Movement matters: short-term impacts of physical activity on mood and well-being.

Few studies have investigated the short-term, momentary relationships between physical activity (PA) and well-being. This study focuses on investigating the dynamic relationships between PA and affective well-being among adults with type 1 diabetes. Participants (n = 122) wore an accelerometer and completed daily EMA surveys of current activities and affective states (e.g., happy, stressed, excited, anxious) via smartphone over 14 days. Within-person, increased sedentary time was associated with less positive affect (r = - 0.11, p < 0.001), while more PA of any intensity was associated with greater positive affect and reduced fatigue, three hours later. Between-person, increased light PA was associated with increased stress (r = 0.21, p = 0.02) and diabetes distress (r = 0.30, p = 0.001). This study provides evidence that positive affect and fatigue are predicted by previous activity regardless of the different activities that people engaged in. Positive affect increased after engaging in PA. However, participants with higher amounts of light PA reported higher stress ratings.

High-Resolution Transcriptomic Landscape of the Human Submandibular Gland.

Saliva-secreting and transporting cells are part of the complex cellular milieu of the human salivary gland, where they play important roles in normal glandular physiology and diseased states. However, comprehensive molecular characterization, particularly at single-cell resolution, is still incomplete, in part due to difficulty in procuring normal human tissues. Here, we perform an in-depth analysis of male and female adult human submandibular gland (SMG) samples by bulk RNA sequencing (RNA-seq) and examine the molecular underpinnings of the heterogeneous cell populations by single-cell (sc) RNA-seq. Our results from scRNA-seq highlight the remarkable diversity of clusters of epithelial and nonepithelial cells that reside in the SMG that is also faithfully recapitulated by deconvolution of the bulk-RNA data sets. Our analyses reveal complex transcriptomic heterogeneity within both the ductal and acinar subpopulations and identify atypical SMG cell types, such as mucoacinar cells that are unique to humans and ionocytes that have been recently described in the mouse. We use CellChat to explore ligand-receptor interactome predictions that likely mediate crucial cell-cell communications between the various cell clusters. Finally, we apply a trajectory inference method to investigate specific cellular branching points and topology that offers insights into the dynamic and complex differentiation process of the adult SMG. The data sets and the analyses herein comprise an extensive wealth of high-resolution information and a valuable resource for a deeper mechanistic understanding of human SMG biology and pathophysiology.

Glycemic Risk Index Profiles and Predictors Among Diverse Adults With Type 1 Diabetes.

BACKGROUND: The Glycemia Risk Index (GRI) was introduced as a single value derived from the ambulatory glucose profile that identifies patients who need attention. This study describes participants in each of the five GRI zones and examines the percentage of variation in GRI scores that is explained by sociodemographic and clinical variables among diverse adults with type 1 diabetes. METHODS: A total of 159 participants provided blinded continuous glucose monitoring (CGM) data over 14 days (mean age [SD] = 41.4 [14.5] years; female = 54.1%, Hispanic = 41.5%). Glycemia Risk Index zones were compared on CGM, sociodemographic, and clinical variables. Shapley value analysis examined the percentage of variation in GRI scores explained by different variables. Receiver operating characteristic curves examined GRI cutoffs for those more likely to have experienced ketoacidosis or severe hypoglycemia. RESULTS: Mean glucose and variability, time in range, and percentage of time in high, and very high, glucose ranges differed across the five GRI zones (P values < .001). Multiple sociodemographic indices also differed across zones, including education level, race/ethnicity, age, and insurance status. Sociodemographic and clinical variables collectively explained 62.2% of variance in GRI scores. A GRI score ≥84.5 reflected greater likelihood of ketoacidosis (area under the curve [AUC] = 0.848), and scores ≥58.2 reflected greater likelihood of severe hypoglycemia (AUC = 0.729) over the previous six months. CONCLUSIONS: Results support the use of the GRI, with GRI zones identifying those in need of clinical attention. Findings highlight the need to address health inequities. Treatment differences associated with the GRI also suggest behavioral and clinical interventions including starting individuals on CGM or automated insulin delivery systems.

Impact of Overnight Glucose on Next-Day Functioning in Adults With Type 1 Diabetes: An Exploratory Intensive Longitudinal Study.

OBJECTIVE: While there is evidence that functioning, or ability to perform daily life activities, can be adversely influenced by type 1 diabetes, the impact of acute fluctuations in glucose levels on functioning is poorly understood. RESEARCH DESIGN AND METHODS: Using dynamic structural equation modeling, we examined whether overnight glucose (coefficient of variation[CV], percent time <70 mg/dL, percent time >250 mg/dL) predicted seven next-day functioning outcomes (mobile cognitive tasks, accelerometry-derived physical activity, self-reported activity participation) in adults with type 1 diabetes. We examined mediation, moderation, and whether short-term relationships were predictive of global patient-reported outcomes. RESULTS: Overall next-day functioning was significantly predicted from overnight CV (P = 0.017) and percent time >250 mg/dL (P = 0.037). Pairwise tests indicate that higher CV is associated with poorer sustained attention (P = 0.028) and lower engagement in demanding activities (P = 0.028), time <70 mg/dL is associated with poorer sustained attention (P = 0.007), and time >250 mg/dL is associated with more sedentary time (P = 0.024). The impact of CV on sustained attention is partially mediated by sleep fragmentation. Individual differences in the effect of overnight time <70 mg/dL on sustained attention predict global illness intrusiveness (P = 0.016) and diabetes-related quality of life (P = 0.036). CONCLUSIONS: Overnight glucose predicts problems with objective and self-reported next-day functioning and can adversely impact global patient-reported outcomes. These findings across diverse outcomes highlight the wide-ranging effects of glucose fluctuations on functioning in adults with type 1 diabetes.

Function and Emotion in Everyday Life With Type 1 Diabetes (FEEL-T1D): Protocol for a Fully Remote Intensive Longitudinal Study.

BACKGROUND: Although short-term blood glucose levels and variability are thought to underlie diminished function and emotional well-being in people with type 1 diabetes (T1D), these relationships are poorly understood. The Function and Emotion in Everyday Life with T1D (FEEL-T1D) study focuses on investigating these short-term dynamic relationships among blood glucose levels, functional ability, and emotional well-being in adults with T1D. OBJECTIVE: The aim of this study is to present the FEEL-T1D study design, methods, and study progress to date, including adaptations necessitated by the COVID-19 pandemic to implement the study fully remotely. METHODS: The FEEL-T1D study will recruit 200 adults with T1D in the age range of 18-75 years. Data collection includes a comprehensive survey battery, along with 14 days of intensive longitudinal data using blinded continuous glucose monitoring, ecological momentary assessments, ambulatory cognitive tasks, and accelerometers. All study procedures are conducted remotely by mailing the study equipment and by using videoconferencing for study visits. RESULTS: The study received institutional review board approval in January 2019 and was funded in April 2019. Data collection began in June 2020 and is projected to end in December 2021. As of June 2021, after 12 months of recruitment, 124 participants have enrolled in the FEEL-T1D study. Approximately 87.6% (7082/8087) of ecological momentary assessment surveys have been completed with minimal missing data, and 82.0% (82/100) of the participants provided concurrent continuous glucose monitoring data, ecological momentary assessment data, and accelerometer data for at least 10 of the 14 days of data collection. CONCLUSIONS: Thus far, our reconfiguration of the FEEL-T1D protocol to be implemented remotely during the COVID-19 pandemic has been a success. The FEEL-T1D study will elucidate the dynamic relationships among blood glucose levels, emotional well-being, cognitive function, and participation in daily activities. In doing so, it will pave the way for innovative just-in-time interventions and produce actionable insights to facilitate tailoring of diabetes treatments to optimize the function and well-being of individuals with T1D. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/30901.

Polymorphism of shock loaded fe-mn and fe-ni alloys.

Addition of nickel or manganese to iron lowers the pressure of the "130-k" dynamic polymorphic transition to about 55 kilobars at the limits of the body-centered cubic alloy phase.

The use of photodynamic therapy using 630nm laser light and porfimer sodium for the treatment of oral squamous cell carcinoma.

PDT has been demonstrated in clinical studies to be an efficacious method for the treatment of dysplastic, microinvasive and early forms of cancer. The advantage of PDT for early carcinomas of the oral cavity is the ability to preserve normal tissues while effectively treating cancers up to 1cm in depth. The case presented here successfully demonstrates the ability to use PDT to treat maxillary gingival squamous cell carcinoma thereby sparing the use of surgery or radiation therapy at this point in the management of the disease.

Primary adenocarcinoma of cervical esophagus.

Most upper esophageal malignancies are squamous cell carcinomas, rarely adenocarcinomas arising from Barrett's esophagus and very rarely adenocarcinomas from heterotopic gastric mucosa without evidence of Barrett's especially in the cervical part of the esophagus. We report a case of adenocarcinoma of the polypoid type in the upper esophagus (cervical esophagus) arising from ectopic gastric mucosa, in a 60 year-old man who presented with progressive dysphagia. Accurate diagnosis by esophagogram revealed a large mass in the cervical esophagus; CAT scan showed intraluminal mass at the level of thoracic inlet, esophagogastroscopy showed a fleshy polyp (3.2cm x 3.0cm) at 20 cm from the incisors with a biopsy confirming moderately differentiated adenocarcinoma with no evidence of Barrett's esophagus. Through a left cervical approach and resection of medial third of clavicle, the tumor was removed by partial esophagectomy followed by lymph node dissection, and proved to be T1NOMO, stage I (AJCC staging 6th ed.). Post operatively, the patient received chemoradiation with no evidence of recurrence or metastasis in six years of follow up. It seems this tumor has a much better prognosis than adenocarcinomas arising from Barrett's. To our knowledge only 19 cases have been reported in literature so far.

Intermediate-risk group for differentiated carcinoma of thyroid.

BACKGROUND: We have previously described prognostic factors in differentiated carcinoma of the thyroid gland relating to age, size and extrathyroid extension of the tumor, histologic grade, gender, and distant metastasis. These factors have identified patients in the low-risk group with excellent prognosis and the high-risk group with significant mortality. However, some patients fall within the intermediate-risk category where due deliberation in decision making is required for selection of appropriate treatment. METHODS: A retrospective review of a consecutive series of 1038 previously untreated patients with differentiated carcinoma of thyroid treated during a period of 55 years was undertaken. Data gathered from review of the charts were subjected to univariate and multivariate analysis to assess prognostic factors. On the basis of the patient's age, presence of distant metastasis, and size, grade, and histologic characteristics of the tumor they could be classified into low-, intermediate-, and high-risk categories. Thus 403 (39%) patients were in the low-risk group, 232 (22%) patients in the high-risk category, and 403 (39%) patients in the intermediate-risk category. RESULTS: With a median follow-up of 20 years, 99% survival was achieved in the low-risk group, whereas only 57% survived in the high-risk group. Interestingly, in the intermediate-risk category of 403 patients, the 20-year survival was only 85%. Our results clearly identify a distinct intermediate-risk category that includes low-risk patients with high-risk tumor or high-risk patients with low-risk tumor. CONCLUSION: Patients in the intermediate-risk category should be considered for an aggressive treatment approach based on individual prognostic factors.

Prognostic factors and risk group analysis in follicular carcinoma of the thyroid.

BACKGROUND: The understanding of prognostic factors has facilitated stratification of risk groups in differentiated carcinoma of the thyroid. The prognostic factors have clearly identified the risk groups as low, intermediate, and high risk. Risk group categorization has facilitated a selective surgical approach for thyroid carcinoma. METHODS: A retrospective review of 228 patients with follicular carcinoma of the thyroid was undertaken. Various prognostic factors and risk groups were analyzed. Univariate and multivariate analyses were performed, and the survival curves were plotted by the Kaplan-Meier method. Fifty-nine (26%) patients presented with Hürthle cell histology. The risk groups revealed 62 patients in the low, 84 in the intermediate, and 82 in the high risk groups. RESULTS: The 10-year survival for low, intermediate, and high risk groups was 98%, 88%, and 56%, respectively, and the 20-year survival for the same groups was 97%, 87%, and 49%, respectively. Adverse prognostic factors included age older than 45 years (p < 0.001), Hürthle cell variety (p = 0.05), extrathyroidal extension, tumor size exceeding 4 cm, and the presence or absence of distant metastasis (p < 0.001). Gender, focality, and presence of lymph node metastasis had no significant impact on prognosis. CONCLUSIONS: Patients in the low risk group have excellent survival, whereas the high risk group behaves poorly. Appropriate selection of treatment for the primary disease and adjuvant therapy should be considered on the basis of the prognostic factors and risk group analysis.

Large, deep high-grade extremity sarcomas: when is a myocutaneous flap reconstruction necessary?

The surgical treatment of large, deep high-grade extremity soft tissue sarcomas frequently produces a significant tissue defect. In addition, the management of the surgical wound is often further complicated by preoperative radiation or adjuvant therapies. The use of either pedicled or free myocutaneous flaps allows for more rapid and predictable wound healing in this situation. Myocutaneous flaps provide well-vascularized coverage of lost tissue volume, exposed vital structures, and prosthetic reconstruction materials. When harvested from unirradiated sites, flap coverage can overcome the detrimental effects of radiation therapy and chemotherapy on postoperative wound healing. Reconstruction of the soft tissue defect may also improve patient satisfaction with aesthetic issues. The use of innervated myocutaneous flaps can even address the functionality of the extremity following resection of major muscle groups. Myocutaneous flaps are an extremely versatile option for reconstruction in the treatment of large, deep high-grade extremity soft tissue sarcomas.

Cutaneous melanoma of the head and neck.

We have reviewed a 21-year experience with 289 patients who received definitive surgical treatment for cutaneous melanomas arising in the skin of the head and neck. Elective lymphadenectomy was performed in 39 percent of those who presented with no clinical evidence of nodal metastasis. The cumulative 5- and 10-year survival was 56 percent and 45 percent, respectively. Increased tumor thickness, age greater than 55 years, male sex, ulceration, nodular morphology, and scalp site were significant adverse factors. Patients with ear or neck lesions had the best survival. The risk of distant metastasis was almost equivalent to that of nodal metastasis, regardless of thickness. Elective lymphadenectomy appeared to have minimal impact on survival.

Significance of positive margins in oral cavity squamous carcinoma.

Three hundred ninety-eight consecutive, previously untreated patients undergoing surgery for epidermoid carcinoma of the oral cavity from 1979 to 1983 were reviewed. One hundred twenty-nine patients were classified as having positive surgical margins. Of these, 83 patients had tumor within 0.5 mm of the surgical margin, 9 had premalignant changes at the margin, 9 had in situ carcinoma at the margin, and 28 had invasive cancer at the margin. The remaining 269 patients had uninvolved margins. The significance of positive margins relating to survival, subsequent clinical course, local recurrence, and patterns of treatment failure was examined, along with the impact of adjuvant postoperative radiotherapy on positive margins. The percentage of patients having positive margins progressively increased with increasing T stage: 21% in T1 versus 55% in T4 primary cancer. The overall 5-year survival for patients with negative margins was 60%. For patients with positive margins, 5-year survival was 52%. This difference was statistically significant. The incidence of local recurrence in patients having positive surgical margins was twice as much as in those with negative margins (36% versus 18%). Metastasis rates in the neck and at distant sites were not significantly influenced by the status of the surgical margin. Of the 129 patients with positive margins, 49 received postoperative radiotherapy. In those patients so treated, a trend toward lower recurrence rates was noted. Differences were not statistically significant. This retrospective review confirms the importance of adequate resection of the primary tumor as well as the relative ineffectiveness of adjuvant postoperative radiotherapy in the improvement of local control in patients with positive surgical margins.

Complications of the pectoralis major myocutaneous flap in head and neck reconstruction.

A retrospective review of the complications in 211 patients undergoing pectoralis major myocutaneous flap reconstruction is presented. The flap was used for mucosal lining of the oral cavity or oropharynx in 109 patients, for pharyngoesophageal reconstruction in 44, for skin coverage in 47, and for other locations in 14 patients. Flap-related complications developed in 63% of the patients. These included flap necrosis, suture line dehiscence, fistula formation, infection, and hematoma. Analysis of risk factors for the development of flap complications showed the following factors to be significant: age over 70; female gender; nomographic overweight; albumin less than 4 g/dL; use of the flap in reconstruction of the oral cavity after major glossectomy; and presence of other systemic diseases. The median length of hospitalization for those developing complications was 33 days compared with 16 days for those who did not develop any complications. Thirty-five (26%) of the 135 patients developing complications required reoperation and only 2 among these required a second flap. Similarly, only 13 of the 61 patients who developed fistulas required surgical closure.

Lobectomy versus total thyroidectomy for differentiated carcinoma of the thyroid: a matched-pair analysis.

The extent of surgical resection for differentiated carcinoma of the thyroid gland confined to one lobe remains controversial. Although primary tumor size and extrathyroid extension are associated with a poor prognosis, the presence of multifocal lesions is not associated with an adverse prognosis. Therefore, the role of lobectomy versus total thyroidectomy must be studied in a prospective, randomized trial. Due to the need for long-term follow-up, such a trial has not yet been undertaken. As an alternative to such a trial, we have identified 146 patients from a consecutive series of 931 previously untreated patients undergoing surgical treatment at 1 institution between 1930 and 1980. For this study of matched-pair analysis, 73 patients, aged 45 years or older, were matched in each arm for significant prognostic factors. One group underwent lobectomy, and the other group underwent total thyroidectomy. The 20-year survival rate in the lobectomy group was 82% compared with 73% in the total thyroidectomy group (p = not significant). The patterns of failure in these two groups of patients were examined. A comparison of the patients who underwent lobectomy with an unmatched group of patients who underwent lobectomy showed similar survival rates. On the other hand, unmatched patients undergoing total thyroidectomy had a poorer survival rate than the matched group. This signifies a more aggressive nature of disease in the unmatched group of patients undergoing total thyroidectomy. We therefore conclude that low-risk patients undergoing lobectomy are likely to do as well as those undergoing total thyroidectomy and without the increased risk of the morbidity of total thyroidectomy.

Differentiated thyroid cancer presenting initially with distant metastasis.

BACKGROUND: The initial presentation of distant metastases in patients with differentiated thyroid cancer is a rare event. Interestingly, if managed appropriately, the long-term survival in this group of patients is approximately 43%. We intend to review our experience of patients presenting initially with distant metastatic disease in a large series of differentiated thyroid cancer patients. METHODS: In the entire series of 1,038 consecutive patients treated at Memorial Sloan-Kettering Cancer Center from 1930 to 1985, 44 patients presented initially with distant metastases (4%). There were 22 male and 22 female patients ranging in age from 7 to 75 years with a mean age of 51 years. Patients were analyzed for their prognostic factors, and the survival curves were drawn by the Kaplan-Meier method. Univariate and multivariate analyses were performed by the Cox regression model. RESULTS: There were 19 patients presenting with distant metastases in 810 patients presenting with papillary thyroid cancer (2.3%). The incidence was high in patients with follicular thyroid cancer (11%). It is interesting to note that the highest incidence of presentation with distant metastatic disease was in patients above the age of 45 and with follicular thyroid carcinoma. The long-term survival in this group is 43% compared with 86% in patients presenting without distant metastasis (P < 0.001). There was no statistical difference in survival of patients below or above the age of 45. CONCLUSION: Even though the presence of distant metastasis at the time of initial presentation in other cancers is considered to be of grave prognosis, for patients with differentiated thyroid cancer, the long-term survival is still 43%. The incidence of distant metastasis is highest in patients with follicular thyroid cancer. Appropriate initial evaluation and treatment will lead to satisfactory long-term survival.

Patterns of nodal and distant metastasis based on histologic varieties in differentiated carcinoma of the thyroid.

BACKGROUND: Understanding of differentiated carcinoma of the thyroid has improved in recent years with the definition of prognostic factors and risk group analysis. We intend to review our experience of differentiated thyroid cancer in relation to the risk of nodal and distant metastasis based on various histologic subgroups. METHODS: This is a retrospective review of a consecutive series of 1,038 previously untreated patients with differentiated carcinoma of the thyroid treated over a period of 55 years. Univariate and multivariate analysis of various prognostic factors was performed. The incidence of nodal and distant metastasis was analyzed based on various histologic varieties of differentiated thyroid cancer. RESULTS: There were 337 male and 701 female patients. The various histologic subgroups included papillary (810), follicular (169), and Hurthle cell cancer (59). The cumulative risk of nodal metastasis based on histological group was 61%, 30%, and 21% for papillary, follicular, and Hurthle cell variety, respectively. The risk of distant metastasis for the same histologic varieties was 10%, 22%, and 33%, respectively. The 5- and 20-year survival for these histologic subgroups was papillary (94% and 87%, respectively), follicular (87% and 81%), and Hurthle cell tumors (81% and 65%; P < 0.001). CONCLUSIONS: The incidence of nodal metastasis is highest in the papillary subgroup; however, the incidence of distant metastasis was 33% in the Hurthle cell variety. The risk of nodal and distant metastasis varies considerably based on individual histologic variety.

Major salivary gland lymphoepithelial lesions and the acquired immunodeficiency syndrome.

Presently, there is no consensus regarding the most appropriate diagnostic and therapeutic approach to patients with human immunodeficiency virus (HIV)-associated lymphoepithelial lesions of the major salivary glands. A retrospective review of 60 consecutive patients with lymphoepithelial lesions is presented. Thirty-eight cases were associated with HIV infection. Lesions associated with HIV infection were usually bilateral, multiple, cystic, and associated with lymphadenopathy. In contrast, in those cases without HIV infection, the lesions tended to be solitary and solid. In the HIV-infected group, treatment included surgery, radiotherapy, zidovudine (AZT), and/or cyst aspiration. All therapeutic regimens, other than aspiration alone, were found to be effective. Eighteen of the patients with HIV infection developed the acquired immunodeficiency syndrome (AIDS) during the study period. Surgical treatment is probably not necessary in the majority of HIV-associated cases. Depending upon individual circumstances, treatment with AZT or low-dose radiotherapy is recommended. A diagnostic and therapeutic algorithm is presented as a guide to the management of future cases.

Prognostic factors in differentiated carcinoma of the thyroid gland.

A retrospective review of a consecutive series of 931 previously untreated patients with differentiated thyroid carcinoma treated over a 50-year period was undertaken to analyze prognostic factors. Data pertaining to demographic status, clinical, operative, and pathologic findings, and survival were analyzed. Univariate statistical analysis was performed based on the Kaplan-Meier method and the log-rank test. Multivariate analysis was performed to assess the independent effect of these variables using the Cox model. There were 630 female and 301 male patients, with an average age of 43 years. A total of 532 patients were younger than 45 years. Seven hundred thirty-one patients had either pure or mixed papillary carcinoma, and 200 had follicular carcinoma. In 153 patients, lesions were larger than 4 cm. Extrathyroidal extension was noted in 71 patients. Multifocal lesions were present in 159 patients. Regional lymph node metastasis was present on admission in 451 patients, and distant metastases were noted on presentation in 45 patients. Determinate survival for all patients was 87% at 10 years. Favorable prognostic factors using univariate analysis included female gender, multifocal primary tumors, and regional lymph node metastases. Adverse prognostic factors included age over 45 years, follicular histology, extrathyroidal extension, tumor size exceeding 4 cm, and the presence of distant metastases. On multivariate analysis, the only factors that affected the prognosis were patient age, histology, tumor size, extrathyroidal extension, and distant metastases. These observations support findings of reports from the Mayo Clinic and Lahey Clinic regarding the significance of prognostic factors for differentiated carcinoma of the thyroid gland.

Differentiated carcinoma of the thyroid with extrathyroidal extension.

BACKGROUND: We have analyzed our experience with differentiated thyroid cancer patients with extrathyroidal extension (ETE) to investigate patterns of recurrence and define factors that predict failure. PATIENTS AND METHODS: The records of 1,012 patients treated surgically from 1930 to 1985 were reviewed. A total of 79 patients (8%) had ETE. The median length of follow-up was 10 years. RESULTS: Patients with ETE were more likely to fail treatment and to die of their disease than were patients without ETE (77% versus 34% and 71% versus 13%, respectively; P < 0.0001). Local, regional, and distant failures were more prominent among patients with ETE than among those without ETE (48% versus 9%, 41% versus 16%, and 37% versus 11% respectively; P < 0.0001). Survival of patients with ETE was adversely affected by nonpapillary histology, distant metastasis, age > 45, tumor size > 4 cm, and incomplete excision (P < or = 0.05). After stratification for age, survival in older patients was not affected by tumor size or incomplete excision, while in younger patients tumor size or the presence of distant metastasis did not adversely affect survival. Patients younger than 45 with negative margins had similar survival to patients without ETE (P = 0.46). CONCLUSIONS: Patients with ETE are more likely to die of their disease and to fail at all sites. Survival in older patients was not affected by incomplete excision while it was in younger patients. The presence of distant metastasis did not affect survival in younger patients. Our results suggest that among patients under 45, the presence of ETE does not adversely impact upon survival when the primary tumor is completely resected.