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EIPL is performed after completing resection and lymphadenectomy: the abdominal cavity has to be washed ten times with one liter Ringer's solution. Each liter has to be well dispersed manually in the abdominal cavity, and removed and disposed completely. 100 ml of the last liter of lavage fluid will be harvested and sent for analysis.

Contrary to the Japanese trial, Ringer's solution will be used instead of normal saline solution because of a presumed higher likelihood of peritoneal adhesions when employing the latter (7). Ringer's solution is the standard used for all intraperitoneal lavage procedures at the study centre. To avoid hypothermia, the lavage fluid will be warmed to body temperature (37° Celsius).

Extensive Intraperitoneal Lavage (EIPL)

Ulrich Ronellenfitsch, MD

A Japanese study showed that the additional use of an "Extensive Intraperitoneal Lavage" (EIPL), i.e. an extensive washing of the abdominal cavity with water, during surgery for gastric cancer can lead to a significant increase in survival. However, the study was confined to patients in whom upon commencing surgery, free peritoneal tumor cells were detected, which is only a small fraction of patients.

The primary objective of our study is to assess in all patients undergoing removal of the stomach and adjacent lymph nodes for stomach cancer, if EIPL can eliminate free peritoneal tumor cells which have been present at the beginning of the surgery or after the stomach and lymph node removal. Secondary objectives are to assess how often free peritoneal tumor cells occur in patients with stomach cancer, how often surgical resection itself leads to a release of tumor cells, the safety of the EIPL procedure, and disease-free and overall survival of patients undergoing EIPL. Based on the outcome of this japanese study we want to test with special laboratory methods why this lavage leads to a better outcome.

Specifically, the trial will test the hypotheses that a) lymph node dissection causes a release of tumor cells in the abdominal cavity, and b) EIPL eliminates free peritoneal tumor cells.

In spite of the existence of multimodal therapy, the long-term survival of patients with gastric cancer remains poor. In advanced tumor stages, five-year survival rates rarely exceed 30%. One of the factors limiting overall survival is peritoneal carcinomatosis, which frequently occurs after surgical treatment with curative intention.

Peritoneal carcinomatosis is supposed to develop from peritoneal implantation of tumor cells already present in the abdominal cavity during primary surgery. It is assumed that both serosal tumor infiltration and intraoperative lymphadenectomy, which per se leads to a survival improvement (1) and is therefore considered standard in Europe and Japan ((2), http://www.jpca.jp/PDFfiles/ Guidelines2004_eng.pdf), can release tumor cells into the peritoneal cavity. Of note, a Japanese study found that tumor cells were released into the peritoneal cavity during lymphadenectomy in 14-46% of patients, depending on preoperative tumor stage (3).

A randomized clinical trial from Japan (4) demonstrated that an "extensive intraperitoneal lavage" (EIPL), i.e. an irrigation of the abdominal cavity with ten times one liter of physiological saline solution, in combination with intraperitoneal chemotherapy (IPC) carried out after gastrectomy and lymphadenectomy, led to a significant improvement in overall survival compared to patients who received only surgery and IPC without EIPL, and those who received surgery alone without EIPL and IPC. These results suggest that the largest survival benefit is attributable to the addition of EIPL to IPC (5-year survival rate: 43.8% vs. 4.6%) and not to the addition of IPC to surgery alone (5-year survival rate: 4.6% vs. 0%).

However, it is important to consider that the study included only patients in whom peritoneal tumor cells were detected before resection of the stomach and lymph nodes. Thus, only 90 of 1522 (5.9%) patients operated in the participating centers throughout the study period fulfilled the inclusion criteria. Furthermore, the study design was not appropriate to assess if EIPL really leads to a reduction of free tumor cells as assumed. Regarding this hypothesis, the only available results stem from single patients out of smaller studies (4;5). To date, there is no higher level evidence from larger populations.

The present trial, for the first time, uses EIPL as additional treatment in patients with any tumor stage and regardless of the detection of intraperitoneal tumor cells at the beginning of the operation.

Intraperitoneal lavage fluid will be harvested and assessed for tumor cells at three different points of time:

(i) before gastrectomy and lymphadenectomy (ii) after gastrectomy and lymphadenectomy, directly before EIPL (iii) after EIPL

The trial will test the hypotheses that a) lymph node dissection causes a release of tumor cells in the abdominal cavity, and b) EIPL eliminates free peritoneal tumor cells.

Elimination of Peritoneal Tumor Cells With Extensive Peritoneal Lavage During Surgery in Patients With Gastric Cancer

Elimination of Peritoneal Tumor Cells With "Extensive Intraperitoneal Lavage (EIPL)" During Surgical Treatment of Gastric Adenocarcinoma

The Peritoneal Conversion Rate (PCR) is defined as the proportion of patients in whom no free peritoneal tumor cells are detected after EIPL among all patients in whom free peritoneal tumor cells were detected before EIPL. In other words, the PCR measures in what proportion of patients EIPL leads to an elimination of intraperitoneal tumor cells.

The Peritoneal Release Rate (PRR) is defined as the proportion of patients in whom free peritoneal tumor cells are detected after gastrectomy and lymphadenectomy among all patients in whom no free peritoneal tumor cells were detected before gastrectomy and lymphadnectomy. In other words, this denotes the proportion of patients in whom tumor cells are released into the peritoneal cavity due to the surgical measures performed.

This denotes the proportion of patients in whom free intraperitoneal tumor cells can be detected upon laparotomy among all operated patients.

Overall survival is defined as the time between surgery and death, independent of the cause of death.

Recurrence-free survival is defined as the time between surgery and the appearance of a local recurrence, peritoneal carcinomatosis, or distant metastases.

All complications occuring throughout the hospital stay of the patient are assessed according to the Clavien-Dindo classification for surgical complications (6).

Heidelberg University

Universitätsmedizin Mannheim

Principal Investigator

Gastrectomy with D2 lymphadenectomy is performed. The peritoneal cavity of subject will be washed with 10 liters of warmed normal saline (1 liter per cycle for 10 cycles), followed by complete aspiration of the fluid . The abdomen will be closed as per standard.

Gastrectomy with D2 lymphadenectomy is performed. The peritoneal lavage will be done \< 3 cycles with 3 liters or less of warmed normal saline. The abdomen will be closed as per standard.

Extensive Intraoperative Peritoneal Lavage

The investigators study aims to explore the potential function of extensive intraoperative peritoneal lavage in improving the overall survival and progression-free survival for locally advanced gastric cancer after curative resection.

Hypothesis: Overall survival and progression-free survival of locally advanced gastric cancer are improved by extensive intraoperative peritoneal lavage.

Gastric cancer has been one of the most frequently common cancers and remains the third leading cause of death among malignant tumors all over the world. Surgery has always been considered as the most effective treatment. While significant surgical technique and perioperative management have dramatically improved the survival of patients with advanced gastric cancer, patients with T4 stage or serosal-positive gastric cancer often suffer from recurrence as peritoneal dissemination, and the prognosis of those patients is extremely poor. Despite curatively resected, Peritoneal metastasis is completed by the implantation of peritoneal free cancer cells exfoliated from serosa-invasive tumors. Therefore, things need to be done to eliminate the free exfoliated cancer cells on the peritoneal lining in order to reduce the risk of peritoneal recurrence.

A multi-institutional prospective, randomized trial has been launched by Kuramoto recently. The trail was intended to demonstrate the superiority in overall survival of addition of Extensive Intraoperative peritoneal Lavage (EIPL) to standard treatment in patients with≥T3 carcinoma of stomach. Based on the'limiting dilution theory', after total or distal gastrectomy with D2 lymphadenectomy, the peritoneal cavity is extensively rinsed 10 times with 1 L physiological saline at a time, followed by complete aspiration of the fluid. In total, 10 L saline is to be used. In this study, the EIPL-IPC group had a significantly lower incidence of peritoneal recurrence. Furthermore, the 5-year overall survival rate of the patients in the EIPL-IPC group (43.8%) was significantly better than that of the intraperitoneal chemotherapy (IPC) group (4.6%) and the surgery-alone group (0%). All in all, EIPL is easy to carry out, safe and inexpensive. Therefore, gastrectomy with EIPL will be a new standard treatment of gastric cancer.

To ensure the quality of the study, two interim analyses will be planned at the half and the completion of the study respectively. The Data and Safety Monitoring Committee will independently review the interim analysis and stop the study ahead of schedule if necessary. Furthermore, to improve the study progress and quality, the in-house interim monitoring will be performed.

Extensive Intraoperative Peritoneal Lavage After Curative Gastrectomy for Locally Advanced Gastric Cancer (SEIPLUS)

A Prospective, Multicentral, Open-label, Randomized, Controlled Clinical Trial to Investigation the Value of Extensive Intraoperative Peritoneal Lavage After Curative Gastrectomy for Locally Advanced Gastric Cancer

The survival rate between the surgery to the 3rd year due to all-cause death or last follow-up.

The progression-free or all-cause death rate between the surgery and the 3rd year.

The Peritoneal recurrence rate between the surgery and the 3rd year

complications such bleeding, infection, obstruction and leakage

The postoperative quality of life will be assessed by factors such as Swallowing，Pain and discomfort，Dietary restrictions, Upper gastrointestinal symptoms, mental status and others.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Elimination of Peritoneal Tumor Cells With Extensive Peritoneal Lavage During Surgery in Patients With Gastric Cancer	NCT01476553	Adenocarcinoma Stomach Neoplas...	Extensive Intra...	18 Years -	Universitätsmedizin Mannheim
Extensive Intraoperative Peritoneal Lavage After Curative Gastrectomy for Locally Advanced Gastric Cancer (SEIPLUS)	NCT02745509	Gastric Cancer	Extensive Intra...	18 Years - 80 Years	Sun Yat-sen University

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Every month we try and update this database with for eipl cancer trials from around the world to help patients and their families find trials that might be right for them.
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Spots Global Cancer Trial Database for eipl

Every month we try and update this database with for eipl cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for eipl cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.