Risk of Severe Upper Gastrointestinal Complications among Oral Bisphosphonate Users

Background

Oral bisphosphonates (BPs) are the primary agents for the treatment of osteoporosis. Although BPs are generally well tolerated, serious gastrointestinal adverse events have been observed.

Aim

To assess the risk of severe upper gastrointestinal complications (UGIC) among BP users by means of a large study based on a network of Italian healthcare utilization databases.

Methods

A nested case-control study was carried out by including 110,220 patients aged 45 years or older who, from 2003 until 2005, were treated with oral BPs. Cases were the 862 patients who experienced the outcome (hospitalization for UGIC) until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio (OR) associated with current use of BPs after adjusting for several covariates. A set of sensitivity analyses was performed in order to account for sources of systematic uncertainty.

Results

The adjusted OR for current use of BPs with respect to past use was 0.94 (95% CI 0.81 to 1.08). There was no evidence that this risk changed either with BP type and regimen, or concurrent use of other drugs or previous hospitalizations.

Conclusions

No evidence was found that current use of BPs increases the risk of severe upper gastrointestinal complications compared to past use.     

阿司匹林引发上消化道出血的相关危险因素研究

目的:比较由阿司匹林引发上消化道出血的相关危险因素OR值,探讨其引起消化道大出血的相关机制。方法:收集哈医大四院消化内科及心内科2009年5月份至2013年6月份仅口服阿司匹林一种非甾体抗炎药的100例患者,用药过程中引发上消化道出血的49例患者作为研究组,其余未发生消化道出血的51例患者作为对照组,采集现病史、既往史、吸烟史、行凝血常规、Hp检测及胃镜检查,经单因素统计分析筛选出阿司匹林引发上消化道出血的危险因素;通过多元Logistic回归分析得出阿司匹林引发上消化道出血的独立危险因素。结果:年龄60岁、Hp感染、既往溃疡病史、糖尿病、吸烟的患者在研究组所占比例明显高于对照组,差异具有统计学意义;经多元Logistic回归后表明年龄60岁、Hp感染、既往溃疡病史、糖尿病患者和阿司匹林引发上消化道出血的OR值具有统计学差异。结论:年龄60岁、Hp感染、溃疡病史、糖尿病患者是阿司匹林引发上消化道出血的4个独立危险因素。     

PLCE1 Polymorphism and Upper Gastrointestinal Cancer Risk: A Meta-Analysis

Background

In recent years, the PLCE1 rs2274223 polymorphism has been extensively investigated as a potential risk factor for upper gastrointestinal cancers, including squamous cell carcinoma (ESCC) and gastric cancer. However, the results of these studies have been inconsistent.

Methods

A meta-analysis of 13 case-control studies was performed including more than 11,000 subjects with genotyped PLCE1 rs2274223 polymorphisms. Odds ratios (OR) with 95% confidence intervals (CI) were employed to assess the association of the PLCE1 rs2274223 polymorphism with a susceptibility to ESCC or gastric cancer.

Results

A statistically significant increase in the risk of ESCC was associated with the PLCE1 rs2274223 polymorphism. This included the homozygous genetic model (OR = 1.46), heterozygous genetic model (OR = 1.25) and allelic genetic model (OR = 1.23). Similar results were consistently found for gastric cancer. In a subgroup analysis, the PLCE1 rs2274223 polymorphism was found to be a very sensitive marker for gastric cardia cancer as shown by the homozygous genetic model (OR = 2.23), heterozygous genetic model(OR = 1.59) and allelic genetic model (OR = 1.47). The risk associations of all of the gastric cardia cancer models were statistically significant. In contrast, none of the genetic models for non-cardia gastric cancer were significant.

Conclusions

In this meta-analysis, the PLCE1 rs2274223 polymorphism was confirmed to have a statistically significant association with an increasing risk of ESCC and gastric cancer. The increase risk was especially observed for gastric cardia cancer.     

Circulating HSPs Levels and Risk of Human Gastrointestinal Related Cancers: A Systematic Review and Meta-analysis

International Journal of Peptide Research and Therapeutics - Heat shock proteins (HSPs) have over-expression in the human malignancies. However, many studies reported inconsistent results. The...     

Risk of Gastrointestinal Disease Associated with Exposure to Pathogens in the Sediments of the Lower Passaic River

High levels of pathogenic microorganisms have been documented previously in waters of the Lower Passaic River in northern New Jersey. The purpose of this study was to characterize the microbial contamination of river sediments near combined sewer overflows (CSOs), a known source of pathogens. Concentrations of fecal coliform, total coliform, fecal Streptococcus, fecal Enterococcus, Pseudomonas aeruginosa, Staphylococcus aureus, Giardia lamblia, and Cryptosporidium parvum organisms were measured in 16 samples from three mudflat locations along the Lower Passaic River, as well as from an upstream location. Selected samples were also analyzed for antibiotic resistance. All of the samples contained high concentrations of total coliform, fecal coliform, fecal Streptococcus, and fecal Enterococcus organisms. Analysis of isolates of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli from several samples indicated that each strain was resistant to at least one antibiotic typically used in clinical settings. Eight of 16 samples contained Giardia, and one sample contained Cryptosporidium. With these sampling data, a quantitative microbial risk assessment was conducted to evaluate the probability of infection or illness resulting from incidental ingestion of contaminated sediments over a 1-year period. Three potential exposure scenarios were considered: visitor, recreator, and homeless person. Single-event risk was first evaluated for the three individual exposure scenarios; overall risk was then determined over a 1-year period using Monte Carlo techniques to characterize uncertainty. For fecal Streptococcus and Enterococcus, annualized risk estimates for gastrointestinal illness ranged from approximately 0.42 to 0.53 for recreators, 0.07 to 0.10 for visitors, and 0.62 to 0.72 for homeless individuals across the three sampling locations. Annualized risk of Giardia infection ranged from 0.14 to 0.64 for recreators, 0.01 to 0.1 for visitors, and 0.30 to 0.87 for homeless individuals, across all locations where detected. Cryptosporidium was detected at one location, and the corresponding annualized risk of infection was 0.32, 0.05, and 0.51 for recreators, visitors, and homeless individuals, respectively. This risk assessment suggests that pathogen-contaminated sediments near areas of CSO discharge in the Lower Passaic River could pose a health risk to individuals coming into contact with sediments in the mudflat areas.     

Risk of Gastrointestinal Disease Associated with Exposure to Pathogens in the Water of the Lower Passaic River

During precipitation events, untreated human sewage is often intentionally discharged to surface water bodies via combined sewer overflow (CSO) systems in order to avoid overloading wastewater treatment plants. The purpose of this analysis was to evaluate the risk of pathogen-related disease associated with CSO discharges into the Lower Passaic River. Concentrations of fecal coliform, total coliform, fecal Streptococcus, and fecal Enterococcus bacteria were measured at six river locations on six different days in 2003 (n = 36). In addition, water samples (n = 2) were collected directly from and in the immediate vicinity of a discharging CSO in Newark, NJ. These samples were analyzed for fecal coliforms, total coliforms, fecal Streptococcus, fecal Enterococcus, Giardia lamblia, Cryptosporidium parvum, and several viruses. Risk estimates for gastrointestinal illness and Giardia infection resulting from indirect and direct ingestion of contaminated water were calculated for three potential exposure scenarios: visitor, recreator, and homeless person. Single-event risk was first evaluated for the three individual exposure scenarios; overall risk was then determined over a 1-year period. Monte Carlo techniques were used to characterize uncertainty. Nearly all of the pathogen concentrations measured in the Passaic River exceeded health-based water quality criteria and in some cases were similar to levels reported for raw sewage. The probability of contracting gastrointestinal illness due to fecal Streptococcus and Enterococcus from incidental ingestion of water over the course of a year ranged from 0.14 to nearly 0.70 for the visitor and recreator scenarios, respectively. For the homeless person exposure scenario, the risk for gastrointestinal illness reached 0.88 for fecal Streptococcus and Enterococcus, while the probability of Giardia infection was 1.0. This risk analysis suggests that, due to the levels of pathogens present in the Lower Passaic River, contact with the water poses, and will continue to pose, significant human health risks until CSO discharges are adequately controlled or abated.     

Idiopathic Sporadic Tumoral Calcinosis of the Hip: Successful Oral Bisphosphonate Therapy

ObjectiveTo report the case of a woman with idiopathic sporadic tumoral calcinosis treated successfully with orally administered bisphosphonates.MethodsWe report the clinical, laboratory, and imaging findings and describe the clinical course of tumoral calcinosis. The literature was reviewed for the pathophysiologic features and strategies for treatment of tumoral calcinosis. In addition, we specifically reviewed the use of bisphosphonates in tumoral calcinosis and the possible pharmacologic basis for the therapeutic benefit.ResultsA 45-year-old woman presented with a 6-week history of left-sided pain in the hip in conjunction with stiffness after a trivial fall 4 weeks before the onset of symptoms. The findings on conventional radiology of the hip joint were consistent with tumoral calcinosis of the left hip. The biochemical profile of the patient was unremarkable. Oral treatment with alendronate, 70 mg once a week, yielded alleviation of symptoms within 12 weeks. Radiology of the left hip repeated after a period of 15 months revealed notable regression of the calcified lesion.ConclusionBisphosphonate therapy may be considered as an alternative to surgical treatment in patients with idiopathic sporadic tumoral calcinosis. (Endocr Pract. 2007;13:182-186)     

Risk of Gastrointestinal Cancers among Patients with Appendectomy: A Large-Scale Swedish Register-Based Cohort Study during 1970-2009

Background

Removal of the appendix might induce physiological changes in the gastrointestinal tract, and subsequently play a role in carcinogenesis. Therefore, we conducted a nationwide register-based cohort study in Sweden to investigate whether appendectomy is associated with altered risks of gastrointestinal cancers.

Methods

A population-based cohort study was conducted using the Swedish national registries, including 480,382 eligible patients followed during the period of 1970–2009 for the occurrence of site-specific gastrointestinal cancer (esophageal/gastric/colon/rectal cancer). Outcome and censoring information was collected by linkage to health and demography registers. We examined the incidence of appendectomy in Sweden using data from 1987–2009. We also calculated standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) to estimate the relative gastrointestinal cancer risk through comparison to the general population.

Results

We noted an overall decrease in the age-standardized incidence of appendectomy among the entire Swedish population from 189.3 to 105.6 per 100,000 individuals between 1987 and 2009. Grouped by different discharge diagnosis, acute appendicitis, incidental appendectomy, and entirely negative appendectomy continuously decreased over the study period, while the perforation ratio (18%–23%) stayed relatively constant. Compared to the general population, no excess cancer risk was observed for gastrointestinal cancers under study with the exception of a marginally elevated risk for esophageal adenocarcinoma (SIR 1.32, 95% CI 1.09–1.58).

Conclusions

In Sweden, the incidence of appendectomy and acute appendicitis has decreased during 1987–2009. No excess gastrointestinal cancer risks were observed among these appendectomized patients, with the possible exception of esophageal adenocarcinoma.     

Malignant Potential of Gastrointestinal Cancers Assessed by Structural Equation Modeling

Background

Parameters reported in pathologic reviews have been failing to assess exactly the malignant potential of gastrointestinal cancers. We hypothesized that malignant potential could be defined by common latent variables (hypothesis I), but there are substantial differences in the associations between malignant potential and pathologic parameters according to the origin of gastrointestinal cancers (hypothesis II). We shed light on these issues by structural equation modeling.

Materials and Methods

We conducted a cross-sectional survey of 217 esophageal, 192 gastric, and 175 colorectal cancer patients who consecutively underwent curative surgery for their pathologic stage I cancers at Keiyukai Sapporo Hospital. Latent variables identified by factor analysis and seven conventional pathologic parameters were introduced in the structural equation modeling analysis.

Results

Because latent variables were disparate except for their number, ''three'' in the examined gastrointestinal cancers, the first hypothesis was rejected. Because configural invariance across gastrointestinal cancers was not approved, the second hypothesis was verified. We could trace the three significant paths on the causal graph from latent variables to lymph node metastasis, which were mediated through depth, lymphatic invasion, and matrilysin expression in esophageal cancer, whereas only one significant path could be traced in both gastric and colorectal cancer. Two of the three latent variables were exogenous in esophageal cancer, whereas one factor was exogenous in the other gastrointestinal cancers. Cancer stemness promoted viability in esophageal cancer, but it was suppressed in others.

Conclusion

These results reflect the malignant potential of esophageal cancer is higher than that of the other gastrointestinal cancers. Such information might contribute to refining clinical treatments for gastrointestinal cancers.     

Pulmonary Aspiration after Fibre-endoscopy of the Upper Gastrointestinal Tract

Pulmonary aspiration occurred in 16 out of 65 patients (24·6%) undergoing fibre-endoscopic examinations of the upper gastrointestinal tract under intravenous sedation, but it was rarely followed by serious complications. Aspiration was found to occur under sedation with diazepam alone, diazepam with atropine, and with chlormethiazole. The most important factors contributing to aspiration are the local pharyngeal anaesthesia and the mechanical interference of the fibrescope with laryngeal closure and swallowing. The patient is also at risk of aspiration after completion of the procedure and should remain recumbent until the local anaesthesia has worn off.     

VEGF, MVD 在胃癌预后及上消化道出血风险的研究进展

胃癌是危害人类健康的常见恶性肿瘤,也是上消化道出血常见的病因之一。其发生发展是多因素、多基因改变参与的长期、协同的病理过程。血管生成(angiogenesis)是这一发展过程中的关键步骤,血管内皮生长因子(vascular endothelial growth factor,VEGF)和微血管密度(micro vessel density,MVD)作为调控血管生成的主要因子和微血管的主要评价指标,在胃癌患者预后、临床病理因素中的作用被广泛研究。上消化道出血(upper gastrointestinal hemorrhage)是胃癌患者的常见临床症状威胁和影响患者的生存质量。新近有研究者提出,VEGF及MVD与胃癌患者的上消化道出血风险正相关,本文就相关研究进展进行介绍。     

The Role of the Upper Gastrointestinal Flora in the Malabsorption Syndrome

Bacterial contamination of the upper gastrointestinal tract by colonic flora appears important in the production of some forms of secondary steatorrhea. Gastric contents have been studied in patients with normal intestinal absorption and with malabsorption syndrome. In secondary steatorrhea there is a significantly increased incidence of gastric contamination by colon organisms, and this is usually associated with absence of free hydrochloric acid. It seems probable that such contamination interferes with intestinal digestion and absorption. The benefit resulting from the oral administration of broad-spectrum antibiotics to a group of patients with secondary steatorrhea supports this concept.     

Isotretinoin Exposure and Risk of Celiac Disease

Background

Isotretinoin (13-cis retinoic acid) is a metabolite of vitamin A and has anti-inflammatory and immunoregulatory effects; however, a recent publication by DePaolo et al. demonstrated that in the presence of IL-15, retinoic acid can act as an adjuvant and promote inflammation against dietary proteins.

Objective

To evaluate the risk of overt and latent celiac disease (CD) among users of isotretinoin.

Material and Methods

Medical records of patients from 1995 to 2011 who had a mention of isotretinoin in their records (N = 8393) were searched for CD diagnosis using ICD-09CM codes. Isotretinoin exposure was compared across overt CD patients and their age- and gender-matched controls from the same pool. To evaluate the risk of latent CD with isotretinoin exposure, patients were overlapped with a community-based list of patients with waste serum samples that were tested for CD serology, excluding those with overt CD (2006–2011). Isotretinoin exposure was defined as the use of isotretinoin prior to CD diagnosis or serology.

Results

Of 8393 patients, 25 had a confirmed CD diagnosis. Compared to matched controls (N = 75), isotretinoin exposure was not significantly different between overt CD patients versus controls (36% versus 39%, respectively; P = 0.712). Likewise, latent CD defined as positive serology was not statistically different between isotretinoin exposed (N = 506) versus non-exposed (N = 571) groups (1.8% versus 1.4%, respectively; P = 0.474).

Conclusions

There was no association between isotretinoin use and risk of either overt or latent CD.     

上消化道出血在ICU的诊治近况

近年来,ICU在急重症上消化道出血救治中的作用越来越受到重视。上消化道出血是重症监护病房(ICU)内常见的危重病症 之一,与多器官功能不全密切相关,是多种危重病引起的常见并发症,病情严重者甚至危及生命。引起上消化道出血的病因很多, 其中非特异性粘膜异常、非甾体类抗炎药和抗血小板药物的不合理使用逐渐引起临床的重视。本文对国内外临床诊断和治疗上 消化道出血的近况进行了回顾分析,进一步阐述上消化道出血与多器官功能不全之间的联系,为多学科联合诊断提供参考。     

急性上消化道出血的病因及相关因素分析

目的:分析急性上消化道出血的病因及相关因素.方法:选择2010年1月至2012年6月在我院治疗的急性上消化道出血患者90例为研究对象,统计分析其上消化道出血病因、诱因,分析可能的相关因素.结果:急性上消化道出血常见病因是HG、DU、GU等.不同病因的常见诱因构成比不同,差异有统计学意义(P＜0.01).青年组、中年组、老年组急性上消化道出血的病因分布比较,差异有统计学意义(P＜0.01).男性和女性急性上消化道出血的病因分布差异无统计学意义(P＞0.05).结论:急性上消化道出血的常见病因较多,不同年龄组的常见病因不同.     

上消化道粘膜下肿瘤的内镜下诊断及治疗进展

上消化道粘膜下肿瘤(SMTs)临床较为常见,是一类来源于非粘膜层的肿物,有良恶性之分,良性多见。因其表面覆盖正常粘膜组织,常规的内镜下活检只取到粘膜层,难以深达粘膜下层,肿瘤性质难以判定,因此既往多随访观察,肿瘤在短时间内增大或出现明显的临床症状时才予以外科手术治疗。近年来,由于超声胃镜(EUS)技术的发展,SMTs的诊断不仅可以定位,还可以定性。随着内镜下粘膜切除术(EMR)、内镜下粘膜剥离术(ESD)、经口内镜粘膜下隧道肿瘤切除术(STER)等内镜下微创治疗技术的发展,不仅可获得足够的病理标本更加准确的诊断SMTs,还可以安全、高效的切除病变、避免了外科手术的创伤、减轻了经济负担,本文就内镜下对于SMTs的诊断、微创切除SMTs的方法及相关并发症的处理等予以综述。     

左侧门脉高压症并上消化道出血的诊断与治疗（附14 例临床分析）

目的:探讨左侧门脉高压症合并上消化道出血的诊断和治疗方法。方法:回顾分析我院近10年来收治的14例左侧门脉高压症合并上消化道出血患者的诊治措施和随访结果。结果:14例患者均有呕血或(和)黑便史,无肝硬化、腹水及肝功能异常等表现。14例患者中胰体尾占位6例,胰腺假性囊肿4例,慢性胰腺炎4例。14例患者均采用手术治疗。9例患者获得随访,定期内镜复查,曲张静脉明显改善或消失,随访5月～8年均无再出血。结论:胰腺疾病病史、无肝硬化和肝功能正常、孤立性胃底静脉曲张和脾肿大及脾亢是诊断左侧门脉高压症的基本要点。该疾病可通过脾切除术或联合胃底周围血管离断术结合原发胰腺疾病的治疗来获得治愈。