Intraoperative peritoneal lavage cytology offers prognostic significance for gastric cancer patients with curative resection

Outcomes of patients with gastric cancer who exhibit positive peritoneal lavage cytology findings (CY⁺) vary by diagnostic methods because of quantitative and qualitative cancer cell diversity. This study sought to establish practical diagnostic criteria for performing curative resections, based on peritoneal lavage cytology findings in gastric cancer patients. We enrolled 1028 patients with gastric cancer who underwent R0/1 (n = 911) or R2 (n = 117) resections and analyzed relationships between cancer cell findings in peritoneal lavage fluid and clinicopathological factors in the R0/1 group. We found 68 patients with CY⁺ status. Receiver operating characteristic analyses and multivariate analyses showed that the presence of ≥1 signet ring cell, ≥5 cell clusters or ≥50 isolated cancer cells in peritoneal lavage fluid predicted poor prognoses in the 68 CY⁺ patients. High‐risk CY⁺ group patients with at least one of the above predictors had the highest hazard ratio (HR = 3.28, P < 0.001). The remaining (low‐risk) patients had a survival curve similar to that of patients with a normal cytology. The high‐risk CY⁺ patients who underwent R1 resection had poor prognoses despite no macroscopic peritoneal metastasis (2% 5‐year survival)—equivalent to that of patients who underwent R2 resection. The CY⁺ criteria defined in this study could help identify candidates for curative resection as an initial therapy for gastric cancer.     

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.     

Role of staging laparoscopy with peritoneal lavage cytology in the treatment of locally advanced gastric cancer

Background More accurate preoperative staging is necessary to determine the treatment strategy for locally advanced gastric cancer. Laparoscopy has been suggested as an appropriate staging modality. The aim of this study was to clarify the role of staging laparoscopy in patients with locally advanced gastric cancer. Methods One hundred patients with primary gastric adenocarcinoma underwent laparoscopy with peritoneal lavage cytology. The disease stages determined were compared with those obtained by conventional methods. Results The disease stages were corrected after laparoscopy for 47 of the 100 patients (47%), with downstaging in 3 (3.0%) and upstaging in 44 (44%). Peritoneal deposits were found in 7 patients with peritoneal dissemination diagnosed by conventional examination. An unsuspected peritoneal deposit was found in 21 of 93 patients (22.6%), and unsuspected free cancer cells without deposits were found in 27 of 93 patients (29.0%). Gastrectomy after staging laparoscopy was performed in 39 patients. Laparoscopy showed no peritoneal deposits in any of these patients. Free cancer cells were found in 9 patients (23.1%), but 4 of these had peritoneal deposits at operation. R0 resection was performed in 34 of the 39 patients (87.2%). Neoadjuvant chemotherapy after staging laparoscopy was performed in 35 patients. All 35 patients underwent gastrectomy, which resulted in 27 R0 and 8 R2 resections. Of 18 patients with positive cytology at laparoscopy, 11 had no free cancer cells at operation. Neoadjuvant chemotherapy induced downstaging of the disease in 11 of the 18 patients with positive cytology (61.1%). Of 26 patients with massive peritoneal deposits, 4 underwent palliative resection because of pyloric stenosis. Twenty-two patients (22.0%) were able to avoid unnecessary laparotomy because of the staging laparoscopy. Conclusion Staging laparoscopy with peritoneal lavage cytology is a safe, effective tool in patients with locally advanced gastric cancer, especially in patients receiving neoadjuvant chemotherapy.     

胃癌患者术中腹腔灌洗细胞学检测的临床研究

目的　探讨腹腔游离癌细胞与胃癌的侵润深度、浆膜受侵面积及病理类型等之间的相互关系。方法　对 16 3例胃癌患者行术中腹腔灌洗细胞学检查找游离癌细胞。结果　总的灌洗阳性率为2 6 .3%。不同侵犯深度 (T1～T4)阳性率分别为 0、13.3%、2 9.8%、5 3.8% ;胃浆膜受侵面积≤ 10cm2 者阳性率为 12 .6 %、11～ 2 0cm2 者 2 1.9%、2 1～ 30cm2 者 4 2 .1%、≥ 31cm2 者高达 6 6 .6 %。结论　胃癌腹腔游离癌细胞的阳性率与肿瘤侵润深度、浆膜受侵面积及病理类型等直接相关。     

Evaluation of positive cases with peritoneal lavage cytology in gastric cancer

Peritoneal dissemination with advanced gastric cancer is of significant problem. Peritoneal lavage cytology has been an effective method for the detection of early peritoneal dissemination since 1999. The accurate evaluation of peritoneal lavage cytology is unclear except for the same prognosis of peritoneal dissemination. We examined the clinical findings and the prognosis with positive cases in peritoneal lavage cytology. The prognosis of cases with P1CY1 or P2P3 group was poorer than in the P0CY1 or P0, CY1 group. We thus review the evaluation of peritoneal lavage cytology with gastric cancer in the Japanese and English literature. In addition, we describe the diagnosis of early peritoneal dissemination using peritoneal lavage tumor markers or molecular markers of peritoneal lavage.     

胃癌患者腹腔游离癌细胞的检测及其临床意义

腹腔播散是进展期胃癌常见的转移方式,由于目前尚没有标准的检测胃癌腹腔微转移的方法,故大部分腹腔微转移的胃癌患者难以得到临床诊断.应用腹腔灌洗细胞学（PLC）检测腹腔游离癌细胞（IFCCs）的结果与腹腔镜检查结果相似,但是腹腔镜结合PLC可增加检查的敏感性.应用免疫组化和酶联免疫吸附试验可检测腹腔灌洗液（PLF）中IFCCs肿瘤标志,IFCCs预测胃癌复发的阳性预报值为91%,特异性为97%.应用免疫组化检测IFCCs是一个有效的、独立的预测胃癌生存期的阴性指标.应用酶联免疫吸附试验检测PLF中CEA水平是预测腹腔播散的指标,其诊断腹腔微转移的敏感性和特异性分别是75.8%和90.8%.应用PLF进行分子诊断的敏感性优于PLC、免疫组化和酶联免疫吸附试验.逆转录聚合酶链式反应（RT-PCR）是一种新的诊断腹腔灌洗液中IFCCs的方法,基于靶基因的RT-PCR方法可用于检测腹腔微转移的肿瘤分子标志.在IFCCs中表达的这些分子标志还可用于腹腔微转移治疗.存在IFCCs的胃癌患者的预后很差,无论应用哪种方法预测腹腔微转移都是困难的,但术前均应进行IFCCs检查,以明确诊断和指导治疗.     

胃癌患者腹腔游离癌细胞的检测及其临床意义

腹腔播散是进展期胃癌常见的转移方式,由于目前尚没有标准的检测胃癌腹腔微转移的方法,故大部分腹腔微转移的胃癌患者难以得到临床诊断。应用腹腔灌洗细胞学(PLC)检测腹腔游离癌细胞(IFCCs)的结果与腹腔镜检查结果相似,但是腹腔镜结合PLC可增加检查的敏感性。应用免疫组化和酶联免疫吸附试验可检测腹腔灌洗液(PLF)中IFCCs肿瘤标志,IFCCs预测胃癌复发的阳性预报值为91%,特异性为97%。应用免疫组化检测IFCCs是一个有效的、独立的预测胃癌生存期的阴性指标。应用酶联免疫吸附试验检测PLF中CEA水平是预测腹腔播散的指标,其诊断腹腔微转移的敏感性和特异性分别是75.8%和90.8%。应用PLF进行分子诊断的敏感性优于PLC、免疫组化和酶联免疫吸附试验。逆转录聚合酶链式反应(RTPCR)是一种新的诊断腹腔灌洗液中IFCCs的方法,基于靶基因的RTPCR方法可用于检测腹腔微转移的肿瘤分子标志。在IFCCs中表达的这些分子标志还可用于腹腔微转移治疗。存在IFCCs的胃癌患者的预后很差,无论应用哪种方法预测腹腔微转移都是困难的,但术前均应进行IFCCs检查,以明确诊断和指导治疗。     

胃癌患者腹腔冲洗液细胞学检查的临床研究

目的观察胃癌患者腹腔脱落细胞与临床病理分期的关系,为术中采用杀死脱落癌细胞及术后治疗提供依据.方法对80例胃癌患者腹腔冲洗液行细胞学检查并将结果与临床分期对比分析.结果本组患者脱落癌细胞阳性者52例,占65%.Ⅰ、Ⅱ、Ⅲ、Ⅳ期胃癌患者脱落细胞学检出率分别为0、50%、63.8%、100%.T1、T2和T3以上者脱落癌细胞检出率分别为7.1%、18.9%、54.2%.结论胃癌患者腹腔脱落癌细胞检出率随着病期进展、肿瘤增大而增加.术中腹腔采用杀死癌细胞、术后采用腹腔灌注化疗是必要的.     

A practical application of neural network analysis for predicting outcome of individual breast cancer patients

Summary It has been previously shown that Neural Networks can be trained to recognize individual breast cancer patients at high and low risk for recurrent disease and death. This paper expands on the initial investigation and shows that by coding time as one of the prognostic variables, a Neural Network can use censored survival data to predict patient outcome over time. In this demonstration a Neural Network was trained, tested, and validated using censored survival data from a group of 1373 patients with node-positive breast cancer. The Neural Network method predicted patient outcome as accurately as Cox Regression modeling. The final Neural Network model can be presented with a patient's prognostic information and make a series of predictions about probability of relapse at different times of follow-up, allowing one to draw survival probability curves for individual patients.     

Prognostic significance of peritoneal lavage cytology in staging gastric cancer: systematic review and meta-analysis

Background

Peritoneal cytology has been used as a part of the cancer staging of gastric cancer patients. The primary aim of this systematic review was to evaluate the value of peritoneal cytology as part of the staging of gastric cancer and survival prediction. The second aim was to establish if positive cytology may be modified by neoadjuvant therapy, to improve prognosis.

Methods

An electronic literature search was performed using Embase, Medline, Web of Science, and Cochrane library databases up to January 2016. The logarithm of the hazard ratio (HR) with 95% confidence intervals (CI) was used as the primary summary statistic. Comparative studies were used, and the outcome measure was survival in three groups: (1) positive versus negative cytology at staging laparoscopy immediately preceding surgery; (2) effect of neoadjuvant therapy on cytology and survival; and (3) positive cytology in the absence of macroscopic peritoneal disease was compared with obvious macroscopic peritoneal disease.

Results

Pooled analysis demonstrated that positive cytology was associated with significantly reduced overall survival (HR, 3.46; 95% CI, 2.77–4.31; P < 0.0001). Interestingly, negative cytology following neoadjuvant chemotherapy was associated with significantly improved overall survival (HR, 0.42; 95% CI, 0.31–0.57; P < 0.0001). The absence of macroscopic peritoneal disease with positive cytology was associated with significantly improved overall survival (HR, 0.64; 95% CI, 0.56–0.73; P < 0.0001).

Conclusion

This study suggests that patients with initial positive cytology may have a good prognosis following neoadjuvant treatment if the cytology results change to negative after treatment.

     

Anemia may influence the outcome of patients undergoing neo-adjuvant treatment of rectal cancer.

BACKGROUND: We hypothesized that anemia could represent one of the major factors influencing the outcome of patients undergoing neo-adjuvant treatment of rectal cancer. PATIENTS AND METHODS: This analysis included all the consecutive patients who underwent neo-adjuvant treatment (chemotherapy and/or radiotherapy) before surgery for rectal cancer in three oncology/radiotherapy departments from June 1996 to December 2003. RESULTS: Three hundred and seventeen patients were eligible for our analysis. Median age at diagnosis was 64 years (range 26-88 years); male/female ratio was 184/133. Two hundred and eighty-five patients (89.9%) were diagnosed with adenocarcinoma, while 32/317 (10.1%) with mucinous adenocarcinoma. Neo-adjuvant treatments carried out were as follows: radiotherapy alone in 75/317 patients (23.7%), radiotherapy plus chemotherapy in 242/317 patients (76.3%). At univariate and multivariate analysis, only the hemoglobin (Hb) level (group 1: < or=12 g/dl versus group 2: >12 g/dl) resulted in a significant factor for disease-free survival. The role of the Hb level seemed to be confirmed further by the clinical downstaging obtained in approximately 55% of patients in group 2, in comparison with 35% of the patients achieving a significant downstaging in group 1. CONCLUSION: Our results indicated that anemia could represent an important parameter able to influence the outcome in patients receiving neo-adjuvant treatment of rectal cancer.     

Free intraperitoneal tumor cells and outcome in gastric cancer patients: a systematic review and meta-analysis

Purpose

Despite continuously improving therapies, gastric cancer still shows poor survival in locally advanced stages with local recurrence rates of up to 50% and peritoneal recurrence rates of 17% after curative surgery. We performed a systematic review with meta-analyses to clarify whether positive intraperitoneal cytology (IPC) indicates a high risk of disease recurrence and poor overall survival in gastric cancer.

Methods

Multiple databases were searched in December 2014 to identify studies on the prognostic significance of positive intraperitoneal cytology in gastric cancer, including: Medline, Biosis, Science Citation Index, Embase, CCMed and publisher databases. Hazard ratios (HR) and associated 95% confidence intervals (CI) were extracted from the identified studies. A meta-analysis was performed using a random-effects model on overall survival, disease-free survival and peritoneal recurrence free survival.

Results

A total of 64 studies with a cumulative sample size of 12,883 patients were included. Cytology, quantitative real time polymerase chain reaction (PCR) or both were performed in 35; 21 and 8 studies, respectively. Meta analyses revealed free intraperitoneal tumor cells (FITC) to be associated with poor overall survival in univariate (HR 3.27; 95% CI 2.82 - 3.78]) and multivariate (HR 2.45; 95% CI 2.04 - 2.94) analysis and poor peritoneal recurrence free survival in univariate (4.15; 95% CI 3.10 - 5.57) and multivariate (3.09; 95% CI 2.02 - 4.71) analysis. Subgroup analysis showed this effect to be independent of the detection method, Western or Asian origin or the time of publication.

Conclusions

FITC oder positive peritoneal cytology is associated with poor survival and increased peritoneal recurrence in gastric cancer.     

温热重蒸馏水对人胃癌细胞系杀伤效应与在胃癌根治切除术中腹腔灌洗疗效的分析

Objective:To evaluate the effect andindications of radical gastrectomy combined with peritoneal lavage with thermal double distilled water(DDW)or DDW plus chlorthexidine acetate.Methods:On the bases of the study on the killing effect of 43℃ DDW on human gastric cancer cell line MGC-803 and its inhibiting effect on ascitic tumor of SY86B morse,500 cases of gastric cancer who underwent radical gastectomy from January 1986 to December 1995 were divided into three groups:group A(n=198) subject to radical gastrectomy and peritoneal lavage for 10min with 4000ml DDW at 43℃ ;group B(n=89)subject to radical gastrectomy and peritoneal lavage for 4min with 4000ml DDW plus 0.6g chlorthexidine acetate,and grup C(n=213) subject to radical gastrectomy and peritoneal lavage for 4 min with 4000ml normal saline at room temperature as control.Results Human gastric cancer cells MGC-803 could be completely killed by treatment of either 43℃ DDW for 10min or DDW plus 0.015ml/L chlorhexidine acetate for 4 min.Clinical trials proved group A and group B(called lavage group as a whole)had almost the same curative effects.The 1-year survival rate and 3-year survival rate were similar in different stages among the groups.The 5-year survival rate was 63.8% in the lavage group and 51.2% in the control group respectively.Most of the cases with good effect were at the mid-stage (Ⅱand Ⅲ stage).Conclusion Radical gastrectom combined with peritoneal peritoneal lavage before closing the abdomen has satisfying effect on patients with gastric cancer at stage Ⅱ and stage ⅢA.