Ron J. Karni

Transoral laser microsurgery: A new approach for unknown primaries of the head and neck

To evaluate the efficacy of transoral laser microsurgery (TLM) used at examination under anesthesia (EUA) for detection and management of an unidentified primary site and to determine survival with both TLM EUA and traditional rigid pharyngolaryngoscopy EUA, with directed biopsies.

Robotic surgery for primary head and neck squamous cell carcinoma of unknown site

IMPORTANCE Identification of the primary site in head and neck squamous cell carcinoma (HNSCC) is crucial because it improves the patients prognosis and minimizes morbidity from treatment. OBJECTIVES To determine the efficacy of transoral robotic surgery (TORS) in identifying unknown primary sites of head and neck squamous cell carcinoma. DESIGN, SETTING, AND PARTICIPANTS Retrospective, multi-institutional case series from January 1, 2010, to February 28, 2013, in which data were pooled from the following 6 institutions: University of Washington Medical Center, The University of Texas MD Anderson Cancer Center, University of Alabama-Birmingham Hospital, The University of Texas Medical School at Houston, Johns Hopkins Hospital, and Oregon Health Sciences University. All patients diagnosed as having HNSCC of an unknown primary site who underwent TORS to identify the primary site were included in the study. We excluded those with recurrent disease, a history of radiation therapy to the head and neck, or evidence of a primary tumor site based on previous biopsy results. MAIN OUTCOME AND MEASURE Identification of the primary tumor site. RESULTS Forty-seven patients were eligible for the study. The tumor site was identified by TORS in 34 of 47 patients (72.3%). The primary site was located in the base of tongue for 20 patients (58.8%) and the palatine tonsil for 13 patients (38.2%), with 1 patient having a primary site in both the base of tongue and the palatine tonsil. Suspicious physical examination findings were present in 23 of 47 patients (48.9%), with positive and negative predictive values of 56.5% and 25.0%, respectively. Of those who underwent any imaging, 16 patients had suspicious findings, with positive and negative predictive values of 50.0% and 16.7%, respectively. In 18 of 47 patients (38.3%), both preoperative radiographic and physical examination failed to suggest a primary site. Of these 18 patients, 13 (72.2%) were identified after undergoing TORS. CONCLUSIONS AND RELEVANCE We demonstrate that TORS is a useful approach to identify and treat the primary site in patients with HNSCC who present with an unknown primary site.

Practical guide to understanding the value of case reports

Case reports have been vital to the advancement of medicine, providing a mechanism for scholarly education and for sharing new discovery and rare observations. However, journals are increasingly reluctant to publish this type of manuscript. Additionally, case reports and limited case series are infrequently cited, potentially interfering with the impact factor of a journal. The increasing emphasis on evidence-based medicine may have artificially decreased the value of case reports. This article describes the value of case reports to medicine, citing 3 examples that have significantly improved the practice of medicine. We also provide criteria for effective reporting, which include the elements of both surprise and closure. In summary, we offer support for the contention that case reports are fundamental to the scholarly practice of medicine and enhance the intent of a quality medical journal.

Fluorescent in situ hybridization (FISH) analysis of the relationship between chromosome location and nuclear morphology in human neutrophils

Abstract.Human neutrophil nuclei typically consist of three of four large heterochromatic lobes joined by thin, DNA-containing filaments. In addition, some lobes exhibit appendages of various sizes and shapes. Classical genetic and cytological studies suggest that some appendages contain specific chromsomes. The studies reported here provide the first detailed analysis of the spatial relationship between individual chromosomes and recognizable structures in neutrophil nuclei using fluorescent in situ hybridization. Analysis of DNA sequences in chromosomes 2, 18, X, and Y demonstrate that specific lobes in a population of neutrophil nuclei do not have a fied chromosome content. This result implies that chromosomes partition randomly among lobes during neutrophil differentiation. However, neutrophil nuclear topography is not entirely fortuitous. For instance, none of the sequences probed in this study mapped to a filament and most centromeres lie in clusters near the nuclear periphery. In addition, one of the X chromosome centromeres in females and the Y chromosome centromere in males consistently associate with specific nuclear appendages found in a subset of neutrophil nuclei. Chromosomes 2 and 18 occupy discrete nd separate territories within individual lobes and neither territory ever extends into a filament. Surprisingly, the sizes of these territories are not proportional to chromosome length, suggesting that individual neutrophil chromosomes vary in their degree of compaction. These results are discussed in the light of models that attempt to explain nuclear morphology in terms of chromosome spatial organization.

Applications for transoral robotic surgery in the pediatric airway

To report preliminary experience in the utilization of transoral robotic surgical (TORS) techniques in pediatric airway surgery.

Nonrandom location and orientation of the inactive X chromosome in human neutrophil nuclei.

Abstract. The nuclei of human neutrophils typically consist of a linear array of three or four lobes joined by DNA-containing filaments. Terminal lobes are connected to internal lobes via a single filament, while internal lobes have two filaments, each to an adjacent lobe. Some lobes also have appendages of various shapes and sizes. In particular, up to 17% of neutrophil nuclei of healthy women exhibit a drumstick-shaped appendage that contains the inactive X chromosome. This report provides a detailed analysis of the relationship between nuclear morphology and the location of the X and Y chromosomes in human neutrophils. Fluorescent in situ hybridization analysis revealed that the X and the Y chromosomes of male neutrophil nuclei are randomly distributed among nuclear lobes. Similarly, in female neutrophil nuclei with a drumstick appendage, the active X chromosome is also randomly distributed among lobes. In contrast, the inactive X chromosome is preferentially located in a terminal lobe in over 90% nuclei with drumsticks. Within the terminal lobe of nuclei with drumsticks, the inactive X chromosome lies distal to the point of filament attachment in 80% of the nuclei. The inactive X chromosome also exhibits a specific orientation within the drumstick appendage, with over 95% of nuclei having the X centromere located toward the tip of the appendage. Female nuclei without a drumstick appendage also have one of the X chromosomes (presumably the inactive chromosome) preferentially situated in a terminal lobe. Nonrandom distribution of the inactive X chromosome is discussed in the context of a model that considers chromosomes as determinants of neutrophil nuclear morphology.

A practical guide to understanding outcomes research.

This article is organized into the following sections: (1) history, (2) definition, (3) levels of evidence, (4) overall results and findings, (5) examples in otolaryngology including record based and patient based, and (6) summary to explain this difficult to understand term. To understand “outcomes research,” it is useful to think of it like postmarketing surveillance of a drug in a huge population of diverse patients in which the drug is used in a wide variety of ways, often as off-label interventions. This is in stark contrast to the randomized controlled trials that established the drug efficacy and safety in the premarket or after market phase I, II, and III trials in which the drug was only used in a smaller, tightly defined, sample of subjects for a specific purpose. Perhaps the best way to characterize “outcomes research” is as follows: it seeks to determine how the patient can be made better overall (as ultimately defined by the patient and their family), not just have the disease treated, even with the current accepted treatment of choice. This challenges both the science and the compassionate art of medicine, health care systems, and individuals. The trick is to accomplish this with the best possible scientific methods, as devoid of bias as possible. Outcomes research was originally conceived and described as potentially a new type of study of populations and outcomes after diverse treatments, which would help answer questions about the best treatments for different conditions. Initial hopes were that outcomes-based studies would be able to “find out what works in medicine.” Much of the impetus for the development of outcomes research was the surprising findings of marked differences in health care utilization rates for techniques and procedures in different (often adjacent) geographic regions. These findings included large differences, 2to 5-fold, in population rates of tonsillectomy, carotid endarterectomy, and hysterectomy, for example, and also in hospital admission rates for elective problems. These differences could not be explained by underlying differences in disease prevalence or severity, insurance status, or the patients themselves; de-

A practical guide for understanding confidence intervals and P values

The 95 percent confidence interval about the mean demarcates the range of values in which the mean would fall if many samples from the universal parent population were taken. In other words, if the same observation, experiment, or trial were done over and over with a different sample of subjects, but with the same characteristics as the original sample, 95 percent of the means from those repeated measures would fall within this range. This gives a measure of how confident we are in the original mean. It tells us not only whether the results are statistically significant because the CI falls totally on one side or the other of the no difference marker (0 if continuous variables; 1 if proportions), but also the actual values so that we might determine if the data seem clinically important. In contrast, the P value tells us only whether the results are statistically significant, without translating that information into values relative to the variable that was measured. Consequently, the CI is a better choice to describe the results of observations, experiments, or trials.

The effects of anesthesia on the morphoproteomic expression of head and neck squamous cell carcinoma: a pilot study

The prognosis and disease-free survival rates for head and neck squamous cell carcinoma (HNSCC) have remained relatively stagnant for the last several decades. Moreover, as is the case with other malignancies, locoregional recurrence and distant metastasis are all too common even after seemingly successful oncologic surgery and adjuvant therapy. Recently, increased focus has been placed on understanding the influence of perioperative factors on tumor cell behavior and surgical outcomes. More specifically, emerging research suggests that anesthetic agents may play a role in cancer recurrence by interacting with prosurvival protein signaling pathways which harden tumor cells against oncologic treatments. In the present pilot study, we tested the hypothesis that inhalational anesthesia and total intravenous anesthesia (TIVA) exert differential effects on the proteomic expression of HNSCC. Ten patients with previously untreated oral cavity or oropharyngeal HNSCC were randomized to receive either sevoflurane and remifentanil or propofol and remifentanil for the duration of their respective surgeries. Morphoproteomic analysis using 10 pro-oncogenic protein markers was performed on both pre- and postanesthesia tumor samples to qualitatively grade changes in protein expression. The results of this analysis demonstrated differential expression of several protein markers. Specifically, the exposure to sevoflurane but not TIVA resulted in a statistically significant increase in the expression of cytoplasmic hypoxia-inducible factor-2alpha (P = 0.049) and nuclear p-p38 mitogenic-activated protein kinase (P = 0.041). This study represents one of the first to evaluate the effects of anesthesia on the molecular biology of HNSCC in vivo, and the results suggest that the exposure to sevoflurane may increase the expression of pro-oncogenic protein markers in HNSCC tumor cells.

Post-operative therapy following transoral robotic surgery for unknown primary cancers of the head and neck

OBJECTIVES Our primary objective is to describe the post- operative management in patients with an unknown primary squamous cell carcinoma of the head and neck (HNSCC) treated with trans-oral robotic surgery (TORS). MATERIALS & METHODS We conducted a retrospective multi-institutional case series including all patients diagnosed with an unknown primary HNSCC who underwent TORS to identify the primary site from January 1, 2010 to June 30, 2016. We excluded those with recurrent disease, ≤6months of follow up from TORS, previous history of radiation therapy (RT) to the head and neck, or evidence of primary tumor site based on previous biopsies. Our main outcome measure was receipt of post-operative therapy. RESULTS The tumor was identified in 26/35 (74.3%) subjects. Post-TORS, 2 subjects did not receive adjuvant therapy due to favorable pathology. Volume reduction of RT mucosal site coverage was achieved in 12/26 (46.1%) subjects who had lateralizing tumors, ie. those confined to the palatine tonsil or glossotonsillar sulcus. In addition, for 8/26 (30.1%), the contralateral neck RT was also avoided. In 9 subjects, no primary was identified (pT0); four of these received RT to the involved ipsilateral neck nodal basin only without pharyngeal mucosal irradiation. CONCLUSION Surgical management of an unknown primary with TORS can lead to deintensification of adjuvant therapy including avoidance of chemotherapy and reduction in RT doses and volume. There was no increase in short term treatment failures. Treatment after TORS can vary significantly, thus we advocate adherence to NCCN guideline therapy post-TORS to avoid treatment-associated variability.