Surgery after intraperitoneal and systemic chemotherapy for gastric cancer with peritoneal metastasis or positive peritoneal cytology findings

Background

Despite recent progress in systemic chemotherapy, the prognosis of gastric cancer patients with peritoneal metastasis (P1) or positive peritoneal cytology findings (CY1) is still poor. We developed a regimen combining intraperitoneal (IP) paclitaxel (PTX) with S-1 and PTX, which can produce notable efficacy with regard to peritoneal lesions. Surgery after response to combination chemotherapy is a promising option for P1 or CY1 gastric cancer. A retrospective study was performed to evaluate the safety and efficacy.

Methods

This study enrolled 100 primary P1 or CY1 gastric cancer patients treated with IP PTX plus S-1 and PTX at the University of Tokyo Hospital between 2005 and 2011. Radical gastrectomy was performed when peritoneal cytology findings became negative, and the disappearance or obvious shrinkage of peritoneal metastasis was confirmed by laparoscopy. The same chemotherapy regimen was restarted after surgery and repeated with appropriate dose reduction.

Results

Gastrectomy was performed in 64 (P1 56, P0CY1 8) of 100 (P1 90, P0CY1 10) patients. R0 resection was achieved in 44 patients (69%). The median survival time was 30.5 months [95% confidence interval (CI) 23.6–37.7 months] from the initiation of intraperitoneal chemotherapy and 34.6 months (95% CI 26.8–39.4 months) from the diagnosis of gastric cancer. Postoperative complications included anastomotic leakage and pancreatic fistula, each in two patients, which were cured conservatively. There were no treatment-related deaths. The median survival time of the 36 patients who did not undergo surgery was 14.3 months (95% CI 10.0–17.8 months).

Conclusions

Surgery after response to intraperitoneal and systemic chemotherapy is safe and may prolong the survival of P1 and CY1 gastric cancer patients.

     

Comparison of laparoscopic and open radical gastrectomy for gastric cancer patients with GLIM-defined malnutrition

PurposeMalnutrition is common in the patients with gastric cancer. Radical gastrectomy remained the primary strategy of curable treatment for gastric cancer. This study is performed to explore the effect of laparoscopic radical gastrectomy on clinical outcomes in gastric cancer patients with malnutrition.MethodsGastric cancer patients with GLIM-defined malnutrition between 2014 and 2019 at our center were enrolled. The patients were divided into two groups according to the different type of surgery. Propensity score match analysis was used to balance the clinicopathologic characteristics of two groups. Postoperative outcomes and survival were compared. Multivariate analysis was used to independent risk factors of complication, overall survival (OS), and disease-free survival (DFS).ResultsCompared with patients underwent open radical gastrectomy, patients who underwent laparoscopic radical gastrectomy had lower rate of total, surgical and severe complications. They also had shorter postoperative hospital stay with better OS and DFS. Hypoalbuminemia (P = 0.003) was the independent risk factor of complications. Old age (≥75, P = 0.035) and TNM stage (III: P < 0.001, II: P = 0.015) were the independent risk factors of OS. Combined resection (P = 0.003) and TNM stage (III: P < 0.001, II: P = 0.001) posed independent risk factors of lacking DFS. Laparoscopic surgery proved to be the independent protective factor of complications (P = 0.014), OS (P < 0.001) and DFS (P < 0.001).ConclusionLaparoscopic radical gastrectomy was relative safe and showed favorable outcomes in malnourished gastric cancer patients.     

The survival and prognosticators of peritoneal cytology-positive gastric cancer patients who received upfront gastrectomy and subsequent S-1 chemotherapy

Background

Upfront surgery and subsequent S-1 chemotherapy is frequently selected for peritoneal cytology-positive (CY1) gastric cancer patients without other distant metastases (CY1-only). The objective of this study was to confirm the efficacy of this strategy in clinical practice and to identify the risk factors associated with survival.

Methods

Overall survival (OS) and recurrence-free survival (RFS) were examined in 36 CY1-only patients who underwent macroscopic curative resection followed by postoperative S-1 chemotherapy between January 2000 and June 2015. Univariate and multivariate analyses were performed using a Cox proportional hazards model to identify risk factors.

Results

The median OS was 22.3 months (95% confidence interval 18.7–31.0). When the OS was compared by a log-rank test, significant differences were observed in the status of lymph node metastasis of pathological N3b (pN3b). Moreover, the univariate and multivariate analyses demonstrated that the status of pN3b was a significant independent risk factor for OS and RFS. The median OS in patients with pathological N0–N3a (pN0–N3a) was 31.0 months, while that in patients with pN3b was 18.2 months (P = 0.002). The median RFS in patients with pN0–N3a was 16.4 months, while that in patients with pN3b was 7.9 months (P = 0.007).

Conclusions

The present study confirmed the efficacy of postoperative S-1 chemotherapy for CY1-only gastric cancer patients who received upfront surgery. This strategy might be recommended as clinical practice for patients with CY1 disease but a more effective treatment should be established for CY1-positive patients, especially for those who are diagnosed with CY1 and pN3b disease.

     

Prophylactic hyperthermic intraperitoneal chemotherapy for patients with clinical T4 gastric cancer

IntroductionPatients with clinical T4 gastric cancers have high recurrence rates and low 5-year overall survival (OS) despite radical gastrectomy with D2 lymphadenectomy and adjuvant chemotherapy. The invisible peritoneal metastasis may result in local recurrence due to the tumor invading the serosa and nearby organs. Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) has been suggested as an adjuvant treatment strategy in these patients. We evaluated the efficacy of prophylactic HIPEC post-gastrectomy for patients with clinical T4 gastric cancer.Materials and methodsWe retrospectively reviewed data from 132 patients with clinical T4 gastric cancer who underwent gastrectomy + D2 lymphadenectomy between 2014 and 2020. Thirty-five of these patients also underwent prophylactic HIPEC perioperatively. We used propensity score matching (PSM) to reduce selection bias. We evaluated the risk factors for recurrence and compared the OS and disease-free survival (DFS) between the gastrectomy and prophylactic HIPEC groups.ResultsA total of 132 eligible patients were included in the study. Seventy preoperative patient characteristics were homogeneous post-PSM. Prophylactic HIPEC seemed to reduce the risk of postoperative peritoneal recurrence but did not influence the risk of distant metastasis. The risk factors for recurrence included advanced N stage, ascites, and lymphovascular invasion. OS (adjusted hazard ratio, 0.37; 95% CI, 0.17 to 0.81; p = 0.035) and DFS (adjusted hazard ratio, 0.33; 95% CI, 0.15 to 0.72; p = 0.017) were better in the prophylactic HIPEC group than in the gastrectomy alone group.ConclusionsProphylactic HIPEC plus radical gastrectomy can reduce peritoneal recurrence and improve OS and DFS in patients with clinical T4 gastric cancer.     

Surgery after intraperitoneal and systemic chemotherapy for gastric cancer with peritoneal metastasis or positive peritoneal cytology findings

Background

Despite recent progress in systemic chemotherapy, the prognosis of gastric cancer patients with peritoneal metastasis (P1) or positive peritoneal cytology findings (CY1) is still poor. We developed a regimen combining intraperitoneal (IP) paclitaxel (PTX) with S-1 and PTX, which can produce notable efficacy with regard to peritoneal lesions. Surgery after response to combination chemotherapy is a promising option for P1 or CY1 gastric cancer. A retrospective study was performed to evaluate the safety and efficacy.

Methods

This study enrolled 100 primary P1 or CY1 gastric cancer patients treated with IP PTX plus S-1 and PTX at the University of Tokyo Hospital between 2005 and 2011. Radical gastrectomy was performed when peritoneal cytology findings became negative, and the disappearance or obvious shrinkage of peritoneal metastasis was confirmed by laparoscopy. The same chemotherapy regimen was restarted after surgery and repeated with appropriate dose reduction.

Results

Gastrectomy was performed in 64 (P1 56, P0CY1 8) of 100 (P1 90, P0CY1 10) patients. R0 resection was achieved in 44 patients (69%). The median survival time was 30.5 months [95% confidence interval (CI) 23.6–37.7 months] from the initiation of intraperitoneal chemotherapy and 34.6 months (95% CI 26.8–39.4 months) from the diagnosis of gastric cancer. Postoperative complications included anastomotic leakage and pancreatic fistula, each in two patients, which were cured conservatively. There were no treatment-related deaths. The median survival time of the 36 patients who did not undergo surgery was 14.3 months (95% CI 10.0–17.8 months).

Conclusions

Surgery after response to intraperitoneal and systemic chemotherapy is safe and may prolong the survival of P1 and CY1 gastric cancer patients.

     

Different risk factors for three major recurrence patterns of pathological stage II or III gastric cancer patients who completed adjuvant S-1 monotherapy

IntroductionAfter curative gastrectomy followed by 1-year adjuvant S-1 monotherapy for pathological stage (pStage) II or III gastric cancer, some patients experience peritoneal, hematogenous, or lymph nodal recurrence. However, risk factors for each recurrence pattern despite completed adjuvant S-1 monotherapy remain unclear. The aim of this study was to determine which factors influence each recurrence type after curative gastrectomy followed by 1-year adjuvant S-1 monotherapy.Materials and methodsA total of 380 patients with pStage II or III gastric cancer who completed 1-year adjuvant S-1 monotherapy after R0 gastrectomy between January 2008 and December 2013 were enrolled in this study. The risk factors that were associated with peritoneal, hematogenous, and lymph nodal recurrence were investigated by univariate and multivariate analyses.ResultsEighty (21.1%) of 380 patients developed recurrence. As the first site, peritoneal, hematogenous, and lymph nodal recurrence occurred in 42 (11.1%), 26 (6.8%), and 12 (3.2%) patients, respectively. In multivariate analysis, peritoneal metastasis was associated with signet ring cell carcinoma (P < 0.001), pT4 (P = 0.001), and pN3 (P < 0.001), while hematogenous recurrence was associated with pN3 (P = 0.019) and later initiation of S-1 (P = 0.013), and lymph nodal recurrence was associated with pN3 (P = 0.002).ConclusionThe risk factors for peritoneal, hematogenous, and lymph nodal recurrence in pStage II or III gastric cancer patients who complete adjuvant S-1 monotherapy differ. This information may be helpful for daily surveillance of recurrence in post-operative and chemotherapeutic patients. Furthermore, it may be a useful reference to develop novel perioperative chemotherapy.     

THE EFFECT OF HYPO－OSMOLAR SOLUTIONS WITH HIBITANE ON SHED CANCER CELLS IN PERITONEAL CAVITY OF PATIENTS WITH GASTRIC CANCER

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基于术前 PIV、NLR和CEA水平对胃癌根治术后预后列线图预测模型的构建及评价

目的:基于术前泛免疫炎症（PIV）、中性粒细胞与淋巴细胞比值（NLR）以及癌胚抗原(CEA)水平探讨胃癌根治术后预后的影响因素并建立列线图预后预测模型。方法:回顾性分析2016年03月至2019年11月在徐州医科大学附属医院普外科行胃癌根治术的384例胃癌患者的临床病理资料,采用受试者工作特征（ROC）曲线分析术前PIV、NLR、CEA水平预测总生存期(OS)的最佳截断值,并根据 PIV 的最佳截断值进行分组。采用 χ2 检验分析不同PIV水平与患者临床病理特征的关系。使用Kaplan-Meier 法和Log-rank检验分析不同临床病理特征对患者OS的影响,多因素 Cox 回归分析患者预后的独立影响因素。使用 R4.1.1 软件绘制胃癌根治术后患者 1、3、5年OS的列线图预测模型,并评价预测模型的效能,然后使用 X-tile 软件根据列线图风险得分将该模型分层进一步探讨该模型的临床应用价值。结果:ROC 曲线分析结果显示,PIV、NLR、CEA 曲线下面积(AUC)分别为 0.627、 0.584、0.590,最佳截断值分别为236.8、1.98、4.93 ng/mL。PIV与年龄、肿瘤最大直径、肿瘤浸润深度、淋巴结转移、TNM分期、神经或脉管侵犯、术前NLR水平相关(P＜0.05)。多因素 Cox 回归分析显示,年龄、肿瘤浸润深度、神经或脉管侵犯、PIV、NLR、CEA为胃癌根治术后患者 1、3、5年OS的独立影响因素(P＜0.05)。构建包含以上独立危险因素的列线图预测模型,模型内部验证一致性指数(C指数)分别为0.797、0.805、0.780,校正曲线提示该模型区分度良好,低风险患者的OS明显优于中、高风险组(P＜0.001)。结论:PIV、NLR、CEA对于胃癌预后有较好的预测价值,基于PIV、NLR、CEA水平及胃癌相关病理资料构建的列线图模型对于临床有较高的指导意义。     

The effect of extensive intraoperative peritoneal lavage therapy (EIPL) on stage III B + C and cytology-positive gastric cancer patients

Background

The aim of this study was to investigate the effects of extensive intraoperative peritoneal lavage (EIPL) therapy on stage III B + C and CY1/P0 gastric cancer patients after potentially curative surgery.

Methods

The study included 37 patients with CY1/P0 and 23 patients with stage III B + C gastric cancer who were treated with potentially curative gastrectomy and EIPL therapy between March 1995 and May 2013. D2 lymphadenectomy, R0 resection, and EIPL therapy were performed for all cases.

Results

Multivariate analysis revealed that male gender (P = 0.01) and lymph node metastasis (P = 0.03) were independent prognostic factors, while positive cytology was not (P = 0.21). There was no significant difference in overall survival rates between the CY1/P0 and stage III B + C groups (P = 0.93). There was also no significant difference in peritoneal recurrence rates, i.e., 13 (35.1%) in the CY1/P0 group and 5 (21.7%) in the stage III B + C group (P = 0.39).

Conclusions

EIPL therapy combined with complete resection and sufficient (D2) lymphadenectomy could improve the prognosis of CY1/P0 gastric cancer and, to a similar extent, that of stage III B + C.

     

Prognostic impact of dimensional factors in pT1 gastric cancer

BackgroundThe significance of the dimensional factors (tumor diameter, area and volume) as the prognostic factor has not been precisely evaluated in pT1 gastric cancer.ObjectivesThis study aimed to identify the clinical impact and to confirm the clinical feasibility of the dimensional factors as prognostic factors in pT1 gastric cancer.MethodsWe analyzed prognostic factors for disease-specific survival (DSS), overall survival (OS) using clinicopathological factors by univariate and multivariate analyses and the pattern of recurrence in 2011 pT1 gastric cancer (mucosal and submucosal cancers) undergoing R0 gastrectomy. The cut-off values of each dimensional factor was decided by the ROC curve.ResultsCox proportional hazard regression model showed that older age (≥75) and more advanced pN stage were adverse independent prognostic factors for DSS, and revealed that older age (≥75), greater preoperative co-morbid diseases, proximal and total gastrectomy, operative method and Clavien-Dindo classification (≥grade III) were independent adverse factors for OS. Any dimensional factors were not independent prognostic factors for any survival.ConclusionsThe dimensional factors do not influence both OS and DSS in pT1 gastric cancer patients and so it is difficult to apply these dimensional factors for conducting therapeutic strategies.     

Borrmann Ⅳ型胃癌的临床病理特征及预后分析

目的探讨BorrmannⅣ型胃癌患者的临床病理特征和预后生存情况。方法采用队列性回顾性分析2386例行根治性手术治疗的胃癌患者,筛选出BorrmannⅣ型的患者,分析其临床特征及影响预后的因素。结果2386例胃癌患者中BorrmannⅣ型者363例(15.21%)。与非BorrmannⅣ型胃癌相比,BorrmannⅣ型患者的同时性肝转移率、异时性肝转移率、淋巴结转移率、脉管浸润发生率更高,同时发病年龄更趋于年轻化,病理类型更趋于低分化-未分化类型(均P<0.05)。全组患者5年总生存率为49.32%,5年无病生存率为44.61%,其中BorrmannⅣ型患者5年OS、DFS和非BorrmannⅣ型患者比较,差异均有统计学意义(均P<0.001)。亚组分析显示,同为pT2-pT4a或pN0~pN3a期时BorrmannⅣ型与非BorrmannⅣ型胃癌患者5年OS、DFS差异有统计学意义(均P<0.005)。多因素分析显示,肿瘤组织学类型为低分化-未分化类型、肿瘤浸润深度pT分期为T4a~pT4b期、存在淋巴结转移、肿瘤pTNM分期为ⅢA~ⅢC期、术后出现肝转移及术后发生腹膜转移(均P<0.05)是影响BorrmannⅣ型胃癌患者预后的独立危险因素。结论BorrmannⅣ型胃癌具有易发生肝转移、淋巴结转移、腹膜转移且预后差的特点,其预后受多种独立危险因素影响。     

Prognostic role of lymphatic vessel invasion in early gastric cancer: A retrospective study of 188 cases

BackgroundLymphatic vessel invasion is an important prognostic factor for the gastric cancer without lymph node metastasis. However, the studies on early gastric cancers is still sparse. Therefore, we carried out this study to determine clinicopathological and surgical prognostic factors, especially lymphatic vessel invasion, for early gastric cancers.MethodsClinicopathological characteristics and prognostic outcomes of 188 patients who received a gastrectomy for early gastric cancer between 1980 and 2000 were retrospectively evaluated based on the subclassification of pN category. A multivariate analysis was performed by using the Cox regression model, where lymphatic vessel invasion and other potential prognostic factors were included.ResultsOf the 188 patients, 158 had T1N0M0 and 30 T1N1M0 cancers. In patients with T1N0M0 cancers, the survival rate was significantly lower in those with lymphatic vessel invasion than in those without (χ² = 4.025, P = 0.045). However, in patients with T1N1M0 cancers, the survival rates were not significantly different between those with and those without lymphatic vessel invasion (χ² = 0.253, P = 0.615). The multivariate analysis identified that age (P = 0.033) and lymph node metastasis (P = 0.019) were independent prognostic factors for all early gastric cancers. However, age (P = 0.042), tumor location (P = 0.032), and lymphatic vessel invasion (P = 0.010) were the independent prognostic factors for T1N0M0 cancers.ConclusionsLymphatic vessel invasion was an independent prognostic factor for T1N0M0 early gastric cancers, and thus may be a potential prominent factor that should be considered to be included in the category of lymphoid metastasis (both lymph node metastasis and lymphatic vessel invasion) in patients with early gastric cancer.     

Impact of sarcopenia on clinical outcomes of patients with stage I gastric cancer after radical gastrectomy: A prospective cohort study

BackgroundThe relationships between sarcopenia and postoperative outcomes in patients with early-stage gastric cancer who undergo radical gastrectomy is unclear. We aimed to investigate the predictive value of sarcopenia on adverse outcomes for stage I gastric cancer.MethodsThe clinical data of patients who underwent radical gastrectomy for stage I gastric cancer between July 2013 and May 2019 were prospectively collected. Basic sarcopenia components were measured preoperatively. Univariate and multivariate analyses were conducted to evaluate the risk factors for short- and long-term outcomes.ResultsA total of 507 patients with early-stage gastric cancer were included in the study, and 73 (14.4%) patients were diagnosed as sarcopenia. Patients with sarcopenia had significantly higher incidence of postoperative complications (32.9% vs. 17.5%, P = 0.002), longer postoperative hospital stays (13 days vs. 12 days, P < 0.001), higher hospitalization costs (65210 yuan vs. 55197 yuan, P < 0.001) and one-year mortality (8.2% vs. 1.8%, P = 0.002). During the median follow-up time of 38.8 months, 12 (16.4%) patients dead in the sarcopenic group and 25 (5.8%) patients dead in the non-sarcopenic group. Sarcopenia was an independent risk factor for both short- and long-term clinical outcomes. Moreover, we found that low muscle quantity and low handgrip strength mediated the adverse impacts of sarcopenia on postoperative complications while low muscle quality mediated the adverse impacts of sarcopenia on overall survival.ConclusionSarcopenia was strongly associated with worse short- and long-term clinical outcomes in patients with stage I gastric cancer who undergo radical gastrectomy.     

Is adjuvant chemotherapy necessary for early gastric cancer?

Objective:To quantify the potential benefit of adjuvant chemotherapy (ACT) with respect to survival, and to identify factors for predicting prognoses in early gastric cancer patients.Methods:Patients with pT1 gastric cancer (GC) who underwent radical resection with D2 lymphadenectomy were retrospectively analyzed. Based on lymph node metastasis (LNM) status and treatment regimens, patients were classified into groups, and clinicopathological variables, overall survival (OS), and disease-specific survival (DSS) were compared.Results:Of 1,050 enrolled patients, 151 patients (14.4%) had a positive LNM status. Submucosal invasion, undifferentiated state, tumor size > 2 cm, ulceration, and lymphovascular invasion were independent risk factors for LNM using multivariate analyses. The 5-year OS of all patients was 96.4%. HER2 positive, perineural invasion, and LNM were independent factors for worse survival. Patients with pT1N3 GC had a worse 5-year OS and DSS than pT1N0, pT1N1, and pT1N2 patients (P < 0.001). The 5-year OS and DSS for pT1N1 patients showed no significant difference between ACT and surgery only patients. For pT1N2 patients, the 5-year OS and DSS showed no significant difference between S-1 and Xelox treatments. For pT1N3 patients, 7 (36.8%) received S-1, while 12 (63.2%) received Xelox treatment. Patients receiving Xelox treatment showed a better 5-year OS (75.0% vs. 14.3%) and DSS (81.8% vs. 20.0%) than patients receiving S-1 (P < 0.05).Conclusions:Curative surgery only was adequate for patients with pT1N0 and pT1N1. Xelox showed no survival benefits for pT1N2 patients. Therefore, S-1 is the optimal choice for pT1N2 patients, when considering adverse effects. Xelox is recommended for pT1N3 patients.     

Prognostic value and clinicopathological correlation of the tumor regression grade in neoadjuvant chemotherapy for gastric adenocarcinoma: a retrospective cohort study

BackgroundNeoadjuvant chemotherapy (NACT) and radical gastrectomy are the gold standard treatments for resectable advanced gastric cancer (GC). However, the prognostic value of the pathological tumor regression grade (TRG) of NACT remains controversial. This retrospective study aimed to investigate the correlation between the TRG after NACT and clinicopathological features as well as its prognostic value in advanced GC.MethodsIn total, 551 patients with GC who received NACT combined with surgical resection at the Zhejiang Cancer Hospital from April 2004 to December 2019 were included. The demographic characteristics, treatment response, tumor characteristics, treatment regimens, and survival data were reviewed from the medical records of all patients. The Chi-square test was used to analyze the correlation between TRG and clinicopathological factors. Kaplan-Meier univariate analysis and Cox regression multivariate analysis were used to determine the independent risk factors affecting the prognosis of GC patients.ResultsAmong the 551 patients with advanced GC who accepted NACT treatment, 14 were determined to be in TRG 0, 98 in TRG 1, 257 in TRG 2, and 182 in TRG 3. Also, TRG was significantly correlated with the cT stage (P=0.015), ypT stage (P<0.001), ypN stage (P<0.001), ypTNM stage (P<0.001), vascular tumor thrombus (P<0.001), Borrmann classification (P=0.042), and lymph node ratio (LNR) (P<0.001). Furthermore, patients who had a good pathological response to NACT had a better prognosis, with a 3-year overall survival (OS) of 70.9% versus 48.8% in patients who had a poor pathological response. We also found that TRG (P=0.042, HR =1.65) was an independent prognostic factor affecting the OS of GC patients.ConclusionsTRG plays a significant role in the prognostic value in neoadjuvant chemotherapy for gastric adenocarcinoma. Patients with higher cT stage, higher levels of pre-CA199 and pre-CA125 may have worse pathological response.     

Prospective study to validate the clinical utility of DNA diagnosis of peritoneal fluid cytology test in gastric cancer

The clinical efficacy of DNA cytology test (CY) in gastric cancer (GC) has been retrospectively proposed using cancer-specific methylation of cysteine dioxygenase type 1 (CDO1). We confirmed the clinical utility of DNA CY in a prospective cohort. Four hundred GC samples were prospectively collected for washing cytology (UMIN000026191), and detection of the DNA methylation of CDO1 was assessed by quantitative methylation-specific PCR in the sediments. Endpoint was defined as the match rate between conventional CY1 and DNA CY1 (diagnostic sensitivity), and the DNA CY0 rate (diagnostic specificity) in pStage IA. DNA CY1 was detected in 45 cases (12.5%), while CY1 was seen in 31 cases (8.6%) of 361 chemotherapy-naïve samples, where the sensitivity and specificity of the DNA CY in the peritoneal solutions were 74.2% and 96.5%, respectively. The DNA CY was positive for 3.5/0/4.9/11.4/58.8% in pStage IA/IB/II/III/IV, respectively (P < .01). In the multivariate analysis, DNA CY1 was independently correlated with pathological tumor depth (pT) (P = .0012), female gender (P = .0099), CY1 (P = .0135), P1 (P = .019), and carcinoembryonic antigen (CEA) (P = .036). The combination of DNA CY1 and P factor nearly all covered the potential peritoneal dissemination (P1 and/or CY1 and/or DNA CY1) (58/61:95.1%). DNA CY1 had a significantly poorer prognosis than DNA CY0 in GC patients (P < .0001). DNA CY1 detected by CDO1 promoter DNA methylation has a great value to detect minimal residual disease of the peritoneum in GC clinics, representing poor prognosis as a novel single DNA marker.     

Prognostic significance of peritoneal lavage cytology in gastric cancer in Singapore

Background Peritoneal lavage cytology has been included as part of the staging process in the 13th edition of the Japanese Classification of Gastric Cancer. However, this procedure has neither been studied nor established in our population. We aimed to evaluate its prognostic relevance among our patients with gastric cancer. Methods A total of 142 consecutive patients with gastric carcinoma were recruited prospectively. All had histologically proven gastric carcinomas and had undergone laparotomy and intraoperative peritoneal lavage for cytological examination at Singapore General Hospital. The fluid recovered was centrifuged and stained by the Papanicolau method. All patients were followed up with endpoints of cancer recur-rence and mortality. Results There were 91 men and 51 women; 36 patients (25.4%) had positive peritoneal lavage. Patients with advanced macroscopic features, presence of vascular invasion, nodal involvement, advanced depth of tumor invasion and metastatic disease tended to have positive lavage, by univariate logistic regression analysis. Despite curative resections, patients with positive cytology had a more dismal disease-free survival (mean, 27 months vs 53 months; P < 0.0001 by log rank test) and higher recurrence rate (54.5% vs 19.3%; P = 0.007 by log rank test). There was also a trend towards earlier recurrences (median, 8 months vs 11 months; P = 0.37). By multivariate Cox regression stepwise analysis, advanced depth of tumor invasion and positive lavage cytology were found to be independent poor prognostic factors for disease-free survival. Conclusion Positive peritoneal lavage cytology correlated well with advanced features of gastric cancer. It is an independent poor prognostic factor and the procedure should be routinely performed. Integration of lavage status into our current staging systems may serve as a guide for adjuvant therapeutic options to improve the survival of gastric cancer in our population.     

血清甲胎蛋白阳性胃癌患者的临床病理学特征及预后分析

背景与目的：血清甲胎蛋白（alpha-fetoprotein,AFP）阳性胃癌是一种临床上比较罕见的胃恶性肿瘤,具有与普通胃癌明显不同的生物学特点,探讨血清AFP阳性胃癌患者的临床病理学特征及影响预后的危险因素。方法：采用回顾性队列研究,分析河北医科大学第四医院外三科2012年1月1日—2015年1月1日行根治性手术治疗的2 386例胃癌患者,筛选出术前血清AFP阳性的患者,分析临床病理学特征及影响预后的因素。结果：2 386例胃癌患者中术前血清AFP阳性者245例（AFP≥20 ng/mL,10.27%）,其余2 141例术前血清AFP均为正常（AFP＜20 ng/mL,89.73%）。与血清AFP阴性组相比,血清AFP阳性组患者的同时性肝转移率、异时性肝转移率、淋巴结转移率、脉管浸润发生率更高（P均＜0.05）。2 386例胃癌患者中共有2 273例（95.26%）获得完整随访资料,全组患者5年总生存率（overall survival,OS）为49.32%,5年无病生存率（disease-free survival,DFS）为44.61%。其中血清AFP阳性者5年OS和DFS分别为37.50%和34.17%,而血清AFP阴性者5年OS和DFS分别为50.90%和45.84%,两组患者的5年OS和DFS差异均有统计学意义（P均＜0.001）。单因素分析显示,术前血清AFP的水平、年龄、病灶部位、肿瘤直径、组织学类型、Borrmann分型、肿瘤浸润深度pT分期、淋巴结转移pN分期、肿瘤pTNM分期、Lauren分型、脉管瘤栓有无、Ki-67阳性比例、术后是否化疗、术后有无肝转移是影响血清AFP阳性胃癌患者预后的危险因素（P均＜0.05）。多因素分析发现,血清AFP水平（P=0.001）、肿瘤组织学类型（P=0.002）、肿瘤浸润深度pT分期（P=0.006）、淋巴结转移pN分期（P=0.014）、肿瘤pTNM分期（P=0.001）、脉管瘤栓有无（P=0.024）和术后有无肝转移（P=0.008）是影响其预后的独立危险因素,而术后辅助化疗（P=0.031）是患者预后的保护性因素。结论：AFP阳性胃癌具有易发生肝转移、淋巴结转移且预后差的特点,血清AFP水平是影响其预后的独立危险因素,随着AFP水平的升高,其预后变差。     

Prognostic value of D-dimer levels in patients with gastric cancer undergoing gastrectomy

BackgroundPlasma D-dimer levels have been associated with tumor progression and oncological outcomes in several cancers. This study assessed the relationships of D-dimer levels with clinicopathological features and survival outcomes in patients with gastric cancer undergoing gastrectomy.MethodsData from 666 patients with gastric cancer who underwent gastrectomy between June 2012 and December 2015 were collected and analyzed; these data were acquired during a previous randomized clinical trial (PROTECTOR trial, NCT01448746). Optimal cut-off values of preoperative, immediate postoperative, postoperative-day 1, postoperative-day 4, and postoperative-day 30 D-dimer levels for predicting overall survival (OS) and disease-free survival (DFS) were determined using Contal and O'Quigley's method. The optimal cut-off value of the immediate postoperative D-dimer level for predicting OS was 3.33. Patients were divided into D-dimer high and low groups based on these cut-off values.ResultsHigh immediate postoperative D-dimer levels were significantly associated with advanced T stage and TNM stage (P = 0.001 and P = 0.006, respectively). OS and DFS were significantly lower for patients in the D-dimer high group than for patients in the D-dimer low group; this relationship was consistent for preoperative, immediate postoperative, postoperative-day 1, and postoperative-day 30 D-dimer levels. Multivariate analysis identified the immediate postoperative D-dimer level as an independent prognostic factor for OS (hazard ratio, 2.52; P = 0.010).ConclusionsElevated immediate postoperative D-dimer level was predictive of poor long-term outcomes in patients with gastric cancer after gastrectomy. Immediate postoperative D-dimer levels may offer simple and inexpensive clinical decision-making guidance for patients with gastric cancer after gastrectomy.