Urea Cycle Dysregulation Generates Clinically Relevant Genomic and Biochemical Signatures.

The urea cycle (UC) is the main pathway by which mammals dispose of waste nitrogen. We find that specific alterations in the expression of most UC enzymes occur in many tumors, leading to a general metabolic hallmark termed "UC dysregulation" (UCD). UCD elicits nitrogen diversion toward carbamoyl-phosphate synthetase2, aspartate transcarbamylase, and dihydrooratase (CAD) activation and enhances pyrimidine synthesis, resulting in detectable changes in nitrogen metabolites in both patient tumors and their bio-fluids. The accompanying excess of pyrimidine versus purine nucleotides results in a genomic signature consisting of transversion mutations at the DNA, RNA, and protein levels. This mutational bias is associated with increased numbers of hydrophobic tumor antigens and a better response to immune checkpoint inhibitors independent of mutational load. Taken together, our findings demonstrate that UCD is a common feature of tumors that profoundly affects carcinogenesis, mutagenesis, and immunotherapy response.

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.

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.

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.

Reckless administration of QT interval-prolonging agents in elderly patients with drug-induced torsade de pointes.

A systematic review was conducted for all published case reports on drug-induced torsade de pointes (TdP) in elderly (≥80 years) patients to study if the administration of the offending agent was reckless. Overall, 61 reports on drug-induced TdP in patients aged 80-97 years were included in the analysis. Non-modifiable risk factors for drug-induced TdP (e.g. acute coronary syndrome, female gender and congestive heart failure), modifiable risk factors (e.g. hypokalemia, severe hypomagnesemia and digitalis toxicity) and reckless administration of a QT interval-prolonging agent (e.g. despite a known QT interval prolongation or a history of TdP, together with other QT interval prolonging agents in higher than recommended doses) were recorded in each case. Overall, 54 (88.5%) patients had non-modifiable risk factors for drug-induced TdP and 21 (34.4%) patients had modifiable risk factors. The administration of the offending agent was reckless in one half (n = 31; 50.8%) of the patients. The most prevalent reckless administration of a QT interval-prolonging agent was together with other QT interval-prolonging agents (n = 16; 51.6%) or despite QT interval prolongation (n = 8; 25.8%). In conclusion, although risk factors for drug-induced TdP are prevalent in elderly patients with drug-induced TdP, in approximately 50% of patients it appeared following a reckless administration of a QT interval-prolonging agent. In this population physicians should particularly avoid administration of two or more QT interval-prolonging agents simultaneously or administration of a QT interval-prolonging agent despite QT interval prolongation.

Revision endoscopic stapler Zenker's diverticulotomy.

BACKGROUND: Endoscopic stapler diverticulotomy (ESD) has become an accepted primary treatment for Zenker's diverticulum (ZD). Recurrence of symptoms after surgical treatment of ZD is not uncommon, and traditionally patients with recurrent symptomatic ZD were referred to revision surgery by the transcervical Zenker's diverticulectomy approach. Our objective was to evaluate the technical feasibility, safety and effectiveness of revision endoscopic stapler diverticulotomy (RESD) for recurrent ZD. METHODS: A case series with chart review study conducted in a tertiary referral center. The records of all patients who underwent ESD at our institute between 2002 and 2013 were retrieved and those who underwent RESD were identified and screened for primary surgical history, symptoms of recurrent ZD, time to recurrence, intraoperative and postoperative RESD course, complications and symptom resolution. The surgical history and outcome results of RESD and primary ESD (PESD) patients were compared. RESULTS: Eighty-nine ESDs were performed. Twenty were RESDs for recurrent ZD, and 69 were PESDs. Nine RESDs were performed for recurrent ZD after transcervical Zenker's diverticulectomy, 10 RESDs for recurrent ZD after ESD, and one initial surgical approach was unknown. The mean time from first operation for ZD to RESD was 4.7 years. The average RESD surgery time and hospital stay were 21.4 min and 2.8 days, respectively. Endoscopic stapling of the ZD was feasible in 19 of 20 RESDs. Relief of symptoms without recurrence was achieved after 18 RESDs. Four RESD patients experienced minor postoperative complications. There were no significant differences in operative time, technical feasibility, hospital stay and complication rate between the RESD and PESD groups (P > .05). CONCLUSION: RESD for ZD is technically feasible, safe and effective. The results are comparable to those of PESD.

One stage combined endoscopic and per-oral buccal fat pad approach for large oro-antral-fistula closure with secondary chronic maxillary sinusitis.

There are numerous surgical approaches for oro-antral-fistula (OAF) closure. Secondary sinus disease is still considered by many experts a relative contra indication for primary closure. To describe a single-stage combined endoscopic sinus surgery and per-oral buccal fat pad (BFP) flap approach for large OAF causing chronic maxillary sinusitis. The records of all the patients with OAF and chronic manifestations of secondary rhinosinusitis that were treated between 2010 and 2013 in our tertiary care medical center were reviewed. The exclusion criteria were: OAF ≤ 5 mm, resolved sino-nasal disease, OAF secondary to malignancy, recurrent fistula, medical history that included radiotherapy to the maxillary bone and age <18 years. Each procedure was performed by a team consisting of a rhinologist and a maxillofacial surgeon. The surgical approach included an endoscopic middle antrostomy with maxillary sinus drainage, and a per-oral BFP regional flap for OAF closure. Total OAF closure, complications and need for revision surgeries. Forty-five patients that underwent OAF closure together with sinus surgery using a combined endoscopic sinus surgery (ESS) and BFP flap approach met the inclusion criteria. There were 28 males and 17 females with a mean ± SD age of 53.5 ± 14.9 years (range 22-80 years). The presenting signs and symptoms included purulent rhinorrhea (n = 22, 48.9 %), foreign body in sinus (n = 10, 22.2 %) nasal congestion (n = 7, 15.5 %), halitosis (n = 6, 13.3 %) and pain (n = 5, 12.2 %). Surgical complications included local pain (n = 2, 4.4 %), persistent rhinitis (n = 2, 4.4 %) and synechia (n = 1, 2.2 %). One patient required revision surgery due to an unresolved OAF. The OAF of all the other 44 patients (97.8 %) was closed after the first procedure and the paranasal sinuses on the treated side were completely recovered. The mean follow-up time for the group was 7.6 ± 4.3 months (7-21 months), and no untoward sequelae or recurrence were reported. Combined, one step, endoscopic Maxillary sinus drainage together with per-oral BFP flap approach is an efficacious surgical approach for safe closure of OAFs that are complicated with secondary chronic maxillary sinusitis.

Head and Neck Cutaneous Squamous Cell Carcinoma Clinicopathological Risk Factors according to Age and Gender: A Population-based Study.

BACKGROUND: Clinicopathological risk factors for cutaneous squamous cell carcinoma of the head and neck (CSCCHN) are associated with local recurrence and metastasis. OBJECTIVES: To compare the incidence and risk factors of CSCCHN by age and gender in order to help refine the clinical evaluation and treatment process. METHODS: Clinical and pathological data of all patients diagnosed with CSCCHN during 2009-2011 were obtained from a central pathology laboratory in Israel. Estimated incidence rate calculation was standardized to the 2010 Israeli population. Independent risk factors for poorly differentiated CSCCHN were analyzed using logistic regression. RESULTS: CSCCHN was diagnosed in 621 patients. Mean age was 75.2 years; mean tumor horizontal diameter was 11.1 ± 6.8 mm. The overall estimated incidence rate in males was higher than in females (106.2 vs. 54.3 per 1,000,000, P 0.001). Twenty cases (3.2%) had poorly differentiated CSCCHN. Scalp and ear anatomic locations were observed more often in males than in females (22.1% vs. 6.1% and 20.3% vs. 3.3%, respectively, P < 0.001). Per 1 mm increment, tumor horizontal diameter increased the risk for poorly differentiated CSCCHN by 6.7% (95% CI 1.3-12.4%, P = 0.014). CONCLUSIONS: CSCCHN clinicopathological risk factors are not distributed evenly among different age and gender groups.

Nasopharyngeal biopsy in adults: a large-scale study in a non endemic area.

BACKGROUND: Limited data exist on the referral criteria for endoscopic-guided nasopharyngeal biopsy to rule out nasopharyngeal malignancy among adults in a non-endemic area. METHODS: Retrospective study of all adult patients that had been referred to our outpatient clinic to undergo endoscopic-guided nasopharyngeal biopsy to exclude nasopharyngeal malignancy between 1/2006-10/2013. All medical consultation referral letters were reviewed, and statistical analyses were conducted to evaluate clinically significant predictors (demographics, clinical manife- stations, nasopharyngeal endoscopic findings) for nasopharyngeal malignancy. RESULTS: A total of 470 patients (470 nasopharyngeal biopsies, 54.9% males and 66% smokers) were included. The most common pathological result was adenoid/lymphoid hyperplasia (76.2%). The overall negative rate of all biopsies for malignancy was 94.2%. Twenty-seven patients had nasopharyngeal malignancy: 22 had squamous cell carcinoma and 5 had non-Hodgkin`s lymphoma. Advanced age, cervical mass, and suspicious nasopharyngeal mass were independent risk factors for nasopharyngeal malignancy on univariate and multivariate analyses. CONCLUSIONS: Nasopharyngeal biopsy may safely be avoided in adults living in a non-endemic area for NPC who are free of the risk factors of advanced age, the presence of a cervical mass, and suspicious nasopharyngeal mass.

Vitamin D Antibodies in Systemic Sclerosis Patients: Findings and Clinical Correlations.

BACKGROUND: Vitamin D is a pivotal factor in calcium homeostasis and exerts immunomodulatory effects. Hypovitamin D has been demonstrated in systemic sclerosis (SSc) patients and may be related to more severe disease of longer duration and with extensive skin involvement. OBJECTIVES: To seek anti-vitamin D antibodies in SSc patients, as found by previous research in patients with systemic lupus erythematosus (SLE). METHODS: The study included 54 SSc patients and 41 volunteers. Immunoglobulin (Ig) G and IgM autoantibody levels against 25(OH)D and 1,25(OH)D were obtained from patients and controls and were compared. SSc patients were assessed for autoantibody profile and disease severity. RESULTS: Vitamin D antibodies were present in 87% of SSc patients and 42% of controls. Higher levels of anti-25(OH)D IgM antibodies were detected in SSc patients compared to controls (0.48 ± 0.22 vs. 0.29 ± 0.29, respectively, P = 0.002); however, IgG levels were lower in the SSc patients. No such discriminative. effect was found regarding anti-1,25(OH)D antibodies between SSc and controls. No correlation was found between,vitamin D antibodies and other autoantibodies, disease severity, or target organ damage. CONCLUSIONS: To the best of our knowledge; this is the first study of these novel, anti-vitamin D antibodies in SSc patients and the first time a correlation between IgM 25(OH) vitamin D antibodies and scleroderma has been identified. Further research on the pathophysiological significance and therapeutic potential of vitamin D is required.

A substitute for skin grafts, flaps, or internal tissue expanders in scalp defects following tumor ablative surgery.

BACKGROUND: The skin of the scalp is relatively thick, minimally mobile, with distinct hair distribution. TopClosure® is a novel device for skin stretching and secure wound closure. OBJECTIVES: To evaluate the efficacy of the TopClosure® system in primary closure of moderate and large scalp defects, as a substitute for skin grafts, flaps, and tissue expanders. METHODS: We report a retrospective series of 8 patients requiring resection of 9 scalp tumors resulting with moderate to large size defects that otherwise would have required reconstruction with skin grafts, flaps, or tissue expanders. TopClosure® was applied for intraoperative cycles of stress-relaxation, followed, when indicated, by additional steps of mechanical creep and scar secure. RESULTS: Skin defects, averaging 3.5 cm, were managed by TopClosure®, enabling, primary closure in all wounds. Immediate wound edge approximation was reached through stress-relaxation in 2 wounds by heavy tension sutures within one hour. Further skin stretching by mechanical creep was required in 7 wounds, achieving staged primary closure in an outpatient setting. TopClosure® was further applied to secure the skin for up to 3 weeks following surgery. CONCLUSIONS: The TopClosure system, effectively, aided closure of moderate and large scalp defects by stress-relaxation and mechanical creep and serving as a topical tension-relief platform for tension sutures, allowing mobilization of skin and subcutaneous tissue without undermining or need of drainage, for early, direct wound closure. Local complications were minimal and donor site morbidity was eliminated. Surgical time, hospital stay and costs were reduced, and post-operative wound aesthetics were improved.

Regional Antibiotic Delivery for Implanted Cardiovascular Electronic Device Infections.

BACKGROUND: Present guidelines endorse complete removal of cardiovascular implantable electronic devices (pacemakers/defibrillators), including extraction of all intracardiac electrodes, not only for systemic infections, but also for localized pocket infections. OBJECTIVES: The authors evaluated the efficacy of delivering continuous, in situ-targeted, ultrahigh concentration of antibiotics (CITA) into the infected subcutaneous device pocket, obviating the need for device/lead extraction. METHODS: The CITA group consisted of 80 patients with pocket infection who were treated with CITA during 2007-2021. Of them, 9 patients declined lead extraction because of prohibitive operative risk, and 6 patients had questionable indications for extraction. The remaining 65 patients with pocket infection, who were eligible for extraction, but opted for CITA treatment, were compared with 81 patients with pocket infection and similar characteristics who underwent device/lead extraction as primary therapy. RESULTS: A total of 80 patients with pocket infection were treated with CITA during 2007-2021. CITA was curative in 85% (n = 68 of 80) of patients, who remained free of infection (median follow-up 3 years [IQR: 1.0-6.8 years]). In the case-control study of CITA vs device/lead extraction, cure rates were higher after device/lead extraction than after CITA (96.2% [n = 78 of 81] vs 84.6% [n = 55 of 65]; P = 0.027). However, rates of serious complications were also higher after extraction (n = 12 [14.8%] vs n = 1 [1.5%]; P = 0.005). All-cause 1-month and 1-year mortality were similar for CITA and device/lead extraction (0.0% vs 3.7%; P = 0.25 and 12.3% vs 13.6%; P = 1.00, respectively). Extraction was avoided in 90.8% (n = 59 of 65) of extraction-eligible patients treated with CITA. CONCLUSIONS: CITA is a safe and effective alternative for patients with pocket infection who are unsuitable or unwilling to undergo extraction. (Salvage of Infected Cardiovascular Implantable Electronic Devices [CIED] by Localized High-Dose Antibiotics; NCT01770067).

Diagnostic efficacy of positron emission computerized tomography scans in suspicious laryngeal findings postorgan preservation treatment.

BACKGROUND: Larynx preservation protocols (LPP) for glottic primary squamous cell carcinoma has gained popularity worldwide. Direct laryngoscopy (DL) with biopsy is mandated when recurrence is suspected. The efficacy of 18Fluoro-deoxy-glucose positron emission computerized tomography (PET-CT) as alternative first-line diagnostic investigation in suspected recurrence was evaluated. METHODS: A retrospective study of patients with suspicious fiber-optic findings at more than 12 weeks after LPP. Sensitivity, specificity, and the negative predictive value (NPV) of DL and PET-CT were compared. RESULTS: Seventy-two patients presenting 105 cases of suspicious events were included in this study. Fifty-two events were initially investigated by DL and 53 events by PET-CT. The sensitivity of DL and PET-CT was 56.25% and 100%, respectively. The NPV was 84% for DL and 100% for PET-CT (p = 0.015). CONCLUSION: Negative PET scans after LPP are highly accurate in ruling out recurrent/persistent disease and may spare the patient from negative biopsies.

The rate of occult nodal metastasis in submandibular gland malignancies: A case series and meta-analysis.

OBJECTIVE: Submandibular gland (SMG) malignancies are exceedingly rare. Lymph node metastasis is one of the most important determinants of outcome in SMG malignancies. The aim of this study was to investigate the overall rate of occult neck nodal metastasis in SMG malignancies. STUDY DESIGN: The study design is a meta-analysis of all studies on patients with a primary SMG malignancy, without evidence of neck nodal metastasis, who underwent an elective neck dissection (END). The search strategy identified 158 papers that appeared in print from January 1980 to July 2020. All eligible patients from the Tel-Aviv Medical Center were analyzed and consolidated into a case series. A total of 12 retrospective studies that included 306 suitable patients met inclusion criteria. RESULTS: The risk for occult metastasis in primary SMG malignancies was 0.0% to 50.0%, with a fixed effect model of 19.52% (95% CI, 14.9%-24.5%). The analyzed studies included a wide range of pathologies. The most common malignancies were adenoid cystic carcinoma and mucoepidermoid carcinoma. CONCLUSIONS: The overall rate of occult neck metastasis in SMG malignancies is relatively high, and an END should be the default intervention in these cases. An END is unwarranted in tumors judged clinically to be low stage and low grade.

Achieving negative resection margins in oral cavity cancer with masticator space involvement-Is it feasible? International collaborative study.

BACKGROUND: Masticator space involvement in oral cavity squamous cell carcinoma (OCSCC) is considered an unresectable disease. Nevertheless, achieving negative resection margins is feasible in limited masticatory space involvement. MATERIALS AND METHODS: A multi-institutional study on OCSCC patients with masticator space invasion who underwent surgical resection. Margin status was assessed according to anatomic tumor involvement of the inframandibular and supra-mandibular notch. RESULTS: One-hundred and thirty-two patients met the inclusion criteria. Then, 67 patients (50.8%) were diagnosed with a supra-notch tumor and 65 (49.2%) with an infra-notch disease. Negative margins were more common in the infra-notch group (43.3 vs. 23.1%, p = 0.014), and positive margins were more common in the supra-notch group (41.5 vs. 23.9%, p = 0.041). Multivariable analysis demonstrated that supra-notch tumors had an increased likelihood for involved resection margins (odds ratio = 2.46, p = 0.036). CONCLUSION: OCSCC patients with masticator space involvement are prone for positive surgical margins in tumors extending above the supra-mandibular notch.

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.

Immunological and inflammatory mapping of vascularized composite allograft rejection processes in a rat model.

BACKGROUND: Hand and face vascularized composite allotransplantation (VCA) is an evolving and challenging field with great opportunities. During VCA, massive surgical damage is inflicted on both donor and recipient tissues, which may contribute to the high VCA rejection rates. To segregate between the damage-induced and rejection phase of post-VCA responses, we compared responses occurring up to 5 days following syngeneic versus allogeneic vascularized groin flap transplantations, culminating in transplant acceptance or rejection, respectively. METHODS: The immune response elicited upon transplantation of a syngeneic versus allogeneic vascularized groin flap was compared at Post-operative days 2 or 5 by histology, immunohistochemistry and by broad-scope gene and protein analyses using quantitative real-time PCR and Multiplex respectively. RESULTS: Immune cell infiltration began at the donor-recipient interface and paralleled expression of a large group of wound healing-associated genes in both allografts and syngrafts. By day 5 post-transplantation, cell infiltration spread over the entire allograft but remained confined to the wound site in the syngraft. This shift correlated with upregulation of IL-18, INFg, CXCL9, 10 and 11, CCL2, CCL5, CX3CL1 and IL-10 in the allograft only, suggesting their role in the induction of the anti-alloantigen adaptive immune response. CONCLUSIONS: High resemblance between the cues governing VCA and solid organ rejection was observed. Despite this high resemblance we describe also, for the first time, a damage induced inflammatory component in VCA rejection as immune cell infiltration into the graft initiated at the surgical damage site spreading to the entire allograft only at late stage rejection. We speculate that the highly inflammatory setting created by the unique surgical damage during VCA may enhance acute allograft rejection.

Elective Neck Dissection vs Observation in Early-Stage Squamous Cell Carcinoma of the Oral Tongue With No Clinically Apparent Lymph Node Metastasis in the Neck: A Systematic Review and Meta-analysis.

IMPORTANCE: The elective management of no clinical or radiologic evidence of lymph node metastasis in the neck (cN0) in early stage T1-T2 oral tongue squamous cell carcinoma (OTSCC) has been the subject of much debate during the past 3 decades and continues to be controversial. OBJECTIVE: To systematically review the literature and carry out a meta-analysis of studies that compared elective neck dissection (END) with observation in patients with early-stage T1-T2 OTSCC and cN0 neck. DATA SOURCES: The MEDLINE, Scopus, Google scholar, and Cochrane databases were systematically searched for articles published between January 1, 1970, and June 1, 2015. Search terms used were squamous cell carcinoma, oral tongue, mobile tongue, T1, T2, early stage, elective neck dissection, no neck treatment, observation, wait and watch, node-negative neck, and N0 neck. STUDY SELECTION: Controlled clinical trials, prospective and retrospective cohorts, case-control studies, and case series that compared END with observation in patients with early-stage T1-T2 OTSCC who had no clinical or radiologic evidence of lymph node metastasis to the neck were eligible for inclusion in this meta-analysis. All patients included had a histopathologic diagnosis of SCC and at least 6 months of follow-up. Regional (neck) nodal recurrence, overall survival (OS), and disease-specific survival (DSS) were tested. DATA EXTRACTION AND SYNTHESIS: Four researchers independently extracted information on population characteristics, outcomes of interest, and study design. Discrepancies were resolved by consensus. Fixed effects were used to determine hazard ratios (HRs) and odds ratio (ORs) were used for studies including samples without substantial heterogeneity; random effects were evaluated for samples with significant heterogeneity. RESULTS: A total of 20 retrospective and 3 prospective randomized studies that met the inclusion criteria, with a total of 3244 patients, were included in the meta-analysis The results showed that END significantly reduced risk of regional recurrence (random-effects model: OR, 0.32; 95% CI, 0.22-0.46; P < .001) and improved DSS (fixed-effects model: HR, 0.49; 95% CI, 0.33-0.72; P < .001) compared with management by observation. However, END did not significantly improve OS (random-effects model: HR, 0.71; 95% CI, 0.41-1.22; P = .21). CONCLUSIONS AND RELEVANCE: The findings of this systematic review and meta-analysis indicate that END can significantly reduce the rate of regional nodal recurrence and improve DSS in patients with cT1T2N0 OTSCC.

Impact of preoperative embolization on the outcomes of carotid body tumor surgery: A meta-analysis and review of the literature.

BACKGROUND: There is no consensus on the impact of preoperative embolization (EMB) on the surgical outcomes of carotid body tumor (CBT) resections. METHODS: A systematic review and a meta-analysis were conducted to clarify the role of preoperative EMB in patients undergoing surgical removal of CBTs. RESULTS: Fifteen studies with a total number of 470 patients met the inclusion criteria. The results of the meta-analysis showed that there is no significant difference in estimated blood loss, operative time, length of hospital stay, or risks of cranial nerve injury, vascular injury, and stroke between the EMB and nonembolization (NEMB) groups. CONCLUSION: This systemic review and meta-analysis demonstrate that preoperative EMB does not confer any operative or postoperative advantage in patients scheduled for CBT surgery. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2386-E2394, 2016.

Predictive factors for perioperative blood transfusion in neck dissection.

OBJECTIVES/HYPOTHESIS: There is growing interest in reducing the exposure of patients to allogeneic blood transfusions by lowering preoperative cross-matched blood ordering and adopting alternative practices, such as autologous blood donations. Our aim was to investigate the predictors for perioperative blood transfusion (PBT) in head and neck cancer patients undergoing neck dissection (ND). STUDY DESIGN: Retrospective cohort study. METHODS: Retrospective observational study. All patients who underwent ND between January 2011 and August 2014. The primary outcome measure was PBT. Predictors tested included: gender, age, American Society of Anesthesiologists comorbidity score, Charlson comorbidity index, preoperative hemoglobin level, head and neck primary tumor location, tumor and nodal staging, side and laterality of ND, central versus lateral ND, elective ND, preoperative chemotherapy/radiotherapy/I(131) therapy, history of previous ND, other surgical procedures in addition to the ND, bone resection, use and type of reconstruction, and the use of bony free flap reconstruction. RESULTS: Twenty-one preoperative and operative variables were tested for an association with PBT using univariate and multivariate analyses. Multivariate analysis found only the following three predictors to be significantly associated with PBT in patients undergoing ND: low preoperative hemoglobin level, advanced N stage, and concurrent reconstructive surgery. CONCLUSION: Evaluation of specific risk factors for predicting the need for PBT prior to neck dissection may be helpful in identifying the head and neck cancer patients in whom preoperative ordering of cross-matched blood is required or who could benefit from alternative means, such as preoperative autologous blood donation. LEVEL OF EVIDENCE: 4.