Gianluigi Orgera

High-Intensity Focused Ultrasound Ablation: Effective and Safe Therapy for Solid Tumors in Difficult Locations

OBJECTIVE The aim of this study was to evaluate the safety and efficacy of ultrasound-guided high-intensity focused ultrasound therapeutic ablation of solid tumors in difficult locations. SUBJECTS AND METHODS A procedure was performed with a focused ultrasound tumor therapeutic system which provides real-time ultrasound guidance. All patients underwent MDCT or MRI, and some patients underwent PET/CT. From November 2007 through April 2009, 31 patients with 38 lesions of the liver and pancreas in difficult locations were treated. Six patients had hepatocellular carcinoma, 13 patients had hepatic metastasis from colorectal cancer, two had hepatic metastases of breast cancer, two had hepatic metastasis of neuroendocrine tumors, one patient had lymph node metastasis of breast cancer at the hepatic hilum, six patients had pancreatic cancer, and one patient had a neuroendocrine tumor. Difficult location was defined as tumor adjacent to a main blood vessel, the heart, the gallbladder and bile ducts, the bowel, or the stomach. RESULTS The mean diameter of tumors was 2.7 +/- 1.4 cm. PET/CT, MDCT, or both on the day after one session of high-intensity focused ultrasound treatment showed complete response in all six patients with hepatocellular carcinoma, the patient with lymph node metastasis, and 22 of 24 patients with hepatic metastasis. The symptoms of all seven patients with pancreatic caner or neuroendocrine tumors were palliated, and PET/CT or MRI showed complete response of six of seven lesions. Portal vein thrombosis occurred after high-intensity focused ultrasound ablation in one patient with pancreatic cancer. No other side effects were detected in a median follow-up period of 12 months. CONCLUSION According to our short- and long-term follow-up results, ultrasound-guided high-intensity focused ultrasound ablation can be considered a safe and feasible approach to the management of solid tumors in difficult locations.

High-intensity focused ultrasound (HIFU) in patients with solid malignancies: evaluation of feasibility, local tumour response and clinical results.

PurposeThe purpose of this study was to evaluate the safety and efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for ablation of solid tumours without damaging the surrounding structures.Materials and methodsA specific written informed consent was obtained from every patient before treatment. From September 2008 to April 2009, 22 patients with 29 lesions were treated: nine patients with liver and/or soft-tissue metastases from colorectal carcinoma (CRC), six with pancreatic solid lesions, three with liver and/or bone metastases from breast cancer, one with osteosarcoma, one with muscle metastasis from lung cancer, one with iliac metastasis from multiple myeloma and one with abdominal liposarcoma. The mean diameter of tumours was 4.2 cm. All patients were evaluated 1 day, 1 month and 3 months after HIFU treatment by multidetector computed tomography (MDCT), positron-emission tomography (PET)-CT and clinical evaluation. The treatment time and adverse events were recorded.ResultsAll patients had one treatment. Average treatment and sonication times were, respectively, 162.7 and 37.4 min. PET-CT or/and MDCT showed complete response in 11/13 liver metastases; all bone, soft-tissue and pancreatic lesions were palliated in symptoms, with complete response to PET-CT, MDCT or magnetic resonance imaging (MRI); the liposarcoma was almost completely ablated at MRI. Local oedema was observed in three patients. No other side effects were observed. All patients were discharged 1–3 days after treatment.ConclusionsAccording to our preliminary experience in a small number of patients, we conclude that HIFU ablation is a safe and feasible technique for locoregional treatment and is effective in pain control.RiassuntoObiettivoL’obiettivo di questo studio è stato quello di valutare la sicurezza e l’efficacia dell’applicazione degli ultrasuoni focalizzati ad elevata intensità (USgHIFU) nell’ablazione terapeutica di tumori solidi senza danneggiare le strutture circostanti.Materiali e metodiUno specifico consenso informato scritto è stato ottenuto da tutti i pazienti prima del trattamento. Da settembre 2008 ad aprile 2009 sono stati trattati 22 pazienti con 29 lesioni: 9 pazienti con metastasi epatiche e/o dei tessuti molli da carcinoma del colon retto (CRC), sei pazienti con lesioni solide del pancreas, tre con metastasi epatiche e/o ossee da tumore mammario, uno con osteosarcoma, uno con metastasi muscolare da tumore del polmone, uno con lesione iliaca da mieloma multiplo ed uno con liposarcoma addominale. Il diametro medio era di 4,2 cm. Tutti i pazienti sono stati valutati ad 1 giorno, 1 mese e a 3 mesi di distanza dal trattamento HIFU con tomografia computerizzata multidetettore (MDCT), tomografia computerizzata con tomografia ad emissione di positroni (PET-CT) e valutazione clinica. La durata del trattamento e gli eventi avversi sono stati registrati.RisultatiTutti i pazienti sono stati trattati in una unica sessione. Il tempo medio di trattamento e di sonazione sono stati di 162,7 e 37,4 minuti, rispettivamente. PET-CT e/o MDCT hanno mostrato risposta completa in 11/13 metastasi epatiche; tutte le lesioni ossee, dei tessuti molli e le lesioni pancreatiche sono state palliate nei sintomi, con risposta completa all’esame PET-CT, MDCT o risonanza magnetica (RM); il liposarcoma ha mostrato una ablazione quasi completa all’esame RM. Edema locale è stato osservato in tre pazienti senza ulteriori eventi avversi. Tutti i pazienti sono stati dimessi da 1 a 3 giorni dopo il trattamento.ConclusioniSecondo la nostra esperienza preliminare da un limitato numero di pazienti, l’ablazione USgHIFU può essere considerata una metodica sicura e fattibile in assenza di alternative terapeutiche locoregionali e valida per il controllo del dolore.

High Intensity Focused Ultrasound Ablation of Pancreatic Neuroendocrine Tumours: Report of Two Cases

We describe the use of ultrasound-guided high-intensity focused ultrasound (HIFU) for ablation of two pancreatic neuroendocrine tumours (NETs; insulinomas) in two inoperable young female patients. Both suffered from episodes of severe nightly hypoglycemia that was not efficiently controlled by medical treatment. After HIFU ablation, local disease control and symptom relief were achieved without postinterventional complications. The patients remained free of symptoms during 9-month follow-up. The lesions appeared to be decreased in volume, and there was decreased enhancing pattern in the multidetector computed tomography control (MDCT). HIFU is likely to be a valid alternative for symptoms control in patients with pancreatic NETs. However, currently the procedure should be reserved for inoperable patients for whom symptoms cannot be controlled by medical therapy.

Ultrasound-Guided High-Intensity Focused Ultrasound (USgHIFU) Ablation in Pancreatic Metastasis from Renal Cell Carcinoma

Dear Editor, We would like to share our experience of the treatment of an inoperable renal cell carcinoma (RCC) pancreatic metastasis with high-intensity focused ultrasound (USgHIFU) in a 55-year-old patient. The lesion was unresponsive to chemotherapy. After HIFU ablation, tumor necrosis and reduction in size was achieved without any procedure related complications and there was no evidence of recurrence in the 9-month follow-up. This is a promising result of USgHIFU, which seems to be safe and effective for the midterm control of the nonresponsive to chemotherapy renal cell carcinoma metastatic disease. The pancreas is an uncommon location for metastasis from other primary cancers and pancreatic metastases account for less than 5% of all pancreatic malignancies [1, 2]. Indeed renal cell carcinoma usually metastasizes to lymph nodes, lung, liver, and bones, and very rarely to the pancreas [3, 4]. High-intensity focused ultrasound (HIFU) is a novel minimally invasive ablative method that is capable of producing coagulation necrosis at a precise focal point within the body, without the necessity of a needle insertion [5–7]. In our case, a 55-year-old woman underwent left nephrectomy and adrenalectomy in 2008 for a RCC incidentally discovered in a routine ultrasound (US) examination. The CT characteristics were suggesting a malignant lesion that was confirmed with histology (RCC—clear cell variant, middle grade). There was no evidence of other sites of metastatic disease, and the patient stage was T3bN0M0. The patient did not receive any postoperative chemotherapy. In the 3-month follow-up CT scan, a 9-mm solitary nodule was detected in the pancreatic head. The lesion was enhancing in arterial phase (Fig. 1) and was considered highly suspicious for metastatic disease.

High-Intensity Focused Ultrasound Effect in Breast Cancer Nodal Metastasis

To the Editor, The aim of this letter is to describe our experience with the treatment of a nonresectable retroperitoneal lymph node with high-intensity focused ultrasound (HIFU). A 69-year-old woman developed a malignant tumor in the left breast in February 2006 and underwent quadrantectomy and sentinel lymph node excision at our institution. Pathological examination showed invasive mixed ductal and lobular carcinoma, and no invasion was seen in the adjacent blood vessels, lymphatics, or lymph nodes. The patient also has a past positive oncologic history for squamous cell carcinoma of the anal canal, which was treated with radical surgery and radiochemotherapy 2 years earlier, with no evidence of recurrence at the time of the quadrantectomy. After breast tumor excision, the patient received radiotherapy (21 Gy) and adjuvant hormonal therapy from May 2006 to February 2008. She remained free of disease until March 2008, when in a follow-up ultrasound (US) scan a single 30-mm hypoechoic solid mass was detected close to the hepatic hilum and was considered likely to be a metastatic lymph node. Multidetector computed tomography (MDCT) showed the presence of a large hilar hepatic node with inhomogeneous enhancement after contrast injection. It also excluded any other apparent site of disease. To characterize the finding, percutaneous US-guided core biopsy of the mass was performed using an 18 G needle. Pathology and immunohistochemistry confirmed the presence of metastatic cells from breast cancer. The surgical team did not consider the patient a suitable candidate for resection due to her history of cardiac failure and existing comorbidities. The lesion was also not considered suitable for percutaneous ablation due to the potential risk of thermal injury of the adjacent structures; therefore, observation of the lesion and continuation of chemotherapy with nonsteroid aromatase inhibitors was decided. Two months later (May 2009), the lesion showed growth of 1 cm on MDCT. The patient was re-evaluated in a multidisciplinary meeting comprising surgeons, oncologists, radiotherapists, and interventional radiologists. A consensus regarding the patient’s disease state was reached, thus leading to a new treatment plan. The patient was enrolled in a phase I study for HIFU treatment of solid tumors associated with chemotherapy using aromatase inhibitors. The patient had a Karnofsky performance scale score of 80%, with no contraindication to general anesthesia. The lesion was visualized before the procedure using US, and no gas interfered in the acoustic pathway. Informed consent was obtained. She was status NPO for 6 h before the procedure. The skin overlying the lesion was carefully shaved to avoid also any possible interference of hair in the acoustic pathway of HIFU, and a urinary catheter was inserted before treatment. General anesthesia was administered by the anesthetics team to achieve the patient’s complete immobilization and to prevent any pain. A purified-water balloon was used to push and compress bowel loops to avoid the presence of air G. Orgera (&) G. Bonomo L. Monfardini P. Della Vigna F. Orsi Unit of Interventional Radiology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy e-mail: gianluigi.orgera@ieo.it

Current Status of Interventional Radiology in the Management of Gastro-Entero-Pancreatic Neuroendocrine Tumours (GEP-NETs)

Within the group of Gastro-Entero-Pancreatic Neuroendocrine tumours (GEP-NETs), several heterogeneous malignancies are included with a variety of clinical manifestations and imaging characteristics. Often these cases are inoperable and minimal invasive treatment offered by image-guided procedures appears to be the only option. Interventional radiology offers a valid solution in the management of primary and metastatic GEP-NETs. The purpose of this review article is to describe the current status of the role of Interventional Radiology in the management of GEP-NETs.

Management of renal arteriovenous malformations: A pictorial review.

BackgroundArteriovenous malformations (AVMs) are communications between an artery and a vein outside the capillary level. This pathologic communication may be either a fistula, a simple communication between a single artery and a dilated vein, or a more complex communication, a nidus of tortuous channels between one or more arteries/arterioles and one or more draining veins. The latter type of lesion is most frequently seen in the extremities; in the kidney they tend to appear more rarely. The most common clinical presentation of renal arteriovenous malformations (RAVMs) is haematuria. Percutaneous treatment with selective endovascular techniques offers a minimally invasive, nephron-sparing option in comparison to the more invasive surgical approaches. The purpose of this pictorial review is to highlight the general lines of management and to show the range of imaging findings of the percutaneous treatment of RAVMs.MethodsThe imaging characteristics of a selection of cases of percutaneously managed congenital RAVMs are presented and the most common lines of approach are discussed.ConclusionThe imaging spectrum of diagnosis and percutaneous treatment of RAVMs is presented in order to aid interpretation and endovascular management.Teaching points• Renal arteriovenous malformations are very rare lesions.• Clinical expression is usually haematuria.• Diagnosis is made with CT or MRI but the gold standard is digital subtraction angiography.• Catheter-directed treatment with the use of coils or liquid embolics is minimally invasive, safe and effective.

Giant Hepatic Artery Aneurysm Associated with Immunoglobulin G4-Related Disease Successfully Treated Using a Liquid Embolic Agent

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Regulatory T CD4 + CD25+ lymphocytes increase in symptomatic carotid artery stenosis

Abstract Background: Atherosclerosis is a multifactorial disease characterized by an immune-inflammatory remodeling of the arterial wall. Treg and Th17 subpopulations are detectable inside atherosclerotic plaque; however, their behavior in symptomatic carotid artery stenosis (CAS) is not fully elucidated. The aim of this study was to evaluate Th17 and Treg subsets and their ratio in patients affected by symptomatic and asymptomatic CAS. Methods: 14 patients with symptomatic CAS (CAS-S group), 41 patients with asymptomatic CAS (CAS-A group), 32 subjects with traditional cardiovascular risk factors (RF group), and 10 healthy subjects (HS group) were enrolled. Th17 and Treg frequency was determined by flow cytometry and by histology and immunohistochemistry. Interleukin (IL)-10, IL-17, and metalloproteinase (MMP)-12 levels were measured by ELISA. Results: Th17 were significantly increased in CAS-A versus RF and versus HS. Tregs were significantly increased in CAS-S versus CAS-A. Tregs/Th17 ratio was significantly reduced in CAS-A versus RF and versus HS, whereas it was significantly increased in CAS-S versus CAS-A. Conclusions: The results of this study suggest that Th17 are related to the late stages of CAS but not to plaque instability. Moreover, Treg expansion seems to represent a specific cellular pattern displayed by patients with symptomatic CAS and associated with brain injury. KEY MESSAGES Tregs expansion seems to represent a specific cellular pattern displayed by patients with symptomatic CAS and associated with CD4+ effector depletion and brain ischemic injury. Th17 lymphocytes are related to the late stages of CAS but not to plaque instability.

Tratamiento endovascular de aneurismas y pseudoaneurismas de arterias viscerales mediante stenstents recubiertos: : análisis de resultados inmediatos y a largo plazo

INTRODUCTION The aim of this study is to analyze the safety and efficacy of stent-graft endovascular treatment for visceral artery aneurysms and pseudoaneurysms. METHODS Multicentric retrospective series of patients with visceral aneurysms and pseudoaneurysms treated by means of stent graft. The following variables were analyzed: Age, sex, type of lesion (aneurysms/pseudoaneurysms), localization, rate of success, intraprocedural and long term complication rate (SIR classification). Follow-up was performed under clinical and radiological assessment. RESULTS Twenty-five patients (16 men), with a mean age of 59 (range 27-79), were treated. The indication was aneurysm in 19 patients and pseudoaneurysms in 6. The localizations were: splenic artery (12), hepatic artery (5), renal artery (4), celiac trunk (3) and gastroduodenal artery (1). Successful treatment rate was 96% (24/25 patients). Intraprocedural complication rate was 12% (4% major; 8% minor). Complete occlusion was demonstrated during follow up (mean 33 months, range 6-72) in the 24 patients with technical success. Two stent migrations (2/24; 8%) and 4stent thrombosis (4/24; 16%) were detected. Mortality rate was 0%. CONCLUSION In our study, stent-graft endovascular treatment of visceral aneurysmns and pseudoaneurysms has demonstrated to be safe and is effective in the long-term in both elective and emergent cases, with a high rate of successful treatment and a low complication rate.