Dozois, Eric J.

Abstract Background:Presacral tumors are a rare entity typically treated with an open surgical approach. A limited number of minimally invasive resections have been described. Aim of the study was to evaluate the safety and efficacy of robotic resection of presacral tumors. Methods: This was a retrospective single system analysis, conducted at a quaternary referral academic healthcare system, and included all patients who underwent a robotic excision of a presacral tumor between 2015 and 2023. Outcomes of interest were operative time, estimated blood loss, complications, length of stay, margin status, and recurrence rates. Results: Sixteen patients (11 females, 5 males) were included. Median age of the cohort was 51 years (range 25-69). Median operative time was 197 minutes (range 98-802). Median estimated blood loss was 40 ml, ranging from 0 to 1800 ml, with one patient experiencing conversion to open surgery after uncontrolled hemorrhage. Urinary retention was the only post-operative complication that occurred in 3 patients (19%) and was solved within 30 days in all cases. Median length of stay was one day (range 1-6). Median follow-up was 6.7 months (range 1-110). All tumors were excised with appropriate margins, but one benign and one malignant tumor recurred (12.5%). Ten tumors were classified as congenital (one was malignant), two were mesenchymal (both malignant), and five were miscellaneous (one malignant). Conclusions:Robotic resection of select presacral pathology is feasible and safe. Further studies must be conducted to determine complication rates, outcomes, and long-term safety profiles.

BACKGROUND: Using standard anterior approaches, consistent R0 resection of locally advanced primary and recurrent rectal and anal cancer involving the deep pelvic sidewall may be unattainable. Therefore, to improve R0 resection rates, we have used a posterior-first, then anterior 2-stage approach to resection of tumors in this location. OBJECTIVE: To assess the R0 resection rate and surgical outcomes of the first 10 patients operated on using this approach. DESIGN: We conducted a retrospective case series review of our prospectively maintained surgical pathology and tumor registries. SETTING: This study was conducted at the Mayo Clinic in Rochester, Minnesota. PATIENTS: Ten patients (6 female individuals, median age 53.5 years) with primary or recurrent anal or rectal cancer treated with a posterior-first, then anterior 2-stage approach were identified. MAIN OUTCOME MEASURES: The primary outcome measures were the R0 resection rate and surgical outcomes. RESULTS: An R0 resection was achieved in all 10 patients. Nine patients developed 1 or more 30-day Clavien-Dindo grade III complications. Nine patients developed gluteal wound complications ranging from superficial wound dehiscence to flap necrosis. During the follow-up period, 4 patients were found to have metastatic disease and 1 patient had local re-recurrence. LIMITATIONS: Small cohort with heterogeneous tumors and a short follow-up duration. CONCLUSION: A posterior-first, then anterior 2-stage approach has allowed us to achieve consistent R0 resection margins in locally advanced primary and recurrent rectal and anal cancers involving the deep pelvic sidewall. Poor wound healing of the posterior gluteal incision is a common complication. See Video Abstract. MEJORANDO LAS TASAS DE RESECCIÓN R0 CON UN ABORDAJE DE DOS ETAPAS PRIMERO POSTERIOR PARA LA RESECCIÓN EN BLOQUE DE CÁNCERES ANORRECTALES PRIMARIOS Y RECURRENTES LOCALMENTE AVANZADOS QUE AFECTAN LA PARED LATERAL PÉLVICA PROFUNDA ANTECEDENTES: Utilizando abordajes anteriores estándares, la resección R0 consistente del cáncer de recto y ano primario y recurrente localmente avanzado involucrando la pared lateral pélvica profunda puede ser inalcanzable. Por lo tanto, para mejorar las tasas de resección R0, hemos empleado un abordaje de 2 etapas primero posterior y luego anterior para la resección de tumores en esta ubicación. OBJETIVO: Este estudio tuvo como objetivo evaluar la tasa de resección R0 y los resultados quirúrgicos de los primeros 10 pacientes operados con este abordaje. DISEÑO: Realizamos una revisión retrospectiva de series de casos de nuestros registros de patología quirúrgica y tumores mantenidos prospectivamente. AJUSTE: Este estudio se realizó en la Clínica Mayo en Rochester, Minnesota, EE. UU. PACIENTES: Se identificaron diez pacientes (6 mujeres, mediana de edad 53.5 años) con cáncer anal o rectal primario o recurrente tratados con un abordaje de dos etapas, primero posterior y luego anterior. PRINCIPALES MEDIDAS DE RESULTADO: Las medidas de resultado primarias fueron la tasa de resección R0 y los resultados quirúrgicos. RESULTADOS: Se logró una resección R0 en los 10 pacientes. Nueve pacientes desarrollaron una o más complicaciones de grado III de Clavien-Dindo a los 30 días. Nueve pacientes desarrollaron complicaciones de la herida del glúteo que variaron desde dehiscencia superficial de la herida hasta necrosis del colgajo. Durante el período de seguimiento, se encontró que 4 pacientes tenían enfermedad metastásica y un paciente tuvo recurrencia local. LIMITACIONES: Cohorte pequeño con tumores heterogéneos y corta duración de seguimiento. CONCLUSIÓN: Un abordaje en 2 etapas, primero posterior y luego anterior, nos ha permitido lograr márgenes de resección R0 consistentes en cánceres de recto y anal primarios y recurrentes localmente avanzados que afectan la pared lateral pélvica profunda. La mala cicatrización de la incisión glútea posterior es una complicación común. (Traducción—Dr. Aurian Garcia Gonzalez)

Background SCN5A ‐encoded Na V 1.5 is a mechanosensitive voltage‐gated sodium channel expressed in human gastrointestinal smooth muscle cells. In the gastrointestinal tract, alterations in Na V 1.5 current density by naturally occurring mutations or by pharmaceutical block of channel function are associated with constipation. In the heart loss of Na V 1.5 current is associated with cardiac contractility disorders such as dilated cardiomyopathy. Ion channel expression level is regulated by miRNAs, and Na V 1.5 is known to be regulated by miRNA in heart. However , it is not known if miRNAs regulate Na V 1.5 expression in GI smooth muscle. Aim To identify miRNAs that regulate Na V 1.5 expression in gastrointestinal smooth muscle in health and disease. Methods A qPCR array was used to screen for differential expression of 372 of the most common miRNAs in the miRBase database to test the differential expression of miRNA between control tissue and tissues from patients with slow transit constipation. qRT‐PCR was done to determine expression levels of SCN5A mRNA. A cell line (HuJej) was derived from human jejunum smooth muscle cells by immortalization using the SV40 large T antigen. Whole cell voltage clamp experiments were done by standard patch clamp techniques. Results SCN5A mRNA expression was reduced by 66±0.08% in patients with slow transit constipation (57.5±1.8 years) compared to age matched controls (53±1.7 years). qPCR array screening showed that 12 miRNAs were significantly upregulated in colonic muscularis externa from patients with STC compared to controls. Let‐7f miRNA was increased 6.46‐fold in slow transit constipation compared to controls and was the only miRNA with strong negative correlation to SCN5A mRNA expression in the same tissues. HuJej cells express Na V 1.5; therefore, we investigated the effect of let‐7f on Na V 1.5 currents by transfection with a stable miRNA mimic. 48 hours after transfection with let‐7f mimic, Na V 1.5 currents were significantly decreased compared to untransfected cells or to cells transfected with non‐targeting miRNA (let‐7f, −0.6±0.1 pA/pF versus untransfected, −3.9±0.6 pA/pF or non‐targeting, −2.3±0.6 pA/pF). Summary and Conclusions SCN5A mRNA is decreased in slow transit constipation. Expression levels of let‐7f and Na V 1.5 RNA are negatively correlated in human colonic smooth muscle. miRNA let‐7f regulates Na V 1.5 current density. Regulation of Na V 1.5 current density may have relevance in health and disease. Support or Funding Information This work was supported by grant DK52766.

No standard treatment paradigm exists for previously irradiated locally recurrent rectal cancer (PILRRC). Carbon-ion radiotherapy (CIRT) may improve oncologic outcomes and reduce toxicity compared with combined modality therapy (CMT). Eighty-five patients treated at Institution A with CIRT alone (70.4 Gy/16 fx) and eighty-six at Institution B with CMT (30 Gy/15 fx chemoradiation, resection, intraoperative electron radiotherapy (IOERT)) between 2006 and 2019 were retrospectively compared. Overall survival (OS), pelvic re-recurrence (PR), distant metastasis (DM), or any disease progression (DP) were analyzed with the Kaplan–Meier model, with outcomes compared using the Cox proportional hazards model. Acute and late toxicities were compared, as was the 2-year cost. The median time to follow-up or death was 6.5 years. Median OS in the CIRT and CMT cohorts were 4.5 and 2.6 years, respectively (p ≤ 0.01). No difference was seen in the cumulative incidence of PR (p = 0.17), DM (p = 0.39), or DP (p = 0.19). Lower acute grade ≥ 2 skin and GI/GU toxicity and lower late grade ≥ 2 GU toxicities were associated with CIRT. Higher 2-year cumulative costs were associated with CMT. Oncologic outcomes were similar for patients treated with CIRT or CMT, although patient morbidity and cost were lower with CIRT, and CIRT was associated with longer OS. Prospective comparative studies are needed.

BACKGROUND: Refractory perianal Crohn’s disease remains notoriously difficult to treat. We developed a novel technology using a commercially available bioabsorbable fistula plug to deliver autologous adipose-derived mesenchymal stem cells. OBJECTIVE: This study aimed to assess therapeutic safety and feasibility in the completed STOMP (stem cells on matrix plugs) phase 1 clinical trial. DESIGN: Prospective single-arm phase I clinical trial. SETTING: Tertiary academic medical center. PATIENTS: Adults (aged 18–65 y) with complex single-tract Crohn’s disease perianal fistula who have failed conventional therapy were included in this study. INTERVENTION: Autologous adipose-derived mesenchymal stem cells were isolated, ex vivo culture expanded, and seeded onto a commercially available bioabsorbable fistula plug. Six weeks later, patients returned to the operating room for removal of the seton and placement of the stem cell-loaded plug. MAIN OUTCOME MEASURES: Patients were followed up for a total of 8 visits through 12 months. Safety was the primary end point; clinical healing and MRI response were secondary end points. RESULTS: Twenty patients (12 females; mean age 36 y) were treated with the stem cell–loaded plug. Of the 20 patients enrolled, 3 were not included in the 12-month analysis because of study withdrawal. Through 12 months, no patient experienced a serious adverse event related to the stem cell–loaded plug. Four patients experienced 7 serious adverse events and 12 patients experienced 22 adverse events. Complete clinical healing occurred in 14 of 18 patients at 6 months and 13 of 17 patients at 12 months. MRI response was observed in 12 of 18 patients at 6 months. LIMITATIONS: The main limitations were the small sample size and restrictive inclusion criteria. CONCLUSIONS: A stem cell–loaded plug can safely and effectively deliver cell-based therapy for patients with single-tract fistulizing perianal Crohn’s disease. See Video Abstract at http://links.lww.com/DCR/C70. RESPUESTA DURADERA OBSERVADA EN PACIENTES CON ENFERMEDAD DE CROHN PERIANAL FISTULIZANTE REFRACTARIA MEDIANTE EL USO DE CÉLULAS MADRE MESENQUIMALES AUTÓLOGAS EN UNA MATRIZ DISOLUBLE: RESULTADOS DEL ENSAYO DE FASE I STEM CELL ON MATRIX PLUG ANTECEDENTES: La enfermedad de Crohn perianal refractaria sigue siendo notoriamente difícil de tratar. Desarrollamos una tecnología novedosa utilizando un tapón de fístula bioabsorbible disponible comercialmente para administrar células madre mesenquimales derivadas de tejido adiposo autólogo. OBJETIVO: Evaluar la seguridad y viabilidad terapéutica en el ensayo finalizado STOMP. DISEÑO: Ensayo clínico prospectivo de fase I de un solo brazo. AJUSTE: Centro médico académico terciario. PACIENTES: Adultos (18-65) con fístula perianal compleja de la enfermedad de Crohn de un solo tracto que han fracasado con la terapia convencional. INTERVENCIÓN: Se aislaron células madre mesenquimales derivadas de tejido adiposo autólogo, se expandieron en cultivo ex vivo y se sembraron en un tapón de fístula bioabsorbible disponible comercialmente. Seis semanas después, los pacientes regresaron al quirófano para retirar el setón y colocar el tapón cargado de células madre. PRINCIPALES MEDIDAS DE RESULTADO: Los pacientes fueron seguidos durante un total de 8 visitas durante 12 meses. La seguridad fue el criterio principal de valoración; la curación clínica y la respuesta a la resonancia magnética fueron criterios de valoración secundarios. RESULTADOS: Veinte pacientes (12 mujeres, edad media 36 años) fueron tratados con el tapón cargado de células madre. De los 20 pacientes inscritos, tres no se incluyeron en el análisis de 12 meses porque se retiraron del estudio. A lo largo de 12 meses, ningún paciente experimentó un evento adverso grave relacionado con el tapón cargado de células madre. Cuatro pacientes experimentaron 7 eventos adversos graves y 12 pacientes experimentaron 22 eventos adversos. La curación clínica completa ocurrió en 14 de 18 pacientes a los 6 meses y en 13 de 17 pacientes a los 12 meses. La respuesta a la resonancia magnética se observó en 12 de 18 pacientes a los 6 meses. LIMITACIONES: Las principales limitaciones son el tamaño pequeño de la muestra y los criterios de inclusión restrictivos. CONCLUSIONES: Un tapón cargado de células madre se puede administrar de manera segura y efectiva, una terapia basada en células para pacientes con enfermedad de Crohn perianal fistulizante de un solo tracto. Consule Video Resumen en http://links.lww.com/DCR/C70. (Traducción— Dr. Yesenia Rojas-Khalil)

BACKGROUND Schwannomas of the peripheral nerves are benign tumors that can very rarely undergo malignant transformation. These lesions are particularly challenging to diagnose via noninvasive techniques but can have significant implications for treatment. OBSERVATIONS This is a case of a 70-year-old female with a prior history of a right sciatic notch tumor that was diagnosed as a conventional schwannoma via histology from an initial biopsy and subsequent surgical debulking. Unfortunately, she experienced significant worsening of her motor deficit, whereby her postoperative foot weakness progressed to complete foot drop in less than 2 years. In addition, she demonstrated significant radiological progression, with more than 1 to 2 cm of growth in each dimension at her subsequent evaluation, along with intractable right leg pain. An additional operation was performed to completely remove the 7 × 8 cm tumor, and histology demonstrated angiosarcoma within a schwannoma. There was no evidence of recurrence at 15 months, and the patient had significant improvement in her pain. LESSONS Rapidly worsening function and radiological progression are not typically seen with conventional benign nerve sheath tumors and should prompt consideration of other lesions. Angiosarcoma within schwannoma is a rare pathology and optimal therapies for these tumors in terms of surgical timing and adjuvant therapy are still unknown.

Objective: To investigate the steps faculty surgeons take upon experiencing intraoperative error and synthesize these actions to offer a framework for coping with errors. Background: While intraoperative errors are inevitable, formal training in error recovery is insufficient and there are no established curricula that teach surgeons how to deal with the intraoperative error. This is problematic because insufficient error recovery is detrimental to both patient outcomes and surgeon psychological well-being. Methods: We conducted a thematic analysis. One-hour in-depth semistructured interviews were conducted with faculty surgeons from 3 hospitals. Surgeons described recent experiences with intraoperative error. Interviews were transcribed and coded. Analysis allowed for development of themes regarding responses to errors and coping strategies. Results: Twenty-seven surgeons (30% female) participated. Upon completion of the analysis, themes emerged in 3 distinct areas: (1) Exigency, or a need for training surgical learners how to cope with intraoperative errors, (2) Learning, or how faculty surgeons themselves learned to cope with intraoperative errors, and (3) Responses, or how surgeons now handle intraoperative errors. The latter category was organized into the STOPS framework: Intraoperative errors could produce STOPS: Stop, Talk to your Team, Obtain Help, Plan, Succeed. Conclusions and Relevance: This study provides both novel insight into how surgeons cope with intraoperative errors and a framework that may be of great use to trainees and faculty alike.

Abstract Purpose To examine associations of social support and social isolation with burnout, program satisfaction, and organization satisfaction among a large population of U.S. residents and fellows and to identify correlates of social support and social isolation. Method All residents and fellows enrolled in graduate medical education programs at Mayo Clinic sites were surveyed in February 2019. Survey items measured social support (emotional and tangible), social isolation, burnout, program satisfaction, and organization satisfaction. Factors of potential relevance to social support were collected (via the survey, institutional administrative records, and interviews with program coordinators and/or program directors) and categorized as individual, interpersonal, program, or work-related factors (duty hours, call burden, elective time, vacation days used before survey administration, required away rotations, etc.). Multivariable regression analyses were conducted to examine relationships between variables. Results Of 1,146 residents surveyed, 762 (66%) from 58 programs responded. In adjusted models, higher emotional and tangible support were associated with lower odds of burnout and higher odds of program and organization satisfaction, while higher social isolation scores were associated with higher odds of burnout and lower odds of program satisfaction and organization satisfaction. Independent predictors of social support and/or social isolation included age, gender, relationship status, parental status, postgraduate year, site, ratings of the program leadership team, ratings of faculty relationships and faculty professional behaviors, satisfaction with autonomy, and vacation days used before survey administration. Conclusions This study demonstrates that social support and social isolation are strongly related to burnout and satisfaction among residents and fellows. Personal and professional relationships, satisfaction with autonomy, and vacation days are independently associated with social support and/or social isolation, whereas most program and work-related factors are not. Additional studies are needed to determine if social support interventions targeting these factors can improve well-being and enhance satisfaction with training.

BACKGROUND: Intraoperative frozen-section analysis provides real-time margin resection status that can guide intraoperative decisions made by the surgeon and radiation oncologist. For patients with locally recurrent rectal cancer undergoing surgery and intraoperative radiation therapy, intraoperative re-resection of positive margins to achieve negative margins is common practice. OBJECTIVE: This study aimed to assess whether re-resection of positive margins found on intraoperative frozen-section analysis improves oncologic outcomes. DESIGN: This is a retrospective cohort study. SETTINGS: This study was an analysis of a prospectively maintained multicenter database. PATIENTS: All patients who underwent surgical resection of locally recurrent rectal cancer with intraoperative radiation therapy between 2000 and 2015 were included and followed for 5 years. Three groups were compared: initial R0 resection, initial R1 converted to R0 after re-resection, and initial R1 that remained R1 after re-resection. Grossly positive margin resections (R2) were excluded. MAIN OUTCOME MEASURES: The primary outcome measures were 5-year overall survival, recurrence-free survival, and local re-recurrence. RESULTS: A total of 267 patients were analyzed (initial R0 resection, n = 94; initial R1 converted to R0 after re-resection, n = 95; initial R1 that remained R1 after re-resection, n = 78). Overall survival was 4.4 years for initial R0 resection, 2.7 years for initial R1 converted to R0 after re-resection, and 2.9 years for initial R1 that remained R1 after re-resection (p = 0.01). Recurrence-free survival was 3.0 years for initial R0 resection and 1.8 years for both initial R1 converted to R0 after re-resection and initial R1 that remained R1 after re-resection (p ≤ 0.01). Overall survival did not differ for patients with R1 and re-resection R1 or R0 (p = 0.62). Recurrence-free survival and freedom from local re-recurrence did not differ between groups. LIMITATIONS: This study was limited by the heterogeneous patient population restricted to those receiving intraoperative radiation therapy. CONCLUSIONS: Re-resection of microscopically positive margins to obtain R0 status does not appear to provide a significant survival advantage or prevent local re-recurrence in patients undergoing surgery and intraoperative radiation therapy for locally recurrent rectal cancer. See Video Abstract at http://links.lww.com/DCR/B886. LA RE-RESECCIÓN DE LOS MÁRGENES MICROSCÓPICAMENTE POSITIVOS ENCONTRADOS DE MANERA INTRAOPERATORIA MEDIANTE LA TÉCNICA DE CRIOSECCIÓN, NO DA COMO RESULTADO UN BENEFICIO DE SUPERVIVENCIA EN PACIENTES SOMETIDOS A CIRUGÍA Y RADIOTERAPIA INTRAOPERATORIA PARA EL CÁNCER RECTAL LOCALMENTE RECIDIVANTE ANTECEDENTES: El análisis de la ténica de criosección para los margenes positivos encontrados de manera intraoperatoria proporciona el estado de la resección del margen en tiempo real que puede guiar las decisiones intraoperatorias tomadas por el cirujano y el oncólogo radioterapeuta. Para los pacientes con cáncer de recto localmente recurrente que se someten a cirugía y radioterapia intraoperatoria, la re-resección intraoperatoria de los márgenes positivos para lograr márgenes negativos es una práctica común. OBJETIVO: Evaluar si la re-resección de los márgenes positivos encontrados en el análisis de la ténica por criosecciónde manera intraoperatorios mejora los resultados oncológicos. DISEÑO: Estudio de cohorte retrospectivo. AJUSTES: Análisis de una base de datos multicéntrica mantenida de forma prospectiva. POBLACIÓN: Todos los pacientes que se sometieron a resección quirúrgica de cáncer de recto localmente recurrente con radioterapia intraoperatoria entre 2000 y 2015 fueron incluidos y seguidos durante 5 años. Se compararon tres grupos: resección inicial R0, R1 inicial convertido en R0 después de la re-resección y R1 inicial que permaneció como R1 después de la re-resección. Se excluyeron las resecciones de márgenes macroscópicamente positivos (R2). PRINCIPALES MEDIDAS DE RESULTADO: Supervivencia global a cinco años, supervivencia sin recidiva y recidiva local. RESULTADOS: Se analizaron un total de 267 pacientes (resección inicial R0 n = 94, R1 inicial convertido en R0 después de la re-resección n = 95, R1 inicial que permaneció como R1 después de la re-resección n = 78). La supervivencia global fue de 4,4 años para la resección inicial R0, 2,7 años para la R1 inicial convertida en R0 después de la re-resección y 2,9 años para la R1 inicial que permaneció como R1 después de la re-resección (p = 0,01). La supervivencia libre de recurrencia fue de 3,0 años para la resección inicial R0 y de 1,8 años para el R1 inicial convertido en R0 después de la re-resección y el R1 inicial que permaneció como R1 después de la re-resección (p ≤ 0,01). La supervivencia global no difirió para los pacientes con R1 y re-resección R1 o R0 (p = 0,62). La supervivencia libre de recurrencia y la ausencia de recurrencia local no difirieron entre los grupos. LIMITACIONES: Población de pacientes heterogénea, restringida a aquellos que reciben radioterapia intraoperatoria. CONCLUSIONES: La re-resección de los márgenes microscópicamente positivos para obtener el estado R0 no parece proporcionar una ventaja de supervivencia significativa o prevenir la recurrencia local en pacientes sometidos a cirugía y radioterapia intraoperatoria para el cáncer de recto localmente recurrente. Consulte Video Resumen en http://links.lww.com/DCR/B886. (Traducción—Dr. Daniel Guerra)

Abstract Aim The aim of this study was to describe the surgical management, outcomes and risk of malignancy of presacral tailgut cysts. Method A retrospective analysis of all patients who underwent resection of tailgut cyst at Mayo Clinic in Arizona, Florida and Minnesota between 2008 and 2020 was performed. Demographics, presentation, evaluation, surgical approach, postoperative complications, pathology and recurrence rates were reviewed. Results Seventy‐three patients were identified (81% female) with a mean age of 45 years. Thirty‐nine patients (53%) were symptomatic, most commonly with pelvic pain (26 patients). Digital rectal examination identified a palpable mass in 68%. Mean tumour size was 6 cm. Resection was primarily performed through a posterior approach (77%, n = 56), followed by a transabdominal approach (18%, n = 13) and a combined approach (5%, n = 4). Six patients underwent a minimally invasive resection (laparoscopic/robotic). Coccygectomy or distal sacrectomy was performed in 41 patients (56%). Complete resection was achieved in 94% of patients. Thirty‐day morbidity occurred in 18% and was most commonly wound related; there was no mortality. Malignancy was identified in six patients (8%). For the 30 patients with follow‐up greater than 1 year, the median follow‐up was 39 months (range 1.0–11.1 years). Local recurrence was identified in three patients and distant metastatic disease in one patient. Conclusion The rate of malignancy in presacral tailgut cysts based on this current review was 8%. Overall recurrence was 5% at a median of 24 months.