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Purpose:To assess whether the combination of letrozole, metronomic cyclophosphamide and sorafenib (LCS) is well tolerated and shows activity in primary breast cancer (BC).Methods:Thirteen oestrogen receptor-positive, postmenopausal, T2-4, N0-1 BC patients received the LCS combination for 6 months. In these patients we examined the pharmacokinetics of sorafenib and cyclophosphamide, toxicity of the regimen, the clinical response to therapy and changes in the levels of biologically relevant biomarkers.Results:Adequate plasma concentrations of sorafenib were achieved in patients when it was dosed in combination with L+C. The mean plasma concentrations of C were consistently lower following administration of LCS, compared with administration of L+C only. The most common drug-related grade 3/4 adverse events were skin rash (69.3%), hand-foot skin reaction (69.3%) and diarrhoea (46.1%). According to RECIST Criteria, a clinical complete response was observed in 6 of 13 patients. A significant reduction in tumour size, evaluated with MRI, was also observed between baseline and 14 days of treatment in all 13 patients (P=0.005). A significant reduction in SUV uptake, measured by 18FDG-PET/CT, was observed in all patients between baseline and 30 days of treatment (P=0.015) and between baseline and definitive surgery (P=0.0002). Using modified CT Criteria, a response was demonstrated in 8 out of 10 evaluable patients at 30 days and in 11 out of 13 evaluable patients at the definitive surgery. A significant reduction in Ki67 expression was observed in all patients at day 14 compared with baseline (P<0.00001) and in 9 out of 13 patients at the definitive surgery compared with baseline (P<0.03). There was also a significant suppression of CD31 and VEGF-A expression in response to treatment (P=0.01 and P=0.007, respectively).Conclusions:The LCS combination is feasible and tolerable. The tumour response and target biomarker modulation indicate that the combination is clinically and biologically active. [ABSTRACT FROM AUTHOR]

Background:Although Trastuzumab has improved survival of HER2+ breast cancer patients, resistance to the agent pre-exists or develops through the course of therapy. Here we show that a specific metabolism and autophagy-related cancer cell phenotype relates to resistance of HER2+ breast cancer to Trastuzumab and chemotherapy.Methods:Twenty-eight patients with locally advanced primary breast cancer were prospectively scheduled to received one cycle of Trastuzumab followed by a new biopsy on day 21, followed by taxol/Trastuzumab chemotherapy for four cycles before surgery. FDG PET/CT scan was used to monitor tumour response. Tissue samples were immunohistochemically analysed for metabolism and autophagy markers.Results:In pre-Trastuzumab biopsies, the LC3A+/HER2+ cell population was correlated with HIF1α expression (P=0.01), while GLUT1 and LC3B expression were correlated with Ki67 proliferation index (P=0.01 and P=0.01, respectively). FDG PET tumour dimensions before therapy were correlated with LC3B expression (P=0.005). Administration of Trastuzumab significantly reduced clinical and PET-detected tumour dimensions (P<0.01). An inverse association of tumour response with the percentage of cells expressing HIF1α at baseline was documented (P=0.01). Administration of Trastuzumab resulted in a decrease of the proliferation index (P=0.004), GLUT1 (P=0.04) and HER2 (P=0.01) expression. In contrast, the percentage of LC3A+/HER2+ cells was increased (P=0.01). High baseline HIF1α expression was the only parameter associated with poorer pathological response to preoperative chemotherapy (P=0.001).Conclusions:As the HER2+/LC3A+ phenotype, which often overexpresses HIF1α, is a major subpopulation increasing after therapy with Trastuzumab, LC3A- and HIF1α-targeting therapies should be investigated for the augmentation of anti-HER2 therapy efficacy. [ABSTRACT FROM AUTHOR]

The criteria to define therapeutic response in oncology are those proposed by Miller, characterized by four response categories (complete response, partial response, no change, progression of disease), and based upon both measurable and non-measurable (and otherwise assessable) morphological parameters in comparison with baseline and subsequently modified following the Response Evaluation Criteria In Solid Tumors. In addition to these classical morphological criteria, we review the predictive value of structural changes in the evaluation of response to antineoplastic therapies. The goal of the present review is to evaluate in detail structural variations (calcification, fibrosis, differentiation, necrosis, cavitation, vascularization, edema, and pseudocapsule formation) induced by therapy, and to ascertain their significance in terms of biological evolution of the neoplastic process. [ABSTRACT FROM AUTHOR]

Hemangiosarcomas of the adrenal gland, both benign and malignant, are exceedingly rare; only a dozen of them have been reported in literature to our knowledge. We describe herein the findings at CT of 2 primary hemangiosarcomas of the adrenal glands. We also discuss their etiology, incidence, and differential diagnosis, particularly in relation to more frequent primary adrenal lesions, such as adrenal adenomas and carcinomas. CT will generally show a heterogeneous mass with frequent necrosis, contrast-enhancement, and occasional calcifications. A prospective diagnosis cannot be made by imaging alone, and pathology represents the discriminating method for a correct diagnosis. [ABSTRACT FROM AUTHOR]

We report the CT appearance of pancreatic metastases and describe their features in relation to the originating primary tumor. We also discuss some limitations in their differential diagnosis and report some theories explaining the pathogenesis of their occurrence. A total of 20 cases (9 males and 11 females) of pancreatic metastases were diagnosed at staging or follow-up of oncologic patients. All patients were evaluated with CT before and after contrast medium administration and had subsequent pathologic confirmation. In 1 case metastases were located solely in the pancreas; in 6 there was only another metastatic location, and in the remaining 13 there was diffuse spread throughout the body. Two of our patients exhibited a multinodular metastatic involvement of the pancreas, 11 had a solitary nodule or mass, and the remaining 7 had a diffusely enlarged pancreas, without any signs of focal disease. All but one of the solitary lesions measured more than 4 cm. In 2 cases a metachronous malignancy was detected at follow-up. Primary malignancies were located: 6 in the lungs, 2 on the skin (melanomas), 3 in breasts, 2 in the ovaries, 3 in the colon, 1 in the stomach, 2 in the kidney, and 1 the thyroid. Our findings confirm the existence of three patterns of metastatization to the pancreas: large solitary masses, multinodular lesions, and diffuse enlargement of the pancreas without focal signs at CT. In contrast to other studies, the large solitary lesion was our most frequent encounter, therefore making differential diagnosis vs primary cancer difficult. Metastases tended to repeat the imaging pattern of the primary. Nevertheless, we wrongly diagnosed pancreatitis due to a small nondetected metastasis, pseudo-cystic mass as a mucinous cystadenocarcinoma, conglomerate of peripancreatic lymph nodes, and a solitary pancreatic mass diagnosed as primary pancreatic cancer. Thus, when faced with a solitary pancreatic lesion at follow-up, histologic diagnosis is strongly recommended. In 2 cases changes in aspect and size were related to therapy. [ABSTRACT FROM AUTHOR]

Although the etiopathogenetic correlation between AIDS and malignant neoplasm still remains controversial, a number of miscellaneous malignancies have been reported in patients with HIV infection. For Kaposi's sarcoma, B-cell non-Hodgkin's lymphoma and carcinoma of the uterine cervix alternatively a concurrent oncoviral infection or dysregulation of cellular growth have been advocated. For all the remaining neoplasms, besides their increased occurrence in other forms of immunodeficiency, we can only speculate a similar pathogenetic origin in consideration of their more aggressive biological behaviour and younger age of occurrence. Our goal is to report the imaging findings of the most frequent HIV-related malignant neoplasms and outline them in relation to their atypical biological and structural behaviour. It is our opinion that a careful evaluation of clinical history and status is mandatory for the proper diagnosis and staging in such pathologies. We also review the current etiopathogenetic theories that attempt to link these two deadly pathologies. [ABSTRACT FROM AUTHOR]

Primary hepatic leiomyosarcomas are exceedingly rare tumors. To the best of our knowledge, only 17 cases have been reported in literature. We report the computed tomographic findings of two cases of primary location in the liver. We also discuss the differential diagnosis of such lesions. [ABSTRACT FROM AUTHOR]

Primary effusion lymphomas represent an unusual subset of AIDS-related non-Hodgkin's lymphomas. They are associated with herpes virus 8 and Epstein-Barr virus and characterized by predominant involvement of the serous body cavities (pleura, pericardium, peritoneum) as lymphomatous effusion without any identifiable tumour mass. We report herein CT findings in two patients with primary effusion lymphoma emphasizing the possible neoplastic nature of a pleural effusion in a patient with AIDS. [ABSTRACT FROM AUTHOR]

Peliosis hepatis is an uncommon benign disorder characterized by blood-filled cavities within the liver. We describe the sonographic, computed tomographic, and magnetic resonance appearance of a patient affected by peliosis hepatis with pseudotumoral and hemorrhagic evolution and direct demonstration of the ectatic vascular components. [ABSTRACT FROM AUTHOR]

A patient with neurofibromatosis type 1 was found to have an enhancing mass in the hypothalamus and in the anterior optic pathway. A 3-month MR study showed a reduction in the size and enhancement of the mass. At a 9-month MR follow-up the mass disappeared and ceased to enhance. This report shows the unusual behaviour of a hypothalamic/chiasmatic mass confirming that in such asymptomatic cases the conservative management can be considered the treatment of choice. [ABSTRACT FROM AUTHOR]

The differential diagnosis of renal masses containing fatty foci is limited to a small number of well-defined tumors, angiomyolipoma being the most frequent. In recent years clear cell carcinomas with intratumoral fatty foci have been reported, due to either entrapment of local fat or to regressive adipose metaplasia. Demonstration of focal calcifications is a valuable sign, being relatively common in carcinomas while rare in more benign lesions. We report a case of a foreign-body granuloma of the kidney, containing both calcifications and foci of fat. The value of this case, in our opinion, is that it demonstrates that detection of the previously mentioned features in a renal mass does not necessarily imply a presumptive diagnosis of renal cell carcinoma. [ABSTRACT FROM AUTHOR]

Detection of fat within an adrenal primary mass is virtually pathognomonic of myelolipoma, and in most cases such a diagnosis excludes any further diagnostic and therapeutic approaches. We report our findings, with computed tomography (CT) and magnetic resonance (MR), of the first, to our knowledge, pathologically proven case of fat tissue within an adrenal cortical carcinoma. We also discuss the possible origin of fat within such malignancies and the potential diagnostic dilemmas it might cause. [ABSTRACT FROM AUTHOR]

Computed tomographic (CT) appearance of two cases of gastric metastases from retroperitoneal leiomyosarcoma are reported. In both cases tumors infiltrated the gastric wall with endoluminal growth. The use of water-filling technique in opacifying the lumen and distending the gastric wall is also emphasized. [ABSTRACT FROM AUTHOR]

Two cases of liposarcoma of the stomach are described. At computed tomography (CT) the neoplasms showed features of an aggressive malignant tumor, with no fatty values within. We discuss the differential diagnosis of such lesions and conclude that, although rare, liposarcoma should be considered as a possible diagnosis when a large exophytic gastric mass is detected at CT. [ABSTRACT FROM AUTHOR]