Advancements in dendritic cell vaccination: enhancing efficacy and optimizing combinatorial strategies for the treatment of glioblastoma.

Glioblastomas (GBM) are highly invasive, malignant primary brain tumors. The overall prognosis is poor, and management of GBMs remains a formidable challenge, necessitating novel therapeutic strategies such as dendritic cell vaccinations (DCVs). While many early clinical trials demonstrate an induction of an antitumoral immune response, outcomes are mixed and dependent on numerous factors that vary between trials. Optimization of DCVs is essential; the selection of GBM-specific antigens and the utilization of 18F-fludeoxyglucose Positron Emission Tomography (FDG-PET) may add significant value and ultimately improve outcomes for patients undergoing treatment for glioblastoma. This review provides an overview of the mechanism of DCV, assesses previous clinical trials, and discusses future strategies for the integration of DCV into glioblastoma treatment protocols. To conclude, the review discusses challenges associated with the use of DCVs and highlights the potential of integrating DCV with standard therapies.

Pediatric Trauma Care Standardization: A Statewide Survey of Trauma Providers and Program Managers.

INTRODUCTION: Rural-urban disparities in pediatric trauma outcomes are well documented. However, few studies examine how differences in setting and resources impact rural providers' approach to trauma. We sought to understand the provider experience in managing injured children across our state and assess the potential for standardization of care. METHODS: A statewide cross-sectional survey was distributed to trauma providers and program managers through the American College of Surgeons, the Oregon Medical Board lists, and the State Trauma Advisory Board. Topics included pediatric management processes, challenges, and transfer or admission procedures. Rural-urban commuting codes were used to categorize responses. RESULTS: Of the 350 individuals who sent the survey, 68 responded (response rate 19%), representing 67% of trauma-verified hospitals and 72% of Oregon counties. Fifty-six respondents (82%) care for injured children, with 58% practicing rurally and 22% at critical access hospitals. Rural providers experienced lower trauma volumes (<1 patient/month, 63% versus 0%, P < 0.001), more difficulties obtaining pediatric-appropriate material resources (44% versus 30%), and challenges caring for infants/toddlers (25% versus 17%). Despite 77% of rural providers stating that <10% of patients had multisystem injuries, they described using full-body CT often (41% versus 10%, P = 0.007). Transfer interruptions were common (93%), with 44% having cancelled a transfer. The majority supported admission/transfer (85%) and imaging (82%) protocols. CONCLUSIONS: Rural providers experience lower pediatric trauma volumes, greater material-resource issues, and discomfort with traumatically injured small children. Lack of care standardization may lead to reliance on full-body CT, and potentially complex/avoidable transfers. Adoption of standardized protocols could facilitate a state-wide collaborative approach to pediatric trauma management.

Minimizing variance in pediatric surgical care through implementation of a perioperative colon bundle: A multi-institution retrospective cohort study.

BACKGROUND: Employing an institutional initiative to minimize variance in pediatric surgical care, we implemented a set of perioperative bundled interventions for all colorectal procedures to reduce surgical site infections (SSIs). METHODS: Implementation of a standard colon bundle at two children's hospitals began in December 2014. Subjects who underwent a colorectal procedure during the study period were analyzed. Demographics, outcomes, and complications were compared with Wilcoxon Rank-Sum, Chi-square and Fisher exact tests, as appropriate. Multivariable logistic regression was performed to assess the influence of time period (independent of protocol implementation) on the rate of subsequent infection. RESULTS: One hundred and forty-five patients were identified (preprotocol=68, postprotocol= 77). Gender, diagnosis, procedure performed and wound classification were similar between groups. Superficial SSIs (21% vs. 8%, p=0.031) and readmission (16% vs. 4%, p=0.021) were significantly decreased following implementation of a colon bundle. Median hospital days, cost, reoperation, intraabdominal abscess, and anastomotic leak were unchanged before and after protocol implementation (all p > 0.05). Multivariable logistic regression found time period to be independent of SSIs (OR: 0.810, 95% CI: 0.576-1.140). CONCLUSION: Implementation of a standard pediatric perioperative colon bundle can reduce superficial SSIs. Larger prospective studies are needed to evaluate the impact of colon bundles in reducing complications, hospital stay and cost. LEVEL OF EVIDENCE: III - Retrospective cohort study.

Utilizing Technology for Global Surgery: A Survey of the West African College of Surgeons.

BACKGROUND: Information and communication technology (ICT) has been heralded as a possible mechanism for expanding global surgery collaborations. However, little is known regarding feasibility of ICT use in low- and middle-income countries (LMIC). We sought to determine the appropriate ICT platforms for surgical education initiatives and international collaborations. MATERIALS AND METHODS: We conducted a survey of members of the West African College of Surgeons. Topics included computer and internet access/utilization, familiarity with ICT, such as social media (SM), virtual document sharing platforms (VDS), virtual meeting applications (VM), and learning management systems (LM), and interest in ICT adoption. Statistical analyses were done using chi-squared tests, with Bonferroni corrections. RESULTS: Survey respondents included 83 individuals from 10 countries, 50% of whom had been in practice >10 y. All had computer access, with most (95%) using SM compared to all other modalities (P < 0.001); 77% used SM for professional reasons and 57% for education. Sixty percent of participants used VDS, 73% of whom used it for education. The utilization of other ICTs was lower (VM 43%, LM 32%). Unreliable Wi-Fi hindered every ICT, less often SM (41%) and VDS (23%), and more commonly VM (64%) and LM (52%). Despite this, VM was most often used in international collaboration (79%, P < 0.01). Most respondents (98%) supported ICT use for international collaboration. CONCLUSIONS: ICT platforms can support education initiatives and international collaborations in resource-limited areas. Deployment of similar surveys and ICT workshops across other LMIC regions could maximize ICT utilization, further expanding global surgical collaborations.

Localization and upregulation of survivin in cancer health disparities: a clinical perspective.

Survivin is one of the most important members of the inhibitors of apoptosis protein family, as it is expressed in most human cancers but is absent in normal, differentiated tissues. Lending to its importance, survivin has proven associations with apoptosis and cell cycle control, and has more recently been shown to modulate the tumor microenvironment and immune evasion as a result of its extracellular localization. Upregulation of survivin has been found in many cancers including breast, prostate, pancreatic, and hematological malignancies, and it may prove to be associated with the advanced presentation, poorer prognosis, and lower survival rates observed in ethnically diverse populations.

Rate of re-excision after breast-conserving surgery for invasive lobular carcinoma.

Invasive lobular carcinoma (ILC) accounts for approximately 5 to 20 per cent of all breast cancers and is often multicentric. Despite pre- and intraoperative assessments to achieve negative margins, ILC is reported to be associated with higher rates of positive margin. This cross-sectional study examined patients with breast cancer treated at our institution from 2000 to 2010. The objective was to investigate the rate of re-excision resulting from positive or close margin (1 mm or less) in patients who underwent breast-conserving surgery (BCS) for ILC compared with invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS). Of the 836 patients treated, 416 patients underwent BCS. The rate of re-excision after BCS for ILC was 35.1 versus 17.7 per cent for IDC and 20.0 per cent for DCIS (P = 0.04). Re-excisions were more often performed for positive margin in patients with ILC (11 of 37 [29.7%]) versus IDC (36 of 334 [10.8%]) and DCIS (five of 45 [11.1%];(P = 0.004). In this single-institution review, BCS for ILC had significantly higher rates of re-excision as a result of positive margins when compared with IDC and DCIS. Tumor size greater than 2 cm and lymph node involvement were identified as factors associated with positive surgical margin in ILC. The higher possibility of positive margins and the need for additional procedures should be discussed with patients undergoing BCS for ILC.

Plasma-derived exosomal survivin, a plausible biomarker for early detection of prostate cancer.

BACKGROUND: Survivin is expressed in prostate cancer (PCa), and its downregulation sensitizes PCa cells to chemotherapeutic agents in vitro and in vivo. Small membrane-bound vesicles called exosomes, secreted from the endosomal membrane compartment, contain RNA and protein that they readily transport via exosome internalization into recipient cells. Recent progress has shown that tumor-derived exosomes play multiple roles in tumor growth and metastasis and may produce these functions via immune escape, tumor invasion and angiogenesis. Furthermore, exosome analysis may provide novel biomarkers to diagnose or monitor PCa treatment. METHODS: Exosomes were purified from the plasma and serum from 39 PCa patients, 20 BPH patients, 8 prostate cancer recurrent and 16 healthy controls using ultracentrifugation and their quantities and qualities were quantified and visualized from both the plasma and the purified exosomes using ELISA and Western blotting, respectively. RESULTS: Survivin was significantly increased in the tumor-derived samples, compared to those from BPH and controls with virtually no difference in the quantity of Survivin detected in exosomes collected from newly diagnosed patients exhibiting low (six) or high (nine) Gleason scores. Exosome Survivin levels were also higher in patients that had relapsed on chemotherapy compared to controls. CONCLUSIONS: These studies demonstrate that Survivin exists in plasma exosomes from both normal, BPH and PCa subjects. The relative amounts of exosomal Survivin in PCa plasma was significantly higher than in those with pre-inflammatory BPH and control plasma. This differential expression of exosomal Survivin was seen with both newly diagnosed and advanced PCa subjects with high or low-grade cancers. Analysis of plasma exosomal Survivin levels may offer a convenient tool for diagnosing or monitoring PCa and may, as it is elevated in low as well as high Gleason scored samples, be used for early detection.