Introduction: In metastatic colorectal cancer (mCRC), RAS mutations impart inferior survival and resistance to anti-epidermal growth factor receptor (EGFR) antibodies. KRAS G12C inhibitors have been developed and we evaluated how KRAS G12C differs from other RAS mutations. Patients and Methods: This retrospective review evaluated patients in British Columbia, Canada with mCRC and RAS testing performed between 1 January 2016 and 31 December 2018. Sequencing information from The Cancer Genome Analysis (TCGA) was also obtained and analysed. Results: Age at diagnosis, sex, anatomic location and stage at diagnosis did not differ by RAS mutation type. Progression free survival on first chemotherapy for patients with metastatic KRAS G12C tumours was 11 months. Median overall survival did not differ by RAS mutation type but was worse for both KRAS G12C (27 months) and non-G12C alterations (29 months) than wildtype (43 months) ( p = 0.01). Within the TCGA, there was no differential gene expression between KRAS G12C and other RAS mutations. However, eight genes with copy number differences between the G12C and non-G12C RAS mutant groups were identified after adjusting for multiple comparisons ( FITM2, PDRG1, POFUT1, ERGIC3, EDEM2, PIGU, MANBAL and PXMP4). We also noted that other RAS mutant mCRCs had a higher tumour mutation burden than those with KRAS G12C mutations (median 3.05 vs 2.06 muts/Mb, p = 4.2e–3) and that KRAS G12C/other RAS had differing consensus molecular subtype distribution from wildtype colorectal cancer (CRC) ( p < 0.0001) but not each other ( p = 0.14). Conclusion: KRAS G12C tumours have similar clinical presentation to other RAS mutant tumours, however, are associated with differential copy number alterations.
Operative classification of ventral abdominal hernias: new and practical classification. Yasser Selim. From the Ministry of Health.Background: Ventral hernias of the abdomen are defined as a noninguinal, nonhiatal defect in the fascia of the abdominal wall. Unfortunately, there is not currently a universal classification system for ventral hernias. One of the more accepted classification systems is that of the European Hernia Society (EHS). Its limitation is that it does not include individual patient risk factors and wound classification. The aim of this work was to find out the basic principles of hernia etiology and pathogenesis, clarify the factors that are important in treatment of ventral hernias, and categorize hernia patients according to those factors. Methods: This retrospective study included 238 patients who presented to our surgery department between 2010 and 2020. A full description of ventral hernias was made, including their type according to the EHS. In addition, abdominal wall components were assessed, including strength of rectus muscles, lateral abdominal muscles, and abdominal fascia, namely the linea alba. Patients with spontaneous hernias were grouped according to the size of the defect and the condition of the rectus abdominis muscles, the fascia and other abdominal muscles. Results: Patients were put into 6 clinical categories: type 1A, type 1B, type 2, type 3, type 4, and type 5. The grouping of patients was done according to the factors we believed affect the choice of surgical procedure and the prognosis of repair. Patients with types 1 and 2 have normal abdominal muscles, whereas those with types 3 and 4 have weak muscles and weak stretched fascia (linea alba). Type 5 includes incisional hernias. Conclusion: The primary purpose of any classification should be to improve the possibility of comparing different studies and their results. By describing hernias in a standardized way, different patient populations can be compared. Numerous classifications for groin and ventral hernias have been proposed over the past 5-6 decades. For primary abdominal wall hernias, there was agreement with EHS classification on the use of localization and size as classification variables.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.