Liver-directed therapies for liver metastases from neuroendocrine neoplasms: Can laser ablation play any role?

Aggressive cytoreduction can prolong survival in patients with unresectable liver metastases (LM) from neuroendocrine neoplasms (NEN), and minimally invasive, liver-directed therapies are gaining increasing interest. Catheter-based treatments are used in disseminated disease, whereas ablation techniques are usually indicated when the number of LM is limited. Although radiofrequency ablation (RFA) is by far the most used ablative technique, the goal of this opinion review is to explore the potential role of laser ablation (LA) in the treatment of LM from NEN. LA uses thinner needles than RFA, and this is an advantage when the tumors are in at-risk locations. Moreover, the multi-fiber technique enables the use of one to four laser fibers at once, and each fiber provides an almost spherical thermal lesion of 12-15 mm in diameter. Such a characteristic enables to tailor the size of each thermal lesion to the size of each tumor, sparing the liver parenchyma more than any other liver-directed therapy, and allowing for repeated treatments with low risk of liver failure. A recent retrospective study reporting the largest series of LM treated with LA documents both safety and effectiveness of LA, that can play a useful role in the multimodality approach to LM from NEN.

Percutaneous Laser Ablation of Liver Metastases from Neuroendocrine Neoplasm. A Retrospective Study for Safety and Effectiveness.

PURPOSE: To retrospectively assess safety and efficacy of laser ablation (LA) of multiple liver metastases (LM) from neuroendocrine neoplasms (NEN). METHODS: Twenty-one patients with NEN and at least 3 LM ≤ 4 cm in diameter underwent ultrasonography-guided LA. Up to seven LM were ablated in a single session; if the number of LM exceeded seven, the remaining LM were ablated in further LA sessions with a time interval of 3-4 weeks. LA was performed according to the multifiber technique. The patients underwent contrast-enhanced CT 1 month after LA, and were subsequently monitored every 3 months for the first 2 years and then every 6 months. RESULTS: In total, 189 LM were treated in 21 patients (mean 9 ± 8.2, median 6) in 41 LA sessions (range 1-5). The diameter of LM ranged from 5 to 35 mm (median 19 mm, mean 17.9 ± 6.4 mm). One grade 4 complication occurred (0.53%): a bowel perforation managed by surgery. Technical efficacy was 100%, primary efficacy rate 94.7%, and secondary efficacy rate 100%. Complete relief of hormone-related symptoms was obtained in all the 13 symptomatic patients. Median follow-up was 39 months (range 12-99). 1-, 2-, 3-, and 5-year survival rates were 95%, 86%, 66%, and 40%, respectively. Overall survival resulted higher for patients with Ki-67 expression ≤ 7% than for those with Ki-67 > 7% (p = 0.0347). CONCLUSIONS: LA is a promising and safe technique to treat LM from NEN. A longer follow-up should provide definitive information on the long-term efficacy of this liver-directed therapy. LEVEL OF EVIDENCE: Retrospective study, local non-random sample, level 3.

Ultrasound-guided percutaneous laser ablation is safe and effective in the treatment of small renal tumors in patients at increased bleeding risk.

PURPOSE: The aim of this retrospective study was to assess the safety and effectiveness of laser ablation (LA) in patients with small renal cell carcinomas (RCC) and increased risk of bleeding. MATERIAL AND METHODS: From 2013 to 2017, nine patients (six males, three females, aged 68.5 ± 12.2 years) at high risk of bleeding underwent ultrasonography-guided LA for an RCC. Patients were considered at increased risk of bleeding because of impairment of coagulation parameters, concomitant antiplatelet therapy, or at-risk location of the tumor (one, five, and three patients, respectively). RCC diameter ranged from 11 to 23 mm. According to tumor size, two or three laser fibers were introduced through 21-gauge needles and 1800 J per fiber were delivered in 6 min with a fixed power of 5 W. Major and minor complications, technical success, and primary and secondary technical effectiveness and tumor recurrence were recorded. RESULTS: Just one Grade 1 complication was observed: a small asymptomatic hematoma that spontaneously resolved. Technical success was 100%, 1 month technical efficacy was 88.9% (8/9 patients). One patient with residual tumor was successfully retreated 1 month later, and secondary efficacy rate was 100%. No local tumor recurrence occurred during a median follow-up of 26 months (range 11-49 months). CONCLUSIONS: LA is safe and effective in the treatment of small RCC and might represent a valid option in patients with increased risk of bleeding.

Contrast-enhanced ultrasonography of post-interventional hematoma: the bleeding mushroom is growing inside.

Catheter ablation is an effective treatment in patients with symptomatic atrial fibrillation. Complications are infrequent and usually resolve with minimal or no intervention, but active bleeding due to arterial injury during the vascular access can sometimes represent a life-threatening complication. Contrast-enhanced computed tomography is the standard technique to detect active bleeding, but it may not be immediately available. We report a case of iatrogenic hemorrhage after catheter ablation, in which contrast-enhanced ultrasonography played a decisive role in the recognition of active arterial bleeding due to injury to the right common femoral artery.

Unusual tumour ablations: report of difficult and interesting cases.

Image-guided ablations are nowadays applied in the treatment of a wide group of diseases and in different organs and regions, and every day interventional radiologists have to face more difficult and unusual cases of tumour ablation. In the present case review, we report four difficult and unusual cases, reporting some tips and tricks for a successful image-guided treatment.

Laser ablation of liver tumors: An ancillary technique, or an alternative to radiofrequency and microwave?

Radiofrequency ablation (RFA) is currently the most popular and used ablation modality for the treatment of non surgical patients with primary and secondary liver tumors, but in the last years microwave ablation (MWA) is being technically improved and widely rediscovered for clinical use. Laser thermal ablation (LTA) is by far less investigated and used than RFA and MWA, but the available data on its effectiveness and safety are quite good and comparable to those of RFA and MWA. All the three hyperthermia-based ablative techniques, when performed by skilled operators, can successfully treat all liver tumors eligible for thermal ablation, and to date in most centers of interventional oncology or interventional radiology the choice of the technique usually depends on the physician's preference and experience, or technical availability. However, RFA, MWA, and LTA have peculiar advantages and limitations that can make each of them more suitable than the other ones to treat patients and tumors with different characteristics. When all the three thermal ablation techniques are available, the choice among RFA, MWA, and LTA should be guided by their advantages and disadvantages, number, size, and location of the liver nodules, and cost-saving considerations, in order to give patients the best treatment option.

Management of incidental renal masses: Time to consider contrast-enhanced ultrasonography.

Proliferation of imaging studies for different clinical purposes and continuous improvement of imaging technology have led to an increasing number of incidental findings of renal masses. It is estimated that over 50% of patients older than 50 years have at least one renal mass. The majority of incidental renal masses are simple cysts that can be easily diagnosed by conventional ultrasonography. However, some incidental renal masses are not simple cysts, and differentiation between benign and malignant entities requires further imaging modalities. In the past, multiphase contrast-enhanced computed tomography and magnetic resonance imaging were considered the primary imaging modalities used to characterize and stage complex cystic and solid renal lesions. Currently, contrast-enhanced ultrasonography represents a novel alternative to contrast-enhanced computed tomography and magnetic resonance imaging. Contrast-enhanced ultrasonography employs microbubble contrast agents that allow the study of different enhancement phases of the kidney without risk of nephrotoxicity and radiation exposure. The diagnostic accuracy of contrast-enhanced ultrasonography in the characterization of complex renal cysts is comparable to that of computed tomography and magnetic resonance imaging, and several studies have demonstrated its reliability also in identifying solid lesions such as pseudotumors, typical angiomyolipomas, and clear cell renal carcinomas. Considering the high incidence of incidental renal masses and the need for rapid and reliable diagnosis, contrast-enhanced ultrasonography could be proposed as the first step in the diagnostic work-up of renal masses because of its safety and cost effectiveness. In this paper, we propose a diagnostic algorithm for the characterization of cystic and solid renal masses.

Thermal ablation in colorectal liver metastases: Lack of evidence or lack of capability to prove the evidence?

Many studies suggest that combined multimodality treatments including ablative therapies may achieve better outcomes than systemic chemotherapy alone in patients with colorectal liver metastases. Nevertheless, ablative therapies are not yet considered as effective options because their efficacy has never been proved by randomized controlled trials (RCT). However, there are in literature no trials that failed in demonstrating the effectiveness of ablative treatments: what are lacking, are the trials. All the attempts to organize phase III studies on this topic failed as a result of non accrual. Just one prospective RCT comparing radiofrequency ablation combined with systemic chemotherapy vs chemotherapy alone has been published. It was designed as a phase III study, but it was closed early because of slow accrual, and was downscaled to phase II study, with the consequent limits in drawing definite conclusions on the benefit of combined treatment. However, the combination treatment met the primary end point of the study and obtained a significantly higher 3-year progression-free survival than systemic chemotherapy alone. It is very unlikely that ultimate efficacy of ablation treatments will ever be tested again, and the best available evidence points toward a benefit for the combination strategy using ablative treatments and chemotherapy.

Coagulation areas produced by cool-tip radiofrequency ablation and microwave ablation using a device to decrease back-heating effects: a prospective pilot study.

PURPOSE: To compare the ablation area produced by a single application of a microwave ablation (MWA) system, equipped with a miniaturized device on the tip of the antenna entrapping reflected microwaves, with that produced by an internally cooled radiofrequency ablation (RFA) system. MATERIALS AND METHODS: Forty patients with primary or secondary inoperable liver tumors, selected to undergo percutaneous thermal ablation, were randomly assigned to MWA or RFA procedure. The ablation areas produced by a single application of MWA (ablation time 10 min) or RFA (ablation time 12 min) energy were assessed by contrast-enhanced ultrasonography immediately after the end of the procedure. The long- and short-axis diameters of the ablation areas were measured and compared using Student t test. RESULTS: Long- and short-axis diameters of the ablation areas produced by MWA were significantly greater than those produced by RFA: 48.5 ± 6.7 versus 30.9 ± 1.1 mm (p < 0.0001) and 38.5 ± 4.6 versus 26.8 ± 2.9 mm (p < 0.0001), respectively. CONCLUSION: The MWA system can achieve significantly larger ablation areas than the internally cooled RFA system. Broader randomized trials are strongly warranted to investigate whether such superiority can translate into better long-term outcome of the ablation procedure.

Virtual CT sonographically guided biopsy of a retroperitoneal mass in a patient with Erdheim-Chester disease.

Image fusion between sonography and CT allows real-time synchronization of CT multiplanar reconstructed images with the corresponding sonographic images. This technique has mainly been used in liver imaging. We report the use of image fusion to target and successfully guide the percutaneous biopsy of a retroperitoneal a mass. This technique represents a promising tool in abdominal imaging, and it should be considered for the biopsy of lesions that are difficult to approach with conventional imaging guidance techniques.

Contrast-enhanced ultrasonography in peripheral lung consolidations: What's its actual role?

AIM: To evaluate the diagnostic accuracy of contrast-enhanced ultrasonography (CEUS) in the differential diagnosis between neoplastic and non-neoplastic peripheral pleuro-pulmonary lesions. METHODS: One hundred patients with pleural or peripheral pulmonary lesions underwent thoracic CEUS. An 8 microliters/mL solution of sulfur hexafluoride microbubbles stabilized by a phospholipid shell (SonoVue(®)) was used as US contrast agent. The clips were stored and independently reviewed by two readers, who recorded the following parameters: presence/absence of arterial enhancement, time to enhancement (TE), extent of enhancement (EE), pattern of enhancement (PE), presence/absence of wash-out, time to wash-out, and extent of wash-out. After the final diagnosis (based on histopathologic findings or follow-up of at least 15 mo) was reached, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR) of each CEUS parameter in the differential diagnosis between neoplastic and non-neoplastic lesions were calculated. Furthermore, an arbitrary score based on the ratio between the PPVs of each CEUS parameter was calculated, to evaluate if some relationship could exist between overall CEUS behaviour and neoplastic or non-neoplastic nature of the lesions. RESULTS: Five patients were lost at follow-up before a conclusive diagnosis was reached, 53 lesions resulted neoplastic and 42 non-neoplastic. Enhancement in the arterial phase was observed in 53/53 neoplastic lesions and 30/42 non-neoplastic lesions. On the whole, 40/42 non-neoplastic lesions showed absence of enhancement or early enhancement (95.2%) vs 3/53 neoplastic lesions (5.7%). EE was marked in 29/53 (54.7%) neoplastic lesions and 25/30 (83.3%) non-neoplastic lesions, moderate in 24/53 (45.5%) and 5/30 (16.7%), respectively. PE was homogeneous in 6/53 (11.3%) neoplastic lesions and 18/30 (60%) non-neoplastic lesions, inhomogeneous in 47/53 (88.7%) and 12/30 (40%), respectively. 19/30 (63.3%) non-neoplastic lesions enhancing in the arterial phase had no wash-out in the venous phase, 11/30 (36.7%) had late and mild wash-out. Wash-out was early in 26/53 (49%) neoplastic lesions, late in 26/53 (49%), absent in 1 (2%); marked in 16/53 (30.2%), and moderate in 36/53 (67.9%). The delayed enhancement in the arterial phase showed a sensitivity of 94.32%, specificity of 95.2%, PPV of 96.2%, NPV of 93%, PLR of 19.81, and NLR of 0.06 in identifying the neoplastic lesions. All other parameters individually considered showed unsatisfactory values of sensitivity, or specificity, or both, in differentiating neoplastic from non-neoplastic lesions. The median of the overall arbitrary score was 3 (range 0-14) in non-neoplastic lesions, and 16.5 (range 7.0-17.5) in neoplastic lesions (P < 0.001). The correlation between the diagnosis of neoplastic vs non-neoplastic lesion and the score value was statistically significant (r = 0.858, P < 0.001). Based on the score distribution, a cut-off of 7.5 enabled to reach a sensitivity of 98.1%, specificity of 95.1%, PPV 96.3%, NPV 97.5%, PVR 20.1 and NVR 0.02 in differentiating neoplastic from non-neoplastic lesions. CONCLUSION: CEUS could be useful in the diagnostic workup of pleuropulmonary lesions. A delayed TE or a score ≥ 7.5 suggest the neoplastic nature of a lesion.

Contrast-enhanced ultrasound (CEUS) and CEUS-guided biopsy in the diagnosis of lung abscess in a patient with achalasia: Case report.

Primary achalasia is a rare disorder of unknown aetiology characterized by dysfunction of esophageal motility secondary to degeneration of esophageal neurons. Some diseases, in particular neoplastic diseases, can cause symptoms similar to achalasia, and this condition is called pseudoachalasia. Pseudoachalasia can be indistinguishable from primary achalasia, and many investigations are often necessary to detect or exclude an underlying neoplasia. We report a case in which thoracic contrast-enhanced ultrasound (CEUS) and percutaneous CEUS-guided lung biopsy played a central role in differentiating aspiration pneumonia secondary to achalasia and complicated by lung abscess from pseudoachalasia secondary to lung carcinoma, after computed tomography (CT) yielded inconclusive findings. US contrast agent SonoVue® has an exclusively intravascular distribution, and its ability to discriminate between contrast vascular signal and tissue signal is greater than that of CT, making CEUS superior to CT in distinguishing perfused, viable tissues from avascular necrotic tissues. Although its use in pleuropulmonary pathology is still off-label, CEUS can play a useful role in characterizing peripheral pulmonary masses in selected cases.

Role of ultrasonography and contrast-enhanced ultrasonography in a case of Krukenberg tumor.

We report a case of Krukenberg tumor of gastric origin with adnexal metastasis, in which ultrasonography (US) and contrast-enhanced US (CEUS) played a key diagnostic role. An 64-year-old female patient was referred to our department for abdominal pain, nausea and ascites. US examination was performed as first line diagnostic imaging approach, confirming the presence of ascites and detecting marked thickness of the gastric wall and a right adnexal mass. CEUS was immediately performed and showed arterial enhancement followed by wash-out in the venous phase of both the gastric wall and the adnexal mass, suggesting the diagnosis of gastric cancer with right adnexal metastasis (Krukenberg syndrome). The patient underwent US-guided paracentesis and esophagogastroduodenoscopy that showed linitis plastica. Cytologic examination of the peritoneal fluid revealed the presence of signet-ring cells, and histologic examination of the specimen obtained by endoscopic biopsy showed primary gastric mucus-producing adenocarcinoma with signet-ring cells. Although transvaginal US is undoubtedly the method of choice to evaluate ovarian tumors, abdominal US and CEUS can provide key diagnostic elements, supporting clinicians in the first steps of the diagnostic work-up of abdominal and pelvic masses.

Resection vs thermal ablation of small hepatocellular carcinoma: What's the first choice?

Nowadays, hepatocellular carcinoma (HCC) is frequently diagnosed at an early stage, opening good perspectives to radical treatment by means of liver transplantation, surgical resection, or percutaneous ablation. Liver transplantation is considered the best option, but the lack of liver donors represents a major limitation. Therefore, surgical resection, offering a 5-year-survival rate of over 50%, is considered the first-choice treatment for patients with early stage HCC, whereas percutaneous ablation is usually reserved to patients who are not candidate to surgery. However, in the recent years some trials showed that percutaneous radiofrequency ablation (RFA) can be as effective as surgical resection in terms of overall survival and recurrence-free survival rates in patients with small HCC, and a retrospective comparative study reported 1-, 3-, and 5-year overall survival rates and recurrence-free survival rates significantly better in patients with central HCC measuring 2 cm or smaller treated with RFA than in those treated with surgical resection. RFA is less expensive, less invasive, with lower complication rate and shorter hospital stay than surgical resection, and on the basis of the results of these studies it should be considered the first option in the treatment of very early HCC. However, RFA is size-dependent, so at present the need to achieve an adequate safety margin around the tumor limits to about 2 cm the diameter of the nodules that can be ablated with long-term outcomes comparable to or better than surgical resection. The main goal of the next technical developments of the thermal ablation systems should be the achievement of larger ablation areas with a single needle insertion. In this regard, the recent improvements in microwave energy delivery systems seem to open interesting perspectives to percutaneous microwave ablation, which could become the ablation technique of choice in the next future.