Squamous Cell Carcinoma Of The Esophagus Research Articles

Endoscopic or Surgical Resection for Gastro-Esophageal Cancer.

Early gastro-esophageal cancer is staged as m1 to m3 depending on the infiltration of the anatomical layers of the mucosa or, analogously, as sm1 to sm3 depending on the depth of infiltration into the submucosa. The risk of lymph node metastases is low in mucosal carcinoma but increases with the depth of infiltration into the submucosa. This review is based on pertinent publications retrieved by a selective search in MEDLINE, PubMed, the Cochrane Library, and the International Standard Randomised Controlled Trial Number (ISRCTN) registry. New technologies such as narrow-band imaging have improved the endo- scopic diagnosis and staging of early gastro-esophageal cancer. The development of endoscopic submucosal dissection has led to a higher R0 resection rate, a lower risk of recurrence, and an increase in the number of endoscopic resections that are performed with curative intent. In squamous-cell carcinoma of the esophagus, surgical oncological esophagectomy is indicated if the cancer infiltrates into the third mucosal layer (T1a, m3) or deeper. In esophageal adenocarcinoma, the prevalence of lymph node metastases is low if the cancer is restricted to the mucosa and in- creases only when the submucosa is infiltrated. In the current German S3 guideline, endoscopic resection is recommended for intramucosal adenocarcinoma as long as there are no further histopathological risk factors. Lymph node metastasis in gastric carcinoma begins in the deep mucosal infiltration stage (m3). If certain special con- ditions ("extended criteria") are met, carcinoma expanding into the first submucosal layer (sm1) can be removed endoscopically. All further stages must be treated with total or subtotal gastrectomy with systematic D2 lymphadenectomy. Borderline cases between endoscopic and surgical resection of early carcinoma of the esophagus or stomach must be managed with an interdisciplinary treatment algorithm. If there is a risk of lymph node metastasis, surgical oncological resection is indicated. Such resections of gastroesophageal cancer in the locally advanced stage should always be part of a multimodal treatment approach.

Comparison of definite chemoradiation therapy with carboplatin/paclitaxel or cisplatin/5-fluoruracil in patients with squamous cell carcinoma of the esophagus

BackgroundWhile neoadjuvant chemoradiation therapy (nCRT) with subsequent surgery is the treatment of choice for patients with locally advanced or node-positive squamous cell carcinoma of the esophagus (SCC) suitable for surgery, patients who are unsuitable for surgery or who refuse surgery should be treated with definite chemoradiation therapy (dCRT). Purpose of this study was to compare toxicity and oncologic outcome of dCRT with either cisplatin and 5-fluoruracil (CDDP/5FU) or carboplatin and paclitaxel (Carb/TAX) in patients with SCC.MethodsTwenty-two patients who received dCRT with carboplatin (AUC2, weekly) and paclitaxel (50 mg per square meter of body-surface area, weekly) were retrospectively compared to 25 patients who were scheduled for dCRT with cisplatin (20 mg/m2/d) and 5-fluoruracil (500 mg/m2/d) on day 1–5 and day 29–33. For the per-protocol (PP) analysis, PP treatment was defined as complete radiation therapy with at least 54Gy and at least three complete cycles of Carb/TAX or complete radiation therapy with at least 54Gy and at least one complete cycle of CDDP/5FU. While patients who were scheduled for dCRT with Carb/TAX received a significantly higher total radiation dose (median dose 59.4Gy vs. 54Gy, p < 0.001) than patients who were scheduled for dCRT with CDDP/5FU, no significant differences were seen for other parameters (age, sex, TNM-stage, grading and tumor extension).ResultsForty-seven patients (25 patients treated with CDDP/5FU and 22 patients treated with Carb/TAX) were evaluated for the intention-to-treat (ITT) analysis and 41 of 47 patients (23 patients treated with CDDP/5FU and 18 patients treated with Carb/TAX) were evaluated for the PP analysis. Severe myelotoxicity (≥ III°) was seen in 52% (CDDP/5FU) and 55% of patients (Carb/TAX), respectively (p = 1.000). In the univariate binary logistic regression analysis, patients age was the only factor associated with an increased risk of ≥ III° myelotoxicity (hazard ratio 1.145, 95% CI 1.035; 1.266; p = 0.009). Regarding treatment efficiency, no significant differences were seen for overall survival (OS) and freedom from relapse (FFR) between both treatment groups.ConclusionMyelotoxicity and oncologic outcome under dCRT were not different for patients with SCC of the esophagus treated with either CDDP/5FU or Carb/TAX. The putative equivalence of dCRT with Carb/TAX in this setting should be further investigated in prospective trials. However, our data reveal that the risk of significant myelotoxicity increases with patient age and therefore other chemotherapy regimens might be evaluated in elderly patients.

Expression of vasohibin-1 and -2 predicts poor prognosis among patients with squamous cell carcinoma of the esophagus.

Vasohibin (VASH) -1 and -2 are novel angiogenic regulators. The aim of the present study was to assess the prognostic values of VASH1 expression and VASH2 expression in esophageal squamous cell carcinoma (ESCC). A total of 209 patients with ESCC were investigated. Resected tumor specimens were immunostained using anti-CD34 antibody, anti-VASH1 antibody and anti-VASH2 antibody. The ratio of the microvessels density and the VASH1 density as the VASH1-positive ratio were defined and the patients were divided into two groups (a high VASH1 group and a low VASH1 group) according to the average value. The patients were also divided into two groups (a high VASH2 group and a low VASH2 group) according to VASH2 expression upon immunostaining. The clinical outcomes of these two groups were then evaluated. The high VASH1 group contained 106 patients (50.7%). The high VASH2 group contained 48 patients (23.0%). Long-term survival was significantly poorer in the high VASH1 group compared with that in the low VASH1 group. A slight correlation between VASH1 expression and VASH2 expression was observed. The low VASH1/low VASH2 group had a better prognosis than the other three groups with different combinations of VASH1 and VASH2 expression levels. The present study showed that high VASH1 expression and high VASH2 expression may be novel independent predictors of a poor prognosis in patients with ESCC and that a slight correlation between VASH1 and VASH2 expression existed. The present findings suggest that combined evaluation of VASH1 and VASH2 expression should provide an improved understanding of their clinicopathological features.

Esophageal cancer associated with a sarcoid-like reaction and systemic sarcoidosis in lymph nodes: supportive findings of [18F]-fluorodeoxyglucose positron emission tomography\u2013computed tomography during neoadjuvant therapy

BackgroundIn patients with esophageal cancer, differentiation between lymph node metastasis and lymphadenopathies from sarcoidosis or sarcoid-like reactions of lymph nodes is clinically important. Herein, we report two esophageal cancer cases with lymph node involvement of sarcoid-like reaction or sarcoidosis.Case presentationOne patient received chemotherapy and the other chemoradiotherapy as initial treatments. In both cases, [18F]-fluorodeoxyglucose positron emission tomography–computed tomography (FDG-PET/CT) was performed before and after chemo(radio)therapy. After the treatment, FDG uptake was not detected in the primary tumor, but it was slightly reduced in the hilar and mediastinal lymph nodes in both cases. These non-identical responses to chemo(radio)therapy suggest the presence of sarcoid-like reaction of lymph nodes associated with squamous cell carcinoma of the esophagus. Curative surgical resection was performed as treatment.ConclusionsThese FDG-PET/CT findings may be helpful to distinguish between metastasis and sarcoidosis-associated lymphadenopathy in esophageal cancer.

Timing of esophagectomy after neoadjuvant chemoradiation treatment in squamous cell carcinoma

BackgroundTime interval between neoadjuvant (combined) chemotherapy and radiation (nCRT) and surgery has been linked to pathologic response rates and outcomes in patients with various solid cancers. The optimal timing between nCRT and esophagectomy in patients with esophageal squamous cell carcinoma (SCC), however, is not known. Our aim was to analyze the relation between elapsed time from completion of nCRT to esophagectomy and postsurgical mortality and overall survival. MethodsWe reviewed the National Cancer Database for patients with SCC (n = 1,244) of the esophagus diagnosed between 2003 and 2011 who were treated with nCRT followed by esophagectomy within 26 weeks after completion of nCRT. ResultsThirty-day mortality was 5.6% and 90-day mortality was 11.1%. The duration of post-nCRT interval was not a predictor of 30-day and 90-day postoperative mortality in multivariate models, but 30-day postoperative mortality was predictable based on increasing Charlson-Deyo comorbidities (adjusted odds ratio [aOR] 1.77, P = .054) and improved in academic institutions (aOR 0.66, P = .005). Similar findings were found for 90-day mortality (comorbidity index aOR 1.58, P = .046) and for treatment at an academic facility (0.82, P = .062). In a multivariate survival analysis, the duration of the post-nCRT interval was not found to be a predictor of overall survival (P = .769), whereas increasing age (hazard ratio [HR] 1.02, P = .005), increasing comorbidity score (HR 1.38, P = .005), treatment at an academic hospital (HR 0.84, P = .001), and post-treatment nodal status (HR 1.73, P < .001) were predictors. ConclusionPerioperative mortality and overall survival are not affected by the time interval between completion of nCRT and esophagectomy among patients with SCC histology.

Recent advancements in esophageal cancer treatment in Japan.

The 11th edition of the Japanese Classification of Esophageal Cancer (EC) was published in 2017. Some correction was made in the depth of tumor invasion to be consistent with the TNM classification by the Union for International Cancer Control (UICC). With regard to surgery, short‐term safety and long‐term effectiveness under thoracotomy/video‐assisted thoracoscopic surgery are expected to be proven by the Japan Clinical Oncology Group (JCOG)1409 study. Results of nutritional management and countermeasures for adverse events not only during the perioperative period but also during EC chemotherapy were reported. From now on, the pursuit of low invasiveness and radicality is desired. Esophageal surgery is also expected to be safe at all institutions. To determine the optimal modality of preoperative treatment and a novel chemo(radio)therapy regimen for patients with distant metastasis, the results of the ongoing JCOG1109 and 0807 studies are being released. The effect of the addition of molecular targeted drugs on chemotherapy and concurrent chemoradiation has not yet improved overall survival. Immune checkpoint inhibitor drugs could offer a potential new treatment approach for patients with treatment‐refractory advanced squamous cell carcinoma (SCC). The Cancer Genome Atlas Research Network reported the results of a comprehensive genome analysis and molecular analysis of SCC and adenocarcinoma of the esophagus. Further differentiation of SCC and adenocarcinoma by molecular characterization analysis may be useful for the development of clinical trials and targeted drug therapies as precision medicine. The era of ultimate minimally invasive surgery and personalized treatment has begun. Large, prospective studies will be required to confirm the value of these advancements.

Pembrolizumab for patients with previously treated metastatic adenocarcinoma or squamous cell carcinoma of the esophagus: Phase 2 KEYNOTE-180 study.

Pembrolizumab for patients with previously treated metastatic adenocarcinoma or squamous cell carcinoma of the esophagus: Phase 2 KEYNOTE-180 study.

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

BackgroundMicroRNAs (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.MethodsFormalin-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.ResultsThe 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.ConclusionsOur results indicate that miRNAs are involved in the therapeutic response in ESCC and suggest that miRNA profiles could facilitate pretherapeutic patient selection.

Clinical outcome of Radical Chemoradiation in Squamous cell carcinoma of the Esophagus

Clinical outcome of Radical Chemoradiation in Squamous cell carcinoma of the Esophagus

Treatment of Squamous Cell Carcinoma of the Esophagus Synchronously Associated with Head and Neck Cancer.

The aim of this study was to clarify the treatment strategy for synchronous squamous cell carcinoma of the esophagus (ESCC) and head and neck cancer (HNC). Treatment outcomes of 91 patients with synchronous ESCC and HNC were evaluated. Thirty-eight patients received simultaneous definitive chemoradiotherapy (CRT) and 15 patients underwent simultaneous resection. Among the patients who received simultaneous CRT, adverse events (grade 3-5) were recognized in 14 patients (40%), including one case of death due to aspiration pneumonia. Complete response was observed in 22 patients with ESCC (58%) and 19 patients with HNC (50%). The five-year survival rate was 44%. There were no in-hospital deaths after simultaneous resection; however, postoperative complications were recognized in 4 patients. The five-year OS was 70%. The treatment of synchronous ESCC and HNC must be decided by adopting a strategy that is appropriate for each case. Both simultaneous CRT and simultaneous resection are feasible and effective treatment options.

A Genetic Polymorphism in the CYP1B1 Gene in Patients with Squamous Cell Carcinoma of the Esophagus: An Iranian Mashhad Cohort Study Recruited Over 10 Years

Esophageal cancer is the eighth most common cancer globally and the seventh most common cause of cancer-related deaths in men. Recent studies have shown that CYP450, family 1, subfamily B, polypeptide 1, which plays a role in the metabolism of xenobiotics, is associated with several cancers. Therefore, in the present study we investigated the association between a genetic variant, CYP1B1-rs1056836 gene, with the clinical characteristics of patients with squamous cell carcinoma of the esophagus (ESCC). In this study, 117patients with ESCC and 208 healthy controls were recruited. DNA was extracted and genotyped using real-time PCR-based TaqMan. Kaplan-Meier curves were utilized to assess overall and progression-free survival. To evaluate the relationship between clinicopathological data, genotypic frequencies, disease prognosis and survival, Pearson's χ2 and t-test were used. Logistic regression was utilized to assess the association between the risk of ESCC and genotypes. The genotypic frequency for GG, GC and CC were 58.6, 29.8 and11.5%, respectively, in the healthy subjects and 51.8, 36.14 and 12% in the ESCC group. An association between the GG genotype and stage of ESCC was found. Also, statistically significant results were not found for this variation and risk of ESCC. Our findings suggest a relationship between the CYP1B1-rs1056836 genetic polymorphism and clinical features of ESCC, supporting further studies in larger populations in different ethnic groups, taking into account potentially important environmental factors such as diet.

Radical Chemoradiation and intraluminal brachytherapy boost in Squamous cell carcinoma of the Esophagus

Radical Chemoradiation and intraluminal brachytherapy boost in Squamous cell carcinoma of the Esophagus

Expression of some molecular and biological markers in esophageal tumors of various stages and grades

Objectives: immunohistochemical study of the expression of molecular and biological markers (p53, bcl-2 and ki-67) in esophageal tumors of various stages and grades, and evaluation of the markers in the disease prognosis. Material and methods: the study included 30 patients of a retrospective group with stage II-III squamous cell carcinoma of the esophagus. Immunohistochemical study of paraffi n sections was performed using primary mouse monoclonal antibodies against p53, bcl-2 and ki67, and Reveal Polyvalent HRP-DAB Detection System. Results: diff erences in the rates and expression of molecular and biological markers (p53, bcl-2 and ki-67), controlling apoptosis and proliferation, depended on the tumor stage and grade. Conclusions: fdvanced cancer of the esophagus demonstrated an increase in rates and expression of p53+ and ki-67, as well as in the proliferative activity of tumor cells. Bcl-2 expression was more frequent and intensive in stage II tumors, compared to stage III. Esophageal tumors of higher grades were characterized with higher rates and expression of p53 and ki-67, and conversely for the bcl-2 expression. Th e revealed diff erences can be used in the disease prognosis.

A comparative analysis between pegfilgrastim and lenograstim administered to patients receiving cytotoxic chemotherapy for squamous cell carcinoma of the esophagus

A comparative analysis between pegfilgrastim and lenograstim administered to patients receiving cytotoxic chemotherapy for squamous cell carcinoma of the esophagus

Risk factors for adenocarcinoma and squamous cell carcinoma of the esophagus and lung

Background: The incidence of adenocarcinoma of the esophagus and lung has been rising in the USA along with a parallel rise in obesity. This study was conducted to investigate possible common risk factors for these two types of cancer. Methods: Retrospective chart review was done and electronic medical records (EMR) of patients with a diagnosis of esophageal and lung cancer for the last 20 years were reviewed and data analyses done. Results: Esophageal and lung adenocarcinoma patients shared some common risk factors such as higher body mass index (BMI), diabetes mellitus (DM), hypertension, hyperlipidemia and gastroesophageal reflux disease (GERD). Conclusions: This study shows that obesity, GERD and metabolic syndrome are common risk factors for adenocarcinoma of esophagus and lung. Obesity may be contributing to the increasing incidence of these two types of cancer.

Risk assessment of metachronous squamous cell carcinoma after endoscopic resection for esophageal carcinoma based on the genetic polymorphisms of alcoholdehydrogense-1B aldehyde dehydrogenase-2: temperance reduces the risk.

Metachronous multiple squamous cell carcinoma (SCC) of the esophagus and the head and neck is commonly observed in patients who have previously undergone endoscopic resection (ER) for SCC of the esophagus (ESCC). We evaluated the risk for developing metachronous SCC following ER for ESCC based on the genetic polymorphisms for alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) as well as the alcohol consumption and smoking habits. We studied 158 patients who underwent ER for ESCC (median follow-up 80months). Genotyping of ADH1B/ALDH2 was performed using saliva sampling. The alcohol consumption and smoking histories of the patients before and after the ER were documented. Multivariate analyses revealed that inactive heterozygous ALDH2 [hazard ratio (HR) 2.25] and alcohol consumption after ER (HR 1.94) were independently associated with the risk of developing secondary SCC. Moreover, inactive heterozygous ALDH2 (HR 4.39) and alcohol consumption after the ER (HR 2.82) were independently associated with the risk of a third SCC. We analyzed 110 patients who had a history of moderate or heavy alcohol consumption before the ER. The 3-year cumulative incidence rates of secondary SCC in the temperance (n=65) and non-temperance groups (n=45) were 14.0 and 42.1% (p=0.0002). Further, the 5-year cumulative incidence rates of a third SCC in the temperance and non-temperance groups were 0 and 15.6% (p=0.0011), respectively. In addition, the 7-year cumulative incidence rates of a fourth SCC in the temperance and non-temperance groups were 0 and 15.3% (p=0.0015), respectively. Continued alcohol consumption is an important risk factor for the onset of metachronous SCC and is a risk factor for the third and subsequent SCCs. Strict advice in favor of temperance is crucial.

Phase II trial of palbociclib in patients with advanced esophageal or gastric cancer.

68 Background: Dysregulation of the cell cycle is a hallmark of cancer. Progression through the G1/S transition requires phosphorylation of retinoblastoma (RB) by cyclin-dependent kinases 4 and 6 (CDK4/6), which are regulated by cyclins D and E. A positive feedback loop between apoptosis signal-regulating kinase 1 (ASK1), a member of the MAP kinase pathway, and cyclin D1 has been shown to drive cell proliferation in gastric cancer. In addition, amplification of cyclin D loci and/or activating mutations in CDKs are frequent molecular aberrations in gastroesophageal malignancies. We hypothesized that palbociclib, a potent inhibitor of CDK4/6 would disrupt proliferative signaling, and arrest the growth of gastric cancer. We conducted a phase II trial of palbociclib in gastric and esophageal cancers as an initial test of efficacy. Methods: We screened 38 subjects with gastric, GE junction, or esophageal cancer for RB nuclear expression by immunohistochemistry, and 38/38 (100%) were positive. We enrolled 21 subjects, of whom 5 had gastric adenocarcinoma, 3 had GE junction adenocarcinoma, 8 had esophageal adenocarcinoma, and 5 had esophageal squamous cell carcinoma. Four of 19 subjects tested positive for CCND1 overexpression by FISH. Patients received 125mg daily of palbociclib for days 1-21 of 28-day cycles. Results: Subjects remained on treatment for a median of 1.7 months. By the initial 2-month assessment, 5 of 21 subjects had stable disease, and 16 subjects had progressive disease by imaging and/or clinical progression. No objective responses were seen. The maximum duration of therapy was 5.5 months in two subjects. One of these subjects had progressing HER2-amplified gastric adenocarcinoma, and continued concurrent trastuzumab with palbociclib, while the other had squamous cell carcinoma of the esophagus. Grade 3 or 4 cytopenias occurred in 9 of 21 subjects (43%), with neutropenia in 8 (38%), anemia in 4 (19%), and thrombocytopenia in 1 (5%). One subject discontinued therapy due to grade 4 thrombocytopenia with GI bleed. All other subjects discontinued therapy due to disease progression. Conclusions: Palbociclib has modest single-agent activity in gastroesophageal tumors despite universal RB expression. Clinical trial information: NCT01037790.

SOX2-silenced squamous cell carcinoma: a highly malignant form of esophageal cancer with SOX2 promoter hypermethylation

This study originally aimed to investigate whether the overexpression of SOX2 is associated with the poor prognosis of patients with squamous cell carcinoma of the esophagus. However, we unexpectedly found that esophageal squamous cell carcinomas completely lacking SOX2 expression showed distinct pathologic features and highly aggressive clinical courses. The study cohort consisted of 113 consecutive patients with esophageal squamous cell carcinoma who underwent surgical resection without neoadjuvant therapy. Immunostaining on tissue microarrays and whole sections revealed that 8/113 (7%) cases were entirely negative for this transcriptional factor. SOX2-negative cancers were histologically less differentiated (P=0.002) and showed higher pT and pStages (P=0.003 and 0.007, respectively) than SOX2-positive cases. A remarkable finding was widespread lymphatic infiltration distant from the primary invasive focus, which was observed in 4 SOX2-negative cancers (50%), but none of the SOX2-positive cases. All separate dysplastic lesions observed in SOX2-negative cases were also SOX2-negative. The negative expression of SOX2 appeared to be an independent poor prognostic factor (OR=7.05, 95% CI=1.27–39.0). No mutations were identified in the coding or non-coding regions of SOX2. Fluorescent in situ hybridization did not show any copy-number variations in this gene. Since the SOX2 promoter contains an extensive CpG island, SOX2-negative cases underwent methylation-specific PCR, which disclosed promoter hypermethylation in all cases. In conclusion, SOX2-silenced squamous cell carcinomas of the esophagus appear to be a minor, but distinct form of malignancy characterized by extensive lymphatic invasion, a poor prognosis, and potential association with multiple SOX2-negative neoplastic lesions. The hypermethylation of the promoter region is seemingly a critical epigenetic event leading to SOX2 silencing.

Renal Metastasis of Esophageal Squamous Cell Carcinoma- A Case Report and Literature Review

Esophageal cancer rarely metastasizes to the kidney. The metastatic organs known more commonly are the liver, lung, and bone. Here, we report a case of a 58 year-old male, who had been diagnosed with squamous cell carcinoma of the esophagus 22 months ago, developed renal metastasis. He subsequently received nephrectomy and adjuvant chemotherapy. We also reviewed similar cases in the literature. This case report could alert physicians caring patients of esophageal carcinoma to pay more attention to the less common renal metastasis.

A Case of Squamous Cell Carcinoma of the Esophagus Associated with Systemic Sclerosis

A Case of Squamous Cell Carcinoma of the Esophagus Associated with Systemic Sclerosis