Jacques Monteil

How can grafted breast cancer models be optimized

Breast cancer is the most frequent spontaneous malignancy diagnosed in women and is characterized by a broad histological diversity. Progression of the disease has a metastasizing trend and can be resistant to hormonal and chemotherapy. Animal models have provided some understanding of these features and have allowed new treatments to be proposed. However, these models need to be revised because they have some limitations in predicting the clinical efficacy of new therapies. In this review, we discuss the biological criteria to be taken into account for a realistic animal model of breast cancer graft (tumor implantation site, animal immune status, histological diversity, modern imaging). We emphasize the need for more stringent monitoring criteria, and suggest adopting the human RECIST (Response Evaluation Criteria in Solid Tumors) criteria to evaluate treatments in animal models.

Comparison of detection of F-18 fluorodeoxyglucose positron emission tomography and 99mTc-hexamethylpropylene amine oxime labelled leukocyte scintigraphy for an aortic graft infection

To compare F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG-PET) and (99m)Tc-hexamethylpropylene amine oxime ((99m)TC-HMPAO) labelled leukocyte scintigraphy for the diagnosis of vascular graft infection. A thoraco-abdominal CT-angiography and a (99m)TC-HMPAO labelled leukocyte scintigraphy did not show any graft infection in this case report whereas an F-18 FDG-PET showed a metabolic uptake around and all along the vascular graft. Further comparison between these two explorations is needed since the two techniques have not been compared in vascular graft infection.

CD68-positive tumor-associated macrophages predict unfavorable treatment outcomes in classical Hodgkin lymphoma in correlation with interim fluorodeoxyglucose-positron emission tomography assessment

Abstract Finding new prognostic factors to identify patients with Hodgkin lymphoma (HL) at risk of treatment resistance or relapse remains challenging in daily practice. We evaluated the relationship between CD68 expression, interim positron emission tomography (iPET) results and outcome in 158 patients with HL diagnosed from February 1995 to July 2011. Immunohistochemistry (anti-CD68) gave two groups: low with ≤ 25% positive cells (121 patients) and high with > 25% (37 patients). Five-year overall survival was higher in the low group (88.4% vs. 63.2%, p = 0.0151), as was progression-free survival (74.5% vs. 40.7%, p = 0.0003). In 68 patients evaluable, iPET correlated with CD68: 13/52 patients (25%) in the low group had positive iPET as compared to 11/16 patients (68%) in the high group (p = 0.0016). This study confirms the prognostic value of CD68 in HL. We found a correlation between CD68 and iPET suggesting potential for a better stratification.

18F-FDG PET SUVmax Correlates with Osteosarcoma Histologic Response to Neoadjuvant Chemotherapy: Preclinical Evaluation in an Orthotopic Rat Model

Assessment of osteosarcoma response to neoadjuvant chemotherapy is performed by histopathologic analysis after surgical resection of the primary tumor. The purpose of this study was to evaluate whether 18F-FDG PET could be a noninvasive surrogate to histopathologic analysis and allow for earlier response evaluation to neoadjuvant chemotherapy in osteosarcoma. Methods: Metabolic response to neoadjuvant chemotherapy was assessed in immunocompetent rats with a preestablished orthotopic osteosarcoma using 18F-FDG PET before and after receiving 2 doses of ifosfamide. Comparison was then made by assessing histologic responses on euthanized animals. Results: Maximum standardized uptake value (SUVmax) measured by 18F-FDG PET after 2 doses of chemotherapy was correlated to histologic classification (P < 0.01). An SUVmax less than 15 corresponded to good responders, whereas an SUVmax greater than 15 but less than 20 and an SUVmax greater than 20 corresponded to partial responders or nonresponders, respectively. A 40% decrease in SUVmax between the first and second 18F-FDG PET scans distinguished between partial and good response to chemotherapy. Conclusion: Determination of SUVmax using semiquantitative 18F-FDG PET predicts response to neoadjuvant chemotherapy earlier than does histologic analysis.

Tumoral Hypoxia in Osteosarcoma in Rats: Preliminary Study of Blood Oxygenation Level–Dependent Functional MRI and 18F-Misonidazole PET/CT With Diffusion-Weighted MRI Correlation

OBJECTIVE The prognostic implication of oxygen concentration as a factor in recurrence of solid tumors has been proved. Hypoxic osteosarcoma, imaged with (18)F-misonidazole PET/CT, is the most frequent primary malignant bone tumor. The aim of our study was to determine the role of blood oxygenation level-dependent (BOLD) functional MRI in an osteosarcoma rodent model by comparison of oxygenation levels in BOLD functional MRI and (18)F-misonidazole PET/CT and correlating the findings with those of diffusion-weighted MRI (DWI). MATERIALS AND METHODS After validation of a hypoxic rodent model, 3-T MRI of osteosarcoma grafted in eight rats, including anatomic, DWI, and BOLD sequences in ambient air and after 2 and 3 minutes of impregnation of 8 L/min of oxygen, was performed on days 10, 17, and 24 after tumor grafting. (18)F-misonidazole PET/CT was performed on day 26, and the rats were sacrificed on day 27 for specific screening of markers of hypoxia. We measured BOLD signal intensity in tumors and normal tissue and compared these results with those on apparent diffusion coefficient maps and (18)F-misonidazole uptake according to maximum standardized uptake value ratio between tumor and healthy spongy bone. RESULTS Hypoxia was confirmed by histologic study in all cases. We found a significant difference (day 17, p = 0.0038; day 24, p = 0.0051) in the decrease in signal intensity of hypoxic tumor in the presence of oxygen compared with ambient air without relation to duration of oxygen impregnation (p = 0.06). We found a significant correlation (p = 0.003) between BOLD signal intensity and maximum standardized uptake value at (18)F-misonidazole PET/CT. We found no correlation between the decrease in BOLD signal intensity and apparent diffusion coefficient (p = 0.07). CONCLUSION BOLD functional MRI may be a promising tool for noninvasive functional imaging of bone tumors, but additional developments are necessary to permit its use in clinical practice.

Outcomes and Future Directions of Per-Oral Endoscopic Pyloromyotomy

Gastroparesis is a challenging functional gastroenterological disorder, the complex pathophysiology of which hampers development of therapeutic modalities. Per-oral pyloromyotomy (POP) is a promising endoscopic therapy with a short-term clinical success rate of greater than 80%. Interest in POP is increasing, particularly in France, a country in which there is considerable expertise in submucosal endoscopy and functional disorders. Long-term follow-up and pyloric function evaluation are needed to assess the efficacy of POP in gastroparetic patients.

Peroral endoscopic pyloromyotomy is efficacious and safe for refractory gastroparesis: prospective trial with assessment of pyloric function

BACKGROUND Gastroparesis is a functional disorder with a variety of symptoms that is characterized by delayed gastric emptying in the absence of mechanical obstruction. A recent series of retrospective studies has demonstrated that peroral endoscopic pyloromyotomy (G-POEM) is a promising endoscopic procedure for treating patients with refractory gastroparesis. The aim of this prospective study was to evaluate the feasibility, safety, and efficacy of G-POEM. METHODS 20 patients with refractory gastroparesis (10 diabetic and 10 nondiabetic) were prospectively included in the trial. Patients were treated by G-POEM after evaluation of pyloric function using an endoscopic functional luminal imaging probe. Clinical responses were evaluated using the Gastroparesis Cardinal Symptom Index (GCSI), and quality of life was assessed using the Patient Assessment of Upper Gastrointestinal Disorders - Quality of Life scale and the Gastrointestinal Quality of Life Index scores. Gastric emptying was measured using 4-hour scintigraphy before G-POEM and at 3 months. RESULTS Feasibility of the procedure was 100 %. Compared with baseline values, G-POEM significantly improved symptoms (GCSI: 1.3 vs. 3.5; P < 0.001), quality of life, and gastric emptying (T½: 100 vs. 345 minutes, P < 0.001; %H2: 56.0 % vs. 81.5 %, P < 0.001; %H4: 15.0 % vs. 57.5 %, P = 0.003) at 3 months. The clinical success of G-POEM using the functional imaging probe inflated to 50 mL had specificity of 100 % and sensitivity of 72.2 % (P = 0.04; 95 % confidence interval 0.51 - 0.94; area under the curve 0.72) at a distensibility threshold of 9.2 mm2/mmHg. CONCLUSION G-POEM was efficacious and safe for treating refractory gastroparesis, especially in patients with low pyloric distensibility.

Surveillance du cancer de l’endomètreFollow-up of endometrial cancer

Available data on appropriate follow-up in endometrial cancer highlight the need of well-conducted studies. Most recurrences tend to occur within three years and involve symptoms. Routine tests are not advocated without symptoms. In case of suspicious recurrence, TEP/CT seems to be the most sensitive and specific method. There is limited evidence to decide whether follow-up schedules with multiple visits result in survival benefits. An appropriate follow-up should be discussed based upon the risk of recurrence. Counselling on the potential symptoms of recurrence should be a major aim.

Surveillance du cancer de l’endomètre

Available data on appropriate follow-up in endometrial cancer highlight the need of well-conducted studies. Most recurrences tend to occur within three years and involve symptoms. Routine tests are not advocated without symptoms. In case of suspicious recurrence, TEP/CT seems to be the most sensitive and specific method. There is limited evidence to decide whether follow-up schedules with multiple visits result in survival benefits. An appropriate follow-up should be discussed based upon the risk of recurrence. Counselling on the potential symptoms of recurrence should be a major aim.