Cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) depends on binding of the viral spike (S) proteins to angiotensin-converting enzyme 2 and on S protein priming by TMPRSS2. ...Inhibition of TMPRSS2 may work to block or decrease the severity of SARS-CoV-2 infections. Intriguingly, TMPRSS2 is an androgen-regulated gene that is up-regulated in prostate cancer where it supports tumor progression and is involved in a frequent genetic translocation with the ERG gene. First- or second-generation androgen-deprivation therapies (ADTs) decrease the levels of TMPRSS2. Here we put forward the hypothesis that ADTs may protect patients affected by prostate cancer from SARS-CoV-2 infections.
We extracted data regarding 9280 patients (4532 males) with laboratory-confirmed SARS-CoV-2 infection from 68 hospitals in Veneto, one of the Italian regions that was most affected by the coronavirus disease 2019 (COVID-19) pandemic. The parameters used for each COVID-19-positive patient were sex, hospitalization, admission to intensive care unit, death, tumor diagnosis, prostate cancer diagnosis, and ADT.
There were evaluable 9280 SARS-CoV-2-positive patients in Veneto on 1 April 2020. Overall, males developed more severe complications, were more frequently hospitalized, and had a worse clinical outcome than females. Considering only the Veneto male population (2.4 million men), 0.2% and 0.3% of non-cancer and cancer patients, respectively, tested positive for SARS-CoV-2. Comparing the total number of SARS-CoV-2-positive cases, prostate cancer patients receiving ADT had a significantly lower risk of SARS-CoV-2 infection compared with patients who did not receive ADT (OR 4.05; 95% CI 1.55–10.59). A greater difference was found comparing prostate cancer patients receiving ADT with patients with any other type of cancer (OR 4.86; 95% CI 1.88–12.56).
Our data suggest that cancer patients have an increased risk of SARS-CoV-2 infections compared with non-cancer patients. However, prostate cancer patients receiving ADT appear to be partially protected from SARS-CoV-2 infections.
•SARS-CoV-2-infected men have a worse clinical outcome than women.•Cancer patients have an increased risk of SARS-CoV-2 infection.•Prostate cancer patients receiving androgen-deprivation therapies appear to be partially protected from the infection.
Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori ...were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.
Despite major advances in the management of metastatic colorectal cancer (mCRC) with liver-only involvement, relapse rates are high and reliable prognostic markers are needed.
To assess the ...prognostic impact of BRAF and RAS mutations in a large series of liver-resected patients, medical records of 3024 mCRC patients were reviewed. Eligible cases undergoing potentially curative liver resection were selected. BRAF and RAS mutational status was tested on primary and/or metastases by means of pyrosequencing and mass spectrometry genotyping assay. Primary endpoint was relapse-free survival (RFS).
In the final study population (N=309) BRAF mutant, RAS mutant and all wild-type (wt) patients were 12(4%), 160(52%) and 137(44%), respectively. Median RFS was 5.7, 11.0 and 14.4 months respectively and differed significantly (Log-rank, P=0.043). At multivariate analyses, BRAF mutant had a higher risk of relapse in comparison to all wt (multivariate hazard ratio (HR)=2.31; 95% CI, 1.09-4.87; P=0.029) and to RAS mutant (multivariate HR=2.06; 95% CI, 1.02-4.14; P=0.044). Similar results were obtained in terms of overall survival. Compared with all wt patients, RAS mutant showed a higher risk of death (HR=1.47; 95% CI, 1.05-2.07; P=0.025), but such effect was lost at multivariate analyses.
BRAF mutation is associated with an extremely poor median RFS after liver resection and with higher probability of relapse and death. Knowledge of BRAF mutational status may optimise clinical decision making in mCRC patients potentially candidate to hepatic surgery. RAS status as useful marker in this setting might require further studies.
The stomach is traditionally regarded as a hollow muscular sac that initiates the second phase of digestion. Yet this simple view ignores the fact that it is the most sophisticated endocrine organ ...with unique physiology, biochemistry, immunology and microbiology. All ingested materials, including our nutrition, have to negotiate this organ first, and as such, the stomach is arguably the most important segment within the GI tract. The unique biological function of gastric acid secretion not only initiates the digestive process but also acts as a first line of defence against food-borne microbes. Normal gastric physiology and morphology may be disrupted by Helicobacter pylori infection, the most common chronic bacterial infection in the world and the aetiological agent for most peptic ulcers and gastric cancer. In this state-of-the-art review, the most relevant new aspects of the stomach in health and disease are addressed. Topics include gastric physiology and the role of gastric dysmotility in dyspepsia and gastroparesis; the stomach in appetite control and obesity; there is an update on the immunology of the stomach and the emerging field of the gastric microbiome. H. pylori-induced gastritis and its associated diseases including peptic ulcers and gastric cancer are addressed together with advances in diagnosis. The conclusions provide a future approach to gastric diseases underpinned by the concept that a healthy stomach is the gateway to a healthy and balanced host. This philosophy should reinforce any public health efforts designed to eradicate major gastric diseases, including stomach cancer.
Aliment Pharmacol Ther 31, 1104–1111
Summary
Background Intestinal‐type gastric cancer (GC) still ranks among the high‐incidence, highly lethal malignancies. Atrophic gastritis is the cancerization ...field in which GC develops. The current histological reporting formats for gastritis do not include any (atrophy‐based) ranking of GC risk.
Aim To test the gastritis OLGA‐staging (Operative Link for Gastritis Assessment) in prognosticating neoplastic progression.
Methods Ninety‐three Italian patients were followed up for more than 12 years (range: 144–204 months). Clinical examinations, pepsinogen serology, endoscopy and histology (also assessing Helicobacter pylori status) were performed both at enrolment (T1) and at the end of the follow‐up (T2).
Results All invasive or intra‐epithelial gastric neoplasia were consistently associated with high‐risk (III/IV) OLGA stages. There was a significant inverse correlation between the mean pepsinogen ratio and the OLGA stage (test for trend; P < 0.001). OLGA‐staging at T1 predicted both the OLGA stage (Kaplan–Maier log‐rank test, P = 0.001) and the neoplasia at T2 (Kaplan–Maier log‐rank test, P = 0.001).
Conclusions This long‐term follow‐up study provides the first evidence that gastritis OLGA‐staging conveys relevant information on the clinico‐pathological outcome of gastritis and therefore for patient management. According to OLGA‐staging and H. pylori‐status, gastritis patients could be confidently stratified and managed according to their different cancer risks.
Background: The available classifications of gastritis are inconsistently used, possibly because none provides immediate prognostic/therapeutic information to clinicians. As histology reporting of ...hepatitis in terms of stage is clinically useful and widely accepted, an international group (Operative Link on Gastritis Assessment (OLGA)) proposed an equivalent staging system for reporting gastric histology. Gastritis staging integrates the atrophy score (obtained by biopsy) and the atrophy topography (achieved through directed biopsy mapping). Aim: To test in a prospective cross-sectional study whether OLGA staging consistently stratified patients according to their cancer risk and provided clear prognostic/therapeutic information. Methods: OLGA staging for gastric cancer risk (0–IV) and gastritis grading (overall score of the inflammatory infiltrate, grade 1–4) were applied in 439 prospectively enrolled, consecutive, dyspeptic outpatients who underwent endoscopy with standardised biopsy sampling. Incidental neoplastic lesions and coexisting peptic ulcers were recorded. Results were presented as stage (including antral (A) and corpus (C) atrophy scores) and H pylori status (eg, A = 3; C = 2: stage IV; Hp+ve). Results: Benign conditions (including duodenal ulcers; p<0.001) consistently clustered in stages 0–II, whereas all neoplastic (invasive and non-invasive) lesions clustered in stages III–IV (p<0.001). Conclusions: Gastritis staging, combined with H pylori status, provided clinically relevant information on the overall status of the gastric mucosa with implications for prognosis, therapy and management.
Abstract Introduction The simultaneous assessment of multiple indicators for quality of care is essential for comparisons of performance between hospitals and health care systems. The aim of this ...study was to assess the rates of in-hospital mortality and 30-day readmission and length of hospital stay (LOS) in patients who underwent surgical procedures for colorectal cancer between 2005 and 2014 in Italy. Methods All patients in the National Italian Hospital Discharge Dataset who underwent a surgical procedure for colorectal cancer during the study period were included. The adjusted odd ratios for risk factors for in-hospital mortality, 30-day readmission, and LOS were calculated using multilevel multivariable logistic regression. Results Among the 353 941 patients, rates of in-hospital mortality and 30-day readmission were 2.5% and 6%, respectively, and the median LOS was 13 days. High comorbidity, emergent/urgent admission, male gender, creation of a stoma, and an open approach increased the risks of all the outcomes at multivariable analysis. Age, hospital volume, hospital geographic location, and discharge to home/non-home produced different effects depending on the outcome considered. The most frequent causes of readmission were infection (19%) and bowel obstruction (14.6%). Conclusions We assessed national averages for mortality, LOS and readmission and related trends over a 10-year time. Laparoscopic surgery was the only one that could be modified by improving surgical education. Higher hospital volume was associated with a LOS reduction, but our findings only partially support a policy of centralization for colorectal cancer procedures. Surgical site infection was identified as the most preventable cause of readmission.