Although a randomized trial demonstrated a survival benefit of cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) over systemic chemotherapy alone, the treatment of peritoneal carcinomatosis from colorectal cancer (CRPC) is still a matter of debate. The aims of this study were to evaluate long-term outcome after CRS and IPC and to identify the prognostic factors associated with a cure. Patients were considered cured if the disease-free survival interval lasted at least 5 years after the treatment of CRPC or its last recurrence. Patients who had died postoperatively, or from non-cancer-related deaths, or patients with a follow-up of less than 5 years since the last curative treatment were excluded from the analysis. From 1995 to 2006, 107 patients (median age, 48 years; range, 19-67 years) underwent complete CRS, followed by IPC. Postoperative complications occurred in 50 patients (53%), including 4 postoperative deaths. After a median follow-up of 77 months (range, 60-144 months), 5-year and 10-year overall survival rates were 35% and 15%, respectively. Seventeen patients (16%) were considered cured after a disease-free interval of at least 5 years, of whom 14 never developed a recurrence. Cured patients had a significantly lower median peritoneal cancer index than noncured patients, respectively 4 (3-16) and 12 (2-36) (P = 0.0002). In multivariate analysis, a peritoneal cancer index of 10 or less was the only independent factor predicting cure. The cure rate (16%) after complete CRS of colorectal peritoneal carcinomatosis, followed by IPC, in selected patients is close to that obtained after resection of colorectal liver metastases.
Cyclophosphamide–dacarbazine–vincristine regimen is recommended for the treatment of malignant pheochromocytoma and paraganglioma (MPP); however, dacarbazine is the only recognized active drug in neuroendocrine tumours. We investigated the therapeutic benefit of temozolomide (TMZ), an oral alternative to dacarbazine, in patients with MPP. This is a retrospective study of consecutive patients with documented progressive MPP. We examined the correlation between Succinate dehydrogenase B (SDHB) mutation and O(6)‐methylguanine‐DNA methyltransferase (MGMT) promoter methylation and MGMT expression in the French nation‐wide independent cohort of 190 pheochromocytomas or paragangliomas (PP). Progression‐free survival (PFS) according to RECIST 1.1 and PERCIST 1.0 criteria was the primary end point. Fifteen consecutive patients with MPP were enrolled; ten (67%) carried a mutation in SDHB. The mean dose intensity of TMZ was 172 mg/m2/d for 5 days every 28 days. Median PFS was 13.3 months after a median follow‐up of 35 months. There were five partial responses (33%), seven stable (47%) and three progressive diseases (20%). Grade 3 toxicities were lymphopenia in two patients and hypertension in one. Partial responses were observed only in patients with mutation in SDHB. MGMT immunohistochemistry was negative in tumour samples from four patients who responded to treatment. SDHB germline mutation was associated with hypermethylation of the MGMT promoter and low expression of MGMT in 190 samples of the French nation‐wide independent cohort. This study demonstrates that TMZ is an effective antitumour agent in patients with SDHB‐related MPP. The silencing of MGMT expression as a consequence of MGMT promoter hypermethylation in SDHB‐mutated tumours may explain this finding.
Purpose: To analyze the impact of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) performed 1 year after resection of the primary tumor in asymptomatic patients at high risk of developing peritoneal carcinomatosis (PC). Patients and Methods: From 1999 to 2009, 41 patients without any sign of recurrence on imaging studies underwent second-look surgery aimed at treating limited PC earlier and more easily. They were selected based on 3 primary tumor-associated criteria: resected minimal synchronous macroscopic PC (n = 25), synchronous ovarian metastases (n = 8), and perforation (n = 8). Results: PC was found and treated with complete surgery plus HIPEC in 23 of the 41 (56%) patients. The other patients underwent complete abdominal exploration plus systematic HIPEC. Median follow-up was 30 (9–109) months. One patient died postoperatively at day 69. Grade 3-4 morbidity was low (9.7%). The 5-year overall survival rate was 90% and the 5-year disease-free survival rate was 44%. Peritoneal recurrences occurred in 7 patients (17%), 6 of whom had macroscopic PC discovered during the second-look (26%), and one patient had no macroscopic PC (6%). In the univariate analysis, the presence of PC at second-look surgery was a significant risk factor for recurrence (P = 0.006). Conclusion: Selection criteria for high-risk patients appear to be accurate. In these patients, the second-look strategy treated peritoneal carcinomatosis preventively or at an early stage, yielding promising results. This study has allowed us to design a multicentric randomized trial (comparing the second-look + HIPEC approach versus standard follow-up alone), which is beginning.
To prospectively compare the results of the pathologic examination including thin 3- to 4-mm thick serial slices of the surgical specimen in a well-defined anatomic part of the liver with those of 4 different liver imaging techniques. BACKGROUNDS SUMMARY DATA: Liver metastases (LM) of neuroendocrine origin are frequent and accuracy of pretherapeutic liver imaging in detecting small-sized LM is questioned, but no study has compared the different techniques used to image large liver specimens and meticulous pathologic examination. Eleven patients with a metastatic endocrine tumor were selected before undergoing a right hepatectomy or a left hepatectomy passing along the median hepatic vein. Before the hepatectomy, patients underwent somatostatin receptor scintigraphy, computed tomography, magnetic resonance imaging, and ultrasonography (US). An intraoperative assessment (palpation and US) was also performed. Liver specimens were systematically cut into thin serial slices, 3- to 4-mm thick. A final histologic count of the total number of LM was obtained and compared with findings from each imaging technique. Compared with the final histologic count of LM, fewer than 50% of the LM were detected preoperatively. The accuracy was 24% for somatostatin receptor scintigraphy, 38% for computed tomography and US, and 49% for magnetic resonance imaging (the only imaging technique that detected half the number of LM). The size of the smallest LM was not greater than 2 mm in 54% of the patients. Half the number of LM from neuroendocrine tumors are undetectable on preoperative imaging.