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Surgical treatment of gallbladder cancer.

Gallbladder cancer is usually a fatal illness because early stages of this carcinoma cause no specific signs or symptoms. Although the best chance of cure for gallbladder cancer remains incidental discovery, radical resection of the gallbladder, with the adjacent liver, adherent structures, plus a regional lymphadenectomy, has been suggested to improve survival. We retrospectively analyzed all patients with gallbladder cancer who were treated surgically at Mayo Clinic (Rochester) between 1984 and 2000. There were 131 patients for whom complete survival information was available. Patients who underwent a radical cholecystectomy had a significantly longer median survival (24 months) than patients who had a simple cholecystectomy (6 months) or noncurative treatment (4 months) (P<0.0001). The radical cholecystectomy group had significantly longer survival than the simple cholecystectomy group for all American Joint Committee on Cancer (AJCC) stages except stage I. Of the different variables tested in a univariate analysis (sex, surgical treatment modality, AJCC stage, tumor grade, jaundice, hyperbilirubinemia, and adjuvant therapy), all variables except sex, tumor grade, and adjuvant therapy were statistically significant predictors for the survival of patients with gallbladder cancer. AJCC stage and surgical treatment modality were the only significant predictors in a multivariate analysis. Our results support radical surgical resection for the treatment of gallbladder cancer to improve patient survival.

Adult↗

A close relationship between intestinal metaplasia and Cdx2 expression in human gallbladders with cholelithiasis.

We previously reported a case of a human gallbladder with cholelithiasis consisting of intestinal metaplasia with the expression of caudal-related homeobox transcription factor (Cdx2). However, it is unclear how often intestinal metaplasia and Cdx2 expression occur in human, nontumorous gallbladders with cholelithiasis. We studied the incidence of intestinal metaplasia and Cdx2 expression in human gallbladders with cholelithiasis. Gallbladders were resected under laparoscopy from 103 patients with cholelithiasis between September 2003 and March 2005. The mean age of the patients was 59.6 +/- 15.0 years (range, 22-92 years). We retrospectively reviewed these cases to look for the presence of intestinal metaplasia and the expression of Cdx2. In addition, the characteristics of intestinal metaplasia were examined by immunostaining for Muc2, chromogranin A, and serotonin. Intestinal metaplasia was found in 11.7% (12/103) of the gallbladders with cholelithiasis. The mean ages of patients with and without intestinal metaplasia were 60.8 +/- 15.4 and 59.4 +/- 14.9 years, respectively. Cdx2, Muc2, chromogranin A, and serotonin were expressed in 91.7% (11/12), 91.7% (11/12), 83.3% (10/12), and 50.0% (6/12) in intestinal metaplastic mucosa, respectively. Only one case (1.1%) that expressed Cdx2 without intestinal metaplasia did not express Muc2, chromogranin A, and serotonin. We found that 10.7% (11/103) of nontumorous gallbladders resected because of cholelithiasis under laparoscopy revealed intestinal metaplasia with Cdx2 expression.

Adult↗

Cholecystokinin (CCK) down regulates PGE2 and PGI2 release in inflamed Guinea pig gallbladder smooth muscle cell cultures.

This study examines the hypothesis that cholecystitis down-regulates Guinea pig gallbladder (GPGB) smooth muscle cholecystokinin (CCK)-stimulated prostaglandin (PG) release. Guinea pig gallbladder from Control and 48 h bile duct ligated (BDL) animals were placed in cell culture and grown to confluence. The cultures underwent Western Blot analysis for smooth muscle cell content of COX-1, COX-2, Prostacyclin Synthase (PS), or were incubated with CCK at 10(-8)M or 10(-6)M with and without indomethacin for 1h and analyzed for release of 6-keto-PGF1alpha, PGE2 and TxB2 by EIA. BDL increased Guinea pig gallbladder cell culture basal PGE2 and PGI2 release which was in part due to increased COX-2 content. CCK incubation down-regulated BDL Guinea pig gallbladder cell culture release of 6-keto-PGF1alpha and PGE2 and down-regulated COX-2 content but did not alter the Control group. The decrease in CCK-mediated BDL cell Guinea pig gallbladder release may be an endogenous mechanism to limit physiologic derangements induced by increased endogenous gallbladder PG synthesis during early acute cholecystitis.

Animals↗

Routine gallbladder screening not necessary in patients undergoing laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Management of the gallbladder in patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGBP) is controversial. We reviewed our experience in patients undergoing LRYGBP without routine gallbladder screening. METHODS: The data of 644 patients who underwent LRYGBP at our institution were analyzed. Preoperative ultrasonography was routinely obtained early in our series and selectively thereafter in patients with suspected symptomatic biliary disease. Cholecystectomy at LRYGBP was performed in symptomatic patients with positive ultrasound findings. Postoperatively, patients with intact gallbladders were prescribed ursodiol for 6 months. RESULTS: Of the 644 patients, 155 (24%) had history of cholecystectomy. A total of 104 patients underwent preoperative ultrasonography. Of the 104 patients, 20 had positive ultrasound findings and symptoms consistent with biliary disease and underwent concomitant cholecystectomy. Twelve patients had positive ultrasound findings and no biliary symptoms and did not undergo cholecystectomy. At a mean follow-up of 26.4 months, only 1 (8.3%) of the 12 patients had required cholecystectomy. Of the 104 patients, 72 had negative ultrasound findings. At a mean follow-up of 21.2 months, 5 of them (6.9%) had required cholecystectomy. The remaining 385 patients did not undergo any gallbladder screening. At a mean follow-up of 14 months, 32 (8.3%) of 385 patients had required cholecystectomy. Compliance with ursodiol for >4 months was only 39%. A time-to-event analysis did not reveal a significant difference in the cholecystectomy rate between asymptomatic patients with preoperative gallbladder screening and patients with no screening. CONCLUSION: Omission of gallbladder screening in asymptomatic patients undergoing LRYGBP is a reasonable approach that spares the patient a potentially unnecessary procedure with all its associated risks.

Adolescent↗

High-level microsatellite instability is not involved in gallbladder carcinogenesis.

The molecular alterations involved in the pathogenesis of gallbladder cancer are not yet well defined. Our aim was to determine the microsatellite status of gallbladder carcinomas and its possible correlation with alterations in K-ras and p53 genes as well as the clinicopathological characteristics of these tumors. A group of 37 gallbladder carcinomas was analyzed for alterations in a proposed panel of mononucleotide and dinucleotide markers of microsatellite instability. Somatic frameshift mutations at repeated sequences in the coding regions of TGF-betaRII, Bax, hMSH3, hMSH6 were also examined. The findings were correlated with the presence of K-ras and p53 alterations, and tumors' clinicopathological features. Microsatellite instability and/or LOH was observed in 9 gallbladder carcinomas. Cases showing microsatellite instability displayed alterations only in dinucleotide markers and were classified as MSI-L carcinomas. A subset of gallbladder carcinomas is characterized by low-level instability, based on the analysis of the above mentioned panel of markers. The pathway of microsatellite instability seems to play a minor role in the pathogenesis of gallbladder cancer.

Adult↗

Gallbladder disease in the morbidly obese.

During a 7 year period, 200 consecutive morbidly obese patients underwent a standardized gastric exclusion procedure. Group A was composed of the first 120 patients and Group B of the last 80 patients. In Group A, 22 patients had undergone a previous cholecystectomy and 12 patients had a cholecystectomy at the time of gastric exclusion because of positive diagnostic studies or palpation of stones. Of the remaining 87 patients in this initial group who were at risk for the development of gallbladder disease, 24 (27.6 percent) required a cholecystectomy in the first 3 postoperative years (mean 15.6 months). Twelve patients had acute cholecystitis, 3 patients had choledocholithiasis, and 1 patient had acute gallstone pancreatitis. In Group B, 18 patients had a previous cholecystectomy, 15 had positive diagnostic studies (ultrasonography and oral cholecystography) preoperatively, and 47 had negative studies. Cholecystectomy was routinely performed at the time of gastric exclusion surgery in the 62 patients with gallbladders in Group B. Of the 47 patients who had normal preoperative diagnostic studies, 40 (85.1 percent) had abnormal histologic findings in the gallbladder. Only seven patients in Group B had a normal gallbladder (14.7 percent). We conclude that gallbladder disease is considerably more frequent in the morbidly obese population (91.3 percent) than has previously been recognized, that diagnostic studies are frequently inaccurate, and that postoperative gallbladder disease is common (28.7 percent). On the basis of these results, routine cholecystectomy at the time of gastric exclusion surgery is recommended.

Adolescent↗

Gallstones in chronic spinal cord injury: is impaired gallbladder emptying a risk factor?

OBJECTIVE: To confirm that spinal cord injured persons are susceptible to gallstones and to evaluate the role of gallbladder stasis as a risk factor. STUDY DESIGN: Twenty-nine subjects with chronic spinal cord injury underwent fasting ultrasonography to determine the incidence of gallstones and to quantitate gallbladder emptying response to a 20g fat liquid meal. Gallbladder emptying fraction was compared to that of healthy subjects studied concurrently. RESULTS: Gallstones or sludge were found in 6 spinal cord injured men, a minimal prevalence of 21%. Four additional subjects had prior cholecystectomy for stones, giving a potential maximal prevalence of 30%. Four of the 6 subjects had gallstone risk factors of diabetes, obesity, and/or family history. Gallbladder stasis was not apparent in chronic spinal cord injured subjects. Only 5 subjects had poor gallbladder emptying, and 4 of them had diabetes and/or obesity. CONCLUSIONS: The study confirms an increased prevalence of gallstones after spinal cord injury. However, gallbladder stasis did not appear to be etiologic, and most gallstones were associated with conventional risk factors. The results do not support a general policy of gallstone screening or prophylactic therapy after spinal cord injury.

Adult↗

p53 protein overexpression in gallbladder carcinoma and its precursor lesions: an immunohistochemical study.

Gallbladder carcinoma is one of the most frequent neoplasms diagnosed in Chile. Although the premalignant lesions have been extensively studied and are well characterized, there is only limited information about the genetic abnormalities that might be important in the pathogenesis of gallbladder carcinoma or that might have prognostic implications. The present study evaluates the immunohistochemical expression of p53 protein in premalignant lesions and invasive carcinoma of the gallbladder, and correlates the p53 expression with histological type, grade of differentiation, and level of invasion of the tumor. The authors studied the immunohistochemical p53 protein overexpression in 52 gallbladder carcinomas, 47 carcinomas in situ (CISs), 34 dysplasias, and 10 specimens with chronic cholecystitis containing normal and metaplastic epithelium. A semiquantitative scoring system was used to assess the p53 reactivity. p53 overexpression was found in 34 of 52 (65.4%) carcinomas, 21 of 47 (44.7%) CISs, and 11 of 34 (32.4%) dysplasias. There were no significant differences in p53 expression in premalignant lesions associated with invasive carcinoma and those that were not. Normal and metaplastic epithelium did not overexpress p53 protein. In adenocarcinomas, no correlation was found between p53 protein overexpression and histological subtype, grade of differentiation, or level of invasion. The high incidence of p53 overexpression in gallbladder carcinoma and its presence in dysplasia, even in specimens without invasive carcinomas, suggests that this abnormality is an important and early event in the pathogenesis of the tumor. The progressively increasing incidence of p53 overexpression observed from premalignant lesions to invasive tumor provides additional support to the view that this is the usual route for the development of infiltrating gallbladder carcinoma.

Carcinoma↗

Association between serum concentration of apolipoproteins A-I and B with gallbladder disease.

BACKGROUND: A total of 1,255 subjects attending a private health care facility in Mexico City were studied to evaluate the association of serum concentration of Apo A-I and Apo B with presence of gallbladder disease (gallstones or cholecystectomy). METHODS: A cross-sectional study was carried out. All participants provided data on sociodemographic status and previous diagnoses of type 2 diabetes, hypertension, cardiovascular events, alcohol consumption, and smoking habits. Women additionally reported their obstetric-gynecologic history. Weight and height were measured; liver and biliary tract ultrasound assessed gallbladder disease. Plasma levels of total cholesterol, triglycerides, high-density lipoproteins (HDL) cholesterol, and apolipoproteins A-I (Apo A-I) and B (Apo B) were determined after a 12-h fasting period. RESULTS: In multivariate models, Apo A-I > or = 120 mg/dL was positively associated with gallbladder disease with odds ratio (OR) = 1.64, 95% confidence interval (95% CI) = 1.03-2.62, whereas Apo B > or = 120 mg/dL showed an inverse association (OR = 0.71, 95% CI = 0.48-1.05). Ratio of Apo B/Apo A-I > or = 1 was inversely associated with risk of gallbladder disease (OR = 0.54, 95% CI = 0.37-0.80). All models were adjusted for age, gender, body mass index (BMI), previous diagnosis of type 2 diabetes, triglycerides, alcohol consumption, tobacco, and contraceptive use, as well as for total cholesterol in HDL-cholesterol and Apo A-I models. CONCLUSIONS: Our results suggested the relationship between serum concentration of apolipoproteins and gallbladder disease. These findings support the hypothesis of increased biliary catabolism of cholesterol in subjects with gallbladder disease characterized by lower Apo B and higher Apo A-I serum concentrations.

Adult↗

Biologic activity of the tachykinins on lamb and sheep gallbladder.

In this study, we examined the activity of the tachykinins (TKs) on lamb and sheep isolated gallbladder and whether the TKs are involved in the capsaicin-induced activity in these tissues. Substance P (SP) and physalaemin (PHYS) contracted lamb gallbladder, PHYS-induced striking tachyphylaxis. This tissue was nearly insensitive to neurokinin A (NKA), neurokinin B (NKB), septide, and capsaicin. As in lamb tissues, SP and PHYS both contracted sheep gallbladder although PHYS induced no tachyphylaxis. At doses that had no effect on lamb tissue, NKA, NKB, septide, and capsaicin contracted sheep gallbladder. Our findings indicate that TK receptors differ in adult and young ovine gallbladder. The activity of PHYS on lamb gallbladder could depend on the existence of an unusual binding site, carrying one or more residues critical for the N-terminal sequence present in PHYS but not in SP.

Animals↗

Entero-endocrine cell differentiation in carcinomas of the gallbladder and mucinous cystadenocarcinomas of the pancreas.

Forty two carcinomas of the gallbladder and 25 mucinous cystadenocarcinomas of the pancreas were analyzed using silver stains and immunohistochemical techniques. Fourteen (33.3%) gallbladder carcinomas had argyrophil and argentaffin cells and 17 (40%) contained endocrine cells as shown by immunoperoxidase stains. The gallbladder tumors that had the largest number of endocrine cells were the well differentiated adenocarcinomas with colonic features. The most common endocrine cell in these tumors was the serotonin-containing (EC) cell followed by somatostatin-containing cells and cells that reacted to pancreatic polypeptide and gastrin. Intestinal metaplasia with pseudopyloric gland hyperplasia was present in the gallbladder mucosa adjacent to 11 carcinomas and had an endocrine cell population similar to that of the tumors. Endocrine cells were demonstrated in 18 (70%) of the 25 mucinous cystadenocarcinomas of the pancreas by the immunoperoxidase method although only 9 had argyrophil and argentaffin cells. The population of endocrine cells in these mucinous pancreatic tumors was similar to that found in gallbladder carcinomas. Endocrine cells were more numerous in areas with colonic-type glands, goblet cells and Paneth cells. The secretory products of the endocrine cells in these gallbladder and pancreatic tumors did not give rise to systemic endocrine manifestations. The presence of endocrine cells in these tumors can be explained on the basis of intestinal differentiation.

Cell Transformation, Neoplastic↗

Chemical ablation of the gallbladder: is it feasible?

PURPOSE: Transcatheter ablation of the gallbladder has been attempted in animals and humans with a variety of chemical and physical agents. Initial in vitro experiments suggested sodium hydroxide and hydrogen peroxide were more effective sclerosants than previously reported chemical agents. A phase I trial of escalating concentrations of and exposure times to these agents was performed in vivo. MATERIALS AND METHODS: Fourteen domestic pigs underwent cholecystostomy tube placement and cystic duct ligation. Two weeks later, sclerosis was performed with sodium hydroxide/ethanol solutions and hydrogen peroxide. RESULTS: Sequential 15- or 30-minute exposures to 0.1 N solutions of sodium hydroxide in ethanol followed by 3% peroxide failed to completely eliminate the pig gallbladder epithelium in vivo; 0.5 N and 1.0 N sodium hydroxide in ethanol caused gross gallbladder hemorrhage, mural dissection, and one perforation. Although the gallbladder lumen was ablated, the gallbladder epithelium was not completely eliminated in any animal. CONCLUSION: Chemical ablation of the pig gallbladder epithelium was not feasible in this experimental model.

Animals↗

Decreased gallbladder response in leptin-deficient obese mice.

Obesity is a major risk factor for gallstone formation, but the pathogenesis of this phenomenon remains unclear. Human data on gallbladder emptying are conflicting, and no animal data exist on the effect of obesity on gallbladder motility. Leptin, a hormone produced by adipocytes, is known to have central effects on neuropeptide Y and cholecystokinin, but the influence of leptin on the biliary effects of these hormones is unknown. Therefore we tested the hypothesis that leptin-deficient C57BL/6J-lep(ob) obese mice would have decreased gallbladder responses to excitatory stimuli. Twelve-week-old lean control (C57BL/6J) (n = 22) and C57BL/6J-lep(ob) obese (n = 20) female mice were fed a nonlithogenic diet. The mice were fasted overnight and underwent cholecystectomy. Whole gallbladders were placed in 3 ml muscle baths. After optimal length was determined with acetylcholine (10(-5) mol/L, responses to increasing doses of neuropeptide Y (10(-8) to 10(-6) mol/L) and cholecystokinin-8 (10(-10) to 10(-7) mol/L) were measured. Student's t test and two-way analysis of variance were used where appropriate. Results were expressed as Newtons per cross-sectional area. The lean control mice had significantly greater excitatory responses to acetylcholine than the obese mice (0.37 +/- 0.05 vs. 0.16 +/- 0.02, P < 0.01). The gallbladder responses were also greater when mice were treated with neuropeptide Y (10(-8) mol/L: 0.00 +/- 0.00 vs. 0.00 +/- 0.00, NS; 10(-7) mol/L: 0.12 +/- 0.02 vs. 0.05 +/- 0.01, P < 0.01; 10(-6) mol/L: 0.26 +/- 0.08 vs. 0.06 +/- 0.01, P < 0.01) and cholecystokinin (10(-10) mol/L: 0.27 +/- 0.04 vs. 0.13 +/- 0.02, P < 0.01; 10(-9) mol/L: 0.59 +/- 0.08 vs. 0.27 +/- 0.04, P < 0.01; 10(-8) mol/L: 0.80 +/- 0.11 vs. 0.37 +/- 0.05, P < 0.01; 10(-7) mol/L: 0.86 +/- 0.11 vs. 0.44 +/- 0.06, P < 0.01). These data suggest that genetically obese, leptin-deficient mice have decreased responses to acetylcholine, neuropeptide Y, and cholecystokinin. We conclude that decreased gallbladder motility contributes to the increased incidence of gallstones associated with obesity.

Animals↗

Histologic findings of gallbladder mucosa in 87 patients with morbid obesity without gallstones compared to 87 control subjects.

Obesity is an important risk factor for the development of gallstones. The purpose of this study was to determine histologic alterations in the gallbladder mucosa and the prevalence of gallstone disease in patients with severe and morbid obesity compared to histologic findings in the gallbladder mucosa of control subjects. Two groups were studied: 125 severely obese patients (38 with and 87 without gallstones) and 87 control subjects. Ultrasonography was performed in all of them before surgery. During surgery, cholecystectomy was performed in 87 obese patients with a "normal" gallbladder and in all 87 control subjects. Specimens were immediately sent for histologic analysis. The prevalence of gallstones was twice as high among obese women compared to obese men (P < 0.001). Normal gallbladder mucosa was found in 28.7% of obese women compared to 34.2% of control women (P > 0.59). Findings were similar among the men. The most frequent histologic abnormality in the gallbladder mucosa among obese women was cholesterolosis (37%), followed by chronic cholecystitis and cholesterolosis (18%), with frequencies of 23% and 12%, respectively, in control women (P > 0.1). Among men, a similar proportion of histologic abnormalities was seen in obese men and control subjects. In our population of obese patients compared to control subjects, a similarly high proportion of histologic abnormalities of the gallbladder mucosa was found in the absence of stones. These findings could have been attributed to the fact that the Chilean population has a high incidence of gallstones.

Adolescent↗

Carcinoma of the gallbladder.

Carcinoma of the gallbladder is the most common malignant tumour of the biliary tract and a particularly high incidence is observed in Chile, Japan, and northern India. The aetiology of this tumour is complex, but there is a strong association with gallstones. Owing to its non-specific symptoms, gallbladder carcinoma is generally diagnosed late in the disease course, but if a patient with gallstones experiences a sudden change of symptoms, then a cancer diagnosis should be considered. Treatment with radical or extended cholecystectomy is potentially curative, although these procedures are only possible in 10-30% of patients. There is no role for cytoreductive surgery in this disease. If a gallbladder carcinoma is discovered via pathological examination of tissue samples, then the patient should be examined further and should have radical surgery if the tumour is found to be T1b or beyond. Additional port-site excision is necessary if the patient has already had their gallbladder removed during laparoscopy; however, patients with an intact gallbladder who are suspected to have gallbladder carcinoma should not undergo laparoscopic cholecystectomy. Patients with advanced inoperable disease should receive palliative treatment; however, the role of chemotherapy and radiation in these patients needs further evaluation.

Algorithms↗

Carcinoma of the gallbladder--is it a sequel of typhoid?

Gallbladder diseases, including carcinoma, are common in the northern part of India and so are Salmonella typhi infection and typhoid carrier state. This study was aimed to find out the association of typhoid carrier state in patients with cholelithiasis, carcinoma of the gallbladder, and controls. The three groups are comparable in age and sex composition. This is the first study of its kind from an area of high endemicity for both typhoid infection and carcinoma of the gallbladder. A case-control study was carried out to detect typhoid carrier state among the patients with biliary diseases and healthy controls, using indirect haemagglutination assay measuring antibodies against highly purified S. typhi Vi polysaccharide antigen. A significantly high Vi positivity was observed in patients with gallbladder carcinoma (29.4%) compared to controls (5%) (chi2 = 6.325, P < 0.004, OR = 7.19) and patients with cholelithiasis (10.7%) (chi2 = 5.066, P < 0.01, OR = 3.86). There is 8.47 times more risk of developing carcinoma of the gallbladder in culture-positive typhoid carriers than the noncarriers. The present study suggests the typhoid carrier state to be one of the possible mechanisms of gallbladder carcinogenesis.

Adult↗

Gastrin-releasing peptide stimulates gallbladder motility but not sphincter of Oddi motility in Australian brush-tailed possum.

The neural distribution and action of gastrin-releasing peptide in the extrahepatic biliary tree of the Australian brush-tailed possum was investigated. Immunohistochemical staining of fixed specimens demonstrated gastrin-releasing peptide-containing nerves throughout the neural plexuses of the gallbladder, sphincter of Oddi, and mucosa of the common bile duct. Gastrin-releasing peptide (5-2000 ng/kg) increased gallbladder tone to a level equivalent to that produced by cholecystokinin octapeptide (160 ng/kg). This action was tetrodotoxin-insensitive. Sphincter of Oddi motility and transsphincteric flow were not altered. Possible mediation of the gallbladder response by gastrin was examined. Gastrin (50-2500 ng/kg) stimulated gastric acid secretion, elevated gallbladder motility to 64% of that produced by gastrin-releasing peptide, and did not alter sphincter of Oddi motility. In conclusion, gastrin-releasing peptide-containing nerves are found in the neural plexus of the possum extrahepatic biliary tree. Gastrin-releasing peptide induces gallbladder contraction in part by a direct action on gallbladder smooth muscle and also via release of gastrin.

Animals↗

A case-control assessment of risk factors for gallbladder carcinoma.

Gallbladder carcinoma is an uncommon, but highly fatal disease. Its symptoms frequently mirror those of gallstone disease, and in most instances, diagnosis is an incidental finding at surgery. While risk factors have been suggested for this cancer, many may in reality simply be a consequence of the older age of the population. This study is one of the few to approach this question by using a case-control study design comparing gallbladder carcinoma patients with a gallstone population, coupled with multivariate analysis to determine age-independent risk factors. Univariate analyses showed gallbladder carcinoma patients to be older than gallstone patients and to have many age-associated diseases. Following multiple regression adjustment for age, this disease was associated with female gender and with a previous history of gallstone symptoms. Carcinoma patients were less likely to have cholesterol gallstones in their gallbladders at surgery. A previous history of smoking was a substantial risk but of borderline statistical significance. Previous studies report associations that may be due to the older age of the gallbladder carcinoma patient. Our results show that after adjusting for age with multivariate analysis, gallbladder cancer subjects were predominantly female, more likely to report previous gallstone symptomology, and to smoke. While gallstones were not universally isolated from carcinoma patients at cholecystectomy, when present, they were less frequently classified as cholesterol gallstones based on visual inspection. Further cohort studies which target these populations will allow us to gain a more solid consensus on the risk factors for this disease.

Aged↗