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Objective: Circulating tumor DNA assays have robust potential as molecular surveillance tools. They may also exacerbate patient distress without improving outcomes. We investigate patient acceptability of a validated ctHPVDNA assay (NavDx) during cancer surveillance for HPV(+) oropharyngeal cancer (OPC)., Methods: Consented HPV(+) OPC participants completed the NCCN Distress Thermometer, the Hospital Anxiety Depression Scale (HADS), and the Functional Assessment of Cancer Therapy-General (FACT-G) scale both (1) before NavDx blood draw, and (2) after results were provided. Patients then completed a series of focused questions related to their perceptions of the assay., Results: Overall, 55 patients completed the study, with 98.2 % showing no recurrence. For the NCCN Distress Thermometer, median patient distress decreased (2.0 (IQR 1-5) vs. 1.0 (IQR 0-3)) (p < 0.001) in association with NavDx. Using scores ≥ 4 as a cutoff point to define clinically elevated distress, scores also improved (36.4 % vs. 18.2 %, p = 0.031). For HADS, anxiety significantly improved (5.0 (IQR 2.0-7.0) vs. 3.0 (IQR 1.0-6.5)) (p = 0.037), but not depression (3.0 (IQR 1.0-7.0) vs. 3.0 (IQR 1.0-6.5)) (p = 0.870). FACT-G scores showed no substantial differences. On survey questionnaires, 95.5 % of patients believed the test to be helpful, and 100 % felt "somewhat" or "extremely" confident in the assay as a monitoring tool. While 59.1 % felt that it reduced anxiety, 88.4 % concordantly felt that it did not introduce anxiety., Conclusion: ctHPVDNA as a molecular surveillance tool reduced distress levels in HPV(+) OPC patients, with notably high patient confidence in the approach. Further investigation is warranted to judiciously incorporate this emerging modality in surveillance guidelines., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Dr. Zumsteg’s spouse does legal work for Johnson & Johnson, Merck, Allergan, and Boehringer Ingelheim through her law firm]., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: As a surrogate of malnutrition, degree of weight loss and recovery from head and neck cancer (HNC) treatment is understudied. The influence of modifiable factors that affect weight, including speech/language pathology (SLP) and nutrition counseling, is also poorly defined. We characterize weight loss trends, baseline weight recovery (BWR), and the impact of interdisciplinary care on oncologic outcomes., Methods: Retrospective cohort study assessing 266 newly diagnosed patients with HNC who completed curative-intent radiation (definitive or adjuvant) between January 2016 to January 2022. Relevant treatment factors were analyzed using multivariable Cox regression models., Results: Altogether, 266 patients completed full-course radiation therapy (RT), encompassing definitive chemoRT (53.0%), surgery with chemoRT (18.4%), surgery with RT (17.7%), and RT alone (10.9%). Patient weight reached a nadir at median 3.0 months (IQR 3.0-11.3) after radiation, with a median weight loss of 12.6% (IQR 7.9-18.7). Notably, only 47.4% exhibited BWR. For those who recovered, median time to BWR was 10.5 months (IQR 3.0-24.0). On multivariable analysis, BWR by 6 months was significantly associated with overall survival (HR 0.28 [95% CI 0.10-0.76], p = 0.013), as was SLP consultation (HR 0.40 [95% CI 0.17-0.92], p = 0.031) and nutrition consultation (HR 0.34 [95% CI 0.13-0.89], p = 0.028)., Conclusion: A high proportion of patients with HNC fail to recover baseline weight after treatment; those that do can take longer than expected to return. Failure to recover baseline weight is associated with a notable decrease in survival. Similarly, SLP and nutrition consultation are independent, modifiable determinants correlated with outcomes, supporting the emphasis on multidisciplinary management. Measures to promote BWR may reduce mortality., (© 2024 Wiley Periodicals LLC.)

Background: The comparative impact of histologic variants and grade has not been well described., Methods: Salivary cancer histologies were profiled using hospital and population-based cancer registries. Multivariable models were employed to assess relationships between histology, grade, and survival., Results: On univariate analysis, histologic variants exhibited a wide spectrum of mortality risk (5-year overall survival (OS): 86% (acinic cell carcinoma), 78% (mucoepidermoid carcinoma), 72% (adenoid cystic carcinoma), 64% (carcinoma ex-pleomorphic adenoma), 52% (adenocarcinoma NOS), and 47% (salivary duct carcinoma) (p < 0.001). However, on multivariable analysis these differences largely vanished. Worsening grade corresponded with deteriorating survival (5-year OS: 89% [low-grade], 81% [intermediate-grade], 45% [high-grade]; p < 0.001), which was upheld on multivariable analysis and propensity score matching. Recursive partitioning analysis generated TNM + G schema (c-index 0.75) superior to the existing system (c-index 0.73)., Conclusion: Grade represents a primary determinant of salivary cancer prognosis. Integrating grade into stage strengthens current staging systems., (© 2023 Wiley Periodicals LLC.)

Background: Elective neck dissection is a standard of care for pharynx and most larynx cancer patients undergoing surgery, based largely on historical series. It is unclear if this is necessary for all patients in the modern era., Methods: Patients with cN0 oropharynx, larynx, and hypopharynx cancers diagnosed from 2010-2015 undergoing primary surgery were identified in the National Cancer Data Base., Results: Inclusion criteria were met by 4117 cN0 patients. The presence of lymphovascular invasion (LVI) was the strongest independent predictor of pN+ (odds ratio [OR] = 4.19, 95% confidence interval [CI] 3.56-4.93, p < 0.001). Histologic grade strongly predicted pN+ (OR 2.58, 95% CI 1.88-3.59, p < 0.001). A nomogram predicted less than 10% of cN0 patients had pN+ risk <15%., Conclusion: LVI and grade are the strongest predictors of pN+ among patients with cN0 pharynx and larynx cancer. Even in the modern era, pN+ rates warrant neck dissection for cN0 patients., Level of Evidence: 3 Laryngoscope, 133:1660-1666, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Nodal staging systems vary substantially across solid tumors, implying heterogeneity in the behavior of nodal variables in various contexts. We hypothesized, in contradiction to this, that metastatic lymph node (LN) number is a universal and dominant predictor of outcome across solid tumors., Methods: We performed a retrospective cohort analysis of 1 304 498 patients in the National Cancer Database undergoing surgery between 2004 and 2015 across 16 solid cancer sites. Multivariable Cox regression analyses were constructed using restricted cubic splines to model the association between nodal number and mortality. Recursive partitioning analysis (RPA) was used to derive nodal classification systems for each solid cancer based on metastatic LN count. The reproducibility of these findings was assessed in 1 969 727 patients from the Surveillance, Epidemiology, and End Results registry. Two-sided tests were used for all statistical analyses., Results: Consistently across disease sites, mortality risk increased continuously with increasing number of metastatic LNs (P < .001 for all spline segments). Each RPA-derived nodal classification system produced multiple prognostic groups spanning a wide spectrum of mortality risk (P < .001). Multivariable models using these RPA-derived nodal classifications demonstrated improved concordance with mortality compared with models using American Joint Committee on Cancer staging in sites where nodal classification is not based on metastatic LN count. Each RPA-derived nodal classification system was reproducible in a large validation cohort for all-cause and cause-specific mortality (P < .001). High quantitative nodal burden was the single strongest tumor-intrinsic variable associated with mortality in 12 of 16 disease sites., Conclusions: Quantitative metastatic LN burden is a fundamental driver of mortality across solid cancers and should serve as a foundation for pathologic nodal staging across solid tumors., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Modern disease staging systems have restructured human papillomavirus (HPV)-negative (HPV-) and HPV-positive (HPV+) oropharyngeal carcinoma (OPC) into distinct pathologic nodal systems. Given that quantitative lymph node (LN) burden is the dominant prognostic factor in most head and neck cancers, we investigated whether HPV- and HPV+ OPC warrant divergent pathologic nodal classification., Methods: Multivariable Cox regression models of OPC surgical patients identified via U.S. cancer registry data were constructed to determine associations between survival and nodal characteristics. Nonlinear associations between metastatic LN number and survival were modeled with restricted cubic splines. Recursive partitioning analysis (RPA) was used to derive unbiased nodal schema., Results: Mortality risk escalated continuously with each successive positive LN in both OPC subtypes, with analogous slope. Survival hazard increased by 18.5% (hazard ratio [HR], 1.19 [95% CI, 1.16-1.21]; P < .001) and 19.1% (HR, 1.19 [95% CI, 1.17-1.21]; P < .001), with each added positive LN for HPV- and HPV+ OPC, respectively, up to identical change points of 5 positive LNs. Extranodal extension (ENE) was an independent predictor of HPV- OPC (HR, 1.55 [95% CI, 1.20-1.99]; P < .001) and HPV+ OPC (HR 1.73 [95% CI, 1.36-2.20]; P < .001) mortality. In RPA for both diseases, metastatic LN was the principal nodal covariate driving survival, with ENE as a secondary determinant. Given the similarities across analyses, we propose a concise, unifying HPV-/HPV+ OPC pathologic nodal classification schema: N1, 1-5 LN+/ENE-; N2, 1-5 LN+/ENE+; N3, >5 LN+., Conclusion: HPV- and HPV+ OPC exhibit parallel relationships between nodal characteristics and relative mortality. In both diseases, metastatic LN number represents the principal nodal covariate governing survival, with ENE being an influential secondary element. A consolidated OPC pathologic nodal staging system that is based on these covariates may best convey prognosis., Lay Summary: The current nodal staging system for oropharyngeal carcinoma (OPC) has divided human papillomavirus (HPV)-negative (HPV-) and HPV-positive (HPV+) OPC into distinct systems that rely upon criteria that establish them as separate entities, a complexity that may undermine the core objective of staging schema to clearly communicate prognosis. Our large-scale analysis revealed that HPV- and HPV+ pathologic nodal staging systems in fact mirror each other. Multiple analyses produced conspicuously similar nodal staging systems, with metastatic lymph node number and extranodal extension delineating the highest risk groups that shape prognosis. We propose unifying HPV- and HPV+ nodal systems to best streamline prognostication and maximize staging accuracy., (© 2021 American Cancer Society.)

Background: Although pathologic tumor grade is a well-established prognostic risk factor that impacts staging and treatment decisions across multiple cancer types, its role in head and neck squamous cell carcinoma (HNSCC) is less certain., Methods: HNSCC patients diagnosed from 2010 to 2015 and undergoing primary surgery in the National Cancer Data Base were identified. Propensity score matching and multivariable Cox regression were performed., Results: Among 27 041 HNSCC patients, 13 941 had oral cavity cancers (OCC). Intermediate-grade (hazard ratio [HR] 1.16, 95% CI 1.07-1.26, P < .001) and high-grade (HR 1.38, 95% CI 1.26-1.52, P < .001) tumors had worse survival than low-grade tumors. This magnitude was comparable to other well-established prognostic factors, including margin positivity, extranodal extension, and lymphovascular invasion. By contrast, there was no association between grade and survival in larynx/hypopharynx or HPV(-) oropharynx cancer., Conclusions: The prognostic impact of pathologic grade is highly variable across head and neck subsites and is the strongest among OCC patients., (© 2020 Wiley Periodicals LLC.)

Importance: Transoral robotic surgery has been widely adopted since approval by the US Food and Drug Administration in December 2009, despite limited comparative data., Objective: To compare the long-term outcomes of transoral robotic surgery with those of nonrobotic surgery for patients with early-stage oropharyngeal cancer., Design, Setting, and Participants: A retrospective cohort comparative effectiveness analysis was performed of patients in the National Cancer Database with clinical T1 and T2 oropharyngeal squamous cell carcinoma diagnosed between January 1, 2010, and December 31, 2015, who underwent definitive robotic and nonrobotic surgery. Multivariable Cox proportional hazards regression analysis and propensity score matching were performed in patients with known human papillomavirus status to adjust for patient- and disease-related covariates. Survival after robotic and nonrobotic surgery was also compared in 3 unrelated cancers: prostate, endometrial, and cervical cancer. Statistical analysis was performed from April 10, 2019, to May 21, 2020., Main Outcomes and Measures: Overall survival., Results: Of 9745 patients (7652 men [78.5%]; mean [SD] age, 58.8 [9.6] years) who met inclusion criteria, 2694 (27.6%) underwent transoral robotic surgery. There was a significant increase in the use of robotic surgery from 18.3% (240 of 1309) to 35.5% (654 of 1841) of all surgical procedures for T1 and T2 oropharyngeal cancers from 2010 to 2015 (P = .003). Robotic surgery was associated with lower rates of positive surgical margins (12.5% [218 of 1746] vs 20.3% [471 of 2325]; P < .001) and lower use of adjuvant chemoradiotherapy (28.6% [500 of 1746] vs 35.7% [831 of 2325]; P < .001). Among 4071 patients with known human papillomavirus status, robotic surgery was associated with improved overall survival compared with nonrobotic surgery in multivariable Cox proportional hazards regression (hazard ratio [HR], 0.74; 95 CI, 0.61-0.90; P = .002). Similar results were seen when analyzing only the subset of facilities offering both robotic and nonrobotic surgery. The 5-year overall survival was 84.8% vs 80.3% among patients undergoing robotic vs nonrobotic surgery in propensity score-matched cohorts (P = .001). By contrast, there was no evidence that robotic surgery was associated with improved survival in other cancers, such as prostate cancer (HR, 0.92; 95% CI, 0.79-1.07; P = .26), endometrial cancer (HR, 0.97; 95% CI, 0.90-1.04; P = .36), and cervical cancer (HR, 1.27; 95% CI, 0.96-1.69; P = .10)., Conclusions and Relevance: This study suggests that transoral robotic surgery was associated with improved surgical outcomes and survival compared with nonrobotic surgery in patients with early-stage oropharyngeal cancer. Evaluation in comparative randomized trials is warranted.

Objective: Older adults with cancer are at higher risk for costly and potentially dangerous hospital readmissions. Identifying risk factors for readmission in this population is important for future prevention of readmission., Materials and Methods: Hospital discharges among patients ≥ 65 years with solid tumors on non-surgical services from 2006-2011 were reviewed in this matched case-control study. We abstracted patient/cancer characteristics; functional status; fall risk; chemotherapy line; comorbidities; laboratory values; discharge parameters; and miscellaneous information (Do Not Resuscitate Order, pain scores) from medical records. Conditional logistic regression was used for univariate and multivariable analysis., Results: This analysis included 184 case-patients readmitted within 30 days after discharge from the index admission and 184 sex- and age-matched control-patients discharged from index admission within three months of the cases with no readmission. Cases and controls had no differences in terms of primary cancer type, treatment, and index admission reason. Cases were more likely to have abnormal hemoglobin, albumin, sodium, and SGOT on discharge. Compared to those with ≤1 abnormal laboratory test, patients with 2 or more abnormal test results were 3 times more likely to be readmitted within 30 days., Conclusion: This study demonstrated that older adults with cancer who had at least 2 abnormal laboratory results (hemoglobin, albumin, sodium, and SGOT) at discharge were 3 times more likely to be readmitted within 30 days compared to those with ≤1 abnormal results. These laboratory values may be predictive of the risk of readmission, and should be monitored before discharge to potentially prevent readmission., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest, (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Patients with clinical stage I human papillomavirus (HPV)-positive oropharyngeal squamous cell cancer (OPSCC) according to the American Joint Committee on Cancer (AJCC) eighth edition classification comprise a heterogeneous group formerly classified as stage I to stage IVA according to the seventh edition of the AJCC classification. These patients historically were treated with disparate treatment regimens, particularly with respect to the use of concurrent chemotherapy., Methods: The National Cancer Data Base was queried for patients with AJCC eighth edition clinical stage I HPV-positive OPSCC (AJCC seventh edition stage T1-2N0-2bM0) who were diagnosed from 2010 to 2014 and underwent definitive radiotherapy. Concurrent chemotherapy with definitive radiotherapy was defined as chemotherapy administered within 7 days of the initiation of radiotherapy., Results: The current analysis included 4473 patients with HPV-positive stage I OPSCC with a median follow-up of 36.3 months. A total of 3127 patients (69.9%) received concurrent chemotherapy. Concurrent chemotherapy was found to be associated with improved overall survival on multivariable analyses (hazard ratio [HR], 0.782; 95% CI, 0.645-0.948 [P = .012]). The effect of chemotherapy on survival varied based on lymph node involvement (P for interaction = .001). Specifically, chemotherapy was associated with improved survival for patients with lymph node-positive stage I disease (stage III-IVA according to the AJCC seventh edition: HR, 0.682; 95% CI, 0.557-0.835 [P < .001]), but not for patients with N0 disease (stage I-II according to the AJCC seventh edition: HR, 1.646; 95% CI, 1.011-2.681 [P = .05]). Similar results were noted among propensity score-matched cohorts., Conclusions: Treatment with concurrent chemotherapy was associated with improved overall survival for patients with lymph node-positive, but not lymph node-negative, AJCC eighth edition stage I HPV-positive OPSCC undergoing definitive radiotherapy, thereby supporting different treatment paradigms for these patients., (© 2019 American Cancer Society.)

Background: Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has dramatically increased in incidence and prevalence among patients aged 70 and older. There are virtually no data regarding outcomes in this population, and thus optimal therapy, including the role of chemotherapy for those undergoing radiotherapy (RT), remains unclear., Methods: The National Cancer Database was queried for older adults (defined as age 70 years and older) with locally advanced OPSCC (cT1-2N1-3, cT3-4N0-3) diagnosed from 2010 to 2014 with known HPV-status undergoing definitive RT alone or chemoradiation (CRT)., Results: Overall, 1,965 older adults with locally advanced OPSCC met inclusion criteria, including 1,141 HPV-positive (58%) and 824 HPV-negative (42%) patients. 1,211 patients (62%) received CRT. In multivariable analysis, CRT was associated with improved survival in older patients when compared to RT alone (hazard ratio [HR] = 0.74, 95% confidence interval [CI] 0.64-0.86, P < 0.001). CRT was associated with improved survival in both HPV-positive (HR = 0.80, 95% CI: 0.64-1.00, P = 0.05) and HPV-negative (HR = 0.69, 95% CI: 0.56-0.85, P < 0.001) subgroups. There was no significant interaction between HPV status and the impact of CRT on survival (P interaction = 0.57)., Conclusions: Despite the radiosensitivity of HPV-positive OPSCC and the challenges in delivering CRT to older adults, CRT was associated with improved survival in older patients with HPV-positive OPSCC, similar in magnitude to the benefit in HPV-negative patients. As the incidence of HPV-positive OPSCC in older patients continues to increase, further studies are needed to investigate optimal therapeutic strategies in this population., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Multidisciplinary management of head and neck cancer (HNC) must reconcile increasingly sophisticated subspecialty care with timeliness of care. Prior studies examined the individual effects of delays in diagnosis-to-treatment interval, postoperative interval, and radiation interval but did not consider them collectively. The objective of the current study was to investigate the combined impact of these interwoven intervals on patients with HNC., Methods: Patients with HNC who underwent curative-intent surgery with radiation were identified in the National Cancer Database between 2004 and 2013. Multivariable models were constructed using restricted cubic splines to determine nonlinear relations with overall survival., Results: Overall, 15,064 patients were evaluated. After adjustment for covariates, only prolonged postoperative interval (P < .001) and radiation interval (P < .001) independently predicted for worse outcomes, whereas the association of diagnosis-to-treatment interval with survival disappeared. By using multivariable restricted cubic spline functions, increasing postoperative interval did not affect mortality until 40 days after surgery, and each day of delay beyond this increased the risk of mortality until 70 days after surgery (hazard ratio, 1.14; 95% confidence interval, 1.01-1.28; P = .029). For radiation interval, mortality escalated continuously with each additional day of delay, plateauing at 55 days (hazard ratio, 1.25; 95% confidence interval, 1.11-1.41; P < .001). Delays beyond these change points were not associated with further survival decrements., Conclusions: Increasing delays in postoperative and radiation intervals are associated independently with an escalating risk of mortality that plateaus beyond certain thresholds. Delays in initiating therapy, conversely, are eclipsed in importance when appraised in conjunction with the entire treatment course. Such findings may redirect focus to streamlining those intervals that are most sensitive to delays when considering survival burden. Cancer 2018. © 2018 American Cancer Society., (© 2018 American Cancer Society.)

Importance: Nodal staging for laryngohypopharyngeal cancers is based primarily on size and laterality, with less value placed on absolute number of metastatic lymph nodes (LNs). We are aware of no studies to date that have specifically addressed the prognostic effect of quantitative nodal burden in larynx or hypopharynx malignancies., Objective: To assess the independent impact of quantitative metastatic LN burden on mortality risk., Design, Setting, and Participants: Univariate and multivariable models were constructed to evaluate the association between patients' number of metastatic LNs and their survival, adjusting for factors such as nodal size, laterality, extranodal extension, margin status, and adjuvant treatment. Participants were patients with squamous cell carcinoma of the larynx or hypopharynx undergoing upfront surgical resection for curative intent at a US hospital between 2004 and 2013, as identified in the National Cancer Database. A neck dissection of a minimum of 10 LNs was required., Main Outcomes and Measures: Overall survival., Results: Overall, 8351 cases were included (mean [SD] age, 61 [10.1] years; 6499 men [77.8%]; 4710 patients with metastatic LNs and 3641 with no metastatic LNs). Mortality risk escalated continuously without plateau as number of metastatic nodes increased, with the hazard per node (hazard ratio [HR], 1.19; 95% CI, 1.16-1.23; P < .001) most pronounced up to 5 positive LNs. Extranodal extension was also associated with increased mortality (HR, 1.34; 95% CI, 1.13-1.59; P < .001). Increasing number of nodes examined was associated with improved survival, albeit to a lesser degree (per 10 LNs: HR, 0.97; 95% CI, 0.96-0.98; P < .001) and without a detectable change point. Other nodal factors, including nodal size, contralateral LN involvement (TNM stage N2c), and lower LN involvement (levels 4-5), were not associated with mortality in multivariable models when accounting for number of positive LNs. A novel, parsimonious nodal staging system derived by recursive partitioning analysis exhibited greater concordance with survival than the TNM staging system outlined in the American Joint Committee on Cancer's AJCC Staging Manual, 8th edition., Conclusions and Relevance: The number of metastatic nodes is a predominant independent factor associated with mortality in hypopharyngeal and laryngeal cancers. Moreover, standard nodal staging factors like LN size and contralaterality have no independent prognostic value when accounting for positive LN number. Deeper integration of quantitative metastatic nodal disease may simplify staging and better triage the need for adjuvant therapy.

Background: There is increasing evidence that primary tumor ablation can improve survival for some cancer patients with distant metastases. This may be particularly applicable to head and neck squamous cell carcinoma (HNSCC) because of its tropism for locoregional progression., Methods: This study included patients with metastatic HNSCC undergoing systemic therapy identified in the National Cancer Data Base. High-intensity local treatment was defined as radiation doses ≥ 60 Gy or oncologic resection of the primary tumor. Multivariate Cox regression, propensity score matching, landmark analysis, and subgroup analysis were performed to account for imbalances in covariates, including adjustments for the number and location of metastatic sites in the subset of patients with this information available., Results: In all, 3269 patients were included (median follow-up, 51.5 months). Patients undergoing systemic therapy with local treatment had improved survival in comparison with patients receiving systemic therapy alone in propensity score-matched cohorts (2-year overall survival, 34.2% vs 20.6%; P < .001). Improved survival was associated only with patients receiving high-intensity local treatment, whereas those receiving lower-intensity local treatment had survival similar to that of patients receiving systemic therapy without local treatment. The impact of high-intensity local therapy was time-dependent, with a stronger impact within the first 6 months after the diagnosis (adjusted hazard ratio [AHR], 0.255; 95% confidence interval [CI], 0.210-0.309; P < .001) in comparison with more than 6 months after the diagnosis (AHR, 0.622; 95% CI, 0.561-0.689; P < .001) in the multivariate analysis. A benefit was seen in all subgroups, in landmark analyses of 1-, 2-, and 3-year survivors, and when adjusting for the number and location of metastatic sites., Conclusions: Aggressive local treatment warrants prospective evaluation for select patients with metastatic HNSCC. Cancer 2017;123:4583-4593. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Purpose Current staging systems for oral cavity cancers incorporate lymph node (LN) size and laterality, but place less weight on the total number of positive metastatic nodes. We investigated the independent impact of numerical metastatic LN burden on survival. Methods Adult patients with oral cavity squamous cell carcinoma undergoing upfront surgical resection for curative intent were identified in the National Cancer Data Base between 2004 and 2013. A neck dissection of a minimum of 10 LNs was required. Multivariable models were constructed to assess the association between the number of metastatic LNs and survival, adjusting for factors such as nodal size, laterality, extranodal extension, margin status, and adjuvant treatment. Results Overall, 14,554 patients met inclusion criteria (7,906 N0 patients; 6,648 node-positive patients). Mortality risk escalated continuously with increasing number of metastatic nodes without plateau, with the effect most pronounced with up to four LNs (HR, 1.34; 95% CI, 1.29 to 1.39; P < .001). Extranodal extension (HR, 1.41; 95% CI, 1.20 to 1.65; P < .001) and lower neck involvement (HR, 1.16; 95% CI, 1.06 to 1.27; P < .001) also predicted increased mortality. Increasing number of nodes examined was associated with improved survival, plateauing at 35 LNs (HR, 0.98; 95% CI, 0.98 to 0.99; P < .001). In multivariable models accounting for the number of metastatic nodes, contralateral LN involvement (N2c status) and LN size were not associated with mortality. A novel nodal staging system derived by recursive partitioning analysis exhibited greater concordance than the American Joint Committee on Cancer (8th edition) system. Conclusion The number of metastatic nodes is a critical predictor of oral cavity cancer mortality, eclipsing other features such as LN size and contralaterality in prognostic value. More robust incorporation of numerical metastatic LN burden may augment staging and better inform adjuvant treatment decisions.

Background: The treatment of head and neck cancers is complex and associated with significant morbidity, requiring multidisciplinary care and physician expertise. Thus, facility characteristics, such as clinical volume and academic status, may influence outcomes., Methods: The current study included 46,567 patients taken from the National Cancer Data Base who were diagnosed with locally advanced invasive squamous cell carcinomas of the oropharynx, larynx, and hypopharynx and were undergoing definitive radiotherapy. High-volume facilities (HVFs) were defined as the top 1% of centers by the number of patients treated from 2004 through 2012. Multivariable Cox regression and propensity score matching were performed to account for imbalances in covariates., Results: The median follow-up was 55.1 months. Treatment at a HVF (hazard ratio, 0.798; 95% confidence interval, 0.753-0.845 [P<.001]) and treatment at an academic facility (hazard ratio, 0.897; 95% confidence interval, 0.871-0.923 [P<.001]) were found to be independently associated with improved overall survival in multivariable analysis. In propensity score-matched cohorts, the 5-year overall survival rate was 61.6% versus 55.5% for patients treated at an HVF versus lower-volume facilities, respectively (P<.001). Similarly, the 5-year overall survival rate was 52.3% versus 49.7% for patients treated at academic versus nonacademic facilities (P<.001). Analysis of facility volume as a continuous variable demonstrated continual improvement in survival with an increased number of patients treated. The impact of facility volume and academic designation on survival was observed when using a variety of thresholds to define HVF, and across the vast majority of subgroups, including both oropharyngeal and nonoropharyngeal subsites., Conclusions: Patients with locally advanced head and neck squamous cell carcinoma who are undergoing curative radiotherapy at HVFs and academic centers appear to have improved survival. Cancer 2017;123:3933-42. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

This case report describes the rare occurrence of a T790M resistance mutation found in a central nervous system (CNS) parenchymal metastasis. A concomitant squamous histology transformation in a lung non-T790M-resistant metastasis is also described. The authors hypothesize that this CNS resistance and histology transformation may have resulted from intermittent use of erlotinib treatment. This case report emphasizes the complexities of using erlotinib in the induction setting.

Introduction: Dasatinib is a novel tyrosine kinase inhibitor with activity against the Src family kinases. The Src pathway is active in breast cancer and has been shown to promote cell proliferation, invasiveness, and metastases. Preclinical data support the use of dasatinib to inhibit breast cancer cell growth, modulate hormone and EGFR signaling, and alter cell migration., Areas Covered: This article details the preclinical data supporting dasatinib's use in breast cancer treatment. Additionally, Phase I/II studies that have tested dasatinib as a single agent and in combination with chemotherapy and antihormonal agents are discussed., Expert Opinion: Phase I/II studies to date have shown only limited responses to dasatinib among breast cancer patients. Dasatinib has no current role in the treatment of breast cancer, and its future is uncertain. No specific subset of patients has been identified which preferentially responds to treatment. Studies are under way to identify specific molecular markers that might predict response to dasatinib.

Background: Coordination of care has grown in importance with the advent of new modalities of treatment that require specialized expertise. In cancer care, multidisciplinary approaches have shown improvements in quality of care. Tumor boards may provide a mechanism for improving coordination of care. We evaluated physician and practice characteristics that predict frequency of tumor board attendance., Materials and Methods: This cross-sectional study used data obtained by surveying physicians of a population-based sample of women with incident breast cancer. Physicians were queried regarding tumor board attendance, specialty [medical oncologist (MO), radiation oncologist (RO), surgeon at a hospital with American College of Surgeons accreditation (ACOSSg) and surgeon without such affiliation (non-ACOSSg)], physician characteristics (gender, race/ethnicity, teaching involvement, patient volume, ownership interest) and practice setting (type, size, reimbursement method). Univariate, bivariate, and multivariate analyses were performed for the dependent variable characterizing provider report of frequency of tumor board attendance., Results: Most surveyed physicians (83%) report attending tumor board weekly (58%) or monthly (25%). Specialty and higher patient volumes are significant predictors of more frequent attendance. Compared with the most prevalent specialty category (low-volume ACOSSgs), high-volume MOs attend more frequently (P = .01) and low volume non-ACOSSgs attend less frequently (P = .00)., Conclusions: Tumor board provides a structure for engaging providers in discussion of cancer cases that is designed to enhance quality of care. Tumor board agendas and formalized institution-wide policies could be designed to engage low-frequency attendees as a means to improve quality measures, promote multidisciplinary care, and potentially improve health outcomes.

Purpose: To evaluate excimer laser photorefractive keratectomy (PRK) for myopia using a repetition rate of 15 Hz instead of 10 Hz., Setting: The Cornea and Laser Eye Institute, Teaneck, and Department of Ophthalmology, UMDNJ-New Jersey Medical School, Newark, New Jersey, USA., Methods: Photorefractive keratectomy using a 15 Hz repetition rate was performed in 23 eyes of 14 patients by a single surgeon at 1 center. The attempted corrections ranged from -2.8 diopters (D) to -5.5 D. Preoperative and postoperative uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), predictability, corneal haze, and subjective glare/halo were evaluated over 6 months., Results: At 6 months, UCVA was 20/32 or better in all eyes and at least 20/20 in 14 eyes (73.7%). Two eyes (10.5%) lost 2 or more Snellen lines of BSCVA; postoperative BSCVA was at least 20/25 in 100% of eyes and 20/20 or better in 95.0%. Fifteen eyes (78.9%) were within +/-0.5 D of attempted correction, and 19 (100%) were within +/-1.0 D. Mean spherical equivalent refraction was -4.62 D preoperatively, +0.15 D at 1 month, -0.09 D at 3 months, and -0.37 D at 6 months. At 6 months, 4 eyes (21.0%) had no corneal haze and 14 (73.7%) had trace subepithelial haze. Fifteen eyes (78.9%) had no glare/halo effect at 6 months, and 4 (21.0%) had minimal glare/halo effect., Conclusions: Clinical outcomes after excimer laser PRK for myopia using an increased repetition rate of 15 Hz were good and similar to those in studies conducted with a 10 Hz repetition rate.

Objective: This study aimed to compare qualitative patterns of corneal topography early in the postoperative course after excimer laser photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) when used for the treatment of myopia of 6.0 to 15.0 diopters., Design: The study design was a prospective, multicenter, randomized clinical trial., Participants: A total of 64 eyes were treated with PRK and 54 eyes were treated with LASIK., Intervention: Using the Summit Apex excimer laser, patients received either PRK or LASIK using a single pass, multizone excimer laser ablation. Computer-assisted videokeratography was performed at designated postoperative examinations., Main Outcome Measures: Videokeratography maps at 1 and 3 months after surgery were classified using a standard classification scheme. The association of topography patterns to loss of spectacle-corrected visual acuity was tested., Results: At 1 month, for the PRK (n = 60) and LASIK (n = 51) groups, respectively, 63.3% and 19.6% of eyes fell into one of the four optically irregular groups (central island, keyhole, semicircular, or irregularly irregular; P < 0.001). At 3 months, for the PRK (n = 49) and LASIK (n = 39) groups, respectively, 36.7% and 10.3% of eyes fell into one of the optically irregular groups (P = 0.004). Comparing the 1- and 3-month examination results in the PRK and LASIK groups, respectively, 19 (42%) of 45 eyes and 11 (31%) of 36 eyes had a change in topography, generally to an optically smoother pattern. The irregular groups, taken together, were associated with a greater tendency toward loss of spectacle-corrected visual acuity of two or more Snellen lines (P = 0.01). There also was greater tendency toward loss of spectacle-corrected visual acuity in the PRK group that diminished with time (P < 0.01 at 1 month, P = 0.05 at 3 months)., Conclusions: After treatment for moderate-to-high myopia, LASIK topography patterns generally are more regular than are PRK patterns. This may be a result either of masking of underlying topography perturbations by the lamellar corneal flap, thus mitigating induced topography changes, or differences in surface wound healing. This study suggests that more rapid return of spectacle-corrected visual acuity found in patients treated with LASIK may be a result of more regular topography patterns early in the postoperative course.

Patients undergoing 801 elective, clean-contaminated operations were assigned to one of the three following antibiotic regimens: 1) 1 g of cefazolin preoperatively, 2) 1 g of cefazolin preoperatively and another 1-g dose 3 hours later, and 3) 1 g of cefotetan preoperatively. These antibiotic regimens resulted in similar wound infection rates for procedures completed within 3 hours. When the procedure lasted more than 3 hours, the 6.1 per cent infection rate noted when a single dose of cefazolin was given proved significantly greater than the 1.3 per cent infection rates associated with the use of two doses of cefazolin or a single dose of the longer acting antibiotic, cefotetan (P < 0.01). Another series of 768 patients undergoing biliary and gastrointestinal tract operations were assigned to one of two antibiotic regimens: 1) a preoperative dose of 1 g of cefazolin and another 1-g dose 3 hours later if still in the operating room; 2) same as (1), plus 1-g doses every 8 hours for 24 hours. The longer period of antibiotic administration failed to improve the wound infection rate compared to the use of perioperative coverage only. These studies suggest that a single dose of preoperative antibiotic is sufficient for surgical prophylaxis when the operation is completed within 3 hours. Antibiotic coverage must extend for the duration of longer operations. A second dose of antibiotic or a single preoperative dose of an extended half-life antibiotic are equally effective. There is no value to administering antibiotics after the operation has been completed.

Background: The peer review process used in most hospitals is largely anecdotal, leading to criticisms about the objectivity of the methods employed., Methods: The results of 1,500 consecutive abdominal operations performed by general surgeons working at three hospitals in a single community were reviewed. The outcome profile of each surgeon was compared statistically to the cumulative profile of the surgical community with adjustments for physiologic status of the patient, difficulty of the operation, and indications for surgery., Results: A problem surgeon was thus identified whose poor results were significantly different from the rest of the surgical community and could not be explained on the basis of unfavorable patient mix or complexity of the procedures undertaken., Conclusions: Statistical comparison of a surgeon's outcome profile with those of his colleagues working in the same practice environment is suggested as an approach to the task of peer review that might prove preferable to the usual retrospective review of problem cases.

Thirty (0.46%) patients required one or more reoperations to control bleeding after 6499 elective surgical procedures. A specific bleeding site was identified in 10 (0.15%), and bleeding was diffuse in 20 (0.31%). Bleeding occurred despite normal prothrombin and partial thromboplastin times and adequate platelet counts in all 30 cases. Diffuse bleeding was associated with the preoperative use of aspirin alone or in combination with other nonsteroidal anti-inflammatory drugs (NSAIDS) in 19 of 20 patients (95%). None of the patients with a discrete bleeding point identified at reoperation were taking these products (P < 0.001). More than one reoperation was more often required in the patients with diffuse postoperative bleeding than those with a specific site of hemorrhage. Many of these subsequent procedures were required to manage infections that developed after the first reoperation to control bleeding. Intensive care unit use, length of intensive care unit stay, total hospital stay, and hospital charges were all significantly increased when diffuse postoperative bleeding was noted. Postoperative bleeding, especially when it is diffuse rather than from a specific bleeding point, significantly prolongs hospital stay and increases costs. Bleeding is not prevented by obtaining routine screening coagulation profiles. A medication history with special attention to the recent use of aspirin and NSAIDS is advised before elective operations. Delaying surgery until the antiplatelet effects of these drugs have worn off may be advisable.

Sprague-Dawley rats were challenged with intraperitoneal injection of 10(7) Streptococcus pneumoniae 10 days after common duct ligation (BDL) or sham celiotomy (SC). Quantitative bacterial cultures were performed on liver, spleen, lung, kidney, and heart blood samples obtained 4 hours after injection. All 13 (100%) BDL animals had positive heart blood cultures, but only 6 of 12 (50%) SC animals remained bacteremic (p < 0.05). Significantly more viable organisms were recovered from lung, liver, spleen, and kidney of BDL animals compared with SC controls. BDL impaired the host's ability to kill this encapsulated gram-positive organism. Viable bacteria remained in all organs studied, which was associated with continuing bacteremia.

An animal wound model was used to compare the effectiveness of topical and systemic antibiotics and to examine the validity of using a combined regimen of both routes of antibiotic delivery. Gross infection rates and wound bacterial concentrations were determined after contamination with Staphylococcus aureus or Escherichia coli. Both moderate (10(8) colony-forming units [CFU]) and heavy (10(12) CFU) contamination were studied for each organism. Following moderate contamination, topical and systemic antibiotics were equally effective in reducing both wound bacterial content and infection rate, but there was no benefit from the combined use of both modes of antibiotic delivery. An additive effect of the combined regimen was noted only when the level of wound contamination was heavy.

The medical records of all patients subjected to lower extremity amputations during a 3-year period were reviewed. It was shown that advanced age and the presence of multiple medical problems do not predispose to higher levels of limb loss. Although diabetic patients more frequently undergo amputation because of sepsis than their nondiabetic counterparts, the diabetic state was not found to be associated with a greater likelihood of above knee (AK) procedures. Prior arterial surgery was not shown to make AK amputation more likely, but it was disconcerting to note that limb salvage was not achieved in many individuals despite patent proximal inflow revascularization procedures. This initial study showed that several presumed risk factors were not predictors of amputation level. Those patients requiring AK amputations had a greater frequency of combined segment (aortoiliac and femoropopliteal) occlusive disease than those who had successful amputations at more distal levels. A follow-up study of 41 consecutive patients presenting with tissue loss due to combined segment occlusive disease was performed. Eighteen (Group I) underwent inflow procedures only, while 23 (Group II) also underwent distal revascularization. The groups were similar with respect to age, risk factors, extent of tissue loss and sepsis. At 1 year 10 (56%) Group I and only 3 (13%) Group II patients required major amputation (P = 0.01). Distal bypass, in addition to an inflow procedure, is recommended for those who present with tissue loss due to multilevel arterial occlusion.

The medical records of 54 patients treated for sigmoid volvulus from 1983 to 1987 were reviewed. Patient demographics were very similar to previously published results. Four patients (7.4 percent) underwent emergency resection for gangrene with a mortality of 75 percent. Of the 50 patients who presented without ischemia, 23 (46 percent) were managed by nonoperative detorsion while 3 (6 percent) detorsed spontaneously. Fourteen of these 26 patients received no further treatment. Nonoperative mortality was 0 percent. Celiotomy was performed on 36 patients. The type of operative procedure performed had no significant bearing on outcome. Fifteen patients underwent resection and anastomosis; two of these patients died (13 percent). Fifteen patients underwent resection and colostomy with two deaths (13 percent), and six had open detorsion alone with one death (17 percent). The two factors associated with adverse outcome after surgical intervention were patient age and history of previous volvulus. All five deaths occurred in patients older than 70 years presenting with a first episode of volvulus (N = 15, mortality = 33 percent). No deaths occurred among patients younger than 70 years regardless of volvulus history or among those older than 70 years who were being treated for a recurrence (P less than or equal to 0.01). Patients older than 70 years with a first episode of volvulus represent a high risk if subjected to surgical intervention. Nonoperative detorsion alone should be considered for this subgroup of patients.

A time study was done to ascertain the number of hours spent in the hospital and the types of duties performed by residents enrolled in a multiple-institution, university-sponsored surgical training program. On the average, residents in the Wright State University program spent 90.1 +/- 27.1 hours in the hospital per week. Direct patient care activities required 62.7 +/- 18.8 hours (69.6%) of the average workweek. Purely educational endeavors accounted for 10.0 +/- 6.1 hours (11.1%) of the workweek. Ancillary tasks consumed an average of 8.5 +/- 8.5 hours (9.4%) of the surgical residents' time on duty per week. House officers did obtain a mean of 9.1 +/- 11.0 hours of sleep in those working hours (10.1% of the total time spent in the hospital). Although much variation existed among hospitals in the program, on-duty hours were greater in the private hospitals compared to the federal hospitals; the principal difference was the amount of time spent doing ancillary tasks (10.0 +/- 9.4 hours vs 5.6 +/- 5.6 hours; p less than 0.01). Hours worked by residents on private surgical services were longer than those of residents assigned to staff services (96.4 +/- 22.1 hours vs 86.0 +/- 29.3 hours; p less than 0.04). Again, the major difference was the greater amount of ancillary tasks performed by residents on private services (12.0 +/- 9.5 hours vs 6.2 +/- 7.0 hours; p less than 0.001). This finding could not be attributed to differences in patient census or turnover rates. Longer hours were noted on the general/thoracic surgery services compared to other surgical subspecialties (94.1 +/- 27.3 hours vs 81.5 +/- 24.8 hours; p less than 0.02). More time was spent in direct patient care on general/thoracic surgery (66.3 +/- 19.3 hours vs 54.9 +/- 15.1 hours; p less than 0.002). Despite the shorter workweek, residents on subspecialty rotations spent more time doing ancillary tasks (11.3 +/- 9.7 hours vs 7.3 +/- 7.6 hours; p less than 0.02). More than 60% of the residents' working hours in this program exceeded the arbitrary 80-hour limit, emphasizing the challenge of complying with the imposition of maximum work hours. We recommend that each program closely monitor the activities and hours of its residents to best respond to the pressures for regulation.

Two hundred and five consecutive explorations of the common bile duct were evaluated to assess the value of routine choledoschoscopic examination in preventing retained stones. Conventional exploration was performed in 139 instances (group 1), while routine choledochoscopy was added in 66 procedures (group 2). Preoperative temperature, leukocyte count, total bilirubin, amylase and alkaline phosphatase levels were not significantly different between the groups. Nine retained stones were demonstrated by postoperative cholangiography among the patients in group 1 as compared with three retained stones noted in those in group 2. This difference was not significant. Postoperative mortality and complication rates were unaffected by the performance of an endoscopic study of the biliary tract during ductal exploration. Choledochoscopy added an average of 36 minutes to the duration of the operative procedure (p less than 0.001). Choledochoscopy may prove helpful in selected instances, but the current data do not support its routine use during exploration of the common bile duct.

A four-part program was implemented in order to control the rising cost of prophylactic antibiotics: limiting the number of cephalosporins on formulary; prohibiting the use of third- and most second-generation cephalosporins for prophylaxis; using a special order form to designate use as empiric, therapeutic, or prophylactic; and mandatory discontinuance of prophylactic antibiotics after 24 hours. The total cost for administration of prophylactic antibiotics was reduced from an average of $37.35 per case for the six months preceding the start of these restrictive policies to an average of $21.99 per case during the next twelve months. Class I and class II wound-infection rates were 2.0 per cent and 4.9 per cent, respectively, prior to the adoption of the new antibiotic practices. Comparable infection rates were 1.8 per cent and 2.1 per cent, respectively, after this program was initiated. The rising cost of antibiotic prophylaxis can be reduced without adversely affecting wound-infection rates.

The effect of dividing the left renal vein was studied in Sprague-Dawley rats. Immediately after the left renal vein is divided near the renal hilum, the left kidney becomes markedly edematous and dusky. Twenty-four hours later, the kidney remains edematous and boggy. In contrast, the edema that immediately follows division of the left renal vein adjacent to the inferior vena cava is much less dramatic and virtually resolves within 24 hours. When the left renal vein was divided near the hilum simultaneously with right nephrectomy, all animals died within 48 hours. When the vein was divided adjacent to the vena cava with simultaneous nephrectomy, all animals survived. The effect of dividing the renal vein on perfusion of the left kidney was studied in Sprague-Dawley rats using intra-arterial injection of copper pigment. Division of the left renal vein reduced perfusion of that kidney to 68.9 per cent of control levels. This reduction was demonstrated to be totally reversible within 10 days.

To compare the results of sutured and stapled anastomoses in the performance of gastric operations, 112 consecutive patients, operated upon by the same group of surgeons, were reviewed. Of 80 gastric resections, 44 were done with conventionally sutured anastomoses, while 36 had stapled anastomoses. Of 42 gastrojejunostomies without resection, 18 were sutured and 24 stapled. The incidence of leaks, bleeding and stasis was similar for stapled and sutured procedures. This was true for both gastric resections and gastrojejunal anastomoses without resection. No significant differences were noted between the stapled and sutured procedures with regard to operative time and length of postoperative stay. Patients in the sutured gastrectomy group regained intestinal function more rapidly than when the staples were used, 3.9 compared with 5.1 days. Stapling devices can be safely used to perform gastric operations. Complication rates with these devices are the same as those noted for more conventional suture techniques. Data from this study do not substantiate claims that stapling instruments reduce operative time or speed recovery of intestinal function.

Topical hemostatic agents may be used to control bleeding from a variety of surgical sites. Oxidized cellulose (Surgicel), gelatin sponge (Gelfoam), and microfibrillar collagen (Avitene) are the hemostatic agents in widest use. Oxidized cellulose has previously been shown to be superior to gelatin sponge with respect to infection. Microfibrillar collagen has not been studied in this regard. Contamination of experimental wounds with an inoculum of 3.2 to 3.6 X 10(4) colony-forming units of Staphylococcus aureus did not produce any infection. The addition of 20 mg of oxidized cellulose to wounds that received the same level of bacterial contamination resulted in nine infected wounds of 20 (45%). When the wounds were treated with 20 mg of microfibrillar collagen prior to contamination, 18 of 20 (90%) developed infection. The observed difference between the two hemostatic agents was significant (P less than 0.008). When 5 and 10 mg of oxidized cellulose was added to experimentally contaminated wounds, infection did not ensue. The incidence of infection increased strikingly when the amount of oxidized cellulose employed was increased to 20 and 30 mg. No such dose effect was observed for microfibrillar collagen. Infection developed even when very small quantities of the agent were used. Both oxidized cellulose and microfibrillar collagen may promote infection. The present study, in which a subcutaneous wound model was used, suggests an advantage of oxidized cellulose as compared with microfibrillar collagen from the standpoint of infection. Further studies with these agents in other body sites seem warranted.

A series of 335 consecutive patients treated for acute appendicitis is presented. The incidence of perforation in the series was 32.2 per cent. The mortality was 0.3 per cent for the total series and 0.9 per cent for those patients with perforating appendicitis. When perforation occurs, a twofold increase in the hospital stay and a threefold increase in hospital costs result. A complication rate of 47.2 per cent in instances of perforation was significantly greater than that noted in instances of nonperforation. A 40 per cent incidence of perforation was noted during the first decade of life, after which the frequency of perforation declines. Beginning with the fifth decade, a progressive increase in the incidence of perforation was noted. Prior to hospital admission, a significant delay was noted among patients with perforation. In addition, those with perforating appendicitis were far more likely to have been seen previously by a physician who failed to advise hospital admission. Finally, a significant inhospital delay, from admission to operation, was noted in patients with perforating appendicitis. While geographic access to health care did influence the incidence of perforation, insurance status and possession of a telephone did not.

Alterations in the sequestration and destruction of bacteria were studied after 10 days of biliary obstruction. Intraperitoneal injection of radiolabeled Escherichia coli was used to study bacterial localization in rats 10 days after common duct ligation and transection or sham celiotomy. Animals were sacrificed 4 hours later and uptake by liver, spleen, lung, and kidney were studied with a scintillation counter. No significant difference in localization between the two groups was noted. Bacteremia was induced in a second set of animals and quantitative bacterial organ cultures were performed. Significantly more viable organisms were identified in lung, liver, and kidney of animals that underwent common duct ligation and transection, when compared with controls that underwent sham celiotomy. This suggests that there is a defect in bacterial killing after 10 days of biliary obstruction. The inability to effectively clear and kill gram-negative bacteria in patients with biliary obstruction may account for some of the clinical complications seen in this patient population.

Fifty-two patients who required reexploration through the groin incision within seven days of an arterial procedure were studied to assess the value of sartorius transposition. Twenty-four group I patients had the sartorius muscle used to cover the vascular graft at reoperation while 28 group II patients had a standard closure. The groups were similar with respect to age, initial arterial operation, incidence of diabetes, and use of antibiotics and postoperative anticoagulation. Wound complications were frequent in both groups (62.5% vs. 57.1%, respectively) but outcome of these wound problems was quite different. Graft infection and anastomotic disruption were significantly less frequent in group I patients. Because fewer infected prostheses had to be removed group I patients were less likely to require high level amputations. Sartorius transposition is an effective method of protecting vascular grafts jeopardized by the high frequency of wound problems associated with early reoperation.

Adult male rats underwent common bile duct ligation or sham celiotomy. At intervals of 7 and 14 days postoperatively, bacteremia was induced by intravenous injection of 10(9) Escherichia coli or intraperitoneal injection of 10(6) E. coli. Serial quantitative blood cultures and quantitative whole organ cultures were obtained. One week after surgery, clearance of bacteremia was impaired in all of the animals. Clearance of intraperitoneally injected E. coli was less efficient in the duct ligation rats. Fourteen days postoperatively, clearance of bacteremia induced by intravenous or intraperitoneal injection had improved in the sham celiotomy rats but was still significantly impaired in the duct ligation rats. An increased number of viable E. coli were recovered from the lungs of duct ligation rats after intravenous administration. We found that rats with obstructive jaundice do not respond normally to a bacteremia challenge. This impairment in reticuloendothelial function can be noted as early as 1 week after common duct ligation.

Both clinical and laboratory studies have demonstrated an increased risk of fatal sepsis after splenectomy. The importance of the spleen in clearing a bacterial challenge from pneumococci or other encapsulated organisms is now well accepted. The role of the spleen in handling a bacteremia due to nonencapsulated (Gram negative) organisms is not well established. Rats were subjected to either sham operation or splenectomy. Two weeks after surgery, all animals received 10(6) E. coli by intraperitoneal injection. Tail vein blood samples for quantitative culture were obtained at multiple time intervals after the bacterial challenge. All animals developed a bacteremia. Initially, the mean bloodstream bacterial counts were comparable in the sham and splenectomy groups. Sham-operated rats cleared all bacteria from the bloodstream within 240 minutes. In contrast, 240 minutes after bacterial injection, E. coli could still be recovered from the blood of asplenic rats at levels comparable to those noted at the start of the experiment. The present study shows that splenectomy does impair the animal's ability to clear a Gram-negative bacteremia.

The mortality from perforating appendicitis has decreased, but the incidence of perforation has not changed in 30 years. We found that among 335 consecutive patients treated for acute appendicitis, 108 (32%) had evidence of perforation. No significant differences between the groups were noted with respect to race, sex, educational level, family income, health insurance coverage, availability of transportation, and possession of a telephone. Perforation was more likely in patients who lived more than 20 miles from the hospital and in patients under age 10 years or over age 60. Patients with perforation were ill for a mean of 2.5 days before seeking medical attention, compared to a mean of 1.5 days for those without perforation (P < .001). Yet, approximately 75% of patients in each group stated that they had a "family doctor." Patients with perforation had significantly more physician visits before hospital admission (mean 1.61 vs 1.33, P < .005); 54.3% of patients with perforation had previous contact with a physician who failed to make the correct diagnosis.