Background and Aim
Primary biliary cholangitis (PBC) patients who are refractory to ursodeoxycholic acid (UDCA) are at risk for progression to cirrhosis and liver failure. Bezafibrate could be an ...alternative second‐line therapeutic option in these patients. This study aimed to evaluate the long‐term outcome(s) of combined UDCA and bezafibrate therapy in UDCA‐refractory PBC patients and identify prognostic factors.
Methods
Among 445 patients treated with UDCA, 150 patients inadequately responded to UDCA monotherapy and received long‐term UDCA plus bezafibrate (median, 15 years). Data from these patients were used for this retrospective analysis.
Results
Combination therapy resulted in significant improvements in serum biochemistry and liver transplantation risk estimated using the UK‐PBC‐risk and the GLOBE scores. The cumulative normalization rates of alkaline phosphatase, gamma‐glutamyltransferase, and immunoglobulin M (IgM) were significantly higher in patients without cirrhosis‐related symptoms or liver‐related events than in those with them. Overall, IgM constantly emerged as a significant factor associated with cirrhosis‐related symptoms and liver‐related events at all time points. Cumulative survival rates were significantly lower in patients with IgM ≥ 240 mg/dL than in patients with IgM < 240 mg/dL. Thus, normalization of IgM levels was a good surrogate predictor of long‐term prognosis. None of the patients discontinued combination therapy due to any adverse events during the follow‐up period.
Conclusions
Our findings point to the beneficial effects of long‐term UDCA plus bezafibrate combination therapy for UDCA‐refractory PBC patients, and IgM response can be a useful predictive biomarker of long‐term clinical outcomes.
Precise identification of the marginal line of gastric mucosal neoplasms is necessary for endoscopic curative resection by ESD. The use of an acetic acid-indigocarmine mixture (AIM) has been reported ...as safe and convenient for detecting gastric mucosal cancers and adenomas. It needs no special light instruments and magnifying endoscopic observation. We retrospectively investigated the usefulness of AIM-spraying for appropriate marking by detecting the marginal line of gastric mucosal neoplasms just before ESD. From June 2008 to February 2011, ESD was performed in 165 cases of gastric mucosal neoplasm in our hospital. Retrospectively, 8 endoscopists evaluated the marginal line of these cases by endoscopic images that were stored in the digital filing system. In 71 of the 165 cases in which the marginal line could not be decided by white light it was verified whether AIM-spraying made the marginal line clear and whether appropriate marking was performed according both endoscopic and pathological findings. A clear margin line was identified in 62 cases (87%) by AIM-spraying, and endoscopic findings agreed with pathological mapping. AIM-spraying can be a useful method for identifying gastric mucosal neoplasms and can be used to detect these horizontal margin lines just before ESD. In the other 9 cases, the lesions were not washed out by AIM-spraying. These cases were small depressed lesions or/and mucus stained lesions.
The consumption of processed meat has been associated with noncardia gastric cancer, but evidence regarding a possible role of red meat is more limited. Our study aims to quantify the association ...between meat consumption, namely white, red and processed meat, and the risk of gastric cancer, through individual participant data meta‐analysis of studies participating in the “Stomach cancer Pooling (StoP) Project”. Data from 22 studies, including 11,443 cases and 28,029 controls, were used. Study‐specific odds ratios (ORs) were pooled through a two‐stage approach based on random‐effects models. An exposure‐response relationship was modeled, using one and two‐order fractional polynomials, to evaluate the possible nonlinear association between meat intake and gastric cancer. An increased risk of gastric cancer was observed for the consumption of all types of meat (highest vs. lowest tertile), which was statistically significant for red (OR: 1.24; 95% CI: 1.00–1.53), processed (OR: 1.23; 95% CI: 1.06–1.43) and total meat (OR: 1.30; 95% CI: 1.09–1.55). Exposure‐response analyses showed an increasing risk of gastric cancer with increasing consumption of both processed and red meat, with the highest OR being observed for an intake of 150 g/day of red meat (OR: 1.85; 95% CI: 1.56–2.20). This work provides robust evidence on the relation between the consumption of different types of meat and gastric cancer. Adherence to dietary recommendations to reduce meat consumption may contribute to a reduction in the burden of gastric cancer.
What's new?
Consumption of processed meat has been associated with non‐cardia gastric cancer, but evidence regarding a possible role of red meat is more limited. Here, the authors explore associations between white, red, and processed meat consumption and gastric cancer risk through an individual participant data meta‐analysis of case‐control studies within the Stomach cancer Pooling Project. An increased risk of gastric cancer was observed with high intakes of red and processed meat, with further confirmation through the computational and graphical depiction of the exposure‐response associations. Adherence to dietary recommendations to reduce meat consumption may contribute to reducing the burden of gastric cancer.
Early-onset colorectal cancer diagnosed before the age of 50 years has been increasing. Likely reflecting the pathogenic role of the intestinal microbiome, which gradually changes across the entire ...colorectal length, the prevalence of certain tumor molecular characteristics gradually changes along colorectal subsites. Understanding how colorectal tumor molecular features differ by age and tumor location is important in personalized patient management.
Using 14,004 cases with colorectal cancer including 3,089 early-onset cases, we examined microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF mutations in carcinomas of the cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum and compared early-onset cases with later-onset cases.
The proportions of MSI-high, CIMP-high, and BRAF -mutated early-onset tumors were lowest in the rectum (8.8%, 3.4%, and 3.5%, respectively) and highest in the ascending colon (46% MSI-high; 15% CIMP-high) or transverse colon (8.6% BRAF -mutated) (all Ptrend <0.001 across the rectum to ascending colon). Compared with later-onset tumors, early-onset tumors showed a higher prevalence of MSI-high status and a lower prevalence of CIMP-high status and BRAF mutations in most subsites. KRAS mutation prevalence was higher in the cecum compared with that in the other subsites in both early-onset and later-onset tumors ( P < 0.001). Notably, later-onset MSI-high tumors showed a continuous decrease in KRAS mutation prevalence from the rectum (36%) to ascending colon (9%; Ptrend <0.001), followed by an increase in the cecum (14%), while early-onset MSI-high cancers showed no such trend.
Our findings support biogeographical and pathogenic heterogeneity of colorectal carcinomas in different colorectal subsites and age groups.
Abstract
Background
Epidemiological studies have shown inconsistent results regarding the link between smoking and breast cancer risk, despite the biological plausibility of a positive association.
...Methods
Participants were 166 611 women from nine prospective cohort studies in Japan which launched in 1984–1994 and followed for 8–22 years. Information on smoking and secondhand smoke was obtained through self-administered baseline questionnaires. Breast cancer was defined as code C50 according to the International Classification of Diseases for Oncology, 3rd Edition or the International Classification of Diseases, 10th Revision. After adjusting for several potential confounders, relative risks for breast cancer were calculated in the individual studies according to the current or previous status of active and passive smoking using Cox regression, followed by a summary estimate of hazard ratios using random-effects meta-analyses.
Results
Of the 60 441 participants who reported being premenopausal and 106 170 who reported being postmenopausal at baseline, 897 and 1168 developed breast cancer during follow-up, respectively. Compared with never smokers, current smokers had a higher risk of developing breast cancer before the age of 50 years. In addition, ever smokers who started smoking at 30 years of age or younger, or who started smoking before first childbirth, had a higher risk of developing breast cancer before the age of 50 years. No association between adulthood or childhood exposure to secondhand smoke and breast cancer was observed.
Conclusion
Smoking may increase the risk of premenopausal breast cancer, and smoking earlier in life might be especially harmful. The impact of secondhand smoke needs further investigation.
Purpose
Previous studies show that consuming foods preserved by salting increases the risk of gastric cancer, while results on the association between total salt or added salt and gastric cancer are ...less consistent and vary with the exposure considered. This study aimed to quantify the association between dietary salt exposure and gastric cancer, using an individual participant data meta-analysis of studies participating in the Stomach cancer Pooling (StoP) Project.
Methods
Data from 25 studies (10,283 cases and 24,643 controls) from the StoP Project with information on salt taste preference (tasteless, normal, salty), use of table salt (never, sometimes, always), total sodium intake (tertiles of grams/day), and high-salt and salt-preserved foods intake (tertiles of grams/day) were used. A two-stage approach based on random-effects models was used to pool study-specific adjusted (sex, age, and gastric cancer risk factors) odds ratios (aORs), and the corresponding 95% confidence intervals (95% CI).
Results
Gastric cancer risk was higher for salty taste preference (aOR 1.59, 95% CI 1.25–2.03), always using table salt (aOR 1.33, 95% CI 1.16–1.54), and for the highest tertile of high-salt and salt-preserved foods intake (aOR 1.24, 95% CI 1.01–1.51)
vs.
the lowest tertile. No significant association was observed for the highest
vs.
the lowest tertile of total sodium intake (aOR 1.08, 95% CI 0.82–1.43). The results obtained were consistent across anatomic sites, strata of
Helicobacter pylori
infection, and sociodemographic, lifestyle and study characteristics.
Conclusion
Salty taste preference, always using table salt, and a greater high-salt and salt-preserved foods intake increased the risk of gastric cancer, though the association was less robust with total sodium intake.
The causal pathway between high education and reduced risk of gastric cancer (GC) has not been explained. The study aimed at evaluating the mediating role of lifestyle factors on the relationship ...between education and GC METHODS: Ten studies with complete data on education and five lifestyle factors (smoking, alcohol drinking, fruit and vegetable intake, processed meat intake and salt consumption) were selected from a consortium of studies on GC including 4349 GC cases and 8441 controls. We created an a priori score based on the five lifestyle factors, and we carried out a counterfactual-based mediation analysis to decompose the total effect of education on GC into natural direct effect and natural indirect effect mediated by the combined lifestyle factors. Effects were expressed as odds ratios (ORs) with a low level of education as the reference category.
The natural direct and indirect effects of high versus low education were 0.69 (95% CI: 0.62-0.77) and 0.96 (95% CI: 0.95-0.97), respectively, corresponding to a mediated percentage of 10.1% (95% CI: 7.1-15.4%). The mediation effect was limited to men.
The mediation effect of the combined lifestyle factors on the relationship between education and GC is modest. Other potential pathways explaining that relationship warrants further investigation.
A low intake of fruits and vegetables is a risk factor for gastric cancer, although there is uncertainty regarding the magnitude of the associations. In our study, the relationship between fruits and ...vegetables intake and gastric cancer was assessed, complementing a previous work on the association betweenconsumption of citrus fruits and gastric cancer. Data from 25 studies (8456 cases and 21 133 controls) with information on fruits and/or vegetables intake were used. A two‐stage approach based on random‐effects models was used to pool study‐specific adjusted (sex, age and the main known risk factors for gastric cancer) odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Exposure‐response relations, including linear and nonlinear associations, were modeled using one‐ and two‐order fractional polynomials. Gastric cancer risk was lower for a higher intake of fruits (OR: 0.76, 95% CI: 0.64‐0.90), noncitrus fruits (OR: 0.86, 95% CI: 0.73‐1.02), vegetables (OR: 0.68, 95% CI: 0.56‐0.84), and fruits and vegetables (OR: 0.61, 95% CI: 0.49‐0.75); results were consistent across sociodemographic and lifestyles categories, as well as study characteristics. Exposure‐response analyses showed an increasingly protective effect of portions/day of fruits (OR: 0.64, 95% CI: 0.57‐0.73 for six portions), noncitrus fruits (OR: 0.71, 95% CI: 0.61‐0.83 for six portions) and vegetables (OR: 0.51, 95% CI: 0.43‐0.60 for 10 portions). A protective effect of all fruits, noncitrus fruits and vegetables was confirmed, supporting further dietary recommendations to decrease the burden of gastric cancer.
What's new?
Low intake of fruits and vegetables has long been associated with a higher risk of gastric cancer, and citrus fruits may be especially protective. However, results from various studies have been inconsistent. In this large, pooled analysis from a global consortium, the authors found that a higher intake of all types of fruits and vegetables was protective. This effect was seen regardless of gastric cancer location and histological type. These results reinforce current recommendations for an increased intake of both fruits and vegetables to decrease the burden of gastric cancer.
Background
Gastric cancer incidence is higher in men, and a protective hormone-related effect in women is postulated. We aimed to investigate and quantify the relationship in the Stomach cancer ...Pooling (StoP) Project consortium.
Methods
A total of 2,084 cases and 7,102 controls from 11 studies in seven countries were included. Summary odds ratios (ORs) and 95% confidence intervals (CIs) assessing associations of key reproductive factors and menopausal hormone therapy (MHT) with gastric cancer were estimated by pooling study-specific ORs using random-effects meta-analysis.
Results
A duration of fertility of ≥ 40 years (vs. < 20), was associated with a 25% lower risk of gastric cancer (OR = 0.75; 95% CI: 0.58–0.96). Compared with never use, ever, 5–9 years and ≥ 10 years use of MHT in postmenopausal women, showed ORs of 0.73 (95% CI: 0.58–0.92), 0.53 (95% CI: 0.34–0.84) and 0.71 (95% CI: 0.50–1.00), respectively. The associations were generally similar for anatomical and histologic subtypes.
Conclusion
Our results support the hypothesis that reproductive factors and MHT use may lower the risk of gastric cancer in women, regardless of anatomical or histologic subtypes. Given the variation in hormones over the lifespan, studies should address their effects in premenopausal and postmenopausal women. Furthermore, mechanistic studies may inform potential biological processes.
BACKGROUND/AIMMalignant lymphoma (ML) cases with overlapping gastrointestinal (GI) lesions are often encountered. We aimed to elucidate the importance of examining the GI tract in patients with ML ...and assess the overlap rate. PATIENTS AND METHODSWe analysed 190 patients diagnosed with GI MLs. We compared the overlap rates among the different histopathological types. RESULTSTwenty-five (13.2%) patients had overlapping GI lesions in more than two segments. The overlap rates were 100% in mantle cell lymphomas (MCL), 27.6% in follicular lymphomas (FL), and 16.3% in diffuse large B-cell lymphomas (DLBCL). MCL, FL, and DLBCL cases showed significantly higher overlap rates than mucosa-associated lymphoid tissue lymphoma cases (p<0.01). About 64.0% of cases of ML with overlapping lesions involved the small intestine. CONCLUSIONIn GI ML cases, it is ideal to examine the entire GI tract by esophagogastroduodenoscopy, colonoscopy, and capsule endoscopy and/or balloon-assisted endoscopy, especially in MCL, FL, and DLBCL.
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