Ancient DNA at the edge of the world: Continental immigration and the persistence of Neolithic male lineages in Bronze Age Orkney.

Orkney was a major cultural center during the Neolithic, 3800 to 2500 BC. Farming flourished, permanent stone settlements and chambered tombs were constructed, and long-range contacts were sustained. From ∼3200 BC, the number, density, and extravagance of settlements increased, and new ceremonial monuments and ceramic styles, possibly originating in Orkney, spread across Britain and Ireland. By ∼2800 BC, this phenomenon was waning, although Neolithic traditions persisted to at least 2500 BC. Unlike elsewhere in Britain, there is little material evidence to suggest a Beaker presence, suggesting that Orkney may have developed along an insular trajectory during the second millennium BC. We tested this by comparing new genomic evidence from 22 Bronze Age and 3 Iron Age burials in northwest Orkney with Neolithic burials from across the archipelago. We identified signals of inward migration on a scale unsuspected from the archaeological record: As elsewhere in Bronze Age Britain, much of the population displayed significant genome-wide ancestry deriving ultimately from the Pontic-Caspian Steppe. However, uniquely in northern and central Europe, most of the male lineages were inherited from the local Neolithic. This suggests that some male descendants of Neolithic Orkney may have remained distinct well into the Bronze Age, although there are signs that this had dwindled by the Iron Age. Furthermore, although the majority of mitochondrial DNA lineages evidently arrived afresh with the Bronze Age, we also find evidence for continuity in the female line of descent from Mesolithic Britain into the Bronze Age and even to the present day.

Long-term Outcomes of the Kono-S Anastomosis: A Multicenter Study.

BACKGROUND: Postoperative recurrence remains a significant problem in Crohn's disease, and the mesentery is implicated in the pathophysiology. The Kono-S anastomosis was designed to exclude the mesentery from a wide anastomotic lumen, limit luminal distortion and fecal stasis, and preserve innervation and vascularization. OBJECTIVE: To review postoperative complications and long-term outcomes of the Kono-S anastomosis in a large series of consecutive unselected patients with Crohn's disease. DESIGN: Retrospective study of prospectively collected patients. SETTINGS: Four tertiary referral centers. PATIENTS: Consecutive patients with Crohn's disease who underwent resection with Kono-S anastomosis between May 2010 and June 2022. INTERVENTIONS: Extracorporeal handsewn Kono-S anastomosis. MAIN OUTCOME MEASURES: Postoperative outcomes and recurrence defined as endoscopic, clinical, laboratory, or surgical, including endoscopic, intervention. RESULTS: A total of 262 consecutive patients (53.4% male) were included. The mean duration of disease at surgery was 145.1 months. One hundred thirty-five patients (51.5%) had previous abdominal surgery for Crohn's disease. Forty-four patients (17%) were actively smoking and 150 (57.3%) were on biologic therapy. Anastomotic failure occurred in 4 (1.5%), with 2 patients requiring reoperation (0.7%). Sixteen patients had postoperative surgical site infection (6.1%). With a median follow-up of 49.4 months, 20 patients (7.6%) were found to have surgical recurrence. In the multivariate analysis, perianal disease (OR = 2.83, p = 0.001), urgent/emergent surgery (OR = 3.23, p = 0.007), and postoperative use of steroids (OR = 2.29, p = 0.025) were associated with increased risk of overall recurrence. LIMITATIONS: Retrospective study and variability of perioperative medical therapy. CONCLUSIONS: This study showed very low postoperative complication rates despite the complexity of the patient population. There was a low rate of surgical recurrence, likely due to the intrinsic advantages of the anastomotic configuration and the low rate of postoperative septic complications. In experienced hands, the Kono-S anastomosis is a safe technique with very promising short- and long-term results. Randomized controlled trials are underway to validate this study's findings. See Video Abstract . RESULTADO A LARGO PLAZO DE LA ANASTOMOSIS KONOS UN ESTUDIO MULTICNTRICO: ANTECEDENTES:La recurrencia posoperatoria sigue siendo un problema importante en la enfermedad de Crohn y el mesenterio está implicado en la fisiopatología. La anastomosis Kono-S fue diseñada para excluir el mesenterio de una anastomosis amplia, limitar la distorsión luminal y la estasis fecal y preservar la inervación y vascularización.OBJETIVO:Revisar las complicaciones posoperatorias y los resultados a largo plazo de la anastomosis Kono-S en una gran serie de pacientes consecutivos no seleccionados con enfermedad de Crohn.DISEÑO:Estudio retrospectivo de pacientes recolectados prospectivamente.ESCENARIO:Cuatro centros de referencia terciarios.PACIENTES:Pacientes consecutivos con enfermedad de Crohn sometidos a resección con anastomosis Kono-S entre mayo de 2010 y junio de 2022.INTERVENCIONES:Anastomosis Kono-S extracorpórea manual.PRINCIPALES MEDIDAS DE RESULTADO:Resultados posoperatorios y recurrencia definidos como endoscópicos, clínicos, de laboratorio o quirúrgicos, incluida la intervención endoscópica.RESULTADOS:Se incluyeron un total de 262 pacientes consecutivos (53,4% varones). La duración media de la enfermedad al momento de la cirugía fue de 145,1 meses. Ciento treinta y cinco pacientes (51,5%) habían tenido cirugía abdominal previa por enfermedad de Crohn. Cuarenta y cuatro pacientes (17%) eran fumadores activos y 150 (57,3%) estaban en tratamiento biológico. Se produjo filtración anastomótica en 4 (1,5%) y 2 pacientes requirieron reoperación (0,7%). Dieciséis pacientes tuvieron infección postoperatoria del sitio quirúrgico (6,1%). Con una mediana de seguimiento de 49,4 meses, se encontró que 20 pacientes (7,6%) tuvieron recurrencia quirúrgica. En el análisis multivariado, la enfermedad perianal (OR = 2,83, p = 0,001), la cirugía urgente/emergente (OR = 3,23, p = 0,007), el uso postoperatorio de esteroides (OR = 2,29, p = 0,025) se asociaron con un mayor riesgo de recurrencia general.LIMITACIÓN:Estudio retrospectivo. Variabilidad del tratamiento médico perioperatorio.CONCLUSIONES:Nuestro estudio mostró tasas de complicaciones postoperatorias muy bajas a pesar de la complejidad de la población de pacientes. Hubo una baja tasa de recurrencia quirúrgica, probablemente debido a las ventajas intrínsecas de la configuración anastomótica y la baja tasa de complicaciones sépticas posoperatorias. En manos experimentadas, la anastomosis Kono-S es una técnica segura con resultados muy prometedores a corto y largo plazo. Se están realizando estudios randomizados controlados para validar nuestros hallazgos. (Traducción-Dr. Felipe Bellolio ).

Protective ileostomy creation after anterior resection of the rectum: Shared decision-making or still subjective?

AIM: The choice of whether to perform protective ileostomy (PI) after anterior resection (AR) is mainly guided by risk factors (RFs) responsible for the development of anastomotic leakage (AL). However, clear guidelines about PI creation are still lacking in the literature and this is often decided according to the surgeon's preferences, experiences or feelings. This qualitative study aims to investigate, by an open-ended question survey, the individual surgeon's decision-making process regarding PI creation after elective AR. METHOD: Fifty four colorectal surgeons took part in an electronic survey to answer the questions and describe what usually led their decision to perform PI. A content analysis was used to code the answers. To classify answers, five dichotomous categories (In favour/Against PI, Listed/Unlisted RFs, Typical/Atypical, Emotions/Non-emotions, Personal experience/No personal experience) have been developed. RESULTS: Overall, 76% of surgeons were in favour of PI creation and 88% considered listed RFs in the question of whether to perform PI. Atypical answers were reported in 10% of cases. Emotions and personal experience influenced surgeons' decision-making process in 22% and 49% of cases, respectively. The most frequently considered RFs were the distance of the anastomosis from the anal verge (96%), neoadjuvant chemoradiotherapy (88%), a positive intraoperative leak test (65%), blood loss (37%) and immunosuppression therapy (35%). CONCLUSION: The indications to perform PI following rectal cancer surgery lack standardization and evidence-based guidelines are required to inform practice. Until then, expert opinion can be helpful to assist the decision-making process in patients who have undergone AR for adenocarcinoma.

Development and Validation of an Image-based Deep Learning Algorithm for Detection of Synchronous Peritoneal Carcinomatosis in Colorectal Cancer.

OBJECTIVE: The aim of this study was to build a SVM classifier using ResNet-3D algorithm by artificial intelligence for prediction of synchronous PC. BACKGROUND: Adequate detection and staging of PC from CRC remain difficult. METHODS: The primary tumors in synchronous PC were delineated on preoperative contrast-enhanced computed tomography (CT) images. The features of adjacent peritoneum were extracted to build a ResNet3D + SVM classifier. The performance of ResNet3D + SVM classifier was evaluated in the test set and was compared to routine CT which was evaluated by radiologists. RESULTS: The training set consisted of 19,814 images from 54 patients with PC and 76 patients without PC. The test set consisted of 7837 images from 40 test patients. The ResNet-3D spent only 34 seconds to analyze the test images. To increase the accuracy of PC detection, we have built a SVM classifier by integrating ResNet-3D features with twelve PC-specific features (P < 0.05). The ResNet3D + SVM classifier showed accuracy of 94.11% with AUC of 0.922 (0.912-0.944), sensitivity of 93.75%, specificity of 94.44%, positive predictive value (PPV) of 93.75%, and negative predictive value (NPV) of 94.44% in the test set. The performance was superior to routine contrast-enhanced CT (AUC: 0.791). CONCLUSIONS: The ResNet3D + SVM classifier based on deep learning algorithm using ResNet-3D framework has shown great potential in prediction of synchronous PC in CRC.

Impact of Patient-Reported Penicillin Allergy on Antibiotic Prophylaxis and Surgical Site Infection Among Patients Undergoing Colorectal Surgery.

BACKGROUND: Surgical site infections are a major preventable source of morbidity, mortality, and increased health care expenditures after colorectal surgery. Patients with penicillin allergy may not receive the recommended preoperative antibiotics, putting them at increased risk for surgical site infections. OBJECTIVE: This study aimed to evaluate the impact of patient-reported penicillin allergy on preoperative antibiotic prophylaxis and surgical site infection rates among patients undergoing major colon and rectal procedures. DESIGN: This is a retrospective observational study. SETTING: This study was conducted at a tertiary teaching hospital in Dallas. PATIENTS: Adults undergoing colectomy or proctectomy between July 2012 and July 2019 were included. MAIN OUTCOME MEASURES: The primary outcomes measured were preoperative antibiotic choice and surgical site infection. RESULTS: Among 2198 patients included in the study, 12.26% (n = 307) reported a penicillin allergy. Patients with penicillin allergy were more likely to be white (82%) and female (54%; p < 0.01). The most common type of allergic reaction reported was rash (36.5%), whereas 7.2% of patients reported anaphylaxis. Patients with self-reported penicillin allergy were less likely to receive beta-lactam antibiotics than patients who did not report a penicillin allergy (79.8% vs 96.7%, p < 0.001). Overall, 143 (6.5%) patients had surgical site infections. On multivariable logistic regression, there was no difference in rates of surgical site infection between patients with penicillin allergy vs those without penicillin allergy (adjusted OR 1.14; 95% CI, 0.71-1.82). LIMITATIONS: A limitation of this study was its retrospective study design. CONCLUSIONS: Self-reported penicillin allergy among patients undergoing colorectal surgery is common; however, only a small number of these patients report any serious adverse reactions. Patients with self-reported penicillin allergy are less likely to receive beta-lactam antibiotics and more likely to receive non-beta-lactam antibiotics. However, this does not affect the rate of surgical site infection among these patients, and these patients can be safely prescribed non-beta-lactam antibiotics without negatively impacting surgical site infection rates. See Video Abstract at http://links.lww.com/DCR/B838 .IMPACTO DE LA ALERGIA A LA PENICILINA INFORMADA POR EL PACIENTE EN LA PROFILAXIS ANTIBIÓTICA Y LA INFECCIÓN DEL SITIO OPERATORIO ENTRE PACIENTES DE CIRUGÍA COLORECTAL. ANTECEDENTES: Las infecciones del sitio operatorio son una de las principales fuentes prevenibles de morbilidad, mortalidad y aumento del gasto sanitario después de cirugía colorrectal. Es posible que los pacientes con alergia a la penicilina no reciban los antibióticos preoperatorios recomendados, lo que los pone en mayor riesgo de infecciones en el sitio operatorio. OBJETIVO: Este estudio tuvo como objetivo evaluar el impacto de la alergia a la penicilina informada por el paciente sobre la profilaxis antibiótica preoperatoria y las tasas de infección del sitio operatorio entre pacientes sometidos a procedimientos mayores de colon y recto. DISEO: Estudio observacional retrospectivo. AJUSTE: Hospital universitario terciario en Dallas. PACIENTES: Adultos sometidos a colectomía o proctectomía entre julio de 2012 a julio de 2019. PRINCIPALES MEDIDAS DE DESENLACE: Elección de antibióticos preoperatorios e infección del sitio operatorio. RESULTADOS: Entre los 2198 pacientes incluidos en el estudio, el 12,26% (n = 307) informó alergia a la penicilina. Los pacientes con alergia a la penicilina tenían más probabilidades de ser blancos (82%) y mujeres (54%) ( p < 0,01). El tipo más común de reacción alérgica notificada fue erupción cutánea (36,5%), mientras que el 7,2% de los pacientes notificó anafilaxia. Los pacientes con alergia a la penicilina autoinformada tenían menos probabilidades de recibir antibióticos betalactámicos en comparación con los pacientes que no informaron alergia a la penicilina (79,8% frente a 96,7%, p < 0,001). En general, hubo 143 (6,5%) pacientes con infecciones del sitio operatorio. En la regresión logística multivariable no hubo diferencias en las tasas de infección del sitio operatorio entre los pacientes con alergia a la penicilina frente a los que no tenían alergia a la penicilina (razón de probabilidades ajustada 1,14; intervalo de confianza del 95%, 0,71-1,82). LIMITACIONES: Diseño de estudio retrospectivo. CONCLUSIONES: La alergia a la penicilina autoinformada entre los pacientes de cirugía colorrectal es común, sin embargo, solo un pequeño número de estos pacientes informan reacciones adversas graves. Los pacientes con alergia a la penicilina autoinformada tienen menos probabilidades de recibir antibióticos betalactámicos y más probabilidades de recibir antibióticos no betalactámicos. Sin embargo, esto no afecta la tasa de infección del sitio quirúrgico entre estos pacientes y se les puede recetar de forma segura con antibióticos no betalactámicos sin afectar negativamente las tasas de infección del sitio quirúrgico. Consulte Video Resumen en http://links.lww.com/DCR/B838 . (Traducción-Dr. Juan Carlos Reyes ).

Helena's Many Daughters: More Mitogenome Diversity behind the Most Common West Eurasian mtDNA Control Region Haplotype in an Extended Italian Population Sample.

The high number of matching haplotypes of the most common mitochondrial (mt)DNA lineages are considered to be the greatest limitation for forensic applications. This study investigates the potential to solve this constraint by massively parallel sequencing a large number of mitogenomes that share the most common West Eurasian mtDNA control region (CR) haplotype motif (263G 315.1C 16519C). We augmented a pilot study on 29 to a total of 216 Italian mitogenomes that represents the largest set of the most common CR haplotype compiled from a single country. The extended population sample confirmed and extended the huge coding region diversity behind the most common CR motif. Complete mitogenome sequencing allowed for the detection of 163 distinct haplotypes, raising the power of discrimination from 0 (CR) to 99.6% (mitogenome). The mtDNAs were clustered into 61 named clades of haplogroup H and did not reveal phylogeographic trends within Italy. Rapid individualization approaches for investigative purposes are limited to the most frequent H clades of the dataset, viz. H1, H3, and H7.

Understanding Patients' Decisions to Obtain Unplanned, High-Resource Health Care After Colorectal Surgery.

Readmissions and emergency department (ED) visits after colorectal surgery (CRS) are common, burdensome, and costly. Effective strategies to reduce these unplanned postdischarge health care visits require a nuanced understanding of how and why patients make the decision to seek care. We used a purposefully stratified sample of 18 interview participants from a prospective cohort of adult CRS patients. Thirteen (72%) participants had an unplanned postdischarge health care visit. Participant decision-making was classified by methodology (algorithmic, guided, or impulsive), preexisting rationale, and emotional response to perceived health care needs. Participants voiced clear mental algorithms about when to visit an ED. In addition, participants identified facilitators and barriers to optimal health care use. They also identified tangible targets for health care utilization reduction efforts, such as improved care coordination with streamlined discharge instructions and improved communication with the surgical team. Efforts should be directed at improving postdischarge communication and care coordination to reduce CRS patients' high-resource health care utilization.

The Landmark Series: Minimally Invasive (Laparoscopic and Robotic) Colorectal Cancer Surgery.

Current high-quality evidence supports the routine use of the laparoscopic approach for patients with colon cancer. Laparoscopic colectomy is associated with earlier resumption of gastrointestinal function and shorter hospital stay, with no increased morbidity or mortality. Pathology and long-term oncologic outcomes are similar to those achieved with open surgery. The absolute benefits of laparoscopic resection for rectal cancer are still under evaluation. While its safety in terms of early postoperative clinical outcomes has been confirmed, two recent randomized controlled trial (RCTs) have questioned its routine use even in expert hands, since its non-inferiority has not been demonstrated when compared with the gold standard of open surgery. Furthermore, the impact of robotic technology is still unclear, since the only RCT available so far failed to demonstrate any benefits compared with standard laparoscopic rectal resection.

Surgical Treatment for Crohn's Disease: A Role of Kono-S Anastomosis in the West.

More than 80% of patients with Crohn's disease (CD) will require surgical intervention during their lifetime, with high rates of anastomotic recurrence and stenosis necessitating repeat surgery. Current data show that pharmacotherapy has not significantly improved the natural history of postoperative clinical and surgical recurrence of CD. In 2003, antimesenteric hand-sewn functional end-to-end (Kono-S) anastomosis was first performed in Japan. This technique has yielded very desirable outcomes in terms of reducing the incidence of anastomotic surgical recurrence. The most recent follow-up of these patients showed that very few had developed surgical recurrence. This new approach is superior to stapled functional end-to-end anastomosis because the stumps are sutured together to create a stabilizing structure (a "supporting column"), serving as a supportive backbone of the anastomosis to help prevent distortion of the anastomotic lumen due to disease recurrence and subsequent clinical symptoms. This technique requires careful mesenteric excision for optimal preservation of the blood supply and innervation. It also results in a very wide anastomotic lumen on the antimesenteric side. The Kono-S technique has shown efficacy in preventing surgical recurrence and the potential to become the new standard of care for intestinal CD.

Disease-free Survival and Local Recurrence for Laparoscopic Resection Compared With Open Resection of Stage II to III Rectal Cancer: Follow-up Results of the ACOSOG Z6051 Randomized Controlled Trial.

OBJECTIVE: To determine the disease-free survival (DFS) and recurrence after the treatment of patients with rectal cancer with open (OPEN) or laparoscopic (LAP) resection. BACKGROUND: This randomized clinical trial (ACOSOG [Alliance] Z6051), performed between 2008 and 2013, compared LAP and OPEN resection of stage II/III rectal cancer, within 12 cm of the anal verge (T1-3, N0-2, M0) in patients who received neoadjuvant chemoradiotherapy. The rectum and mesorectum were resected using open instruments for rectal dissection (included hybrid hand-assisted laparoscopic) or with laparoscopic instruments under pneumoperitoneum. The 2-year DFS and recurrence were secondary endpoints of Z6051. METHODS: The DFS and recurrence were not powered, and are being assessed for superiority. Recurrence was determined at 3, 6, 9, 12, and every 6 months thereafter, using carcinoembryonic antigen, physical examination, computed tomography, and colonoscopy. In all, 486 patients were randomized to LAP (243) or OPEN (243), with 462 eligible for analysis (LAP = 240 and OPEN = 222). Median follow-up is 47.9 months. RESULTS: The 2-year DFS was LAP 79.5% (95% confidence interval [CI] 74.4-84.9) and OPEN 83.2% (95% CI 78.3-88.3). Local and regional recurrence was 4.6% LAP and 4.5% OPEN. Distant recurrence was 14.6% LAP and 16.7% OPEN.Disease-free survival was impacted by unsuccessful resection (hazard ratio [HR] 1.87, 95% CI 1.21-2.91): composite of incomplete specimen (HR 1.65, 95% CI 0.85-3.18); positive circumferential resection margins (HR 2.31, 95% CI 1.40-3.79); positive distal margin (HR 2.53, 95% CI 1.30-3.77). CONCLUSION: Laparoscopic assisted resection of rectal cancer was not found to be significantly different to OPEN resection of rectal cancer based on the outcomes of DFS and recurrence.

Consolidation mFOLFOX6 Chemotherapy After Chemoradiotherapy Improves Survival in Patients With Locally Advanced Rectal Cancer: Final Results of a Multicenter Phase II Trial.

BACKGROUND: Adding modified FOLFOX6 (folinic acid, fluorouracil, and oxaliplatin) after chemoradiotherapy and lengthening the chemoradiotherapy-to-surgery interval is associated with an increase in the proportion of rectal cancer patients with a pathological complete response. OBJECTIVE: The purpose of this study was to analyze disease-free and overall survival. DESIGN: This was a nonrandomized phase II trial. SETTINGS: The study was conducted at multiple institutions. PATIENTS: Four sequential study groups with stage II or III rectal cancer were included. INTERVENTION: All of the patients received 50 Gy of radiation with concurrent continuous infusion of fluorouracil for 5 weeks. Patients in each group received 0, 2, 4, or 6 cycles of modified FOLFOX6 after chemoradiation and before total mesorectal excision. Patients were recommended to receive adjuvant chemotherapy after surgery to complete a total of 8 cycles of modified FOLFOX6. MAIN OUTCOME MEASURES: The trial was powered to detect differences in pathological complete response, which was reported previously. Disease-free and overall survival are the main outcomes for the current study. RESULTS: Of 259 patients, 211 had a complete follow-up. Median follow-up was 59 months (range, 9-125 mo). The mean number of total chemotherapy cycles differed among the 4 groups (p = 0.002), because one third of patients in the group assigned to no preoperative FOLFOX did not receive any adjuvant chemotherapy. Disease-free survival was significantly associated with study group, ypTNM stage, and pathological complete response (p = 0.004, <0.001, and 0.001). A secondary analysis including only patients who received ≥1 cycle of FOLFOX still showed differences in survival between study groups (p = 0.03). LIMITATIONS: The trial was not randomized and was not powered to show differences in survival. Survival data were not available for 19% of the patients. CONCLUSIONS: Adding modified FOLFOX6 after chemoradiotherapy and before total mesorectal excision increases compliance with systemic chemotherapy and disease-free survival in patients with locally advanced rectal cancer. Neoadjuvant consolidation chemotherapy may have benefits beyond increasing pathological complete response rates. See Video Abstract at http://links.lww.com/DCR/A739.

Dynamic plasma microRNAs are biomarkers for prognosis and early detection of recurrence in colorectal cancer.

BACKGROUND: Plasma microRNAs (miRNAs) are promising non-invasive biomarkers for colorectal cancer (CRC) prognosis. However, the published studies to date have yielded conflicting and inconsistent results for specific plasma miRNAs. METHODS: We have conducted a study using robust assays to assess a panel of nine miRNAs for CRC prognosis and early detection of recurrence. Plasma samples from 144 patients in a prospective CRC cohort study were collected at diagnosis, 6, 12, and 24 months after diagnosis. miRNAs were assayed by Taqman qRT-PCR to generate miRNA normalised copy numbers. RESULTS: Preoperative high plasma miRNA levels were associated with increased recurrence risk for miR-200b (HR [95% CI]=2.04 [1.00, 4.16], P=0.05), miR-203 (HR=4.2 [1.48, 11.93], P=0.007), miR-29a (HR=2.61 [1.34,5.07], P=0.005), and miR-31 (HR=4.03 [1.76, 9.24], P=0.001). Both plasma miR-31 (AUC: 0.717) and miR-29a (AUC: 0.703) could discriminate recurrence from these patients without recurrence. In addition, high levels of miR-31 during surveillance was associated with a three-fold increased risk of recurrence across all time points. Dynamic postoperative plasma miR-141 and 16 levels correlated with recurrence in the surveillance samples. CONCLUSIONS: Pre-operative plasma miR-29a, 200b, 203, and 31 are potential CRC prognosis biomarkers. In addition, dynamic postoperative miR-31, 141 and 16 levels are potential biomarkers for the early detection of recurrence during CRC surveillance.

Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology.

This portion of the NCCN Guidelines for Colon Cancer focuses on the use of systemic therapy in metastatic disease. Considerations for treatment selection among 32 different monotherapies and combination regimens in up to 7 lines of therapy have included treatment history, extent of disease, goals of treatment, the efficacy and toxicity profiles of the regimens, KRAS/NRAS mutational status, and patient comorbidities and preferences. Location of the primary tumor, the BRAF mutation status, and tumor microsatellite stability should also be considered in treatment decisions.

Preoperative Immunonutrition and Elective Colorectal Resection Outcomes.

BACKGROUND: Randomized controlled trials demonstrate the efficacy of arginine-enriched nutritional supplements (immunonutrition) in reducing complications after surgery. The effectiveness of preoperative immunonutrition has not been evaluated in a community setting. OBJECTIVE: This study aims to determine whether immunonutrition before elective colorectal surgery improves outcomes in the community at large. DESIGN: This is a prospective cohort study with a propensity score-matched comparative effectiveness evaluation. SETTINGS: This study was conducted in Washington State hospitals in the Surgical Care Outcomes Assessment Program from 2012 to 2015. PATIENTS: Adults undergoing elective colorectal surgery were selected. INTERVENTIONS: Surgeons used a preoperative checklist that recommended that patients take oral immunonutrition (237 mL, 3 times daily) for 5 days before elective colorectal resection. MAIN OUTCOME MEASURES: Serious adverse events (infection, anastomotic leak, reoperation, and death) and prolonged length of stay were the primary outcomes measured. RESULTS: Three thousand three hundred seventy-five patients (mean age 59.9 ± 15.2 years, 56% female) underwent elective colorectal surgery. Patients receiving immunonutrition more commonly were in a higher ASA class (III-V, 44% vs 38%; p = 0.01) or required an ostomy (18% vs 14%; p = 0.02). The rate of serious adverse events was 6.8% vs 8.3% (p = 0.25) and the rate of prolonged length of stay was 13.8% vs 17.3% (p = 0.04) in those who did and did not receive immunonutrition. After propensity score matching, covariates were similar among 960 patients. Although differences in serious adverse events were nonsignificant (relative risk, 0.76; 95% CI, 0.49-1.16), prolonged length of stay (relative risk, 0.77; 95% CI, 0.58-1.01 p = 0.05) was lower in those receiving immunonutrition. LIMITATIONS: Patient compliance with the intervention was not measured. Residual confounding, including surgeon-level heterogeneity, may influence estimates of the effect of immunonutrition. CONCLUSIONS: Reductions in prolonged length of stay, likely related to fewer complications, support the use of immunonutrition in quality improvement initiatives related to elective colorectal surgery. This population-based study supports previous trials of immunonutrition, but shows a lower magnitude of benefit, perhaps related to compliance or a lower rate of adverse events, highlighting the value of community-based assessments of comparative effectiveness.

Initiation of universal tumor screening for Lynch syndrome in colorectal cancer patients as a model for the implementation of genetic information into clinical oncology practice.

BACKGROUND: Lynch syndrome confers a hereditary predisposition to colorectal and other cancers. Universal tumor screening (UTS) for Lynch syndrome is recommended by several professional societies, but the implementation can be complex. This article describes the evaluation, process development, and initiation of Lynch syndrome UTS at a tertiary referral cancer center. METHODS: A multidisciplinary team developed the new process design. Issues in 5 themes were noted: timing, funding, second-opinion patients, result processing, and the role of genetics providers. A committee approach was used to examine each issue for process-improvement development. RESULTS: The issues related to testing were addressed individually for the successful implementation of UTS at the institutional level. In the conventional-care period, 9 of 30 cases (30%) received Lynch syndrome screening, and 4 cases were referred to medical genetics. During the 6 months following the implementation of UTS, 32 of 44 patients (73%) received Lynch syndrome screening. The 13 unscreened patients all had identified reasons for nonscreening (eg, financial limitations). Ten patients were referred to medical genetics, which identified no new cases of Lynch syndrome, but a low-risk adenomatous polyposis coli (APC) variant was detected in 1 individual. CONCLUSIONS: The implementation of effective Lynch syndrome UTS can feasibly alter practice at the institutional level. This experience with the assessment and management of issues relevant to the successful implementation of a new clinical care paradigm based on emerging technology has implications for the uptake of advances across molecular oncology into clinical practice, and this is highly relevant in the current era of rapidly evolving genomic technology.

The Impact of Elective Colon Resection on Rates of Emergency Surgery for Diverticulitis.

OBJECTIVE: To determine the impact of elective colectomy on emergency diverticulitis surgery at the population level. BACKGROUND: Current recommendations suggest avoiding elective colon resection for uncomplicated diverticulitis because of uncertain effectiveness at reducing recurrence and emergency surgery. The influence of these recommendations on use of elective colectomy or rates of emergency surgery remains undetermined. METHODS: A retrospective cohort study using a statewide hospital discharge database identified all patients admitted for diverticulitis in Washington State (1987-2012). Sex- and age-adjusted rates (standardized to the 2000 state census) of admissions, elective and emergency/urgent surgical and percutaneous interventions for diverticulitis were calculated and temporal changes assessed. RESULTS: A total of 84,313 patients (mean age 63.3 years and 58.9% female) were hospitalized for diverticulitis (72.2% emergent/urgent). Elective colectomy increased from 7.9 to 17.2 per 100,000 people (P < 0.001), rising fastest since 2000. Emergency/urgent colectomy increased from 7.1 to 10.2 per 100,000 (P < 0.001), nonelective percutaneous interventions increased from 0.1 to 3.7 per 100,000 (P = 0.04) and the frequency of emergency/urgent admissions (with or without a resection) increased from 34.0 to 85.0 per 100,000 (P < 0.001). In 2012, 47.5% of elective resections were performed laparoscopically compared to 17.5% in 2008 (when the code was introduced). CONCLUSIONS: The elective colectomy rate for diverticulitis more than doubled, without a decrease in emergency surgery, percutaneous interventions, or admissions for diverticulitis. This may reflect changes in thresholds for elective surgery and/or an increase in the frequency or severity of the disease. These trends do not support the practice of elective colectomy to prevent emergency surgery.

Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial.

BACKGROUND: Patients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiation have an improved prognosis. The need for surgery in these patients has been questioned, but the proportion of patients achieving a pathological complete response is small. We aimed to assess whether adding cycles of mFOLFOX6 between chemoradiation and surgery increased the proportion of patients achieving a pathological complete response. METHODS: We did a phase 2, non-randomised trial consisting of four sequential study groups of patients with stage II-III locally advanced rectal cancer at 17 institutions in the USA and Canada. All patients received chemoradiation (fluorouracil 225 mg/m(2) per day by continuous infusion throughout radiotherapy, and 45·0 Gy in 25 fractions, 5 days per week for 5 weeks, followed by a minimum boost of 5·4 Gy). Patients in group 1 had total mesorectal excision 6-8 weeks after chemoradiation. Patients in groups 2-4 received two, four, or six cycles of mFOLFOX6, respectively, between chemoradiation and total mesorectal excision. Each cycle of mFOLFOX6 consisted of racemic leucovorin 200 mg/m(2) or 400 mg/m(2), according to the discretion of the treating investigator, oxaliplatin 85 mg/m(2) in a 2-h infusion, bolus fluorouracil 400 mg/m(2) on day 1, and a 46-h infusion of fluorouracil 2400 mg/m(2). The primary endpoint was the proportion of patients who achieved a pathological complete response, analysed by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00335816. FINDINGS: Between March 24, 2004, and Nov 16, 2012, 292 patients were registered, 259 of whom (60 in group 1, 67 in group 2, 67 in group 3, and 65 in group 4) met criteria for analysis. 11 (18%, 95% CI 10-30) of 60 patients in group 1, 17 (25%, 16-37) of 67 in group 2, 20 (30%, 19-42) of 67 in group 3, and 25 (38%, 27-51) of 65 in group 4 achieved a pathological complete response (p=0·0036). Study group was independently associated with pathological complete response (group 4 compared with group 1 odds ratio 3·49, 95% CI 1·39-8·75; p=0·011). In group 2, two (3%) of 67 patients had grade 3 adverse events associated with the neoadjuvant administration of mFOLFOX6 and one (1%) had a grade 4 adverse event; in group 3, 12 (18%) of 67 patients had grade 3 adverse events; in group 4, 18 (28%) of 65 patients had grade 3 adverse events and five (8%) had grade 4 adverse events. The most common grade 3 or higher adverse events associated with the neoadjuvant administration of mFOLFOX6 across groups 2-4 were neutropenia (five in group 3 and six in group 4) and lymphopenia (three in group 3 and four in group 4). Across all study groups, 25 grade 3 or worse surgery-related complications occurred (ten in group 1, five in group 2, three in group 3, and seven in group 4); the most common were pelvic abscesses (seven patients) and anastomotic leaks (seven patients). INTERPRETATION: Delivery of mFOLFOX6 after chemoradiation and before total mesorectal excision has the potential to increase the proportion of patients eligible for less invasive treatment strategies; this strategy is being tested in phase 3 clinical trials. FUNDING: National Institutes of Health National Cancer Institute.