Oncologic Outcomes of Salvage Abdominoperineal Resection for Anal Squamous Cell Carcinoma Initially Managed with Chemoradiation.

Background: Abdominoperineal resection (APR) has been advocated for persistent or recurrent disease after failure of chemoradiation (CRT) for anal squamous cell cancer (SCC). Treatment with salvage APR can potentially achieve a cure. This study aimed to analyze oncological outcomes for salvage APR in a recent time period at a comprehensive cancer center. Methods: A retrospective review of all patients who underwent APR for biopsy-proven persistent or recurrent anal SCC between 1 January 2007 and 31 December 2020 was performed. Patients with stage IV disease at the time of initial diagnosis and patients with missing data were excluded. Univariate analysis was used with a chi-square test for categorical variables, and non-parametric tests were used for continuous variables. Kaplan-Meier survival analysis was performed to evaluate disease-specific (DSS), post-APR local recurrence-free (RFS), and disease-free survival (DFS). Results: A total of 96 patients were included in the analysis: 39 (41%) with persistent disease and 57 (59%) with recurrent SCC after chemoradiation had been completed. The median follow-up was 22 months (IQR 11-47). Forty-nine patients (51%) underwent extended APR and/or pelvic exenteration. Eight (8%) patients developed local recurrence, 30 (31%) developed local and distant recurrences, and 16 (17%) developed distant recurrences alone. The 3-year DSS, post-APR local recurrence-free survival, and disease-free survival were 53.8% (95% CI 43.5-66.5%), 54.5% (95% CI 44.4-66.8%), and 26.8% (95% CI 18.6-38.7%), respectively. In multivariate logistic regression analysis, positive microscopic margin (OR 10.0, 95% CI 2.16-46.12, p = 0.003), positive nodes in the surgical specimen (OR 9.19, 95% CI 1.99-42.52, p = 0.005), and lymphovascular invasion (OR 2.61 95% CI 1.05-6.51, p = 0.04) were associated with recurrence of disease. Gender, indication for APR (recurrent vs. persistent disease), HIV status, extent of surgery, or type of reconstruction did not influence survival outcomes. Twenty patients had targeted tumor-sequencing data available. Nine patients had PIK3CA mutations, seven of whom experienced a recurrence. Conclusions: Salvage APR for anal SCC after failed CRT was associated with poor disease-specific survival and low recurrence-free survival. Anal SCC patients undergoing salvage APR should be counseled that microscopic positive margins, positive lymph nodes, or the presence of lymphovascular invasion in the APR specimen are prognosticators for disease relapse. Our results accentuate the necessity for additional treatment strategies for the ongoing treatment challenge of persistent or recurrent anal SCC after failed CRT.

Development and perception of surgery-specific goals of care discussions in the preoperative setting: A learning pilot.

BACKGROUND: Goals of care discussions are infrequently documented in the preoperative period. Furthermore, documentation does not consistently address what matters most to patients, although patient values (PV) are central to person-centered care. METHODS: A multidisciplinary working group was formed. An electronic note comprised of (1) topics of discussion, (2) PV, and (3) advance care planning (ACP), was created and embedded into existing note templates for Gynecologic Surgical Oncology. Surgeons and advanced practice providers (APPs) were educated to conduct and document these conversations in preoperative clinic for patients undergoing cancer surgery for a pilot period. Data were collected regarding usage of the template. Focus groups with surgeons, APPs, and patients were conducted. Qualitative analysis was performed on transcripts. RESULTS: During the pilot, 7 surgeon/APP teams utilized the template on a total of 55 notes. Average number of notes completed per surgeon was 7.8 (SD 8.5). Forty-six notes (84%) included topics of discussion, 15 (27%) included PV, 4 (7%) included ACP. Qualitative analysis of focus group transcripts revealed that clinicians and patients perceived the initiative to be useful and important, although implementation barriers were identified. CONCLUSION: Creating a surgery-specific GOC template is feasible. Iterative revisions are needed to increase utility in clinic workflows.

Perspectives on Perioperative Team-Based Morbidity and Mortality Conferences: A Mixed Methods Study.

BACKGROUND: Morbidity and mortality conferences (MMCs) are quality improvement mechanisms during which adverse events are reviewed, often by physicians within a single discipline. There is a growing desire to include nonphysicians and physicians from other disciplines in team-based morbidity and mortality conferences (TBMMs). This mixed methods study investigates perioperative perspectives on MMCs generally and TBMMs specifically. METHODS: A national survey of perioperative health care professionals, including surgeons, anesthesiologists, and nurses, was used to explore opinions about MMCs and TBMMs. Semistructured qualitative interviews and focus groups were conducted with health care professionals and leaders at a single study site. Quantitative data were compared using a Kruskal-Wallis test. Interview transcripts were inductively analyzed. Data were analyzed using a concurrent mixed methods approach, triangulating both sources of data. RESULTS: Survey respondents (N = 1,466) were generally positive about both MMCs and TBMMs, agreeing that conferences were respectful, affected practice, and were educational. Nurses, compared to surgeons and anesthesiologists, were more likely to find conferences educational (p = 0.004) and were less comfortable speaking up in conferences (p < 0.001). Attendees who had more experience with TBMMs rated conferences as having significantly higher utility in achieving educational and safety goals. Qualitative data from 14 participants identified barriers and facilitators at the micro, meso, and macro level. Barriers include negative personal interactions, unsupportive leadership, and legal and regulatory issues. Facilitators include interpersonal relationships between professionals, buy-in from leadership, and external motivators. CONCLUSION: Perceptions of TBMMs were overall positive, but significant barriers to implementation remain. Team members may be invited to the table, but more effort is needed to make the entire team feel included in the discussion and optimize the value of these conferences. Strategies for overcoming identified barriers remains an open area of research.

Anal Adenocarcinoma Treated in the Era of Total Neoadjuvant Therapy and Nonoperative Management.

BACKGROUND: Anal adenocarcinoma bears a treatment strategy unique to other anal cancers. OBJECTIVE: This study aimed to describe oncologic outcomes of total neoadjuvant therapy followed by watch-and-wait approach for anal adenocarcinoma. DESIGN: Retrospective analysis. SETTINGS: This study was conducted at a comprehensive cancer center. PATIENTS: Patients with anal adenocarcinoma treated between 2004 and 2019 were selected. INTERVENTIONS: Fifty-four patients received neoadjuvant therapy and were divided into 2 groups according to their treatment strategy: total neoadjuvant therapy versus single neoadjuvant modality therapy. MAIN OUTCOME MEASURES: Organ preservation, tumor regrowth, local failure, distant metastasis rates, recurrence-free survival, and overall survival. RESULTS: This study included 70 patients with anal adenocarcinoma. Fifty-four patients (77%) received neoadjuvant therapy, of whom 30 (42%) received total neoadjuvant therapy and 24 (34%) received single neoadjuvant modality. Twenty-three (33%) patients achieved complete clinical response and were managed by watch-and-wait approach. The proportion of patients able to continue to watch-and-wait approach was higher after receiving total neoadjuvant therapy (60%) compared with single neoadjuvant modality therapy (20%; p = 0.004). A tumor regrowth rate of 22% was observed in the total neoadjuvant therapy group. The 5-year overall survival rate was 70% (95% CI, 59%-83%), including 61% (95% CI, 42%-88%) for the total neoadjuvant therapy and 65% (95% CI, 48%-88%) for the single neoadjuvant modality groups. Colostomy was avoided in 50% of patients who received total neoadjuvant therapy and 83% of watch-and-wait patients. Five-year recurrence-free survival rates of 55% (95% CI, 39%-79%) and 30% (95% CI, 15%-58%) were observed in the total neoadjuvant therapy and single neoadjuvant modality groups. LIMITATIONS: Retrospective nature. CONCLUSIONS: This is the first report in the literature describing the safety and feasibility of nonoperative management for anal adenocarcinoma. Anal adenocarcinoma treated with total neoadjuvant therapy and nonoperative management achieve regrowth rates comparable to those observed in rectal cancer, with oncologic outcomes similar to those of traditional treatment strategies. See Video Abstract . ADENOCARCINOMA ANAL TRATADO EN LA ERA DE LA TERAPIA NEOADYUVANTE TOTAL Y EL TRATAMIENTO NO QUIRRGICO: ANTECEDENTES:El adenocarcinoma anal conlleva una estrategia de tratamiento único para otros cánceres anales.OBJETIVO:Describir los resultados oncológicos de la terapia neoadyuvante total seguida de observar y esperar en adenocarcinoma anal.DISEÑO:Análisis retrospectivo.AJUSTE:Este estudio se llevó a cabo en un centro oncológico integral.PACIENTES:Se seleccionaron pacientes con adenocarcinoma anal tratados entre 2004-2019.INTERVENCIONES:Cincuenta y cuatro pacientes recibieron terapia neoadyuvante y se dividieron en dos grupos según su estrategia de tratamiento: terapia neoadyuvante total versus terapia de modalidad neoadyuvante única.PRINCIPALES MEDIDAS DE RESULTADO:Preservación de órganos, recurrencia tumoral, falla local, tasas de metástasis a distancia, libre de recurrencia y supervivencia general.RESULTADOS:El estudio incluyó a 70 pacientes con adenocarcinoma anal. Cincuenta y cuatro pacientes (77%) recibieron terapia neoadyuvante, de los cuales 30 (42%) recibieron terapia neoadyuvante total y 24 (34%) recibieron modalidad neoadyuvante única. Veintitrés (33%) pacientes presentaron una respuesta clínica completa y fueron tratados con vigilancia y espera. La proporción de pacientes capaces de continuar en observar y esperar fue mayor después de recibir terapia neoadyuvante total (60%) en comparación con la terapia de modalidad neoadyuvante única (20%) ( p = 0,004). Se observó una tasa de recurrencia tumoral del 22% en el grupo de terapia neoadyuvante total. La tasa de supervivencia general a 5 años fue del 70% (IC95% 59%-83 %), incluido el 61% (IC95% 42%-88%) para la terapia neoadyuvante total y el 65% (IC95% 48%-88%) para grupos de modalidad neoadyuvante única. Se evitó la colostomía en el 50% de los pacientes que recibieron terapia neoadyuvante total y el 83% de los pacientes en observar y esperar. Se observaron tasas de supervivencia libre de recurrencia a cinco años del 55% (IC95% 39%-79%) y del 30% (IC95% 15%-58%) en los grupos de terapia neoadyuvante total y modalidad neoadyuvante única, respectivamente.LIMITACIONES:Diseño retrospectivo.CONCLUSIONES:Este es el primer informe en la literatura que describe la seguridad y viabilidad del tratamiento no quirúrgico del adenocarcinoma anal. El adenocarcinoma anal tratado con terapia neoadyuvante total y manejo no quirúrgico logra tasas de recurrencia comparables a las observadas en el cáncer de recto, con resultados oncológicos similares a las estrategias de tratamientos tradicionales. (Traducción-Dr. Fidel Ruiz Healy ).

Perioperative Team-Based Morbidity and Mortality Conferences: A Systematic Review of the Literature.

Objective: This systematic review aimed to identify key elements of perioperative team-based morbidity and mortality conferences (TBMMs) and their impact on patient safety, education, and quality improvement outcomes. Background: Patient safety in the perioperative period is influenced by system, team, and individual behaviors. However, despite this recognition, single-discipline morbidity and mortality conferences remain a mainstay of educational and quality improvement efforts. Methods: A structured search was conducted in MEDLINE Complete, Embase, Web of Science, ClinicalTrials.gov, Cochrane CENTRAL, and ProQuest Dissertations and Theses Global in July 2022. Search results were screened, and the articles meeting inclusion criteria were abstracted. Results: Seven studies were identified. Key TBMM elements were identified, including activities done before the conference-case selection and case investigation; during the conference-standardized presentation formats and formal moderators; and after the conference-follow-up emails and quality improvement projects. The impacts of TBMMs on educational, safety, and quality improvement outcomes were heterogeneous, and no meta-analysis could be conducted; however, improvement was typically shown in each of these domains where comparisons were made. Conclusions: Recommendations for key TBMM elements can be drawn from the reports of successful perioperative TBMMs. Possible benefits of structured TBMMs over single-discipline conferences were identified for further exploration, including opportunities for rich educational contributions for trainees, improved patient safety, and the potential for system-wide quality improvement. Design and implementation of TBMM should address meticulous preparation of cases, standardized presentation format, and effective facilitation to increase the likelihood of realizing the potential benefits.

Rectal Cancer after Prostate Radiation: A Complex and Controversial Disease.

A small proportion of rectal adenocarcinomas develop in patients many years after the treatment of a previous cancer using pelvic radiation, and the incidence of these rectal cancers depends on the length of follow-up from the end of radiotherapy. The risk of radiation-associated rectal cancer (RARC) is higher in patients treated with prostate external beam radiotherapy than it is in patients treated with brachytherapy. The molecular features of RARC have not been fully investigated, and survival is lower compared to non-irradiated rectal cancer patients. Ultimately, it is unclear whether the worse outcomes are related to differences in patient characteristics, treatment-related factors, or tumor biology. Radiation is widely used in the management of rectal adenocarcinoma; however, pelvic re-irradiation of RARC is challenging and carries a higher risk of treatment complications. Although RARC can develop in patients treated for a variety of malignancies, it is most common in patients treated for prostate cancer. This study will review the incidence, molecular characteristics, clinical course, and treatment outcomes of rectal adenocarcinoma in patients previously treated with radiation for prostate cancer. For clarity, we will distinguish between rectal cancer not associated with prostate cancer (RCNAPC), rectal cancer in non-irradiated prostate cancer patients (RCNRPC), and rectal cancer in irradiated prostate cancer patients (RCRPC). RARC represents a unique but understudied subset of rectal cancer, and thus requires a more comprehensive investigation in order to improve its treatment and prognosis.

Accuracy of Pathology Reports on Neck Dissection Specimens: A Retrospective Case Series Study.

BACKGROUND: Accuracy of the number and location of pathological lymph nodes (LNs) in the pathology report of a neck dissection (ND) is of vital importance. OBJECTIVES: To quantify the error rate in reporting the location and number of pathologic LNs in ND specimens. METHODS: All patients who had undergone a formal ND that included at least neck level 1 for a clinical N1 disease between January 2010 and December 2017 were included in the study. The error rate of the pathology reports was determined by various means: comparing preoperative imaging and pathological report, reporting a disproportionate LN distribution between the different neck levels, and determining an erroneous location of the submandibular gland (SMG) in the pathology report. Since the SMG must be anatomically located in neck level 1, any mistake in reporting it was considered a categorical error. RESULTS: A total of 227 NDs met the inclusion criteria and were included in the study. The study included 128 patients who had undergone a dissection at levels 1-3, 68 at levels 1-4, and 31 at levels 1-5. The best Kappa score for correlation between preoperative imaging and final pathology was 0.50. There were nine cases (3.9%) of a disproportionate LN distribution in the various levels. The SMG was inaccurately reported outside neck level 1 in 17 cases (7.5%). CONCLUSIONS: At least 7.5% of ND reports were inaccurate in this investigation. The treating physician should be alert to red flags in the pathological report.

Outcomes of Tracheal Resections in Well-Differentiated Thyroid Cancer-A case series and meta-analysis.

BACKGROUND: Tracheal invasion in thyroid cancer is a well-known form of advanced disease. There is an ongoing controversy over outcomes of tracheal shaving in this situation. The aim of this study was to compare the results of tracheal shaving to radical resections in patients with low-volume tracheal involvement. METHODS: An institutional case series and a meta-analysis was conducted. All studies that included patients diagnosed with well-differentiated thyroid cancer (WDTC) and tracheal invasion were analyzed. Patients with low-volume tracheal invasion (according to the Shin classification) were extracted from the various studies and subsequently included in this study. The outcomes of tracheal shaving and radical resection were consolidated and compared. All recurrences and mortality over 10 years of follow-up were calculated using the Kaplan-Meier method. RESULTS: Institutional case series included 22 patients diagnosed with WDTC and tracheal invasion that underwent resection. There was one case of recurrence (4.5%) during the follow-up period and no mortality. The meta-analysis yielded a total of 284 patients from six studies who met the inclusion criteria. The 10-year overall survival was 82.4% for the shave group and 80.8% for the resection group. The combined Kaplan-Meier curves revealed no statistically significant difference between the two techniques (hazard ratio [HR] = 0.86, P = .768). The combined 10-year local control rate of the shave group was 90.2%. CONCLUSIONS: The outcomes of tracheal shaving in low-volume invasion are similar to more aggressive forms of tracheal resections. Shave resection is oncologically safe in carefully selected WDTC patients demonstrating minimal tracheal invasion.

Diastolic function as an early marker for systolic dysfunction and all-cause mortality among cancer patients.

BACKGROUND: Increased survival among active cancer patients exposes a wide range of side effects, including cardiotoxicity, manifested by systolic dysfunction and associated with morbidity and mortality. Early diagnosis of subclinical function changes and cardiac damage is essential in the management of these patients. Diastolic dysfunction is considered common among cancer patients; however, its effect on systolic dysfunction or mortality is still unknown. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry, enrolling and prospectively following all patients evaluated in the cardio-oncology clinic in the Tel Aviv Sourasky Medical Center. All patients underwent echocardiographic examinations including evaluation of diastolic parameters and global longitudinal strain (GLS). Systolic dysfunction was defined as either an absolute reduction >10% in left ventricular ejection fraction to a value below 53% or GLS relative reduction >10% between the 1st and 3rd echocardiography examinations. RESULTS: Overall, 190 active cancer patients were included, with a mean age of 58 ± 15 years and a female predominance (78%). During a median follow-up of 243 days (interquartile ranges [IQR]: 164-401 days), 62 (33%) patients developed systolic dysfunction. Over a median follow-up of 789 days (IQR: 521-968 days), 29 (15%) patients died. There were no significant differences in baseline cardiac risk factors between the groups. Using multivariate analysis, E/e' lateral and e' lateral emerged as significantly associated with systolic dysfunction development and all-cause mortality (P = .015). CONCLUSION: Among active cancer patients, evaluation of diastolic function may provide an early marker for the development of systolic dysfunction, as well as all-cause mortality.

Longitudinal diastolic strain slope as an early sign for systolic dysfunction among patients with active cancer.

BACKGROUND: Diastolic dysfunction is a common finding in patients receiving cancer therapy. This study evaluated the correlation of diastolic strain slope (Dss) with routine echocardiography diastolic parameters and its role in early detection of systolic dysfunction and cardiovascular (CV) mortality within this population. METHODS: Data were collected from the Israel Cardio-Oncology Registry (ICOR), a prospective registry enrolling adult patient receiving cancer therapy. All patients performed at least three echocardiography exams (T1, T2, T3), including left ventricle Global Longitudinal Strain (LV GLS) and Dss. Systolic dysfunction was determined by either LV GLS relative reduction of ≥ 15% or LV ejection fraction reduction > 10% to < 53%. Dss was assessed as the early lengthening rate, measured by the diastolic slope (delta%/sec). RESULTS: Among 144 patients, 114 (79.2%) were female with a mean age of 57.31 ± 14.3 years. Dss was significantly correlated with e' average. Mid segment Dss change between T1 and T2 showed significant association to systolic dysfunction development (Odds Ratio (OR) = 1.04 [1.01,1.06]. p = 0.036). In multivariate prediction, Dss increase was a significant predictor for the development of systolic dysfunction (OR = 1.06 [1.03,1.1], P < 0.001).An 8% increase in Dss between T1 and T2 was associated with a trend in increased CV mortality (HR = 3.4 [0.77,15.4], p = 0.085). CONCLUSIONS: This study is the first to use the novel measurement of Dss in patients treated with cancer therapies and to show significant correlation between routine diastolic dysfunction parameters and Dss. Changes in the mid segment were found to have significant independent early predictive value for systolic dysfunction development in univariate and multivariate analyses.

Rate of Occult Neck Nodal Metastasis in Parotid Cancer: A Meta-Analysis.

BACKGROUND: The risk for occult neck nodal metastasis in carcinoma of the parotid gland is inconclusive. Therefore, addressing a negative neck prophylactically and the extent to do so remain controversial. This systematic review aimed to determine the rate of occult nodal metastasis for each neck level, and consequently, to elucidate the proper extent of elective neck dissection (END). METHODS: A meta-analysis of all studies that included patients with a diagnosis of parotid malignancies who underwent an END was performed. The risk for occult nodal metastasis was calculated for each neck level separately. RESULTS: The search strategy identified 124 papers from January 1980 to December 2019 in the various databases. Nine retrospective studies (n =548) met the inclusion criteria. The risk for occult neck nodal metastasis ranged from 0.0 to 9.43% with a random-effect model of 2.2% for level 1 (n =459), from 3.4 to 28.38% with a random-effect model of 16.51% for level 2 (n =548), from 0.0 to 21.63% with a random-effect model of 4.23% for level 3 (n =518), from 0.0 to 17.02% with a fixed-effect model of 0.39% for level 4 (n =310), and from 0.0 to 11.63% with a fixed-effect model of 1.7% for level 5 (n =417). CONCLUSION: The rate of occult neck nodal metastasis in parotid malignancies is low, with neck level 2 the most commonly involved. The results of this meta-analysis prevented the authors from substantiating the appropriate extent of an END in parotid cancer.

Core needle biopsy for diagnosing lymphoma in cervical lymphadenopathy: Meta-analysis.

BACKGROUND: The diagnostic yield of core needle biopsies (CNB) in cervical lymphadenopathy for lymphoma diagnosis is controversial. The aim of this study was to calculate the accuracy of cervical CNB in diagnosing lymphoma. METHODS: We conducted a meta-analysis of all studies on patients presenting with cervical lymphadenopathy and referred to CNB. Patients with a diagnosis other than lymphoma were excluded. All cases diagnosed with lymphoma sufficient to guide treatment based on CNB outcome were considered accurate (actionable) results. A separate meta-analysis was performed for various lymphoma subtypes. RESULTS: Three prospective and 19 retrospective studies, comprising 1120 patients, met the inclusion criteria. The rate of actionable lymphoma diagnoses following CNB ranged from 30% to 96.3%, with a random-effects model of 82.45% (95% confidence interval [CI] =0.76-0.88) and a fixed-effects model of 78.3% (95% CI =0.75-0.80). CONCLUSION: CNB for cervical lymphadenopathy in lymphoma cases is relatively accurate in guiding treatment.

Diastolic strain time as predictor for systolic dysfunction among patients with active breast cancer.

BACKGROUND: Although diastolic dysfunction is common among patients treated with cancer therapy, no clear evidence has been shown that it predicts systolic dysfunction. This study evaluated the correlation of diastolic strain time (Dst) with the routine echocardiography diastolic parameters and estimated its role in the early detection of cardiotoxicity among patients with active breast cancer. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry (ICOR), a prospective registry enrolling all adult patients referred to the cardio-oncology clinic. All patients with breast cancer, planned for Doxorubicin therapy, were included. Echocardiography, including global longitudinal systolic strain (GLS) and Dst, was assessed at baseline before chemotherapy (T1), during Doxorubicin therapy (T2) and after the completion of Doxorubicin therapy (T3). Cardiotoxicity was determined by GLS relative reduction of ≥15%. Dst was assessed as the time measured (ms) of the myocardium lengthening during diastole. RESULTS: Among 69 patients, 67 (97.1%) were females with a mean age of 52 ± 13 years. Dst was significantly associated with the routine diastolic parameters. Significant GLS reduction was observed in 10 (20%) patients at T3. Both in a univariate and a multivariate analyses, the change in Ds basal time from T1 to T2 emerged to be significantly associated with GLS reduction at T3 (P < .04). CONCLUSIONS: Among breast cancer patients, Dst showed high correlation to the routine diastolic echocardiography parameters. Change in Ds basal time emerged associated with clinically significant systolic dysfunction as measured by GLS reduction.

Assessment of the Rate of Skip Metastasis to Neck Level IV in Patients With Clinically Node-Negative Neck Oral Cavity Squamous Cell Carcinoma: A Systematic Review and Meta-analysis.

Importance: The rate of skip metastasis to neck level IV in patients with clinically node-negative neck (cN0) oral cavity squamous cell carcinoma (OCSCC) remains controversial. Objective: To provide a high level of evidence using a meta-analysis on the rate of skip metastasis to level IV in this subset of patients. Data Sources: The Embase, PubMed, and Google Scholar databases were searched for articles published during the period of January 1, 1970, through December 31, 2017, using the following key terms: neck dissection, N0 neck, squamous cell carcinoma, skip metastasis, radical neck dissection, lymph node management, neck metastasis, oral cavity cancer, and tongue cancer. Some terms were also used in combination, and the reference section of each article was searched for additional potentially relevant publications. Data were analyzed from January 8 through 11, 2018. Study Selection: Inclusion criteria were all cohorts, including from any randomized clinical trial, case-control study, case study, and case report; studies of patients with the histopathologic diagnosis of OCSCC; and studies that differentiated data between skip metastasis and sequential metastasis to neck level IV. Of the 115 articles retrieved from the literature, 11 retrospective studies and 2 prospective randomized clinical trials (n = 1359 patients) were included. Data Extraction and Synthesis: Meta-analysis of Observational Studies in Epidemiology guidelines were followed. Fixed-effects model and 95% CIs were estimated, and data of included studies were pooled using a fixed-effects model. Main Outcomes and Measures: Overall proportion of neck involvement and the rate of level IV skip metastasis. Subgroup analysis for primary site and tumor staging. Results: The rate of level IV involvement in patients with cN0 ranged between 0% and 11.40% with a fixed-effects model of 2.53% (95% CI, 1.64%-3.55%). The rate of skip metastasis ranged from 0% to 5.50% with a fixed-effects model of 0.50% (95% CI, 0.09%-1.11%). The rate of level IV skip metastasis did not increase significantly in cases that involved neck levels I through III. Tumor staging and primary site tumor did not significantly affect the rate of skip metastasis. Conclusions and Relevance: This meta-analysis showed very low rates of skip metastasis to neck level IV in patients diagnosed with cN0 OCSCC. Encountering an allegedly positive lymph node during neck dissection does not portend high rates of level IV involvement. Supraomohyoid neck dissection is therefore adequate for this subset of patients.

Long-term health-related quality of life after mandibular resection and reconstruction.

PURPOSE: To compare short- and long-term quality of life (QOL) scores in patients undergoing mandibular resection and reconstruction. MATERIALS AND METHODS: All the patients who underwent resection and reconstruction of the mandible between 2000 and 2015 at a large tertiary center were retrospectively reviewed. Their QOL was measured by the University of Washington QOL questionnaire. Between 12 and 189 months (median 83.5 months) had elapsed since the end of treatment. The QOL of the short-term (< 5 years) and long-term (> 5 years) follow-up groups was compared and analyzed. RESULTS: Fifty-eight patients completed the questionnaire. The scores for physical function, emotional function, activity, recreation, and taste domains were significantly higher for the long-term follow-up group. The activity and pain domains posed a significant problem for significantly more patients in the short-term follow-up group. CONCLUSION: Comparison of the short- and long-term QOL scores of patients undergoing mandibular resection and reconstruction revealed that the scores for the latter were significantly higher in several domains. This finding might be indicative of a cumulative effect of time on patients' QOL, even many years post-treatment.

Retinoid signaling in progenitors controls specification and regeneration of the urothelium.

The urothelium is a multilayered epithelium that serves as a barrier between the urinary tract and blood, preventing the exchange of water and toxic substances. It consists of superficial cells specialized for synthesis and transport of uroplakins that assemble into a tough apical plaque, one or more layers of intermediate cells, and keratin 5-expressing basal cells (K5-BCs), which are considered to be progenitors in the urothelium and other specialized epithelia. Fate mapping, however, reveals that intermediate cells rather than K5-BCs are progenitors in the adult regenerating urothelium, that P cells, a transient population, are progenitors in the embryo, and that retinoids are critical in P cells and intermediate cells, respectively, for their specification during development and regeneration. These observations have important implications for tissue engineering and repair and, ultimately, may lead to treatments that prevent loss of the urothelial barrier, a major cause of voiding dysfunction and bladder pain syndrome.