Standardized uptake value (SUV) in PET/CT for esophageal cancer correlates with pathological stage and predicts R-category of resection

postprin

Use of flow cytometry in the analysis of stage III squamous cell carcinoma of the oesophagus and its association with MIB-1

Aims - To examine the prognostic and pathobiological importance of DNA content in oesophageal squamous cell carcinomas in Hong Kong Chinese subjects; to evaluate its association with the immunohistochemical proliferative marker MIB-1. Methods - Paraffin wax embedded tumour tissue and adjacent normal tissue (control tissue) samples from 45 resected stage III oesophageal squamous cell carcinomas were studied using flow cytometric analysis. The DNA content and the clinicopathological data of these patients were analysed together with the MIB-1 labelling index. Results - DNA aneuploidy was present in 14 (31%) of the 45 cases. However, the DNA content did not correlate significantly with the age, sex, or survival of the patients, nor the length, location, differentiation and MIB-1 labelling index of the oesophageal carcinomas. The synthetic (S) phase fraction of diploid tumours bore no relation to the patients' survival or MIB-1 score. Conclusions - Flow cytometry was not as useful as the MIB-1 labelling index in predicting the biological characteristics of the tumours and the prognosis of patients with oesophageal squamous cell carcinomas. This study does not support the routine use of DNA flow cytometric analysis in oesophageal cancers.published_or_final_versio

Suppression of esophageal tumor growth and chemoresistance by directly targeting the PI3K/AKT pathway

Esophageal cancer is the sixth most common cause of cancer-related deaths worldwide. Novel therapeutic intervention is urgently needed for this deadly disease. The functional role of PI3K/AKT pathway in esophageal cancer is little known. In this study, our results from 49 pairs of human esophageal tumor and normal specimens demonstrated that AKT was constitutively active in the majority (75.5%) of esophageal tumors compared with corresponding normal tissues. Inhibition of the PI3K/AKT pathway with specific inhibitors, wortmannin and LY294002, significantly reduced Bcl-xL expression, induced caspase-3-dependent apoptosis, and repressed cell proliferation and tumor growth in vitro and in vivo without obvious toxic effects. Moreover, significantly higher expression level of p-AKT was observed in fluorouracil (5-FU)-resistant esophageal cancer cells. Inactivation of PI3K/AKT pathway markedly increased the sensitivity and even reversed acquired resistance of esophageal cancer cells to chemotherapeutic drugs in vitro. More importantly, the resistance of tumor xenografts derived from esophageal cancer cells with acquired 5-FU resistance to chemotherapeutic drugs was significantly abrogated by wortmannin treatment in animals. In summary, our data support PI3K/AKT as a valid therapeutic target and strongly suggest that PI3K/AKT inhibitors used in conjunction with conventional chemotherapy may be a potentially useful therapeutic strategy in treating esophageal cancer patients.published_or_final_versio

Role of AMPK signaling in mediating the anticancer effects of silibinin in esophageal squamous cell carcinoma

postprin

A prospective randomized trial comparing the use of omeprazole-based dual and triple therapy for eradication of Helicobacter pylori

Conference Theme: Challenges to specialists in the 21st centurypublished_or_final_versio

The pattern of recurrence of adenocarcinoma of the oesophago-gastric junction

Knowledge of the pattern of recurrence of surgically treated cases of adenocarcinoma of the oesophago-gastric junction is important both for better understanding of their biological nature and for future strategic planning of therapy. The aim of this study is to demonstrate and compare the pattern of dissemination and recurrence in patients with Type I and Type II adenocarcinoma of oesophago-gastric junction. A prospective audit of the clinico-pathological features of patients who had undergone surgery with curative intent for adenocarcinoma of oesophago-gastric junction between 1991 and 1996 was undertaken. Patients were followed up by regular clinical examination. Clinical evaluation was supported by ultrasound, computerised tomography, radio-isotope bone scan, endoscopy and laparotomy each with biopsy and histology where appropriate. One hundred and sixty-nine patients with oesophago-gastric junction tumours (94 Type I and 75 Type II) have been followed up for a median of 75.3 (57–133) months. One hundred and three patients developed proven recurrent disease. The median time to recurrence was 23.3 (14.2–32.4) months for Type I and 20.5 (11.6–29.4) for Type II cancers. The most frequent type of recurrence was haematogenous (56% of Type I recurrences and 54% of Type II) of which 56% were detected within 1 year of surgery. The most frequent sites were to liver (27%), bone (18%) brain (11%) and lung (11%). Local recurrence occurred in 33% of Type I cancer and 29% of Type II recurrences. Nodal recurrence occurred in 18 and 25% of Type I and Type II cancer recurrences, most frequently to coeliac or porta hepatis nodes (64%). Only 7% of Type I and 15% of Type II cancer recurrences were by peritoneal dissemination. Type I and Type II adenocarcinoma of the oesophago-gastric junction have a predominantly early, haematogenous pattern of recurrence. There is a need to better identify the group of patients with small metastases at the time of diagnosis who are destined to develop recurrent disease in order that they may be spared surgery and those with micro metastases in order that they can be offered multi-modality therapy including early post operative or neo-adjuvant chemotherapy

A phase 1 trial of the safety, tolerability and biological effects of intravenous Enadenotucirev, a novel oncolytic virus, in combination with chemoradiotherapy in locally advanced rectal cancer (CEDAR)

Background: Chemoradiotherapy remains the standard of care for locally advanced rectal cancer. Efforts to intensify treatment and increase response rates have yet to yield practice changing results due to increased toxicity and/or absence of increased radiosensitization. Enadenotucirev (EnAd) is a tumour selective, oncolytic adenovirus which can be given intravenously. Pre-clinical evidence of synergy with radiation warrants further clinical testing and assessment of safety with radiation. Methods: Eligibility include histology confirmed locally advanced rectal cancer that require chemoradiation. The trial will use a Time-to-Event Continual Reassessment Model-based (TiTE-CRM) approach using toxicity and efficacy as co-primary endpoints to recommend the optimal dose and treatment schedule 30 patients will be recruited. Secondary endpoints include pathological complete response the neoadjuvant rectal score. A translational program will be based on a mandatory biopsy during the second week of treatment for ‘proof-of-concept’ and exploration of mechanism. The trial opened to recruitment in July 2019, at an expected rate of 1 per month for up to 4 years. Discussion: Chemoradiation with Enadenotucirev as a radiosensitiser in locally Advanced Rectal cancer (CEDAR) is a prospective multicentre study testing a new paradigm in radiosensitization in rectal cancer. The unique ability of EnAd to selectively infect tumour cells following intravenous delivery is an exciting opportunity with a clear translational goal. The novel statistical design will make efficient use of both toxicity and efficacy data to inform subsequent studies. Trial registration: ClinicalTrial.gov, NCT03916510. Registered 16th April 2019

Worldwide Esophageal Cancer Collaboration : clinical staging data

Peer reviewe

Value of MRI and diffusion-weighted MRI for the diagnosis of locally recurrent rectal cancer

OBJECTIVES: To evaluate the accuracy of standard MRI, diffusion-weighted MRI (DWI) and fusion images for the diagnosis of locally recurrent rectal cancer in patients with a clinical suspicion of recurrence. METHODS: Forty-two patients with a clinical suspicion of recurrence underwent 1.5-T MRI consisting of standard T2-weighted FSE (3 planes) and an axial DWI (b0,500,1000). Two readers (R1,R2) independently scored the likelihood of recurrence; [1] on standard MRI, [2] on standard MRI+DWI, and [3] on T2-weighted+DWI fusion images. RESULTS: 19/42 patients had a local recurrence. R1 achieved an area under the ROC-curve (AUC) of 0.99, sensitivity 100% and specificity 83% on standard MRI versus 0.98, 100% and 91% after addition of DWI (p = 0.78). For R2 these figures were 0.87, 84% and 74% on standard MRI and 0.91, 89% and 83% with DWI (p = 0.09). Fusion images did not significantly improve the performance. Interobserver agreement was kappa0.69 for standard MRI, kappa0.82 for standard MRI+DWI and kappa0.84 for the fusion images. CONCLUSIONS: MRI is accurate for the diagnosis of locally recurrent rectal cancer in patients with a clinical suspicion of recurrence. Addition of DWI does not significantly improve its performance. However, with DWI specificity and interobserver agreement increase. Fusion images do not improve accuracy