Stopping drinking and risk of oesophageal cancer.

OBJECTIVE--To examine the effect of stopping drinking on the risk of oesophageal cancer. DESIGN--Hospital based case-control study. SETTING--Surgical departments of four district general hospitals and general practices in Hong Kong. SUBJECTS--Cases were 400 consecutive admissions of patients with histologically confirmed diagnosis of oesophageal cancer during a 21 month period in 1989-90 (87% response rate). Controls were 1598 patients selected from the same surgical departments as the cases and from the general practices from which the cases were originally referred (95% response rate). MAIN OUTCOME MEASURE--Relative risk of developing oesophageal cancer after stopping drinking (adjusted for age, education, place of birth, smoking, and diet). RESULTS--Current light drinking (< 200g ethanol/week) was not associated with significant increase in risk. Among former drinkers risk fell more quickly in moderate (200-599 g/week) than heavy (> or = 600 g/week) drinkers. Even among heavy drinkers, however, risk had dropped substantially after five to nine years of not drinking. The results suggest that the time taken for risk to return to that in subjects who never drink was 10-14 years for moderate drinkers and 15 years or more, if ever, for heavy drinkers. CONCLUSION--Risk of oesophageal cancer decreases fairly rapidly with time after abstaining from drinking. This new finding could be used in health promotion to encourage behavioural changes, especially in heavy drinkers, who have a very high risk of developing oesophageal cancer. It also suggests that alcoholic beverages have a strong effect on the late stage of carcinogenesis.     

Probing the link between oestrogen receptors and oesophageal cancer

Background

Elevated pre-operative neutrophil: lymphocyte ratio (NLR) has been identified as a predictor of survival in patients with hepatocellular and colorectal cancer. The aim of this study was to examine the prognostic value of an elevated preoperative NLR following resection for oesophageal cancer.

Methods

Patients who underwent resection for oesophageal carcinoma from June 1997 to September 2007 were identified from a local cancer database. Data on demographics, conventional prognostic markers, laboratory analyses including blood count results, and histopathology were collected and analysed.

Results

A total of 294 patients were identified with a median age at diagnosis of 65.2 (IQR 59-72) years. The median pre-operative time of blood sample collection was three days (IQR 1-8). The median neutrophil count was 64.2 × 10^-9/litre, median lymphocyte count 23.9 × 10^-9/litre, whilst the NLR was 2.69 (IQR 1.95-4.02). NLR did not prove to be a significant predictor of number of involved lymph nodes (Cox regression, p = 0.754), disease recurrence (p = 0.288) or death (Cox regression, p = 0.374). Furthermore, survival time was not significantly different between patients with high (≥ 3.5) or low (< 3.5) NLR (p = 0.49).

Conclusion

Preoperative NLR does not appear to offer useful predictive ability for outcome, disease-free and overall survival following oesophageal cancer resection.     

YAP-TEAD up-regulates IRS2 expression to induce and deteriorate oesophageal cancer

Oesophageal cancer (EC) represents a significant cause of cancer worldwide. Yes-associated protein (YAP) is reported to correlate with the initiation of multiple cancers including EC, but the underlying mechanism remains elusive. The current study aimed to investigate the molecular mechanism of YAP-TEAD in the occurrence and progression of EC. EC tissues and cells were obtained, followed by determination of the expression of YAP, c-Jun, pc-Jun and IRS2. The effect of YAP-TEAD on the biological EC cell processes was explored through gain- and loss-of-function approaches. The interaction between YAP and TEAD was detected by co-immunoprecipitation. The binding of TEAD to the c-Jun promoter was determined using chromatin immunoprecipitation. Tumour formation in the nude mice was detected in order to ascertain the effect of YAP and IRS2 in vivo. We found elevated YAP in the EC tissues and cells. YAP silencing led to a decrease in EC cell proliferation, invasion and sphere formation. YAP-TEAD complex bound to the promotor of c-Jun, and c-Jun led to an increase in the expression of IRS2 through the JNK/c-Jun pathway. Additionally, pc-Jun and phosphorylated JNK were localized in the nuclear in addition to displaying enhanced expression in the EC tissues. IRS2 overexpression negated the inhibition of cell proliferation, invasion and sphere formation triggering YAP silencing. YAP up-regulated IRS2 and aggravated EC in vivo. Taken together, YAP-TEAD activates the JNK/c-Jun pathway to up-regulate IRS2, ultimately promoting EC progression. Therefore, YAP-TEAD inhibition could be a promising therapeutic approach for EC treatment.     

Concomitant chemo-radiotherapy for unresectable oesophageal cancer: A mono-institutional study on 40 patients

Background/AimTo analyse clinical response, overall (OS) and disease free survival (DFS) and toxicity in patients with unresectable oesophageal cancer treated by concomitant chemo-radiotherapy (CRT).Materials and methodsForty patients with stage IIa–IVa biopsy proven oesophageal carcinoma were treated with CRT. All patients were studied with endoscopy and CT and judged unresectable after multidisciplinary discussion. CRT consisted of 3 cycles of cisplatin 100 mg/m² or carboplatin 300 mg/m² on day 1 and 5-fluorouracil 1000 mg/m² as a continuous infusion of 96 h associated with concurrent 3D-conformal RT. By using 15 MeV X-rays, a total dose of 60–66 Gy was delivered with daily fractions of 1.8–2.0 Gy.ResultsComplete response (CR), partial response (PR) and no response (NR) were observed in 50%, 20% and 20% of cases, respectively. Of the 20 patients with CR, 15 developed loco-regional recurrent disease. OS and DFS rates at 3 and 5 years were 38%, 8%, 49% and 10%, respectively. Total radiation dose ≥60 Gy improved loco-regional control and complete response (CR vs. PR + NR; p = 0.004) influenced both DFS and loco-regional control. Grade 3 gastrointestinal and haematological acute toxicity occurred in 3/40 patients (7.5%). One patient developed grade 4 renal failure. Late toxicity was reported in 2/40 patients (5.0%), consisting of grade 3 radiation pneumonitis.ConclusionsConcomitant CRT for unresectable oesophageal cancer can result in an acceptable loco-regional control with limited toxicity. Response after treatment and total radiation dose influenced the outcome.     

MicroRNAs as oncogenes or tumour suppressors in oesophageal cancer: potential biomarkers and therapeutic targets

MicroRNAs are a class of small, non‐coding RNAs that can negatively regulate protein‐coding genes, and are associated with almost all known physiological and pathological processes, especially cancer. The number of studies documenting miRNA expression patterns in malignancy continues to expand rapidly, with continuously gained critical information regarding how aberrantly expressed miRNAs may contribute to carcinogenesis. miRNAs can influence cancer pathogenesis, playing a potential role as either oncogenes or tumour suppressors. Recently, several miRNAs have been reported to exert different regulatory functions in oesophageal cancer – the carcinoma typically arising from the epithelial lining of the oesophagus. These miRNAs also have potential clinical applications towards developing biomarkers or targets for possible use in diagnosis or therapy in oesophageal cancer. In this review, we have summarized the two (oncogenic or tumour suppressive) roles of miRNAs here, and their applications as potential biomarkers or therapeutic targets, which may illuminate future treatment for oesophageal cancer.     

Alcohol consumption and risk of upper-tract urothelial cancer

BackgroundUpper-tract urothelial cancer (UTUC), which includes renal pelvic cancer and ureter cancer, is a rare cancer and its prognosis is poor. Smoking and high-risk occupations (e.g., printing and dyestuff working which involves exposure to aniline dyes) are well-known risk factors for UTUC. However, the risk of alcohol consumption in UTUC remains unclear. This study aimed to determine whether alcohol consumption is an independent risk factor for UTUC.MethodsThe study was a case–control study which used the nationwide clinical inpatient database of the Rosai Hospital group in Japan. We identified 1569 cases and 506,797 controls between 1984 and 2014. We estimated the odds ratio (OR) and 95% confidence interval (95%CI) of alcohol consumption for UTUC – never, up to 15 g/day, >15–30 g/day, or >30 g/day – using unconditional logistic regression. We adjusted for the following covariates: age, sex, study period, hospital, history of smoking, and high-risk occupation.ResultsThe risk of UTUC was significantly higher in ever-drinkers compared with never-drinkers (OR = 1.23, 95%CI, 1.08–1.40; P = 0.001). Compared with never-drinkers, the risk threshold for UTUC was >15 g of alcohol consumption per day (equivalent to 6 ounces of Japanese sake containing 23 g of alcohol). A dose-response was observed (P < 0.001).ConclusionAlcohol consumption may be an independent risk factor for UTUC, with a low-risk threshold of 15 g of alcohol per day.     

Incidence trends in oesophageal cancer by histological type: An updated analysis in Sweden

BackgroundWe aimed to update incidence trends of oesophageal cancer by histological type in Sweden.MethodsUsing data from the Swedish Cancer Registry, we examined incidence trends of oesophageal cancer by histological types in individuals aged ≥50 years in 1970–2014 using log-linear joinpoint regressions.ResultsThe age-standardised incidence rate of oesophageal adenocarcinoma in men increased on average by 3.0% per year in 1970–1994, followed by a more rapid increase of 13.7% per year in 1994–2000, and a slower increase of 2.6% per year in 2010–2014. The rate of oesophageal adenocarcinoma in women increased on average by 4.2% per year during the entire period. The rate of squamous cell carcinoma generally decreased over the past 2–3 decades in both sexes.ConclusionsThe incidence of oesophageal adenocarcinoma continues to rise in Sweden, although the increase seems to have slowed down in men since 2000. The incidence of oesophageal squamous cell carcinoma is decreasing.     

Computer-aided oesophageal manometry: Prospects and problems

We describe a method in which computer-aided analysis has been applied to oesophageal manometry, and address some of the major problems which were encountered. The elimination of pressure artefacts caused by respiration and normal cardiac function is necessary in order to define accurately the parameters required from the analysis. The most promising method of solving this signal/noise problem is to include a fast Fourier transform in the analytical program.     

Diverging trends in recent population-based survival rates in oesophageal and gastric cancer

Background

Survival trends in oesophageal and gastric cancer need to be updated. A nationwide Swedish population-based study in 1961–2009 was based on registry data.

Methodology/Principal Findings

Relative survival rate, i.e. the ratio of the observed to the expected survival, adjusted for age, sex, and calendar period, and presented with 95% confidence intervals (CI), was the main outcome measure. The expected survival was calculated using the corresponding Swedish general population with no exclusions. The relative survival rates in oesophageal and gastric cardia adenocarcinoma have improved since the 1990s (p for trend <0.001), but not in oesophageal squamous cell carcinoma or gastric non-cardia adenocarcinoma. The relative 5-year survival rates during the two recent periods 1990–1999 and 2000–2008 were 12.5% (95%CI 10.1%–14.9%) and 10.3% (95%CI 8.5–12.0%) for oesophageal squamous cell carcinoma, 12.5% (95%CI 10.1%–14.9%) and 14.6% (95%CI 12.6–16.6%) for oesophageal adenocarcinoma, 11.1% (95%CI 9.6%–12.6%) and 14.3% (95%CI 12.3–16.3%) for gastric cardia adenocarcinoma, and 20.2% (95%CI 19.2%–21.1%) and 19.0% (95%CI 17.7–20.2%) for gastric non-cardia adenocarcinoma. The 3-year survival in tumour stage III in 2004–2008 was about 25% for all four tumour types.

Conclusions/Significance

The survival in oesophageal and cardia adenocarcinoma is increasing, but the lack of such increase in oesophageal squamous cell carcinoma and gastric non-cardia adenocarcinoma is a concern.     

Predicting the response of localised oesophageal cancer to neo-adjuvant chemoradiation

Background

One of the most exciting and talked about new surgical techniques in breast cancer surgery is the sentinel lymph node biopsy. It is an alternative procedure to standard axillary lymph node dissection, which makes possible less invasive surgery and side effects for patients with early breast cancer that wouldn't benefit further from axillary lymph node clearance. Sentinel lymph node biopsy helps to accurately evaluate the status of the axilla and the extent of disease, but also determines appropriate adjuvant treatment and long-term follow-up. However, like all surgical procedures, the sentinel lymph node biopsy is not appropriate for each and every patient.

Methods

In this article we review the absolute and relative contraindications of the procedure in respect to clinically positive axilla, neoadjuvant therapy, tumor size, multicentric and multifocal disease, in situ carcinoma, pregnancy, age, body-mass index, allergies to dye and/or radio colloid and prior breast and/or axillary surgery.

Results

Certain conditions involving host factors and tumor biologic characteristics may have a negative impact on the success rate and accuracy of the procedure. The overall fraction of patients unsuitable or with multiple risk factors that may compromise the success of the sentinel lymph node biopsy, is very small. Nevertheless, these patients need to be successfully identified, appropriately advised and cautioned, and so do the surgeons that perform the procedure.

Conclusion

When performed by an experienced multi-disciplinary team, the SLNB is a highly effective and accurate alternative to standard level I and II axillary clearance in the vast majority of patients with early breast cancer.