CRC is the second leading cause of cancer-related death, and the third most common cancer globally (1). Approx imate ly 10–15% of CRC harbor a BRAF mutat ion (2) . This molecular subtype of CRC is more commonly associated with right-sided tumours, more advanced stage at presentation, and mucinous histopathology (3). BRAF-mutant CRC are more frequently found in microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumours compared to microsatellite stable (MSS) tumours (4) and are associated with higher mutation burden and CpG island methylator phenotype (CIMP)-high status (5). The presence of a BRAF mutation results in activation of BRAF kinase and sustained downstream activation of the RAS-RAF-mitogen-activated protein kinase (MAPK) signaling pathway. This disruption to key cellular responses drives cancer cell proliferation and survival, which in turn leads to more aggressive tumour biology (2). The presence of a BRAF mutation is considered a poor prognostic biomarker, translating to poor patient outcomes. Compared to BRAF-wildtype CRC, BRAF-mutant CRC are associated with a 70% increase in mortality (6) and a median overall survival (mOS) of 12 vs. 25 months in patients with BRAFwildtype CRC (7).
{"title":"A BEACON of hope for BRAF-mutant metastatic colorectal cancer","authors":"J. Mooi, Belinda Lee","doi":"10.21037/dmr-22-20","DOIUrl":"https://doi.org/10.21037/dmr-22-20","url":null,"abstract":"CRC is the second leading cause of cancer-related death, and the third most common cancer globally (1). Approx imate ly 10–15% of CRC harbor a BRAF mutat ion (2) . This molecular subtype of CRC is more commonly associated with right-sided tumours, more advanced stage at presentation, and mucinous histopathology (3). BRAF-mutant CRC are more frequently found in microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumours compared to microsatellite stable (MSS) tumours (4) and are associated with higher mutation burden and CpG island methylator phenotype (CIMP)-high status (5). The presence of a BRAF mutation results in activation of BRAF kinase and sustained downstream activation of the RAS-RAF-mitogen-activated protein kinase (MAPK) signaling pathway. This disruption to key cellular responses drives cancer cell proliferation and survival, which in turn leads to more aggressive tumour biology (2). The presence of a BRAF mutation is considered a poor prognostic biomarker, translating to poor patient outcomes. Compared to BRAF-wildtype CRC, BRAF-mutant CRC are associated with a 70% increase in mortality (6) and a median overall survival (mOS) of 12 vs. 25 months in patients with BRAFwildtype CRC (7).","PeriodicalId":72814,"journal":{"name":"Digestive medicine research","volume":"60 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41316260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. de Pastena, G. Montagnini, C. Filippini, E. Andreotti, R. Montorsi, A. Esposito
Objective: The review aims to summarize and describe surgical techniques and outcomes of a minimally invasive total pancreatectomy (MITP). Background: The minimally invasive approach has gained popularity in the last decades, even in complex abdominal surgery such as pancreatic resections. Currently, many meta-analyses focused on the benefit and advantages of the minimally invasive approach compared to open surgery, especially during distal pancreatectomy. Methods: Literature research in PubMed was performed on 1 st July 2021, using minimally invasive, laparoscopic, or robotic total pancreatectomy (TP) keywords. Case reports, case series on chronic pancreatitis, and no English language manuscripts were excluded. Considering the different MI approaches, laparoscopic or robotic, the literature research identified 416 and 221 manuscripts, respectively. After Authors’ revision, 8 papers for each technique were included. The MITP is safe, feasible, and reproducible. The conversion rate was slightly higher in the laparoscopic approach (26% vs. 7%) than the robotic. Major postoperative complication, mortality, and length of hospital stay were higher in laparoscopic series compared to the robotic ones. However, the MI technique seems to offer better intraoperative and postoperative outcomes, reducing intraoperative blood loss, major postoperative complications, and length of hospital stay compared to an open approach. Conclusions: Considering the widespread of the MI approach and the increased indication for TP, further studies, including randomized controlled trials, should be performed to assess the safety and feasibility of the MITP.
{"title":"Minimally invasive total pancreatectomy for treatment of pancreatic neoplasms: a narrative review","authors":"M. de Pastena, G. Montagnini, C. Filippini, E. Andreotti, R. Montorsi, A. Esposito","doi":"10.21037/dmr-21-70","DOIUrl":"https://doi.org/10.21037/dmr-21-70","url":null,"abstract":"Objective: The review aims to summarize and describe surgical techniques and outcomes of a minimally invasive total pancreatectomy (MITP). Background: The minimally invasive approach has gained popularity in the last decades, even in complex abdominal surgery such as pancreatic resections. Currently, many meta-analyses focused on the benefit and advantages of the minimally invasive approach compared to open surgery, especially during distal pancreatectomy. Methods: Literature research in PubMed was performed on 1 st July 2021, using minimally invasive, laparoscopic, or robotic total pancreatectomy (TP) keywords. Case reports, case series on chronic pancreatitis, and no English language manuscripts were excluded. Considering the different MI approaches, laparoscopic or robotic, the literature research identified 416 and 221 manuscripts, respectively. After Authors’ revision, 8 papers for each technique were included. The MITP is safe, feasible, and reproducible. The conversion rate was slightly higher in the laparoscopic approach (26% vs. 7%) than the robotic. Major postoperative complication, mortality, and length of hospital stay were higher in laparoscopic series compared to the robotic ones. However, the MI technique seems to offer better intraoperative and postoperative outcomes, reducing intraoperative blood loss, major postoperative complications, and length of hospital stay compared to an open approach. Conclusions: Considering the widespread of the MI approach and the increased indication for TP, further studies, including randomized controlled trials, should be performed to assess the safety and feasibility of the MITP.","PeriodicalId":72814,"journal":{"name":"Digestive medicine research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46886076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diagnostic conundrum of hepatobiliary ascariasis: catch me if you can—case report and literature review","authors":"K. Chiam, R. Muthukaruppan","doi":"10.21037/dmr-22-10","DOIUrl":"https://doi.org/10.21037/dmr-22-10","url":null,"abstract":"","PeriodicalId":72814,"journal":{"name":"Digestive medicine research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46370446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peter MacCallum Cancer Centre, Melbourne, Australia; Brighton and Sussex Medical School, University of Brighton, Brighton, UK; Anaesthetic Department, Royal Surrey County Hospital, Guildford, UK Contributions: (I) Conception and design: EM Tyson, C Jones; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: EM Tyson; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Emma M. Tyson. Anaesthetic Fellow, Peter MacCallum Cancer Centre, Melbourne 3000, Australia. Email: ems.tyson@gmail.com.
{"title":"The effects of exercise prehabilitation in upper gastrointestinal oncology patients undergoing surgical resection: a systematic review","authors":"E. Tyson, Muzaffar Malik, Christy W. Jones","doi":"10.21037/dmr-21-84","DOIUrl":"https://doi.org/10.21037/dmr-21-84","url":null,"abstract":"Peter MacCallum Cancer Centre, Melbourne, Australia; Brighton and Sussex Medical School, University of Brighton, Brighton, UK; Anaesthetic Department, Royal Surrey County Hospital, Guildford, UK Contributions: (I) Conception and design: EM Tyson, C Jones; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: EM Tyson; (V) Data analysis and interpretation: All authors; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Emma M. Tyson. Anaesthetic Fellow, Peter MacCallum Cancer Centre, Melbourne 3000, Australia. Email: ems.tyson@gmail.com.","PeriodicalId":72814,"journal":{"name":"Digestive medicine research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47042920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Duke-NUS Medical School, Singapore; Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore; Medicine Academic Clinical Program, Duke-NUS Medical School, Singapore; Center of Quantitative Medicine, Duke-NUS Medical School, Singapore Contributions: (I) Conception and design: C Weng, R Kumar, R Sultana, WC Chow; (II) Administrative support: C Weng; (III) Provision of study materials or patients: C Weng, R Kumar; (IV) Collection and assembly of data: C Weng, R Kumar; (V) Data analysis and interpretation: C Weng, R Sultana; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Rajneesh Kumar. Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore 169608, Singapore. Email: Rajneesh.kumar@singhealth.com.sg.
{"title":"Occult hepatitis B virus infection and the risk of hepatocellular carcinoma: a systematic review and meta-analysis","authors":"Chao Weng, Rajneesh Kumar, R. Sultana, W. Chow","doi":"10.21037/dmr-21-50","DOIUrl":"https://doi.org/10.21037/dmr-21-50","url":null,"abstract":"Duke-NUS Medical School, Singapore; Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore; Medicine Academic Clinical Program, Duke-NUS Medical School, Singapore; Center of Quantitative Medicine, Duke-NUS Medical School, Singapore Contributions: (I) Conception and design: C Weng, R Kumar, R Sultana, WC Chow; (II) Administrative support: C Weng; (III) Provision of study materials or patients: C Weng, R Kumar; (IV) Collection and assembly of data: C Weng, R Kumar; (V) Data analysis and interpretation: C Weng, R Sultana; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Rajneesh Kumar. Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore 169608, Singapore. Email: Rajneesh.kumar@singhealth.com.sg.","PeriodicalId":72814,"journal":{"name":"Digestive medicine research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45555360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Narrative review on alcoholic liver disease: from fibrosis to cancer","authors":"H. Seitz, M. Neuman","doi":"10.21037/dmr-21-91","DOIUrl":"https://doi.org/10.21037/dmr-21-91","url":null,"abstract":"","PeriodicalId":72814,"journal":{"name":"Digestive medicine research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47826475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Intrathecal (spinal), epidural and the combined spinalepidural (CSE) are neuraxial techniques that can be used to provide postoperative analgesia and, in some circumstances, anaesthesia for surgery. They feature in many current enhanced recovery after surgery (ERAS) protocols with a bias towards epidurals for open surgery because it is thought they provide superior opiate-sparing analgesia and reduce the stress response to surgery through blunting sympathetic outflow. Both are key components of the ERAS concept. We aim to provide an evidenced-based overview for the use of neuraxial techniques in major surgery and their use within an ERAS protocol. We present the following article in accordance with the Narrative Review reporting checklist (available at https:// dx.doi.org/10.21037/dmr-21-86). Review Article
{"title":"Neuraxial anaesthesia and its role in enhanced recovery after surgery: a narrative review","authors":"R. Agarwala, Ben L Morrison","doi":"10.21037/dmr-21-86","DOIUrl":"https://doi.org/10.21037/dmr-21-86","url":null,"abstract":"Intrathecal (spinal), epidural and the combined spinalepidural (CSE) are neuraxial techniques that can be used to provide postoperative analgesia and, in some circumstances, anaesthesia for surgery. They feature in many current enhanced recovery after surgery (ERAS) protocols with a bias towards epidurals for open surgery because it is thought they provide superior opiate-sparing analgesia and reduce the stress response to surgery through blunting sympathetic outflow. Both are key components of the ERAS concept. We aim to provide an evidenced-based overview for the use of neuraxial techniques in major surgery and their use within an ERAS protocol. We present the following article in accordance with the Narrative Review reporting checklist (available at https:// dx.doi.org/10.21037/dmr-21-86). Review Article","PeriodicalId":72814,"journal":{"name":"Digestive medicine research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44357857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Our understanding of the molecular profile and associated targeted therapies has revolutionised the approach to treatment of metastatic colorectal cancer (mCRC). Approximately 10% (range, 8–21%) of mCRC carry a BRAF mutation which occurs primarily (>90%) at the V600E codon and leads to overactivation of the RAS/RAF/MEK/ ERK signalling [mitogen-activated protein kinases (MAPK)] pathway (1). BRAF mutant (MT) mCRC are renowned for their poor prognosis with a median overall survival (OS) inferior ranging from 10 to 20 months with resistance to standard systemic therapy, often not even reaching secondline treatment (2,3). The exception is the subset of MSI-H/ dMRR patients (up to 30% of BRAF MT CRC) who benefit from immunotherapy with checkpoint inhibitors (CPI) following the recent Keynote-177 trial (4). Unlike melanoma, previous trials with BRAF inhibition monotherapy (or combination with MEK inhibition) for BRAF MT mCRC show only minimal activity. This is due to feedback upregulation of epidermal growth factor receptor (EGFR) that re-activates the oncogenic pathway bypassing BRAF. Benefit of combining BRAF and EGFR inhibitors to overcome this pharmacological escape has been seen in several trials now. The BEACON phase 3 trial (5) is the pivotal study of this approach showing that the combination of the BRAF inhibitor encorafenib with anti-EGFR treatment (cetuximab) with or without a MEKinhibitor (binimetinib) led to significantly better OS and overall response rates (ORR) compared to irinotecan (FOLFIRI) or irinotecan with cetuximab. One strategy to ameliorate outcomes of these patients might be to combine multiple mitogen-activated protein kinases (MAPK) targeting agents with cytotoxic agents. Encouraging preclinical data combining irinotecan with anti-BRAF molecules (6,7), led Kopetz et al. (8) to explore the addition of the BRAF inhibitor vemurafenib to a backbone of irinotecan and cetuximab in previously treated BRAF MT mCRC.
{"title":"The evolving landscape of BRAF inhibitors in BRAF mutant colorectal cancer and the added value of cytotoxic chemotherapy","authors":"Barbara Geerinckx, Annabel Smith, T. Price","doi":"10.21037/dmr-21-99","DOIUrl":"https://doi.org/10.21037/dmr-21-99","url":null,"abstract":"Our understanding of the molecular profile and associated targeted therapies has revolutionised the approach to treatment of metastatic colorectal cancer (mCRC). Approximately 10% (range, 8–21%) of mCRC carry a BRAF mutation which occurs primarily (>90%) at the V600E codon and leads to overactivation of the RAS/RAF/MEK/ ERK signalling [mitogen-activated protein kinases (MAPK)] pathway (1). BRAF mutant (MT) mCRC are renowned for their poor prognosis with a median overall survival (OS) inferior ranging from 10 to 20 months with resistance to standard systemic therapy, often not even reaching secondline treatment (2,3). The exception is the subset of MSI-H/ dMRR patients (up to 30% of BRAF MT CRC) who benefit from immunotherapy with checkpoint inhibitors (CPI) following the recent Keynote-177 trial (4). Unlike melanoma, previous trials with BRAF inhibition monotherapy (or combination with MEK inhibition) for BRAF MT mCRC show only minimal activity. This is due to feedback upregulation of epidermal growth factor receptor (EGFR) that re-activates the oncogenic pathway bypassing BRAF. Benefit of combining BRAF and EGFR inhibitors to overcome this pharmacological escape has been seen in several trials now. The BEACON phase 3 trial (5) is the pivotal study of this approach showing that the combination of the BRAF inhibitor encorafenib with anti-EGFR treatment (cetuximab) with or without a MEKinhibitor (binimetinib) led to significantly better OS and overall response rates (ORR) compared to irinotecan (FOLFIRI) or irinotecan with cetuximab. One strategy to ameliorate outcomes of these patients might be to combine multiple mitogen-activated protein kinases (MAPK) targeting agents with cytotoxic agents. Encouraging preclinical data combining irinotecan with anti-BRAF molecules (6,7), led Kopetz et al. (8) to explore the addition of the BRAF inhibitor vemurafenib to a backbone of irinotecan and cetuximab in previously treated BRAF MT mCRC.","PeriodicalId":72814,"journal":{"name":"Digestive medicine research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44553103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Robotics as the natural evolution for minimally invasive surgery liver surgery: technological advances for patient and surgeon benefit","authors":"Y. Fong, T. Gall, Abigail J. Fong","doi":"10.21037/dmr-21-71","DOIUrl":"https://doi.org/10.21037/dmr-21-71","url":null,"abstract":"","PeriodicalId":72814,"journal":{"name":"Digestive medicine research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45131040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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