Case Report: Potential role of selective venous sampling for liquid biopsy in complex clinical settings: Three case presentations.

Tumor mutation profiling from a blood sample, known as liquid biopsy, is a reality that has already been approved for some cancers. This molecular diagnostic method complements tissue biopsy but is less invasive and therefore more easily applied, especially during tumor evolution. Its use should allow detection of residual disease, evaluation of treatment response or resistance, and selection of targeted treatments. However, implementation of liquid biopsy in routine clinical practice is hindered by unsolved issues, one of which is the scarcity of circulating tumor DNA in blood samples drawn from peripheral veins. To address this problem, we propose minimally invasive selective venous sampling from the region of interest, as used for some hormonal studies and for mapping of endocrine tumors. Intuitively, selective sampling should improve the sensitivity of liquid biopsy by avoiding the dilution of tumor biomarkers that occurs in the peripheral circulation. We report three cases that illustrate the potential utility of selective liquid biopsy in complex clinical settings, providing implications for diagnosis and treatment as well as for monitoring over time, disease localization, identification of drug resistance, and differential diagnosis.

Beyond Standard Practice in Liquid Biopsy: Selective Venous Sampling.

Liquid biopsy is a molecular diagnostic procedure that aims to provide readily accessible genetic profiling of tumors for primary diagnosis, detection of minimal residual or metastatic disease, and therapeutic decision-making, especially for molecularly targeted treatments. Cancers release various biological markers into the circulation, although the most widely used are cell-free tumor DNA and circulating tumor cells. The paucity of biological material means that laboratory methods mainly based on genetic sequencing expose this innovative diagnostic method to a considerable incidence of false negatives. The 3 cases presented here show how the sensitivity and specificity of liquid biopsy may be improved through selective venous sampling.

Percutaneous ultrasound-guided central venous catheters: the lateral in-plane technique for internal jugular vein access.

PURPOSE: To describe the possible ultrasound guidance techniques for the insertion of central venous catheters (CVCs), with emphasis particularly to the lateral short axis in-plane technique. METHODS: Numerous articles have shown significant benefits of using ultrasound guidance for venous access. Two main approaches to vein puncture are available, when considering visualization of the needle during its entry into the vein under the ultrasound beam: in-plane and out-of-plane, which can be combined with two types of vein visualization, placing the ultrasound probe on the vein long axis or short axis. RESULTS: Advantages and limitations in internal jugular vein (IJV) cannulation for long-term dialysis CVCs are described for the above-mentioned approaches and visualizations. The lateral short axis in-plane technique has virtually no limitations, ensuring most benefits. CONCLUSIONS: The lateral short axis in-plane technique should be considered the first-line technique for IJV cannulation.

Revaluation of breast cytology with pathologist on-site of lesions with suspicious sonographic features.

OBJECTIVE: Evaluating correlation estimation between diagnostic ultrasound (U.S.) of breast lesions and fine needle aspiration cytology (FNAC), and the correlation between cytology and histology (I) of these lesions undergo surgery. MATERIALS AND METHODS: In 2010 we performed 1589 ultrasound breast. We identified 210 suspicious lesions to be subjected to FNAC, which was performed with pathologist on site, and extemporaneous analysis of the sample to assess their appropriateness. We classified the lesions in 5 ultrasound (U) classes according to the criteria defined by Echographic BIRADS Lexicon. The results of cytology were classified in 5 classes (C) according to the guidelines of F.O.N.Ca.M. Then we evaluated the diagnostic correlation between U.S. and FNAC, and between FNAC and Histology. RESULTS: The distribution of lesions in U classes was: 57U2, 55U3, 36U4 and 62U5. The diagnostic concordance between U and FNAC was 96.7%, with a sensitivity of 98%, specificity 93%, negative and positive predictive value respectively of 94.9% and 97.3%, and diagnostic accuracy of 96.6%. The 98 patients with C4-C5 lesions were subjected to surgery and the histology confirmed high-grade malignancy of lesions with a concordance of 99.7%. CONCLUSIONS: Having achieved high diagnostic concordance between U and FNAC, and then between FNAC and histology, we may say that the FNAC, less invasive and traumatic for the patient than needle biopsy (CB), may be still a valid method when performed with pathologist on-site to assess the adequacy of the sample taken.

Catheter-based radiofrequency renal sympathetic denervation for resistant hypertension.

PURPOSE: To evaluate the feasibility, efficacy, and safety of catheter-based radiofrequency renal sympathetic denervation for treatment of resistant hypertension. MATERIALS AND METHODS: Twenty-four patients with essential hypertension unresponsive to at least three antihypertensive agents underwent renal denervation (RDN). Three patients had variant renal anatomy. Comorbidities included diabetes (n = 11), renal failure (n = 4), and obstructive sleep apnea (n = 2). The effect on 24-hour ambulatory blood pressure (BP) was assessed at 6 months. Patients with a decrease in systolic BP of at least 10mm Hg were considered responders. RESULTS: RDN was bilateral in 19 patients and single-sided in five. The 19 patients with bilateral RDN showed mean reductions in 24-hour ambulatory BP of 20.7/8.7mm Hg±18.1/9.9 (systolic/diastolic; P = .0001/P = .0012). Sixteen bilaterally treated patients (84.2%) showed a systolic BP reduction of at least 10mm Hg and were considered responders, whereas only one of the five patients with single-sided RDN showed a response. Two responders with sleep apnea showed improvement in polysomnography indices, and one with left concentric ventricular hypertrophy showed complete cardiac remodeling 11 months after the RDN procedure. Renal function remained unchanged in all patients, including those with renal failure. Optical coherence tomography of the renal arteries in one patient showed sporadic endothelial scarring. Renal angiograms at 9 months (one patient) and 12 months (two patients) had normal findings. CONCLUSIONS: Catheter-based RDN was carried out safely, even in patients with comorbidities, abnormal renal arteries, or anatomic variants. The response rate for bilateral RDN (84.2%) was comparable to previous reports.

Use of a retrievable vena cava filter with low-intensity anticoagulation for prevention of pulmonary embolism in patients with cancer: an observational study in 106 cases.

PURPOSE: To evaluate a retrievable inferior vena cava (IVC) filter in combination with low-intensity oral anticoagulation for prevention of pulmonary embolism (PE) in patients with malignancy complicated by thromboembolic disease. MATERIALS AND METHODS: From October 2005 to December 2009, 107 Bard G2 filters were placed in 106 patients. Forty-eight patients had deep vein thrombosis (DVT) alone, 53 had PE with DVT, and five had PE with no evidence of DVT. After an initial period of anticoagulation with heparin, low-intensity oral anticoagulant therapy to achieve a target International Normalized Ratio of 1.5-2.0 was instituted. Follow-up computed tomography to evaluate the pulmonary circulation, IVC, and lower limbs was performed at 3 and 6 months. RESULTS: PE recurred in three of 58 patients (5.2%). None of the 48 patients with DVT alone developed PE, nor was there any recurrence of DVT. The filter was removed in 14 patients (13.2%). No complications occurred during the retrieval procedure. A total of 16 complications occurred in seven patients: one migration (0.9%); four cases of vena cava thrombosis (3.7%), three of which were associated with recurrent PE (2.8%); one filter fracture (0.9%); and one IVC penetration (0.9%). Filter tilting greater than 15° occurred in six patients (5.7%) and was associated with other complications in five (4.7%). CONCLUSIONS: In patients with malignancies complicated by venous thromboembolic disease, an IVC filter together with low-intensity anticoagulation may be a possible treatment strategy for PE prophylaxis. Controlled studies are warranted.

GAVeCeLT* consensus statement on the correct use of totally implantable venous access devices for diagnostic radiology procedures.

The use of totally implantable venous access devices in radiology may be associated with complications such as occlusion of the system (because of the high density of some contrast), infection (if the port is not handled in aseptic conditions, using proper barrier protections), and mechanical complications due to the high-pressure administration of contrast by automatic injectors (so-called power injector), including extravasation of contrast media into the soft tissues, subintimal venous or myocardial injection, or serious damage to the device itself (breakage of the external connections, dislocation of the non-coring needle, or breakage of the catheter). The last problem - i.e., the damage of the device from a power injection - is not an unjustified fear, but a reality. A warning by the US Food and Drug Administration of July 2004 reports around 250 complications of this kind, referring to both port and central venous catheters and peripherally inserted central catheter systems, which occurred over a period of several years; in all cases, the damage occurred during the injection of contrast material by means of power injectors for computed tomography or magnetic resonance imaging procedures. Though the risk associated with the use of ports in radiodiagnostics is thus clear, it has been suggested that administration of the contrast material via the port may have some advantage in terms of image quality, increased comfort for the patient, and maybe more accurate reproducibility of the patient's own follow-up exams. This contention needs to be supported by evidence. Also, since many cancer patients who need frequent computed tomography studies already have totally implantable systems, it would seem reasonable to try to define how and when such systems may safely be used. The purpose of this consensus statement is to define recommendations based on the best available evidence, for the safe use of implantable ports in radiodiagnostics.

Successful intra-arterial chemotherapy for extramammary Paget's disease of the axilla in a patient with Parkinson's disease.

Extramammary Paget's disease (EMPD) is a rare intraepithelial neoplasm occurring less frequently in men and even more rarely in the axilla. A 59-year-old man with severe Parkinson's disease presented with axillary EMPD. The neurological comorbidity made treatment of the EMPD problematical and prompted us to propose locoregional intra-arterial chemotherapy in single short sessions. Two innovative chemotherapeutic macrocomplexes were used: doxorubicin incorporated in large liposomes and the taxane paclitaxel incorporated in albumin nanoparticles. A therapeutic response was seen right from the first treatment and was macroscopically close to complete after four cycles. Five months after the end of treatment the patient had minimal visible disease and had enjoyed a distinct improvement in quality of life, with no noteworthy complications related to the intra-arterial chemotherapy with percutaneous transfemoral catheterization.

Large renal artery aneurysm treated with Guglielmi detachable coils: procedural and 4-year follow-up results.

A large aneurysm of the left renal artery was found incidentally during abdominal ultrasound in a 39-year-old woman with no medical or family history of cardiovascular disease. Vascular pathology with a dysplastic appearance was confirmed by magnetic resonance angiography and the patient was offered transcatheter embolization. Since the position and size of the neck of the aneurysm could not be determined at angiography, detachable platinum coils were used for occlusion. The procedure was performed without complications. During a 4-year follow-up no alterations of renal function, recanalization of the aneurysm, or perfusion defects in the rest of the left renal circulation were noted.

Feasibility and efficacy of percutaneous transcatheter intraarterial chemotherapy with paclitaxel in albumin nanoparticles for advanced squamous-cell carcinoma of the oral cavity, oropharynx, and hypopharynx.

PURPOSE: In view of the promising results of a phase I trial, this phase II trial was conducted to study the efficacy and safety of intraarterial induction chemotherapy with a novel nanoparticle albumin-bound paclitaxel formulation in advanced head and neck cancer. MATERIALS AND METHODS: Sixty previously untreated patients with locally advanced squamous-cell carcinoma (SCC) of the oral cavity, oropharynx, or hypopharynx in stage T3/4 and any nodal stage received two to four cycles of nanoparticle albumin-bound paclitaxel by infusion into the external carotid artery or one of its branches, without premedication, at an initial dose of 230 mg/m2 and subsequently a reduced dose of 150 mg/m2. Response was evaluated by physical examination and multidetector computed tomography in all patients, and also by positron emission tomography with [18F]fluorodeoxyglucose in 38 patients. Definitive treatment was surgery, chemotherapy, radiation therapy, or chemoradiation therapy. RESULTS: Intraarterial chemotherapy had a low incidence of complications and produced complete or partial responses in 45 of 60 treated patients (75%). Seven patients (11.67%) had stable disease and eight (13.33%) had disease progression. High-grade bone marrow depression was rare. An unexpected toxicity was reversible facial nerve palsy on the side of infusion, which occurred in six patients at initial dosage. Reduction of the dose eliminated this specific toxicity without any loss of efficacy. CONCLUSION: The promising response rates and tolerability of intraarterial chemotherapy with nanoparticle albumin-bound paclitaxel justify further investigation of this formulation, alone or in combination with other agents, in advanced SCC of the head and neck.

A novel intraarterial chemotherapy using paclitaxel in albumin nanoparticles to treat advanced squamous cell carcinoma of the tongue: preliminary findings.

OBJECTIVE: The purpose of our study was to evaluate the effectiveness of intraarterial infusion of paclitaxel incorporated into human albumin nanoparticles for use as induction chemotherapy before definitive treatment of advanced squamous cell carcinoma of the tongue. SUBJECTS AND METHODS: Twenty-three previously untreated patients (age range, 27-75 years) who had carcinoma of the tongue (stage T3-T4, any N) received intraarterial therapy with paclitaxel incorporated into albumin nanoparticles delivered by transfemoral catheterization into the external carotid artery (10 patients), selectively into the lingual artery (12 patients), or into a faciolingual trunk (1 patient). Each patient received two to four infusions, with a 3-week interval between infusions. The dose administered was 230 mg/m(2) in eight patients, 180 mg/m(2) in six patients, and 150 mg/m(2) in nine patients. Sixteen patients underwent surgery. Of these 16 patients, eight subsequently received radiotherapy, and three received a combination of chemotherapy and radiotherapy. Of the remaining seven patients, one received chemotherapy alone, four received radiotherapy alone, one received chemotherapy plus radiotherapy, and one refused any further treatment. RESULTS: Sixty-seven infusions were performed successfully. Eighteen patients (78%) had a clinical and radiologic objective response (complete, 26%; partial, 52%). Three patients (13%) showed stable disease, and two (9%) showed disease progression. The four patients with complete clinical response who underwent surgery showed microscopic residual carcinoma measuring less than 1 mm in two patients, less than 5 mm in one patient, and less than 1 cm in one patient. The toxicities encountered were hematologic (grade 3) in two patients (8.6%) and neurologic (grade 4) in two patients (reversible paralysis of the facial nerve, 8.6%). Two catheter-related complications occurred: one reversible brachiofacial paralysis and one asymptomatic occlusion of the external carotid artery. CONCLUSION: Intraarterial infusion of paclitaxel in albumin nanoparticles proved reproducible and effective and deserves further investigation as induction chemotherapy before definitive treatment of advanced tumors of the tongue, with a view to organ preservation.