Surgical treatment of giant liver hydatid cysts: comparison of cystojejunostomy and partial cystectomy

Purpose

The aim of this study was to compare partial cystectomy and internal drainage of the cyst cavity with cystojejunostomy for the surgical treatment of giant hepatic hydatid cysts.

Methods

Patients who underwent any type of surgical treatment between March 2009 and May 2013 for giant hepatic hydatid cysts were retrospectively evaluated. The data collected included demographic variables, diagnostic methods, surgical procedures, morbidity and mortality rates.

Results

Twenty-eight patients who underwent surgery for giant hepatic hydatid cysts were included. There were 16 (57 %) female patients, with a mean age of 32.8 years. The diagnostic methods primarily included abdominal ultrasonography and computed tomography, which were performed in 62 % of the patients. The patients were divided into two groups with respect to the treatment modality: Group A (n = 13) treated with cystojejunostomy and Group B (n = 15) treated with partial cystectomy. The overall rate of cavity-related complications was 25 % in Group B, whereas none of the patients in Group A had a cavity-related complication during the follow-up period (p < 0.05).

Conclusion

Cystojejunostomy is an effective and safe surgical approach for the treatment of giant hepatic hydatid cysts, with a lower rate of morbidity than partial cystectomy, and thus may be the surgical treatment of choice for giant hepatic hydatid cysts.     

Impaired Metabolic Reactivity to Oxidative Stress in Early Psychosis Patients

Because increasing evidence point to the convergence of environmental and genetic risk factors to drive redox dysregulation in schizophrenia, we aim to clarify whether the metabolic anomalies associated with early psychosis reflect an adaptation to oxidative stress. Metabolomic profiling was performed to characterize the response to oxidative stress in fibroblasts from control individuals (n = 20) and early psychosis patients (n = 30), and in all, 282 metabolites were identified. In addition to the expected redox/antioxidant response, oxidative stress induced a decrease of lysolipid levels in fibroblasts from healthy controls that were largely muted in fibroblasts from patients. Most notably, fibroblasts from patients showed disrupted extracellular matrix- and arginine-related metabolism after oxidative stress, indicating impairments beyond the redox system. Plasma membrane and extracellular matrix, 2 regulators of neuronal activity and plasticity, appeared as particularly susceptible to oxidative stress and thus provide novel mechanistic insights for pathophysiological understanding of early stages of psychosis. Statistically, antipsychotic medication at the time of biopsy was not accounting for these anomalies in the metabolism of patients’ fibroblasts, indicating that they might be intrinsic to the disease. Although these results are preliminary and should be confirmed in a larger group of patients, they nevertheless indicate that the metabolic signature of reactivity to oxidative stress may provide reliable early markers of psychosis. Developing protective measures aimed at normalizing the disrupted pathways should prevent the pathological consequences of environmental stressors.Key words: mental disorder, glutathione, arginine, extracellular matrix, phospholipid, metabolism     

Molecular Imaging of Tumor-Associated Angiogenesis Using a Novel Magnetic Resonance Imaging Contrast Agent Targeting αvβ3 Integrin

Background

The recent introduction of biological anticancer therapy has renewed the interest in functional imaging of tumor-associated angiogenesis (TAA) as a tool to monitor early therapy response. The present study evaluated imaging of TAA using P1227, a novel, small molecular magnetic resonance imaging (MRI) probe targeting α_vβ₃ integrin.

Methods

HT29 human colorectal cancers were grown in athymic mice. Dynamic MRI was performed using a three-dimensional VIBE sequence up to 110 min after injection of P1227 or gadolinium–tetraazacyclododecane tetraacetic acid (Gd–DOTA). Specificity was assessed by using P1227 1 h after intravenous administration of the α_vβ₃ inhibitor cilengitide. Regions of interest were drawn encompassing the tumor rim and normal muscle. Imaging data were compared with microvessel density and α_vβ₃ expression.

Results

Using P1227, specific enhancement of the angiogenic tumor rim, but not of normal muscle, was observed, whereas Gd–DOTA enhanced tumor and normal muscle. After administering cilengitide, enhancement with P1227, but not with DOTA, was significantly suppressed during the first 20 min. When using P1227, a significant correlation was observed between normalized enhancement of the tumor rim and immunohistochemical α_vβ₃ integrin expression.

Conclusions

Molecular MRI using a small monogadolinated tracer targeting α_vβ₃ integrin and moderate magnetic field strength holds promise in assessing colorectal TAA.     

Bevacizumab Doubles the Early Postoperative Complication Rate after Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Peritoneal Carcinomatosis of Colorectal Origin

Background

Patients with stage IV colorectal cancer and peritoneal carcinomatosis are increasingly treated with curative intent and perioperative systemic chemotherapy combined with targeted therapy. The aim of this study was to analyze the potential impact of bevacizumab on early morbidity after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis of colorectal origin.

Methods

From 2004 to 2010, in three referral centers, 182 patients with colorectal carcinomatosis were treated with complete cytoreduction followed by HIPEC after either preoperative systemic chemotherapy alone or in combination with bevacizumab. Because there was no control on treatment allocation, propensity score methods were used to control for this bias.

Results

The median time from discontinuation of bevacizumab to HIPEC was 7 weeks (range 6–10 weeks). Major morbidity was greater in the bevacizumab group (34 vs. 19 %, p = 0.020). Nine patients died postoperatively, 5 (6.2 %) in the bevacizumab group (n = 80) and 4 (3.9 %) in the group treated with chemotherapy alone (n = 102) (p = 0.130). The rate of digestive fistulas was greater in the bevacizumab group, although not statistically significant (18 vs. 10 %, p = 0.300). The effect of bevacizumab on major morbidity (including death) was found to be statistically significant (odds ratio 2.28, 95 % confidence interval 1.05–4.95) (p = 0.04).

Conclusions

Administration of bevacizumab before surgery with complete cytoreduction followed by HIPEC for colorectal carcinomatosis is associated with twofold increased morbidity. The oncologic benefit of bevacizumab before HIPEC remains to be evaluated.     

Effect of tumor size on recurrence-free survival of upper tract urothelial carcinoma following surgical resection

ObjectiveTo identify predictors of recurrence-free survival (RFS) based on the clinicopathological features of patients with upper tract urothelial carcinoma (UTUC) who have undergone radical nephroureterectomy (RNU) with bladder cuff resection.Materials and methodsWe retrospectively reviewed the records of patients from October 1998 to July 2012 at our tertiary institution and identified 120 patients with sufficient data who underwent RNU for UTUC. We recorded various clinical and histopathological parameters as potential predictors of outcome. Recurrence was defined as any occurrence of urothelial carcinoma after RNU either intravesically, local/regionally, or at distant sites. Univariate, multivariate, and RFS analyses were conducted using the Cox regression and Kaplan-Meier methods.ResultsThe median age of our cohort was 71 years (interquartile range: 64–78). Median RNU-specimen tumor size was 3.0 cm (interquartile range: 2.0–5.0 cm). Fifty-four patients (45%) had a tumor<3.0 cm and 66 (55%) had a tumor≥3.0 cm. Eighty patients (66.7%) had organ-confined UTUC (≤pT2) and 40 (33.3%) had non–organ-confined UTUC (≥pT3). Sixty-five patients (54.2%) experienced at least 1 recurrence. Forty-three patients (35.8%) had at least 1 episode of intravesical recurrence and 28 (23.3%) had distant recurrence. A multivariate analysis revealed non–organ-confined disease (hazard ratio [HR] = 3.62, P<0.001), tumor diameter≥3 cm (HR = 1.97, P = 0.011), and male gender (HR = 1.81, P = 0.047) to be significant independent predictors of disease recurrence. The 5-year RFS rate was 46.9% and 25.8% for patients with tumor size<3 and≥3 cm, respectively.ConclusionsFollowing RNU, the incidence of recurrence remains high among patients with UTUC. In our cohort of patients, tumor diameter≥3.0 cm, non–organ-confined UTUC, and male gender constitute important risk factors for poor RFS outcomes following RNU. These patients require diligent postoperative surveillance and may potentially benefit from perioperative systemic therapy.     

Association of rs11190870 near LBX1 with adolescent idiopathic scoliosis in East Asians: a systematic review and meta-analysis

Background contextThe rs11190870 single nucleotide polymorphism in the 3'-flanking region of the LBX1 gene has been implicated in the etiology of adolescent idiopathic scoliosis (AIS). A thorough appraisal of the evidence supporting this association has not been previously attempted.PurposeTo provide a comprehensive assessment and synthesis of the currently available evidence on the association between rs11190870 and AIS.Study designA systematic review and meta-analysis.MethodsThis review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. PubMed (MEDLINE), EMBASE, Scopus, and HuGE Literature Finder databases were systematically searched through November 2013 to identify relevant studies following a sensitive strategy. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using the fixed-effect inverse variance model for allelic (T vs. C) and genotypic comparisons.ResultsMeta-analysis of four studies conducted in East Asian populations (n=3,215 AIS cases and n=15,347 controls) found a highly statistically significant and robust association between rs11190870 and AIS. Comparison of summary ORs indicated a codominant model effect of the T allele. Carriers of the TC and TT genotypes were 69% (OR=1.69, 95% CI: 1.48–1.94, p<.001) and 162% (OR=2.62, 95% CI: 2.28–3.02, p<.001), respectively, more likely to have AIS compared with carriers of the CC genotype.ConclusionsBased on a comprehensive analysis of the currently available evidence, rs11190870 is likely a susceptibility variant for AIS in East Asians. Further investigation of this association is necessary in other populations.     

F 16915 prevents heart failure-induced atrial fibrillation: a promising new drug as upstream therapy

Atrial fibrillation (AF) is a common complication of heart failure. The aim of the present study was to investigate the effects of a new pure docosahexaenoic acid derivative called F 16915 in experimental models of heart failure-induced atria dysfunction. The atrial dysfunction-induced AF was investigated (1) in a dog model of tachypacing-induced congestive heart failure and (2) in a rat model of heart failure induced by occlusion of left descending coronary artery and 2 months reperfusion. F 16915 (5 g/day for 4 weeks) significantly reduced the mean duration of AF induced by burst pacing in the dog model (989?±?111 s in the vehicle group to 79?±?59 s with F 16915, P?<?0.01). This dose of F 16915 also significantly reduced the incidence of sustained AF (5/5 dogs in the vehicle group versus 1/5 with F 16915, P?<?0.05). In the rat model, the percentage of shortening fraction in the F 16915 group (100 mg/kg p.o. daily) was significantly restored after 2 months (32.6?±?7.4 %, n?=?9 vs 17.6?±?3.4 %, n?=?9 in the vehicle group, P?<?0.01). F 16915 also reduced the de-phosphorylation of connexin43 from atria tissue. The present results show that treatment with F 16915 reduced the heart dilation, resynchronized the gap junction activity, and reduced the AF duration in models of heart failure. Thus, F 16915 constitutes a promising new drug as upstream therapy for the treatment of AF in patients with heart failure.