胰腺实性假乳头状瘤的临床特征及治疗

Clinical features and treatment of solid pseudopapillary neoplasm of the pancreas

目的探讨胰腺实性假乳头状瘤（SPN）的临床特征与治疗方法。方法采用回顾性横断面研究方法。收集2012年1月至2017年7月山东大学齐鲁医院收治的69例胰腺SPN患者的临床病理资料。患者术前行血清肿瘤标志物、腹部增强CT或MRI检查，部分患者行EUS检查。完善检查后制订手术方案。观察指标：（1）临床特征。（2）治疗情况。（3）病理学检查情况。（4）随访情况。采用门诊和电话方式进行随访，了解患者生存及肿瘤复发、转移情况。随访时间截至2017年7月。正态分布的计量资料以x±s表示，比较采用Student’st检验。计数资料比较采用爿。检验。结果（1）临床特征：①流行病学特征：69例患者中，男女比例为1：5．9；年龄9～65岁，〈30岁40例，≥30岁29例。男性患者发病年龄为（34±15）岁，女性患者为（28±11）岁，两者比较，差异无统计学意义（t=-1．364，P〉0．05）。69例患者中，胰腺SPN位于胰头钩突25例，胰颈12例，胰体尾32例。②病史：69例患者均无急、慢性胰腺炎病史。无腹部外伤病史。③临床表现：69例患者中，26例无明显症状，健康体检时发现；31例有腹上区胀满不适、腹痛、恶心、呕吐等症状；10例因发现腹上区包块就诊；1例因黄疸就诊；1例患者因恶心、排便困难就诊。④实验室检查：69例患者术前血清CEA和CA19-9水平均正常。⑤影像学检查：69例患者均行腹部CT检查，CT平扫示肿瘤为圆形或类圆形低密度影，51例囊实性，13例单纯实性，5例单纯囊性；64例肿瘤有完整包膜，5例与胰腺实质邻近脏器界限模糊；14例实性部分或者包膜可见钙化灶。10例患者行腹部MRI检查，MRI平扫示T1加权成像呈等或稍低信号，T2加权成像呈稍高信号，肿瘤包膜T1加权成像和T2加权成像呈现连续或不连续环形低信号带。MRI增强扫描示肿瘤囊壁与实性成分动脉期为轻度不均匀强化，静脉期及延迟期为渐进性强化，但均低于正常胰腺实质强化程度，实性成分呈“浮云状”“乳头状”及“壁结节”样强化；囊性成分不强化；包膜明显强化。5例患者行EUS检查示肿瘤边界清楚，包块呈低回声、等回声或高回声，包块均为囊实性，其中1例可见明显钙化灶。（2）治疗情况：69例患者中，27例行腹腔镜手术，其中肿瘤摘除术13例、保留脾脏胰体尾切除术8例、胰体尾＋脾切除术2例、胰中段切除术2例、保留幽门胰十二指肠切除术1例、腹腔镜辅助保留十二指肠胰头切除术1例；42例行开腹手术，其中肿瘤摘除术12例、保留脾脏胰体尾切除术10例、胰体尾＋脾切除术6例、胰中段切除术5例、胰十二指肠切除术7例（其中保留幽门2例）、保留十二指肠胰头切除术1例，1例胰腺SPN合并肝转移患者行开腹胰体尾切除＋小网膜囊转移灶切除术，术后行肝转移灶RFA。术后并发症情况：69例患者中21例发生术后并发症，其中胰瘘17例、腹腔出血2例、不完全性肠梗阻1例、胸腔积液合并肺不张1例，均经相应处理后治愈。（3）病理学检查情况：69例患者手术切缘均为阴性，肿瘤直径为（7±4）cm，直径〈5cm21例，≥5cm48例。10例男性患者中4例肿瘤直径≥5cm，59例女性患者中44例肿瘤直径≥5cm，两者比较，差异有统计学意义（χ2=4．828，P〈0．05）。40例年龄〈30岁患者中32例肿瘤直径≥5cm，29例年龄≥30岁患者中16例肿瘤直径≥5cm，两者比较，差异有统计学意义（χ2=4．895，P〈0．05）。光镜下肿瘤组织分为实性区、假乳头区和囊性区。实性区肿瘤细胞包绕血管呈巢状或片状排列；假乳头区由一层或多层肿瘤细胞包绕纤维血管呈轴心或假乳头状排列：囊性区可见大量黏液和成团血细胞。免疫组织化学染色检测结果显示：α1-抗胰蛋白酶阳性率为100％．0（39／39）；波形蛋白阳性率为96．6％（28／29）；β-catenin阳性率为95．7％（45／47）；孕激素受体阳性率为94．4％（51／54）；CD10阳性率为92．5％（49／53）；突触素阳性率为72．9％（35／48）；嗜铬素A阳性率为5．6％（3／54）。（4）随访情况：69例患者中63例获得连续随访，随访时间为1—68个月，中位随访时间为29个月。随访期间患者均未发现胰腺SPN复发和转移，1例术后35个月死于肺癌，其余患者均生存良好。结论胰腺SPN多见于青年女性，可囊性或实性。腹部增强CT或MRI检查可基本明确诊断，仍不能明确可行EUS细针穿刺活组织检查获得病理学证据。病理学检查典型的细胞形态和假乳头状结构提示胰腺SPN．可联合α1-抗胰蛋白酶、波形蛋白等指标免疫组织化学染色检测明确诊断。胰腺SPN完整切除，切缘阴性是手术基本原则。

Objective To investigate the clinical features and treatment of solid pseudopapillary neoplasm （SPN） of the pancreas. Methods The retrospective cross-sectional study was conducted. The clinicopathological data of 69 patients with SPN of the pancreas who were admitted to the Qilu Hospital of Shandong University from January 2012 to July 2017 were collected. Serum tumor markers detection, enhanced computed tomography （CT） and magnetic resonance imaging （MRI） of abdomen were carried out preoperatively for all the patients, and a part of the patients received endoscopic uhrasonography （EUS）. Surgery plans were formulated after completion of examinations. Observation indicators ： （ 1 ） clinical features ; （2） treatment situation ; （ 3 ） resuhs of pathological examination; （4）follow-up. All the patients were followed up via outpatient examination and telephone interview to detect the survival and tumor recurrence and metastasis till July 2017. Measurement data with normal distribution were presented by x＋s and were compared by Student＇s t test. Count data were compared by chi-square test. Results （1） Clinical features ： （1） epidemiologic features ： the ratio of male to female was 1：5.9 ; patients were aged between 9 and 65 years, including 40 under 30 years and 29 above or equal to 30 years. The onset age was （34±15） years for male patients and （28 ±11）years for female patients, respectively, with no statistically significant difference （t=-1. 364, P〉0. 05）. Of 69 patients, SPN was located at pancreatic uncinate process in 25 patients, at neck of pancreas in 12 patients, body and tail of pancreas in 32 patients. （2） Medical history： history of acute or chronic pancreatitis and abdominal trauma were denied by all the 69 patients. （3） Clinical manifestation： 26 patients had no obvious symptoms and were detected by physical examination; 31 patients had discomfort in upper abdomen, nausea and vomiting; other patients were admitted to the hospital because of upper abdominal mass （10 patients）, jaundice （1 patient） or nausea, constipation （1 patient）. （4）Laboratory examination： the levels of preoperative carcinoembryonic antigen （CEA） and CA19-9 were norulal. （5） Imaging examination ： plane scan of the CT examination showed round or round-like low-density shadows in the 69 patients, including 51 of cystic solid lesion, 13 of solid lesion and 5 of cystic lesion. Complete capsules were observed in 64 patients, blurred boundary between pancreas and adjacent viscera in 5 patients, calcified foci in the pancreatic parenchyma and capsules in 14 patients. Ten patients received MRI examination, and the Tl-weighted images showed equal or slightly lower signal, T2-weighted images showed slightly higher signal in the plane scan, and T1- weighted and T2-weighted images of the tumor capsule showed continuous or non-continuous ring-like signal. The results of enhanced scan showed slightly heterogeneous enhancement of the capsule and the parenchyma of the pancreas in the arterial phase, and progressive enhancement in the venous and delayed phase, while the enhancement degree was lower than that of the normal pancreas parenchyma. The parenchyma was cloud-, papilla- or mural nodule-like enhanced. Obvious enhancement was observed in capsule while not in the cystic components. The boundaries of the tumors in 5 patients were clear under EUS. Hypo-, iso- and hyperechoic regions were found in the masses, and the masses were confirmed as cyst- solidary type. Obvious calcified foci were found in 1 patient. （2） Treatment outcome： twenty-seven patients received laparoscopic surgery, including tumor expiration in 13 patients, distal pancreatectomy with preservation of spleen in 8 patients, distal pancreatectomy combined with splenectomy in 2 patients, middle pancreatectomy in 2 patients, pancreaticoduodenectomy with preservation of pylorus in 1 patient, pancreatic head resection with preservation of duodenum under the assistance of laparoscopy in 1 patient. Forty-two patients received open surgery, including tumor expiration in 12 patients, distal pancreatectomy with preservation of spleen in 10 patients, distal pancreatectomy combined with splenectomy in 6 patients, middle pancreatectomy in 5 patients, pancreaticoduodenectomy in 7 patients （with preservation of pylorus in 2 patients） and pancreatic head resection combined with preservation of duodenum in 1 patient. One patient with SPN ＋ hepatic metastasis received distal pancreatectomy＋ metastatic foci resection in the lesser omental bursa, and then followed by radiofrequency ablation in the hepatic metastatic foci. Postoperative complications： 21 of 69 patients had postoperative complications, including 17 intestinal fistulas, 2 abdominal bleedings, l incomplete obstruction, 1 pleural effusion ＋ atelectasis, and all of them were cured by symptomatic treatment. （3） Pathological examination： the resection margins of 69 patients were negative. The mean diameter of the tumor was （7±4） cm （21 patients with tumor diameter 〈 5 cm, and 48 with tumor diameter ≥5 cm）. The tumor diameters of 4 in 10 male patients were above or equal to 5 cm, and the number was 44 in 59 female patients, with statistically significant difference （χ2 = 4. 828, P〈0.05）. The tumor diameters of 32 in 40 patients who aged under 30 years were above or equal to 5 cm, and the number was 16 in 29 patients who were aged above or equal to 30 years, with statistically significant difference （χ2= 4. 895, P〈0. 05）. Solid, pseudo-papillary and cystic regions in the SPN tissues were seen under the light microscope. Tumor cells were surrounded the blood vessels and were arranged in the nest or sheet shape in the solid region ; blood vessels were surrounded by one or multiple layers of tumor cells in the axis or pseudopapillary shape in the pseudopapillary region; large amount of mucus and clusters of blood cells were seen in the cystic regions. The result of immunohistochemistry showed that the positive rates of α1-antitrypsin, vimentin, β-eatenin, progesterone receptor, CD10, synaptophysin and ehromogranin A were 100. 0% （39/39）, 96. 6% （28/29）, 95.7% （45/47）, 94. 4% （ 51/54）, 92. 5% （49/53）, 72. 9% （35/48） and 5.6% （3/54）, respectively. （4） Follow-up： 63 of 69 patients were followed up for 1-68 months, with median time of 29 months. No SPN recurrence or metastasis was detected. One patient died of lung cancer at postoperative month 35 and other patients survived well. Conclusions SPN of pancreas is mostly detected in young female patients, and it could be solid or cystic. Abdominal＇ enhanced CT or MRI examination could clarify the diagnosis. EUS-fine needle aspiration examination could provide pathological evidence for definitive diagnosis. Typical cellular morphology and pseudopapillary regions may provide hints for the diagnosis of SPN, and the diagnosis could be clarified when combined with the detection of vimentin, α1-antitrypsin or other indexes. Complete resection of SPN and ensure negative resection margin are fundamental principles of treatment.