【请教】:疑似胆囊癌病变的确诊及治疗
诸位高手,现有一老年男性患者,以胆囊占位性病变入院治疗,肝区有些疼痛,尤以背侧为甚,肝功能基本正常,仅黄疸指数稍高,CT检查未发现结石,胆道基本无堵塞,胆囊壁增厚,胆囊增大,也未见肿瘤,已排除胰腺炎，肝部病变。甲胎抗原及癌胚抗原检测阴性。入院10天，以胆囊炎治疗（曲松钠加一些中成药），肝区现仅有些轻微胀痛，但胆囊体积未见缩小。患者入院至今饮食及大小便均非常正常，现主任认为是胆囊癌，要求切除，请教高手，这么做是否草率？还有何方法可以确诊？这种疑似胆囊癌病变应如何治疗？转自丁香园
1、不知道这例患者原来有没有胆道结石和胆囊炎反复发作的病史。
2、CT检查“胆道基本无堵塞”是否表明仍疑有胆道病变（如轻微的狭窄）？若是，我认为有必要ERCP明确有无肝内外胆道病变。
3、有无胆囊炎症的其他证据，如发热及热型，白细胞高等。抗感染治疗后相关指标如何变化？
从现在的资料看，这例患者可能是慢性胆囊炎、病变较小的胆囊癌（尚未出现明显可见的占位及局部压迫症状如梗阻性黄疸等），或良性胆囊肿瘤。
这3种情况在不经手术，很难从临床上区分开来。尤其病变较早期的胆囊癌，绝大多数是在手术后病理学检查证实的。鉴于患者老年、有症状、怀疑胆囊占位性病变，而抗感染治疗似乎效果不佳。我认为，若患者条件允许，选择腹腔镜胆囊切除应该是首选的方案，开腹手术次选，短期随访最下。因为对病变进展至明显的胆囊癌，术后5年生存率实在太低。
甲胎抗原及癌胚抗原这些血清肿瘤标记物，对胆囊癌的确诊和排除，意义不大。 这位朋友的描述欠清楚，特别是胆囊壁增厚的情况和详细病史。这些在诊断中会有较大的作用，尤其是竟然没有描述超声检查的情况。在胆道疾病的诊断中，一个可靠的超声诊断要比普通的CT有更重要的价值！
关于治疗，应该剖腹探查。
怀疑上级大夫的判断是年轻大夫成长中的重要一环，只有不断怀疑，不断求证才能更快的进步。但是要在理解上级大夫的根本意图上下点功夫。本例中，主人肯定有自己采取手术治疗的依据，你有没有了解过？对于诸如胆囊癌之类早期诊断困难，晚期疗效极差的病例，经验是很重要的判断因素。本身剖腹探查就是一个诊断的过程，也是一个治疗的过程。对于老年无结石性胆囊炎的治疗不能过于保守！况且，根据流行病学资料提示，此类患者诊断为胆囊癌的可能性较高。
剖腹探查在临床实际中对于那些经济较为困难的患者来说，避免了过多辅助检查的经济负担，恰当的剖腹探查是很多实际情况下的最佳选择。 昨天做的胆囊CT三维成像加口服胆囊照影的结果出来了，患者胆囊可以排空，但碘制剂未被胆囊吸收，所以照影的结果不好，三维成像的结果除了胆囊内壁不规则收缩外也未发现结石及肿瘤（3mm扫描）。患者前日遵放射科医嘱食用油性食物后，胆囊未疼痛，但有油性稀便（一日2次）。
患者白细胞数量一直不高，入院初也只有1.1万，以后也一直是1万左右，中性粒细胞有些增高，抗感染治疗后白细胞稍有下降。体温一直未超过37度。
B超检查结果发现，胆总管有轻微扩张，胆囊壁厚0.7cm,脂肪肝，胆囊占位性病变。
患者从未因胆囊病变求医，但自述一年前开始有相似症状（后背部疼痛可放射至右肩部），但自贴膏药或拔火罐后即缓解。本次入院后也只疼痛了2－4天。
另患者有原发性高血压、冠心病，脑基底部有脑梗，但未显明显功能障碍。
我认为很可能是慢性胆囊炎。可否不手术？ **** Hidden Message ***** 该患者胆囊壁厚0.7cm且外周血象wbc偏高，首先考虑胆囊炎，不能完全排除胆囊隆起样变，按理CT（增强扫描）应该能提供一定的诊断依据，是否可与影像科同仁一起读片。
处理原则：尽早行开腹胆囊切除术，术中根据情况决定是否快速病理。腹腔镜对该患者没有必要。 1是否可以做一下MRCP,较为彻底明确胆管问题。
2在改善全身情况后，尽早手术。
3如果怀疑肿瘤，还有必要谈什么腹腔镜吗？
4如果术中证实肿瘤，胆囊加局部肝切除应当可以。不宜再扩大，毕竟基础疾病多。 我在最近一年碰到过4例胆囊癌，有2例是术中发现，1例术前并没有考虑胆囊癌，但是由于病人有黄疸，由于b超胆总管下端显示不清（没有提示胆囊癌）而行mrcp发现胆囊癌，还有一例外院行腹腔镜胆囊切除，术后病检提示胆囊癌，病人没有进一步手术治疗，2月多过后，复查ct提示肝左叶占位，约直径6cm大小，病人没有梗阻症状，显示还有切除机会，但开进去以后，发现肝十二指肠韧带已经完全粘成一把，肝门无法解剖，只好放弃手术。
所以我的感觉是，只要怀疑胆囊癌，一定要开腹行标准的胆囊切除＋肝切除＋肝十二指肠韧带骨骼化，否则做了在多，都可能是无用功 REVIEW
Carcinoma of the gall-bladder
E Kyriacou
Carcinoma of the gall-bladder remains the fifth commonest gastrointestinal malignancy. Its associations, predisposing factors and epidemiology worldwide are reviewed in this article. The clinical presentation of carcinoma of the gall-bladder is frequently late, which accounts for the poor prognosis: this is also discussed. The use of relevant imaging techniques and aggressive management offer an improved outlook. These important aspects and others, such as the use of frozen section histology, the risks of trocar seeding and inadequate resection are mentioned.
INTRODUCTION Go to: Choose Top of page INTRODUCTION << PREDISPOSING FACTORS GENETIC STUDIES CLINICAL FEATURES PROGNOSIS OF STAGING AND ... CONCLUSION REFERENCES References
Gall-bladder cancer is not common: it accounts for less than 1% of all cancer deaths. 1 Older reports quote an approximate figure of 6000 for deaths due to gall-bladder cancer per year in the USA, 2 whereas a more recent paper quotes this as approximately 5000. 3 The figure is certainly not rising, at least. 3 Primary carcinoma of the gall-bladder occurs in approximately 1% of patients coming to cholecystectomy. 4,5 It remains the fifth commonest gastrointestinal malignancy and the commonest lesion in the biliary tract. 6 It is more common with advancing years, especially in women. 1,4 7 The youngest case reported in the literature was male and 22 years old, 6 which is exceptionally rare. Gall-bladder cancer accounts for up to 10% of all deaths in women and is more prevalent in certain populations or countries, such as American Indians. 6,8 11 Abnormal hepatic bile with low ratios of bile acid and lecithin to cholesterol have been identified in the South-Western American Indian populations studied. 12,13 In South America, the highest prevalence observed was in Chile, Mexico and Bolivia. 6,14 It is also commoner in some populations in Central Europe, especially Poland, 15 but also Hungary, Germany, Czechoslovakia and Austria. 1
PREDISPOSING FACTORS Go to: Choose Top of page INTRODUCTION PREDISPOSING FACTORS << GENETIC STUDIES CLINICAL FEATURES PROGNOSIS OF STAGING AND ... CONCLUSION REFERENCES References
Certain predisposing factors have been linked to gall-bladder cancer. In the population-based case-control study by Zatonski et al., 73 cases and 186 controls were interviewed. 1 Fifty-six per cent of cases and 8% of controls had a previous history of gall-bladder disease, although the breakdown of the pathology was not given in the paper. The odds ratio (OR) for a previous history of gall-bladder disease was 12.5, with an overall 95% confidence interval (CI) of 5.8-26.6. 1 Previous gall-bladder disease, notably cholelithiasis, was the major determinant of subsequent gall-bladder cancer and the association with gall-bladder disease appeared to pre-date the onset of gall-bladder cancer by > 20 years (OR 12.1, CI 0.8-7.3). This ties in well with epidemiological data that it is more common in women and in the obese. 16 20 Other studies report a consistent link with gallstones, 4,21 29 although this link is not causal. 28 The aetiology is likely to be multifactorial and may be due to chronic mechanical irritation, biliary stasis, the presence of infection, host susceptibility, metabolic and various other exogenous factors. 28 The prevalence in females may be partly or largely hormonal in aetiology. How important other confounding factors, such as obesity, diet, smoking, presence of coexistent diabetes, pancreatic or other systemic illnesses are, is difficult to determine. These factors have been previously linked epidemiologically with a higher incidence of cholelithiasis, 28,30 33 even if the relationship with gall-bladder cancer is weak and not causal.
The study by Zatonski et al. showed lifetime smoking and coffee consumption were not related to gall-bladder cancer. 1 In that study, there was an inverse relationship with vitamin C, E and fibre, but only the vitamin C result reached statistical significance and that was weak. The same study reports a mildly protective effect of drinking tea, the meaning of which is unclear. There was also a small, non-significant increased risk with vodka intake. 1 A recent Indian study found a high incidence of carcinoma of the gall-bladder in patients with blood groups A and AB. 34
It is also known that anatomically anomalous cystic and biliary ducts are more frequently linked with gall-bladder carcinoma. 29,35 38 This occurs especially in cases where the gall-bladder has a very low junction or an anomalous pancreaticobiliary junction, especially in those without congenital cystic common bile duct dilatation. 29,35 38 The mechanism of this is unclear, but bile stasis possibly alters bile acid biochemistry producing abnormal bile acids making mucosal inflammation more likely; alternatively, reflux of enzyme-containing pancreatic juice could be mutagenic or an irritant to the gall-bladder mucosa. 23,35
GENETIC STUDIES Go to: Choose Top of page INTRODUCTION PREDISPOSING FACTORS GENETIC STUDIES << CLINICAL FEATURES PROGNOSIS OF STAGING AND ... CONCLUSION REFERENCES References
More recently, genetic, immunohistochemical and molecular biology techniques have been applied to further explore the pathogenesis of this malignancy. The p53 tumour suppressor gene, located on the short arm of chromosome 17, has roles in cell division and apoptosis. Mutations of this gene are the most frequent genetic abnormality found in human tumours. 38,39 The p53 tumour suppressor gene has been studied in various gastrointestinal malignancies, such as those of the liver and biliary tract. 39 42 In addition, gall-bladder cancer is being studied and the data suggest a correlation exists between p53 abnormalities and the development of gall-bladder carcinoma. 39 In one study, eight of 11 gall-bladder carcinomas expressed marked p53 immunopositivity. 39 p53 Protein expression was related to higher grades of malignancy and it was postulated that this could be explained by the relatively late presentation of many tumours due to the deep-seated location of the gall-bladder, delaying diagnosis. 39 The k-ras mutation has also been investigated in the wider context of the liver and pancreaticobiliary tract 43 and more recent evidence suggests the k-ras mutation may also be an important factor in the early stage of carcinogenesis when associated with an anomalous junction of the pancreaticobiliary tract. 44 Malats et al. found that k-ras 12 mutations were an independent prognostic indicator in patients with extrahepatic biliary system cancer, including gall-bladder cancers and also postulated that mutations at codons 13 and 61 might have oncogenic potential. 43 Biliary phospholipase A2 is also associated with such cancers. 35,36 Most carcinomas of the gall-bladder are adenocarcinomas; other gall-bladder tumours include sarcoma, melanoma, leiomyosarcoma, signet-ring cells and spindle cells. 6
CLINICAL FEATURES Go to: Choose Top of page INTRODUCTION PREDISPOSING FACTORS GENETIC STUDIES CLINICAL FEATURES << PROGNOSIS OF STAGING AND ... CONCLUSION REFERENCES References
The clinical presentation of carcinoma of the gall-bladder is frequently late and usually asymptomatic for some time, which accounts for the poor prognosis. 28,45,46 Three presentation patterns mainly occur: 28 (i) absence of symptoms (unless benign gall-bladder disease occurs concomitantly, causing right upper quadrant pain, nausea and fatty food intolerance); (ii) pain and obstructive jaundice; and (iii) a hidden primary malignancy presenting with marked weight loss, poorly localized pain or vague symptoms. 28 Liver metastases are usually present if the alkaline phosphatase level in blood is raised. 28 In one study, the main presenting symptoms were right upper quadrant pain in 52% of cases, weight loss in 44% and jaundice in 40%. 45 Interestingly, 48 of 69 cases of cancer of the gall-bladder were found to also have gallstones, confirming previously discussed epidemiology. 45
PROGNOSIS OF STAGING AND SPREAD Go to: Choose Top of page INTRODUCTION PREDISPOSING FACTORS GENETIC STUDIES CLINICAL FEATURES PROGNOSIS OF STAGING AND ... << CONCLUSION REFERENCES References
Five year survival is usually quoted as less than 5%. 33 In one study, the overall 5 year survival was only 1.4%, with a 4.5 month mean survival time. 45 Even post- resection, the prognosis is < 5% overall, but is better when the cancer is confined to the mucosa, giving at least 64 and 44%, 5 and 10 year survival rates, respectively. 30,47 More importantly, Japanese postoperative 5 year survival rates, especially after extended cholecystectomy for gall-bladder carcinomas limited to the mucosa, are nearer to 100%. 46 Figures such as these are achieved by resected specimens being sectioned every 3-5 mm and histology being performed to prevent advanced carcinomas being misdiagnosed as early ones. Survival, therefore, depends on grade and histological stage. In-depth description of staging and tumour node metastasis classification is beyond the scope of this review and is well reported elsewhere. 46 Briefly, stage I tumour is limited to the gall-bladder wall, stage II involves the local gall-bladder and regional lymph nodes, stage III involves extension to adjacent organs and at stage IV distant metastases are present. 6 Five year cumulative survival rates fall as the stage increases from I to IV, from average values of approximately 80% in stage I to 8% in stage IV, respectively. 46
Of the different histological types, papillary carcinoma has the most favourable prognosis, quoted in one study as 47% at 2 years. 6 Higher tumour grades are associated with poor survival rates. 46 50
In a recent study, 87 patients with cancer of the gall-bladder were investigated in order to predict which factors negatively influenced survival using univariate and multivariate analyses and it was found that the presence of a palpable mass, tumour status and stage, local infiltration including lymphadenopathy, distant metastases and resection type (bypass vs full resection) were significantly implicated. 48 Gall-bladder cancer limited to within the Rokitansky-Aschoff sinus is usually regarded as an early lesion. 49,51
Hyperplastic polyps less than 6 cm are not premalignant, 52 as they represent reactive overgrowth. Adenomas and dysplasia are widely accepted as pre-cancerous. 52 Spread occurs via nodal metastases to pericholedochal and pancreaticoduodenal nodes and direct extension to surrounding structures as well as venous invasion into local blood vessels. Blood-borne metastases occur but are uncommon. 30,53 Most patients who survive long term after surgical resection are those who were operated on for cholecystolithiasis and were found incidentally to have carcinoma of the gall-bladder. In Japan, early carcinoma of the gall-bladder is defined as that invading, but confined within, the muscularis propria. 54 Simple cholecystectomy is widely regarded as adequate for non-invasive gall-bladder cancer and achieves cure if the resection margins are clear on microscopy. 30,46,54 In Japan, cholecystectomy tends to be performed whenever a gall-bladder full of stones is identified, where the stones are > 1 cm in size or where a thickened gall-bladder wall is found on ultrasound (the best imaging modality in this situation to date) or an equivocal cholangiogram (oral or intravenous) where the gall-bladder outline is not identified entirely. 46 It has, therefore, been advocated that during cholecystectomy the gall-bladder should be opened and frozen sections of suspicious lesions taken, as carcinoma in situ is well treated by cholecystectomy alone, but micro-invasive carcinoma requires wider resection (usually wedge resection of locally adjacent liver) and dissection of lymph nodes in the porta hepatis. 30,55
Newer techniques in imaging, such as the use of colour Doppler ultrasound to aid in the early diagnosis of gall-bladder carcinoma have been used with promising results. 55,56 Colour signals are seen within the lesions and the gall-bladder wall and high-speed resistive indices (1.0) are typically found on fast Fourier transform analysis. These are accompanied by abnormal blood flow velocities and represent neovascularization and abnormal haemodynamics. 55 This non-invasive method is clearly more advantageous than angiography, but does need further evaluation in a much larger series of patients. Radiological techniques commonly in use include conventional and endoscopic (more expensive) ultrasound. Computerized tomography scanning and cholangiography are less commonly used. Recently, ultrasound-guided percutaneous transhepatic fine needle aspiration cytology (PTFNAC) has been used in the differential diagnosis of polyps larger than 1 cm, 57 where it correctly identified cholesterol polyps and adenomas, as well as one case of adenocarcinoma in a polyp, but missed 75% focal malignant change confined to the mucosa. It also misdiagnosed three benign lesions (adenomyomatosis, chronic cholecystitis and a gallstone with a poor acoustic shadow). 57 Therefore, one must have reservations as to its reliability at this early stage. The authors advocated the procedure as being free of tumour seeding after 25-32 months of follow up. 57
Certain conditions, such as adenomyomatosis, which although benign are associated with gall-bladder wall thickening based on radiology should be differentiated histologically from carcinoma. 33,58 Xanthogranulomatous cholecystitis is known to masquerade as carcinoma of the gall-bladder and diagnosis may only be made definitively on histology. 59 Ultrasound should be performed on all patients early in the investigation as it enhances the detection of early gall-bladder carcinoma. 60 Polypoid lesions found on ultrasound are more likely to be malignant if large. 60 For gall-bladder adenomas or true polypoid adenomas, there is a risk of malignant change which tends to be size (greater than 10 mm) and depth dependent. 33,60,61 There is an established adenoma-carcinoma sequence which accounts for the histogenesis of gall-bladder cancer. 33 65 In one study, histopathological examination was conducted on 1605 cholecystectomy specimens. 61 This showed clear transition of benign adenoma into carcinoma and, furthermore, no case of de novo carcinoma was found in any of the 79 cases of invasive carcinoma. 61 The most common pathway to adenocarcinoma histogenetically is via the metaplastic gall-bladder epithelium. 62,63,65 Eighty-four per cent of gall-bladder cancers are adenocarcinomas, either well, moderately or poorly differentiated. The rest are papillary, mucinous or colloid carcinomas. 63 The other type of adenoma-carcinoma evolution is derived form non-metaplastic or normal epithelium, beginning with epithelial hyperplasia and progressing through dysplasia to adenocarcinoma. 64
The increasing use of laparoscopic cholecystectomy for the treatment of cholelithiasis has revolutionized hospital inpatient stay times and morbidity of this condition, but serious potential drawbacks are becoming apparent. There are increasing reports of tumour seeding at trocar sites following laparoscopic cholecystectomy in patients with unexpected or inapparent gall-bladder cancer 66 or in cases only identified after laparoscopic cholecystectomy. Suggested precautions would be to avoid laparoscopic surgery in cases where malignancy is strongly suspected or to proceed to open operation if malignancy is found at laparoscopy, with removal of the gall-bladder pouch intact before opening and obtaining a frozen section histology. 67 Giving surgical and adjuvant radiotherapy to the trocar sites and treating the gall-bladder bed and adjacent areas 67 has been suggested as improving outcome.
CONCLUSION Go to: Choose Top of page INTRODUCTION PREDISPOSING FACTORS GENETIC STUDIES CLINICAL FEATURES PROGNOSIS OF STAGING AND ... CONCLUSION << REFERENCES References
Carcinoma of the gall-bladder is the commonest malignancy of the biliary tract. Its dismal prognosis may be slightly improved as better imaging techniques are employed to detect early cases. 60,66 Appropriate operative techniques and rigorous histological sampling can further increase early detection as only stage I is potentially curable at present. Further epidemiological study and biochemical bile acid analysis could help target prevention. Histopathological and tumour marker work needs to be done to improve diagnosis. New molecular biology techniques and gene mapping are promising tools with which to further explore pathogenesis and develop new treatment modalities for the future.
记得以前看到过一篇文章,作者感叹说六十年来胆囊癌的治疗就几乎没有进展,可见胆囊癌的可怕 病人老年，有基础疾病，如再发胆囊炎不见得很好控制。另考虑胆囊癌非常差的预后，在基本情况改善后，尽快以开腹手术胆囊切除，备快速冰冻为妥。腹腔镜应权衡利弊。。。 胆囊璧厚7mm，是否均匀增厚，还是局部增厚，建议CT增强可显示胆囊璧真正厚度，有助于鉴别慢性胆囊炎和厚壁型胆囊癌、是否侵犯肝脏或肝脏转移，也可显示局部浸润情况和局部淋巴结转移等。 I think what your department head said is correct. The gallbladder carcinoma is very difficult to cure. The sooner to make an open operation, the sooner to figure it out. That could make a huge difference for the patient.
Try to get CA19-9, CEA and AFP data.
If possible make a T-lymp transc Ag-NORs.
Those index could help to figure out if it is a malignent one. 1.患者的疼痛症状有无明显改变有时有助诊断。
2.仔细的超声检查在早期胆囊病变诊断上往往比cT有效.
3.早期胆囊癌诊断往往要依靠手术病理。该患者的情况首先考虑慢性炎或和并早期肿瘤。
4. 腹腔镜对胆囊癌疑似病例有争议，但针对该患者有其它心脑疾病的具体情况我偏向与首先考虑腹腔镜，其次开腹手术，但病理不可少。即使手术发现肿瘤手术也不宜为追求根治而太大。
5.积极的治疗是手术，但要和病人及家属交代 好各种可能。 诸位高手,现有一老年男性患者,以胆囊占位性病变入院治疗,肝区有些疼痛,尤以背侧为甚,肝功能基本正常,仅黄疸指数稍高,CT检查未发现结石,胆道基本无堵塞,胆囊壁增厚,胆囊增大,也未见肿瘤,已排除胰腺炎，肝部病变。甲胎抗原及癌胚抗原检测阴性。入院10天，以胆囊炎治疗（曲松钠加一些中成药），肝区现仅有些轻微胀痛，但胆囊体积未见缩小。患者入院至今饮食及大小便均非常正常，现主任认为是胆囊癌，要求切除，请教高手，这么做是否草率？还有何方法可以确诊？这种疑似胆囊癌病变应如何治疗？
楼上的各位真是仁者见仁，智者见智，我提出几点意见：
1，对老年无结石性胆囊炎，如无内科禁忌症，应当手术治疗，因其是胆囊癌的高危人群，何况本身也不能排除胆囊癌。
2，再是否选择腹腔镜的问题上，对怀疑恶性的病人，应直接手术治疗为妥。但是国内确实有这个观点，先腹腔镜，然后术中冰冻，如果浸润超过粘膜下层，中转开腹行根治术。如果病人经济实力高的话是可以考虑的。
3，如果术中冰冻是恶性的情况下，采取什么术式，不能一概而论。术中应看，肝脏浸润情况，淋巴结转移情况，胆管浸润情况来决定相应的术式，根治为目的，根治毕竟比姑息切除的生存率高，根据鄙人的经验，老年的长期的胆道病人，往往较廋（病人长期消化不好），手术相对好做。关于胆管浸润，鄙人曾经遇到一例，术前怀疑慢性胆囊炎，术中证实是恶性的，但胆囊壁内浸润未超过粘膜下层，行胆囊切除后，因病人胆总管增粗，切开探查，同时搔爬，送病理，粘膜浸润癌，直到壶腹部，于是行PD术。所以对浸润未超过粘膜下层的胆囊癌，应警惕癌的粘膜下蔓延浸润。
页:
[1]
