BACKGROUND.Programmed cell death 4 (Pdcd4) inhibits malignant transformation, and initial studies of Pdcd4 suggested the regulation of Pdcd4 localization by protein kinase B (Akt). However, supporting patient tissue data are missing, and the diagnostic/prognostic potential of Pdcd4 rarely has been studied. The objectives of the current were 1) to determine Pdcd4 as a diagnostic marker in the adenoma‐carcinoma sequence, 2) to support phosphorylated Akt (pAkt)‐mediated Pdcd4 regulation in vivo, and 3) to obtain the first prognostic evidence of Pdcd4 in colorectal cancer.METHODS.Tumor samples and normal tissues from 71 patients with colorectal cancer who were followed prospectively (median follow‐up, 36 months) and 42 adenomas were analyzed for Pdcd4, Akt, and pAkt in immunohistochemical and Western blot analyses.RESULTS.A significant reduction in Pdcd4 was observed between normal mucosa and adenomas and between adenomas and tumor samples (P < .01 and P < .01, respectively). Normal mucosa demonstrated strong nuclear Pdcd4, which was reduced significantly in adenomas (P < .01) and almost was lost in tumors (P < .01). pAkt was correlated inversely with Pdcd4 and with the transition of Pdcd4 from nucleus to cytoplasm (P < .01). Kaplan‐Meier analysis (using the Mantel‐Cox log‐rank test) indicated a significant correlation between the loss of total and nuclear Pdcd4 in tumors and overall survival (P < .05 and P < .02, respectively) and disease‐specific survival (P < .01 and P < .01, respectively). In multivariate analysis, loss of total or nuclear Pdcd4 was an independent predictor of disease‐specific or overall survival.CONCLUSIONS.To the authors' knowledge, this is the first study to demonstrate an independent prognostic impact of Pdcd4 and its expression pattern in colorectal cancer. Data from this study support the regulation of Pdcd4 localization by pAkt in vivo. Pdcd4 immunohistochemistry may be useful as a supportive diagnostic tool for the transition between normal, adenoma, and tumor tissues. Cancer 2007. Published 2007 by the American Cancer Society.

The identification of high-risk patients with thyroid cancer and the preoperative differentiation between follicular adenoma and carcinoma remain clinically challenging. Our study was conducted to analyze whether the quantification of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator receptor (u-PAR) and transcription factor binding to the u-PAR promoter improve prognostic predictability and differential diagnosis of thyroid tumors. Tumor/normal tissue was collected from 69 prospectively followed patients with thyroid carcinomas (papillary, medullary, follicular and anaplastic, PTC, MTC, FTC and ATC) or follicular adenomas. U-PAR, MMP-1, MMP-7 and MMP-9 amounts were determined by ELISA, and transcription factor binding was determined by electrophoretic mobility shift assay. Binding of transcription factors to the u-PAR promoter was observed, but not associated with u-PAR expression. Carcinomas except MTC expressed significantly more u-PAR/MMPs than adenomas/normal tissues, this being associated with advanced pT- or M-stages. MMP-1 and MMP-9 were significantly higher in follicular carcinomas than in adenomas. In carcinomas, high u-PAR-gene expression correlated significantly with high MMP-9, the latter being associated with MMP-7 in normal tissues. Poor survival in differentiated tumors was associated in trend (p = 0.07); poor survival of all patients (p = 0.043) and especially of patients with carcinomas of follicular origin (including ATC), but not medullary carcinomas, were significantly associated with high u-PAR-protein (p = 0.015). Quantification of u-PAR is of prognostic relevance in thyroid carcinomas of non-c-cell origin, and u-PAR in part may be regulated nontranscriptionally in thyroid cancers. This is the first study to suggest MMP-1/-9 as significant differentiation markers between follicular adenoma and follicular carcinoma.

Annulus fibrosus repair techniques for the intervertebral disc (IVD) address the unsolved problem of reherniation after IVD herniation and might facilitate the development of nucleus pulposus replacement techniques for IVD diseases. This study investigates the suitability of a bio-integrative annulus implant.Standardized box defects were applied to the annulus L3/4 and L4/5 of 16 sheep, followed by randomized insertion of the textile polyglycolic acid/polyvinylidene fluoride annulus implant in one of the defects. Explantation was conducted after 2, 6 and 12 weeks, followed by provocative pressure testing and histological analysis. At 2 weeks' follow-up, all specimens of the control defect group demonstrated uncontained herniated nucleus pulposus tissue in the annulus defects. For the treated specimens, the annulus implant consistently provided an effective barrier for herniating nucleus pulposus tissue, with no implant dislocation at all time-points. After 2 weeks, a homogeneous cell infiltration of the annulus implant was observed, leading to a progressive directional matrix build-up. Repair tissue thickness was significantly stronger with the annulus implant at all follow-ups (p < 0.01). No pronounced foreign body reaction and no difference in the amount of supra-annular scar tissue over the defect sites were observed. The implantation procedure inflicted annulus damage adjacent to the defect. At later time-points, however, no difference in comparison with the control defect group was evident. The investigated biointegrative annulus implant showed promising results with regard to biointegration, enhancement of repair tissue and function as a mechanical barrier in an ovine model.

The common variations of the branching pattern of the STA are described in this study. Furthermore, surgically relevant inner diameters and lengths of the main branches of the STA are determined. These findings should improve our understanding of the suitability and usefulness of the STA for various surgical procedures.

Background We evaluated the time course and differences in the sensory recovery of three commonly used free flaps for lower extremity reconstruction. Furthermore, the sensory recovery of skin‐grafted muscle and skin paddle in latissimus dorsi flaps (LDMF) were differentiated. Methods In a prospective study, 26 patients who had undergone free flap lower extremity reconstruction were enrolled. Among them, 9 received LDMF, 9 received gracilis muscle flaps (GMF), and 8 received anterior lateral thigh flaps (ALTF). The sensory recovery was investigated by using the Semmes–Weinstein test (SWT) at 6 and 12 months after the surgery. Results All flaps recorded spontaneous sensory recovery. The GMF showed the smallest anesthetic area after 12 months as compared with the ALTF and LDMF (1 ± 3% vs. 18 ± 39% (p < .05) vs. 35 ± 35% (p < .05), respectively). Qualitatively, ALTF exhibited the best sensory recovery with the lowest SWT values (ALTF 4.57 ± 1.12 vs. GMF 5.01 ± 0.81 8 [p < .05], vs. LDMF 5.84 ± 0.52 [p < .05]). The sensory recovery of skin‐grafted muscle was superior to that of the skin paddle in the LDMF (anesthetic area 29 ± 36% vs. 54 ± 33% [p < .05], SWT 5.85 ± 0.60 vs. 6.30 ± 0.18 [p < .05], respectively). Conclusion All flaps displayed spontaneous sensory recovery potential over the investigation period, which appeared to be influenced by the flap type and size. The LDMF skin paddle showed lower potential for sensory recovery as compared with the skin‐grafted muscle area of the same flap. The GMF demonstrated a near‐complete sensory recovery after 12 months.

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Background: A two center retrospective cohort study of simultaneous bilateral breast reconstructions using double deep inferior epigastric perforator (DIEP) flaps and double transverse myocutaneous/upper gracilis (TMG) flaps was conducted. The aim of this study was to compare surgical procedures, complications, and overall outcome. Patients and Methods: Two study groups, either receiving a simultaneous bilateral breast reconstruction, with double DIEP flaps (n = 152) in group 1, or double TMG flaps (n = 86) in group 2, were compared. A detailed risk and complication analysis was performed. Patient characteristics, operative time and the need for further operations were evaluated. Results: Double DIEP patients had donor site complications in 23.7% and double TMG patients in 16.3% (p = 0.9075, RR 1.45). Flap loss rates of 3.5% (double TMG) and 2.6% (double DIEP) were recorded (p = 0.7071, RR 1.33). The need for postoperative lipofilling was significantly higher in double TMG patients (65.1% vs. 38.2 %, p = 0.0047, RR 1.71). Conclusion: Complication analysis favors the double DIEP procedure. Donor site morbidity was lower and less severe in the double TMG group. Later fat grafting was more frequently needed after double TMG reconstructions. Further studies, preferably of prospective nature, are needed to evaluate the benefit of bilateral simultaneous breast reconstructions.

Background The need for plastic and reconstructive surgery on elderly patients has been on the rise due to an increase in life expectancy in the past decades. Therefore, a study was conducted on young and elderly patients following microsurgical extremity reconstructions with free gracilis muscle flaps with the primary aim to investigate the influence of age and the American Society of Anesthesiologists (ASA) score on the general outcome, as well as surgical and medical complications. Methods A retrospective analysis of 153 patients receiving free gracilis muscle flaps for extremity reconstructions between November 2009 and January 2018 was performed at two partner institutions specialized in microsurgical reconstructions. A logistic regression analysis was performed to correlate age and the ASA score with postoperative complication probability. Patients younger than 70 years were directly compared with elderly patients with respect to age, gender, ASA score, preexisting comorbidities, localization, and postoperative medical and surgical complications. Results Age turned out to be not significantly associated with major flap complications (p = 0.925) but with higher ASA scores (p = 0.016). However, an age-related significant increase in minor flap complications could be observed in the elderly (p = 0.008). A significant correlation between minor medical complications and age could be observed (p = 0.001) in contrast to ASA score (p = 0.912). Conclusion An increased minor flap, as well as minor and major medical complications, must be expected in extremity reconstructions with free gracilis flaps in elderly patients. Higher ASA scores correlate with a higher incidence of major flap complications. Septuagenarians are more prone to develop perioperative major medical complications than patients younger than 70 years. Age and general medical condition, coupled with the performance of each patient, should be thoroughly assessed individually to facilitate a tailored reconstructive approach using risk assessment tools and established scoring systems.