Elimination of Peritoneal Tumor Cells With "Extensive Intraperitoneal Lavage (EIPL)" During Surgical Treatment of Gastric Adenocarcinoma
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.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Peritoneal Conversion Rate (PCR)
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.
intraoperative (day of surgery)
Ulrich Ronellenfitsch, MD
University Hospital Mannheim, Department of Surgery
Germany: Ethics Commission