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PubMed1983

In vitro effects of pancreatic polypeptide and motilin on contractility of human gallbladder.

In vivo studies have indicated that pancreatic polypeptide induces gallbladder relaxation, whereas motilin initiates contraction of the gallbladder. To determine if these two polypeptides act directly on the gallbladder muscle, their effect on strips of human gallbladder was studied in vitro. Preparations were suspended in an organ bath and the isometric tension recorded. Dose-response curves to cholecystokinin and acetylcholine were first established. The ability of pancreatic polypeptide to cause relaxation under basal conditions and during 50% maximal stimulation by cholecystokinin-octapeptide (2 X 10(-8) M) was assessed on four strips at approximate physiological concentration (300 pmol/liter) and on four additional strips at 10(3) higher concentration. Pancreatic polypeptide did not have any effect on the basal or the cholecystokinin-generated tension at either concentration. The response to motilin was evaluated on four gallbladder strips at concentrations ranging from 10(-11) to 6.7 X 10(-7) M. Although the highest concentration was more than 10(5) greater than levels reported in fasting serum, motilin did not initiate any gallbladder strip contraction. Whereas the preparation was unresponsive to pancreatic polypeptide and motilin, it was capable of contracting in a dose-related fashion to the known agonists cholecystokinin and acetylcholine, and the response was blocked by the respective antagonists dibutyryl cyclic GMP and atropine. It thus seems that pancreatic polypeptide and motilin exert their respective actions as sites remote from the gallbladder without directly affecting gallbladder muscle.

Acetylcholine↗

PubMed1990

Neurohumoral control of gallbladder motility in healthy subjects and diabetic patients with or without autonomic neuropathy.

Patients affected by diabetes mellitus are reported to have an increased incidence of gallbladder abnormalities. The pathophysiologic mechanisms for this phenomenon are unclear. In the present study ultrasonography was used to determine gallbladder emptying in response to a meal or separate cephalic or hormonal stimulation in 21 diabetic patients and 10 healthy subjects. Gallbladder emptying and refilling after a meal were similar in diabetic patients and healthy subjects. When diabetics were divided according to the presence or absence of cardiac autonomic neuropathy (AN), a significant reduction of gallbladder emptying in response to cephalic stimulation was found in diabetics with AN (P less than 0.01 in comparison with diabetics without AN or healthy subjects). A dose-response curve of gallbladder emptying in response cerulein, a cholecystokinin analog, at concentrations of 0.25, 1, and 4 micrograms/kg/min was evaluated. No differences of gallbladder emptying were found in the three groups of subjects, indicating that gallbladder sensitivity to hormonal stimulation is not changed in diabetic patients with or without AN. Diabetic patients with AN have a significant reduction of gastric acid output and pancreatic polypeptide (PP) secretion in response to cephalic stimulation (P less than 0.05 in comparison with diabetic patients without AN or healthy subjects). Cerulein-induced PP secretion was similar in all three groups of subjects (P greater than 0.05). This study indicates that in diabetic patients with AN, gallbladder emptying as well as gastric acid and PP secretions induced by neural stimulation are markedly reduced in comparison to diabetics without AN.

Adult↗

PubMed1981

Sonographic features of carcinoma of the gallbladder.

The sonographic features of carcinoma of the gallbladder are reviewed. Four cases of carcinoma of the gallbladder are presented which illustrate some, but not all, of the sonographic findings resulting from this abnormality. The findings illustrated are (a) a small gallbladder containing stones associated with a mass in the porta hepatis, (b) diffuse gallbladder thickening, fixation, and irregularity, (c) a papillary mass with an irregular border projecting from the gallbladder wall, and (d) a small, localized area of gallbladder wall thickening associated with cholelithiasis. Although inflammatory disease of the gallbladder can present similar sonographic findings, the correlation of the clinical findings and close inspection of the sonographic changes illustrated and described in this publication may allow the only means of a preoperative diagnosis of carcinoma of the gallbladder.

Adenocarcinoma↗

PubMed1981

Stimulation of gallbladder fluid and electrolyte absorption by butyrate.

Gallbladder fluid and electrolyte transport was investigated in vitro. In guinea pig gallbladder, equimolar substitution of acetate, propionate, butyrate or valerate for HCO3 was increasingly effective in stimulating fluid absorption. The stimulatory potency of these compounds was a function of their chloroform water partition coefficients. The stimulatory effects of the isomers isobutyrate and isovalerate were less than predicted from their partition coefficients. Acidification of the gallbladder lumen, however, was strictly dependent on the partition coefficients for all of the above fatty acids. Unidirectional 22Na fluxes were measured in rabbit and guinea pig gallbladders under short-circuit conditions. In the presence of butyrate stimulation of net Na flux was due entirely to an increase in the mucosal-to-serosal Na flux. Stimulation by butyrate was abolished by its omission from the mucosal bathing solution. The transepithelial electrical potential difference in both rabbit and guinea pig gallbladder became more lumen positive following mucosal but not serosal addition of butyrate. Net 14C-butyrate fluxes were too small to account for stimulation of Na absorption in either species. Butyrate stimulation of Na absorption by guinea pig gallbladder was abolished by increasing the bathing pH from 7.4 to 8.1. Tris buffer (25 mM) partially inhibited butyrate-dependent gallbladder fluid absorption by rabbit and guinea pig at pH 6.4 and 7.0, respectively, and completely at pH 8.4. These results reveal a marked similarity between butyrate and HCO stimulation of gallbladder NaCl and fluid absorption. The results are best explained by a double ion-exchange model, in which butyrate (HCO3) in the mucosal solution acts to maintain the intracellular supply of H+ and butyrate (HCO3) for countertransport of Na and Cl, respectively.

Animals↗

PubMed1992

The size and contractility of the gallbladder in infants.

The size of the gallbladder and the common bile duct as well as the contractility of the gallbladder were measured in infants under the age of 1 year. A total of 43 healthy infants were studied at their routine visit to the well-baby clinic at the ages of 6 weeks, 4 months, 8 months or 12 months. Gallbladder size was measured before and after a test meal. Fasting gallbladder size increased with the age of the infants. However, when the size was corrected for the infant's weight, no age-related variation was found. The contraction index (CI) was determined as a percentage decrement of planimetric gallbladder size from the initial size. The mean CI declined with age from 75% (+/- 27%) (mean (+/- SD)) at the age of 6 weeks to 24% (+/- 28%) at the age of 12 months. Overall CI varied from -44% to 100%. An increase in gallbladder size after the test meal was observed in 4 infants. Gallbladder volumes were also calculated, but two-dimensional measurements were regarded as more accurate in infants. A large variation was found in the size as well as in the contractility of the gallbladder in infants less than 1 year of age.

Common Bile Duct↗

PubMed1996

Relationship between gastric and gallbladder emptying and refilling in normal subjects and patients with H. pylori-positive and -negative idiopathic dyspepsia and correlation with symptoms.

Gastric and gallbladder emptying and refilling was studied in 10 normal subjects and in 38 dyspeptic patients. H. pylori was determined in each dyspeptic on mucosal antral biopsy performed during endoscopy. Gastric and gallbladder emptying was evaluated by real-time ultrasonography. Normal subjects were evaluated after two solid-liquid meals of 340 kcal and 680 kcal. Dyspeptics were studied after the 340-kcal meal only. For each subject and patient, minimum gallbladder volume and percentage of gastric emptying at this point was determined. Gastric and gallbladder slope was also drawn, and the crossing point between the two slopes identified. In normal subjects with the 340-kcal and 680-kcal meal, minimum gallbladder volume occurred for a similar percentage of gastric emptying. The crossing point between the two slopes was computed at the same percentage of gastric and gallbladder refilling with both meals. With the 680-kcal meal, however, peak gallbladder contraction and the crossing point between the two slopes occurred significantly later than with the 340-kcal meal (P < 0.05). In dyspeptics with the 340-kcal meal, the parameters evaluated were similar to the ones computed in controls after the meal of 680-kcal, suggesting delayed gastric emptying and gallbladder refilling. The presence or absence of H. pylori and symptom score were not correlated with any of the parameters studied.

Adult↗

PubMed1995

Radioactive choline metabolism in guinea pig gallbladder. Is there measurable acetylcholine release?

Acetylcholine may be released from gallbladder intrinsic nerves in response to cholecystokinin stimulation. This study characterized metabolites of [14C]choline produced in the gallbladder and released during incubation, with or without cholecystokinin-octapeptide. Radiolabeled [14C]choline was applied to the mucosal or muscle surface of intact guinea pig gallbladders in an organ bath. After radiolabeling, gallbladders were incubated with or without the contractile agonist cholecystokinin-octapeptide. Metabolites of [14C]choline were identified in gallbladder tissue and incubation buffers using HPLC and thin-layer chromatography. The major metabolites of [14C]choline were betaine and phosphocholine. [14C]Phosphocholine was incorporated slowly into [14C]phosphatidylcholine. [14C]Choline was released into buffers during incubation. [14C]Acetylcholine constituted less than 1% of radiolabel in the gallbladder. There was no identifiable [14C]acetylcholine released in buffers. Cholecystokinin-octapeptide did not affect choline metabolism. These studies showed that choline in the gallbladder is metabolized along pathways similar to those in the liver. Gallbladders released mostly choline, rather than acetylcholine, even during hormonally induced contraction.

Acetylcholine↗

PubMed1995

Effect of NSAIDs on gallbladder bile composition.

Secretion of gallbladder mucin is an important step in gallstone pathogenesis. Previous studies have demonstrated that aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) can both inhibit gallbladder mucin secretion and prevent gallstone formation in animal models of cholesterol gallstone disease. The present study was performed to determine if chronic NSAID use was associated with a reduction in the mucin content or affected the lipid components of human gallbladder bile. Four groups of patients were identified retrospectively from a cohort of 230 morbidly obese patients who underwent gastric bypass surgery. The index group consisted of 18 patients who were found to have gallstones at gastric bypass surgery and had a history of chronic NSAID use. Three other patient groups were identified from the cohort by matching this index population for sex, race, and age according to the following criteria: (1) patients with gallstones who had not utilized NSAIDs, (2) patients without gallstones but with chronic NSAID use, and (3) patients without gallstones and without a history of NSAID use. Gallbladder bile was obtained from all patients by direct aspiration from the gallbladder at the time of surgery. Patients with gallstones had a significantly (P < 0.02) greater concentration of gallbladder mucin in their gallbladder bile compared to patients without gallstones (0.897 +/- 0.226 vs 0.173 +/- 0.039 mg/ml). Among gallstone patients, gallbladder mucin was reduced in those patients with a history of chronic NSAID use (1.18 +/- 0.43 vs 0.74 +/- 0.19 mg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2006

[Isolated injury of the gallbladder. A rare cause of hemorrhagic shock after blunt abdominal trauma in a patient with liver cirrhosis].

Isolated injuries to the gallbladder are extremely rare in blunt abdominal trauma, with a reported incidence of less than 2%. We report a case with partial avulsion of the gallbladder and subsequent hemorrhagic shock in a patient with liver cirrhosis. Although the gallbladder injury was demonstrated on CT images (with contrast enhancement in the bed of the gallbladder), the correct diagnosis was not established preoperatively. Emergency laparotomy revealed partial avulsion of the gallbladder and the underlying condition of severe liver cirrhosis with ascites. We estimate that the gallbladder avulsion occurred due to compressional waves of the ascites (during blunt abdominal injury) which may have sheared off the gallbladder from the cirrhotic liver. The patient received cholecystectomy, which is recommended as standard in case of gallbladder injury.

Abdominal Injuries↗

PubMed2003

Biliary atresia: making the diagnosis by the gallbladder ghost triad.

OBJECTIVE: To describe the gallbladder ghost triad and evaluate its usefulness in the sonographic diagnosis of extrahepatic biliary atresia (BA). METHODS: From October 1997 to February 2002, 217 fasted infants with cholestatic jaundice aged 2-12 weeks were examined sonographically. We defined the gallbladder ghost triad as gallbladder length <1.9 cm, lack of smooth/complete echogenic mucosal lining with an indistinct wall and irregular/lobular contour, and used it as a criteria for BA. Gallbladder wall thickness, triangular cord, diffuse periportal echogenicity and hepatic artery calibre were also recorded. Diagnosis of BA was confirmed surgically and histologically. RESULTS: Thirty of 31 babies with BA demonstrated the gallbladder ghost triad. No false-positives were recorded. The 31st BA baby showed a normal gallbladder at 6 weeks, but developed the ghost triad at 8 weeks. Gallbladder wall thickening was seen in 46/186 non-BA babies, but not in BA. Triangular cord was observed in 24/31 babies. Twenty-two of 186 non-BA babies and 5/31 BA babies showed diffuse periportal echogenicity. The hepatic artery appeared more prominent in BA. All 31 babies diagnosed sonographically as BA had surgery. Three non-BA babies had "negative" laparotomies showing hypoplastic bile ducts. CONCLUSIONS: The gallbladder ghost triad is a very accurate sign of BA. Indeterminate cases require close follow-up.

Bile Ducts, Extrahepatic↗

PubMed2003

Gallbladder duplication successfully removed laparoscopically using endoscopic nasobiliary tube.

Laparoscopic cholecystectomy is sometimes difficult due to complicated biliary anatomy including gallbladder duplication, a rare anomaly of the biliary tract. We report a case of duplicated gallbladder successfully removed under laparoscopy using endoscopic nasobiliary (ENB) tube cholangiography. A 61-year-old Japanese woman presented us with right upper abdominal pain. Ultrasonography revealed two cystic structures lying in the gallbladder fossa, and the upper one contained multiple stones. Endoscopic retrograde cholangiography showed two gallbladders, each of which has a cystic duct draining into the common bile duct separately. Laparoscopic cholecystectomy was planned under the preoperative diagnosis of double gallbladder with gallstones in the accessory gallbladder. The ENB tube was inserted just before the operation. Laparoscopic removal of the double gallbladder was successfully done using the ENB tube to identify the biliary tree anatomy and to close the stump of the cystic duct. In this communication, we would like to stress the usefulness of the ENB tube at the time of laparoscopic biliary surgery in patients with biliary anomalies including gallbladder duplication.

Bile Ducts↗

PubMed2006

Laparoscopic cholecystectomy for early gallbladder carcinoma: long-term outcome in comparison with conventional open cholecystectomy.

BACKGROUND: The role of laparoscopic surgery for malignant gallbladder tumors remains uncertain. This study compared the surgical results of laparoscopic versus conventional open cholecystectomy for patients with early-stage gallbladder carcinoma and examined the role of laparoscopic surgery for early gallbladder carcinomas. METHODS: Data for the treatment of gallbladder carcinomas were gathered from Chang Gung Memorial Hospital (Linkou, Taiwan). A retrospective analysis of 40 patients with either stage 0 or stage 1 gallbladder carcinoma was performed. The patients were categorized into two groups on the basis of cholecystectomy procedures. The long-term outcomes for the two groups were compared. RESULTS: During the follow-up period, which ranged from 6.5 to 197.6 months, four patients in the conventional open cholecystectomy group encountered tumor recurrence, and one patient in the laparoscopic cholecystectomy group experienced distant tumor recurrence (p = 0.216). No local port-site tumor recurrence was identified in patients who underwent laparoscopic cholecystectomy. The overall 5-year survival rate in this series was 87.1%. A comparison of survival rates between the two groups demonstrated no significant difference (p = 0.340). CONCLUSION: The laparoscopic cholecystectomy procedure did not adversely influence the prognosis of patients with early-stage gallbladder carcinomas. Furthermore, meticulous removal of gallbladders during laparoscopic surgery, in which early gallbladder carcinoma can be managed successfully using laparoscopic cholecystectomy, achieved a satisfactory surgical result and a low port-site tumor recurrence rate.

Adult↗

PubMed2000

Long-term prognosis of gallbladder cancer diagnosed after laparoscopic cholecystectomy.

BACKGROUND: Several clinical and laboratory studies concerning port-site recurrence have raised the concern that laparoscopic procedures might worsen the prognosis of malignant disease. However, the long-term prognosis of patients with malignancy who undergo laparoscopic surgery is still unknown. The purpose of this study was to examine the long-term prognosis of patients with unexpected gallbladder cancer diagnosed after laparoscopic cholecystectomy (LC). METHODS: A clinicopathologic study was performed on 41 patients with postoperatively diagnosed gallbladder cancer from among 5,027 patients undergoing LC at 24 institutions. The cumulative survival rate was compared with that reported for gallbladder cancer diagnosed after open cholecystectomy (OC). RESULTS: Of 26 patients with early gallbladder cancer (pTis or pT1), 23 were simply followed up, and 9 of 15 patients with advanced cancer (pT2 or pT3) had additional resection after the diagnosis of gallbladder cancer. Port-site recurrence occurred in four patients, and two of them died of the cancer. However, at this writing, the other two are still alive after abdominal wall resection or radiation therapy, having survived for 31 and 71 months, respectively. The 5-year survival rate was 92% for early cancer and 59% for advanced cancer. These results were comparable with 5-year survival rates for gallbladder cancer diagnosed after OC. CONCLUSIONS: Although port-site recurrence occurred in four patients with advanced gallbladder cancer, the long-term prognosis of patients with undiagnosed gallbladder cancer who underwent LC was not worsened by the laparoscopic procedure. We conclude that surgeons can perform LC with reasonable confidence, even if the lesion is possibly malignant.

Adenocarcinoma↗

PubMed2006

Immunohistochemical demonstration of c-Kit protooncogene product in gallbladder cancer.

BACKGROUND/PURPOSE: Although some gallbladder carcinomas are immunoreactive for c-Kit, the reasons for the c-Kit expression and its clinicopathologic implications are unknown. METHODS: We investigated the prevalence of c-Kit immunoreactivity, its clinicopathologic correlates (including microvessel density and postoperative outcome), and the possible mechanisms of c-Kit expression. We reviewed retrospectively, the clinicopathologic records of 47 patients who had undergone macroscopically complete gallbladder carcinoma resection. The numbers of patients at pathologic stages I to IV, according to current TNM-based staging, were 10, 5, 18, and 14, respectively. For immunohistochemical examination, we used monoclonal antibodies against c-Kit and CD 34 (progenitor cell markers), cytokeratin 7 and cytokeratin 19 (cholangiocyte markers), and OCH1E5 (a hepatocyte marker). Control tissue samples were from five gallbladder specimens each with chronic cholecystitis, polyp, and adenoma. RESULTS: Cytoplasmic immunostaining for c-Kit was detected in 21 of the 47 gallbladder carcinomas (45%), and in 1 of the 15 control specimens (diagnosis, chronic cholecystitis). Young age was significantly associated with c-Kit positivity; however, there were no significant differences in the incidence of c-Kit positivity among other variables, including tumor stage and outcome. However, microvessel density was significantly higher in c-Kit-positive gallbladder carcinoma compared with c-Kit-negative gallbladder carcinoma. None of the 47 cancer specimens or the 15 control specimens were stained for CD34 and OCH1E5, but all 47 cancer specimens were stained for cytokeratins 7 and 19. CONCLUSIONS: Gallbladder carcinomas positive for c-Kit are unlikely to arise from immature cells, but may be associated with neovascularization. Angiogenesis inhibitors, such as tyrosine kinase inhibitors, therefore, may suppress the growth of some gallbladder cancers.

Adult↗

PubMed2001

An immunohistochemical study of metaplastic endocrine cells in human gallbladder cancer.

BACKGROUND/PURPOSE: In order to better understand the genesis of gallbladder cancer, we investigated the metaplastic changes and the presence of endocrine cells in mucosal tissue in the tissues of 100 patients with cholecystitis and 50 patients with gallbladder cancer. METHODS: All the tissue samples were submitted to Hematoxylin-eosin and Alcian blue-periodic acid-Schiff stain. To identify endocrine cells, we utilized Grimelius or Fontana-Masson stain. To detect intestinal hormones, we used streptavidin-biotin staining. If a given tissue sample presented with goblet cells or pseudopyloric cells, we determined that it was undergoing metaplasia. To locate a focus of endocrine cells, we used the presence of argyrophil cells and argentaffin cells. RESULTS: Metaplastic changes and endocrine cells were observed in 50% or more of the studied tissues that had been sampled from the lesions of chronic cholecystitis, and from the tumor and nontumor sites of gallbladder cancer. The tissues sampled from chronic cholecystitis patients showed endocrine cells releasing gut hormones, and the incidence of tissue presenting with such hormone-secreting cells tended to increase with the degree of metaplasia. The tissues sampled from the gallbladder cancer patients also showed endocrine cells, but the incidence in these tissues was not significantly correlated with the degree of metaplasia. In the tissue sampled from gallbladder cancer patients, the degree of metaplasia and the incidence of the tissues presenting with endocrine cells was not significantly different from the corresponding results obtained from chronic cholecystitis tissues. However, tissues presenting with endocrine cells occurred more frequently in samples from nontumor sites than in samples from chronic cholecystitis sites. The incidence of metaplastic cells and of endocrine cells correlated closely with the genesis of highly differentiated cancers. Lysozyme, a nonspecific defensive factor against infections, was frequently observed in the tissues sampled from patients with chronic cholecystitis as well as those with gallbladder cancer. CONCLUSIONS: Although metaplastic changes and endocrine cells were observed in the tissues of chronic cholecystitis as well as gallbladder cancer, these markers were most frequently observed in nontumor sites close to the tumors themselves, suggesting that these markers are closely involved in the genesis of gallbladder cancer.

Adult↗

PubMed2005

Enhancement of EFS-induced contractions, by agmatine, in guinea pig gallbladder smooth muscle strips.

BACKGROUND: Electrical field stimulation of gallbladder muscle strips produces frequency-dependent contractions by activating cholinergic nerves. The cholinergic motor function of the gallbladder and enteric system is also modulated by other mediators. The aim of this study was to investigate the role of agmatine, a ligand for alpha 2-adrenoceptors and imidazoline binding sites, in the cholinergic motor activity of guinea pig gallbladder smooth muscle. METHODS: Gallbladder muscle strips obtained from guinea pigs were subjected to electrical field stimulation (1-64 Hz, 100 V, 1-ms pulse width, and 10-s train duration). Frequency-response contractions of gallbladder muscle strips were traced before and after the addition of cumulative concentrations of agmatine (10(-5)-10(-3) M) to the tissue bath. The same set of experiments was repeated in the presence of different antagonists. RESULTS: Agmatine by itself did not produce any contractions in guinea pig gallbladder muscle strips, but significantly enhanced the contractile response produced by electrical field stimulation. Yohimbine (10(-6) M), a selective alpha 2-adrenergic blocker, neither decreased nor increased the enhancement induced by agmatine. However, idazoxan (10(-4) M), an alpha-receptor blocker and imidazoline receptor antagonist, abolished this enhanced contractile response. Pretreatment with N(W)-nitro L-arginine methyl ester (L-NAME; 30 microM), and indomethacin (10 microM) did not inhibit the effect of agmatine. CONCLUSIONS: Our findings indicate that agmatine has a modulator role in the electrical field stimulation-induced cholinergic contractions of guinea pig gallbladder smooth muscle strips, and this role could be mediated by imidazoline receptors. Receptor binding studies should be done to determine the presence of endogenous agmatine and imidazoline receptors in gallbladder smooth muscle.

Agmatine↗

PubMed2000

Heterotopic gastric mucosa in the gallbladder.

We report on a case of heterotopic gastric mucosa in the body of the gallbladder. A 39-year-old man, who was asymptomatic, visited our hospital because of a polypoid lesion in the gallbladder, discovered during a routine health screening. Ultrasonography (US) revealed a broad-based polypoid lesion 1.7 cm in diameter in the body of the gallbladder, which was free of gallstones. The gallbladder mass was faintly enhanced by helical computed tomography. Laparoscopic cholecystectomy was performed because of the possibility of malignancy. The specimen revealed a 1.7 x 1.3 cm polypoid lesion with deep delle in the body, with no gallstones in the gallbladder. Intraoperative frozen examination yielded a diagnosis of hyperplastic polyp of the gallbladder. Histologically, the polypoid lesion consisted of gastric fundic glands located in the whole wall of the gallbladder. The surrounding mucosa consisted of almost normal epithelium without any metaplastic changes. Postoperative technetium 99m-pertechnetate scintigraphy demonstrated no evidence of gastric heterotopia elsewhere in the body. We also review 18 other reports of heterotopic gastric mucosa in the gallbladder in the Japanese medical literature.

Adult↗

PubMed2005

Genetic alterations in gallbladder carcinoma.

Gallbladder carcinoma is an aggressive cancer associated with a poor prognosis. Unfortunately, the precise molecular mechanisms of development and progression of this highly malignant tumor remain unknown. It is still unclear whether loss of heterozygosity (LOH) plays a significant role in gallbladder carcinogenesis, but recent studies have found a high incidence of LOH at several chromosomes in gallbladder carcinoma. In particular, LOH on chromosomes 1p, 3p, 5p, 8p, 9p, 9q, 13q, 16q, and 17p has been highlighted and LOH on 3p, 9p, 13q, 16q, and 17p has been detected in preneoplastic lesions and in the early phase of gallbladder carcinoma during multistep carcinogenesis. The proto-oncogene, K-ras, is the best known genetic alteration in several human neoplasms, including gallbladder carcinoma. The accumulation of these genetic changes leads to a disruption in cell-cycle regulation and also continuous cell proliferation. We present an overview of K-ras alteration and LOH at several chromosome loci in gallbladder carcinoma. Further studies of the molecular mechanism in gallbladder carcinoma and the delineation of the genetic influence involved should promote our understanding of gallbladder carcinogenesis.

Carcinoma↗