Refining colorectal cancer classification and clinical stratification through a single-cell atlas.

BACKGROUND: Colorectal cancer (CRC) consensus molecular subtypes (CMS) have different immunological, stromal cell, and clinicopathological characteristics. Single-cell characterization of CMS subtype tumor microenvironments is required to elucidate mechanisms of tumor and stroma cell contributions to pathogenesis which may advance subtype-specific therapeutic development. We interrogate racially diverse human CRC samples and analyze multiple independent external cohorts for a total of 487,829 single cells enabling high-resolution depiction of the cellular diversity and heterogeneity within the tumor and microenvironmental cells. RESULTS: Tumor cells recapitulate individual CMS subgroups yet exhibit significant intratumoral CMS heterogeneity. Both CMS1 microsatellite instability (MSI-H) CRCs and microsatellite stable (MSS) CRC demonstrate similar pathway activations at the tumor epithelial level. However, CD8+ cytotoxic T cell phenotype infiltration in MSI-H CRCs may explain why these tumors respond to immune checkpoint inhibitors. Cellular transcriptomic profiles in CRC exist in a tumor immune stromal continuum in contrast to discrete subtypes proposed by studies utilizing bulk transcriptomics. We note a dichotomy in tumor microenvironments across CMS subgroups exists by which patients with high cancer-associated fibroblasts (CAFs) and C1Q+TAM content exhibit poor outcomes, providing a higher level of personalization and precision than would distinct subtypes. Additionally, we discover CAF subtypes known to be associated with immunotherapy resistance. CONCLUSIONS: Distinct CAFs and C1Q+ TAMs are sufficient to explain CMS predictive ability and a simpler signature based on these cellular phenotypes could stratify CRC patient prognosis with greater precision. Therapeutically targeting specific CAF subtypes and C1Q + TAMs may promote immunotherapy responses in CRC patients.

A New Bibliometric Index: The Top 100 Most Disruptive and Developmental Publications in Colorectal Surgery Journals.

BACKGROUND: A new bibliometric index called the disruption score was recently proposed to identify innovative and paradigm-changing publications. OBJECTIVE: The goal was to apply the disruption score to the colorectal surgery literature to provide the community with a repository of important research articles. DESIGN: This study is a bibliometric analysis. SETTINGS: The 100 most disruptive and developmental publications in Diseases of the Colon & Rectum, Colorectal Disease, International Journal of Colorectal Disease, and Techniques in Coloproctology were identified from a validated data set of disruption scores and linked with the iCite National Institutes of Health tool to obtain citation counts. MAIN OUTCOME MEASURES: The primary outcomes measured were the disruption score and citation count. RESULTS: We identified 12,127 articles published in Diseases of the Colon & Rectum (n = 8109), International Journal of Colorectal Disease (n = 1912), Colorectal Disease (n = 1751), and Techniques in Coloproctology (n = 355) between 1954 and 2014. Diseases of the Colon & Rectum had the most articles in the top 100 most disruptive and developmental lists. The disruptive articles were in the top 1% of the disruption score distribution in PubMed and were cited between 1 and 671 times. Being highly cited was weakly correlated with high disruption scores (r = 0.09). Developmental articles had disruption scores that were more strongly correlated with citation count (r = 0.18). LIMITATIONS: This study is subject to the limitations of bibliometric indices, which change over time. DISCUSSION: The disruption score identified insightful and paradigm-changing studies in colorectal surgery. These studies include a wide range of topics and consistently identified editorials and case reports/case series as important research. This bibliometric analysis provides colorectal surgeons with a unique archive of research that can often be overlooked but that may have scholarly significance. See Video Abstract at http://links.lww.com/DCR/B639.UN NUEVO INDICE BIBLIOMÉTRICO: LAS 100 MAS IMPORTANTES PUBLICACIONES EN INNOVACIONES DESESTABILIZADORAS Y DE DESARROLLO EN LAS REVISTAS DE CIRUGÍA COLORRECTALANTECEDENTES:Un nuevo índice bibliométrico llamado innovación desestabilizadora y de desarrollo ha sido propuesto para identificar publicaciones de vanguardia y que pueden romper paradigmas.OBJETIVO:La meta fué aplicar el índice de desestabilización a la literature en cirugía colorectal para aportar a la comunidad con un acervo importante de artículos de investigación.DISEÑO:Un análisis bibliométrico.PARAMETROS:Las 100 publicaciones mas desestabilizadores y de desarrollo en las revistas: Diseases of the Colon and Rectum, Colorectal Disease, International Journal of Colorectal Disease, y Techniques in Coloproctology se recuperaron de una base de datos validada con puntuaciones de desestabilización y se ligaron con la herramienta iCite NIH para obtener la cuantificación de citas.PRINCIPAL MEDIDA DE RESULTADO:El índice desestabilizador y la cuantificación de citas.RESULTADOS:Se identificaron 12,127 articulos publicados en Diseases of the Colon and Rectum (n = 8,109), International Journal of Colorectal Disease (n = 1,912), Colorectal Disease (n = 1,751), y Techniques in Coloproctology (n = 355) de 1954-2014. Diseases of the Colon and Rectum representó la mayoría de las publicaciones dentro de la lista de los 100 mas desestabilizadores y de desarrollo. Esta literatura desestabilizadora se encuentra en el principal 1% de la distribución de la puntuacón desestabilizadora en PubMed y se citaron de 1 a 671 veces. El ser citado con frecuencia se relacionó vagamente con las puntuaciones de desastibilización (r = 0.09). Los artículos de desarrollo tuvieron puntuaciones de desestabilización que estuvieron muy correlacionados con la cuantificación de las citas (r = 0.18).LIMITACIONES:Las sujetas a las limitaciones de los índices bibliométricos, que se modifican en el tiempo.DISCUSION:La putuación de desestabilicación identificó trabajos perspicaces, pragmáticos y modificadores de paradigmas en cirugía colorrectal. Es de interés identificar que se incluyeron una gran variedad de temas y en forma consistente editoriales, reportes de casos y series de casos que representaron una investigación importante. Este análisis bibliométrico aporta a los cirujanos colorrectales de un acervo de investigación único que puede con frecuencia pasarse por alto, y sin embargo tener una gran importancia académica. Consulte Video Resumen en http://links.lww.com/DCR/B639. (Traducción- Dr. Miguel Esquivel-Herrera).

Blend mode reduces unintended thermal injury by laparoscopic monopolar instruments: a randomized controlled trial.

BACKGROUND: The purpose of this study was to compare histologic evidence of thermal injury at the epigastric and umbilical incisions after elective laparoscopic cholecystectomy performed using the monopolar "Bovie" instrument set on the higher voltage coag mode versus the lower voltage blend mode. We hypothesized that the higher voltage coag mode would create more unintended thermal tissue injury at the epigastric trocar's incision. METHODS: A prospective blinded randomized controlled trial of patients undergoing elective laparoscopic cholecystectomy was performed. Patients were randomized to have their operation performed with the monopolar instrument set at 30 W on either the coag mode or the blend mode. Immediately at the end of the operation, a biopsy sample of skin was obtained from the lower edge of the epigastric incision (through which the monopolar instrument was inserted) and the umbilical incision (through which the camera/telescope was inserted). The outcomes measured were histologic evidence of thermal injury at the epigastric and umbilical incisions (determined by a blinded pathologist). RESULTS: Forty patients were randomized (20 per group). Baseline demographics in the two groups were similar for age, gender, body mass index, preoperative diagnosis, operative time, and blood loss. Unintentional thermal injury was found at 20 % of epigastric incisions and 35 % of umbilical incisions in the total group. The incidence of thermal injury was higher after operations using the coag mode compared to the blend mode at both the epigastric (35 vs. 5 %; p = 0.044) and umbilical (55 vs. 15 %; p = 0.019) trocar incisions. CONCLUSIONS: Radiofrequency energy from the monopolar Bovie instrument causes unintentional thermal injury to skin adjacent to the epigastric and umbilical trocar incisions. The incidence of thermal injury was reduced by using the lower voltage blend mode compared to the coag mode at both the epigastric and umbilical trocar incisions. REGISTRATION NUMBER: NCT016648060 ( www.clinicaltrials.gov ).

Antenna coupling--a novel mechanism of radiofrequency electrosurgery complication: practical implications.

OBJECTIVES: (1) To determine if antenna coupling occurs in common operating room scenarios. (2) To define modifiable clinical variables that reduce the magnitude of antenna coupling. BACKGROUND: Mechanisms of electrosurgical burns where monitoring devices contact the surgical patient are unclear. Antenna coupling occurs when the "bovie" active electrode (electrically active transmitting antenna) emits energy, which is captured by a nonelectrically active wire (electrically inactive receiving antenna) in close proximity without direct contact. METHODS: Monopolar radiofrequency energy was delivered to a laparoscopic instrument (electrically active transmitting antenna), whereas other nonelectrically active wires (electrically inactive receiving antenna) including electrocardiogram (EKG) lead, nonactive "bovie" pencil, and nerve electrode monitor were placed in proximity. Temperature changes of tissue placed adjacent to the electrically inactive receiving antennae were measured. RESULTS: Nonelectrically active wires (receiving antenna) increase tissue temperature when lying parallel to the active electrode cord: EKG pad 2.4°C ± 1.2°C (P = 0.002), "bovie" pencil tip 90°C ± 9°C (P < 0.001), and nerve electrode monitor 106°C ± 12°C (P < 0.001). Factors that reduced the heat generated by antenna coupling included the following: increasing angulation between transmitting and receiving antennae (parallel = 90°C ± 9°C; 45° angle = 53°C ± 10°C; perpendicular = 35°C ± 11°C; P < .001), increasing separation distance between parallel transmitting and receiving antenna (<1 cm = 90°C ± 9°C; 15 cm = 44°C ± 18°C; 30 cm = 39°C ± 2°C; P < .001); and decreasing generator power setting (15 W = 59°C ± 11°C; 30 W = 90°C ± 9°C; 45 W = 98°C ± 8°C; P < .001). CONCLUSIONS: Antenna coupling occurs in common operating room scenarios. Simple, practical measures by the surgeon, such as orienting the receiving antenna at a greater angle and with greater separation to the active electrode cord, or lowering the generator power setting reduce antenna coupling.

Radiofrequency energy antenna coupling to common laparoscopic instruments: practical implications.

BACKGROUND: Electromagnetic coupling can occur between the monopolar "Bovie" instrument and other laparoscopic instruments without direct contact by a phenomenon termed antenna coupling. The purpose of this study was to determine if, and to what extent, radiofrequency energy couples to other common laparoscopic instruments and to describe practical steps that can minimize the magnitude of antenna coupling. METHODS: In a laparoscopic simulator, monopolar radiofrequency energy was delivered to an L-hook. The tips of standard, nonelectrical laparoscopic instruments (either an unlit 10 mm telescope or a 5 mm grasper) were placed adjacent to bovine liver tissue and were never in contact with the active electrode. Thermal imaging quantified the change in tissue temperature nearest the tip of the telescope or grasper at the end of a 5 s activation of the active electrode. RESULTS: A 5 s activation (30 watts, coagulation mode, 4 cm separation between instruments) increased tissue temperature compared with baseline adjacent to the grasper tip (2.2 ± 2.2 °C; p = 0.013) and telescope tip (38.2 ± 8.0 °C; p < 0.001). The laparoscopic telescope tip increased tissue temperature more than the laparoscopic grasper tip (p < 0.001). Lowering the generator power from 30 to 15 Watts decreased the heat generated at the telescope tip (38.2 ± 8.0 vs. 13.5 ± 7.5 °C; p < 0.001). Complete separation of the camera/light cords and the active electrode cord decreased the heat generated near the telescope tip compared with parallel bundling of the cords (38.2 ± 8.0 vs. 15.7 ± 11.6 °C; p < 0.001). CONCLUSIONS: Commonly used laparoscopic instruments couple monopolar radiofrequency energy without direct contact with the active electrode, a phenomenon that results in heat transfer from a nonelectrically active instrument tip to adjacent tissue. Practical steps to minimize heat transfer resulting from antenna coupling include reducing the monopolar generator power setting and avoiding of parallel bundling of the telescope and active electrode cords.

Effect of monopolar radiofrequency energy on pacemaker function.

BACKGROUND: This study aimed to quantify the clinical parameters of mono- and bipolar instruments that inhibit pacemaker function. The specific aims were to quantify pacer inhibition resulting from the monopolar instrument by altering the generator power setting, the generator mode, the distance between the active electrode and the pacemaker, and the location of the dispersive electrode. METHODS: A transvenous ventricular lead pacemaker overdrive paced the native heart rate of an anesthetized pig. The primary outcome variable was pacer inhibition quantified as the number of beats dropped by the pacemaker during 5 s of monopolar active electrode activation. RESULTS: Lowering the generator power setting from 60 to 30 W decreased the number of dropped paced events (2.3 ± 1.2 vs 1.6 ± 0.8 beats; p = 0.045). At 30 W of power, use of the cut mode decreased the number of dropped paced beats compared with the coagulation mode (0.6 ± 0.5 vs 1.6 ± 0.8; p = 0.015). At 30 W coagulation, firing the active electrode at different distances from the pacemaker generator (3.75, 7.5, 15, and 30 cm) did not change the number of dropped paced beats (p = 0.314, analysis of variance [ANOVA]). The dispersive electrode was placed in four locations (right/left gluteus, right/left shoulder). More paced beats were dropped when the current vector traveled through the pacemaker/leads than when it did not (1.5 ± 1.0 vs 0.2 ± 0.4; p < 0.001). CONCLUSIONS: Clinical parameters that reduce the inhibition of a pacemaker by monopolar instruments include lowering the generator power setting, using cut (vs coagulation) mode, and locating the dispersive electrode so the current vector does not traverse the pacemaker generator or leads.

Residual heat of laparoscopic energy devices: how long must the surgeon wait to touch additional tissue?

BACKGROUND: Energy devices are essential laparoscopic tools. Residual heat is defined as the increased instrument temperature after energy activation is completed. This study aimed to determine the length of time a surgeon needs to wait before touching other tissue using four common laparoscopic energy sources. METHODS: Thermal imaging quantified instrument and tissue temperature ex vivo using monopolar coagulation, argon beam coagulation, ultrasonic dissection, and bipolar tissue fusion devices. To simulate realistic operative usage, each instrument was activated for 5 s four consecutive times with 5 s pauses between fires. Thermal conductivity to bovine liver tissue was measured 2.5, 5, 10, and 20 s after final activation. RESULTS: The maximum increase in instrument tip temperature was 172 ± 63°C for the ultrasonic dissection, 81 ± 18°C for the monopolar coagulation, 46 ± 19°C for the bipolar tissue fusion, and 1 ± 1°C for the argon beam coagulation (P < 0.05 for all comparisons). Touching the instrument tip to tissue at four intervals after the final activation (2.5, 5, 10, and 20 s) found that ultrasonic energy raised the tissue temperature higher (maximum change, 58°C) than the other three energy devices at all four time points (P < 0.05). CONCLUSIONS: Ultrasonic energy instruments have greater residual heat than monopolar electrosurgery, bipolar tissue fusion, and argon beam. The ultrasonic energy instrument tips heated tissue more than 20°C from baseline even 20 s after activation; whereas all the other energy sources raised the tissue temperature less than 20°C by 5 s. These practical findings may alter a surgeon's usage of these common energy devices.