Drug-induced interstitial lung disease during cancer therapies: expert opinion on diagnosis and treatment.

BACKGROUND: Drug-induced interstitial lung disease (DIILD) is a form of interstitial lung disease resulting from exposure to drugs causing inflammation and possibly interstitial fibrosis. Antineoplastic drugs are the primary cause of DIILD, accounting for 23%-51% of cases, with bleomycin, everolimus, erlotinib, trastuzumab-deruxtecan and immune checkpoint inhibitors being the most common causative agents. DIILD can be difficult to identify and manage, and there are currently no specific guidelines on the diagnosis and treatment of DIILD caused by anticancer drugs. OBJECTIVE: To develop recommendations for the diagnosis and management of DIILD in cancer patients. METHODS: Based on the published literature and their clinical expertise, a multidisciplinary group of experts in Italy developed recommendations stratified by DIILD severity, based on the Common Terminology Criteria for Adverse Events. RESULTS: The recommendations highlight the importance of multidisciplinary interaction in the diagnosis and management of DIILD. Important components of the diagnostic process are physical examination and careful patient history-taking, measurement of vital signs (particularly respiratory rate and arterial oxygen saturation), relevant laboratory tests, respiratory function testing with spirometry and diffusing capacity of the lung for carbon monoxide and computed tomography/imaging. Because the clinical and radiological signs of DIILD are often similar to those of pneumonias or interstitial lung diseases, differential diagnosis is important, including microbial and serological testing to exclude or confirm infectious causes. In most cases, management of DIILD requires the discontinuation of the antineoplastic agent and the administration of short-term steroids. Steroid tapering must be undertaken slowly to prevent reactivation of DIILD. Patients with severe and very severe (grade 3 and 4) DIILD will require hospitalisation and often need oxygen and non-invasive ventilation. Decisions about invasive ventilation should take into account the patient's cancer prognosis. CONCLUSIONS: These recommendations provide a structured step-by-step diagnostic and therapeutic approach for each grade of suspected cancer-related DIILD.

Metastatic endo and perineural involvement of the ulnar nerve from malignant melanoma: ultrasound (US) and magnetic resonance imaging (MRI) findings.

Malignant melanoma metastases occur in about 15% of patients. The most common localizations are lymph nodes, lungs, pancreas, bones. The central nervous system and the perineural region are rarely affected. In case of distant metastases, the survival rate is lower (about 25%). Involvement of peripheral nerve metastases from melanoma is reported in the literature just in one case. We report the ultrasound (US) integrated with Color-Doppler Ultrasound (CDU), elastosonography, and magnetic resonance imaging (MRI) findings of a rare case of metastatic endo- and perineural involvement of the ulnar nerve from cutaneous melanoma. Our purpose is to increase the clinicians' and radiologists' awareness on the possibility of metastatic spread to the peripheral nervous system and improve the differential diagnosis with other peripheral nerve sheath tumors.

Superficial temporal artery pseudoaneurysm: what is the role of ultrasound?

PURPOSE: The superficial temporal artery (STA) is one of the terminal branches of the external carotid artery; STA pseudoaneurysms are uncommon vascular lesion, generally subsequent to blunt or penetrating trauma that could represent a trick for radiologist, especially when the only anamnestic information is "palpable superficial swelling". In this article, we describe our ultrasonographic experience about STA pseudoaneurysm reporting several cases with different etiopatogenesis. METHODS: Between January 2004 and March 2015 six patients (4F and 2M; aged 15-55 years, mean 36 year) presented at our department with superficial palpable swelling in temporal region (four with trauma history, two with iatrogenic cause) underwent to ultrasonographic study to assess the presence of STA pseudoaneurysm. Ultrasonographic findings suggestive of pseudoaneurysm was a well-defined, pulsatile, anechoic mass in B-mode, a swirling or disorganized pattern of blood flow in the lesion with demonstration of direct communication between arterial lumen and pseudoaneurysm at colour-Doppler and a typical to-and-fro waveform on pseudoaneurysm neck at pulsed-Doppler. RESULTS: B-mode proves the presence of anechoic mass in five on six patients. Colour-Doppler demonstrates the presence of flow inside the lesion in five patients and a direct communication in all patients. To-and-fro typical waveform has been demonstrated in five patients. Ultrasound made diagnosis in all patients with a sensibility and specificity of 100 %. CONCLUSION: US is the imaging modality of choice, since it can provide detailed information about vascular anatomy without incurring the risks of invasive methods like angiography or radiation.

Contrast-enhanced ultrasound in the characterization of complex cystic focal liver lesions.

Complex cystic focal liver lesions (FLLs) found at non-contrast ultrasound (US) may turn out to be malignant. In this prospective, monocentric study we investigated the value of contrast-enhanced US (CEUS) in the differential diagnosis of complex cystic FLLs. In the past 3 years, all patients with complex cystic FLLs unclassifiable at US underwent CEUS with low-transmit insonation power. We evaluated 36 consecutive patients with 61 FLLs (1-6/patient, mean = 2). The diameter of the lesions ranged from 1.1 to 7.9 cm (mean = 3.9 cm). Sixteen patients had an extrahepatic malignancy. There were 42 malignant lesions and 19 benign lesions. No lesion had a certain diagnosis at conventional US, whereas 16 FLLs were classified as probable (benign or malignant) and 45 as uncertain. CEUS correctly categorized 95% of the malignant cases. CEUS was not able to differentiate the biliary cystadenoma from its malignant counterpart and misdiagnosed two abscesses. Complete non-enhancement throughout three phases or sustained enhancement in the portal/late phase was exhibited in most benign complex cystic FLLs, except for 1 (of the 3) cystadenomas and in 2 (of the 4) abscesses. On the other hand, all malignant lesions presented a contrast washout with a hypo-enhancing appearance. CEUS may provide added diagnostic value in all complex cystic FLLs found uncertain at conventional US, potentially avoiding the use of more invasive and expensive imaging modalities.

Can high-resolution ultrasound avoid the sentinel lymph-node biopsy procedure in the staging process of patients with stage I-II cutaneous melanoma?

PURPOSE: The objective of our study was to define the diagnostic accuracy of high-resolution ultrasound (US) in detecting nodal involvement before sentinel lymph node biopsy (SLNB) in patients with cutaneous melanoma, to define the sonographic criteria used to assess nodal metastases, and to establish if high-resolution US can directly select patients to radical lymphadenectomy, sparing selective lymphadenectomy. MATERIALS AND METHODS: 623 patients underwent high-resolution US of the regional lymph nodes, 24 hours prior being submitted to the sentinel lymph node biopsy procedure. The US findings were compared with histological findings. RESULTS: In 14.7 % out of 122 excised lymph nodes, high-resolution US showed sonographic features consistent with malignant involvement before the surgical step. US scan sensitivity and specificity were 15 and 100 %, respectively, since positive and negative predictive values were 100 and 87 % respectively. CONCLUSION: US is an effective modality in the presurgical detection of subclinical deposits within sentinel lymph nodes. However, preoperative staging work-up with high-resolution US cannot substitute the SLNB, mainly because of low sensitivity due to missing many micrometastases.

Source and clinical motivation of orders for contrast-enhanced sonography (CEUS) of the liver: A prospective single-center survey.

Contrast-enhanced sonography (CEUS) has become a routine part of diagnostic imaging of the liver. Its possibilities, limitations, and indications have been defined in adequately large clinical series and in guidelines and recommendations. We prospectively evaluated physicians' orders for hepatic CEUS received in the radiology department of a large oncology center in Naples, Italy from May 2009 to April 2010. Radiologists performing the CEUS examinations filled out a form that included patient demography, source and type of patient referral, and clinical indications for the examination. During the study period, 564 patients aged 17-86 years (mean, 58 years) were referred to our department for CEUS liver studies (total: 644; 491 outpatient studies, 153 inpatient studies). This included 4 examinations that were ordered by the patient's physician but not performed by our staff. The majority of the CEUS examinations (n = 583; 90.5%) were regularly scheduled procedures ordered by clinical specialists from our center (77.3%) or other centers (11.8%); by general practitioners (on their own initiative) (0.8%); or by other figures (0.6%). The remaining 61 examinations (9.5%) were unscheduled procedures done on the initiative of a radiologist following conventional sonography (US). Fewer than half (47.8%) of the examinations were requested as first-line assessments. The others were ordered to clarify inconclusive findings generated by conventional US (30%) or by a more sophisticated imaging study (CT, MRI, PET) (16.1%) or to resolve discrepancies between CT, MRI, and/or PET findings (6%). CEUS is a relatively noninvasive, low-cost imaging study that is simple to perform and requires no particular patient preparation. This may explain its increasing use to clarify doubts raised by conventional US and other more sophisticated imaging studies.

Indeterminate, subcentimetric focal liver lesions in cancer patients: additional role of contrast-enhanced ultrasound.

PURPOSE: To evaluate whether the use of contrast-enhanced ultrasound (CEUS) could improve the characterization of indeterminate subcentimetric focal liver lesions (FLLs) seen with multidetector computed tomography (MDCT) in cancer patients. MATERIALS AND METHODS: For 12 months all patients with extrahepatic tumors showing small (< 10 mm), indeterminate focal liver lesions on whole-body or abdominal computed tomography (CT) underwent immediate, targeted ultrasound (US) to rule out a cystic lesion. Whenever unenhanced US demonstrated a non-cystic lesion or failed to recognize any focal abnormality within the suspected area, CEUS was carried out. During the arterial phase, CEUS was focused on the area reflecting the CT finding, while the entire organ was explored during the portal-sinusoidal phase. RESULTS: Among the 132 patients with MDCT evidence of indeterminate, subcentimetric focal liver lesions (206 lesions), US proved the cystic nature of 138 lesions in 87 patients. In 45 cases US failed to recognize any abnormality or cystic image and these subjects underwent CEUS. The CEUS results were confirmed by further assessment or follow-up for 43 / 45 patients (3 cysts, 8 hemangiomas, 47 metastases, 2 areas of focal steatosis, 2 eosinophilic necroses, 1 granuloma, 1 abscess, 1 fistula). CEUS failed to detect 3 lesions (1 metastasis and 2 benign lesions). In 8 cases CEUS recognized additional liver metastases. CONCLUSION: CEUS can be helpful in demonstrating or excluding metastases in cancer patients with MDCT evidence of subcentimetric, indeterminate focal liver lesions.

Contrast-enhanced sonography of the kidney.

Contrast-enhanced sonography (CEUS) is a recently introduced, promising technique in the evaluation of the kidney. CEUS allows real-time assessment of normal and abnormal renal perfusions. As a consequence of the macrocirculation analysis allowed by Doppler techniques, it is possible to obtain real-time information about microcirculation. US contrast media are not nephrotoxic and can be employed safely, even in subjects with impaired renal function. There are several clinical scenarios where CEUS may play the role of a low-cost, scarcely invasive tool, including renal tumors (with special reference to small, indeterminate masses, i.e., differentiation between carcinoma and angiomyolipoma), renal atypical cystic masses (i.e., differentiation of malignant from benign cysts and follow-up of cystic lesions managed conservatively), renal infarction, renal infections, and renal injuries. In addition, CEUS can be useful in the assessment of renal pseudotumors (including any case with possible renal mass on conventional US imaging) and has been employed in radiofrequency ablation guidance. This pictorial review illustrates the CEUS findings recognizable in a wide spectrum of renal disorders and discusses the strengths and limitations of renal imaging with CEUS.

Helical CT findings in patients with hepatocellular carcinoma treated with percutaneous ablation procedures.

Nonsurgical treatment of hepatocellular carcinoma is used worldwide as a result of the early detection and slow growth of this tumor in patients with chronic liver disease. Multiple-phase helical computed tomography is a commonly used method for evaluating the main features related to percutaneous ablation procedures: nodular changes, tumor necrosis, parenchymal changes, complications, and tumor recurrence. Knowledge of all features recognizable after local ablation therapy is mandatory to avoid diagnostic pitfalls and to optimally assess treatment response.

Levovist-enhanced Doppler sonography versus spiral computed tomography to evaluate response to percutaneous ethanol injection in hepatocellular carcinoma.

The aim of the current study was to compare Levovist-enhanced power Doppler (PD) imaging with contrast-enhanced spiral computed tomography (CT) in the evaluation of intratumoral vascularity of hepatocellular carcinomas at diagnosis and after percutaneous ethanol injection (PEI). Nineteen patients with hepatocellular carcinoma (HCC) underwent PD with and without Levovist and spiral CT at diagnosis and 1 month after PEI treatment. Compared to spiral CT at baseline evaluation, the PD showed intratumoral vascularity in 36.8% of the cases; this percentage reached 78.9% after Levovist enhancement. One month after PEI, only 5 out of 19 treated HCCs appeared as hypodense areas at CT and showed no contrast enhancement. Only 3 of the 14 patients with a positive spiral CT scan were positive at the PD performed without the Levovist administration (sensitivity, 21.4%). The use of contrast-enhanced ultrasonography led to detection of residual signal in six other HCCs treated by ethanol injection (sensitivity, 64.2%). We confirm that spiral CT is the most sensitive and accurate technique in evaluating the effect of ethanol injection in HCC. It correctly identifies most cases of treatment failure as enhanced areas within the lesion. The lower rate of detection of tumoral vascularity by Doppler sonography was significantly increased by Levovist. The evidence of residual vascularity within HCC at Levovist Doppler sonography allows the targeting of additional ethanol injections.

[Multiphasic helical computerized tomography of hepatocarcinoma. Assessment after chemoembolization]. / Tomografia Computerizzata spirale multifasica dell'epatocarcinoma. Valutazione dopo chemioembolizzazione.

PURPOSE: To report our personal experience with the addition of contrast-enhanced multiphase helical CT to unenhanced CT (Lipiodol CT) in the evaluation of patients with hepatocellular carcinoma treated with chemoembolization and to analyze the present role of oily agent CT. MATERIAL AND METHODS: We retrospectively reviewed the examinations of 42 consecutive patients submitted to global chemoembolization over a 2-year period. CT was performed 18-30 days after the treatment. The Lipiodol CT study was carried out with volume acquisitions. We considered as nodules all well-defined areas with dense oily agent uptake; uptake itself was classified as: 0 = absent, I = lower than 10% of the tumor volume, II = lower than 50%, III = higher than 50%, IV = homogeneous. Contrast-enhanced helical CT was performed with the 2-phase technique in 28 patients and with the 3-phase technique in 14; we considered as nodules all well-defined and relatively homogeneous areas with hyperattenuation in the arterial phase and hypo-isoattenuation in the portal and/or delayed phase, or with hypo-isoattenuation in the arterial phase and in the portal and/or delayed phase. RESULTS: Lipiodol CT permitted to recognize 65 nodules (1-5/patient, mean 1.5), namely 15 grade I, 21 grade II, 20 grade III and 9 grade IV. Multiphase CT identified 6 additional nodules in 5 patients, 5 hypervascular and 1 hypovascular, and better assessed the correct morphology and volume of grade I nodules. Only 4 of 6 nodules missed on Lipiodol CT showed oily agent uptake after a new chemoembolization session. Moreover after retreatment, carried out in 6 of 9 patients with grade I uptake (11 nodules in all), we found persistence of the grade I pattern in 5 nodules, grade II in 5, and grade III in 1. CONCLUSION: Lipiodol CT may miss liver nodules and underestimate the volume of nodules with poor uptake. Though Lipiodol CT should still be considered slightly more sensitive than multiphase CT, in our opinion this technique has several limitations, as also shown in recent literature papers, and its clinical applications should be reduced. Multiphase helical studies may provide useful information and should be performed routinely in patients treated with chemoembolization. The present availability of alternative tools such as contrast-enhanced Doppler US and MRI should also be stressed and their potential role investigated.

[Multiple-phase spiral computerized tomography of small hepatocellular carcinoma: technique optimization and diagnostic yield]. / Tomografia Computerizzata spirale multifasica del piccolo epatocarcinoma: ottimizzazione metodologica e interesse diagnostico.

PURPOSE: Spiral imaging has dramatically increased the diagnostic capabilities of Computed Tomography (CT) in the evaluation of small hepatocellular carcinomas (HCCs, O < 3 cm). We report our experience with multiple-phase CT of small HCC relative to both examination technique and lesion patterns. We compared the yield of biphasic (arterial-dominant + portal-dominant phases) and triphasic (arterial-dominant + portal-dominant + delayed phases) and also reviewed the literature for a meta-analysis of the techniques used. MATERIAL AND METHODS: December 1996 to July 1998, forty-eight patients with small nodular HCCs were examined--98 nodules in all (range 1-9, mean 2 per patient). After baseline CT, a nonionic contrast agent (350 mgI/mL, 130-140 mL, 4 mL/s) was administered through a power injector and a 16-gauge needle. Biphasic volume images were acquired in 19 subjects (early-phase delay 24 s, venous-phase delay 75 s) and triphasic images in 29 (early-phase delay 24 s, venous-phase delay 60 s, delayed-phase delay 100 s). Retrospectively we assessed the number of nodules detected with each protocol in every phase, nodule conspicuity (graded I-IV) relative to surrounding parenchyma, and nodule patterns in the various phases. Nodule patterns were distinguished into homogeneous, peripheral, central and mixed hyperdensity, and homogeneous hypodensity. RESULTS: Thirty-seven lesions were found in the patients examined with the biphasic technique: baseline images showed 35% of the nodules, arterial images 92%, portal images 76% and combined arterial and portal acquisitions 95%. Sixty-one lesions were found in the patients examined with the triphasic technique: baseline images showed 43% of the nodules, arterial images 93%, portal images 70%, and delayed images 77%; combined arterial and portal acquisitions detected 93% of the nodules, combined arterial and delayed images 95%, combined arterial and delayed images 80%. Finally, 95% of lesions were demonstrated when the three phases were combined. Overall conspicuity grades were I in 44% of cases, II in 28%, III in 18% and IV in 10% of cases at baseline scanning; I in 9%, II in 24%, III in 34% and IV in 33% in the arterial phase; I in 28%, II in 41%, III in 18% and IV in 13% in the portal phase; I in 23%, II in 30%, III in 26% and IV in 21% of cases in the delayed phase. At baseline, 10% of lesions were hyperdense (homogeneously and peripherally in 5% each); mixed density was seen in 8%, and hypodensity in 82%. In the arterial phase, 93% of lesions were hyperdense (homogeneously in 80%, peripherally in 10% and centrally in 3%); mixed density was seen in 5%, and hypodensity in 1%. In the portal phase, 4% of lesions were hyperdense (homogeneously in 1% and centrally in 3%); mixed density was seen in 11%, and hypodensity in 85%. In the delayed phase, the lesions appeared mixed in 11% of cases and hypodense in 89%. CONCLUSIONS: Spiral CT scanning of small HCCs requires dedicated and meticulous technique. Multipassage assessment is mandatory, with 2 or 3 dynamic acquisitions of the whole liver. No major difference in nodule detection was demonstrated between these two options and thus the choice rests with the radiologist's preference. Early CT images proved best for lesion detection, followed by delayed, venous, and baseline studies; lesion recognition depends largely on nodular diameter. The same applies to conspicuity, which however depends on tumor volume less. Lesion patterns are quite typical and constant in all phases and are independent of lesion diameter.

[Contrast media extravasation in upper abdominal injuries: detection with spiral computerized tomography]. / Stravaso del mezzo di contrasto nei traumi dell'addome superiore: riconoscimento con tomografia computerizzata spirale.

PURPOSE: The possibility of detecting contrast agent extravasation (i.e., active hemorrhage) with dynamic conventional Computed Tomography (CT) in patients with abdominal trauma has already been reported in small series. We report our experience in the demonstration of contrast material extravasation using helical CT; we also investigate the diagnostic and clinical value of this finding. MATERIAL AND METHODS: January 1997 to July 1998, we examined 41 consecutive patients with upper abdominal trauma. Twelve patients (29%) had contrast material extravasation. The examinations were performed with a helical unit and volumetric acquisitions (thickness 8-10 mm, pitch 1, reconstruction interval 5-8 mm). The intravenous contrast medium (350 mgI/mL, 130-140 mL) was administered with rapid infusion (2-2.5 mL/s, 40-50 s acquisition delay from bolus starting) and using a power injector. We reviewed the CT studies and clinical records of these 12 patients. Contrast agent extravasation was considered present when this finding, not recognizable on plain scans, showed equal attenuation to or higher attenuation than the vessels within the same level. Moreover we assessed leak site, CT appearance, the direct visualization of the involved vessel, the evidence of other abdominal or extra-abdominal injuries, the CT signs of hypovolemic shock, clinical and surgical data. For comparison, we finally evaluated 50 examinations performed with a conventional CT scanner in subjects with abdominal trauma. RESULTS: Active hemorrhage involved the abdominal wall in 1 case (intercostal artery), the solid organs in 4 (splenic in 2, hepatic in 1, of the middle hepatic vein in 1), the peritoneal cavity in 3 (splenic, midcolic, and gastroduodenal artery in 1 each), the retroperitoneum in 4 (renal pedicle in 2, renal parenchyma in 1, lumbar artery in 1). In all cases the site of contrast extravasation corresponded at surgery to the site of active bleeding. The pattern was localized in 10 cases and diffuse in 2. The involved vessel could be identified in 5 cases while in the other ones the origin could be inferred from the leakage site. Associated injuries of upper abdominal organs were seen in 11 of 12 patients and extra-abdominal trauma in 6. In 4 cases there were CT features of hypovolemia. One patient died during transport to the operating room and another after surgery, while all the others survived. Contrast extravasation was identified in 9 (18%) of the patients examined with a conventional CT unit. CONCLUSIONS: Active contrast material extravasation can be recognized with conventional CT scanners, though it has been considered a rare finding. Helical CT seems to increase the detection rate and especially to boost the radiologist's confidence in this diagnosis. Though active bleeding is identified in severely-injured subjects requiring urgent intervention and may be associated with findings of hypovolemic shock, it should not be considered itself as a negative prognostic factor. Contrast extravasation is due to ongoing hemorrhage and its detection is critical for urgent treatment. Accurate anatomical location permits to choose surgical management or transcatheter embolization and thus decreases time consumption for precise bleeding site identification.

[The angiogram sign in pulmonary atelectases studied by spiral computed tomography. Its incidence and semeiologic value]. / Il segno dell'angiogramma nelle atelettasie polmonari studiate con Tomografia Computerizzata spirale. Incidenza e validità semeiologica.

PURPOSE: We investigated the yield of Helical CT in the study of lung vessels, the incidence of the angiogram sign and its actual value. MATERIAL AND METHODS: July 1997 to December 1998, we studied 30 cases of pulmonary collapse of different origin. We found 15 cases of passive collapse (10 from pleural effusion, 2 from diaphragmatic compression, 2 from traumatic pneumothorax, and 1 from isthmic aortic aneurysm), 12 cases of obstructive collapse (9 from bronchogenic carcinoma, 1 from mucoid obstruction, 1 from hilar lymphadenopathy, and 1 from mediastinal cancer), 2 cases of adhesive collapse and 1 case of round atelectasis. All the examinations were performed with the Helical technique during nonionic iodinated contrast agent injection (bolus, 300-350 mg/mL); we used an automatic injector set at 2-3 mL/s. We studied the images for the angiogram sign, that is hyperdense bands, usually longer than 2 cm, through the collapsed lung, which correspond to normal pulmonary vascular branches. RESULTS: The angiogram sign was found in 95% of passive (14/15) and in 80% of obstructive (10/12) collapses. However in 2 of those we also found some hyperdense spots referable to vessels seen on transverse slices. The angiogram sign was missing in 1 of 2 adhesive collapses because of vascular distortion from irradiation-related fibrosis. The "comet-tail" vascular pattern was seen in round atelectasis. We had no cases of cicatricial collapse. CONCLUSIONS: Thanks to its fast acquisition capabilities, Helical CT well depicts peak vascular enhancement, which permitted identification of the angiogram sign in several pulmonary collapse cases. Thus, this sign becomes even less specific, and just one of the signs of pulmonary consolidation.