Combination of letrozole, metronomic cyclophosphamide and sorafenib is well-tolerated and shows activity in patients with primary breast cancer.

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 (18)FDG-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.

Prospective neoadjuvant analysis of PET imaging and mechanisms of resistance to Trastuzumab shows role of HIF1 and autophagy.

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.

The study of visual evoked potentials in patients with thyroid-associated ophthalmopathy identifies asymptomatic optic nerve involvement.

In the present study we have recorded visual evoked cortical potentials (VECP) in 88 patients affected by autoimmune thyroid disease and thyroid-associated ophthalmopathy (TAO) without clinical signs of optic neuropathy. At the time of ophthalmological examination, 37 of these patients were hyperthyroid, 41 were euthyroid, and 8 were hypothyroid; 2 were not assessed. Twenty-nine normal subjects served as controls. We performed pattern reversal visual stimulation and recorded the amplitude and latency of the cortical electric response at 100 ms (P100 wave). There were no differences in the mean P100 amplitude of TAO patients and normal subjects. The mean P100 latency in patients was 105.6 +/- 0.5 ms, significantly higher than that in normal subjects (102.0 +/- 0.5 ms; P < 0.00003). Latency in euthyroid patients did not differ from that in either hypo- or hyperthyroid patients. The VECP test was positive (latency, > or = 110.0 ms) in 21 (23.8%) TAO patients. In patients with proptosis greater than 21 mm, latency was 106.7 +/- 0.7 ms, significantly higher than that in patients with normal Hertel measurements (104.3 +/- 0.6 ms; P < 0.01). Latency was not increased in patients with acute inflammatory signs compared to those with inactive eye disease and in patients with altered extrinsic motility. In patients with an abnormal visual field study, the mean latency was 110.3 +/- 1.5 ms, significantly higher than that in patients with a normal visual field (104.7 +/- 0.4; by t test, P < 0.000003). In conclusion, we observed a prolongation of the latency of the evoked cortical response in patients with TAO without subjective visual complaints and without optic nerve compression. We believe that the study of VECP in TAO is complementary to the study of the visual field in identifying early optic nerve dysfunction in the absence of decreased visual acuity.

Magnetic resonance findings and ophthalmologic abnormalities are correlated in patients with neurofibromatosis type 1 (NF1).

In subjects with neurofibromatosis type 1 (NF1), we show that a reduction in the visual field is the most sensitive indicator of gliomas along the optic pathway. Therefore, we conclude that a visual field evaluation is the most sensitive clinical test among those evaluated to predict the presence of optic pathway pathology on an MRI examination. These data may contribute to the establishment of more precise guidelines for the evaluation and treatment of children with NF1.

Computed tomography of renal metastases.

Since the advent of CT, secondary neoplastic lesions of the kidneys have been detected with increasing frequency. After reviewing a large series of cases of renal metastases, we have been able to classify the CT findings into seven major categories that are discussed and illustrated in this article. The differential diagnoses between metastatic disease of the kidneys and other lesions such as renal infarctions, renal lymphoma, and primary malignancies are also considered.

Cystic primary neoplasms of the liver of the adult. CT features.

Although rather rare, primary cystic neoplasms of the liver of the adult may represent a diagnostic challenge in everyday practice. We describe the features of such tumors visualized on computed tomography. This shows a wide range of morphological changes such as septa, papillary growths, solid/liquid ratio, wall characteristics, and vascularization. We conclude that although the differential diagnosis between these tumors and nontumoral cystic lesions may occasionally be reliable on computed tomography, proper management of hepatic cystic neoplasms still relies on the pathological findings.

Focal Castleman disease of the lung: MRI findings.

Castleman disease is an uncommon benign disorder mainly affecting mediastinal lymph nodes and rarely visceral organs. The most typical structural finding is hypervascularity which can be well demonstrated both by CT and MRI. We report MR findings of an unusual case of solitary parenchymal lung involvement.

Enlarging tongue masses in neurofibromatosis type 1: MR findings of two cases.

Plexiform neurofibromas usually occur in the neck, pelvis, and extremities. Jaws and oral cavity plexiform neurofibromas have also been described. Magnetic resonance (MR) patterns for neurofibromas are typical. They include low-to-intermediate signal intensity on T1-weighted images, enhancement of the solid component of the tumor after contrast medium administration, heterogeneity on T2-weighted images, and in some cases, multiple target signs due to a collagen central area. We report MR findings of two neurofibromatosis type 1 (NF1) patients with enlarging tongue plexiform neurofibromas.

Hemangioendothelioma of the spleen: imaging findings at color Doppler, US, and CT.

The ultrasonographic, color Doppler, and computed tomography findings of an unusual vascular primary tumor of the spleen are reported. A brief clinical and histopathological analysis of this entity is discussed and the differential diagnosis of other primary lesions of the spleen is attempted.

CT of secondary neoplasms. Unusual structural features--a pictorial essay.

The newer anticancer therapies, the routine employment of cross-sectional imaging modalities for staging and follow-up, and the increased survival rate of patients with neoplastic lesions have markedly widened the range of pathological and imaging features of secondary neoplasms. Moreover, the changes occurring in morphological and structural aspects of metastases may be the direct effect of the improved therapeutic tools, and in turn may offer revealing clues to the clinician regarding the outcome of therapy itself. The scope of this essay is to show the atypical computed tomographic (CT) aspects of a series of metastatic lesions. We selected the lesions on the basis of their unusual structural features, such as calcification; hemorrhage; superinfection; pseudocystic, cystic, and lipoid appearance; and hypervascularity. A highly detailed assessment of such changes is nowadays possible and appears mandatory.

CT of renal metastatic disease. A pictorial essay.

The routine use of computed tomography (CT) for the staging and follow-up of malignant neoplasm has improved the detection of secondary spread to the kidneys. This essay illustrates the gamut of the CT aspects of such secondary lesions. Seven main patterns of metastatic features are identified. Some of these patterns appear to reproduce the same radiological features seen in the corresponding primary lesions. Where feasible, differential diagnostic criteria are offered.

An unusual MR presentation of the neurohypophyseal "bright spot" in pituitary dwarfism.

Abnormalities of the hypothalamo-hypophyseal axis are frequently associated with pituitary deficiency. We describe a previously unknown morphological presentation of the ectopic posterior neurohypophyseal "bright spot."

Duodenal hemangiopericytoma: CT and MRI findings.

Hemangiopericytoma (HPC) is a rare mesenchymal tumor generally occurring in adults and originating from the pericytes. The tumor more commonly affects the soft tissues of the extremities, the pelvis, and the retroperitoneum. We describe the computed tomographic and magnetic resonance appearance of a patient affected by HPC of the duodenum.

Calcified ovarian metastases from mucinous carcinoma of the colon.

The authors report a case of calcified ovarian metastases from a mucinous carcinoma of the colon observed in an 85-year-old woman. The radiological aspects observed at computed tomography (CT) are described and the possible mechanisms of tumoral calcifications are discussed.

Adrenal carcinomas in AIDS. Report of three cases.

With the recent advances in treatment of AIDS, we have seen an increase in detection of malignant neoplasms in our patients. While some malignancies have an undoubted relationship with the HIV infection, others represent nothing more than sporadic reports and their relationship with the underlying immunological deficit is all but clear. We report the imaging findings in three patients with AIDS and an adrenal adenocarcinoma. We also discuss the peculiar imaging aspects of these pathological entities and report some pathogenetic theories on the relationship between AIDS and neoplasms.

US and CT findings of secondary neoplasms of the thyroid--a pictorial essay.

Although clinical series report a low (3%) incidence of metastases to the thyroid gland, autoptic studies have showed occurrences as high as 17%, probably because of the high vascularization of the thyroid. We selected 9 patients who had pathologically proven thyroid metastases at CT and US, during follow-up for a known primary neoplasm. The most common originating neoplastic primaries include mostly those that generally give rise to blood-borne metastases such as breast and lung cancers, mucoid adenocarcinoma of the stomach, colon cancer and renal cancer, as well as melanoma and leiomyosarcoma. Because of its diffusion, sensitivity, and noninvasiveness, ultrasonography can justifiably be introduced in the staging protocols of those neoplasm that more frequently give blood-borne metastases to the thyroid, but a US-guided biopsy is warranted for hypoechoic or otherwise suspicious nodules. This holds particularly true in disease-free patients or previously diagnosed with generally slow-growing malignancies (breast or kidney), since the secondary localization, often metachronous in our experience, may be effectively managed surgically. CT features, on the other hand, are extremely variable and are directly dependent on the histology of the primary lesion, as well as the size of the secondary lesions.

Thin-section CT follow-up of metastatic ovarian carcinoma correlation with levels of CA-125 marker and clinical history.

Second-look laparotomy and CA-125 are the gold standard in follow-up of ovarian carcinoma. Since no definite role seems established for cross-sectional imaging in assessment of recurrence we employed thin-section computed tomography (CT), correlated with CA-125 levels and detailed knowledge of the clinical history as a follow-up protocol One hundred seventy-seven patients with ovarian carcinoma were selected because of: (a) pathologically proven remission after first-line chemotherapy, (b) follow-up by means of thin-section CT every 6 months for the fist 3 years and every 10 months subsequently, (c) monitoring CA-125 serum levels every 3 months for the first 3 years and every 6 months subsequently; (d) pathologic confirmation or clinical and laboratory follow-up after 12 months or longer for the CT findings. Fifty percent of the patients showed recurrence of disease. Our protocol yielded 93.2% true positive, dubious findings in 5.6% 1.0% false negatives, 97.7% true negative, and 2.3% false positive. With a tailored technique, CT was particularly sensitive in early diagnosis of peritoneal seeding, even in the absence of ascites or increases in the levels of CA-125. Repeated administration of contrast medium, water enemas, and repeated scanning of suspicious volumes with differing scanning parameters were the factors managed by the radiologist. We conclude that thin-section CT, correlated with CA-125 levels and careful review of the clinical history could represent a valid alternative to repeated explorative laparotomies in the follow-up of ovarian carcinomas.

Central nervous system atypical teratoid/rhabdoid tumour of infancy. CT and mr findings.

In 1995, as a result of the observation of Rhabdoid elements among the other components of a Teratoid/Rhabdoid tumor (TRT), a new nomenclature was introduced, Atypical Teratoid/Rhabdoid Tumor (ATRT) of infancy and childhood. We report the clinical history and radiological findings in a child affected by central nervous system (CNS) ATRT.

[X-ray computed tomographic aspects of calcifying metastases. Apropos of 40 cases]. / Aspects tomodensitométriques des métases à forme calcifiante. A propos de 40 cas.

The authors report the results of a study on 40 patients affected by metastases of the calcifying type detected during CT scan imaging for cancer of different origin (colorectum 18 cases, stomach 5, ovary 10, lung 2, bone 2, breast, skin, thyroid 1 case). The sites involved include liver (22), spleen (5), lymph nodes (10), peritoneum (7), diaphragm (2), pleura (2), ovary (1), soft tissue (3), lung (3). Calcification in metastases arises through a double mechanism: primary, with bone formation in osteoid neoplasia (orthoplastic calcification) or ossification of tumour cartilage (metaplastic calcification); secondary as a result of necrosis, hemorrhage and regressive changes (dystrophic and mucoid calcification), particularly after radiation or systemic treatment. Since calcified metastases can strongly mimic granulomatous, parasitic and other neoplastic disease, the clinical history is essential for the diagnosis.

[Idiopathic retroperitoneal fibrosis]. / La fibrosi retroperitoneale idiopatica.

Retroperitoneal fibrosis is an uncommon disease, characterized by the replacement of normal retroperitoneal tissue with fibrosis and/or chronic inflammation. In two thirds of the cases retroperitoneal fibrosis is idiopathic (IRF), whereas in the remaining ones it is secondary/associated to cancer, infections, drugs, autoimmune disease and vasculitis. IRF appears as a dense, fibrous plaque that usually arises between the level of the lower aorta and the common iliac arteries. As the plaque progresses, it engulfs the adjacent structures (e. g., ureters). In its early stages IRF is characterized by a rich infiltrate of lymphocytes, plasma cells and macrophages interspersed within fibroblasts and collagen bundles. In its advanced stages it becomes relatively avascular and acellular with abundant collagen bundles and scattered calcifications. The pathogenesis is unknown: some Authors suggest that IRF is a consequence of a local autoimmune reaction against atherosclerotic plaque antigens whereas others propose that it is the manifestation of a systemic autoimmune disease. The presenting signs and symptoms are non-specific; systemic manifestations (fever, anorexia, weight loss), often associated with local symptoms, are usually found to be related to the entrapment of retroperitoneal structures. The most common local symptom is lumbar and/or abdominal pain. The treatment can be surgical and/or medical: the former is required when obstructive complications are present; the latter, associated or not with surgery, can significantly improve the outcome of IRF patients and usually modifies the natural history of the disease. Steroids and tamoxifen are the most used drugs, whereas other agents such as azathioprine, methotrexate and cyclosporine are usually given to non-responder patients.