Tumour-associated and non-tumour-associated microbiota in colorectal cancer

We read with interest the elegant study published by Flemer et al1 and commend the authors on their work. The authors provide convincing data to illustrate that faecal microbiota does not reflect accurately the underlying mucosal microbiota in patients with colorectal cancer (CRC).1 The authors also provide supporting evidence to illustrate that microbiota from sampled mucosa both on and off the cancer site is not significantly different. As previously demonstrated, they also provide corroboratory evidence to further conclude that microbiota is different in patients with CRC.

We are however concerned about the conclusions relating to the variability of mucosal microbiota based on tumour site. They present data to suggest that Faecalibacterium, Blautia and Clostridium were significantly more abundant in patients with proximal cancer. It is clear from established work that many environmental factors, including body mass index and diet (red meat), influence both mucosal and faecal microbiota.

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Epidermal growth factor receptor inhibition downregulates Helicobacter pylori-induced epithelial inflammatory responses, DNA damage and gastric carcinogenesis

Objective

Gastric cancer is the third leading cause of cancer death worldwide and infection by Helicobacter pylori is the strongest risk factor. We have reported increased epidermal growth factor receptor (EGFR) phosphorylation in the H. pylori-induced human carcinogenesis cascade, and association with DNA damage. Our goal was to determine the role of EGFR activation in gastric carcinogenesis.

Design

We evaluated gefitinib, a specific EGFR inhibitor, in chemoprevention of H. pylori-induced gastric inflammation and cancer development. Mice with genetically targeted epithelial cell-specific deletion of Egfr (Efgr^epi mice) were also used.

Results

In C57BL/6 mice, gefitinib decreased Cxcl1 and Cxcl2 expression by gastric epithelial cells, myeloperoxidase-positive inflammatory cells in the mucosa and epithelial DNA damage induced by H. pylori infection. Similar reductions in chemokines, inflammatory cells and DNA damage occurred in infected Egfr^epi versus Egfr^fl/fl control mice. In H. pylori-infected transgenic insulin-gastrin (INS-GAS) mice and gerbils, gefitinib treatment markedly reduced dysplasia and carcinoma. Gefitinib blocked H. pylori-induced activation of mitogen-activated protein kinase 1/3 (MAPK1/3) and activator protein 1 in gastric epithelial cells, resulting in inhibition of chemokine synthesis. MAPK1/3 phosphorylation and JUN activation was reduced in gastric tissues from infected wild-type and INS-GAS mice treated with gefitinib and in primary epithelial cells from Efgr^epi versus Egfr^fl/fl mice. Epithelial EGFR activation persisted in humans and mice after H. pylori eradication, and gefitinib reduced gastric carcinoma in INS-GAS mice treated with antibiotics.

Conclusions

These findings suggest that epithelial EGFR inhibition represents a potential strategy to prevent development of gastric carcinoma in H. pylori-infected individuals.

http://ift.tt/2pa7Eby

The microbiota: an underestimated actor in radiation-induced lesions?

The co-evolution of humans and microbes that colonise the GI tract is shaped by environmental factors and evolved to promote health.1 Microbial derangements (termed dysbiosis) have been observed for a variety of intestinal and extraintestinal diseases.1 Metabolic, autoimmune, liver and intestinal disorders have been linked to microbial dysbiosis which promotes susceptibility to inflammatory disease in some cases as largely assessed in animal models.2 Intestinal dysbiosis has also been implicated in colorectal cancer3 and microbes may determine treatment response for non-intestinal malignancies.4

For more than 10 years, intestinal microbial alterations have been associated with localised radiation in humans and mouse models.5–8 Importantly, mice that lack colonisation of microbes (ie, raised germ free) were resistant to lethal radiation enteritis, indicating that the microbiota controls intestinal disease processes consequent to radiation-induced damage.9 In this context, however,...

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Ethnic differences in colon cancer care in the Netherlands: a nationwide registry-based study

Abstract

Background

Ethnic differences in colon cancer (CC) care were shown in the United States, but results are not directly applicable to European countries due to fundamental healthcare system differences. This is the first study addressing ethnic differences in treatment and survival for CC in the Netherlands.

Methods

Data of 101,882 patients diagnosed with CC in 1996–2011 were selected from the Netherlands Cancer Registry and linked to databases from Statistics Netherlands. Ethnic differences in lymph node (LN) evaluation, anastomotic leakage and adjuvant chemotherapy were analysed using stepwise logistic regression models. Stepwise Cox regression was used to examine the influence of ethnic differences in adjuvant chemotherapy on 5-year all-cause and colorectal cancer-specific survival.

Results

Adequate LN evaluation was significantly more likely for patients from 'other Western' countries than for the Dutch (OR 1.09; 95% CI 1.01–1.16). 'Other Western' patients had a significantly higher risk of anastomotic leakage after resection (OR 1.24; 95% CI 1.05–1.47). Patients of Moroccan origin were significantly less likely to receive adjuvant chemotherapy (OR 0.27; 95% CI 0.13–0.59). Ethnic differences were not fully explained by differences in socioeconomic and hospital-related characteristics. The higher 5-year all-cause mortality of Moroccan patients (HR 1.64; 95% CI 1.03–2.61) was statistically explained by differences in adjuvant chemotherapy receipt.

Conclusion

These results suggest the presence of ethnic inequalities in CC care in the Netherlands. We recommend further analysis of the role of comorbidity, communication in patient-provider interaction and patients' health literacy when looking at ethnic differences in treatment for CC.

http://ift.tt/2pdl87n

Relationship between Hospital Volume and Outcomes in Patients with Traumatic Brain Injury: A Retrospective Observational Study using a National Inpatient Database in Japan

Publication date: Available online 3 May 2017
Source:Injury
Author(s): Tomoki Wada, Hideo Yasunaga, Kent Doi, Hiroki Matsui, Kiyohide Fushimi, Yoichi Kitsuta, Susumu Nakajima
BackgroundThe relationship between hospital volume and outcome after traumatic brain injury (TBI) is not completely understood in a real clinical setting. We investigated whether patients admitted with TBI achieved better outcomes in high-volume hospitals than in low-volume hospitals using a national inpatient database in Japan.MethodsThis retrospective cohort study used the Diagnosis Combination Procedure database in Japan. We included patients with TBI admitted to hospitals with a Japan Coma Scale (JCS) score ≥2 between April 1, 2013 and March 31, 2014. Hospital volume was defined as the annual number of all admissions with TBI in individual hospitals. The hospital volume was categorized into four volume groups: low (≤60 admissions per hospital), medium-low (61–120 admissions per hospital), medium-high (121–180 admissions per hospital) and high (≥181 admissions per hospital). The outcomes of interest included 28-day mortality and survival discharge with complete dependency defined as a Barthel Index score of 0 at discharge. We used multiple logistic regression models fitted with generalized estimating equations to evaluate relationships between the hospital volume and the outcomes. The hospital volume was evaluated both as categorical variables defined above and as continuous variables.ResultsThe analysis dataset consisted of 20,146 eligible patients. Of these, 2,784 died within 28days (13.8%) and 3,409 were completely dependent among 16,996 patients discharged alive (20.1%). Multivariable analyses found that there was no significant relationship between hospital volume and 28-day mortality (adjusted odds ratio [OR] 0.79, 95% confidence interval [CI] 0.58–1.06 for the high-volume group) or complete dependency at discharge (adjusted OR 0.94, 95% CI 0.71–1.23 for the high-volume group). The results were the same when the hospital volume was evaluated as a continuous variable.ConclusionsHospital volume did not appear to influence outcomes in patients with TBI. High-volume hospitals may not be necessarily beneficial for patients with TBI exhibiting impaired consciousness as a whole.



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The Epidemiology and Hotspots of Road Traffic Injuries in Moshi, Tanzania: an observational study

Publication date: Available online 3 May 2017
Source:Injury
Author(s): Joseph M. Reardon, Luciano Andrade, Julian Hertz, George Kiwango, Anneth Teu, Msafiri Pesambili, Deena El-Gabri, Michael Hocker, Mark Mvungi, João Ricardo N. Vissoci, Catherine A. Staton
Road traffic injuries (RTIs) continue to increase with the proliferation of motor vehicles, especially in low-income countries where safe road infrastructure is lacking Knowing where and why RTIs occur would allow for increased safety and prevention planning. In this study, police records of 300 motor vehicle collisions which occurred between February 2013 and January 2014 in Moshi, Tanzania, were reviewed. Analysis of variables including victim age, gender, type of collision, conditions, and use of safety equipment were analyzed. Geographic information system (GIS) analysis was performed to identify areas with the most collisions. Most injuries occurred at four intersections on two main corridor. Car crashes represented 48% of reports while motorcycle collisions were 35% of reports. Victims were predominantly male. The majority (64%) of RTI victims in cars used seatbelts while only 43% of motorcyclists wore helmets; none of those who used the helmet or seatbelt suffered a grievous injury. These data demonstrate that RTIs in Moshi occur in predictable high traffic locations. RTIs injure victims of all backgrounds and safety equipment is not universally utilized. More investment is needed in improved data collection methods, and a greater emphasis on intersection safety is needed to reduce these preventable injuries.



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Bronchoalveolar Lavage of Murine Lungs to Analyze Inflammatory Cell Infiltration

The health status of the lung is reflected by the type and number of immune cells that are present in the bronchioles of the lung. We describe a bronchoalveolar lavage technique that allows the isolation and study of nonadherent cells and soluble factors from the lower respiratory tract of mice.

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