Implication of breast cancer phenotype for patients with leptomeningeal carcinomatosis

BackgroundWe aimed to study the implications of breast cancer (BC) subtypes for the development and prognosis of leptomeningeal carcinomatosis (LC).Patients and methodsData from the breast cancer patients diagnosed with LC between 2005 and 2010 were retrieved. Patients were classified in luminal A, B, HER2 positive and triple negative (TN) and their BC diagnosis, treatment, and outcome were analyzed according to each subtype. Pearson's chi-square and Fisher's exact test were used for categorical variables. Survival analyses were performed by Kaplan–Meier method and compared with the log-rank test.ResultsA total of 38 BC patients were identified, with a median age of 54.8 years (range 36–79). The proportion of luminal A, B, HER2 positive and TN was 18.4%, 31.6%, 26.3% and 23.7%, respectively. LC was the first evidence of metastatic disease in 5 BC patients. Twenty patients received the systemic chemotherapy, with 16 (80%) whole brain radiotherapy (WBRT). Nine patients received only WBRT. TN patients had the shorter interval between metastatic breast cancer diagnosis and the development of LC. Median survival after the diagnosis of LC (OSLC) was 2.6 months (range 1.2–6.4), and did not differ across breast cancer subtypes. In univariate analysis, performance status (ECOG = 0–2) and chemotherapy were prognostic for OSLC, but only the treatment stood as an independent prognostic factor in multivariate analysis.ConclusionsBreast cancer subtype influences the timing of LC appearance, but not OSLC. Patients with LC from breast cancer should be offered systemic treatment, as it appears to associate with the improved outcome. New therapeutic strategy, including, targeted and intrathecal therapy are deserved for BC patients with LC.     

Endorectal coil MRI in local staging of rectal cancer

PURPOSE: The choice of the therapeutic strategies in patients affected with rectal cancer is strictly dependent by the tumor stage. So, in order to obtain an improvement in preoperative staging accuracy, new imaging modalities are now under investigation. The aim of this work is the evaluation of endorectal-coil MRI in the local staging of rectal cancer. MATERIAL AND METHODS: Fourty-three patients affected with histologically proven rectal cancer, have been evaluated by an high-field strength magnet (1.5 T). In 14/43 patients neoadjuvant pre-operative chemotherapy had been previously performed. In all cases axial SE T1w and FSE T2w sequences and coronal or sagittal FSE T2w sequences, with and without fat suppression, were performed. Basing upon the TNM staging system and the previously reported MRI signs the local extent of the tumor was evaluated, focusing about the rectal wall infiltration and the perirectal lymph nodes involvement. All the patients underwent surgery and a comparative evaluation of MRI and pathological staging was done. RESULTS: At MRI the tumor was detected in 38/43 patients. In evaluating wall infiltration the MRI results agreed with pathological results in 89% of patients and showed 92% accuracy in T1-T2 stage and 94% in T3. In evaluating perirectal lymph nodes metastases MRI showed 69% accuracy, 82% sensitivity and 55%specificity. DISCUSSION AND CONCLUSIONS: The poor accuracy of CT and body-coil MRI in evaluating wall involvement in patients with rectal cancer is mainly related to their inability to demonstrate the single layers of the rectal wall. So transrectal ultrasound is now the first choice modalitiy in local staging of rectal cancer. However transrectal ultrasound showed low sensitivity in detecting perirectal lymph nodes metastases and low accuracy in evaluating the patients previously undergone to neoadjuvant chemotherapy or radiotherapy. On the other hand the improvement of MRI sequences and the availability of the endorectal coils allowed to visualize the single layers of the rectal wall so making the endorectal-coil MRI a reliable imaging technique to stage rectal cancer. The results of our work demonstrate a good diagnostic accuracy of endorectal-coil MRI in local staging of rectal cancer, in particular the degree of rectal wall infiltration was well demonstrated, while the perirectal lymph nodes metastases were demonstrated with less accuracy. The long examination time, the costs and the movement-related artefacts are the main limits of MRI. In particular the movement-related artifacts sometime do not allow the visualization of the wall layers so lowering the diagnostic accuracy in demonstrating the tumor wall infiltration. In conclusion, even though endorectal coil MRI proved to be a reliable imaging technique in local staging of rectal cancer, at present we are not able to state what may be its real role in diagnostic evaluation of the patients with rectal cancer, in particular if compared to endorectal ultrasound. Further, comparative studies, based upon larger patients series are probably needed to draw a definitive conclusion.     

Bone quality, as measured by trabecular bone score in patients with adrenal incidentalomas with and without subclinical hypercortisolism

Patients with adrenal incidentalomas (AIs) and subclinical hypercortisolism (SH) have increased risk of fracture independent of bone mineral density (BMD) and possibly due to reduced bone quality. The trabecular bone score (TBS) has been proposed as a index of bone microarchitecture. The aim of the study was to investigate TBS in AI. In 102 AI patients, SH was diagnosed in the presence of at least two of the following: (1) urinary free cortisol >70 µg/24 h (193.1 nmol/L); (2) cortisol after 1‐mg dexamethasone suppression test (1‐mg DST) >3.0 µg/dL (82.8 nmol/L); or (3) adrenocorticotropic hormone (ACTH) <10 pg/mL (<2.2 pmol/L). In patients and in 70 matched controls, BMD was measured at lumbar spine (LS) and femur (neck [FN] and total [FT]) by dual X‐ray absorptiometry and TBS was assessed in the region of LS‐BMD; BMD and TBS data were reported as Z‐scores. In patients, vertebral deformities were assessed by radiograph. Patients with SH (n = 34) had lower LS‐BMD (?0.31 ± 1.17), FT‐BMD (?0.29 ± 0.91), and TBS (?3.18 ± 1.21) than patients without SH (n = 68, 0.31 ± 1.42, p = 0.03; 0.19 ± 0.97, p = 0.01; ?1.70 ± 1.54, p < 0.0001, respectively) and controls (0.42 ± 1.52, p = 0.02; 0.14 ± 0.76, p = 0.02; ?1.19 ± 0.99, p < 0.0001, respectively). TBS was inversely correlated with 1‐mg DST (β = ?0.26, t = ?2.79, p = 0.006) regardless of age, LS‐BMD, body mass index (BMI), and gender. The presence of fracture was associated with low TBS alone (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.85–12.42, p = 0.001) and with the cluster low TBS plus low LS‐BMD (OR, 4.37; 95% CI, 1.71–11.4, p = 0.002), after adjustment for age, BMI, and gender. Low TBS plus low LS‐BMD showed a good specificity (79%) for predicting fractures, whereas normal TBS (ie, > ?1.5) plus normal LS‐BMD high specificity (88.1%) for excluding fractures. Finally, TBS predicted the occurrence of a new fracture in 40 patients followed for 24 months (OR, 11.2; 95%CI, 1.71–71.41, p = 0.012) regardless of LS‐BMD, BMI, and age. In SH, bone quality, as measured by TBS, is altered. TBS is useful in detecting AI patients at risk of fractures. © 2012 American Society for Bone and Mineral Research.     

The modern treatment of early gastric cancer: our experience in an Italian cohort

Background  Endoscopic submucosal dissection (ESD) has been developed as treatment for early gastric cancer (EGC) by Japanese authors. However, there are no reports about its possible implementation in the Western setting. The aim of the present work is to determine the safety and efficacy of the endoscopic treatments for EGC in an Italian cohort. Methods  Forty-five patients for a total of 48 gastric lesions were enrolled in the study. Thirty-six EMR procedures were performed with the strip biopsy technique using a double-channel endoscope. En bloc resection refers to resection in one piece, while piecemeal refers to resections in which the lesion was removed in multiple fragments. A total of 12 ESD were performed and completed with IT knife. We define as curative treatment lateral and vertical margins of the resected specimens free of cancer and repeat endoscopic finding of no recurrent disease. Results  Out of 36 EMR procedures, 10 were piecemeal resections (28%), while 26 were en bloc (72%). ESD led to en bloc resection in 11/12 cases (92%). Histological assessment of curability in the EMR group was achieved in 56% of the cases, and in 92% of the ESD group. Mean follow-up period was 31 months (range: 12–71 months). There was no local recurrence or distant metastasis in the curative group patients. Conclusions  These results seem to confirm the safety and the clinical efficacy of the ESD procedure in the Western world too.     

Defining a new diagnostic assessment parameter for wound care: Elevated protease activity,an indicator of nonhealing,for targeted protease‐modulating treatment

It is widely accepted that elevated protease activity (EPA) in chronic wounds impedes healing. However, little progress has occurred in quantifying the level of protease activity that is detrimental for healing. The aim of this study was to determine the relationship between inflammatory protease activity and wound healing status, and to establish the level of EPA above which human neutrophil‐derived elastase (HNE) and matrix metalloproteases (MMP) activities correlate with nonhealing wounds. Chronic wound swab samples (n = 290) were collected from four wound centers across the USA to measure HNE and MMP activity. Healing status was determined according to percentage reduction in wound area over the previous 2–4 weeks; this was available for 211 wounds. Association between protease activity and nonhealing wounds was determined by receiver operating characteristic analysis (ROC), a statistical technique used for visualizing and analyzing the performance of diagnostic tests. ROC analysis showed that area under the curve (AUC) for HNE were 0.69 for all wounds and 0.78 for wounds with the most reliable wound trajectory information, respectively. For MMP, the corresponding AUC values were 0.70 and 0.82. Analysis suggested that chronic wounds having values of HNE >5 and/or MMP ≥13, should be considered wound healing impaired. EPA is indicative of nonhealing wounds. Use of a diagnostic test to detect EPA in clinical practice could enable clinicians to identify wounds that are nonhealing, thus enabling targeted treatment with protease modulating therapies.     

Efficacy and safety of pegylated liposomal doxorubicin in primary cutaneous B‐cell lymphomas and comparison with the commonly used therapies

Objectives: The therapy of advanced, relapsed or refractory primary cutaneous lymphomas is often unsatisfactory. Recent data indicate a favourable pharmacokynetic, pharmacodynamic and toxicity profile of pegylated liposomal doxorubicin (Peg‐Doxo) in primary cutaneous T‐cell lymphomas, while in primary cutaneous B‐cell lymphomas (PCBCLs), the drug efficacy has never been assessed so far. Methods: We performed a prospective phase II pilot clinical trial of Peg‐Doxo monotherapy (20 mg/m²) in PCBCLs. One patient had a marginal zone B‐cell lymphoma and four were affected by diffuse large B‐cell lymphoma‐leg type, all with widespread nodular lesions. Results: All the patients achieved a complete response (CR = 100%) in a short period of time (median 3 months), even when pretreated with radio‐chemotherapy. Two experienced a relapse. At follow‐up, one patient died for progressive disease; four are in CR after 5, 52, 63 and 69 months. As concerning the toxicity profile, the treatment was well‐tolerated, no one decreased or delayed the dose. The haematological toxicity was mild with only one case of grade III neutropenia; a patient showed a grade I neurotoxicity. Dermatological toxicity, in particular the palmar–plantar erythrodysesthesia, did not occurred, probably because of both the low dosages of Peg‐Doxo monotherapy and the oral prophylaxis with pyridoxine. Conclusions: In spite of the small number of patients, it emerges that monochemotherapy with Peg‐Doxo has a significantly high clinical activity and a good safety profile in PCBCLs, even in aggressive forms, compared with other therapeutic regimens, which are completely reviewed. It suggests the need of further investigations in this field.     

Allergic rhinitis phenotypes based on mono-allergy or poly-allergy

Inflammation Research - Allergic rhinitis (AR) is characterized by typical symptoms that are dependent on inflammation. Poly-allergy is a frequent phenomenon. Phenotyping AR represents an...