Capecitabine or Capecitabine Plus Oxaliplatin Versus Fluorouracil Plus Cisplatin in Definitive Concurrent Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma (CRTCOESC): A Multicenter, Randomized, Open-Label, Phase 3 Trial.

PURPOSE: This phase 3 trial aimed to compare the efficacy and safety of capecitabine or capecitabine plus oxaliplatin (XELOX) with those of fluorouracil plus cisplatin (PF) in definitive concurrent chemoradiotherapy (DCRT) for inoperable locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Patients were randomly assigned to receive two cycles of capecitabine, XELOX, or PF along with concurrent intensity-modulated radiation therapy. Patients in each arm were again randomly assigned to receive two cycles of consolidation chemotherapy or not. The primary end points were 2-year overall survival (OS) rate and incidence of grade ≥3 adverse events (AEs). RESULTS: A total of 246 patients were randomly assigned into the capecitabine (n = 80), XELOX (n = 85), and PF (n = 81) arms. In capecitabine, XELOX, and PF arms, the 2-year OS rate was 75%, 66.7%, and 70.9% (capecitabine v PF: hazard ratio [HR], 0.91 [95% CI, 0.61 to 1.35]; nominal P = .637; XELOX v PF: 0.86 [95% CI, 0.58 to 1.27]; P = .444); the median OS was 40.9 (95% CI, 34.4 to 49.9), 41.9 (95% CI, 28.6 to 52.1), and 35.4 (95% CI, 30.4 to 45.4) months. The incidence of grade ≥3 AEs during the entire treatment was 28.8%, 36.5%, and 45.7%, respectively. Comparing the consolidation chemotherapy with the nonconsolidation chemotherapy groups, the median OS was 41.9 (95% CI, 34.6 to 52.8) versus 36.9 (95% CI, 28.5 to 44) months (HR, 0.71 [95% CI, 0.52 to 0.99]; nominal P = .0403). CONCLUSION: Capecitabine or XELOX did not significantly improve the 2-year OS rate over PF in DCRT for inoperable locally advanced ESCC. Capecitabine showed a lower incidence of grade ≥3 AEs than PF did.

Codelivery of CuS and DOX into Deep Tumors with Size and Charge-Switchable PAMAM Dendrimers for Chemo-photothermal Therapy.

Accurate targeting of therapeutic agents to specific tumor tissues, especially via deep tumor penetration, has been an effective strategy in cancer treatments. Here, we described a flexible nanoplatform, pH-responsive zwitterionic acylsulfonamide betaine-functionalized fourth-generation PAMAM dendrimers (G4-AB), which presented multiple advantages for chemo-photothermal therapy, including template synthesis of ultrasmall copper sulfide (CuS) nanoparticles and further encapsulation of doxorubicin (DOX) (G4-AB-DOX/CuS), long-circulating performance by a relatively large size and zwitterionic surface in a physiological environment, combined size shrinkage, and charge conversions via pH-responsive behavior in an acidic tumor microenvironment (TME). Accordingly, high tumor penetration and positive cell uptake for CuS and DOX have been determined, which triggered an excellent combination treatment under near-infrared irradiation in comparison to the monochemotherapy system and irresponsive chemo-photothermal system. Our study represented great promise in constructing multifunctional carriers for the effective delivery of photothermal nanoparticles and drugs in chemo-photothermal therapy.

Characteristics and Prognostic Analysis of 55 Patients With Pulmonary Sarcomatoid Carcinoma.

Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subtype of non-small-cell lung cancer (NSCLC). Here, we present information on the clinicopathologic characteristics and clinical outcomes of this type of cancer. Clinicopathologic data from 55 patients treated at a single cancer center from January 2011 to December 2018 were retrospectively analyzed. The patients were mostly male (76.4%), with a median age of 66 years and a history of smoking (54.5%). Most had symptoms, and about 60% presented with locally advanced or metastatic disease at diagnosis. Of the 55 cases, 21 were diagnosed by surgical resection. Pleomorphic cancer was the most common subtype (58.1%). With a median follow-up period of 13.2 months, the average survival time of the patients was 16.1 months, and the median survival time was 12 months. The overall survival rates for 1, 2, and 3 years were 52.7%, 18.2%, and 9.1%, respectively. Univariate analysis showed that prognosis of the patients was influenced by tumor size, T stage, metastatic status, and surgery (p < 0.05). Multivariate analysis showed that T stage (p = 0.034) was an independent prognostic factor. There are few reports on the natural history of PSC, and its clinicopathological characteristics remain unclear. Herein, a retrospective review 55 individuals with PSC found that T stage was an independent predictor of survival. Surgical resection was associated with better prognosis.

Chemoradiation versus oesophagectomy for locally advanced oesophageal cancer in Chinese patients: study protocol for a randomised controlled trial.

BACKGROUND: Surgery is the gold standard treatment for local advanced disease, while definitive concurrent chemoradiotherapy (DCRT) is recommended for those who are medically unable to tolerate major surgery or medically fit patients who decline surgery. The primary aim of this trial is to compare the outcomes in Chinese patients with oesophageal squamous cell cancer with locally advanced resectable disease who have received either surgery or DCRT. METHODS/DESIGN: One hundred ninety-six patients with T1bN + M0 or T2-4aN0-2 M0 oesophageal squamous cell cancer will be randomised to the DCRT group or the surgery group. In the DCRT group, patients will be given intensity-modulated radiation therapy (IMRT) with 50 Gy/25 fractions and basic chemotherapy with 5-fluorouracil regimens. In the surgery group, patients will receive neoadjuvant chemoradiotherapy (NCRT) and standard oesophagectomy. Five years of follow-up will be scheduled for patients. The primary endpoints are 2-year/5-year overall survival; the secondary endpoints are 2-year/5-year progression-free survival, treatment-related adverse events and the patients' quality of life. The main evaluation methods include oesophagoscopy, endoscopic ultrasonography and biopsy, oesophageal barium meal, computed tomography, positron emission tomography-computed tomography, blood tests and questionnaires. DISCUSSION: The preponderant oesophageal cancer pathology type is dramatically different in western Caucasian and Asian oesophageal cancer patients: Caucasian patients present with 80% adenocarcinomas, and Asians patients present with 95% squamous cell carcinomas. This phenomenon needs more in-depth studies to elucidate the differences in these populations. Based on the results of this study, we will show whether DCRT will benefit patients more than oesophagectomy. This study will contribute more evidence to the management of oesophageal squamous cell cancer. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02972372 . Registered on 26 November 2016.

Comparative transcriptome analysis of the global circular RNAs expression profiles between SHEE and SHEEC cell lines.

Esophageal squamous cell carcinoma (ESCC) is widely regarded as one of the most lethal types of cancer around the world. The fact that early detection of ESCC could dramatically improve the treatment outcome of the patients has sparked considerable interest in searching for reliable and accurate diagnostic biomarkers. Recently, circular RNAs (circRNA) have emerged as a new type of non-coding RNAs with significant RNase resistance, wide abundance and remarkable internal diversity. There is also increasing evidence suggesting that circRNAs could be implicated in the pathogenesis of cancer and other diseases. In this study, we performed a comparative analysis of the global circRNA expression profiles in normal and malignant esophageal epithelial cell lines by a combination of RNA sequencing and bioinformatics analysis. We identified 813 significantly up-regulated and 445 down-regulated circRNA candidates, of which 32 were subsequently validated by quantitative real-time reverse transcription polymerase chain reaction analysis. The differentially expressed circRNAs were found to be associated with pathways involved in metabolism, cell apoptosis, proliferation and migration, which are commonly altered in cancer cells. Based on the obtained data, we constructed a circRNA-miRNA interaction network, in which circRNA9927-NBEAL1 represented the biggest node. Our study could lay the groundwork for further investigation concerning the pathological roles of circRNAs in ESCC.

Presence of Porphyromonas gingivalis in esophagus and its association with the clinicopathological characteristics and survival in patients with esophageal cancer.

BACKGROUND: Mounting evidence suggests a causal relationship between specific bacterial infections and the development of certain malignancies. However, the possible role of the keystone periodontal pathogen, Porphyromonas gingivalis, in esophageal squamous cell carcinoma (ESCC) remains unknown. Therefore, we examined the presence of P. gingivalis in esophageal mucosa, and the relationship between P. gingivalis infection and the diagnosis and prognosis of ESCC. METHODS: The presence of P. gingivalis in the esophageal tissues from ESCC patients and normal controls was examined by immunohistochemistry using antibodies targeting whole bacteria and its unique secreted protease, the gingipain Kgp. qRT-PCR was used as a confirmatory approach to detect P. gingivalis 16S rDNA. Clinicopathologic characteristics were collected to analyze the relationship between P. gingivalis infection and development of ESCC. RESULTS: P. gingivalis was detected immunohistochemically in 61 % of cancerous tissues, 12 % of adjacent tissues and was undetected in normal esophageal mucosa. A similar distribution of lysine-specific gingipain, a catalytic endoprotease uniquely secreted by P. gingivalis, and P. gingivalis 16S rDNA was also observed. Moreover, statistic correlations showed P. gingivalis infection was positively associated with multiple clinicopathologic characteristics, including differentiation status, metastasis, and overall survival rate. CONCLUSION: These findings demonstrate for the first time that P. gingivalis infects the epithelium of the esophagus of ESCC patients, establish an association between infection with P. gingivalis and the progression of ESCC, and suggest P. gingivalis infection could be a biomarker for this disease. More importantly, these data, if confirmed, indicate that eradication of a common oral pathogen could potentially contribute to a reduction in the overall ESCC burden.

Apoptotic effects of Photofrin-Diomed 630-PDT on SHEEC human esophageal squamous cancer cells.

Photodynamic therapy (PDT) using photofrin-II is a clinically effective treatment for both non-neoplastic and neoplastic diseases. Herein, we performed an in vitro experiment to study the anti-tumor effect and mechanisms of photofrin-II mediated PDT for esophageal squamous cell carcinoma (ESCC) cell line, SHEEC. In this study, human ESCC cell line SHEEC and parental normal cell line SHEE were used. The anti-tumor effect of PDT was determined by evaluating cell viability using CCK-8 assay, apoptosis and generation of reactive oxygen species (ROS). PDT induced significant apoptosis in SHEEC and SHEE cells in a time- and photofrin-II dose-dependent manner. Furthermore, PDT treatment induced significant death of SHEEC, instead of SHEE cells. The apoptotic outcome was accompanied by concurrent generation of ROS. In summary, PDT shed light on therapy of ESCC, functioning as a useful tool for ESCC clinical treatment, providing a better understanding of Photofrin-Diomed 630-PDT in SHEEC cells.

Evaluation of combined argon plasma coagulation and Savary Bougienage for the relief of anastomotic-stenosis after esophageal squamous cancer surgery.

BACKGROUND: Several endoscopic dilation techniques have been reported for treatment of anastomotic-stenosis of esophageal cancer, but the high incidence of dysphagia has remained unchanged. The aim of this study was to compare the effect of Argon Plasma Coagulation (APC) combined with Savary Bougienage (SB) compared to APC alone or SB alone for anastomotic-stenosis after radical operation for squamous cell carcinoma of the esophagus. METHODS: Patients with anastomotic-stenosis that was diagnosed for the first time following esophageal squamous cell carcinoma resection surgery were randomly assigned to undergo APC combined with SB, APC alone, or SB alone. Primary endpoints were the dysphagia-free survival (DFS defined as the time from first dilatation of effectively relieved dysphagia to dysphagia relapse expressed in days) after 6 months of follow up. RESULTS: A total of 90 patients from the Cancer Institute, First Affiliated Hospital of Henan University of Science and Technology were entered into the study (APC group, n = 30, SB group, n = 30, combination group [APC combined with SB], n = 30). Primary endpoints: 6 months after treatment, DFS of combination group (115.63 days; 95% CI, 105.31-125.95) was significantly longer than the APC alone group (39.53 days; 95% CI, 35.95-43.11, p = 0.000) and the SB alone group (16.93 days; 95% CI, 15.01-18.84, p = 0.000). No severe complications occurred within the three treatment groups. CONCLUSIONS: APC combined with SB was a safe and well-tolerated method for relieving dysphagia of esophageal squamous cell cancer patients with anastomotic-stenosis. (Registered with randomized controlled trials, ChiCRT, registration number ChiCTR-TRC-13003757.)

Therapeutic effects of combined oxaliplatin and S-1 in older patients with advanced gastric cardiac adenocarcinoma.

AIM: To evaluate the effects and safety of combination chemotherapy with oxaliplatin (L-OHP) and S-1 (SOX regimen) in older patients with advanced gastric cardiac adenocarcinoma (GCA). METHODS: Seventy patients with advanced GCA were classified according to age into an older group (≥ 75 years) and a control group (< 75 years). The SOX regimen was administered to the two groups as follows: S-1 (40 mg/m² po bid) on days 1 to 14 followed by a 7-d off period, plus L-OHP (65 mg/m² iv) for 2 h on days 1 and 8 of a 21-d cycle. This regimen was repeated for four to six cycles. Response and swallow statuses were evaluated after two cycles (6 wk). Effects and toxicity were evaluated four weeks after chemotherapy was completed. RESULTS: The response rate was 65.6% (21/32) in the older group and 68.4% (26/38) in the control group (χ² = 0.062 and P = 0.804). Improvement in swallowing was 78.1% (25/32) in the older group and 76.3% (29/38) in the control group (χ² = 0.032 and P = 0.857). Efficacy was 68.8% (22/32) in the older group and 65.8% (25/38) in the control group (χ² = 0.069 and P = 0.793). Toxicities were reversible and similar in both groups (P > 0.05). CONCLUSION: The SOX regimen is an effective, safe and well-tolerated regimen for older patients with advanced GCA.

[Absorption and elimination of photofrin-II in human immortalization esophageal epithelial cell line SHEE and its malignant transformation cell line SHEEC].

BACKGROUND AND OBJECTIVE: The mechanism of tumor tissues selectively uptake the photosensitizer in photodynamic therapy (PDT) is still unclear. This study was to investigate the affinity of tumor cells to the photosensitizer photofrin-II. METHODS: Ultraviolet spectrophotometer was applied to measure the absorption spectra of various cell culture media. The fluorescence spectrum of photofrin-II was determined by spectrofluorometer. The absorption and elimination condition of photofrin-II were detected in immortalized human esophageal epithelial cell line SHEE and its malignant transformation cell line SHEEC. RESULTS: The maximum excitation wavelength of fluorescence for photofrin-II was (395.0+/-0.5) nm, and the maximum emission wavelength of that was (634.1+/-0.5) nm. The laser at the wavelength of 630 nm used in this experiment could permeate various types of cell culture media. There was no significant difference in the absorption and elimination of photofrin-II between SHEE and SHEEC at the same concentration and time. The absorption of photofrin-II in SHEE and SHEEC increased with the increase in photofrin-II concentration and duration, and reached the platform at the concentration of 30 microg/mL and a time point of 150 min, respectively. The photofrin-II contents of SHEE and SHEEC showed a slight change after 15-30 min, and diminished rapidly after 30 min. CONCLUSION: High photosensitizer concentration in tumor tissues may be not correlated with the affinity of tumor cells.