Spatial transcriptomic analysis reveals local effects of intratumoral fusobacterial infection on DNA damage and immune signaling in rectal cancer.

Mucinous colorectal cancer (CRC) is a common histological subtype of colorectal adenocarcinoma, associated with a poor response to chemoradiotherapy. The commensal facultative anaerobes fusobacteria, have been associated with poor prognosis specifically in mesenchymal CRC. Interestingly, fusobacterial infection is especially prevalent in mucinous CRC. The objective of this study was therefore to increase our understanding of beneficial and detrimental effects of fusobacterial infection, by contrasting host cell signaling and immune responses in areas of high vs. low infection, using mucinous rectal cancer as a clinically relevant example. We employed spatial transcriptomic profiling of 106 regions of interest from 8 mucinous rectal cancer samples to study gene expression in the epithelial and immune segments across regions of high versus low fusobacterial infection. Fusobacteria high regions were associated with increased oxidative stress, DNA damage, and P53 signaling. Meanwhile regions of low fusobacterial prevalence were characterized by elevated JAK-STAT, Il-17, Il-1, chemokine and TNF signaling. Immune masks within fusobacterial high regions were characterized by elevated proportions of cytotoxic (CD8+) T cells (p = 0.037), natural killer (NK) cells (p < 0.001), B-cells (p < 0.001), and gamma delta T cells (p = 0.003). Meanwhile, fusobacteria low regions were associated with significantly greater M2 macrophage (p < 0.001), fibroblast (p < 0.001), pericyte (p = 0.002), and endothelial (p < 0.001) counts.

Acute colonic pseudo-obstruction post-cesarean section is not a benign entity: A case series and review of the literature.

Acute colonic pseudo-obstruction (ACPO) is an infrequent occurrence after cesarean section. Anecdotal evidence suggests that the clinical course of ACPO in the obstetric setting is different to that seen in non-pregnant adult patients with ACPO secondary to alternative causes, such as systemic illnesses, the use of certain medications, and after non-abdominal surgery. The risk of progression to ischemia and perforation, as well as the need for emergency surgery, appears to be higher after cesarean section. Here we describe the clinical course of ACPO in four patients after cesarean section from our institution, followed by a review of the literature and a discussion of the important issues surrounding this condition in the postpartum time period. The findings from our cohort of patients and the reports from the medical literature support a hands-on combined approach from a group of specialists including obstetricians, surgeons, radiologists, and enterostomal therapists. Immediate imaging followed by regular observation is mandatory for any patient being managed conservatively. Early use of endoscopic decompression should be considered for patients who are not resolving with a conservative approach. Clinical signs of peritonism or radiological signs of ischemia or perforation in patients with ACPO mandate immediate surgical intervention. Appropriate postoperative care is necessary to deal with the complex physiological and psychological consequences of emergency surgery and potential stoma formation so soon after cesarean section.

Comparing neoadjuvant therapy followed by local excision to total mesorectal excision in the treatment of early stage rectal cancer: a systematic review and meta-analysis of randomised clinical trials.

INTRODUCTION: Total mesorectal excision (TME) is the standard-of-care in early, clinical stage (cT2-3 N0 M0) rectal cancer. Local excision (LE) may be an alternative after adequate response to neoadjuvant therapy (NAT), with either long-course chemoradiotherapy (nCRT) or short-course radiotherapy (SCRT), as a means of preserving the rectum and potentially obviating the morbidity of TME. METHODS: A systematic review was performed according to PRISMA guidelines for studies that randomly assigned patients with cT2-3 N0 M0 rectal cancer to either NAT + LE or TME that reported radiologic, oncologic, surgical, and morbidity outcomes. RESULTS: A total of 4 RCTs comprise 462 patients (232 patients receiving NAT + LE; nCRT n = 205; SCRT n = 27) and 230 undergoing TME, respectively. NAT compliance was 98.86%. The rate of early completion TME in the NAT + LE group was 22.3%, while the proportion of patients achieving durable organ preservation was 75.4% at mean follow-up of 5.6 years. There was no difference in disease-free survival (DFS) (HR [hazard ratio] 1.19; 95% CI 0.95, 1.49; p = 0.13) or overall survival (OS) (HR 0.94; 95% CI 0.72, 1.23; p = 0.63]) according to the assigned treatment arm. The local recurrence rate (LRR) (HR 1.22; 95% CI 0.5-3.02; p = 0.66) and distant metastases (HR 0.92; 95% CI 0.45, 1.90; p = 0.82) were also comparable between the groups. There was a significant reduction in major (OR 0.45; 95% CI 0.21, 0.95; p = 0.04) and minor morbidity (OR 0.45; 95% CI 0.24, 0.85; p = 0.01) for patients undergoing NAT + LE. Overall stoma formation was decreased in the NAT + LE group (OR 0.03; 95% CI 0.0, 0.23; p ≤ 0.00001). CONCLUSION: NAT + LE reduces adverse effects of TME, without any compromise in oncological outcomes, and the potential for an organ preserving strategy should be discussed with patients with T2-3N0 rectal cancers prior to treatment.

Corrigendum: Mucinous adenocarcinoma of the rectum: a whole genome sequencing study.

[This corrects the article DOI: 10.3389/fonc.2020.01682.].

Is Delaying a Coloanal Anastomosis the Ideal Solution for Rectal Surgery?: Analysis of a Multicentric Cohort of 564 Patients From the GRECCAR.

OBJECTIVES: To assess the specific results of delayed coloanal anastomosis (DCAA) in light of its 2 main indications. BACKGROUND: DCAA can be proposed either immediately after a low anterior resection (primary DCAA) or after the failure of a primary pelvic surgery as a salvage procedure (salvage DCAA). METHODS: All patients who underwent DCAA intervention at 30 GRECCAR-affiliated hospitals between 2010 and 2021 were retrospectively included. RESULTS: Five hundred sixty-four patients (male: 63%; median age: 62 years; interquartile range: 53-69) underwent a DCAA: 66% for primary DCAA and 34% for salvage DCAA. Overall morbidity, major morbidity, and mortality were 57%, 30%, and 1.1%, respectively, without any significant differences between primary DCAA and salvage DCAA ( P = 0.933; P = 0.238, and P = 0.410, respectively). Anastomotic leakage was more frequent after salvage DCAA (23%) than after primary DCAA (15%), ( P = 0.016).Fifty-five patients (10%) developed necrosis of the intra-abdominal colon. In multivariate analysis, intra-abdominal colon necrosis was significantly associated with male sex [odds ratio (OR) = 2.67 95% CI: 1.22-6.49; P = 0.020], body mass index >25 (OR = 2.78 95% CI: 1.37-6.00; P = 0.006), and peripheral artery disease (OR = 4.68 95% CI: 1.12-19.1; P = 0.030). The occurrence of this complication was similar between primary DCAA (11%) and salvage DCAA (8%), ( P = 0.289).Preservation of bowel continuity was reached 3 years after DCAA in 74% of the cohort (primary DCAA: 77% vs salvage DCAA: 68%, P = 0.031). Among patients with a DCAA mannered without diverting stoma, 75% (301/403) have never required a stoma at the last follow-up. CONCLUSIONS: DCAA makes it possible to definitively avoid a stoma in 75% of patients when mannered initially without a stoma and to save bowel continuity in 68% of the patients in the setting of failure of primary pelvic surgery.

The Impact of Bariatric Surgery on the Incidence of Colorectal Cancer in Patients with Obesity-a Systematic Review and Meta-analysis of Registry Data.

PURPOSE: Cancer and obesity represent two of the most significant global health concerns. The risk of malignancy, including colorectal cancer (CRC), increases with obesity. The aim of this study was to perform a systematic review and meta-analysis to determine the value of bariatric surgery in reducing CRC risk in patients with obesity using registry data. MATERIALS AND METHODS: A systematic review and meta-analysis were performed as per PRISMA guidelines. The risk of CRC was expressed as a dichotomous variable and reported as odds ratios (OR) with 95% confidence intervals (CIs) using the Mantel-Haenszel method. A multi-treatment comparison was performed, examining the risk reduction associated with existing bariatric surgery techniques. Analysis was performed using RevMan, R packages, and Shiny. RESULTS: Data from 11 registries including 6,214,682 patients with obesity were analyzed. Of these, 14.0% underwent bariatric surgery (872,499/6,214,682), and 86.0% did not undergo surgery (5,432,183/6,214,682). The mean age was 49.8 years, and mean follow-up was 5.1 years. In total, 0.6% of patients who underwent bariatric surgery developed CRC (4,843/872,499), as did 1.0% of unoperated patients with obesity (54,721/5,432,183). Patients with obesity who underwent bariatric surgery were less likely to develop CRC (OR: 0.53, 95% CI: 0.36-0.77, P < 0.001, I2 = 99%). Patients with obesity undergoing gastric bypass surgery (GB) (OR: 0.513, 95% CI: 0.336-0.818) and sleeve gastrectomy (SG) (OR: 0.484, 95% CI: 0.307-0.763) were less likely to develop CRC than unoperated patients. CONCLUSION: At a population level, bariatric surgery is associated with reduced CRC risk in patients with obesity. GB and SG are associated with the most significant reduction in CRC risk. PROSPERO REGISTRATION: CRD42022313280.

Increased Fusobacterium tumoural abundance affects immunogenicity in mucinous colorectal cancer and may be associated with improved clinical outcome.

There is currently an urgent need to identify factors predictive of immunogenicity in colorectal cancer (CRC). Mucinous CRC is a distinct histological subtype of CRC, associated with a poor response to chemotherapy. Recent evidence suggests the commensal facultative anaerobe Fusobacterium may be especially prevalent in mucinous CRC. The objectives of this study were to assess the association of Fusobacterium abundance with immune cell composition and prognosis in mucinous CRC. Our study included two independent colorectal cancer patient cohorts, The Cancer Genome Atlas (TCGA) cohort, and a cohort of rectal cancers from the Beaumont RCSI Cancer Centre (BRCC). Multiplexed immunofluorescence staining of a tumour microarray (TMA) from the BRCC cohort was undertaken using Cell DIVE technology. Our cohorts included 87 cases (13.3%) of mucinous and 565 cases (86.7%) of non-mucinous CRC. Mucinous CRC in the TCGA dataset was associated with an increased proportion of CD8 + lymphocytes (p = 0.018), regulatory T-cells (p = 0.001) and M2 macrophages (p = 0.001). In the BRCC cohort, mucinous RC was associated with enhanced CD8 + lymphocyte (p = 0.022), regulatory T-cell (p = 0.047), and B-cell (p = 0.025) counts. High Fusobacterium abundance was associated with an increased proportion of CD4 + lymphocytes (p = 0.031) and M1 macrophages (p = 0.006), whilst M2 macrophages (p = 0.043) were under-represented in this cohort. Patients with increased Fusobacterium relative abundance in our mucinous CRC TCGA cohort tended to have better clinical outcomes (DSS: likelihood ratio p = 0.04, logrank p = 0.052). Fusobacterium abundance may be associated with improved outcomes in mucinous CRC, possibly due to a modulatory effect on the host immune response. KEY MESSAGES: • Increased Fusobacterium relative abundance was not found to be associated with microsatellite instability in mucinous CRC. • Increased Fusobacterium relative abundance was associated with an M2/M1 macrophage switch, which is especially significant in mucinous CRC, where M2 macrophages are overexpressed. • Increased Fusobacterium relative abundance was associated with a significant improvement in disease specific survival in mucinous CRC. • Our findings were validated at a protein level within our own in house mucinous and non-mucinous rectal cancer cohorts.

Comparing minimally invasive surgical and open approaches to pelvic exenteration for locally advanced or recurrent pelvic malignancies - Systematic review and meta-analysis.

INTRODUCTION: Pelvic exenteration (PE) is a complex multivisceral surgical procedure indicated for locally advanced or recurrent pelvic malignancies. It poses significant technical challenges which account for the high risk of morbidity and mortality associated with the procedure. Developments in minimally invasive surgical (MIS) approaches and enhanced peri-operative care have facilitated improved long term outcomes. However, the optimum approach to PE remains controversial. METHODS: A systematic literature search was conducted in accordance with PRISMA guidelines to identify studies comparing MIS (robotic or laparoscopic) approaches for PE versus the open approach for patients with locally advanced or recurrent pelvic malignancies. The methodological quality of the included studies was assessed systematically and a meta-analysis was conducted. RESULTS: 11 studies were identified, including 2009 patients, of whom 264 (13.1%) underwent MIS PE approaches. The MIS group displayed comparable R0 resections (Risk Ratio [RR] 1.02, 95% Confidence Interval [95% CI] 0.98, 1.07, p = 0.35)) and Lymph node yield (Weighted Mean Difference [WMD] 1.42, 95% CI -0.58, 3.43, p = 0.16), and although MIS had a trend towards improved towards improved survival and recurrence outcomes, this did not reach statistical significance. MIS was associated with prolonged operating times (WMD 67.93, 95% CI 4.43, 131.42, p < 0.00001) however, this correlated with less intra-operative blood loss, and a shorter length of post-operative stay (WMD -3.89, 955 CI -6.53, -1.25, p < 0.00001). Readmission rates were higher with MIS (RR 2.11, 95% CI 1.11, 4.02, p = 0.02), however, rates of pelvic abscess/sepsis were decreased (RR 0.45, 95% CI 0.21, 0.95, p = 0.04), and there was no difference in overall, major, or specific morbidity and mortality. CONCLUSION: MIS approaches are a safe and feasible option for PE, with no differences in survival or recurrence outcomes compared to the open approach. MIS also reduced the length of post-operative stay and decreased blood loss, offset by increased operating time.

Short notice cancellations - an insight into Irish surgical waiting lists.

BACKGROUND: The reasons underlying prolonged waiting lists for surgery in Ireland are multifactorial. Patient-related factors including non-attendances contribute in part to the current waiting times. AIMS: To determine the rate of short notice cancellation for day case surgery in a model 2 HSE hospital over a 1-month period and to implement an intervention to try and reduce the rate of cancellation. METHODS: The cancellation rate was documented over a 1-month period in the hospital. An intervention was then implemented, involving a phone call to the patient from a member of the surgical team to attempt to reduce the cancellation rate. Cancellations were re-audited after the implementation of the phone intervention. RESULTS: The initial audit revealed a cancellation rate of 39.7% during the first month prior to implementation of the phone intervention. A phone call intervention from a member of the surgical team was associated with a decrease in cancellations from 39.7 to 14.6% (p < 0.01). CONCLUSIONS: While cancellations remained high even after our intervention, a simple phone call was effective and more than halved our cancellation rate. Future efforts need to focus on increasing awareness of patient responsibility for attending scheduled appointments and procedures.

Obesity and outcomes in trauma - a systematic review and meta-analysis.

BACKGROUND: The physiological abnormalities relating to obesity and metabolic syndrome can contribute to worse outcomes following trauma especially in class 2 and 3 obesity. The aim of this systematic review was to determine whether patients with a higher class of obesity who suffer traumatic injury have a higher risk of worse outcomes including in-hospital mortality than normal-weight patients. METHODS: A systematic search of MEDLINE, EMBASE, CENTRAL, Web of Science and CINAHL was performed for studies that reported a comparison of in-hospital obesity-related outcomes against normal-weight individuals aged 15 years and older following trauma. Single or multiple injuries from either blunt and/or penetrating trauma were included. Burn-related injuries, isolated head injury and studies focusing on orthopaedic related perioperative complications were excluded. RESULTS: The search yielded 7405 articles; 26 were included in this systematic review. 945,511 patients had a BMI>30. A random-effects meta-analysis was performed for analysis of all four outcomes. Patients with class 3 obesity (BMI>40) have significantly higher odds of in-hospital mortality than normal-BMI individuals following blunt and penetrating trauma (OR, 1.75; 95% CI, 1.39-2.19, p=<0.00001), significantly longer hospital LOS (SMD, 0.23; 95% CI, 0.21-0.25; p<0.00001) and significantly longer ICU LOS (SMD, 0.19; 95% CI, 0.12-0.26; p<0.0001). In contrast, studies that examined blunt and penetrating trauma and classified obesity with a threshold of BMI>30 found no significant difference in the odds of in-hospital mortality (OR, 0.94; 95% CI, 0.86-1.02, p=0.13). CONCLUSIONS: There is a higher risk of in-hospital mortality in patients living with class 3 obesity following trauma when compared with individuals with normal BMI. The management of patients with obesity is complex and trauma systems should develop specific weight related pathways to manage and anticipate the complications that arise in these patients. Systematic review registration number PROSPERO registration: CRD42021234482 Level of Evidence: Level 3.

Apoptotic and Necroptotic Mediators are Differentially Expressed in Mucinous and Non-Mucinous Colorectal Cancer.

Background: Mucinous colorectal cancer (CRC) represents 10% of all CRC and is associated with chemotherapy resistance. This study aimed to determine expression of apoptosis and necroptosis mediators in mucinous CRC. Methods: RNA gene expression data were extracted from TCGA. Protein levels in 14 mucinous and 39 non-mucinous tumors were measured by multiplexed immunofluorescence. Levels of apoptosis and necroptosis signalling proteins were analysed in SW1463 (mucinous rectal), SW837 (non-mucinous rectal), LS174T (mucinous colon) and HCT116 (non-mucinous colon) cell lines by western blot. Cell death was investigated by flow cytometry measurement of propidium iodide stained cells. Results: High cleaved-Caspase 3 expression was noted in resected mucinous tumors. Western blot identified alterations in apoptosis proteins in mucinous CRC, most prominently downregulation of Bcl-xL protein levels (p=0.029) which was also observed at the mRNA level in patients by analysis of TCGA gene expression data (p<0.001). Treatment with 5-FU did not significantly elevate cell death in mucinous cells, while non-mucinous cells showed robust cell death responses. However, 5-FU-induced phosphorylation of MLKL in mucinous cancer cells, suggestive of a switch to necroptotic cell death signaling. Conclusion: Apoptotic and necroptotic mediators are differentially expressed in mucinous and non-mucinous colorectal cancers and represent targets for investigation of cell death mechanisms in the mucinous subtype.

Hepatic resection for breast cancer related liver metastases: A single institution experience.

BACKGROUND & OBJECTIVE: Liver resection for breast cancer liver metastases is becoming a more widely accepted therapeutic option for selected groups of patients. The aim of this study was to describe the outcomes of patients undergoing liver resection for breast cancer-related liver metastases and identify any variables associated with recurrence or survival. METHODS: A retrospective review of a prospectively maintained database was undertaken for the 12 year period between 2009 and 2021. Clinicopathological, treatment, intraoperative, recurrence, survival and follow-up data were collected on all patients. Kaplan-Meier methods, the log-rank test and Cox proportional hazards regression analysis were used to identify variables that were associated with recurrence and survival. RESULTS: A total of 20 patients underwent 21 liver resections over the 12-year period. There were no deaths within 30 days of surgery and an operative morbidity occurred in 23.8% of cases. The median local recurrence free survival and disease free survival times were both 50 months, while the 5 year overall survival rate was 65%. The presence of extrahepatic metastases were associated with a decreased time to local recurrence (p < 0.01) and worse overall survival (p = 0.02). CONCLUSIONS: This study has demonstrated that liver resection for breast cancer-related liver metastases is feasible, safe and associated with prolonged disease free and overall survival in selected patients. It is likely that this option will be offered to more patients going forward, however, the difficulty lies in selecting out those who will benefit from liver resection particularly given the increasing number of systemic treatments and local ablative methods available that offer good long-term results.

An Analysis of Clinicopathological Outcomes and the Utility of Preoperative MRI for Patients Undergoing Resection of Mucinous and Non-Mucinous Colorectal Cancer Liver Metastases.

Background and Aims: Mucinous colorectal cancer has traditionally been associated with high rates of recurrence and poor long-term survival. There is limited published data on outcomes for patients undergoing liver resection for metastatic mucinous colorectal cancer. The aim of this study was to compare the clinicopathological outcomes for patients with mucinous colorectal cancer liver metastases (CRCLM) undergoing liver resection to a matched group of patients with adenocarcinoma not otherwise specified (NOS) and to evaluate the accurary of preoperative magnetic resonance imaging (MRI) at detecting the presence of mucin in liver metastases. Materials and Methods: Patients with mucinous CRCLM undergoing liver resection were matched 1:3 to patients with adenocarcinoma NOS CRCLM. Clinicopathological data from the primary tumour and metastatic lesion were collected and compared between the groups. Hepatic recurrence-free, disease-free and overall survival were compared between the groups. The ability of preoperative MRI to detect mucin in CRCLM was also evaluated. Results: A total of 25 patients with mucinous CRCLM underwent surgery over the 12-year period and were matched to 75 patients with adenocarcinoma NOS. Clinicopathological findings were similar between the groups. Resection of mucinous CRCLM was feasible and safe with similar levels of morbidity to adenocarcinoma NOS. There were no differences identified in hepatic recurrence-free (p=0.85), disease-free (p=0.25) and overall survival (p=0.98) between the groups. MRI had a sensitivity of 31.3% in detecting the presence of mucin in CRCLM. Conclusion: Patients with mucinous CRCLM in this study had similar outcomes to patients with adenocarcinoma NOS. Based on our findings, histological subtype should not be taken into account when deciding on resectability of CRCLM.

Association between availability of medications for opioid use disorder in specialty treatment and use of medications among patients: A state-level trends analysis.

INTRODUCTION: Access to medication for opioid use disorder (MOUD) is a recognized public health challenge to improving the health of people with opioid use disorder (OUD) in many communities. Prior studies have shown that although MOUD availability has increased over time, particularly in some states, many substance use treatment facilities still do not offer medications. The relationship between greater availability of MOUD and use of MOUD among patients in treatment programs is not well understood. METHODS: We used the National Survey of Substance Abuse Treatment Services to calculate the percent of specialty facilities per state providing MOUD from 2007 to 2018 and the Treatment Episode Data Set-Admissions (TEDS-A) to estimate the likelihood that a patient would have MOUD as part of their treatment plan during the same time period. We estimated models with patient-level TEDS-A data as the outcome and state-aggregated one-year lagged availability of MOUD in facilities as the main predictor, stratifying by treatment facility type (intensive outpatient, non-intensive outpatient, and residential). RESULTS: We found that increasing MOUD availability at the facility level was associated with increased MOUD use in non-intensive and residential facilities at the patient level. Specifically, a 10 percentage point increase in MOUD availability was associated with a 4.5 percentage point increase in MOUD use among patients of non-intensive outpatient facilities (p-value = 0.03), and a 2.5 percentage points increase in residential facilities (p-value = 0.02). Non-Whites and patients in the Northeast had greater likelihoods of increased MOUD use in response to increased availability by facilities. CONCLUSION: Increasing MOUD availability among specialty treatment facilities is likely to promote better access to MOUD for patients seeking treatment for OUD.

An Insight Into the Driver Mutations and Molecular Mechanisms Underlying Mucinous Adenocarcinoma of the Rectum.

BACKGROUND: Mucinous adenocarcinoma of the rectum accounts for 10% of all rectal cancers and has an impaired response to neoadjuvant chemoradiotherapy and worse overall survival. To date, insufficient genomic research has been performed on this histological subtype. OBJECTIVE: This study aims to define the mismatch repair deficiency rate and the driver mutations underpinning mucinous adenocarcinoma of the rectum and to compare it with rectal adenocarcinoma not otherwise specified. DESIGN: Immunohistochemistry and sequencing were performed on tumor samples from our tumor biobank. SETTINGS: This study was conducted across 2 tertiary referral centers. PATIENTS: Patients with mucinous adenocarcinoma and rectal adenocarcinoma not otherwise specified who underwent rectal resection between 2008 and 2018 were included. MAIN OUTCOME MEASURES: Mismatch repair status was performed by immunohistochemical staining. Mutations in the panel of oncogenes and tumor suppressor genes were determined by sequencing on the MiSeq V3 platform. RESULTS: The study included 33 patients with mucinous adenocarcinoma of the rectum and 100 patients with rectal adenocarcinoma not otherwise specified. Those with mucinous adenocarcinoma had a mismatch repair deficiency rate of 12.1% compared to 2.0% in the adenocarcinoma not otherwise specified cohort (p = 0.04). Mucinous adenocarcinoma and adenocarcinoma not otherwise specified rectal tumors had similar mutation frequencies in most oncogenes and tumor suppressor genes. No difference was found in the KRAS mutation rate (50.0% vs 37.1%, p = 0.29) or BRAF mutation rate (6.7% vs 3.1%, p = 0.34) between the cohorts. No difference was found between the cohorts regarding recurrence-free (p = 0.29) or overall survival (p = 0.14). LIMITATIONS: The major limitations of this study were the use of formalin-fixed, paraffin-embedded tissue over fresh-frozen tissue and the small number of patients included, in particular, in the mucinous rectal cohort. CONCLUSIONS: Most mucinous rectal tumors develop and progress along the chromosomal instability pathway. Further research in the form of transcriptomics, proteomics, and analysis of the effects of the mucin barrier may yield valuable insights into the mechanisms of resistance to chemoradiotherapy in this cohort. See Video Abstract at http://links.lww.com/DCR/B464. UNA PERCEPCIN SOBRE MUTACIONES IMPULSORAS Y MECANISMOS MOLECULARES SUBYACENTES AL ADENOCARCINOMA MUCINOSO DEL RECTO: ANTECEDENTES:El adenocarcinoma mucinoso del recto, representa el 10% de todos los cánceres rectales y tiene una respuesta deficiente a la quimioradioterapia neoadyuvante y una peor supervivencia en general. A la fecha, se han realizado muy pocas investigaciones genómicas sobre este subtipo histológico.OBJETIVO:Definir la tasa de deficiencia en la reparación de desajustes y mutaciones impulsoras, que sustentan el adenocarcinoma mucinoso del recto y compararlo con el adenocarcinoma rectal no especificado de otra manera.DISEÑO:Se realizaron inmunohistoquímica y secuenciación en muestras tumorales de nuestro biobanco de tumores.AJUSTE:El estudio se realizó en dos centros de referencia terciarios.PACIENTES:Se incluyeron pacientes con adenocarcinoma mucinoso y adenocarcinoma no especificado de otra manera, sometidos a resección rectal entre 2008 y 2018.PRINCIPALES MEDIDAS DE RESULTADO:El estado de reparación de desajustes se realizó mediante tinción inmunohistoquímica. Las mutaciones en el panel de oncogenes y genes supresores de tumores, se determinaron mediante secuenciación en la plataforma MiSeq V3.RESULTADOS:El estudio incluyó a 33 pacientes con adenocarcinoma mucinoso del recto y 100 pacientes con adenocarcinoma del recto no especificado de otra manera. Aquellos con adenocarcinoma mucinoso, tenían una tasa de deficiencia de reparación de desajustes del 12,1% en comparación con el 2,0% en la cohorte de adenocarcinoma no especificado de otra manera (p = 0,04). El adenocarcinoma mucinoso y el adenocarcinoma no especificado de otra manera, tuvieron frecuencias de mutación similares en la mayoría de los oncogenes y genes supresores de tumores. No se encontraron diferencias en la tasa de mutación de KRAS (50,0% frente a 37,1%, p = 0,29) o la tasa de mutación de BRAF (6,7% frente a 3,1%, p = 0,34) entre las cohortes. No se encontraron diferencias entre las cohortes con respecto a la supervivencia libre de recurrencia (p = 0,29) o la supervivencia global (p = 0,14).LIMITACIONES:Las mayores limitaciones de este estudio, fueron el uso de tejido embebido en parafina y fijado con formalina, sobre el tejido fresco congelado y el pequeño número de pacientes incluidos, particularmente en la cohorte mucinoso rectal.CONCLUSIONES:La mayoría de los tumores rectales mucinosos se desarrollan y progresan a lo largo de la vía de inestabilidad cromosómica. La investigación adicional en forma transcriptómica, proteómica y análisis de los efectos de la barrera de la mucina, puede proporcionar información valiosa sobre los mecanismos de resistencia a la quimioradioterapia, en esta cohorte. Consulte Video Resumen en http://links.lww.com/DCR/B464.