Lorenzo Monfardini

Best choice of central venous insertion site for the prevention of catheter-related complications in adult patients who need cancer therapy: a randomized trial

BACKGROUND Central venous access is extensively used in oncology, though practical information from randomized trials on the most convenient insertion modality and site is unavailable. METHODS Four hundred and three patients eligible for receiving i.v. chemotherapy for solid tumors were randomly assigned to implantation of a single type of port (Bard Port, Bard Inc., Salt Lake City, UT), through a percutaneous landmark access to the internal jugular, a ultrasound (US)-guided access to the subclavian or a surgical cut-down access through the cephalic vein at the deltoid-pectoralis groove. Early and late complications were prospectively recorded until removal of the device, patients death or ending of the study. RESULTS Four hundred and one patients (99.9%) were assessable: 132 with the internal jugular, 136 with the subclavian and 133 with the cephalic vein access. The median follow-up was 356.5 days (range 0-1087). No differences were found for early complication rate in the three groups {internal jugular: 0% [95% confidence interval (CI) 0.0% to 2.7%], subclavian: 0% (95% CI 0.0% to 2.7%), cephalic: 1.5% (95% CI 0.1% to 5.3%)}. US-guided subclavian insertion site had significantly lower failures (e.g. failed attempts to place the catheter in agreement with the original arm of randomization, P = 0.001). Infections occurred in one, three and one patients (internal jugular, subclavian and cephalic access, respectively, P = 0.464), whereas venous thrombosis was observed in 15, 8 and 11 patients (P = 0.272). CONCLUSIONS Central venous insertion modality and sites had no impact on either early or late complication rates, but US-guided subclavian insertion showed the lowest proportion of failures.

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.

Surgical outcomes for colon and rectal cancer over a decade: results from a consecutive monocentric experience in 902 unselected patients

BackgroundThis study evaluates the surgical morbidity and long-term outcome of colorectal cancer surgery in an unselected group of patients treated over the period 1994–2003.MethodsA consecutive series of 902 primary colorectal cancer patients (489 M, 413 F; mean age: 63 years ± 11 years, range: 24–88 years) was evaluated and prospectively followed in a university hospital (mean follow-up 36 ± 24 months; range: 3–108 months). Perioperative mortality, morbidity, overall survival, curative resection rates, recurrence rates were analysed.ResultsOf the total, 476 colorectal cancers were localized to the colon (CC, 53%), 406 to the rectum (RC, 45%), 12 (1%) were multicentric, and 8 were identified as part of HNPCC (1%). Combining all tumours, there were 186 cancers (20.6%) defined as UICC stage I, 235 (26.1%) stage II, 270 (29.9%) stage III and 187 (20.6%) stage IV cases. Twenty-four (2.7%) cases were of undetermined stage. Postoperative complications occurred in 38% of the total group (37.8% of CC cases, 37.2% of the RC group, 66.7% of the synchronous cancer patients and 50% of those with HNPCC, p = 0.19) Mortality rate was 0.8%, (1.3% for colon cancer, 0% for rectal cancer; p = 0.023). Multivisceral resection was performed in 14.3% of cases. Disease-free survival in cases resected for cure was 73% at 5-years and 72% at 8 years. The 5- and 8-year overall survival rates were 71% and 61% respectively (total cases). At 5-year analysis, overall survival rates are 97% for stage I disease, 87% for stage II, 73% for stage III and 22% for stage IV respectively (p < 0.0001). The 5-year overall survival rates showed a marked difference in R0, R1+R2 and non resected patients (82%, 35% and 0% respectively, p < 0.0001). On multivariate analysis, resection for cure and stage at presentation but not tumour site (colon vs. rectum) were independent variables for overall survival (p < 0.0001).ConclusionA prospective, uniform follow-up policy used in a single institution over the last decade provides evidence of quality assurance in colorectal cancer surgery with high rates of resection for cure where only stage at presentation functions as an independent variable for cancer-related outcome.

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.

Risk factors for complications of CT-guided lung biopsies

PurposeThis study assessed the risk factors for pneumothorax and intrapulmonary haemorrhage after computed tomography (CT)-guided lung biopsies.Materials and methodsCT-guided lung biopsies performed between January 2007 and July 2008 were retrospectively evaluated to select the study cohort. Whenever possible, emphysema was quantified by using dedicated software. Features related to the patient, the lesion and the needle and its intrapulmonary path were recorded, along with the pathology findings and operators’ experience. The occurrence of pneumothorax and parenchymal haemorrhage was recorded. Univariate and multivariate statistical analyses were performed to assess the association between risk factors and complications. P values <0.05 were considered significant.ResultsIn 157/222 of the procedures considered, complications were associated with small lesion size and length of the intrapulmonary needle path. Transfissural course and type of needle were associated with pneumothorax using univariate analysis, whereas transfissural course was associated with intrapulmonary haemorrhage using both univariate and multivariate analysis. Emphysema, nodule type, patient position, access site and needle diameter were not significant. Fine-needle aspirates and operator experience were significantly correlated with inadequate biopsy samples.ConclusionsThe size of the lesion and the length of the intrapulmonary trajectory are risk factors for pneumothorax and parenchymal haemorrhage. The transfissural course of the needles is frequently related to pneumothorax and intrapulmonary haemorrhage, and the type of the needle is related to pneumothorax.RiassuntoObiettivoScopo del presente lavoro è stato valutare i fattori di rischio per l’insorgenza di pneumotorace e soffusione polmonare dopo biopsie polmonari guidate tramite tomografia computerizzata (TC).Materiali e metodiSono state valutate retrospettivamente le biopsie polmonari TC-guidate eseguite nel periodo gennaio 2007-luglio 2008. Ove possibile, è stato quantificato l’enfisema mediante software dedicato. Sono state valutate caratteristiche relative al paziente, alla lesione, all’ago e al tragitto intrapolmonare in relazione al risultato patologico e all’esperienza degli operatori, all’eventuale presenza post-bioptica di pneumotorace e di soffusione parenchimale. È stata eseguita un’analisi statistica univariata e multivariata. Valori di p<0,05 sono stati considerati significativi.RisultatiIn 157/222 procedure incluse, le complicanze sono state associate con lesioni piccole e lunghezza del tragitto intrapolmonare dell’ago. Tragitto trans-scissurale e tipo di ago sono associati allo pneumotorace nell’analisi univariata; il tragitto trans-scissurale è correlato alla soffusione polmonare sia nell’analisi univariata che multivariata. Quantificazione dell’enfisema, tipo di nodulo, posizione del paziente, accesso e diametro dell’ago non sono risultati significativi. Gli ago-aspirati e l’esperienza degli operatori sono correlati con l’inadeguatezza del campione bioptico.ConclusioniDimensione della lesione e lunghezza del tragitto intrapolmonare dell’ago sono fattori di rischio sia per pneumotorace che per soffusione parenchimale. Il tragitto trans-scissurale dell’ago è spesso associato con pneumotorace e soffusione, gli aghi citologici con pneumotorace.

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.

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.