ICORG 10-14: NEOadjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study (Neo-AEGIS).

BACKGROUND: Neoadjuvant therapy is increasingly the standard of care in the management of locally advanced adenocarcinoma of the oesophagus and junction (AEG). In randomised controlled trials (RCTs), the MAGIC regimen of pre- and postoperative chemotherapy, and the CROSS regimen of preoperative chemotherapy combined with radiation, were superior to surgery only in RCTs that included AEG but were not powered on this cohort. No completed RCT has directly compared neoadjuvant or perioperative chemotherapy and neoadjuvant chemoradiation. The Neo-AEGIS trial, uniquely powered on AEG, and including comprehensive modern staging, compares both these regimens. METHODS: This open label, multicentre, phase III RCT randomises patients (cT2-3, N0-3, M0) in a 1:1 fashion to receive CROSS protocol (Carboplatin and Paclitaxel with concurrent radiotherapy, 41.4Gy/23Fr, over 5 weeks). The power calculation is a 10% difference in favour of CROSS, powered at 80%, two-sided alpha level of 0.05, requiring 540 patients to be evaluable, 594 to be recruited if a 10% dropout is included (297 in each group). The primary endpoint is overall survival, with a minimum 3-year follow up. Secondary endpoints include: disease free survival, recurrence rates, clinical and pathological response rates, toxicities of induction regimens, post-operative pathology and tumour regression grade, operative in-hospital complications, and health-related quality of life. The trial also affords opportunities for establishing a bio-resource of pre-treatment and resected tumour, and translational research. DISCUSSION: This RCT directly compares two established treatment regimens, and addresses whether radiation therapy positively impacts on overall survival compared with a standard perioperative chemotherapy regimen Sponsor: Irish Clinical Research Group (ICORG). TRIAL REGISTRATION: NCT01726452 . Protocol 10-14. Date of registration 06/11/2012.

Retrospective Review of Midpoint Vestibular Aqueduct Size in the 45° Oblique (Pöschl) Plane and Correlation with Hearing Loss in Patients with Enlarged Vestibular Aqueduct.

BACKGROUND AND PURPOSE: Vestibular aqueduct measurements in the 45° oblique (Pöschl) plane provide a reliable depiction of the vestibular aqueduct; however, adoption among clinicians attempting to counsel patients has been limited due to the lack of correlation with audiologic measures. This study aimed to determine the correlation between midpoint vestibular aqueduct measurements in the Pöschl plane in patients with an enlarged vestibular aqueduct with repeat audiologic measures. MATERIALS AND METHODS: Two radiologists independently measured the midpoint vestibular aqueduct diameter in the Pöschl plane reformatted from CT images in 54 pediatric patients (77 ears; mean age at first audiogram, 5 years) with an enlarged vestibular aqueduct. Four hundred nineteen audiograms were reviewed, with a median of 6 audiograms per patient (range, 3-17; mean time between first and last audiograms, 97.4 months). The correlation between midpoint vestibular aqueduct size and repeat audiologic measures (pure tone average, speech-reception threshold, and word recognition score) using a linear mixed-effects model was determined. RESULTS: The mean midpoint vestibular aqueduct size was 1.78 mm (range, 0.81-3.46 mm). There was excellent interobserver reliability with intraclass correlation coefficients for the 2 readers measuring 0.92 (P < .001). Each millimeter increase in vestibular aqueduct size was associated with an increase of 10.5 dB (P = .006) in the pure tone average, an increase of 14.0 dB (P = .002) in the speech-reception threshold, and a decrease in the word recognition score by 10.5% (P = .05). CONCLUSIONS: Midpoint vestibular aqueduct measurements in the Pöschl plane are highly reproducible and demonstrate a significant correlation with audiologic data in this longitudinal study with repeat measures. These data may be helpful for clinicians who are counseling patients with an enlarged vestibular aqueduct using measurements obtained in the Pöschl plane.

"Finding a Voice": Imaging Features after Phonosurgical Procedures for Vocal Fold Paralysis.

Altered communication (hoarseness, dysphonia, and breathy voice) that can result from vocal fold paralysis, secondary to numerous etiologies, may be amenable to surgical restoration. In this article, both traditional and cutting-edge phonosurgical procedures targeting the symptoms resulting from vocal fold paralysis are reviewed, with emphasis on the characteristic imaging appearances of various injectable materials, implants, and augmentation procedures used in the treatment of vocal fold paralysis. In addition, complications of injection laryngoplasty and medialization laryngoplasty are illustrated. Familiarity with the expected imaging changes following treatment of vocal fold paralysis may prevent the misinterpretation of posttreatment changes as pathology. Identifying common complications related to injection laryngoplasty and localization of displaced implants is crucial in determining specific management in patients who have undergone phonosurgical procedures for the management of vocal fold paralysis.

Level 5 Lymphadenopathy Warrants Heightened Suspicion for Clinically Significant Pathology.

We conclude that patients presenting with level 5 lymphadenopathy should be investigated with heightened clinical vigilance. Our results suggest that up to 80 % will harbour clinically significant pathology requiring further medical treatment, three quarters of which will be malignancy. We report an observational study of histological outcomes of level 5 lymph node biopsies from a regional histopathology department across 5 years. 184 subjects were identified as having a biopsy of a lymph node from the level 5 region within the study period. One hundred and fifty six cases (84.8 %) had clinically significant pathology on final histology requiring further medical treatment. Lymphoma accounted for the highest number of cases (n = 72, 39.1 %), followed by metastatic carcinoma (n = 65, 35.3 %) and granulomatous change (n = 17, 9.2 %). Gender and laterality were not shown to be independent predictors of pathology significance (p > 0.05).

The TRK-T1 fusion protein induces neoplastic transformation of thyroid epithelium.

Genetic analysis of human papillary thyroid carcinomas (PTC) has revealed unique chromosomal translocations that form oncogenic fusion proteins and promote thyroid tumorigenesis in up to 60% of tumors examined. Although, the majority of thyroid specific translocations involve the growth factor receptor c-RET, variant rearrangements of the receptor for nerve growth factor, NTRK1 have also been described. One such translocation, TRK-T1, forms a fusion protein composed of the carboxyl terminal tyrosine kinase domain of NTRK1 and the amino terminal portion of TPR (Translocated Promoter Region). To determine if TRK-T1 expression can cause thyroid cancer in vivo, we developed transgenic mice that express the human TRK-T1 fusion protein in the thyroid. Immunohistochemical analysis of TRK-T1 transgenic mouse thyroids revealed TRK-T1 staining within the thyroid follicular epithelium. In contrast to nontransgenic littermates, 54% of transgenic mice developed thyroid abnormalities that included follicular hyperplasia and papillary carcinoma. Furthermore, all transgenic mice examined greater than 7 months of age developed thyroid hyperplasia and/or carcinoma. These data support the conclusion that TRK-T1 is oncogenic in vivo and contributes to the neoplastic transformation of the thyroid.

Identification of semen in 500 patients seen because of rape.

Of 500 patients seen because of rape, semen was identified in vaginal secretions by the identification of spermatozoa in 61%, by an acid phosphatase value of 50 units or more in 40%, and by the identification of a foreign blood group substance or a high titer of own blood group substance in 16%. The addition of the determination of the acid phosphatase to the search for spermatozoa identified semen in only 1.4% more patients, or a total of 62.4%. Identification and titers of blood group substance were confirmatory only, but further characterized the source of the semen in 25% of those patients with spermatozoa. Spermatozoa were identified for as long as 48 hours, and elevated acid phosphatase was not found after 18 hours. Acid phosphatase was elevated in only 62% of patients with spermatozoa.

Extended carbon dioxide laser vaporization in the treatment of subclinical papillomavirus infection of the lower genital tract.

This study examined the use of extended carbon dioxide laser vaporization in 25 women with histologically confirmed, multicentric subclinical papillomavirus infection of the lower genital tract to determine whether carbon dioxide laser can eradicate subclinical papillomavirus infection. An extended carbon dioxide laser procedure involved vaporization of the epithelium of the entire lower genital tract. We performed the procedure under colposcopic guidance. Vaporization was carried out in continuity, to an appropriate tissue depth, while using recommended power densities for the respective target tissue. For sexually active study patients, male consorts were evaluated and treated concurrently to reduce the risk of recurrent infection. Postoperative morbidity was considerable, with moderate to severe vulvar pain and febrile reactions occurring in 100 and 76% of patients, respectively. Histologic persistence of subclinical papillomavirus infection was documented in 88% of study patients at follow-up examination. Neither treatment of the male consort nor sexual abstinence significantly improved treatment outcome. These data suggest that extended carbon dioxide laser procedures cause significant short-term morbidity without effectively eradicating subclinical papillomavirus infection of the female lower genital tract.

Magnified penile surface scanning in diagnosis of penile condyloma.

To determine the incidence of penile condyloma in a group of high risk males, we have performed magnified penile surface scanning and biopsy of suspicious lesions in 51 men. All men were partners of women with proven condyloma. Of these men, 45 were found to have histologic evidence of condyloma, only 8 of which were grossly visible.

Transfer of uterine implantation blastocysts to the oviduct in mice.

Although ectopic pregnancy is a common occurrence in humans, it occurs only rarely in other species. In the mouse, confinement of the blastocyst to the oviduct fails to result in implantation at that level. In prior studies, these confined blastocysts had not been exposed to the uterine environment. We transferred blastocysts from the uterus, at a time when implantation would normally occur, to ligated oviducts of pseudopregnant mice. Although enlargement of the blastocysts, loss of the zona pellucida, and adherence to the tubal epithelium were noted, implantation did not occur. The contributions to the embryo by the uterine environment were not sufficient to allow implantation within the oviduct.

Endometrial effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate.

OBJECTIVE: To determine the endometrial safety of lower doses of continuous combined conjugated equine estrogens (CEE) and medroxyprogesterone acetate (MPA). DESIGN: Randomized, double-blind, placebo-controlled study (the Women's Health, Osteoporosis, Progestin, Estrogen study). SETTING: Study centers across the United States. PATIENT(S): Healthy, postmenopausal women (n = 2,673) with an intact uterus. INTERVENTION(S): Patients received CEE 0.625 mg/day, CEE 0.625/MPA 2.5 mg/day, CEE 0.45 mg/day, CEE 0.45/MPA 2.5 mg/day, CEE 0.45/MPA 1.5 mg/day, CEE 0.3 mg/day, CEE 0.3/MPA 1.5 mg/day, or placebo for 1 year. Endometrial biopsies were evaluated at baseline, cycle 6, and year 1 using a centralized protocol. MAIN OUTCOME MEASURE(S): Efficacy of lower doses of CEE/MPA in reducing the incidence of endometrial hyperplasia rates associated with unopposed CEE. RESULT(S): Endometrial hyperplasia rates ranged from 0 to 0.37% for all CEE/MPA doses. Twenty-nine of the 32 cases of endometrial hyperplasia developed in women who were administered CEE 0.625 mg or CEE 0.45 mg. The incidence of endometrial hyperplasia increased with age for patients administered CEE alone. As expected, there were some inconsistencies among pathologists' ratings in the numbers of hyperplasias and incidence rates for the CEE-alone regimens. There were too few cases of hyperplasia in the combination groups to evaluate consistency among pathologists. CONCLUSION(S): One year of treatment with lower doses of CEE/MPA provides endometrial protection comparable to commonly prescribed doses. These regimens may be used by clinicians to individualize hormone replacement therapy in postmenopausal women.

Leiomyoma uteri in a rudimentary uterine horn in a woman with the Rokitansky-Kuster-Hauser syndrome. A case report.

A 4-cm leiomyoma was found in a woman with the Rokitansky-Kuster-Hauser syndrome. It was discovered six years after she presented to a gynecologist. In the ensuing years she successfully developed vaginal dilation. This is the fourth reported case of leiomyoma associated with the Rokitansky-Kuster-Hauser syndrome.

Vaginal and vulvar adenosis. An unsuspected side effect of CO2 laser vaporization.

During a 15-month period, September 1984 through January 1986, 10 women who were treated in the Section of Gynecologic Oncology, Department of Obstetrics and Gynecology, Pennsylvania Hospital, Philadelphia, Pennsylvania, developed vaginal or vulvar adenosis after CO2 laser vaporization. The indications for therapy were condylomata of the cervix, vagina and vulva refractory to conservative management in 3 patients, vulvar intraepithelial neoplasia in 3, lichen sclerosus in 1 and cervical intraepithelial neoplasia with condylomata on the cervix and vagina in 3. All the patients underwent treatment of the vagina. Most underwent treatment of the cervix, and some underwent treatment of the vulva at various degrees of intensity and depth. During the posttreatment colposcopic follow-up examination, all the patients demonstrated lesions colposcopically consistent with adenosis of the vagina or vulva within the area treated with the CO2 laser. Biopsies of the lesions were performed, adenosis was confirmed histologically, and endometriosis was ruled out histologically. This entity has not been previously associated with CO2 laser vaporization, and its clinical significance is undetermined. Further follow-up is indicated.

Facial reanimation procedures depicted on radiologic imaging.

Various facial reanimation procedures can be performed for treating patients with chronic facial nerve paralysis. The radiologic imaging features of static and dynamic techniques are reviewed in this article with clinical correlation, including brow lift, eyelid weights and springs, gracilis free flaps, fascia lata grafts, temporalis flaps, and Gore-Tex suspension slings. Although the anatomic alterations resulting from facial reanimation surgery may not necessarily be the focus of the imaging examination, it is important to recognize such changes and be familiar with MR imaging compatibility of the associated implanted materials. Furthermore, imaging is sometimes used to specifically evaluate the postoperative results, such as vessel patency following free gracilis transfer.

Imaging findings in auto-atticotomy.

BACKGROUND AND PURPOSE: An acquired attic cholesteatoma may spontaneously drain externally into the external auditory canal, leaving a cavity in the attic with the shape of the original cholesteatoma but now filled with air, a phenomenon referred to as "nature's atticotomy" or auto-atticotomy. We describe and quantify the CT appearance of the auto-atticotomy cavity as it pertains to the appearance of the scutum and the lateral attic wall. MATERIALS AND METHODS: Twenty-one patients with erosion of the scutum and loss of the lower attic wall on MDCT were identified during a 5-year span. Images were assessed for measureable widening of the space between the ossicles and the lower lateral attic wall in the axial and coronal planes. Three measurements of the lateral attic were made on the axial images. Findings were compared with the same measurements in 20 control subjects. RESULTS: The 21 patients had a characteristic blunting of the scutum with loss of the lower lateral attic wall and widening of the lateral attic, consistent with an auto-atticotomy. There was a statistically significant (P < .001) widening of the lateral attic dimensions in the axial plane in the patients with auto-atticotomy. CONCLUSIONS: Spontaneously evacuated cholesteatoma may mimic a surgical atticotomy on MDCT. Scutal erosion and attic enlargement with a smoothly contoured bony remodeling of the lower lateral attic wall in a patient with no history of surgery suggest that a cholesteatoma was previously present and spontaneously drained.

Imaging appearance of the lateral rectus-superior rectus band in 100 consecutive patients without strabismus.

BACKGROUND AND PURPOSE: The lateral rectus-superior rectus band is an orbital connective tissue structure that has been implicated in a form of strabismus termed sagging eye syndrome. Our purpose was to define the normal MR imaging and CT appearance of this band in patients without strabismus. MATERIALS AND METHODS: Orbital MR imaging and CT examinations in 100 consecutive patients without strabismus were evaluated. Readers graded the visibility of the lateral rectus-superior rectus band on coronal T1WI, coronal STIR, and coronal CT images. Readers determined whether the band demonstrated superotemporal bowing or any discontinuities and whether a distinct lateral levator aponeurosis was seen. Reader agreement was assessed by κ coefficients. Association between imaging metrics and patient age/sex was calculated by using the Fisher exact test. RESULTS: The lateral rectus-superior rectus band was visible in 95% of coronal T1WI, 68% of coronal STIR sequences, and 70% of coronal CT scans. Ninety-five percent of these bands were seen as a continuous, arc-like structure extending from the superior rectus/levator palpebrae muscle complex to the lateral rectus muscle; 24% demonstrated superotemporal bowing; and in 82% of orbits, a distinct lateral levator aponeurosis was visible. Increasing patient age was negatively associated with lateral rectus-superior rectus band visibility (P=.03), positively associated with lateral rectus-superior rectus band superotemporal bowing (P=.03), and positively associated with lateral levator aponeurosis visibility (P=.01). CONCLUSIONS: The lateral rectus-superior rectus band is visible in most patients without strabismus on coronal T1WI. The age effect with respect to its visibility and superotemporal bowing could represent age-related connective tissue degeneration.