[F-18]-fluorodeoxyglucose PET-CT of the normal prostate gland

Objective  We determined the glucose metabolism and computed tomographic (CT) density of the normal prostate gland in relation to age and prostate size on [F-18] fluorodeoxyglucose positron emission tomography (PET)-CT. Methods  We determined the CT density (Hounsfield Units, HU) and glucose metabolism (standardized uptake value, SUV) of the normal prostate in 145 men (age range 22–97 years) on PET-CT scans which were performed for indications unrelated to prostate pathology. Correlations among SUV, HU, prostate size, and age were calculated using Pearson’s correlation coefficients, scatter plots, and linear regression trend lines. The SUV and HU values were also compared among different primary cancer types using the Kruskal-Wallis test. Results  The population average and range of the normal prostate size were 4.3 ± 0.5 cm (mean ± SD) and 2.9–5.5 cm, respectively. The population average of mean and maximum CT densities was 36.0 ± 5.1 HU (range 23-57) and 91.7 ± 20.1 HU (range 62-211), respectively. The population average of mean and maximum SUV was 1.3 ± 0.4 (range 0.1–2.7) and 1.6 ± 0.4 (range 1.1–3.7), respectively. Mean SUV tended to decrease as the prostate size increased (r = −0.16, P = 0.058). Higher mean HU was correlated with higher mean SUV (r = 0.18, P = 0.033). The strongest association was observed between age and prostate size. The prostate gets larger as age increases (r = 0.32, P < 0.001). Prostate mean SUV, max SUV, mean HU, and max HU were not significantly different among different types of primary cancers. Conclusions  Although the normal prostate size increases with age, it does not significantly affect the gland’s metabolism and CT density, and therefore age-correction of these parameters may be unnecessary.     

Control of aerostasis in pulmonary metastasectomy by precision resection. Standard technique versus fibrin glue modification

The control of aerostasis after performing non-anatomical pulmonary resections constitutes a serious problem. The presence of an air leak in the postoperative period requires a prolonged thoracic drainage and consequently a longer hospital stay. The aim of our study was to evaluate the usefulness of fibrin glue and its effectiveness in the prevention of air leaks. At the Department of Thoracic Surgery of the National Cancer Institute of Milan, we conducted a case-control study in 90 patients submitted to metastasectomy for secondary lung cancer, removing multiple small nodules < or = 1.5 cm using the precision resection technique. We divided the patients into two groups, both of 45 subjects: group 1 treated with fibrin glue and group 2 submitted to cauterization of the pulmonary parenchyma. The patient characteristics were well matched for age, type of approach and operation, number of resections performed and type of pathology. The assessment parameters investigated were the duration of the air leak, expected complications, drainage time and length of hospital stay. In group 1 we performed fewer than 5 precision resections in 21 cases, from 5 to 10 in 16, and more than 10 in 8. In group 2 we executed fewer than precision resections in 21 cases, from 5 to 10 in 17, and more than 10 in 7. In group 1 the duration of the air leak was 2.93 +/- 1.91 days as against 6.95 +/- 7.01 days in group 2 (p = 0.000). In group 1 we had one complication (2%) (a long-term air leak lasting > 10 days), while in group 2 we had a long-term air leak in 11 cases (24%) (p = 0.000). Mean thoracic drainage time was 4.22 +/- 1.43 days in group 1, and 8.13 +/- 7.37 in group 2 (p = 0.000). The mean postoperative hospital stay was 6.22 +/- 1.43 days in group 1 compared to 10.13 +/- 7.37 days in group 2 (p = 0.000). In the group of patients treated with fibrin glue we obtained a significant reduction in drainage time, complications and postoperative hospital stay. The results of our experience show that the use of fibrin glue in non-anatomical resections with a high risk of developing air leakage is effective in reducing the expected complications, with a favourable impact also on the quality of life of patients with metasases.     

Prognostic role of nuclear factor/IB and bone remodeling proteins in metastatic giant cell tumor of bone: A retrospective study

Giant cell tumor of bone (GCTb) represents 5% of bone tumors, and although considered benign, 5% metastasize to the lung. The expression of proteins directly or indirectly associated with osteolysis and tumor growth was studied on 163 samples of GCTb. Of these, 33 patients developed lung metastasis during follow‐up. The impact of tumor–host interaction on clinical aspects was evaluated with the aim of finding specific markers for new biological therapies, thus improving clinical management of GCTb. Protein expression was evaluated by immunohistochemical analysis on Tissue Microarray. The majority of GCTb samples from patients with metastatic disease were strongly positive to RANKL and its receptor RANK as well as to CAII and MMP‐2 and to pro‐survival proteins NFIB and c‐Fos. Kaplan–Meier analysis indicated a significant difference in metastasis free survival curves based on protein staining. Interestingly, the statistical correlation established a strong association between all variables studied with a higher τ coefficient for RANK/RANKL, RANK/NFIB, and RANKL/NFIB pairs. At multivariate analysis co‐overexpression of NFIB, RANK and RANKL significantly increased the risk of metastasis with an odds ratio of 13.59 (95%CI 4.12–44.82; p < 0.0005). In conclusion, the interconnection between matrix remodeling and tumor cell activity may identify tumor–host endpoints for new biological treatments. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1205–1211, 2015.     

A new bioabsorbable sleeve for lung staple-line reinforcement (FOREseal™): report of a three-center phase II clinical trial

Objective: To investigate on the feasibility, safety, and effectiveness of a new bioabsorbable material for lung staple-line reinforcement. Methods: This prospective open trial included 66 patients (mean age of 56 ± 17 years) who underwent various types of lung resection using staplers with knitted calcium alginate sleeves for buttressing (FOREseal™, Laboratoires Brothier, Nanterre, France) at three academic centers: 29 lobectomies, 22 emphysema surgeries, 15 wedge resections or lung biopsies. Intraoperative air leakage was assessed at a mean respiratory peak pressure of 30 cmH₂O, and rated as grade 1, 2, or 3. Persistent air leakage in the postoperative course, as well as any relevant event, was assessed daily. The follow-up period was of 6 months. Results: No technical problem linked to the device occurred. Hemostasis of the cutting edges was completed in all patients. Fifty-six percent of the patients had no intraoperative air leak and 27.3% had grade 1 leaks. Mean postoperative air leaks and thoracic drainage times were 1.9 ± 2.3 days and 6 ± 5.3 days, respectively. In-hospital mortality was nil. There was no empyema. Mean hospital stay was 9.1 ± 6.6 days. At follow-up, one patient underwent lung transplantation, and pathology of the explanted specimen showed the absence of device-related foreign-body inflammation. One patient complained from metalloptysis, and another one, with a metastatic invasive aspergillosis, developed an infectious recurrence that required reoperation. Conclusions: FOREseal is an ergonomic, safe, and promising new material instead of nonabsorbable materials and xenomaterials for staple-line reinforcement. A randomized comparative study is now in progress.     

An Open,Randomised, Multicentre,Phase 3 Trial Comparing the Efficacy of Two Tamoxifen Schedules in Preventing Gynaecomastia Induced by Bicalutamide Monotherapy in Prostate Cancer Patients

Background

Bicalutamide monotherapy is a valuable option for prostate cancer (PCa) patients who wish to avoid the consequences of androgen deprivation; however, this treatment induces gynaecomastia and mastalgia in most patients. Tamoxifen is safe and effective in preventing breast events induced by bicalutamide monotherapy without affecting antitumor activity, but possible interference between bicalutamide and tamoxifen remains a matter of concern. To reduce the exposure to tamoxifen, we considered the putative advantages of weekly administration.

Objective

To compare the efficacy of two different schedules of tamoxifen in preventing breast events. Toxicity, prostate-specific antigen behaviour, and sexual-functioning scores were also evaluated.

Design, setting, and participants

This was a noninferiority trial. From December 2003 to February 2006, 80 patients with localised/locally advanced or biochemically recurrent PCa who were also candidates for bicalutamide single therapy were randomised to receive two different schedules of tamoxifen: daily (n = 41) and weekly (n = 39). Median follow-up was 24.2 mo.

Intervention

Daily bicalutamide (150 mg) plus daily tamoxifen 20 mg continuously (daily group) or the same but with tamoxifen at 20 mg weekly after the first 8 wk of daily treatment (weekly group). Three patients in the weekly group and one in the daily group were discontinued for adverse events.

Measurements

For gynaecomastia, we used ultrasonography. For mastalgia and sexual functioning, we used questionnaires.

Results and limitations

Gynaecomastia developed in 31.7% of patients in the daily group and in 74.4% of patients in the weekly group (p < 0.0001), and it was more severe in patients who switched to weekly tamoxifen (p = 0.001). Mastalgia occurred in 12.2% and 46.1% of patients, respectively (p = 0.001). There were no major differences among treatment schedules relative to sexual functioning scores and incidence and severity of adverse events. No differences between groups in PSA behaviour and disease progression have been detected so far.

Conclusions

This study demonstrated that tamoxifen 20 mg/wk is inferior to tamoxifen 20 mg/d in preventing the incidence and severity of bicalutamide-induced breast events. The safety and efficacy of tamoxifen at the common daily dose of 20 mg for the prophylaxis of bicalutamide-induced breast events were confirmed.     

Life-threatening intrathoracic complications during treatment with extracorporeal membrane oxygenation

Extracorporeal membrane oxygenation (ECMO) has been successful (greater than 80% survival) in 35 centers in greater than 900 newborns with severe respiratory failure having an estimated mortality of greater than 80% on conventional management. During the last 3 years we have treated 79 newborns with 74 survivors (94%). Their diagnoses included meconium aspiration, persistent fetal circulation, respiratory distress syndrome, congenital diaphragmatic hernia, and sepsis. Seven patients (9%) had life-threatening intrathoracic complications requiring emergent intervention while on ECMO: tension hemothorax (3), tension pneumothorax (2), and pericardial tamponade (2). Pericardial tamponade and tension hemothorax and pneumothorax show a similar pathophysiology of increasing intrapericardial pressure and decreasing venous return. Perfusion is initially maintained by the nonpulsatile flow of the ECMO circuit before further decrease in venous return results in decreasing ECMO flow and progressive hemodynamic deterioration. Each of the seven patients demonstrated a clinical triad that includes increasing PaO2 and decreasing peripheral perfusion (as evidenced by decreasing pulse pressure and decreasing SvO2) followed by decreasing ECMO flow with progressive deterioration. The diagnoses were confirmed by transillumination, chest x-ray, or cardiac echocardiogram. Initial emergent placement of a percutaneous drainage catheter was temporizing in all seven cases. However, four patients required emergent thoracotomy for definitive treatment while still on ECMO. All seven patients were weaned from ECMO and are short-term survivors (6 months to 3.5 years). As use of ECMO for newborn severe respiratory failure increases, responsible physicians must be familiar with life-threatening intrathoracic complications and appropriate treatment strategies.     

The regenerative potential of fibroblasts in a new diabetes‐induced delayed humanised wound healing model

Cutaneous diabetic wounds greatly affect the quality of life of patients, causing a substantial economic impact on the healthcare system. The limited clinical success of conventional treatments is mainly attributed to the lack of knowledge of the pathogenic mechanisms related to chronic ulceration. Therefore, management of diabetic ulcers remains a challenging clinical issue. Within this context, reliable animal models that recapitulate situations of impaired wound healing have become essential. In this study, we established a new in vivo humanised model of delayed wound healing in a diabetic context that reproduces the main features of the human disease. Diabetes was induced by multiple low doses of streptozotocin in bioengineered human‐skin‐engrafted immunodeficient mice. The significant delay in wound closure exhibited in diabetic wounds was mainly attributed to alterations in the granulation tissue formation and resolution, involving defects in wound bed maturation, vascularisation, inflammatory response and collagen deposition. In the new model, a cell‐based wound therapy consisting of the application of plasma‐derived fibrin dermal scaffolds containing fibroblasts consistently improved the healing response by triggering granulation tissue maturation and further providing a suitable matrix for migrating keratinocytes during wound re‐epithelialisation. The present preclinical wound healing model was able to shed light on the biological processes responsible for the improvement achieved, and these findings can be extended for designing new therapeutic approaches with clinical relevance.