BACKGROUND: The prognosis of locally advanced Gastric Cancer following surgical therapy alone is poor. Peritoneum represents a preferential site of dissemination in such neoplasm. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been used in association with cytoreductive surgery (CRS) in the treatment of GC peritoneal carcinomatosis (PC). Aim of our preliminary experience is reporting our data on prophylactic HIPEC (P-HIPEC) in patients with GC at high risk of developing PC. METHODS: Eleven patients underwent P-HIPEC at our General and Emergency Surgery Department. All the patients were affected of high risk GC: serosa invasive tumors (T4), conventional cytology-positive or quantitative PCR detection of CEA mRNA on peritoneal lavage. Seven subtotal and four total gastrectomies with D2 or D2+ were performed. All the anastomoses were made before HIPEC. The procedure was carried out for 60 minutes with Mytomicin C and Cisplatin in all patients. Post-operative monitoring in Intensive Care Unit least for 24-48 hours. Oral nutrition was started precociously (day 5) also according with bowel movements and stool/gas passage. Follow-up took place in all patients at 1 month from surgery then every 6 months for 2 years and every 12 months for the following years. RESULTS: In four patients a neoadjuvant treatment was scheduled due to T or N stage at pre-operative evaluation. Gastric resection was guided on tumor location while the choice of performing a D2 or D2 + lymphadenectomy was up to preoperative imaging and intra-operative nodal status. No intra-operative complications were recorded. Median operation time was 398 minutes. In our series we recorded 20 adverse events. Median number for each patient was 1 adverse effect (range 0-2). Eight patients experienced a surgical adverse effect (G2-G3) that did not require any surgical treatment. Only one patient with duodenal stump dehiscence and intra-abdominal sepsis (G4-G5) underwent re-operation and died for severe hemorrhagic pancreatitis. Another patient died for ARDS. Per-operative mortality was 18%. Both patients were older then 70 years old. Median hospital stay was 14 days. Median follow-up was 15.9 months. Median survival was 29.6 months and median DFS was 20 months. Only one patient developed a peritoneal recurrence at 12 months and died for disease progression. Seven patients are still alive and disease free at last follow-up. One patient affected of variable immunodeficiency died at 9 months for pulmonary sepsis without any sign of local recurrence. CONCLUSIONS: Peritoneal dissemination appears to be a strong determinant in defining GC patients prognosis. Even after curative resection, peritoneal recurrence develops in about 60% of the patients with T3 and T4 tumors, and up to 40% of resected gastric cancer patients die as a direct result of peritoneal dissemination. Clinical trials showed that surgery plus HIPEC was associated with a significant improvement in survival compared to surgery alone in patients affected of GC with resectable PC. At present day there are not studies evaluating the role of P-HIPEC in patients at high risk of developing PC. The rationale of P-HIPEC is based on the concept that positive peritoneal lavage is considered an M1 (stage IV) similarly to macroscopic PC by the 7th TNM classification. Also analogous is the median survival of this 2 groups of patients. Detection of peritoneal micrometastases with cytologic examination has been considered a major method to predict peritoneal recurrences; the sensitivity of this assay is low. Recently, molecular approaches using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) technique has made possible the increase in the sensitivity. We can conclude, although the preliminary experience, that prophylactic HIPEC in locally advanced gastric cancer is feasible, increasing median survival compared to surgery alone. For sure this procedure need to be performed in the highly specialized centres strongly respecting the eligibility criteria.
BACKGROUND: The prognosis of locally advanced Gastric Cancer following surgical therapy alone is poor. Peritoneum represents a preferential site of dissemination in such neoplasm. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been used in association with cytoreductive surgery (CRS) in the treatment of GC peritoneal carcinomatosis (PC). Aim of our preliminary experience is reporting our data on prophylactic HIPEC (P-HIPEC) in patients with GC at high risk of developing PC. METHODS: Eleven patients underwent P-HIPEC at our General and Emergency Surgery Department. All the patients were affected of high risk GC: serosa invasive tumors (T4), conventional cytology-positive or quantitative PCR detection of CEA mRNA on peritoneal lavage. Seven subtotal and four total gastrectomies with D2 or D2+ were performed. All the anastomoses were made before HIPEC. The procedure was carried out for 60 minutes with Mytomicin C and Cisplatin in all patients. Post-operative monitoring in Intensive Care Unit least for 24-48 hours. Oral nutrition was started precociously (day 5) also according with bowel movements and stool/gas passage. Follow-up took place in all patients at 1 month from surgery then every 6 months for 2 years and every 12 months for the following years. RESULTS: In four patients a neoadjuvant treatment was scheduled due to T or N stage at pre-operative evaluation. Gastric resection was guided on tumor location while the choice of performing a D2 or D2 + lymphadenectomy was up to preoperative imaging and intra-operative nodal status. No intra-operative complications were recorded. Median operation time was 398 minutes. In our series we recorded 20 adverse events. Median number for each patient was 1 adverse effect (range 0-2). Eight patients experienced a surgical adverse effect (G2-G3) that did not require any surgical treatment. Only one patient with duodenal stump dehiscence and intra-abdominal sepsis (G4-G5) underwent re-operation and died for severe hemorrhagic pancreatitis. Another patient died for ARDS. Per-operative mortality was 18%. Both patients were older then 70 years old. Median hospital stay was 14 days. Median follow-up was 15.9 months. Median survival was 29.6 months and median DFS was 20 months. Only one patient developed a peritoneal recurrence at 12 months and died for disease progression. Seven patients are still alive and disease free at last follow-up. One patient affected of variable immunodeficiency died at 9 months for pulmonary sepsis without any sign of local recurrence. CONCLUSIONS: Peritoneal dissemination appears to be a strong determinant in defining GC patients prognosis. Even after curative resection, peritoneal recurrence develops in about 60% of the patients with T3 and T4 tumors, and up to 40% of resected gastric cancerpatients die as a direct result of peritoneal dissemination. Clinical trials showed that surgery plus HIPEC was associated with a significant improvement in survival compared to surgery alone in patients affected of GC with resectable PC. At present day there are not studies evaluating the role of P-HIPEC in patients at high risk of developing PC. The rationale of P-HIPEC is based on the concept that positive peritoneal lavage is considered an M1 (stage IV) similarly to macroscopic PC by the 7th TNM classification. Also analogous is the median survival of this 2 groups of patients. Detection of peritoneal micrometastases with cytologic examination has been considered a major method to predict peritoneal recurrences; the sensitivity of this assay is low. Recently, molecular approaches using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) technique has made possible the increase in the sensitivity. We can conclude, although the preliminary experience, that prophylactic HIPEC in locally advanced gastric cancer is feasible, increasing median survival compared to surgery alone. For sure this procedure need to be performed in the highly specialized centres strongly respecting the eligibility criteria.
Authors: Jason M Foster; Richard Sleightholm; Asish Patel; Valerie Shostrom; Bradley Hall; Beth Neilsen; David Bartlett; Lynette Smith Journal: JAMA Netw Open Date: 2019-01-04