Prognostic value of BRAF(V6°°) mutations in melanoma patients after resection of metastatic lymph nodes.

PURPOSE: BRAF (V600) mutations are frequent in melanomas, and BRAF(V600)-targeted therapy have dramatic, but often transitory, efficacy in stage IV patients. Prognosis of patients with American Joint Committee on Cancer (AJCC) stage III melanoma is heterogeneous. We aimed to determine the overall survival (OS) of stage III patients with a nodal deposit of ≥2 mm according to BRAF (V600) mutations and other previously reported prognostic criteria. METHODS: This retrospective study included 105 consecutive patients with stage III cutaneous melanomas. Most patients underwent a prospective follow-up. BRAF (V600) mutations were detected by sequencing and pyrosequencing of DNA in samples containing >60 % melanoma cells. RESULTS: BRAF mutations (p.V600E and p.V600K in 83 and 14 % of cases, respectively) were detected in 40 % of the patients. For patients with and without BRAF mutations, death occurred in 83.3 and 60.3 %, with a median OS of 1.4 and 2.8 years, respectively. Patient age, primary melanoma ulceration, number of invaded lymph nodes, AJCC staging at study entry, and BRAF status were linked to OS in the univariate analysis. The only characteristics associated with OS in the multivariate analysis were number of invaded lymph nodes (P = 0.005, hazard ratio 2.2, 95 % confidence interval 1.3-3.9) and BRAF status (P = 0.005, hazard ratio 1.9, 95 % confidence interval 1.2-3.1). CONCLUSIONS: BRAF (V600) status could be used to stage melanoma patients with nodal deposits. Our results may also help to plan adjuvant trials in these patients, for whom the low tumor load may induce longer efficacy of BRAF-targeted therapies.

Impact of chemotherapy on the accuracy of computed tomography scan for the evaluation of colorectal liver metastases.

BACKGROUND: The aim of this study was to determine the effect of chemotherapy on the accuracy of CT scan for the preoperative evaluation of colorectal liver metastases (LM). METHOD: Between 1999 and 2005, 92 patients with less than six LM at diagnosis underwent surgery within four weeks of CT scan. Of these 92 patients, 60 had received chemotherapy before surgery (chemotherapy group), whereas 32 were operated without preoperative treatment (control group). Histological and surgical findings were compared with helical CT results. RESULTS: On a per lesion basis, the sensitivity of CT scan for the detection of LM was 71% in the chemotherapy group and 76% in the control group. On a per patient basis, the sensitivity of CT scan was 54% in the chemotherapy group and 69% in the control group. Discrepancies between CT scan and surgical or histological findings, including both false-negative and false-positive lesions, were found in 32 patients from the chemotherapy group and 10 patients from the control group (p=0.0471). In multivariate analysis, chemotherapy (p=0.032), number of LM > 3 (p=0.034), and steatosis > 30% (p=0.012) were risk factors for inadequate staging of LM by CT scan. CONCLUSIONS: Chemotherapy reduces the accuracy of CT scan for preoperative evaluation of colorectal LM.

The contribution of high-resolution ultrasonography in preoperatively detecting sentinel-node metastases in melanoma patients.

To evaluate the ability of high-resolution ultrasonography (hrUS) to detect sentinel-node (SN) melanoma metastases preoperatively before sentinel-node biopsy (SNB), to define hrUS resolution, and to evaluate which US criteria should be used. During a 6.5-year period, 131 consecutive patients with 132 >or=1-mm thick or ulcerated cutaneous melanomas, who were followed up at a single center, were enrolled. All patients underwent preoperative regional lymph-node hrUS and SNB. We used the recently evaluated ultrasonographic stringent and nonstringent hrUS criteria to detect SN metastases. Sizes of the SN metastatic deposits were measured under light microscopy. Thirty-five (27%) patients had a positive SNB. HrUS identified only three positive SNs as being metastatic. Sensitivity and specificity using stringent criteria were 8.8% [95% confidence interval (CI, 2.3-24.8%) and 95.9% (95% CI, 89.3-98.7%)], respectively. Positive-predictive value was 42.9% (95% CI, 11.9-79.9%). The nonstringent criteria provided four additional true-positive results, but lowered specificity (89.8%; 95% CI, 81.6-94.7%) with no significant improvement in sensitivity (20.6%; 95% CI, 9.3-38.4%). Positive-predictive value using nonstringent criteria was 41.2% (95% CI, 19.3-66.4%). HrUS failed to detect all metastatic deposits <5 mm in diameter. HrUS assessment of early-stage melanomas cannot replace surgical SNB. Owing to its low positive-predictive value, hrUS was unable to identify patients who would have to proceed directly to completion lymphadenectomy.

Ultrasonography using simple diagnostic criteria vs palpation for the detection of regional lymph node metastases of melanoma.

OBJECTIVES: Our aims were (1) to compare the respective ability of ultrasonography and palpation to detect nodal metastasis during initial staging and follow-up in patients having melanomas and (2) to assess, we believe for the first time, which ultrasound criteria should be used to define metastasis in cases of cutaneous or mucosal melanoma. DESIGN: Prospective single-center study. Nodal metastasis was confirmed by histopathologic evaluation. SETTING: Dermatology and radiology departments of a university hospital. PATIENTS: A total of 160 new consecutive patients with stage I to stage III melanoma. INTERVENTION: Experienced operators independently performed 391 paired palpation and ultrasonographic examinations. MAIN OUTCOME MEASURES: Firm enlarged nodes found on palpation were considered metastatic. On ultrasonographic examination, circular or oval hypoechoic lymph nodes lacking hyperechoic hila were considered metastatic (stringent criteria). Nodes with 2 or fewer of these patterns and other published signs of metastasis (ie, intranodal nodular hypoechoic focus and irregularity of the node margin) were considered suspicious. RESULTS: Over the 6-year study period 33 patients developed nodal metastasis. For palpation and ultrasonography using the stringent criteria, respectively, sensitivity was 41.5% (95% confidence interval [95% CI], 29.6-53.5) and 76.9% (95% CI, 66.7%-87.2%) (P<.001) and specificity was 95.7% (95% CI, 93.5%-97.9%) and 98.4% (95% CI, 97.1%-99.8%) (P<.05). Including ultrasonographically suspicious lymph nodes significantly lowered specificity (86.2% [95% CI, 82.5-89.9]) (P<.05) without improving sensitivity. Previous lymphadenectomy had little impact on ultrasonographic findings. CONCLUSION: Ultrasonography using stringent criteria of nodal metastasis, which are easy to identify and reliable, is superior to palpation for early detection of regional lymph node metastases of melanoma.

Pulmonary artery interventions: an overview.

Interventional radiologists should be familiar with minimally invasive procedures used to treat various abnormalities of the pulmonary arteries. These well-established techniques, which obviate open surgery, are safe and effective when performed by an experienced interventionalist. Catheter-based thrombolysis with intrapulmonary arterial infusion of thrombolytic drugs, percutaneous thrombectomy, or embolus fragmentation can be performed in patients with life-threatening pulmonary embolism. Pulmonary artery stenoses, mainly encountered in patients with pulmonary vasculitis (as in Behçet disease or Takayasu arteritis), may be treated with balloon angioplasty and stent placement. Transcatheter embolization of pulmonary arteriovenous malformation is the standard treatment for hereditary hemorrhagic telangiectasia and is a very effective alternative to surgery to correct an aneurysm or pseudoaneurysm. In cases of hemoptysis that originates in the pulmonary artery, early diagnosis is mandatory for treatment with embolization. Percutaneous retrieval of foreign bodies from the heart or the pulmonary arteries and endovascular biopsy should also be part of the armamentarium of interventional radiologists.

Uterine fibroid vascularization and clinical relevance to uterine fibroid embolization.

Embolization has become a first-line treatment for symptomatic uterine fibroid tumors. Selective catheterization and embolization of both uterine arteries, which are the predominant source of blood flow to fibroid tumors in most cases, is the cornerstone of treatment. Although embolization for treatment of uterine fibroid tumors is widely accepted, great familiarity with the normal and variant pelvic arterial anatomy is needed to ensure the safety and success of the procedure. The uterine artery classically arises as a first or second branch of the anterior division of the internal iliac artery and is usually dilated in the presence of a uterine fibroid tumor. Angiography is used for comprehensive pretreatment assessment of the pelvic arterial anatomy; for noninvasive evaluation, Doppler ultrasonography, contrast material-enhanced magnetic resonance (MR) imaging, and MR angiography also may be used. After the uterine artery is identified, selective catheterization should be performed distal to its cervicovaginal branch. For targeted embolization of the perifibroid arterial plexus, injection of particles with diameters larger than 500 mum is generally recommended. Excessive embolization may injure normal myometrium, ovaries, or fallopian tubes and lead to uterine necrosis or infection or to ovarian failure. Incomplete treatment or additional blood supply to the tumor (eg, via an ovarian artery) may result in clinical failure. The common postembolization angiographic end point is occlusion of the uterine arterial branches to the fibroid tumor while antegrade flow is maintained in the main uterine artery.

Validation of dynamic contrast-enhanced ultrasound in predicting outcomes of antiangiogenic therapy for solid tumors: the French multicenter support for innovative and expensive techniques study.

OBJECTIVES: Dynamic contrast-enhanced ultrasound (DCE-US) has been used in single-center studies to evaluate tumor response to antiangiogenic treatments: the change of area under the perfusion curve (AUC), a criterion linked to blood volume, was consistently correlated with the Response Evaluation Criteria in Solid Tumors response. The main objective here was to do a multicentric validation of the use of DCE-US to evaluate tumor response in different solid tumor types treated by several antiangiogenic agents. A secondary objective was to evaluate the costs of the procedure. MATERIALS AND METHODS: This prospective study included patients from 2007 to 2010 in 19 centers (8 teaching hospitals and 11 comprehensive cancer centers). All patients treated with antiangiogenic therapy were eligible. Dynamic contrast-enhanced ultrasound examinations were performed at baseline as well as on days 7, 15, 30, and 60. For each examination, a perfusion curve was recorded during 3 minutes after injection of a contrast agent. Change from baseline at each time point was estimated for each of 7 fitted criteria. The main end point was freedom from progression (FFP). Criterion/time-point combinations with the strongest correlation with FFP were analyzed further to estimate an optimal cutoff point. RESULTS: A total of 1968 DCE-US examinations in 539 patients were analyzed. The median follow-up was 1.65 years. Variations from baseline were significant at day 30 for several criteria, with AUC having the most significant association with FFP (P = 0.00002). Patients with a greater than 40% decrease in AUC at day 30 had better FFP (P = 0.005) and overall survival (P = 0.05). The mean cost of each DCE-US was 180&OV0556;, which corresponds to $250 using the current exchange rate. CONCLUSIONS: Dynamic contrast-enhanced ultrasound is a new functional imaging technique that provides a validated criterion, namely, the change of AUC from baseline to day 30, which is predictive of tumor progression in a large multicenter cohort. Because of its low cost, it should be considered in the routine evaluation of solid tumors treated with antiangiogenic therapy.

Standardization of dynamic contrast-enhanced ultrasound for the evaluation of antiangiogenic therapies: the French multicenter Support for Innovative and Expensive Techniques Study.

OBJECTIVES: The objectives of this study are to describe the standardization and dissemination of dynamic contrast-enhanced ultrasound (DCE-US) for the evaluation of antiangiogenic treatments in solid tumors across 19 oncology centers in France and to define a quality score to account for the variability of the evaluation criteria used to collect DCE-US data. MATERIALS AND METHODS: This prospective Soutien aux Techniques Innovantes Coûteuses (Support for Innovative and Expensive Techniques) DCE-US study included patients with metastatic breast cancer, melanoma, colon cancer, gastrointestinal stromal tumors, renal cell carcinoma and patients with primary hepatocellular carcinoma tumors treated with antiangiogenic therapy. The DCE-US method was made available across 19 oncology centers in France. Overall, 2339 DCE-US examinations were performed by 65 radiologists in 539 patients.One target site per patient was studied. Standardized DCE-US examinations were performed before treatment (day 0) and at days 7, 15, 30, and 60. Dynamic contrast-enhanced ultrasound data were transferred from the different sites to the main study center at the Institut Gustave-Roussy for analysis. Quantitative analyses were performed with a mathematical model to determine 7 DCE-US functional parameters using raw linear data. Radiologists had to evaluate 6 criteria that were potentially linked to the precision of the evaluation of these parameters: lesion size, target motion, loss of target, clear borders, total acquisition of wash-in, and vascular recognition imaging window adapted to the lesion size.Eighteen DCE-US examinations were randomly selected from the Soutien aux Techniques Innovantes Coûteuses (Support for Innovative and Expensive Techniques) database. Each examination was quantified twice by 8 engineers/radiologists trained to evaluate the perfusion parameters. The intraobserver variability was estimated on the basis of differences between examinations performed by the same radiologist. The mean coefficient of variability associated with each quality criterion was estimated. The final quality score, ranging from 0 to 5, was defined according to the value of coefficient of variability for each criterion. RESULTS: A total of 2062 examinations were stored with raw linear data. Five criteria were found to have a major impact on quality: lesion size, motion, loss of target, borders, and total acquisition of wash-in. Only 3% of the examinations were of poor quality (quality of 0); quality was correlated with the radiologists' experience, such that it was significantly higher for radiologists who had performed more than 60 DCE-US examinations (P < 0.0001). CONCLUSIONS: The DCE-US methodology has been successfully provided to several centers across France together with strict rules for quality assessment. Only 3% of examinations carried out at these centers were considered not interpretable.

Complete response of colorectal liver metastases after chemotherapy: does it mean cure?

PURPOSE: Most patients with colorectal liver metastases (LMs) receive systemic chemotherapy. This study aimed to determine the significance of a complete response on imaging of LMs after chemotherapy. PATIENTS AND METHODS: Between 1998 and 2004, 586 patients were treated for colorectal LMs in one institution. Of these, 38 with the following criteria were included in the study: fewer than 10 LMs before chemotherapy; disappearance of one or several LMs on computed tomography (CT) scan and ultrasound; surgery with intraoperative ultrasound within 4 weeks of imaging; no extrahepatic disease; follow-up at least 1 year after surgery. RESULTS: Overall, 66 LMs disappeared after chemotherapy as seen on CT scan. Persistent macroscopic disease was observed at surgery at the site of 20 of 66 LMs, despite CT scan showing a complete response. The sites of 15 initial LMs that were not visible at surgery were resected. Pathologic examination of these sites of LMs, considered in complete response, showed viable cancer cells present in 12 of 15 cases. The sites of 31 initial LMs that were not visible at surgery were left in place during surgery; after 1 year of follow-up, 23 of 31 LMs considered in complete response had recurred in situ. Overall, persistent macroscopic or microscopic residual disease or early recurrence in situ were observed in 55 (83%) of 66 LMs having a complete response on imaging. CONCLUSION: In most patients receiving chemotherapy for colorectal LMs, a complete response on CT scan does not mean cure.

Ascaris in gallbladder: report of a case and review.

A case of an Ascaris infection of the gallbladder is reported in a 29 years old female. The biological check-up was normal. The diagnosis was confirmed by ultrasonography and the patient was cured by albendazole. Such a localization is uncommon (2.1% of the hepatobiliary ascariasis), and the abdominal ultrasonography is the best way to confirm the diagnosis. Albendazole is the current treatment, but cholecystectomy is sometimes a must.

Ultrasonography or palpation for detection of melanoma nodal invasion: a meta-analysis.

Because treatment of distant melanoma metastases is not very effective, nodal spread should be diagnosed early so that therapeutic lymphadenectomy can be started as early as possible. Physical examination alone often does not detect nodal metastases and palpable nodes cannot be clasified unambiguously. Whether lymph-node ultrasonography-an inexpensive procedure-improves detection of nodal invasion during the initial staging and follow-up of patients with melanoma is controversial. We used meta-analysis techniques for diagnostic tests to assess the merit of ultrasonography and palpation in detection of nodal invasion in patients with melanoma. Five databases were screened until December, 2003. 12 studies, including 6642 patients and 18?610 paired palpation and ultrasound examinations, were eligible. The main limitations were variations in the definition of false negatives, and verification bias. Ultrasonography had a higher discriminatory power (odds ratio 1755; 95% CI 726-4238) than did palpation (21 [4-111]; p=0.0001). Furthermore, positive-likelihood ratios were 41.9 (95% CI 29-75) for ultrasonography and 4.55 (2-18) for palpation; negative-likelihood ratios were 0.024 (0.01-0.03) and 0.22 (0.06-0.31), respectively. Our results showed clearly that ultrasonography detects lymph-node invasion more accurately than palpation, and should therefore probably be used routinely in patients with melanoma.

Assessment of radiological referral practice and effect of computer-based guidelines on radiological requests in two emergency departments.

AIM: To assess medical emergency radiology referral practice compared with a set of French guidelines and to measure the efficiency of computer-based guidelines on unnecessary medical imaging. MATERIALS AND METHODS: All radiological requests were computerized in the medical emergency departments of two French teaching hospitals. During control periods, radiological requests were recorded but no action was taken. During intervention periods, reminder displays on screen indicated the appropriate recommendations. Three control and three intervention periods of 1 month each were conducted. The percentage of requests that did not conform to the guidelines and variation related to periods of control and intervention were measured. RESULTS: The proportion of requests that did not conform to the guidelines was 33.2% when the guidelines were inactive and decreased to 26.9% when the recommendations were active (P < 0.0001). The three imaging examinations (chest radiographs, abdominal plain radiographs and CT of the brain) accounted for more than 80% of all requests; more than 50% of abdominal plain radiographs requests did not conform with recommendations while this percentage was respectively 24.9% and 15.8% for chest radiographs and computed tomography (CT) of the brain. Seven situations accounted for 70% of non-conforming radiological referrals; in these situations, junior practitioners' knowledge was inadequate. CONCLUSION: While the computer provided advice that was tailored to the needs of individual patients, concurrent with care, the effect of our intervention was weak. However, our study identified the few situations that were responsible for the majority of unnecessary radiological requests; we expect that this result could help clinicians and radiologists to develop more specific actions for these situations.