Clarisse Dromain

Progression of medullary thyroid carcinoma: assessment with calcitonin and carcinoembryonic antigen doubling times

OBJECTIVE The progression of medullary thyroid cancer is difficult to assess with imaging modalities; we studied the interest of calcitonin and carcinoembryonic antigen (CEA) doubling times and of Ki-67 labeling and mitotic index (MI). PATIENTS AND METHODS Fifty-five consecutive medullary thyroid carcinoma (MTC) patients with elevated calcitonin levels underwent repeated imaging studies in order to assess tumor burden and progression status. We looked for relationships between tumor burden and levels of calcitonin and CEA and between progression status according to the response evaluation criteria in solid tumors (RECIST) and calcitonin and CEA doubling times, and Ki-67 labeling and MI. RESULTS The calcitonin and CEA levels were correlated with tumor burden. Ten patients with calcitonin levels below 816 pg/ml had no imaged tumor foci. Among the 45 patients with imaged tumor foci, 19 had stable disease and 26 had progressive disease, according to the RECIST. The calcitonin and CEA doubling times were strongly related to disease progression, with very few overlaps: 94% of patients with doubling times shorter than 25 months had progressive disease and 86% of patients with doubling times longer than 24 months had stable disease. Ki-67 labeling and MI were not significantly associated with disease progression. CONCLUSION For MTC patients, the doubling times of both calcitonin and CEA are efficient tools for assessing tumor progression.

Results of Systematic Second-look Surgery Plus HIPEC in Asymptomatic Patients Presenting a High Risk of Developing Colorectal Peritoneal Carcinomatosis

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.

Hepatic Arterial Infusion of Oxaliplatin and Intravenous LV5FU2 in Unresectable Liver Metastases from Colorectal Cancer after Systemic Chemotherapy Failure

BackgroundWe have previously shown promising activity of hepatic arterial infusion (HAI) oxaliplatin combined with intravenous (IV) 5-fluorouracil (5-FU) and leucovorin (LV) as first-line chemotherapy in patients with colorectal liver metastases (CRLM) (intent-to-treat [ITT] objective response rate [ORR], 64%; secondary resection rate, 18%; overall survival [OS], 27 months). Whether this regimen could be beneficial after systemic chemotherapy failure is unknown.MethodsPatients with unresectable CRLM and history of systemic chemotherapy failure were treated bimonthly with HAI oxaliplatin (100 mg/m2 2 hours) combined with IV LV and IV bolus and infusional 5FU (modified LV5FU2 regimen).ResultsForty-four consecutive patients (median age 56 years; median number of prior systemic chemotherapy regimens, 2 range 1–5) were included, of whom 43 (98%) had previously received oxaliplatin (n = 34), irinotecan (n = 37), or both (n = 28). Patients received a median of nine cycles of HAI oxaliplatin and IV modified LV5FU2 (range 0–25). Toxicity included grade 3–4 neutropenia (43%), grade 2–3 neuropathy (43%), and grade 3–4 abdominal pain (14%). We observed 24 partial ORs (62%) among the 39 assessable patients (ITT ORR, 55%; 95% CI, 40–69%), including 17, 12, and 12 patients who had failed to respond to prior systemic chemotherapy with FOLFIRI, FOLFOX, or both, respectively. Tumor response allowed further R0 surgical resection (n = 7) or radiofrequency ablation (n = 1) of initially unresectable CRLM in eight patients (18%). Median progression-free survival and OS were 7 and 16 months, respectively.ConclusionsHAI oxaliplatin and IV LV5FU2 is feasible, safe, and shows promising activity after systemic chemotherapy failure, allowing surgical resection of initially unresectable CRLM in 18% of patients.

Staging of peritoneal carcinomatosis: enhanced CT vs. PET/CT.

PurposeTo assess and compare the performance of CT and 18F-FDG-PET/CT in the evaluation of peritoneal carcinomatosis (PC).Method and materialsThirty consecutive patients with PC and scheduled for a surgery underwent a CT of the abdomen and pelvis and a whole-body 18F-FDG PET/CT. The extent of PC was assessed precisely using the peritoneal cancer index combining the distribution of tumor throughout 11 abdominopelvic regions with a lesion size score. CT and PET/CT imaging results were compared in all patients with intraoperative findings using an interclass correlation test.ResultsThe presence of PC was correctly determined on CT and PET/CT in 23/28 and 16/28 patients, respectively. The extent of PC was understaged with CT and PET/CT in 27 patients and overstaged with CT and PET/CT in 1 and 2 patients, respectively. The interclass correlation was 0.53 (moderate) between CT and surgery and 0.12 (low) between PET/CT and surgery. The interclass correlation was higher for mucinous tumor (0.63) than for non-mucinous (0.16) on CT imaging whereas no difference was found in PET/CT.ConclusionThe intraperitoneal assessment of the extent of carcinomatosis, necessary to assess prognosis and treatment planning, is not accurate enough with CT and PET/CT imaging.

Results of Systematic Second-Look Surgery in Patients at High Risk of Developing Colorectal Peritoneal Carcinomatosis

Objective:The aim of this prospective study was to analyze the impact of second-look surgery in an attempt to treat peritoneal carcinomatosis (PC) at an early stage in a series of patients at high risk of developing PC from colorectal cancer. Background:The prognosis of colorectal PC has recently been improved with hyperthermic intraperitoneal chemotherapy (HIPEC) after complete cytoreductive surgery (CCRS), and could be further improved if PC could be treated at an early stage. But, currently, the diagnosis of early PC is not accessible to imaging. Patients and Methods:From 1999 to 2006, 29 patients without any sign of recurrence on imaging studies underwent second-look surgery 13 months after resection of the primary tumor. Patients were selected according to primary tumor-associated criteria: resected minimal synchronous macroscopic PC (n = 16), synchronous ovarian metastases (n = 4), perforated primary tumor (n = 9). Results:PC was found and treated with CCRS plus HIPEC in 16 of 29 (55%) cases, corresponding to 10 of 16 patients with initial PC, 3 of 4 patients with synchronous ovarian metastases and 3 of 9 patients with a perforated primary tumor. There was no postoperative mortality, and morbidity (grade III/IV) occurred in 14% of cases. After a median follow-up of 27 months (range, 6–96), 8 of 16 patients treated with CCRS and HIPEC are free of disease, 4 relapsed in the peritoneum, and 4 developed isolated visceral metastases. Conclusion:Performing second-look surgery at 1 year in selected patients at high risk of developing PC allowed the early detection and treatment of PC in 55% of cases. Our preliminary results have encouraged us to pursue this strategy and to evaluate it in a prospective multicenter trial.

Hepatic Metastases From Neuroendocrine Tumors With a Thin Slice Pathological Examination: They are Many More Than You Think...

Objectives: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. Patients and Methods: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. Results: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. Conclusion:Half the number of LM from neuroendocrine tumors are undetectable on preoperative imaging.

Evaluation of Tumor Angiogenesis of Breast Carcinoma Using Contrast-Enhanced Digital Mammography

OBJECTIVE The purpose of this article is to assess the accuracy of contrast-enhanced digital mammography in the detection of breast carcinoma and to correlate the findings on the images with those of histologic analysis using microvessel quantification. SUBJECTS AND METHODS Twenty patients with a suspicious breast abnormality underwent contrast-enhanced digital mammography using a full-field digital mammography unit that was modified to detect iodinated enhancement. For each patient, a total of six contrast-enhanced craniocaudal views were acquired from 30 seconds to 7 minutes after the injection of a bolus of 100 mL of an iodinated contrast agent. Image processing included a logarithmic subtraction and the analysis of enhancement kinetic curves. Contrast-enhanced digital mammography findings were compared with histologic analysis of surgical specimens, including intratumoral microvessel density quantification evaluated on CD34-immunostained histologic sections obtained from all patients. RESULTS An area of enhancement was depicted on contrast-enhanced digital mammograms in 16 of the 20 histologically proven breast carcinomas. Excellent correlation was seen between the size of enhancement and the histologic size of tumors, which ranged from 9 to 22 mm. Early enhancement with washout was observed in four cases, early enhancement followed by a plateau in four cases, gradual enhancement in seven cases, and unexpected decrease of enhancement in one case. Intratumoral microvessel density ranged from 11.7 to 216.6 microvessels per square millimeter. A poor correlation was found between data measured on contrast-enhanced digital mammography and intratumoral microvessel density measured on CD34-immunostained histologic sections. CONCLUSION Contrast-enhanced digital mammography is able to depict angiogenesis in breast carcinoma. Breast compression and projective images acquisition alter the quantitative assessment of enhancement parameters.

Outcome of Posthepatectomy-Missing Colorectal Liver Metastases after Complete Response to Chemotherapy: Impact of Adjuvant Intra-arterial Hepatic Oxaliplatin

BackgroundDramatic responses to chemotherapy are occurring more and more frequently in patients with multiple colorectal liver metastases (LMs), leading to resection. In a few patients, some LMs vanish on imaging studies, remain undetected during hepatectomy, and are left in place, which defines the “missing LMs.” The aim of our study was to assess the long-term outcome of such “missing LMs.”PatientsBetween January 1999 and June 2004, among 228 patients treated for colorectal LMs, missing LMs were observed in 16 patients. All the patients were operated within 4 weeks of imaging. Hepatic arterial infusion (HAI) with oxaliplatin was administrated in 12 patients (75%): seven before hepatectomy and five after.ResultsOverall, 69 missing LMs were diagnosed and left in place. Among the persistent LMs resected, a complete pathological response was significantly more often observed in the group with preoperative HAI (6 of 7), than in the group without (2 of 9, P < .02). With a mean follow-up of 51 months (24–90), missing LMs did not reappear in 10 patients (62%). Adjuvant HAI was significantly correlated with the definitive eradication of missing LMs (P < .01), as it was not a complete pathological response. The overall 3-year survival rate of these highly selected 16 patients was 94%.ConclusionColorectal LMs under chemotherapy that vanish on high-quality imaging studies, remain undetected during hepatectomy, and are left in place, are definitively cured in 62% of cases. This excellent result seems to be due to the administration of adjuvant hepatic arterial infusion of chemotherapy and should stimulate new investigations.

Prolonged survival of initially unresectable hepatic colorectal cancer patients treated with hepatic arterial infusion of oxaliplatin followed by radical surgery of metastases.

Purpose:The aim of this study was to analyze the impact of hepatic arterial infusion (HAI) of oxaliplatin with systemic 5-Fluorouracil and leucovorin on patients with isolated unresectable liver metastases. Patients and Methods:A total of 87 patients treated in our hospital with HAI of oxaliplatin with systemic 5-Fluorouracil and leucovorin for isolated unresectable colorectal liver metastases from May 1999 to May 2007 were extracted from a prospective database and analyzed. The resectability rate, perioperative findings, postoperative outcomes, and long-term follow-up were evaluated. Results:HAI was delivered after failure of previous systemic chemotherapy in 69 patients (79%). The main criterion for unresectability was massive liver involvement (86% of patients). Most patients had synchronous (85%), bilateral metastases (89%). The median number of HAI courses was 8 (0–25). About 31 patients experienced technical catheter-related problems, which were responsible for withdrawal of HAI in only 7 patients (8%). Finally, a total of 23 patients (26%) were operated on, and resection or radiofrequency ablation was performed in 21 patients (24%). No postoperative mortality was observed and the morbidity rate was 35%. Five-year overall survival was 56% in the surgery group versus none in the nonsurgery group (P < 0.0001). After a median follow-up of 63 months, intrahepatic recurrence occurred in 10 patients among the 23 operated patients. Conclusions:HAI of oxaliplatin with systemic 5-Fluorouracil and leucovorin offers a second chance to remove initially unresectable isolated colorectal liver metastases in 24% of patients, and appears to be more efficient when performed as first-line therapy. Long-term overall survival can be obtained with this approach.

Contrast-enhanced digital mammography

CEDM is a recent development of digital mammography using the intra-venous injection of an iodinated contrast agent in conjunction with a mammography examination. Two techniques have been developed to perform CEDM examinations: the temporal subtraction technique with acquisition of high-energy images before and after contrast medium injection and the dual energy technique with acquisition of a pair of low and high-energy images only after contrast medium injection. The temporal subtraction technique offered the possibility to analyze the kinetic curve of enhancement of breast lesions, similarly to breast MRI. The dual energy technique do not provide information about the kinetic of tumor enhancement but allows the acquisition of multiples views of the same breast or bilateral examination and is less sensitive to patient motion than temporal CEDM. Initial clinical experience has shown the ability of CEDM to map the distribution of neovasculature induced by cancer using mammography. Moreover, previous studies have shown a superiority of MX+CEDM, either for the assessment of the probability of malignancy than for BIRADS assessment comparing to MX alone. The potential clinical applications are the clarification of mammographically equivocal lesions, the detection of occult lesions on standard mammography, particularly in dense breast, the determination of the extent of disease, the assessment of recurrent disease and the monitoring of the response to chemotherapy. CEDM should result in a simple way to enhance the detection and the characterization of breast lesions.