Circulating RNAs as new biomarkers for detecting pancreatic cancer

Pancreatic cancer remains difficult to treat and has a high mortality rate. It is difficult to diagnose early, mainly due to the lack of screening imaging modalities and specific biomarkers. Consequently, it is important to develop biomarkers that enable the detection of early stage tumors. Emerging evidence is accumulating that tumor cells release substantial amounts of RNA into the bloodstream that strongly resist RNases in the blood and are present at sufficient levels for quantitative analyses. These circulating RNAs are upregulated in the serum and plasma of cancer patients, including those with pancreatic cancer, compared with healthy controls. The majority of RNA biomarker studies have assessed circulating microRNAs (miRs), which are often tissue-specific. There are few reports of the tumor-specific upregulation of other types of small non-coding RNAs (ncRNAs), such as small nucleolar RNAs and Piwi-interacting RNAs. Long ncRNAs (lncRNAs), such as HOTAIR and MALAT1, in the serum/plasma of pancreatic cancer patients have also been reported as diagnostic and prognostic markers. Among tissue-derived RNAs, some miRs show increased expression even in pre-cancerous tissues, and their expression profiles may allow for the discrimination between a chronic inflammatory state and carcinoma. Additionally, some miRs and lncRNAs have been reported with significant alterations in expression according to disease progression, and they may thus represent potential candidate diagnostic or prognostic biomarkers that may be used to evaluate patients once detection methods in peripheral blood are well established. Furthermore, recent innovations in high-throughput sequencing techniques have enabled the discovery of unannotated tumor-associated ncRNAs and tumor-specific alternative splicing as novel and specific biomarkers of cancers. Although much work is required to clarify the release mechanism, origin of tumor-specific circulating RNAs, and selectivity of carrier complexes, and technical advances must also be achieved, such as creating a consensus normalization protocol for quantitative data analysis, circulating RNAs are largely unexplored and might represent novel clinical biomarkers.     

Circulating microRNA-208 family as early diagnostic biomarkers for acute myocardial infarction: A meta-analysis

Objective:Many recent studies have demonstrated that serum miRNA-208 (miR-208) could be a powerful biomarker in the early diagnosis of acute myocardial infarction (AMI). However, the result of previous studies was not accurate due to the small sample sizes and controversial issues. Therefore, this study was performed to investigate the relationship between the expression levels of miR-208 and AMI.Materials and methods:According to the inclusion and exclusion criteria, a preliminary literature search was performed. The study was based on articles published in PubMed, Embase, Cochrane databases before September 30, 2019. Two staff members extracted data from the included articles for meta-analysis. These data were analyzed for sensitivity, specificity, diagnostic odds ratio, and summary receiver operator curve (SROC) analyses.Results:This study included 13 pieces of literature, which contains 1703 patients with AMI and 1589 controls. The main results of our meta-analysis were as follows: The pool sensitivity and specificity of miR-208 for diagnosing AMI was 83% and 97%. The area under the SROC curve (AUC) was 93%. Mir-208 had a highly effective diagnostic capacity to distinguish AMI from chest pain patients with an AUC of 93%.Conclusions:The results showed that circulating miR-208 was a reliable biomarker both for diagnosting ST-elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI). MiR-208 was sufficient to distinguish AMI patients with chest pain from healthy controls.     

微创外科在结直肠肿瘤手术的新进展

微创外科结直肠手术在我国的开展已超过20个年头。20余年来,以腹腔镜结直肠手术为代表的结直肠外科微创手术在我国蓬勃发展,尤其是进入21世纪以来发展势头迅猛,微创结直肠肿瘤手术的开展已经得到广泛认可,并得到循证医学证据的支持,由此更使其成为一种外科理念逐步深入结直肠外科领域。不断成熟的技术、不断更新的设备与器械,都为微创结直肠外科的进一步发展起到了重要推动作用。     

Development of a novel intraoperative difficulty score for minimally invasive cholecystectomy

BackgroundThe rate of biliary injuries from minimally invasive cholecystectomy has remained high for over two decades. To improve outcomes there are multiple bail-out methods described, including aborting the procedure, converting to open, or performing a sub-total cholecystectomy. However, the intraoperative difficulty threshold for when a bail-out method should be implemented is poorly understood.MethodsFrom 1/2014 to 2/2019 cholecystectomy videos were collected, de-identified, edited to include the 2–3 minutes when the gallbladder was first visualized, and accelerated. They were then rated on a 5-point difficulty scale. Inter-coder reliability was evaluated using Krippendorff's alpha and regression models were used to evaluate the scores ability to predict the need for a bail-out technique.Results62 videos were analyzed with a median length after editing of 37.5 (29.0–43.3) seconds. A median time of 46.2 (38.3–53.4) seconds was required for grading. The bail-out rate was 42.9%. The inter-coder reliability between 2 surgeons and 8 non-clinical reviewers was 0.675 with an average difficulty score of 3.0 (SD = 1.01). Regression models showed that the scale was able to significantly predict conversion (β=0.56,p<.01).ConclusionThis novel difficulty score was able to predict conversion to a bail-out technique early in the course of minimally invasive cholecystectomy.     

Somatic deletions in hereditary breast cancers implicate 13q21 as a putative novel breast cancer susceptibility locus

A significant proportion of familial breast cancers cannot be explained by mutations in the BRCA1 or BRCA2 genes. We applied a strategy to identify predisposition loci for breast cancer by using mathematical models to identify early somatic genetic deletions in tumor tissues followed by targeted linkage analysis. Comparative genomic hybridization was used to study 61 breast tumors from 37 breast cancer families with no identified BRCA1 or BRCA2 mutations. Branching and phylogenetic tree models predicted that loss of 13q was one of the earliest genetic events in hereditary cancers. In a Swedish family with five breast cancer cases, all analyzed tumors showed distinct 13q deletions, with the minimal region of loss at 13q21-q22. Genotyping revealed segregation of a shared 13q21 germ-line haplotype in the family. Targeted linkage analysis was carried out in a set of 77 Finnish, Icelandic, and Swedish breast cancer families with no detected BRCA1 and BRCA2 mutations. A maximum parametric two-point logarithm of odds score of 2.76 was obtained for a marker at 13q21 (D13S1308, theta = 0.10). The multipoint logarithm of odds score under heterogeneity was 3.46. The results were further evaluated by simulation to assess the probability of obtaining significant evidence in favor of linkage by chance as well as to take into account the possible influence of the BRCA2 locus, located at a recombination fraction of 0.25 from the new locus. The simulation substantiated the evidence of linkage at D13S1308 (P < 0.0017). The results warrant studies of this putative breast cancer predisposition locus in other populations.     

Circulating microRNAs: Novel biomarkers for esophageal cancer

Esophageal carcinogenesis is a multi-stage process, involving a variety of changes in gene expression and physiological structure change. MicroRNAs (miRNAs) are a class of small non-coding endogenous RNA molecules. Recent innovation in miRNAs profiling technology have shed new light on the pathology of esophageal carcinoma (EC), and also heralded great potential for exploring novel biomarkers for both EC diagnosis and treatment. Frequent dysregulation of miRNA in malignancy highlights the study of molecular...     

The role of microRNA-31 and microRNA-21 as regulatory biomarkers in the activation of T lymphocytes of Egyptian lupus patients

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by familial aggregation and genetic predisposition. MicroRNAs (MiRNAs) serve as critical biomarkers in lupus patients because of their aberrant expression in different SLE stages. The study aimed to investigate the correlation of miR-31 and miR-21 with IL-2 in SLE patients as regulatory biomarkers in the activation of T lymphocytes of Egyptian lupus patients. Quantitative RT-PCR is carried out to estimate the expressions of miR-31 and miR-21, and IL-2 levels were determined using ELISA in plasma of 40 patients with SLE, 20 of their first-degree relatives and 20 healthy controls. The study also determined the systemic lupus erythematosus disease activity index (SLEDAI) score and proteinuria in SLE patients. The results revealed that miR-31 was lower expressed, while miR-21 was high expressed in SLE patients compared to their first-degree relatives and controls. MiR-31 was negatively correlated with SLEDAI and proteinuria in lupus patients, while miR-21 showed positive correlation with them. Also we found that there is a significant positive correlation between miR-31 and IL-2 in SLE patients, while miR-21 was negatively correlated with IL-2 level in patients. In conclusion, the study disclosed a significant association between miR-31 and miR-21 expression with IL-2 level in SLE patients. The regulatory biomarkers of miR-31 and miR-21 might have an impact on regulating IL-2 pathway expression and in turn on the activation of T lymphocytes in SLE.     

Role of minimally invasive surgery for rectal cancer

Rectal cancer is one of the most common malignancies worldwide.Surgical resection for rectal cancer usually requires a proctectomy with respective lymphadenectomy(total mesorectal excision).This has traditionally been performed transabdominally through an open incision.Over the last thirty years,minimally invasive surgery platforms have rapidly evolved with the goal to accomplish the same quality rectal resection through a less invasive approach.There are currently three resective modalities that complement the traditional open operation:(1) Laparoscopic surgery;(2) Robotic surgery;and(3) Transanal total mesorectal excision.In addition,there are several platforms to carry out transluminal local excisions(without lymphadenectomy).Evidence on the various modalities is of mixed to moderate quality.It is unreasonable to expect a randomized comparison of all options in a single trial.This review aims at reviewing in detail the various techniques in regard to intra-/perioperative benchmarks,recovery and complications,oncological and functional outcomes.     

Partial prolapsectomy and fixation proctomucopexy: a novel minimally invasive procedure

A novel minimally invasive procedure for the management of anterior external and posterior internal mucosal prolapse is described. The operation, carried out via a transanal route, consists of a partial prolapsectomy and a mucosal proctopexy. Out of six patients, one had severe postoperative bleeding and one had a recurrence of internal prolapse and obstructed defecation. Three patients had pelvic floor rehabilitation for associated dysfunctions. The advantage of the operation is that a circumferential anastomosis is avoided, thus decreasing the risk of dehiscence, and only a short sphincter dilation is required. Moreover, the procedure has very little effect on the rectal reservoir, thus preventing fecal urgency. No reintervention was needed, and almost all patients were cured after 2 years.     

胸腹腔镜联合与常规三切口手术治疗食管癌的同期临床及远期预后对照研究

目的探讨和评价胸腹腔镜联合与常规三切口手术治疗食管癌的安全性、有效性以及远期临床疗效。方法回顾性分析2009年2月至2011年12月同期收治的行胸腹腔镜联合食管癌根治术（微创组,94例）与常规三切口开放食管癌根治术（开放组,89例）的食管癌患者的临床资料。结果两组患者年龄、性别、体质量等基本资料以及肿瘤位置及分期等临床资料具有可比性。两组总手术时间、淋巴结清扫数无明显差异,并发症如吻合口瘘、脓胸、乳糜胸、声带麻痹、胃排空障碍发生率以及二次手术率、病死率亦无统计学差异。但微创组术中出血量[（86．6±38．3）ml比（217．4±87．2）ml,P=0．000]及需输血人数（1．1％比6．7％,P=0．045）明显少于开放组,总并发症（23．4％比38．2％,P=0．030）、呼吸系统并发症（9．6％比27．0％,P=0．002）及心律失常（4．1％比12．4％,P=0．046）发生率也均有统计学差异。微创组术后住院时间较开放组时间明显缩短,差异有统计学意义[（13．9±7．5）d比（17．1±10．2）d,P：0．017）。术后中位随访时间（28．0±2．0）月（95％CI为24．2～31．8）,微创组和开放组患者生存率分别为44．2％和42．2％（P=0．954）,差异无统计学意义。结论胸腹腔镜联合手术治疗食管癌安全、有效,在完全切除肿瘤的同时具有明显微创优势,尽管远期生存期并无明显提高,但仍值得推广。     

Circulating serum microRNAs as novel diagnostic and prognostic biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance

Multiple myeloma still remains incurable in the majority of cases prompting a further search for new and better prognostic markers. Emerging evidence has suggested that circulating microRNAs can serve as minimally invasive biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance. In this study, a global analysis of serum microRNAs by TaqMan Low Density Arrays was performed, followed by quantitative real-time PCR. The analyses revealed five deregulated microRNAs: miR-744, miR-130a, miR-34a, let-7d and let-7e in monoclonal gammopathy of undetermined significance, newly diagnosed and relapsed multiple myeloma when compared to healthy donors. Multivariate logistical regression analysis showed that a combination of miR-34a and let-7e can distinguish multiple myeloma from healthy donors with a sensitivity of 80.6% and a specificity of 86.7%, and monoclonal gammopathy of undetermined significance from healthy donors with a sensitivity of 91.1% and a specificity of 96.7%. Furthermore, lower levels of miR-744 and let-7e were associated with shorter overall survival and remission of myeloma patients. One-year mortality rates for miR-744 and let-7e were 41.9% and 34.6% for the ‘low’ expression and 3.3% and 3.9% for the ‘high’ expression groups, respectively. Median time of remission for both miR-744 and let-7e was approximately 11 months for the ‘low’ expression and approximately 47 months for the ‘high’ expression groups of myeloma patients These data demonstrate that expression patterns of circulating microRNAs are altered in multiple myeloma and monoclonal gammopathy of undetermined significance and miR-744 with let-7e are associated with survival of myeloma patients.