelithiasis were studied in 136 consecutive patients referred for US examination with clinically suspected acute cholecystitis (AC). Of the patients, 56 had AC, 21 chronic cholecystitis, 2 carcinoma of the gallbladder, and 57 extrabiliary diseases. In AC, frequent findings in addition to cholelithiasis were wall thickening (79%) and an increased volume (64%). Almost one third of the patients had local tenderness (sonographic Murphy sign) (29%), and 27% of the gallbladders had a rounded form. All these features were, however, rather frequently detected also in chronic cholecystitis (5-33%) and in the 2 carcinoma patients, and also sporadically in extrabiliary diseases. A anechoic layer in the gallbladder wall was the only sign confined to AC, but was detected only in 2 cases. Roundness of the gallbladder occurred only in either acute or chronic cholecystitis. The combination of at least two diagnostic findings was noticed in 91% in AC, rather frequently in chronic cholecystitis (43%) and in both carcinoma patients, but only in 1 patient in the extrabiliary disease group. Three or more signs were seen only in gallbladder diseases (48%), but AC, chronic cholecystitis or carcinoma groups could not be completely differentiated (prevalences 63, 10 and 50%).

Acute Disease↗

Differential gallbladder contractility in fundal adenomyomatosis: demonstration by cholecystokinin cholescintigraphy.

The cholecystokinin cholescintigraphic findings of fundal adenomyomatosis in a 29-yr-old male with severe post-prandial pain are presented. Planar cholescintigraphy demonstrated a trilobed gallbladder contour. Following the administration of 0.02 micrograms/kg of cholecystokinin at maximal gallbladder filling, fundal dyskinesia was observed. Regional gallbladder ejection fractions were: whole gallbladder, 43%; proximal two-thirds of the gallbladder, 70%; and gallbladder fundus, 32%. First harmonic Fourier phase and amplitude images demonstrated: (a) decreased fundal amplitude values, and (b) a phase shift of the pixels in the gallbladder fundus.

Adult↗

[Gallbladder motility following intake of mineral bicarbonate-alkaline water. Ultrasonographic assessment].

Sonographic measurement of gallbladder volume has allowed us to assay the influence of many substances (hormones, drugs, etc.) on gallbladder kinetics playing a pivotal role in digestive mechanisms. The aim of the present study has been to evaluate the effect of an alkaline bicarbonate water (Donata) on gallbladder emptying. The study was performed in cross-over. Ten healthy volunteers randomly assumed alkaline bicarbonate water or saline (400 ml). Gallbladder volumes were measured by ultrasonography, according to ellipsoid method, before and 15', 30', 45', 60', 90', 120' after water or saline intake. A week later the test was repeated. Gallbladder kinetics was evaluated referring to fasting volume, residual volume, absolute emptying and maximum percent emptied. Student's "t" test for paired data was used for statistical evaluation of the results. Gallbladder volumes were significantly reduced 15', 30', 45' and 60' after alkaline bicarbonate water administration, whereas saline did not induced gallbladder emptying. The present results suggest that Donata water may be employed in order to ameliorate dyspepsia due to biliary dyskinesia, moreover it may play a complementary role in the prevention and in the medical treatment of biliary lithiasis.

Adult↗

[Study on CCK-induced gallbladder emptying with real-time ultrasonography].

In the present study, we adopted real-time ultrasonography to investigate the effect of atropine on the gallbladder emptying induced by CCK-OP in the normal subjects, and the difference of gallbladder emptying induced by CCK-OP between the "silent" gallstone patients and the controls. The results showed that: (a) CCK-induced gallbladder emptying in normal subjects was inhibited from 88.7% +/- 5.5% without atropine to 43.4% +/- 9.4% with atropine (P < 0.001). (b) The fasting gallbladder volume in the "silent" gallstone patients (26.7 +/- 10.9cm3) was significantly larger than that in the control (19.2 +/- 7.3cm3) (P < 0.05) and gallbladder emptying in the "silent" gallstones patients (44.0% +/- 8.7%) was significantly lower than that in the control (53.4% +/- 6.4%) (P < 0.01). We concluded that, significantly inhibited CCK-induced gallbladder emptying and there was significantly impaired gallbladder emptying in the patients with gallstones.

Adult↗

Gallbladder motility in diabetes mellitus using real time ultrasonography.

OBJECTIVES: Diabetes mellitus is one of the risk factors in cholesterol gallstones. Individuals with diabetes mellitus are reported to have a 2-fold to 3-fold increase in the incidence of cholesterol gallstones. Though the pathophysiologic mechanisms of this phenomenon are unclear, hypotheses such as reduced gallbladder motility were presented to explain the higher incidence of gallstones in diabetes. METHODS: We compared the gallbladder volume and ejection fraction of 24 diabetics with those of 19 age-matched and weight-matched controls using real-time ultrasonography. Blood sampling for biochemical study of all the subjects were performed. RESULTS: No significant differences in any physiochemical parameters between the diabetic group and control group could be found. Fasting gallbladder volume increased significantly in the diabetic group (21.90 +/- 9.53 cm3) compared with the control group (16.99 +/- 5.97 cm3). Gallbladder volume measured after a fatty meal were greater in the diabetic group (10.76 +/- 7.19 cm3) than in the control group (4.22 +/- 3.31 cm3) (p < 0.04). When the diabetic group was divided according to the presence or absence of autonomic neuropathy, a significant reduction of ejection fraction was found in diabetics with autonomic neuropathy (42.75 +/- 19.37%) in comparison with diabetics without autonomic neuropathy (61.75 +/- 17.63%) (p < 0.02). CONCLUSIONS: Gallbladder volume in diabetics was significantly greater compared with that of the control. Moreover, in diabetics with autonomic neuropathy, gallbladder motility was markedly reduced in comparison to diabetics without autonomic neuropathy. Thus, we suggest that impairment of gallbladder motility complicated with autonomic neuropathy causes stasis and results in cholesterol gallstone crystal formation and gallstone growth.

Autonomic Nervous System Diseases↗

Changes in gallbladder volume do not affect cystic duct resistance.

To our knowledge, the relationship between gallbladder volume and cystic duct function has not been studied. We hypothesized that changes in gallbladder volume would influence cystic duct resistance. The effect of gallbladder volume changes on cystic duct resistance to both prograde (emptying) and retrograde (filling) steady-state flow was tested in 12 dogs under basal cholecystokinin-stimulated conditions utilizing a multiport catheter with a highly compliant balloon placed within the gallbladder fundus. Gallbladder volume was regulated by varying balloon volume from empty to just beyond physiologic distention. Cystic duct resistance was not affected by balloon volume under basal or stimulated conditions or by the direction of perfusate flow. This study demonstrated no relationship between gallbladder volume and cystic duct resistance and did not demonstrate a cystic duct sphincter mechanism at physiologic gallbladder volumes.

Animals↗

Carcinoma of the gallbladder. A clinicopathology of 103 patients and a newly proposed staging.

Tissue samples from 103 patients with gallbladder carcinoma were examined, using 5-mm stepwise tissue sections. Three pathologic stages were used: Stage I; carcinoma invading not further than the muscle coat of the gallbladder, with or without extension along Rokitansky-Aschoff sinuses in the subserosa (11 cases); Stage II, carcinoma extending to the subserosal fibroadipose tissue of the gallbladder (73 cases); and Stage III: carcinoma invading the adjacent organs such as the duodenum, liver, and colon (19 cases). In the 11 patients with Stage I carcinoma, there was no apparent lymph node metastasis and all remained well for 3 months to 14 years after the initial operation. The cumulative 3-year survival rate of Stage I (100%) was significantly higher than of Stage II (40%) and Stage III (10%) (P less than 0.01, P less than 0.001). The Stage I tumors, therefore, can be defined as early carcinoma of the gallbladder. Dysplastic epithelium was seen in the mucosa adjacent to the malignant lesion in 57% of those with gallbladder carcinoma: 73% in Stage I, 59% in Stage II, and 42% in Stage III. Nine gallbladders had multiple foci of adenocarcinoma in a background of a diffuse dysplasia. Immunohistochemical study for carcinoembryonic antigen and carbohydrate antigen 19-9 resulted in positive staining of the dysplastic epithelial element adjacent to the invasive carcinoma and, in a similar fashion, in the carcinoma itself, thereby indicating a close relation between the epithelial dysplasia and adenocarcinoma of the gallbladder.

Adenocarcinoma↗

Clinicopathologic study of asymptomatic gallbladder carcinoma found at autopsy.

Of 3000 autopsy cases, consisting primarily of older patients, asymptomatic gallbladder carcinomas were found in 15 (0.5%); the incidence among all gallbladder carcinomas (80 cases) was 18.8%. In contrast to symptomatic gallbladder carcinomas, all of which were classified as Stage III (9.3%) or Stage IV (90.7%) disease, 80.0% of asymptomatic cases were classified as Stage 0 (13.3%), I (20.0%), or II (46.7%). Histologically, all the symptomatic cases of gallbladder carcinoma had invasion to the serosal or subserosal layer of the gallbladder as well as to the hepatoduodenal ligament. Lymphatic and hematogenous metastases of the symptomatic carcinomas were found in 94.4% and 64.8%, respectively. On the other hand, the carcinoma in the asymptomatic group was retained in the mucosal layer (M) in four cases, in the muscular layer (MUS) in one case, in the subserosal layer (SS) in nine cases (INF beta in seven cases and INF r in two in the mode of infiltration), and in the serosa (SE) in one case. However, cancerous invasion to the hepatoduodenal ligament or lymphatic metastasis was found in only two cases, whereas hematogenous metastasis was not found in any of them. Cancerous extension beyond the gallbladder wall was apparently rare in the cases of SS invasion, as well as in those of M or MUS invasion. It was suggested that, for radical resection of gallbladder carcinoma, it is very important to find it in an asymptomatic stage.

Adenocarcinoma↗

Elevated serum alpha-fetoprotein levels in primary gallbladder carcinoma without hepatic involvement.

BACKGROUND: Elevated serum alpha-fetoprotein (AFP) levels, although frequently associated with hepatocellular carcinoma, have also been reported in cases of primary gallbladder carcinoma. METHODS: The case of a 56-year-old man with a markedly elevated serum AFP level and primary gallbladder carcinoma without detectable hepatic involvement is reported. RESULTS: The patient had right upper quadrant abdominal pain and a palpable right upper quadrant mass. Computerized tomography scan of the abdomen showed a large, subhepatic mass consistent with the gallbladder, and normal liver parenchyma. Liver enzyme levels were normal. Management included cholecystectomy followed by postoperative radiation therapy to the gallbladder bed and portal areas and systemic chemotherapy. At the end of therapy, the AFP level had returned to normal. CONCLUSIONS: Gallbladder carcinoma is rarely diagnosed before surgery, which sometimes inhibits operative planning. AFP may be a useful preoperative tumor marker in differentiating the patient with primary gallbladder carcinoma from the patient with gallbladder hydrops.

Adenocarcinoma, Papillary↗

CD44 variant overexpression in gallbladder carcinoma associated with tumor dedifferentiation.

BACKGROUND: Recent studies have suggested a correlation between increased or decreased expression of CD44 variant molecules and tumor metastasis. CD44 expression in gallbladder carcinoma was examined and compared with tumor differentiation. METHODS: Eighty-three samples of gallbladder carcinoma, 17 gallbladder adenoma samples, and 66 normal control mucosa samples were stained immunohistochemically for CD44 standard form (CD44s), variant 3 (CD44v3), and variant 6 (CD44v6). RNA extracted from nine patients with carcinoma also was investigated with reverse transcriptase-polymerase chain reaction (RT-PCR) analysis and Southern blot hybridization (SBH) for the CD44 gene. RESULTS: Normal gallbladder mucosa showed strong, membranous staining for CD44s but not for CD44v3 or CD44v6. In gallbladder tumors, CD44s was stained as strongly as it was in normal mucosa, but immunoreactivity for CD44v3 and CD44v6 also was significant. In well differentiated, advanced adenocarcinomas (n = 38), CD44s immunoreactivity was significantly lower in the invasive component than in the intramucosal component of the tumors (P = 0.0048). Immunoreactivity for CD44v3 and CD44v6 in moderately and poorly differentiated areas was significantly higher than in well differentiated areas (P < 0.0001 and P = 0.0378, respectively). RT-PCR and SBH signals for CD44v3 and CD44v6, including exons 7 and 10, were strong in carcinoma samples but weak in normal samples, in line with the results of immunohistochemistry. The prognosis of patients with gallbladder carcinoma was not associated significantly with altered expression of CD44s, CD44v3, or CD44v6. CONCLUSIONS: The current study demonstrated that CD44 variant overexpression in patients with gallbladder carcinoma was linked closely with histologic dedifferentiation rather than clinicopathologic factors, including prognosis.

Adenocarcinoma↗