IMRT and SBRT Treatment Planning Study for the First Clinical Biology-Guided Radiotherapy System.

Purpose: The first clinical biology-guided radiation therapy (BgRT) system-RefleXionTM X1-was installed and commissioned for clinical use at our institution. This study aimed at evaluating the treatment plan quality and delivery efficiency for IMRT/SBRT cases without PET guidance. Methods: A total of 42 patient plans across 6 cancer sites (conventionally fractionated lung, head, and neck, anus, prostate, brain, and lung SBRT) planned with the EclipseTM treatment planning system (TPS) and treated with either a TrueBeam® or Trilogy® were selected for this retrospective study. For each Eclipse VMAT plan, 2 corresponding plans were generated on the X1 TPS with 10 mm jaws (X1-10mm) and 20 mm jaws (X1-20mm) using our institutional planning constraints. All clinically relevant metrics in this study, including PTV D95%, PTV D2%, Conformity Index (CI), R50, organs-at-risk (OAR) constraints, and beam-on time were analyzed and compared between 126 VMAT and RefleXion plans using paired t-tests. Results: All but 3 planning metrics were either equivalent or superior for the X1-10mm plans as compared to the Eclipse VMAT plans across all planning sites investigated. The Eclipse VMAT and X1-10mm plans generally achieved superior plan quality and sharper dose fall-off superior/inferior to targets as compared to the X1-20mm plans, however, the X1-20mm plans were still considered acceptable for treatment. On average, the required beam-on time increased by a factor of 1.6 across all sites for X1-10mm compared to X1-20mm plans. Conclusions: Clinically acceptable IMRT/SBRT treatment plans were generated with the X1 TPS for both the 10 mm and 20 mm jaw settings.

Surgical management of atypical mycobacterial cervical lymphadenitis in an outbreak of odontological infection.

INTRODUCTION: We report on our experience with surgical management of nosocomial Mycobacterium abscessus cervical lymphadenitis in the setting of an epidemic linked to a dental practice in the community. METHODS: This is an observational case series of children who required surgical treatment of cervical lymphadenitis as part of multidisciplinary management of nosocomial M. abscessus infections. We describe the criteria for surgical management of cervical lymphadenitis as well as patient characteristics and outcomes. RESULTS: Over 1000 children undergoing pulpectomies and pulpotomies at a local dental practice with a contaminated water source were identified as potentially susceptible to atypical mycobacteria infection, identified as M. abscessus. Between August 2016 and May 2017 108 children underwent inpatient evaluation at our institution by general pediatricians and pediatric infectious disease specialists. 90 children required at least 1 surgical intervention by pediatric otolaryngology and/or oral and maxillofacial surgery (OMFS). Children were evaluated by the Pediatric Otolaryngology service if computer tomography (CT) scan of the neck demonstrated lymph nodes of at least 1.5 cm in shortest dimension or lymph nodes with central hypolucencies suspicious for infection with central necrosis. Pediatric Otolaryngology intervened on 11 patients all of whom required selective cervical lymphadenectomy with or without curettage. These patients ranged in age from 3 to 8 years; 8 were male, 6 had concurrent pulmonary nodules. Two patients underwent curettage in addition to lymphadenectomy. Five patients required at least 2 surgical interventions by Pediatric Otolaryngology. CONCLUSION: We found M. abscessus to be an aggressive infection requiring early cervical lymphadenectomy in select patients.

[Evaluation of cone-beam computed tomography on upper airway changes after alternating rapid palatal expansion and constriction].

OBJECTIVE: To evaluate the changes of different parts of upper airway after alternating rapid palatal expansion and constriction via three dimensional measurement, compared with the protocol of rapid palatal expansion alone. METHODS: In the study, 36 patients with retrognathic maxilla were selected and randomized to either group A or group B. The patients in group A were treated with rapid palatal expansion alone. The patients in group B were treated with alternating rapid palatal expansion and constriction. Three dimensional analyses were performed on all pre- and post-treatment cone-beam computed tomography (CBCT) images with the software Dolphin. RESULTS: Two subjects in group B were lost to follow up during the treatment. The gender distributions, ages and all measuring items before treatment had no significant difference between group A and group B (P>0.05). Nasal floor width, nasal lateral width, nasal volume, and nasopharynx volume increased significantly in each group after rapid palatal expansion alone or rapid palatal expansion and constriction (P<0.05). The variations of oropharyngeal volume and hypopharyngeal volume had no significant difference (P>0.05). No significant difference was observed in the nasal floor width and nasal lateral width increment among the anterior, median and posterior parts in each group either (P>0.05). No significant difference in all the measuring items was observed between the two groups (P>0.05). CONCLUSION: Alternating rapid palatal expansion and constriction could increase the volume of nasal and naopharynx cavities by the similar way of rapid palatal expansion alone, and had no obvious effect on oropharynx and hypopharynx cavities.

[Clinical efficacy of clear aligners in treating bimaxillary protrusion].

Objective: To evaluate the efficiency of clear aligners in treating bimaxillary protrusion patients with first premolar extractions. Methods: Eleven patients with bimaxillary protrusion were selected in this study. All of them were treated by using clear aligners with four first premolar extractions and need maximal anchorage. Cephalometric analysis was carried out before and after treatment. Results: Cephalometric analysis results showed that significant changes in teeth and profile could be detected after clear aligner treatment and no change could be found in skeletal pattern. Upper and lower anterior teeth were retracted. The control of anterior torque and posterior anchorage were effective. The soft tissue analysis showed that position of upper and lower lip was significantly changed which improve the profile of patients. After treatment, the distance of U1 to NA and L1 to NB reduced by (5.19±4.12) mm and (4.53±1.20) mm, respectively. The differences were statistically significant (P<0.01). Conclusions: Bimaxillary protrusion patients who needed premolar extractions and maximal anchorage could be treated with clear aligners.

Using mobile technology to overcome language barriers in medicine.

Australia has a large migrant population with variable fluency in English. Interpreting services help ensure that healthcare services are delivered appropriately to these populations. However, the use of professional interpreters in hospitals is expensive. There are also issues with service availability and convenience. Mobile devices containing software with translating abilities have promising potential to improve communication between patients and hospital staff as an adjunct to professional interpreters. It is highly convenient and inexpensive. There are concerns about the accuracy of the interpretation done with such software and more research needs to be carried out to support or allay these concerns. For now, clinically important and medicolegal related interpretation should be undertaken by professional interpreters whereas less crucial tasks may be performed with the help of interpreting software on mobile devices.

Development of a consumer product ingredient database for chemical exposure screening and prioritization.

Consumer products are a primary source of chemical exposures, yet little structured information is available on the chemical ingredients of these products and the concentrations at which ingredients are present. To address this data gap, we created a database of chemicals in consumer products using product Material Safety Data Sheets (MSDSs) publicly provided by a large retailer. The resulting database represents 1797 unique chemicals mapped to 8921 consumer products and a hierarchy of 353 consumer product "use categories" within a total of 15 top-level categories. We examine the utility of this database and discuss ways in which it will support (i) exposure screening and prioritization, (ii) generic or framework formulations for several indoor/consumer product exposure modeling initiatives, (iii) candidate chemical selection for monitoring near field exposure from proximal sources, and (iv) as activity tracers or ubiquitous exposure sources using "chemical space" map analyses. Chemicals present at high concentrations and across multiple consumer products and use categories that hold high exposure potential are identified. Our database is publicly available to serve regulators, retailers, manufacturers, and the public for predictive screening of chemicals in new and existing consumer products on the basis of exposure and risk.

Esophageal tolerance to high-dose stereotactic ablative radiotherapy.

Dose-volume parameters are needed to guide the safe administration of stereotactic ablative radiotherapy (SABR). We report on esophageal tolerance to high-dose hypofractionated radiation in patients treated with SABR. Thirty-one patients with spine or lung tumors received single- or multiple-fraction SABR to targets less than 1 cm from the esophagus. End points evaluated include D(5cc) (minimum dose in Gy to 5 cm(3) of the esophagus receiving the highest dose), D(2cc) , D(1cc) , and D(max) (maximum dose to 0.01 cm(3) ). Multiple-fraction treatments were correlated using the linear quadratic and linear quadratic-linear/universal survival models. Three esophageal toxicity events occurred, including esophagitis (grade 2), tracheoesophageal fistula (grade 4-5), and esophageal perforation (grade 4-5). Chemotherapy was a cofactor in the high-grade events. The median time to development of esophageal toxicity was 4.1 months (range 0.6-6.1 months). Two of the three events occurred below a published D(5cc) threshold, all three were below a D(2cc) threshold, and one was below a D(max) threshold. We report a dosimetric analysis of incidental dose to the esophagus from SABR. High-dose hypofractionated radiotherapy led to a number of high-grade esophageal adverse events, suggesting that conservative parameters to protect the esophagus are necessary when SABR is used, especially in the setting of chemotherapy or prior radiotherapy.

Multimodality treatment with intensity modulated radiation therapy for esophageal cancer.

The objective of this study is to determine the feasibility and report the outcome of patients with locally advanced esophageal cancer treated with preoperative or definitive chemoradiotherapy (CRT) using intensity-modulated radiation therapy (IMRT). Between 2003 and 2007, 30 patients with non-cervical esophageal cancer received concurrent chemotherapy and IMRT at Stanford University. Eighteen patients were planned for definitive CRT and 12 were planned for preoperative CRT. All patients had computed tomography-based treatment planning and received IMRT. The median dose delivered was 50.4 Gy. Patients planned for preoperative CRT underwent surgery 4-13 weeks (median 8.3 weeks) following completion of CRT. Median follow-up of surviving patients from start of RT was 24.2 months (range 8.2-38.3 months). The majority of tumors were adenocarcinomas (67%) and poorly differentiated (57%). Tumor location was 7% upper, 20% mid, 47% lower, and 27% gastroesophageal junction. Actuarial 2-year local-regional control (LRC) was 64%. High tumor grade was an adverse prognostic factor for LRC and overall survival (OS) (P= 0.015 and 0.012, respectively). The 2-year LRC was 83% vs. 51% for patients treated preoperatively vs. definitively (P= 0.32). The 2-year disease-free and OS were 38% and 56%, respectively. Twelve patients (40%) required feeding tube placement, and the average weight loss from baseline was 4.8%. Twelve (40%) patients experienced grade 3+ acute complications and one patient died of complications following feeding tube placement. Three patients (10%) required a treatment break. Eight patients (27%) experienced grade 3 late complications. No grade 4 complications were seen. IMRT was effective and well tolerated. Disease recurrence remains a challenge and further investigation with dose escalation to improve LRC and OS is warranted.

Pathological response after chemoradiation for T3 rectal cancer.

OBJECTIVE: The aim of this study was to investigate the effect of preoperative chemoradiotherapy (CRT) on nodal disease in locally advanced rectal adenocarcinoma. METHOD: Thirty-two patients staged uT3N0 and 27 patients staged uT3N1 rectal adenocarcinoma who underwent pre-CRT staging using endoscopic ultrasound or rectal protocol CT were included. The median radiation dose was 50.4 Gy (range: 45-50.4 Gy) at 1.8 Gy per fraction and all patients received concurrent 5-FU or capecitabine-based chemotherapy. Low anterior resection or abdomino-perineal resection occurred at a median of 46 days (range: 27-112 days) after CRT. RESULTS: Eleven of 32 uT3N0 patients (34.4%) and 13 of 26 uT3N1 patients (50.0%) had ypN+ (P = 0.29). For patients with uT3N0, 10 of 20 (50.0%) with ypT2-3 and 1 of 12 (8.3%) with ypT0-1 were ypN+ (P = 0.02). For patients with uT3N1, 12 of 20 (60.0%) with ypT2-3 and 1 of 6 (16.7%) with ypT0-1 were ypN+ (P = 0.16). Overall, the ypN+ rate was 11.1% in the ypT0-yT1 group compared with 55.0% in the ypT2-yT3 group (P = 003). Among patients with uT3N0 disease, the ypN+ rate in patients who had surgery > 46 days vs 46 days vs 46 days vs

Differences in mitochondrial movement and morphology in young and mature primary cortical neurons in culture.

Mitochondria have many roles critical to the function of neurons including the generation of ATP and regulation of intracellular Ca2+. Mitochondrial movement is highly dynamic in neurons and is thought to direct mitochondria to specific cellular regions of increased need and to transport damaged or old mitochondria to autophagosomes. Morphology also varies between individual mitochondria and is modulated by fusion and fission proteins such as mitofusin-1 and dynamin-related protein-1, respectively. Although mitochondrial movement and morphology are thought to be modulated to best meet cellular demands, few regulatory signals have been identified. In this study, we examined how the different cellular environments of synaptically immature and mature rat cortical neurons affect mitochondrial movement, morphology, distribution and function. In younger cells, mitochondria were more mobile, were shorter, occupied a smaller percentage of neuronal processes, and expressed greater mitofusin-1 and lower dynamin-related protein-1 protein levels compared with older cells. However, the number of mitochondria per mum of neuronal process, mitochondrial membrane potential and the amount of basally sequestered mitochondrial Ca2+ were similar. Our results suggest that while mitochondria in young neurons are functionally similar to mature neurons, their enhanced motility may permit faster energy dispersal for cellular demands, such as synaptogenesis. As cells mature, mitochondria in the processes may then elongate and reduce their motility for long-term support of synaptic structures.

Reconstructive surgery for children with pelvic rhabdomyosarcoma.

Rhabdomyosarcoma is the most common soft-tissue sarcoma found in children and can arise almost anywhere skeletal muscle is found. It represents 4% to 8% of malignant solid tumors in children, ranking behind central nervous system tumors, lymphoma, neuroblastoma, and Wilms' tumor. Reconstructive surgery has become an integral part of the total plan in patients undergoing radical surgery for rhabdomyosarcoma. Advances in surgical techniques can often provide a reasonable lifestyle for patients.

Nonobstetrical abdominal surgery during pregnancy in Women's Hospital.

OBJECTIVE: To determine if nonobstetrical abdominal surgery during pregnancy in Women's Hospital at the University of Southern California School of Medicine was associated with increased rates of preterm delivery or spontaneous loss. Preoperative diagnostic accuracy was also evaluated. METHODS: We performed a retrospective review of all cases of nonobstetrical abdominal surgery in our institution during a 7-year period from November 1991 to November 1998. RESULTS: One hundred-six cases of nonobstetrical abdominal surgery were identified. Eighty-eight women underwent laparotomy and 18 had laparoscopic abdominal surgery. Seventy-three women had emergent surgery and 31 had elective surgery. Seventy-six percent (80/106) of subjects had the same preoperative and postoperative diagnoses. We obtained delivery data for 62 of 106 (59%) subjects. Eleven of 62 (18%) subjects who had nonobstetrical abdominal surgery during pregnancy delivered preterm (<37 weeks' gestation). This was not significantly different from the institutional preterm delivery rate of Women's Hospital (8999/56305 [16%]) (P = 0.84). Two of 106 (2%) women experienced spontaneous pregnancy loss following surgery; both occurred in the second trimester. CONCLUSIONS: Nonobstetrical abdominal surgery during pregnancy in Women's Hospital was not associated with higher frequencies of preterm deliveries or spontaneous losses than our institutional rates.

Vaginal reconstruction.

Absence of the vagina presents a challenging problem for the reconstructive urologist. This article reviews the pertinent diagnostic and pretreatment considerations and the surgical options, in particular, bowel vaginoplasty, for these patients.

Use of a laparoscopic insufflation port for ileal conduit endoscopy.

We present an effective and simple technique for performing endoscopy of an ileal conduit. With a laparoscopic insufflation port in the stoma, a flexible cystoscope or ureteroscope can be inserted. The one-way valve of the port prevents leakage of irrigation fluid and allows the conduit to distend for optimal visualization. This technique is particularly useful when access to the upper urinary tracts is needed.

Declining sperm counts in the United States? A critical review.

PURPOSE: Recent reports suggest declining sperm counts in the United States. These reports did not include all available data and did not account for geographic variations noted in prior studies. We examined all available data on U.S. sperm counts and evaluated whether geographic variations account for the decline suggested. MATERIALS AND METHODS: We reviewed all 29 U.S. studies from 1938 to 1996 reporting manually counted semen analyses of 9,612 fertile or presumably fertile men. We determined mean sperm concentrations by geographic location with weighted analysis of variance, and assessed any changes with time by linear regression analysis. RESULTS: Mean sperm concentrations from New York were significantly higher than from all other U.S. cities (98.6 versus 71.6 x 10(6) sperm per cc, respectively, p = 0.006). There has been no statistically significant change with time for mean sperm concentrations reported from New York (p = 0.49) or from U.S. cities other than New York (p = 0.62). Analysis without separating by location revealed a decline (p = 0.047). CONCLUSIONS: Sperm concentrations are highest in New York compared to other U.S. cities. When accounting for this geographic difference and examining all available data, there appears to be no significant change in sperm counts in the U.S. during the last 60 years. Further studies addressing the causes of geographic variations are needed.

Transurethral cystotomy repair.

We present a novel transurethral technique for cystotomy repair. This method can be used for immediate bladder repair following limited bladder injury and avoids the morbidity associated with laparotomy.

Rapid reduction in blood flow to the rat ventral prostate gland after castration: preliminary evidence that androgens influence prostate size by regulating blood flow to the prostate gland and prostatic endothelial cell survival.

BACKGROUND: Androgenic steroids regulate the development and size of the mammalian prostate gland. The mechanism(s) for this growth control might involve a direct effect on prostate cell proliferation and survival as well as more complex effects on the tissue environment supporting nourishment and oxygenation. In this study, we evaluated an animal model of androgen action on the prostate, the rat ventral prostate gland, to determine whether acute androgen withdrawal, by means of castration, might alter the primary blood flow to the prostate gland and for the effects of castration on prostatic endothelial cell viability. METHODS: Groups of rats studied included intact control males, males that had been surgically castrated, or males that received a sham-surgical castration. Relative blood flow (RBF) to the rat ventral prostate glands and rat bladders were measured at 18 and 24 hr after castration or sham castration using a fluorescent microsphere infusion technique. Thin sections from fixed and embedded rat ventral prostate glands obtained from unoperated or 12-hr castrated rats were analyzed by the TUNEL immunostaining technique to microscopically identify and quantify apoptotic epithelial, stromal, and endothelial cells. RESULTS: RBF to the rat ventral prostate was reduced by 38%, at 18 hr after castration when compared with intact or sham-operated rats and by 45% at 24 hr after castration (P=0.038 unoperated/0.025 sham operated). In contrast, RBF to the bladder was not significantly different between any of the groups in the 24-hr castrate experiment. TUNEL staining analysis of ventral prostate tissues obtained from 12-hr castrated rats showed only rare TUNEL-positive epithelial cells similar to the control tissue but significantly increased TUNEL labeling for endothelial and other ventral prostate stromal cells. CONCLUSIONS: Castration resulted in a rapid and significant reduction of blood flow to the mature rat ventral prostate gland that was not seen in the bladder. This reduction precedes the appearance of apoptosis in the epithelial cells of the tissue but more coincided with the appearance of TUNEL-positive prostate vascular endothelial and stromal cells, suggesting that androgens support the survival of cells in the vascular and stromal compartment of the rat prostate as well as in the prostatic epithelium. These preliminary data support the concept that androgen action on the prostate might involve primary regulation of prostate blood flow and prostate vascular cell vitality.

The Malone antegrade continence enema procedure in the management of patients with spina bifida.

BACKGROUND: In patients with spina bifida, traditional bowel management programs such as suppositories, retrograde enemas, and manual disimpaction have been largely unsatisfactory. The Malone antegrade continence enema (ACE) procedure has largely changed our approach to bowel management in this patient group. STUDY DESIGN: Over a 3-year period between January 1994 and January 1997, 27 patients with spina bifida underwent the Malone ACE procedure at our institutions. At the time of their ACE procedure, four patients underwent simultaneous continent urinary diversion and three had simultaneous small-bowel bladder augmentation. All the patients were evaluated for 9 months or more after their procedure, and 10 of the patients have been followed for more than 2 years. RESULTS: Postoperatively, predictable bowel control and continence were achieved in 19 of the 27 patients, but 6 had some rectal soiling requiring a sanitary pad. All patients were out of diapers and none reported stomal leakage. Eighteen of the 27 patients were able to manage independently and 9 required assistance. Two patients had stopped using their ACE stoma despite good technical results. The appendix was used as a catheterizable stoma in 15 of the 27 patients. The appendix was not available in 12 patients, so a tubularized cecal flap was used in 9 and a small-bowel neoappendix was created in 3. Complications included stomal stenosis in 5 patients, cecal-flap necrosis in 1, and stomal granulations in 3. CONCLUSIONS: We believe that the ACE procedure provides reliable colonic emptying and avoids fecal soiling in the majority of individuals, and we find it widely and enthusiastically accepted by patients with spina bifida.

Hypospadias repair by laser tissue soldering: intraoperative results and follow-up in 30 children.

OBJECTIVES: We examined the use of laser tissue soldering (LTS) as an adjunct to suturing of, as well as a primary means of, tissue closure in urethral reconstruction. METHODS: Since June 1994, 26 boys ranging in age from 3 months to 14 years (mean 3.0 years) underwent hypospadias repair using LTS techniques. The classification of hypospadias was subcoronal in 13, midpenile in 5, penoscrotal in 7, and scrotal in 1. Laser tissue soldering was used in an additional 4 patients: tunica vaginalis patch graft corporoplasty in 2 (scrotal hypospadias), epispadias fistulae in 1, and urethral diverticulum in 1. Of these cases, 3 hypospadias repairs were completely sutureless. An intraoperative comparision was made between suturing and LTS with respect to operative time and degree of difficulty in performing LTS. Postoperatively, patients were examined to determine complications, including stricture, fistula, or impaired wound healing. An unselected group of 25 consecutive boys undergoing hypospadias repair between 1991 and 1992 served as a historical control group. RESULTS: No intraoperative complications resulted from laser activation. In 5 of the 30 procedures (16.6%), suture disruption was noted to occur, with a higher incidence seen with finer, dyed suture material. For hypospadias repair, the average time to suture was 6.7 min/cm (n = 23), whereas it was 3.1 min/cm for adjunctive LTS (n = 23) and 1.4 min/cm for sutureless urethroplasty (n = 3). Follow-up ranged from 3 to 22 months (average 9.6). Four fistulae were noted (1 onlay, 2 skin tube grafts, 1 Thiersch tube) each following penoscrotal or scrotal hypospadias repair; a fifth fistula developed following a traumatic catheterization in a sutureless repair. The overall complication rate in the LTS group was 19% (5 of 26) versus 24% (6 of 25) for controls, whereas that for the distal forms of hypospadias was 11% (2 of 18) and 13.6% (3 of 22), respectively. CONCLUSIONS: Tissue soldering with laser and chromophore-doped solder is feasible, safe, and easy to perform. Laser tissue soldering may be an alternative to standard microsuture technique for hypospadias repair.