Experiences of African Americans Living With Sickle Cell Disease.

INTRODUCTION: About 100,000 individuals in the United States live with sickle cell disease (SCD). Palliative care (PC) can improve symptom management for these individuals. The purpose of the study was to explore (a) the experiences of people living with SCD, and (b) their knowledge and perceptions of PC. METHOD: Using a qualitative, descriptive design, adults with SCD were recruited from a foundation in the southeastern United States. Data included social and SCD-related demographics and audio-recorded, semi-structured focus groups. Analysis took a thematic analysis approach. RESULTS: Participants: There were 16 African Americans who participated in the study, 75% of whom were females, and aged 22 to 71 years. Five themes were identified: unique and unpredictable impact of SCD on daily life, the changing experience of SCD over time, stigmatization/marginalization in health care interactions, perceptions of support in managing SCD symptoms/crises, and PC: "What is it?" DISCUSSION: Participants lacked PC knowledge. PC should be offered to individuals with SCD as part of comprehensive SCD management.

Variable disease manifestations and metabolic management within a single family affected by ornithine transcarbamylase deficiency.

We report on a family with ornithine transcarbamylase (OTC) deficiency, an X-linked urea cycle disorder, with variable disease severity and tailored management strategies based on each family member's biochemical profile and clinical presentation. Our primary patient is a female monozygotic twin who presented to medical care at 10 months of age with acute liver failure, gastrointestinal symptoms, altered mental status, hypoglycemia, and hyperammonemia. The patient's older brother, known to have hemizygous OTC deficiency, died at 8 months of age from cardiac arrest after complications secondary to his diagnosis. Despite her family history, manifestation of symptoms of heterozygous (partial) OTC deficiency went unrecognized by multiple providers based on misconceptions regarding a female's risk for X-linked disease. Despite barriers related to the family's low socioeconomic status, follow-up care by a multidisciplinary metabolic care team, including moderate protein restriction and nitrogen scavenger therapy, led to positive outcomes for the patient. Her twin sister and mother are also heterozygous for variants in OTC and remain controlled on moderate protein restriction. This case illustrates the importance of genotyping all individuals with genetic risk factors for OTC deficiency and the variability in disease manifestation that necessitates tailored treatment approaches for individuals with partial OTC deficiency.

Dengue Virus Infections among Peace Corps Volunteers in Timor-Leste, 2018-2019.

Dengue is an ongoing health risk for Peace Corps Volunteers (PCVs) working in the tropics. On May 2019, the Peace Corps Office of Health Services notified the Centers for Disease Control and Prevention (CDC) of a dengue outbreak among PCVs in Timor-Leste. The purpose of this investigation was to identify the clinical, demographic, and epidemiological characteristics of PCVs with dengue and recommend dengue preventive measures. To identify PCVs with dengue and describe disease severity, the medical records of PCVs reporting fever during September 2018-June 2019 were reviewed. To identify factors associated with dengue virus (DENV) infection, we administered a questionnaire on demographics, travel history, and mosquito avoidance behaviors and collected blood specimens to detect the anti-DENV IgM antibody to diagnose recent infection. Of 35 PCVs in-country, 11 (31%) tested positive for dengue (NS1, IgM, PCR), eight requiring hospitalization and medical evacuation. Among 27 (77%) PCVs who participated in the investigation, all reported having been recently bitten by mosquitoes and 56% reported being bitten most often at home; only 16 (59%) reported having screens on bedroom windows. Nearly all (93%) PCVs reported using a bed net every night; fewer (70%) reported using mosquito repellent at least once a day. No behaviors were significantly associated with DENV infection. Raising awareness of dengue risk among PCVs and continuing to encourage mosquito avoidance behavior to prevent dengue is critical. Access to and use of measures to avoid mosquito bites should be improved or implemented. Peace Corps medical officers should continue to receive an annual refresher training on dengue clinical management.

Significance of tumour regression in lymph node metastases of gastric and gastro-oesophageal junction adenocarcinomas.

The presence of lymph node (LN) metastases is one of the most important negative prognostic factors in upper gastrointestinal carcinomas. Tumour regression similar to that in primary tumours can be observed in LN metastases after neoadjuvant therapy. We evaluated the prognostic impact of histological regression in LNs in 480 adenocarcinomas of the stomach and gastro-oesophageal junction after neoadjuvant chemotherapy. Regressive changes in LNs (nodular and/or hyaline fibrosis, sheets of foamy histiocytes or acellular mucin) were assessed by histology. In total, regressive changes were observed in 128 of 480 patients. LNs were categorised according to the absence or presence of both residual tumour and regressive changes (LN-/+ and Reg-/+). 139 cases were LN-/Reg-, 28 cases without viable LN metastases revealed regressive changes (LN-/Reg+), 100 of 313 cases with LN metastases showed regressive changes (LN+/Reg+), and 213 of 313 metastatic LN had no signs of regression (LN+/Reg-). Overall, LN/Reg categorisation correlated with overall survival with the best prognosis for LN-/Reg- and the worst prognosis for LN+/Reg- (p < 0.001). LN-/Reg+ cases had a nearly significant better outcome than LN+/Reg+ (p = 0.054) and the latter had a significantly better prognosis than LN+/Reg- (p = 0.01). The LN/Reg categorisation was also an independent prognostic factor in multivariate analysis (HR = 1.23; 95% CI 1.1-1.38; p < 0.001). We conclude that the presence of regressive changes after neoadjuvant treatment in LNs and LN metastases of gastric and gastro-oesophageal junction cancers is a relevant prognostic factor.

Macroscopic Evaluation of the Trimmed Frozen Block Is a Helpful Tool for Intraoperative Assessment of Resection Margins of Breast Cancer Specimens.

INTRODUCTION: The evaluation of the trimming surfaces (TS) of tissue blocks from frozen sections may serve as a supplementary examination tool for the intraoperative determination of resection margins of breast cancer specimens. This study aimed at the investigation of the feasibility and reliability of this technique, which has been described only very rarely in literature. METHODS: Two observers assessed digital images from TS obtained from 57 resection margins. Findings were correlated with the diagnosis of the frozen section (FS) alone and the final diagnosis on formalin-fixed paraffin-embedded (FFPE) material. RESULTS: The determination of the resection margin on TS was estimated as feasible for all cases. Interobserver congruence rate for TS was 96% (κ = 0.81), which was lower compared with FFPE (100%, κ = 1.0) but superior to FS (89%, κ = 0.67). Intraobserver congruence of the 2 reviewers was 96.5% and 93.0% between TS and FFPE, and 91.1% and 92.5% between FS and FFPE, respectively. The combination of both intraoperative consultation techniques showed similar congruence but a slight improvement for the sensitivity (0.75 to 0.875) for the diagnosis of tumor at the resection margin in FFPE for Reviewer 1 but was unchanged for Reviewer 2. CONCLUSION: The additional evaluation of TS can be a helpful additional tool for intraoperative margin assessment of breast cancer specimens, in particular, when processing artifacts of FS are encountered.

Correction to: MicroRNA expression profiling for the prediction of resistance to neoadjuvant radiochemotherapy in squamous cell carcinoma of the esophagus.

Following publication of the original article [1], the authors reported that for one of the authors, Stephanie E. Combs, the middle name was accidentally omitted. They also reported that for two of the authors, Daniel Habermehl and Stephanie E. Combs, two affiliations were accidentally omitted. In this Correction the incorrect and correct author name are shown and the two omitted affiliations are listed.

MicroRNA expression profiling for the prediction of resistance to neoadjuvant radiochemotherapy in squamous cell carcinoma of the esophagus.

BACKGROUND: MicroRNAs (miRNAs) play an important role in cancer biology. Neoadjuvant radiochemotherapy followed by surgery is a standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). However, a subset of patients do not respond. We evaluated whether miRNA profiles can predict resistance to radiochemotherapy. METHODS: Formalin-fixed, paraffin-embedded pretherapeutic biopsies of patients treated by radiochemotherapy followed by esophagectomy were analyzed. The response was determined by histopathological tumor regression grading. miRNA profiling was performed by microarray analysis (Agilent platform) in 16 non-responders and 15 responders. Differentially expressed miRNAs were confirmed by real-time quantitative PCR (qRT-PCR) in an expanded cohort of 53 cases. RESULTS: The miRNA profiles within and between non-responders and responders were highly similar (r = 0.96, 0.94 and 0.95). However, 12 miRNAs were differentially expressed (> twofold; p ≤ 0.025): non-responders showed upregulation of hsa-miR-1323, hsa-miR-3678-3p, hsv2-miR-H7-3p, hsa-miR-194*, hsa-miR-3152, kshv-miR-K12-4-3p, hsa-miR-665 and hsa-miR-3659 and downregulation of hsa-miR-126*, hsa-miR-484, hsa-miR-330-3p and hsa-miR-3653. qRT-PCR analysis confirmed the microarray findings for hsa-miR-194* and hsa-miR-665 (p < 0.001 each) with AUC values of 0.811 (95% CI 0.694-0.927) and 0.817 (95% CI 0.704-0.930), respectively, in ROC analysis. CONCLUSIONS: Our results indicate that miRNAs are involved in the therapeutic response in ESCC and suggest that miRNA profiles could facilitate pretherapeutic patient selection.

Protracted Outbreak of Salmonella Newport Infections Linked to Ground Beef: Possible Role of Dairy Cows - 21 States, 2016-2017.

In January 2017, CDC identified a cluster of Salmonella enterica serotype Newport infections with isolates sharing an indistinguishable pulsed-field gel electrophoresis (PFGE) pattern, JJPX01.0010 (pattern 10), through PulseNet, the national molecular subtyping network for foodborne disease surveillance. This report summarizes the investigation by CDC, state and local health and agriculture departments, and the U.S. Department of Agriculture's Food Safety and Inspection Service (USDA-FSIS) and discusses the possible role of dairy cows as a reservoir for strains of Salmonella that persistently cause human illness. This investigation combined epidemiologic and whole genome sequencing (WGS) data to link the outbreak to contaminated ground beef; dairy cows were hypothesized to be the ultimate source of Salmonella contamination.

Intensified Sampling in Response to a Salmonella Heidelberg Outbreak Associated with Multiple Establishments Within a Single Poultry Corporation.

On June 28, 2013, the Food Safety and Inspection Service (FSIS) was notified by the Centers for Disease Control and Prevention (CDC) of an investigation of a multistate cluster of illnesses of Salmonella enterica serovar Heidelberg. Since case-patients in the cluster reported consumption of a variety of chicken products, FSIS used a simple likelihood-based approach using traceback information to focus on intensified sampling efforts. This article describes the multiphased product sampling approach taken by FSIS when epidemiologic evidence implicated chicken products from multiple establishments operating under one corporation. The objectives of sampling were to (1) assess process control of chicken slaughter and further processing and (2) determine whether outbreak strains were present in products from these implicated establishments. As part of the sample collection process, data collected by FSIS personnel to characterize product included category (whole chicken and type of chicken parts), brand, organic or conventional product, injection with salt solutions or flavorings, and whether product was skinless or skin-on. From the period September 9, 2013, through October 31, 2014, 3164 samples were taken as part of this effort. Salmonella percent positive declined from 19.7% to 5.3% during this timeframe as a result of regulatory and company efforts. The results of intensified sampling for this outbreak investigation informed an FSIS regulatory response and corrective actions taken by the implicated establishments. The company noted that a multihurdle approach to reduce Salmonella in products was taken, including on-farm efforts such as environmental testing, depopulation of affected flocks, disinfection of affected houses, vaccination, and use of various interventions within the establishments over the course of several months.

Tumor regression grading of gastrointestinal cancers after neoadjuvant therapy.

Neoadjuvant therapy has been successfully introduced in the treatment of locally advanced gastrointestinal malignancies, particularly esophageal, gastric, and rectal cancers. The effects of preoperative chemo- or radiochemotherapy can be determined by histopathological investigation of the resection specimen following this treatment. Frequent histological findings after neoadjuvant therapy include various amounts of residual tumor, inflammation, resorptive changes with infiltrates of foamy histiocytes, foreign body reactions, and scarry fibrosis. Several tumor regression grading (TRG) systems, which aim to categorize the amount of regressive changes after cytotoxic treatment in primary tumor sites, have been proposed for gastroesophageal and rectal carcinomas. These systems primarily refer to the amount of therapy-induced fibrosis in relation to the residual tumor (e.g., the Mandard, Dworak, or AJCC systems) or the estimated percentage of residual tumor in relation to the previous tumor site (e.g., the Becker, Rödel, or Rectal Cancer Regression Grading systems). TRGs provide valuable prognostic information, as in most cases, complete or subtotal tumor regression after neoadjuvant treatment is associated with better patient outcomes. This review describes the typical histopathological findings after neoadjuvant treatment, discusses the most commonly used TRG systems for gastroesophageal and rectal carcinomas, addresses the limitations and critical issues of tumor regression grading in these tumors, and describes the clinical impact of TRG.

Macroscopy predicts tumor progression in gastric cancer: A retrospective patho-historical analysis based on Napoleon Bonaparte's autopsy report.

BACKGROUND: The cause of Napoleon Bonaparte's death remains controversial. Originally suggested to be gastric cancer, whether this was truly neoplastic or a benign lesion has been recently debated. AIMS: To interpret findings of original autopsy reports in light of the current knowledge of gastric cancer and to highlight the significance of accurate macroscopy in modern-day medicine. METHODS: Using original autopsy documents, endoscopic images and data from current literature, Napoleon's gastric situation was reconstructed. In a multicenter collection of 2071 gastric cancer specimens, the relationship between tumor size and features of tumor progression was assessed. RESULTS: Greater tumor size was associated with advanced pT, nodal metastases and Borrmann types 3-4 (p<0.001). The best cut-off for predicting pT3-4 tumors was 6.5cm (AUC 0.8; OR 1.397, 95% CI 1.35-1.446), and 6cm for lymph node metastases (AUC 0.775; OR 1.389, 95% CI 1.338-1.442). The 6cm cut-off of had a positive predictive value of 0.820 for nodal metastases and a negative predictive value of 0.880 for distant metastases. CONCLUSION: This analysis combines Napoleon's autopsy with present-day knowledge to support gastric cancer as his terminal illness and emphasizes the role of macroscopy, which may provide valuable information on gastric cancer progression and aid patient management.

Maffucci syndrome and neoplasms: a case report and review of the literature.

BACKGROUND: Maffucci syndrome is characterized by the sporadic occurrence of multiple enchondromas together with multiple hemangiomas. Patients with Maffucci syndrome are at increased risk of developing different kinds of malignant tumors. CASE PRESENTATION: We report on a 39-year-old woman who was diagnosed with Maffucci syndrome together with intrahepatic cholangiocarcinoma (IHCC). Heterozygous somatic mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) genes are associated with a number of different tumor types (e.g. IHCC) and also with Maffucci syndrome. For IHCC, mutations in IDH1/IDH2 are associated with higher survival rates. IHCC tissue as well as normal liver tissue and peripheral blood were analyzed for IDH1/IDH2-mutations in our patient. In the tumor sample, we identified a recurrent somatic IDH1-mutation affecting Arg132, while in normal liver tissue and peripheral blood, no variants were detected, as expected. CONCLUSION: This case report presents the second patient in the literature exhibiting the features of Maffucci syndrome along with cholangiocarcinoma. This supports the hypothesis that IDH1/2-mutations, which can be present in different types of tumor tissue simultaneously, arise during embryonic development in a mosaic pattern; as a result, a more aggressive follow-up is proposed in patients with Maffucci syndrome to exclude neoplasms.

Bronchogenic cancer: It still exists.

OBJECTIVES/HYPOTHESIS: Branchial cleft cysts rank among the most common differential diagnoses of cystic cervical masses. Rarely, classic cystic structures exhibit a squamous cell carcinoma differentiation that represents a bronchogenic carcinoma. The existence of bronchogenic carcinoma is controversial due to the lack of systematic immunohistologic workup. The present study aimed to identify the clinical and immunohistologic features of bronchogenic carcinoma to clearly distinguish this entity from other cystic cervical masses. METHODS: Immunohistologic (epidermal growth factor receptor; cytokeratin 5, 6, 7, 13; and p16) and epidemiologic assessments were performed for branchial cleft cysts (n = 63), bronchogenic carcinomas (n = 5), cystic metastasized oropharyngeal carcinomas (n = 97), and carcinomas of unknown primary (n = 51). The study was conducted as a retrospective case series study with comparison. RESULTS: The patients with bronchogenic carcinomas differed significantly in age and in the number of involved lymph nodes compared with the cystic metastasized oropharyngeal carcinoma (and carcinoma of unknown primary) patients. Regular histologic wall structures were only observed in the bronchogenic carcinomas and branchial cleft cysts. Solitary cytokeratin-7 staining was only observed in the bronchogenic carcinomas, and all of the bronchogenic carcinomas were p16 negative. CONCLUSIONS: The existence of bronchogenic carcinoma seems to be plausible based on clinical findings. Cytokeratin-7 and p16 staining might be helpful in the diagnostic workflow. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:638-642, 2016.

Clinical Significance of NOTCH1 and NOTCH2 Expression in Gastric Carcinomas: An Immunohistochemical Study.

BACKGROUND: NOTCH signaling can exert oncogenic or tumor suppressive functions and can contribute to chemotherapy resistance in cancer. In this study, we aimed to clarify the clinicopathological significance and the prognostic and predictive value of NOTCH1 and NOTCH2 expression in gastric cancer (GC). METHODS: NOTCH1 and NOTCH2 expression was determined immunohistochemically in 142 primarily resected GCs using tissue microarrays and in 84 pretherapeutic biopsies from patients treated by neoadjuvant chemotherapy. The results were correlated with survival, response to therapy, and clinico-pathological features. RESULTS: Primarily resected patients with NOTCH1-negative tumors demonstrated worse survival. High NOTCH1 expression was associated with early-stage tumors and with significantly increased survival in this subgroup. Higher NOTCH2 expression was associated with early-stage and intestinal-type tumors and with better survival in the subgroup of intestinal-type tumors. In pretherapeutic biopsies, higher NOTCH1 and NOTCH2 expression was more frequent in non-responding patients, but these differences were statistically not significant. CONCLUSION: Our findings suggested that, in particular, NOTCH1 expression indicated good prognosis in GC. The close relationship of high NOTCH1 and NOTCH2 expression with early tumor stages may indicate a tumor-suppressive role of NOTCH signaling in GC. The role of NOTCH1 and NOTCH2 in neoadjuvantly treated GC is limited.

Cisplatin fails to induce puma mediated apoptosis in mucosal melanomas.

OBJECTIVES: Mucosal melanomas (MM) are aggressive subtypes of common melanomas. It remains unclear whether limitations in their resectability or their distinctive molecular mechanisms are responsible for the aggressive phenotype. METHODS: In total, 112 patients with cutaneous melanomas (CM) and 27 patients with MM were included. Clinical parameters were analysed using Chi square, Fisher exact and student's t-test. Survival rates were calculated by Kaplan-Meier. Analysis of p53, p21, Mdm2, Hipk2, Gadd45, Puma, Bax, Casp9 and Cdk1 via quantitative PCR and immunohistochemistry (IHC) was performed. TP53 induction after cisplatin treatment was analysed in 10 cell lines (melanocytes, four MM and five CM) using western blot (WB) and qPCR. RESULTS: The overall/recurrence-free survival differed significantly between MM (40 months and 30 months) and CM (90 months and 107 months; p < 0.001). IHC and WB confirmed high p53 expression in all melanomas. Hipk2 and Gadd45 showed significantly higher expressions in CM (p < 0.005; p = 0.004). QPCR and WB of wild-type cell lines demonstrated no differences for p53, p21, Mdm2, Bax and Casp9. WB failed to detect Puma in MM, while Cdk1 regulation occurred exclusively in MM. CONCLUSIONS: The aggressive phenotype of MM did not appear to be due to differential expressions of p53, p21, Mdm2, Bax or Casp9. A non-functional apoptosis in MM may have further clinical implications.

Post-therapeutic response evaluation by a combination of endoscopy and CT scan in esophagogastric adenocarcinoma after chemotherapy: better than its reputation.

BACKGROUND: Neoadjuvant chemotherapy is an accepted standard of care for locally advanced esophagogastric cancer. As only a subgroup benefits, a response-based tailored treatment would be of interest. The aim of our study was the evaluation of the prognostic and predictive value of clinical response in esophagogastric adenocarcinomas. METHODS: Clinical response based on a combination of endoscopy and computed tomography (CT) scan was evaluated retrospectively within a prospective database in center A and then transferred to center B. A total of 686/740 (A) and 184/210 (B) patients, staged cT3/4, cN0/1 underwent neoadjuvant chemotherapy and were then re-staged by endoscopy and CT before undergoing tumor resection. Of 184 patients, 118 (B) additionally had an interim response assessment 4-6 weeks after the start of chemotherapy. RESULTS: In A, 479 patients (70%) were defined as clinical nonresponders, 207 (30%) as responders. Median survival was 38 months (nonresponders: 27 months, responders: 108 months, log-rank, p < 0.001). Clinical and histopathological response correlated significantly (p < 0.001). In multivariate analysis, clinical response was an independent prognostic factor (HR for death 1.4, 95% CI 1.0-1.8, p = 0.032). In B, 140 patients (76%) were nonresponders and 44 (24%) responded. Median survival was 33 months, (nonresponders: 27 months, responders: not reached, p = 0.003). Interim clinical response evaluation (118 patients) also had prognostic impact (p = 0.008). Interim, preoperative clinical response and histopathological response correlated strongly (p < 0.001). CONCLUSION: Preoperative clinical response was an independent prognostic factor in center A, while in center B its prognostic value could only be confirmed in univariate analysis. The accordance with histopathological response was good in both centers, and interim clinical response evaluation showed comparable results to preoperative evaluation.

The impact of neural invasion severity in gastrointestinal malignancies: a clinicopathological study.

OBJECTIVES: Because neural invasion (NI) is still inconsistently reported and not well characterized within gastrointestinal malignancies (GIMs), our aim was to determine the exact prevalence and severity of NI and to elucidate the true impact of NI on patient's prognosis. BACKGROUND: The union internationale contre le cancer (UICC) recently added NI as a novel parameter in the current TNM classification. However, there are only a few existing studies with specific focus on NI, so that the distinct role of NI in GIMs is still uncertain. MATERIALS AND METHODS: NI was characterized in approximately 16,000 hematoxylin and eosin tissue sections from 2050 patients with adenocarcinoma of the esophagogastric junction (AEG)-I-III, squamous cell carcinoma (SCC) of the esophagus, gastric cancer (GC), colon cancer (CC), rectal cancer (RC), cholangiocellular cancer (CCC), hepatocellular cancer (HCC), and pancreatic cancer (PC). NI prevalence and severity was determined and related to patient's prognosis and survival. RESULTS: NI prevalence largely varied between HCC/6%, CC/28%, RC/34%, AEG-I/36% and AEG-II/36%, SCC/37%, GC/38%, CCC/58%, and AEG-III/65% to PC/100%. NI severity score was uppermost in PC (24.9±1.9) and lowest in AEG-I (0.8±0.3). Multivariable analyses including age, sex, TNM stage, and grading revealed that the prevalence of NI was significantly associated with diminished survival in AEG-II/III, GC, and RC. However, increasing NI severity impaired survival in AEG-II/III and PC only. CONCLUSIONS: NI prevalence and NI severity strongly vary within GIMs. Determination of NI severity in GIMs is a more precise tool than solely recording the presence of NI and revealed dismal prognostic impact on patients with AEG-II/III and PC. Evidently, NI is not a concomitant side feature in GIMs and, therefore, deserves special attention for improved patient stratification and individualized therapy after surgery.

Epidermal growth factor receptor (EGFR) is an independent adverse prognostic factor in esophageal adenocarcinoma patients treated with cisplatin-based neoadjuvant chemotherapy.

Neoadjuvant platin-based therapy is accepted as a standard therapy for advanced esophageal adenocarcinoma (EAC). Patients who respond have a better survival prognosis, but still a significant number of responder patients die from tumor recurrence. Molecular markers for prognosis in neoadjuvantly treated EAC patients have not been identified yet. We investigated the epidermal growth factor receptor (EGFR) in prognosis and chemotherapy resistance in these patients. Two EAC patient cohorts, either treated by neoadjuvant cisplatin-based chemotherapy followed by surgery (n=86) or by surgical resection (n=46) were analyzed for EGFR protein expression and gene copy number. Data were correlated with clinical and histopathological response, disease-free and overall survival. In case of EGFR overexpression, the prognosis for neoadjuvant chemotherapy responders was poor as in non-responders. Responders had a significantly better disease-free survival than non-responders only if EGFR expression level (p=0.0152) or copy number (p=0.0050) was low. Comparing neoadjuvantly treated patients and primary resection patients, tumors of non-responder patients more frequently exhibited EGFR overexpression, providing evidence that EGFR is a factor for indicating chemotherapy resistance. EGFR overexpression and gene copy number are independent adverse prognostic factors for neoadjuvant chemotherapy-treated EAC patients, particularly for responders. Furthermore, EGFR overexpression is involved in resistance to cisplatin-based neoadjuvant chemotherapy.