Genome Analysis Reveals Interplay between 5′UTR Introns and Nuclear mRNA Export for Secretory and Mitochondrial Genes

In higher eukaryotes, messenger RNAs (mRNAs) are exported from the nucleus to the cytoplasm via factors deposited near the 5′ end of the transcript during splicing. The signal sequence coding region (SSCR) can support an alternative mRNA export (ALREX) pathway that does not require splicing. However, most SSCR–containing genes also have introns, so the interplay between these export mechanisms remains unclear. Here we support a model in which the furthest upstream element in a given transcript, be it an intron or an ALREX–promoting SSCR, dictates the mRNA export pathway used. We also experimentally demonstrate that nuclear-encoded mitochondrial genes can use the ALREX pathway. Thus, ALREX can also be supported by nucleotide signals within mitochondrial-targeting sequence coding regions (MSCRs). Finally, we identified and experimentally verified novel motifs associated with the ALREX pathway that are shared by both SSCRs and MSCRs. Our results show strong correlation between 5′ untranslated region (5′UTR) intron presence/absence and sequence features at the beginning of the coding region. They also suggest that genes encoding secretory and mitochondrial proteins share a common regulatory mechanism at the level of mRNA export

Spontaneous iliac vein rupture showed by femoral contrast bolus: A case report

Introduction: Spontaneous iliac vein rupture (SIVR) is an uncommon disease with less than sixty cases reported before. This disease often requires surgical intervention. SIVR has never been imaged in the literature. This report shows how to image this diagnosis. Case report: A 71-year-old female was diagnosed with SIVR with the use of CT venography. Endovascular repair with 2 endografts and a sinus XL stent was performed. Postoperatively, the patient developed abdominal compartment syndrome and a large part of the intestines had to be removed because of ischemia. Discussion: This is the first report that shows SIVR before and after endovascular treatment with the use of CT venography by injecting a contrast bolus in the femoral vein. This information is of high interest for a broad range of clinicians to show or exclude a venous abdominal bleeding in an early stage

Multidisciplinary management of early rectal cancer – The role of surgical local excision in current and future clinical practice

The implementation of bowel cancer screening programs has led to a rise in the incidence of early rectal cancer. The combination of increased incidence and the growing interest in organ-sparing treatment options has led to an amplified importance of local excision techniques in treatment strategies for early rectal cancer. In addition, developments in new technologies of single-port surgery have popularized surgical techniques. Although local treatment of early rectal cancer seems promising, a multidisciplinary approach is necessary and awareness of the oncological robustness is warranted to enable shared decision-making. This review illustrates the position of surgical local excision in the treatment of early rectal cancer and reflects on its role in current and future clinical practice

Video-based tools for surgical quality assessment of technical skills in laparoscopic procedures: a systematic review

Background: Quality of surgery has substantial impact on both short- and long-term clinical outcomes. This stresses the need for objective surgical quality assessment (SQA) for education, clinical practice and research purposes. The aim of this systematic review was to provide a comprehensive overview of all video-based objective SQA tools in laparoscopic procedures and their validity to objectively assess surgical performance. Methods: PubMed, Embase.com and Web of Science were systematically searched by two reviewers to identify all studies focusing on video-based SQA tools of technical skills in laparoscopic surgery performed in a clinical setting. Evidence on validity was evaluated using a modified validation scoring system. Results: Fifty-five studies with a total of 41 video-based SQA tools were identified. These tools were used in 9 different fields of laparoscopic surgery and were divided into 4 categories: the global assessment scale (GAS), the error-based assessment scale (EBAS), the procedure-specific assessment tool (PSAT) and artificial intelligence (AI). The number of studies focusing on these four categories were 21, 6, 31 and 3, respectively. Twelve studies validated the SQA tool with clinical outcomes. In 11 of those studies, a positive association between surgical quality and clinical outcomes was found. Conclusion: This systematic review included a total of 41 unique video-based SQA tools to assess surgical technical skills in various domains of laparoscopic surgery. This study suggests that validated SQA tools enable objective assessment of surgical performance with relevance for clinical outcomes, which can be used for training, research and quality improvement programs

Circulating tumour DNA as biomarker for rectal cancer: A systematic review and meta-analyses

Background: Circulating tumour DNA (ctDNA) has been established as a promising (prognostic) biomarker with the potential to personalise treatment in cancer patients. The objective of this systematic review is to provide an overview of the current literature and the future perspectives of ctDNA in non-metastatic rectal cancer. Methods: A comprehensive search for studies published prior to the 4th of October 2022 was conducted in Embase, Medline, Cochrane, Google scholar, and Web of Science. Only peer-reviewed original articles and ongoing clinical trials investigating the association between ctDNA and oncological outcomes in non-metastatic rectal cancer patients were included. Meta-analyses were performed to pool hazard ratios (HR) for recurrence-free survival (RFS). Results: A total of 291 unique records were screened, of which 261 were original publications and 30 ongoing trials. Nineteen original publications were reviewed and discussed, of which seven provided sufficient data for meta-analyses on the association between the presence of post-treatment ctDNA and RFS. Results of the meta-analyses demonstrated that ctDNA analysis can be used to stratify patients into very high and low risk groups for recurrence, especially when detected after neoadjuvant treatment (HR for RFS: 9.3 [4.6 – 18.8]) and after surgery (HR for RFS: 15.5 [8.2 – 29.3]). Studies investigated different types of assays and used various techniques for the detection and quantification of ctDNA. Conclusions: This literature overview and meta-analyses provide evidence for the strong association between ctDNA and recurrent disease. Future research should focus on the feasibility of ctDNA-guided treatment and follow-up strategies in rectal cancer. A blueprint for agreed-upon timing, preprocessing, and assay techniques is needed to empower adaptation of ctDNA into daily practice

Circulating tumour DNA as biomarker for rectal cancer: A systematic review and meta-analyses

Background: Circulating tumour DNA (ctDNA) has been established as a promising (prognostic) biomarker with the potential to personalise treatment in cancer patients. The objective of this systematic review is to provide an overview of the current literature and the future perspectives of ctDNA in non-metastatic rectal cancer. Methods: A comprehensive search for studies published prior to the 4th of October 2022 was conducted in Embase, Medline, Cochrane, Google scholar, and Web of Science. Only peer-reviewed original articles and ongoing clinical trials investigating the association between ctDNA and oncological outcomes in non-metastatic rectal cancer patients were included. Meta-analyses were performed to pool hazard ratios (HR) for recurrence-free survival (RFS). Results: A total of 291 unique records were screened, of which 261 were original publications and 30 ongoing trials. Nineteen original publications were reviewed and discussed, of which seven provided sufficient data for meta-analyses on the association between the presence of post-treatment ctDNA and RFS. Results of the meta-analyses demonstrated that ctDNA analysis can be used to stratify patients into very high and low risk groups for recurrence, especially when detected after neoadjuvant treatment (HR for RFS: 9.3 [4.6 – 18.8]) and after surgery (HR for RFS: 15.5 [8.2 – 29.3]). Studies investigated different types of assays and used various techniques for the detection and quantification of ctDNA. Conclusions: This literature overview and meta-analyses provide evidence for the strong association between ctDNA and recurrent disease. Future research should focus on the feasibility of ctDNA-guided treatment and follow-up strategies in rectal cancer. A blueprint for agreed-upon timing, preprocessing, and assay techniques is needed to empower adaptation of ctDNA into daily practice

DataSheet_2_Circulating tumour DNA as biomarker for rectal cancer: A systematic review and meta-analyses.docx

BackgroundCirculating tumour DNA (ctDNA) has been established as a promising (prognostic) biomarker with the potential to personalise treatment in cancer patients. The objective of this systematic review is to provide an overview of the current literature and the future perspectives of ctDNA in non-metastatic rectal cancer.MethodsA comprehensive search for studies published prior to the 4th of October 2022 was conducted in Embase, Medline, Cochrane, Google scholar, and Web of Science. Only peer-reviewed original articles and ongoing clinical trials investigating the association between ctDNA and oncological outcomes in non-metastatic rectal cancer patients were included. Meta-analyses were performed to pool hazard ratios (HR) for recurrence-free survival (RFS).ResultsA total of 291 unique records were screened, of which 261 were original publications and 30 ongoing trials. Nineteen original publications were reviewed and discussed, of which seven provided sufficient data for meta-analyses on the association between the presence of post-treatment ctDNA and RFS. Results of the meta-analyses demonstrated that ctDNA analysis can be used to stratify patients into very high and low risk groups for recurrence, especially when detected after neoadjuvant treatment (HR for RFS: 9.3 [4.6 – 18.8]) and after surgery (HR for RFS: 15.5 [8.2 – 29.3]). Studies investigated different types of assays and used various techniques for the detection and quantification of ctDNA.ConclusionsThis literature overview and meta-analyses provide evidence for the strong association between ctDNA and recurrent disease. Future research should focus on the feasibility of ctDNA-guided treatment and follow-up strategies in rectal cancer. A blueprint for agreed-upon timing, preprocessing, and assay techniques is needed to empower adaptation of ctDNA into daily practice.</p

DataSheet_1_Circulating tumour DNA as biomarker for rectal cancer: A systematic review and meta-analyses.pdf

BackgroundCirculating tumour DNA (ctDNA) has been established as a promising (prognostic) biomarker with the potential to personalise treatment in cancer patients. The objective of this systematic review is to provide an overview of the current literature and the future perspectives of ctDNA in non-metastatic rectal cancer.MethodsA comprehensive search for studies published prior to the 4th of October 2022 was conducted in Embase, Medline, Cochrane, Google scholar, and Web of Science. Only peer-reviewed original articles and ongoing clinical trials investigating the association between ctDNA and oncological outcomes in non-metastatic rectal cancer patients were included. Meta-analyses were performed to pool hazard ratios (HR) for recurrence-free survival (RFS).ResultsA total of 291 unique records were screened, of which 261 were original publications and 30 ongoing trials. Nineteen original publications were reviewed and discussed, of which seven provided sufficient data for meta-analyses on the association between the presence of post-treatment ctDNA and RFS. Results of the meta-analyses demonstrated that ctDNA analysis can be used to stratify patients into very high and low risk groups for recurrence, especially when detected after neoadjuvant treatment (HR for RFS: 9.3 [4.6 – 18.8]) and after surgery (HR for RFS: 15.5 [8.2 – 29.3]). Studies investigated different types of assays and used various techniques for the detection and quantification of ctDNA.ConclusionsThis literature overview and meta-analyses provide evidence for the strong association between ctDNA and recurrent disease. Future research should focus on the feasibility of ctDNA-guided treatment and follow-up strategies in rectal cancer. A blueprint for agreed-upon timing, preprocessing, and assay techniques is needed to empower adaptation of ctDNA into daily practice.</p