Sacral Neural Crest-Independent Origin of the Enteric Nervous System in Mouse.

BACKGROUND & AIMS: The enteric nervous system (ENS), the gut's intrinsic nervous system critical for gastrointestinal function and gut-brain communication, is believed to mainly originate from vagal neural crest cells (vNCCs) and partially from sacral NCCs (sNCCs). Resolving the exact origins of the ENS is critical for understanding congenital ENS diseases but has been confounded by the inability to distinguish between both NCC populations in situ. Here, we aimed to resolve the exact origins of the mammalian ENS. METHODS: We genetically engineered mouse embryos facilitating comparative lineage-tracing of either all (pan-) NCCs including vNCCs or caudal trunk and sNCCs (s/tNCCs) excluding vNCCs. This was combined with dual-lineage tracing and 3-dimensional reconstruction of pelvic plexus and hindgut to precisely pinpoint sNCC and vNCC contributions. We further used coculture assays to determine the specificity of cell migration from different neural tissues into the hindgut. RESULTS: Both pan-NCCs and s/tNCCs contributed to established NCC derivatives but only pan-NCCs contributed to the ENS. Dual-lineage tracing combined with 3-dimensional reconstruction revealed that s/tNCCs settle in complex patterns in pelvic plexus and hindgut-surrounding tissues, explaining previous confusion regarding their contributions. Coculture experiments revealed unspecific cell migration from autonomic, sensory, and neural tube explants into the hindgut. Lineage tracing of ENS precursors lastly provided complimentary evidence for an exclusive vNCC origin of the murine ENS. CONCLUSIONS: sNCCs do not contribute to the murine ENS, suggesting that the mammalian ENS exclusively originates from vNCCs. These results have immediate implications for comprehending (and devising treatments for) congenital ENS disorders, including Hirschsprung's disease.

Longitudinal Fluctuations in Treatment Response After OnabotulinumToxinA and Sacral Neuromodulation for Refractory Urgency Incontinence.

PURPOSE: We compared fluctuations in treatment response after onabotulinumtoxinA and sacral neuromodulation for urgency incontinence using Markov models. MATERIALS AND METHODS: We fit data from a randomized trial to Markov models to compare transitions of success/failure over 6 months between 200 U onabotulinumtoxinA and sacral neuromodulation. Objective failure was <50% reduction in urgency incontinence episodes from baseline; subjective failure "strongly disagree" to "neutral" to the Patient Global Symptom Control questionnaire. RESULTS: Of the 357 participants (median baseline daily urgency incontinence episodes 4.7 [IQR 3.7-6.0]) 61% vs 51% and 3.2% vs 6.1% reported persistent states of objective success and failure over 6 months after onabotulinumtoxinA vs sacral neuromodulation. Participants receiving onabotulinumtoxinA vs sacral neuromodulation had lower 30-day transition probabilities from objective and subjective success to failure (10% vs 14%, ratio 0.75 [95% CI 0.55-0.95]; 14% vs 21%, ratio 0.70 [95% CI 0.51-0.89]). The 30-day transition probability from objective and subjective failure to success did not differ between onabotulinumtoxinA and sacral neuromodulation (40% vs 36%, ratio 1.11 [95% CI 0.73-1.50]; 18% vs 17%, ratio 1.14 [95% CI 0.65-1.64]). CONCLUSIONS: Over 6 months after treatment, 2 in 5 women's symptoms fluctuate. Within these initial 6 months, women receiving onabotulinumtoxinA transitioned from success to failure over 30 days less often than sacral neuromodulation. For both treatments, there was an almost 20%-40% probability over 30 days that women returned to subjective and objective success after failure. Markov models add important information to longitudinal models on how symptoms fluctuate after urgency incontinence treatment.

Unfolding the Art of Methodical Approach for Total Sacrectomy.

BACKGROUND: Total sacrectomy is a technically demanding surgery with substantial risks, including high morbidity and mortality due to the likelihood of exsanguination.1-3 Despite the evolution of surgical techniques,4,5 the incidence of postoperative complications remains significant.1 This study presents a systematic approach to total sacrectomy, with a particular focus on a modified technique for isolating the iliac vessels, aimed at effective management of complex sacrococcygeal masses and the reduction of operative complications. PATIENTS AND METHODS: Employing our approach, a 45-year-old male patient presenting with a sacrococcygeal mass involving the lower S1 bone and sacroiliac joint underwent total sacrectomy. A meticulous preoperative workup, including magnetic resonance imaging (MRI), was followed by precise surgical steps: sigmoid colon and rectal mobilization, isolation of the iliac vessels,2,6 lumbosacral nerve trunk preservation, and strategic anterior and posterior osteotomies. The procedure concluded with reconstruction using mesorectal fat and bilateral gluteus maximus flaps.5-7 RESULTS: The patient's operation was conducted successfully without any perioperative complications, culminating in a chordoma resection with clear margins. Postoperative recovery was swift, allowing for discharge on the seventh day. CONCLUSIONS: The application of our systematic sacrectomy method, with particular emphasis on the isolation of the external iliac veins, significantly minimized intraoperative bleeding risks and other perioperative complications. Our technique offers a reproducible and effective strategy for the surgical management of sacrococcygeal masses.

Presacral Neuroendocrine Neoplasms: A Multi-site Review of Surgical Outcomes.

INTRODUCTION: Presacral neuroendocrine neoplasms (PNENs) are rare tumors, with limited data on management and outcomes. METHODS: A retrospective review of institutional medical records was conducted to identify all patients with PNENs between 2008 and 2022. Data collection included demographics, symptoms, imaging, surgical approaches, pathology, complications, and long-term outcomes. RESULTS: Twelve patients were identified; two-thirds were female, averaging 44.8 years of age, and, for the most part, presenting with back pain, constipation, and abdominal discomfort. Preoperative imaging included computed tomography scans and magnetic resonance images, with somatostatin receptor imaging and biopsies being common. Half of the patients had metastatic disease on presentation. Surgical approach varied, with anterior, posterior, and combined techniques used, often involving muscle transection and coccygectomy. Short-term complications affected one-quarter of patients. Pathologically, PNENs were mainly well-differentiated grade 2 tumors with positive synaptophysin and chromogranin A. Associated anomalies were common, with tail-gut cysts prevalent. Mean tumor diameter was 6.3 cm. Four patients received long-term adjuvant therapy. Disease progression necessitated additional interventions, including surgery and various chemotherapy regimens. Skeletal, liver, thyroid, lung, and pancreatic metastases occurred during follow-up, with no mortality reported. Kaplan-Meier analysis showed a 5-year local recurrence rate of 23.8%, disease progression rate of 14.3%, and de novo metastases rate of 30%. CONCLUSION: The study underscores the complex management of PNENs and emphasizes the need for multicenter research to better understand and manage these tumors. It provides valuable insights into surgical outcomes, recurrence rates, and overall survival, guiding future treatment strategies for PNEN patients.

Variation in the sacrum of phytosaurs: New evidence from a partial skeleton of Machaeroprosopus mccauleyi.

Phytosaurs are a group of Upper Triassic semi-aquatic archosauriform reptiles. Their variable skull morphology forms the foundation of our understanding of their relationships and paleoecology, while only a few studies have focused on demonstrating the existence of postcranial variation. The numbers of vertebrae in the sacrum are thought to vary from two, the plesiomorphic condition for archosauriforms, to three, with the addition of a sacralized dorsal (i.e., dorsosacral) vertebra. In this study, we demonstrate the presence of a sacralized first caudal (i.e., caudosacral) vertebra in a sacrum belonging to Machaeroprosopus mccauleyi. We rule out taphonomic distortion or pathology as explanations for the inclusion of this element in the sacrum, suggesting instead that it occurred through modifications of the same developmental processes that likely produced dorsosacral vertebrae in phytosaurs. Additionally, we show that a dorsosacral vertebra is common in phytosaur specimens from the Chinle Formation and Dockum Group of the southwestern United States and suggest that it may be widespread among phytosaurs. The addition of sacral vertebrae potentially aided adaptation to larger body sizes or more terrestrial lifestyles in certain taxa.

The influence of lumbosacral transitional vertebrae on lumbar lordosis and the angle of pelvic incidence.

Pelvic incidence and lumbar lordosis have only normative values for spines comprising five lumbar and five sacral vertebrae. However, it is unclear how pelvic incidence and lumbar lordosis are affected by the common segmentation anomalies at the lumbo-sacral border leading to lumbosacral transitional vertebrae, including lumbarisations and sacralisations. In lumbosacral transitional vertebrae it is not trivial to identify the correct vertebral endplates to measure pelvic incidence and lumbar lordosis because ontogenetically the first sacral vertebra represents the first non-mobile sacral segment in lumbarisations, but the second segment in sacralisations. We therefore assessed pelvic incidence and lumbar lordosis with respect to both of these vertebral endplates. The type of segmentation anomaly was differentiated using spinal counts, spatial relationship with the iliac crest and morphological features. We found significant differences in pelvic incidence and lumbar lordosis between lumbarisations, sacralisations and the control group. The pelvic incidence in the sacralised group was mostly below the range of the lubarisation group and the control group when measured the traditional way at the first non-mobile segment (30.2°). However, the ranges of the sacralisation and lubarisation groups were completely encompassed by the control group when measured at the ontogenetically true first sacral vertebra. The mean pelvic incidence of the sacraliation group thus increased from 30.2° to 58.6°, and the mean pelvic incidence of the total sample increased from 45.6° to 51.2°, making it statistically indistinguishable from the control sample, whose pelvic incidence was 50.2°. Our results demonstrate that it is crucial to differentiate sacralisations from lumbarisation in order to assess the reference vertebra for pelvic incidence measurement. Due to their significant impact on spino-pelvic parameters, lumbosacral transitional vertebrae should be evaluated separately when examining pelvic incidence and lumbar lordosis.

Postoperative venous thromboembolism after surgery for locally recurrent rectal cancer.

BACKGROUND: Local recurrence is common after curative resections of rectal cancer. Surgical resection is considered a primary curative treatment option for patients with locally recurrent rectal cancer (LRRC). LRRC often requires a combined resection of other organs, especially in the case of posterior recurrence, which requires a combined resection of the sacrum, making the surgery highly invasive. Venous thromboembolism (VTE) is one of the lethal complications in the postoperative period, particularly in the field of pelvic surgery. We found no reports regarding the risks of postoperative VTE in surgery for LRRC, a typical highly invasive procedure in the field of colorectal surgery. This study aims to evaluate the risk of postoperative VTE in surgery for LRRC patients. METHODS: From April 2010 to March 2022, a total of 166 patients underwent surgery for LRRC in the pelvic region at our institutions. Clinicopathological background and VTE incidence were compared retrospectively. RESULTS: Among the 166 patients included in the study, 55 patients (33.1%) needed sacral resection. Pharmacological prophylaxis for prevention of VTE was performed in 121 patients (73.3%), and the incidence of VTE was 9.09% (5/55 patients) among those who underwent surgery for LRRC with sacral resection, while it was 1.8% (2/111 patients) in those without sacral resection. In univariate analysis, the combination with sacral resection was identified as a risk factor for VTE in surgery for LRRC (p = 0.047). CONCLUSIONS: This study demonstrates that surgery for LRRC combined with sacral resection could be a significant risk factor for VTE.

Conserved patterns and locomotor-related evolutionary constraints in the hominoid vertebral column.

The evolution of the hominoid lineage is characterized by pervasive homoplasy, notably in regions such as the vertebral column, which plays a central role in body support and locomotion. Few isolated and fewer associated vertebrae are known for most fossil hominoid taxa, but identified specimens indicate potentially high levels of convergence in terms of both form and number. Homoplasy thus complicates attempts to identify the anatomy of the last common ancestor of hominins and other taxa and stymies reconstructions of evolutionary scenarios. One way to clarify the role of homoplasy is by investigating constraints via phenotypic integration, which assesses covariation among traits, shapes evolutionary pathways, and itself evolves in response to selection. We assessed phenotypic integration and evolvability across the subaxial (cervical, thoracic, lumbar, sacral) vertebral column of macaques (n = 96), gibbons (n = 77), chimpanzees (n = 92), and modern humans (n = 151). We found a mid-cervical cluster that may have shifted cranially in hominoids, a persistent thoracic cluster that is most marked in chimpanzees, and an expanded lumbosacral cluster in hominoids that is most expanded in gibbons. Our results highlight the highly conserved nature of the vertebral column. Taxa appear to exploit existing patterns of integration and ontogenetic processes to shift, expand, or reduce cluster boundaries. Gibbons appear to be the most highly derived taxon in our sample, possibly in response to their highly specialized locomotion.

The Long-term Outcomes of Sacral Neuromodulation for Fecal Incontinence: A Single-Center Experience.

BACKGROUND: Sacral neuromodulation is an effective treatment for fecal incontinence. OBJECTIVE: To assess the long-term outcomes of sacral neuromodulation and establish the outcomes of patients with inactive devices. DESIGN: This is an observational study of patients treated for >5 years. A positive outcome was defined as a more than 50% reduction in fecal incontinence episodes or improvement in a symptom severity score. Data were reviewed from a prospectively managed database. SETTINGS: This study was conducted at a single tertiary referral center. PATIENTS: Data from 74 patients (72 women) were available at long-term follow-up. MAIN OUTCOME MEASURES: Bowel diary, St. Mark's incontinence score, and Manchester Health Questionnaire data were prospectively recorded at baseline, after percutaneous nerve evaluation, and at last follow-up. RESULTS: Patients were analyzed in cohorts based on time since sacral neuromodulation implantation: group 1: 5 to 10 years (n = 20), group 2: >10 years (n = 35), and group 3: inactive sacral neuromodulation devices (n = 19). Median St. Mark's incontinence score and Manchester Health Questionnaire improved from baseline to last follow-up in group 1 ( p ≤ 0.05) and group 2 ( p ≤ 0.05), but in group 3, results returned to baseline levels at the last follow-up. Similarly, weekly fecal incontinence episodes improved in both active device groups at the last follow-up. However, in group 3, incontinence episodes were no different from baseline ( p = 0.722). Despite active devices, fecal urgency episodes increased at the last follow-up after >10 years since percutaneous nerve evaluation ( p ≤ 0.05). Complete continence was reported by 44% of patients, and at least a 50% improvement was seen in 77% of patients with active devices. LIMITATIONS: This study is retrospective with some gaps in the available data at the last follow-up. CONCLUSIONS: Sacral neuromodulation is an effective treatment for fecal incontinence in the long term, but all outcomes are adversely affected by device inactivity. Therefore, ongoing stimulation is required for continued benefit. See Video Abstract. RESULTADOS A LARGO PLAZO DE LA NEUROMODULACIN SACRA PARA LA INCONTINENCIA FECAL EXPERIENCIA DE UN SOLO CENTRO: ANTECEDENTES:La neuromodulación sacra es un tratamiento eficaz para la incontinencia fecal.OBJETIVO:Este estudio tuvo como objetivo evaluar los resultados a largo plazo de la neuromodulación sacra y establecer los resultados de los pacientes con dispositivos inactivos.DISEÑO:Este es un estudio observacional de pacientes tratados durante más de 5 años. Un resultado positivo se definió como una reducción >50 % en los episodios de incontinencia fecal o una mejoría en la puntuación de gravedad de los síntomas. Los datos se revisaron a partir de una base de datos administrada prospectivamente.ENTERNO CLINICO:Este estudio se realizó en un solo centro de referencia terciario.PACIENTES:Los datos de 74 pacientes (72 mujeres) estaban disponibles en el seguimiento a largo plazo.PRINCIPALES MEDIDAS DE RESULTADO:Diario intestinal, puntuación de incontinencia de St. Mark y datos del Cuestionario de salud de Manchester se registraron prospectivamente al inicio, después de la evaluación de nervio periférico y en el último seguimiento.RESULTADOS:Los pacientes se analizaron en cohortes según el tiempo transcurrido desde la implantación de la neuromodulación sacra: Grupo 1: 5-10 años (n = 20), Grupo 2: >10 años (n = 35) y Grupo 3: dispositivos SNM inactivos (n = 19). La mediana de la puntuación de incontinencia de St. Mark y Questionnaire Cuestionario de salud de Manchester mejoraron desde el inicio hasta el último seguimiento en el Grupo 1 (p = < 0,05) y el Grupo 2 (p = < 0,05), pero en el Grupo 3 los resultados volvieron a los niveles iniciales en el último seguimiento. arriba. De manera similar, los episodios semanales de incontinencia fecal mejoraron en ambos grupos de dispositivos activos en el último seguimiento. Sin embargo, en el Grupo 3 los episodios de incontinencia no fueron diferentes de los basales (p = 0,722). A pesar de los dispositivos activos, los episodios de urgencia fecal aumentaron en el último seguimiento después de más de 10 años desde la evaluación del nervio periférico (p = < 0,05). Continencia completa se reportó en el 44 % de los pacientes, y al menos una mejora del 50 % en el 77 % con dispositivos activos.LIMITACIONES:Este estudio es retrospectivo con algunas vacíos en los datos disponibles en el último seguimiento.CONCLUSIONES:La neuromodulación sacra es un tratamiento eficaz para la incontinencia fecal a largo plazo, pero todos los resultados se ven afectados negativamente por la inactividad del dispositivo. Por lo tanto, se requiere estimulación continua para un beneficio continuo. (Traducción- Dr. Francisco M. Abarca-Rendon ).

Sacral Neuromodulation in Patients With Low Anterior Resection Syndrome: The SANLARS Randomized Clinical Trial.

BACKGROUND: Sacral neuromodulation might be effective to palliate low anterior resection syndrome after rectal cancer surgery, but robust evidence is not available. OBJECTIVE: To assess the impact of sacral neuromodulation on low anterior resection syndrome symptoms as measured by validated scores and bowel diaries. DESIGN: Randomized, double-blind, 2-phased, controlled, multicenter crossover trial (NCT02517853). SETTINGS: Three tertiary hospitals. PATIENTS: Patients with major low anterior resection syndrome 12 months after transit reconstruction after rectal resection who had failed conservative treatment. INTERVENTIONS: Patients underwent an advanced test phase by stimulation for 3 weeks and received the pulse generator implant if a 50% reduction in low anterior resection syndrome score was achieved. These patients entered the randomized phase in which the generator was left active or inactive for 4 weeks. After a 2-week washout, the sequence was changed. After the crossover, all generators were left activated. MAIN OUTCOME MEASURES: The primary outcome was low anterior resection syndrome score reduction. Secondary outcomes included continence and bowel symptoms. RESULTS: After testing, 35 of 46 patients (78%) had a 50% or greater reduction in low anterior resection syndrome score. During the crossover phase, all patients showed a reduction in scores and improved symptoms, with better performance if the generator was active. At 6- and 12-month follow-up, the mean reduction in low anterior resection syndrome score was -6.2 (95% CI -8.97 to -3.43; p < 0.001) and -6.97 (95% CI -9.74 to -4.2; p < 0.001), with St. Mark's continence score -7.57 (95% CI -9.19 to -5.95, p < 0.001) and -8.29 (95% CI -9.91 to -6.66; p < 0.001). Urgency, bowel emptiness sensation, and clustering episodes decreased in association with quality-of-life improvement at 6- and 12-month follow-up. LIMITATIONS: The decrease in low anterior resection syndrome score with neuromodulation was underestimated because of an unspecific measuring instrument. There was a possible carryover effect in sham stimulation sequence. CONCLUSIONS: Neuromodulation provides symptoms and quality-of-life amelioration, supporting its use in low anterior resection syndrome. See Video Abstract . NEUROMODULACIN SACRA EN PACIENTES CON SNDROME DE RESECCIN ANTERIOR BAJA ENSAYO CLNICO ALEATORIZADO SANLARS: ANTECEDENTES:La neuromodulación sacra podría ser eficaz para paliar el síndrome de resección anterior baja después de la cirugía de cáncer de recto, pero no hay pruebas sólidas disponibles.OBJETIVO:Evaluar el impacto de la neuromodulación sacra en los síntomas del síndrome de resección anterior baja, medido mediante puntuaciones validadas y diarios intestinales.DISEÑO:Ensayo cruzado multicéntrico, controlado, aleatorizado, doble ciego, de dos fases (NCT02517853).LUGARES:Tres hospitales terciarios.PACIENTES:Pacientes con puntuación de resección anterior baja importante, 12 meses después de la reconstrucción del tránsito después de la resección rectal en quienes había fracasado el tratamiento conservador.INTERVENCIONES:Los pacientes se sometieron a una fase de prueba avanzada mediante estimulación durante tres semanas y se les implantó el generador de impulsos si se lograba una reducción del 50% en la puntuación del síndrome de resección anterior baja, ingresando a la fase aleatorizada en la que el generador se dejaba activo o inactivo durante cuatro semanas. Después de observar por 2 semanas, se cambió la secuencia. Después del cruce, todos los generadores quedaron activados.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la reducción de la puntuación del síndrome de resección anterior baja. Los resultados secundarios incluyeron continencia y síntomas intestinales.RESULTADOS:Después de las pruebas, 35 de 46 pacientes (78%) tuvieron una reducción ≥50% en la puntuación del síndrome de resección anterior baja. Durante el cruce, todos los pacientes mostraron una reducción en las puntuaciones y una mejora de los síntomas, con un mejor rendimiento si el generador estaba activo. A los 6 y 12 meses de seguimiento, la reducción media en la puntuación del síndrome de resección anterior baja fue -6,2 (-8,97; -3,43; p < 0,001) y -6,97 (-9,74; -4,2; p < 0,001), con Puntuación de continencia de St. Mark's -7,57 (-9,19; -5,95, p < 0,001) y -8,29 (-9,91; -6,66; p < 0,001). La urgencia, la sensación de vacío intestinal y los episodios de agrupamiento disminuyeron en asociación con una mejora en la calidad de vida a los 6 y 12 meses de seguimiento.LIMITACIONES:La disminución en la puntuación del síndrome de resección anterior baja con neuromodulación se subestimó debido a un instrumento de medición no específico. Posible efecto de arrastre en la secuencia de estimulación simulada.CONCLUSIONES:La neuromodulación mejora los síntomas y la calidad de vida, lo que respalda su uso en el síndrome de resección anterior baja. (Traducción-Dr. Mauricio Santamaria ).

Outcomes Following Pelvic Exenteration for Locally Recurrent Rectal Cancer With and Without En Bloc Sacrectomy.

BACKGROUND: Extended radical resection is often the only chance of cure for locally recurrent rectal cancer. Recurrence in the posterior compartment often necessitates en bloc sacrectomy as part of pelvic exenteration to obtain clear resection margins and provide survival benefit. OBJECTIVE: To compare oncological outcomes, morbidity, and quality-of-life outcomes following pelvic exenteration with and without en bloc sacrectomy for recurrent rectal cancer. DESIGN: Comparative cohort study with retrospective analysis of prospectively collected data. SETTING: This study was conducted at a high-volume pelvic exenteration center. PATIENTS: Patients who underwent pelvic exenteration for locally recurrent rectal cancer between 1994 and 2022. MAIN OUTCOME MEASURES: Overall survival, postoperative morbidity, R0 resection margin, and quality-of-life outcomes. RESULTS: Of 965 patients, 305 (31.6%) underwent pelvic exenteration for locally recurrent rectal cancer. Among these patients, 64.3% were men and the median age was 62 years (range, 29-86). One hundred eighty-five patients (60.7%) underwent en bloc sacrectomy, 65 (35.1%) underwent high transection, and 119 (64.3%) had sacrectomy below S2. R0 resection was achieved in 80% of patients with sacrectomy and 72.5% of patients without sacrectomy. Sacrectomy patients experienced more postoperative complications without increased mortality. The median overall survival was 52 months; median survival was 47 months with sacrectomy and 73 months without ( p = 0.059). Quality-of-life scores were not significantly different across physical component ( p = 0.346), mental component ( p = 0.787), or Functional Assessment of Cancer Therapy-Colorectal ( p = 0.679) scores at 24-month follow-up. LIMITATIONS: The generalizability of these findings may be limited outside of subspecialist exenteration units. Selection bias exists in a retrospective analysis. CONCLUSIONS: Patients undergoing pelvic exenteration with and without en bloc sacrectomy for locally recurrent rectal cancer experience similar rates of R0 resection, survival, and quality-of-life outcomes. As R0 remains the most important predictor of survival, the requirement of sacral resection should prompt referral to a subspecialist center that performs sacrectomy routinely. See Video Abstract . RESULTADOS DESPUS DE LA EXENTERACIN PLVICA PARA EL CNCER DE RECTO CON RECURRENCIA LOCAL, CON Y SIN SACRECTOMA EN BLOQUE: ANTECEDENTES:La resección radical ampliada es generalmente la única posibilidad de curación para el cáncer de recto con recurrencia local. La recurrencia en el compartimento posterior generalmente requiere sacrectomía en bloque como parte de la exenteración pélvica para obtener márgenes de resección claros y proporcionar un beneficio de supervivencia.OBJETIVO:Comparar los resultados oncológicos, de morbilidad y de calidad de vida después de la exenteración pélvica con y sin sacrectomía en bloque para el cáncer de recto recurrente.DISEÑO:Estudio de cohorte comparativo con análisis retrospectivo de datos recopilados prospectivamente.AMBIENTE AJUSTE:Estudio realizado en un centro de exenteración pélvica de alto volumen.PACIENTES:Aquellos sometidos a exenteración pélvica por cáncer de recto con recurrencia local entre 1994 y 2022.PRINCIPALES MEDIDAS DE RESULTADO:Supervivencia general, morbilidad posoperatoria, margen de resección R0 y resultados de calidad de vida.RESULTADOS:305 (31,6%) de 965 pacientes se sometieron a exenteración pélvica por cáncer de recto con recurrencia local. El 64,3% de los pacientes eran hombres con una mediana de edad de 62 años (rango 29-86). 185 pacientes (60,7%) fueron sometidos a sacrectomía en bloque, 65 (35,1%) fueron sometidos a transección alta, 119 (64,3%) tuvieron sacrectomía por debajo de S2. La resección R0 se logró en el 80% de los pacientes con sacrectomía y en el 72,5% sin ella. Los pacientes de sacrectomía experimentaron más complicaciones postoperatorias sin aumento de la mortalidad. La mediana de supervivencia global fue de 52 meses, 47 meses con sacrectomía y 73 meses sin sacrectomía ( p = 0,059). Las puntuaciones de calidad de vida no fueron significativamente diferentes entre las puntuaciones del componente físico ( p = 0,346), componente mental ( p = 0,787) o la evaluación funcional de la terapia contra el cáncer - colorrectal ( p = 0,679) a los 24 meses de seguimiento.LIMITACIONES:La generalización de estos hallazgos puede estar limitada fuera de las unidades de exenteración de subespecialistas. Existe un sesgo de selección en un análisis retrospectivo.CONCLUSIONES:Los pacientes sometidos a exenteración pélvica con y sin sacrectomía en bloque por cáncer de recto con recurrencia local experimentan tasas similares de resección R0, supervivencia y resultados de calidad de vida. Como R0 sigue siendo el predictor más importante de supervivencia, la necesidad de resección sacra debe provocar la derivación a un centro subespecialista que realice sacrectomía de forma rutinaria. (Traducción-Dr. Fidel Ruiz Healy ).

Spina bifida, the normal, the pathological and the in-between: first evidence from a forensic osteological collection.

Spina bifida (SB), a rare congenital disorder, is often mentioned as an individualizing factor in Forensic Anthropology. A lack of empirical data regarding SB is noticed in the scientific literature. Moreover, within the scope of anthropological research on SB disparities in terminology, classification systems, and methodological approaches result in incomparable results. The wide range (1,2%-50%) of "spina bifida occulta" reported prevalences is a good example. This research aims to analyze and debate the standard diagnostic criteria of SB on human skeletal remains, and attempts to elaborate on an universal system, premised on the distinction between SB as a pathology, and cleft neural arch (CNA) as an anatomical variant, according to Barnes (1994, p. 360 [1). A study-base of 209 individuals (88 males; 121 females; 44-99 years old) from the 21st Century Identified Skeletal Collection from the University of Coimbra (CEI/XXI) was macroscopically analyzed, focusing on the sacrum and remaining vertebrae. Four individuals presented complete posterior opening of the sacral canal (2,6%[4/156]). The observed bone changes, combined with the analysis of the entire skeleton, indicate that CNA, rather than SB linked to a neural tube defect, is the most reliable explanation for these cases. Overall, CNA was observed on 11 skeletons (7.05% of 156). The viability and applicability of the developed methodology for the identification of SB/CNA in forensic and/or osteological contexts are discussed, as well as the possibility of a lower prevalence of SB occulta, in the general population, than speculated before. HIGHLIGHTS: • Spina bifida has been studied so far under different methodologies, classification systems and nomenclature, leading to unstandardized and incomparable data. • Spina bifida as a pathological manifestation of a neural tube defect, as opposed to cleft neural arch as a simple form of skeletal variation. • Both spina bifida and complete sacral cleft fit the criteria of an individualizing trait in Forensic Anthropology.

Does choice of anesthesia during stage 1 sacral neuromodulation testing influence outcomes?

INTRODUCTION: Staged sacral neuromodulation (SNM) testing has been shown to have a high rate of progression to permanent implantation for the management of voiding dysfunction. Stage 1 lead placement (SNM-I) can be performed under monitored anesthesia care (MAC) or general anesthesia (GA). MAC allows for interpretation of sensory and motor responses to optimize lead placement while GA only permits for motor assessment. However, patient discomfort and movement can make lead placement challenging during MAC. Herein we evaluate whether the anesthesia type impacts the progression rate to permanent implantation (SNM-II). MATERIALS AND METHODS: A retrospective chart review was performed for patients who underwent SNM-I in the operating room for wet overactive bladder between 2005 and 2023. Patients were divided into two groups based on the type of anesthesia used, MAC or GA. Clinical variables and progression to SNM-II were compared between cohorts. Progression to SNM-II was based on ≥50% symptomatic improvement during a 1-2 week trial period following SNM-I. RESULTS: Of 121 patients included in the study, 95 (79%) underwent MAC and 26 (21%) GA for SNM-I. No difference in the progression rate to SNM-II was noted between groups (MAC, 68/95 patients, 72%; GA, 19/26, 73%; p = 0.39). We also found no difference when comparing the GA group to the 26 most recent MAC patients (MAC, 20/26 patients, 77%; GA, 19/26, 73%; p = 0.48). CONCLUSION: Types of anesthesia for SNM-I did not affect rate of progression to SNM-II. The result lends support to the reliance on motor responses alone for lead placement during SNM-I.

Radiation exposure during sacral neuromodulation lead placement: Multi-institutional descriptive study.

OBJECTIVES: Fluoroscopy has significantly improved lead placement and decreased surgical time for implantable sacral neuromodulation (SNM). There is a paucity of data regarding radiation and safety of fluoroscopy during SNM procedures. Our study aims to characterize fluoroscopy time and dose used during SNM surgery across multiple institutions and assess for predictors of increased fluoroscopy time and radiation dose. METHODS: Electronic medical records were queried for SNM procedures (Stage 1 and full implant) from 2016 to 2021 at four academic institutions. Demographic, clinical, and intraoperative data were collected, including fluoroscopy time and radiation dose in milligray (mGy). The data were entered into a centralized REDCap database. Univariate and multivariate analysis were performed to assess for predictive factors using STATA/BE 17.0. RESULTS: A total of 664 procedures were performed across four institutions. Of these, 363 (54.6%) procedures had complete fluoroscopy details recorded. Mean surgical time was 58.8 min. Of all procedures, 79.6% were performed by Female Pelvic Medicine and Reconstructive Surgery specialists. There was significant variability in fluoroscopy time and dose based on surgical specialty and institution. Most surgeons (76.4%) were considered "low volume" implanters. In a multivariate analysis, bilateral finder needle testing, surgical indication, surgeon volume, and institution significantly predicted increased fluoroscopy time and radiation dose (p < 0.05). CONCLUSIONS: There is significant variability in fluoroscopy time and radiation dose utilized during SNM procedures, with differences across institutions, surgeons, and subspecialties. Increased radiation exposure can have harmful impacts on the surgical team and patient. These findings demonstrate the need for standardized fluoroscopy use during SNM procedures.

Sacral neuromodulation in nursing home residents: Predictors of success and complications in a national cohort of older adults.

AIMS: There is limited evidence to support the efficacy of sacral neuromodulation (SNM) for older adults with overactive bladder (OAB). This study aims to report outcomes following SNM among nursing home (NH) residents, a vulnerable population with high rates of frailty and comorbidity. METHODS: This is a retrospective cohort study of long-stay NH residents who underwent a trial of percutaneous nerve evaluation (PNE) or Stage 1 permanent lead placement (Stage 1) between 2014 and 2016. Residents were identified using the Minimum Data Set linked to Medicare claims. The primary outcome of this study was successful progression from trial to implant. Rates of 1-year device explant/revisions were also investigated. RESULTS: Trial of SNM was observed in 1089 residents (mean age: 77.9 years). PNE was performed in 66.9% of residents and 33.2% underwent Stage 1. Of Stage 1 procedures, 23.8% were performed with simultaneous device implant (single-stage). Overall, 53.1% of PNEs and 72.4% of Stage 1 progressed to device implant, which was associated with Stage 1 procedure versus PNE (adjusted relative risk [aRR]: 1.34; 95% confidence interval [95% CI]: 1.21-1.49) and female versus male sex (aRR: 1.26; 95% CI: 1.09-1.46). One-year explant/revision was observed in 9.3% of residents (6.3% for PNE, 10.5% for Stage 1, 20.3% single-stage). Single stage procedure versus PNE was significantly associated with device explant/revision (aRR: 3.4; 95% CI: 1.9-6.2). CONCLUSIONS: In this large cohort of NH residents, outcomes following SNM were similar to previous reports of younger healthier cohorts. Surgeons managing older patients with OAB should use caution when selecting patients for single stage SNM procedures.

Sacral neuromodulation device biofilm differs in the absence and presence of infection, harbors antibiotic resistance genes, and is reproducible in vitro.

INTRODUCTION/PURPOSE: Sacral neuromodulation (SNM) is effective therapy for overactive bladder refractory to oral therapies, and non-obstructive urinary retention. A subset of SNM devices is associated with infection requiring surgical removal. We sought to compare microbial compositions of explanted devices in the presence and absence of infection, by testing phase, and other clinical factors, and to investigate antibiotic resistance genes present in the biofilms. We analyzed resistance genes to antibiotics used in commercially-available anti-infective device coating/pouch formulations. We further sought to assess biofilm reconstitution by material type and microbial strain in vitro using a continuous-flow stir tank bioreactor, which mimics human tissue with an indwelling device. We hypothesized that SNM device biofilms would differ in composition by infection status, and genes encoding resistance to rifampin and minocycline would be frequently detected. MATERIALS/METHODS: Patients scheduled to undergo removal or revision of SNM devices were consented per IRB-approved protocol (IRB 20-415). Devices were swabbed intraoperatively upon exposure, with controls and precautions to reduce contamination of the surrounding field. Samples and controls were analyzed with next-generation sequencing and RT-PCR, metabolomics, and culture-based approaches. Associations between microbial diversity or microbial abundance, and clinical variables were then analyzed using t-tests and ANOVA. Reconstituted biofilm deposition in vitro using the bioreactor was compared by microbial strain and material type using plate-based assays and scanning electron microscopy. RESULTS: Thirty seven devices were analyzed, all of which harbored detectable microbiota. Proteobacteria, Firmicutes and Actinobacteriota were the most common phyla present overall. Beta-diversity differed in the presence versus absence of infection (p = 0.014). Total abundance, based on normalized microbial counts, differed by testing phase (p < 0.001), indication for placement (p = 0.02), diabetes mellitus (p < 0.001), cardiac disease (p = 0.008) and history of UTI (p = 0.008). Significant microbe-metabolite interaction networks were identified overall and in the absence of infection. 24% of biofilms harbored the tetA tetracycline/minocycline resistance gene and 53% harbored the rpoB rifampin resistance gene. Biofilm was reconstituted across tested strains and material types. Ceramic and titanium did not differ in biofilm deposition for any tested strain. CONCLUSIONS: All analyzed SNM devices harbored microbiota. Device biofilm composition differed in the presence and absence of infection and by testing phase. Antibiotic resistance genes including to rifampin and tetracycline/minocycline, which are used in commercially-available anti-infective pouches, were frequently detected. Isolated organisms from SNM devices demonstrated the ability to reconstitute biofilm formation in vitro. Biofilm deposition was similar between ceramic and titanium, materials used in commercially-available SNM device casings. The findings and techniques used in this study together provide the basis for the investigation of the next generation of device materials and coatings, which may employ novel alternatives to traditional antibiotics. Such alternatives might include bacterial competition, quorum-sensing modulation, or antiseptic application, which could reduce infection risk without significantly selecting for antibiotic resistance.

SIRT1 as a potential therapeutic target in pelvic organ prolapse due to protective effects against oxidative stress and cellular senescence in human uterosacral ligament fibroblasts.

INTRODUCTION: The pathogenesis of pelvic organ prolapse (POP), an age-related disease, has not been fully elucidated. Therapeutic targets of POP are limited. Silencing information regulator 2 related enzyme 1 (SIRT1), a gene considered capable of regulating oxidative stress and cellular senescence, has been widely demonstrated involved in aging and age-related diseases. The present study aimed to explore the role of SIRT1 in POP in vivo and in vitro. METHODS: Expression levels of SIRT1 in uterosacral ligament (USL) tissues from patients with or without POP were measured using immunohistochemical assays. SRT1720, a SIRT1 agonist, was used to upregulate SIRT1, and hydrogen peroxide (H2O2) was used to establish an oxidative stress model in human uterosacral ligament fibroblasts (hUSLFs). The effects of SIRT1 on cell viability, apoptosis, senescence, and reactive oxygen species (ROS) levels were detected, respectively. Western blot assays were used to examine expression levels of apoptosis- and senescence-associated biomarkers. Unpaired Student's t test, Mann-Whitney U test, χ2 test, and one-way ANOVA were performed for determining statistically significant differences. RESULTS: Compared to the control group, expression levels of SIRT1 were downregulated in USL tissues and hUSLFs from patients with POP, and associated with stage (p < 0.05). hUSLFs of patients with POP had lower growth rates (p < 0.0001) than those of the control group, which were improved by upregulating SIRT1 (p < 0.05). The senescent proportion was higher in the POP group than the control group (43.63 ± 10.62% vs. 4.84 ± 5.32%, p < 0.0001), which could be reduced by upregulating SIRT1 (p < 0.0001). High ROS levels in the POP group were also alleviated by SRT1720. H2O2 exposure increased ROS levels, inhibited proliferation, and triggered apoptosis and senescence in hUSLFs of patients without POP in a concentration-dependent manner. Further, these damages were alleviated by pretreatment with SRT1720. CONCLUSIONS: SIRT1 is downregulated in patients with POP, and the development of SIRT1 activators or agonists may have applications in the treatment and prevention of POP through antioxidative stress and antisenescence effects.

Management of Tarlov cysts: an uncommon but potentially serious spinal column disease-review of the literature and experience with over 1000 referrals.

Tarlov cysts were thought to be anatomic variants of uncertain etiology and clinical significance when initially described over 80 years ago. They are often detected in routine lumbosacral imaging and generally not reported in a differential diagnosis. There is increasing evidence that at least some Tarlov cysts are symptomatic and can have a significant adverse impact on patients' health and well-being. Women are disproportionately affected with this condition, often presenting with long-standing pain and neurological dysfunctions. Significant gender bias has been a concern in the management of these patients. Unfortunately, there is no consensus on patient selection or management approaches for symptomatic Tarlov cysts. This review article updates information on the prevalence, diagnosis, clinical significance, and treatments of these cysts. Based on these findings and experience with over 1000 patient referrals, a treatment decision algorithm for symptomatic Tarlov cysts was constructed to provide guidance for appropriate management of patients with these complex cysts.

Angiographic challenges of spinal dural and epidural arteriovenous fistulas: report on 45 cases.

PURPOSE: The localization of the fistula level in spinal dural arteriovenous fistulas (dAVFs) and epidural arteriovenous fistulas (edAVFs) remains a diagnostic challenge. METHODS: Consecutive patients with spinal dAVFs and edAVFs in the thoracic, lumbar, and sacral regions were included. The primary endpoint was to describe the characteristics of patients who required angiography with multiple catheterizations of segmental arteries (10 or more). RESULTS: Forty-five patients (median age 69 years; male 89%; dAVFs, n = 31; edAVFs, n = 14) were included. Spinal dAVFs commonly developed in the thoracic region and edAVFs in the lumbosacral region. Fistulas were predicted at the correct level or plus/minus 2 level in less invasive examinations using multi-detector CT angiography (n = 28/36, 78%) and/or contrast-enhanced MR angiography (n = 9/14, 64%). We encountered diagnostic challenges in the localization of fistulas in 6 patients. They underwent angiography a median of 2 times. In each patient, spinal levels were examined at a median of 25 levels with a median radiation exposure of 3971 mGy and 257 ml of contrast. Fistulas were finally localized at the high thoracic region (T4-6) in 3 patients, the sacral region (S1-2) in 2, and the lumbar region (L3) in 1. Four patients were diagnosed with edAVFs and 2 with dAVFs. The correlation coefficient between the fistula level and the rostral end of the intramedullary T2 high-signal intensity on MRI was interpreted as none. CONCLUSION: In patients in whom less invasive examinations failed for fistula localization, high thoracic or sacral AVFs need to be considered.

Effectiveness, safety and cost-effectiveness of sacral neuromodulation for idiopathic slow-transit constipation: a systematic review.

AIM: Sacral neuromodulation (SNM) is a minimally invasive treatment option for functional constipation. Evidence regarding its effectiveness is contradictory, driven by heterogeneous study populations and designs. The aim of this study was to assess the effectiveness, safety and cost-effectiveness of SNM in children and adults with refractory idiopathic slow-transit constipation (STC). METHOD: OVID Medline, OVID Embase, Cochrane Library, the KSR Evidence Database, the NHS Economic Evaluation Database and the International HTA Database were searched up to 25 May 2023. For effectiveness outcomes, randomized controlled trials (RCTs) were selected. For safety outcomes, all study designs were selected. For cost-effectiveness outcomes, trial- and model-based economic evaluations were selected for review. Study selection, risk of bias and quality assessment, and data extraction were independently performed by two reviewers. For the intervention 'sacral neuromodulation' effectiveness outcomes included defaecation frequency and constipation severity. Safety and cost-effectiveness outcomes were, respectively, adverse events and incremental cost-effectiveness ratios. RESULTS: Of 1390 records reviewed, 67 studies were selected for full-text screening. For effectiveness, one cross-over and one parallel-group RCT was included, showing contradictory results. Eleven studies on safety were included (four RCTs, three prospective cohort studies and four retrospective cohort studies). Overall infection rates varied between 0% and 22%, whereas reoperation rates varied between 0% and 29%. One trial-based economic evaluation was included, which concluded that SNM was not cost-effective compared with personalized conservative treatment at a time horizon of 6 months. The review findings are limited by the small number of available studies and the heterogeneity in terms of study populations, definitions of refractory idiopathic STC and study designs. CONCLUSION: Evidence for the (cost-)effectiveness of SNM in children and adults with refractory idiopathic STC is inconclusive. Reoperation rates of up to 29% were reported.