Paolo Della Vigna

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.

Discordant hormone receptor and human epidermal growth factor receptor 2 status in bone metastases compared to primary breast cancer

Abstract Background. In patients with metastatic breast cancer, the evaluation of the biological characteristics of metastatic bone deposits may be a valuable adjunct in clinical practice. We assessed the discordance in expression levels for estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) between primary tumor and bone metastases and its clinical impact on patient management. Material and methods. We retrospectively reviewed 363 CT-guided bone biopsies performed from January 1997 to December 2009. The proportions of ER, PgR and HER2 positive tumors at primary diagnosis and bone metastases, determined by IHC and/or FISH, were compared using McNemars test. The impact of the biopsy reassessment on treatment choice was evaluated with Fishers exact test. Results. We selected 109 metastatic breast cancer patients with histologically confirmed bone metastases. Among 107 assessable patients the overall discordance rate was detected in 22 (20.5%) and in 47 (43.9%) patients for ER and PgR, respectively, and in six of 86 assessable patients (6.9%) for HER2 status. The indication to change endocrine therapy occurred in 62% and 30% of patients with ER discordance and ER concordance, respectively (p = 0.01). The indication to change targeted therapy occurred in 67% and 8% of patients with HER2 discordance and HER2 concordance, respectively (p = 0.002). Conclusions. We confirm that biopsy of metastases, including bone metastases, for reassessment of biology should be considered, since it is likely to impact on treatment choice.

Coagulation Disorders in Patients with Cancer: Nontunneled Central Venous Catheter Placement with US Guidance—A Single-Institution Retrospective Analysis

PURPOSE To assess the feasibility and safety of ultrasonographic (US) guidance in the placement of nontunneled central venous catheters (CVCs) in patients with cancer who had altered coagulation profiles. MATERIALS AND METHODS The study was approved by the institutional review board; informed consent was obtained. Medical charts of all patients with cancer who underwent nontunneled CVC placement at the European Institute of Oncology, Milan, from September 2001 to August 2008 were retrospectively reviewed. Patients were considered to have coagulation disorders or risk of bleeding when they had the following: prothrombin time more than 1.2 times normal or activated partial thromboplastin time more than 1.2 times normal and/or platelet count less than 150 x 10(9)/L. Patients with a prothrombin time and partial thromboplastin time more than 2.2 times normal and/or a platelet count less than 50,000/mm(3) were considered to be at high risk for bleeding. Two hundred thirty-nine nontunneled CVCs were placed with US guidance in 157 patients. RESULTS One hundred twenty-two (51%) of 239 nontunneled CVCs were inserted in patients with cancer who had hemostasic disorders. Forty-five (37%) of 122 nontunneled CVCs were implanted in patients considered to be at high risk for bleeding. All catheters were successfully placed at the first needle pass with no major complications such as bleeding or pneumothorax. Two hundred thirty-three (97%) nontunneled CVCs were placed in the subclavian vein, and six (3%) were placed in the internal jugular vein. No patient underwent any correction for an abnormal coagulation profile. CONCLUSION In patients with cancer who had coagulation disorders, nontunneled CVC placement with US guidance was feasible and safe and did not require correction of coagulation parameters.

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.

Percutaneous placement of peritoneal port-catheter in oncologic patients

The aim of this paper is to describe the technique of percutaneous ultrasound (US)-guided placement of a peritoneal port-catheter in an interventional radiological setting. Nineteen patients with peritoneal carcinomatosis were selected for intraperitoneal port-catheter placement in order to perform intracavitary receptor-immuno- or radio-immunotherapy with Ytrium-90. All the procedures were performed percutaneously under US and fluoro guidance; the insertion site for catheters was chosen according to abdominal conditions and US findings: all devices were implanted at the lower abdominal quadrants. All patients were followed up with CT and US according to the therapy protocol. The procedure was successfully completed in 15/19 patients, in 4 being contraindicated by peritoneal adhesions. No procedure-related complications and device occlusions during therapy were observed; one catheter displaced 7 months later the placement. In our experience, this procedure was feasible, reliable and easy to perform, allowing the correct administration of the planned intracavitary therapy. Peritoneal adhesions are the main limitation of peritoneal port placement.

Ultrasound guided high intensity focused ultrasound (USgHIFU) ablation for uterine fibroids: Do we need the microbubbles?

Abstract Purpose: The aim of this study was to assess the safety and effectiveness of contrast-enhanced ultrasound (CEUS) on ultrasound guided high intensity focused ultrasound (USgHIFU) ablation of uterine fibroids. Methods: Thirty-three patients (37 fibroids) were randomly assigned to two groups: group A (17 patients, 20 fibroids) in which CEUS was used before, during and after HIFU treatment, and group B (16 patients, 17 fibroids) in which CEUS was not administered at all. Follow-up including contrast-enhanced magnetic resonance imaging (MRI) and a clinical questionnaire was performed, and technical success, ablation efficacy, volume reduction and complications were assessed. Results: Technical success was 100% in both groups. CEUS revealed residual enhancement in 40% of the patients in group A and the treatment was continued until the completion of ablation. MRI at 1 month after treatment revealed significant difference in the relative fibroid volume reduction rate between the two groups: 16.1% in group A versus 4.8%, in group B (p = 0.01). There was no statistically significant relative volume reduction rate for the results at 3, 6 and 12 months and no significant changes in the quality of life results or the complication rate. Conclusions: CEUS was safe and effective in enhancing US guidance during HIFU ablation of uterine fibroids. Moreover, the use of CEUS during HIFU sonication increased the ablation efficacy, leading to a more relevant fibroid volume reduction at 1 and 3 months. This gap disappeared after 6 months, when there were no differences between the two groups of patients at MRI. However, in our experience, USgHIFU represented a very effective method for the treatment of uterine fibroids, and the use of CEUS during HIFU procedure reduced the treatment time and treatment repetitions for incomplete fibroid ablation.

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

Treatment of Ureterointestinal Anastomotic Strictures by Diathermal or Cryoplastic Dilatation

BackgroundUreterointestinal anastomotic strictures (UAS) complicate 10–15% of surgeries for urinary diversion and are the main cause of deterioration in renal function. Treatments are surgical revision, management with autostatic stent, balloon dilatation, endoscopic incision, and percutaneous transrenal diathermy (Acucise). A new option is cryoplastic dilatation (Polar-Cath).PurposeTo assess the feasibility, complications, and preliminary results of UAS treatment using the Acucise and Polar-Cath systems.MethodsNineteen UAS, diagnosed by ultrasonography or computed tomography and sequential renal scintigraphy, occurred in 15 cancer patients after radical cystectomy and urinary diversion. Fifteen were managed with balloon diathermy and 4 by balloon cryoplasty in a three-stage procedure—percutaneous nephrostomy, diathermal or cryoplastic dilatation, and transnephrostomic control with nephrostomy removal—each separated by 15 days. All patients gave written informed consent.ResultsDilatations were successful in all cases. The procedure is simple and rapid (about 45 min) under fluoroscopic control and sedation. Procedural complications occurred in 1 (5%) patient with UAS after Wallace II uretero-ileocutaneostomy: a common iliac artery lesion was induced by diathermal dilatation, evident subsequently, and required surgical repair. Patency with balloon diathermy was good, with two restenoses developing over 12 months (range 1–22) of follow-up. With balloon cryoplastic dilatation, one restenosis developed in the short term; follow-up is too brief to assess the long-term efficacy.ConclusionOur short-term results with diathermal and cryoplastic dilatation to resolve UAS are good. If supported by longer follow-up, the techniques may be considered as first-choice approaches to UAS. Surgery should be reserved for cases in which this minimally invasive technique fails.

Targeting the microenvironment in solid tumors

Tumorigenesis is a complex and dynamic process involving different cellular and non-cellular elements composed of tumor microenvironment (TME). The interaction of TME with cancer cells is responsible for tumor development, progression and drug resistance. TME consists of non malignant cells of the tumor such as cancer associated fibroblasts (CAFs), endothelial cells and pericytes composing tumor vasculature, immune and inflammatory cells, bone marrow derived cells, and the extracellular matrix (ECM) establishing a complex cross-talk with tumor. These interactions contribute towards proliferation and invasion of the tumor by producing growth factors, chemokines and matrix-degrading enzymes. ECM is a complex system containing macromolecules with distinctive physical, biochemical and biomechanical properties. During tumorigenesis this system is deregulated favoring the generation of tumorigenic microenvironment enhancing tumor-associated angiogenesis and inflammation. An important step of anticancer treatment is the identification of the biological alterations present in TME in order to target these key molecular players. Multitargeted approaches, providing a simultaneous inhibition of TME components, may offer a more efficient way to treat cancer. In this manuscript we overview the function of each components of TME and the treatments targeting the key players.