Gastric cancer: Hyperthermic intraperitoneal chemotherapy and gastrectomy are good choices?
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Gastric cancer: Hyperthermic intraperitoneal chemotherapy and gastrectomy are good choices?
In the United States, there will be an estimated 28,000 new cases and 10,960 deaths from gastric adenocarcinoma each year.
Despite current treatment modalities of surgical resection and systemic therapy aimed at improving recurrence-free and overall survival, peritoneal carcinomatosis remains a major source of morbidity and a common cause of death.
Nearly 40% of patients with gastric adenocarcinoma will develop peritoneal metastasis during the course of the disease.
In approximately 70% of patients the disease is primarily confined to the peritoneum.
Peritoneal dissemination begins early and often goes undetected until overt peritoneal metastases have occurred.
Based on retrospective studies, 7-13% of patients had positive peritoneal cytology at the time of curative surgery.
Patients with positive peritoneal cytology had a median survival of 12 months, similar to patients with macroscopic peritoneal metastases.
Current data suggest that intraoperative intraperitoneal chemotherapy in appropriately selected patients with carcinoma of gastric origin improves survival.
Yang and colleagues conducted a prospective phase III randomized trial to evaluate the efficacy of chemotherapy combined with cytoreductive surgery versus cytoreductive surgery alone in the treatment of gastric cancer with peritoneal carcinomatosis.
The median overall survival was significantly improved with surgery plus chemotherapy compared with surgery alone, the authors reported, at 11.9 months.
Rudloff et al reported a prospective randomized study of cytoreductive surgery, gastrectomy, and heated IP chemotherapy (HIPEC) with or without systemic chemotherapy in patients with metastatic gastric cancer.
Although the study was underpowered, this study demonstrates that patients with peritoneal cancer and limited disease burden can prolong survival with cytoreduction, including gastrectomy and IP chemotherapy.
In most similar studies of IP chemotherapy, key factors associated with improved survival included small disease burden [i.e., low peritoneal cancer index (PCI)] and the ability to achieve complete cytoreduction (CC-0).
Although gastrectomy in the presence of peritoneal disease is associated with improved survival, a clear benefit is lacking.
The REGATTA trial remains the only prospective randomized trial evaluating the role of palliative gastrectomy (i.e., noncurative, without resection of metastases) before systemic therapy in patients with limited (solitary site) gastric cancer metastases.
Gastric cancer patients with metastases from a single site, such as the liver, para-aortic lymph nodes, or peritoneum, were randomly assigned to chemotherapy alone or chemotherapy plus gastrectomy.
Of note, the most common non-curable factor was peritoneal metastases.
There was no difference in survival between treatment groups, however, the study design did not allow for metastatic resection.
In other words, the impact of resecting the primary tumor and aggressively managing metastatic disease was not assessed.
Ishigami and colleagues recently evaluated the safety and efficacy of gastrectomy in patients with gastric cancer following systemic and intraperitoneal chemotherapy.
In 100 patients with cytopathological, clinical, and/or radiological response to systemic and intraperitoneal chemotherapy, gastrectomy (without peritonectomy or intraoperative intraperitoneal chemotherapy) was considered.
Median overall survival was 30.5 months for the 64 patients who opted for surgery, starting with IP chemotherapy.
Factors associated with prolonged survival included surgical options including low-volume peritoneal disease (P0/cytologically positive or P1) and histologic response to treatment (viable tumors ≤1/3 tumor area).
Therefore, identification of early peritoneal metastases may reveal a cohort of patients in whom local therapy can be rationally applied to interrupt the peritoneal metastatic cascade and thus prolong survival.
Based on these data, it is expected that patients with isolated peritoneal disease and the lowest metastatic burden will benefit most from strategies including local therapy. We believe that gastrectomy combined with HIPEC will improve the survival rate of gastric cancer patients with positive peritoneal cytology and/or very small volume peritoneal cancer.
Originally published in Journal of Gastrointestinal Oncology , 2017
Article link: doi: 10.21037/jgo.2017.09.01
Summary:
Peritoneal metastasis is a common final metastasis route in patients with gastric adenocarcinoma. Microscopic evidence of early peritoneal dissemination of gastric cancer is present in a substantial proportion of patients with limited disease on examination.
Even for patients with microscopic and small-volume peritoneal carcinomas, the prognosis is poor, highlighting the need for more effective treatment strategies.
Intraperitoneal chemotherapy for peritoneal cancer has been evaluated in gastric cancer and is associated with improved survival in selected patients.
We hypothesized that primary tumor resection combined with treatment of small-volume peritoneal metastases might improve survival in patients with gastric cancer.
Our group is investigating the role of heated intraperitoneal chemotherapy in patients with gastric adenocarcinoma and metastases confined to the peritoneum during gastrectomy.
To date, trials devoted to the study of local therapy for peritoneal metastases from gastric cancer have mainly originated in Asian centers.
Although gastric cancer has a relatively low incidence in the United States, its high mortality rate warrants prospective studies of intraperitoneal chemotherapy in patients with this fatal disease.
Gastric cancer: Hyperthermic intraperitoneal chemotherapy and gastrectomy are good choices?
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