RESUMEN

Esophagitis is described as an inflammation of the esophagus and can result from multiple etiologies. Esophageal squamous cell carcinoma (ESCC), presenting as diffuse esophagitis in the absence of a mass or lesion, is rare. We present a case of a 61-year-old man who presented to the gastroenterology clinic for dysphagia and heartburn of 3 months duration. The patient had lost about 15 pounds unintentionally over 6 months. The patient underwent esophagogastroduodenoscopy, which revealed significant diffuse Grade 4 esophagitis without any overt bleeding. Random biopsies were taken with cold forceps from proximal, middle, and distal esophageal segments because of the striking endoscopic appearance. Histopathology revealed high-grade dysplasia and carcinoma in situ. The patient underwent endoscopic ultrasound (EUS) of the esophagus, which revealed a focal lesion. EUS-guided fine-needle aspiration showed squamous cell carcinoma of the esophagus. ESCC usually presents as a mass or a gross lesion seen on endoscopy. However, it rarely presents as severe diffuse esophagitis seen on routine endoscopy. From our observation, it would be reasonable for physicians to bear this unusual endoscopic presentation in mind and perform multiple random biopsies if encountered with such a case to rule out the possibility of any underlying malignancy.

RESUMEN

Aim: To find out differences in biomarkers between Japanese and German patients responsible for response after neoadjuvant radio/chemotherapy and survival for esophageal squamous cell carcinoma. Materials & methods: A total of 60 patients from Japan and 127 patients from Germany with esophageal squamous cell carcinoma were analyzed according to three SNPs by real-time PCR. Results: The distribution of the genotypes of ERCC1 rs16115 and ABCB1 C3435T rs1045642 was significantly different between both patients' groups. Japanese patients had significantly less good response to 5-fluorouracil/cisplatin chemotherapy. The influence of the three SNPs on response varied between patients from Japan and Germany. Conclusion: Different expressions of ERCC1 and ABCB1 SNPs of Japanese patients compared with the German patients partially explain the different response.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Biomarcadores de Tumor , Proteínas de Unión al ADN/genética , Manejo de la Enfermedad , Endonucleasas/genética , Carcinoma de Células Escamosas de Esófago/diagnóstico , Carcinoma de Células Escamosas de Esófago/etiología , Femenino , Genotipo , Alemania , Humanos , Inmunohistoquímica , Japón , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Farmacogenética/métodos , Variantes Farmacogenómicas , Polimorfismo de Nucleótido Simple , Resultado del Tratamiento , Adulto Joven

RESUMEN

Treatment of squamous cell carcinoma is associated with an increased risk of other primary malignancies, mainly within the head and neck, as well as in the oesophageal gastric graft. More frequent recognition of multiple primary cancers associated with esophageal cancer, both synchronous and metachronous, is associated with longer follow-up after radical cancer treatment for esophageal cancer and high quality diagnostic procedures, both before and after surgery. The paper reviews the available literature and describes the molecular basis of the formation of multiple primary tumors associated with squamous cell carcinoma of the esophagus.

Asunto(s)

Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Neoplasias Primarias Múltiples/patología , Neoplasias Primarias Múltiples/cirugía , Esófago/patología , Neoplasias de Cabeza y Cuello/cirugía , Humanos

RESUMEN

BACKGROUND: Multimodal treatment with neoadjuvant chemoradiation followed by surgery (nCRT + S) is the treatment of choice for patients with locally advanced or node-positive esophageal squamous cell carcinoma (E-SCC). Those who are unsuitable or who decline surgery can be treated with definitive chemoradiation (dCRT). This study compares the oncologic outcome of nCRT + S and dCRT in E-SCC patients. METHODS: Between 2011 and 2017, 95 patients with E-SCC were scheduled for dCRT or nCRT+ S with IMRT at our department. Patients undergoing dCRT received at least 50 Gy and those undergoing nCRT + S received at least 41.4 Gy. All patients received simultaneous chemotherapy with either carboplatin and paclitaxel or cisplatin and 5-fluoruracil. We retrospectively compared baseline characteristics and oncologic outcome including overall survival (OS), progression-free survival (PFS) and site of failure between both treatment groups. RESULTS: Patients undergoing dCRT were less likely to have clinically suspected lymph node metastases (85% vs. 100%, p = 0.019) than patients undergoing nCRT + S and had more proximally located tumors (median distance from dental arch to cranial tumor border 20 cm vs. 26 cm, p < 0.001). After a median follow up of 25.6 months for surviving patients, no significant differences for OS and PFS were noticed comparing nCRT + S and dCRT. However, the rate of local tumor recurrence was significantly higher in patients treated with dCRT than in those treated with nCRT + S (38% vs. 10%, p = 0.002). Within a multivariate Cox regression model, age, tumor location, and tumor grading were the only independent parameters affecting OS and PFS. In addition to that, proximal tumor location was the only parameter independently associated with an increased risk for local treatment failure. CONCLUSION: In E-SCC patients treated with either dCRT or nCRT + S, a higher rate of local tumor recurrence was seen in patients treated with dCRT than in patients treated with nCRT + S. There was at least a trend towards an improved OS and PFS in patients undergoing nCRT + S. However, this should be interpreted with caution, because proximal tumor location was the only parameter independently affecting the risk of local tumor recurrence.

Asunto(s)

Carcinoma de Células Escamosas/terapia , Quimioradioterapia/mortalidad , Neoplasias Esofágicas/terapia , Terapia Neoadyuvante/mortalidad , Anciano , Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia

RESUMEN

BACKGROUND: Treatment options for patients with advanced esophageal or esophagogastric junction (EGJ) cancer are limited. Current guidelines for first-line treatment of advanced esophageal or EGJ cancer recommend chemotherapy containing a platinum and a fluoropyrimidine agent. Pembrolizumab demonstrated antitumor activity in previously treated patients with advanced esophageal cancer and in patients with gastroesophageal junction cancer. AIM: To describe the design and rationale for the randomized, double-blind, placebo-controlled Phase III KEYNOTE-590 study, which will be conducted to investigate pembrolizumab in combination with chemotherapy as first-line treatment in patients with advanced esophageal or EGJ cancer. Clinical trial registry & ID: ClinicalTrials.gov : NCT03189719.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias Esofágicas/tratamiento farmacológico , Proyectos de Investigación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/administración & dosificación , Carcinoma de Células Escamosas/secundario , Método Doble Ciego , Neoplasias Esofágicas/patología , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Adulto Joven

RESUMEN

Effect of STAT3 decoy oligodeoxynucleotides (ODN) transduced by ultrasound microbubbles combined with ultrasound on the growth of esophageal squamous cell carcinoma and its mechanism were analyzed. EC9706 cells were cultured in vitro and divided into four groups: group E (ultrasound microbubble + ultrasound irradiation), group P (liposome + ultrasound irradiation), group C (ultrasound), and group CC (ultrasound microbubbles). Mutant ODNs were used in groups E and P and the control group was group EC and PC, respectively. Immunofluorescence assay and flow cytometry were used to detect the transfection efficiency of each group. MTT colorimetric assay was performed to analyze the inhibition rate in each group. The effect of STAT3 decoy ODN on the proliferation of esophageal squamous carcinoma cells was calculated. Revese transcription-quantitative PCR (RT-qPCR) and western blotting were performed to detect the expression of the STAT signaling pathway downstream of gene expression levels. The model of subcutaneous transplantation of nude mice was used to show the effect of different transfections and STAT3 decoy ODN on the weight and volume of the transplanted tumor in mice. The cell inhibition rate was higher in group E than in groups P (F=8.382, P<0.001) and CC (F=6.469, P<0.001). Compared with groups EC, PC and C, respectively, the mRNA expression of STAT3, bcl-xL and Cyclin D1 decreased in groups E, P and CC (F=5.328, P<0.001). The weight and volume of nude mice in groups E, P and CC exhibited an inhibitory effect on the weight and volume of nude mice. Ultrasound irradiation combined with ultrasound microbubbles is an effective transfection method. The transfection of STAT3 decoy ODN can significantly inhibit the activity of esophageal squamous cell carcinoma cells and enhance apoptosis of cells, which has potential clinical value.

RESUMEN

BACKGROUND: While 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. METHODS: Twenty-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). RESULTS: Forty-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. CONCLUSION: Myelotoxicity 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.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/terapia , Quimioradioterapia/métodos , Neoplasias Esofágicas/terapia , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Superficie Corporal , Carboplatino/administración & dosificación , Carcinoma de Células Escamosas/patología , Quimioradioterapia/efectos adversos , Cisplatino/administración & dosificación , Neoplasias Esofágicas/patología , Femenino , Fluorouracilo/administración & dosificación , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Paclitaxel/administración & dosificación , Estudios Prospectivos , Estudios Retrospectivos

RESUMEN

Our previous trial with a docetaxel, cisplatin, and 5-fluorouracil (DCF) regimen showed high response rates in metastatic squamous cell carcinoma of the esophagus (SCCE). The observed increased toxicity of the DCF regimen, however, was clinically harmful. S-1, an oral anticancer drug, has been approved as a combination therapy for SCCE, and alternate-day regimen with S-1 has shown lower levels of toxicity. This prospective single-center phase I/II trial examines the efficacy and toxicity of a combination of docetaxel, cisplatin, and an alternate-day regimen of S-1 (modified DCS) for patients with metastatic SCCE. We use a two-stage design. Phase I is undertaken to determine the maximum tolerated dose and the recommended dose. The phase I trial adopts a three-patient cohort with escalating dose study design. In the phase II trial, the primary endpoint is the assessment of the overall response rate (Response Evaluation Criteria in Solid Tumors 1.1). The secondary endpoints are the evaluation of drug-related toxicity (National Cancer Institute Common Toxicity Criteria 4.0), overall survival, and progression-free survival. Fifty patients with metastatic SCCE participate in the phase II section. This study protocol is the first to test the effects of the modified DCS regimen for metastatic SCCE.

Asunto(s)

Antimetabolitos Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Cisplatino/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Ácido Oxónico/uso terapéutico , Taxoides/uso terapéutico , Tegafur/uso terapéutico , Antimetabolitos Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Docetaxel , Combinación de Medicamentos , Carcinoma de Células Escamosas de Esófago , Esófago/patología , Humanos , Dosis Máxima Tolerada , Ácido Oxónico/efectos adversos , Estudios Prospectivos , Taxoides/efectos adversos , Tegafur/efectos adversos

RESUMEN

PURPOSE: Neoadjuvant chemoradiation (nCRT) is the treatment of choice for patients with locally advanced squamous cell carcinoma of the esophagus (SCC). Today radiation oncologists can choose between two different therapy regimes including chemoradiation with cisplatin and 5-fluoruracil (CDDP/5FU) and chemoradiation analogue to the CROSS-regime with carboplatin and paclitaxel (Carb/TAX). However, there is a lack of studies comparing these regimes, especially for the subgroup of patients with SCC. In this study, we want to compare nCRT with CDDP/5FU and nCRT with Carb/TAX for patients with locally advanced SCC. PATIENTS AND METHODS: We retrospectively compared 20 patients who were scheduled for nCRT with a total radiation dose of 41.4 Gy (daily dose of 1.8 Gy) and weekly chemotherapy with carboplatin (Area under the curve 2) and Paclitaxel (50 mg per square meter of body-surface area) according to the CROSS-regime to 31 patients who were scheduled for nCRT with a total radiation dose of 45 Gy (daily dose of 1.8 Gy) and simultaneous chemotherapy 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, per protocol treatment was defined as either complete radiation with 41.4 Gy, at least three complete cycles of Carb/TAX and subsequent surgery or complete radiation with 45 Gy, at least one complete cycle of CDDP/5FU and subsequent surgery. RESULTS: Fifty-one patients (31 patients treated with CDDP/5FU and 20 patients treated with Carb/TAX) were evaluated for the intention-to-treat (ITT) analysis and 44 patients (26 patients treated with CDDP/5FU and 18 patients treated with Carb/TAX) were evaluated for the PP analysis. No significant differences were seen for baseline and tumor characteristics like age, sex, TNM-stage, grading and tumor extension between patients treated with Carb/TAX and patients treated with CDDP/5FU. The most common tumor regression grade after nCRT was grade I as classified by Becker et al., which was observed in 84 and 79% of patients. No significant differences in tumor regression grades were seen between both regimes. Postoperative insufficiency of the anastomosis was seen in 6 patients (33%) who were treated with Carb/TAX and 4 patients (15%) who were treated with CDDP/5FU (p = 0.273). Patients treated with CDDP/5FU developed significantly more cumulative hematologic III° (CTCAE) toxicities (58% vs 20%; p = 0.010) than patients treated with Carb/TAX. In contrast to that, there was no significant difference for overall survival (OS) and freedom from relapse (FFR) between treatment groups. CONCLUSION: In this retrospective analysis, no significant difference was seen for OS and FFR between nCRT with CDDP/5FU and nCRT with Carb/TAX. However, the application of CDDP/5FU was associated with significantly more hematologic III°- toxicities compared to Carb/TAX. Future prospective trials should investigate if these results are reproducible in randomized patient cohorts.

Asunto(s)

Carboplatino/administración & dosificación , Carcinoma de Células Escamosas/tratamiento farmacológico , Cisplatino/administración & dosificación , Neoplasias Esofágicas/tratamiento farmacológico , Fluorouracilo/administración & dosificación , Paclitaxel/administración & dosificación , Anciano , Carcinoma de Células Escamosas/cirugía , Quimioterapia Adyuvante , Neoplasias Esofágicas/cirugía , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estudios Retrospectivos , Resultado del Tratamiento

RESUMEN

Adenocarcinoma and squamous cell carcinoma are the most common types of esophageal cancer with a constant tendency to increase the incidence of growth on the background of the high mortality, which makes particularly the development of new biomarkers that complement and improve the early diagnosis of this disease. Despite the impressive number of studies in routine clinical practice is used only marker of esophageal cancer - ERBB2/HER2 status. This review summarizes data on the identified epigenetic markers of the aberrant methylation of the genome, which may be useful for early detection of esophageal cancer, prognosis estimation and / or prediction of response to treatment. The development of new high-tech genome-wide screening, such as beadarray and immunoprecipitation sequencing method used for the wideband genotyping, but for the analysis of transcriptome and metilom, provides a comprehensive picture of genetic and epigenetic changes during tumorigenesis. Note the need to verify the most biomarkers on large representative samples for the development of valid diagnostic panels, suitable for large-scale screening of risk groups.

Asunto(s)

Biomarcadores de Tumor/metabolismo , Metilación de ADN , ADN de Neoplasias/metabolismo , Epigénesis Genética , Neoplasias Esofágicas/metabolismo , Regulación Neoplásica de la Expresión Génica , Receptor ErbB-2/metabolismo , Biomarcadores de Tumor/genética , ADN de Neoplasias/genética , Neoplasias Esofágicas/genética , Humanos , Receptor ErbB-2/genética

RESUMEN

A 48-year-old female who presented with a history of dysphagia for 5 months and regurgitation for 1 week was referred to the Sir Run Run Shaw Hospital (Hangzhou, China) for further evaluation, since the gastroscopy and endoscopic ultrasound performed in local hospitals did not reveal the presence of cancer. High-resolution manometry (HRM) of the esophagus was performed to determine the patient's condition, and revealed an abnormal high-pressure zone that was located 33 cm from the incisor and did not relax upon swallowing. Synchronous waves were observed, and the pressure of the esophageal lumen was found to increase with secondary synchronous peristaltic waves. The lower esophageal sphincter was 39 cm from the incisor and relaxed upon swallowing. The abnormal high-pressure zone could have been caused by an obstruction, and therefore an upper gastrointestinal series (barium swallow) test and gastroscopy were recommended to further pinpoint the cause. Following the two examinations, mid-esophageal cancer was considered as a possible diagnosis. A biopsy was performed and the final diagnosis was that of basaloid squamous cell carcinoma. The findings of the present study suggest that, for patients with evident symptoms of esophageal motor dysfunction without significant gastroscopy findings, HRM is recommended.

RESUMEN

In Japan, the first paper on endoscopic resection (ER) for squamous cell carcinoma (SCC) of the esophagus confined to the mucosa was reported as endoscopic mucosal resection (EMR) in 1988. Since publication of that article, ER has been recommended as the standard treatment for squamous and mucosal cancer of the esophagus. T1a-EP and T1a-LPM esophageal cancer seldom involves lymph node metastasis. However, in cases of T1a-MM and T1b-SM1 esophageal cancer with lymph node metastasis (10% to 30%), the indication of ER is limited. The risk factors for lymph node metastasis in T1a-MM and T1b-SM1 esophageal cancer were cleared by clinical and pathological studies. Endoscopic findings such as type 0-I or type 0-III, size of 50 mm or more, and pathological findings such as lymphatic permeation, venous permeation, poorly differentiated SCC and INFb or INFc were suggestive of high risk for lymph node metastasis. In addition, histopathological findings of small cancer nests, defined as "budding" or "droplet infiltration," suggest frequent lymph node metastasis. In cases of T1a-MM and T1b-SM1 esophageal cancer with high risk of lymph node metastasis, adjuvant therapy including chemoradiotherapy and radical esophagectomy are recommended after ER. A recent advance in ER for esophageal cancer is the establishment of endoscopic submucosal dissection (ESD). It has allowed us to perform an en-block resection of a large mucosal lesion of the esophagus and detailed histopathological examination. However, ESD requires more difficult manipulation than EMR. The indication of EMR or ESD is sought.