High risk of gallbladder carcinoma in elderly patients with segmental adenomyomatosis of the gallbladder

The clinical significance of adenomyomatosis of the gallbladder remains unclear. This study aimed to clarify the relationship between segmental adenomyomatosis and gallbladder carcinoma, and to elucidate the histogenesis of gallbladder carcinoma associated with segmental adenomyomatosis. A total of 4,560 consecutive patients underwent cholecystectomy. The specimens were examined grossly and histologically. Adenomyomatosis of the gallbladder was divided into segmental, fundal, and diffuse types. Sixty noncancerous gallbladders with segmental adenomyomatosis were examined for epithelial metaplasia. The incidence of gallbladder carcinoma was higher in patients with segmental adenomyomatosis (22/334, 6.6%) than in those without (181/4226, 4.3%; P=0.049). This difference was more marked among patients equal to or older than 60 years of age (15/96,15.6% versus 147/2407, 6.1%, respectively; P<0.001). The other types of adenomyomatosis did not show any significant increases in the incidence of gallbladder carcinoma. In all 22 patients with both segmental adenomyomatosis and carcinoma, the tumors developed only in the fundal mucosa. Epithelial metaplasia was more marked in the fundal mucosa of segmental adenomyomatosis than in the neck mucosa (P=0.003). Segmental adenomyomatosis is a high-risk condition for gallbladder carcinoma, especially in elderly patients. Epithelial metaplasia appears to be related to increased carcinogenesis in the fundal mucosa of segmental adenomyomatosis.     

Relationship between gallbladder carcinoma and the segmental type of adenomyomatosis of the gallbladder.

Specimens from 3197 consecutive and unselected cholecystectomies performed during a 6-year period were studied. Adenomyomatosis of the gallbladder was defined as a lesion characterized by a thickened wall that consisted of Rokitansky-Aschoff sinuses surrounded by proliferated fibromuscular tissue. Adenomyomatosis was found in 279 specimens and classified as one of three types: segmental, fundal, or diffuse. Segmental adenomyomatosis was found in 188 specimens; gallbladder cancer (GBC) developed in 12 (6.4%) of the patients with segmental type adenomyomatosis. GBC developed in the mucosa of the fundal compartment distal to the annular stricture of the segmental type adenomyomatosis in all 12 of these patients. Conversely, GBC developed in 93 (3.1%) of the other 3009 patients (those with fundal alone, diffuse, or no adenomyomatosis). The prevalence of GBC in patients with segmental adenomyomatosis was significantly (P less than 0.025) higher than that of patients without segmental adenomyomatosis. Clinicians should be aware that segmental adenomyomatosis often coexists with GBC.     

Combined diagnostic imaging of adenomyomatosis of the gallbladder

The consistency of a request for liver MRI and MR-cholangiopancreatography in a patient with an occasional US-finding of mural thickening of gallbladder fundus > or = 3 mm in size was assessed. The differential US diagnosis in case of focal mural thickening was analyzed in combination with the other findings to justify the radiologicoclinical reliability of the request. Overall, these findings suggested the diagnostic hypothesis of adenomyomatosis, then confirmed by a second level in-depth examination, namely liver MRI and MR-cholangiopancreatography.     

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.     

Polyps of the gallbladder

One of the unusual problems associated with gallbladder disease is a polyp discovered by either ultrasonography or by oral cholecystogram. We report a recent experience of two cases of polyps of the gallbladder removed by cholecystectomy. The incidence of gallbladder polyps of any type is quite varied in the medical literature. Eighty percent of polyps occur in females, and these occur after the third decade of life. The polyps can either be cholesterol or inflammatory polyps that are not really benign tumors but just reactions of the gallbladder wall. The true mucosal benign lesions are either adenomyomas or papillomas. The adenomyomas and papillomas have malignant potential. There are case reports of carcinoma in situ and cancer arising from these lesions. The treatment for a gallbladder polyp is a cholecystectomy.     

胆囊腺肌瘤病20例临床病理分析

目的:探讨胆囊腺肌瘤病的临床病理特点。方法:对817例胆囊切除标本中病理确诊的20例胆囊腺肌瘤病的临床资料进行回顾性分析。结果:20 例胆囊腺肌瘤病临床表 与慢性胆囊炎胆石症类似。病变大体形态:局限型11例(均位于胆囊底部)、节段型7例和弥漫型2例。组织学特征为胆囊黏膜上皮增生、上皮陷于肌层或浆膜下形成数量较多的罗 阿氏窦、以及肌层增生肥厚。结论:胆囊腺肌瘤病是一种好发于成年女性的瘤样病变,此病常与慢性胆囊炎、胆石症并存,临床诊断困难,确诊需依赖病理检查。     

Early carcinoma of the gallbladder: An elusive disease

Prognosis of carcinoma of the gallbladder can be improved by diagnosing the disease in the early stages. Records of 14 patients with early (UICC AJCC TNM stages I and II) carcinoma of the gallbladder were analyzed. Clinical presentation in all these patients was like benign biliary disease. Ultrasonography could diagnose carcinoma of the gallbladder in only five patients; in the remaining nine patients, even the ultrasonographic diagnosis was benign biliary disease. All patients were operated; carcinoma of the gallbladder was diagnosed at operation in two more patients, but it was first detected only after histological examination in seven patients. All patients except four had associated gallstones. Preoperative diagnosis of early carcinoma of the gallbladder is difficult. The only way to diagnose early carcinoma of the gallbladder is by early surgical treatment of patients with clinical features of benign biliary disease. © 1996 Wiley-Liss, Inc.     

原发性胆囊癌基因诊断现状

 原发性胆囊癌（PGC）是胆道系统常见的恶性肿瘤,恶性程度高、预后差。因其临床表现不典型,常与胆囊炎、胆囊结石的症状相似,早期诊断比较困难。而且随着腹腔镜胆囊切除术（LC）在临床上的普及,术后诊断胆囊癌的病例也逐渐增多。因此,如何提高PGC的早期诊断水平,为其早期治疗创造条件一直是人们所关注的问题。现代医学在基因学水平上研究PGC的生物学行为,有助于提高其早期诊断率。就近年来国内外有关PGC基因诊断的研究状况进行综述。     

Minute squamous cell carcinoma of the gallbladder: a case report

Following a simple cholecystectomy, a 63-year-old woman with gallstones was histologically diagnosed as having minute squamous cell carcinoma of the gallbladder. A laparotomy revealed a small, firm nodule that appeared to be an adenoma, which was palpated in the fundus of the gallbladder. The resected gallbladder contained 37 small stones and a small and firm mass (0.4 x 0.4 x 0.3 cm in size) on the mucosal side. Histologically, a pure type of well-differentiated squamous cell carcinoma of the gallbladder was diagnosed. To our knowledge, this is the first case of a minute and pure type of squamous cell carcinoma in the gallbladder. This case may have implications for the histogenesis of squamous cell carcinoma of the gallbladder.     

胆囊癌前病变的病理研究

Precancerous lesions of the gallbladder in 150 consecutive cholecystectomy specimens resected from the patients with cholelithiasis or cholecystitis are studied. Of these specimens, 80% had simple epithelial hyperplasia, 16% atypical hyperplasia, 1.3% carcinoma in situ and 2.7% invasive carcinoma. Atypical hyperplasia was observed in the mucosa adjacent to carcinoma in situ which, in turn, was found in the mucosa adjacent to invasive carcinoma. This finding suggests that some of simple hyperplasia of the gallbladder evolve towards atypical hyperplasia, carcinoma in situ which finally becomes invasive carcinoma. In addition, the authors put forward a morphologic criteria for grading the atypical hyperplasia of the gallbladder.     

抑癌基因PTEN蛋白在胆囊癌中的表达及临床病理意义

目的:研究抑癌基因PTEN蛋白在胆囊癌组织中的表达及临床病理意义。方法:应用免疫组化检测PTEN在20例慢性胆囊炎,30例胆囊癌中的表达,并结合临床病理资料进行分析。结果:PTEN蛋白在20例胆囊炎中全都呈阳性表达,而癌组织中PTEN的表达率为70.0%,癌组织中PTEN蛋白阳性表达与患者性别及年龄无明显相关性,但与组织分化程度明显相关。结论:PTEN蛋白在胆囊癌组织中阳性表达率降低,说明该基因表达下调可能在胆囊癌的发生发展中起重要作用。     

Electrophoretic pattern of proteins in carcinoma of the gallbladder.

Carcinoma of the gallbladder is a common health problem in the northern region of India and in spite of improved diagnostic techniques it is generally diagnosed at an advanced stage. This study was carried out in 60 patients, 30 of whom were diagnosed with gallbladder carcinoma and 30 with cholelithiasis. The protein content in tissue extracts and serum was determined using the Folin method of Lowry. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis was performed for the identification of proteins according to Laemmli. The results showed the mean concentration of total protein in gallbladder tissue of patients with carcinoma of the gallbladder was 51.83 +/- 3.36 mg/g tissue (45.33-57.80) and in patients with cholelithiasis it was 38.82 +/- 9.11 mg/g tissue (29.55-50.99) (P<0.001). Protein electrophoresis of gallbladder tissue from the patients with carcinoma of the gallbladder showed three additional bands of protein (two protein bands were present in the region of 50-55 kDa and the third band was present in the region of 35 kDa), which were absent in the gallbladder tissue of cholelithiasis patients. Mean total protein content in serum was 72.2 +/- 1.73 g/l (67.98-74.99) in patients of carcinoma of the gallbladder, whereas it was 71.01 +/- 3.4 g/l (60.00-78.99) (P>0.05) in the patients with cholelithiasis. Electrophoretic analysis of serum protein revealed at least two additional protein bands in patients with carcinoma of the gallbladder as compared with electrophoretic pattern in cholelithiasis. These two bands were in the range of 80 and 25 kDa proteins. In conclusion, the presence of these new bands of protein in the gallbladder tissue and serum of the patients with carcinoma of the gallbladder indicate their role in the pathogenesis of the carcinoma of the gallbladder.     

化生在胆囊癌组织发生中的意义

 我们应用组织化学和免疫组织化学技术对134例胆囊良恶性病变的各类化生及其化生与胆囊癌的关系进行研究。结果发现，胆囊粘膜上皮异型增生均发生在化生区内，且多数发生在肠上皮化生区内。癌旁组织与异型增生的化生改变相似。65.1%的胆囊癌可见化生改变，分化好的胆囊癌化生出现率高于分化差的胆囊癌(P<0.01)。我们认为胆囊粘膜上皮化生与胆囊癌的组织发生有重要关系，且肠上皮化生尤为重要。     

Organochlorine pesticides in carcinoma of the gallbladder: a case-control study.

Carcinoma of the gallbladder is the third most common malignancy of the gastrointestinal tract in the Eastern Uttar Pradesh and Western Bihar regions of India. The main source of drinking water in this region is the river Ganges, which is heavily polluted with agricultural pesticides. Organochlorine pesticides were estimated in bile by gas liquid chromatography in 60 patients (30 carcinoma of the gallbladder and 30 cholelithiasis) to observe its association with aetiopathogenesis of carcinoma of the gallbladder. The mean biliary concentration of benzene hexachloride (BHC) was found to be significantly higher in carcinoma of the gallbladder (0.0471 ppm) than in cholelithiasis (0.0352 ppm) (P < 0.04). The mean biliary concentration of dichlorodiphenyltrichloroethane (DDT) was also significantly higher in carcinoma of the gallbladder (0.418 ppm) than in cholelithiasis (0.0103 ppm) (P < 0.03). Biliary aldrin and endosulfan concentrations were higher in carcinoma of the gallbladder (0.0008 and 0.00132 ppm) than in cholelithiasis (0.0005 and 0.0126 ppm) but the difference was statistically not significant (P < 0.06 and P < 0.9). The levels of pesticides in blood did not show significant differences in either carcinoma of the gallbladder or cholelithiasis. Significantly high biliary BHC and DDT concentrations suggest that these pesticides might be associated with gallbladder carcinogenesi.     

Polyposis coli associated with adenocarcinoma of the gallbladder. Report of a case

A case of malignant polyposis coli, occurring in a 71-year-old man in association with a primary invasive adenocarcinoma of the gallbladder is presented. The eventuality that the carcinoma of the gallbladder could be a metastasis from the colonic neoplasia was excluded due to the observation in the mucosa of the gallbladder of changes corresponding to carcinoma in situ. This is the fourth case reported of polyposis coli coexisting with a carcinoma of the biliary tract.     

胆囊癌组织的比较蛋白质组学分析

目的 通过分离、鉴定胆囊癌和胆囊良性组织的差异表达蛋白质,探讨可能用于早期诊断或治疗胆囊癌的肿瘤标志物.方法 对6例人胆囊癌组织和胆囊良性组织进行比较蛋白质组学研究,采用双向凝胶电泳分离蛋白,经图像分析识别差异表达的蛋白.应用基质辅助激光解析电离飞行时间质谱(MALD-TOF-MS)鉴定差异蛋白质.采用免疫组化技术对差异蛋白磷脂酰乙醇胺结合蛋白1(PEBP1)进行验证.结果 获得了分辨率和重复性均较好的凝胶蛋白图谱.共筛选出46个在胆囊癌组织中明显差异表达的蛋白点,其中17个蛋白质鉴定成功.在这17个蛋白质中,胆囊癌组织中高表达9个,低表达8个.PEBP1在胆囊癌组织中的阳性表达率为74.0%.结论 成功鉴定了17个胆囊癌相关蛋白,为进一步筛选胆囊癌的诊断、治疗和预后评估的分子标志物奠定了基础.     

热休克蛋白（HSP70）在胆囊癌中的表达及其意义

目的探讨热休克蛋白（HSP70）与胆囊癌的发生及发展的关系。方法用免疫组化S P法检测45例胆囊癌中热休克蛋白的表达情况,并与41例慢性胆囊炎标本做对照。结果热休克蛋白（HSP70）在胆囊癌中普遍呈现高表达,而在慢性胆囊炎组织中不同程度地呈现弱表达;HSP70在胆囊癌组织中的表达明显高于慢性胆囊炎组（P〈0．01）,且强阳性表达高于后者（P〈0．01）。结论胆囊癌是HSP70高表达肿瘤,HSP70在原发性胆囊癌中普遍高表达,提示与胆囊癌的发生发展有关。     

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.     

P-糖蛋白在胆囊良恶性肿瘤中的表达

目的 检测Ｐ－糖蛋白在不同胆囊组织中的表达，以探讨该蛋白与胆囊癌抗化疗特性的关系及作为胆囊生物标志物的潜在价值。方法 采用碱性磷酸酶－抗碱性磷酸酶（ＡＰＡＡＰ）的免疫且化方法，用二种决定簇不同的抗人Ｐ－糖蛋白的单克隆抗体ＪＳＢ－１和ＵＴＣ－２，检测２６例胆囊癌、１４例胆囊良性肿瘤及９例正常胆囊组织中Ｐ－糖蛋白 表达情况，并分析其表达程度与不同临床资料的相关关系。结果 单缺测得Ｐ－糖蛋白在胆囊癌中表     

Copper, zinc, and Cu/Zn ratio in carcinoma of the gallbladder

INTRODUCTION: The exact role of copper and zinc in the etiology of carcinoma of the gallbladder is unclear. Some studies suggest the Cu/Zn ratio is a good indicator of the extent and prognosis in carcinoma of the gastrointestinal tract. The aim of the present study is to estimate the micronutrient profile and Cu/Zn ratio in the serum, tissues, and bile of patients with benign and malignant gallbladder diseases. METHODS: The present study was carried out in 60 patients comprising 30 each of carcinoma of the gallbladder and cholelithiasis, and 30 age and sex matched controls. Copper and zinc levels were estimated in blood, bile, and tissue using a Perkin Elmer Model 2380 Atomic absorption Spectrophotometer. RESULTS: The mean serum zinc levels were significantly lower in patients with carcinoma of the gallbladder than in patients with cholelithiasis and in healthy controls (P < 0.001). The mean serum copper levels were significantly higher in patients with carcinoma of the gallbladder as compared to patients with cholelithiasis and healthy controls (P < 0.001). Biliary and tissue zinc levels were significantly lower in patients with carcinoma of the gallbladder than in patients with cholelithiasis. Biliary and tissue copper levels were higher in patients with carcinoma of the gallbladder than in patients with cholelithiasis. The serum Cu/Zn ratio showed a gradual and significant increase from 1.11 in healthy controls to 1.35 in patients with cholelithiasis and 2.12 in patients with carcinoma of the gallbladder. The biliary and tissue Cu/Zn ratios were also significantly increased in patients with carcinoma of the gallbladder than in patients with cholelithiasis (P < 0.001). CONCLUSIONS: Our data support an association between lower zinc levels and consequently an increased Cu/Zn ratio and carcinoma of the gallbladder. Whether zinc supplementation has a protective effect in preventing carcinoma of the gallbladder needs to be studied further.