Rational Second-Generation Antiandrogen Use in Prostate Cancer.

The second-generation antiandrogens have achieved an ever-growing list of approvals and indications in subsets of prostate cancer. Here, we provide an overview of second-generation antiandrogen trials and FDA approvals and outline a rational sequencing approach for the use of these agents as they relate to chemotherapy and other available treatment modalities in advanced prostate cancer. All published phase II-III randomized controlled trials reporting outcomes with the use of second-generation antiandrogens in prostate cancer are included as well as all published trials and retrospective studies of second-generation antiandrogen sequencing and/or combinations. Complete tabular and graphical representation of all available evidence is provided regarding the use and sequencing of second-generation antiandrogens in prostate cancer. In metastatic castration-resistant prostate cancer, evidence suggests prioritization of abiraterone before chemotherapy, chemotherapy after second-generation antiandrogen failure, and postchemotherapy enzalutamide in select patients to maximize agent efficacy and tolerability. We conclude that a rational, optimized sequencing of second-generation antiandrogens with other treatment options is feasible with present data.

Chemotherapy with atezolizumab for small cell or neuroendocrine carcinoma of the prostate: A single institution experience.

INTRODUCTION: Chemotherapy in combination with immunotherapy has a proven survival benefit compared to chemotherapy alone in extensive stage small cell lung cancer (SCLC) and is the new standard of care. Since extrapulmonary small cell carcinomas (SCCs) are less common, treatment paradigms are reasonably extrapolated from SCLC regimens. We examined our institution's experience utilizing the combination of chemotherapy and immunotherapy (as used in SCLC) for SCC and neuroendocrine carcinoma of the prostate. METHODS: Utilizing an institutional database search tool, we queried the electronic medical record to identify patients with SCC or neuroendocrine carcinoma of the prostate who had been treated with atezolizumab and chemotherapy. We recorded patient characteristics, including age, pathology, and disease extent. Treatment characteristics included number of prior treatments, use of concominant androgen deprivation, number of cycles of immunotherapy, and prior systemic therapies (including those for adenocarcinoma of the prostate). Progression free survival (PFS) and overall survival (OS) were the primary outcomes. RESULTS: We identified seven men who received atezolizumab for metastatic prostate cancer with a small cell or neuroendocrine component. In six of the seven patients, the combination of carboplatin, etoposide, and atezolizumab was the first-line of treatment after diagnosis of small cell or neuroendocrine carcinoma. Two of the seven patients had de novo small cell/neuroendocrine pathology, while the other five had transformation from a preexisting adenocarcinoma. In the patients who received chemotherapy plus immunotherapy in the first-line setting, at a median follow-up of 6.5 months (range: 1.5-15.1) the median PFS was 3.4 months and median OS was 8.4 months. CONCLUSION: Small cell or neuroendocrine carcinoma of the prostate was associated with poor survival outcomes despite adding immunotherapy (atezolizumab) to chemotherapy (carboplatin and etoposide). To our knowledge, there has been no demonstrable benefit of adding immunotherapy to chemotherapy in this setting.

Chemoimmunotherapy after progression on single-agent pembrolizumab for metastatic urothelial carcinoma: a case series.

Those with metastatic urothelial carcinoma generally respond more poorly to chemotherapy after they have progression on a checkpoint inhibitor (CPI). There is interest in combining CPIs with conventional cytotoxic chemotherapies as a strategy to exploit the efficacy and immunomodulatory effects of chemotherapy. We conducted a single institution, retrospective analysis including all patients treated between May 2018 and May 2020 with carboplatin and paclitaxel, concurrently or sequential with pembrolizumab, after having progression on a CPI alone. Clinical characteristics, response by RECIST 1.1, progression-free survival, and safety/tolerance of the treatment are reported. Median age was 80 years (64-85). Five patients (100%) had visceral metastases when starting carboplatin and paclitaxel. Chemotherapy was given with concurrent pembrolizumab (four patients) or following pembrolizumab (one patient) and continued until maximum response, significant toxicity, or progression. Two patients subsequently remained on maintenance pembrolizumab. There were four partial responses and one patient with stable disease. All patients on follow-up have progressed with median time to progression of 47 weeks (18-75). Two patients died from disease progression. This case series suggests that the combination of carboplatin, paclitaxel, and pembrolizumab leads to durable freedom from progression in some with metastatic urothelial cancer, who have progressed on a CPI alone. Larger studies of chemoimmunotherapy for metastatic urothelial carcinoma are warranted.

Deep brain stimulation for treatment-resistant depression: an integrative review of preclinical and clinical findings and translational implications.

Although deep brain stimulation (DBS) is an established treatment choice for Parkinson's disease (PD), essential tremor and movement disorders, its effectiveness for the management of treatment-resistant depression (TRD) remains unclear. Herein, we conducted an integrative review on major neuroanatomical targets of DBS pursued for the treatment of intractable TRD. The aim of this review article is to provide a critical discussion of possible underlying mechanisms for DBS-generated antidepressant effects identified in preclinical studies and clinical trials, and to determine which brain target(s) elicited the most promising outcomes considering acute and maintenance treatment of TRD. Major electronic databases were searched to identify preclinical and clinical studies that have investigated the effects of DBS on depression-related outcomes. Overall, 92 references met inclusion criteria, and have evaluated six unique DBS targets namely the subcallosal cingulate gyrus (SCG), nucleus accumbens (NAc), ventral capsule/ventral striatum or anterior limb of internal capsule (ALIC), medial forebrain bundle (MFB), lateral habenula (LHb) and inferior thalamic peduncle for the treatment of unrelenting TRD. Electrical stimulation of these pertinent brain regions displayed differential effects on mood transition in patients with TRD. In addition, 47 unique references provided preclinical evidence for putative neurobiological mechanisms underlying antidepressant effects of DBS applied to the ventromedial prefrontal cortex, NAc, MFB, LHb and subthalamic nucleus. Preclinical studies suggest that stimulation parameters and neuroanatomical locations could influence DBS-related antidepressant effects, and also pointed that modulatory effects on monoamine neurotransmitters in target regions or interconnected brain networks following DBS could have a role in the antidepressant effects of DBS. Among several neuromodulatory targets that have been investigated, DBS in the neuroanatomical framework of the SCG, ALIC and MFB yielded more consistent antidepressant response rates in samples with TRD. Nevertheless, more well-designed randomized double-blind, controlled trials are warranted to further assess the efficacy, safety and tolerability of these more promising DBS targets for the management of TRD as therapeutic effects have been inconsistent across some controlled studies.

Identification of Recurrence Sites Following Post-Prostatectomy Treatment for Prostate Cancer Using 11C-Choline Positron Emission Tomography and Multiparametric Pelvic Magnetic Resonance Imaging.

PURPOSE: We describe anatomical sites of recurrence in patients with prostate cancer who had biochemical recurrence following radical prostatectomy and who received radiotherapy and/or androgen deprivation therapy postoperatively. We performed 11C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging. MATERIALS AND METHODS: After radiotherapy and/or androgen deprivation therapy patients who underwent radical prostatectomy were evaluated by 11C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging to determine recurrence patterns and clinicopathological features. Recurrent sites were described as local only (seminal vesicle bed/prostate fossa, vesicourethral anastomosis and bladder neck) or distant metastatic disease. Features associated with the identification of any distant metastatic disease were evaluated by multivariable logistic regression. RESULTS: A total of 550 patients were identified. Treatment included androgen deprivation therapy in 108, radiotherapy in 201, and androgen deprivation therapy and radiotherapy in 241. Median prostate specific antigen at evaluation was 3.9, 3.6 and 2.8 ng/ml in patients treated with androgen deprivation therapy, radiotherapy and a combination, respectively. Recurrence developed locally in 77 patients (14%), as distant metastasis only in 411 (75%), and as local and distant metastatic disease in 62 (11%). On multivariable analysis treatment with radiotherapy (OR 7.18, 95% CI 2.92-17.65), and radiotherapy and hormonal therapy (OR 9.23, 95% CI 3.90-21.87, all p <0.01) was associated with increased odds of distant failure at evaluation. CONCLUSIONS: The combination of 11C-choline positron emission tomography/computerized tomography and multiparametric magnetic resonance imaging successfully identified patterns of recurrence after postoperative radiotherapy and/or androgen deprivation therapy at a median prostate specific antigen of less than 4 ng/ml. Half of this cohort had local only recurrence and/or a low disease burden limited to pelvic lymph nodes. These patients may benefit from additional local therapy. These data and this analysis may facilitate the evaluation of such patients with biochemically recurrent prostate cancer.

Microbiological stabilization of tiger nuts' milk beverage using ultra-high pressure homogenization. A preliminary study on microbial shelf-life extension.

Tiger nuts' milk beverages are highly perishable products. For this reason, the interest of food industry for their commercialization makes necessary the application of preservation treatments to prolong their shelf-life. In the current study, the effect of ultra-high pressure homogenization (UHPH) on the microbiological and sensory qualities of tiger nuts' milk beverage was evaluated. Characteristics of UHPH-treated products (at 200 and 300 MPa, with inlet temperature of 40 °C) were compared with those of raw (RP) and conventionally homogenized-pasteurized (H-P) beverages, after treatment and during cold storage at 4 °C. Microbiological quality of beverages was studied by enumerating total counts, psychrotrophic bacteria, lactobacilli, enterobacteria, molds and yeasts, and mesophilic spores. Evolution of color and sensory characteristics of beverages were also determined. Microbiological shelf-life of the tiger nuts' milk beverages was extended from 3 to 25, 30 and 57 days by applying H-P and UHPH treatments at 200 and 300 MPa, respectively. Color of beverages was the only attribute that differentiated UHPH samples from the others, with greater luminosity and whiteness. Hence, UHPH treatments showed to be an alternative to the conventional H-P for obtaining tiger nuts' milk beverages with an improved microbiological shelf-life and good sensorial characteristics.

Lithium and memantine improve spatial memory impairment and neuroinflammation induced by ß-amyloid 1-42 oligomers in rats.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. The main hallmarks of this disease include progressive cognitive dysfunction and an accumulation of soluble oligomers of ß-amyloid (Aß) 1-42 peptide. In this research, we show the effects of lithium and memantine on spatial memory and neuroinflammation in an Aß1-42 oligomers-induced animal model of dementia in rats. Aß 1-42 oligomers were administered intrahippocampally to male wistar rats to induce dementia. Oral treatments with memantine (5mg/kg), lithium (5mg/kg), or both drugs in combination were performed over a period of 17days. 14days after the administration of the Aß1-42 oligomers, the radial arm-maze task was performed. At the end of the test period, the animals were euthanized, and the frontal cortex and hippocampus were removed for use in our analysis. Our results showed that alone treatments with lithium or memantine ameliorate the spatial memory damage caused by Aß1-42. The animals that received combined doses of lithium and memantine showed better cognitive performance in their latency time and total errors to find food when compared to the results from alone treatments. Moreover, in our study, lithium and/or memantine were able to reverse the decreases observed in the levels of interleukin (IL)-4 that were induced by Aß1-42 in the frontal cortex. In the hippocampus, only memantine and the association of memantine and lithium were able to reverse this effect. Alone doses of lithium and memantine or the association of lithium and memantine caused reductions in the levels of IL-1ß in the frontal cortex and hippocampus, and decreased the levels of TNF-α in the hippocampus. Taken together, these data suggest that lithium and memantine might be a potential therapy against cognitive impairment and neuroinflammation induced by Aß1-42, and their association may be a promising alternative to be investigated in the treatment of AD-like dementia.

Optimal duration of risperidone or olanzapine adjunctive therapy to mood stabilizer following remission of a manic episode: A CANMAT randomized double-blind trial.

Atypical antipsychotic adjunctive therapy to lithium or valproate is effective in treating acute mania. Although continuation of atypical antipsychotic adjunctive therapy after mania remission reduces relapse of mood episodes, the optimal duration is unknown. As many atypical antipsychotics cause weight gain and metabolic syndrome, they should not be continued unless the benefits outweigh the risks. This 52-week double-blind placebo-controlled trial recruited patients with bipolar I disorder (n=159) who recently remitted from a manic episode during treatment with risperidone or olanzapine adjunctive therapy to lithium or valproate. Patients were randomized to one of three conditions: discontinuation of risperidone or olanzapine and substitution with placebo at (i) entry ('0-weeks' group) or (ii) at 24 weeks after entry ('24-weeks' group) or (iii) continuation of risperidone or olanzapine for the full duration of the study ('52-weeks' group). The primary outcome measure was time to relapse of any mood episode. Compared with the 0-weeks group, the time to any mood episode was significantly longer in the 24-weeks group (hazard ratio (HR) 0.53; 95% confidence interval (CI): 0.33, 0.86) and nearly so in the 52-weeks group (HR: 0.63; 95% CI: 0.39, 1.02). The relapse rate was similar in the 52-weeks group compared with the 24-weeks group (HR: 1.18; 95% CI: 0.71, 1.99); however, sub-group analysis showed discordant results between the two antipsychotics (HR: 0.48, 95% CI: 0.17; 1.32 olanzapine patients; HR: 1.85, 95% CI: 1.00, 3.41 risperidone patients). Average weight gain was 3.2 kg in the 52-weeks group compared with a weight loss of 0.2 kg in the 0-weeks and 0.1 kg in the 24-weeks groups. These findings suggest that risperidone or olanzapine adjunctive therapy for 24 weeks is beneficial but continuation of risperidone beyond this period does not reduce the risk of relapse. Whether continuation of olanzapine beyond this period reduces relapse risk remains unclear but the potential benefit needs to be weighed against an increased risk of weight gain.

Bias in emerging biomarkers for bipolar disorder.

BACKGROUND: To date no comprehensive evaluation has appraised the likelihood of bias or the strength of the evidence of peripheral biomarkers for bipolar disorder (BD). Here we performed an umbrella review of meta-analyses of peripheral non-genetic biomarkers for BD. METHOD: The Pubmed/Medline, EMBASE and PsycInfo electronic databases were searched up to May 2015. Two independent authors conducted searches, examined references for eligibility, and extracted data. Meta-analyses in any language examining peripheral non-genetic biomarkers in participants with BD (across different mood states) compared to unaffected controls were included. RESULTS: Six references, which examined 13 biomarkers across 20 meta-analyses (5474 BD cases and 4823 healthy controls) met inclusion criteria. Evidence for excess of significance bias (i.e. bias favoring publication of 'positive' nominally significant results) was observed in 11 meta-analyses. Heterogeneity was high for (I 2 ⩾ 50%) 16 meta-analyses. Only two biomarkers met criteria for suggestive evidence namely the soluble IL-2 receptor and morning cortisol. The median power of included studies, using the effect size of the largest dataset as the plausible true effect size of each meta-analysis, was 15.3%. CONCLUSIONS: Our findings suggest that there is an excess of statistically significant results in the literature of peripheral biomarkers for BD. Selective publication of 'positive' results and selective reporting of outcomes are possible mechanisms.

Whiplash-Associated Disorders : Clinical and medico-legal guidelines on the methods of ascertainment.

The manuscript presents the International Guidelines developed by the Working Group on Personal Injury and Damage under the patronage of the International Academy of Legal Medicine (IALM) regarding the Methods of Ascertainment of any suspected Whiplash-Associated Disorders (WAD).The document includes a detailed description of the logical and methodological steps of the ascertainment process as well as a synoptic diagram in the form of Flow Chart.

Automatic control of pollutant on a shallow river using surface water systems: application to the Ebro River.

In this paper, the problem of automatic control of pollutant on a shallow river using surface water systems is addressed using a benchmark test case based in the Ebro River. The Ebro River presents flooding episodes in the city of Zaragoza in Spring when snow melts in the Pyrenees. To avoid flooding and high pollutant levels in living areas, some lands outside the city are prepared to be flooded. Going one step further, this paper is focused on the pollutant level control at a certain point downstream of the river under flooding episodes, and several control strategies for that purpose are presented and tested.

Genomic attributes of prostate cancer across primary and metastatic noncastrate and castrate resistant disease states: a next generation sequencing study of 183 patients.

Primary prostatic adenocarcinoma (pPC) undergoes genomic evolution secondary to therapy-related selection pressures as it transitions to metastatic noncastrate (mNC-PC) and castrate resistant (mCR-PC) disease. Next generation sequencing results were evaluated for pPC (n = 97), locally advanced disease (involving urinary bladder/rectum, n = 12), mNC-PC (n = 21), and mCR-PC (n = 54). We identified enrichment of TP53 alterations in high-grade pPC, TP53/RB1 alterations in HGNE disease, and AR alterations in metastatic and castrate resistant disease. Actionable alterations (MSI-H phenotype and HRR genes) were identified in approximately a fifth of all cases. These results help elucidate the landscape of genomic alterations across the clinical spectrum of prostate cancer.

"Malignant" perivascular epithelioid cell neoplasm: risk stratification and treatment strategies.

Purpose. Perivascular epithelioid cell tumors (PEComas) are a rare collection of tumors characterized by a myomelanocytic phenotype, and PEComas occurring in "nonclassic" anatomic distributions are known as perivascular epithelioid cell tumor not otherwise specified (PEComa-NOS). This review aims to compile and analyze cases of PEComa-NOS in an effort to better define their natural history. Design. We evaluated all 234 cases of PEComa-NOS reported in the English literature, extracting information regarding diagnostic features, treatment approaches, and outcomes. Multivariate analysis of a number of variables evaluable on pathologic review was performed to refine preexisting risk stratification criteria. Outcomes for patients receiving nonsurgical treatment are also reported. Results. Primary tumor size ≥5 cm (P = 0.02) and a high (1/50 HPF) mitotic rate (P < 0.0001) were the only factors significantly associated with recurrence following surgical resection. Cytotoxic chemotherapy and radiation therapy have shown little benefit in treating PEComa-NOS; mTOR inhibition is emerging as a treatment option. Conclusion. Progress has been made in understanding the natural history and molecular biology of PEComa-NOS. This review further clarifies risk of recurrence in this disease, allowing clinicians to better risk stratify patients. Further work should focus on applying this knowledge to making treatment decisions for patients with this disease.

Secondary prevention program for osteoporotic fractures and long-term adherence to bisphosphonates.

UNLABELLED: Our purpose was to assess the impact of a secondary prevention program for osteoporotic fractures in patients with fragility fracture and to determine its effect on long-term compliance with bisphosphonate treatment. Persistence with bisphosphonate use was 71%. Attending follow-up visits was the only variable significantly associated with adherence to bisphosphonates. INTRODUCTION: The aim of this study is to assess the impact a secondary prevention program for osteoporotic fractures in a prospective cohort of patients with at least one fragility fracture and to determine the effect of this intervention on long-term compliance with bisphosphonate treatment. METHODS: All patients older than 50 years with a fragility fracture attended at the emergency department over a 2-year period were appointed for a clinical visit through a telephone call. Two follow-up controls at 4 and 12 months were scheduled. After a mean of 4 years, a telephone survey was conducted to assess compliance with treatment. RESULTS: Of 683 eligible patients, 380 (55.6%) were visited at the hospital. Previous treatment with bisphosphonates was recorded in 17.9% of patients. DXA scan was considered normal in 61 patients and revealed osteopenia in 184 and osteoporosis in 135. Pharmacological treatment was indicated in 90% of patients (alendronate in 76%). Among 241 patients who participated in the survey, eight patients had new fractures (four were on treatment with bisphosphonates and four had discontinued treatment). Of 187 patients in which bisphosphonates were prescribed at the initial visit, 133 (71.1%) continued using bisphosphonates. Attendance of scheduled visits was associated with adherence to bisphosphonates (odds ratio, 3.33; 95% confidence interval, 2.99-3.67). CONCLUSIONS: The efficacy of the program to recruit patients was 55%. In patients visited at the hospital, treatment with bisphosphonates increased from 17.9% to 76%. Persistence with bisphosphonate use after a mean of 4 years was 71%. Attending follow-up visits was significantly associated with adherence to bisphosphonates.

Systemic blockade of TNF-α does not improve insulin resistance in humans.

The purpose of this study was to determine whether long-term modulation of inflammatory activity by tumor necrosis factor (TNF)-α inhibitors has some influence on insulin resistance (IR). 16 active rheumatoid arthritis (RA) patients without CV risk factors treated with anti-TNF-α agents were included in this study. RA activity by disease activity score 28, IR by HOMA2-IR, body composition by impedance analysis, physical activity by accelerometry, abdominal fat distribution by magnetic resonance imaging, and serum level of key adipokines by ELISA were measured at baseline and during a 1-year follow-up period. Patient body mass index increased significantly (26.94 ± 3.88 vs. 28.06 ± 4.57 kg/m2, p=0.02) after 1 year of treatment. Body composition, in terms of fat and fat-free mass, remained unchanged except for a significant elevation in body cell mass (25.50 ± 4.60 vs. 26.60 ± 3.17 kg, p=0.02). Basal levels of IR in the RA patients included in this study were significantly higher than healthy controls (1.6 ± 0.8 vs. 1.11 ± 0.56, p=0.011) but did not change during the follow-up. Nor did basal concentrations of adiponectin, visfatin, leptin, ghrelin, resistin, and apelin in response to anti-TNF-α treatment; only retinol-binding protein 4, showed a significant increase (51.7 ± 32.7 vs. 64.9 ± 28.4 µg/ml, p=0.03) at the end of the study. IR, adiposity distribution, and serum levels of most adipokines are not significantly affected by long-term inhibition of TNF-α in RA patients. Our data suggest that although systemic blockade of TNF-α exerts an anticachectic effect in RA patients, it does not seem to play a major role in IR.

PLIO: a generic tool for real-time operational predictive optimal control of water networks.

This paper presents a generic tool, named PLIO, that allows to implement the real-time operational control of water networks. Control strategies are generated using predictive optimal control techniques. This tool allows the flow management in a large water supply and distribution system including reservoirs, open-flow channels for water transport, water treatment plants, pressurized water pipe networks, tanks, flow/pressure control elements and a telemetry/telecontrol system. Predictive optimal control is used to generate flow control strategies from the sources to the consumer areas to meet future demands with appropriate pressure levels, optimizing operational goals such as network safety volumes and flow control stability. PLIO allows to build the network model graphically and then to automatically generate the model equations used by the predictive optimal controller. Additionally, PLIO can work off-line (in simulation) and on-line (in real-time mode). The case study of Santiago-Chile is presented to exemplify the control results obtained using PLIO off-line (in simulation).

Phase II Evaluation of Stereotactic Ablative Radiotherapy (SABR) and Immunity in 11C-Choline-PET/CT-Identified Oligometastatic Castration-Resistant Prostate Cancer.

PURPOSE: Outcomes for resistant metastatic castration-resistant prostate cancer (CRPC) are poor. Stereotactic ablative radiotherapy (SABR) induces antitumor immunity in clinical and preclinical studies, but immunologic biomarkers are lacking. PATIENTS AND METHODS: Eighty-nine patients with oligometastatic CRPC were identified by 11C-Choline-PET (Choline-PET) from August 2016 to December 2019 and treated with SABR. Prespecified coprimary endpoints were 2-year overall survival (OS) and PSA progression. Secondary endpoints included 2-year SABR-treated local failure and 6-month adverse events. Correlative studies included peripheral blood T-cell subpopulations before and after SABR. RESULTS: 128 lesions in 89 patients were included in this analysis. Median OS was 29.3 months, and 1- and 2-year OS were 96% and 80%, respectively. PSA PFS was 40% at 1 year and 21% at 2 years. Local PFS was 84.4% and 75.3% at 1 and 2 years, respectively, and no grade ≥3 AEs were observed. Baseline high levels of tumor-reactive T cells (TTR; CD8+CD11ahigh) predicted superior local, PSA, and distant PFS. Baseline high levels of effector memory T cells (TEM; CCR7-CD45RA-) were associated with improved PSA PFS. An increase in TTR at day 14 from baseline was associated with superior OS. CONCLUSIONS: This is the first comprehensive effector T-cell immunophenotype analysis in a phase II trial before and after SABR in CRPC. Results are favorable and support the incorporation of immune-based markers in the design of future randomized trials in patients with oligometastatic CRPC treated with SABR.

The prognostic importance of pathologically involved celiac node metastases in node-positive patients with carcinoma of the distal esophagus or gastroesophageal junction: a surgical series from the Mayo Clinic.

The management of esophageal cancer with involvement of celiac lymph nodes is controversial. The purpose of this retrospective study was to evaluate the clinical importance of metastases to celiac lymph nodes in patients with carcinoma of the distal esophagus or gastroesophageal junction (GEJ) who undergo surgical treatment with curative intent. We reviewed the medical records of 310 patients who underwent definitive esophagectomy at the Mayo Clinic, Rochester, Minnesota, between 1976 and 1999 for carcinoma of the distal esophagus or GEJ. The disease location was distal esophagus in 163 and GEJ in 147. Fifty-two patients (17%) were found to have celiac node involvement. The survival of these patients was compared with that of 97 N0 patients and 161 N1 patients without celiac node involvement. Squamous cell carcinoma and adenocarcinomas were found in 24% and 76%, respectively. Ivor Lewis esophagectomy was the most common surgical procedure (76%), followed by transhiatal resection (14%) and modified Ivor Lewis procedure (5%). The median number of nodes resected was 15 (range, 2-45). The median survival of the entire group was 18.8 months. The median survival was 48 months (range, 1.6 months-22 years) for N0 patients and 15.9 months (range, 0.03 months-14.4 years) for N1 patients without celiac node disease (P < 0.001). The median survival was 11.7 months (range, 2.2 months-15.7 years) for celiac node-positive patients, and this difference was statistically significant when compared with survival in N0 patients (P= 0.001) but not when compared with that in N1 patients without celiac node disease (P= 0.57). Survival at 3 and 5 years was 61% and 45% for N0 patients, 21% and 9% for N1 patients without celiac node disease, and 18% and 11% for patients with celiac node disease, respectively. At 10 years, 7% of patients with celiac node involvement in their resected specimen were alive. By multivariate analysis, patients with 4 or more positive lymph nodes had the worst prognosis (risk ratio [RR], 2.63; 95% confidence interval [CI], 1.98-3.48), regardless of their location. We concluded that celiac node metastases were not an adverse prognostic indicator in patients with celiac node involvement compared with N1 patients without celiac node disease. Overall, the number of positive nodes, not their location, correlated best with survival. Although median survival was poor, a small number of patients with resected celiac node disease had long-term survival. Patients with undetected celiac node disease at the time of surgical resection who were subsequently found to have celiac node involvement appeared to have a prognosis similar to that of patients with stage III disease. Therefore, treatment with curative intent should be considered for fit patients with celiac node disease.