胰腺癌(Pancreatic cancer, PC)是常见的恶性程度较高的消化系统肿瘤,5年生存率仅3%,中位生存时间低于6个月[1]。在欧洲已成为最主要的致死疾病之一[2]。胰腺癌起病隐匿,早期症状不典型,进展快,多数患者就诊时已属晚期。20年来胰腺癌的总手术切除率和5年生存率无显著变化[3]。因此早期诊断和综合治疗已成为改善胰腺癌治疗效果的关键所在。癌前病变是恶性肿瘤发展的起始阶段,是给予治疗、阻断恶变的最佳时机。胰腺癌癌前病变包括胰腺上皮内瘤变、慢性胰腺炎、导管内乳头状粘液性肿瘤和粘液性囊性肿瘤等。近年来流行病学调查及病理组织学研究的进展对于上述病变有了一些新的观念。本文就如何认识和处理胰腺癌癌前病变做一简要述评。<!--[if !supportLists]-->1 <!--[endif]-->胰腺上皮内瘤变胰腺上皮内瘤变( Pancreatic intraepithelial neoplasia, Pan IN)是近些年来提出的新术语,为胰腺小导管上皮细胞非典型增生至原位癌这一系列癌前病变演变发展的连续过程。Pan IN与胰腺癌的关联首先由Sommers 和Meissner发现,而后Klimstra和Longnecker提出该病变的名称及分级和诊断标准,并在1999年世界胰腺癌研讨会上得到学术界的认可和采纳。2000年Hruban等[4]通过检测胰腺正常导管、各级Pan IN和胰腺癌的基因改变,阐述了正常胰腺导管上皮经过上皮内瘤变发展至胰腺癌的不同阶段涉及到的不同基因变化,将胰腺癌的组织学变化与分子遗传学改变联系了起来。胰腺上皮内瘤变可分为3级,其中1级又可分为A、B两个等级。正常导管上皮是单层立方或低柱状上皮,无粘液性胞质及排列拥挤和异型的核。Pan IN-lA上皮由高柱状细胞组成,核位于基底,有丰富的粘液性胞质。Pan IN-1B上皮病变较Pan IN-lA出现了乳头、微乳头或基本上为假复层结构。Pan IN-2上皮病变大多为乳头状结构,细胞出现核的异常改变,包括极性消失,核增大,排列拥挤,假复层等。Pan IN-3上皮病变通常是乳头或微乳头状结构,细胞核失去极性,出现营养不良性杯状细胞,偶可见异常核分裂。此类细胞核形态类似于癌,但无基底膜的侵袭[5]。已有多项研究证实Pan IN为胰腺癌发展过程中的重要阶段。从正常胰腺到慢性胰腺炎和<!--[if !vml]-->胰腺导管腺癌,组织中Pan IN发生率逐渐增加,尤以高级别Pan IN更为显著,而高级别的Pan IN病变仅见于胰腺腺癌和慢性胰腺炎组织中[6]。Swartz等[7]发现浸润癌恒定表达粘蛋白24, Pan IN随着级别的增加,粘蛋白24表达也随之增强。新近的多项研究结果显示,COX-2及p53在高级别Pan IN组织及胰腺癌组织中的表达明显强于低级别Pan IN组织及正常胰腺组织中,两者具有统计学差异[8-10]。国外已有学者应用二甲基苯并蒽 (DMBA)制作大鼠胰腺癌模型, 动态观察到Pan IN向胰腺癌发展的形态学变化过程[11]。由于Pan IN为胰腺上皮组织形态学变化,非肿块形成阶段,临床上无腹痛、黄疸、消瘦等特殊症状,给早期诊断带来巨大困难。至今尚未见有人分离和建立出Pan IN细胞株,既往获得的有关Pan IN细胞特性认识主要源于对Pan IN和胰腺癌混合性组织的分析,故目前医学家对Pan IN的生物学特性缺乏系统而全面的认识。如何识别和诊断胰腺上皮内瘤变已成为提高胰腺癌早期诊断和改善胰腺癌预后的关键之一。随着基因生化分析手段的进一步发展,我们有理由相信Pan IN将成为未来的早期阻断胰腺癌发展的理想靶点。2 慢性胰腺炎慢性胰腺炎(Chronic pancreatitis, CP)已公认为胰腺癌的病因因素之一。多个流行病学调查、循证医学论著均支持慢性胰腺炎与胰腺癌存在着密切联系。一项由6个国家对2000多例确诊为CP的患者进行2年以上的联合调查表明,CP患者PC发病的相对危险度增加16倍[12]。另一项大规模流行病学调查发现,胰腺癌的发生与慢性胰腺炎病程呈正相关,慢性胰腺炎患者随访10年及20年后,分别有2%和4%发展为胰腺癌[13]。目前认为反复出现的慢性炎症逐渐破坏和损伤胰腺的正常生物屏障,长期刺激诱发胰腺癌。胰腺癌的高发年龄较慢性胰腺炎发病年龄晚10~20年,符合炎症癌变的时间。慢性胰腺炎和胰腺癌都好发于胰头,胰头肿块型胰腺炎患者的病理标本中常可见灶性癌变。近年证实部分CP和PC具有一些相同的基因突变谱,如约40%的CP存在K-ras基因12密码子点突变,约30%的CP存在p16,BRCA1,PRSS1,CFTR等基因突变,约20%的CP存在p53基因突变,提示CP与PC发生存在着遗传变异上的密切关系[14-15]。肿块型慢性胰腺炎和胰头癌在临床上有时难以区分。两者通常均以梗阻性黄疸和胰头肿块为首发表现。肿块型慢性胰腺炎所表现的黄疸和腹痛的主要特点为轻微、波动性、间歇性,而胰头癌的黄疸和腹痛常以渐进性加重为特点。病史在一定程度上有利于两者鉴别。肿瘤标志物CA19-9、CA242、CEA对于鉴别诊断具有参考价值,有报道称CA19-9对胰腺癌诊断的特异性为90%,而肿块型慢性胰腺炎CA19-9通常低于100U/dl[13]。影像学方面,CT可以发现胰腺钙化、胰管扩张和胰管结石等慢性胰腺炎的典型变化,而胰头癌表现为胰头肿块、胰管扩张及胰腺萎缩等。ERCP可清楚显示胰胆管的病变部位、梗阻性质,有无狭窄及扩张情况、结石等,刷取胰管壁细胞、抽取胰液行细胞学检查及K- ras突变基因检测。同时可放置胰管、胆管支架行内引流术进行治疗。在大多数慢性胰腺炎的早期阶段,规范的内科保守治疗至关重要。早期内科治疗不但可以缓解临床症状,对于减慢疾病的自然进程也有显著效果。但随着时间的延长,慢性胰腺炎可进展为胰腺癌,尤其肿块型慢性胰腺炎与胰腺癌在临床上常不易区分,给患者及临床医师带来较大困惑。我们认为,对于术前明确诊断为慢性胰腺炎患者,可行胆肠吻合、胰管空肠吻合术等解决黄疸、腹痛等临床症状。近年来内镜技术及相应器械的不断改进,对位于壶腹周围的肿块型慢性胰腺炎已可行内镜下胰胆管取石,胰管、胆管支架置入内引流术等,成功替代开腹手术,有效降低了开腹手术所带来的巨大风险。对于高度怀疑为胰头癌或无法除外者,由于胰头癌所带来的巨大危害,应积极采用肿物根治性切除术包括胰十二指肠切除术,避免遗漏胰腺癌患者,错过治疗最佳时期。3 导管内乳头状粘液性肿瘤胰腺导管内乳头状粘液性肿瘤(Intraductal papillary mucinous neoplasms, IPMNs) 的WHO定义为导管内产生粘液的肿瘤,具有高柱状富含粘液的上皮细胞,有或没有乳头状突起,累及主胰管和/或主要侧枝胰管并且缺乏粘液性腺瘤所特有的巢状基质[16]。IPMNs占胰腺肿瘤的5%-7.5%,胰腺囊性肿瘤的21%-33%[17]。其生物学行为多样,根据导管内肿瘤发生部位又可分为主胰管型、分支胰管型和混合型。根据上皮不典型增生程度可分为导管内乳头状粘液腺瘤、交界性导管内乳头状粘液腺瘤和导管内乳头状粘液癌。近年来日本学者认为应将导管内乳头状粘液癌再细分为非侵袭性癌、微小侵袭癌和侵袭癌,通过此分层分析后发现:非侵袭性癌与微小侵袭癌远期生存率相同,而侵袭癌预后较差,出现淋巴结转移或远处转移后与晚期胰腺导管腺癌相似[18-20]。目前已公认IPMT可以通过类似结肠息肉癌变的方式(增生-腺瘤-癌)逐步进展为恶性肿瘤[21-22]。IPMT如具备如下特点常提示恶性:①黄疸:在侵袭性IPMNs患者中更为常见,黄疸可能是由于胶样粘液堵塞十二指肠壶腹部、恶性的IPMNs压迫胆总管或壁结节累及胆总管及十二指肠壶腹部所致。②主胰管型及混合型IPMNs:Kawamoto等[23]报道,在主胰管型及混合胰管型IPMNs中,侵袭性IPMNs分别占40%和60%,而在分支胰管型IPMNs中仅占9%。③主胰管的直径:在主胰管型和混合型IPMNs中,显著扩张的主胰管与恶性或侵袭性IPMNs密切相关。但目前区分良恶性的主胰管直径界值尚无定论。④病变的大小:有研究报道,囊性肿块的最大径超过2.8cm往往提示恶性的可能性大[24]。⑤肿瘤的部位:发生于胰头或钩突部的IPMNs通常提示恶性或侵袭性,而发生于胰腺体尾部通常提示良性[25]。⑥壁结节及导管内乳头出现、十二指肠乳头扩张及软组织肿块均提示恶性或侵袭性IPMNs。IPMN预后报道不一。良性IPMN手术切除后的5年生存率报告在77%至100%之间,而导管内乳头状粘液癌的5年生存率报道为24%至60%不等,日本学者认为此现象与未将恶性IPMN细分为侵袭性和非侵袭性癌有关[18]。IPMN治疗目前尚存争议,有文献指出对于直径小于3cm、无附壁结节或乳头状突起、无症状的分支胰管型IPMN可行观察随访[26]。而有学者对上述观念提出质疑,认为由于IPMN存在潜在恶性变可能,长期随访加重患者经济、精神负担,术前诊断为分支型IPMN的患者术后病理几乎均证实为混合型IPMN,因此主张对于所有IPMN病患行手术治疗[27]。我们认为,如果患者无绝对手术禁忌,预期寿命较长,坚持长期随访困难,原则上应积极手术治疗。对于高度怀疑恶性患者,术前应充分评估肿瘤的侵犯部位、潜在的导管外或胰腺外侵犯、患者的年龄以及手术拟切除的范围和清扫范围,做到彻底根治性切除。4 粘液性囊性肿瘤粘液性囊性肿瘤(Mucinous cystic neoplasms, MCN)为一类由产生粘液的上皮细胞形成的囊性胰腺肿瘤,可分为粘液性囊腺瘤、交界性粘液性囊腺瘤和粘液性囊腺癌。本病多见于中年女性,好发于胰体尾部,占胰腺肿瘤的1%,占胰腺囊性病变的10%~45%[28]。粘液性囊腺瘤有潜在恶性倾向,国外文献报道其恶变率为17.5%[29]。从以下几个方面可帮助鉴别囊腺瘤与囊腺癌:①年龄:囊腺癌发病年龄高于囊腺瘤,平均超出5.5岁,而侵袭性囊腺癌发病年龄较非侵袭性囊腺癌晚11岁[29]。②黄疸:囊腺癌黄疸发生率明显高于囊腺瘤,分别为28%和6%。③肿瘤标志物:血液及囊液的CEA、CA19-9值升高提示囊腺瘤癌变或囊腺癌的诊断。④影像学检查:B 超或CT检查如发现囊壁厚薄不一,有乳头状突起,与周围粘连或出现肿大淋巴结等征象,提示恶性可能性大。⑤肿物直径:超过6cm者高度怀疑恶性。⑥术中冰冻:肿瘤良恶性的判定主要依靠术中多点冰冻切片检查。Warshaw 等[30]报道胰腺囊性肿瘤在同一囊内可见囊腺瘤、囊腺癌和囊腺瘤恶变的病理学表现,所以活体组织检查应多点多次取材,可以提高诊断率。非侵袭性的MCN5年存活率可达100%,而粘液性囊腺癌仅为57%。目前已有多项证据证明粘液性囊腺瘤可逐步进展为囊腺癌,因此对于MCN,原则上应手术彻底切除肿瘤。粘液性囊腺瘤应连同周围正常胰腺组织一并切除,而明确诊断为粘液性囊腺癌的患者应行根治性切除,包括胰十二指肠切除术甚至全胰切除术。任何肿瘤单纯切除或部分切除及内引流术都是不恰当的。只有肿瘤直径小于3cm,无淋巴结转移征象,存在严重合并症的老年患者可予观察治疗[31]。胰腺恶性肿瘤为近年来临床医师关注和讨论的热点问题之一,但目前对于进展期胰腺癌,无论在手术治疗,还是辅助放化疗方面均无突破性进展,综合治疗效果无法令人满意。提高恶性肿瘤治疗效果的关键仍在于早期诊断与早期治疗,因此,正确鉴别胰腺良恶性肿瘤,加强胰腺癌癌前病变认识,规范胰腺癌癌前病变处理,为胰腺恶性肿瘤治疗另辟新径,将会使胰腺癌治疗疗效得以改善。
Objective: To investigate the clinical featureand treatment strategy of primary pancreatic lymphoma (PPL). Methods: 39cases of PPL reportedin Chinawere reviewed retrospectively with their clinical characters, treatment and outcome,as well as a literature review of worldwide reports.Results: The major clinicalpresentations included discomfort or pain in the upper abdomen and jaundicewithout specificity. Only 2 cases wereidentified correctly by CT scan. 6 patients accepted biopsy beforeoperation, and 5 cases obtained a positive finding. 32 patientsaccepted operation, 13 pancreatoduodenectomy and 6 distal pancreatectomy were performed. 31 patientsaccepted postoperative chemotherapy. Until now, 26 patients werestill alive at a range of 3 to 72 months, 5 patients died at 5 to 24 monthsafter operation. Literature review revealed 85 additional cases ofpancreatic lymphoma in English reports. Their diagnosis and treatment methods varied. Conclusions:Due tothe rare incidence and similar clinical manifestations, PPL was misdiagnosed as pancreatic adenocarcinoma frequently. Fine-needleaspiration biopsy technique is most valuable method in preoperative diagnosis.CHOP is still the most common used regimen of chemotherapy. The value of surgeryand radiotherapy remains controversial, operation combining chemotherapy seemsto be an appropriate method of treatment for the patient who can not rule outmalignancy.Key words: Pancreatic tumor, Lymphoma,Non-Hodgkin’s lymphoma, Diagnosis, TreatmentIntroductionNon-Hodgkinlymphoma (NHL) involves extranodal tissues in more than 40% of all patients1,while the gastrointestinal tract represents the most commonly involvedextranodal site, accounting for half of such cases. Although secondaryinvolvement of the pancreas by NHL is not uncommon in clinic, primarypancreatic lymphoma (PPL) is a rare disease, accounting for only 1% of extranodallymphomas and 0.5% of all pancreatic masses2, 3. Behrns4pointed out the clinical and diagnostic criteria of PPL to distinguish fromsecondary involvement of the pancreas, which included: mass predominantlywithin the pancreas with grossly involved lymph nodes confined to theperipancreatic region, no palpable superficial lymphadenopathy, no hepatic orsplenic involvement, no mediastinal nodal enlargement on chest radiograph, andnormal white cell count.Clinically,it is difficult to differentiate PPL from pancreatic adenocarcinoma withoutpathological support. However, due to a much better prognosis of PPL, correctdiagnosis becomes so important. Treatment strategy remains controversial,particularly the essentiality of surgery and radiotherapy. Here we concludedall the cases of PPL reported in China, most of which weremisdiagnosed as pancreatic adenocarcinoma before operation. Associating withreview of the world literature, we expect to analyze and discuss the clinicalfeature and treatment strategy of this rare disease.Materials andMethodsAnelectronic search of “primary pancreatic lymphoma” through China KnowledgeResource Integrated Database, from 1979 to 2009, was performed. 39 cases werefinally identified as primary pancreatic lymphoma. Medical records of thesepatients were reviewed retrospectively for the following information: patientcharacteristics, presenting symptoms and signs, radiological appearance,laboratory finding, preoperative biopsy, operative management, pathologic diagnosis,treatment modality and follow-up.To realize this rare disease more comprehensively, we usekeywords of "pancreas" and "lymphoma" to search the similarreports in the PubMed database. A total of 85 patients with PPL or NHLinvolving the pancreas have been revealed in the literature. These cases’clinical feature, treatment strategy, and outcome were summarized and analyzed.ResultsClinical characteristicThere were 25 male and 14 female in Chinese reports ofPPL, ranged in age from 16 to 76 years old, with a mean age of 55 years.Discomfort of epigastrium or abdominal pain was the most common symptoms,occurred in 30 of 39 patients (77%). 18 patients (46%) presented obstructivejaundice, 6 patients (15%) complained of nausea and vomit, and 6 patients (15%)got a fever. 2 patients developed acute pancreatitis, 1 patient was asymptomatic,pancreatic mass was an incidental finding during regularly scheduled physicalexaminations. It is notable that the classic symptoms of non-Hodgkin's lymphomaas fever, chills, night sweats and weight loss were uncommon in this group. Isolatedsuperficial lymphadenectasis was found in only 3 cases in physical examination.Laboratory examination was commonly nondiagnostic. Totaland differential white blood cell count, haemoglobin level, and platelets werewithin normal range in 32 cases. 3 patients’ microscopic evaluation ofperipheral blood smears revealed no positive finding. Serum bilirubin, alkalinephosphatase, and alanine aminotransferase were abnormally high level in 16 patientswho presented jaundiced. Only 4 patients had an increased CA19-9 value, 3 ofwhich were less than 100U/ml.Abdominal CT and Ultrasound (US) examinations showedpancreatic mass in all 39 cases, 21 cases located in the head of pancreas and 17cases located in the body and tail of pancreas. 1 patient’s pancreas was totallyinvolved by the tumor. Most CT scans showed a bulky hypodense masswith unclear edge, and it commonly presented inhomogeneous enhancement in thearterial phase. Peripancreatic lymphadenectasis were described in 16 cases.Only 2 cases wereidentified as PPL correctly by the CT imagine, the remainderswere all misdiagnosed as pancreatic malignancy.6 patients accepted biopsy before operation, all thecases were conducted fine-needle aspiration biopsy by CT or EUS, and 5 cases werediagnosed or suggestive of lymphoma.Surgicalprocedure32 patients accepted operation, 13 patients with aneoplasm in the head of pancreas underwent pancreaticoduodenectomy, while 6 patientswith a neoplasm in the body and tail underwent distal pancreatectomy. 4patients accepted palliative operation including cholangioenterostomy or gastroenterostomy.9 patients underwent exploratory laparotomy and tissue biopsy due to theextensive accretion or infiltration of vessel. Pathology,chemotherapy and outcomeAll 39 cases were confirmed the diagnosis as pancreatic lymphoma. The histopathologicresults are listed in Table 1. 31 patients accepted chemotherapy; most patientsaccepted CHOP scheme based intravenous chemotherapy, which includingcyclophosphamide, doxorubicin, vincristine and prednisone. The detailedchemotherapy scheme is described in Table 1. According to the author’sfollow-up, 26 patients were still alive at a range of 3 to 72 months, 5patients died at 5 to 24 months after operation, 4 patients lost follow-up.LiteraturereviewLiterature review revealed 85 additional cases of pancreatic lymphoma inEnglish literature1,4-24. Most literature was only isolated casereport. These patients’ baseline characteristics, pathology, non-operativebiopsy, treatment choice and prognosis are described detailedly in Table 1. Weconcluded these results with our Chinese reports together. The data showed a strong male predominance (male tofemale ratio of 1.9) and increased trend with age (most patients were olderthan 40). Totally 121 pieces of pathological results were obtained in 124 patients;diffuse large B-cell lymphoma was the most common histotype (23.5%), followedby large B-cell (11.3%), histiocytic (5.2%) and diffuse B-cell (5.2%). Thediffuse mixed cleaved, diffuse large cleaved and diffuse histiocytic lymphoma wasrare types of pancreatic lymphoma, all of which were single case report. 37 patients accepted non-operative biopsy, anddramatically 35 cases got a positive result (94.6%). Operations were performedin 81 of 121 cases, but only 40 patients obtained a radical resection of tumor(49.4%). Chemotherapy was administered in 87 of 110 cases (79%). CHOP was stillthe most common used regimen. Radiotherapy was only administered in 17 of 113 cases(15 %). We concluded the outcome of surgery alone, surgery withchemotherapy or radiotherapy, chemotherapy alone, chemotherapy plusradiotherapy. The main goal was to compare surgery based treatment withchemotherapy based treatment. It seems like that the prognosis of surgery aloneor associating with chemotherapy or radiotherapy is better than chemotherapyalone or with radiotherapy, because the former’s Survival rate divide Death ratewas 1.7, and the latter was 1.1. However, due to the retrospective character ofthis research, the formal statistical comparison was unable to be performed,and it is impossible to obtain an unambiguous conclusion. DiscussionPrimary pancreatic lymphoma is a rare disease in clinic. Untilnow, the definition of PPL hasn’t come to consensus yet. Behrns’ clinical anddiagnostic criteria of PPL were most acceptable, but sometimes it’s real difficultto identify the exact origin of lymphoma. Besides this, the precise morbidityof PPL remains unclear. Freeman25 analyzed 1467 extranodal lymphomacases, only 9 cases involved pancreas, accounted for less than 1%. In a reviewof 620 cases of primary gastrointestinal non-Hodgin’s lymphoma, only 1.2%originated from pancreas26. Our literature review data shows PPLhas a strong male predominance in gender and increased trend with age. PPLhas no specific clinical manifestation. The most common symptoms are abdominalpain (83%), abdominal mass (58%) and weight loss (50%)3. Obstructivejaundice is also frequent, presents 42% in a review of 89 PPL cases1, which is similar to ourreview. It is deemed that mostly jaundice was caused by the compressionof extrahepatic bile duct by the involved lymph nodes. Therefore, it should be consideredas PPL for doctors when the radiological image showed lymphopathy around portahepatis or pancreas. On the other hand, it is noticeable that the classicsymptoms of non-Hodgkin's lymphoma like fever, chills and night sweats wererare in PPL, found in only 2% of patients10,14. Thereis no specific biochemical marker which can help physician make correctdiagnosis of PPL. Lactate dehydrogenase (LDH) and beta-2-microglobulin arethought to elevate in lymphoproliferative disorders, but it wasn’t certified inour literature review. The serum carbohydrate antigen 19-9 (CA19-9) level inPPL patients is normal or slightly elevated, while in pancreatic adenocarcinomapatients 80% of cases have a high CA19-9 level27. Forsmark et al28 reported that ahigher than 200 U/ml value of CA19-9 is strongly suggestive of pancreaticadenocarcinoma, which make sense for the differential diagnosis.Radiologicalexaminations can provide support in diagnosis of PPL. Ultrasonography andradiography may find a mass of pancreas, but they are of little value on thedifferential diagnosis. CT scan was widely applied in clinic, and the typicalmorphologic picture of PPL included two patterns: one is a localized,well-circumscribed tumoral form, and other is a diffuse enlargementinfiltrating or replacing most of the pancreatic gland. Some radiologicalfindings have been found to be beneficial to differentiate PPL from thepancreatic adenocarcinoma: the combination of a bulky localized tumor in thepancreatic head without significant dilatation of the main pancreatic ductstrengthens a diagnosis of pancreatic lymphoma over adenocarcinoma; enlargedlymph nodes below the level of the renal veins and invasive tumor growth notrespecting anatomic boundaries and infiltrating retroperitoneal or upperabdominal organs and the gastrointestinal tract are additional reliable signsfor PPL29. There are fewer signs of invaded large vessel andmetastasis of the liver and spleen, and dilation of pancreatic duct is littleto find in PPL than pancreatic cancer. There is no calcification or necrosis within the tumormass has been described in any case of untreated PPL, the presence ofcalcification or necrosis is helpful findings for ruling out non-Hodgkin'slymphoma14. Theappearance of ERCP on PPL includes following patterns: mild duct stenosis(50%), normal duct appearance (30%), stricture of the main pancreatic duct (10%)and ductal displacement (10%). No severe distal dilatation of Wirsung’s duct hasbeen seen in PPL, while pancreatic adenocarcinoma always presents moderate tosevere dilatation. Endoscopicultrasonography (EUS) has also been widely used to evaluate pancreatic massesand surrounding structures in recent years. Flamenbaum et al30described the typical endoscopic sonography findings of PPL as a strongly hypoechogenicappearance in the pancreas, hypertrophy in all its segments, a hyperechoic wallin the common pancreatic duct contrasting with the adjacent parenchyma, andmultiple isoechogenic peripancreatic lymph nodes. Thoughimaging procedure can provide a suggestion of PPL, clinicians have to obtain acyto-histological evidence for the precise diagnosis and further treatmentplanning. CT or US-guided fine-needle aspiration biopsy (FNAB) or tissue corefine-needle biopsy (FNB) of the pancreas has been considered as a safe, rapidand easy procedure with high diagnostic accuracy. EUS-guided tissue sampling ofpancreatic masses is a superior method because it is dynamic and real-time. EUScan clearly show the vein path, sequentially guide the needle aspiration andavoid the vessel damage. Volmar et al12 concluded 1,050 pancreatic FNAcases in his hospital, 503 of which had neoplastic diagnoses. 14 cases werediagnosed or suggestive of lymphoma, constituting 1.3% of total FNA cases and 2.8%of neoplastic cases. Moreover, there was no relative complication developed. However,clinician must consider the existence of false-negative result. Hartwig et al31summarized 1743 patients in 21 studies of US/CT-guided FNA and 2268 patients in28 studies of EUS-guided FNA of pancreatic masses retrospectively, the mediansensitivity, specificity and accuracy of US/CT-guided FNA and EUS-guided FNA were87%, 100%, 84% and 83%, 100%, 88% respectively. Nevertheless, the negativepredictive value of these two diagnostic methods was only 58% and 72%. Theauthor considered that it is not generally advisable about preoperative biopsyof potentially resectable pancreatic tumors, as malignancy cannot be ruled outwith adequate reliability. Thetreatment strategy of PPL is a major argumentative topic, which consists ofsurgery, chemotherapy, radiotherapy or a combination of above. The standardtherapy of NHL is chemotherapy, which have a good response in most cases.Therefore chemotherapy is also the central choice of treatment for patientswith pancreatic lymphoma. From our literature review, CHOP was still the mostcommon used regimen. Recent years, some authors used CHOP plus rituximab toincrease the complete response rate and prolong event-free and overall survivalin patients with diffuse large-B-cell lymphoma, and have gained a satisfying outcome3.Therole of surgery remains controversial in the review of literature. Bouvet et al32reported 10 PPL patients had been performed explorative surgery, only in 3 ofthem the tumor could be fully resected. Koniaris et al33 compared 15surgically treated patients of PPL with non-operatively treated stage I or IIpancreatic lymphoma patients, which have homogeneity in age, gender, histologicsubtypes, stage; and found that the surgically treated group had a markedlyimproved complete remission and cure rate. The successfully resected grouprepresented a dramatic complete response rate of 100% and long-term survivalrate of 94%. This author suggested that surgery was a beneficial role for stageI or early stage II PPL patients. Battula et al1 has also reported similaroutcome. Ourdata showed that only 40 patients (49.4%) in 81 cases who accepted operationobtained a radical resection of tumor, but the total prognosis of surgeryassociating with chemotherapy or radiotherapy is likely better than non-operativelytreatment, despite it is not a formal statistical comparison.Radiotherapyhas been widely used in the multimodality therapy of malignancy, which always playsa role as an adjuvant treatment to surgery and chemotherapy. The new techniquesuch as three dimensional treatment planning and conformal radiotherapy has minimizedradiation complications. However the benefit of radiotherapy in PPL is poorlydefined. Miller et al 34reported that chemotherapy using the CHOPregimen plus adjuvant radiotherapy is superior to chemotherapy alone inlocalized intermediate and high-grade non-Hodgkin's lymphoma. But someresearchers found intensive chemotherapy without radiotherapy was superior toCHOP plus involved field radiation35. We have little experience on thiskind of treatment, but it seems to be unnecessary to use radiotherapy to every PPLpatient due to the low recurrence rate of NHL. ConclusionPrimary pancreatic lymphoma is a rare neoplasm whichmimics pancreatic adenocarcinoma in many aspects, but it showed total differentcharacteristics in clinical progression, treatment response and prognosis.Making correct preoperative diagnosis is very important, but sometimes reallydifficult. FNA technique is most valuable non-operative method in differentialdiagnosis; however, the existing high false-negative rate makes it still unreliable.Due to this clinic quandary, we consider that if the diagnosis of pancreaticlymphoma is clear by the non-operative method, chemotherapy should be the leadingchoice of treatment. Moreover, we advocate explorative laparotomy for thepatient who can not rule out malignancy and is regarded having a potentiallyresectable tumor. Basing on the literature review, surgery is not an impropertreatment choice at least. Contrarily, operation can provide precise pathologicdiagnosis, decrease tumor burden and prevent or manage obstructive jaundice.There are many researches proved the benefit of surgery on PPL. Associatingwith adjuvant chemotherapy and radiation, we believe it will make PPL patientto have a good prognosis.
直肠癌是全球最常见的消化系统恶性肿瘤之一,2010年美国预计发病人数39670,占消化系统肿瘤的第3位[1]。经过200多年的发展,直肠癌的治疗模式已由最初的单纯手术治疗演变为如今的以手术治疗为主的多学科综合治疗模式,这其中包括近年来取得显著突破的术前新辅助治疗。在我国,低位直肠癌(肿瘤距离肛缘<6 cm)约占所有直肠癌患者的75%,且就诊时已属局部进展期。在传统的治疗观念中Miles手术为治疗该部分患者的“金标准”,然后其带来的永久性人工肛门造口、泌尿生殖功能障碍给患者带来了诸多难言之隐,生活质量明显下降。上世纪90年代首次提出的新辅助治疗(neo-adjuvant therapy)为低位直肠癌患者带来了新的希望。本文拟对低位直肠癌新辅助治疗的发展与现况做一综述。一、新辅助治疗的发展历史新辅助治疗的发展要追溯到20世纪80年代辅助放疗概念的首次应用,由于当时全直肠系膜切除(total mesorectum excision,TME)的理念尚未提出,直肠癌术后的局部复发率高达50%[2],医学家应用了术后放疗来控制局部进展期直肠癌的复发,并取得了良好的效果[3]。不过10年时间,一项小规模的临床研究报告首次将放疗应用于手术前,并获得了与术后放疗相当的疗效,且毒副反应更轻,这就是真正意义上新辅助治疗概念的首次提出[4]。欧洲一项纳入466例患者的EORTC实验对直肠癌患者行小剂量长疗程术前放疗,结果显示较之直接手术者,术前放疗可显著降低局部复发率,但并未改善总体预后[5]。一项多中心临床随机试验CR07/C016显示,术前为期5天的短程放疗较之术后放化疗直肠癌患者的局部复发率显著降低,3年无病生存率增加,但总生存时间无明显延长[6]。新近的来自荷兰的一篇研究将1861名无远处转移的可切除直肠癌患者随机分为单纯TME切除组和术前短程放疗+TME切除组,结果显示术前放疗减少了术后10年局部复发率近50%,且提高了环周切缘阴性的III期直肠癌患者10年生存率[7]。另一方面研究热点关注于新辅助放疗与化疗联合应用是否优于单纯术前放疗,法国 FFCD 9203临床试验将733例中晚期直肠癌患者随机分为术前放化疗组和术前放疗组,结果显示术前放化疗组有较高的病理完全缓解率和较低的局部复发率,但5年无病生存率及总生存率、保肛率均无统计学意义,且不良反应率较高[8]。2004年德国一项大样本研究比较了术前联合放化疗较之术后放化疗临床受益有无差异,结果显示,术前新辅助放化疗虽无法改善5年生存率,却可显著降低局部复发,且患者对放化疗的毒副反应明显降低[9]。因此,直肠癌新辅助治疗经历了术后放疗、术前放疗、术前联合放化疗的3个发展阶段,而如今联合放化疗已成为公认的新辅助治疗首选方案。二、新辅助治疗优势与适应证新辅助放化疗较之术后辅助治疗,具有多方面的优势:1、术前患者体力状况较好,耐受性高,毒性反应轻。2、术前肿瘤病灶的血供及淋巴管未受损伤,化疗药在肿瘤局部浓度高,对肿瘤细胞杀伤作用更强。3、控制术前存在的微小癌及亚临床灶,抑制由于手术诱发的肿瘤增殖刺激,减少医源性转移。4、缩小原发病灶、降低临床分期,部分肿瘤甚至可达到病理学完全缓解(pathologic completeresponse, pCR),从而提高根治性切除率以及低位直肠癌的保肛率。5、提高放疗效果及减少并发症。术后肿瘤由于被纤维化瘢痕包裹,组织处于相对缺氧的状态,放射敏感性下降。其次,手术后部分小肠可能落入盆腔并粘连固定,术后放疗易出现放射性肠炎,而手术前小肠并未进入盆腔,且有良好的活动性,不易受到放疗的损伤。因此新辅助放疗可避免因手术造成组织缺氧状态,提高肿瘤组织对放疗的敏感性,也不会因手术后小肠粘连于盆腔而导致放射性肠炎甚至肠瘘。6、通过术前影像学分期和手术切除标本的病理检查,判断肿瘤细胞对化疗药物的敏感性,指导术后化疗药物的选择,实现个体化治疗。根据美国癌症综合网(National ComprehensiveCancer Network,NCCN,www.nccn.org)2010版指南,结合我国国情推出的直肠癌临床实践指南(中国版)2010年第1版明确指出:对于大部分的Ⅱ期(淋巴结阴性,肿瘤穿透肠壁肌层)和Ⅲ期(淋巴结阳性,无远处转移)直肠癌病人,推荐施行新辅助放疗或新辅助放化疗。但一般不推荐使用单纯的新辅助化疗。美国结直肠外科医师协会(American Society Colon& Rectal Surgeons,ASCRS)治疗指南同样提出,根据循证医学一级证据,对II 和III 期的直肠癌推荐使用新辅助化疗加盆腔放疗。三、新辅助治疗方案1.新辅助放疗目前新辅助放疗照射范围应上方至骶骨岬,下方达肛缘,包括直肠周围、骶前、髂内血管和淋巴结,方案多采用如下两种:(1)长疗程放疗:每日剂量1.8-2 Gy,持续5周,总剂量45-50 Gy,放疗结束4-8周后进行手术,此方案多应用于美国及部分欧洲国家。(2)短疗程放疗:每日5 Gy剂量,连续5日,总剂量25 Gy,1周后手术,多应用于瑞典、荷兰。两种方案各有利弊,长疗程放疗总剂量较大,分次剂量小,毒副作用轻,对部分患者可实现肿瘤缩小、降期,提高手术切除率与保肛率,降低术后局部复发。由于经历长疗程放疗后4-8周肿瘤组织坏死与纤维化才最为明显,肿瘤缩小与降期均可得以体现,因此一般推荐此时是进行手术介入的较佳时机。但对术前新辅助放化疗不敏感的患者无疑延误手术时机,肿瘤进展未得到有效控制,影响了远期预后[10]。短剂量放疗总剂量小,分次剂量大,疗程短,患者依从性好,可控制术后局部复发,但难以实现肿瘤降级降期,对提高根治性切除及保肛率帮助不大,且神经放射性损伤及手术并发症发生的风险较高,如急性腰骶神经丛损伤、术后会阴部伤口感染、迟发肠梗阻等[10-12]。目前上述方案孰优孰劣尚无定论,寻求准确预测新辅助放化疗敏感性的指标将是未来研究的热点。2.新辅助放化疗单纯术前放疗对于控制肿瘤全身性播散无任何意义,因此术前联合应用全身化疗弥补这一局限。新辅助化疗方案层出不穷,传统方案多采用5-Fu单药化疗,随着新一代化疗药物如亚叶酸钙(leucovorin,LV)、奥沙利铂(oxaliplatin)、伊立替康(irinotecan, CPT-11)的出现,目前临床上多是以5-Fu为基础联合四氢叶酸、铂类药物的化疗方案。第3代5-Fu类药物希罗达(卡培他滨,Xeloda)的诞生为直肠癌新辅助化疗提供了更多的选择。希罗达是一种口服氟嘧啶氨基甲酸酯类药物,通过胸苷磷酸化酶(TP)将其转化为对肿瘤有活性的5-Fu,而TP在肿瘤组织细胞中含量远高于正常细胞,因此希罗达在结直肠癌组织中的浓度高于临近组织5倍,从而提高化疗药物的利用。此外,有研究证实放疗可上调肿瘤细胞中胸苷磷酸化酶的表达,故放疗与希罗达二者存在协同作用。口服卡培他滨被认为与5-Fu灌注化疗效果相当,且显著减少静脉化疗相关并发症,预计在未来将全面替代5-Fu[13, 14]。奥沙利铂(oxaliplatin)是一种新型铂类抗癌药物,在结直肠癌治疗中表现出比传统卡铂、顺铂更强的抗肿瘤活性作用,同时具有放疗增敏性。有研究报道将其与氟尿嘧啶/甲酰四氢叶酸(5-Fu/LV)或卡培他滨联合用于直肠癌新辅助放化疗,获得了较高的病理缓解率(pCR)[15-17]。另有I期临床试验证实联合应用奥沙利铂与拓尤得于T3期直肠癌患者,可有效提高保肛率和降低术后复发[18],而拓尤得单药应用并无法使患者受益[19]。伊立替康是喜树碱的半合成衍生物,特异性地与拓扑异构酶I结合,引起DNA双链断裂,目前认为该药与传统药物联用并不增加疗效,且可能引起毒副作用[20],故成为治疗转移性结直肠癌的一线药物或5-Fu化疗失败的二线治疗,同时其具有较强的放射增敏作用。有研究采用伊立替康+5-Fu的新辅助化疗方案使pCR率达22%,并初步显示抑制远处转移的作用[21]。此外,包括血管内皮生长因子(VEGF)受体抑制剂(贝伐珠单抗)和表皮生长因子受体(EGFR)抑制剂(西妥昔单抗)在内的新型靶向治疗药物被证实可持续抑制肿瘤新生血管生长和转移,已被美国食品药品管理局(FDA)批准应用于临床。贝伐珠单抗与5-Fu或卡培他滨联合应用可获得满意的pCR率[22, 23],西妥昔单抗对于携带野生型K-ras基因的直肠癌患者有较好疗效[24-26]。更多大规模的临床实验需进一步验证上述药物在新辅助治疗中的作用。四、新辅助治疗疗效大量研究显示术前新辅助放化疗可提高保肛率,降低术后局部复发率,但能否改善总体生存尚存争议。Machiels等[27]报道了一组新辅助放化疗后患者手术根治性切除率可达到60%-89%。Sauer 等[9]比较直肠癌术前放化疗+术后化疗与术后放化疗,5 年局部复发率分别为6%和13%,两者具有统计学差异;而5年生存率分别为76%和74%,并无显著差异。一项纳入14项临床随机对照研究的Meta分析显示,术前辅助放疗可降低癌症相关死亡率、局部复发率,提高5年生存率[28]。但亦有研究认为低危复发因素的II期直肠癌患者并不从新辅助治疗中受益[29]。来自美国的NSABP R-03研究显示术前新辅助放化疗较术后辅助放化疗仅在5年无病生存率上存在差异,并未延长5年生存率,降低局部复发率和增加括约肌保留的几率[30]。但该研究并未对手术方式进行标准化规范。Weiser等[31]对148例距肛6cm低位直肠癌实施术前化疗+长疗程放疗,结果发现新辅助治疗可显著增加保肛率。而术前短程放疗虽可控制局部复发,但在肿瘤降体积、降期、肛门括约肌保留上无法达到与长疗程放疗相似的效果[9, 32]。此外,应用腹腔镜技术切除新辅助治疗后的低位直肠癌可获得开腹手术相同的总体疗效[33, 34]。五、小结毋庸置疑,新辅助治疗为低位直肠癌治疗策略增添了新的选择和希望,其治疗效果令人鼓舞。局部进展期直肠癌患者总体上可从术前新辅助放化疗中获益,但结合我国国情,在临床实际工作,必须结合患者身体条件、肿瘤部位、大小、术前分期、发展速度、病理学特征等多方面因素综合考虑,制定个体化治疗方案。另一方面,围绕新辅助治疗相关的基础与临床研究仍在继续,目前比较重要的几项大样本随机对照试验包括EORTC(卡培他滨单药与卡培他滨联合奥沙利铂疗效比较)、NSABP R-04(5-Fu、卡培他滨及奥沙利铂三药单用或两两联合疗效比较)、Stockholm Ⅲ(研究短程化疗与手术时间相关问题)正在进行;关于直肠癌新辅助治疗敏感性预测的相关指标如P21、P53基因,凋亡通路相关蛋白,EGFR等,已得以初步验证。上述研究结果以及后续的深入研究,有望为直肠癌新辅助治疗中的热点与难点问题做出系列解答,期待能够引领直肠癌综合治疗进入新的篇章!
1 临床资料患者,男, 62岁,因“直肠癌放疗后2年半,出现粘液血便、大便变细、次数增多1年半,加重1月”于2007 年3月入院。患者2004 年10 月于当地医院行结肠镜检查示距肛门3 cm截石位6点至9点处有一直肠肿物,呈溃疡型,占据1 /2周肠腔,取活检病理示直肠腺癌。因瘤体较大、固定,直接手术可能会影响其远期疗效,遂决定先行新辅助治疗( neoadjuvant therapy) 。患者行放疗5周共25次, 剂量50 Gy (2 Gy/次,5次/周)后自觉症状明显好转。放疗后曾于2004 年12 月行经肛门直肠肿物活检术2次,病理结果均显示坏死炎性渗出物、肉芽组织及平滑肌组织。仍建议患者行直肠癌根治术,但被拒绝。患者于2005 年9 月再次出现粘液血便、大便变细、次数增多,未就诊。直至2007年2月,患者上述症状加重,并伴肛门及下腹部剧烈疼痛,再次来诊,遂以“直肠癌复发”再次入院。入院直肠指诊:胸膝位,肛周3~6点处见一直径2 cm左右肿物,表面尚光滑。进指约0. 5 cm于3~6点处触及一质硬肿物,侵及整个肛管及直肠末段,表面不光滑,呈菜花状,活动度差,并伴疼痛,退出指套可见鲜红血迹。腹部CT检查未发现肝转移。入院后完善术前检查,于2007年3月29日在全麻下行经腹会阴联合直肠癌根治术(Miles术) ,术后病理: 直肠中分化腺癌, 侵透肠壁全层达外周脂肪; 肛门鳞状上皮下见癌累及; 上断端未见癌, 淋巴结未见转移癌(0 /10) 。TNM分期: T4NxM0。2 讨 论新辅助治疗是指手术切除前在恶性肿瘤局部给予局部放疗和局部或全身化疗,包括术前进行的新辅助化疗、新辅助放疗和新辅助化放疗等治疗措施。直肠癌新辅助放疗的目的在于: ①使肿瘤降期,并使肿瘤缩小, 使起初不能根治性切除的局部进展期直肠癌最终得以根治性切除; ②使靠近肛门的直肠癌通过放疗得以保肛; ③对于可切除的直肠癌, 新辅助放疗术前杀伤肿瘤细胞可降低术中肿瘤细胞扩散的风险;④术前放疗对肿瘤的杀伤效果更强,因为手术破坏了局部血供,使肿瘤内的氧含量下降, 因此术后放疗敏感性下降[ 1 ]。新辅助治疗的疗效判断, 依据Rou等[ 2 ]报道分为: ①肿瘤病理完全消退(pathologic comp lete relieve, PCR ) ,术后标本中肿瘤完全消失; ②肿瘤部分缓解(partial relieve, PR) ,术后标本病理显示肿瘤T分期下降及新辅助治疗后肿瘤最大径缩小50%以上者; ③无效( no relieve, NR) ,肿瘤无变化。对于直肠癌新辅助治疗后PCR的患者是否还需要进行根治性手术,目前尚存在争议[ 3 ]。Habr2Gama等[ 4 ]报道,直肠癌新辅助放化疗后,即使局部肿瘤在组织学上完全消失也有一定的局部复发率,其发生远处转移的可能性,单纯手术组与新辅助化疗后手术组相似,建议密切随访。本例直肠癌患者采用新辅助放疗,共5周,总剂量为50Gy。放疗后2次活检均未见癌细胞,判断为PCR。但患者拒绝接受根治性手术治疗,放疗后1年肿瘤复发。行Miles术后病理提示直肠中分化腺癌。根据本例的诊治经验,结合文献报道,笔者认为对于直肠癌新辅助治疗后,即便是肿瘤在组织学上完全消失,仍应积极行根治性手术治疗。
AbstractBackground: The indications of laparoscopic spleen-preserving distal pancreatectomy (LSPDP) andits morbidity compared with laparoscopic distal pancreatectomywith splenectomy (LDPS) were ill-defined. The aim of this study was to shareour institution’s indication of spleen-preservation and investigate the safetyand outcome of LSPDP.Methods: A retrospective review was conductedfor patients whom were scheduled to accept laparoscopic surgery for distalpancreatic lesions. The indication, surgical procedure, intra-operative data, andoutcome of two procedures were collected and compared by statistical analysis. Results:Sixteen LDPS and 21 LSPDP were finally successfully performed, whereas other 9 cases were converted to open surgery. There were no significant differences between LDPS and LSPDP groups in patients age(48 vs 48 yrs, p =0.948), operation time (291.6 vs 253.1min, p =0.077), blood loss (296.9 vs 181.4 ml, p =0.079) as well as gender and conversion rate (p >0.05). The mean tumor size had a significant intergroupdifference (5.05 vs 2.53 cm, p <0.001).There were no significant differences of complication and morbidity ratebetween two groups (p >0.05). All patients remain alive withoutrecurrence duringfollow-up of 9 to 67 months (median: 35 months).Conclusions:Laparoscopicspleen-preserving distal pancreatectomy has a comparable morbidity and outcomewith laparoscopic distal pancreatectomywith splenectomy.
AbstractBackground: Primary pancreaticleiomyosarcoma (PLMS) is a rare disease; its clinical characters and prognosisare poorly demonstrated. This study aimed to investigate the tumor’s clinicalcharacters and to reveal the true outcome.Methodology:A retrospectivereview of both Chinese and worldwide PLMS patients were performed. Data wascollected and analyzed, and overall survival was described by Kaplan-Meiercurve.Results: There were totally 9 casesand 55 cases identified in Chinaand worldwide literature respectively. Incidence rate was general equal ingender and had an increased trend with age (mean±SD: 55±14y). Abdominal pain, mass andweight loss were the most common presentations, mean tumor size was 10 cm (SD: 7.2 cm), and most of them presented as a solid mass. 46cases accepted operation, while 33 of which obtained a radical resection.Median overall survival time was 27 months. The patients who accepted radical resectionhad an obvious better prognosis over non-resectable patients.Conclusions: PLMS commonly occurred inthe mid-age people, there was lack of specific noninvasive methods for precise preoperativediagnosis. PLMS has a much better prognosis compared with pancreatic ductal adenocarcinoma.Radical resection is the only hope for improving the outcome of thismalignancy.
AbstractIn recent years, laparoscopicpancreatic surgery is gaining more and more recognition and is increased inpractice though the technique has a much more complex procedure and longerlearning curve compared with other abdominal organs. Laparoscopic distalpancreatectomy and tumor enucleation are fastest developed and currently inwidely use due to their comparable technical simplicity. Literature reviewshowed that laparoscopic distal pancreatectomy and enucleation were safe andefficient approaches for benign and low-degree malignant tumors, whereas theindication for malignant tumors still remained controversial. Laparoscopicpancreaticoduodenectomy was applied in limited surgical centers and presentedas case reports or small series. Although feasibility was demonstrated by manysurgeons, whether laparoscopic procedure can achieve the comparable or evenmore prominent benefits over open procedure has not been proven in clinical. Inthe future, prospective randomized controlled trials of laparoscopic versusopen pancreatic surgery are needed to justify the wide application and routinepractice of laparoscopic procedure for pancreatic lesions.
【摘要】 目的 探讨胆囊腺肌增生症的临床特点及治疗方法。 方法 回顾性分析1992年至2007年收治的33例胆囊腺肌增生症临床资料。 结果 本组33例患者中弥漫型14例(42.4%),节段型10例(30.3%),局限型9例(27.3%)。合并胆囊结石21例(63.6%),合并胆囊炎11例(33.3%)。临床症状无特征性表现,以上腹疼痛、进食后不适、恶心呕吐为主。术前临床疑诊4例,影像学正确诊断2例。28例行腹腔镜胆囊切除术,3例行开腹胆囊切除术,1例同时行胆总管探查、T管引流术,1例同时行肝血管瘤切除术。术后病理诊断均为胆囊腺肌增生症。 结论 胆囊腺肌增生症常合并胆囊结石、胆囊炎,临床表现不具特异性,术前确诊依赖于影像学检查。该病有潜在恶性变可能,胆囊切除术为有效的治疗方法。【关键词】 胆囊疾病;胆囊腺肌增生症;诊断;治疗【Abstact】 ObjectiveTo investigate theclinical feature and treatment of adenomyomatosis of the gallbladder (GBA). MethodsThirty-three cases of GBA admitted from 1992 to 2007 were reviewedretrospectively and their clinical characters have been summarized. Results All the cases are divided into threetypes grossly:14 for diffuse type,10 for segmental type and 9 cases forlocalized type. 21 cases associated with cholelithiasis and 11 cases with cholecystitis. The major clinical presentations includedpainfulness in the upper abdomen, discomfort after ingesting, nausea and vomit whichhave no specificity. Only six cases of this group were diagnosed correctlybefore operation. Twenty-eight laparoscopic cholecystectomy and three opencholecystectomy were performed. 2 patients respectively accepted exploration ofcommon bile duct with T tube drainage and resection of liver angioma simultaneously.All cases have been proven to be adenomyomatosis of the gallbladder by pathologicexamination. Conclusions Due to the highrate of combination with cholelithiasis and cholecystitis, GBA has no specificclinical manifestations. The preoperative diagnosis lies on radiologicalexaminations. Cholecystectomy is an appropriate method in treatment as the adenomyomatosis of the gallbladder has a malignant potential.【Key words】 Gallbladder disease; Adenomyomatosis of the gallbladder; Diagnosis;Treatment