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Objective The study aimed to assess the impact of the coronavirus disease 2019 (COVID-19) pandemic on head and neck oncologic care at a tertiary care facility. Study Design This was a cross-sectional study conducted between March 18, 2020, and May 20, 2020. The primary planned outcome was the rate of treatment modifications during the study period. Secondary outcome measures were tumor conference volume, operative volume, and outpatient patient procedure and clinic volumes. Setting This single-center study was conducted at a tertiary care academic hospital in a large metropolitan area. Methods The study included a consecutive sample of adult subjects who were presented at a head and neck interdepartmental tumor conference during the study period. Patients were compared to historical controls based on review of operative data, outpatient procedures, and clinic volumes. Results In total, 117 patients were presented during the review period in 2020, compared to 69 in 2019. There was an 8.4% treatment modification rate among cases presented at the tumor conference. There was a 61.3% (347 from 898) reduction in outpatient clinic visits and a 63.4% (84 from 230) reduction in procedural volume compared to the prior year. Similarly, the operative volume decreased by 27.0% (224 from 307) compared to the previous year. Conclusion Restrictions related to the COVID-19 pandemic resulted in limited treatment modifications. Transition to virtual tumor board format observed an increase in case presentations. While there were reductions in operative volume, there was a larger proportion of surgical cases for malignancy, reflecting the prioritization of oncologic care during the pandemic.

In the drive towards faster patient access to treatments, health technology assessment (HTA) agencies are increasingly faced with reliance on evidence from surrogate endpoints, leading to increased decision uncertainty. This study undertook an updated survey of methodological guidance for using surrogate endpoints across international HTA agencies. We reviewed HTA and economic evaluation methods guidance from European, Australian and Canadian HTA agencies. We considered how guidelines addressed the methods for handling surrogate endpoints, including (1) level of evidence, (2) methods of validation, and (3) thresholds of acceptability. Across the 73 HTA agencies surveyed, 29 (40%) had methodological guidelines that made specific reference to consideration of surrogate outcomes. Of the 45 methods documents analysed, the majority [27 (60%)] were non-technology specific, 15 (33%) focused on pharmaceuticals and three (7%) on medical devices. The principles of the European network for Health Technology Assessment (EUnetHTA) guidelines published in 2015 on the handling of surrogate endpoints appear to have been adopted by many European HTA agencies, i.e. preference for final patient-relevant outcomes and reliance on surrogate endpoints with biological plausibility and epidemiological evidence of the association between the surrogate and final endpoint. Only a small number of HTA agencies (UK National Institute for Care and Excellence; the German Institute for Medical Documentation and Information and Institute for Quality and Efficiency in Health Care; the Australian Pharmaceutical Benefits Advisory Committee; and the Canadian Agency for Drugs and Technologies in Health) have developed more detailed prescriptive criteria for the acceptance of surrogate endpoints, e.g. meta-analyses of randomised controlled trials showing strong association between the treatment effect on the surrogate and final outcomes. As the decision uncertainty associated with reliance on surrogate endpoints carries a risk to patients and society, there is a need for HTA agencies to develop more detailed methodological guidance for consistent selection and evaluation of health technologies that lack definitive final patient-relevant outcome evidence at the time of the assessment.

Objectives/hypothesis Obstructive sleep apnea (OSA) is associated with higher risk of morbidity and mortality related to cardiovascular disease (CVD). Due to overlapping clinical risk factors, identifying high-risk patients with OSA who are likely to develop CVD remains challenging. We aimed to identify baseline clinical factors associated with the future development of CVD in patients with OSA. Study design Retrospective analysis of prospectively collected data. Methods We performed a retrospective analysis of 967 adults aged 45 to 84 years and enrolled in the Multi-Ethnic Study of Atherosclerosis. Six machine learning models were created using baseline clinical factors initially identified by stepwise variable selection. The performance of these models for the prediction of additional risk of CVD in OSA was calculated. Additionally, these models were evaluated for interpretability using locally interpretable model-agnostic explanations. Results Of the 967 adults without baseline OSA or CVD, 116 were diagnosed with OSA and CVD and 851 with OSA alone 10 years after enrollment. The best performing models included random forest (sensitivity 84%, specificity 99%, balanced accuracy 91%) and bootstrap aggregation (sensitivity 84%, specificity 100%, balanced accuracy 92%). The strongest predictors of OSA and CVD versus OSA alone were fasting glucose >91 mg/dL, diastolic pressure >73 mm Hg, and age >59 years. Conclusion In the selected study population of adults without OSA or CVD at baseline, the strongest predictors of CVD in patients with OSA include fasting glucose, diastolic pressure, and age. These results may shape a strategy for cardiovascular risk stratification in patients with OSA and early intervention to mitigate CVD-related morbidity. Level of evidence 3 Laryngoscope, 2021.

Background Chronic rhinosinusitis (CRS) causes a great deal of morbidity. There are a multitude of causal factors, though their precise contribution to symptom severity has yet to be defined. We hypothesized that exposure to both primary and secondhand tobacco smoke would correlate with more severe symptoms of CRS. Methods This is a prospective cross-sectional study performed at an academic tertiary care medical center from 2010 to 2013. A total of 85 consecutive patients with chronic sinusitis were screened; 70 with medically refractory CRS requiring functional Endoscopic sinus surgery (FESS) were enrolled. Recent tobacco exposure was assessed using serum cotinine levels. Sinonasal mucosa was biopsied to assess ciliary architecture. Demographics, medical history, tobacco and environmental exposures, and computed tomography (CT) imaging were also collected. Two quality of life (QOL) surveys were administered: one disease specific, Sinonasal Outcomes Test-20 (SNOT-20), and one general, Short Form-12 (SF-12). Results were correlated with the aforementioned exposures. Results The 70 patients had an average age of 46 years, and 42% were male. Variables that correlated with worse SNOT-20 scores included serum cotinine (r = 0.43, p = 0.002), number of cigarettes smoked daily (r = 0.27, p = 0.03), and number of secondhand cigarettes exposed to per day (r = 0.29, p = 0.04). There were no significant correlations between SNOT-20 scores and Lund-MacKay or axonemal ultrastructural abnormalities (AUA)-ciliary scores. The two five-variable models best predicted disease-specific QOL. Conclusions Increased amounts of serum cotinine and primary and secondhand smoke exposure were associated with worse sinonasal QOL. This study establishes an objective relationship between smoke exposure and patient-perceived severity of CRS, emphasizing the importance of tobacco cessation counseling as part of management.

BACKGROUND Lateral skull base tumors often necessitate temporal bone resection (TBR), although clinical outcomes can be unfavorable. Factors influencing survival and recurrence after TBR for cutaneous and salivary malignancies were evaluated. METHODS Twenty-six TBR subjects were included. Survival and recurrence outcomes were estimated at 1, 2, and 5 years postresection. Prognostic factors were analyzed using univariate and multivariate Cox regression. RESULTS Two years postresection, the overall survival (OS), disease-specific survival (DSS) and recurrence-free survival (RFS) rates were 61%, 74%, and 49%, respectively, and 51%, 63%, and 45% at 5 years. On univariate analysis, preoperative facial nerve dysfunction and intraoperative nerve sacrifice worsened OS, DSS, and RFS. Prior surgery and adjuvant radiation independently predicted reduced OS, DSS, and RFS on multivariate analysis. CONCLUSIONS Mortality is highest in the first 2 years following resection. Preoperative facial nerve dysfunction, facial nerve sacrifice, and prior radiation are negative predictors of survival and recurrence.

Objective: The study aimed to assess the impact of the coronavirus (COVID-19) pandemic on head and neck oncologic care at a tertiary care hospital. The pandemic caused by the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has led to policies designed to limit its spread. Policies including eliminating routine appointments, statewide stay-at-home orders, and restricting surgical cases to emergent surgeries have limited access to care. Therefore, we hypothesized that treatment modifications would be implemented for patients and cancer consultations would decrease compared to historical data. Methods: Information regarding treatment modifications was collected prospectively during interdepartmental tumor conferences from March 18, 2020 to May 20, 2020. Information regarding patient demographics, tumor characteristics, and incidence of new cancer consultations was collected via chart review. Treatment modifications were categorized as follows: Elimination of Systemic Therapy, Treatment Delay, Change to Non-Surgical Management, or Alteration in Adjuvant Therapy. Rationales for modification were similarly grouped as follows: Operating Room Limitations, Medical Co-Morbidities, COVID-19 positive, Patient concern, or System limitations. We determined the rate of treatment modifications and the frequencies of rationales and modification types. Demographic and tumor characteristics were compared between this population and a retrospectively collected cohort from 2019. Results: 117 patients were presented during the review period in 2020. There were 69 patients presented across the same time period in 2019. There were no differences in demographic characteristics between the groups. There was no difference between the tumor or nodal stages of the presented cases year over year. During the 2020 time period there were more total case presentations and new cancer cases compared to the 2019 time period. Of the 117 cases presented during the study period, there were 10/117 (8.4%) treatment modifications. The most common reason for modification was limited PPE supply. The most common modification was treatment delay. The second most common modification was change from primary surgical management to nonsurgical management. Treatment modifications occurred most commonly early in the review period and declined subsequently. Conclusions: Despite the ongoing pandemic and resulting state and institutional restrictions, there was no appreciable reduction in new cancer consultations for head and neck cancer. There were a small number of treatment modifications, particularly early in the course of our state and institutional response to the virus. However, over the 2-month period examined, patient care for these patients remained largely unaffected. While the restriction in elective surgical care was implemented across the state of Maryland, the oncologic triage and emergency surgery prioritization sustained the volume of oncologic practice. Citation Format: Joshua A. Thompson, Reju Joy, Joshua E. Lubek, Ranee Mehra, Jason K. Molitoris, Rodney J. Taylor, Jeffrey S. Wolf, Matthew E. Witek, Kyle M. Hatten. Evaluating the impact of the coronavirus (COVID-19) pandemic on treatment paradigms in head and neck cancer at a tertiary care hospital [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr PO-017.

6536 Background: For patients with primary untreated locally advanced head and neck squamous cell carcinoma (PULA-HNSCC), high dose once every 3 weeks cisplatin (HDC; 100 mg/m2) added to curative radiotherapy (RT) prolongs survival, but is associated with severe toxicities. Concurrent chemoradiation (CRT) with low dose weekly cisplatin (LDC; 30-40 mg/m2), carboplatin (C), or RT alone is often substituted for HDC. We estimated and compared overall survival (OS) and acquired toxicities among Medicare beneficiaries treated with CRT using HDC, LDC, C, or RT. Methods: Patients diagnosed from 2004-2011 with PULA-HNSCC (stages III-IVB AJCC 6th and 7th editions) of the oropharynx (OPC), hypopharynx (HP), or larynx (L) who received definitive RT or CRT were identified using the linked SEER-Medicare database. An analytic cohort of patients receiving CRT with HDC, LDC, or C was constructed using well-established eligibility criteria. OS was estimated and compared between patients grouped by treatment received utilizing a multivariable stratified propensity scores weighted Cox regression model, including demographic and disease characteristics. Toxicities were compared using exact common odds-ratio and Fisher’s tests. Results: We identified 1,335 patients that received RT: OPC (n = 731), HP (n = 174), or L (n = 430). Out of those, patients were treated with HDC (n = 264), LDC (n = 259), C (n = 353), or RT alone (n = 459). Median OS (years) was 5.61 (95% CI = 4.58-7.69) for HDC, 3.7 (95% CI = 3.1-4.79) for LDC, 3.1 (95% CI = 2.48-3.86) for C, and 1.36 (95% CI = 1.19-1.58) for RT, respectively. OS was significantly greater for HDC than for LDC (HR = 1.35, 95% CI = 1.06-1.72, p= 0.02), C (HR = 1.41, 95% CI = 1.12-1.76, p= 0.003), or RT (HR = 2.1, 95% CI = 1.68-2.61, p= < 0.001). Treatment with HDC compared to LDC was not associated with increased prevalence of dysphagia or neutropenia. HDC was associated with hearing loss when assessed at 9-12 months post-diagnosis ( p =0.03). Conclusions: In SEER-Medicare beneficiaries with PULA-HNSCC of the OPC, HP, or L, OS was significantly better for HDC than LDC when accounting for baseline clinical and demographic characteristics and propensity score weights. Toxicities were similar between regimens, except for an increased incidence of the late acute toxicity of hearing loss in HDC. A regimen of HDC improves OS, but needs to be carefully assessed against increased toxicity risk, with hearing loss in particular.

Background Racial outcome disparities have been observed in head and neck squamous cell carcinoma (HNSCC) with diminished survival for black patients compared with white patients. Methods We retrospectively analyzed 1318 patients with primary HNSCC treated at the University of Maryland Greenebaum Cancer Center (UMGCC) from 2000 to 2010. Results Of all the patients, 65.9% were white, 30.7% were black, and 3.3% were of other races. Black patients were less likely to present with oral cavity cancer, and more likely to present with laryngeal or hypopharyngeal cancers. White patients were more likely to have early stage disease, especially in the oral cavity. Black race was independently associated with worse overall survival (OS) in the entire cohort. Black patients had a significantly worse OS among oral cavity and oropharyngeal cancers, with the largest disparity in oropharyngeal cancer. However, in multivariate analysis, race was only still significant in oropharyngeal cancer. Conclusion We observed differences by race in distribution of disease site, stage, and OS. Survival disparity in the entire cohort was driven mostly by differences among oropharyngeal cancer.

We conducted a phase I dose escalation study to evaluate the safety and immunologic response to peptide immunomodulatory vaccines GL-0810 (HPV16) and GL-0817 (MAGE-A3) in HPV16 and MAGE-A3-positive RM–SCCHN patients, respectively. Three dose levels (500, 1,000, and 1,500 µg) of GL-0810 or GL-0817 with adjuvants Montanide (1.2 ml) and GM-CSF (100 µg/m2) were administered subcutaneously q2 weeks for a total of four vaccinations in HPV16 and MAGE-A3-positive RM–SCCHN patients, respectively. Nine and seven patients were enrolled in the HPV16 and MAGE-A3 cohorts, respectively. No dose-limiting toxicities were observed, and toxicity was predominantly local and grade 1 (erythema, pain, and itching at the injection site). In those patients who received all four vaccinations, 80 % (4/5) of the HPV16 cohort and 67 % (4/6) of the MAGE-A3 cohort developed antigen-specific T cell and antibody responses to the vaccine. Significant concordance between T cell and antibody responses was observed for both groups. No clear dose–response correlation was seen. All patients progressed by RECIST at first repeat imaging, except for one patient in the MAGE-A3 500 µg cohort who had stable disease for 10.5 months. The median PFS and OS for the MAGE-A3 cohorts were 79 and 183 days, respectively, and for the HPV16 cohort 80 and 196 days, respectively. GL-0810 and GL-0817 were well tolerated in patients with RM–SCCHN with T cell and antibody responses observed in the majority of patients who received all four vaccinations.

(1) To evaluate the effectiveness of the superficial musculoaponeurotic system (SMAS) flap and free fat graft in reconstructing the parotidectomy defect. (2) To evaluate the long-term viability of the free fat graft following parotidectomy for benign and malignant disease, including in the postradiation setting.Prospective study of consecutive patients.Academic tertiary care medical center. Subjects and Methods Thirty-one consecutive patients underwent parotidectomy with SMAS flap and free fat graft reconstruction from 2006 to 2012. Data were compiled through a manual chart review.Twenty-three of the 31 total patients had benign disease, including pleomorphic adenoma, oncocytoma, and Warthin tumor. The 8 remaining patients (9 parotidectomies) underwent surgery for malignant disease, followed by postoperative radiation. The average age was 56 years (range, 16-84 years). The mean follow-up was 22.5 months. Satisfactory volumetric symmetry was achieved in all procedures for benign and malignant disease. Magnetic resonance imaging confirmed long-term fat graft viability in the postradiation setting. There was 1 case of Frey syndrome and no cases of unexpected, permanent facial nerve weakness among the patients.The combined technique of SMAS flap and free fat graft is effective for immediate reconstruction of the parotidectomy defect with minimal morbidity and low complication rates. This study demonstrates long-term viability of the free fat graft even in the setting of postoperative radiation.

The tumor volume has been established as a significant predictor of outcomes among patients with head-and-neck cancer undergoing radiotherapy alone. The present study attempted to add to the existing data on tumor volume as a prognostic factor among patients undergoing chemoradiotherapy.A total of 78 patients who had undergone definitive chemoradiotherapy for Stage III-IV squamous cell cancer of the hypopharynx, oropharynx, and larynx were identified. The primary tumor volumes were calculated from the treatment planning computed tomography scans, and these were correlated to the survival and tumor control data obtained from the retrospective analysis.The interval to progression correlated with the primary tumor volume (p = .007). The critical cutoff point for the tumor volume was identified as 35 cm(3), and patients with a tumor volume35 cm(3) had a significantly better prognosis than those with a tumor volume35 cm(3) at 5 years (43% vs. 71%, p = .010). Longer survival was also correlated with smaller primary tumor volumes (p = .022). Similarly, patients with a primary tumor volume35 cm(3) had a better prognosis in terms of both progression-free survival (61% vs. 33%, p = .004) and overall survival (84% vs. 41%, p =.001). On multivariate analysis, the primary tumor volume was the best predictor of recurrence (hazard ratio 4.7, 95% confidence interval 1.9-11.6; p = .001) and survival (hazard ratio 10.0, 95% confidence interval 2.9-35.1; p =.001). In contrast, the T stage and N stage were not significant factors. Analysis of variance revealed that tumors with locoregional failure were on average 21.6 cm(3) larger than tumors without locoregional failure (p = .028) and 27.1-cm(3) larger than tumors that recurred as distant metastases (p = .020).The results of our study have shown that the primary tumor volume is a significant prognostic factor in patients with advanced cancer of the head and neck undergoing definitive chemoradiotherapy and correlated with the treatment outcomes better than the T or N stage.

Background. We performed a pilot study using Trojan vaccines in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). These vaccines are composed of HLA-I and HLA-II restricted melanoma antigen E (MAGE)-A3 or human papillomavirus (HPV)-16 derived peptides, joined by furin-cleavable linkers, and linked to a "penetrin'' peptide sequence derived from HIV- TAT. Thirty-one patients with SCCHN were screened for the trial and 5 were enrolled. Methods. Enrolled patients were treated with 300 lg of Trojan peptide supplemented with Montanide and granulocyte-macrophage colony- stimulating factor (GM-CSF) at 4-week intervals for up to 4 injections. Results. Following vaccination, peripheral blood mononuclear cells (PBMCs) from 4 of 5 patients recognized both the full Trojan constructs and constituent HLA-II peptides, whereas responses to HLA-I restricted peptides were less pronounced. Conclusion. This treatment regimen seems to have acceptable toxicity and elicits measurable systemic immune responses against HLA-II restricted epitopes in a subset of patients with advanced SCCHN. V C 2012 Wiley Periodicals, Inc. Head Neck 34: 1734-1746, 2012

Climate change, characterized by higher surface and water temperatures, will likely lead to more frequent and severe storms, floods, rising sea levels, wildfires, and loss of a variety of species. The monetary loss attributable to these events could be enormous, resulting in a variety of first-party insurance claims and third-party lawsuits. The availability of insurance coverage to pay these claims will depend on the nature of weather-related losses and the particular policies in force. Insurers have also begun to develop products that pay to rebuild to “greener” standards after fortuitous losses, encourage lower carbon emissions, and provide incentives for the implementation of sustainable business and personal practices.

Objectives/Hypothesis: To determine if supraglottoplasty (SGP) is effective in reversing abnormal respiratory parameters in children with laryngomalacia and obstructive sleep apnea (OSA). Study Design: Retrospective case series at a tertiary referral children's hospital. Methods: Ten patients with laryngomalacia and OSA as documented by polysomnography underwent SGP between 2005 and 2007. Data collected included age, findings on flexible and rigid endoscopy, type of procedure performed, and postoperative course. The postoperative polysomnographies were reviewed to identify changes in obstructive apnea index, obstructive apnea/hypopnea index, respiratory disturbance index, and low arterial oxygen saturation (O2 nadir) after SGP. Results: All 10 patients were successfully extubated after SGP. There were no peri- or postoperative complications, and no patient required a subsequent airway procedure. Each patient had a postoperative nocturnal polysomnography performed after SGP at 11 weeks (range 2–29 weeks). Caregivers reported mild improvement (10%), significant improvement (70%), and complete resolution (20%) of stridor and nocturnal snoring at a follow-up visit 4 weeks after discharge. Marked improvements were observed in obstructive apnea index, obstructive apnea/hypopnea index, respiratory disturbance index and O2 nadir, all of which were statistically significant (P < .05). Conclusions: Polysomnography should be considered in the initial evaluation of infants with moderate laryngomalacia to rule out OSA. SGP is an effective treatment for infants with laryngomalacia and OSA. The significant benefits of the procedure outweigh thelow morbidity. Improvement after surgery was reliably confirmed by polysomnography in this study.

Strategies for vascular control and limiting warm ischemia time (WIT) vary between institutions for laparoscopic live donor nephrectomy (LLDN). We refined our technique and retrospectively determined whether it safely provides an allograft of comparable quality to published series.Fifty consecutive LLDN between February 2003 and November 2006 were reviewed. Key technical aspects include placing the perfused kidney and transected ureter entirely within an endocatch bag, with the string externalized through an extended lateral port site incision. Vessels are then controlled with clips, or a Satinsky clamp for right sided veins. The extraction incision is completed and the bag immediately withdrawn and placed on ice. WIT ends with perfusion with cold UW solution.The series includes 42 left and 8 right kidneys. 13/50 (26%) demonstrated anatomical complexity (more than one artery, vein and/or ureter). Average operative time was 178 minutes. Average WIT was 128 seconds. Conversion to open surgery occurred in two patients, one to define challenging anatomy, and another for hemorrhage from the renal artery stump. Average blood loss was 76 ml. Average length of stay was 3.6 days. Average recipient creatinine was 1.26 mg/dl at discharge. Delayed graft function occurred in three recipients. ATN/slow normalization of creatinine occurred in four. Graft survival at one year was 96%.The refined technique of LLDN mimics important principles of open donor nephrectomy. Controllable variables which may impact graft function are optimized. WIT is amongst the lowest reported for pure laparoscopy, without increasing complication rates, blood loss, or operative time.

Purpose: To examine the prognostic significance of expression of glutathione s-transferase π (GST-π) and p53 in patients treated with radiation alone for locally advanced head and neck cancer [Radiation Therapy Oncology Group (RTOG), trial 9003] or radiation ± concomitant chemotherapy as postoperative adjuvant therapy (RTOG trial 9501).Experimental Design: Immunohistochemical staining for p53 and GST-π was done on tissue samples from 393 patients in RTOG 9003 and 142 patients in RTOG 9501. Kaplan-Meier survival analyses were done.Results: Patients who had low expression of both markers had longer survival than patients who had high expression of both markers. In trial 9003, median survival was 2.4 years for patients with low expression of both markers versus 1.4 years for patients who had elevated expression of both markers (P = 0.07). These differences were highly significant in trial 9501 and were accounted for by the chemotherapy treated arm. In this group, patients with low expression of both markers had a median survival of 7.0 years compared with 1.4 years for patients with elevated expression of both markers (P = 0.006). In both trials, black patients had lower survival rates than did white patients and there was a trend toward higher expression of both markers in blacks compared with whites.Conclusion: Given the poor outcome of chemoradiotherapy treatment patients with elevated expression of both p53 and GST-π, these patients may not be appropriate candidates for chemoradiotherapy based on standard protocols. Some of the adverse outcome for black patients in both studies may be attributed to elevated expression of p53 and GST-π.

While environmental incidents tend to occur infrequently, they are often serious enough to disrupt the operations of the entities that experience releases of hazardous materials. The consequences of such events may include third-party claims for bodily injury and property damage, orders to clean up contamination, and regulatory actions against responsible parties. Fortunately, environmental insurance is available to provide protection against the financial consequences of a wide variety of pollution events. This article looks at the role of the broker in assisting clients to identify, analyze, and insure against environmental liability. With properly drafted policies and active participation in the claims management process, the broker can play a significant role in assuring that an environmental insurance policy responds as anticipated when an unexpected incident threatens a client's operations.

We conducted in vitro studies and a clinical trial for patients with squamous cell carcinoma of the head and neck (SCCHN) to study the relationship between FcγRIIIa polymorphisms and antibody-dependent cellular cytotoxicity (ADCC). In vitro, FcγRIIIa genotype was correlated with ADCC and innate cytotoxicity using natural killer (NK) cells harvested from healthy donors. In the phase II study, patients with recurrent or metastatic SCCHN were treated with cetuximab (500 mg/m2 i.v. every 2 weeks) and lenalidomide (25 mg daily). FcγRIIIa genotype and ex vivo ADCC were correlated with clinical response, progression-free survival (PFS), and overall survival (OS). In vitro, healthy donors with a FcγRIIIa 158-V allele demonstrated more effective ADCC against two colon cancer cell lines HT29 and SW480, mean cytotoxicity: FF 16.1%, VF/VV 24.3% (P = 0.015) and FF 11.7%, VF/VV 21.0% (P = 0.008), respectively. We observed a linear relationship between ADCC response and innate cytotoxicity. In the phase II trial, 40 patients received cetuximab and lenalidomide with median PFS of 7.2 weeks and OS of 16.4 weeks. Thirty-six patients had FcγRIIIa genotype: VV (2), VF (20), and FF (14), and 25 patients had sufficient NK-cell yield to perform ex vivo ADCC. FcγRIIIa genotype was not associated with any clinical outcomes. Patients mounting ex vivo ADCC response had a higher likelihood of stable disease (P = 0.01) and showed a trend toward increased PFS: 14 weeks versus 6.8 weeks, respectively (P = 0.13). Enhanced ex vivo ADCC and innate immunity responses were more predictive of clinical response than FcγRIIIa and may offer a functional assay to select patients suitable for cetuximab therapy. Cancer Immunol Res; 3(5); 567–74. ©2015 AACR.

Anticancer drugs docetaxel and vinorelbine suppress cell growth by altering microtubule assembly and activating the proapoptotic signal pathway. Vinorelbine and docetaxel have been approved for treating several advanced cancers. However, their efficacy in the management of advanced hormone-refractory prostate cancer remains to be clarified. Microtubule damage by some anticancer drugs can activate the ERK survival pathway, which conversely compromises chemotherapeutic efficacy. We analyzed the effect of ERK inhibitors PD98059 and U0126 on vinorelbine- and docetaxel-induced cell growth suppression of androgen-independent prostate cancer cells. In androgen-independent C-81 LNCaP cells, inhibition of ERK by PD98059, but not U0126, plus docetaxel resulted in enhanced growth suppression by an additional 20% compared to the sum of each agent alone (p < 0.02). The combination treatment of docetaxel plus PD98059 also increased cellular apoptosis, which was in part due to the inactivation of Bcl-2 by increasing phosphorylated Bcl-2 by more than 6-fold and Bax expression by 3-fold over each agent alone. At these dosages, docetaxel alone caused only marginal phosphorylation of Bcl-2 (10%). Docetaxel plus U0126 had only 20% added effect on Bcl-2 phosphorylation compared to docetaxel alone. Nevertheless, both U0126 and PD98059 exhibited an enhanced effect on docetaxel-induced growth suppression in PC-3 cells. No enhanced effect was observed for vinorelbine plus PD98059 or U0126. Thus, the combination therapy of docetaxel plus PD98059 may represent a new anticancer strategy, requiring lower drug dosages compared to docetaxel monotherapy. This may lower the cytotoxicity and enhance tumor suppression in vivo. This finding of a combination effect could be of potential clinical importance in treating hormone-refractory prostate cancer.

Objective We report a multigeneration family where colorectal cancer and cancer of multiple diverse anatomic sites, inclusive of transitional cell carcinoma of the upper uroepithelial tract, were manifested in several relatives. Methods A specific pattern of cancer of the colorectum, endometrium, ovary, small bowel, and transitional cell carcinoma, with a vertical distribution of this cancer phenotype through multiple generations, was consonant with a diagnosis of hereditary nonpolyposis colorectal cancer. Results Germline mutation testing identified the MSH2 mutation, which segregated with the cancer phenotype. This family study clearly demonstrates the value of genetic testing in the management and treatment decision process. Conclusions We document, perhaps for the first time, how molecular genetic testing in hereditary nonpolyposis colorectal cancer can aid in the identification of a potential renal transplant donor for a relative with the MSH2 mutation who is experiencing renal insufficiency secondary to transitional cell carcinoma.

Lactoferrin, a naturally occurring glycoprotein found in breast milk, has previously been shown to have antimicrobial properties and recently has been demonstrated to inhibit malignant tumor growth, presumably through immunomodulation. We hypothesized that intratumoral injection of human and murine recombinant lactoferrin would decrease the growth of malignant tumors in vivo. Using an orthotopic murine model for both squamous cell carcinoma and fibrosarcoma of the floor of the mouth, we administered lactoferrin directly into the tumors using variable dosing strategies. Additionally, we performed in vitro experiments to assess whether the effects of lactoferrin are due to direct cytotoxicity. Our results revealed growth inhibition of 50% (p = 0.03)and 54% (p = 0.01) as compared with controls for both human and murine tumor cells in immunodeficient and immunocompetent mice, respectively. There was a more dramatic effect in immunocompetent models which may identify immunomodulation as an important mechanism of action for lactoferrin. Support for immunomodulation as a possible mechanism was the lack of any difference between controls and the experimental groups in vitro. Lactoferrin proved effective in reducing malignant tumor growth in a murine model. These properties offer hope for its use as a primary or adjuvant chemotherapeutic agent. Further investigation focused on mechanism and delivery is needed.

Objective Our objective was to determine the proportion of patients disease free in the neck, with the primary site controlled, who have been treated with a selective neck dissection (SND) for squamous cell carcinoma (SCCa) of the upper aerodigestive tract, and who had cervical metastasis less than 3 cm. Study Design A cohort of patients who fit the inclusion/exclusion criteria was identified retrospectively. Then all surviving patients were followed for a minimum of 2 years. Methods A group of 52 patients who had 58 selective neck dissections for cervical metastases from SCCa of the upper aerodigestive tract were identified. The mean age was 56 years (range, 20–85 y), there were 40 males and 12 females, and mean follow-up was 24.5 months (range, 1–64 mo). Twenty-six patients had clinically negative (cN0) neck examinations and 26 had clinically positive neck examinations. Postoperative radiation was given for extracapsular spread, greater than 2 positive nodes, T3, T4, or recurrent disease if the patient had not received radiation before surgery. These radiation criteria excluded 18 patients from postoperative radiation treatment. Results Kaplan-Meier survival analysis showed that the regional control rate with the primary site controlled was 0.94. Six patients developed recurrent neck disease. Three of these 6 patients were surgically salvaged. Four recurrences were in the dissected field and 2 were out of the dissected field (level V). Conclusions With similar indications for radiation therapy, the regional control rate in this cohort is comparable to control rates obtained with modified radical neck dissection.

Background Digital subtraction angiography (DSA) is considered the gold standard for the evaluation of head and neck vascular abnormalities. It serves as a useful diagnostic and, in many cases, therapeutic tool for treatment of acute head and neck bleeding. Case description We report the case of a patient who presented with life threatening, uncontrollable epistaxis several weeks after resection of a large recurrent chondrosarcoma of the nasal cavity and anterior skull base. A DSA study, with an adjunctive C-arm computed tomography (CT) (Dyna CT), was ultimately helpful in revealing and precisely localizing a large anterior ethmoidal artery pseudoaneurysm adjacent to the tumor resection cavity. Conclusion This additional information helped define the arterial anatomy in postoperative region, allowed precise localization and direct ligation of the pseudoaneurysm to resolve the bleeding with a favorable patient outcome.

En bloc transplantation of pediatric kidneys into adults is a suitable measure to help correct the shortage of available kidneys. This practice, however, is not widespread because of the high incidence of vascular complications. Our institution has previously described a vicryl mesh technique for en bloc kidneys, with an attempt to reduce the incidence of vascular complications. The purpose of this study was to evaluate the long-term results of recipients with en bloc kidneys stabilized with this technique. The charts of 644 adult renal transplants performed between July 1987 and July 1999 were reviewed. During this period, 14 adult patients have received 14 pairs of en bloc pediatric kidneys using the vicryl mesh technique. All patients received OKT3 as an induction immunosuppression with cyclosporine started 10-14 d after the transplant. The median donor age was 24 months (range 14-84 months), and the median recipient age was 49 yr (range 23-68 yr). The mean recipient weight was 79 kg (range 60-114 kg). The mean cold ischemia time was 14.2 hr. None of the patients developed vascular or urological complications. Delayed graft function and moderate acute rejection occurred in one patient each. At a mean follow-up of 51 months (range 7-96 months), all 14 patients maintained excellent renal function with a mean creatinine of 1.01 mg/dL. Renal measurements pre-operatively and at follow-up ultrasound examinations were available in 9 patients, and the mean length of the kidneys had grown approximately 5.0 cm. These data demonstrate that minimal vascular and immunological complication rates can be achieved with pediatric en bloc kidneys using the vicryl mesh envelope technique.

Urinary tract anomalies or dysfunction leaves the bladder unsuitable for urine drainage in a significant proportion of children presenting for kidney transplantation. We reviewed a multi-institutional experience to determine the ramifications of kidney transplantation in children with bladder augmentation or urinary diversion.During a 28-year period 18 boys and 12 girls 1.7 to 18 years old (mean age 12.1) received 31 kidney transplants. Cause of end stage renal disease was renal dysplasia in 8 cases, posterior urethral valves in 5, obstructive uropathy in 5, neurogenic bladder/chronic pyelonephritis in 4, spina bifida/chronic pyelonephritis in 3, prune belly syndrome in 3 and reflux in 2.Of the patients 17 had augmented bladder (ileum 9, ureter 5, sigmoid 2 and stomach 1), 12 had incontinent urinary conduits (8 ileum, 6 colon) and 1 had a continent urinary reservoir. Surgical complications included 1 case each of stomal stenosis, stomal prolapse, renal artery stenosis, urine leak, enterovesical fistula and wound dehiscence. Medical complications included urinary tract infection in 21 cases and metabolic acidosis in 5. A bladder stone developed in 1 patient. There was no correlation between the incidence of symptomatic urinary tract infections and type of urinary drainage. Acidosis was more common in patients with augmented bladder (4 of 17 versus 1 of 14) but there was no correlation between the bowel segment used and the occurrence of acidosis. Graft survival was 90% at 1 year, 78% at 5 years and 60% at 10 years. Etiology of graft loss included chronic rejection in 6 cases, noncompliance in 4 and acute rejection in 1. There were no deaths.Drainage of transplanted kidneys into an augmented bladder or urinary conduit is an appropriate management strategy when the native bladder is unsuitable or absent. Patients with kidney transplants drained into augmented bladder or urinary conduit are at increased risk for urine infection. Graft survival is not adversely affected compared to historical controls when a kidney transplant is drained into a urinary conduit or augmented bladder.

Purpose: The dire shortage of cadaveric kidneys has led to a gradual expansion of donor criteria in the transplant community. The use of kidneys with anatomical fusion anomalies is uncommon and has not been well defined in the literature. We evaluated the surgical strategies and postoperative outcomes of transplanting cadaveric kidneys with congenital fusion anomalies.Materials and Methods: Three cadaveric kidneys with congenital fusion anomalies were procured and transplanted between May 1994 and November 1999. None of the 3 donors had any significant urological history. All fusion anomalies were identified during the organ procurement process.Results: Anomalies included 1 L-shaped cross-fused ectopic and 2 horseshoe kidneys. All 3 kidneys were procured en bloc. One horseshoe kidney with a narrow isthmus was split and the 2 kidneys were transplanted into separate recipients, while the other horseshoe kidney was transplanted en bloc into a single recipient. The L-shaped kidney was transplanted en bloc int...

Background: The selection of patients for solitary pancreas transplantation (PTA) requires identification of individuals who will not develop acute renal dysfunction in response to immunosuppressants. A cyclosporine challenge test (CCT) was developed to predict post-PTA kidney dysfunction secondary to calcineurin inhibitor immunosuppressants. We now report on the long-term follow-up of patients who received a PTA after undergoing a CCT. Methods: Twelve potential PTA recipients were administered cyclosporine A (CsA) for 6 wk. Creatinine clearance (CrCl) was measured at 2, 4, and 6 wk. Those who did not fail the CCT received PTA. Baseline and post-transplant CrCl were retrospectively evaluated in the original cohort and in a group of matched patients who received PTA without a CCT. Results: Of the original 12 recipients evaluated with the CCT, 6 received PTA. CrCl was followed for a mean of 45.8 months. Of the 4 who remained alive, 2 went on to develop renal failure (CrCl < 30 mL/min) at 18 and 65 months post-transplant. The baseline CrCl was higher in PTA recipients who had not been selected to be studied with CCT than those that were (117 ± 32 vs 78 ± 13 mL/min). By 12 months post-PTA, the CrCl was no longer different between the groups selected to be screened with CCT and those that were not. Conclusions: CCT may help predict risk for short-term changes in renal function ( < 18 months) in response to CsA. CCT may be most helpful in candidates for PTA with borderline renal insufficiency (60-80 mL/min).

We evaluated tumor uptake and systemic distribution of intravesically instilled iododeoxyuridine (IUdR) in patients with superficial bladder cancer.We performed 24 intravesical instillation studies in 11 patients with a mean age of 71 years. Radio-iodinated IUdR was administered through a Foley catheter. Gamma camera imaging was done after instillation and after 5 to 7 bladder irrigations. Tumor uptake was estimated by region of interest analysis. Bladder biopsy samples and surgical tumor specimens were tested for acid insoluble (deoxyribonucleic acid incorporated) radioactivity. Blood samples were obtained and analyzed for systemic absorption.Imaging was positive in all patients with bladder cancer. Average tumor uptake plus or minus standard deviation was 0.185+/-0.120% of the instilled dose. Preferential uptake of IUdR in the tumor was observed in all 6 patients undergoing tissue analysis. The tumor-to-normal bladder ratio ranged from 3.2 to 74,000 (median 202). Systemic absorption of IUdR was minimal. Blood sample analysis performed after intravesical instillation in all 11 cases revealed an average uptake of 3.2x10(-5)% instilled dose per ml. (range 0.69x10(-5) to 6.7x10(-5)) in the systemic circulation. Instillation within 24 hours after transurethral bladder tumor resection in 5 cases resulted in a higher but not dangerous average systemic uptake of 7.3x10(-4)% instilled dose per ml. (range 1.3x10(-5) to 2.6x10(-3)). Instillation 1 to 4 weeks after transurethral surgery in 8 cases resulted in no increased systemic absorption with an average blood level of 3.4+/-1.8x10(-5)% instilled dose per ml. There was no detectable distribution of radioactivity into other organs, including the thyroid. We noted no evidence of systemic toxicity in the study.Intravesical instillation of radio-iodinated IUdR achieves selective localization in the bladder tumor with minimal uptake by the normal bladder and minimal systemic absorption. The use of intravesical IUdR therapy for bladder cancer appears to be promising and requires further study.

Environmental legacies are unpleasant leftovers of the industrial development of this nation. Unlike family legacies, which usually involve assets that are to be distributed among the heirs, environmental legacies most often involve liabilities. These liabilities were created by releases of contaminants, and exposures to toxic materials that have caused and, in some cases, will continue to cause, bodily injury and property damage. In most cases, resolving liability claims also requires the remediation of contaminated sites or the removal of asbestos‐containing building materials. The sources of historic pollution include: onsite disposal of hazardous materials generated by industrial processes; steady‐state discharges of solids, liquids, and gases from manufacturing operations into the air, surfacewater or groundwater; leaks and spills from underground and above‐ground storage tanks; intentional dumping of materials that were not known to be hazardous (and in some cases, intentional dumping of those that ...

Objectives. We conducted a multicenter retrospective study to determine the results of treatment for prostate cancer in solid organ transplant recipients. Methods. A retrospective analysis of all patients diagnosed with prostate cancer after organ transplantation at five centers was conducted. Data were obtained by chart review and a multipoint data sheet was used to abstract the data from the patient charts. Results. Eighteen cases of prostate cancer were identified from six institutions. Most (84%) of the cancers were clinically localized at the time of diagnosis. Nine (50%) of 18 patients underwent radical prostatectomy, which was the predominant mode of treatment. Overall survival at a mean follow-up of 32 months was 66%, with a cancer specific mortality of 16%. Mortality was 13% for the 15 patients with localized disease and 33% for the 3 patients with metastatic disease at the time of diagnosis. Conclusions. Most of the patients with prostate cancer being detected after solid organ transplantation were diagnosed with localized disease. Aggressive therapeutic intervention as in the general (nontransplant) population yields good results and should be pursued. Diligent surveillance for prostate cancer in this population using periodic digital rectal examination, serum prostate-specific antigen, and prostate needle biopsy as needed will ensure earlier cancer detection and allow for definitive therapeutic intervention.

Background. Thymoglobulin, a rabbit anti-human thymocyte globulin, was compared with Atgam, a horse anti-human thymocyte globulin for the treatment of acute rejection after renal transplantation. Methods. A multicenter, double-blind, randomized trial with enrollment stratification based on standardized histology (Banff grading) was conducted. Subjects received 7-14 days of Thymoglobulin (1.5 mg/kg/ day) or Atgam (15 mg/kg/day). The primary end point was rejection reversal (return of serum creatinine level to or below the day 0 baseline value). Results. A total of 163 patients were enrolled at 25 transplant centers in the United States. No differences in demographics or transplant characteristics were noted. Intent-to-treat analysis demonstrated that Thymoglobulin had a higher rejection reversal rate than Atgam (88% versus 76%, P=0.027, primary end point). Day 30 graft survival rates (Thymoglobulin 94% and Atgam 90%, P=0.17), day 30 serum creatinine levels as a percentage of baseline (Thymoglobulin 72% and Atgam 80%; P=0.43), and improvement in posttreatment biopsy results (Thymoglobulin 65% and Atgam 50%; P=0.15) were not statistically different. T-cell depletion was maintained more effectively with Thymoglobulin than Atgam both at the end of therapy (P=0.001) and at day 30 (P=0.016). Recurrent rejection, at 90 days after therapy, occurred less frequently with Thymoglobulin (17%) versus Atgam (36%) (P=0.011).

Purpose: We assessed the location of urethral arteries in patients with urethral stricture using color Doppler ultrasound.Materials and Methods: We performed 41 color ultrasound studies of the urethra in 33 patients 17 to 76 years old. The linear array transducer was placed on the ventral surface of the penis and perineum to image the urethra and periurethral structures. In addition of evaluating the extent of stricture disease, color Doppler ultrasound determined the location of the urethral arteries at the segment with stricture.Results: The number and site of the urethral arteries vary among individuals. Contrary to the common belief that these arteries are located at the 3 and 9 o'clock positions, we have found that in the bulbous urethra the arteries are at the 1 to 2 o'clock positions in 14% of cases, 3 to 4 in 22%, 5 to 6 in 17%, 7 to 8 in 18%, 9 to 10 in 18% and 11 to 12 in 11%. The arteries may be close to the surface of the urethral lumen, especially in patients who have undergone previo...

Contaminated property transactions include sales of real estate, leases, mergers, and acquisitions that involve a transfer of property that is impacted by historic pollution. Problems have been created in these transactions for parties on both sides by environmental laws that impose strict, joint and several and retroactive liability for environmental conditions on either the buyer or seller (lessor or lessee) who may have caused a release of contaminants. SEC environmental disclosure requirements have further complicated the situation by making it difficult for either party to agree to indemnify the other for such liabilities. Insurance policies have taken the place of indemnity agreements in these transactions and they can provide additional protection that addresses a wide range of environmental uncertainties. This article will consider a number of contaminated property transactions and review the use of insurance to facilitate their completion. It also provides briefcase studies that demonstrate the c...

Objectives: To understand patient expectations during the informed consent process for functional endoscopic sinus surgery (FESS). Study Design: Multi-institutional, cross-sectional survey design. Methods: Anonymous surveys were administered to patients in two tertiary academic centers with a chief complaint relating to “allergy and sinus” problems. Patients completed an eight-item questionnaire that assessed both the nature and the level of risks that they wished to be informed of prior to FESS. Results: Three hundred eighty-nine surveys were returned. Sixty-nine percent of patients wished to be informed of complications that occur as infrequently as 1 in 100 cases, regardless of severity. Ninety percent of patients wanted to know of a risk that occurred as frequently as 1 in 10 cases. Patients also reported whether or not they wished to be told in detail about specific complications during the informed consent process, regardless of their infrequency. Affirmative responses were as follows: 83% for cerebrospinal fluid leak and orbital injury, 81% for infection, 76% for revision surgery, 74% for impairment of smell, 73% for bleeding and myocardial infarction, 72% for cerebrovascular accident, and 58% for scarring. Conclusions: Patients wanted to be informed about severe FESS complications at a higher rate than physicians previously surveyed, even if the incidence is low. This study, combined with our previous examination of the physicians' perspective, highlights that there may be a discrepancy between what the physician and the patient believe are priority topics during the informed consent process.

Combined pancreas-kidney transplantation (PKT) has become generally accepted as an effective treatment option, but controversy exists regarding the early morbidity rate of the procedure. To address this issue, we retrospectively analyzed all readmissions occurring in the first 3 months after PKT. Over a 5-year period, we performed 98 PKTs with bladder drainage. The mean recipient age was 36.6 years, with a mean pretransplant duration of diabetes of 23.5 years. All patients received quadruple immunosuppression with antilymphocyte induction therapy. The mean length of initial hospital stay was 20 days. One hundred forty-five readmissions occurred in 73 patients (74.5%), with the initial readmission occurring at a mean of 8.5 days after hospital dismissal and 28 days after PKT. Twenty-five patients (25.5%) had no readmissions, 35 (36%) had one readmission, 17 (17%) had two readmissions, and the remaining 21 patients (21.5%) had three or more readmissions in the first 3 months. The mean number of readmissions was 1.5 per patient. Forty-seven patients (48%) were readmitted within 1 week, and all but one initial readmission occurred within 1 month of hospital dismissal. Causes of readmission included rejection (51), infection (32), pancreas-specific morbidity (such as dehydration, hematuria, or pancreatitis; 50), and miscellaneous causes (12). Thirteen patients (13%) underwent reoperation during readmission. The mean length of hospital stay during readmission was 7.6 days. The mean total length of hospitalization in the first 3 months after PKT was 31 days. Over the span of 5 years, no changes have occurred either in the incidence, timing, causes, or duration of readmissions. The patient survival rate is 96%, the kidney graft survival rate is 90%, and the pancreas graft survival rate is 88% after a mean follow-up of 2.6 years. Mean rehabilitation time (return to work or normal activity) after PKT was 4.0 months. In conclusion, PKT is associated with a fixed morbidity characterized by early readmission (within 1 week) in nearly half of patients and pancreas-specific morbidity as the cause in 35% of readmissions. During evaluation, prospective candidates should be counseled regarding the unique morbidity of PKT. Successful management strategies must emphasize the intensity of early follow-up and recognize the propensity toward immunologic, metabolic, exocrine, and urologic side effects.

Endoscopic sinus surgery (ESS) is one of the most commonly performed procedures in otorhinolaryngology and is associated with a definite risk for both intraoperative and postoperative complications. Intraoperative image guidance is expected to have a major effect on procedures such as ESS by allowing the clinician to more efficiently remove pathology and by improving surgeon confidence and knowledge of anatomy, particularly in revision procedures or in patients with altered anatomy. As a consequence, complications during these pro-’ cedures will decrease and patient safety will increase. Several guidance modalities are available including computed tomography (CT), magnetic resonance imaging (MRI), and fluoroscopy. This article will describe current applications of each of these three techniques with respect to ESS while focusing on innovative techniques that use MRI and CT to provide intraoperative guidance with unmatched convenience, reliability, and utility.

To determine the usefulness of sonographically obtained resistive indexes (RIs) in the diagnosis of pancreas allograft rejection.Findings were studied from 78 transduodenal pancreas allograft biopsies that were ultrasound-guided and cystoscopically directed. The 78 biopsies included 40 that were compared directly with baseline RI data. Biopsies were categorized by result and correlated with concurrent RIs (including 26 RIs obtained within 24 hours of biopsy) with the chi2 test for categoric variables and the Student t test for continuous variables. Sensitivity, specificity, and positive and negative predictive values were calculated with standardized formulas.The mean RIs between the no rejection, mild acute rejection, and moderate acute rejection groups were not statistically significantly different; however, the mean RI associated with chronic rejection was statistically significantly higher (P.05) than that in the other groups. The sensitivity, specificity, and positive and negative predictive values of either an elevated RI (0.70) or greater than 10% increase in the RI above the baseline value in the diagnosis of acute rejection were approximately 50%.Neither the absolute level of the RI nor the relative increase was correlated with acute rejection proved at biopsy. Changes in RIs after pancreas transplantation were a poor indicator of acute rejection, but the absolute value of the RI was elevated in cases of chronic rejection.

The early detection of allograft rejection remains elusive after solitary pancreas transplantation (PTX). We have previously described a modified technique of cystoscopic transduodenal PTX biopsy using the Biopty gun under ultrasound guidance. During the last 2 years, we performed 24 solitary PTXs with prospective protocol biopsy monitoring as well as biopsies performed whenever clinically indicated. The study group included 17 pancreas transplants alone, 6 sequential pancreas after kidney transplants, and 1 sequential pancreas after liver transplant. Five patients received pancreas retransplants. A total of 92 cystoscopically directed core PTX biopsies were performed, including 50 protocol biopsies (mean 2.1 per patient). Protocol biopsies were performed at 1 month (19), 2 months (3), 3 months (20), 6 months (7), and 12 months (1) after PTX. Adequate PTX tissue for histopathologic examination was obtained in 49 cases (98%). Biopsy findings included no rejection (34), mild rejection (13), pancreatitis (1), and cytomegalovirus infection (1). Overall, 15 of the 49 evaluable biopsies (31%) had significant histopathologic findings. All but 1 of the cases of mild rejection were treated with bolus steroids. Eight of these patients subsequently developed recurrent biopsy-proven rejection within 2 months; 5 grafts were subsequently lost to rejection between 3 and 13 months after PTX. Three biopsy complications occurred: 1 hematoma, 1 pancreatitis, and 1 ileus. Patient survival is 96% and PTX graft survival (complete insulin independence) is 75% after a mean follow-up of 15 months. In the remaining 42 clinically indicated biopsies, 3 were insufficient, 8 showed no rejection, and 31 (79%) had rejection. In half of these cases, the rejection was graded as moderate to severe. In conclusion, prospective monitoring with protocol PTX biopsies may result in the earlier detection of allograft rejection and have a direct effect on improving results after solitary PTX.

Background: We have noted a significant incidence of renal cell carcinoma (RCC) detected during evaluation for aneurysmal and aortoiliac occlusive disease. The approach to synchronous malignancy and aortic disease (staged versus concurrent resection) is controversial, as is the management of incidental RCC (partial versus radical nephrectomy). Patients and methods: We reviewed our experience with incidental RCC in patients undergoing aortic reconstruction between 1991 and 1994. Ninety-seven patients underwent aortic reconstruction for aneurysmal (72), occlusive (20), or embolic disease (5) during the time frame under review. All were men. Of the 80 preoperative computerized tomographic (CT) scans obtained, 7 (9%) demonstrated renal lesions suspicious for RCC. All lesions were explored and excised by partial or radical nephrectomy before heparinization and completion of the planned aortic procedure. Results: The overall mortality rate was 3%. None of the deaths occurred in patients undergoing combined procedures. Four partial and three radical nephrectomies were performed. Of the 7 renal lesions, 2 were complex cysts and 5 were RCC. Both patients with complex cysts were treated with wedge resection. One patient required surgical drainage of a wound abscess after partial nephrectomy. No significant differences were found between preoperative (1.4 ± 0.1 mg/dL) and postoperative (1.8 ± 0.2 mg/dL) creatinine levels following combined procedures. On follow-up CT scans done at 6-month intervals (mean follow-up 24 months), no evidence exists of recurrence, metastasis, or graft infection. Conclusions: This patient population demonstrated an unexpectedly high prevalence of incidental RCC (5 of 80 CTs, 6%). No increase in mortality was found when RCC and aortic disease were treated at the same operation. While partial nephrectomy was associated with one wound infection in this series, it is an effective treatment for small incidental RCC and may avoid unnecessary nephrectomy in patients with benign disease. Based on the high incidence of RCC in this population, we recommend exploration of all suspicious lesions. Nephrectomy can be performed safely in the same setting as aortic reconstruction. Because underlying renal dysfunction is not uncommon in patients with aneurysmal and aortoiliac occlusive disease, nephron-sparing surgery should be considered.

Objective: 1) Evaluate the effectiveness of the superficial musculoaponeurotic system (SMAS) flap and free fat graft in reconstructing the parotidectomy defect. 2) Evaluate the long-term viability of the free fat graft, including in the setting of postoperative radiation.Method: A prospective, consecutive analysis of patients undergoing parotidectomy for benign and malignant disease from 2006-2011 was performed at an academic university setting. The main outcome measures were the effectiveness of achieving symmetric volume of the ipsilateral parotid defect, long-term viability of the free fat graft, and presence of Frey’s syndrome.Results: Twenty-four consecutive patients received parotidectomy with SMAS flap and free fat graft from 2006-2011. The average age was 56 (range 16-84). Nineteen patients had benign disease, including pleomorphic adenoma, oncocytoma, and Warthin tumor. Five procedures were done for malignant disease, and, in each instance, postoperative radiation was administered. Satisfactory v...

We have previously demonstrated that the lipid profile improves following successful combined pancreas-kidney transplantation (PKT). In this study, we examined whether changes in the lipid profile were different in men than in women following PKT. Fasting total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), and the TC to HDL ratio (TC/HDL) were evaluated in 47 patients (27 men and 20 women) with normal graft function following PKT. Lipids were evaluated at regular intervals 3.5 months to 2.2 years post-PKT (a total of 317 observations). After PKT, TC/HDL decreased (P.05), TC was unchanged, and HDL increased (P.05) in both men and women. Although TG decreased in both men and women, it reached statistical significance in men only (P.05). There were no significant differences in any lipid parameters between men and women before PKT, but after PKT, TC, TG, and HDL were higher in women (240 +/- 11, 183 +/- 17, and 64 +/- 19 mg/dL, respectively) than in men (207 +/- 6, 143 +/- 11, and 53 +/- 2 mg/dL, P.05 for each). When post-PKT values were analyzed for trends over time, both TC and TG decreased (P.05 for both) without any significant difference in trends between men and women. When six individuals who had received lovastatin at any time during their postoperative course were removed from analysis, the gender differences in TG post-PKT and the decrease in TG over time were no longer statistically significant (P.05).(ABSTRACT TRUNCATED AT 250 WORDS)

This study describes the effect of adjuvant treatment on shoulder-related quality of life, leisure activities, and employment for patients undergoing neck dissection for head and neck cancer.To explore the association between treatment outcome and shoulder-related on critical daily life functions such as employment and recreation.Cross-sectional study of patients with head and neck cancer at a tertiary care hospital.Level V–sparing selective neck dissection or modified radical neck dissection sparing the accessory nerve, with or without radiation therapy and/or chemotherapy.Patients completed the Neck Dissection Impairment Index (NDII), with scores ranging from 0 to 100 and higher scores indicating better shoulder functioning and shoulder-related quality of life, and underwent objective testing with the Constant-Murley Shoulder Function Test (Constant test) at least 12 months after the completion of all adjuvant treatment. Additional outcome measures related to physical therapy, pain medication use, leisure activity, and employment status.We evaluated 167 patients who underwent 121 selective neck dissections and 46 modified radical neck dissections. The median (range) NDII score was 90 (10-100). Patients with modified radical neck dissection reported lower scores than those with selective neck dissection (85 [10-100] vs. 92 [30-100]; P = .01). Multivariable analysis showed that advanced-stage disease (mean, 77 [range, 25-100] vs. 87 [18-100]; P = .006), radiation therapy (80 [10-100] vs. 88 [50-100]; P = .03), and chemotherapy (77 [30-100] vs. 83 [18-100]; P = .002) were associated with greater shoulder impairment. The NDII and Constant test were well correlated (0.64; P.001). Change in leisure activity was correlated with greater impairment (median [range] NDII score, 90 [18-100] for patients with no change vs. 53 [10-100] for patients with change, P = .005; Constant score, 85 [12-100] vs. 68 [10-88], P = .004). Patients who remained employed or resumed working had higher median (range) NDII scores (94 [10-100] and 88 [75-100], respectively) than those who limited or stopped working (70 [10-100]), which also correlates with greater shoulder impairment (P.001).More aggressive treatment, either in the form of increased surgical dissection, radiation therapy, or chemotherapy, was associated with worse shoulder function and quality of life. The degree of impairment perceived by the patient and measured in objective testing was correlated with leisure activity and employment status. These findings may stimulate further investigation related to optimizing quality of life following neck dissection.

Combined kidney-pancreas transplantation has become the treatment of choice for many patients with end-stage diabetic nephropathy. Pancreas transplantation (PTx) alone is an option for type I diabetic patients without end-stage diabetic nephropathy. Knowledge of factors contributing to or predicting the rate of renal deterioration (including the effect of CsA on the patient's renal function before transplantation) is necessary to determine candidacy for either kidney-pancreas transplantation or PTx alone. To address this issue, we selected 12 pre-uremic patients with creatinine clearances (CrCl) above 40 ml/min and less than 100 ml/min to participate in a 6-week oral CsA challenge test. Serum chemistries, including serum creatinine (SCr) and CsA level, were measured weekly. Urinary protein and CrCl were measured at 0, 2, 4, and 6 weeks. Glomerular filtration rate (GFR) (by 125I-sodium iothalamate clearance) was measured at 0, 3, and 6 weeks. All patients initially received oral CsA at 10 mg/kg/day in 2 divided doses. Doses were adjusted to maintain a 12-hr trough level of 500-1000 ng/ml using a whole blood polyclonal TDX assay. Data are presented as mean +/- SEM and as box-plot graphs. One patient was a CsA challenge test failure because SCr exceeded 3.0 mg/dl despite a reduction in CsA dose and level. Therefore, this patient was not a candidate for PTx alone and was excluded from further analysis. Among the 11 nonfailures, the mean CsA level at 6 weeks was 640 +/- 76 ng/ml. SCr increased from 1.2 +/- 0.1 mg/dl to 1.6 +/- 0.1 mg/dl (33% increase) (P = 0.0001). CrCl decreased from 82 +/- 9 ml/min to 63 +/- 8 ml/min (24% decrease) (P = 0.03). GFR decreased from 95 +/- 15 ml/min to 70 +/- 10 ml/min (26% decrease) (P = 0.009). CrCl and GFR did not differ from one another at 0 and 6 weeks (r = 0.77 and 0.98; P = 0.3 and 0.7, respectively). Urinary protein decreased from 1.0 +/- 0.3 g/day to 0.7 +/- 0.3 g/day at both 4 and 6 weeks (P = 0.03 and 0.06, respectively). Three of the 11 patients have not yet received transplants. Eight patients subsequently received PTx alone and were followed prospectively. Two allografts were lost early to rejection. Six were followed from 5 to 19 months after PTx alone. Serum creatinine and CrCL measurements during the CsA challenge test predicted post-PTx levels: SCr 1.6 +/- 0.1 vs. 1.7 +/- 0.3 mg/dl, P = 0.48, and CrCl 68 +/- 10 vs. 53 +/- 3 ml/min, P = 0.17, respectively.

Urological complications are common following pancreas transplantation with bladder drainage. Some investigators have excluded patients from pancreas transplantation because of abnormal preoperative urodynamics. To determine the risk of an abnormal bladder in bladder-drained pancreas transplantation, we prospectively evaluated 23 type I diabetic patients undergoing pancreas transplantation with preoperative urodynamics. For study purposes, criteria for an abnormal urodynamic evaluation were a bladder capacity of greater than 1,000 cc, absence of normal detrusor contractility and an abnormal voiding pattern. In addition, an abnormal study was defined by the presence of 2 or more of the following: 1) suppressed proprioception at 250 cc or at a volume of greater than 50% of bladder capacity, 2) peak flow of less than 10 cc per second, 3) interval to peak flow of greater than 30 seconds or 4) post-void residual of greater than 150 cc. Of the 23 patients 10 (43%) had abnormal preoperative urodynamic studies. All 23 patients underwent pancreas transplantation with bladder drainage, alone or in combination with a kidney transplant. The incidence of urological complications was 3.1 and 3.4 per patient, respectively, in the normal and abnormal groups (p = 0.126). Patient and graft survival rates were similar between the 2 groups (p0.5). We were unable to show that abnormal preoperative urodynamic studies preclude successful pancreas transplantation with bladder drainage or predict an increase in postoperative complications.

Fifty-five kidneys were transplanted into 50 patients with supravesical urinary diversion at 16 transplant centers between 1970 and 1991. Of the 32 males and 18 females, 40 were adults (> or = 18 years) and 10 were less than 18 years old at the time of first transplant. Mean follow-up was 7.8 years. At last follow-up, 94% of recipients were alive and 73% of the kidneys were functioning. Fifteen kidneys were lost: 9 to rejection, 3 to noncompliance, and 3 patients died with a functioning kidney. Ten (18%) transplants were followed by surgical complications. Twenty-four (44%) were followed by medical complications of which urinary tract infection was most common. Recipients age 18 or younger had more urinary tract infections than older patients. No patient had urinary stones and no patient required medical treatment for metabolic abnormalities. We conclude that drainage of kidney transplants into a supravesical urinary diversion is an effective treatment for end-stage renal disease patients without adequate urinary bladders.

Although combined pancreas-kidney transplantation (PKT) has become a valid treatment option for selected type I diabetics, the timing of PKT relative to the degree of nephropathy remains controversial. We analyzed results and morbidity in 30 type I diabetics undergoing PKT after starting dialysis (PKT:D) versus 31 type I diabetics undergoing PKT prior to dialysis (PKT:ND). The two groups were similar with the respect to age, duration and severity of diabetes, gender, race, preservation time, retransplants, sensitization, HLA-matching, and CMV status. The mean preoperative serum creatinine was higher in the PKT:D group (9.9 +/- 3.4 vs. 3.9 +/- 1.9 mg/dl PKT:ND, P0.01). All patients were managed with quadruple immunosuppression with OKT3 induction. Actuarial patient survival is 100% (PKT:D) and 96.8% (PKT:ND). Renal and pancreas allograft survival are 97% and 93%, respectively, in both groups. The incidence of rejection, infection, operative complications, reflux pancreatitis, and total hospital days was similar in both groups. Long-term renal and pancreas allograft function and quality of life were like-wise comparable. No adverse coagulation or immunologic effects were noted in the PKT:ND group. Rehabilitation potential favored the PKT:ND group. PKT can be performed safely and effectively in the absence of uremia. In selected type I diabetics with significant nephropathy, we believe that PKT is the best treatment option and need not be considered as preemptive, especially in view of increasing waiting times and the variable progressive nature of diabetic complications.

Vascularized pancreas transplantation (PT) is becoming an accepted therapy for selected type I diabetic patients. However, selection and evaluation criteria remain uncertain. In the last 3.5 years, we have interviewed 205 and evaluated 151 diabetic patients for PT. The degree of renal dysfunction (creatinine clearance below 45 ml/min) was used to select patients for combined pancreas-kidney transplantation (PKT) or solitary pancreas transplantation (PTA) (clearance above 70 ml/min). The cardiovascular evaluation (stress thallium study with liberal use of coronary angiography) was used to determine operative risk and provided the other major selection criterion. A total of 104 patients were selected as candidates for PT; 70 have undergone PKT with 98.6% patient survival (1 cardiovascular death), 97.1% kidney graft survival, and 94.2% pancreas graft survival. Thirty-three evaluated patients (24.1%) were not accepted as candidates for PT; 13 have undergone cadaveric kidney transplantation, 5 were placed on the kidney waiting list, and 9 have died. Criteria for PTA include 2 or more diabetic complications or hyperlabile diabetes. Patient (n = 12) and pancreas graft survival after PTA is 83.3 and 50%, respectively. Our conclusion is that a multidisciplinary approach was used for recipient selection for PT based on degree of nephropathy, cardiovascular risk, and presence of diabetic complications. Nearly 75% of diabetic patients evaluated were acceptable candidates for PT. Only 4 (3.8%) of these selected patients died while awaiting or undergoing PT, thus optimizing the use of scarce allograft resources and providing evidence for appropriate patient selection.