Undergarment Needs and Challenges for Breast Cancer Survivors: A Qualitative Study.

Purpose: Breast cancer surgery, even with reconstruction, can make it difficult for patients to find a bra that fits properly, is comfortable, and meets their aesthetic standards. We explored breast cancer survivors' experiences with bras over time to identify preferences, needs, and challenges throughout their journeys. Methods: Fifteen women who had undergone mastectomy and either delayed or immediate breast reconstruction participated in the study. Focus groups were conducted to explore the participants' current experiences with bras. They were also prompted to recall their experiences before mastectomy and immediately after reconstruction. The discussion included bra materials, styles, construction techniques, color, quality, and price. Results: Thematic analysis generated five major themes: "Sense of normalcy and personal well-being," "Struggles immediately following surgery," "Transitions in bra experiences and preference," "Practicality with outfit," and "Association between quality and price". Conclusion: Breast cancer survivors' well-being is linked to their experiences with bras and the associated purchasing process, and bra needs change throughout the cancer care journey. Survivors' experiences with bras impact their sense of normalcy and sense of control over significant bodily changes arising from cancer and its treatment. The study underscores the importance of future research on examining the relationship between survivors' quality of life and garment experiences, including factors such as color choices, closure options, and adjustability for individual needs.

Impact of autologous breast reconstruction on bra fit.

PURPOSE: To inform bra design by analyzing 3D surface images of breast cancer patients who underwent autologous breast reconstruction. METHODS: We computed bra design measurements on 3D surface images of patients who underwent unilateral and bilateral autologous breast reconstruction. Breast measurements and right-left symmetry between preoperative baseline and postoperative time points were compared using either paired Student t-test or Wilcoxon signed-rank test, depending on the data's distribution. Regression analysis determined associations between measurements and patient characteristics such as age. Postoperative measurements and symmetry differences were also compared between autologous and implant-based breast reconstruction. RESULTS: Among participants who underwent bilateral autologous breast reconstruction, the reconstructed breasts were smaller and positioned higher on the chest wall than their native breasts. For patients who underwent unilateral reconstruction, similar postoperative changes were observed in the contralateral breast due to symmetry procedures. Overall, for participants whose baseline breast measurements showed substantial asymmetry, unilateral reconstruction decreased right-left asymmetry whereas bilateral reconstruction amplified right-left asymmetry. Preoperative baseline breast measurements, age, and BMI were statistically significantly associated with most postoperative breast measurements for participants who underwent bilateral autologous reconstruction. Compared to implant-based reconstruction, autologous reconstruction resulted in fewer changes in breast shape and symmetry that are pertinent to bra fit. CONCLUSION: Preoperative baseline breast measurements, age, and BMI can impact bra designs for breast cancer survivors who undergo autologous reconstruction due to size, shape, and symmetry changes. Bra needs of people who undergo autologous reconstruction differ from those who undergo implant-based reconstruction.

Impact of Autologous Breast Reconstruction on Bra Fit.

Purpose: To inform bra design by analyzing 3D surface images of breast cancer patients who underwent autologous breast reconstruction. Methods: We computed bra design measurements on 3D surface images of patients who underwent unilateral and bilateral autologous breast reconstruction. Breast measurements and right-left symmetry between preoperative baseline and postoperative time points were compared using either paired Student t test or Wilcoxon signed rank test, depending on the data's distribution. Regression analysis determined associations between measurements and patient characteristics such as age. Postoperative measurements and symmetry differences were also compared between autologous and implant-based breast reconstruction. Results: Among participants who underwent bilateral autologous breast reconstruction, the reconstructed breasts were smaller and positioned higher on the chest wall than their native breasts. For patients who underwent unilateral reconstruction, similar postoperative changes were observed in the contralateral breast due to symmetry procedures. Overall, for participants whose baseline breast measurements showed substantial asymmetry, unilateral reconstruction decreased right-left asymmetry whereas bilateral reconstruction amplified right-left asymmetry. Preoperative baseline breast measurements, age, and BMI were statistically significantly associated with most postoperative breast measurements for participants who underwent bilateral autologous reconstruction. Compared to implant-based reconstruction, autologous reconstruction resulted in fewer changes in breast shape and symmetry that are pertinent to bra fit. Conclusion: Preoperative baseline breast measurements, age, and BMI can impact bra designs for breast cancer survivors who undergo autologous reconstruction due to size, shape, and symmetry changes. Bra needs of people who undergo autologous reconstruction differ from those who undergo implant-based reconstruction.

High-Risk Features of Esophageal Adenocarcinoma Following Neoadjuvant Chemoradiation: Patients for Whom Surgery Should Not Be Delayed.

OBJECTIVE: Clinical predictors of pathological complete response have not reliably identified patients for whom an organ-sparing approach following neoadjuvant chemoradiation be undertaken for esophageal cancer patients. We sought to identify high-risk predictors of residual carcinoma that may preclude patients from a selective surgical approach. BACKGROUND: Patients treated with neoadjuvant chemoradiation followed by esophagectomy for esophageal adenocarcinoma were identified. PATIENTS AND METHODS: Correlation between clinical and pathologic complete responses were examined. Regression models and recursive partitioning were utilized to identify features associated with residual carcinoma. External validation of these high-risk factors was performed on a data set from an independent institution. RESULTS: A total of 326 patients were identified, in whom clinical complete response was noted in 104/326 (32%). Pathologic complete response was noted in only 33/104 (32%) of these clinical complete responders. Multivariable analysis identified that the presence of stricture ( P =0.011), positive biopsy ( P =0.010), and signet ring cell histology ( P =0.019) were associated with residual cancer. Recursive partitioning corroborated a 94% probability of residual disease, or greater, for each of these features. The positive predictive value was >90% for these characteristics. A SUV max >5.4 at the esophageal primary in the absence of esophagitis was also a high-risk factor for residual carcinoma. External validation confirmed these high-risk factors to be implicated in the finding of residual carcinoma. CONCLUSIONS: Clinical parameters of response are poor predictors of complete pathologic response leading to challenges in selecting candidates for active surveillance. However, we characterize several high-risk features for residual carcinoma which indicate that esophagectomy should not be delayed.

Cytoplasmic Cyclin E Expression Predicts for Response to Neoadjuvant Chemotherapy in Breast Cancer.

BACKGROUND: Pathologic complete response (pCR) has been shown to be associated with favorable outcomes in breast cancer. Predictors of pCR could be useful in guiding treatment decisions regarding neoadjuvant therapy. The objective of this study was to evaluate cyclin E as a predictor of response to neoadjuvant chemotherapy in breast cancer. METHODS: Patients (n = 285) with stage II-III breast cancer were enrolled in a prospective study and received neoadjuvant chemotherapy with anthracyclines, taxanes, or combination of the two. Pretreatment biopsies from 190 patients and surgical specimens following chemotherapy from 192 patients were available for immunohistochemical analysis. Clinical and pathologic responses were recorded and associated with presence of tumor infiltrating lymphocytes, cyclin E, adipophilin, programmed cell death-ligand 1, and elastase staining and other patient, tumor and treatment characteristics. RESULTS: The pCR rate was significantly lower in patients with cytoplasmic cyclin E staining compared with those who had no cyclin E expression (16.1% vs 38.9%, P = 0.0005). In multivariable logistic regression analysis, the odds of pCR for patients who had cytoplasmic negative tumors was 9.35 times (P value < 0.0001) that compared with patients with cytoplasmic positive tumors after adjusting for ER, PR, and HER2 status. Cytoplasmic cyclin E expression also predicts long-term outcome and is associated with reduced disease free, recurrence free, and overall survival rates, independent of increased pretreatment tumor infiltrating lymphocytes. CONCLUSIONS: Cyclin E independently predicted response to neoadjuvant chemotherapy. Hence, its routine immunohistochemical analysis could be used clinically to identify those breast cancer patients expected to have a poor response to anthracycline/taxane-based chemotherapy.

IL-24 Promotes Apoptosis through cAMP-Dependent PKA Pathways in Human Breast Cancer Cells.

Interleukin 24 (IL-24) is a tumor-suppressing protein, which inhibits angiogenesis and induces cancer cell-specific apoptosis. We have shown that IL-24 regulates apoptosis through phosphorylated eukaryotic initiation factor 2 alpha (eIF2α) during endoplasmic reticulum (ER) stress in cancer. Although multiple stresses converge on eIF2α phosphorylation, the cellular outcome is not always the same. In particular, ER stress-induced apoptosis is primarily regulated through the extent of eIF2α phosphorylation and activating transcription factor 4 (ATF4) action. Our studies show for the first time that cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) activation is required for IL-24-induced cell death in a variety of breast cancer cell lines and this event increases ATF4 activity. We demonstrate an undocumented role for PKA in regulating IL-24-induced cell death, whereby PKA stimulates phosphorylation of p38 mitogen-activated protein kinase and upregulates extrinsic apoptotic factors of the Fas/FasL signaling pathway and death receptor 4 expression. We also demonstrate that phosphorylation and nuclear import of tumor suppressor TP53 occurs downstream of IL-24-mediated PKA activation. These discoveries provide the first mechanistic insights into the function of PKA as a key regulator of the extrinsic pathway, ER stress, and TP53 activation triggered by IL-24.

Eukaryotic Translation Initiation Factor 4A Down-Regulation Mediates Interleukin-24-Induced Apoptosis through Inhibition of Translation.

Dysregulated activity of helicase eIF4A drives transformation to and maintenance of cancer cell phenotype by reprogramming cellular translation. Interleukin 24 (IL-24) is a tumor-suppressing protein, which has the ability to inhibit angiogenesis, sensitize cancer cells to chemotherapy, and induce cancer cell-specific apoptosis. In this study, we found that eIF4A is inhibited by IL-24. Consequently, selective reduction of translation was observed for mRNAs harboring strong secondary structures in their 5'-untranslated regions (5'UTRs). These mRNAs encode proteins, which function in cell survival and proliferation. Consistently, overexpression of eIF4A conferred cancer cells with resistance to IL-24-induced cell death. It has been established that inhibition of eIF4A triggers mitochondrial-mediated apoptosis. We showed that IL-24 induces eIF4A-dependent mitochondrial depolarization. We also showed that IL-24 induces Sigma 1 Receptor-dependent eIF4A down-regulation and mitochondrial depolarization. Thus, the progress of apoptosis triggered by IL-24 is characterized by a complex program of changes in regulation of several initiation factors, including the eIF4A.

Translation Control by p53.

The translation of mRNAs plays a critical role in the regulation of gene expression and therefore, in the regulation of cell proliferation, differentiation and apoptosis. Unrestricted initiation of translation causes malignant transformation and plays a key role in the maintenance and progression of cancers. Translation initiation is regulated by the ternary complex and the eukaryotic initiation factor 4F (eIF4F) complex. The p53 tumor suppressor protein is the most well studied mammalian transcription factor that mediates a variety of anti-proliferative processes. Post-transcriptional mechanisms of gene expression in general and those of translation in particular play a major role in shaping the protein composition of the cell. The p53 protein regulates transcription and controls eIF4F, the ternary complex and the synthesis of ribosomal components, including the down-regulation of rRNA genes. In summary, the induction of p53 regulates protein synthesis and translational control to inhibit cell growth.

CDK4/6 Inhibitors Sensitize Rb-positive Sarcoma Cells to Wee1 Kinase Inhibition through Reversible Cell-Cycle Arrest.

Research into the biology of soft tissue sarcomas has uncovered very few effective treatment strategies that improve upon the current standard of care which usually involves surgery, radiation, and chemotherapy. Many patients with large (>5 cm), high-grade sarcomas develop recurrence, and at that point have limited treatment options available. One challenge is the heterogeneity of genetic drivers of sarcomas, and many of these are not validated targets. Even when such genes are tractable targets, the rarity of each subtype of sarcoma makes advances in research slow. Here we describe the development of a synergistic combination treatment strategy that may be applicable in both soft tissue sarcomas as well as sarcomas of bone that takes advantage of targeting the cell cycle. We show that Rb-positive cell lines treated with the CDK4/6 inhibitor palbociclib reversibly arrest in the G1 phase of the cell cycle, and upon drug removal cells progress through the cell cycle as expected within 6-24 hours. Using a long-term high-throughput assay that allows us to examine drugs in different sequences or concurrently, we found that palbociclib-induced cell-cycle arrest poises Rb-positive sarcoma cells (SK-LMS1 and HT-1080) to be more sensitive to agents that work preferentially in S-G2 phase such as doxorubicin and Wee1 kinase inhibitors (AZD1775). The synergy between palbociclib and AZD1775 was also validated in vivo using SK-LMS1 xenografts as well as Rb-positive patient-derived xenografts (PDX) developed from leiomyosarcoma patients. This work provides the necessary preclinical data in support of a clinical trial utilizing this treatment strategy. Mol Cancer Ther; 16(9); 1751-64. ©2017 AACR.

Effects of filament size on critical current density in overpressure processed Bi-2212 round wire.

Bi2Sr2CaCu2Ox (Bi-2212) conductor is the only high temperature superconductor manufactured as a round wire and is a very promising conductor for very high field applications. One of the key design parameters of Bi-2212 wire is its filament size, which has been previously reported to affect the critical current density (Jc ) and ac losses. Work with 1 bar heat treatment showed that the optimal filament diameter was about 15 µm but it was not well understood at that time that gas bubbles were the main current limiting mechanism. Here we investigated a recent Bi-2212 wire with a 121×18 filament architecture with varying wire diameter (1.0 to 1.5 mm) using 50 bar overpressure processing. This wire is part of a 1.2 km piece length of 1.0 mm diameter made by Oxford Superconducting Technology. We found that Jc is independent of the filament size in the range from 9 to 14 µm, although the n value increased with increasing filament size. A new record Jc (4.2 K, 15 T) of 4200 A/mm2 and JE (4.2 K, 15 T) of 830 A/mm2 were achieved.

Global Adverse Event Reports of Breast Implant-Associated ALCL: An International Review of 40 Government Authority Databases.

BACKGROUND: Tracking world cases of breast implant-associated anaplastic large cell lymphoma (ALCL) is currently limited to patient registries at a few academic centers, dependent upon patient referral and case reports in the literature. The purpose of this study was to review and compare federal database adverse event reports of breast implant-associated ALCL encompassing the major breast implant markets worldwide. METHODS: Federal implantable device regulatory bodies were contacted and database queries were performed for 40 countries. Demographics, device characteristics, pathology, treatment modalities, and outcomes were assessed when available. RESULTS: For the countries queried, 363 unique cases were reported for breast implant-associated ALCL. Search terms "anaplastic" and "ALCL" were queried of the U.S. Manufacturer and User Facility Device Experience (MAUDE) database and yielded 258 unique cases as of September 2015, of which only 130 had pathologic markers performed. Implant surface was textured significantly more than smooth (50 percent versus 4.2 percent; p = 0.0001). Treatment, when reported (n = 136), included explantation [n = 125 (91.9 percent)], chemotherapy [n = 42 (30.8 percent)], radiation therapy [n = 25 (18.4 percent)], and/or stem cell transplant [n = 9 (6.6 percent)], and five deaths were reported. CONCLUSIONS: Federal reporting of breast implant-associated ALCL has limitations in providing clinical history, treatment, and oncologic follow-up. Worldwide and country-specific total and textured implant sales data are needed to determine critical incidence and prevalence analysis. International multi-institutional collaborations and centralized tissue consortiums working in concert with federal authorities are necessary to acquire accurate complete data on breast implant-associated ALCL.

Is Sentinel Lymph Node Dissection Warranted for Patients with a Diagnosis of Ductal Carcinoma In Situ?

BACKGROUND: Positive sentinel lymph node (SLN) findings in ductal carcinoma in situ (DCIS) range from 1 to 22 % but have unknown biologic significance. This study sought to identify predictors of positive SLNs and to assess their clinical significance for patients with an initial diagnosis of DCIS. METHODS: The study identified 1234 patients with an initial diagnosis of DCIS who underwent SLN dissection (SLND) at our institution from 1997 through 2011. Positive SLN findings were categorized as isolated tumor cells (ITCs) (≤0.2 mm), micrometastases (>0.2-2 mm), or macrometastases (>2 mm). Predictors of positive SLNs were analyzed, and survival outcomes were examined. RESULTS: Positive SLN findings were identified in 132 patients (10.7 %): 66 patients with ITCs (5.4 %), 36 patients with micrometastases (2.9 %), and 30 patients with macrometastases (2.4 %). Upstaging to microinvasive (n = 68, 5.5 %) or invasive (n = 259, 21.0 %) cancer occurred for 327 patients (26.5 %). Factors predicting positive SLNs included diagnosis by excisional biopsy (odds ratio [OR] 1.90; P = 0.007), papillary histology (OR 1.77; P = 0.006), DCIS larger than 2 cm (OR 1.55; P = 0.030), more than three interventions before SLND (4 interventions: OR 2.04; P = 0.022; ≥5 interventions: OR 3.87; P < 0.001), and occult invasion (microinvasive: OR 3.44; P = 0.001; invasive: OR 6.21; P < 0.001). The median follow-up period was 61.7 months. Patients who had pure DCIS with and without positive SLNs had equivalent survival rates (100.0 vs 99.7 %; P = 0.679). Patients with occult invasion and positive SLNs had the worst survival rate (91.7 %; P < 0.001). CONCLUSIONS: Occult invasion and more than three total interventions were the strongest predictors of positive SLN findings in patients with an initial diagnosis of DCIS. This supports the theory of benign mechanical transport of breast epithelial cells. Except for patients at high risk for invasive disease, routine use of SLND in DCIS is not warranted.

The influence of histopathologic tumor viability on long-term survival and recurrence rates following neoadjuvant therapy for esophageal adenocarcinoma.

OBJECTIVE: Our aim was to validate the effect of histopathologic tumor viability (HTV) on extended survival outcomes and assess the prognostic ability of the current staging system in patients receiving preoperative chemoradiotherapy (CRT). BACKGROUND: The American Joint Committee on Cancer, 7th Edition, esophageal carcinoma staging system is derived from patients treated with surgery alone and does not account for the treatment effect of CRT. The extent of HTV after CRT is based on response to neoadjuvant therapy and has been shown to correlate with patient outcome. METHODS: Medical records of 1278 patients who underwent esophagectomy (1990-2011) were reviewed; 784 patients underwent preoperative CRT. Histologic tumor viability was assessed in 602 patients and classified as 0% to 10%, 11% to 50%, and more than 50%. Survival was estimated using the Kaplan-Meier method at potential median follow-up of 67 months. Univariate and multivariate analyses identified variables associated with survival. RESULTS: Multivariate analysis identified HTV of greater than 50% (P < 0.001, HR 2.5), positive pathologic nodal status (P < 0.001, HR 1.6), and positive clinical nodal status (P = 0.002, HR 1.5) but not pathologic T status (P = 0.816, HR 1.2) to be independently associated with survival. Actuarial 5- and 10-year survival was 52% and 43% (HTV of 0%-10%), 45% and 33% (HTV of 11%-50%), and 16% for both (HTV of >50%). The best 5-year survival 56% was achieved in N0 patients with HTV of 0% to 10% (P = 0.056, HR 1.0), contrary to 6% observed in node-positive patients with HTV of greater than 50% (P < 0.001, HR 3.1). Patients with HTV of greater than 50% demonstrated distant recurrence more frequently than those with HTV of less than 50% (51% vs 33%, P = 0.010, OR: 2.2) CONCLUSIONS:: After preoperative chemoradiation, long-term outcomes of esophageal carcinoma are best predicted utilizing histologic tumor viability; HTV may be a practical early endpoint predicting efficacy of therapy.

Impact of tumor length on long-term survival of pT1 esophageal adenocarcinoma.

INTRODUCTION: The impact of esophageal tumor length on pT1 esophageal adenocarcinoma has not been well evaluated. METHODS: Case histories of all patients (n = 133) undergoing esophageal resection from 1979 to 2007 with pT1 adenocarcinoma of the esophagus were reviewed. Univariate and multivariate analyses of esophageal tumor length and other standard prognostic factors were performed. RESULTS: Patients with early-stage pT1 esophageal adenocarcinoma with tumors less than 3 cm demonstrate decreased long-term survival (3 years: >3 cm = 46% vs 93%; P < .001) and higher risk of lymph node involvement (lymph node positive: >3 cm = 47% vs 10%; P < .001). Multivariable analysis shows that esophageal tumor length (>3 cm) is an independent risk factor for survival in patients with pT1 early-stage esophageal cancer (hazard ratio: 4.8, 95% confidence intervals: 1.4-16.5; P < .001) even when controlled for submucosal involvement, lymph node involvement, and lymphatic/vascular invasion status. In combination with submucosal involvement, esophageal tumor length (>3 cm) identifies a high-risk population of pT1 esophageal adenocarcinoma (3 years: group 1 [0 risk factors] = 100%, group 2 [1 risk factor] = 87%, and group 3 [2 risk factors] = 33%; P < .001). CONCLUSIONS: This study demonstrates that esophageal tumor length (>3 cm) is a risk factor for long-term survival and lymph node involvement in early-stage pT1 esophageal adenocarcinoma. Esophageal tumor length (>3 cm) in combination with submucosal involvement may help to identify a high-risk group of patients with pT1 esophageal adenocarcinoma.

Esophageal tumor length is independently associated with long-term survival.

BACKGROUND: Esophageal cancer staging uses tumor depth as the sole criterion for assessment of the primary tumor (pT). To the authors' knowledge the impact of esophageal tumor length on long-term outcome and the esophageal cancer staging system has not been fully evaluated in the current era. METHODS: All esophageal cancer patients (n = 209) undergoing surgery from 1995 to 2005 who did not receive preoperative chemotherapy or radiotherapy were reviewed. Maximum esophageal tumor length along a craniocaudal axis was determined pathologically after surgical resection. Univariate and multivariate analyses were used to assess the impact of esophageal tumor length (< or = 3 cm vs >3 cm) on long-term survival. RESULTS: Esophageal tumor length was closely associated with long-term survival (hazards ratio [HR] of 6.14 [95% confidence interval (95% CI), 4.1-9.25]; 5-year survival: < or = 3 cm = 68%, >3 cm = 10% [P < .001]). Multivariate Cox regression analyses demonstrated tumor length (HR of 2.13 [95% CI, 1.26-3.63]) was found to be a significant independent predictor of long-term survival even when controlled for sex, age, tumor location, histology, margin positivity, surgical procedure, and current pTNM criteria. The incorporation of tumor length in pTNM staging significantly improves the ability to predict the long-term survival of patients (5-year survival for patients with tumors < or = 3 cm and stages I, IIA, IIB, and III disease = 86%, 62%, 49%, and 22%, respectively; survival for patients with tumors measuring >3 cm and stages I, IIA, IIB, and III disease = 27%, 22%, 0%, and 8%, respectively [P < .1]). CONCLUSIONS: Esophageal tumor length is an independent predictor of long-term survival in the current era and should be considered for incorporation into the current esophageal cancer staging system to better predict long-term survival and identify high-risk patients for postoperative therapy.

Followup of patients with papillary thyroid cancer: in search of the optimal algorithm.

BACKGROUND: Cervical recurrence occurs in up to 30% of patients after surgical treatment for papillary thyroid cancer. This study sought to determine an appropriate algorithm for followup evaluation. STUDY DESIGN: Patients undergoing total thyroidectomy for papillary thyroid cancer were identified. Clinicopathologic data were recorded, as were the results of all followup evaluations including radioiodine scan, cervical ultrasonography, and serum thyroglobulin levels. The disease recurrence-free survival probability was estimated, and risk factors for recurrence were determined. RESULTS: Thyroidectomy with or without neck dissection was performed in 162 patients. We excluded 36 patients (followup less than 6 months in 26, extracervical disease at diagnosis in 4, unknown tumor size in 6) from the analysis. Of the remaining 126 patients, 109 (86.5%) had no evidence of disease, with serum thyroglobulin < 1 ng/mL at last followup; 4 (3.2%) had no evidence of disease (negative imaging), with serum thyroglobulin > 1 ng/mL, and 13 (10.3%) had recurrent disease. Cervical recurrence occurred in nine patients, all detected by routine ultrasonography. Pulmonary metastases occurred in four patients; three were diagnosed by chest CT and one by radioiodine scan. Thyroid stimulating hormone-suppressed thyroglobulin levels were available in 11 of the 13 patients and were elevated in 9. Patients with high T stage (extrathyroidal extension), or high N stage had an increased risk of recurrence. CONCLUSIONS: A followup strategy emphasizing routine cervical ultrasonography and unstimulated thyroglobulin is effective in identifying patients with recurrent papillary thyroid cancer, and may minimize the indiscriminate use of therapeutic radioiodine for radiographically occult disease. Surgery remains the optimal treatment of cervical recurrence, which is the dominant pattern of treatment failure.

Proposed modification of nodal status in AJCC esophageal cancer staging system.

BACKGROUND: The current American Joint Committee on Cancer (AJCC) esophageal cancer staging for nodal status is difficult to interpret and is based solely on lymph node location relative to the primary tumor's esophageal location. Recent reports suggest that the number of lymph nodes involved is also an important factor. We reviewed our esophageal experience to propose an improved nodal staging system. METHODS: In all, 1,027 patients with resected esophageal cancer from 1970 to 2005 were reviewed. Lymph nodes stations were assigned according to AJCC criteria. Overall survival was assessed by Kaplan-Meier analysis. The impact of location, number of involved lymph nodes, and use of preoperative chemotherapy or radiation therapy, or both, was assessed. RESULTS: Nonregional nodal involvement (n = 17) was associated with decreased survival compared with regional (n = 441) or celiac nodal (n = 73) involvement (3-year: 0% versus 24% and 23%; p < 0.001). The number of involved lymph nodes was strongly associated with survival (3-year: 0 nodes = 63%, 1 to 3 nodes = 31%, more than 3 nodes = 13%; p < 0.001), and multivariable Cox proportional-hazards analysis suggested that the location and number of involved lymph nodes were independent predictors of survival (p < 0.001). We propose a modified nodal staging system that designates celiac nodes as regional and includes number of involved nodes: pN0, no nodes (3 years = 63%, n = 496); pN1-regional, 1 to 3 nodes (3 years = 32%, n = 292); pN2-regional, more than 3 nodes (3 years = 14%, n = 222); pN3-nonregional node (3 years = 0%, n = 17 [p < 0.0001]). This modified nodal staging system better predicts survival than the current AJCC nodal staging system in which survival for pN1 (3 years = 24%) and pM1a (3 years = 23%) do not differ (p = 0.67). The use of induction before surgical resection did not alter the predictive effect of the new nodal staging system. CONCLUSIONS: Modification of the AJCC nodal classification system to incorporate the number of involved lymph nodes with regional and nonregional node location simplifies and better predicts long-term survival than does the current AJCC nodal system.