Screening for colorectal cancer by full colonoscopy in first-degree relatives of colorectal cancer patients: a multicentric study by the Italian League for the Fight against Cancer.

Background: Colorectal cancer currently presents the third-highest incidence of cancers worldwide, making secondary prevention through screening programs for colorectal cancer, usually by Fecal Occult Blood Testing, an essential preventive medicine intervention. First-degree relatives of colorectal cancer patients are a particularly at-risk group, with indications to consider direct screening by full colonoscopy. Colonoscopy is considered the gold standard for diagnosing colorectal cancer, as it has high sensitivity and specificity, and is both a diagnostic and therapeutic tool. However, it requires significant organizational and financial resources, and has a small but relatively higher risk of complications as opposed to fecal occult blood testing. The present study aimed to assess the appropriateness of a screening program without age restrictions of CRC by full colonoscopy in asymptomatic, first-degree adult relatives of patients with colorectal cancer, aiming both to actively increase screening coverage and to determine the detection rate of precancerous lesions and colorectal cancer in this population. Study Design: Uncontrolled interventional study - colorectal cancer screening by full colonoscopy for at-risk population. Methods: The Italian League for the Fight against Cancer started a colorectal cancer screening program by full colonoscopy for first-degree relatives of colorectal cancer patients in 1998 in the province of Latina, Lazio Region, Italy. The program was expanded to the provinces of Rieti, Lazio Region, and Sassari, Sardinia Region, in 2014 and 2016 respectively, and was concluded in 2018. Subjects were actively and voluntarily recruited by the study's working group. Subjects that had already been subjected to a full colonoscopy in the preceding 5 years were excluded from this study. Identified neoplastic lesions were treated either directly or referred to the Day Hospital setting, and histologically diagnosed following World Health Organization guidelines. Results: In total, 2,288 subjects (age range 15-88, mean 52.3 yrs, M/F = 946/1,204) were screened by colonoscopy, of which 103 (4.5%) were incomplete and 2,173 (95.0%) complete, with data on colonoscopy performance missing for 12 participants. Out of 468 positive outcomes on colonoscopy, diagnosis for 422 (204M/173F), 19.4% of total subjects, was adenomatous polyps and 46 (20M/20F), 2.1% of total subjects, was colorectal cancer. Female sex was a protective factor against a positive test outcome, with a 35% reduction compared to male sex, with OR=0.64 95%CI (0.52-0.80). On the other hand, being over 50 years of age was found to be a risk factor, making a positive outcome more than twice as likely, with OR=2.3 95%CI (1.8-2.9). Subjects over 50 also had significantly more instances of multiple adenomas being found, however the size distribution of found adenomas was not significantly different between subjects under and over 50, despite size being a predictor of risk of neoplastic progression. Conclusions: Given the high detection rate of precancerous lesions and colorectal cancer in the studied population, it is our opinion that guidelines should continue to recommend earlier and more frequent screening in first-degree relatives of patients with colorectal cancer, and, barring the introduction of more cost-effective and/or lower risk procedures with a similar efficacy profile, maintain the use of colonoscopy as the main screening option.

An interactive augmented reality software for facial reconstructive surgeries.

BACKGROUND AND OBJECTIVE: Surgical trainees need a lot of training and practice before being able to operate independently. The current approach of surgical education mainly involves didactic teaching and psychomotor training through physical models or real tissue. Due to the unavailability of physical resources and lack of objective ways of evaluation, there is a demand for developing alternative training methods for surgeons. In this paper, we present an application that provides additional training opportunities to surgical trainees in the field of facial reconstructive surgeries. METHODS: We built a mobile augmented reality application that helps the user to visualize important concepts and experiment with different surgical plans for facial reconstructive surgeries. The application can overlay relaxed skin tension lines on a live video input or a patient's photo, which serve as bases for aligning a skin flap. A surgical trainee can interactively compare different skin flap design choices with estimated final scars on a photo of a patient. Data collection capability is also added to the application, and we performed a Monte Carlo experiment with simulated users (five classes of 100 users each) as an example of objectively measuring user performance. RESULTS: The application can overlay relaxed skin tension lines on a patient's face in real time on a modern mobile device. Accurate overlays were achieved in over 91% as well as 84% and 88% out of 263 generated face images, depending on the method. Visual comparisons of the three overlay methods are presented on sample faces from different population groups. From the Monte Carlo experiment, we see that user actions in each class follow a normal distribution with a distinct set of parameters. CONCLUSIONS: This application can serve as a basis for teaching surgical trainees the fundamentals of different facial reconstructive procedures, especially concepts related to relaxed skin tension lines and skin flaps. It can objectively evaluate the performance of surgical trainees in a course. This setup focuses on illustrating the relationship between the orientation of skin flaps and relaxed skin tension lines, which is a prerequisite of minimizing scarring in patients in addition to good surgical techniques.

Multidisciplinary perinatal management of the compromised airway on placental support: lessons learned.

OBJECTIVE: The aims of this study were to review fetal and maternal outcomes after management of the compromised perinatal airway via operation on placental support or ex utero intrapartum treatment and to discuss implications for future management of these complex and rare cases. METHODS: We have presented a retrospective case series of 12 neonates requiring airway management on placental support at a single tertiary care, academic center. RESULTS: One mother experienced significant blood loss. Operative recovery times were unremarkable. Eight neonates required airway management due to mass obstruction, two for removal of an endotracheal balloon for fetoscopic treatment of congenital diaphragmatic hernia, one for laryngeal atresia, and one for severe retrognathia. One of our series is an unusual case of management on placental support after vaginal delivery. Another child would have ideally been managed on placental support, but an extremely short umbilical cord prevented this. Even though the airway was secured in all 12 cases, five neonates died in the perinatal period. CONCLUSIONS: These procedures have a risk for substantial maternal blood loss. Despite excellent rates of success securing the neonatal airway, children who require management on placental support still have high mortality. A formalized multidisciplinary approach at our institution has enhanced preparedness for these cases.

Diverse Oncogenic Fusions and Distinct Gene Expression Patterns Define the Genomic Landscape of Pediatric Papillary Thyroid Carcinoma.

Pediatric papillary thyroid carcinoma (PPTC) is clinically distinct from adult-onset disease. Although there are higher rates of metastasis and recurrence in PPTC, prognosis remains highly favorable. Molecular characterization of PPTC has been lacking. Historically, only 40% to 50% of childhood papillary thyroid carcinoma (PTC) were known to be driven by genomic variants common to adult PTC; oncogenic drivers in the remainder were unknown. This contrasts with approximately 90% of adult PTC driven by a discrete number of variants. In this study, 52 PPTCs underwent candidate gene testing, followed in a subset by whole-exome and transcriptome sequencing. Within these samples, candidate gene testing identified variants in 31 (60%) tumors, while exome and transcriptome sequencing identified oncogenic variants in 19 of 21 (90%) remaining tumors. The latter were enriched for oncogenic fusions, with 11 nonrecurrent fusion transcripts, including two previously undescribed fusions, STRN-RET and TG-PBF. Most fusions were associated with 3' receptor tyrosine kinase (RTK) moieties: RET, MET, ALK, and NTRK3. For advanced (distally metastatic) tumors, a driver variant was described in 91%. Gene expression analysis defined three clusters that demonstrated distinct expression of genes involved in thyroid differentiation and MAPK signaling. Among RET-CCDC6-driven tumors, gene expression in pediatric tumors was distinguishable from that in adults. Collectively, these results show that the genomic landscape of pediatric PTC is different from adult PTC. Moreover, they identify genomic drivers in 98% of PPTCs, predominantly oncogenic fusion transcripts involving RTKs, with a pronounced impact on gene expression. Notably, most advanced tumors were driven by a variant for which targeted systemic therapy exists. SIGNIFICANCE: This study highlights important distinctions between the genomes and transcriptomes of pediatric and adult papillary thyroid carcinoma, with implications for understanding the biology, diagnosis, and treatment of advanced disease in children.

Time course of juvenile onset recurrent respiratory papillomatosis caused by human papillomavirus.

BACKGROUND: With the recent licensure of a new quadrivalent vaccine, many diseases caused by human papillomavirus (HPV) can now be prevented, including recurrent respiratory papillomatosis (RRP). The purpose of this study was to describe the burden and time course of juvenile onset RRP. METHODS: A retrospective chart review was conducted of children with airway papillomatosis at the Hospital for Sick Children in Toronto, Canada, between 1994 and 2004. Statistical methods included descriptive statistics of the cohort, a repeated events survival model, and nonlinear modeling equations to describe the time course of illness. RESULTS: Nine hundred twenty-six surgical procedures in 67 patients were identified through a review of surgical records. The median age at diagnosis was 3.2 years (range, 0.1-14.8 years) and the most common presenting symptom was hoarseness (75%). Adjuvant pharmacologic therapy (interferon or cidofovir) was used in 13 cases (19%). HPV types 6 or 11 were identified most commonly as the etiologic agent. Nonlinear modeling equations (exponential and quadratic) fit the observed data well, and were superior to linear models. Repeated events survival analysis identified significant prognostic variables: surgeon, adjuvant therapy, and anatomic score. A decision rule is presented that allows the time to next surgery to be predicted based on the previous surgery and the anatomic score. CONCLUSIONS: Most patients have a decelerating rate of debulking surgeries over time, well described by our nonlinear modeling equations. Factors affecting the time course of RRP include: inter-surgeon variability, the extent and severity of papillomas at the time of laryngoscopy, and the use of adjuvant medical therapies.

Aneurysmal bone cysts of the head and neck in pediatric patients: a case series.

OBJECTIVES: To characterize aneurysmal bone cysts (ABCs) of the head and neck as seen at a tertiary care center. DESIGN: A case series. METHODS: A retrospective chart review of pediatric patients with aneurysmal bone cyst of the head and neck treated at the Hospital for Sick Children during the years 1994-2006 was carried out. RESULTS: Nine patients with ABC were treated. The average age at diagnosis was 9.3 years (range: 5 months-15 years), six males and three females. Four cysts originated in the paranasal sinuses, two in the mandible, one in the zygoma, one in the mastoid and one in the parietal bone. Two cases were associated with a previous localized trauma (mandible, zygoma). 5/9 presented with pain, 4/9 presented as an asymptomatic mass, 2/9 were associated with proptosis and nasal obstruction, 2/9 with nasal obstruction and 1/9 presented with an aural polyp. Seven cysts were successfully excised while one (in the pterygomaxillary fossa) is being followed conservatively. In one case the ABC was found to be secondary to an extensive osteoblastoma and this child continuous to be problematic. Follow-up time ranged from 2 years and 6 months to 10 years. CONCLUSIONS: ABC of the head and neck may vary in presentation and severity. Surgical removal is the treatment of choice at our institution and may provide a satisfying outcome. ABC may be secondary to an underlying bone pathology (e.g., osteoblastoma) which may make it refractory to treatment.

Effectiveness of discovery learning using a mobile otoscopy simulator on knowledge acquisition and retention in medical students: a randomized controlled trial.

BACKGROUND: Portable educational technologies, like simulators, afford students the opportunity to learn independently. A key question in education, is how to pair self-regulated learning (SRL) with direct instruction. A cloud-based portable otoscopy simulator was employed to compare two curricula involving SRL. Pre-clerkship medical students used a prototype smartphone application, a 3D ear attachment and an otoscope to complete either otoscopy curriculum. METHODS: Pre-clerkship medical students were recruited and randomized to two curriculum designs. The "Discovery then Instruction" group received the simulator one week before a traditional lecture, while the "Instruction then Discovery" group received it after the lecture. To assess participants' ability to identify otoscopic pathology, we used a 100-item test at baseline, post-intervention and 2-week retention time points. Secondary outcomes included self-reported comfort, time spent using the device, and a survey on learning preferences. RESULTS: Thirty-four students completed the study. Analysis of knowledge acquisition and retention showed improvement in scores of both groups and no significant effects of group (F1,31 = 0.53, p = 0.47). An analysis of participants' self-reported comfort showed a significant group x test interaction (F1,36 = 4.61, p = 0.04), where only the discovery then instruction group's comfort improved significantly. Overall device usage was low, as the discovery then instruction group spent 21.47 ± 26.28 min, while the instruction then discovery group spent 13.84 ± 18.71 min. The discovery first group's time spent with the simulator correlated moderately with their post-test score (r = 0.42, p = 0.07). After the intervention, most participants in both groups (63-68%) stated that they would prefer the instruction then discovery sequence. CONCLUSIONS: Both curricular sequences led to improved knowledge scores with no statistically significant knowledge differences. When given minimal guidance, students engaged in discovery learning minimally. There is value in SRL in simulation education, and we plan to further improve our curricular design by considering learner behaviours identified in this study.

Branchial sinus of the piriform fossa: reappraisal of third and fourth branchial anomalies.

OBJECTIVE: The objective of this study was to review clinical and embryologic aspects of third and fourth branchial anomalies. STUDY DESIGN: Retrospective study. METHODS: We reviewed the institutional and departmental databases at our institution to identify all cases of third and fourth branchial anomalies encountered from 1992 to 2006. All patient records were examined with respect to demographics, clinical history, and radiologic and pathologic reports. RESULTS: We identified 17 cases of third and fourth branchial anomalies, the largest series of its kind reported to date. The lesions were predominantly left sided, all presenting with neck infection. Fistula formation was iatrogenic, secondary to incision and drainage. Preoperative direct laryngoscopy always revealed a pit within the apex of the piriform fossa. Surgical excision involved ipsilateral thyroidectomy as the lesion passed through the thyroid gland. No lesions following the classical course of a either a third or fourth branchial anomaly were identified. CONCLUSIONS: The clinical presentation of branchial sinuses arising from the piriform fossa is more in keeping with derivation from the thymopharyngeal duct (of the third pouch) than the hypothetical course of third and fourth branchial fistulae.

Utility of head and neck biopsies in the evaluation of posttransplant lymphoproliferative disorder.

OBJECTIVE: To determine the diagnostic yield of head and neck biopsies in the evaluation of PTLD in children and to explore whether this yield was related to pretransplant Epstein-Barr virus (EBV) serostatus. STUDY DESIGN: This is a retrospective study of pediatric, post-solid-organ transplant recipients who have undergone a biopsy in the head and neck region to establish a diagnosis of PTLD. RESULTS: Fifty-six biopsies were performed in 46 patients four to 120 months after solid-organ transplantation. Biopsies yielded PTLD in 39.1% of patients. The odds of developing PTLD if a patient was seropositive for EBV at the time of transplantation was 0.26 (95% confidence interval, 0.064-1.056; P = 0.054). CONCLUSIONS: The high diagnostic yield of PTLD suggests that biopsies should be performed if PTLD is suspected in pediatric posttransplant patients. The results demonstrate a trend toward lower risk of PTLD among patients with pretransplant exposure to EBV.

Piloting a novel porcine model for endolaryngeal injury following prolonged intubation.

OBJECTIVES: (1) To develop a practical animal model of endolaryngeal damage secondary to prolonged endotracheal intubation. (2) To demonstrate the contribution of chronic hypoxia to laryngeal injury in the context of this model. METHODS: Four Sus scrofa piglets were anaesthetized and intubated for 24h. Two animals were maintained in a state of constant hypoxia (pO(2)<60 mmHg) while two others were ventilated with 100% oxygen. Prior to sacrifice, fluorescein dye was infused intravenously to highlight areas of hypoperfusion. The larynx and trachea were then harvested for gross and histological examination. RESULTS: All four specimens demonstrated areas of edema, erythema, and ulceration on gross examination. Areas of significant histological inflammation, ulceration, and necrosis involved tube-mucosa contact, in particular, the arytenoids, the interarytenoid area, and the subglottis. CONCLUSIONS: This animal model represents a practical and novel means for the investigation and treatment of laryngeal injury secondary to prolonged endotracheal intubation. Significant injury to the endolarynx was evident after only 24h of intubation and the injury involved similar areas within the larynx as described in human studies. Although clinical experience suggests that chronic hypoxia is a risk factor for endolaryngeal injury, this model did not provide experimental evidence to support this observation, most likely due to the small study size.

Primary squamous cell carcinoma of the maxillary alveolus in a 10-year-old girl.

Oral squamous cell carcinoma is rare in the pediatric population. When it does occur, it is most commonly seen on the tongue or lip. In this article, we report a rare case of squamous cell carcinoma of the maxillary gingiva and alveolus in a 10-year-old girl and review the literature concerning oral squamous cell carcinoma in the pediatric population.

Partial neurolysis of the hypoglossal nerve for selective lingual atrophy in a porcine model.

OBJECTIVES: Obstructive sleep apnea in children is most commonly treated with adenotonsillectomy; however, in cases of significant tongue base prolapse, this may prove inadequate. Surgical procedures used to increase the retroglossal airway have significant morbidities and low patient acceptability. We theorized that effective reduction of the tongue base can be achieved through partial denervation of the hypoglossal nerve, which is easily accessed in the submandibular space with minimal morbidity. METHODS: We performed a prospective, experimental study in which topographic innervation maps of porcine tongue were generated by stimulating the hypoglossal main trunk and peripheral branches. The effects of complete unilateral nerve sectioning on tongue base volume and linear dimensions were measured and compared to the contralateral control side. In the final stage, only the peripheral nerve that was determined as the main supply to the tongue base was sectioned, and the results were compared to those in the matched controls. RESULTS: A medial branch of the hypoglossal nerve was consistently identified as the main motor supply to the tongue base. Complete denervation resulted in a measurable decrease in the volume of the tongue base as compared to that of controls. Partial neurolysis produced inconsistent changes in 2 subjects, with decreases in linear dimensions that were not proportional to the decrease in volume. Histologically, complete denervation was followed by a significantly greater replacement of muscle with fat and connective tissue as compared with partial neurolysis. CONCLUSIONS: There were inconsistent changes in volume and linear dimensions of the tongue base following partial neurolysis of the hypoglossal nerve over the 3-month experimental period.

Pediatric tracheostomy.

Tracheotomy refers to a surgical incision made into a trachea. Tracheostomy, on the other hand, refers to a surgical procedure whereby the tracheal lumen is positioned in close proximity to the skin surface. Tracheostomy is an uncommon procedure in the pediatric population. When required tracheostomy is typically performed as an open surgical procedure under general anesthesia with the patient intubated. However, it may need to be performed under local anesthesia or over a rigid bronchoscope in the patient with a precarious airway. Over the past half century, the primary indication for pediatric tracheostomy has shifted from acute infectious airway compromise to the need for prolonged ventilatory support in neurologically compromised children. The surgical technique, choice of tracheostomy tube, and post-operative care requires a nuanced approach in infants and young children. This article will review these topics in a comprehensive fashion.

Objective Evaluation of Otoscopy Skills Among Family and Community Medicine, Pediatric, and Otolaryngology Residents.

INTRODUCTION: The objective of this study is to evaluate and compare the perceived need for otolaryngology training and otoscopy diagnostic skills in primary care (Family and Community Medicine, Pediatric Medicine), and Otolaryngology Head and Neck Surgery (OTO-HNS) postgraduate trainees. Participant otoscopy skills were evaluated using the OtoSim simulator. METHODS: Family and Community Medicine, Pediatric, and OTO-HNS residents were recruited. Each resident participated in 3 separate otoscopy training and assessment sessions. The ability to correctly identify middle ear pathology was objectively evaluated using OtoSim™. Pretest, posttest, and 3-month retention test results were compared among residents in a paired comparison paradigm. Survey data assessing exposure to OTO-HNS during undergraduate and postgraduate training were also collected. RESULTS: A total of 57 residents participated in the study. All residents reported limited exposure to OTO-HNS during undergraduate medical training. Primary care trainees performed poorly on pretest assessments (30% ± 7.8%; 95% CI). Significant improvement in diagnostic accuracy was demonstrated following a single 1-hour teaching session (30%-62%; p < 0.001). Primary care residents demonstrated a significant decrease in diagnostic accuracy at a 3-month follow-up assessment (62%-52%, p < 0.001). Self-perceived comfort with otology was poorly correlated to pretest performance among primary care trainees (r = 0.26) and showed a stronger positive correlation among OTO-HNS trainees (r = 0.56). CONCLUSIONS: A single teaching session with an otoscopy simulator significantly improved diagnostic accuracy in primary care and OTO-HNS trainees. Improved performance is susceptible to deterioration at 3 months if acquired skills are not frequently used. Self-perceived comfort with otology may not be an accurate predictor of otoscopic diagnostic skill.

Unusual presentation of squamous cell carcinoma of the maxilla in an 8-year-old child.

Oral squamous cell carcinoma (OSCC) is extremely rare in patients younger than 20 years of age. We present here a case of OSCC of the maxillary alveolar ridge in an otherwise healthy 8-year-old patient. The clinicohistologic presentation was not typical for mucosal SCC, and the possibility of an intrabony origin from the odontogenic epithelium was considered. The patient was treated with surgical resection, and treatment decisions were made with consideration of the need for eradication of tumor as well as tissue preservation to allow normal growth and development. A review of the literature indicated a preponderance of gingival-alveolar ridge as the site of OSCC in children with no known genetic predisposition to cancer. More studies of this rare subset of OSCC will help understand the underlying biology and guide treatment decisions.

A collagenase-targeted multiplex PCR assay for identification of Vibrio alginolyticus, Vibrio cholerae, and Vibrio parahaemolyticus.

A multiplex PCR assay using three collagenase-targeted primer pairs for the species-specific detection of Vibrio alginolyticus, Vibrio cholerae, and Vibrio parahaemolyticus was developed. The results highlight the species specificity of the three primer sets designed. Because of the increasing importance of Vibrio spp. in human foodborne diseases, molecular approaches for routine microbial screening and monitoring of clinical, environmental, and food samples also have become more important. The results of this study indicate that the gene coding for collagenase should be used as an alternative molecular target to discriminate among the three Vibrio species.

An unusual case of bilateral submandibular sialolithiasis in a young female patient.

Salivary calculi in the pediatric population comprise only 3% of all cases of sialolithiasis. In addition, the presentation of bilateral calculi in children is rare. The formation of stones in the salivary glands has been attributed to slow salivary flow, salivary stagnation and unknown metabolic events. There is no report in the literature of an association between dietary calcium intake and calculi formation. We describe the clinical findings and management in a patient with bilateral sialolithiasis thought to be linked to high dietary calcium intake and review the literature.

Evaluation of an otoscopy simulator to teach otoscopy and normative anatomy to first year medical students.

OBJECTIVE/HYPOTHESIS: Our study evaluates the effectiveness of the OtoSim as an educational tool for teaching otoscopy and normal middle ear anatomy to first-year medical students. STUDY DESIGN: Cross-sectional survey design. METHODS: A large group otoscopy simulator teaching session was held in January 2014 for 29 first-year medical students at the University of Toronto. Following the training session, survey questions were administered to assess the student experience. RESULTS: A total of 29 students completed the survey. All respondents rated the overall quality of the event as very good or excellent. Ninety-three percent of respondents indicated that the simulator increased their confidence in otoscopy. Students also commented that they were able to learn normal middle ear anatomy without causing discomfort to patients. CONCLUSIONS: The use of otoscopy simulation is a novel addition to traditional learning methods for undergraduate medical students. Students can effectively learn normal external and middle ear anatomy and improve their confidence in performing otoscopy examination. LEVEL OF EVIDENCE: NA.

Ultrasound to differentiate thyroglossal duct cysts and dermoid cysts in children.

OBJECTIVES/HYPOTHESIS: To determine if ultrasound could differentiate between thyroglossal duct cysts (TGDC) and midline dermoid cysts (DC). STUDY DESIGN: Cohort study. METHODS: A search of pathology reports yielded 91 patients with TGDC or midline DC. Ultrasound images were presented to a radiologist blinded to pathology who evaluated the following: 1) depth of lesion from skin, 2) maximum diameter, 3) dimensions, 4) midline location, 5) distance from base of tongue, 6) tract, 7) wall regularity, 8) wall thickness, 9) margin definition, 10) heterogeneity, 11) internal septae, 12) solid components, 13) intralesional Doppler flow, and 14) posterior enhancement. The predictive power of these variables was evaluated in a multiple logistic regression model. RESULTS: There were 53 TGDC and 38 DC. TGDC were significantly more likely than DC to have the following features: 1) smaller distance from base of tongue, 2) tract, 3) irregular wall, 4) ill-defined margin, 5) internal septae, 6) solid components, and 7) intralesional Doppler flow. Three clinically reliable ultrasound variables were independently able to discriminate between TGDC and DC. A predictive model was fashioned whereby each variable was scored as 0 or 1, with a total score calculated (septae + irregular wall + solid components = TGDC [or SIST] score). We propose a scoring system whereby 0 = suggestive of DC; 1 = suggestive of TGDC; and ≥2 = highly suggestive of TGDC. CONCLUSIONS: It may be possible to differentiate between TGDC and midline DC preoperatively using ultrasound.