Gallbladder carcinoma associated with pancreatobiliary reflux

INTRODUCTIONIt is well known that pancreatobiliary reflux is an important risk factor for the carcinogenesis of the biliary system in patients with pancreaticobiliary maljunction(PBM)[1,2],which is a congenital anomaly defined as an abnormal union of the …     

Gallbladder carcinoma associated with occult pancreatobiliary reflux in the absence of pancreaticobiliary maljunction

We herein report a case of gallbladder carcinoma associated with occult pancreatobiliary reflux (PR) in the absence of pancreatobiliary maljunction. A 67‐year‐old woman was referred to our hospital for the evaluation and treatment of a gallbladder tumor. Ultrasonography and computed tomography showed a nodular lesion in the fundus of the gallbladder, indicating the possibility of a gallbladder carcinoma. Endoscopic ultrasonography showed the nodular tumor and thickness of the surrounding epithelium. Endoscopic retrograde cholangiopancreatography revealed a normal pancreaticobiliary junction without the common channel and a slight dilatation of the common bile duct (15 mm in diameter). An open cholecystectomy and partial resection of the liver bed of the gallbladder with regional lymphadenectomy was performed. A C‐tube was inserted from the cut end of the cystic duct into the common bile duct to prevent bile stasis. Biliary amylase and lipase levels sampled in the gallbladder were 2604 IU/l and 775 IU/l, respectively. Biliary amylase level in the bile collected from the C‐tube in the common bile duct was 119 550 IU/l on postoperative day (POD) 6 and 22 265 IU/l on POD 12. These observations suggested that PR was present in this patient. The histopathological findings of the resected specimen showed a well‐differentiated adenocarcinoma of the gallbladder with invasion to the muscle layer and no metastasis of the resected lymph nodes. A high index of nuclear staining for MIB‐I in the cancer cells (about 10%) was exhibited, and a few cells in the normal epithelium also stained positive.     

Occult pancreatobiliary reflux and gallbladder carcinoma]

A total of 108 patients with a normal pancreaticobiliary junction who had gallbladder wall thickness as shown by ultrasonography or computed tomography underwent secretin injection magnetic resonance cholangiopancreatography. Based on the changes in the diameter of the biliary system after secretin injection, patients were categorized into the intensified group (n = 19) or the non-intensified group (n = 89). The mean (+/- SD) biliary amylase level in the bile duct was 41674 (+/- 59779) IU/L in the intensified group, which was significantly higher than that in the non-intensified group (210 (+/- 418)) IU/L (p < 0.0001). There were four patients with carcinoma of the gallbladder in the intensified group and their biliary amylase level in the bile duct was 90783 (+/- 82528) IU/L. Pancreatobiliary reflux similar to that seen in patients with pancreaticobiliary maljunction can occur in persons with a normal pancreaticobiliary junction and this may be associated with carcinoma of the gallbladder. Secretin injection magnetic resonance cholangiopancreatography proved useful to identify such persons.     

Severe dysplasia of the gallbladder associated with occult pancreatobiliary reflux

Pancreatobiliary reflux usually occurs in patients with pancreaticobiliary maljunction and can be associated with the occurrence of gallbladder carcinoma. We present the case of a patient with pancreatobiliary reflux despite having a normal pancreatobiliary junction (occult pancreatobiliary reflux; OPBR), in whom the resected gallbladder presented severe dysplasia. The patient, a 61-year-old woman, showed thickness of the gallbladder wall, detected by ultrasonography and computed temography (CT). Her biliary amylase level in the common bile duct was 103 000 IU/l, and in the gallbladder it was 153 500 IU/l, although endoscopic retrograde cholangiopancreatography revealed a normal pancreaticobiliary junction. Immunohistochemical staining showed many p53-positive nuclei in the dysplastic lesion, and about 50% of the dysplastic cells exhibited diffuse nuclear staining for Ki-67. In the present patient, early diagnosis of occult pancreatobiliary reflux led to early detection of a precancerous lesion of the gallbladder mucosa.     

正常胰胆管汇合Oddi括约肌功能与胰液胆管逆流的关系

目的 探讨Oddi括约肌(SO)压力对胰液胆管逆流(PBR)的影响.方法 对23例SO基础压力正常(正常组)、55例压力升高(升高组)和24例曾行EST(EST组)患者的SO基础压力值、胆汁淀粉酶(BA)检测结果及细菌培养结果进行对比分析.结果 正常组和升高组在细菌培养阳性率、BA升高发生率及其BA值方面差异均无统计学意义(P＞0.05),升高组中SO压力与BA呈负相关,但胆总管直径≥15 mm与＜15 mm的BA值[中位数(四分位间距),4270(12 337) U/L比279.5 (1370) U/L]差异有统计学意义(P＜0.05).EST组与完整乳头组(正常组+升高组)在BA升高发生率[83.3％ (20/24)比59.0％ (46/78)]及细菌培养阳性率[75.0％ (18/24)比33.3％ (26/78)]方面差异均有统计学意义(P＜0.05).结论 SO基础压力升高与PBR无直接关联.但胆管直径显著增加时会导致BA值升高,对PBR的程度产生间接性影响;胰胆管高位汇合逆流程度明显,共同管长度可能与PBR的发生存在一定关联.而EST虽可引起PBR和胆汁细菌感染,但能减轻胆汁淤积,可能有利于逆流的胰液排出.     

Periampullary diverticula cause pancreatobiliary reflux

BACKGROUND: Periampullary diverticula are associated with dysfunction of the sphincter of Oddi. Papillary dysfunction may allow reflux of pancreatic juice as well as intestinal contents into the common bile duct. We prospectively investigated pancreatobiliary reflux in patients with and without periampullary diverticula. METHODS: The ductal bile was sampled for amylase concentration during endoscopic retrograde cholangiopancreatography in 47 patients with choledocholithiasis (n = 29; with (n = 14) or without (n = 15) periampullary diverticula) or gallbladder cholesterol polyps (n = 18; with (n = 6) or without (n = 12) diverticula). RESULTS: The amylase concentration within the ductal bile was significantly higher in choledocholithiasis patients with periampullary diverticula (1621 +/- 587 IU/l) than in those without diverticula (1155 +/- 418 IU/l). The amylase concentration tended to be higher in gallbladder polyp patients with diverticula (1087 +/- 275 IU/l) than in those without diverticula (833 +/- 272 IU/l). Irrespective of the presence or absence of diverticula, patients with bile duct stones had significantly higher amylase concentrations than those with gallbladder polyps. CONCLUSIONS: Periampullary diverticula cause pancreatobiliary reflux. Further investigation is required to determine the clinical implication of pancreatobiliary reflux.     

正常胰胆管汇合胰液胆管逆流对胆囊的影响

目的 探讨正常胰胆管汇合胰液胆管逆流(PBR)对胆囊的影响.方法 54例行胆囊疾病需行胆囊切除患者,手术前腹部超声检测胆囊壁和内膜厚度并行胆囊壁血流检测,45例伴胆总管结石ERCP治疗时和9例手术中取胆汁测胆汁淀粉酶水平,根据胆汁淀粉酶水平分成PBR组(胆汁淀粉酶升高)和对照组(胆汁淀粉酶正常),切除胆囊标本行病理学及免疫组化(COX2、Ki-67、p53)检测,比较分析两组各项检测结果.结果 PBR组24例,包括胆囊结石20例和胆囊息肉4例,23例为潜在性胰液胆管逆流(OPBR),1例为胰胆管高位汇合(HCPBD),后者与胰胆管汇合异常(PBM)有相似的病理改变;对照组30例,包括胆囊结石28例和胆囊息肉2例.胆囊壁和内膜厚度,胆囊壁血流,胆囊炎症、增生、化生,以及p53表达情况两组间比较差异均无统计学意义(P＞0.05),细胞异型、COX2和Ki-67表达水平两组间比较差异有统计学意义(P＜0.05).结论 OPBR患者胆囊黏膜增生和化生变化与胆囊结石所引起的病理改变无明显区别,但显示细胞异型和增殖活跃,OPBR可能为发生为胆囊癌的因素.     

A case of gallbladder carcinoma associated with pancreatobiliary reflux in the absence of a pancreaticobiliary maljunction： A hint for early diagnosis of gallbladder carcinoma

A 62-year-old man with progressive thickening of the gallbladder wall visited our outpatient clinic. The biliary amylase level in the common bile duct was 19900 IU/L and that of the gallbladder was 127000 IU/L, although endoscopic retrograde cholangiopancreatography revealed no pancreaticobiliary maljunction. Histology demonstrated a moderately differentiated adenocarcinoma of the gallbladder. Pancreatobiliary reflux and associated gallbladder carcinoma were confirmed in the present case, in the absence of a pancreaticobiliary maljunction. Earlier detection of the pancreatobiliary reflux and progressive thickening of the gallbladder wall might have led to an earlier resection of the gallbladder and improved this patient's poor prognosis.     

Gallbladder carcinoma associated with anomalous pancreaticobiliary duct junction.

BACKGROUND: 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 AND METHODS: 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). RESULTS: 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). CONCLUSION: 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.     

Diagnosis and clinical implications of pancreatobiliary reflux

The sphincter of Oddi is located at the distal end of the pancreatic and bile ducts and regulates the outflow of bile and pancreatic juice. A common channel can be so long that the junction of the pancreatic and bile ducts is located outside of the duodenal wall, as occurs in pancreaticobiliary maljunction （PBM）; in such cases, sphincter action does not functionally affect the junction. As the hydropressure within the pancreatic duct is usually greater than in the bile duct, pancreatic juice frequently refluxes into the biliary duct （pancreatobiliary reflux） in PBM, resulting in carcinogenetic conditions in the biliary tract. Pancreatobiliary reflux can be diagnosed from elevated amylase level in the bile, secretinstimulated dynamic magnetic resonance cholangiop ancreatography, and pancreatography via the minor duodenal papilla. Recently, it has become obvious that pancreatobiliary reflux can occur in individuals without PBM. Pancreatobiliary reflux might be related to biliary carcinogenesis even in some individuals without PBM. Since few systemic studies exist with respect to clinical relevance and implications of the pancreatobiliary reflux in individuals with normal pancreaticobiliary junction, further prospective clinical studies including appropriate management should be performed.     

Occult pancreatobiliary reflux in patients with a normal pancreaticobiliary junction

BACKGROUND: The aim of this study was to investigate pancreatobiliary reflux in individuals with a normal pancreaticobiliary junction. METHODS: Seventy-four patients with a normal pancreaticobiliary junction, as determined by ERCP, underwent secretin injection MRCP before cholecystectomy. Based on changes in the diameter of the biliary system after secretin injection, patients were categorized into enhanced or nonenhanced groups. RESULTS: Biliary amylase was measured in the 4 patients allocated to the enhanced group and 60 in the nonenhanced group. The mean (SD) biliary amylase level in the gallbladder was 123,723 (115,125) IU/L in the enhanced group and 238 (507) IU/L in the nonenhanced group (p < 0.0001). The mean (SD) biliary amylase level in gallbladders with carcinoma (n = 7) was 68,281 (106,500) IU/L, which was significantly higher than that in gallbladders without carcinoma (p < 0.01). CONCLUSION: Pancreatobiliary reflux similar to that seen in patients with pancreaticobiliary maljunction can occur in individuals with a normal pancreaticobiliary junction and may be associated with carcinoma of the gallbladder. Secretin injection MRCP is useful for identifying these individuals.     

Assessment of occult pancreatobiliary reflux in patients with pancreaticobiliary disease by ERCP

Background The aim of this study was to evaluate the degree of occult pancreatobiliary reflux by measuring the biliary amylase levels in the common bile duct (CBDA) and gallbladder (GBA) at endoscopic retrograde cholangiopancreatography (ERCP).Methods Eligible patients included 86 consecutive cases of pancreaticobiliary disease with prospective implementation of bile collection during an ERCP procedure. Patients with pancreatobiliary maljunction (PBM) were excluded. Nineteen cases of eligible patients had simultaneous collection of gallbladder bile. Bile was further collected by cholecystectomy in 8 cases.Results Twenty-two cases (26%) revealed a CBDA level higher than serum amylase (high bile amylase level, HBA group) and 64 cases exhibited a CBDA level lower than serum (LBA group). The mean values of CBDA in the HBA and LBA groups were 5502IU/l and 29IU/l, respectively. The rate of HBA was significantly higher in patients who were elderly, had a dilated common bile duct, and those with choledocholithiasis (P < 0.05). Three cases (16%) showed a CBDA greater than twice the GBA. Eleven cases (58%) exhibited a GBA higher than the CBDA. The values of GBA obtained during ERCP and cholecystectomy were consistent.Conclusions These findings suggest that even non-PBM cases can exhibit occult pancreatobiliary reflux, which can thereby cause biliary disease.     

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.     

Gallbladder cancer associated with cholesterosis

We report herein two cases of carcinoma in situ of the gallbladder associated with cholesterosis. The patient in case 1 was an 81-year-old man who underwent a cholecystectomy for cholelithiasis. The resected specimens revealed gallbladder cancer in the fundus which was diagnosed histologically as mucinous carcinoma. Other findings included 13-mm, 12-mm, and 5-mm poly-poid lesions in the neck of the gallbladder which macroscopically appeared to be cholesterol polyps, but histologically demonstrated carcinoma in situ with cholesterosis. The patient in case 2 was a 76-year-old man in whom ultrasonography revealed a highly echogenic, elevated lesion in the gallbladder. Cholecystectomy was performed, and a 33×28-mm papillary, elevated lesion with cholesterosis was resected from the neck of the gallbladder. Histologically, this was demonstrated to be papillary adenocarcinoma in situ with cholesterosis surrounded by glandular dysplasia. The distribution of the carcinomas and cholesterosis in both of these patients suggests that the adenoma or carcinoma of the gallbladder had occurred first. Then, the tumor epithelium absorbed cholesterol from the bile, and foamy cells were produced. Thus, when treating cholesterol polyps, it should be remembered that it is often difficult to distinguish between cholesterol polyp and gallbladder cancer with cholesterosis.     

胆汁反流性胃炎患者胆囊排空功能研究

目的研究胆汁反流性胃炎（ＢＲＧ）患者胆囊（ＧＢ）排空功能及其与胆汁反流的关系．方法采用随机、双盲和对照的方法，应用实时超声检查研究了３２例ＢＲＧ患者和２６例健康对照者的空腹ＧＢ容量（ＦＧＶ）和餐后ＧＢ排空功能．结果ＦＧＶ（ｃｍ３，ｘ±ｓｘ）ＢＲＧ患者（２３５±１５）明显大于对照组（１９７±１３，Ｐ＜００１）．餐后１５ｍｉｎＧＢ排出量（ＧＥＦ）ＢＲＧ患者即显著减少（Ｐ＜００１），餐后４５ｍｉｎ减少达最大（４５３％ｖｓ７０３％）．最大ＧＥＦＢＲＧ患者（６５４％）明显少于对照组（８０２％，Ｐ＜００１）．ＧＢ排空速度ＢＲＧ患者显著慢于对照组（Ｐ＜００１）．结论ＢＲＧ患者ＧＢ排空明显不良，可能系ＧＢ收缩无力和（或）Ｏｄｄｉ括约肌松弛不良所致；餐后ＧＥＦ减少与ＦＧＶ增多有关，从而使消化间期排入肠道的胆汁增多，当同时存在胃肠运动功能紊乱时即可反流入胃     

Endoscopic papillary balloon dilation causes transient pancreatobiliary and duodenobiliary reflux

BACKGROUND: Endoscopic papillary balloon dilation reduces sphincter function at least transiently or partially, which may allow pancreatobiliary and duodenobiliary reflux to occur. This study prospectively evaluated pancreatobiliary and duodenobiliary reflux after endoscopic papillary balloon dilation. METHODS: In 12 patients with choledocholithiasis, ductal bile was sampled for amylase concentration and bacterial culture during ERCP, before and at 7 days to 5 years after endoscopic papillary balloon dilation. To provide comparative and control data, ductal bile was sampled in 12 patients with gallbladder cholesterol polyps and 6 with anomalous pancreaticobiliary junction who did not undergo endoscopic papillary balloon dilation. RESULTS: Amylase concentrations in ductal bile from patients with choledocholithiasis before endoscopic papillary balloon dilation were marginally significantly higher (before Bonferroni correction) compared with concentrations in bile from patients with gallbladder polyps. The concentration of amylase in bile was significantly increased at 7 days after endoscopic papillary balloon dilation compared with that before endoscopic papillary balloon dilation; the level was comparable with that of patients with an anomalous pancreaticobiliary junction. Subsequently, the amylase concentration gradually decreased and was approximately equal to the pre-endoscopic papillary balloon dilation level at 1 year. Bacteriocholia was frequent (67%-92%) for up to 3 months after endoscopic papillary balloon dilation but was rare thereafter. CONCLUSIONS: Endoscopic papillary balloon dilation causes transient pancreatobiliary and duodenobiliary reflux. However, reflux is no longer present at 1 year after endoscopic papillary balloon dilation.     

Oddi括约肌压力对胰液胆管逆流的影响

目的探讨正常胰胆管汇合Oddi括约肌（SO）压力对胰液胆管逆流（PBR）的影响。方法选择因胆道疾病需要ERCP治疗的患者作为研究对象。ERCP时测SO基础压力、取胆汁测胆汁淀粉酶（BA）及细菌培养。结果 83例中正常组21例,9例（42.9%）BA升高;升高组47例,SO压力与BA值呈负相关（r=-0.43）,28例（59.6%）BA升高。两组间PBR发生的频度、其BA值及细菌培养阳性率差异均无统计学意义（P〉0.05）。升高组中胆总管直径≥15mm与〈15mm比较,BA值明显升高（P〈0.05）。EST组（15例）与完整乳头组（正常组和升高组）比较,PBR发生的频度和细菌培养阳性率差异有统计学意义（P〈0.05）。结论 SO基础压力升高不是影响PBR的直接因素,但胆管显著扩张时会导致BA值升高。EST可能有利于逆流胰液的排出。