crossing96/oncoscreening huggingface dataset:
Efficacy and safety of irinotecan combined with raltitrexed or irinotecan monotherapy for salvage chemotherapy of esophageal squamous cell cancer: A prospective, open label, randomized phase II study.	BACKGROUND: Esophageal squamous cell cancer (ESCC) accounts for approximately 90% of esophageal cancer cases in China. There are no standard regimens for second or third-line chemotherapy of metastatic squamous esophageal cancer. The objective of this study was to investigate the security and effectiveness of irinotecan combined with raltitrexed or irinotecan monotherapy for salvage chemotherapy of ESCC. METHODS: One hundred and twenty-eight patients with metastatic ESCC confirmed by histopathology were enrolled into this study. These patients had failure of the first-line chemotherapy combination of fluorouracil or platinum or paclitaxel and had not undergone chemotherapy with irinotecan or raltitrexed previously. Patients were randomly divided into irinotecan combined with raltitrexed group (experiment group) and irinotecan monotherapy group (control group). Overall survival (OS) and progression-free survival (PFS) were the primary endpoint. RESULTS: In the control group, the median PFS (mPFS) and median OS (mOS) of patients were 3.37 and 5.3 months. In the experiment group, mPFS and mOS were 3.91 and 7.0 months. There was statistical significance of PFS and OS between two groups (PFS P = 0.002, OS P = 0.01). In subgroup analysis, in the second-line treatment, the mPFS of control and experiment group, was 3.90 and 4.60 months, mOS was 6.95 and 8.5 months, which was statistically significant differences between the two groups. (PFS P = 0.001, OS P = 0.005), In the third-line and beyond treatment, mPFS of control and experiment group was 2.80 and 3.19 months, mOS were 4.5 and 4.8 months. But there was no significant difference of PFS or OS between the two groups (PFS P = 0.19, OS P = 0.31). There was no statistical significance of toxicity side effects between two groups. CONCLUSIONS: The PFS and OS of irinotecan plus raltitrexed may be better than that of irinotecan monotherapy, especially in second line treatment, which should be confirmed with a phase III study including much more patients.	esophagus
Sintilimab as maintenance treatment for local/regional recurrent esophageal squamous carcinoma after concurrent chemoradiotherapy: a single-arm Ib/II phase study.	BACKGROUND: Esophageal cancer (EC) is an aggressive neoplasm of the gastrointestinal tract that is usually treated with a combination of chemotherapy, radiotherapy (RT), and/or surgery, according to disease status. Despite the availability of multimodal therapeutic strategies, local recurrence is frequently observed. However, there is no standard treatment or promising therapeutic approach for local recurrence or metastatic esophageal carcinoma after the RT. This study tended to investigate the efficacy and safety of sintilimab maintenance after concurrent chemoradiotherapy (CCRT) for local/regional recurrent esophageal squamous carcinoma. METHODS: This study was a single-arm, phase Ib/II trial conducted in a single site in China. Patients previously radically treated (surgery or CCRT), histologically confirmed, local or regional recurrence esophageal squamous carcinoma, qualified for the study design, were treated with 25-28 times radiotherapy plus raltitrexed once every 3 weeks for up to two cycles. Patients who have not progressed after CCRT received sintilimab as maintenance once every 3 weeks up to 1 year. Primary endpoints were overall survival (OS) and safety. Secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR). RESULTS: Between September 2019 and March 2022, in a total of 36 enrolled patients, 34 pts completed CCRT. Three patients excluded due to violation of the exclusion criteria (1 pt) and consent withdrawal (2 pts). Finally, 33 pts were included in the final analysis, in which 3 pts had disease progression, and the remaining 30 entered maintenance therapy with sintilimab. The median follow-up time was 12.3 months. Median OS was 20.6 months (95%CI 10.5-NA) and the 1-year OS rate was 64%. Median PFS was 11.5 months (95%CI 5.29-21.3) and the 1-year PFS rate was 43.6%. The ORR was 63.6% (95%CI 44.6-77.8), including 2 cases of CR and 19 cases of PR. The DCR was 19.9%, the median DOR was 19.5 months, and the median TTR was 2.4 months. The rate of any grade TRAEs was 96.7%; ≥Grade 3 TRAE was 23.4%. The incidence of immune-related AE was 60%, most of which were grade 1-2, and only one case of thyroid-stimulating hormone increased was irAE with grade 3 or above. CONCLUSION: Sintilimab has shown promising clinical efficacy and a manageable safety profile as maintenance therapy after CCRT for local/regional recurrent esophageal squamous carcinoma. In addition, further confirmation from a large-scale real-world study is still needed.	esophagus
Effect of ghrelin administration on postoperative inflammatory response and bodyweight loss in patients with oesophageal cancer undergoing oesophagectomy: a systematic review and meta-analysis.	OBJECTIVES: To investigate the effect of postoperative ghrelin therapy on postoperative inflammatory response and bodyweight loss in patients undergoing an oesophagectomy for oesophageal cancer. METHODS: We conducted a systematic search using electronic information databases in accordance to PRISMA standards to identify studies comparing outcomes after oesophagectomy in patients who were and were not administered ghrelin in the postoperative period. Meta-analysis of the outcomes using random effects modelling was conducted. The Cochrane collaboration's tool and ROBINS-I tool were used for risk of bias assessment of the included studies. RESULTS: Five studies including 192 patients were selected for analysis. Ghrelin therapy was associated with a significantly shorter duration of systemic inflammatory response syndrome (SIRS) (MD: - 2.72, P = 0.0001), lower CRP level on postoperative day 3 (MD: - 3.64, P < 0.0001), and less total bodyweight loss (MD: - 1.87, P = 0.14). There was no differences between the two groups in IL-6 level on postoperative day 3 (MD: - 19.65, P = 0.32), total lean body weight loss (MD: - 1.87, P = 0.14), total body fat loss (MD: 0.15, P = 0.84), pulmonary complications (OR: 0.47, P = 0.12), anastomotic leak (OR: 1.17, P = 0.78), wound complications (OR: 1.64, P = 0.63), postoperative bleeding (OR: 0.32, P = 0.33), arrhythmia (OR: 1.22, P = 0.77). CONCLUSIONS: Administration of ghrelin following oesophagoectomy may reduce duration of postoperative SIRS and bodyweight loss. Whether shorter duration of SIRS and less bodyweight loss resulted from postoperative ghrelin therapy can translate into improved morbidity or mortality outcomes remains unknown. There is a need for randomised controlled trials with robust statistical power to investigate the role of postoperative ghrelin therapy on morbidity and mortality outcomes in patients undergoing oesophagectomy.	esophagus
NRF2/HO-1 axis, BIRC5, and TP53 expression in ESCC and its correlation with clinical pathological characteristics and prognosis.	BACKGROUND: Many types of cancer exhibit high nuclear factor erythroid 2-related factor 2 (NRF2), which is effective in resisting drugs and radiation. However, the role of NRF2 gene expression in predicting the prognosis of esophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: The association between NRF2, heme oxygenase-1 (HO-1), baculovirus IAP repeat 5 (BIRC5), P53 gene expression levels and their relationship to immune-infiltrating cells were assessed using the Cancer Genome Atlas dataset, the Human Protein Atlas and the TISDB database. The expression of NRF2, HO-1, BIRC5, and TP53 in 118 ESCC patients was detected by immunohistochemistry, and the relationship between their expression level and clinicopathological parameters and prognosis was analyzed. RESULTS: In ESCC, NRF2 overexpression was significantly associated with Han ethnicity, lymph node metastasis, and distant metastasis. HO-1 overexpression was significantly associated with differentiation, advanced clinical staging, lymph node metastasis, nerve invasion, and distant metastasis. BIRC5 overexpression was significantly associated with Han ethnicity and lymph node metastasis. TP53 overexpression was significantly associated with Han ethnicity and T staging. The NRF2/HO-1 axis expression was positively correlated with BIRC5 and TP53. Kaplan-Meier and multivariate Cox regression analysis showed that NRF2, BIRC5, and TP53 genes co-expression was an independent prognostic risk factor. TISIDB dataset analysis showed that immune-infiltrating cells were significantly negatively correlated with NRF2 and BIRC5. CONCLUSION: NRF2, BIRC5, and TP53 axis gene expressions are predictors of poor prognosis for ESCC. The overexpression of the NRF2/HO-1/BIRC5 axis may not be related to immune-infiltrating cells.	esophagus
Accurate Preoperative Evaluation of the Location of Esophagogastric Junction Adenocarcinoma Using Positron Emission Tomography-Computed Tomography.	BACKGROUND: The surgical procedure for esophagogastric junction (EGJ) adenocarcinoma usually depends on the location of its epicenter or proximal margin, but accurate evaluation of these positions is often difficult. The usefulness of positron emission tomography-computed tomography (PET-CT) for this purpose is unknown. METHODS: Between June 2005 and February 2015, we enrolled 30 patients with cT2-4 EGJ adenocarcinoma (Siewert type I/II) who underwent surgical resection. We ascertained the sensitivity and specificity of preoperative PET-CT for identifying the primary tumor and regional lymph node metastasis, and compared PET-CT and pathological findings in terms of the distance from the EGJ to the tumor epicenter or proximal tumor margin. RESULTS: PET-CT detected the primary tumor with a sensitivity of 97% (29/30), and detected lymph node metastasis with a sensitivity and specificity of 22% (4/18) and 100% (8/8), respectively. No significant association was observed between the maximal standardized uptake value and histological type, tumor size, or pT status. Regarding the accuracy of evaluating tumor location, the median differences between PET-CT and pathological measurements were .6 cm for the tumor epicenter and .5 cm for the proximal margin from the EGJ. PET-CT and pathological findings showed agreement regarding Siewert classification type (I or II) and lengths of esophageal involvement exceeding 4 cm or 2 cm in 77% (10/13), 85% (11/13), and 85% (11/13) of cases, respectively. DISCUSSION: PET-CT had high sensitivity for primary EGJ adenocarcinoma. It may effectively locate the tumor epicenter and proximal margin and thus help clinicians determine the optimal surgical procedure.	esophagus
Could tumour volume and major and minor axis based on CTA statistical anatomy improve the pre-operative T-stage in oesophageal cancer?	OBJECTIVES: To statistically study the 3D shape of oesophageal cancer (EC) and its spatial relationships based on computed tomography angiography (CTA) 3D reconstruction, to determine its relationship with T-stages, and to create an optimal T-stage diagnosis protocol based on CTA calculation. METHODS: Pre-operative CTA images of 155 patients with EC were retrospectively collected and divided into four groups: T1-T4. We used Amira software to segment and 3D reconstruct the EC, oesophagus, aorta, pericardium and peripheral lymph nodes and measured their surface area, volume, major axis, minor axis, longitudinal length, roughness and relationship to the aorta of the EC. One-way ANOVA, independent sample t-test, ROC, etc., were performed and critical values between different T-stages were calculated. We also invited two radiologists to evaluate the measurements. RESULTS: There were no significant differences in EC longitudinal length, roughness score and relationship with the aorta between the different T-stages of EC. There were significant differences in EC surface area, EC volume and mean major and minor axis among the different T-stages. The volumes of the T1-T4 tumours were 12,934.36 ± 7739.25, 23,095.27 ± 14,975.67, 37,577.98 ± 36,085.64 and 58,579.25 ± 41,073.96 mm(3) separately (p < 0.05), and the T1-T4 volume cut-off values were 11,712.00, 19,809.00 and 44,103.50 mm(3) separately. For comparison with radiologists, the AUC value of our measurements was 0.704, which was higher than the radiologists of AUC = 0.630. CONCLUSIONS: EC volume, major and minor axis can be used as important factors for surgeons in the T-stage diagnosis of EC, which helps to improve prognosis and treatment decisions after CTA.	esophagus
Downregulation of Claudin5 promotes malignant progression and radioresistance through Beclin1-mediated autophagy in esophageal squamous cell carcinoma.	BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a highly prevalent and aggressive cancer with poor treatment outcomes. Despite the critical role of tight junction proteins in tumorigenesis, the involvement of Claudin5 in ESCC remains poorly understood. Thus, this study aimed to investigate the role of Claudin5 in ESCC malignant progression and radioresistance, as well as the underlying regulatory mechanisms. METHODS: The expression of Claudin5 was evaluated in esophageal cancer tissue using both public databases and 123 clinical samples. CCK-8, transwell invasion, wound healing and clonogenic survival assays were used to examine the proliferation, invasion, migration and radiosensitivity of ESCC cells in vitro. Xenograft and animal lung metastasis experiments were conducted to examine the impact of Claudin5 on tumor growth and lung metastasis in vivo. The effect of Claudin5 on autophagy was detected via transmission electron microscopy, western blotting and autophagy flux. Immunohistochemical staining was used to detect Claudin5 expression in ESCC patient samples. The statistical difference was assessed with Student t test or one-way ANOVA. The correlation between Claudin5 expression and radiotherapy response rate was performed by the Chi-square test. The significance of Kaplan-Meier curves was evaluated by the Logrank test. RESULTS: Claudin5 expression was downregulated in ESCC tissues. Downregulation of Claudin5 promoted ESCC cell proliferation, invasion, and migration both in vitro and in vivo. Downregulation of Claudin5 decreased the radiosensitivity of ESCC cells. Moreover, downregulation of Claudin5 promoted autophagy and the expression of Beclin1. Beclin1 knockdown reversed the effect of Claudin5 downregulation on autophagy induction and the promotion of ESCC cell malignant progression and radioresistance. Additionally, low expression of Claudin5 in ESCC cancer tissues was associated with poor radiotherapy response and prognosis. CONCLUSIONS: In summary, these findings suggest that downregulation of Claudin5 promotes ESCC malignant progression and radioresistance via Beclin1-autophagy activation and may serve as a promising biomarker for predicting radiotherapy response and patient outcome in ESCC.	esophagus
Location and appearance of dysplastic Barrett's esophagus recurrence after endoscopic eradication therapy: no additional yield from random biopsy sampling neosquamous mucosa.	BACKGROUND AND AIMS: Surveillance after complete remission of intestinal metaplasia (CRIM) is essential. Current recommendations are to sample visible lesions first, followed by random 4-quadrant biopsy sampling of the original Barrett's esophagus (BE) length. To inform post-CRIM surveillance protocols, we aimed to identify the anatomic location, appearance, and histology of BE recurrences. METHODS: We performed an analysis of 216 patients who achieved CRIM after endoscopic eradication therapy for dysplastic BE at a Barrett's Referral Unit between 2008 and 2021. The anatomic location, recurrence histology, and endoscopic appearance of dysplastic recurrences were evaluated. RESULTS: After a median of 5.5 years (interquartile range, 2.9-7.2) of follow-up after CRIM, 57 patients (26.4%) developed nondysplastic BE (NDBE) recurrence and 18 patients (8.3%) developed dysplastic recurrence. From 8158 routine surveillance biopsy samplings of normal-appearing tubular esophageal neosquamous epithelium, the yield for recurrent NDBE or dysplasia was 0%. One hundred percent of dysplastic tubular esophageal recurrences were visible and in BE islands, whereas 77.8% of gastroesophageal junction dysplastic recurrences were nonvisible. Four distinct endoscopic features suspicious for recurrent advanced dysplasia or neoplasia were identified: buried or subsquamous BE, irregular mucosal pattern, loss of vascular pattern, and nodularity or depression. CONCLUSIONS: The yield of routine surveillance biopsy sampling of normal-appearing tubular esophageal neosquamous epithelium was zero. BE islands with indistinct mucosal or loss of vascular pattern, nodularity or depression, and/or signs of buried BE should raise clinician suspicion for advanced dysplasia or neoplasia recurrence. We suggest a new surveillance biopsy sampling protocol with a focus on meticulous inspection, followed by targeted biopsy sampling of visible lesions and random 4-quadrant biopsy sampling of the gastroesophageal junction.	esophagus
Factors Associated with Complications after Total Pharyngo-Laryngo-Esophagectomy and Free Jejunal Flap Reconstruction.	INTRODUCTION: Free jejunal flap (FJF) reconstruction is a standard procedure for pharyngeal and cervical esophageal defects resulting from head and neck cancer resection. However, improvements in patients' quality of life after surgery require a further statistical approach. METHODS: An observational, retrospective, multivariate analysis was designed to report the incidence of postoperative complications and their association with clinical factors in 101 patients who underwent total pharyngo-laryngo-esophagectomy and FJF reconstruction for head and neck cancer at a university hospital between January 2007 and December 2020. RESULTS: Postoperative complications were observed in 69% of patients. In the reconstructive site, anastomotic leak, observed in 8% of patients was associated with vascular anastomosis in the external jugular vein system (age-adjusted odds ratio [OR]: 9.05, p = 0.044) and anastomotic stricture, observed in 11% of patients was associated with postoperative radiotherapy (age-adjusted OR: 12.60, p = 0.02). Cervical skin flap necrosis was the most common complication (34%) and was associated with vascular anastomosis on the right cervical side (age- and sex-adjusted OR: 4.00, p = 0.005). CONCLUSION: Although FJF reconstruction is a useful procedure, 69% of patients suffer a postoperative complication. We suppose that anastomotic leak is related to the low blood flow resistance of the FJF and inadequate drainage of the external jugular venous system, and anastomotic stricture is related to the vulnerability of the intestinal tissue to radiation. Furthermore, we hypothesized that the location of the vascular anastomosis may affect the mesenteric location of the FJF and the dead space in the neck, leading to the development of cervical skin flap necrosis. These data contribute to increasing our knowledge about postoperative complications related to FJF reconstruction.	esophagus
Carbonic Anhydrase IX Targeting Mn(II)-Based Magnetic Resonance Molecular Imaging Probe for Hypoxia Tumors.	Physiological hypoxic conditions in the tumor microenvironment and consequential overexpression of carbonic anhydrase IX (CA IX) are two characteristics shared by numerous types of solid malignant tumors. Early detection with hypoxia assessment is crucial to improve the prognosis and therapy outcomes of hypoxia tumors. Herein, using acetazolamide (AZA) as a CA IX-targeting moiety, we design and synthesize an Mn(II)-based MR imaging probe (named AZA-TA-Mn) incorporating AZA and two Mn(II) chelates of Mn-TyEDTA on a rigid triazine (TA) scaffold. The per Mn relaxivity of AZA-TA-Mn is 2-fold higher than its monomeric Mn-TyEDTA, which allows it for low-dose imaging of hypoxic tumors. In a xenograft mice model of esophageal squamous cell carcinoma (ESCC), a low dosage of AZA-TA-Mn (0.05 mmol/kg) can selectively produce prolonged and stronger contrast enhancement in the tumor compared to the non-specific Gd-DTPA (0.1 mmol/kg). A competition study of co-injection of free AZA and Mn(II) probes confirms the in vivo tumor selectivity of AZA-TA-Mn, resulting in a more than 2.5-fold decreased tumor-to-muscle contrast-to-noise ratio (ΔCNR) at 60 min post-injection. MR imaging results were further supported by the quantitative analysis of Mn tissue levels, as the co-injection of free AZA resulted in significantly reduced Mn accumulation in tumor tissues. Finally, immunofluorescence staining of tissue sections confirms the positive correlation between the tumor accumulation of AZA-TA-Mn and CA IX overexpression. Hence, using CA IX as the hypoxia biomarker, our results illustrate a practical strategy for the development of novel imaging probes for hypoxic tumors.	esophagus
Updates of perioperative multidisciplinary treatment for surgically resectable esophageal cancer.	Esophageal cancer has one of the poorest prognoses among all cancer types, due to the propensity for an early spread through the lymphatics and the difficulty to perform surgical treatment. To improve the prognosis, the management of esophageal cancer has been developed through the conduct of several clinical trials worldwide. In western societies, neoadjuvant chemoradiotherapy has been established as the standard treatment approach, as indicated by the results of the CROSS trial. Recently, the Japanese JCOG1109 trial demonstrated the significant improvement of survival by neoadjuvant triplet chemotherapy. As an adjuvant treatment, an immune checkpoint inhibitor has shown promising results in the CheckMate-577 trial. Including adjuvant S-1 mono therapy as another option, a randomised control phase III study will determine the ideal treatment for surgically resectable esophageal cancer. Furthermore, the efficacy and safety of neoadjuvant cisplatin +5-fluorouracil or DCF plus nivolumab are examined in the JCOG1804E (FRONTiER) study. In addition to definitive chemoradiation therapy, the SANO trial is examining the safety and efficacy of active surveillance after neoadjuvant chemoradiotherapy, which might give us the choice to adopt organ preservation approach. The development of treatment has progressed dramatically with the advent of immunotherapy. Considering the biomarkers to predict the treatment response and prognosis, individualised multidisciplinary treatment strategies should be established for esophageal cancer patients.	esophagus
Systematic review of quality of life after esophagectomy and total gastrectomy in patients with gastro-esophageal junction cancer.	The optimal management of cancer of the gastro-esophageal junction (GEJ) is an area of contention. GEJ tumors are typically resected via total gastrectomy or esophagectomy. Despite many studies aiming to determine the superiority of either procedure based on surgical or oncological outcomes, the evidence is equivocal. Data focusing specifically on quality of life (QoL), however, is limited. This systematic review was performed to determine if there is any difference in patient's QoL after total gastrectomy or esophagectomy. A systematic search of PubMed, Medline and Cochrane libraries was conducted for literature published between 1986 and 2023. Studies that used the internationally validated questionnaires EORTC QLQ-C30 and EORTC-QLQ-OG25, to compare QoL after esophagectomy to gastrectomy for the management of GEJ cancer were included. Five studies involving 575 patients undergoing either esophagectomy (n = 365) or total gastrectomy (n = 210) for GEJ tumors were included. QoL was predominantly assessed at 6, 12 and 24 months postoperatively. Although individual studies demonstrated significant differences in certain domains, these differences were not consistently demonstrated in more than one study. There is no evidence to suggest any significant differences in QoL after total gastrectomy compared to esophagectomy for management of gastro-esophageal junction cancer.	esophagus