Enrico Martone

Safety and Feasibility of Irreversible Electroporation (IRE) in Patients with Locally Advanced Pancreatic Cancer: Results of a Prospective Study

Purpose: To evaluate the safety of the NanoKnife Low Energy Direct Current (LEDC) System (Irreversible Electroporation, IRE) in order to treat patients with unresectable pancreatic adenocarcinoma. Methods: Prospective, nonrandomized, single-center clinical evaluation of ten patients with a cytohystological diagnosis of unresectable locally advanced pancreatic cancer (LAPC) that was no further responsive to standard treatments. The primary outcome was the rate of procedure-related abdominal complications. The secondary endpoints included the evaluation of the short-term efficacy of IRE through the evaluation of tumor reduction at imaging and biological tumor response as shown by CA 19-9, clinical assessments and patient quality of life. Results: Ten patients (5 males, 5 females) were enrolled, with a median age of 66 and median tumor size of 30 mm. All patients were treated successfully with a median procedure time of 79.5 min. Two procedure-related complications were described in one patient (10%): a pancreatic abscess with a pancreoduodenal fistula. Three patients had early progression of disease: one patient developed pulmonary metastases 30 days post-IRE and two patients had liver metastases 60 days after the procedure. We registered an overall survival of 7.5 months (range: 2.9-15.9). Conclusions: IRE is a safe procedure in patients with LAPC and may represent a new technological option in the treatment and multimodality management of this disease.

Focal liver lesions: sinusoidal phase of CEUS

Ultrasound examination is the first imaging modality for hepatic study in neoplastic and chronic liver diseases. Focal liver lesions frequently cause diagnostic problems in terms of characterization, especially when small and hypoechoic to the rest of the parenchyma. Contrast- enhanced ultrasonography (CEUS) has shown its value in the characterization of focal liver lesions. This study assessed the value of the sinusoidal phase of CEUS with a second-generation contrast agent in the characterization of focal liver lesions to distinguish benign from malignant. Two hundred hepatic lesions with suspicious features at baseline ultrasound were prospectively studied with CEUS. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of the sinusoidal phase in the characterization of benign versus malignant liver lesions were evaluated. Hypoechogenicity of the focal liver lesion, during the sinusoidal phase of CEUS, allowed the diagnosis of malignancy with a sensitivity of 85%, specificity of 88%, positive predictive value of 92%, negative predictive value of 77%, and diagnostic accuracy of 86%. The diagnostic confidence in the diagnosis of malignancy significantly increased, with receiver operating characteristic curve areas from 0.536 for baseline ultrasound to 0.902 for the sinusoidal phase of CEUS.

Ultrasonography of the pancreas. 3. Doppler imaging

Ultrasonography is probably the most widely used medical imaging technique. In fact, its non-invasivity, portability, widespread distribution and good clinical results have made it the preferred method for a first imaging approach to patients in a large variety of clinical settings. Ultrasound technology is advancing rapidly, aimed to increase image quality. In particular, increased color-Doppler sensitivity is contributing to the diagnosis and staging of pancreatic disease. Doppler studies are in fact integral part of ultrasound examination of the pancreas evaluating the peripancreatic vascular structures enclose portal vein, splenic artery and vein, superior mesenteric artery and vein, aorta, and inferior vena cava. While flows in all peri-pancreatic vessels are well recognized, only few parenchymal vessels are usually appreciable in normal conditions. Anyway the increased Doppler sensitivity allows the visualization of smaller peri-pancreatic and intra-pancreatic vessels. This article will review the technical background underlying the clinical application of Doppler ultrasonography in pancreatic imaging, with particular emphasis to normal vascular anatomy of the pancreas, and to the main applications of Doppler techniques in the different pancreatic pathologies.

Contrast-enhanced ultrasonography (CEUS) immediately after percutaneous ablation of hepatocellular carcinoma.

PurposeThis study evaluated the effectiveness of contrast-enhanced ultrasound (CEUS), performed immediately after percutaneous ethanol injection (PEI) or radiofrequency thermal ablation (RFTA), by comparing results with the computed tomography (CT) follow-up.Materials and methodsSixty-nine consecutive patients with a diagnosis of hepatocellular carcinoma (HCC) were included in this prospective study. All patients underwent PEI or RFTA. After treatment, three CEUS enhancement patterns were observed: isovascular, hypovascular and avascular, which were compared with the CT findings. Sensitivity of the avascular pattern at CEUS and effectiveness of the ablative procedures were evaluated and compared with the chi-square test.ResultsNinety hypervascular HCCs, with a mean diameter of 2.6 cm (0.5–4.9 cm), underwent PEI (n=54) and RFTA (n=36). In the first group, CT identified complete necrosis in 28/54 (52%) lesions, 21 (75%) of which had avascular, one (4%) isovascular and six (21%) hypovascular patterns at CEUS. In the second group, CT showed complete necrosis in 31/36 (86%) lesions, all (100%) of which had a corresponding avascular pattern at CEUS. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the avascular pattern at CEUS compared with CT findings were 75%, 69%, 72%, 72% and 72% for PEI and 100%, 20%, 89%, 100% and 89%, for RFTA, respectively. A statistically significant difference (p<0.05) between the sensitivity of CEUS after PEI and after RFTA and between the necrosis obtained by RFTA and PEI were observed.ConclusionsCEUS performed immediately after percutaneous ablation of hepatocellular carcinoma to evaluate treatment efficacy is compulsory in the case of RFTA but not for PEI.RiassuntoObiettiviStimare l’efficacia dell’ecografia con mezzo di contrasto (CEUS) eseguita immediatamente dopo iniezione percutanea di etanolo (PEI) o termoablazione con radiofrequenza (RFTA), confrontando i risultati con la tomografia computerizzata (TC) di follow-up.Materiali e metodiSessantanove pazienti consecutivi con diagnosi di epatocarcinoma (HCC) sono stati studiati prospetticamente. Le lesioni sono state trattate con PEI o RFTA. Sono stati descritti tre pattern di enhancement alla CEUS (1, isovascolare; 2, ipovascolare; 3, avascolare) e quindi confrontati con la TC di follow-up. La sensibilitá nel riconoscimento del pattern CEUS avascolare dopo PEI e RFTA e l’efficacia delle procedure ablative sono state valutate e confrontate tra loro con il test del gC2.RisultatiNovanta HCC ipervascolari, con diametro medio di 2,6 cm (0,5–4,9 cm), sono stati sottoposti a PEI (54) e RFTA (36). Nel primo gruppo, la TC ha evidenziato necrosi completa in 28/54 (52%) lesioni, di cui 21 (75%) con pattern CEUS avascolare, 1 (4%) isovascolare e 6 (21%) ipovascolare. Nel secondo gruppo, la TC ha mostrato necrosi completa in 31/36 (86%) lesioni, tutte (100%) con pattern CEUS avascolare. Sensibilità, specificità, valore predittivo positivo e negativo ed accuratezza diagnostica per necrosi completa alla TC del pattern CEUS avascolare sono 75%, 69%, 72%, 72% e 72% dopo PEI, 100%, 20%, 89%, 100% e 89% dopo RFTA. La differenza tra la sensibilita della CEUS dopo PEI o RFTA e la differenza tra l’efficacia dei trattamenti è risultata statisticamente significativa (p<0,05).ConclusioniLa CEUS al termine della procedura ablativa dell’epatocarcinoma ai fini della valutazione del successo terapeutico è mandatoria dopo RFTA, ma non dopo PEI.

Palliative therapy in pancreatic cancer—interventional treatment with radiofrequency ablation/irreversible electroporation

Pancreatic cancer (PC) is a solid tumor with still a dismal prognosis. Diagnosis is usually late, when the disease is metastatic or locally advanced (LAPC). Only 20% of PC are amenable to surgery at the time of diagnosis and the vast majority of them, despite radically resected will unavoidably recur. The treatment of LAPC is a challenge. Current guidelines suggest to adopt systemic therapies upfront, based on multi-drugs chemotherapy regimens. However, the vast majority of patients will never experience conversion to surgical exploration and radical resection. Thus, there a large subgroup of LAPC patients where the only therapeutic chance is to offer palliative treatments, such as interventional ablative treatments, in order to obtain a cytoreduction of the tumor, trying to delay its growth and spread. Radiofrequency ablation (RFA) and irreversible electroporation (IRE) demonstrated to be safe and effective in obtaining a local control of the disease with some promising oncological results in terms of overall survival (OS). However, they should be adopted as a treatment strategy to adopt in parallel with other systemic therapies, within multidisciplinary choices. They are not free from complications, even serious, thus they should applied only in specialized centers of pancreatology. This review depicts the state of the art of the two techniques.

Intraoperative ultrasonography of the pancreas

Intraoperative ultrasonography (IOUS) still remains a useful and occasionally a problem-solving technique in pancreatic diseases, even though its role has recently been downsized owing to preoperative imaging advances [1]. Since its introduction in the 1980s, progressive technical developments have led to an increase in the diagnostic accuracy of IOUS. The availability of scanners that provide the depiction of fine anatomic details and the detection of small lesions in real-time with excellent spatial and contrast resolution allow the widespread application of this imaging method [1, 2]. Moreover, IOUS is able to clearly show lesions not detectable with other preoperative imaging modalities, and to accurately define the extension of the tumor and its relationship with vessels, sometimes determining significant changes in the therapeutic management of patients [3]–[5]. In addition, its ability in guiding interventional procedures (i.e. biopsy, duct cannulation and drainage of abscesses or cysts) has been widely reported [2, 6]. Lastly, its impact has significantly increased since both the development of mini-invasive laparoscopic approaches, due to the impossibility for the surgeon to visually and manually inspect the affected organ and the retroperitoneum, and the recent introduction of alternative palliative treatments under IOUS-guidance [7, 8].

Detection of focal liver lesions: from the subjectivity of conventional ultrasound to the objectivity of volume ultrasound

PurposeThis study was undertaken to establish the reliability of automated volumetric liver scans in detecting focal liver lesions by evaluating the degree of agreement between conventional and volume ultrasound (US) examinations.Materials and methodsOver a period of 3 months, we prospectively studied 100 consecutive patients (36 men and 64 women; age range 15–87 years; mean age 63 years) referred to our institute for US imaging of the liver. Volumetric acquisition of the liver was achieved with a 3D transducer (2.0–5.0 MHz) and a Logiq 9 US scanner. All patients underwent both 2- and 3D US studies performed by two expert radiologists. Volumetric acquisitions were subsequently reviewed by the second radiologist, who was blinded to the first radiologist’s report. Three categories were established: 1=presence of focal liver lesions; 2=doubtful finding; 3=absence of focal liver lesions. Concordance between volume US and conventional US was calculated by using the k statistic.ResultsOut of 100 patients examined, 39 were found to be affected by focal liver lesions. All volume US examinations were technically adequate, allowing exploration of all hepatic sectors, except for five cases that were marred by major respiratory motion artefacts. Conventional and volume US identified the same number of focal liver lesions, with the exception of four cases of doubtful findings at volume US. Concordance between automated volume US and conventional US of the liver was high (k=0.92).ConclusionsThe identification of focal liver lesions on automated volume US is possible, and the examination shows a high level of concordance with conventional US.RiassuntoObiettivoStabilire l’affidabilità dell’acquisizione volumetrica automatica del fegato nell’identificazione delle lesioni focali epatiche, valutando la concordanza tra gli esami ecografici volumetrico e convenzionale.Materiali e metodiIn un periodo di tre mesi, sono stati studiati consecutivamente, in modo prospettico, 100 pazienti (36 uomini e 64 donne; range di età: 15–87 anni; media: 63 anni) giunti alla sezione di ecografia del nostro Istituto in regime di ricovero per eseguire un esame ecografico del fegato. L’acquisizione volumetrica del fegato è stata effettuata mediante sonda volumetrica (2,0–5,0 MHz) su ecografo Logiq 9. Gli esami ecografici, sia 2D che volumetrici, sono stati effettuati su tutti i pazienti da due radiologi esperti. È stata quindi successivamente effettuata una rilettura del volume dal secondo radiologo, all’oscuro del referto del primo. Sono state poi stabilite tre categorie: 1, presenza di lesioni focali; 2, dubbio di lesioni focali; 3, assenza di lesioni focali. La concordanza dell’acquisizione volumetrica con l’esame ecografico convenzionale è stata calcolata con il k test.RisultatiSu 100 pazienti studiati, in 39 sono state identificate lesioni focali epatiche. Tutti gli esami volumetrici sono risultati tecnicamente adeguati, in relazione alla esplorabilità ecografica di tutti i settori epatici, tranne 5 gravati da importanti artefatti da movimento respiratorio. Gli esami ecografici convenzionale e volumetrico hanno identificato lo stesso numero di lesioni focali epatiche, ad eccezione di 4 casi risultati dubbi per la presenza di lesione focale epatica all’esame ecografico volumetrico. La concordanza tra acquisizione volumetrica automatica del fegato ed esame ecografico convenzionale è risultata elevata (k=0,92).ConclusioniL’identificazione delle lesioni focali epatiche su acquisizioni volumetriche automatiche del fegato è possibile, risultando elevata la concordanza a tal fine dell’esame volumetrico ecografico rispetto all’esame ecografico convenzionale.

Identificazione delle lesioni focali epatiche: Dalla soggettività dell'esame ecografico convenzionale all'oggettività dell'esame ecografico volumetrico

PurposeThis study was undertaken to establish the reliability of automated volumetric liver scans in detecting focal liver lesions by evaluating the degree of agreement between conventional and volume ultrasound (US) examinations.Materials and methodsOver a period of 3 months, we prospectively studied 100 consecutive patients (36 men and 64 women; age range 15–87 years; mean age 63 years) referred to our institute for US imaging of the liver. Volumetric acquisition of the liver was achieved with a 3D transducer (2.0–5.0 MHz) and a Logiq 9 US scanner. All patients underwent both 2- and 3D US studies performed by two expert radiologists. Volumetric acquisitions were subsequently reviewed by the second radiologist, who was blinded to the first radiologist’s report. Three categories were established: 1=presence of focal liver lesions; 2=doubtful finding; 3=absence of focal liver lesions. Concordance between volume US and conventional US was calculated by using the k statistic.ResultsOut of 100 patients examined, 39 were found to be affected by focal liver lesions. All volume US examinations were technically adequate, allowing exploration of all hepatic sectors, except for five cases that were marred by major respiratory motion artefacts. Conventional and volume US identified the same number of focal liver lesions, with the exception of four cases of doubtful findings at volume US. Concordance between automated volume US and conventional US of the liver was high (k=0.92).ConclusionsThe identification of focal liver lesions on automated volume US is possible, and the examination shows a high level of concordance with conventional US.RiassuntoObiettivoStabilire l’affidabilità dell’acquisizione volumetrica automatica del fegato nell’identificazione delle lesioni focali epatiche, valutando la concordanza tra gli esami ecografici volumetrico e convenzionale.Materiali e metodiIn un periodo di tre mesi, sono stati studiati consecutivamente, in modo prospettico, 100 pazienti (36 uomini e 64 donne; range di età: 15–87 anni; media: 63 anni) giunti alla sezione di ecografia del nostro Istituto in regime di ricovero per eseguire un esame ecografico del fegato. L’acquisizione volumetrica del fegato è stata effettuata mediante sonda volumetrica (2,0–5,0 MHz) su ecografo Logiq 9. Gli esami ecografici, sia 2D che volumetrici, sono stati effettuati su tutti i pazienti da due radiologi esperti. È stata quindi successivamente effettuata una rilettura del volume dal secondo radiologo, all’oscuro del referto del primo. Sono state poi stabilite tre categorie: 1, presenza di lesioni focali; 2, dubbio di lesioni focali; 3, assenza di lesioni focali. La concordanza dell’acquisizione volumetrica con l’esame ecografico convenzionale è stata calcolata con il k test.RisultatiSu 100 pazienti studiati, in 39 sono state identificate lesioni focali epatiche. Tutti gli esami volumetrici sono risultati tecnicamente adeguati, in relazione alla esplorabilità ecografica di tutti i settori epatici, tranne 5 gravati da importanti artefatti da movimento respiratorio. Gli esami ecografici convenzionale e volumetrico hanno identificato lo stesso numero di lesioni focali epatiche, ad eccezione di 4 casi risultati dubbi per la presenza di lesione focale epatica all’esame ecografico volumetrico. La concordanza tra acquisizione volumetrica automatica del fegato ed esame ecografico convenzionale è risultata elevata (k=0,92).ConclusioniL’identificazione delle lesioni focali epatiche su acquisizioni volumetriche automatiche del fegato è possibile, risultando elevata la concordanza a tal fine dell’esame volumetrico ecografico rispetto all’esame ecografico convenzionale.

Detection of focal liver lesions: from the subjectivity of conventional ultrasound to the objectivity of volume ultrasound@@@Identificazione delle lesioni focali epatiche: dalla soggettività dell’esame ecografico convenzionale all’oggettività dell’esame ecografico volumetrico

PurposeThis study was undertaken to establish the reliability of automated volumetric liver scans in detecting focal liver lesions by evaluating the degree of agreement between conventional and volume ultrasound (US) examinations.Materials and methodsOver a period of 3 months, we prospectively studied 100 consecutive patients (36 men and 64 women; age range 15–87 years; mean age 63 years) referred to our institute for US imaging of the liver. Volumetric acquisition of the liver was achieved with a 3D transducer (2.0–5.0 MHz) and a Logiq 9 US scanner. All patients underwent both 2- and 3D US studies performed by two expert radiologists. Volumetric acquisitions were subsequently reviewed by the second radiologist, who was blinded to the first radiologist’s report. Three categories were established: 1=presence of focal liver lesions; 2=doubtful finding; 3=absence of focal liver lesions. Concordance between volume US and conventional US was calculated by using the k statistic.ResultsOut of 100 patients examined, 39 were found to be affected by focal liver lesions. All volume US examinations were technically adequate, allowing exploration of all hepatic sectors, except for five cases that were marred by major respiratory motion artefacts. Conventional and volume US identified the same number of focal liver lesions, with the exception of four cases of doubtful findings at volume US. Concordance between automated volume US and conventional US of the liver was high (k=0.92).ConclusionsThe identification of focal liver lesions on automated volume US is possible, and the examination shows a high level of concordance with conventional US.RiassuntoObiettivoStabilire l’affidabilità dell’acquisizione volumetrica automatica del fegato nell’identificazione delle lesioni focali epatiche, valutando la concordanza tra gli esami ecografici volumetrico e convenzionale.Materiali e metodiIn un periodo di tre mesi, sono stati studiati consecutivamente, in modo prospettico, 100 pazienti (36 uomini e 64 donne; range di età: 15–87 anni; media: 63 anni) giunti alla sezione di ecografia del nostro Istituto in regime di ricovero per eseguire un esame ecografico del fegato. L’acquisizione volumetrica del fegato è stata effettuata mediante sonda volumetrica (2,0–5,0 MHz) su ecografo Logiq 9. Gli esami ecografici, sia 2D che volumetrici, sono stati effettuati su tutti i pazienti da due radiologi esperti. È stata quindi successivamente effettuata una rilettura del volume dal secondo radiologo, all’oscuro del referto del primo. Sono state poi stabilite tre categorie: 1, presenza di lesioni focali; 2, dubbio di lesioni focali; 3, assenza di lesioni focali. La concordanza dell’acquisizione volumetrica con l’esame ecografico convenzionale è stata calcolata con il k test.RisultatiSu 100 pazienti studiati, in 39 sono state identificate lesioni focali epatiche. Tutti gli esami volumetrici sono risultati tecnicamente adeguati, in relazione alla esplorabilità ecografica di tutti i settori epatici, tranne 5 gravati da importanti artefatti da movimento respiratorio. Gli esami ecografici convenzionale e volumetrico hanno identificato lo stesso numero di lesioni focali epatiche, ad eccezione di 4 casi risultati dubbi per la presenza di lesione focale epatica all’esame ecografico volumetrico. La concordanza tra acquisizione volumetrica automatica del fegato ed esame ecografico convenzionale è risultata elevata (k=0,92).ConclusioniL’identificazione delle lesioni focali epatiche su acquisizioni volumetriche automatiche del fegato è possibile, risultando elevata la concordanza a tal fine dell’esame volumetrico ecografico rispetto all’esame ecografico convenzionale.

Ecografia con mezzo di contrasto (CEUS) immediatamente dopo ablazione percutanea dell'epatocarcinoma

PurposeThis study evaluated the effectiveness of contrast-enhanced ultrasound (CEUS), performed immediately after percutaneous ethanol injection (PEI) or radiofrequency thermal ablation (RFTA), by comparing results with the computed tomography (CT) follow-up.Materials and methodsSixty-nine consecutive patients with a diagnosis of hepatocellular carcinoma (HCC) were included in this prospective study. All patients underwent PEI or RFTA. After treatment, three CEUS enhancement patterns were observed: isovascular, hypovascular and avascular, which were compared with the CT findings. Sensitivity of the avascular pattern at CEUS and effectiveness of the ablative procedures were evaluated and compared with the chi-square test.ResultsNinety hypervascular HCCs, with a mean diameter of 2.6 cm (0.5–4.9 cm), underwent PEI (n=54) and RFTA (n=36). In the first group, CT identified complete necrosis in 28/54 (52%) lesions, 21 (75%) of which had avascular, one (4%) isovascular and six (21%) hypovascular patterns at CEUS. In the second group, CT showed complete necrosis in 31/36 (86%) lesions, all (100%) of which had a corresponding avascular pattern at CEUS. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the avascular pattern at CEUS compared with CT findings were 75%, 69%, 72%, 72% and 72% for PEI and 100%, 20%, 89%, 100% and 89%, for RFTA, respectively. A statistically significant difference (p<0.05) between the sensitivity of CEUS after PEI and after RFTA and between the necrosis obtained by RFTA and PEI were observed.ConclusionsCEUS performed immediately after percutaneous ablation of hepatocellular carcinoma to evaluate treatment efficacy is compulsory in the case of RFTA but not for PEI.RiassuntoObiettiviStimare l’efficacia dell’ecografia con mezzo di contrasto (CEUS) eseguita immediatamente dopo iniezione percutanea di etanolo (PEI) o termoablazione con radiofrequenza (RFTA), confrontando i risultati con la tomografia computerizzata (TC) di follow-up.Materiali e metodiSessantanove pazienti consecutivi con diagnosi di epatocarcinoma (HCC) sono stati studiati prospetticamente. Le lesioni sono state trattate con PEI o RFTA. Sono stati descritti tre pattern di enhancement alla CEUS (1, isovascolare; 2, ipovascolare; 3, avascolare) e quindi confrontati con la TC di follow-up. La sensibilitá nel riconoscimento del pattern CEUS avascolare dopo PEI e RFTA e l’efficacia delle procedure ablative sono state valutate e confrontate tra loro con il test del gC2.RisultatiNovanta HCC ipervascolari, con diametro medio di 2,6 cm (0,5–4,9 cm), sono stati sottoposti a PEI (54) e RFTA (36). Nel primo gruppo, la TC ha evidenziato necrosi completa in 28/54 (52%) lesioni, di cui 21 (75%) con pattern CEUS avascolare, 1 (4%) isovascolare e 6 (21%) ipovascolare. Nel secondo gruppo, la TC ha mostrato necrosi completa in 31/36 (86%) lesioni, tutte (100%) con pattern CEUS avascolare. Sensibilità, specificità, valore predittivo positivo e negativo ed accuratezza diagnostica per necrosi completa alla TC del pattern CEUS avascolare sono 75%, 69%, 72%, 72% e 72% dopo PEI, 100%, 20%, 89%, 100% e 89% dopo RFTA. La differenza tra la sensibilita della CEUS dopo PEI o RFTA e la differenza tra l’efficacia dei trattamenti è risultata statisticamente significativa (p<0,05).ConclusioniLa CEUS al termine della procedura ablativa dell’epatocarcinoma ai fini della valutazione del successo terapeutico è mandatoria dopo RFTA, ma non dopo PEI.