Abdominal Emergencies in Cancer Patients.

Abdominal emergencies in cancer patients encompass a wide spectrum of oncologic conditions caused directly by malignancies, paraneoplastic syndromes, reactions to the chemotherapy or often represent the first clinical manifestation of an unknown malignancy. Not rarely, clinical symptoms are the tip of an iceberg. In this scenario, the radiologist is asked to exclude the cause responsible for the patient's symptoms, to suggest the best way to manage and to rule out the underlying malignancy. In this article, we discuss some of the most common abdominal oncological emergencies that may be encountered in an emergency department.

A monocentric phase I study of vemurafenib plus cobimetinib plus PEG-interferon (VEMUPLINT) in advanced melanoma patients harboring the V600BRAF mutation.

BACKGROUND: Studies carried out in vitro and in a mouse model have shown that BRAF inhibitors enhance the effects of IFN-α on BRAFV600E melanoma cells through the inhibition of ERK. Therefore, the combination of vemurafenib and IFN-α in patients with BRAFV600E melanoma may provide therapeutic benefits; MEK inhibition may prevent the reactivation of the MAPK pathway induced by BRAF inhibitor resistance. PATIENTS AND METHODS: In a phase I study, adult patients with advanced BRAFV600-mutated melanoma were treated with vemurafenib + PEG-IFN-α-2b or vemurafenib + cobimetinib + PEG-IFN-α-2b, to assess the safety of the combination and the upregulation of IFN-α/ß receptor-1 (IFNAR1). RESULTS: Eight patients were treated; 59 adverse events with four serious ones (three related to study treatments) were reported. Patients with a pre-treatment IFNAR1 expression on ≤ 35% melanoma cells had a median progression-free survival of 12.0 months (range: 5.6-18.4 months) and a median overall survival of 31.0 months (range: 19.8-42.2 months), while patients with a pre-treatment IFNAR1 expression on > 35% of melanoma cells had a median progression-free survival of 4.0 months (range: 0-8.8; p = 0.03), and a median overall survival of 5 months (p = 0.02). Following treatment, responders had higher levels of growth-suppressor genes, including GAS1 and DUSP1, and genes involved in a metabolically robust immune response, including FAP. CONCLUSION: Our study supports the overall safety of the vemurafenib + PEG-IFN-α-2b + cobimetinib combination. IFNAR1 expression levels correlated with response to treatment, including survival. Vemurafenib + PEG-IFN-α-2b + cobimetinib would have difficulty finding a niche in the current treatment scenario for advanced melanoma, but we speculate that our findings may contribute to identify subjects particularly responsive to treatment. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov (NCT01959633). Registered 10 October 2013, https://clinicaltrials.gov/ct2/show/NCT01959633.

Synchronous tumours detected during cancer patient staging: prevalence and patterns of occurrence in multidetector computed tomography.

PURPOSE: The incidental detection of one or more additional primary tumours during computed tomography (CT) staging of a patient with known malignancy is rare but possible. This occurrence should be considered by the radiologist when a new lesion is detected, especially if the lesion location is atypical for metastases. The purpose of this report was to document the usefulness of total body CT scan to detect synchronous primary malignancies in cancer patients undergoing a staging workup. MATERIAL AND METHODS: This was done by reviewing the staging CT studies of the adult patients with a newly diagnosed cancer evaluated during a five-year period in a single cancer institute in order to identify any possible correlation, establishing which tumours are more frequently combined with a second tumour and which second tumours are more commonly present. RESULTS: Among the patients with a second tumour, the most frequent first primary tumours were melanoma (eight patients, 17.8%), lymphoma (seven patients, 15.6%), and prostate carcinoma (seven patients, 15.6%). The most frequent incidentally detected second tumours were hepatocellular carcinoma (nine patients, 20% of 45 incidental tumours), renal carcinoma (eight patients, 17.8%), lung carcinoma (seven patients, 15.6%), and bladder carcinoma (four patients, 8.9%). One patient had three primary tumours synchronously. CONCLUSIONS: We believe that the radiologist's knowledge of the prevalence and pattern of occurrence of these multiple primary malignancies represents added diagnostic value.

Impact of ultrasonographic features, cytomorphology and mutational testing on malignant and indeterminate thyroid nodules on diagnostic accuracy of fine needle cytology samples: A prospective analysis of 141 patients.

OBJECTIVE: Fine needle cytology (FNC) is the first-line diagnostic method to determine the benign or malignant nature of thyroid nodules. The gray zone of cytological classifications remains, however, a crucial and challenging area for cytopathologists. DESIGN, PATIENTS AND MEASUREMENTS: In the present study, 141 thyroid cytological samples, with ultrasonographic suspicious features, have been prospectively analysed. Molecular analyses were performed by an innovative technology using two multiplex PCRs for the amplification of BRAF, N-H-K-RAS and RET exon genes. RNA samples were studied for RET/PTC1 and RET/PTC3 rearrangements by PCR amplification, and the conditions were set-up to study, with a single experiment, both wild-type PAX8 and PAX8/PPARÉ£ rearrangements. In total, 111 samples were examined for BRAF, N-H-KRAS and RET genes. An ultrasonographic, cytological and molecular correlation was also carried out in an attempt to suggest a possible way to manage the patients with thyroid nodules. Cyto-histological correlation was available in 115 cases, and it was used to verify the global diagnostic accuracy of this combined approach. RESULTS: According to the histopathological diagnosis, FNC accuracy was 100% for TIR5 and metastases; 89% for TIR4; 84% for TIR3A and 58% for TIR3B. About 11% of the studied samples showed either RET-PTC1 or RET/PTC3 chromosomal rearrangements, and only one sample simultaneously presented RET/PTC1 and RET/PTC3 rearrangements. PAX8/PPARÉ£ rearrangement was found in 6% of the samples. CONCLUSIONS: A multidisciplinary approach to the thyroid is therefore necessary to develop innovative methods suitable for an improved diagnostic and prognostic definition of thyroid cancer.

Diagnostic Performance and Confidence of Contrast-Enhanced Ultrasound in the Differential Diagnosis of Cystic and Cysticlike Liver Lesions.

OBJECTIVE: The aims of this study were to assess the diagnostic performance of contrast-enhanced ultrasound (CEUS) in the characterization of atypical cystic and cysticlike focal liver lesions in comparison with conventional US and to determine whether the use of CEUS can reduce the need for further diagnostic workup. SUBJECTS AND METHODS: In a 3-year period 48 patients with 50 atypical cystic and cysticlike lesions found at conventional US underwent CEUS. Diagnostic confirmation was obtained in cytohistopathologic examinations, with other imaging modalities, and in follow-up. Overall, there were 24 cystic lesions and 26 cysticlike solid lesions, specifically 32 benign and 18 malignant lesions. The conventional US and CEUS images and cine loops were reviewed by two blinded readers independently. Sensitivity, specificity, area under the ROC curve (Az), and interobserver agreement were calculated. RESULTS: Diagnostic performance improved after review of CEUS examinations by both readers (conventional US Az = 0.781 vs 0.972; CEUS Az = 0.734 vs 0.957). Interreader agreement increased, although slightly (conventional US weighted κ = 0.894; CEUS weighted κ = 0.953). In terms of differential diagnosis, the occurrence of correctly characterized lesions increased after CEUS for both readers (reader 1, 62% to 98%; reader 2, 56% to 96%). CONCLUSION: The development of low-acoustic-power CEUS has made it possible to identify several imaging features of cystic and cysticlike focal liver lesions that, in association with history and clinical findings, may help to correctly characterize them. Our data indicate the usefulness of CEUS in the evaluation of patients with these lesions.

Phase II clinical study of valproic acid plus cisplatin and cetuximab in recurrent and/or metastatic squamous cell carcinoma of Head and Neck-V-CHANCE trial.

BACKGROUND: Recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN) has a poor prognosis and the combination of cisplatin and cetuximab, with or without 5-fluorouracil, is the gold standard treatment in this stage. Thus, the concomitant use of novel compounds represents a critical strategy to improve treatment results. Histone deacetylase inhibitors (HDACi) enhance the activity of several anticancer drugs including cisplatin and anti-Epidermal Growth Factor Receptor (anti-EGFR) compounds. Preclinical studies in models have shown that vorinostat is able to down regulate Epidermal Growth Factor Receptor (EGFR) expression and to revert epithelial to mesenchimal transition (EMT). Due to its histone deacetylase (HDAC) inhibiting activity and its safe use as a chronic therapy for epileptic disorders, valproic acid (VPA) has been considered a good candidate for anticancer therapy. A reasonable option may be to employ the combination of cisplatin, cetuximab and VPA in recurrent/metastatic SCCHN taking advantage of the possible positive interaction between histone deacetylase inhibitors, cisplatin and/or anti-EGFR. METHOD/DESIGN: V-CHANCE is a phase 2 clinical trial evaluating, in patients with recurrent/metastatic squamous cell carcinoma of the head and neck never treated with first-line chemotherapy, the concomitant standard administration of cisplatin (on day 1, every 3 weeks) and cetuximab (on day 1, weekly), in combination with oral VPA given daily from day -14 with a titration strategy in each patient (target serum level of 50-100 µg/ml). Primary end point is the objective response rate measured according to Response Evaluation Criteria in Solid Tumors (RECIST). Sample size, calculated according to Simon 2 stage minimax design will include 21 patients in the first stage with upper limit for rejection being 8 responses, and 39 patients in the second stage, with upper limit for rejection being 18 responses. Secondary endpoints are time to progression, duration of response, overall survival, safety. Objectives of the translational study are the evaluation on tumor samples of markers of treatment efficacy/resistance (i.e. γH2AX, p21/WAF, RAD51, XRCC1, EGFR, p-EGFR, Ki-67) and specific markers of VPA HDAC inhibitory activity (histones and proteins acetylation, Histone deacetylase isoforms) as well as valproate test, histones and proteins acetylation of peripheral blood mononuclear cell, tested on blood samples at baseline and at different time points during treatment. DISCUSSION: Overall, this study could provide a less toxic and more effective first-line chemotherapy regimen in patients with recurrent/metastatic squamous cell carcinoma of the head and neck by demonstrating the feasibility and efficacy of cisplatin/cetuximab plus valproic acid. Moreover, correlative studies could help to identify responder patients, and will add insights in the mechanism of the synergistic interaction between these agents. EUDRACT NUMBER: 2014-001523-69 TRIAL REGISTRATION: ClinicalTrials.gov number, NCT02624128.

Follicular thyroid carcinoma with skull metastases.

Thyroid carcinoma with distant metastases at initial presentation, is uncommon. Skull metastases occur very rarely, with a reported incidence of 2.5-5.8%. Here we report two cases of follicular thyroid cancer with skull involvement, and describe the diagnostic and therapeutic approach to metastatic thyroid cancer. We present the cases of a 70-year-old female and a 74-year-old female who presented with painless, large slow-growing masses of the skull. The patients underwent surgical excision of the skull masses, which were histologically diagnosed as metastatic follicular thyroid cancer, and total thyroidectomy, which confirmed the diagnosis of follicular thyroid carcinoma. They were treated with radioiodine and suppressive levothyroxine, which achieved local control of the disease. Management of metastatic thyroid cancer, requires a multidisciplinary approach and multimodality treatment. Distant metastases should be surgically removed whenever possible. Initial aggressive treatment is crucial in the management of metastatic thyroid carcinoma, providing the best chance to prolong patient survival.

Integrating contrast-enhanced sonography in the follow-up algorithm of hepatocellular carcinoma treated with radiofrequency ablation: single cancer center experience.

BACKGROUND: Hepatocellular carcinoma (HCC) patients treated with percutaneous ablation require close follow-up for early detecting and treating tumor recurrence. PURPOSE: To illustrate our single-center prospective experience on using contrast-enhanced ultrasound (CEUS) as a follow-up tool alternated with computed tomography (CT). MATERIAL AND METHODS: In a 7-year period 588 patients with one to three HCCs were treated with radiofrequency ablation (alone or combined with ethanol injection). Patients with completely ablated tumors at 1-month CT scan were followed up serially, using alternated CEUS (one microbubbles injection per lobe) and CT every 3 months for 2 years. In few cases magnetic resonance imaging (MRI) was employed instead of or in addition to CT. The following patterns of recurrence were considered: A, enhancing tissue within the lesion; B, enhancing tissue adherent to the lesion; C, enhancing tissue within the same liver segment of the treated nodule; and D, enhancing tissue within a different segment. Patients with positive CEUS underwent confirmatory CT/MRI (standard reference). RESULTS: Median follow-up was 19 months. There were 221 recurrences. Three pattern A recurrences (2 detected by CEUS and 1 by CT), 86 pattern B recurrences (44 detected by CEUS and 42 by CT), 70 pattern C recurrences (32 detected by CEUS and 38 by CT), and 62 pattern D recurrences (23 detected by CEUS and 39 by CT). CT detected additional nodules in 16/101 patients with positive CEUS. CONCLUSION: CEUS follow-up of HCC patients after ablation is feasible. Since 72% recurrences develop in the same segment of the necrotic nodule, CEUS proves to be effective despite the minor visualization of the entire liver during the arterial phase when compared to CT and MRI. Including CEUS in patient follow-up may reduce the number of CT and MRI examinations.

Emergency radiology.

US has a relevant role in the initial assessment of non-traumatic emergencies of the abdomen, sometimes being conclusive and some other times for selecting the patients for further imaging with CT. Injection of a contrast medium may give to the radiologist additional information to that obtained at baseline US and Doppler examination, since real-time, contrast-enhanced US (CEUS) may allow observing findings in the abdomen not recognizable at baseline US or even at color Doppler imaging. Extravascular use of microbubbles may also be useful in clinical practice to rapidly solve a number of unclear aspects. CEUS has a number of distinct advantages in acute patients, including its quickness, low invasiveness, and its possible bedside use. The information based on contrast enhancement is useful for initial diagnosis, therapeutic decision making, and follow-up of the critically ill patients. The purpose of this review is to illustrate the possibilities and limitations of abdominal CEUS in the acute setting, with special emphasis on the detection and characterization of acute inflammatory processes, infarcts, and hemorrhages.

Immunological and biological changes during ipilimumab treatment and their potential correlation with clinical response and survival in patients with advanced melanoma.

BACKGROUND: Ipilimumab can induce durable disease control and long-term survival in patients with metastatic melanoma. Identification of a biomarker that correlates with clinical benefit and potentially provides an early marker of response is an active area of research. PATIENTS AND METHODS: Ipilimumab was available upon physician request for patients aged ≥16 years with stage III (unresectable) or IV cutaneous, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Tumour assessments were conducted at baseline, Week 12 and Week 24 using immune-related response criteria. Patients were monitored continuously for adverse events (AEs), including immune-related AEs. Candidate immunological markers were evaluated in peripheral blood and sera samples collected at baseline and Weeks 4, 7, 10 and 12. RESULTS: Among 95 patients treated with ipilimumab 3 mg/kg, the immune-related disease control rate at Week 24 was 38 %. With a median follow-up of 24 months, median overall survival was 9.6 months. Both disease control and survival were significantly associated with decreasing levels of lactate dehydrogenase, C-reactive protein and FoxP3/regulatory T cells, and increasing absolute lymphocyte count, between baseline and the end of dosing (Week 12). CONCLUSION: Ipilimumab is a feasible treatment option for heavily pretreated patients with metastatic melanoma. Changes in some immunological markers between baseline and the fourth ipilimumab infusion appear to be associated with disease control and survival, but verification in prospective clinical trials is required.

Free-hand ultrasound strain elastography in evaluation of soft tissue tumors.

OBJECTIVE: The purpose of this study is to evaluate elastography in a wide spectrum of soft tissue superficial lesions by correlating the elastographic characteristics of these lesions with the elastographic score (ES) system established by Asteria. METHODS: Forty patients with different superficial lesions of the soft tissues were studied, including lipomas, schwannomas, neuromas, epidermal inclusion cysts, "in transit" melanoma metastasis, arterio-venous malformation, and giant-cell tumor. An ultrasound examination was performed combined with color-Doppler and elastographic module. The B-mode criteria were echogenicity, margins, and structural homogeneity of the lesion. The color-Doppler criterion was irregular and mainly intra-nodular vascularization. ES 1-4 was attributed, in relation with the increasing tissue stiffness, according to the classification of Asteria adapted for soft tissues. Subsequently, we added to each single B-mode and color-Doppler criterion the ES 3 and 4, thus crossing two parameters of malignancy. All the presumptive diagnoses formulated were confirmed with the clinical data or with the histopathological result. RESULTS: The hypoechoic appearance had the best diagnostic performance. Sensitivity was 87%, specificity 71%, positive predictive value (PPV) 80%, negative predictive value (NPV) 80%, and diagnostic accuracy 80%. There was a good correlation with the clinical and biopsy data, the irregularity of margins the worst performance, the inhomogeneity an intermediate. Color-Doppler had sensitivity 74%, specificity 82%, PPV 85%, NPV 70% and diagnostic accuracy 77.5%. Elastography had sensitivity 87%, specificity 94%, PPV 95%, NPV 84%, and diagnostic accuracy 90%. The combination hypoechoic appearance + ES3/ES4 showed sensitivity 83%, specificity 100%, PPV 100%, NPV 81%,and diagnostic accuracy of 90%. The combination of irregularity of margins + ES3/ES4 showed sensitivity 43%, specificity 100%, PPV 100%, NPV 59%, and diagnostic accuracy of 67.5%. The combination of inhomogeneity of the lesion + ES3/ES4 showed sensitivity 65%, specificity 94%, PPV 94%, NPV 68%, and diagnostic accuracy of 78%. The combination of the color-Doppler with the ES3/ES4 showed sensitivity 69.5%, specificity 100%, PPV 100%, NPV 71%, and diagnostic accuracy of 82.5%.In the combined evaluation, there was a significant increase in specificity, allowing healthy subjects to be categorized as correctly negative, with a reduction in false positives which also translates into an increase in PPV. CONCLUSIONS: Elastography alone is not sufficient for a correct diagnostic classification and must be considered as an additional parameter in the study of soft-tissue lesions. Although there was a good agreement between B-mode malignancy criteria and ES3/ES4, there is no significant improvement in sensitivity. Ultrasound assessment, especially of superficial lesions, cannot be separated from an integrated approach that foresees the additional and routine use of the elastographic examination.

A rare case of De Garengeot hernia: CT findings.

We report a case of "De Garengeot's hernia" (DGH), a rare condition that occurs when the inflamed appendix is localized inside a femoral hernia. The appendix may be involved in inflammatory or necrotic processes and the treatment is emergency surgery. It is usually discovered by chance during surgery. It occurs in 0.5%-5% of all femoral hernias. In 0.08%-0.13% of cases, the appendix can present inflammatory or necrotic processes due to the narrowness of the neck of the femoral canal; in these cases, an emergency surgery is required through a no standard surgical procedure. In the other cases, it is usually found accidentally during surgical repair of the hernia or more rarely diagnosed preoperatively by CT. Therefore, the purpose of our study is to report a case of DGH describing CT main findings in order to improve the preoperative diagnosis.

Induction chemotherapy with docetaxel, cisplatin and capecitabine, followed by combined cetuximab and radiotherapy in patients with locally advanced inoperable squamous cell carcinoma of the head and neck: a phase I-II study.

OBJECTIVES: To replace 5-fluorouracil with capecitabine within a trial of induction chemotherapy followed by cetuximab plus radiotherapy (RT) in patients with locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN). Also, to replace cisplatin with cetuximab after induction chemotherapy. METHODS: Docetaxel and cisplatin were given at 75 mg/m(2), while capecitabine was initially given at 500 mg/m(2) twice a day and subsequently escalated. The maximum tolerated dose was used for the phase II study. RESULTS: Seven patients were enrolled. At dose level 1, two dose-limiting toxicities were observed in the first 4 patients (grade 4 neutropenia and grade 3 diarrhea). In both patients, capecitabine was withdrawn and toxicities resolved. Dose escalation was halted and a lower capecitabine dose (750 mg/m(2) daily) was selected. Two complete responses and five partial responses were observed after induction chemotherapy. Four patients were evaluable for response after cetuximab-RT (3 complete response and 1 partial response). CONCLUSION: Combined chemoradiotherapy is still the gold standard in LA SCCHN and no studies currently support the use of early induction chemotherapy. Our study did not contribute toward addressing this issue since it was discontinued early because of toxicity.

Spontaneously Ruptured Hepatocellular Carcinoma: Computed Tomography-Based Assessment.

Spontaneously ruptured hepatocellular carcinoma (SRHCC) is an uncommon and life-threatening complication in patients with hepatocellular carcinoma (HCC). It is usually associated with chronic liver disease and has a poor prognosis with a high mortality rate during the acute phase. SRHCC can cause a severe and urgent condition of acute abdomen disease and requires a correct diagnosis to achieve adequate treatment. Clinical presentation is related to the presence of hemoperitoneum, and abdominal pain is the most common symptom (66-100% of cases). Although the treatment approach is not unique, trans-arterial (chemo)embolization (TAE/TACE) followed by staged hepatectomy has shown better results in long-term survival. A multi-phase contrast-enhanced CT (CECT) scan is a pivotal technique in the diagnosis of SRHCC due to its diagnostic accuracy and optimal temporal resolution. The correct interpretation of the main CT findings in SRHCC, such as active contrast extravasation and the sentinel clot sign, is fundamental for a prompt and correct diagnosis. Furthermore, CT also plays a role as a post-operative control procedure, especially in patients treated with TAE/TACE. Therefore, a multi-phase CECT scan should be the diagnostic tool of choice in SRHCC since it suggests an immediate need for treatment with a consequent improvement in prognosis.

Complications of biliary and gastrointestinal stents: MDCT of the cancer patient.

OBJECTIVE: The goal of this article is to discuss and show the common complications of biliary and gastrointestinal stents as depicted by MDCT in cancer patients. Major complications include stent misplacement or displacement, bleeding, obstruction, perforation, stent fracture or collapse, and infection. This topic encompasses several relevant issues, including interpretative difficulties, therapeutic decisions, and potential malpractice concerns. CONCLUSION: Awareness and methodical assessment of stents could allow detection of stenting complications, potentially sparing the patient from associated morbidity and mortality.

Multidetector Computed Tomography (MDCT) Findings of Complications of Acute Cholecystitis. A Pictorial Essay.

Acute cholecystitis stands out as one of the most common surgical pathologies that should always be considered in a right-upper abdominal pain emergency. For this, the importance of a correct diagnosis is well described. However, it has been demonstrated that the simple combination of clinical (pain, Murphy's sign) and laboratory (leukocytosis) parameters alone does not provide for ruling in or ruling out the diagnosis of this condition, unless accompanied by a radiological exam. For a long time, and still today, ultrasonography (US) is by far the first-to-proceed radiologic exam to perform, thanks to its rapidity and very high sensibility and specificity for the diagnosis of simple acute cholecystitis. However, acute cholecystitis can undergo some complications that US struggles to find. In addition to that, studies suggest that multidetector computed tomography (MDCT) is superior in showing complicated forms of cholecystitis in relation to sensibility and specificity and for its capability of reformatting multiplanar (MPR) reconstructions that give a more detailed view of complications. They have shown to be useful for a precise evaluation of vascular complications, the anatomy of the biliary tree, and the extension of inflammation to surrounding structures (i.e., colitis). Therefore, based also on our experience, in patients with atypical presentation, or in cases with high suspicion for a complicated form, a MDCT abdomen scan is performed. In this review, the principal findings are listed and described to create a CT classification of acute complications based on anatomical and topographic criteria.

Imaging Assessment of Interval Metastasis from Melanoma.

Interval metastasis is a particular metastatic category of metastatic localizations in the lymph nodes in patients with melanoma. Interval nodes are generally located at nonregional lymphatic stations placed along the pathway of the spread of melanoma, such as the epitrochlear lymph node station, the popliteal fossa, and the retroareolar station. Imaging techniques for evaluation of patients with interval metastasis from melanoma diseases include ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), lymphoscintigraphy (LS), and positron emission tomography (PET). A literature review was conducted through a methodical search on the Pubmed and Embase databases. The evaluation of lymph node metastases represents a critical phase in the staging and follow-up of melanoma patients. Therefore, a thorough knowledge of the imaging methods available and the interactions between the clinician and the radiologist are essential for making the correct choice for individual patients, for a better management, and to improve treatment and survival.

Previously reported sonographic appearances of regional melanoma metastases are not likely due to necrosis.

OBJECTIVES: Sonography has proven to be a reliable tool in early detection of lymph node and in-transit cutaneous-subcutaneous metastases. Those metastases normally appear as hypoechoic or even anechoic lesions on sonography. It has been assumed that this appearance is due to necrosis of the lesions, but so far, that assumption has never been proven. The purpose of this retrospective study was to evaluate whether the hypoechoic appearance of melanoma metastasis is really due to tumor necrosis. METHODS: From a radiographic database, we retrieved 212 melanoma cases imaged with sonography over a 2-year period for disease staging or follow-up. We selected 37 positive cases with 84 nodal and extranodal (satellite and in-transit) metastatic lesions and reviewed the sonograms and pathologic slides (slides available for 40 of 84 lesions). We retrospectively assessed the vascularization pattern (color Doppler images available for 78 of 84 lesions), categorizing it as poor, intermediate, or consistent. We also looked for necrosis on the histopathologic material, categorizing it into scores of 0, 1, 2, and 3 for absence of necrosis, less than 20% necrosis, 20% to 40% necrosis, and greater than 40% necrosis, respectively. RESULTS: Despite their gray scale appearance, most melanoma lesions were vascularized on color Doppler imaging and showed limited necrosis at histopathologic analysis. Consistent vascularization on Doppler imaging, excluding substantial necrosis, was found in 44 of 78 lesions (56.4%). Poor vascularization on Doppler imaging, suggesting necrosis, was present in only 14% of the lesions. Substantial necrosis (scores of 2 and 3) was found pathologically in only 10% of the lesions. CONCLUSIONS: Necrosis seems to be an uncommon event in melanoma metastasis and is probably not the basis for its low-level echo pattern on sonography. The hypoechoic appearance is very typical of melanoma metastasis and is likely due to massive melanomatous infiltration (with the poor echo reflectivity of melanin). However, confirmation in larger pathologically proven series is required.

Kinase-inhibitors for iodine-refractory differentiated thyroid cancer: still far from a structured therapeutic algorithm.

The kinase-inhibitors (KIs) sorafenib and lenvatinib demonstrated efficacy in iodine-refractory DTC upon phase III studies. However, evidence allowing a punctual balance of benefits and risks is poor. Furthermore, the lack of a direct comparison hampers to establish the proper sequence of administration. However, some insights may provided: a) indirect comparison between phase III trials showed milder toxicity for sorafenib, which should be preferred in case of cardiovascular comorbidities; b) prospective evidence of efficacy in KIs pre-treated patients is available only for lenvatinib, which should be used as second-line. Promising activity was found for the majority of other tested KIs, but no placebo-controlled trials are available. Emerging, but still early, frontiers include the restoration of iodine-sensitivity and the selective activity on pathogenic mutations. In conclusion, the use of KIs in iodine-refractory DTC is far from a structured therapeutic algorithm.

Management of HPV-Related Squamous Cell Carcinoma of the Head and Neck: Pitfalls and Caveat.

: Head and neck squamous cell carcinomas (HNSCCs) are a very heterogeneous group of malignancies arising from the upper aerodigestive tract. They show different clinical behaviors depending on their origin site and genetics. Several data support the existence of at least two genetically different types of HNSCC, one virus-related and the other alcohol and/or tobacco and oral trauma-related, which show both clinical and biological opposite features. In fact, human papillomavirus (HPV)-related HNSCCs, which are mainly located in the oropharynx, are characterized by better prognosis and response to therapies when compared to HPV-negative HNSCCs. Interestingly, virus-related HNSCC has shown a better response to conservative (nonsurgical) treatments and immunotherapy, opening questions about the possibility to perform a pretherapy assessment which could totally guide the treatment strategy. In this review, we summarize molecular differences and similarities between HPV-positive and HPV-negative HNSCC, highlighting their impact on clinical behavior and on therapeutic strategies.