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Role of laparoscopic cholecystectomy in the management of polypoid lesions of the gallbladder.

This retrospective clinicohistopathologic study was performed to delineate the role of laparoscopic cholecystectomy in the management of polypoid lesions of the gallbladder. One hundred forty-three consecutive patients who had a preoperative sonographic diagnosis of polypoid lesions of the gallbladder with a diameter less than 1.5 cm and who underwent laparoscopic cholecystectomy at Cathay General Hospital were included in the analysis. Histopathologic study showed that 22 (15.4%) patients had true tumors, including adenoma (16), adenoma with focal adenocarcinoma (2), adenocarcinoma (3), and carcinoid tumor (1). Tumorlike lesions were found in 121 (84.6%) patients and included cholesterol polyp (106), adenomyomatous hyperplasia (10), inflammatory polyp (3), and papillary hyperplasia (2). The mean diameter of malignant polypoid lesions of the gallbladder was 1.35 +/- 0.42 cm, which was significantly larger than that of cholesterol polyps (0.66 +/- 0.40 cm, P = 0.0001) but not significantly larger than that of adenomyomatous hyperplasias (1.12 +/- 0.42 cm) and adenomas (1.08 +/- 0.47 cm). The mean age of patients with malignant polypoid lesions of the gallbladder (61.2 +/- 13.3 years old) was significantly older than that of patients with adenomyomatous hyperplasia (46.6 +/- 13.4 years, P = 0.03), cholesterol polyps (44.5 +/- 10.5 years, P = 0.0003), and adenomas (41.4 +/- 9.4 years, P = 0.0008). Clinical follow-up showed that most (98.6%) patients benefited from the minimal invasiveness of laparoscopic cholecystectomy with satisfactory surgical results. We conclude that laparoscopic cholecystectomy is a reliable, safe, and minimally invasive biopsy procedure and definite management of polypoid lesions of the gallbladder with a diameter less than 1.5 cm.

Adult↗

Increased gallbladder trypsin in acute cholecystitis indicates functional disorder in the sphincter of oddi and could make EPT a logical procedure.

Clinical and surgical observations confirm that acute cholecystitis (ACh) and acute biliary pancreatitis can coexist and that differentiation may be difficult even at surgery. Synchronous appearance of ACh and acute biliary pancreatitis suggests a similar etiology. Endoscopic sphincterotomy, with relief of the common channel outlet obstruction, has become the established therapeutical modality that improves the outcome in acute biliary pancreatitis. Patients suffering from ACh could be treated in a similar manner to prevent reflux of pancreatic juice into the common bile duct and the gallbladder with the intention to improve the clinical course. The present study investigated the presence and amount of pancreatic trypsin in the gallbladder bile in 73 patients operated on for gallstone disease with ACh and in controls. The average gallbladder bile trypsin level in the "edematous cholecystitis" group ranged between 0.525 and 4500 ng/mL, significantly exceeding that of controls, 0.5-53 ng/mL (P < 0.0001). The average gallbladder bile trypsin level in the "gangrenous cholecystitis" group, 0.1-71.5 ng/mL, was within the range of controls (n.s.), most likely to be explained as a consequence of consumption of trypsin due to the fulminant development of the disease. Further controlled studies are mandatory before it would be acceptable to recommend endoscopic sphincterotomy as a valuable choice in the initial/early management of patients suffering from ACh. Such a study is underway to assess the possible role of obstruction at, or other disorders of, the sphincter of Oddi with consequent pancreatic juice reflux into the gallbladder as a possible initial cause of ACh.

Bile↗

Double gallbladder-a laparoscopic management.

A rare case of gallbladder duplication, an unusual biliary anomaly is reported in a young female patient presenting with acute cholecystitis. After a confirmed diagnosis of double gallbladder was made by sonography, endoscopic retrograde cholangio-pancreaticography (ERCP), and magnetic retrograde cholangio-pancreaticography(MRCP), both gallbladders were removed laparoscopically. On histology both gallbladders showed cholesterolosis. Detailed preoperative investigations are required for an accurate preoperative diagnosis before considering laparoscopic cholecystectomy to avoid inadvertent damage to biliary ductal system and overlooking of second gallbladder during surgery.

Adult↗

Immunohistochemically demonstrated lymph node micrometastasis and prognosis in patients with gallbladder carcinoma.

OBJECTIVE: To investigate whether immunohistochemically demonstrated lymph node micrometastasis has a survival impact in patients with advanced gallbladder carcinoma (pT2-4 tumors). SUMMARY BACKGROUND DATA: The clinical significance of immunohistochemically detected lymph node micrometastasis recently has been evaluated in various tumors. However, few reports have addressed this issue with regard to gallbladder carcinoma. METHODS: A total of 1476 lymph nodes from 67 patients with gallbladder carcinoma (pN0, n = 40; pN1, n = 27) who underwent curative resection were immunostained with monoclonal antibody against cytokeratins 8 and 18. The results were correlated with clinical and pathologic features and with patient survival. RESULTS: Lymph node micrometastases were detected immunohistochemically in 23 (34.3%) of the 67 patients and in 37 (2.5%) of the 1476 nodes examined. Of the 37 nodal micrometastases, 21 (56.8%) were single-cell events, and the remaining 16 were clusters. Five micrometastases were detected in the paraaortic nodes. Clinicopathologic features showed no significant associations with the presence of lymph node micrometastases. Survival was worse in the 27 patients with pN1 disease than in the 40 with pN0 disease (5-year survival; 22.2% vs. 52.6%, P = 0.0038). Similarly, survival was worse in the 23 patients with micrometastasis than in the 44 without micrometastasis (5-year survival; 17.4% vs. 52.7%, P = 0.0027). Twenty-eight patients without any lymph node involvement had the best prognosis, whereas survival for the 11 patients with both types of metastasis was dismal. The grade of micrometastasis (single-cell or cluster) had no effect on survival. The Cox proportional hazard model identified perineural invasion, lymph node micrometastasis, and microscopic venous invasion as significant independent prognostic factors. CONCLUSIONS: Lymph node micrometastasis has a significant survival impact in patients with pN0 or pN1 gallbladder carcinoma who underwent macroscopically curative resection. Extensive lymph node sectioning with keratin immunostaining is recommended for accurate prognostic evaluation for patients with gallbladder carcinoma.

Adult↗

Gallbladder and gastric motility in patients with idiopathic slow-transit constipation.

OBJECTIVE: Idiopathic slow-transit constipation (STC) has been suggested to be a pangastrointestinal motility disorder. We investigated scintigraphically whether motility in the gallbladder and stomach was impaired in slow-transit constipation. METHODS: Twenty-four patients with STC were studied. Colon transit time, gallbladder motility, and solid-phase gastric emptying were measured by scintigraphy. RESULTS: Gallbladder dysmotility was observed in 8 of 18 (44.4%) patients. Mean gallbladder ejection fraction was 41.6 +/- 13.6% (range, 16.3-67.0%). Gastric emptying was delayed in 9 of 18 (50%) patients. Mean solid-phase gastric half-emptying time was 75 minutes. STC may be associated with impaired function of other gastrointestinal organs. Approximately half of patients with STC presented gallbladder or gastric dysmotility. CONCLUSION: STC may not be a pure colonic abnormality; it may be a component of a pangastrointestinal tract motility disorder involving several organs.

Constipation↗

Induction of invasive growth in a gallbladder cancer cell line by hepatocyte growth factor in vitro.

To study the mechanism of invasion and metastasis of gallbladder cancer cells, we established a cancer cell line, GB-d1, from a metastatic lymphnode of poorly differentiated adenocarcinoma of the gallbladder. GB-d1 cells proliferate well in a dish culture and form small cystic cell clusters in a collagen gel containing 10% fetal bovine serum. A conditioned medium of human embryonic lung fibroblasts (HEL) stimulated the proliferation of GB-d1 cells and induced cell scattering in the dish culture. In the gel culture, the conditioned medium induced a transformation of the spherical clusters to arborizating colonies with tubular projections that mimicked an invasion of cancer cells into the surrounding tissue. Similar results were obtained when 10 ng/ml of human recombinant hepatocyte growth factor (h-rHGF) was added to the culture medium. The proliferative and morphological changes induced by the conditioned medium were inhibited by antiserum against h-HGF. HEL and human gallbladder stromal fibroblast-like cells produced substantial levels of HGF in the culture media, while GB-d1 did not produce any detectable level of HGF. These results suggest that HGF promotes the invasive growth of gallbladder cancer cells in vitro, and it was also suggested that stromal fibroblasts may play an important role in the invasive progression of gallbladder cancer in a paracrine fashion.

Adenocarcinoma↗

Bowel movement frequency, medical history and the risk of gallbladder cancer death: a cohort study in Japan.

Few risk factors for gallbladder cancer have been identified with sufficient statistical power, because this cancer is rare. The present study was conducted to evaluate the association of bowel movement frequency and medical history with the risk of death from gallbladder cancer using the data set from a large-scale cohort study. A total of 113,394 participants (42.0% males), aged 40 to 89 years, were followed up for 11 years. Information on the medical history of selected diseases, history of blood transfusions, frequency of stools, and tendency toward diarrhea at baseline was collected through a self-administered questionnaire. The Cox proportional hazard model was used to estimate the hazard ratio (HR). During the follow-up period, a total of 116 deaths (46 males, 70 females) from gallbladder cancer were identified. After adjustments for age and gender, history of hepatic disease (HR: 2.28; 95% confidence intervals (95% CI): 1.24-4.21), frequency of stool, and tendency toward diarrhea (HR: 0.26; 95% CI: 0.08-0.83) were found to be significantly associated with the risk of death from gallbladder cancer. Compared with those who had a stool at least once a day, the HR was 2.06 (95% CI: 0.82-5.18) for those who had a stool less than once in 6 days (P for trend = 0.050). In this prospective study, constipation and a history of hepatic disease were found to elevate the risk of gallbladder cancer death, whereas a tendency toward diarrhea diminished it.

Adult↗

Contractility of human gallbladder muscle in vitro.

This study examined the effects of transmural nerve stimulation, acetylcholine, adrenoceptor agonists and several peptides on the contractility of strips of human gallbladder in vitro. Acetylcholine caused concentration-related contractions of the tissues and the sensitivity to acetylcholine was similar in gallbladders with mild and severe chronic cholecystitis. Noradrenaline and adrenaline relaxed gallbladder strips, probably via beta 2-adrenoceptor stimulation. Transmural nerve stimulation always caused contractions, but in the presence of atropine inhibitory responses were demonstrable and these were antagonized by propranolol. There was no evidence of non-adrenergic inhibitory neural responses. Of the peptides tested, only cholecystokinin octapeptide (CCK-OP), gastrin, pentagastrin, substance P and caerulein caused contractions. Responses to CCK-OP, gastrin and pentagastrin were antagonized by dibutyryl cyclic GMP. Hormones which had no effect upon human gallbladder strips included motilin, secretin, bombesin, neurotensin, glucagon, vasopressin, VIP and somatostatin. Considerable differences therefore exist between human tissues and those from experimental animals with respect to the direct actions of neural and hormonal stimuli on gallbladder contractility.

Electric Stimulation↗

Cisapride increases gallbladder volume in gallstone patients before and after extracorporeal shock wave lithotripsy.

We have previously shown that oral cisapride causes a dose-related increase of fasting gallbladder volume in healthy subjects. The present study investigates the effect of cisapride on gallbladder motility in 16 patients with gallbladder stones; 8 patients had no biliary symptoms, but the other 8 patients with symptomatic gallstone disease were studied before and 6 weeks after extracorporeal shock wave lithotripsy (ESWL). For each study the patients received a single oral dose of 20 mg cisapride; fasting gallbladder volume was measured by ultrasound before, and for 120 minutes after, drug administration. In the 8 asymptomatic patients a mean maximal increase of the fasting volume to 152.7 +/- 7.6% of the initial value was observed at a mean 97.5 +/- 8.3 minutes after cisapride ingestion. Similarly, in the 8 patients with biliary pain mean fasting volume after cisapride ingestion increased to 141.3 +/- 5.7% before ESWL treatment and to 145.0 +/- 5.8% after ESWL and 6 weeks of oral litholytic therapy. There were no significant differences between the results in the symptomatic and asymptomatic patients. Our results indicate that cisapride increases the gallbladder volume in gallstone patients regardless of biliary symptoms. Similar volume changes were observed before therapy and after ESWL with bile acid therapy. The therapeutic efficacy of litholytic agents could be diminished by simultaneous cisapride administration.

Administration, Oral↗

Occurrence of cholesterol monohydrate crystals in gallbladder and hepatic bile in man: influence of bile acid treatment.

The occurrence of cholesterol monohydrate crystals was examined and related to the degree of cholesterol saturation in gallbladder bile and hepatic bile of gallstone (GS) patients (n = 34), gallstone-free (GSF) subjects (n = 33) and GS patients treated with chenodeoxycholic acid (CDCA (n = 7) or ursodeoxycholic acid (UDCA) (n = 11) for 3 weeks prior to cholecystectomy. Twenty-five untreated GS patients (74%) and four UDCA-treated patients (40%) displayed cholesterol crystals in the gallbladder bile. Only two GSF subjects (6%) and none of the CDCA-treated patients had crystals. Half of the patients with crystals in the gallbladder bile had crystals also in the hepatic bile. Cholesterol saturation of the gallbladder bile was higher in GS (142 +/- 15%, mean +/- SEM) than in GSF patients (74 +/- 5%). Saturation was also higher in GS patients with crystals (157 +/- 20%) than in those without crystals (99 +/- 12%). Gallbladder bile was unsaturated in all CDCA- and UDCA-treated patients. The results underline the importance of the degree of cholesterol saturation for the formation of cholesterol crystals. The data also give further support to the concept that the mechanism for inducing gallstone dissolution is different for CDCA and UDCA.

Adult↗

Gallbladder changes in neonatal hepatitis: markedly thickened wall and lack of contractility.

The gallbladder wall changes were observed on ultrasonography during the course of a patient with neonatal hepatitis. The gallbladder was not detected at 53 days of age, but on the next day its wall was observed to be markedly thickened and without contraction following the administration of cerulein. It had a thinner wall at 57 days of age and reacted to cerulein. The wall thickness and contractility went together with the improvement of jaundice and liver function tests. Histological diagnosis was compatible with neonatal hepatitis. Ultrasonographic detection of the gallbladder has been helpful to differentiate neonatal hepatitis from biliary atresia. It is reported to be compatible with neonatal hepatitis to detect a normal-sized gallbladder or its contraction following cerulein administration or feeding. Since this case did not meet these criteria initially, thickened wall of the gallbladder may be an additional finding indicating neonatal hepatitis. The importance of repeated ultrasonography and clinical correlation was stressed.

Biliary Atresia↗

Is it possible to predict the clinical course of gallstone disease? Usefulness of gallbladder motility evaluation in a clinical setting.

OBJECTIVE: A knowledge of the predictive factors of the development and persistence of symptoms in gallstone patients (GS) plays a key role in clinical decision making. The aim of this study was to evaluate the presence of predictive factors for biliary pain development in GS, stressing the role of gallbladder motility. METHODS: A total of 153 (104 women, 49 men) consecutive GS were enrolled. Gallbladder motility (%Emptying [%E], residual volume [RV]) was evaluated by ultrasonography and biliary symptoms were evaluated using a specific questionnaire in all GS at baseline and after 4 yr of follow-up. RESULTS: At enrolment, 61 GS reported recent (GSr) and 31 GS remote (GSo) (>2 yr before) episodes of biliary pain, and 61 were asymptomatic (GSa). At baseline, GSr showed a greater %E and a smaller RV than both GSo and GSa (p < 0.001). After follow-up, biliary pain developed more frequently in GSr (33.3%) than in GSo (16%) and GSa (15%) (p= 0.04). The search for predictive factors of biliary pain development (by univariate and multivariate analyses) revealed a high %E, a small RV, and a history of biliary pain as risk factors. CONCLUSIONS: Efficient gallbladder motility is present in symptomatic GS and it represents a risk factor for biliary pain development while sluggish motility seems to play a protective role. Thus, gallbladder motility evaluation is a useful diagnostic tool in clinical decision making for GS; in symptomatic GS, a progressive reduction of gallbladder motility could suggest a "wait and see" management policy instead of an immediate surgical approach.

Female↗

Defect in bile acid concentrating ability of the gallbladder in congenital chloride diarrhoea.

Congenital chloride diarrhoea is assumed to be caused by a defect in the coupled NaCl influx mechanism in the ileum. As a similar coupled NaCl transport mechanism has been postulated in the gallbladder, the concentrating ability of the gallbladder was studied in a patient with congenital chloride diarrhoea. Bile acid concentrations were measured in the duodenal fluid before and after stimulation of gallbladder contraction by cholecystokinin. In the chloride-diarrhoea patient no increase in bile acid concentration was established after cholecystokinin injection, in contrast to a pronounced increase in three control children, suggesting that the absorption of salt and water by the gallbladder may be disturbed in the patient. The results support the postulated similarity of the NaCl transport mechanisms in the ileum and gallbladder. In congenital chloride diarrhoea one defect in a NaCl transport protein could explain the disturbances in electrolyte absorption.

Bile Acids and Salts↗

Relationship between interdigestive gallbladder emptying, plasma motilin and migrating motor complex in man.

The aim of this study was to elucidate the importance of biliary output for the regulation of migrating motor complex and the release of plasma motilin. Gallbladder emptying was monitored by hepatobiliary scintigraphy, plasma motilin concentration by radioimmunoassay and gastrointestinal motility by a perfused catheter system. During a total recording time of 46 h and 20 min in 16 volunteers, we observed 29 episodes of gallbladder emptying, 27 plasma motilin peaks and 23 activity fronts (phase 3 activity) of the migrating motor complex (MMC). Twelve episodes of gallbladder emptying started in phase 1 and continued into phase 2 of the MMC. The remaining 17 episodes of gallbladder emptying started in phase 2, and three of these continued into phase 3 of the MMC. Biliary output was associated with a significant rise in plasma motilin concentration, whereas plasma motilin significantly decreased after the activity fronts. These observations may explain the well-known fluctuations of plasma motilin concentration in the fasted state. Motilin is released into the circulation as a result of biliary output, while the ensuing activity front of the MMC removes this stimulant from the proximal small bowel, resulting in a fall in plasma motilin. In conclusion, we have confirmed a temporal relationship between biliary output into the duodenum and the release of plasma motilin. The observed transition from phase 1 to phase 2 and from phase 2 to phase 3 of the MMC during gallbladder emptying episodes suggests that biliary output stimulates gastrointestinal motility in the fasted state.

Adolescent↗

Association of the presence of Helicobacter in gallbladder tissue with cholelithiasis and cholecystitis.

The presence of Helicobacter DNA species has been investigated in the biliary epithelium of patients with biliary diseases. However, conflicting results have been observed that may have been due to the small number of subjects studied, difficulty in obtaining a healthy control group, absence of controlling for confounding factors, or differences among populations. Therefore, we investigated the presence of Helicobacter species by culture and nested PCR of 16S rRNA genes in gallbladder tissue and bile from 46 Brazilian subjects with and 18 without cholelithiasis. The control group was mainly composed of liver donors and of patients who had submitted to cholecystectomy as part of the surgical treatment for morbid obesity. No Helicobacter species were grown from the bile or gallbladder tissues. Helicobacter DNA was detected in the gallbladder tissue and bile from 31.3 and 42.9% of the patients, respectively. In a logistic regression model, cholelithiasis was positively and independently associated with the female gender (P = 0.02), increasing age (P = 0.002), and the presence of Helicobacter DNA in the gallbladder tissue (P = 0.009). The presence of Helicobacter DNA in the bile was not associated with cholelithiasis (P = 0.8). A significant association between the presence of Helicobacter DNA in the gallbladder epithelium and histological cholecystitis, even after adjusting for gender and age (P = 0.002), was also observed. The sequences of the 16S rRNA genes were >99% similar to that of Helicobacter pylori. In conclusion, our results support the hypothesis that Helicobacter is associated with the pathogenesis of human cholelithiasis and cholecystitis.

Adult↗

The effects of vasoactive intestinal polypeptide on the motility of human and guinea pig gallbladder.

The effects of several preparations of vasoactive intestinal polypeptide (VIP) on the motility of strips of human and guinea pig gallbladder were investigated in vitro. VIP (10(-12) to 10(-6) M) had no measurable effects on the spontaneous activity, resting tone or cholecystokinin-octapeptide induced tone of human gallbladder strips. However, VIP (10(-12) to 10(-6) M) caused biphasic effects on the tone of guinea pig gallbladder strips. At low concentrations (10(-12) to 10(-10) M) contractions were observed that became smaller at higher concentrations (10(-9) to 10(-8) M). At still higher concentrations (10(-7) to 10(-6) M) relaxations were elicited. It appears that VIP is not as potent a relaxant of gallbladder muscle as first described. Human gallbladder tissue was totally unresponsive to the VIP preparations tested.

Animals↗

Calcitonin gene-related peptide: an inhibitor of guinea pig gallbladder contraction.

Calcitonin gene-related peptide (CGRP) relaxes vascular and intestinal smooth muscle. This study localized CGRP in the guinea pig gallbladder, examined the effects of CGRP on KCl- and ACh-induced contraction, and determined CGRPs site of action in the gallbladder. The gallbladder of male Hartley guinea pigs was used in in vitro tension studies, radioimmunoassay, or immunocytochemical studies. Radioimmunoassay showed that 8.0 +/- 0.5 pmol/g of immunoreactive CGRP was present. Immunocytochemistry demonstrated that immunoreactive-CGRP nerve fibers occurred around blood vessels, in gallbladder smooth muscle layers, and were associated with ganglia. No immunoreactive cell bodies were observed, even after colchicine treatment. The in vitro tension studies showed that CGRP inhibits either KCl- or acetylcholine-stimulated contraction. CGRP may in part act directly on the gallbladder smooth muscle to inhibit contraction.

Acetylcholine↗

Differential sensitivities of the sphincter of Oddi and gallbladder to cholecystokinin in the guinea pig: their role in transsphincteric bile flow.

Cholecystokinin (CCK) is considered to simply contract the gallbladder and relax the sphincter of Oddi with meals. In this study, we examined this hypothesis by investigating the action of CCK on the sphincter of Oddi and gallbladder of the guinea pig. The experimental design used an in vitro preparation of the sphincter of Oddi to measure contraction of the circular muscle. CCK increased tone in both the gallbladder and the sphincter of Oddi in a concentration-dependent manner. The normalized concentration-response curves for CCK, however, revealed that the gallbladder had a greater sensitivity to CCK (ED50 7 nM) than the sphincter of Oddi (ED50 22 nM; p < 0.01). Conversely, the sphincter was more sensitive to bethanechol than was the gallbladder. When the sphincter of Oddi was stimulated maximally with CCK in the presence of atropine (10(-6) M) or tetrodotoxin (10(-6) M), the contractile response was significantly reduced (p < 0.05) although not abolished. Conversely, atropine completely abolished the responses to bethanechol (10(-3) M) and transmural field stimulation (70 V, 10 Hz, 1 ms, for 20 s). Transmural field stimulation of the sphincter that had been precontracted with CCK (26 nM) caused a transient, initial relaxation followed by contraction. Pretreatment with atropine augmented the duration of this relaxation, which could be completely abolished by tetrodotoxin. Thus, CCK contracts the sphincter of Oddi in the guinea pig by a direct (myogenic) and a neural (likely cholinergic) mechanism. Relaxation of the sphincter of Oddi also occurs in the guinea pig via noncholinergic inhibitory nerves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗