Objective: To explore the clinical significance of laparoscopic exploration combined with abdominal exfoliative cytology in the diagnosis and treatment of patients with locally advanced gastric cancer. Methods: Inclusion criteria: (1) cancer confirmed by gastroscopy and pathology without preoperative anti-tumor treatment; (2) no distant metastases found in preoperative imaging examinations; (3) patients without surgical contraindications and being tolerant to surgery; (4) patients were willing to undergo laparoscopic exploration and abdominal exfoliative cytology examination, and signed informed consent. A retrospective cohort study method was used to collect and analyze the clinicopathological data of 225 patients with advanced gastric cancer based on the above inclusion criteria from a prospective, multicenter, open, randomized controlled phase III clinical trial (registration No. NCT01516944) conducted between February 2012 and December 2018 in The Fourth Hospital of Hebei Medical University, including 162 males and 63 females with age ranged from 23 to 78 years old. Forty-five patients (20.0%) were classified as Borrmann type I to II, and 180 (80.0%) were classified as type III to IV. All the patients underwent laparoscopy and peritoneal lavage cytology under general anesthesia. Laparoscopic exploration sequence: left and right diaphragm→liver and spleen→parietal peritoneum→pelvic cavity→greater omentum, small intestine, mesentery→transverse colon mesentery →stomach. Contents of exploration: (1) with or without ascites; (2) whether metastatic lesions existed in the peritoneum, mesentery, omentum and Douglas pouch; (3) whether metastasis existed on the liver surface; (4) whether the gastric lymph nodes were swollen; (5) whether infiltration occurred on the gastric serosa surface; (6) whether gastric wall was stiff. The left and right subphrenic, the abdominal and pelvic peritoneum, and the mesentery were rinsed with 500 ml of sterilized normal saline. Position of the reverse Trendelenburg was used in the Douglas pouch. The peritoneal lavage fluid under the liver and spleen fossa was collected. Cytological examination was carried out for exfoliative tumor cells. Evaluation criteria: (1) peritoneal metastasis (P): P0 meant no peritoneal metastasis, P1 meant peritoneal metastasis; (2) free peritoneal cancer cells (CY): CY0 meant no cancer cells in peritoneal lavage fluid cytology, CY1 meant cancer cells in peritoneal lavage fluid cytology. The results of patients undergoing laparoscopic exploration combined with abdominal exfoliative cytology, treatment options and prognosis were analyzed. Kaplan-Meier method was used to calculate the survival rate and a survival curve was drawn. Log-rank test was used for survival analysis. Results: After laparoscopic exploration in 225 patients, clinical staging was corrected in 68 (30.2%) patients, of whom 7 (3.1%) downstaged and 61 (27.1%) increased in staging. Of 164 patients evaluated as P0CY0 after the first laparoscopy and peritoneal cytology examination, 126 underwent radical D2 surgery, and the other 38 patients were found to have later local lesions or extensive fusion of local lymph nodes, so then received neoadjuvant chemotherapy. Twenty-nine patients evaluated as P1CY0 or P1CY1 and 32 patients as P0CY1 underwent intraperitoneal hyperthermic chemotherapy+conversion therapy, and then a second laparoscopic exploration was performed to determine the treatment plan. In total, the original treatment regimens were changed after laparoscopic exploration in 99(44.0%) cases. The follow-up period ended in January 2019. The overall 2-year survival rate of 225 patients was 64.0%. As for those who were evaluated as P0CY0, P0CY1 and P1CY0-1 after the first laparoscopic exploration, the 2-year overall survival rate was 70.7%, 65.6% and 24.1%, respectively (P=0.002). The stratified analysis showed that among 180 patients with stage III tumor, after laparoscopic exploration combined with abdominal exfoliative cytology, 125 patients were found to be P0CY0, 28 were P0CY1, and 27 were P1CY0-1, whose 2-year overall survival rates were 70.4%, 64.3%, and 29.6% respectively, and the difference among these 3 groups was statistically significant (P=0.009). Conclusion: Laparoscopic exploration combined with abdominal exfoliative cytology in patients with locally advanced gastric cancer has important clinical guiding significance in improving accurate staging, treatment options and prognosis evaluation, and can avoid non-therapeutic open-close abdominal surgery.
目的: 探讨局部进展期胃癌患者腹腔镜探查联合腹腔脱落细胞学检查的诊疗意义。 方法: 病例纳入标准:(1)经胃镜病理证实为癌,术前未接受过抗肿瘤药物治疗;(2)术前影像学检查均未发现远处转移;(3)无手术禁忌证,能耐受手术;(4)愿意接受腹腔镜探查和腹腔脱落细胞学检查,并签署知情同意书。采用回顾性队列研究方法,根据上述纳入标准,收集分析河北医科大学第四医院2012年2月至2018年12月期间开展的一项前瞻性、多中心、开放、随机对照三期临床试验(注册号:NCT01516944)中的225例进展期胃癌患者临床病理资料,其中男162例,女63例,年龄23~78岁。45例(20.0%)为Borrmann分型Ⅰ~Ⅱ型,180例(80.0%)为Ⅲ~Ⅳ型。所有患者均在全身麻醉下行腹腔镜探查和腹腔冲洗脱落细胞学检查。腹腔镜探查顺序:左右膈下→肝脏和脾脏→腹腔壁层腹膜→盆腔→大网膜和小肠及系膜→横结肠系膜→胃;探查内容:(1)有无腹水;(2)腹盆腔腹膜、肠系膜、大网膜和Douglas腔有无转移灶;(3)肝表面有无转移;(4)胃周淋巴结是否肿大;(5)胃浆膜面有无浸润;(6)胃壁是否僵硬。以500 ml灭菌生理盐水分别冲洗左右膈下、腹盆腔腹膜及肠系膜,取头高脚低位于Douglas腔、肝下及脾窝收集腹腔冲洗液,细胞学检查有无脱落的肿瘤细胞。评估标准:(1)腹膜转移(P):P(0)为无腹膜转移;P(1)为有腹膜转移。(2)腹腔游离癌细胞(CY):CY(0)为腹腔灌洗液细胞学检查无癌细胞;CY(1)为腹腔灌洗液细胞学检查有癌细胞。分析患者腹腔镜探查联合腹腔脱落细胞学检查结果、治疗方案选择及预后情况。采用Kaplan-Meier法计算生存率并绘制生存曲线,采用log-rank检验进行生存分析。 结果: 225例患者经腹腔镜探查后,有68例(30.2%)纠正了临床分期,其中分期下降7例(3.1%),上升61例(27.1%)。经第一次腹腔镜探查及腹腔脱落细胞学检查后评估为P(0)CY(0)的164例进展期胃癌患者中,126例行D(2)根治术,另38例因发现肿瘤局部病期较晚或局部淋巴结广泛融合,予以新辅助化疗。29例被评估为P(1)CY(0)或P(1)CY(1)的患者及32例P(0)CY(1)的患者术后均行腹腔热灌注化疗+转化治疗,经相应治疗后进行第二次腹腔镜探查,以明确治疗方案。全组有44.0%(99/225)的患者腹腔镜探查后改变了原治疗方案。随访时间截至2019年1月。225例患者的总体2年生存率为64.0%,经第一次腹腔镜探查后评估为P(0)CY(0)、P(0)CY(1)、P(1)CY(0~1) 3组患者2年总体生存率分别为70.7%、65.6%和24.1%,3组间差异有统计学意义(P=0.002);分层分析显示,180例术前分期为Ⅲ期患者,经腹腔镜探查及腹腔脱落细胞检查后发现125例为P(0)CY(0),28例为P(0)CY(1),27例为P(1)CY(0~1),3组2年总体生存率分别为70.4%、64.3%和29.6%,3组间差异具有统计学意义(P=0.009)。 结论: 局部进展期胃癌患者行腹腔镜探查联合腹腔脱落细胞学检查对提高精准分期、治疗方案选择及预后情况评估具有重要的临床指导意义,可以避免非治疗性的开-关腹手术。.
Keywords: Cytology, abdominal exfoliative cytology; Laparoscopy; Stomach neoplasms, local advanced gastric cancer.