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Background: According to the AJCC third to seventh edition staging manuals (1988-2010), the presence of through cortex and/or skin invasion in oral cavity squamous cell carcinoma (OCSCC) identifies T4a tumors. The AJCC eighth edition (2018) introduced a depth of invasion (DOI) > 20 mm as a criterion for pT4a. Subsequently, a revision maintained that tumors > 4 cm with a DOI > 10 mm should be classified as pT4a. We sought to analyze the prognostic impact of the three distinct criteria identifying pT4a disease., Methods: We examined 667 consecutive patients with pT3-4 buccal/gum/hard palate/retromolar SCC who underwent surgery between 1996 and 2016. pT1/pT2 (n = 108/359) disease were included for comparison purposes., Results: The 5-year outcomes of patients with pT1/pT2/without (n = 406)/with tumor > 4 cm/DOI > 10 mm (n = 261), pT1/pT2/DOI ≤ 20 mm (n = 510)/> 20 mm (n = 157), and pT1/pT2/without (n = 305)/with through cortex/skin invasion (n = 362) were as follows: disease-specific survival (DSS), 98%/89%/79%/65%, p < 0.001, 98%/89%/78%/59%, p < 0.001, and 98%/89%79%/69%, p < 0.001; overall survival (OS), 90%/79%/63%/51%, p < 0.001, 90%/79%/63%/42%, p < 0.001, and 90%/79%/65%/52%, p < 0.001. In pT3-4 disease, a tumor > 4 cm/DOI > 10 mm was an independent adverse prognosticator for 5-year DSS rate, DOI > 20 mm was an independent adverse prognosticator for 5-year DSS and OS rates, whereas through cortex/skin invasion independently predicted 5-year OS rates., Conclusions: All of the three criteria (tumor > 4 cm/DOI > 10 mm, DOI > 20 mm, and through cortex/skin invasion) identify high-risk patients, which should be reflected in further revisions of pT4a classification in OCSCC.

Background: Pliability describes a flaps' ability to bend under spatial limitations, yet a quantifiable measurement for this flexibility does not exist., Methods: Between January 2015 and January 2017, we applied a novel measuring mechanism to two free flaps for head and neck reconstruction. We allocated a flap pliability score (FPS) to these flaps and observed correlations to common variables., Results: Forty profunda artery perforator (PAP) and 52 anterolateral thigh (ALT) flaps were allotted a score depending on how pliable they performed on our test. Proximal PAP and distal ALT were more pliable than their respective opposite ends. Other interesting conclusions regarding these flaps were also made., Conclusions: With our technique, pliability of the proximal and distal ends of PAP and ALT flaps was ascertained. Herein, we describe an innovative measuring mechanism via which we can allocate a FPS to any flap and thus obtain information regarding how suitable they are for a given recipient site., (© 2019 Wiley Periodicals, Inc.)

Objectives: The marsupialization of Stensen's duct after buccal cancer excision and free flap reconstruction has seldom been reported. In this study, we evaluated the alteration in Stensen's duct and parotid gland, without marsupialization or relocation, between the time of surgery and 24 months postoperatively to determine whether ductal management is needed in patients with buccal squamous cell carcinoma (BSCC)., Methods: Eighty-five patients with BSCC receiving primary radical surgery and free flap reconstruction were recruited. Alterations in Stensen's duct and parotid gland were assessed by computed tomography during the postoperative period., Results: The 81 males and 4 females enrolled in study had a tumor status of cT2 (n = 52, 61%) or cT3 (n = 33, 39%). In total, 52 (61%) patients received surgery alone, and 33 (39%) received adjuvant concurrent chemoradiotherapy (CCRT) postoperatively. Stensen's duct on the affected side was significantly dilated compared to the non-affected side (p < 0.001). The difference in diameter of Stensen's duct between the surgery plus CCRT group and the surgery alone group was not significant (p > 0.05), indicating that changes in parotid gland occurred mainly due to surgery. In both the surgery and surgery plus CCRT groups, inflammation of parotid gland had regressed by 24 months., Conclusions: Stensen's duct in BSCC dilatation peaked in the 3rd month after surgery. Changes in parotid gland on the surgically treated side regressed into fatty change by 24 months after surgery., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background/aim: Tumor-related and inflammation-related markers were reported to be prognostic in cancer patients. In this study, we evaluated squamous cell carcinoma antigen (SCC-Ag), cytokeratin 19 fragment (CYFRA 21-1) and C-reactive protein (CRP) simultaneously in oral cavity squamous cell carcinoma (OSCC) patients., Patients and Methods: Two hundred and forty-six newly diagnosed OSCC patients were retrospectively recruited between December 2010 and December 2016., Results: The elevation of CRP levels (≥5.0 mg/l) and SCC-Ag levels (≥2.0 ng/ml) were significantly related with tumor invasion parameters and metastatic factors. In contrast, the elevation of CYFRA 21-1 levels (≥3.3 ng/ml) was related with extranodal extension alone. For patients with all three markers being elevated before surgery, their overall survival and disease-free survival were significantly worse than others., Conclusion: Concurrent elevation of preoperative SCC-Ag, CYFRA 21-1 and CRP serum levels can be correlated with worse survival rates in OSCC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: According to the AJCC 2017 Staging Manual, oral cavity squamous cell carcinoma (OCSCC) with pN2 disease (based on the AJCC 2010 criteria) and extra-nodal extension (ENE) should be classified as pN3b. We performed a detailed outcome analyses in this patient subgroup., Material and Methods: We retrospectively reviewed the clinical records of consecutive OCSCC patients who underwent radical surgery between 1996 and 2017. Patients with pN3b disease (n = 365) were divided into a pN+ ≥8/ENE ≥5 subgroup (defined by the presence of pN+ ≥8 nodes or ENE ≥5 nodes, n = 77) and a pN+ ≤7/ENE ≤4 subgroup (defined by the presence of pN+ ≤7 nodes and ENE ≤4 nodes, n = 288). Patients with pN0/pN1/pN2 (n = 1192/179/197) disease were included for comparison purposes., Results: Patients in the pN+ ≥8/ENE ≥5 subgroup had less favorable 5-year outcomes than those in the pN+ ≤7/ENE ≤4/pN2/pN1/pN0 groups (local control, 64%/79%/86%/83%/88%, p < 0.001; neck control, 55%/75%/80%/86%/93%, p < 0.001; distant metastases, 67%/28%/20%/12%/3%, p < 0.001; disease-free survival, 21%/51%/64%/72%/82%, p < 0.001; disease-specific survival, 25%/55%/71%/82%/92%, p < 0.001; overall survival, 19%/40%/54%/64%/82%, p < 0.001; respectively). Among patients with pN3b disease, multivariable analysis identified the pN+ ≥8/ENE ≥5 subgroup, lower neck (level IV/V) metastases, and depth of invasion ≥25 mm as independent adverse prognostic factors for 5-year distant metastases and survival rates., Conclusions: Patients in the pN+ ≥8/ENE ≥5 subgroup have an unfavorable prognosis and their classification as pN3b is advisable. In contrast, patients in the pN+ ≤7/ENE ≤4 subgroup should be classified as pN3a., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Photoreceptor (PR) axons project from the retina to the optic lobe in brain and form a precise retinotopic map in the Drosophila visual system. Yet the role of retinal basal glia in the retinotopic map formation is not previously known. We examined the formation of the retinotopic map by marking single PR pairs and following their axonal projections. In addition to confirming previous studies that the spatial information is preserved from the retina to the optic stalk and then to the optic lamina, we found that the young PR R3/4 axons transiently overshoot and then retract to their final destination, the lamina plexus. We then examined the process of wrapping glia (WG) membrane extension in the eye disc and showed that the WG membrane extensions also follow the retinotopic map. We show that the WG is important for the proper spatial distribution of PR axons in the optic stalk and lamina, suggesting an active role of wrapping glia in the retinotopic map formation.

Introduction: Optimal design of PAP flaps requires precise perforator mapping. In a systematic review, Doppler ultrasonography demonstrated the highest sensitivity and positive predictive value (PPV). We present a prospective study of PAP flap design comparing PDU, handheld Doppler (HHD), and clinical findings., Methods: From May to July 2016, 12 head and neck cancer patients receiving PAP flaps were examined with PDU and HHD. We used PDU to evaluate number, course, emergence point, peak systolic velocity (PSV), and arterial diameter of perforators. PDU skin markings were measured in relation to the groin and gracilis. Distances to the adjacent HHD marking were determined. Diagnostic results were compared with intraoperative findings., Results: All perforators identified with PDU were confirmed intraoperatively. No sizable perforators found surgically were missed by PDU. Detecting perforators with diameters of ≧0.5 mm, false-negative rate of PDU was zero percent, sensitivity was 100%. Musculocutaneous courses were identified in all perforators and sensitivity of PDU was 96.7%. Arterial diameter was overestimated by PDU (1.49 ± 0.39 vs. 0.75 ± 0.31 mm, P > .05). PSV at the emergence point was 24.5 ± 11.9 cm/s. Average distance from the emergence point to the PDU marking was 2.45 ± 1.90 mm (0-6 mm). The PPV of PDU was calculated at 93.10%. Mean distance from the HHD to the PDU markings was 20.76 ± 16.5 mm (1-70 mm). Assuming PDU findings demonstrated the true anatomy, sensitivity of HHD was calculated with 89.7%, and PPV was 66.7%. All PAP flaps were successful, only minor revisions were needed., Conclusions: PDU facilitated PAP flap design in all cases and offers a precise, non-invasive diagnostic tool for flap planning., (© 2017 Wiley Periodicals, Inc.)

Background: The optimal management after the resection of mandibular ameloblastoma has been very challenging to surgeons. The aim of this study is to evaluate the functional, aesthetic, and quality of life outcomes of patients who had a segmental mandibular resection and immediate reconstruction with or without osseointegrated implants., Method: Patients' demographics, tumor characteristics, treatment, and complications were retrieved. Patients were divided into two groups: dental rehabilitated vs. nondental rehabilitated depending on the placement of osseointegrated implants followed by an implanted-retained prosthesis. Functional outcomes and quality of life were assessed using the Performance Status Scale, the University of Washington Quality of Life (UW-QOL) scale, and the 14-item Oral Health Impact Profile (OHIP-14). Aesthetic outcome was evaluated by patients using a Visual Analog Scale., Results: Thirty-four patients were reviewed. Twenty-two patients were included in the dental rehabilitated group and 12 in the nondental rehabilitated group. No recurrence of the tumor was found during the average follow-up period of 7.4 years. Although both groups reported a similar satisfaction in appearance, patients in the dental rehabilitated group scored significantly higher in masticatory function and "eating in public" (p < 0.01). There were significant differences (p < 0.05) regarding "chewing," "activity," and "anxiety" when assessed using the UW-QOL scale. Indeed, patients in the dental rehabilitated group showed a definitively better outcome in "physical disability" and "psychological discomfort" dimensions when assessed using the OHIP-14., Conclusion: Vascularized bone graft reconstruction followed by immediate or delayed placement of osseointegrated implants showed as an ideal and predictable treatment modality for patients with ameloblastoma. The results suggested that patients with osseointegrated implants had a significantly better masticatory function, improved quality of life, and less psychological consequences., (Copyright © 2018 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: The effect of cardio-metabolic profile on the relationship of body mass index (BMI) with mortality is unclear. The aim of this study was to explore association between BMI and mortality at all ages, taking account of cardio-metabolic disorders., Methods: We followed 377,929 individuals (≥ 20 years), who registered for health checkups in 1996-2007, until 2008 and found 9490 deaths. From multivariable Cox proportional hazards models we estimated mortality hazard ratios (HR) for those in high blood pressure, hyperglycemia, high waist circumference, dyslipidemia, and different BMIs categories (the underweight [< 18.5 kg/m 2 ], low normal weight [18.5-21.9 kg/m 2 ], normal weight [22-23.9 kg/m 2 , the referent], overweight [24-26.9 kg/m 2 ], obese1 [27-29.9 kg/m 2 ], and obese2 [≥ 30 kg/m 2 ]). Population attributable risk (PAR) provided estimates of the population mortality burden attributable to high blood pressure, hyperglycemia, high waist circumference, dyslipidemia, and deviant BMIs., Results: Higher blood pressure, hyperglycemia, high waist circumference, and dyslipidemia were significantly predictive of higher mortality for nearly all ages. Compared with the referent BMI, underweight (HR = 1.69, 95% confidence interval = 1.51-1.90) and low normal weight (HR = 1.19, 1.11-1.28) were significant mortality risks, while overweight (HR = 0.82, 0.76-0.89) and obese1 (HR = 0.88, 0.79-0.97) were protective against premature death. The mortality impact of obesity was largely attributable to cardio-metabolic profile and attenuated by age. The population mortality burden with high blood pressure (PAR = 7.29%), hyperglycemia (PAR = 5.15%), high waist circumference (PAR = 4.24%), and dyslipidemia (PAR = 5.66%) was similar to that in the underweight (PAR = 5.50%) or low normal weight (PAR = 6.04%) groups. Findings for non-smokers and by gender were similar., Conclusions: The effect of BMI on mortality varies with age and is affected by cardio-metabolic status. Compared to any deviant BMI, abnormal cardio-metabolic status has a similar or even greater health impact at both the individual and population levels.

Background and Objectives: This study aims to review our experience in trismus release followed by free flap reconstruction after radiotherapy in oral and oropharyngeal cancer, describe the results obtained in long-term follow-up and identify possible predictors of outcome., Methods: Patients' demographics, tumor characteristics and treatment where retrieved. Surgical release and reconstructive procedures were detailed. Interincisor distances (IIDs) where measured preoperatively (PO-IID), intraoperatively after release (IO-IID) and in the last follow-up (FU-IID). Potential predictors of outcome in terms of interincisor long-term gain (LT-gain) and postoperative loss (PO-loss) were analyzed., Results: Twenty-eight patients were included in our study. The mean LT-gain was 8.9 ± 7.0 mm, and the PO-loss was 22.14 ± 7.27 mm. Patients with a PO-IID of 10 mm or less had a significant higher LT-gain (P = 0.038). Predictors of worse outcome included having received a previous maxillectomy during tumor ablation (lower LT-gain, P = 0.035), and previous buccal mucosa resection (higher PO-loss, P = 0.044)., Conclusions: Trismus release and free flap reconstruction after radiotherapy in oral and oropharyngeal cancer patients seems to be associated with modest long term results and a high incidence of trismus recurrence, particularly in cases of prior buccal resections or maxillectomy. Patients should be adequately informed and carefully selected before indicating the procedure., (© 2017 Wiley Periodicals, Inc.)

Successful reconstruction of an oromandibular defect with the osteoseptocutaneous fibula flap necessitates flawless design and inset, which is an experience-demanding endeavor. Laterality of the fibula flap has been thought to pose a certain challenge to reconstruction. To address this concern and guide flap design and inset, the authors proposed using the surgeon's fist with the thumb up to replicate key anatomical landmarks of the fibula flap: the peroneal vessels and proximal bone end, and the posterior crural septum including the septal vessels, the skin, and the lateral surface of the fibula bone. This method facilities recipient vessels selection and skin paddle design, orientation, and inset to avoid complications regardless of laterality.

Purpose: Level 1 evidence supports the use of neoadjuvant chemotherapy (NAC) for the treatment of muscle-invasive bladder cancer (MIBC), but observational data demonstrate that this approach is underused. A barrier to shared decision making is difficulty in predicting and communicating survival estimates after cystectomy with or without NAC., Methods: We included patients with MIBC from the National Cancer Database treated with cystectomy. A state-transition model was constructed for calculating 5-year death risk using baseline patient-, tumor-, and facility-level variables. Internal-external cross-validation by geographic region was performed. The effect of NAC was integrated using a literature-derived hazard ratio. Bladder cancer-specific and other-cause mortality was estimated from all-cause mortality rates from US life tables. From the state-transition model, a Web-based tool was developed and pilot usability testing performed., Results: A total of 9,824 patients with MIBC who underwent cystectomy were eligible for inclusion. Median overall survival was 39.6 months (95% CI, 37.4 to 42.4 months). Increasing age, higher clinical T stage, higher comorbidity index, and black race were associated with shorter survival. Private insurance, higher income, and cystectomy at a high-volume facility were associated with longer survival. The prediction model was well calibrated across geographic regions, with observed-to-predicted 5-year death risks ranging from 0.85 to 1.17. Absolute risk reductions with NAC varied from 8.6% to 10.1%. The Web-based tool allowed input of the predictor variables and a user-defined hazard ratio associated with the effect of NAC to generate individualized survival estimates. The tool demonstrated good usability with clinicians., Conclusion: A Web-based tool was developed to individualize outcome prediction and communication in patients with MIBC treated with cystectomy with or without NAC to facilitate shared decision making.

Background/purpose: Osteoporosis has been linked to an increased fracture risk and subsequent mortality in the later life. Previous prediction models have focused on osteoporosis in postmenopausal women; however, a prediction tool for osteopenia is needed. Our objective was to establish a prediction model for osteopenia risk in women aged 40-55 years., Methods: This was a cross-sectional study. A total of 1350 Taiwanese women aged 40-55 years were recruited from a health checkup center from 2009 to 2010. The main outcome measure was osteopenia (-1≥bone mineral density T-score > -2.5)., Results: The Osteoporosis Preclinical Assessment Tool (OPAT) developed in this study was based on variables with biological importance to osteopenia and variables that remained significant (p<0.05) in the multivariable analysis, which include age, menopausal status, weight, and alkaline phosphatase level. The OPAT has a total score that ranges from 0 to 7, and categorizes women into high-, moderate-, and low-risk groups. The predictive ability of the OPAT (area under the receiver operating characteristic curve=0.77) was significantly better than that of the Osteoporosis Self-assessment Tool for Asians (area under the receiver operating characteristic curve=0.69). The inclusion of serum total alkaline phosphatase level in the model, which is easy to obtain from routine health checkups, significantly enhanced the sensitivity (McNemar test, p=0.004) for detecting osteopenia in women aged 40-55 years., Conclusion: Our findings provide an important tool for identifying women at risk of osteoporosis at the preclinical phase., (Copyright © 2017. Published by Elsevier B.V.)

Purpose: Clinical trials are critical to informing cancer care but often are hampered by slow accrual and lack of generalizability because of poor geographic accessibility. We tested the feasibility of replacing onsite study visits with telemedicine visits in a prospective clinical trial., Methods: Castration-naïve patients with prostate cancer and a rising serum prostate-specific antigen after definitive local therapy were eligible. Patients were required to have a single onsite visit for enrollment. Study treatment consisted of oral metformin 850 mg daily for 1 month followed by 850 mg twice daily for 5 months. Telehealth video visits (televisits) were conducted monthly by using a Health Insurance Portability and Accountability Act-compliant smartphone application. The primary objective was to determine the feasibility of telemedicine-enabled study visits. Secondary objectives were defining safety, anticancer activity, quality of life, and patient satisfaction., Results: Fifteen patients with a median age of 68 years (range, 57 to 83 years) and median one-way driving time to the study center of 71 minutes (range, 12 to 147 minutes) were enrolled. The patients completed 84 eligible televisits (completion rate, 100%; 95% CI, 0.80 to 1). Diarrhea was the most common adverse event but was limited to grade 1 in severity; a single patient experienced grade ≥ 3 adverse events. Seven patients (46.7%; 95% CI, 24.8% to 69.9%) had a ≤ 20% increase in prostate-specific antigen relative to baseline. Patients agreed or strongly agreed that they would participate in a telemedicine-enabled clinical trial in the future., Conclusion: To our knowledge, this interventional oncology clinical trial is the first to be conducted through telemedicine. Telemedicine-enabled trials are feasible and may overcome geographic barriers to trial participation. Metformin was generally well tolerated but associated with modest anticancer activity.

Purpose The TAXYNERGY trial ( ClinicalTrials.gov identifier: NCT01718353) evaluated clinical benefit from early taxane switch and circulating tumor cell (CTC) biomarkers to interrogate mechanisms of sensitivity or resistance to taxanes in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 2:1 to docetaxel or cabazitaxel. Men who did not achieve ≥ 30% prostate-specific antigen (PSA) decline by cycle 4 (C4) switched taxane. The primary clinical endpoint was confirmed ≥ 50% PSA decline versus historical control (TAX327). The primary biomarker endpoint was analysis of post-treatment CTCs to confirm the hypothesis that clinical response was associated with taxane drug-target engagement, evidenced by decreased percent androgen receptor nuclear localization (%ARNL) and increased microtubule bundling. Results Sixty-three patients were randomly assigned to docetaxel (n = 41) or cabazitaxel (n = 22); 44.4% received prior potent androgen receptor-targeted therapy. Overall, 35 patients (55.6%) had confirmed ≥ 50% PSA responses, exceeding the historical control rate of 45.4% (TAX327). Of 61 treated patients, 33 (54.1%) had ≥ 30% PSA declines by C4 and did not switch taxane, 15 patients (24.6%) who did not achieve ≥ 30% PSA declines by C4 switched taxane, and 13 patients (21.3%) discontinued therapy before or at C4. Of patients switching taxane, 46.7% subsequently achieved ≥ 50% PSA decrease. In 26 CTC-evaluable patients, taxane-induced decrease in %ARNL (cycle 1 day 1 v cycle 1 day 8) was associated with a higher rate of ≥ 50% PSA decrease at C4 ( P = .009). Median composite progression-free survival was 9.1 months (95% CI, 4.9 to 11.7 months); median overall survival was not reached at 14 months. Common grade 3 or 4 adverse events included fatigue (13.1%) and febrile neutropenia (11.5%). Conclusion The early taxane switch strategy was associated with improved PSA response rates versus TAX327. Taxane-induced shifts in %ARNL may serve as an early biomarker of clinical benefit in patients treated with taxanes.

Opinion Statement: Non-clear cell renal cell carcinoma (RCC) encompasses a diverse group of diseases, with research yielding different histologic findings and genetic profiles with each distinct subgroup. Simply mirroring the management techniques of clear cell RCC and borrowing from its growing armamentarium of therapeutic agents, while somewhat productive at first, but will ultimately be limiting. Further investigation into the molecular pathogenesis of disease, similarities and differences between specific subtypes, and mechanisms of resistance to therapeutics will help identify new targets, stimulate development of novel agents, and improve clinical trial offerings for non-clear cell RCC (nccRCC). As nccRCC has been largely excluded from past trials, there will be a need for future trials to be designed either to evaluate nccRCC specifically, or to include nccRCC as a prespecified subgroup. Multi-center collaborative trials should be supported, as many of the nccRCC subtypes are rare and remain underrepresented even within the construct of trials that only enroll nccRCC. Given the absence of clear molecular targets at present, patients with metastatic nccRCC should be offered and encouraged enrollment on clinical studies whenever possible.

Background: The identification of extrinsic tongue muscle invasion in oral cavity cancer remains challenging. Notably, the most recent American Joint Committee on Cancer (AJCC 2017, 8th edition) staging manual indicates that extrinsic muscle invasion does not lead to the diagnosis of a T4 tumor. Because this approach carries the risk of tumor downstaging, we compared the clinical outcomes of patients with oral tongue squamous cell carcinoma (SCC) staged as pT3 vs. pT4 according to the AJCC 2010, 7th edition criteria., Methods: We retrospectively examined the records of consecutive patients with pT3 (n = 135) and pT4 (n = 68) tongue SCC who underwent radical surgery. Of the 68 pT4 tongue SCC, 63 (93%) had extrinsic muscle involvement alone. The 5-year locoregional control (LRC), distant metastasis (DM), and disease-free survival (DFS) rates served as outcome measures., Results: Compared with pT3 tongue SCC, pT4 patients presented significantly more frequently with pN2 disease, extranodal extension, poor tumor differentiation, tumor depth >15 and >20 mm, margin status ≤4 mm, perineural invasion, vascular invasion, and were more frequently treated with surgery plus concurrent chemoradiotherapy. Less favorable 5-year outcomes were observed in patients with pT4 than pT3 tumors (LRC 50 vs. 75%, p < 0.001; DM 27 vs. 14%, p = 0.013; DFS 43 vs. 69%, respectively, p < 0.001). We identified pT4 disease (vs. pT3) as an independent adverse prognostic factor for LRC and DFS., Conclusions: We suggest classifying patients with tongue SCC and extrinsic muscle invasion as having pT4 disease.

This study aimed to identify the excess risks associated with diabetic patients with early kidney involvement (early diabetic kidney disease). The mortality risks of early diabetic kidney disease, defined as diabetes in early stages 1-3 chronic kidney disease (CKD), were assessed from a cohort of 512,700 adults in Taiwan participating in a health surveillance program from 1994-2008. Three related groups were identified and compared: diabetes without CKD, early diabetic kidney disease, and early CKD without diabetes. Deaths were ascertained through the National Death Registry. One-third of diabetics had early kidney disease, and approximately two-thirds of patients were classified with early CKD due to proteinuria. Patients with early diabetic kidney disease had more lifestyle risks such as inactivity or obesity, which characteristically amplified excess mortality by up to five times. The three-fold increase in all-cause mortality (hazard ratio 3.16) and a 16-year loss in life expectancy made early diabetic kidney disease a serious and yet often overlooked disease, with most patients unaware of their kidney involvement. Mortality for early diabetic kidney disease was nearly twice as high as that for early CKD (hazard ratio 2.01) or diabetes without CKD (hazard ratio 1.79). The 16-year life span loss is much worse than individually from early CKD (six years) or diabetes (ten years). Thus, identifying early proteinuria among diabetic patients and realizing the importance of reducing lifestyle risks like inactivity is a clinical challenge, but can save lives., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Previous studies have reported inconsistent results of the associations of alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP) with incident type 2 diabetes (diabetes hereafter). We aimed to resolve the controversy by taking nonalcoholic fatty liver disease (NAFLD) into account. The study population comprised 132,377 non-diabetic individuals (64,875 men and 67,502 women) aged 35-79 who had two or more health examinations during 1996-2014. A total of 6,555 incident diabetes (3,734 men and 2,821 women) were identified, on average, over 5.8 years of follow-up. Cox regression was used to calculate the hazard ratio (HR) for incident diabetes, adjusting for classical confounders. The risk of incident diabetes was significantly associated with NAFLD [HR = 2.08 (men) and 2.65 (women)]. Elevated ALT, AST, GGT and ALP were also significantly associated with the increased risk of diabetes, with HRs of 1.27, 1.23, 1.58 and 1.37, respectively, in men, and 1.56, 1.18, 1.48 and 1.44, respectively in women. Our results suggest that NAFLD, ALT, AST, GGT and ALP are independent predictors for incident diabetes in both men and women.

Live imaging provides the ability to continuously track dynamic cellular and developmental processes in real time. Drosophila larval imaginal discs have been used to study many biological processes, such as cell proliferation, differentiation, growth, migration, apoptosis, competition, cell-cell signaling, and compartmental boundary formation. However, methods for the long-term ex vivo culture and live imaging of the imaginal discs have not been satisfactory, despite many efforts. Recently, we developed a method for the long-term ex vivo culture and live imaging of imaginal discs for up to 18 h. In addition to using a high insulin concentration in the culture medium, a low-melting agarose was also used to embed the disc to prevent it from drifting during the imaging period. This report uses the eye-antennal discs as an example. Photoreceptor R3/4-specific mδ0.5-Ga4 expression was followed to demonstrate that photoreceptor differentiation and ommatidial rotation can be observed during a 10 h live imaging period. This is a detailed protocol describing this simple method.

Objectives: Although patients with buccal squamous cell carcinoma (SCC) usually show acceptable outcomes, local control and survival rates are generally lower than those observed for tongue SCC. This study was designed to compare the clinical outcomes of Taiwanese patients with these two common oral cavity malignancies., Methods: Patients with first primary buccal or tongue SCC who were included in the Taiwanese Cancer Registry Database between 2004 and 2012 were eligible. The study sample consisted of 16,379 patients (7870 buccal SCC and 8509 tongue SCC) who received surgery with or without adjuvant therapy. The 5-year disease-specific survival (DSS) and overall survival (OS) rates served as the outcome measures., Results: Compared with tongue SCC, patients with buccal SCC had a higher prevalence of males (95.7% vs. 86.4%, p<0.0001), pT4 disease (21.4% vs. 12.7%, p<0.0001), and p-Stage IV (30.4% vs. 24.8%, p<0.0001) but a lower frequency of pN2 disease (15.2% vs. 18.5%, p<0.0001). The 5-year DSS and OS rates of buccal SCC patients were slightly higher than those of tongue SCC (78% vs. 77%, p=0.0297; and 71% vs. 69%, p=0.0231, respectively). Multivariate analysis identified tumor site (tongue vs. buccal SCC), sex (male vs. female), age (≥65 vs. <65years), pT classification (T4/T3/T2 vs. T1), and pN classification (N3/N2/N1vs. N0) as independent prognostic factors in the entire study cohort., Conclusions: The survival advantage of buccal SCC over tongue SCC appears significant in large clinical samples, despite a higher prevalence of p-Stage IV disease in the former., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Renal cell cancer (RCC) continues to be among the most lethal malignancies in the USA. Introduction of anti-vascular epidermal growth factor receptor tyrosine kinase inhibitors over a decade ago resulted in improvement in disease outcomes, but further development of new therapies largely stagnated for many years. More recently, a better understanding of disease biology and treatment-resistance patterns has led to a second renaissance in drug development, with the anti-programmed cell death protein 1 immune checkpoint inhibitor, nivolumab, paving the way for additional therapies entering clinical trial testing in the treatment of RCC., Competing Interests: Conflict of interest statement: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Free profunda artery perforator (PAP) flap has recently been brought back for head and neck reconstruction. During the course of 1 year, we performed this procedure for reconstruction of partial glossectomy defects with excellent results., Methods: From January through December 2015, 21 patients underwent partial glossectomy reconstruction with PAP flaps. Demographics, surgical technique, anatomic variations, success rates, complications, and characteristics are described. Swallowing and speech results after reconstruction are evaluated., Results: No donor-site complications were observed. Two cases presented complications potentially related to the flap (1 hematoma and 1 prolonged intubation) that were treated successfully. Deglutition and speech assessment resulted in fair to excellent swallowing capacity in all patients. Speech score resulted 4/5 to 5/5 in all patients at 3-month follow-up., Conclusion: The PAP flap should be considered one of the first-line options for hemiglossectomy reconstruction, receiving special consideration in the high-risk population in which future complex reconstructions could be needed. © 2016 Wiley Periodicals, Inc. Head Neck 39: 737-743, 2017., (© 2016 Wiley Periodicals, Inc.)

Background: Multiple free tissue transfer from the same donor site is not well described for microsurgical head and neck reconstruction., Methods: Between (8/2011 and 11/2012), 103 patients received 103 free ALT flaps for head and neck reconstruction; flaps were called first-time ALT flaps. Intra-operative findings were used to assess the presence of a favorable anatomy for a future second flap from the same donor site. And, between 9/2009 and 12/2013, second-time flaps from previously used anterior thighs were attempted either freely or guided by the intra-operative data from the previous surgery., Results: A favorable anatomy for a future second-time flap was noted in (n: 96/103). Future second-time flaps were ALT, AMT, and TFL flaps (n: 32, n: 91, n: 96, respectively). The second-time flap was attempted (n: 11) and was successful (n: 8, 72.7%). Harvested second-time flaps were (5 ALT, 2 AMT, 1TFL). All flaps survived. The donor site was closed primarily (n: 6) and skin grafted (n: 2)., Conclusion: Thorough exploration of the anatomy of the anterior thigh during the first-time ALT flap surgery with detailed documentation in addition to meticulous surgery are essential for success. The proposed concept limits morbidity to one site, and serves as an alternative donor site or a life-boat., (© 2017 Wiley Periodicals, Inc.)

Background: C-reactive protein (CRP) is an early marker for inflammation, and a relationship between serum CRP levels and survival in oral cancer has been demonstrated previously. In this study, we investigated the roles of CRP in different oral cancer subsites., Methods: Three hundred and forty-three oral squamous cell carcinoma patients between June 1999 and March 2015 were retrospectively reviewed. Serum CRP levels were measured preoperatively., Results: The elevation of CRP levels (≥5.0 mg/L) was significantly correlated with pathologic tumor status, pathologic nodal status, nodal extracapsular spread, tumor stage, skin invasion, tumor depth (≥10 mm), and bone invasion. The correlation between elevation of CRP and clinicopathologic factors was more evident in the buccal cancer compared to other tumor subsites. The disease-free survival and overall survival correlation was significant in buccal cancer (p = 0.003 and p < 0.001) but not in tongue cancer (p = 0.119 and p = 0.341) or other oral cancer subsites (p = 0.246 and p = 0.696)., Conclusions: Preoperative serum CRP level was a prognosticator in oral squamous cell carcinoma, and its effect was more prominent in buccal cancer that occurs more frequently in areca-quid (AQ) endemic regions.

Background: Complications arising from anastomotic failure may occur after pharyngoesophageal reconstruction. In this report we present results of pharyngoesophageal reconstruction with free thigh flaps using a refined design and inset strategy in a series of patients., Methods: From May 2011 to December 2012, pharyngoesophageal oncologic defects were reconstructed in 12 men using thigh flaps. Flaps were designed to exceed defect circumference to allow draping of the excess over injury-prone vessels (so-called delta-inset). Patients were 39- to 68-years-old (mean, 51.8-years-old) at the time of surgery. BMI ranged from 17 to 28 kg/m 2 (average, 21.5 kg/m 2 ). The sites of defects were the hypopharynx in 11 cases and the pharynx in 1 case. Ten anterolateral thigh (ALT) flaps and 2 anteromedial thigh (AMT) flaps were used. All patients underwent radiation therapy., Results: The average flap size was 22 × 9 cm (range: 16-26 × 7-11 cm 2 ). There were no partial or total flap losses, and no donor site complications. Follow-up was 19.3 months (range: 2.4-21.6 months) including 8 patients (75%) who succumbed to disease in the follow-up period. Oral intake was achieved in all patients. Recipient site complications occurred in 50% of cases and included fistula (2 cases), fistula and stricture (2 cases), stricture (1 case), and lymphocele (1 case). Four patients required revision for fistula., Conclusions: A refined thigh flap design and inset method in pharyngoesophageal reconstruction may circumvent complications arising from toxic drainage and vascular injury. However, there are insufficient data to make meaningful comparisons to alternative methods. © 2015 Wiley Periodicals, Inc. Microsurgery 37:112-118, 2017., (© 2015 Wiley Periodicals, Inc.)

Significant disparities in survival, incidence and possibly response to current therapies exist between black and white patients with renal cell carcinoma (RCC). Recent genomic evidence to account for these disparities has been reported for clear cell RCC. However, racial disparities at the genomic level for papillary RCC (pRCC) which is a genetically distinct and less responsive histologic subtype of RCC have not been reported. Using The Cancer Genome Atlas (TCGA) data, the present study assessed gene-level expression, somatic mutation and pathway differences between 58 black and 58 white patients with pRCC propensity matched on age, gender and pathologic T stage. Distinct tumor biology with differential expression patterns were observed in black vs. white patients with pRCC. Specifically, significance analysis of microarrays was applied to TCGA gene expression data and identified 163 genes and 120 genes overexpressed in black and white patients, respectively (FDR q<0.05). Gene Set Enrichment Analysis identified 62 gene sets enriched (p<0.10) in blacks. Enrichment of immune immune system pathways were noted in black patients. These included the B cell receptor signaling pathway, the NOD-like receptor signaling pathway and genes involved in defensins. The VEGF pathway was also more significant in black patients. CRYBB2, a gene associated with the WNT pathway was overexpressed in Black patients. While our data requires validation, these findings suggest that race may have implications for distinct immune responses to cancer and that the use of immunotherapies, and VEGFR inhibitors to target these pathways may improve survival in black patients with advanced pRCC.

Lessons Learned: The safety and activity findings of abiraterone acetate plus prednisone treatment in black men with mCRPC were similar to results from previously conducted studies with largely white populations.Poor trial accrual continues to be a challenge in black men with mCRPC and further efforts are needed to address such underrepresentation., Background: Self-identified black men have higher incidence and mortality from prostate cancer in the United States compared with white men but are dramatically underrepresented in clinical trials exploring novel therapies for metastatic castration-resistant prostate cancer (mCRPC)., Methods: Black men with mCRPC were treated with abiraterone acetate (AA), 1,000 mg daily, and prednisone (P), 5 mg twice daily. The primary objective was to determine antitumor activity (defined by a ≥30% decline in prostate-specific antigen [PSA] level) and to correlate germline polymorphisms in androgen metabolism genes with antitumor activity. Secondary objectives included determining safety, post-treatment changes in measurable disease, and time to disease progression., Results: From April 2013 to March 2016, a total of 11 black men were enrolled and received AA plus P (AA+P); 7 of 10 evaluable patients were docetaxel naive. Post-treatment declines in PSA level of ≥30% were achieved in 90% of patients. The side effect profile was consistent with prior clinical trials exploring AA+P in mCRPC. Due to poor accrual, the study was closed prematurely with insufficient sample size for the planned pharmacogenetic analyses., Conclusion: In this small prospective study terminated for poor accrual, the safety and activity of AA+P in black men with mCRPC was similar to that reported in prior studies exploring AA in largely white populations. Further efforts are needed to address underrepresentation of black men in mCRPC trials., (©AlphaMed Press; the data published online to support this summary is the property of the authors.)

The objective of this study was to develop markedly improved risk prediction models for lung cancer using a prospective cohort of 395,875 participants in Taiwan. Discriminatory accuracy was measured by generation of receiver operator curves and estimation of area under the curve (AUC). In multivariate Cox regression analysis, age, gender, smoking pack-years, family history of lung cancer, personal cancer history, BMI, lung function test, and serum biomarkers such as carcinoembryonic antigen (CEA), bilirubin, alpha fetoprotein (AFP), and c-reactive protein (CRP) were identified and included in an integrative risk prediction model. The AUC in overall population was 0.851 (95% CI = 0.840-0.862), with never smokers 0.806 (95% CI = 0.790-0.819), light smokers 0.847 (95% CI = 0.824-0.871), and heavy smokers 0.732 (95% CI = 0.708-0.752). By integrating risk factors such as family history of lung cancer, CEA and AFP for light smokers, and lung function test (Maximum Mid-Expiratory Flow, MMEF 25-75% ), AFP and CEA for never smokers, light and never smokers with cancer risks as high as those within heavy smokers could be identified. The risk model for heavy smokers can allow us to stratify heavy smokers into subgroups with distinct risks, which, if applied to low-dose computed tomography (LDCT) screening, may greatly reduce false positives.

Objectives: A vegetarian diet may prevent elevation of blood pressures and lower the risk for hypertension through lower degrees of obesity, inflammation, and insulin resistance. This study investigated the association between a vegetarian diet and hypertension incidence in a cohort of Taiwanese adult nonsmokers and examined whether this association was mediated through inflammation, abdominal obesity, or insulin resistance (using fasting glucose as a proxy)., Methods: This matched cohort study was from the 1994-2008 MJ Health Screening Database. Each vegetarian was matched with five nonvegetarians by age, sex, and study site. The analysis included 4109 nonsmokers (3423 nonvegetarians and 686 vegetarians), followed for a median of 1.61 years. The outcome includes hypertension incidence, as well as SBP and DBP levels. Regression analysis was performed to assess the association between vegetarian diet and hypertension incidence or future blood pressure levels in the presence/absence of potential mediators., Results: Vegetarians had a 34% lower risk for hypertension, adjusting for age and sex (odds ratio: 0.66, 95% confidence interval: 0.50-0.87; SBP: -3.3 mmHg, P < 0.001; DBP: -1.5 mmHg, P < 0.001). The results stay statistically significant after further adjustment for C-reactive protein, waist circumference, and fasting glucose (odds ratio: 0.72, 95% confidence interval: 0.55-0.86; SBP: -2.4 mmHg, P < 0.05; DBP: -1.1 mmHg, P < 0.05). The protective association between vegetarian diet and hypertension appeared to be consistent across age groups., Conclusion: Taiwanese vegetarians had lower incidence of hypertension than nonvegetarians. Vegetarian diets may protect against hypertension beyond lower abdominal obesity, inflammation, and insulin resistance.

Fistulas, either between oral cavity and external face or between oral and nasal cavity, are major complications after microsurgical head and neck reconstruction. Any flaw in surgical planning, design, and execution may lead to this untoward outcome. Once fistula develops, it may interface with oncologic treatment, endanger the reconstruction, and increase overall patient suffering. This article analyzes individual factors involved in development of fistulas in spite of successful transfer of a free flap and proposes treatment guideline., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Continuous imaging of live tissues provides clear temporal sequence of biological events. The Drosophila imaginal discs have been popular experimental subjects for the study of a wide variety of biological phenomena, but long term culture that allows normal development has not been satisfactory. Here we report a culture method that can sustain normal development for 18 hours and allows live imaging. The method is validated in multiple discs and for cell proliferation, differentiation and migration. However, it does not support disc growth and cannot support cell proliferation for more than 7 to 12 hr. We monitored the cellular behavior of retinal basal glia in the developing eye disc and found that distinct glia type has distinct properties of proliferation and migration. The live imaging provided direct proof that wrapping glia differentiated from existing glia after migrating to the anterior front, and unexpectedly found that they undergo endoreplication before wrapping axons, and their nuclei migrate up and down along the axons. UV-induced specific labeling of a single carpet glia also showed that the two carpet glia membrane do not overlap and suggests a tiling or repulsion mechanism between the two cells. These findings demonstrated the usefulness of an ex vivo culture method and live imaging., Competing Interests: The authors have declared that no competing interests exist.

Widowhood has been increasingly encountered because of increasing longevity of women, often characterized by social stigmatization and poor physical and mental health. However, applied research to overcome its adversity has been quite limited. The goal of this study is to explore the role of physical activity in improving the health of widows.A cohort of 446,582 adults in Taiwan who successively participated in a comprehensive medical screening program starting in 1994, including 232,788 women, was followed up for mortality until 2008. Each individual provided detailed health history, and extensive lab tests results.The number of widows increased with time trend. Every other woman above age 65 was a widow (44%). Widows were less active, more obese, and smoked and drank more, had sleep problems, were more depressed with taking sedatives or psychoactive drugs, leading to more suicides. In the global development of health policies by World Health Organization (WHO), physical activity is one of the main factors to reverse poor health. The poor health of inactive widow was mitigated when becoming fully active in this study. Exercise not only reduced the observed 18% increase in all-cause mortality, but also gained 4 years and as much as 14% mortality advantage over the married but inactive. More importantly, becoming physically active energized their mental status, improved sleep quality and quantity, reduced depressions and the need for psychoactive drugs, and increased socialization circles.Widows, a rapidly growing and socially stigmatized group, suffered from social and financial inequality and tended to develop poorer health. Sustained physical activity could be one of the ways for them to overcome and reverse some of the physical and mental adversities of widowhood, and improve their quality and quantity of life.

Purpose: Patients with bladder cancer with clinical lymph node involvement (cN+) are at high risk for distant metastases, but are potentially curable. Such patients are excluded from neoadjuvant chemotherapy trials and pooled with patients with distant metastases in first-line chemotherapy trials not suited to define the role of combined-modality therapy. To address this evidence void, we performed a comparative effectiveness analysis., Methods: We included cTanyN1-3M0 bladder cancer patients from the National Cancer Data Base (2003-2012) treated with chemotherapy and/or cystectomy. We used multistate survival analysis, allowing for delayed entry, to assess overall survival (OS) according to various treatment strategies. Effectiveness was estimated with multivariable adjustment for tumor-, patient-, and facility-level characteristics., Results: Among 1,739 patients (cN1, 48%; cN2, 45%; cN3, 7%), 1,104 underwent cystectomy and 635 were treated with chemotherapy alone. Of the cystectomy patients, 363 received preoperative and 328 received adjuvant chemotherapy. The crude 5-year OS for chemotherapy alone, cystectomy alone, preoperative chemotherapy followed by cystectomy, and cystectomy followed by adjuvant chemotherapy was 14% (95% CI, 11% to 17%), 19% (95% CI, 15% to 24%), 31% (95% CI, 25% to 38%), and 26% (95% CI, 21% to 34%), respectively. Compared with cystectomy alone, preoperative chemotherapy was associated with a significant improvement in OS (hazard ratio, 0.80; 95% CI, 0.66 to 0.97). Adjuvant chemotherapy was also associated with a significant improvement in survival compared with cystectomy alone. The survival of patients treated with chemotherapy alone was worse than those treated with cystectomy alone., Conclusion: A subset of patients with cN+ bladder cancer achieves long-term survival. Combined-modality therapy, with chemotherapy and cystectomy, is associated with the best outcomes., Competing Interests: Authors’ disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article., (© 2016 by American Society of Clinical Oncology.)

The role of adjuvant therapy for renal cell carcinoma (RCC) after surgical resection has been evaluated in numerous randomized and nonrandomized studies using systemic therapies with distinct mechanisms of action. However, adjuvant therapy has not demonstrated definitive benefit to date and guidelines currently do not support its use. Continued advancement in the understanding of the molecular pathogenesis in RCC is critical, which would lead to identification of new therapeutic targets, as well as novel prognostic and predictive biomarkers, in hopes of improving outcomes in this lethal disease. Herein we summarize the results of randomized studies of the adjuvant treatments of RCC, in hopes to direct future effort in the development of treatment of this disease., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To assess the benefits of regular exercise in reducing harms associated with betel quid (BQ) chewing., Methods: The study cohort, 419,378 individuals, participated in a medical screening program between 1994 and 2008, with 38,324 male and 1,495 female chewers, who consumed 5-15 quids of BQ a day. Physical activity of each individual, based on "MET-hour/week", was classified as "inactive" or "active", where activity started from a daily 15 minutes/day or more of brisk walking (≥3.75 MET-hour/week). Hazard ratios for mortality and remaining years in life expectancy were calculated., Results: Nearly one fifth (18.7%) of men, but only 0.7% of women were chewers. Chewers had a 10-fold increase in oral cancer risk; and a 2-3-fold increase in mortality from lung, esophagus and liver cancer, cardiovascular disease, and diabetes, with doubling of all-cause mortality. More than half of chewers were physically inactive (59%). Physical activity was beneficial for chewers, with a reduction of all-cause mortality by 19%. Inactive chewers had their lifespan shortened by 6.3 years, compared to non-chewers, but being active, chewers improved their health by gaining 2.5 years. The improvement, however, fell short of offsetting the harms from chewing., Conclusions: Chewers had serious health consequences, but being physically active, chewers could mitigate some of these adverse effects, and extend life expectancy by 2.5 years and reduce mortality by one fifth. Encouraging exercise, in addition to quitting chewing, remains the best advice for 1.5 million chewers in Taiwan.

Objective: To investigate the association of resting heart rate with suicide in two large cohorts., Method: The MJ cohort (Taiwan) included 532 932 adults from a health check-up programme (1994-2008). The HUNT cohort (Norway) included 74 977 adults in the Nord-Trøndelag County study (1984-1986), followed up to 2004. In both cohorts heart rate was measured at baseline, and suicide was ascertained through linkage to cause-of-death registers. Risk of suicide was estimated using Cox proportional hazards models., Results: There were 569 and 188 suicides (average follow-up period of 8.1 and 16.9 years) in the MJ and HUNT cohorts respectively. Sex- and age-adjusted hazard ratio for every 10 beat increase in heart rate per minute was 1.08 (95% Confidence Interval 1.00-1.16) and 1.24 (1.12-1.38) in the MJ and HUNT cohorts, respectively. In the MJ cohort this association was confined to individuals with a history of heart diseases vs. those without such a history (P for interaction = 0.008). In the HUNT cohort the association did not differ by history of heart diseases and was robust to adjustment for health-related life style, medication use, and symptoms of anxiety and depression., Conclusion: Elevated resting heart rate may be a marker of increased suicide risk., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The purpose of this study was to investigate whether multidisciplinary team care (MDTC) is associated with outcomes in oral cavity squamous cell carcinoma (SCC)., Methods: We retrospectively examined 1616 patients with oral cavity SCC who underwent radical surgery between 1996 and 2011. The study participants were classified into 2 subgroups according to the use of MDTC., Results: Five-year outcomes were significantly better in the MDTC group than in the no-MDTC group (neck control, 88% vs 84%, p = .0397; disease-specific survival [DSS], 83% vs 78%, p = .0114; and overall survival [OS], 70% vs 64%, p = .0002, respectively). Among patients who were scheduled to undergo adjuvant therapy, the number who completed their adjuvant treatment was significantly higher in the MDTC group than in the no-MDTC group (90% vs 60% to 70%, p < .001)., Conclusion: The association of MDTC with improved outcomes may be potentially explained by a better therapeutic alliance between the patient and the tumor board, and/or a greater thoroughness in clinical management. © 2016 Wiley Periodicals, Inc. Head Neck 38: E1544-E1553, 2016., (© 2016 Wiley Periodicals, Inc.)

The prognostic significance of squamous cell carcinoma antigen (SCC-Ag) and C-reactive protein (CRP) levels and lymph node density (LND) has been individually recognized in oral squamous cell carcinoma (OSCC). We investigated the relationship between preoperative serum markers (SCC-Ag and CRP) and postoperative prognostic marker (LND) in this study. We retrospectively analyzed 277 OSCC patients who underwent primary curative resection and neck dissection with/or without adjuvant therapy between March 2008 and November 2013. Serum SCC-Ag and CRP levels were measured preoperatively. Distant metastasis, overall survival (OS), and disease-free survival (DFS) were used to evaluate the prognostic significance of preoperative SCC-Ag and CRP levels in relation to LND. LND (cutoff point ≥0.06) correlated with the pathologic tumor status, pathologic nodal metastasis, degree of differentiation, tumor stage, tumor depth (≥10 mm vs <10 mm), and perineural invasion (all P values were <0.001). LND was significantly associated with development of distant metastasis, DFS, and OS (all P values were <0.001). Preoperative elevated CRP and SCC-Ag levels were significantly associated with LND (P = 0.006), DFS (P < 0.001), and OS (P < 0.001). LND patients were further stratified into prognostic groups according to their SCC-Ag and CRP levels (DFS: P = 0.010; OS: P = 0.003). LND correlated with the incidence of DM, DFS, and OS in patients with OSCC. Concurrent elevated preoperative SCC-Ag and CRP levels are predictors for LND. In addition, SCC-Ag and CRP are markers for classifying high-risk LND patients with OSCC into subgroups., Competing Interests: The authors report no conflicts of interest.

Purpose: Given that randomized trials exploring adjuvant chemotherapy for bladder cancer have been underpowered and/or terminated prematurely, yielding inconsistent results and creating an evidence gap, we sought to compare the effectiveness of cystectomy versus cystectomy plus adjuvant chemotherapy in real-world patients., Patients and Methods: We conducted an observational study to compare the effectiveness of adjuvant chemotherapy versus observation postcystectomy in patients with pathologic T3-4 and/or pathologic node-positive bladder cancer using the National Cancer Data Base. We compared overall survival using propensity score (-adjusted, -stratified, -weighted, and -matched) analyses based on patient-, facility-, and tumor-level characteristics. A sensitivity analysis was performed to examine the impact of performance status., Results: A total of 5,653 patients met study inclusion criteria; 23% received adjuvant chemotherapy postcystectomy. Chemotherapy-treated patients were younger and more likely to have private insurance, live in areas with a higher median income and higher percentage of high school-educated residents, and have lymph node involvement and positive surgical margins (P < .05 for all comparisons). Stratified analyses adjusted for propensity score demonstrated an improvement in overall survival with adjuvant chemotherapy (hazard ratio, 0.70; 95% CI, 0.64 to 0.76), and similar results were achieved with propensity score matching and weighting. The association between adjuvant chemotherapy and improved survival was consistent in subset analyses and was robust to the effects of poor performance status., Conclusion: In this observational study, adjuvant chemotherapy was associated with improved survival in patients with locally advanced bladder cancer. Although neoadjuvant chemotherapy remains the preferred approach based on level I evidence, these data lend further support for the use of adjuvant chemotherapy in patients with locally advanced bladder cancer postcystectomy who did not receive chemotherapy preoperatively., (© 2016 by American Society of Clinical Oncology.)

The aim of this study was to explore the incidence and outcomes of patients with oral cavity squamous cell carcinoma (OSCC) and fourth primary tumors (PTs) in a betel-chewing endemic area.We retrospectively examined the records of 1836 OSCC patients who underwent radical tumor resection between 1996 and 2014. The outcome measures included the incidence and number of multiple PTs, the main risk factors, and their associations with overall survival (OS).Of the 1836 patients, 1400 (76.3%) had a single PT, 344 (18.7%) a second PT, 67 (3.6%) a third PT, and 25 (1.4%) a fourth PT. Univariate analyses (log-rank test) identified the following factors as significantly associated with a fourth PT: simultaneous first and second PTs, betel quid chewing, buccal subsite, and pT3-4 status. After allowance for the potential confounding effect of other risk factors, all of these factors retained their independent prognostic significance in stepwise multivariate analyses, the only exception being betel chewing. The incidences of second, third, and fourth PTs at 5 and 10 years were 20.2%/34.6%, 4.0%/8.6%, and 1.0%/2.3%, respectively. The 5 and 10-year OS rates (calculated from the diagnosis of each PTs) for patients with a single, second, third, and fourth PTs were 68%/61%, 43%/37%, 45%/39%%, and 30%/30%, respectively (P < 0.0001). Among patients with a fourth PT, those who underwent radical surgery showed a significantly higher 3-year OS than those who did not (57% vs 13%; P = 0.0442).Fourth PTs are rarely observed in OSCC patients in a betel quid-chewing endemic area. Long-term survival rates of patients treated with radical surgery seems acceptable, being 4-fold higher than their counterparts., Competing Interests: This study did not receive any specific funding. The authors report no conflicts of interest.

An improved prognostic stratification of patients with oral cavity squamous cell carcinoma (OSCC) and pathologically positive (pN+) nodes is urgently needed. Here, we sought to examine whether an ultra-deep targeted sequencing (UDT-Seq) gene panel may improve the prognostic stratification in this patient group.A mutation-based signature affecting 10 genes (including genetic mutations in 6 oncogenes and 4 tumor suppressor genes) was devised to predict disease-free survival (DFS) in 345 primary tumor specimens obtained from pN+ OSCC patients. Of the 345 patients, 144 were extracapsular spread (ECS)-negative and 201 were ECS-positive. The 5-year locoregional control, distant metastases, disease-free, disease-specific, and overall survival (OS) rates served as outcome measures.The UDT-Seq panel was an independent risk factor (RF) for 5-year locoregional control (P = 0.0067), distant metastases (P = 0.0001), DFS (P < 0.0001), disease-specific survival (DSS, P < 0.0001), and OS (P = 0.0003) in pN+ OSCC patients. The presence of ECS and pT3-4 disease were also independent RFs for DFS, DSS, and OS. A prognostic scoring system was formulated by summing up the significant covariates (UDT-Seq, ECS, pT3-4) separately for each survival endpoint. The presence of a positive UDT-Seq panel (n = 77) significantly improved risk stratification for all the survival endpoints as compared with traditional AJCC staging (P < 0.0001). Among ECS-negative patients, those with a UDT-Seq-positive panel (n = 31) had significantly worse DFS (P = 0.0005) and DSS (P = 0.0002). Among ECS-positive patients, those with a UDT-Seq-positive panel (n = 46) also had significantly worse DFS (P = 0.0032) and DSS (P = 0.0098).Our UDT-Seq gene panel consisting of clinically actionable genes was significantly associated with patient outcomes and provided better prognostic stratification than traditional AJCC staging. It was also able to predict prognosis in OSCC patients regardless of ECS presence.

Background: The anterolateral thigh perforator flap is a common workhorse flap for head and neck reconstruction. The authors present an alternative method using the posteromedial thigh profunda artery perforator flap and compare its characteristics, outcomes, donor-site morbidity, and donor-site cosmesis with those of the anterolateral thigh perforator flap., Methods: Between May of 2013 and July of 2014, 41 patients undergoing head and neck reconstruction consisting of 18 posteromedial thigh profunda artery perforator flaps and 23 anterolateral thigh perforator flaps were included in this study. Thirty-eight of the patients were men, and the patient age ranged from 32 to 76 years (mean, 54.5 years)., Results: The success rate was 100 percent. The mean number of perforators was significantly higher in the profunda artery perforator flap group (2.0 versus 1.5). There was no significant difference in flap elevation time (66.3 minutes versus 60.7 minutes), pedicle length (9.8 cm versus 10 cm), flap area (166.1 cm versus 156.8 cm), flap width (7.7 cm versus 7.7 cm), reexploration rate, recipient-site complication rate, or donor-site complication rate. Based on patient self-assessment, the profunda artery perforator flap group had significantly better donor-site cosmesis than the anterolateral thigh perforator flap group (satisfaction rate, 100 percent versus 70 percent)., Conclusions: The posteromedial thigh profunda artery perforator flap is a good alternative for head and neck reconstruction. It offers flap size, pedicle length, flap elevation time, and success rate comparable to those of the anterolateral thigh perforator flap. It has more perforators and better donor-site cosmesis than the anterolateral thigh perforator flap., Clinical Question/level of Evidence: Therapeutic, III.