Benefits of Liver Transplantation Surgical Techniques in the Management of Extensive Retroperitoneal Tumors

Background  The potential for massive hemorrhage imposes additional challenge in the management of retroperitoneal tumors. This report details technical considerations for the management of upper retroperitoneal tumors using principles of liver transplantation. Methods  A retrospective chart review of patients who underwent surgery for extensive retroperitoneal tumors using techniques for liver transplantation from December 2002 to November 2007 was done. Results  Twenty-four patients (14 males and 10 females with a mean age 57 years) underwent major retroperitoneal surgery. Renal cell carcinoma was the most common tumor seen in 17 patients. Mean tumor dimension was 12.4 cm. Abdominal exposure was achieved via bilateral subcostal incision with upper midline extension. Right hepatic lobe mobilization and isolation from the inferior vena cava (IVC) was performed in 23 cases. Fourteen patients had IVC involvement by tumor thrombus, which was infrahepatic in six, retrohepatic in five, and intra-atrial in three patients. Tumor thrombus was removed by cavotomy in seven cases, resection and plasty in four cases, IVC graft reconstruction in two cases, and one patient required IVC and atrial graft reconstruction. Liver resection was needed in seven patients to achieve R0 resection. The Pringle maneuver was used in three patients; total liver vascular isolation with venovenous bypass was required in two cases, transdiaphragmatic intrapericardial IVC control in one case, and cardiopulmonary bypass in one patient. There was no intraoperative or postoperative mortality and mean length of stay was 13 days. Conclusion  Liver transplantation surgical principles help achieve exposure and vascular control of major vascular structures that enable safe resection of these extensive retroperitoneal tumors.     

Clusterin expression is significantly enhanced in prostate cancer cells following androgen withdrawal therapy

INTRODUCTION AND OBJECTIVES: Progression of prostate cancer to androgen independence (AI) results in part from the upregulation of anti-apoptotic genes following androgen withdrawal, and androgen-independent disease remains the primary obstacle to improved survival. Testosterone-repressed prostate message-2 (TRPM-2) encodes the anti-apoptotic protein clusterin, which is upregulated in response to cellular compromise as observed in normal and malignant tissues undergoing apoptosis. Systemic administration of antisense clusterin oligonucleotides in prostate cancer xenograft models delays progression to AI and enhances chemosensitivity. The objective of this study was to define changes in clusterin expression following neoadjuvant hormone therapy (NHT) in prostate cancer patients. MATERIALS AND METHODS: Archival radical prostatectomy (RP) specimens were obtained for 128 patients who received either no NHT or treatment for 2-8 weeks, 3 months, or 8 months. Paired needle biopsy specimens were acquired for 30 patients and all tissues were subjected to clusterin immunohistochemistry. Western blot analysis was performed on frozen tissue from 5 untreated and 5 treated patients. RESULTS: Clusterin expression in malignant prostatic tissue was significantly greater in patients who underwent preoperative NHT (P < 0.001). Needle biopsies obtained prior to NHT consistently demonstrated lower staining intensity than corresponding RP specimens (P < 0.001). Western blot analysis confirmed clusterin levels increased 17-fold beginning within 4 weeks after androgen withdrawal. CONCLUSIONS: Upregulation of clusterin levels following androgen ablation therapy may represent an adaptive cell survival response following apoptotic signals like androgen withdrawal. These findings support clusterin as a valid therapeutic target in strategies employing novel multimodality therapy for advanced prostate cancer.     

Fontan completion without surgery.

OBJECTIVE: There are several modifications introduced in the preparation for a subsequent non-surgical transcatheter completion of the Fontan procedure. We report our experience with one type of the modification and the short-term results following its implementation. METHODS: During bidirectional cavopulmonary connection (BCPC) an intra-atrial lateral tunnel is additionally created, as intended for a Fontan procedure but fenestrated with a 10-14 mm aperture. The cardiac end of the superior vena cava (SVC) is then patched to maintain the physiology of BCPC. During the interventional transcatheter completion procedure, the SVC patch is perforated using radio-frequency (RF) energy, balloon-dilated, and stented as well. The aperture is closed with a device when required. Paired t-test was used to compare data before and after the Fontan completion. RESULTS: From June 2003 to February 2006, 16 patients (9 boys and 7 girls, mean age 12 months) underwent the surgical procedure described. The mean bypass time was 137 min and the mean ischemic time was 77 min. There were no operative deaths. One patient with bilateral SVC required a take down due to recurrent effusions. Ten months later, nine patients underwent completion (mean age 20 months, mean weight 10.6 kg). The stents were dilated to a mean diameter of 14.4mm. All except one aperture was closed with a device. The mean fluoroscopy time was 41 min. Oxygen saturation increased from 85 to 94% (p=0.001). Pulmonary artery pressures remained normal (16 mmHg before and 19 mmHg after, p=0.12). No patients required mechanical ventilation and none developed pleural effusions or arrhythmias. All were discharged from hospital within 6 days of the Fontan completion. Twenty-two months after Fontan, all were well. Echocardiography revealed no gradients across the stents. Two patients had minor leaks across the aperture. One underwent further stent dilatation a year later. CONCLUSIONS: Fontan completion without surgery is suitable in patients with single ventricles with lower mortality and morbidity, avoids multiple surgical interventions while maintaining the staged approach and allows for successive dilatation of the Fontan pathway to accommodate for growth.     

Vertebral bone quality score predicts fragility fractures independently of bone mineral density

BackgroundCurrent evidence suggests that dual-energy x-ray absorptiometry (DXA) scans, the conventional method defining osteoporosis, is underutilized and, when used, may underestimate patient risk for skeletal fragility. It has recently been suggested that other imaging modalities may better estimate bone quality, such as the magnetic resonance imaging (MRI)-based vertebral bone quality (VBQ) score which also may assess vertebral compression fracture risk in patients with spine metastases.PurposeTo evaluate whether VBQ score is predictive of fragility fractures in a population with pre-existing low bone density and at high-risk for fracture.Study Design/SettingRetrospective single-center cohort.Patient SamplePatients followed at a metabolic bone clinic for osteopenia and/or osteoporosis.Outcome MeasuresRadiographically-documented new-onset fragility fracture.MethodsPatients with a DXA and MRI scans at the time of consultation and ≥2-year follow-up were included. Details were gathered about patient demographics, health history, current medication use, and serological studies of kidney function and bone turnover. For each patient, VBQ score was calculated using T1-weighted lumbar MRI images. Univariable and multivariable analyses were used to identify the independent predictors of a new fragility fracture. To support the construct validity of VBQ, patient VBQ scores were compared to those in a cohort of 45 healthy adults.ResultsSeventy-two (39.1%) study participants suffered fragility fractures, the occurrence of which was associated with higher VBQ score (3.50 vs. 3.01; p<.001), chronic glucocorticoid use (30.6% vs. 15.2%; p=.014), and a history of prior fragility fracture (36.1% vs. 21.4%; p=.030). Mean VBQ score across all patients in the study cohort was significantly higher than the mean VBQ score in the healthy controls (p<.001). In multivariable analysis, new-onset fracture was independently associated with history of prior fracture (OR=6.94; 95% confidence interval [2.48–19.40]; p<.001), higher VBQ score (OR=2.40 per point; [1.30–4.44]; p=.003), higher body mass index (OR=1.09 per kg/m²; [1.01–1.17]; p=.03), and chronic glucocorticoid use (OR=2.89; [1.03–8.17]; p=0.043). Notably, DXA bone mineral density (BMD) was not found to be significantly predictive of new-onset fractures in the multivariable analysis (p=.081).ConclusionsHere we demonstrate the novel, MRI-derived VBQ score is both an independent predictor of fragility fracture in at-risk patients and a superior predictor of fracture risk than DXA-measured BMD. Given the frequency with which MRIs are obtained by patients undergoing spine surgery consultation, we believe the VBQ score could be a valuable tool for estimating bone quality in order to optimize the management of these patients.     

Donor‐specific chimeric antigen receptor Tregs limit rejection in naive but not sensitized allograft recipients

Cell therapy with autologous donor‐specific regulatory T cells (Tregs) is a promising strategy to minimize immunosuppression in transplant recipients. Chimeric antigen receptor (CAR) technology has recently been used successfully to generate donor‐specific Tregs and overcome the limitations of enrichment protocols based on repetitive stimulations with alloantigens. However, the ability of CAR‐Treg therapy to control alloreactivity in immunocompetent recipients is unknown. We first analyzed the effect of donor‐specific CAR Tregs on alloreactivity in naive, immunocompetent mice receiving skin allografts. Tregs expressing an irrelevant or anti‐HLA‐A2‐specific CAR were administered to Bl/6 mice at the time of transplanting an HLA‐A2⁺ Bl/6 skin graft. Donor‐specific CAR‐Tregs, but not irrelevant‐CAR Tregs, significantly delayed skin rejection and diminished donor‐specific antibodies (DSAs) and frequencies of DSA‐secreting B cells. Donor‐specific CAR‐Treg–treated mice also had a weaker recall DSA response, but normal responses to an irrelevant antigen, demonstrating antigen‐specific suppression. When donor‐specific CAR Tregs were tested in HLA‐A2‐sensitized mice, they were unable to delay allograft rejection or diminish DSAs. The finding that donor‐specific CAR‐Tregs restrain de novo but not memory alloreactivity has important implications for their use as an adoptive cell therapy in transplantation.     

Optimal fluid intake in daily diet: Avicenna’s view

Adequate daily water consumption is an important factor of keeping regular homeostasis. However, the best quantity of daily water consumption for a healthy individual is not virtually stated in the literature. Despite the dearth of evidence-based recommendations, it is commonly thought that ingesting eight glasses of water a day is good for a healthy person. Avicenna had a unique viewpoint. He believed that daily water intake depended on numerous elements together with age, intercourse, body temperament, season, occupation and various internal and external elements. He also cited a few essential and useful measures regarding proper water consumption, which have additionally been emphasized in Islamic hadiths.     

社区药房药师抗生素耐药认知与不凭处方调配抗生素行为调查

目的：评估社区药房药师抗生素耐药认知与不凭处方调配抗生素行为,分析二者之间的关系。方法：于2016年对西安市社区药房药师开展问卷调查,使用视觉模拟量尺,测量受访药师对抗生素耐药的认知,自报不凭处方调配抗生素行为,应答率为77.3%（99/128）。对数据进行描述,检验不同行为组间认识的差异性。结果：多数受访药师对抗生素耐药具有基本认知,74.8%（74/99）的被调查者报告了不凭处方调配抗生素的行为;未发现抗生素耐药认知与不凭处方调配抗生素行为之间的显著性关系。结论：社区药房药师不规范的抗生素调配行为比较普遍。仅通过强化认知水平来降低不凭处方的调配行为难以取得良好效果。管理药师群体和公众抗生素用药习惯,治理社区药房不规范药品销售行为,可能是更好的策略。     

Flixweed vs. Polyethylene Glycol in the Treatment of Childhood Functional Constipation: A Randomized Clinical Trial

Background:

Polyethylene glycol (PEG) is often considered as the first-line treatment for functional constipation in children. Descurainia sophia (L.) Webb et Berth (D. sophia) is a safe recommended medicine in Iranian folk and Traditional Persian Medicine for the treatment of constipation.

Objectives:

To clinically compare D. sophia with PEG 4000 (without electrolyte) in pediatric constipation and to assess its efficacy and side effects.

Patients and Methods:

120 patients aged 2 - 12 years with constipation for at least 3 months were included in an 8 weeks lasting randomized controlled trial within two parallel-groups. Children received either PEG, 0.4 g/kg/day, or D. sophia seeds, 2 grams (for children aged 2 - 4 years) and 3 grams (for those aged > 4 years) per day.

Results:

A total of 109 patients completed the study (56 in D. sophia and 53 in PEG group). At the end of the study, 36 (64.3%) patients in D. sophia group and 29 (54.7%) in PEG group were out of Rome III criteria (P = 0.205). Median weekly stool frequency in 0, 1, 2, 3 weeks of the treatment was found to be 2, 5, 5, 5 in D. sophia and 3, 4, 4, 5 in PEG group (P = 0.139, 0.076, 0.844, 0.294), respectively. The number of patients who suffered flatulence was less (5, 8.9%) in D. sophia group as compared to PEG group (6, 11.3%) at the end of the trial (P = 0.461). D. sophia taste was less tolerated.

Conclusions:

D. sophia is introduced as a cheap and available medication which can be applied as a safe alternative to conventional PEG in the management of pediatric chronic functional constipation.