Intraoperative HDR brachytherapy for rectal cancer using a flexible intraoperative template: standard plans versus individual planning.

HDR intraoperative brachytherapy (IOBT) is applied to locally advanced rectal tumors using a 5 mm thick flexible intraoperative template (FIT). To reduce the procedure time, treatment planning is performed using standard plans that neglect the curvature of the FIT. We have calculated the individual treatment plan, based on the real geometry of the FIT, and the dose at clips placed during surgery. A mean treatment dose of 9.55+/-0.21 Gy was found for the individual plan, compared to the prescribed 10 Gy (P<0.0001) The mean central dose was 10.03+/-0.10 Gy in the standard plan and 9.20+/-0.32 Gy in the individual plan (P<0.0001) The mean dose at the corners of the FIT was 10.3 Gy in the standard plan and ranged between 10.3 and 10.5 Gy in the individual plan. In 63% of the clips, the dose was larger than 15.0 Gy, which is equivalent to a gap between the FIT and the target smaller than 5 mm. In 18% of the clips, the dose was smaller than 13.0 Gy indicating that locally the gap was larger than 5 mm. Clinical practice will have to prove if these small dose deviations influence the clinical outcome.     

Use of AcrySof acrylic foldable intraocular lens for secondary implantation in children.

PURPOSE: Secondary intraocular lens (IOL) implantation is an increasingly viable option in the management of pediatric aphakia. We report our experience of secondary IOL implantation in pediatric patients using the AcrySof (Alcon Surgical, Fort Worth, Texas) 3-piece foldable lenses through a small incision. METHODS: We reviewed the records of all our patients < 18 years undergoing secondary IOL implantation of the AcrySof lens from 1997 to 2001. All patients with a minimum of 6 months follow-up were included. Records were analyzed for age at surgery, postoperative acuity change, postoperative refractive error and anisometropia, surgical complications, and length of follow-up. RESULTS: Fifty-five eyes of 36 patients were included in the review. Mean age at surgery was 7.4 years (1.1 to 15.4), and mean follow-up was 28 months (6.3 months to 5 years). Vision decrease > 2 lines was noted in 3 eyes (5.8%) during the follow-up period. Complications included IOL decentration in 3 eyes (5%), wound leak in 3 eyes (5%), secondary membrane formation in 5 eyes (9%), pupillary block glaucoma in 1 eye (2%), and ptosis in 1 eye (2%). Four eyes (7%) required reoperation for complications. Mean postoperative refractive error was -0.1 +/- 3.2 diopters (D), and mean anisometropia was 2.01 +/- 1.44 D. Glaucoma subsequently developed in 6 eyes (11%), 2 of which required surgical correction. CONCLUSIONS: Secondary placement of the AcrySof IOL in the ciliary sulcus is a safe and effective method to correct aphakia in pediatric patients with adequate capsular support. The incidence of complications requiring reoperation is low.     

Immunogenicity of meningococcal PorA formulations encapsulated in biodegradable microspheres.

The purpose of our study was to investigate the possibility to microencapsulate liposomes and meningococcal outer membrane vesicles (OMV), both containing neisserial pore protein A (PorA), in biodegradable dextran- and mannan-based microspheres and to study the immunogenicity of the encapsulated PorA formulations. PorA-liposomes and OMV were encapsulated in dextran- or mannan-based microspheres by using an aqueous two-phase system consisting of a polyethylene glycol solution and a methacrylated dextran or mannan solution. The formulations were characterized for size distribution, PorA structure and antigen recovery after release. Calcein-containing model liposomes were used to establish the encapsulation efficiency and release profiles from both types of microspheres. The immunogenicity of the PorA-containing formulations was determined in mice after subcutaneous immunization. Liposomes were encapsulated in dextran and mannan microspheres with a high efficiency (70-90%). Calcein liposomes, after a 5-day lag period, exhibited apparent zero-order release kinetics from both types of microspheres between Days 5 and 10 of incubation in vitro. The total release was 80 and 100% from mannan and dextran microspheres, respectively. The trimeric PorA conformation was preserved in the released liposomes and OMV and the antigen was partly recovered. The immunogenicity of PorA-liposomes and OMV encapsulated in dextran or mannan microspheres was preserved. In conclusion, PorA-liposomes and OMV could be encapsulated in dextran- and mannan-based microspheres with high efficiency. The immunogenicity of encapsulated antigen was preserved.     

Locoregional control and survival after lymph node SBRT in oligometastatic disease

Stereotactic body radiotherapy (SBRT) has emerged as an effective option in oligo-metastatic cancer patients affected by lymph node metastases, but its use might be questioned due to risk of regional and distant dissemination through the lymph node chain. The primary aim of our study was to assess the loco-regional control following SBRT in this setting. Ninety-one patients undergoing SBRT for at least one lymph node metastasis from miscellaneous primary tumors were retrospectively evaluated for patterns of failure and toxicity. locoregional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS) at 4 years were 79 and 44%. Repeated use of local therapy after progression resulted in a median interval of 17 months until allocation to systemic therapy or supportive care. Forty-three percent of patients were alive at 4 years. Local failure, occurring in 15% of patients, was the only predictor of poor survival (HR: 3.06). Tumor diameter?≥?30 mm and urothelial primary tumor predicted for impaired local control (HR: 4.59 and 5.43, respectively). Metastases from pulmonary cancer showed a significant earlier distant dissemination (HR: 3.53). Only acute and late grade 1–2 toxicities were reported except for 1 case of G3 dysphagia. Loco-regional failure risk is low (18%) and justifies the use of local therapies for patients with oligometastatic disease. Durable disease remission can be achieved by iterative use of local approaches. Local control is correlated to improved OS. Diameter and primary tumor type may affect response to SBRT and risk for early metastatic dissemination.     

Cytokine expression profile in the bone‐anchored hearing system: 12‐week results from a prospective randomized,controlled study

Objective

To study the effect of implanting the percutaneous bone‐anchored hearing system (BAHS) itself and inflammation of the peri‐abutment skin warrant clarification. In this study, we aimed to acquire further insight into the immune responses related to BAHS surgery and peri‐implant skin inflammation.

Materials and Methods

During surgery and 12 weeks post‐implantation, skin biopsies were obtained. If applicable, additional biopsies were taken during cases of inflammation. The mRNA expression of IL‐1β, IL‐6, IL‐8, TNFα, IL‐17, IL‐10, TGF‐ß, MIP‐1α, MMP‐9, TIMP‐1, COL1α1, VEGF‐A, FGF‐2 TLR‐2, and TLR‐4 was quantified using qRT‐PCR.

Results

Thirty‐five patients agreed to the surgery and 12‐week biopsy. Twenty‐two patients had mRNA of sufficient quality for analysis. Ten were fitted with a BAHS using the minimally invasive Ponto surgery technique. Twelve were fitted with a BAHS using the linear incision technique with soft‐tissue preservation. Five biopsies were obtained during episodes of inflammation. The post‐implantation mRNA expression of IL‐1β (P = .002), IL‐8 (P = .003), MMP9 (P = .005), TIMP‐1 (P = .002), and COL1α1 (P < .001) was significantly up‐regulated. IL‐6 (P = .009) and FGF‐2 (P = .004) mRNA expression was significantly down‐regulated after implantation. Within patients, no difference between post‐implantation mRNA expression (at 12 weeks) and when inflammation was observed. Between patients, the expression of IL‐1β (P = .015) and IL‐17 (P = .02) was higher during cases of inflammation compared with patients who had no inflammation at 12‐week follow‐up.

Conclusions

As part of a randomized, prospective, clinical trial, the present study reports the molecular profile of selected cytokines in the soft tissue around BAHS. Within the limit of this study, the results showed that 12 weeks after BAHS implantation the gene expression of some inflammatory cytokines (IL‐8 and IL‐1β) is still relatively high compared with the baseline, steady‐state, expression. The up‐regulation of anabolic (COL1α1) and tissue‐remodeling (MMP‐9 and TIMP1) genes indicates an ongoing remodeling process after 12 weeks of implantation. The results suggest that IL‐1β, IL‐17, and TNF‐α may be interesting markers associated with inflammation.     

Improving Handoff by Deliberate Cognitive Processing: Results from a Randomized Controlled Experimental Study

BackgroundAlthough a number of successful handoff interventions have been reported, the handoff process remains vulnerable because it relies on memory. The aim of this study was to investigate the effect of deliberate cognitive processing (i.e., analytical, conscious, and effortful thinking) on recall of information from a simulated handoff.MethodsThis two-phased experiment was executed in the Netherlands in 2015. A total of 78 pediatric residents were randomly divided into an intervention group (n = 37) and a control group (n = 41). In phase 1, participants received written handoffs from 8 patients. The intervention group was asked to develop a contingency plan for each patient, deliberately processing the information. The control group received no specific instructions. In phase 2, all participants were asked to write down as much as they recalled from the handoffs. The outcome was the amount and accuracy of recalled information, calculated by scoring for idea units (single information elements) and inferences (conclusions computed by participants based on two or more idea units).ResultsParticipants in the intervention group recalled significantly more inferences (7.24 vs. 3.22) but fewer correct idea units (21.1% vs. 25.3%) than those in the control group. There was no difference with regard to incorrectly recalled information.ConclusionOur study revealed that deliberate cognitive processing leads to creation of more correct inferences, but fewer idea units. This suggests that deliberate cognitive processing results in interpretation of the information into higher level concepts, rather than remembering specific pieces of information separately. This implies better understanding of patients’ problems.     

Normative comparisons for large neuropsychological test batteries: User-friendly and sensitive solutions to minimize familywise false positives

Introduction. In neuropsychological research and clinical practice, a large battery of tests is often administered to determine whether an individual deviates from the norm. We formulate three criteria for such large battery normative comparisons. First, familywise false-positive error rate (i.e., the complement of specificity) should be controlled at, or below, a prespecified level. Second, sensitivity to detect genuine deviations from the norm should be high. Third, the comparisons should be easy enough for routine application, not only in research, but also in clinical practice. Here we show that these criteria are satisfied for current procedures used to assess an overall deviation from the norm—that is, a deviation given all test results. However, we also show that these criteria are not satisfied for current procedures used to assess test-specific deviations, which are required, for example, to investigate dissociations in a test profile. We therefore propose several new procedures to assess such test-specific deviations. These new procedures are expected to satisfy all three criteria. Method. In Monte Carlo simulations and in an applied example pertaining to Parkinson disease, we compare current procedures to assess test-specific deviations (uncorrected and Bonferroni normative comparisons) to new procedures (Holm, one-step resampling, and step-down resampling normative comparisons). Results. The new procedures are shown to: (a) control familywise false-positive error rate, whereas uncorrected comparisons do not; (b) have higher sensitivity than Bonferroni corrected comparisons, where especially step-down resampling is favorable in this respect; (c) be user-friendly as they are implemented in a user-friendly normative comparisons website, and as the required normative data are provided by a database. Conclusion. These new normative comparisons procedures, especially step-down resampling, are valuable additional tools to assess test-specific deviations from the norm in large test batteries.     

From the Cover: Role of a polymorphism in a Hox/Pax-responsive enhancer in the evolution of the vertebrate spine

Patterning of the vertebrate skeleton requires the coordinated activity of Hox genes. In particular, Hox10 proteins are essential to set the transition from thoracic to lumbar vertebrae because of their rib-repressing activity. In snakes, however, the thoracic region extends well into Hox10-expressing areas of the embryo, suggesting that these proteins are unable to block rib formation. Here, we show that this is not a result of the loss of rib-repressing properties by the snake proteins, but rather to a single base pair change in a Hox/Paired box (Pax)-responsive enhancer, which prevents the binding of Hox proteins. This polymorphism is also found in Paenungulata, such as elephants and manatees, which have extended rib cages. In vivo, this modified enhancer failed to respond to Hox10 activity, supporting its role in the extension of rib cages. In contrast, the enhancer could still interact with Hoxb6 and Pax3 to promote rib formation. These results suggest that a polymorphism in the Hox/Pax-responsive enhancer may have played a role in the evolution of the vertebrate spine by differently modulating its response to rib-suppressing and rib-promoting Hox proteins.     

High relapse-free survival after preoperative and intraoperative radiotherapy and resection for sulcus superior tumors

STUDY OBJECTIVES: Relapse-free survival in patients with sulcus superior tumors. DESIGN: Prospective registration study. SETTING: Department of surgical oncology of a university hospital. PATIENTS: Twenty-one patients treated with preoperative radiotherapy (46 Gy), lobectomy and chest-wall resection, and intraoperative radiotherapy (10 Gy). RESULTS: After a median follow-up of 18 months, 18 patients (85%) were free from locoregional relapse, while 8 patients were still alive. CONCLUSIONS: The results show that this protocol can achieve excellent local tumor control and can even be used for palliative treatment.