Intraperitoneal Free Cancer Cells Research Articles

Assessment of Hyperthermic Intraperitoneal Chemotherapy to Eradicate Intraperitoneal Free Cancer Cells

OBJECTIVE: To assess the effect of hyperthermic intraperitoneal chemotherapy (HIPEC) to eradicate intraperitoneal free cancer cells and to explore the feasibility of cytological cure for peritoneal carcinomatosis (PC). METHODS: The peritoneal lavage fluid (or ascites) from 50 PC patients was collected before and after intraoperative HIPEC, respectively, for conventional cytology test, and conventional and real-time quantitative reverse transcript polymerase chain reaction detecting carcinoembryonic antigen (CEA) mRNA and cytokeratin-20 (CK20) mRNA. The blood samples 3 days before and 7 days after intraoperative HIPEC were also collected for detecting the serum tumor markers, including CEA, carbohydrate antigen (CA) 125, and CA19-9. RESULTS: The positive rate of conventional cytology test before HIPEC versus after HIPEC was100.0% versus 22.0% (P = .000). The positive rates of CEA mRNA and CK20 mRNA before HIPEC versus after HIPEC were 100.0% versus 86.0% (P = .012) and 100.0% versus 96.0% (P = .495), respectively. Moreover, after HIPEC, 18 (36.0%) patients had a decline in CEA mRNA (P = .000), and 17 (34.0%) patients had a decline in CK20 mRNA (P = .000). The positive rates of serum CEA, CA125, and CA199 before HIPEC versus after HIPEC were 52.0% versus 28.0% (P = .014), 52.0% versus 44.0% (P = .423), and 40.0% versus 28.0% (P = .205), respectively. CONCLUSION: HIPEC could effectively eradicate intraperitoneal free cancer cells and partially achieve cytological cure for PC.

Role of genetic detection in peritoneal washes with gastric carcinoma: The past, present and future.

The most frequent cause of treatment failure following surgery for gastric cancer is peritoneal dissemination, mainly caused by the seeding of free cancer cells from the primary gastric cancer, which is the most common type of spread. Unfortunately, there is no standard modality of intraperitoneal free cancer cells detection to predict peritoneal metastasis until now. We reviewed English literature in PubMed was done using the MeSH terms for gastric cancer, peritoneal wash, and reverse transcriptase polymerase chain reaction. All the articles were reviewed and core information was tabulated for reference. After a comprehensive review of all articles, the data was evaluated by clinical implication and predictive value of each marker for peritoneal recurrence. There are still many limitations to overcome before the genetic diagnosis for free cancer cells detection can be considered as routine assay. To make it a reliable diagnostic tool for detecting free cancer cells, the process and method of genetic detection with peritoneal washes should be standardized, and the development of simple diagnostic devices and easily available kits are necessary. Herein, we reviewed the past, present and future perspectives of the peritoneal lavage for the detection of intraperitoneal free cancer cells in patients with gastric cancer.

Abstract 3412: Virus-guided fluorescence imaging of intraperitoneal free gastric cancer cells: a preliminary clinical study as a potential clinical biomarker

Abstract Objectives: In patients with gastric cancer, peritoneal dissemination is the most common metastasis. To predict future peritoneal recurrences, peritoneal lavage cytology is performed during operation. But even cytology-negative patients sometimes develop peritoneal recurrences. Thus an additional method to detect intraperitoneal free gastric cancer cells is necessary. We have developed a genetically engineered adenovirus, TelomeScan, which replicates and expresses GFP only in telomerase-activated cancer cells. Here we detected intraperitoneal free gastric cancer cells using TelomeScan, and investigated the correlation between the number of GFP-positive cells and patient prognosis. Methods: Peritoneal wash was obtained from 69 gastric cancer patients during operation. The cells in the wash were infected with TelomeScan for 24 hours. Finally, GFP-positive cells were counted under a fluorescence microscope. In some GFP-positive cases immunofluorescence assay was added. Clinicopathological data were obtained from medical records. Then we examined different cut-off values (the number of GFP-positive cells which indicates TelomeScan-positive) and estimated survival curves using the Kaplan-Meier method, and compared using the Wilcoxon test. Results: For a cut-off value of 10, 25 of the 69 cases were TelomeScan-positive (10 or more GFP-positive cells). And these 25 cases showed the most significant worse prognosis when compared to the 44 TelomeScan-negative cases (p = 0.0040). In addition, 17 of the 69 cases were conventional cytology-positive. Of these 17 cases, 9 were TelomeScan-positive, and these 9 cases showed significantly worse prognosis than the 8 TelomeScan-negative conventional cytology-positive cases (p = 0.0017, MST 195 days). Under fluorescence microscope we observed that GFP-positive cells sometimes formed cell clusters with GFP-negative cells. Immunofluorescence assay showed that these GFP-negative cells expressed CD45, which means these cells were leukocytes. Conclusion: We have successfully detected cancer cells in peritoneal wash using TelomeScan. The presence of GFP-positive cells in peritoneal wash was associated with worse prognosis. TelomeScan-positive patients, especially in conventional cytology-positive cases, showed remarkably worse prognosis than TelomeScan-negative conventional cytology-positive patients. Our data suggest that TelomeScan-guided cytological detection may have clinical implications as a prognostic biomarker in gastric cancer. Citation Format: Megumi Watanabe, Shunsuke Kagawa, Kazuya Kuwata, Michihiro Ishida, Yuuri Hashimoto, Naoto Hori, Satoru Kikuchi, Shinji Kuroda, Hiroyuki Kishimoto, Masahiko Nishizaki, Hiroshi Tazawa, Yasuo Urata, Toshiyoshi Fujiwara. Virus-guided fluorescence imaging of intraperitoneal free gastric cancer cells: a preliminary clinical study as a potential clinical biomarker. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3412. doi:10.1158/1538-7445.AM2015-3412

Detection methods and clinical significance of free peritoneal tumor cells found during colorectal cancer surgery.

Peritoneal washing is now part of the standard clinical practice in several abdominal and pelvic neoplasias. However, in colorectal cancer surgery, intra-peritoneal free cancer cells (IFCC) presence is not routinely investigated and their prognostic meaning is still unclear. When peritoneal washing results are positive for the presence of IFCC a worse outcome is usually expected in these colorectal cancer operated patients, but it what is not clear is whether it is associated with an increased risk of local recurrence. It is authors' belief that one of the main reasons why IFCC are not researched as integral part of the routine staging system for colon cancer is that there still isn't a diagnostic or detection method with enough sensibility and specificity. However, the potential clinical implications of a routine research for the presence IFCC in colon neoplasias are enormous: not only to obtain a more accurate clinical staging but also to offer different therapy protocols, based on the presence of IFCC. Based on this, adjuvant chemotherapy could be offered to those patients found to be positive for IFCC; also, protocols of proactive intraperitoneal chemotherapy could be applied. Although presence of IFCC appears to have a valid prognostic significance, further studies are needed to standardize detection and examination procedures, to determine if there are and which are the stages more likely to benefit from routine search for IFCC.

Abstract 4726: Virus-guided fluorescence imaging of intraperitoneal free gastric cancer cells as a potential clinical biomarker

Abstract Peritoneal dissemination is a common pattern of metastasis in patients with gastric cancer, and associated with worse prognosis. Peritoneal lavage cytology during the operation is an important factor in predicting future development of peritoneal metastasis and determining the treatment strategy, but its sensitivity and specificity are unsatisfactory. TelomeScan is an adenovirus engineered to replicate and express GFP only in telomerase-activating tumor cells, so that we can easily detect viable cancer cells even among numerous normal cells. We hypothesized that TelomeScan might be applicable to detecting free cancer cells in peritoneal wash. Methods: Peritoneal washes were obtained from 42 gastric cancer patients during operation. The number of GFP-positive cells was determined for each sample and compared with cytology results and clinicopathological data Results: Clinical stage was ranged from IA to IV, and thirteen cases were diagnosed as class IV or class V by peritoneal lavage cytology. More than 10 GFP-positive cells were detected in 12 out of 42 cases, and these cases showed a worse prognosis when compared to the other 30 cases. Conclusion: We were able to detect gastric cancer cells as GFP-positive cells in peritoneal wash using TelomeScan. Furthermore, the presence of GFP-positive cells in peritoneal wash was associated with worse prognosis. These results suggest that number of cancer cells detected by TelomeScan in the peritoneal wash may have important clinical implication as prognostic and therapeutic biomarkers in gastric cancer. Citation Format: Megumi Watanabe, Shunsuke Kagawa, Michihiro Ishida, Naoto Hori, Satoru Kikuchi, Shinji Kuroda, Hiroyuki Kishimoto, Masahiko Nishizaki, Hiroshi Tazawa, Toshiyoshi Fujiwara. Virus-guided fluorescence imaging of intraperitoneal free gastric cancer cells as a potential clinical biomarker. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4726. doi:10.1158/1538-7445.AM2014-4726

Intra-operative peritoneal lavage for colorectal cancer.

Free cancer cells can be detected in peritoneal fluid at the time of colorectal surgery. Peritoneal lavage in colorectal surgery for cancer is not used in routine, and the prognostic significance of intraperitoneal free cancer cells (IPCC) remains unclear. Data concerning the technique of peritoneal lavage to detect IPCC and its timing regarding colorectal resection are scarce. However, positive IPCC might be the first step of peritoneal spread in colorectal cancers, which could lead to early specific treatments. Because of the important heterogeneity of IPCC determination in reported studies, no treatment have been proposed to patients with positive IPCC. Herein, we provide an overview of IPCC detection and its impact on recurrence and survival, and we suggest further multi-institutional studies to evaluate new treatment strategies.

EVOCAPE 2 study: Lack of prognostic significance of conventional peritoneal cytology in colorectal and gastric cancer?

With great interest we read the article by Cotte et al.1 concerning the prognostic significance of peritoneal cytology in colorectal and gastric cancer. The authors performed a prospective multicentre analysis on the prognostic significance of intraperitoneal free cancer cells (IPCC) in 1364 patients with various gastrointestinal malignancies. The authors concluded that IPCC was not an independent prognostic factor and did not add any additional prognostic information to known tumour related prognostic factors.

Reply to: EVOCAPE 2 study: Lack of prognostic significance of conventional peritoneal cytology in colorectal and gastric cancer?

We appreciate the interest that Braam et al. have paid to the results of our study EVOCAPE 2. 1 Cotte E. Peyrat P. Piaton E. et al. Lack of prognostic significance of conventional peritoneal cytology in colorectal and gastric cancers: results of EVOCAPE 2 multicentre prospective study. Eur J Surg Oncol. 2013; 39: 707-714 Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar They suggest that the conclusions concerning the prognostic significance of intraperitoneal free cancer cells (IPCC), especially for the development of PC in gastric cancer should be interpreted with caution. We totally agree with them. The main message of our study was that conventional cytology is probably not useful for colorectal and gastric cancers because of its low rate of positivity. It does not bring any additional information in term of recurrence risk or survival than usual prognostic factors (TNM, differentiation…). Despite a standardized procedure for cytology and a panel of 7 cytopathologists for interpretation, the prevalence of IPCC remained low in our study. EVOCAPE 2 study: Lack of prognostic significance of conventional peritoneal cytology in colorectal and gastric cancer?European Journal of Surgical OncologyVol. 39Issue 11PreviewWith great interest we read the article by Cotte et al.1 concerning the prognostic significance of peritoneal cytology in colorectal and gastric cancer. The authors performed a prospective multicentre analysis on the prognostic significance of intraperitoneal free cancer cells (IPCC) in 1364 patients with various gastrointestinal malignancies. The authors concluded that IPCC was not an independent prognostic factor and did not add any additional prognostic information to known tumour related prognostic factors. Full-Text PDF

Author's reply

I read the letter written by Luigina Graziosi. I totally agree with the opinion that the presence of intraperitoneal free cancer cells (IFCCs) may play a significant role in the peritoneal recurrence and be a negative prognostic factor for post-surgical recurrences in advanced gastric cancer. Peritoneal citology as prognostic factor for recurrences in node-negative advanced gastric cancerEuropean Journal of Surgical OncologyVol. 39Issue 7PreviewDear Editor I read with interest the paper written by Lee I.S. titled “Prognostic factors and recurrence pattern in node-negative advanced gastric cancer”. Full-Text PDF

Lack of prognostic significance of conventional peritoneal cytology in colorectal and gastric cancers: Results of EVOCAPE 2 multicentre prospective study

In digestive cancers, the prognostic significance of intraperitoneal free cancer cells remains unclear (IPCC). The main objective of this study was to assess the prognostic significance of IPCC in colorectal and gastric adenocarcinoma. The secondary objectives were to evaluate the predictive significance of IPCC for the development of peritoneal carcinomatosis (PC) and to evaluate the prevalence of synchronous PC and IPCC. This was a prospective multicentre study. All patients undergoing surgery for a digestive tract cancer had peritoneal cytology taken. Patients with gastric and colorectal cancer with no residual tumour after surgery and no evidence of PC were followed-up for 2 years. The primary end point was overall survival. Between 2002 and 2007, 1364 patients were enrolled and 956 were followed-up over 2 years. Prevalence of IPCC was 5.7% in colon cancer, 0.6% in rectal cancer and 19.5% in gastric cancer. The overall 2-year survival rate for patients with IPCC was 34.7% versus 86.8% for patients with negative cytology (p<0.0001). By multivariate analysis, IPCC was not an independent prognostic factor. No relationship between cytology and recurrence was found. The presence of IPCC was not an independent prognostic and didn't add any additional prognostic information to the usual prognostic factors related to the tumour (pTNM and differentiation). Moreover the presence of IPCC detected with this method didn't appear to predict development of PC. Peritoneal cytology using conventional staining doesn't seem to be a useful tool for the staging of colorectal and gastric cancers.

Isolation of intraperitoneal free cancer cells from colorectal cancer by immunomagnetic beads

Objective To explore the value of immuomagnetic beads(IMB) technique for detection of intraperitoneal free cancer cells from colorectal cancer.Methods Peritoneal lavage fluid was obtained from 80 patients with colorectal cancer during laparotomy.Peritoneal lavage cytology (PLC) and IMB were used to detect free cancer cells in peritoneal lavage fluid.10 patients with hysteromyoma during laparotomy were enrolled into the control group.Results The positive rate of PLC was 8.8％ (7/80),the positive rate of IMB was 28.8％ (23/80).The positive case after useing PLC detect,IMB detect also was positive.The detected samples of control group were negative by these two methods.IMB was superior to PLC ( x2 =10.503,P =0.001 ).Conclusion IMB was more sensitive and specific than PLC,which could provide a effective method for finding intraperitoneal free cancer cells. Key words: Colorectal cancer; Immunomagnetic beads; Cytological techniques

A Patient with Gastric Adenosquamous Carcinoma with Intraperitoneal Free Cancer Cells who Remained Recurrence-free with Postoperative S-1 Chemotherapy

The case of a patient with gastric adenosquamous carcinoma with positive cancer cells on intraperitoneal washing cytology (CY1) who achieved a long recurrence-free survival is herein reported. A 74-year-old man was found to have adenosquamous carcinoma of the stomach. Partial gastrectomy was performed, and a pathological examination confirmed a diagnosis of adenosquamous carcinoma with invasion into the serosa and lymph node metastasis. S-1 monotherapy was administered because a cytologic examination revealed that the patient's peritoneal washings were positive for cancer cells. The patient remains alive with no recurrence two years and 10 months after undergoing surgery. Postoperative chemotherapy with S-1 monotherapy is effective for treating adenosquamous carcinoma of the stomach with CY1 and might contribute to long-term survival.

Impact of Intraperitoneal Chemotherapy after Gastrectomy with Positive Cytological Findings in Peritoneal Washings

Background: There is no standard treatment available for gastric cancer patients whose sole ‘non-curative factor’ is positivecytological findings in peritoneal washings (CFPW). The aim of this study was to examine the safety, pharmacokinetics and efficacy for free intraperitoneal cancer cells of intraperitoneal chemotherapy with paclitaxel after gastrectomy with en bloc D2 lymph node dissection in cases of gastric cancer with positive CFPW. Methods: Ten patients with gastric cancer who underwent gastrectomy and systemic lymphadenectomy with D2 dissection, without any other non-curative factors besides positive CFPW, were treated with early postoperative intraperitoneal paclitaxel. Intra-chemotherapeutic toxicity and operative complications were measured using NCI-CTC version 3.0. Intraperitoneal and plasma paclitaxel concentrations were measured using a high-performance liquid chromatographic assay. Results: Grade 3/4 toxic effects included anemia (20%) and neutropenia (10%) that required no treatment. Operative complications were, for example, superficial surgical site infections (10%) that were treated with antibiotics. No viable cancer cells were observed in the intra-abdominal fluid 24 h after intraperitoneal administration of paclitaxel. The intraperitoneal/plasma area under the drug concentration-time curve ratio was 2,003.3:1. Conclusion: Intraperitoneal chemotherapy with paclitaxel is a safe and effective treatment modality for free intraperitoneal cancer cells.

Adopting Extensive Intra-operative Peritoneal Lavage (EIPL) as the Standard Prophylactic Strategy for Peritoneal Recurrence

EIPL (extensive intra-operative peritoneal lavage) therapy was developed as a prophylactic strategy for peritoneal recurrence, with the goal of improving the quality of life and survival span for advanced gastric cancer patients with peritoneal free cancer cells. The purpose of this article is to review the therapy's contribution to a remarkable improvement in the 5-year survival for patients with positive lavage cytology on prospective randomized controlled clinical trials. We also advocate for the adoption of the EIPL as the optimal treatment protocol for advanced gastric cancer.

Safety of intraperitoneal administration of paclitaxel after gastrectomy with en‐bloc D2 Lymph node dissection

The aim of this study was to examine the safety, pharmacokinetics, and cytological efficacy against free intraperitoneal cancer cells of intraperitoneal chemotherapy (IPC) with paclitaxel after gastrectomy with en-bloc D2 lymph node dissection (GD2) in cases of gastric cancer with peritoneal carcinomatosis (PC) and/or positive cytological findings in peritoneal washings (CFPW). Twenty-one patients with gastric cancer with PC and/or positive CFPW who underwent GD2 were treated with early, post-operative, intraperitoneal paclitaxel. Intra-chemotherapeutic toxicity and operative complication were measured using the common toxicity criteria of the National Cancer Institute, version 3.0. Intraperitoneal and plasma paclitaxel concentrations were measured using a high-performance liquid chromatography assay. Grade 3 anemia occurred in two patients (9.5%) and neutropenia was observed in three patients (14.3%). No grade 4 toxicity was observed. A grade 2 operative complication was a superficial surgical site infection (4.8%) that was treated with antibiotics. Cytologically, no viable cancer cells were observed in the intra-abdominal fluid 24 hr after intraperitoneal administration of paclitaxel. The intraperitoneal/plasma area under the drug concentration-time curve (AUC) ratio was 596.9:1. IPC with paclitaxel after GD2 is a safe and cytologically effective treatment modality for free intraperitoneal cancer cells. However, additional data are required to determine the effect on survival.

A systematic review of the accuracy and utility of peritoneal cytology in patients with gastric cancer

There is lack of uniformity in the utilization of peritoneal cytology in gastric cancer management. The identification of intraperitoneal free cancer cells (IFCCs) is believed to confer poor prognosis. However, while some of these patients are palliated, others may undergo more aggressive therapies. In this review, we aimed to identify and synthesize findings on the use of peritoneal cytology in predicting peritoneal recurrence and overall survival in curative gastric cancer patients. Electronic literature searches were conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials from January 1, 1998 to December 31, 2009. We determined the accuracy, sensitivity, and specificity of peritoneal cytology in predicting peritoneal recurrence based on four techniques-conventional cytology, immunoassay, immunohistochemistry, and reverse transcriptase-polymerase chain reaction. Recurrence rates and overall survival rates for curative patients were determined, based on positivity or negativity for IFCCs. Twenty-eight articles were included. All four techniques showed wide variations in accuracy, sensitivity, and specificity in predicting peritoneal recurrence. Recurrence rates for patients positive for IFCCs ranged from 11.1 to 100%, while those negative for IFCCs had recurrence rates of 0-51%. Overall survival was significantly reduced for patients with positive IFCCs. Short follow-up periods and possible duplication of results may limit result interpretation. The presence of IFCCs appears to increase the risk of peritoneal recurrence and is associated with worse overall survival in gastric cancer patients. Further incorporation of peritoneal cytology in clinical decision-making in gastric cancer depends on the development of a consistently accurate and rapid IFCC detection method.

Intraperitoneal free cancer cells in non-gynaecological adenocarcinomas: a reproducibility study

In recent years, therapeutic approaches including cytoreductive surgery followed by intraperitoneal chemotherapy have proven effective in peritoneal carcinomatosis of colorectal origin. If cytology is to be used to include patients in aggressive treatment regimens, it is necessary to evaluate its performance, particularly in terms of specificity. The aim of this study was to assess interobserver agreement for the detection of intraperitoneal free cancer cells (IFCCs) in patients with non-gynaecological adenocarcinomas. Over a 5-year period, 1223 patients were recruited in 19 French surgery departments. Peritoneal samples were examined in 14 dispersed pathology laboratories. Giemsa-stained slides were sent to a control reader blind to the previous diagnosis. Discordant cases, concordant positive results and a random selection of negative concordant cases were reviewed by a panel of seven cytopathologists. The 'final diagnosis' was that of the consensus meetings but took into account locally-processed slides. Gathering dubious cases with negative results, a 95.6% concordance was achieved between local readers and the control reader. IFCCs were ascertained by the panel in 85 cases (7.0%). Eight of 873 colorectal cancers cases viewed locally were falsely positive (0.9%). Radiotherapy and neoadjuvant therapy had no impact on the false-positive rate as assessed by final validation by the panel (P > 0.05). Samples initially considered as dubious were reclassified as negative by the panel in 24 of 25 cases (96.0%). The panel consensus allowed reclassification of most dubious/equivocal peritoneal cytology cases, whereas clearcut distinction between benign and malignant cases was correctly achieved in almost all cases.

Surgical outcomes for gastric cancer patients with intraperitoneal free cancer cell, but no macroscopic peritoneal metastasis

Gastric cancer patients with intraperitoneal cancer cells have extremely poor prognoses, because they frequently develop peritoneal metastasis. The aim of the current study is to clarify the clinicopathologic characteristics of patients with intraperitoneal free cancer cells who do not have recurrences. This study examined 1,985 gastric adenocarcinoma patients who underwent gastrectomies at our institution between January 1975 and December 2000. The 5-year survival rate of advanced gastric cancer patients with intraperitoneal free cancer cells, but no macroscopic peritoneal metastases (P0Cy1), is 15.3%. Multivariate analysis identified only lymph node metastasis as an independent prognostic indicator in P0Cy1 patients. The 5-year survival rates of P0Cy1 patients were 62.5%, 19.1%, 17.6%, and 9.4% in n0, n1, n2, and n3 patients, respectively. Peritoneal recurrence was observed significantly more often in P0Cy1 patients than in advanced gastric cancer patients without intraperitoneal free cancer cells. Our data indicate that prognoses of P0Cy1 patients without lymph node metastasis are good, whereas the prognoses of those with lymph node metastasis are extremely poor. Therefore, radical surgery and adequate adjuvant chemotherapy should be performed for P0Cy1 patients with no lymph node metastasis.

Effects of Intraperitoneal Chemotherapy with Mitomycin C on the Prevention of Peritoneal Recurrence in Colorectal Cancer Patients with Positive Peritoneal Lavage Cytology Findings

The detection of intraperitoneal free cancer cells in colorectal cancer (CRC) patients is associated with a poorer prognosis. The aim of this study was to investigate the effects of intraperitoneal chemotherapy (IPC) with mitomycin C (MMC) on preventing peritoneal recurrence in CRC patients with positive peritoneal lavage cytology findings. A total of 52 CRC patients who had no clinically confirmed peritoneal dissemination and whose status of peritoneal lavage cytology was positive were investigated. Conventional peritoneal lavage cytology was performed. Overall, 31 of the 52 patients (59.6%) were administered IPC with MMC. Before closure of the abdomen, 4 silicon catheters were inserted into peritoneal cavity. After closure, the perfusate (diluting 20 mg MMC with 500 ml saline) was instilled from the catheter, and all catheters were clumped. All catheters were opened 1 h later. The mean follow-up period was 83.1 months. According to univariate analyses of all 52 patients and the subgroup of 36 patients with stage II or III tumors, patients with IPC had a significantly better peritoneal recurrence-free survival and cancer-specific survival than patients who did not receive IPC (P < 0.005). In multivariate analysis, IPC remained an independent prognostic factor for peritoneal recurrence-free survival in all patients. It appears that IPC with MMC is an effective treatment to prevent peritoneal recurrence and prolong the cancer-specific survival in CRC patients without peritoneal dissemination, but who have positive peritoneal lavage cytology. It is necessary to verify the effectiveness of IPC with MMC in a prospective trial.

Connexin 43 expression in intraperitoneal free gastric cancer cells in patients with gastric cancer

To examine the association of connexin 43 (Cx43) in the intraperitoneal free gastric cancer cells and clinicopathological characteristics. Immunohistochemistry and immunofluorescence staining were used to detect connexin 43 in 75 paraffin-embedded gastric cancer tissues, matched paracancerous tissue, and intraperitoneal free gastric cancer cells. The positive rates of Cx43 expression were 33.3% (25/75) in gastric cancer tissue specimens and 100% (75/75) in matched paracancerous tissue (P<0.01). The positive detection rate of free cancer cells in peritoneal lavage was 38.6% (29/75) and the positive rate of Cx43 in peritoneal free gastric cancer cells was 72.4% (21/29), which was significantly higher than that in gastric cancer tissue specimens (P<0.01). Significant association was observed of Cx43 expression of free gastric cancer cells with tumor infiltration and histological type (P<0.05). Cx43 gene may be involved in the mechanism of peritoneal metastasis of gastric cancer.