A randomized trial comparing axillary dissection to no axillary dissection in older patients with T1N0 breast cancer: results after 5 years of follow-up

SUMMARY BACKGROUND DATA: Axillary dissection, an invasive procedure that may adversely affect quality of life, used to obtain prognostic information in breast cancer, is being supplanted by sentinel node biopsy. In older women with early breast cancer and no palpable axillary nodes, it may be safe to give no axillary treatment. We addressed this issue in a randomized trial comparing axillary dissection with no axillary dissection in older patients with T1N0 breast cancer. METHODS: From 1996 to 2000, 219 women, 65 to 80 years of age, with early breast cancer and clinically negative axillary nodes were randomized to conservative breast surgery with or without axillary dissection. Tamoxifen was prescribed to all patients for 5 years. The primary endpoints were axillary events in the no axillary dissection arm, comparison of overall mortality (by log rank test), breast cancer mortality, and breast events (by Gray test). RESULTS: Considering a follow-up of 60 months, there were no significant differences in overall or breast cancer mortality, or crude cumulative incidence of breast events, between the 2 groups. Only 2 patients in the no axillary dissection arm (8 and 40 months after surgery) developed overt axillary involvement during follow-up. CONCLUSIONS: Older patients with T1N0 breast cancer can be treated by conservative breast surgery and no axillary dissection without adversely affecting breast cancer mortality or overall survival. The very low cumulative incidence of axillary events suggests that even sentinel node biopsy is unnecessary in these patients. Axillary dissection should be reserved for the small proportion of patients who later develop overt axillary disease.     

A critical role for collagen II in cartilage matrix degradation: Collagen II induces pro‐inflammatory cytokines and MMPs in primary human chondrocytes

We report a process that results in the acceleration of matrix degradation in human articular cartilage, a phenomenon commonly observed in osteoarthritis (OA). The study was conducted by (1) examining the potential of collagen II in modulating the gene expression profile of primary human chondrocytes (PHCs), and (2) investigating the involvement of pro‐inflammatory signaling cascades. We first tested the collagen II‐dependent induction of pro‐inflammatory cytokines and matrix metalloproteinases (MMPs) in PHCs. PHCs were incubated with or without monomeric (i.e., nonfibrillar) collagen II. Cells were then analyzed by RT‐PCR for the expression of MMP1, MMP3, MMP13, MMP14, and IL‐1β. ELISA was used to quantify IL‐6 and IL‐8 release. To examine the influence of collagen II signaling, specifically the role of MAPK p38, a p38‐inhibitor was added prior to collagen treatment. Changes in IκB concentration were monitored by immunoblot analysis to detect NFκB signaling. Results indicated that incubation of PHCs with collagen II did produce a dose‐dependent induction of MMP1, MMP3, MMP13, MMP14, as well as cytokines IL‐1β, IL‐6, and IL‐8. At the same time, inhibition of p38 and IκB degradation revealed that collagen II‐dependent gene induction also involves MAPK p38 and NFκB signaling. Thus, we provide evidence for a collagen II‐dependent feed‐forward mechanism whereby collagen II induces first MMPs and pro‐inflammatory cytokines and then release of collagen II fragments from mature collagen II fibers. This, in turn, induces more pro‐inflammatory cytokines and MMPs, and the process is repeated, which results in the acceleration and perpetuation of cartilage matrix degradation. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:65–70, 2009     

An In Vivo Autotransplant Model of Renal Preservation: Cold Storage Versus Machine Perfusion in the Prevention of Ischemia/Reperfusion Injury

There is increasing proof that organ preservation by machine perfusion is able to limit ischemia/reperfusion injury in kidney transplantation. This study was designed to compare the efficiency in hypothermic organ preservation by machine perfusion or cold storage in an animal model of kidney autotransplantation.
Twelve pigs underwent left nephrectomy after warm ischemic time; the organs were preserved in machine perfusion ( n  = 6) or cold storage ( n  = 6) and then autotransplanted with immediate contralateral nephrectomy. The following parameters were compared between the two groups of animals: hematological and urine indexes of renal function, blood/gas analysis values, histological features, tissue adenosine-5'-triphosphate (ATP) content, perforin gene expression in kidney biopsies, and organ weight changes were compared before and after preservation.
The amount of cellular ATP was significantly higher in organs preserved by machine perfusion; moreover, the study of apoptosis induction revealed an enhanced perforin expression in the kidneys, which underwent simple hypothermic preservation compared to the machine-preserved ones. Organ weight was significantly decreased after cold storage, but it remained quite stable for machine-perfused kidneys.
The present model seems to suggest that organ preservation by hypothermic machine perfusion is able to better control cellular impairment in comparison with cold storage.     

Saturation‐recovery metabolic‐exchange rate imaging with hyperpolarized [1‐13C] pyruvate using spectral‐spatial excitation

Within the last decade hyperpolarized [1‐¹³C] pyruvate chemical‐shift imaging has demonstrated impressive potential for metabolic MR imaging for a wide range of applications in oncology, cardiology, and neurology. In this work, a highly efficient pulse sequence is described for time‐resolved, multislice chemical shift imaging of the injected substrate and obtained downstream metabolites. Using spectral‐spatial excitation in combination with single‐shot spiral data acquisition, the overall encoding is evenly distributed between excitation and signal reception, allowing the encoding of one full two‐dimensional metabolite image per excitation. The signal‐to‐noise ratio can be flexibly adjusted and optimized using lower flip angles for the pyruvate substrate and larger ones for the downstream metabolites. Selectively adjusting the excitation of the down‐stream metabolites to 90° leads to a so‐called “saturation‐recovery” scheme with the detected signal content being determined by forward conversion of the available pyruvate. In case of repetitive excitations, the polarization is preserved using smaller flip angles for pyruvate. Metabolic exchange rates are determined spatially resolved from the metabolite images using a simplified two‐site exchange model. This novel contrast is an important step toward more quantitative metabolic imaging. Goal of this work was to derive, analyze, and implement this “saturation‐recovery metabolic exchange rate imaging” and demonstrate its capabilities in four rats bearing subcutaneous tumors. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Beating heart ischemic mitral valve repair and coronary revascularization in patients with impaired left ventricular function

OBJECTIVE: The aim of this study is to evaluate in a cohort of patients with impaired left ventricular (LV) function and ischemic mitral valve regurgitation (MVR), the effects of on-pump/beating heart versus conventional surgery in terms of postoperative mortality and morbidity and LV function improvement. MATERIALS AND METHODS: Between January 1993 and February 2001, 91 patients with LVEF between 17% and 35% and chronic ischemic MVR (grade III-IV), underwent MV repair in concomitance with coronary artery bypass grafting (CABG) Sixty-one patients (Group I) underwent cardiac surgery with cardioplegic arrest, and 30 patients (Group II) underwent beating heart combined surgery. Aortic valve insufficiency was considered a contraindication for the on-pump/beating heart procedure. Mean age in Group I was 64.4 +/- 7 years and in Group II, 65 +/- 6 years (p = 0.69). RESULTS: The in-hospital mortality in Group I was 8 (13%) patients versus 2 (7%) patients in Group II (p > 0.1). The cardiopulmonary bypass (CPB) time was significantly higher in Group I (p < 0.001). In Groups I and II, respectively (p > 0.1), 2.5 +/- 1 and 2.7 +/- 0.8 grafts per patient were employed. Perioperative complications were identified in 37 (60.7%) patients in Group I versus 10 (33%) patients in Group II (p = 0.025). Prolonged inotropic support of greater than 24 hours was needed in 48 (78.7%) patients (Group I) versus 15 (50%) patients (Group II) (p = 0.008). Postoperative IABP and low cardiac output incidence were significantly higher in Group I, p = 0.03 and p = 0.027, respectively. Postoperative bleeding greater than 1000 mL was identified in 24 patients (39.4%) in Group I versus 5 (16.7%) in Group II (p = 0.033). Renal dysfunction incidence was 65.6% (40 patients) in Group I versus 36.7% (11 patients) in Group II (p = 0.013). The echocardiographic examination within six postoperative months revealed a significant improvement of MV regurgitation fraction, LV function, and reduced dimensions in both groups. The postoperative RF was significantly lower in Group II patients 12 +/- 6 (%) versus 16 +/- 5.6 (%) in Group I (p = 0.001). The 1, 2, and 3 years actuarial survival including all deaths was 91.3%, 84.2%, and 70% in Group I and 93.3%, 87.1%, and 75% in Group II (p = ns). NYHA FC improved significantly in all patients from both groups. CONCLUSION: We conclude that patients with impaired LV function and ischemic MVR may undergo combined surgery with acceptable mortality and morbidity. The on/pump beating heart MV repair simultaneous to CABG offers an acceptable postoperative outcome in selected patients.     

Minimally invasive video-assisted thyroidectomy in pediatric patients

Background

Minimally invasive video-assisted thyroidectomy (MIVAT) proved to be safe and effective in the treatment of both benign diseases and malignancies. We report our experience in thyroid surgery in pediatric patients.

Methods

From October 1998 to December 2005, 35 patients (27 females and 8 males) underwent MIVAT for thyroid disease. The mean age was 14.0 years (range, 8-18 years); mean ecographically estimated thyroid volume was 11.13 mL (range, 8-25 mL).

Results

A total thyroidectomy was performed in 22 patients, whereas lobectomy was performed in 13. Two patients of the latter group had a second lobectomy for a false-negative result at frozen section during the first operation. One patient underwent also a prophylactic central neck dissection for positive RET oncogene. The histologic examination found a papillary carcinoma in 11 patients, a microfollicular nodule in 7 patients, and multinodular goiter in 17 patients. The mean operative time was 54.1 minutes for thyroidectomy (range, 25-110 minutes) and 38.5 minutes for lobectomy (range, 20-65 minutes). All patients but one was discharged on the first postoperative day. One transient hypoparathyroidism was observed in the patient who underwent total thyroidectomy plus central neck lymphadenectomy.

Conclusions

The MIVAT technique proved to be as safe and effective as conventional thyroidectomy with Kocher approach to treat patients with both benign and malignant diseases of the thyroid gland. The advantages of MIVAT are represented by a better and faster postoperative course and an improved aesthetic result, which is particularly important in this group of patients.     

Recurrence of functional mitral regurgitation in patients with dilated cardiomyopathy undergoing mitral valve repair: how to predict it

This study was aimed at identifying predictive variables for recurrence of mitral regurgitation (MR) in patients with dilated cardiomyopathy (DCM) undergoing mitral valve (MV) repair. From January 1997 to December 2005, 142 patients with DCM, 105 (73.9%) ischemic and 37 (26.1%) non-ischemic, underwent MV repair. Mean age was 66+/-10 years and mean MR grade was 3.2+/-0.7 (scale 1+ to 4+). Ninety-seven (71% ischemic, 29% non-ischemic), out of 98 still alive at follow-up, were included in this retrospective analysis. In all cases MV posterior annuloplasty was performed; all patients were followed-up by echocardiography (mean time interval of 44+/-28 months) to evaluate MR recurrence (>or=2+/4+). Thirty-day mortality was 9.2% (13 patients). Mean MR grade at follow-up was 0.9+/-0.9. Four-year freedom from MR recurrence was 65.5%+/-8.3. Cox analysis showed left ventricular end-diastolic volume index (LVEDVi, OR=1.03, P=0.016, AUC=0.72), left ventricular end-systolic volume index (LVESVi, OR=1.03, P=0.033, AUC=0.71), left ventricular ejection fraction (LVEF, OR=0.82, P=0.001, AUC=0.72), mitral valve coaptation depth (MVCD, OR=1.6, P=0.017, AUC=0.72) to be predictive variables for MR recurrence. Preoperative left ventricular dilatation and function along with degree of papillary muscle displacement can be helpful in identifying patients with higher probability to undergo a durable MV repair.     

Prognostic impact of HER-2/neu expression on squamous head and neck carcinomas

BACKGROUND: HER-2/neu gene amplification and protein overexpression have been identified in various solid tumors, but its prognostic relevance in head and neck squamous cell carcinoma (HNSCC) is still controversial. METHODS: The study investigated the expression of HER-2/neu oncoprotein in HNSCC and sought possible correlations to various clinicopathologic parameters. Expression of HER-2/neu oncoprotein was assessed in archival tumor tissues from 87 untreated HNSCC patients by immunohistochemical technique. Data were correlated with both the clinicopathologic parameters and patient survival. RESULTS: A high membranous HER-2/neu protein expression level was found in 39% of patients. Multivariate analysis indicated that HER-2/neu protein expression and pN lymph-node status were independent prognostic factors for disease-free survival. CONCLUSIONS: HER2/neu overexpression and its relationship with survival suggest that new therapeutic approaches targeting epidermal growth factor receptor (EGFR) family receptors could provide a new way of treating HNSCC patients with HER2/neu-positive neoplastic lesions.