Paolo Arnone

High intensity focused ultrasound ablation: a new therapeutic option for solid tumors.

Surgery has been the standard of care in selected cases with solid tumors. However, a majority of patients are unable to undergo surgical resection because of the tumor sites, advanced stages, or poor general condition. High intensity focused ultrasound (HIFU) is a novel non-invasive technique that is capable of producing coagulative necrosis at a precise focal point within the body, without harming overlying and adjacent structures even within the path of the beam. Diagnostic ultrasound was the first imaging modality used for guiding HIFU ablation in the 1990 s. Over the last decade, thousands of patients with uterine fibroids, liver cancer, breast cancer, pancreatic cancer, bone tumors, renal cancer have been treated with ultrasound imaging-guided HIFU (USgHIFU) worldwide. This USgHIFU system [Chongqing Haifu (HIFU) Tech Co., Ltd., Chongqing, China] was first equipped in Asia, now in Europe. Several research groups have demonstrated that HIFU is safe and effective in treating human solid tumors. In 2004, the magnetic resonance guided focused ultrasound surgery (MRgFUS) was approved by the United States Food and Drug Administration (FDA) for clinical treatments of uterine fibroids. We conclude that HIFU offers patients another choice when no other treatment available or when patients refused surgical operation. This technique may play a key role in future clinical practice.

Stage migration after biopsy of internal mammary chain lymph nodes in breast cancer patients.

BackgroundInvolvement of the internal mammary chain lymph nodes (IMNs) is associated with worsened prognosis in breast cancer. Use of lymphoscintigraphy to visualize sentinel nodes reveals that IMNs often receive lymph from the area containing the tumor.MethodsWe biopsied IMNs in 182 patients because there was radiouptake to the IMNs or because the tumor was located in the medial portion of the breast. After tumor removal, pectoralis major fibers were divided to expose intercostal muscle. A portion of intercostal muscle adjacent to the sternum was removed. Lymph nodes and surrounding fatty tissue in the intercostal space were freed, removed, and analyzed histologically. The pleural cavity was breached in four cases (2.2%), with spontaneous resolution.ResultsIMNs were found in 160 (88%) of 182 patients; 146 (94.4%) were negative and 14 (8.8%) were positive. The latter received internal mammary chain radiotherapy. The axilla was negative in 4 of 14 cases and positive in 10.ConclusionsIMNs can be quickly and easily removed via the breast incision with insignificant risk and no increase in postoperative hospitalization. The patients with a positive IMN migrated from N0 (4 cases) or N1 (10 cases) to N3, prompting modification of both local (radiotherapy to internal mammary chain) and systemic treatment; without IMN sampling, they would have been understaged.

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.

Sentinel Lymph Node Metastasis in Microinvasive Breast Cancer

AbstractBackground:Ductal carcinoma in situ with microinvasion (DCISM) is a separate pathological entity, distinct from pure ductal carcinoma in situ (DCIS). DCISM is a true invasive breast carcinoma with a well-known metastatic potential. Currently, there is controversy regarding the indication for complete axillary dissection (CAD) to stage the axilla in patients with DCISM. The role of CAD is questioned given its morbidity and reported low incidence of axillary involvement. Sentinel lymph node biopsy (SLNB) may obviate the need for CAD in these patients without compromising the staging of the axilla and the important prognostic information. Methods:From March 1996 to December 2002, 4602 consecutive patients with invasive breast carcinoma underwent SLN biopsy. Of these, 41 patients with DCISM were selected. Results:Metastasis in the SLN were detected in 4 of 41 (9.7%) patients. Two of the 4 patients had only micrometastasis in the SLN. In three patients, the SLN was the only positive node after CAD. Conclusions:SLN biopsy should be considered as a standard procedure in DCISM patients. SLNB can detect nodal micrometastasis and accurately stage the axilla avoiding the morbidity of a CAD. Complete AD may not be mandatory if only the SLN contains micrometastatic disease. Informed consent is very important in the decision not to undergo CAD.

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.

Rethinking TNM: A Breast Cancer Classification to Guide to Treatment and Facilitate Research

Abstract:  The TNMUICC classification of breast cancer categorizes tumor size, regional lymph node involvement, and distant metastases. Treatment is influenced by these characteristics, but requires knowledge of several other factors. In fact, effective treatment is dependent on disease extent, hormone receptor status, and other biologic characteristics of the cancer. We propose a new classification [tumor node metastasis (TNM)] that not only includes relevant biologic characteristics and can expand to include others as they are validated but also specifies tumor size exactly (T2.3 indicates a cancer of maximum diameter 2.3 cm), provides more information on regional lymph node involvement, and specifies the site(s) of distant metastases. We also propose abolishing the term “carcinoma” for non‐invasive neoplastic conditions and the term “infiltrating” for carcinomas. The new classification is sufficiently similar to the TNMUICC classification to permit valid comparison of patients classified by both systems, but is more logical, provides information useful for guiding therapy, and is flexible enough to satisfy present and future clinical and research needs.

Sentinel node biopsy interpretation: The Milan experience

Abstract: From March 1996 to December 1999 we performed 1,266 sentinel node biopsies (SNBs) in patients with small breast cancers. The technique is to inject technetium 99m‐labeled albumin particles close to the tumor, locate the sentinel node (SN) scintigraphically, and use a handheld gamma‐detecting probe to guide its removal via a small incision during breast surgery. Our experience was divided into three phases. In the first phase, complete axillary dissection was performed to assess the accuracy of SNB in predicting axillary status. We also assessed safety, perfected tracer injection technique, determined optimal particle size and radioactivity levels, optimized lymphoscintigraphic scanning, and perfected the surgical technique. The SN was identified and removed in 98.7% of cases. Comparison with complete axillary dissection showed that the SN predicted axillary status in 96.8% of cases. However, use of an intraoperative frozen section method predicted axillary status in only 86.5% of cases. In the second phase we developed a new method for intraoperative histologic analysis. Extensive sampling (up to 60 sections/SN) and an experienced pathologist proved more important than use of antikeratin immunostaining in identifying tumor cells, and the new method has the accuracy of a definitive histologic examination. The third phase, a randomized trial, closed at the end of 1999. Trial objectives were to confirm that the SN predicts axillary status, to determine the number of axillary relapses, and to assess overall and disease‐free survival. Patients were randomized in the operating room to complete axillary dissection or SNB. If the SN was positive, complete axillary dissection was performed; if the SN was negative, no further axillary treatment was given. We expect the trial to confirm our clinical experience that SNB is a safe and accurate procedure for staging patients with early breast cancer and a clinically negative axilla.

The Changing Face of Mastectomy (from Mutilation to Aid to BreastReconstruction)

Breast cancer is the most common cancer in women. Primary treatment is surgery, with mastectomy as the main treatment for most of the twentieth century. However, over that time, the extent of the procedure varied, and less extensive mastectomies are employed today compared to those used in the past, as excessively mutilating procedures did not improve survival. Today, many women receive breast-conserving surgery, usually with radiotherapy to the residual breast, instead of mastectomy, as it has been shown to be as effective as mastectomy in early disease. The relatively new skin-sparing mastectomy, often with immediate breast reconstruction, improves aesthetic outcomes and is oncologically safe. Nipple-sparing mastectomy is newer and used increasingly, with better acceptance by patients, and again appears to be oncologically safe. Breast reconstruction is an important adjunct to mastectomy, as it has a positive psychological impact on the patient, contributing to improved quality of life.

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.

The TNM classification of breast cancer: need for change

The need for a unified and internationally accepted cancer staging system was recognized in the first half of the twentieth century and led to the publication of the first International Union Against Cancer (UICC) [1] staging system in the 1950s. This was followed by the International Federation of Gynecology and Obstetrics (FIGO) classification of women’s cancers [2] and the American Joint Committee for Cancer (AJCC) classification, the first edition of which was published in 1977 [3]. These manuals are based on clinical and pathological data and make it possible to assign a stage to a malignancy that indicates the extent of the disease, and also provides indications for treatment and prognosis. The UICC TNM classification (TNMUICC) considers the size of the primary (T), regional lymph node status (N), and presence of distant metastases (M) as the fundamental disease characteristics. Although the TNM classification has been regularly updated since its first edition in 1977 (new 7th edition published in December 2009), the TNMUICC classification of breast cancer is, in our opinion, obsolete and requires radical overhaul, with the introduction of new information to produce a more modern and useful characterization of breast tumours. Based on the experience of an interdisciplinary work group, which over the last 10 years examined over 30,000 breast cancer patients, the European Institute of Oncology has produced proposals for a revision of the TNM classification of breast cancers. One of motives that inspired the new classification was the language of the existing TNMUICC which often has a negative psychological impact on the patient receiving the diagnosis. Words like ‘‘malignancy’’, ‘‘carcinoma’’, and ‘‘infiltrating’’ are particularly at fault here. Psychological problems are present in around 20–40% of persons diagnosed with cancer [4] and the emotive terminology used by the physician or in the diagnostic report—which conjures up images of pain, suffering, and death—are likely to exacerbate these problems. The fear and uncertainty that a cancer diagnosis generates may motivate the person to put her faith in the treating physician, ask questions about the illness, and find out more on the Internet. But the opposite reaction of This article is an extended and modified version of the one published previously in J Clin Oncol 2009; 27(15):2427–2428. Permission has been granted by Prof. Umberto Veronesi, Scientific Director of European Institute of Oncology to reuse the information again for this article.