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.     

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.     

Detection of skeletal muscle metastases on initial staging of lung cancer: a retrospective case series

Purpose

Estimation of skeletal muscle metastases (SMMs) at the time of diagnosis and/or initial staging of lung cancer.

Materials and methods

Retrospective evaluation of clinical charts and imaging data suggestive of SMMs of patients with histology-proved lung cancer over a 5-year period.

Results

SMMs were identified in 46 out of 1,754 patients. Single and multiple (62.9 % of cases) SMMs were detected by total body multi-detector computed tomography (MDCT). They were associated with poorly differentiated (43 %) and advanced adenocarcinomas (52 %) without clinically relevant symptoms and/or signs. Psoas and buttock muscles were most frequently involved (33.3 %). MDCT findings consisted of well-defined homogeneously hyperdense oval masses (31 %), lesions with ring-like enhancement and central hypoattenuation (68 %), or large abscess-like necrotic lesions (24 %). Sonography revealed well-defined hypoechoic masses (41.6 %), ill-defined hypoechoic lesions (33.3 %), or anechoic areas with a necrotic centre (25 %). Positron emission tomography revealed that all SMMs were metabolically active.

Conclusions

SMMs are uncommon but not negligible in lung cancer, with an estimated prevalence of 2.62 % in our series. Although histology remains the recommended method, use of high-performance imaging techniques and increased clinical suspicion may improve their early detection. Efforts addressing their effect on the natural history of lung cancer are needed.     

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.     

Echographic study with high-frequency and high-spatial resolution transducer in the evaluation of renal transplant in pediatric age

PURPOSE: We investigated the role of power Doppler US with a high-frequency and high-resolution transducer (13 MHz) in the visualization of interlobular arterioles in patients with normally functioning renal transplants or with chronic rejection. MATERIAL AND METHODS: We examined 15 patients (mean age 15 years; range 10-18 years) with a General Electric 500 MD unit using 7.5 and 13 MHz linear transducers. In all the patients serum creatinine and diuresis were evaluated; 4 patients underwent US-guided biopsy that resulted in the diagnosis of chronic rejection. RESULTS: Normally functioning renal transplants were found in 11 patients and chronic rejection was seen in 4. In normally functioning renal transplants, interlobular vessels could be depicted as "cortical blush" with the 7.5 MHz transducer; in the same patients power Doppler US with the 13 MHz transducer permitted a correct evaluation of interlobular vessels that were arranged in series like a palisade. In chronic rejection power Doppler US with the 13 MHz transducer better depicted cortical vascularity and showed irregular, narrow arteries. CONCLUSION: Power Doppler US with a 13 MHz transducer is particularly useful in children after renal transplants due to their reduced tissutal thickness. The lateral resolution of 13 MHz transducers (< 0.3 mm) allows to separate interlobular vessels from each other and the high frequency of the probe can depict interlobular vessels in the peripheral cortex. The optimal visualization of cortical vascularity with a 13 MHz transducer allows early detection of chronic rejection.     

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.     

Impact of 18F-fluoride PET-CT on implementing early treatment of painful bone metastases with Sm-153 EDTMP

This study evaluated the diagnostic impact of using skeletal ¹⁸F-fluoride PET/CT on patients with painful bone metastases to schedule an early palliative radionuclide treatment. Methods: The skeletal involvement from prostate cancer metastases was assessed by both ^99mTc-diphosphonate bone scan (BS) and ¹⁸F-fluoride PET/CT within four weeks in 24 patients (67.7 ± 5.1 years) suffering from a borderline degree of bone pain for which radionuclide palliation was not shortly planned for administration. The BS and ¹⁸F-fluoride PET/CT results were compared, assessing the number and extension of the skeletal sites involved. Afterward, the patients were randomly assigned either to the study group (N = 12) receiving radionuclide therapy (Samarium-153 EDTMP) or to the control group (N = 12) not receiving radionuclide therapy. The short-term results from the radionuclide palliation group (evaluated with a visual analogue scale) were compared with the controls. Results: Overall, at BS, 7.6 ± 1.4 sites were considered metastatic, involving at least 5 ± 1 body regions. At ¹⁸F-fluoride PET/CT, 116 ± 19 sites presented metastatic involvement with 12/12 body regions concerned. No differences were found in regards to either the number of metastatic sites or regions at both BS and ¹⁸F-fluoride PET/CT between the study group and controls (p = ns). At CT, 88 blastic metastases were identified, whereas 110 were mainly lytic. Most of mainly lytic lesions were not detectable at BS. The reduction in total discomfort and bone pain in the study group was significantly greater than in the controls (p < 0.0001). Conclusion: Sm-153 EDTMP therapy should be considered for patients with early bone pain from prostate cancer even if their BS only indicates a few metastases before the initiation of a severe pain syndrome. ¹⁸F-fluoride PET/CT may be helpful in deciding if the implementation of bone pain palliation using bone-seeking radionuclides at pain onset is necessary.     

Beneficial treatment with risedronate in long-term survivors after allogeneic stem cell transplantation for hematological malignancies

In this prospective randomized study we evaluated the effect of risedronate, an aminobisphosphonate, on bone mass and turnover in patients who had undergone allogeneic stem cell transplant (SCT) for hematological malignancies. Thirty-four patients (18 females, 16 males, age 32±10 years) with bone mineral density (BMD) –1.5 SD as a T-score at least 6 months after SCT were treated with calcium 1 g/day and vitamin D 800 IU/day and randomized to receive (n=17, group 1) or not receive (n=17, group 2) oral risedronate 5 mg/day. The duration of treatment was 12 months. After 6 months, lumbar BMD increased by 4.4±1.6% in patients of group 1 and decreased by 4.3±1.5% in those of group 2 (P<0.05); at the femoral neck, BMD did not change significantly in patients of group 1 (+1.2±1.2%), while it decreased in those of group 2 (–4.3±2.1%; P<0.05). After 12 months, lumbar BMD further increased (+5.9±1.7%, P<0.05), compared to baseline in group 1 and slightly increased (+1.1±1.4%) in group 2. No further changes were observed at femoral neck in both groups. In conclusion, treatment with risedronate for 12 months increased BMD significantly at the lumbar spine and prevented further bone loss at the femoral neck in long-term survivors after allo-SCT.     

Talactoferrin alfa, a recombinant human lactoferrin promotes healing of diabetic neuropathic ulcers: a phase 1/2 clinical study

BACKGROUND: Talactoferrin alfa, a recombinant form of human lactoferrin, is a novel immunomodulatory protein with demonstrated ulcer healing properties in animal models. METHODS: A phase 1/2 clinical study was conducted at 7 clinical sites to determine if talactoferrin can improve wound healing in diabetic patients with foot ulceration. Fifty-five patients with diabetic neuropathic foot ulcers participated in this 2-phase study. In phase 1, groups of 3 patients each received open-label 1%, 2.5%, or 8.5% talactoferrin gel twice daily, in a sequential design, to their ulcer for 30 days. No drug-related adverse events were found at any dose level. Phase 2 was a randomized, placebo-controlled, single-blind study of 2.5% and 8.5% gels, with patients equally divided between the 3 groups. In combination with good wound care, treatment was administered topically twice daily to the ulcers for 12 weeks. The primary endpoint was the incidence of > or = 75% healing (relative to baseline size). RESULTS: The study, which in phase 2 was powered to detect a difference between the placebo and combined talactoferrin arms with P < .1, met the primary objective. The groups receiving the 2.5% (n = 15) and 8.5% (n = 15) gels had twice the incidence of > or = 75% reduction in ulcer size compared with the placebo group (n = 16): 47%, 53%, and 25%, respectively. On an intent-to-treat basis, the combination of the 2 active groups when compared with the placebo group showed a strong trend toward statistical significance (P = .09). There were no talactoferrin-related adverse events or laboratory abnormalities. CONCLUSIONS: Topical talactoferrin appears to be safe and well tolerated and improves healing of diabetic neuropathic ulcers.