Estimating the value of surgical clips for target volume delineation in external beam partial breast radiotherapy.

AIMS: To investigate the role of surgical clips in defining the clinical target volume (CTV) for three-dimensional conformal external beam radiotherapy-partial breast irradiation (3D-CRT-PBI) using preoperative computed tomography scans. MATERIALS AND METHODS: A group of patients with early breast cancer underwent conservative surgery with placement of surgical titanium clips (at least three clips required). All patients had a treatment planning computed tomography simulation before (CT1) and after surgery (CT2). The two sets of images were co-registered with a match point registration. The relationship between the clips-based CTV for PBI delineated on CT2 and the initial tumour location on CT1 was studied, evaluating the percentage of intersection volume. RESULTS: Twenty-eight patients participated in this study. In total, 13 patients (46.4%) had an intersection volume ≥ 50% and 10 patients (35.7%) had complete intersection (intersection volume = 100%). An increased median intersection volume was observed in patients with more than six clips (P = 0.007) and in patients with a larger portion of breast volume covered by the PBI-CTV (CTV/BV; P = 0.010). Intersection volume increased with the number of clips, after adjustment for CTV/BV (linear coefficient = 5.1693; P = 0.043). Also, a maximum distance from the chest wall ≤0.7 cm and CTV/BV > 9.5% were found to be predictors of an intersection volume ≥50% (area under the curve 0.841; confidence interval 0.649-0.952; P < 0.0001; area under the curve 0.800; confidence interval 0.607-0.926; P = 0.0004) and of an intersection volume of 100% (area under the curve 0.776, confidence interval 0.573-0.916, P = 0.046; area under the curve 0.752, confidence interval 0.536-0.935; P = 0.032). CONCLUSIONS: Titanium clips are essential and six or more increase the accuracy of tumour bed delineation for PBI; also the primary tumour location as well as the percentage of volume of breast covered by PBI-CTV may influence the correct delineation of PBI-CTV.

Urinary complications from breast cancer metastasis: case report and review of the literature.

Breast cancer is the most prevalent malignant disease among women, with the exception of non-melanoma skin cancers. Malignant breast tumours metastasise to lungs, bone, liver, lymph nodes and skin, but the literature also reports few cases of unusual metastases such as to the bladder. We present the case of a 57-year-old woman affected by lobular invasive breast cancer and complaining of high urinary frequency with nicturia. To date this is the seventh reported case of isolated metastatis of breast carcinoma to the bladder.

COX-2 expression in lobular in situ neoplasia of the breast: correlation with histopathological grading system according to the Tavassoli classification.

AIMS: There is considerable evidence to link cyclooxygenase (COX)-2 to the development of cancer. The aim of this study was to assess COX-2 expression and its subcellular localization in lobular in situ neoplasia (LIN) of the breast and to verify differences in COX-2 expression between different grades of lesions according to the Tavassoli classification. METHODS AND RESULTS: We analysed the expression of COX-2 protein by immunohistochemistry in tissue samples of 51 LIN lesions classified into three grades according to the Tavassoli classification. COX-2 immunostaining was observed in 78.4% of LIN samples and showed a prevalent membranous rather than cytoplasmic pattern. COX-2 was expressed in 16/17 (94.1%) LIN1, 22/25 (88%) LIN2 and 2/9 (22.2%) LIN3. As regards COX-2 expression, a statistically significant difference was found between LIN1 and LIN3 (P = 0.001) and between LIN2 and LIN3 (P =0.001). No difference was found between LIN1 and LIN2. Moreover, a significant negative correlation was found between LIN grade and COX-2 expression (P < 0.0001). CONCLUSIONS: COX-2 is highly expressed in LIN, supporting a role for this protein in the early stage of breast carcinogenesis, representing the rationale for using COX-2 selective inhibitors in the earliest stages of breast cancer.

COX-2 expression in DCIS: correlation with VEGF, HER-2/neu, prognostic molecular markers and clinicopathological features.

AIMS: There is considerable evidence that links COX-2 to the development of cancer. The aim of our study was to assess, by immunohistochemistry, COX-2 expression in ductal carcinoma in situ (DCIS) and its possible correlation with HER-2/neu, vascular endothelial growth factor (VEGF) expression and other common immunohistochemical parameters (p53, ER, PGR, Ki67). METHODS AND RESULTS: Tissue samples of 49 archival cases of DCIS without any invasive component were analysed for COX-2, HER-2/neu, VEGF, oestrogen and progesterone receptors, Ki67 and p53 by immunohistochemistry using specific antibodies. COX-2 expression was detected in 43 (87.8%) tissue samples, of which 12 (24.5%) were graded as weak, 22 (44.9%) as moderate and nine (8.4%) as high expression. Only six (12.2%) lesions were negative for COX-2 expression. VEGF expression was detected in 93.8% of samples; 66.7% of lesions were found to be positive for HER-2/neu expression. Furthermore, COX-2 expression was significantly correlated with VEGF expression (P = 0.003). A significant positive correlation was also observed between COX-2 and HER-2/neu expression (P < 0.0001). CONCLUSIONS: Our results suggest that COX-2 is highly expressed in DCIS and takes part in the molecular pathway implicated in progression of breast cancer and may provide a rationale for targeting COX-2 in preinvasive breast cancer therapy.

Huge response to letrozole in inoperable T4 breast cancer: a case report.

A 73 years-old woman presented with locally advanced breast cancer (cT4b cN1 M0, stage IIIB) and atrial flutter. Because of the arrhythmia, chemotherapy or tamoxifen, although malignancy was hormone-sensitive, were discarded. Letrozole was started. Two months later, the breast nodule and skin ulceration cleared up. Surgery was performed. Nowadays, 24 months later, patient does fine, continuing letrozole as adjuvant treatment.

Tumor specific modulation of KU70/80 DNA binding activity in breast and bladder human tumor biopsies.

The Ku70/80 heterodimer is the regulatory subunit of the DNA-dependent protein kinase (DNA-PK) and its DNA-binding activity mediates DNA double-strand breaks repair. Although Ku80 was recently proposed as a caretaker gene involved in the control of genome integrity, no data are available on Ku70/80 DNA-binding activity in human tumors. Heterodimer DNA-binding activity and protein expression were assayed by electrophoretic-mobility-shift-assay (EMSA) and Western blot analysis, in nuclear and cytoplasmic extracts from eight breast, seven bladder primary tumors and three metastatic nodes from breast cancers. Corresponding normal tissues of the same patients were used as controls. Ten out of 15 tumors showed nuclear Ku-binding activity 3-10 times higher than in the normal tissues, irrespective of bladder or breast origin. Conversely, in 5/15 primary tumors and in all the metastatic nodes analysed, nuclear Ku-activity was 1.5-4.5-fold lower than in the corresponding normal tissues. Cytoplasmic heterodimer activity significantly differed between tumor and normal tissues, displaying a 2-10-fold increase in neoplastic tissues. Three different patterns combining both Ku expression and activity with tumor characteristics were identified. In low aggressive breast tumors p70/p80 proteins were expressed in tumor but not in normal tissues. The heterodimer binding-activity matched the protein levels. In non-invasive bladder carcinomas no significant differences in protein expression between tumor and the corresponding normal tissues were found, however heterodimer binding-activity was increased in tumor samples. In breast and bladder tumors, at the advanced stage and in node metastases, the binding activity was strongly reduced in tumor biopsies, however no differences were demonstrated between normal and tumor protein levels. Our results suggest a different modulation of Ku70/80 DNA-binding activity in human neoplastic tissues, possibly related to tumor progression. Findings provide further data on tissue-specific protein expression and post-translational regulation of heterodimer activity.

[Multifocal inflammatory pseudotumor of the liver]. / Pseudotumore infiammatorio multifocale del fegato.

Inflammatory pseudotumor of the liver is a rare entity of unknown etiology; fewer than 80 cases have been reported in the world literature. Its appearance on the computerized tomography, ultrasound and magnetic resonance have been previously described as nonspecific, and clinical presentation is not helpful in the diagnosis. This is why the diagnosis usually is made after laparotomy and often after the excision of the tumor. Several recent reports show that drug therapy is effective and lead to tumor regression, while other authors believe that an aggressive approach should be taken, due to the potential adverse impact of its vascular invasive and biliary obstructive nature. Herein we describe a case of this clinical entity, which occurred in a 52 years old patient, where the operative examination showed bilobar involvement, treated with right hepatectomy and contra-lateral tumor excision in the clinical suspect of hepatocellular carcinoma. The detailed clinical, radiological and pathological picture is described. At 6 months follow-up the patient conditions are excellent. On the basis of the available literature, we discuss the clinical features and the therapeutical problems of such rare clinical entity, and propose a selected use of liver biopsy when the clinical suspicion of pseudotumor can be considered, in order to achieve a preoperative diagnosis and therefore to avoid surgery.

[Clinical manifestations and diagnosis of hemorrhoids]. / Manifestazioni cliniche e diagnosi delle emorroidi.

Haemorroidal disease has often typical presentation with rectal bleeding, anal prolapse and pain. Practitioners and patients usually underestimate the symptoms; in adults and older people the same symptoms may suggest neoplastic disease, which may be synchronous. Proctoscopy is the main diagnostic test for staging; endoscopic examination with biopsy is helpful to differentiate neoplastic, granulomatous and inflammatory anorectal lesions. In our mind, a complete study of anorectal function and morphology is necessary for a correct diagnosis.