Dual responsive oligo(lysine)-modified Pluronic F127 hydrogels for drug release of 5-fluorouracil

Peptide-containing hydrogels have become a research hotspot due to their unique secondary structure and biocompatibility. Herein, we used amino-terminated F127 as a macroinitiator to initiate the ring-opening polymerization of l-lysine(z)-NCA, and the obtained oligo(lysine)-modified F127 (FL) had degrees of polymerization of lysine of 2, 5, and 8. The results showed that the FL hydrogels had reversible temperature-dependent sol–gel transitions, and the introduction of lysine increased the critical gel temperature. In the dilute solution of FL, the micelle size increased and aggregated as the pH increased; the micelle grew into a rod-like shape under alkaline conditions. Scanning electron micrographs showed that the interior of the FL hydrogel had a more complete porous structure. The FL-2 hydrogel loaded with 5-fluorouracil exhibited an approximately linear release trend within 12 h and has good biocompatibility. Therefore, FL hydrogels have potential applications in the field of biomedicine.

Oligo(lysine)-F127 hydrogels have a temperature-responsive sol–gel transition and pH-responsive micelle morphology.     

Diagnosis of female urethral diverticulum using transvaginal contrast-enhanced sonourethrography

Introduction and hypothesis

This study investigated the value of transvaginal contrast-enhanced sonourethrography for the diagnosis of female urethral diverticulum (UD) by comparing results of contrast-enhanced ultrasound images and surgical findings.

Methods

A total of 14 female UD patients underwent preoperative transvaginal contrast-enhanced sonourethrography between July 2010 and June 2012. History and physical examination were initially assessed by the same urologist. Transvaginal contrast-enhanced ultrasound imaging was performed and interpreted by the same ultrasonographer. Definite diagnosis was made by tracking the flow of the microbubbles into the cyst. Additionally, sagittal, cross-sectional, and dynamic images were obtained, and color Doppler ultrasound was applied in all cases. Data on the size, location, configuration, and opening of the UD was documented, and then compared with the surgical findings.

Results

The most common symptoms presenting in the UD patients included urinary incontinence (71.5 %), recurrent urinary tract infection (57.1 %), frequency (50 %), urgency (35.7 %), dysuria (35.7 %), and dyspareunia (21.4 %). On physical examination, 8 out of 14 patients (57.1 %) had a palpable anterior vaginal wall mass, while 6 out of 14 patients (42.9 %) had no palpable mass. Transvaginal contrast-enhanced sonourethrography revealed 17 diverticula orifices in total and correlated well with surgical findings regarding the size, location, configuration, and the opening of the UD.

Conclusions

In patients with chronic irritative bladder symptoms, but with no response to conventional treatment a high index of suspicion for UD should be maintained. Our study demonstrates that transvaginal contrast-enhanced sonourethrography is a useful tool for defining the size, location, configuration, and opening of the UD before surgery.     

Reduced plasma ghrelin levels on day 1 after esophagectomy: a new predictor of prolonged systemic inflammatory response syndrome

Background and purpose

Ghrelin, a stomach-derived hormone, stimulates growth hormone secretion and appetite, and inhibits excessive inflammatory response. Plasma ghrelin might affect the inflammatory response to stressful surgical interventions. The aim of this study was to investigate the relationship between serial changes in plasma ghrelin concentrations and the postoperative clinical course after esophagectomy.

Methods

The prospective cohort study subjects were 20 patients with esophageal cancer, who underwent esophagectomy with gastric tube reconstruction. Blood samples were taken six times perioperatively during the course of esophagectomy.

Results

The plasma ghrelin level decreased to 33 % (range 15?C90 %) on postoperative day (POD) 1, relative to the preoperative level, then recovered to about 50 % by POD 3?C10. The duration of systemic inflammatory response syndrome (SIRS) was significantly longer in patients with a marked ghrelin reduction to <33 % on POD 1, than in those with less marked reduction of ??33 % (6.1 ± 1.3 vs. 2.1 ± 0.6 days, P = 0.019). On POD 1, the only inflammatory marker that correlated with the duration of SIRS was the % ghrelin, whereas C-reactive protein, leukocyte count, and IL-6 did not.

Conclusion

An early postoperative drop in plasma ghrelin correlated with prolonged SIRS after esophagectomy. Thus, the supplementation of low plasma ghrelin may help minimize excess inflammatory response in these patients.     

Surgical treatment for nonspecific esophageal motility disorders

Purpose

Nonspecific esophageal motility disorder (NEMD) is a vague category that includes patients with poorly defined contraction abnormalities observed during esophageal manometry. This study investigated the therapeutic effects of the video-assisted thoracoscopic surgery (VATS) approach using long myotomy and fundopexy for NEMD.

Methods

The VATS approach using myotomy and fundopexy was performed for 4 patients of NEMD between 2005 and 2008. A total of 4 patients with NEMD that underwent treatment at our institution were analyzed retrospectively.

Results

The patients included 2 males and 2 females with a median age of 48 years (range 21–74 years). The median duration of NEMD symptoms was 58 months (range 4–108 months). Dysphagia was a primary symptom in all patients. Chest pain was a primary symptom in 3 of 4 patients (75 %). Treatment with medication was attempted before the operation. The median operative time was 344.5 min (range 210–476 min). The median time before starting oral feeding was 2.5 days (range 2–22 days). All patients achieved a significant improvement of their previous condition.

Conclusions

The VATS approach using myotomy and fundopexy for NEMD is a good treatment in cases resistant to medication and balloon dilation.     

Kinetics of testosterone recovery in clinically localized prostate cancer patients treated with radical prostatectomy and subsequent short-term adjuvant androgen deprivation therapy

Androgen deprivation therapy (ADT) is a standard treatment for metastatic, recurrent and locally advanced prostate cancer (PCa). The aim of this study is to investigate the timing and extent of testosterone recovery in clinically localized PCa patients treated with radical prostatectomy (RP) and subsequent short-term adjuvant ADT. A total of 95 localized PCa patients underwent RP and 9-month adjuvant ADT were included in this prospective study. Serum testosterone level was measured before adjuvant ADT, at ADT cessation, and at 1, 3, 6, 9 and 12 months after cessation of ADT. A Cox proportional hazards model was used to assess variables associated with the time of testosterone normalization. The results showed that median patient age was 67 years and median testosterone level before adjuvant ADT was 361 (230–905) ng dl⁻¹. All patients finished 9-month adjuvant ADT and achieved castrate testosterone level. At 3 months after ADT cessation, testosterone recovered to supracastrate level in 97.9% patients and to normal level in 36.9% patients. The percentage of patients who recovered to normal testosterone level increased to 66.3%, 86.3% and 92.6% at 6, 9 and 12 months, respectively. Cox regression model found that higher baseline testosterone level (≥300 ng dl⁻¹) was the only variable associated with a shorter time to testosterone normalization (hazard ratio: 1.98; P = 0.012). In conclusion, in most patients, testosterone recovered to supracastrate level at 3 months and to normal level at 12 months after 9-month adjuvant ADT cessation. Patients with higher baseline testosterone level need shorter time of testosterone normalization.     

The effectiveness of the TAX 327 nomogram in predicting overall survival in Chinese patients with metastatic castration-resistant prostate cancer

Based on the results of TAX 327, a nomogram was developed to predict the overall survival of metastatic castration-resistant prostate cancer （mCRPC） after first-line chemotherapy. The nomogram, however, has not been validated in an independent dataset, especially in a series out of clinical trials. Thus, the objective of the current study was to validate the TAX 327 nomogram in a community setting in China. A total of 146 patients with mCRPC who received first-line chemotherapy （docetaxel or mitoxantrone） were identified. Because clinical trials are limited in mainland China, those patients did not receive investigational treatment after the failure of first-line chemotherapy. The predicted overall survival rate was calculated from the TAX 327 nomogram. The validity of the model was assessed with discrimination, calibration and decision curve analysis. The median survival of the cohort was 21 months （docetaxel） and 19 months （mitoxantrone） at last follow-up. The predictive c-index of the TAX 327 nomogram was 0.66 （95% CI： 0.54-0.70）. The calibration plot demonstrated that the 2-year survival rate was underestimated by the nomogram. Decision curve analysis showed a net benefit of the nomogram at a threshold probability greater than 30%. In conclusion, the present validation study did not confirm the predictive value of the TAX 327 nomogram in a contemporary community series of men in China, and further studies with a large sample size to develop or validate nomograms for predicting survival and selecting therapies in advanced prostate cancer are necessary.     

Repair of avascular meniscal injuries using juvenile meniscal fragments: An in vitro organ culture study

We investigated whether the implantation of juvenile allograft and minced meniscal fragments could improve the healing of avascular meniscal injuries, which cannot heal spontaneously. Concentric cylindrical explants were excised from the inner two‐thirds of swine medial menisci. The inner cylinder consisted of a “sandwich” structure, with minced juvenile meniscal fragments, juvenile meniscal columns, minced mature meniscal fragments, or mature meniscal columns implanted in the middle. The explants were cultured in vitro for 2, 4, or 6 weeks. Interfacial meniscal repair was assessed by histology, immunohistochemistry, biomechanical testing, and confocal laser scanning microscopy. Histology and confocal microscopy results revealed that tissue repair and cell accumulation at the interface were best at all time points in the juvenile meniscal fragments group, followed by the juvenile columns, minced mature fragments, and mature columns groups, respectively. At 6 weeks, the implantation of juvenile allograft and minced meniscal fragments increased the shear strength, peak force, and energy to failure in the peripheral interface. Picosirius red/polarized light microscopy and immunohistochemistry results showed concurrent expression of type I and II collagen in the interfacial repair tissue. In conclusion, implantation of juvenile allograft and minced meniscal fragments could increase the healing of avascular meniscal injury in vitro. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1514–1519, 2013     

Survival Outcome after Stereotactic Body Radiation Therapy and Surgery for Early Stage Non-Small Cell Lung Cancer: A Meta-Analysis

ABSTRACT

Objective: Treatment modalities in medically compromised patients with early-stage non-small cell lung cancer (NSCLC) are controversial. Stereotactic body radiotherapy (SBRT) or stereotactic ablative radiotherapy has been increasingly recognized as a favorable alternative to surgical resection for early-stage NSCLC. Many retrospective analyses compared the efficacy of stereotactic body radiotherapy (SBRT) with surgery for early-stage non-small cell lung cancer (NSCLC). However, the efficacy between SBRT and surgery regimens for patients with early-stage NSCLC remains unclear. This study aimed to investigate the efficacy between SBRT and surgery. Methods: Publications on comparison SBRT with Surgery in treatment of early stage non-small cell lung cancer (NSCLC) from 2011 to 2017 were collected. Retrospective trials analyzed the summary hazard ratios (HRs) of overall survival (OS), disease-free survival (DFS), local control survival (LC), regional control survival (RC), loco-regional control survival (LRC), and distant control survival (DC) between SBRT and Surgery. The major outcomes measures were hazard ratios (HRs). Meta-analysis Revman 5.3 software was used to analyze the combined Pooled HRs using fixed- or random-effects models according to the heterogeneity. Result: A systematic literature search was conducted including14 studies. In this meta-analysis, patients with SBRT achieved inferior OS, DFS, LC, RC, LRC and DC, compared with surgery. Conclusion: In this study we found more favorable outcomes with stage I NSCLC treated with SBRT. The surgery had no obvious advantages in this meta-analysis. Although surgery has become the recommended treatment at present, SBRT has potential to be an alternative treatment as a novel non-invasive radiation therapy modality in patients with stage I-II NSCLC.