原发性胆囊癌30例诊治体会

报道３０例经手术证实的原发性胆囊癌，其误诊率高达３０．０％（９／３０），合并胆囊结石者占８３．３％（２５／３０），肿瘤向肝脏转移者占５３．３％（１６／３０），且转移早；绝大多数胆囊癌是腺癌。结果表明胆囊癌与胆囊结石关系密切，早期治疗效果好，一旦出现肝转移则预后不良。并就有关术式进行了讨论。     

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目的 了解我国胆囊癌人群、地理和时间分布和特征。方法 回顾性分析３９２例全国胆囊癌临床流行病学调查资料;结果 我国胆囊癌（１）占同期胆道疾病构成比的０．４－３．８％,平均为１．５３％;胆囊癌占同期普通外科疾病的构成比为０．１￣１．１％,平均为０．２８％。（２）以老年女性为主。（３）在我国西北和东北地区发病比长江以南地区高。农村比城市发病率高。（４）合并胆囊结石者为４９．７％,患者胆囊结石发生胆囊癌     

3922例胆囊癌相关危险因素的分析

目的 总结全国２８个省市自治区的３９２２例胆囊癌临床流行病学调查（１９８６～１９９８年）的结果。方法 分析了我国胆囊癌和胆囊结石的,胆囊结石大小和胆囊癌的关系,胆结石的病程,以及胆囊腺瘤和胆道蛔虫病和胆囊癌的关系。结果 （１）我国胆囊癌占同期胆道疾病的构成比０．４％～３．８％,平均为１．５３％,胆囊癌在同期普通外科疾病的构成比为０．１％～１．１％,平均为０．２８％。（２）胆囊癌合并胆结石的发生率为     

CD44v6和基质金属蛋白酶-2表达与胆囊癌的侵袭和转移关系

目的 探讨粘附分子CD44v6，基质金属蛋白－2（MMP－2）在胆囊癌侵袭和转移中的作用。方法 采用免疫组织化学方法检测了42例胆囊癌，10例慢性结石性胆囊炎组织中CD44v6和MMP－2的表达。结果 （1）CD44v6阳性表达率在胆囊癌组（64．3％，72／42）明显高于慢性结石性胆囊炎组（0％，0／10）（P＜0．005）；CD44v6表达强度与胆囊癌的病理学分级相关（P＜0．05），低分化与中，高分化组差异有显著性（P＜0．01）；胆囊癌中转移组阳性率明显高于非转移组（P＜0．01），CD44v6阳性的胆囊癌病人预后较差。（2）MMP－2在胆囊癌组织中表达率（61．9％）明显高于慢性结石性胆囊炎组（10％，P＜0．005）；MMP－2的表达与胆囊癌细胞的分化，转移和预后有关（P＜0．05）；随着分化程度的恶化，其阳性率增高；93）CD44v6和MMP－2在胆囊癌组织中表达呈正相关（P＜0．005）。结论 CD44v6，MMP－2的表达与胆囊癌分化，转移及预后有关，在胆囊癌细胞的侵袭和转移中起重要作用。联合检测有利于评估胆囊癌的生物学行为和判断预后。     

56例胆囊癌的预后因素分析

目的：研究影响胆囊癌预后的因素，探讨提高胆囊癌疗效的途径。方法：回顾性分析了1995年6月至2001年6月收治的56例胆囊癌的临床资料。结果：56例中男20例，女36例，其中34例（61％）合并胆结石。腹痛（47／56，占84％）和黄疸（23／56，占41％），是主要临床症状。B超，CT，CA19－9有助于术前诊断。30例（包括Nevin Ⅱ5例，Ⅲ3例，Ⅳ4例，Ⅴ18例）获得根治性切除或扩大根治性切除，11例NevinⅤ期予以姑息性切除，剖腹探查行改善症状的各种引流术或／和活检术15例。统计学分析显示，生存时间与手术方式，Nevin分期，放疗，化疗，是否合并胆囊结石5个因素呈显著相关。结论：提高胆囊癌的早期诊断率，积极施行根治性切除术，辅以放疗，化疗，可望改善胆囊癌的疗效。     

新疆温宿县成年人胆囊结石患病率调查

目的 了解新疆温宿县成年人胆囊结石的发病情况。方法 2003年7月至2004年7月对多级抽样的18岁以上3199名温宿县居民作空腹胆囊超声检查及问卷调查。统计分析采用SPSS11．5软件包。卡方检验，多因素分析采用Logistic逐步回归。结果 2．4％已行胆囊切除术；温宿县成年人胆囊结石的患病率为13．2％（男性为6．6％，女性为16．6％），其中无症状者占70．9％（292／412）；胆囊结石患病率随年龄的增加而升高，40岁以后高发；维吾尔族（13．7％）和其他少数民族（12．6％）均显著高于汉族（3．8％）（P〈0．001），每日肉食摄入量〉100g者（16．4％）高于肉食摄入〈50g者（14．4％），喜欢油腻食物者（15．6％）显著高于不喜欢油腻食物者（9．6％），脑力劳动者（13．4％）高于体力劳动者（11．8％）。睡眠时间不足8小时者（16．2％）高于超过8小时者（11．6％），肥胖指数〉25者胆囊结石患病率20．9％，高于肥胖指数为23-25者（15．8％）和〈23者（10．0％）。结论 新疆温宿县成年人胆囊结石患病率较高，多因素分析显示胆囊结石发病率与性别、年龄、民族、饮食结构、营养状况、工作性质、睡眠时间、肥胖指数等相关。     

23例胆囊癌回顾性分析

对23例手术并经病理证实为胆囊癌的病例进行回顾性分析。23例患者,男性8例,女性15例,平均年龄64．7±8．6（岁）,21例伴有胆囊结石或／和胆管结石,占91．30％,平均胆石症病程6．9年,临床术前诊断符合率34．78％（8／23）,肿瘤切除率43．48％（10／23）,组织学类型22例为腺癌,1例为未分化癌。认为胆囊癌多与胆石症并发存在,常发生于病史长,年龄较大的胆石症患者,故对长期病程的高龄胆石症病人要警惕癌变的可能,对这些高危人群宜尽早手术。     

血管内皮生长因子及其受体Flt-1和KDR在原发性胆囊癌的表达及其与临床病理特征的关系

目的探讨血管内皮生长因子（VEGF）、Flt-1和KDR的表达与原发性胆囊癌临床病理特征的关系。方法对21例原发性胆囊癌和10例胆囊腺瘤样息肉新鲜组织标本采用逆转录-聚合酶链反应（RT-PCR）和免疫组织化学染色在mRNA和蛋白水平检测VEGF、Flt-1和KDR在原发性胆囊癌和胆囊腺瘤样息肉的表达情况，并分析VEGF、Flt-1和KDR免疫组织化学阳性表达的病例与胆囊癌肝浸润、淋巴转移、病理分级和Nevin分期等临床病理特征的相关性。结果在胆囊癌和胆囊腺瘤样息肉组织中VEGF mRNA阳性表达率为90．47％（19／21）和20％（2／10）；Flt-1mRNA阳性表达率为71．42％（15／21）和0％（0／10）；KDR mRNA阳性表达率为85．71％（18／21）和10％（1／10）；两组差异有统计学意义（P〈0．05）。免疫组织化学染色VEGF蛋白检测阳性表达率为80．95％（17／21）和20％（2／10）；Flt-1蛋白阳性表达率为60．90％（13／21）和10％（1／10）；KDR蛋白阳性表达率为76．19％（16／21）和10％（1／10），两组差异有统计学意义（P〈0．05）。VEGF、Flt-1和KDR蛋白的阳性表达率在胆囊癌肝浸润、淋巴转移和NevinⅣ、Ⅴ期组明显高于无肝浸润、无淋巴转移和NevinⅠ、Ⅱ、Ⅲ期组（P〈0．05），而在高、中和低分化组三者的阳性表达率无统计学意义（P〉0．05）。结论原发性胆囊癌组织中VEGF、Flt-1和KDR在mRNA和蛋白水平均存在高表达，VEGF、Flt-1和KDR蛋白的阳性表达同胆囊癌肝浸润、淋巴转移和Nevin分期明显相关，但与病理分级无明显相关。     

选择性颈胸腹三野淋巴结清扫治疗胸段食管鳞癌

目的 研究胸段食管鳞癌的淋巴结转移规律，探讨合适的淋巴结清扫范围。方法 87例接受食管次全切除术的胸段食管鳞癌患者，根据术前食管腔内超声和颈部超声检查结果，选择性进行胸腹二野或颈胸腹三野淋巴结清扫。结果 超声发现颈部淋巴结肿大并行三野清扫35例（40．2％，三野清扫组），其中原发肿瘤位于胸上段食管者的比例（16／24例，66．7％）显著高于中、下段肿瘤者（19／63例，30．2％）（P=0．002）。三野清扫术扫除淋巴结13．7组／例，显著多于二野清扫组（52例，59．8％）的10．5组／例（P〈0．001）。术后病理检测三野清扫组转移淋巴结1．5组／例，也显著多于二野清扫组的0．8组／例（P〈0．01）。颈淋巴结转移（pM1-LN）17例（占全组19．5％，占三野清扫组48．6％），有区域淋巴结转移者的颈淋巴结转移比例（15／48例，31．3％）显著高于无区域淋巴结转移者（2／39例，5．1％）（P〈0．01）。上、中、下纵隔及上腹部的淋巴结转移率分别为25．3％、23．O％、5．7％和24．1％，颈淋巴结转移与上纵隔（P〈0．01）及中纵隔（P〈0．01）淋巴结转移显著相关，但与下纵隔及上腹部淋巴结转移无关。三野清扫组术后并发症发生率（60．0％）显著高于二野清扫组（34．6％，P=0．020）。喉返神经损伤发生率两组差异无统计学意义（P〉0．05）；但喉返神经损伤者吻合口瘘发生率（7／13例，53．8％）显著高于无喉返神经损伤者（10／74例，13．5％，P=0．001）。术后死亡率两组差异无统计学意义（P〉0．05）。结论 应对肿瘤位于胸上段食管、或上纵隔及中纵隔淋巴结已发生转移的食管癌患者在超声指导下进行选择性颈胸腹三野淋巴结清扫术，以降低手术风险、提高手术根治效果。     

黏蛋白1在胆囊癌中的表达和意义

目的 探讨黏蛋白1（MUC1）在原发性胆囊癌组织中的表达及其在胆囊癌诊断和免疫治疗中的意义。方法 采用免疫组化方法检测42例原发性胆囊癌组织和17例正常胆囊组织中MUC1的表达。结果 MUC1在胆囊癌组织中的阳性表达率为76．19％，明显高于正常胆囊组织（29.41％），两组存在统计学差异（P〈0．05）。MUC1在胆囊癌组织中阳性表达率与胆囊癌组织病理类型、组织学分化、淋巴结转移及Nevin分期也有相关关系。但与有无合并胆囊结石无相关关系。结论 MUC1可作为胆囊癌患者预后评价指标，有可能作为肿瘤微转移的诊断及免疫治疗的靶抗原。     

Number and size of stones in patients with asymptomatic and symptomatic gallstones and gallbladder carcinoma: A prospective study of 592 cases

The development of gallbladder carcinoma has been correlated with the presence of a single large gallstone in two retrospective studies. The objective of the present study was to determine the number and size of gallstones in patients with gallbladder carcinoma compared to asymptomatic and symptomatic female patients with gallstones. The following three groups of patients were included in this prospective trial: (A) 78 asymptomatic patients with gallstones; (B) 365 symptomatic patients with gallstones; and (C) 149 patients with gallbladder carcinoma. At the end of the operation, the resected gallbladder was opened and the number of stones counted. The maximum size of the stones was determined using calipers. Patients with gallbladder carcinoma were significantly older than patients in the other two groups (P <0.001). In the group with asymptomatic gallstones, there were significantly more patients with one single stone, whereas in the group with gallbladder carcinoma there were significantly more patients with multiple stones (more than 11; P <0.01). Patients with gallbladder carcinoma had significantly larger stones, regardless of the number of stones present (P <0.001). We postulate that the increase in the number and size of the stones among patients with gallbladder carcinoma could simply be an effect of aging or it could be a reflection of the long-term presence of stones in the gallbladder rather than some particular chemical or physical influence.     

胆囊癌引起梗阻性黄疸的原因分析

目的 探讨胆囊癌引起梗阻性黄疸的病因.方法 回顾分析我院2000 ～ 2009年10年间84例胆囊癌患者资料.结果 42例出现黄疸,其中肿瘤侵犯肝脏或发生肝内转移9例,肿瘤侵犯肝总管、胆总管11例,肝十二指肠韧带、胰头部肿大淋巴结7例,胆总管结石4例,两种及两种以上上述情况的11例.结论 胆囊癌引起梗阻性黄疸的原因多样...     

胆囊结石并发胆囊癌43例分析

目的 胆囊结石与胆囊癌的发病关系。方法 回顾14年我院收治6000例胆囊结石并发43例胆囊癌，此43例，具有结石病史长，结石大并多次发作胆囊炎症，病理见胆囊上皮增生合并癌变。结果 胆囊结石对胆囊长时间刺激是致癌因素之一，结论 为了早期诊断，早期治疗以及预防胆囊癌，对部分胆囊结石患者应行有选择的预防性胆囊切除术。     

p27蛋白在原发性胆囊癌中的表达及其意义

目的探讨p27蛋白在原发性胆囊癌中的表达及其意义.方法应用免疫组织化学SABC法检测原发性胆囊癌中p27蛋白的表达.结果p27蛋白在原发性胆囊癌中的阳性表达率为25%(11A4),低于良性病变(P<0.05),p27蛋白表达在肿瘤不同病理分级中未见明显差异(P>0.05),但与Nevin分期呈显著负相关(P<0.05),有癌转移者明显低于未转移者(P<0.05).结论p27蛋白可作为原发性胆囊癌的生物学标记物.     

Primary "brown pigment" bile duct stones

Bile duct stones from 42 patients were morphologically and chemically analysed. The calculi from 27 patients had important primary bile duct stone (PBDS) features, consisting of a general ovoid shape and fragile structure, with alternating light and dark brown pigmented layers on cross-section. Chemically these stones contained low levels of cholesterol, with high levels of bilirubin and calcium. Subsequent infrared spectroscopy analysis showed that calcium bilirubinate and calcium palmitate were the only calcium salts present. Calcium palmitate was prominent in the light brown layers. A morphological and chemical comparison with gallbladder stones showed that bile duct "stasis stones" were similar in morphological and chemical composition to the brown pigment gallbladder calculi. However, they were distinct from most gallbladder stones, indicating that primary bile duct calculi have an aetiology that is different to 90% of gallbladder calculi. Primary bile duct calculi were observed to occur with or without the presence of a gallbladder, and more interestingly, in the bile duct of two patients with cholesterol gallbladder stones. Bile duct bile of patients with primary choledocholithiasis were always moderately to profusely infected and with abundant calcium bilirubinate precipitation. Moreover, this study has shown that PBDS chemical analyses profiles were consistent and correlated well with their defined morphology. Consequently, PBDS may be accurately identified at the time of operation by morphology. An important aetiological factor would appear to be infection, which would seem to promote bile duct bile stasis and eventual stone growth.     

Composition and morphologic and clinical features of common duct stones

No systematic study of the composition of common duct stones has been carried out to date. In this study, we assessed the chemical composition and morphologic characteristics of common duct stones from 115 patients, and compared them with gallbladder stones in 67 patients who had both. Visually and chemically, common duct stones could be divided into two groups: cholesterol stones and pigment stones. Cholesterol common duct stones contained 83 ± 1 percent cholesterol, 2.3 ± 0.4 percent bilirubin, and 5.5 ± 1 percent insoluble pigment residue. Pigment common duct stones contained 7 ± 1 percent cholesterol, 24 ± 2 percent bilirubin, and 38 ± 3 percent pigment residue. There were two subgroups of pigment stones: one with large amounts of bilirubin and one with large amounts of pigment residue. A high proportion (46 percent) of common duct stones were composed of pigment. Patients with pigment common duct stones were more likely to have cholangitis and pancreatitis than were patients with cholesterol stones. It was not possible to distinguish primary from secondary stones on morphologic grounds.In 65 of 67 patients (97 percent), gallbladder stones and common duct stones were of the same chemical type. Morphologically, cholesterol common duct stones were very similar (3.6+ on a scale of 0 to 4+) to their counterparts. Pigment common duct stones and gallbladder stones were less similar (2.4+). Chemically, cholesterol common duct stones were identical to their gallbladder counterparts. Pigment common duct stones regularly contained a greater fraction of bilirubin and less pigment residue than associated gallbladder stones (p < 0.05). Earthy common duct stones were associated with earthy gallbladder stones, and were chemically indistinguishable from other pigment stones.These data suggest that all cholesterol common duct stones, and when the gallbladder is present, most pigment common duct stones, are secondary. The latter stones, however, probably grow after entering the duct, adding pigment with a high proportion of bilirubin relative to pigment residue.     

Spontaneous necrosis of gallbladder carcinoma in patient with pancreaticobiliary maljunction

While gallbladder carcinoma is occasionally associated with pancreaticobiliary maljunction, spontaneous necrosis of carcinoma is extremely rare. We herein present a case of spontaneous necrosis of gallbladder carcinoma associated with direct invasion of viable cancer cell nests to the muscularis propria and subserosal layer located beneath the primary nodules. A 65-year-old Japanese man was admitted to a local hospital, complaining of repeated discomfort in the right hypochondrium. Ultrasonography and computed tomography scanning revealed cholecystitis associated with gallstones. Cholecystectomy was performed, and operative cholangiography demonstrated pancreaticobiliary maljunction. The resected gallbladder showed multiple mixed stones filled with necrotic debris and bile sludge. Scrutiny of the mucosal surface revealed multiple small necrotic nodules in the fundus, which were histologically confirmed to be necrotic remnants of a cancerous glandular structure. Small nests of papillary adenocarcinoma were found beneath the nodules in the muscularis propria and in the venous structure located in the connective tissues next to the divided margin of the gallbladder bed. Resection of S4a and S5 of the liver and resection of the extrahepatic bile duct was then performed to remove the remaining cancerous tissues and/or micrometastasis in the liver and bile duct. The biliary tree was reconstructed with a hepaticoduodenostomy. No cancer nests or any precancerous lesions were found in the additionally resected specimens. This case indicates a unique morphological feature of gallbladder carcinoma associated with pancreaticobiliary maljunction, which provides some insight into the pathogenesis of spontaneous necrosis of gallbladder carcinoma. Received: August 8, 2000 / Accepted: October 26, 2000     

意外胆囊癌的外科处理

随着腹腔镜技术的普及,腹腔镜胆囊切除术中、术后发现的意外胆囊癌逐渐增多。高龄、结石病史等胆囊癌高危因素与意外胆囊癌相关;术中操作、人工气腹等原因可导致肿瘤的种植转移。胆囊癌外科治疗的关键在于早期发现,不同分期的胆囊癌应采用不同的手术方式,肿瘤的分期是最重要的预后因素。     

保留迷走神经肝胆支的胃癌根治术对胆囊功能的影响

目的　探讨胃癌根治术附加胆囊切除术的必要性。　方法　选取 1999年 ~2001年我院保留迷走神经肝胆支的胃癌根治术 80例,测量术前、术后空腹胆囊容积、胆囊收缩功能及胆囊结石情况并进行对照分析。　结果　术后空腹胆囊收缩功能较术前明显降低(P<0. 01),术后 2年检查发现有 8例(10. 12% )胆囊结石发生。　结论　胃癌根治术附加保留迷走神经肝胆支不能完全预防术后胆囊炎、胆囊结石的发生;胃癌根治术附加胆囊切除术有其必要性。     

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??Gallbladder stones and gallbladder carcinoma JIANG Zhao-yan, HAN Tian-quan, ZHANG Sheng-dao. Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute of Digestive Surgery,Shanghai 200025, China
Corresponding author: HAN Tian-quan, E-mail: digsurgrj@yahoo.com.cn
Abstract Gallbladder carcinoma is difficult to be early diagnosed leading to poor prognosis. The pathogenesis of gallbladder carcinoma is not clear. Cholelithiasis is shown to be associated with gallbladder carcinoma. Mechanical irritation, bacterial infection, xenobiotic in the bile may induce the carcinogenesis of gallbladder epithelium. Several risk genes associated with gallstone disease are also shown to be related with gallbladder carcinoma. Proper treatment of gallstone disease may provide a protective role in prevention of gallbladder carcinoma.