Multimodality imaging features of desmoid tumors: a head-to-toe spectrum.

Desmoid tumors (DTs) are a rare and biologically heterogeneous group of locally aggressive fibroblastic neoplasm: their biological behavior spectrum ranges from indolent to aggressive tumors. DTs are classified as intra-abdominal, extra-abdominal, and within the abdominal wall lesions.It is well known that abdominal and extra-abdominal DTs are associated with familial adenomatous polyposis (FAP) and Gardner syndrome. Possible risk factors are prior trauma/surgery, pregnancy, and oral contraceptives.There was a real revolution in the management of DT: from aggressive first-line approach (surgery and radiation therapy) to a more conservative one (systemic treatment and "wait-and-see policy").In these clinical settings, radiologists play an important role for assessing lesion resectability, evaluating recurrence, monitoring the biological behavior if an expectant management is chosen, and assessing response to systemic treatment as well as to radiation therapy.Awareness of common locations, risk factors, and imaging features is fundamental for a correct diagnosis and an adequate patient management.

Effects of miRNA-15 and miRNA-16 expression replacement in chronic lymphocytic leukemia: implication for therapy.

Chronic lymphocytic leukemia (CLL) clones are characterized by loss of a critical region in 13q14.3, (del(13)(q14)) involving the microRNA (miRNA) cluster miR-15a and miR-16-1. We have investigated the effects of replacement of miR-15a and miR-16-1. CLL cells transfected with these miRNA mimics exhibited a decrease in cell viability in vitro and impaired capacity for engraftment and growth in NOD/Shi-scid,γcnull (NSG) mice. No synergistic effects were observed when the two miRNA mimics were combined. The phenomena were not restricted to CLL with the del(13)(q14) lesion. Similar effects induced by miRNA mimics were seen in cells with additional chromosomal abnormalities with the exception of certain CLL clones harboring TP53 alterations. Administration of miRNA mimics to NSG mice previously engrafted with CLL clones resulted in substantial tumor regression. CLL cell transfection with miR-15a and miR-16-1-specific inhibitors resulted in increased cell viability in vitro and in an enhanced capacity of the engrafted cells to grow in NSG mice generating larger splenic nodules. These data demonstrate that the strong control by miR-15a and miR-16-1 on CLL clonal expansion is exerted also at the level of full-blown leukemia and provide indications for a miRNA-based therapeutic strategy.

Brachial plexus assessment with three-dimensional isotropic resolution fast spin echo MRI: comparison with conventional MRI at 3.0 T.

OBJECTIVE: The purpose of our study was to determine whether a three-dimensional (3D) isotropic resolution fast spin echo sequence (FSE-cube) has similar image quality and diagnostic performance to a routine MRI protocol for brachial plexus evaluation in volunteers and symptomatic patients at 3.0 T. Institutional review board approval and written informed consent were guaranteed. METHODS: In this prospective study FSE-cube was added to the standard brachial plexus examination protocol in eight patients (mean age, 50.2 years) with brachial plexus pathologies and in six volunteers (mean age, 54 years). Nerve visibility, tissue contrast, edge sharpness, image blurring, motion artefact and acquisition time were calculated for FSE-cube sequences and for the standard protocol on a standardised five-point scale. The visibility of brachial plexus nerve and surrounding tissues at four levels (roots, interscalene area, costoclavicular space and axillary level) was assessed. RESULTS: Image quality and nerve visibility did not significantly differ between FSE-cube and the standard protocol (p>0.05). Acquisition time was statistically and clinically significantly shorter with FSE-cube (p<0.05). Pathological findings were seen equally well with FSE-cube and the standard protocol. CONCLUSION: 3D FSE-cube provided similar image quality in a shorter acquisition time and enabled excellent visualisation of brachial plexus anatomy and pathology in any orientation, regardless of the original scanning plane.

Magnetic resonance imaging at 1.5 T with immunospecific contrast agent in vitro and in vivo in a xenotransplant model.

OBJECT: Demonstrating the feasibility of magnetic resonance imaging (MRI) at 1.5 T of ultrasmall particle iron oxide (USPIO)-antibody bound to tumor cells in vitro and in a murine xenotransplant model. METHODS: Human D430B cells or Raji Burkitt lymphoma cells were incubated in vitro with different amounts of commercially available USPIO-anti-CD20 antibodies and cell pellets were stratified in a test tube. For in vivo studies, D430B cells and Raji lymphoma cells were inoculated subcutaneously in immunodeficient mice. MRI at 1.5 T was performed with T1-weighted three-dimensional fast field echo sequences (17/4.6/13 degrees ) and T2-weighted three-dimensional fast-field echo sequences (50/12/7 degrees ). For in vivo studies MRI was performed before and 24 h after USPIO-anti-CD20 administration. RESULTS: USPIO-anti-CD20-treated D430B cells, showed a dose-dependent decrease in signal intensity (SI) on T2*-weighted images and SI enhancement on T1-weighted images in vitro. Raji cells showed lower SI changes, in accordance to the fivefold lower expression of CD20 on Raji with respect to D430B cells. In vivo 24 h after USPIO-anti-CD20 administration, both tumors showed an inhomogeneous decrease of SI on T2*-weighted images and SI enhancement on T1-weighted images. CONCLUSIONS: MRI at 1.5 T is able to detect USPIO-antibody conjugates targeting a tumor-associated antigen in vitro and in vivo.

Characterization of adrenal adenomas and metastases: correlation between unenhanced computed tomography and chemical shift magnetic resonance imaging.

PURPOSE: To evaluate the correlation of absolute attenuation values of unenhanced computed tomography (CT) with signal intensity (SI) quantitative analysis on chemical shift (CS) magnetic resonance (MR) imaging in differentiating adrenal adenomas from metastases. MATERIAL AND METHODS: Forty-one adrenal masses (27 adenomas, 14 metastases) were studied with CS MR imaging and unenhanced CT. MR included T1-weighted breathhold gradient-echo in-phase (IP) and opposed-phase (OP) sequences. The SI index (SI-i) [(SIIP-SIOP/SIIP)] x 100% and chemical-shift ratio (CS-r) relative to the spleen [(SIlesion/ SIspleen)OP/(SIlesion/SIspleen)IP] were calculated for each lesion. CT absolute attenuation values were also determined. RESULTS: The mean attenuation value of metastases was significantly greater than that of adenomas (< 0.0001). On MR, the mean SI-i of adenomas was significantly greater than that of metastases (P < 0.0001) and no overlaps were evident. The CS-r of malignant and benign lesions overlapped considerably, and five adenomas (all with indeterminate Hounsfield Unit values at CT) were misclassified as potentially malignant. CT attenuation values were significantly correlated with both MR quantitative analyses. CONCLUSION: Since CS MR imaging and CT both depict the presence of lipids within adrenal lesions, absolute attenuation values are highly correlated with MR quantitative analysis. SI-i is the most reliable tool for differentiating adrenal adenomas from metastases, showing better accuracy than lesion-to-spleen CS-r, in particular for adenomas with indeterminate absolute attenuation values.

Inadequacy of the new Response Evaluation Criteria in Solid Tumors (RECIST) in patients with malignant pleural mesothelioma: report of four cases.

Unidimensional Response Evaluation Criteria in Solid Tumor (RECIST) has been recently proposed in the attempt to simplify the standardized bidimensional World Health Organization (WHO) criteria. The complete accord between these two measurement systems was established in a large comparative study [J. Natl. Cancer Inst. 92(3) (2000) 205] that demonstrated the validity and the good performance of RECIST criteria. We report four cases of inadequacy of RECIST criteria in the evaluation of response to chemotherapy in patients with malignant pleural mesothelioma. These four patients were enrolled in two consecutive multicenter phase II clinical trials investigating the activity of a novel chemotherapy regimen in advanced pleural mesothelioma. They were judged as having an objective response to chemotherapy according to WHO criteria. Reassessed according to both methods, we found that results obtained with RECIST criteria do not correspond to WHO underestimating response to chemotherapy. Our data raise doubts about the applicability of unidimensional RECIST response criteria to mesothelioma and, possibly, to any tumor involving the chest wall.

Calcific tendinitis of the rotator cuff as a cause of drooping shoulder.

We describe a case of inferior glenohumeral subluxation or drooping shoulder secondary to acute calcific tendinitis of the rotator cuff. The various etiologies of drooping shoulder and the specific causes determining glenohumeral widening in our report are discussed. The importance in recognizing this uncommon complication of a common abnormal finding and correction by aspiration is stressed.

Gemcitabine, Ifosfamide and Navelbine (GIN): activity and safety of a non-platinum-based triplet in advanced non-small-cell lung cancer (NSCLC).

To evaluate activity and toxicity of a non platinum-based triplet including Gemcitabine, Ifosfamide and Navelbine (GIN) in advanced NSCLC. Stage IIIB/IV NSCLC patients with WHO PS < 2 and bidimensionally measurable disease entered the study. Gemcitabine 1000 mg/sqm day 1 and 1000-800 mg/sqm day 4, Ifosfamide 3 g/sqm day 1 (with Mesna), Navelbine 25 mg/sqm day 1 and 25-20 mg/sqm day 4 were administered intravenously every 3 weeks. Objective responses (ORs) were evaluated every 2 courses: a maximum of 6 courses were administered in responding patients. According to Simon's optimal two-stage design more than 18 ORs out of 54 patients were required to establish the activity of this regimen. Fifty patients entered the study. Main characteristics of the 48 evaluated patients were: median age 63 years, ECOG performance status 0 = 65%, stage IV disease 79% and non-squamous histology 71%. The total number of courses administered was 200, median per patient 4 (range 1-6). Toxicities were evaluated according to WHO criteria: neutropenia grade 3-4 occurred in 47% of the courses; thrombocytopenia grade 3-4 in 6.6%; anaemia grade 3 in 3.5%. Twelve episodes of febrile neutropenia were reported and three patients required hospital admission. No toxic death was reported. Non-haematological toxicity, including skin rash, alopecia and fatigue, were generally. Twenty-five ORs (1 complete response and 24 partial responses) were obtained for a response rate of 52% (95% CI: 37.4-66.5%). One-year survival was 46.5%. This non-platinum-based outpatient triplet showed promising activity against NSCLC with myelosuppression, in particular neutropenia, being dose-limiting. The GIN regimen may represent a valuable alternative to standard platinum-based doublets and triplets in the treatment of advanced NSCLC and further studies with this platinum-free combination are warranted.

[Combined multimodal treatment for liver and lung metastasis from colorectal cancer: a new therapeutic option?]. / Il trattamento multimodale combinato delle metastasi epatiche e polmonari da cancro colorettale: una nuova opzione terapeutica?

The authors analyse which therapeutic strategy to adopt on the basis of prognostic factors and staging of hepatic and pulmonary metastases from colorectal cancer. They underline the effectiveness of combined multimodal therapy in the treatment of very advanced metastatic stages. 218 patients with metastases from colorectal cancer (12 pulmonary and 206 hepatic metastases) were treated from January 1980 to October 2000. Among these patients, 159 underwent surgery (4 pulmonary and 155 hepatic resections), 16 were reoperated on for metastatic relapse, 14 with multiple metastases underwent locoregional therapy and 29, deemed unresectable initially, were treated with neoadjuvant chemo- and radiotherapy. In the operated patient group the 5-year actuarial survival rate was 22% with an operative mortality of 3.8% and a morbidity of 17.5%. The 16 patients reoperated on for metastatic relapse had a 5-year actuarial survival of 21% with an operative mortality of 6.2% and a morbidity of 15.8%. The 14 patients treated with locoregional therapy had a median survival of 6 months whereas the 29 patients treated in two different periods with combined multimodal treatment had a response rate of 59.2%. Five patients had a complete response and 4 are currently disease-free. Surgical resection is at present the best known treatment for metastatic disease. In very advanced, as yet undisseminated stages, in which there is no surgical indication for metastases a neoadjuvant treatment is proposed if the primary tumour has already been completely resected. The aim of this therapeutic strategy, called combined multimodal therapy, is to obtain the disease regression with the aid of systemic chemo- and radiotherapy and to offer a chance of re-staging the disease.

Role of ultrasonography in the staging of gastrointestinal neoplasms.

This article reviews the capabilities and limits of ultrasonography (US) in the staging of gastrointestinal neoplasms. US is a well-established tool in the investigation of abdominal diseases. Its role is very important in the first approach to liver, gallbladder, biliary, and pancreatic diseases, but its abilities for accurate staging may be limited by various factors, which will be discussed. In the evaluation of the stomach and intestine, US is rarely utilized, but it can occasionally demonstrate an unsuspected gastrointestinal mass that usually must be evaluated further with specific techniques (endoscopy and barium studies) to confirm the diagnosis and to perform an accurate staging (with endosonography and computed tomography).

Dose-intensive first-line chemotherapy with epirubicin and continuous infusion ifosfamide in adult patients with advanced soft tissue sarcomas: a phase II study.

This phase II study was designed to verify the activity and safety of an intensive epirubicin/ifosfamide schedule in untreated soft tissue sarcoma (STS) patients by using both the agents at the identified maximal tolerated doses. 39 adult patients were treated with epirubicin at 55 mg/m2, on days 1 and 2 (total dose per cycle 110 mg/m2) combined with ifosfamide at 2.5 g/m2 days 1-4 (total dose per cycle 10 g/m2), with equidose mesna uroprotection and G-CSF support. Treatment was given on an ambulatory basis, at 3-week intervals. The overall objective response (OR) rate was 59% (95% confidence interval, CI, 43-72%), with 5 complete responses (13%) at 18 partial responses (46%); 12 partial responders were rendered disease-free following surgery. The median survival time was 19 months, being 23 and 13 months, respectively, for responding and non-responding patients. The median time to response was 40 days (range 21-60). Treatment-related toxicity was overall acceptable. The OR of 59% was the highest ever reported in our consecutive studies in advanced STS, confirming that improved therapeutic efficacy can be obtained with intensified regimens in such a disease; both the response duration and survival were also longer. The observed activity proved to be interesting with regard to the high response rate in the lung (86%), as well as the proportion of patients rendered disease-free by early surgery after the achievement of a partial response (55%). Both these findings may be important in the multimodality approach to patients with lesions potentially resectable for cure.

Case report: isolated neurofibrosarcoma of the liver: US, CT and MR findings.

Neurofibrosarcomas are rare neoplasms usually associated with von Recklinghausen's disease. In this paper we describe ultrasound (US), computed tomography (CT) and magnetic resonance (MR) appearances of an unusual isolated neurofibrosarcoma of the liver.

Normal prostate gland: examination with color Doppler US.

PURPOSE: To evaluate the vascular anatomy of the prostate gland with transrectal color Doppler ultrasound (US). MATERIALS AND METHODS: Thirty-five normal prostate glands were studied. Imaging findings were interpreted on the basis of findings from previous anatomic studies. RESULTS: Distribution of flow signals within the gland was differentiated into two parenchymal groups of arteries, urethral and capsular. The urethral group entered the prostate at the bladder neck and sent forth branches to supply the periurethral zone and the inner portion of the gland. The capsular group coursed along the anterolateral surface of the prostate and sent forth perforating branches to the outer portion of the gland. Intraprostatic venous signals were seen mainly within the periurethral zone. CONCLUSION: Transrectal color Doppler US can depict the vascular anatomy of the prostate gland. Knowledge of the normal vascular appearance of the gland should aid in the differentiation of normal from abnormal findings.

Staging of hilar cholangiocarcinoma with ultrasound.

The preoperative assessment of the extent of biliary and vascular involvement by hilar cholangiocarcinoma is clinically important because resectability may be limited by tumor extension along the bile ducts into the hepatic parenchyma or to the adjacent hilar vessels. Thirty-five patients with hilar cholangiocarcinoma were studied with ultrasound, and the results were compared with operative findings and other diagnostic modalities. The level of intrahepatic biliary obstruction was determined in 100% of patients with ductal ectasia, and a tumor mass was shown in 37.1%. Imaging and Doppler ultrasound proved accurate in detecting the neoplastic involvement of the portal vein. Both correctly diagnosed portal occlusion and wall infiltration in 4 of 4 and 15 of 18 (83%) patients, respectively, without any false-positives. On the contrary, imaging ultrasound had poor sensitivity in detecting infiltration of the hepatic artery (43%) and metastases in regional lymph nodes (37%), liver (66%), and peritoneum (33%). In conclusion, ultrasound may be valuable in the preoperative staging of hilar cholangiocarcinoma, specially in predicting ductal and portal involvement.

Klatskin tumour: radical and palliative treatment.

Primitive neoplasms of proximal extrahepatic bile ducts keep their peculiar morphological and spreading patterns, as firstly described by J. Klatskin. Diagnostic and therapeutic approach were modified in the last year, on the basis of technological progress in imaging and more aggressive surgical attitude. Authors reviewed their clinical experience from 1970 to 1995 concerning proximal extrahepatic bile ducts tumors management, mainly evaluating the evolution of diagnostic work-up and the role of resection. Preoperative work-up is now trimed to non invasive techniques, in order to evaluate the intra and extra biliary diffusion; PTC-PTBD performed preoperatively give a clear biliary map, and could be the first step of a palliative definitive treatment in case of non operable patients. Radical resection remains the gold standard of therapy, with the best long-term results. Palliation must be obtained by the easiest comfortable method for the patient (i.e. self-blocking percutaneously inserted endoprosthesis).

[Evaluation of rheumatoid arthritis of the knee with Doppler color]. / Valutazione dell'artrite reumatoide del ginocchio con color Doppler.

Color-Doppler US was used to study the vascularization of the synovial membrane and of the periarticular tissues of the knee in 14 normal subjects and 15 patients with active rheumatoid arthritis. The normal subjects exhibited few spot signals within the connectival spaces surrounding the knee and adjacent to the femoral condyles and to the tibial plates. The signals were mostly arterial and impedance was high because of the absence of inversion of diastole. A hypervascular pattern was detected in 13/15 patients with rheumatoid arthritis as a result of hyperemia associated with inflammation and synovial neoangiogenesis. In these patients, the signals came mostly from the synovial pannus and the soft tissues surrounding the joint. Spectral analysis detected both venous and arterial waveforms with lower resistance than normal (resistive index ranging 0.65 to 0.76). After local treatment, both venous and low-impedance arterial signals were no longer detectable in 4/9 patients with clinical remission. In conclusion, color-Doppler US can support gray-scale US in the assessment of joint inflammation in rheumatoid arthritis patients. Vascular findings seem to correlate well with local symptoms. Color-Doppler US could make a useful tool for monitoring the clinical activity of the disease in selected joints.

Case report: US detection of tendinous metastasis from malignant melanoma.

The introduction of high frequency transducers has considerably improved the application of US in the study of musculo-tendinous diseases. We report a rare case of tendinous metastasis from malignant melanoma. The tumour (high karyokinetic index, Clark level IV) arose 4 years earlier in the dorsal region. The patient was admitted for pain in the left knee. A nodular hypoechoic lesion, 0.8 cm in diameter, poorly marginated, located in the subcutaneous tissue and involving the patellar tendon was identified with ultrasound. Histological examination confirmed the diagnosis.