Prospective randomized trial evaluating mandatory second look surgery with HIPEC and CRS vs. standard of care in patients at high risk of developing colorectal peritoneal metastases

<p>Abstract</p> <p>Background</p> <p>The standard of care for colorectal peritoneal carcinomatosis is evolving from chemotherapy to cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with disease limited to the peritoneum. Peritoneal carcinomatosis from colorectal cancer treated with chemotherapy alone results in median survival of 5 to 13 months, whereas CRS with HIPEC for early peritoneal carcinomatosis from colorectal cancer resulted in median survival of 48-63 months and 5 year survival of 51%.</p> <p>Completeness of cytoreduction and limited disease are associated with longer survival, yet early peritoneal carcinomatosis is undetectable by conventional imaging. Exploratory laparotomy can successfully identify early disease, but this approach can only be justified in patients with high risk of peritoneal carcinomatosis. Historical data indicates that patients presenting with synchronous peritoneal carcinomatosis, ovarian metastases, perforated primary tumor, and emergency presentation with bleeding or obstructing lesions are at high risk of peritoneal carcinomatosis. Approximately 55% of these patient populations will develop peritoneal carcinomatosis. We hypothesize that performing a mandatory second look laparotomy with CRS and HIPEC for patients who are at high risk for developing peritoneal carcinomatosis from colorectal cancer will lead to improved survival as compared to patients who receive standard of care with routine surveillance.</p> <p>Methods/Design</p> <p>This study is a prospective randomized trial designed to answer the question whether mandatory second look surgery with CRS and HIPEC will prolong overall survival compared to the standard of care in patients who are at high risk for developing peritoneal carcinomatosis from colorectal cancer (CRC). Patients with CRC at high risk for developing peritoneal carcinomatosis who underwent curative surgery and subsequently received standard of care adjuvant chemotherapy will be evaluated. The patients who remain without evidence of disease by imaging, physical examination, and tumor markers for 12 months after the primary operation will be randomized to mandatory second look surgery or standard-of-care surveillance. At laparotomy, CRS and HIPEC will be performed with intraperitoneal oxaliplatin with concurrent systemic 5-fluorouracil and leucovorin. Up to 100 patients will be enrolled to allow for 35 evaluable patients in each arm; accrual is expected to last 5 years.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov ID: NCT01095523</p

Second-look surgery in patients with peritoneal dissemination from appendiceal malignancy: analysis of prognostic factors in 98 patients

OBJECTIVE: To establish selection criteria for reoperation in patients with peritoneal dissemination from appendiceal malignancy. SUMMARY BACKGROUND DATA: The outcome of patients with mucinous appendiceal neoplasms with peritoneal surface dissemination has changed as a result of a better understanding of the clinical and pathologic features of this disease. This knowledge, combined with aggressive strategies for the use of perioperative intraperitoneal chemotherapy and peritonectomy procedures, has resulted in long-term disease-free survival in many of these patients. However, some of the patients develop progressive disease, and a question regarding additional surgery is appropriate. A critical analysis of the results of second-look surgery should assist in the management of patients with recurrent peritoneal surface dissemination of an appendiceal neoplasm. METHODS: Three hundred twenty-one patients with epithelial peritoneal surface malignancy of appendiceal origin underwent surgery during a 12-year period. Ninety-eight of these patients (30.5%) underwent a second-look procedure. A database of selected clinical features regarding these 98 patients was gathered from the clinical records. A critical statistical analysis of these clinical features and their prognostic impact was performed using survival as an endpoint. All patients were managed by a treatment regimen that used cytoreductive surgery and intraperitoneal chemotherapy. RESULTS: The overall 5-year survival rate of these 98 patients was 73.6%. This compared favorably with a 68% survival rate of 223 patients who did not undergo reoperation. Survival based on the number of cytoreductive surgeries and the free interval between them showed no significant difference. Patients who had second-look surgery with bowel obstruction as a symptom and those in whom the amount of tumor was increased or minimally decreased at the first and second cytoreductions had a significantly inferior 5-year survival rate. A complete second cytoreduction was associated with an improved 5-year survival rate. CONCLUSIONS: Follow-up of patients treated for peritoneal dissemination from neoplasms of appendiceal origin is indicated. Selected patients in whom recurrence develops are candidates for repeat cytoreductive surgery plus intraperitoneal chemotherapy with curative intent

Sclerosing encapsulating peritonitis as a potential complication of cytoreductive surgery and HIPEC: Clinical features and results of treatment in 4 patients

Sclerosing encapsulating peritonitis (SEP) is a rare entity characterized by encapsulation of the small bowel and/or the colon by a fibrous tissue that forms a shell. Intraperitoneal chemotherapy (IPC) has been reported to be a potential causative factor of secondary SEP. However, few studies have reported on secondary SEP related to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Here, we review results from four clinical cases of SEP associated with CRS and HIPEC. In all four patients, additional surgery was necessary to alleviate recurrent episodes of small bowel obstruction. These obstructions can occur as early as several weeks after CRS plus HIPEC or as late as 3 years after treatment. Of utmost importance is the prevention of fistulization which can result in enteric contamination of the peritoneal space. To date, no solution to SEP has been identified except additional surgery but it is evident that these reoperative experiences are difficult for both surgeon and patient. The etiopathogenesis of SEP in this setting remains unknown but it is clear that it is related to chronic inflammation of the peritoneum. Large studies are needed to identify the incidence and potential common causes of SEP after CRS and HIPEC.SCOPUS: ar.jinfo:eu-repo/semantics/publishe