Management of Rectal Cancer in Lynch Syndrome: Balancing Risk Reduction and Quality of Life.

Patients with Lynch syndrome are predisposed to developing colorectal cancer and a variety of extracolonic malignancies, at a young age. The management of rectal cancer in the setting of Lynch syndrome is a complex clinical scenario that requires the expertise of a multidisciplinary management team. In this review, we delve into the approach for rectal cancer in these patients, and specifically focus on several key aspects of treatment. Some unique aspects of rectal cancer in Lynch syndrome include the decision between proctectomy alone versus total proctocolectomy with or without an ileal pouch, the utility of chemotherapy and immunotherapy, nonoperative rectal cancer management, and the management of rectal polyps. Throughout, we highlight the delicate interplay between future cancer risk reduction and quality of life optimization.

Association of county-level food deserts and food swamps on postoperative outcomes among patients undergoing colorectal surgery.

BACKGROUND: Although malnutrition has been linked to worse healthcare outcomes, the broader context of food environments has not been examined relative to surgical outcomes. We sought to define the impact of food environment on postoperative outcomes of patients undergoing resection for colorectal cancer (CRC). METHODS: Patients who underwent surgery for CRC between 2014 and 2020 were identified from the Medicare database. Patient-level data were linked to the United States Department of Agriculture data on food environment. Multivariable regression was used to examine the association between food environment and the likelihood of achieving a textbook outcome (TO). TO was defined as the absence of an extended length of stay (≥75th percentile), postoperative complications, readmission, and mortality within 90 days. RESULTS: A total of 260,813 patients from 3017 counties were included in the study. Patients from unhealthy food environments were more likely to be Black, have a higher Charlson Comorbidity Index, and reside in areas with higher social vulnerability (all P < .01). Patients residing in unhealthy food environments were less likely to achieve a TO than that of patients residing in the healthiest food environments (food swamp: 48.8% vs 52.4%; food desert: 47.9% vs 53.7%; P < .05). On multivariable analysis, individuals residing in the unhealthy food environments had lower odds of achieving a TO than those of patients living in the healthiest food environments (food swamp: OR, 0.86; 95% CI, 0.83-0.90; food desert: OR, 0.79; 95% CI, 0.76-0.82); P < .05). CONCLUSION: The surrounding food environment of patients may serve as a modifiable sociodemographic risk factor that contributes to disparities in postoperative CRC outcomes.

Clinical Utility of Laser Speckle Contrast Imaging and Real-Time Quantification of Bowel Perfusion in Minimally Invasive Left-Sided Colorectal Resections.

BACKGROUND: Left-sided colorectal surgery demonstrates high anastomotic leak rates, with tissue ischemia thought to influence outcomes. Indocyanine green is commonly used for perfusion assessment, but evidence remains mixed for whether it reduces colorectal anastomotic leaks. Laser speckle contrast imaging provides dye-free perfusion assessment in real-time through perfusion heatmaps and quantification. OBJECTIVE: This study investigates the efficacy of advanced visualization (indocyanine green versus laser speckle contrast imaging) perfusion assessment and utility of laser speckle perfusion quantification in determining ischemic margins. DESIGN: Prospective intervention group using advanced visualization with case-matched, retrospective control group. SETTINGS: Single academic medical center. PATIENTS: Forty adult patients undergoing elective, minimally invasive, left-sided colorectal surgery. INTERVENTIONS: Intraoperative perfusion assessment using white-light imaging and advanced visualization at three time points: T1 - proximal colon after devascularization, before transection; T2 - proximal/distal colon before anastomosis; and T3 - completed anastomosis. MAIN OUTCOME MEASURES: Intraoperative indication of ischemic line of demarcation before resection under each visualization method, surgical decision change using advanced visualization, post-hoc laser speckle perfusion quantification of colorectal tissue, and 30-day postoperative outcomes. RESULTS: Advanced visualization changed surgical decision making in 17.5% of cases. For cases in which surgeons changed a decision, the average discordance between line of demarcation in white-light imaging and advanced visualization was 3.7 cm, compared to 0.41 cm (p = 0.01) for cases without decision changes. There was no statistical difference between line of ischemic demarcation using laser speckle versus indocyanine green (p = 0.16). Laser speckle quantified lower perfusion values for tissues beyond the line of ischemic demarcation while suggesting an additional 1 cm of perfused tissue beyond this line. One (2.5%) anastomotic leak occurred in the intervention group. LIMITATIONS: This study was not powered to detect differences in anastomotic leak rates. CONCLUSIONS: Advanced visualization using laser speckle and indocyanine green provides valuable perfusion information that impacts surgical decision-making in minimally invasive left-sided colorectal surgeries. See Video Abstract.

The Association of Food Insecurity and Surgical Outcomes Among Patients Undergoing Surgery for Colorectal Cancer.

BACKGROUND: Food insecurity predisposes individuals to suboptimal nutrition, leading to chronic disease and poor outcomes. OBJECTIVE: We sought to assess the impact of county-level food insecurity on colorectal surgical outcomes. DESIGN: Retrospective cohort study. SETTING: Data from the Surveillance, Epidemiology, and End Results-Medicare database was merged with county-level food insecurity obtained from the Feeding America: Mapping the Meal Gap report. Multiple logistic and Cox regression adjusted for patient-level covariates were implemented to assess outcomes. PATIENTS: Medicare beneficiaries diagnosed with colorectal cancer between 2010 and 2015. MAIN OUTCOME MEASURES: Surgical admission type (nonelective and elective admission), any complication, extended length of stay, discharge disposition (discharged to home and nonhome discharge), 90-day readmission, 90-day mortality, and textbook outcome. Textbook outcome was defined as no extended length of stay, postoperative complications, 90-day readmission, and 90-day mortality. RESULTS: Among 72,354 patients with colorectal cancer, 46,296 underwent resection. Within the surgical cohort, 9091 (19.3%) were in low, 27,716 (59.9%) were in moderate, and 9,489 (20.5%) were in high food insecurity counties. High food insecurity patients had greater odds of nonelective surgery (OR: 1.17; 95% CI, 1.09-1.26; p < 0.001), 90-day readmission (OR: 1.11; 95% CI, 1.04-1.19; p = 0.002), extended length of stay (OR: 1.32; 95% CI, 1.21-1.44; p < 0.001), and complications (OR: 1.11; 95% CI, 1.03-1.19; p = 0.002). High food insecurity patients also had decreased odds of home discharge (OR: 0.85; 95% CI, 0.79-0.91; p < 0.001) and textbook outcomes (OR: 0.81; 95% CI, 0.75-0.87; p < 0.001). High food insecurity minority patients had increased odds of complications (OR 1.59; 95% CI, 1.43-1.78) and extended length of stay (OR 1.89; 95% CI, 1.69-2.12) compared with low food insecurity white patients (all, p < 0.001). Notably, high food insecurity minority patients had 31% lower odds of textbook outcomes (OR: 0.69; 95% CI, 0.62-0.76; p < 0.001) compared with low food insecurity White patients ( p < 0.001). LIMITATIONS: This study was limited to Medicare beneficiaries aged 65 years or older; hence, it may not be generalizable to younger populations or those without insurance or with private insurance. CONCLUSIONS: County-level food insecurity was associated with suboptimal outcomes, demonstrating the importance of interventions to mitigate these inequities. See Video Abstract. LA ASOCIACIN DE INSEGURIDAD ALIMENTARIA Y RESULTADOS QUIRRGICOS ENTRE PACIENTES SOMETIDOS A CIRUGA DE CNCER COLORRECTAL: ANTECEDENTES:La inseguridad alimentaria predispone a las personas a una nutrición subóptima, lo que conduce a enfermedades crónicas y malos resultados.OBJETIVO:Intentamos evaluar el impacto de la inseguridad alimentaria a nivel de condado en resultados de la cirugía colorrectal.DISEÑO:Estudio de cohorte retrospectivo.ENTORNO CLINICO:La base de datos SEER-Medicare fusionada con la inseguridad alimentaria a nivel de condado obtenida del informe Feeding America: Mapping the Meal Gap. Para evaluar los resultados se implementaron regresiones logísticas múltiples y de Cox ajustadas según las covariables a nivel de paciente.PACIENTES:Beneficiarios de Medicare diagnosticados con cáncer colorrectal entre 2010 y 2015.PRINCIPALES MEDIDAS DE RESULTADO:Tipo de ingreso quirúrgico (ingreso no electivo y electivo), cualquier complicación, duración prolongada de la estancia hospitalaria, disposición del alta (alta al domicilio y alta no domiciliaria), reingreso a los 90 días, mortalidad a los 90 días y resultado del libro de texto. El resultado de los libros de texto se definió como ausencia de estancia hospitalaria prolongada, complicaciones postoperatorias, reingreso a los 90 días y mortalidad a los 90 días.RESULTADOS:Entre 72.354 pacientes con cáncer colorrectal, 46.296 se sometieron a resección. Dentro de la cohorte quirúrgica, 9.091 (19,3%) tenían inseguridad alimentaria baja, 27.716 (59,9%) eran moderadas y 9.489 (20,5%) tenían inseguridad alimentaria alta. Los pacientes con alta inseguridad alimentaria tuvieron mayores probabilidades de cirugía no electiva (OR: 1,17, IC 95%: 1,09-1,26, p <0,001), reingreso a los 90 días (OR: 1,11, IC95%: 1,04-1,19, p = 0,002), duración prolongada de la estancia hospitalaria (OR: 1,32; IC95%: 1,21-1,44, p < 0,001) y complicaciones (OR: 1,11; IC95%: 1,03-1,19, p = 0,002). Los pacientes con alta inseguridad alimentaria también tuvieron menores probabilidades de ser dados de alta a domicilio (OR: 0,85, IC del 95%: 0,79-0,91, p <0,001) y resultados de los libros de texto (OR: 0,81, IC del 95%: 0,75-0,87, p <0,001). Los pacientes minoritarios con alta inseguridad alimentaria tuvieron mayores probabilidades de complicaciones (OR 1,59, IC 95%, 1,43-1,78) y duración prolongada de la estadía (OR 1,89, IC 95%, 1,69-2,12) en comparación con los individuos blancos con baja inseguridad alimentaria (todos, p < 0,001). En particular, los pacientes minoritarios con alta inseguridad alimentaria tenían un 31% menos de probabilidades de obtener resultados según los libros de texto (OR: 0,69, IC del 95%, 0,62-0,76, p <0,001) en comparación con los pacientes blancos con baja inseguridad alimentaria ( p <0,001).LIMITACIONES:Limitado a beneficiarios de Medicare mayores de 65 años, por lo tanto, puede no ser generalizable a poblaciones más jóvenes o a aquellos sin seguro o con seguro privado.CONCLUSIONES:La inseguridad alimentaria a nivel de condado se asoció con resultados subóptimos, lo que demuestra la importancia de las intervenciones para mitigar estas desigualdades. (Dr. Francisco M. Abarca-Rendon ).

Assessing prognostic factors of long-term survival after surgery for colorectal gastrointestinal stromal tumours.

AIM: Due to their rarity, the management of colorectal gastrointestinal stromal tumours (CR GISTs) is still under debate. The aim of this study was to assess prognostic factors. METHOD: We performed a retrospective review of patients who underwent surgery with curative intent for CR GIST at our centre from 2002 to 2019. Factors associated with overall (OS) and recurrence-free survival (RFS) were analysed. RESULTS: Fifty-six patients were included [median age 63 years, 29 (52%) female, 30 (54%) Miettinen high-risk, 40 (71%) with rectal GIST]. Nineteen (34%) patients received perioperative (neoadjuvant and/or adjuvant) imatinib. All cases of colonic GIST had an R0 resection, compared with 28 (70%) of rectal GISTs. After a median follow-up of 97 months (interquartile range 48-155 months), 14 (25%) deaths and 14 (25%) recurrences occurred. In the high-risk cohort, factors associated with improved RFS were R0 resection (OR 0.19, 95% CI 0.1-0.5, p = 0.002) and perioperative imatinib (OR 0.33, 95% CI 0.42-0.97, p = 0.04). Patients who had received perioperative imatinib had longer RFS (60% vs. 11% at 5 years, p = 0.006) but not OS. In rectal GISTs, 5-year OS was 85% for R0 and 70% for R1 resections (p = 0.164) and 5-year RFS was 85% for R0 and 12% for R1 resection (p < 0.001). When stratifying patients by perioperative imatinib, there were no differences in OS or RFS in the R0 or R1 groups. CONCLUSION: Perioperative imatinib and R0 resection were associated with improved RFS in high-risk patients with CR GIST. In patients with rectal GIST, R1 resection was associated with worse RFS irrespective of perioperative imatinib treatment.

Latent class symptom profiles of colorectal cancer survivors with cancer-related cognitive impairment.

PURPOSE: Colorectal cancer (CRC) survivors experience cancer-related cognitive impairment and co-occurring symptoms after cancer treatments. There has been little data to inform the risk factors of complex symptom phenotypes in CRC survivors. OBJECTIVES: To determine if subgroups of CRC survivors after cancer treatments could be identified based on the cognitive impairment and common co-occurring symptoms (depression, anxiety, sleep disturbance, fatigue, and pain); and to explore risk factors (sociodemographic and clinical characteristics, perceived stress, and social support) of these subgroups. METHODS: Latent class profile analysis (LCPA) was used to identify subgroups based on self-reported symptoms in 64 CRC survivors. Cognitive impairment was measured by assessing subjective cognitive function using the Patient-Reported Outcome Measurement Information System (PROMIS) measure. The Kruskal-Wallis test and regression analyses were performed. RESULTS: Three distinct latent classes were identified (Class 1: All Low '28.1%'; Class 2: High Psychological Symptoms (depression/anxiety) '25%'; Class 3: High Somatic Symptoms (fatigue, sleep disturbance, and pain) with High Cognitive Impairment'46.9%'). The pain was the most distinguishable symptom across the latent classes. The high symptom burden group was associated with less time since cancer diagnosis, higher perceived stress levels, and poor emotional social support. CONCLUSION: Our study adds to the information on interindividual variability in symptom experience of CRC survivors with cognitive impairment. Findings suggest a need for increased attention to screening for co-occurring symptoms (e.g., high pain) and future interventions focused on stress management and social support.

Real-time quantification of bowel perfusion using Laparoscopic Laser Speckle Contrast Imaging (LSCI) in a porcine model.

BACKGROUND/PURPOSE: Real-time quantification of tissue perfusion can improve intraoperative surgical decision making. Here we demonstrate the utility of Laser Speckle Contrast Imaging as an intra-operative tool that quantifies real-time regional differences in intestinal perfusion and distinguishes ischemic changes resulting from arterial/venous obstruction. METHODS: Porcine models (n = 3) consisted of selectively devascularized small bowel loops that were used to measure the perfusion responses under conditions of control/no vascular occlusion, arterial inflow occlusion, and venous outflow occlusion using laser speckle imaging and indocyanine green fluoroscopy. Laser Speckle was also used to assess perfusion differences between small bowel antimesenteric-antimesenteric and mesenteric-mesenteric anastomoses. Perfusion quantification was measured in relative perfusion units calculated from the laser speckle perfusion heatmap. RESULTS: Laser Speckle distinguished between visually identified perfused, watershed, and ischemic intestinal segments with both color heatmap and quantification (p < .00001). It detected a continuous gradient of relative intestinal perfusion as a function of distance from the stapled ischemic bowel edge. Strong positive linear correlation between relative perfusion units and changes in mean arterial pressure resulting from both arterial (R2 = .96/.79) and venous pressure changes (R2 = .86/.96) was observed. Furthermore, Laser Speckle showed that the antimesenteric anastomosis had a higher perfusion than mesenteric anastomosis (p < 0.01). CONCLUSIONS: Laser Speckle Contrast Imaging provides objective, quantifiable tissue perfusion information in both color heatmap and relative numerical units. Laser Speckle can detect spatial/temporal differences in perfusion between antimesenteric and mesenteric borders of a bowel segment and precisely detect perfusion changes induced by progressive arterial/venous occlusions in real-time.

The Cumulative Incidence and Progression of Ileal Pouch Adenomas in Patients With Familial Adenomatous Polyposis.

BACKGROUND: Patients with familial adenomatous polyposis who have undergone restorative proctocolectomy can develop adenomas in the pouch. OBJECTIVE: To review experience with pouch surveillance and create a classification system for polyposis severity. DESIGN: A retrospective review of patients undergoing IPAA and follow-up at 1 institution. SETTING: A center for hereditary colorectal cancer within a quaternary referral center. PATIENTS: All patients undergoing IPAA and followed endoscopically after surgery by the center. INTERVENTIONS: Yearly pouchoscopy and treatment of polyps as required. MAIN OUTCOME MEASURES: Primary outcome measure was incidence and severity of pouch neoplasia and its changes with time. METHODS: A retrospective study of patients who had a restorative proctocolectomy for familial adenomatous polyposis at Cleveland Clinic. Severity of polyposis was classified on the basis of size, number, and histology. RESULTS: One hundred sixty-five patients were analyzed. The median age at IPAA was 31 years and 52% were male. The median follow-up was 10.1 years; the median number of pouchoscopies per patient was 4. The median interval between pouchoscopies was 21.9 months. Overall, the incidence of pouch adenomas was found in 47 patients (28.5%). The median time from pouch to first pouch adenoma diagnosis was 10.3 years. The estimated cumulative incidence rates of pouch adenoma at 5, 10, 15, 20, and 30 years after IPAA were 5.9%, 21.7%, 40%, 54.8%, and 69.9%, respectively. At the first diagnosis of pouch adenoma, 25 patients had stage 1, 10 had stage 2, 8 had stage 3, and 4 had stage 4. Twenty of 47 patients progressed to a higher stage. No patient developed cancer. LIMITATIONS: Genotype was not available for all patients. CONCLUSIONS: There is an increasing incidence of pouch neoplasia after restorative proctocolectomy, reaching a plateau at 25 years. The polyposis is usually mild but sometimes increases in severity. LA INCIDENCIA ACUMULADA Y LA PROGRESIN DE LOS ADENOMAS DE LA BOLSA ILEAL EN PACIENTES CON POLIPOSIS ADENOMATOSA FAMILIAR: ANTECEDENTES:Los pacientes con poliposis adenomatosa familiar que se han sometido a una proctocolectomía restauradora pueden desarrollar adenomas en la bolsa.OBJETIVO:Revisamos nuestra experiencia con la vigilancia de la bolsa y creamos un sistema de clasificación para la gravedad de la poliposis.DISEÑO:Una revisión retrospectiva de pacientes sometidos a anastomosis de bolsa ileoanal y seguimiento en una institución.ESCENARIO:Un centro para el cáncer colorrectal hereditario dentro de un centro de referencia cuaternarioPACIENTES:Todos los pacientes sometidos a anastomosis reservorio ileoanal y seguidos por vía endoscópica tras la cirugía por el centro.INTERVENCIONES:Bolsascopia anual y tratamiento de pólipos según sea necesarioPRINCIPALES MEDIDAS DE RESULTADO:Primaria: Incidencia y gravedad de la neoplasia del reservorio y sus cambios con el tiempo.MÉTODOS:Un estudio retrospectivo de pacientes que se sometieron a una proctocolectomía restauradora por poliposis adenomatosa familiar en la Clínica Cleveland. La gravedad de la poliposis se clasificó según el tamaño, el número y la histología.RESULTADOS:Se analizaron 165 pacientes. La mediana de edad del IPAA fue de 31 años y el 52% eran hombres. La mediana de seguimiento fue de 10,1 años; número medio de reservorioscopias por paciente = 4. El intervalo medio entre reservorioscopias fue de 21,9 meses. Incidencia global de adenomas de reservorio = 47/165 (28,5%). Tiempo mediano desde el reservorio hasta el primer diagnóstico de adenoma en reservorio = 10,3 años. La tasa de incidencia acumulada estimada de adenoma de bolsa a los 5, 10, 15, 20, y 30 años después de la IPAA es del 5,9%, 21,7%, 40%, 54,8%, y 69,9%, respectivamente. En el primer diagnóstico de adenoma de la bolsa, 25 pacientes tenían estadio 1, 10 estadio 2, 8 estadio 3 y 4 estadio 4. 20/47 pacientes progresaron a un estadio superior Ningún paciente desarrolló cáncer.LIMITACIONES:Genotipo no disponible para todos los pacientesCONCLUSIONES:Hay una incidencia creciente de neoplasia de la bolsa después de la proctocolectomía restauradora, alcanzando una meseta a los 25 años. La poliposis suele ser leve, pero a veces aumenta en severidad. (Traducción-Dr. Yesenia Rojas-Khalil ).

Top Colorectal Articles from 2021 to Inform Your Cancer Practice.

Multimodality treatment for locally advanced rectal cancer is the standard of care. Treatments include surgery, radiation, and chemotherapy, with medical therapies now being favored in the neoadjuvant setting. Various regimens continue to be studied and defined in prospective randomized trials. The PRODIGE 23 and RAPIDO trials showed improved disease-free survival and pathologic complete response rates for split chemotherapy/radiation treatment and short-course radiation with consolidation chemotherapy, respectively; both compared with traditional neoadjuvant long course chemoradiation, surgery, and adjuvant chemotherapy. Furthermore, new regimens are yielding a higher rate of complete clinical response, allowing for non-operative management. Circulating tumor DNA provides a potential novel option for monitoring response to treatment and rectal cancer surveillance. This manuscript summarizes some of the key clinical trials and studies that are defining clinical practice.

Factors associated with long-term gastrointestinal symptoms in colorectal cancer survivors in the women's health initiatives (WHI study).

PURPOSE: Colorectal cancer (CRC) survivors often experience long-term symptoms after cancer treatments. But gastrointestinal (GI) symptom experiences are under-investigated in CRC survivors. We described persistent GI symptoms after cancer treatments in female CRC survivors and assessed GI symptoms' risk and life-impact factors. METHODS: A cross-sectional study utilized data from the Women's Health Initiative (WHI) Life and Longevity After Cancer (LILAC) study that recruited postmenopausal women. Correlation analyses and multivariable linear regression models were used. RESULTS: CRC survivors after cancer treatments were included (N = 413, mean age 71.2 years old, mean time since diagnosis = 8.1 years). 81% of CRC survivors experienced persistent GI symptoms. Bloating/gas was the most prevalent (54.2%± 0.88) and severe GI symptom, followed by constipation (44.1%±1.06), diarrhea (33.4%±0.76), and abdominal/pelvic pain (28.6%±0.62). Significant risk factors for GI symptoms include time since cancer diagnosis (<5 years), advanced cancer stage, high psychological distress, poor dietary habits, and low physical activity. Fatigue and sleep disturbance were the most significant risk factors for long-term GI symptoms (ß = 0.21, t = 3.557; ß = 0.20, t = 3.336, respectively, Ps < .001). High severity of GI symptoms was positively associated with poor quality of life (QOL), increased daily life interferences (social and physical functions), and low body image satisfaction (Ps < .001). CONCLUSIONS: Women CRC survivors experience a high GI symptom burden, highlighting the need to inform policy and improve the QOL of cancer survivors. Our findings will aid in identifying those more vulnerable to symptoms, and inform future survivorship care interventions (i.e., community-based cancer symptom management) by considering multiple risk factors (e.g., psychological distress).

Incidence and prevalence of advanced colorectal neoplasia in Lynch syndrome.

BACKGROUND AND AIMS: Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC) and endometrial cancer (EC). Although colonoscopy reduces CRC in LS, the protection is variable. We assessed the prevalence and incidence of neoplasia in LS during surveillance colonoscopy in the United States and factors associated with advanced neoplasia. METHODS: Patients with LS undergoing ≥1 surveillance colonoscopy and with no personal history of invasive CRC or colorectal surgery were included. Prevalent and incident neoplasia was defined as occurring <6 months before and ≥6 months after germline diagnosis of LS, respectively. We assessed advanced adenoma (AA), CRC, and the impact of mismatch repair pathogenic variant (PV) and typical LS cancer history (personal history of EC and/or family history of EC/CRC) on outcome. RESULTS: A total of 132 patients (inclusive of 112 undergoing prevalent and incident surveillance) were included. The median examination interval and duration of prevalent and incident surveillance was .88 and 1.06 years and 3.1 and 4.6 years, respectively. Prevalent and incident AA were detected in 10.7% and 6.1% and invasive CRC in 0% and 2.3% of patients. All incident CRC occurred in MSH2 and MLH1 PV carriers and only 1 (.7%) while under surveillance in our center. AAs were detected in both LS cancer history cohorts and represented in all PVs. CONCLUSIONS: In a U.S. cohort of LS, advanced neoplasia rarely occurred over annual surveillance. CRC was diagnosed only in MSH2/MLH1 PV carriers. AAs occurred regardless of PV or LS cancer history. Prospective studies are warranted to confirm our findings.

Word of caution: Rectal cancer without response to neoadjuvant treatment - Do not wait for surgery.

BACKGROUND: We hypothesized that prolonging the interval to surgery in non-responders to neoadjuvant chemoradiation therapy (nCRT) could lead to worse oncologic outcomes. METHODS: Rectal adenocarcinoma patients with poor tumor response to nCRT (AJCC tumor regression grade 3) were selected. Oncologic outcomes were evaluated according to the time interval between completion of nCRT and surgery. RESULTS: Among 56 non-responders, 28 patients surgically treated ≥8 weeks after completion of nCRT had worse disease-free survival (31% vs. 49%, p â€‹= â€‹0.05) and worse overall survival (34% vs. 53%, p â€‹= â€‹0.02) compared to patients <8 weeks. Using the three different intervals (≥12 weeks, 6-12 weeks, and< 6 weeks), waiting longer was consistently associated with worse overall (23% vs. 48% vs. 63%, p â€‹= â€‹0.02) and worse cancer-specific survival (35% vs. 61% vs. 71%, p â€‹= â€‹0.04), respectively. CONCLUSION: For rectal cancer patients who are non-responders to nCRT, delay of surgery may lead to worse oncologic outcomes.

Dysbiosis of the stool DNA and RNA virome in Crohn's disease.

Pathogenesis of Crohn's disease (CD) relates to gut microbiome dysbiosis. However, less is known about the viral microbiome, consisting of bacteriophages and eukaryotic viruses, in CD. Here, we profiled the stool virome, viral functions, and viral-bacterial correlations that involved in CD pathogenesis. Metagenomics and metaviromics with novel viral identification and data analysis workflow were performed on stool of non-CD household controls, CD flare and remission patients. Both bacteriome and DNA/RNA virome alterations were characterized and correlated with disease status. There was a decreased diversity and extreme heterogeneity in both DNA and RNA virome in CD. We observed CD-specific dysbiosis in virome, particularly the prominent DNA eukaryotic Torque teno virus (TTV), disease-associated Faecalibacterium phage and Escherichia phage, and RNA tomato diet-related virus in CD, while some diverse prokaryotic viruses were more abundant in healthy subjects. Compared with the remission, inflammation-associated eukaryotic TTV and prokaryotic Staphylococcus phages were predominated in the flare, and displayed a link with complications and multiple therapeutic approaches. Multiple viral functions, particularly functions of viral DNA replication, integration and modification as well as the eukaryotic TTV-related capsid protein, were markedly enriched in CD. Furthermore, the virus-bacteria interactions became more specialized in CD, and the combination of bacteriome and virome composition provided better classification between CD and health. Our study presents a global view of the comprehensive viral component change in the CD patients' gut microbiome, and highlights the great potential of virome biomarkers in pathogenesis and accurate diagnostics of CD risk and disease status.

Universal tumor screening for lynch syndrome on colorectal cancer biopsies impacts surgical treatment decisions.

Universal tumor screening (UTS) for Lynch syndrome (LS) on colorectal cancer (CRC) can be performed on biopsies or resection specimens. The advantage of biopsies is the chance to provide preoperative genetic counseling/testing (GC/T) so patients diagnosed with LS can make informed decisions regarding resection extent. We evaluated utilization of UTS on biopsies, percentage of patients with deficient mismatch repair (dMMR) who underwent GC/T preoperatively, and whether surgical/treatment decisions were impacted. We performed a retrospective review of medical records to assess CRC cases with dMMR immunohistochemical staining from 1/1/2017 to 2/26/2021. 1144 CRC patients had UTS using MMR immunohistochemistry; 559 biopsies (48.9%) and 585 resections (51.1%). The main reason UTS was not performed on biopsy was it occurred outside our health system. 58 (5%) of CRCs were dMMR and did not have MLH1 promoter hypermethylation (if MLH1 and PMS2 absent). 28/58 (48.3%) of dMMR cases were diagnosed on biopsy. Of those 28, 14 (50%) eventually underwent GC/T, and 7 (25%) had GT results prior to surgery. One of the 7 had incomplete documentation of results affecting their treatment plan. Of the remaining 6 with complete documentation, 5 underwent surgery and one was treated with immunotherapy only. Three patients elected a more extensive surgery. 6/28 (21.4%) dMMR patients identified on biopsy made an informed surgical/treatment decision based on their dMMR status/LS diagnosis. When applied, UTS on biopsy followed by genetic counseling and testing informs surgical decision-making. Process and implementation strategies are in place to overcome challenges to more broadly optimize this approach.

Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines.

BACKGROUND & AIMS: Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC. METHODS: After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%. RESULTS: The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients. CONCLUSIONS: The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC.

The importance of genetics for timing and extent of surgery in inherited colorectal cancer syndromes.

Approximately 5% of colorectal cancers arise within an inherited colorectal cancer syndrome, with known underlying genetic etiologies. These syndromes increase the risk of colorectal and extracolonic cancers. Identification of a specific genetic pathogenic variant defines the syndrome, and quantifies the elevated risks compared to the general population. Thus, knowing and understanding the risks associated with each pathogenic variant allows for risk-stratification and a more individualized management strategy. These factors influence both the timing of surgery and the extent of colorectal surgery for patients with these syndromes. Familial Adenomatous Polyposis (FAP) is a dominantly inherited polyposis syndrome caused by pathogenic variant in the APC gene and results in a near 100% chance of developing colorectal cancer if not treated. There is a genotype-phenotype correlation in which the affected gene locus is associated with severity of polyposis and the risk of desmoid disease. Prophylactic surgery ranging from total abdominal colectomy or total proctocolectomy is recommended before cancer develops. Lynch syndrome is a non-polyposis inherited syndrome caused by a pathogenic variant in MLH1, MSH2, MSH6, or PMS2. Although prophylactic colectomy in Lynch syndrome is uncommon, total abdominal colectomy as prophylaxis in the setting of colon cancer is recommended due to the likelihood of metachronous colorectal cancer. This article reviews the role of genetics surgical decision making with respect to the timing and extent of surgery within the hereditary colorectal cancer syndromes.

Hereditary Colorectal Cancer.

Around 10% to 16% of colorectal cancer patients have a pathogenic variant in a cancer susceptibility gene. Some of these variants are in cancer genes that are associated with colorectal cancer while others are not. The hereditary colorectal cancer syndromes can be divided into two major categories, the nonpolyposis and the polyposis conditions. The nonpolyposis conditions can be divided into those that lead to colorectal tumors with defective mismatch repair and those that do not. The polyposis conditions are further divided by predominant histology into the adenomatous, hamartomatous, serrated, and mixed polyposis conditions. All of these conditions are described in detail herein.

Management of Colorectal Cancer in Hereditary Syndromes.

Approximately 5% of all colorectal cancers develop within a hereditary colorectal cancer syndrome. Patients and families with these syndromes have an increased risk of colorectal and extracolonic cancers that develop at an early age. Recognition and diagnosis of these conditions are crucial to management and risk reduction. Surgeons must be aware of the unique aspects of the timing and extent of surgery (both therapeutic and prophylactic) within these syndromes, particularly for the most common syndromes, Lynch syndrome and familial adenomatous polyposis.