Risk Assessment and Preventive Treatment for Peritoneal Recurrence Following Radical Resection for Gastric Cancer

As the most common recurrence pattern after radical gastric cancer resection, peritoneal recurrence is a major cause of mortality, which affects the prognosis of patients to a very large extent. Peritoneal status and risk of peritoneal recurrence can be evaluated by peritoneal lavage cytology, photodynamic diagnosis, imaging examination, and pathologic analysis. Presently, there is no standard approach for preventing peritoneal recurrence after radical surgery; furthermore, controversies exist regarding the effects of some preventive methods. Among the preventive methods, there are high expectations about the potential of preoperative therapy, surgical skill improvement, hyperthermic intraperitoneal chemotherapy, and postoperative treatment to reduce the incidence of peritoneal recurrence after radical gastrectomy. This study aimed to analyze the results of previous studies on the risk assessment and preventive methods of peritoneal recurrence after radical gastrectomy in recent years. We hope to provide references for better approach to clinical diagnosis and treatment strategies for peritoneal recurrence after radical gastrectomy.

Intraperitoneal Chemotherapy as Adjuvant or Perioperative Chemotherapy for Patients with Type 4 Scirrhous Gastric Cancer: PHOENIX-GC2 Trial

The prognosis of patients with type 4 scirrhous gastric cancer remains poor due to a high risk of peritoneal metastasis. We have previously developed combined chemotherapy regimens of intraperitoneal (IP) paclitaxel (PTX) and systemic chemotherapy, and promising clinical efficacy was reported in gastric cancer with peritoneal metastasis. Herein, a randomized, phase III study is proposed to verify the efficacy of IP PTX to prevent peritoneal recurrence. Gastric cancer patients with type 4 tumors and without apparent distant metastasis, including peritoneal metastasis, will be randomized for standard systemic chemotherapy or combined IP and systemic chemotherapy based on peritoneal lavage cytology findings. Those with negative peritoneal cytology will receive radical gastrectomy and adjuvant chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). Those with positive peritoneal cytology will receive three courses of S-1 plus oxaliplatin (control arm), or S-1 plus oxaliplatin and IP PTX (experimental arm). Subsequently, they undergo gastrectomy and receive postoperative chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). The primary endpoint is disease free survival after a 3-year follow-up period. Secondary endpoints are overall survival, survival without peritoneal metastasis, safety, completion rate, curative resection rate, and histological response of preoperative chemotherapy. A total of 300 patients are to be enrolled.

Clinical Significance of Peritoneal Fluid Examination for Free Cancer Cells in Patients Qualified for Surgery for Gastric Cancer

Background: Peritoneal lavage cytology in patients with gastric cancer may correlate with an unfavorable prognosis. This study evaluated the presence of free cancer cells in the peritoneal lavage of a population of patients with gastric cancer and its correlation with the outcome of surgical treatment.Methods: One hundred patients diagnosed with gastric or gastrointestinal junction adenocarcinoma underwent surgery. In all patients, a cytological and immunohistochemical analysis of peritoneal lavage was performed. Based on the presence of free cancer cells (fcc) at the cytological and immunohistochemical examination of peritoneal lavage, patients undergoing surgery for gastric cancer were divided into two groups: fcc (+) and fcc (–).Results: A total of 100 patients, 37 women, and 63 men with a median age of 65 years were included in the study. In the entire study group, 16 (16%) patients were positive for the presence of free cancer cells (fcc +) at peritoneal lavage examination. However, in the group of patients who underwent gastrectomy, fcc (+) was found in 10 out of 77 (13%) patients. The presence of cancer cells in peritoneal lavage was a strong predictive factor in an unfavorable outcome after surgery, and 1-year and 2-year patient survival was 34 and 0% in fcc (+) patients and 79 and 59% in fcc (–), respectively. Moreover, the presence of free cancer cells was associated with a five-fold increased risk of death within 2 years after surgery. When analyzing the group of patients undergoing R0/R1 surgery, this difference was even more significant (p < 0.0001).Conclusions: The presence of free cancer cells in peritoneal lavage may significantly affect the outcome of patients with gastric cancer. Radical surgery in patients with free cancer cells in the peritoneal lavage did not result in a survival advantage. Identification of free cancer cells could help for a better stratification of gastric cancer patients, identifying those patients who could better benefit from a radical surgical treatment, finally improving long-term survival.

Evaluation of Peritoneal Lavage for Gastric Cancer Staging in Patients Without Ascites Based on Cytology and Carcinoembryonic Antigen

Background: Imaging, cytological examination of ascites (if present), laparosco- py, and peritoneal lavage are performed before surgery for gastric cancer staging. Peritoneal lavage aims to diagnose the microscopic presence of tumor cells on the peritoneal surface. Positive cytology may have a prognostic value that classifies the disorder as stage IV, in which the patient is no longer an elective surgical candidate. Thus, our study was designed to assess the ability of peritoneal lavage to stage gastric cancer in non-ascitic patients based on cytological evaluation and carcinoembryonic antigen (CEA) level measurement. Methods: In our prospective study, we examined gastric cancer patients who were candidates for elective surgery. Upon entering the abdominal cavity and before tu- mor manipulation, normal saline (500 ml) was applied, and the abdominal cavity was thoroughly dispersed. After three minutes, the fluid was drained and addressed to cytological analysis and CEA measurement by radioimmunoassay (RIA). Study var- iables including age, sex, family history, tumor position, pathology, staging, grading, the original tumor size, regional lymph node involvement, and distant metastases were recorded during the pre- and postoperative staging. The association between positive peritoneal lavage cytology and various patients’ characteristics was investigated. Results: In this study, 94 patients were screened. Due to lymphoma and gastrointes- tinal stromal tumor (GIST), two patients were excluded. We examined 92 patients, including 63 males (68.5 %) and 29 females (31.5 %). The mean age of patients was 58.52 ± 11.87 years. The most common tumor location was the esophagogastric junction. Moderately differentiated adenocarcinoma was the most frequent micro- scopic diagnosis. T3 was the most prevalent primary tumor size in 51 patients. Sev- enty-two patients (78.26%) were operable, of whom 18 (19.6 %) were positive for peritoneal lavage cytology. Positive cytology of peritoneal lavage was significantly related to tumor size, tumor grade, serosa/adjacent organ invasion (T4), laparoscopic staging findings, locally advanced disease (R0), and stage of the disease (P < 0.05). In the peritoneal lavage fluid, elevated CEA titers were significantly related to the high-grade tumor (P = 0.012). Conclusion: Our study demonstrated that positive cytology and high CEA titers in peritoneal lavage fluid of gastric cancer patients without ascites are significantly correlated to the advanced stages.

Peritoneal Lavage Cytology Following Neoadjuvant Chemotherapy for Gastric Adenocarcinoma: Low Yield in Detecting Peritoneal Metastases

Background Peritoneal lavage cytology (PLC) can detect advanced disease in gastric adenocarcinoma (GC); however, routine practice remains controversial. Furthermore, the effect of neoadjuvant chemotherapy (NAC) on cytological detection of carcinomatosis is unknown. Methods Using a 2012-2020 prospective database, we retrospectively reviewed patients with GC who underwent NAC followed by a staging laparoscopic peritoneal lavage with or without biopsy of suspicious peritoneal nodules. PLC results were considered discordant if they did not align with the peritoneal biopsy results. Patients with benign peritoneal cytology (Cyt-) or biopsy results who had postoperative time to carcinomatosis of <6 months were considered to have diagnostic failure of peritoneal lavage. Results Fifty-five patients with GC who underwent NAC followed by staging diagnostic laparoscopy with peritoneal lavage were identified. The majority of the patients in the cohort had Cyt- lavage (89.1%). Of the patients who underwent resection, 76.1% had T3 or greater disease on final pathology and 66% had nodal metastases. In 23 patients (41.8%) who had both peritoneal lavage and biopsy, four cases (17.4%) had discordant results. Diagnostic failure rate was 20% at 6 months and 42.2% at 12 months. The median time to carcinomatosis in patients who were Cyt- or biopsy negative was 7.9 months. Conclusion PLC after NAC has a high diagnostic failure rate and inaccurately predicts carcinomatosis in 20% of patients with GC. Novel methods for identifying cytology positive GC after NAC should also be developed and evaluated, since the risk of peritoneal dissemination is high.