Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal.

The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. We observe up to 30 driver events per tumor and show that subclonal diversification is associated with known prognostic parameters. By resolving the patterns of driver event ordering, co-occurrence, and mutual exclusivity at clone level, we show the deterministic nature of clonal evolution. ccRCC can be grouped into seven evolutionary subtypes, ranging from tumors characterized by early fixation of multiple mutational and copy number drivers and rapid metastases to highly branched tumors with >10 subclonal drivers and extensive parallel evolution associated with attenuated progression. We identify genetic diversity and chromosomal complexity as determinants of patient outcome. Our insights reconcile the variable clinical behavior of ccRCC and suggest evolutionary potential as a biomarker for both intervention and surveillance.

Norovirus infection causes acute self-resolving diarrhea in wild-type neonatal mice.

Human noroviruses are the leading cause of severe childhood diarrhea worldwide, yet we know little about their pathogenic mechanisms. Murine noroviruses cause diarrhea in interferon-deficient adult mice but these hosts also develop systemic pathology and lethality, reducing confidence in the translatability of findings to human norovirus disease. Herein we report that a murine norovirus causes self-resolving diarrhea in the absence of systemic disease in wild-type neonatal mice, thus mirroring the key features of human norovirus disease and representing a norovirus small animal disease model in wild-type mice. Intriguingly, lymphocytes are critical for controlling acute norovirus replication while simultaneously contributing to disease severity, likely reflecting their dual role as targets of viral infection and key components of the host response.

Microvascular free tissue transfer in reconstructing skull base defects: lessons learned.

OBJECTIVE: To demonstrate the effectiveness of microvascular free tissue transfer in reconstructing complex skull base defects. STUDY DESIGN: Retrospective chart review. METHODS: A retrospective chart review was conducted identifying patients with anterior or lateral skull base defects, or both, who underwent microvascular free flap reconstruction. Appropriate demographic, pathological, and preoperative and postoperative clinical data were collected and analyzed. RESULTS: Thirty-five patients with skull base defects were identified, including 8 women (Mean age, 43.9 y; age range, 28-75 y) and 27 men (mean age, 57.9 y; age range, 19-85 y). Defects were secondary to trauma in two cases, whereas the remaining 33 cases were secondary to ablative procedures for a variety of malignant tumors, of which squamous cell carcinoma was the most common (n = 18). The average defect surface area was 89.3 cm(2), and 36 free flaps were used. The most commonly used flap was the rectus myocutaneous (n = 20); however, six different flap types were employed, including three radial forearm fascial flaps. In all, there were seven flap-related complications and there was one total flap loss. A total of 43 postoperative complications occurred in 23 patients, with the most common complications being grouped as intracranial (n = 10), orbital (n = 9), and cardiac (n = 9). The perioperative mortality rate was 5.7%, and the average hospital stay was 13.5 days (range, 7-37 d). CONCLUSIONS: The use of microvascular free tissue transfer for reconstruction of complex skull base defects has proven highly successful in the large series presented in the current study. The versatility and reliability of free flaps for such reconstruction are discussed, and helpful hints are given to minimize the complication rate.

Quality of life, functional outcome, and costs of early glottic cancer.

OBJECTIVE: To analyze quality of life, functional outcome, and hidden costs by primary treatment with surgery or radiation therapy in patients with early glottic cancer. STUDY DESIGN: Retrospective study in a tertiary care facility. METHODS: A group of 101 patients with carcinoma in situ and T1 invasive squamous cell carcinoma treated primarily with either surgery or radiation, between January 1990 and December 2000, were identified from searching our tumor registry. Patients completed two previously validated questionnaires and one local questionnaire. Statistical significance was assessed with the rank sum test, chi2 test, or Fisher's Exact test. RESULTS: Questionnaires were completed in 59% (44 of 74) of the surgical cohort and 41% (11 of 27) of the radiation therapy cohort. The primary surgical treatments were endoscopic excision (86%), hemilaryngectomy (12%), and total laryngectomy (1%). Patient-reported problems with swallowing, chewing, speech, taste, saliva, pain, activity, recreation, and appearance showed no difference between the endoscopic excision or radiation therapy cohorts. Comparing endoscopic excision versus radiation therapy, respectively, median number of treatments (2 vs. 35), total median travel distance (150 vs. 660 miles), total median travel time (180 vs. 1440 min), and total median number of hours of work missed (76 vs. 24) all differed significantly (P <.01). CONCLUSIONS: Almost all patients with early glottic cancer, whether treated with surgery or radiation therapy, reported excellent quality of life outcomes and functional results. In addition to actual costs, the hidden costs for radiation therapy versus endoscopic excision were all greater in terms of total number of hours of work missed, total travel time, and total travel distance.

Myoepithelial neoplasia of the submandibular gland: case report and therapeutic considerations.

Tumors of the submandibular gland typically arise from the seromucinous acini, which make up the majority of the gland. The most common benign tumor of this structure is the pleomorphic adenoma, whereas the most common malignancy of the submandibular gland is adenoid cystic carcinoma. We describe an unusual case of a neoplastic process of the myoepithelial cells of the submandibular gland in a middle-aged woman. This rare tumor is most commonly diagnosed in the parotid gland and in the minor salivary glands of the hard palate; a review of the literature uncovered only 5 previous reports of myoepithelioma of the submandibular gland. Distinguishing myoepithelioma from benign pleomorphic adenoma and malignant myoepithelial carcinomas can be challenging. Immunohistochemical staining can help to distinguish between the benign neoplasms, but histologic features remain the "gold standard" for diagnosing the malignant tumors. Increasing use of immunohistochemistry panels to assess parotid neoplasms also suggests that myoepithelioma may be underrecognized.

Management and outcome of early glottic carcinoma.

OBJECTIVE AND STUDY DESIGN: We designed a retrospective study to analyze treatment methods and outcomes for patients with lesions ranging from carcinoma in situ to invasive T1 glottic squamous cell carcinoma. Patients with nonsquamous cell carcinoma, verrucous variant of squamous cell carcinoma, anterior commissure involvement, and T2 lesions were excluded. SETTING: University of Pittsburgh School of Medicine, a tertiary referral center. RESULTS: Fifty-four patients met the inclusion criteria. Mean follow-up was 49 months (range 24 to 96 months). Forty-eight of 54 (89%) were treated with endoscopic excision. Forty of these 48 patients (83%) were successfully treated with endoscopic excision(s) as the only treatment modality. Four patients had persistence of disease despite multiple endoscopic excisions. Two of these patients underwent hemilaryngectomy, 1 received radiation treatment, and 1 received radiation therapy followed by a hemilaryngectomy. Four patients had recurrence of disease. Two patients with recurrence required radiation therapy and 2 patients required a total laryngectomy. With the selective application of multiple endoscopic excisions, radiation therapy, and more invasive operation, 100% of patients are without evidence of disease with a laryngeal preservation rate of 96%. CONCLUSIONS: This study supports the use of endoscopic excisional biopsy as the primary treatment modality for lesions ranging from carcinoma in situ to invasive T1 glottic carcinoma. This study also highlights the importance of close clinical follow-up and the potential need for further treatment. By reserving open operation and radiation therapy to selective cases, we successfully treated all patients while limiting the disadvantages of radiation therapy and more invasive operation to the minority of patients.

Giant parapharyngeal space lipoma: case report and surgical approach.

Large parapharyngeal space tumors near critical neurovascular structures pose challenging management problems. Only eight cases of a lipoma in the parapharyngeal space have been reported. We present a surgical approach that permits safe resection of such unusual tumors.A 49-year-old man had a 2-year history of progressive pain in the left neck radiating from the shoulder to the occiput. Contrast-enhanced computed tomography (CT) of the neck demonstrated a fat-attenuation mass located in the poststyloid parapharyngeal space. The mass extended into the foramen transversarium at the level of the second cervical vertebra and encased the vertebral artery. The tumor was removed through an extended transcervical approach that included transection of the attachments of the sternocleidomastoid, trapezius, splenius capitus, and the longissimus capitus muscles. The approach provided access to the first cervical vertebra, allowing dissection of the tumor from the vertebral artery in the foramen transversarium. An extended transcervical approach provides exposure from the carotid artery to the vertebral artery and facilitates the complete excision of large parapharyngeal space masses.

Midline nasal and hard palate destruction in cocaine abusers and cocaine's role in rhinologic practice.

Intranasal cocaine abuse can lead to destruction of the palate and perforation of the nasal septum. The pathophysiology of cocaine-induced midline destructive lesions is multifactorial and includes local ischemia secondary to vasoconstriction, chemical irritation from adulterants put in "cut" cocaine, and infection secondary to trauma, impaired mucociliary transport, and decreased humoral and cell-mediated immunity. Cocaine abuse should be suspected in patients with a palatal or septal perforation of unknown etiology.

Mozart versus new age music: relaxation states, stress, and ABC relaxation theory.

Smith's (2001) Attentional Behavioral Cognitive (ABC) relaxation theory proposes that all approaches to relaxation (including music) have the potential for evoking one or more of 15 factor-analytically derived relaxation states, or "R-States" (Sleepiness, Disengagement, Rested / Refreshed, Energized, Physical Relaxation, At Ease/Peace, Joy, Mental Quiet, Childlike Innocence, Thankfulness and Love, Mystery, Awe and Wonder, Prayerfulness, Timeless/Boundless/Infinite, and Aware). The present study investigated R-States and stress symptom-patterns associated with listening to Mozart versus New Age music. Students (N = 63) were divided into three relaxation groups based on previously determined preferences. Fourteen listened to a 28-minute tape recording of Mozart's Eine Kleine Nachtmusik and 14 listened to a 28-minute tape of Steven Halpern's New Age Serenity Suite. Others (n = 35) did not want music and instead chose a set of popular recreational magazines. Participants engaged in their relaxation activity at home for three consecutive days for 28 minutes a session. Before and after each session, each person completed the Smith Relaxation States Inventory (Smith, 2001), a comprehensive questionnaire tapping 15 R-States as well as the stress states of somatic stress, worry, and negative emotion. Results revealed no differences at Session 1. At Session 2, those who listened to Mozart reported higher levels of At Ease/Peace and lower levels of Negative Emotion. Pronounced differences emerged at Session 3. Mozart listeners uniquely reported substantially higher levels of Mental Quiet, Awe and Wonder, and Mystery. Mozart listeners reported higher levels, and New Age listeners slightly elevated levels, of At Ease/Peace and Rested/Refreshed. Both Mozart and New Age listeners reported higher levels of Thankfulness and Love. In summary, those who listened to Mozart's Eine Kleine Nachtmusik reported more psychological relaxation and less stress than either those who listened to New Age music or read popular recreational magazines. Results suggest the usefulness of ABC relaxation theory in comparing the different effects of music and relaxation techniques.

Idiosyncratic reality claims, relaxation dispositions, and ABC relaxation theory: happiness, literal christianity, miraculous powers, metaphysics, and the paranormal.

This study examined idiosyncratic reality claims, that is, irrational or paranormal beliefs often claimed to enhance relaxation and happiness and reduce stress. The Smith Idiosyncratic Reality Claims Inventory and the Smith Relaxation Dispositions Inventory (which measures relaxation and stress dispositions, or enduring states of mind frequently associated with relaxation or stress) were given to 310 junior college student volunteers. Principal components factor analysis with varimax rotation identified five idiosyncratic reality claim factors: belief in Literal Christianity; Magic; Space Aliens: After Death experiences; and Miraculous Powers of Meditation, Prayer, and Belief. No factor correlated with increased relaxation dispositions Peace, Energy, or Joy, or reduced dispositional somatic stress, worry, or negative emotion on the Smith Relaxation Dispositions Inventory. It was concluded that idiosyncratic reality claims may not be associated with reported relaxation, happiness, or stress. In contrast, previous research strongly supported self-affirming beliefs with few paranormal assumptions display such an association.

Stress symptoms of two groups before and after the terrorist attacks of 9/11/01.

This study investigated stress symptoms before and after the September 11, 2001 terrorist attack on the World Trade Center. Responses to the Smith Stress Symptoms Inventory were compared for Chicago area college students assessed 1 to 5 weeks after 9/11 (n=149) and a comparable sample tested up to 5 months prior to 9/11 (n=320). Post-9/11 participants scored higher on Attention Deficit. Contrary to prior research, post-9/11 participants did not score higher on distress, including Worry, Autonomic Arousal/Anxiety, Striated Muscle Tension, Depression, and Anger. It is suggested that those indirectly exposed to a terrorist attack may display traditional symptoms of distress and arousal (as suggested by previous research). Later symptoms of attention deficit and distancing may emerge. This work was based on independent pre- and post-9/11 samples and must be replicated longitudinally as a test-retest to draw conclusions regarding change over time.

Factor structure of the Smith irrational beliefs inventory: results of analyses on six independent samples.

This study reports the results of six factor analyses (alpha factoring, direct oblimin rotation, Delta= .4) on six items from the Smith Irrational Beliefs Inventory. Six independent samples of 1851 college students (521 men, 1,280 women, 50 sex unstated) were tested. Three factors emerged with identical content for each analysis. Distorted Egocentrism was defined by two items reflecting feelings of entitlement and the naive assumption that events should always turn out favorably the way one desires; Task Exaggeration/Catastrophizing was defined by two items directly depicting a tendency to view challenges as overwhelming and catastrophic; and Isolated Low Self-esteem was defined by two items expressing the feeling that one has unacceptable feelings that could lead to isolation or rejection. Previous research on other irrational belief inventories has yielded inconsistent results, with multifactorial solutions emerging for clinical samples and unifactoral solutions for student samples. That the present six factor analytic studies yielded a consistent multifactoral set of irrational beliefs for a very large student sample suggests that factors do emerge when items are initially screened and the subject population is carefully defined.

Diffuse large B-cell lymphoma of the maxillary sinus.

We report the case of a 25-year-old man with a history of recent facial trauma who presented with a mildly painful swelling of the left maxilla and nasal obstruction. The patient was initially diagnosed with left maxillary sinus osteomyelitis secondary to undiagnosed and untreated left maxillary sinus fractures. However, further evaluation revealed that the patient had diffuse large B-cell lymphoma.

Progressive muscle relaxation, yoga stretching, and ABC relaxation theory.

This study compared the psychological effects of progressive muscle relaxation (PMR) and yoga stretching (hatha) exercises. Forty participants were randomly divided into two groups and taught PMR or yoga stretching exercises. Both groups practiced once a week for five weeks and were given the Smith Relaxation States Inventory before and after each session. As hypothesized, practitioners of PMR displayed higher levels of relaxation states (R-States) Physical Relaxation and Disengagement at Week 4 and higher levels of Mental Quiet and Joy as a posttraining aftereffect at Week 5. Contrary to what was hypothesized, groups did not display different levels of R-States Energized or Aware. Results suggest the value of supplementing traditional somatic conceptualizations of relaxation with the psychological approach embodied in ABC relaxation theory. Clinical and research implications are discussed.