Risk Factor For Gallbladder Carcinoma Research Articles

An overview on diagnosis and surgical management of gallbladder cancer

Gallbladder cancer is among the most deadly cancers, and it continues to present surgeons with numerous challenges. Cholelithiasis, an abnormal pancreaticobiliary junction, and focal mucosal microcalcifications are all known risk factors for gallbladder carcinoma. The most common histologic type in most patients is adenocarcinoma, which is frequently associated with Kras and p53 mutations. Endoscopic ultrasonography, magnetic resonance cholangiopancreatography, as well as helical computed tomography, as well as radiologic or endoscopic improvements in endoscopic ultrasonography as well as magnetic resonance cholangialpancratia, have improved preoperative staging. Cholecystectomy (subsegmental surgical excision of segments IVB but instead V plus a hepatoduodenal ligament lymphadenectomy) for advanced disease without indications of distant metastasis (T2–4/N0-N2) or a radical cholecystectomy (subsegmental resection of segments IVB as well as V plus a hepatoduodenal musculotendinous lymphadenectomy) for severe stages without indications of distant metastasis More extensive hepatic resection, such as extended right hepatectomy or central segmentectomy with caudate lobectomy, has been recommended by certain surgeons. Patients who underwent a pancreaticoduodenectomy to enhance distal ductal margins as well as lymphadenectomy for T3 or T4 malignancies were studied by Japanese surgeons. These patients had a reduced incidence of tumor recurrence but no benefit in terms of survival. Adjuvant treatment options are still restricted. The most frequent postoperative treatment is radiation therapy with fluorouracil radio sensitization. Capecitabine, oxaliplatin, & bevacizumab are now being studied in the treatment of gallbladder cancer in clinical studies.

Incidental Gallbladder Cancer Diagnosed During or After Laparoscopic Cholecystectomy, What Did We Do ?

Objective: Gallbladder cancer is a rare neoplasm. We report our experience with gallbladder cancer that was incidentally diagnosed during or after laparoscopic cholecystectomy performed for gallstone disease. Method: This study included all laparoscopic cholecystectomies due to gallstone disease undertaken from January 2010 to April 2015. Exclusion criteria were suspicion of malignancy and/or existence of gallbladder polyps detected with ultrasonography preoperatively. Patients with incidentally diagnosed gallbladder cancer were recorded, and the clinical and demographic characteristics of these patients were reviewed. Results: Of 6,114 patients in whom laparoscopic cholecystectomy was attempted, 5,948 were included in this study. Incidental gallbladder cancer was found in thirty-six patients, with a mean age of 64.08 years. The histological tumor stages were adenocarcinoma in situ in seven patient, pT1b in nine patient, pT2 in eleven patient, and pT3 in nine patients. Sixteen patients who underwent laparoscopic cholecystectomy alone underwent no additional surgery because of the low stage of the tumors. The twenty remaining patients, whose laparoscopic cholecystectomies were converted to open surgeries, underwent cholecystectomy, excision of the liver bed and lymph node dissection. The overall median survival time was 28 months. Conclusion: The incidence of incidental gallbladder cancer has been reported to vary, up to 2.85%. In this single-center study, the rate of incidental gallbladder cancer was found to be 0.60%. Female gender and advanced age are demographic risk factors for gallbladder carcinoma. Although gallbladder cancer is well known for its poor prognosis, tumors that are incidentally diagnosed are often found at an early stage and have a better prognosis.

The Spectrum of Gallbladder Histopathology at a Tertiary Hospital in a Developing Country: A Retrospective Study.

BackgroundAffections of the gallbladder remain exceedingly ubiquitous and often warrant surgical intervention. The histopathological patterns represent a spectrum, ranging from cholecystitis to gallbladder carcinoma. The present study aims to delineate the occurrence of various gallbladder histopathologies in a tertiary care hospital in Pakistan.MethodsA retrospective study was conducted at Maroof International Hospital, Islamabad, Pakistan. Histopathological records of 442 gallbladder specimens obtained from cholecystectomy were analysed. The prevalence of various histopathological outcomes was assessed. The data were eventually analysed using the SPSS 23.0 software (Armonk, NY: IBM Corp.). Thereafter, the distribution of various gallbladder histopathologies was tabulated across gender. ResultsOf the 442 patients included, 330 were females and 112 were males, with the mean age hovering at 45.77±14.65 years. The most common histopathological findings were chronic cholecystitis and cholesterolosis, observed in 78.6% and 32.8% of the patients, respectively. While only one case of gallbladder adenocarcinoma was observed, multiple specimens divulged premalignant lesions including reactive atypia and intestinal metaplasia.ConclusionsDiseases of the gallbladder often mandate prompt surgical intervention. Of these, chronic cholecystitis, which is an established risk factor for gallbladder carcinoma, is exceedingly common. The employment of histopathological techniques remains imperative in the detection of premalignant and malignant lesions that might otherwise evade macroscopic detection and thus progress to adenocarcinoma.

RNA Sequencing Revealed Signals of Evolution From Gallbladder Stone to Gallbladder Carcinoma.

Gallbladder stone is a major risk factor for gallbladder carcinoma (GBC), while there is still a controversy whether period of follow-up since newly diagnoses of asymptomatic gallstones increases the risk of GBC. In this study, 10 GBC patients and 30 patients with gallstones were admitted to our hospital. Patients with gallstones were divided into 3 groups according to the follow-up time, involving 10 patients with follow-up period of 1–3 years (GS3 group), 10 patients with follow-up period of 5–10 years (GS5 group), and 10 patients with follow-up period of more than 10 years (GS10 group). Tumor and para-tumor tissues of GBC patients, and gallbladder tissues of gallstone patients were collected. RNA sequencing was performed on the 50 samples. Besides, 1,704 differentially expressed genes (DEGs) were identified in tumors compared with para-tumor tissues of 10 GBC patients, which were enriched into some well-known cancer-related pathways, such as PI3K-Akt, mitogen-activated protein kinase (MAPK), Ras, and Wnt signaling pathways, and the most significant pathway was neuroactive ligand-receptor interaction. Patients with gallstones with periods of follow-up equal to 1–3 and > 10 years showed to have higher cancer risk than those with 5–10 years. ALPP and GPR87 are potential biomarkers for predicting cancer risk in patients with gallstones. The in vitro results revealed that GPR-87 can promote the proliferation, migration, and invasion of GBC cells. Herein, we explored the relationship between GBC patients and patients with gallstones with different periods of follow-up in transcriptome level.

Elevated bile amylase level without pancreaticobiliary maljunction is a risk factor for gallbladder carcinoma.

Elevated bile amylase level in patients with pancreaticobiliary maljunction (PBM) or high confluence of pancreaticobiliary ducts (HCPBD) is well known as a risk factor for gallbladder carcinoma (GBC) development. However, the effects of occult pancreaticobiliary reflux (OPR), a condition characterized by high bile amylase level in the presence of an anatomically normal pancreaticobiliary junction, on GBC development remain unclear. The aim of this study was to assess the relationship between OPR and GBC. Clinicopathological data of 52 patients who were preoperatively diagnosed with gallbladder (GB) tumor (22 malignant, 30 benign) were retrospectively reviewed. All of the patients underwent preoperative endoscopic retrograde cholangiopancreatography to evaluate pancreaticobiliary junction morphology and bile amylase level. The relationship between the histological diagnosis of GB lesions, and pancreaticobiliary junction morphology and bile amylase level were investigated. Pancreaticobiliary maljunction, HCPBD, and normal pancreaticobiliary junction (NPJ) were identified in 12, nine, and 31 patients, respectively. The rates of GBC in patients with PBM, HCPBD, and NPJ were 58% (7/12), 67% (6/9), and 29% (9/31), respectively. Of the 31 patients with NPJ, 22 had OPR and nine of these had GBC. None of the patients with NPJ and normal bile amylase level had GBC. Additionally, among patients with NPJ, bile amylase level was significantly higher in patients with GBC than in patients with benign tumors. Occult pancreaticobiliary reflux, like PBM and HCPBD, is a risk factor for GBC development.

TLR4 expression in normal gallbladder, chronic cholecystitis and gallbladder carcinoma.

Chronic inflammation is a risk factor for gallbladder carcinoma. The molecular mechanisms linking inflammation and gallbladder carcinogenesis are incompletely understood. Toll-like receptors are involved in inflammatory response and play an important role in the innate immune system by initiating and directing immune response to pathogens. We tested the hypothesis that TLR4 participated in the development of gallbladder carcinoma through investigating the expression of TLR4 in chronic cholecystitis, gallbladder carcinoma and normal gallbladder. The expression of TLR4 in 30 specimens of chronic calculous cholecystitis, 13 specimens of gallbladder adenocarcinoma and 10 specimens of normal gallbladder tissue was determined by immunohistochemistry, western blotting analysis and quantitative RT-PCR. We showed that TLR4 was mostly localized to the glandular and luminal epithelium of gallbladder. TLR4 expression was lower in gallbladder carcinoma tissue than in chronic cholecystitis and normal gallbladder tissue, whereas the difference between chronic cholecystitis tissue and normal gallbladder tissue was not statistically significant. The expression of TLR4 may be closely associated with the course of gallbladder carcinoma.

Incidental gallbladder cancer diagnosed during or after laparoscopic cholecystectomy in members of the Turkish population with gallstone disease

Gallbladder cancer is a rare neoplasm. We report our experience with gallbladder cancer that was incidentally diagnosed during or after laparoscopic cholecystectomy performed for gallstone disease. This study included all laparoscopic cholecystectomies due to gallstone disease undertaken from May 1999 to June 2010. Exclusion criteria were suspicion of malignancy and/or existence of gallbladder polyps detected with ultrasonography preoperatively. Patients with incidentally diagnosed gallbladder cancer were recorded, and the clinical and demographic characteristics of these patients were reviewed. Of 5,382 patients in whom laparoscopic cholecystectomy was attempted, 5,164 were included in this study. Incidental gallbladder cancer was found in five patients, with a mean age of 66.2 years. The histological tumor stages were adenocarcinoma in situ in one patient, pT1b in one patient, pT2 in one patient, and pT3 in two patients. Two patients who underwent laparoscopic cholecystectomy alone underwent no additional surgery because of the low stage of the tumors. The three remaining patients, whose laparoscopic cholecystectomies were converted to open surgeries, underwent cholecystectomy, excision of the liver bed and lymph node dissection. The overall median survival time was 32 months. The incidence of incidental gallbladder cancer has been reported to vary, up to 2.85%. In this single-center study, the rate of incidental gallbladder cancer was found to be 0.09%. Female gender and advanced age are demographic risk factors for gallbladder carcinoma. Although gallbladder cancer is well known for its poor prognosis, tumors that are incidentally diagnosed are often found at an early stage and have a better prognosis.

Implications of intestinal metaplasia of the gallbladder in children with pancreaticobiliary maljunction

Pancreaticobiliary maljunction (PBM) is associated with an increased frequency of gallbladder malignancy. Intestinal metaplasia is often observed in gallbladder disease and is a risk factor for gallbladder carcinoma in adults. The hyperplasia-dysplasia-carcinoma progression is one of the possible mechanisms involved in biliary carcinogenesis. In this study, we evaluate the gallbladders of children with PBM for intestinal metaplasia and other histological changes. From January 1997 to July 2010, 45 children with PBM were treated at our institution. A total of 42 children were included in our analysis which included histology and medical record review. The median age was 2.9years (range 1month-16.5years). The most common histological finding was villous-type mucosal hyperplasia, found in 24 patients (57.1%). Mucous gland metaplasia and goblet cell metaplasia were observed in 12 (28.6%) and 7 (16.7%) patients, respectively. There were no cases of malignancy. The intra-gallbladder amylase level in patients with mucosal hyperplasia was significantly elevated (81,373±92,442 vs. 38,932±61,466; p=0.042). Patients with mucous gland metaplasia had significantly higher serum amylase levels (833±1,214 vs. 343±358; p=0.024). The incidence of intestinal metaplasia is relatively high even in children with PBM. Such mucosal changes are related to cholangitis resulting from the regurgitation of pancreatic juice into the bile duct, which also causes hyperamylasemia via cholangio-venous reflux.

Advances in diagnosis and treatment of incidental cholangiocarcinoma

Carcinoma of gallbladder is the most frequently encountered malignancy of the biliary system. Early diagnosis is very difficult and the tumour resection rate is low,and the prognosis of carcinoma of gallbladder is very poor. With the increasingly widespread acceptance of laparoscopic cholecystectomy (LC),the number of cases of unsuspected gallbladder carcinoma (UGC) has increased. However,management of UGC is a difficult issue in the absence of established guidelines. High age and history of stones are the risk factors for gallbladder carcinoma and they are related to UGC. Surgical handling and pneumoperitoneum play an important role in the metastasis. The surgical approach used for cholecystectomy would not seem to influence the outcome in patients with UGC. The tumour stage is the most important prognostic factor. To understand UGC better, we review its clinical characteristics,investigation,prognosis and especially the recent advances in the diagnosis and treatment of this disease. Key words: Gallbladder neoplasms; Cholecystectomy; Prognosis

Flowcharts for the management of biliary tract and ampullary carcinomas

No strategies for the diagnosis and treatment of biliary tract carcinoma have been clearly described. We developed flowcharts for the diagnosis and treatment of biliary tract carcinoma on the basis of the best clinical evidence. Risk factors for bile duct carcinoma are a dilated type of pancreaticobiliary maljunction (PBM) and primary sclerosing cholangitis. A nondilated type of PBM is a risk factor for gallbladder carcinoma. Symptoms that may indicate biliary tract carcinoma are jaundice and pain in the upper right area of the abdomen. The first step of diagnosis is to carry out blood biochemistry tests and ultrasonography (US) of the abdomen. The second step of diagnosis is to find the local extension of the carcinoma by means of computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), percutaneous transhepatic cholangiography (PTC), and endoscopic retrograde cholangiopancreatography (ERCP). Because resection is the only way to completely cure biliary tract carcinoma, the indications for resection are determined first. In patients with resectable disease, the indications for biliary drainage or portal vein embolization (PVE) are checked. In those with nonresectable disease, biliary stenting, chemotherapy, radiotherapy, and/or best supportive care is selected.

Gallbladder Carcinoma Associated with Anomalous Pancreaticobiliary Duct Junction

Anomalous pancreaticobiliary ductal junction (APBDJ) is believed to be one of the risk factors for gallbladder carcinoma. The present study aims to delineate the gallbladder carcinoma characteristics associated with APBDJ. Patients with gallbladder carcinoma associated with APBDJ between August 1992 and February 2005 were retrospectively reviewed. Two types of APBDJ classifications were considered: right-angle type (C-P) and acute-angle type (P-C). Ten of 218 patients (4.6%) with gallbladder carcinomas were associated with APBDJ. All patients were female with a mean age of 55.4 years (range 41 to 72 years). Gallstones were absent in nine patients. Seven patients (70%) had the P-C type and three patients (30%) had the C-P type. Survival differences between the P-C type and the C-P type of gallbladder carcinomas were noted (P=0.0269). Patients with incidentally detected gallbladder carcinoma had superior survival (P=0.0316). Gallbladder carcinomas associated with APBDJ were significantly related to relatively young female patients without gallbladder stones. Survival outcomes in these patients were not different from those of gallbladder carcinoma without APBDJ. In particular, the P-C type of APBDJ seemed to be more associated with relatively advanced gallbladder carcinomas, and patients with incidentally detected gallbladder carcinomas with APBDJ had superior survival.

A clinicopathological analysis in unsuspected gallbladder carcinoma: A report of 23 cases

To study the clinicopathological characteristics of unsuspected gallbladder carcinoma (UGC). We retrospectively studied 23 cases of UGC in Tongji Hospital, and compared their clinicopathological characteristics with 33 cases of preoperatively diagnosed gallbladder carcinoma (PDGC). The proportion of UGC coexisting with cholecystolithiasis was significantly higher than that of PDGC (chi(2) = 13.53, P < 0.01). The infection rate of hepatitis B virus was 21.74% (5/23) in UGC and 30.30% (10/33) in PDGC. Nine (39.13%) of 23 patients with UGC and 8/33 (24.24) PDGC had contact with schistosome pestilent water. The rate of multiple pregnancies was 56.52% (13/23) in the patients with UGC and 42.42% (14/33) in PDGC. The primary location of the UGC was mostly in the neck and body of the gallbladder, and that of the PDGC was often in the body and bottom. The incidence of Nevin stage I and II UGC was significantly higher than that of PDGC (chi(2) = 4.44, P < 0.05 and chi(2) = 4.96, P < 0.05) while that of Nevin stage V UGC was significantly lower than that of PDGC (chi(2) = 7.59, P < 0.01). According to the grading of carcinoma, the incidence of well-differentiated UGC was significantly higher than that of PDGC (chi(2) = 4.16, P < 0.05), and that of poorly-differentiated UGC was significantly lower than that of PDGC (chi(2) = 4.48, P < 0.05). There are different characteristics between UGC and PDGC, such as in primary location, malignant degree and incidence of coexistence with cholecystolithiasis. Cholecystolithiasis, hepatitis B, schistosome and multiple pregnancies were high risk factors for gallbladder carcinoma.

Gallbladder Carcinoma Associated with Occult Pancreatobiliary Reflux

Purpose: Pancreatobiliary reflux can occur even if the patient has a normal pancreaticobiliary junction (occult pancreatobiliary reflux) and it can be associated with the occurrence of gallbladder carcinoma. The aim of the present study was to examine the mucosal changes of the gallbladder in patients with occult pancreatobiliary reflux. Methods: The gallbladder mucosa of 15 cholecystectomized patients, who had a normal pancreaticobiliary junction and whose biliary amylase concentration was more than 10,000 IU/L, was examined histologically. The gallbladder of patients without carcinoma was further examined using immunohistochemical techniques to detect Ki-67, and the results were compared with those of normal controls. Results: Six (40%) of the 15 patients had gallbladder carcinoma, and 9 (60%) did not. Of the 9 patients without carcinoma, 4 (44%) had dysplasia accompanied with hyperplasia, and 3 (33%) had only hyperplasia of the gallbladder. The Ki-67 labeling index was significantly higher in hyperplastic and dysplastic mucosa than in control gallbladder mucosa (p < 0.0004). Conclusions: Occult pancreatobiliary reflux could be associated with the cancerous and pre-cancerous mucosal changes such as hyperplasia and dysplasia of the gallbladder with increased cellular proliferation, and could be a possible risk factor for gallbladder carcinoma.

Precancerous mucosal changes in the gallbladder of patients with occult pancreatobiliary reflux

Pancreatobiliary reflux can occur even if the pancreaticobiliary junction is normal (occult pancreatobiliary reflux), and it may be associated with gallbladder carcinoma. The aim of the present study was to examine precancerous mucosal changes in the gallbladder from patients with occult pancreatobiliary reflux. The mucosa of the gallbladder from 13 patients who underwent cholecystectomy was examined histopathologically. These patients had an anatomically normal pancreatobiliary junction and a biliary amylase concentration greater than 10,000 IU/L. The gallbladder of patients without carcinoma was further examined by using immunohistochemical techniques to detect Ki-67, and the results were compared with those from control patients. Of the 13 patients, 5 (38%) had gallbladder carcinoma and 8 (62%) did not. Of the 8 patients without carcinoma, 4 (50%) had dysplasia accompanied by hyperplasia, and 2 (25%) had hyperplasia alone of the gallbladder mucosa. The Ki-67 labeling index was significantly higher in hyperplastic and dysplastic mucosa than in control gallbladder mucosa (p < 0.0004). Occult pancreatobiliary reflux could be associated with precancerous mucosal changes in the gallbladder, such as hyperplasia and dysplasia with increased cellular proliferation, and could be a possible risk factor for gallbladder carcinoma.

Protease-activating-receptor-2 is frequently expressed in papillary adenocarcinoma of the gallbladder

Gallbladder carcinoma is one of the most devastating malignant tumors in Japan. An important risk factor for gallbladder carcinoma is pancreaticobiliary maljunction (PBM), which allows reciprocal reflux of bile and pancreatic juice. Protease-activated-receptor-2 (PAR-2), which is activated by trypsin, may be a key molecule in the process of carcinogenesis in the gallbladder epithelium. We investigated the relation between the expression of PAR-2 and clinicopathological findings in gallbladder carcinoma. The study group comprised 58 patients with gallbladder carcinoma. PAR-2 expression was identified by immunohistochemical staining of all tumor specimens. PAR-2 was expressed in cancerous gallbladder epithelium in 37 of 58 patients (64%). PAR-2 expression occurred more frequently in papillary adenocarcinoma (15 of 16 patients, 94%) than in non-papillary types (20 of 42 patients, 48%, p=0.005). Neither lymphatic invasion (p=0.03) nor venous invasion (p=0.009) occurred more frequently in gallbladder carcinoma with PAR-2 than in that without PAR-2. PAR-2 expression was not directly related to PBM (p=0.46). Papillary adenocarcinoma was associated with polypoid growth (p=0.01), PBM (p=0.01), decreased invasion to lymphatic (p=0.007) and venous vessels (p=0.005), lower T-factor (p<0.001), and lower clinical stage (p=0.02). PAR-2 is frequently expressed in papillary adenocarcinoma of the gallbladder. Trypsin may play an important role for carcinogenesis of the gallbladder through PAR-2 signaling.

Carcinogenesis of malignant lesions of the gall bladder. The impact of chronic inflammation and gallstones.

Gallbladder carcinoma is an uncommon but highly malignant tumor with a poor 5-year survival rate. The presence of gallstones is a well-established risk factor for gallbladder carcinoma, and the risk seems to correlate with stone size. Metaplastic changes of the gallbladder epithelium present in chronic cholecystitis may be a premalignant lesion. Solitary polyps with a size of greater than 1 cm are recognized as a predisposing factor for gallbladder carcinoma when their characteristics are echopenic, sessile, and high cell density. Endoscopic ultrasound is the most useful technique to detect the early changes of malignancy in polyps. Anomalous junction of pancreaticobiliary ducts (AJPBD) without a choledochal cyst and porcelain gallbladder is an additional risk factor for gallbladder malignancy. At the molecular level, it has been proposed that chronic inflammation of the gallbladder may lead to the loss of p53 gene heterozygosity and excessive expression of p53 protein. Furthermore, a proposed mechanism underlying the high risk of gallbladder carcinoma in patients with AJPBD is that chronic reflux of pancreatic juice causes intestinal metaplasia, hyperplasia, and dysplasia with the mutation of p53 and K-ras. In contrast, the causal relationship between porcelain gallbladder and malignancy is yet to be established. In this article, recognition of risk factors for gallbladder carcinoma was summarized with special attention to gallstones and chronic inflammation.

Cellular kinetics and gene mutations in gallbladder mucosa with an anomalous junction of pancreaticobiliary duct.

Anomalous junction of the pancreaticobiliary duct (AJPBD) is thought to be an important risk factor for gallbladder carcinoma in Japan. We have reported the characteristic pathology, cellular kinetics, and gene mutations to clarify the mechanism of carcinogenesis in gallbladder mucosa with AJPBD. A comprehensive review of the literature was undertaken, with referencing of major articles on the subject. A sequence of hyperplastic changes, with a corresponding increase in cellular kinetics with progression through dysplasia to carcinoma is important in carcinogenesis of gallbladder mucosa with AJPBD. p53 mutations may contribute to the transition from premalignancy to malignancy in the early stage of carcinogenesis of the gallbladder mucosa, regardless of the presence of AJPBD. The specific mutation of GGT-to-GAT in codon 12 of K-ras may play an important role in carcinogenesis of gallbladder mucosa with AJPBD.

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.

K-ras andp53 mutations in stage I gallbladder carcinoma with an anomalous junction of the pancreaticobiliary duct

An anomalous junction of the pancreaticobiliary duct (AJPBD) was thought to be an important risk factor for gallbladder carcinoma in Japan. In this report, we compared K-ras and p53 mutations in Stage I gallbladder carcinomas (GC) of patients with AJPBD with those in patients without AJPBD: We examined 6 GC of patients with AJPBD and 20 GC of patients without AJPBD: Immunohistochemistry was performed for p53 protein. K-ras and p53 mutations were examined using genomic DNA extracted from the cancer regions. The methods of polymerase chain reaction (PCR) single strand conformation polymorphism analysis were performed for mutations in exons 5-8 of p53. The methods of PCR restriction fragment length polymorphism were performed for mutation in codon 12 of K-ras. p53 positivity was 67% in GC of patients with AJPBD and 65% in GC of patients without AJPBD: p53 mutations were found in exons 7 and 8 in GC of patients with AJPBD and in exons 5, 6, and 7 in GC of patients without AJPBD: The incidence of K-ras mutation in GC of patients with AJPBD (50%) was greater than that in patients without AJPBD (6%) (P < 0.05). These results suggest that K-ras mutation may be important in the early stage of carcinogenesis of the gallbladder mucosa with AJPBD, and that p53 mutations may also contribute to the early stage of carcinogenesis of the gallbladder mucosa, regardless of AJPBD: