Sexual Function in Patients Suffering from Sacrococcygeal Pilonidal Sinus Disease

Introduction Sexual function is one of the aspects upon which quality of life (QoL) is based. Although previous studies have evaluated the influence of sacrococcygeal pilonidal sinus disease (SPSD) on QoL, no data are available on the influence of SPSD on sexual function in a highly active sexual population based on the age range. The aim of this prospective study was to evaluate whether SPSD has a negative impact on sexual function and whether this is influenced by the surgical treatment of SPSD. Methods Sexual function was pre- and postoperatively assessed by the Sexual Self-Consciousness Scale (SSCS; score range 0-48), subdivided into the sexual embarrassment (SE; score range 0-24) and sexual self-focus subscale (SFF; score range 0-24). The higher the score, the higher is the sexual dysfunction. Patients were also asked whether SPSD influenced their sexual functioning. Results A total of 88 male patients who underwent surgical treatment for SPSD were included in the study. The mean (+/- SD) preoperative SSCS score was 14.5 +/- 9.1 and 13.9 +/- 8.4 two weeks postoperatively (p=0.394). Six and twelve weeks after surgery, there was a significant reduction to 12.2 +/- 9.0 (p=0.002) and 12.3 +/- 8.8 (p=0.013), respectively. SE decreased from 5.5 +/- 5.1 preoperatively to 5.1 +/- 4.6 (p=0.258), 4.2 +/- 4.7 (p=0.004) and 4.0 +/- 4.6 (p=0.013) two, six, and twelve weeks after surgery. For SFF, there was a decrease from 9.0 +/- 5.0 to 8.9 +/- 4.9 (p=0.717), 7.8 +/- 5.2 (p=0.004) and 8.2 +/- 5.3 (p=0.168), respectively. Preoperatively, 70% of the patients totally or partially disagreed that SPSD influenced their sexual functioning, and this increased to 80% of the patients 12 weeks after surgery. Conclusion This prospective study showed a significant decrease in sexual dysfunction, both six and twelve weeks after surgery, compared to preoperatively in patients suffering from SPSD

Endosonography With or Without Confirmatory Mediastinoscopy for Resectable Lung Cancer:A Randomized Clinical Trial

PURPOSE:Resectable non-small-cell lung cancer (NSCLC) with a high probability of mediastinal nodal involvement requires mediastinal staging by endosonography and, in the absence of nodal metastases, confirmatory mediastinoscopy according to current guidelines. However, randomized data regarding immediate lung tumor resection after systematic endosonography versus additional confirmatory mediastinoscopy before resection are lacking.METHODS:Patients with (suspected) resectable NSCLC and an indication for mediastinal staging after negative systematic endosonography were randomly assigned to immediate lung tumor resection or confirmatory mediastinoscopy followed by tumor resection. The primary outcome in this noninferiority trial (noninferiority margin of 8% that previously showed to not compromise survival, Pnoninferior &lt;.0250) was the presence of unforeseen N2 disease after tumor resection with lymph node dissection. Secondary outcomes were 30-day major morbidity and mortality.RESULTS:Between July 17, 2017, and October 5, 2020, 360 patients were randomly assigned, 178 to immediate lung tumor resection (seven dropouts) and 182 to confirmatory mediastinoscopy first (seven dropouts before and six after mediastinoscopy). Mediastinoscopy detected metastases in 8.0% (14/175; 95% CI, 4.8 to 13.0) of patients. Unforeseen N2 rate after immediate resection (8.8%) was noninferior compared with mediastinoscopy first (7.7%) in both intention-to-treat (Δ, 1.03%; UL 95% CIΔ, 7.2%; Pnoninferior =.0144) and per-protocol analyses (Δ, 0.83%; UL 95% CIΔ, 7.3%; Pnoninferior =.0157). Major morbidity and 30-day mortality was 12.9% after immediate resection versus 15.4% after mediastinoscopy first (P =.4940).CONCLUSION:On the basis of our chosen noninferiority margin in the rate of unforeseen N2, confirmatory mediastinoscopy after negative systematic endosonography can be omitted in patients with resectable NSCLC and an indication for mediastinal staging.</p

Towards KRAS-directed therapy : Dependency of metastatic colorectal cancer cells on mutant KRAS

The aims of this thesis were 1) to assess the dependency of late-stage colorectal carcinoma (CRC) cells on mutant KRAS and 2) to test the potential of reovirus T3D and COX-2 inhibitors as RAS-targeted therapeutics in experimental models of CRC and colorectal liver metastases. The role of oncogenic RAS in the formation of colorectal liver metastases is evaluated in chapter 2. We give an overview of the existing literature of both experimental (in vitro and in vivo) and clinical studies that address this issue. Imaging of tumor growth, tumor characteristics and the effect of therapeutic interventions in living animals (intravital imaging) has been made possible by new molecular and optical techniques. In chapter 3 we validate bioluminescence imaging as a minimally invasive tool to monitor tumor growth in the liver. KRAS is important as an initiator of CRC tumorigenesis. In chapters 4 and 5 we asses the dependency of late stage CRC cells on mutant KRAS. We analyze this with a highly aggressive CRC cell line that harbors an endogenous KRAS mutation. In chapter 4 we assess the effect of endogenous mutant KRAS on the interplay between CRC cells and the immune system. In chapter 5 we analyze which distinct stages in the process of liver colonization are affected by endogenous mutant KRAS. RAS proteins signal through a number of distinct signaling cascades. COX-2 is important in the development of multiple cancers, including CRC and bladder carcinoma. The exact relationship between endogenous mutant RAS and COX-2 is unclear. In chapter 6 we investigate this relationship in CRC cells. Furthermore, we investigate the potential therapeutic effects of selective COX-2 inhibitors in a mouse model of established CRC liver metastasis in chapter 6 and in a mouse model of bladder carcinomas in chapter 7. In the ensuing chapters we focus on reovirus, one of the most promising RAS-directed therapeutics. We investigate the mechanism underlying the RAS-specificity of tumor cell killing in chapters 8 and 9. Next, in chapter 10 we assess the potential of reovirus as a therapeutic agent against experimental CRC liver metastases and investigate the role of the immune system on the therapeutic effect. In chapter 11 we investigate the susceptibility of freshly resected human liver metastases to reovirus T3D infection. We conclude that late stage CRC cells are dependent on mutant KRAS for their invasiveness, metastatic potential and for immune evasion. This makes mutant KRAS an interesting therapeutic target with great potential against metastatic colorectal carcinomas. COX-2 is a direct target of mutant KRAS and selective COX-2 inhibitors have therapeutic potential against colorectal liver metastases and bladder carcinomas. Mutant KRAS sensitizes CRC cells to reovirus T3D induced apoptosis. The therapeutic efficacy of reovirus T3D against established liver metastases is hampered by the host immune system but can be increased by concomitant immunosuppression. The mislocalization of the reovirus receptor JAM-1 in human colorectal liver metastases may be an obstacle for its use as a oncolytic agent in the clinic

Phenolisation of the Sinus Tract in Recurrent Sacrococcygeal Pilonidal Sinus Disease:A Prospective Cohort Study

PurposePhenolisation is a minimally invasive treatment option in patients with primary pilonidal disease. However, most studies focus on patients with primary pilonidal sinus disease, while data of patients with recurrent pilonidal disease are very scarce. The purpose of this study was to evaluate phenolisation of the sinus tract in patients with recurrent pilonidal sinus disease after previous surgery for SPSD.MethodsThis single-center prospective cohort study included 60 patients with recurrent pilonidal disease. Loss of days of normal daily activities, surgical site infection, wound epithelization, quality of life, and complaints related to pilonidal disease were postoperatively assessed.ResultsA total of 57 patients (95%) were treated with phenolisation and the median loss of days of normal daily activities was 5.0 (1.0 - 12.0) days. Fifty-one patients (89.5%) resumed normal daily activities after two weeks. Surgical site infection occurred in five patients (8.8%). Compared to preoperative scores, quality of life was significantly higher 12 weeks postoperatively (p=0.014) and pain and itch scores were lower after six and 12 weeks (p = 0.005). Wounds were completely healed in 45 of 51 patients (89.8%) who were available after 12 weeks of follow-up.ConclusionPhenolisation for recurrent pilonidal disease is safe with a median complete return to daily activities within five days and complete wound healing after three months in 90%. Therefore, phenolisation should be considered as a treatment option in patients with recurrent pilonidal sinus disease.</p

Long-term Outcome of Radical Excision Versus Phenolization of the Sinus Tract in Primary Sacrococcygeal Pilonidal Sinus Disease: A Randomized Controlled Trial

BACKGROUND: Phenolization of pilonidal sinus disease has been shown to have advantages over radical excision with regard to short-term outcome; however, long-term outcomes are essentially lacking. OBJECTIVE: The aim of this randomized controlled trial was to compare the long-term outcome of pit excision and phenolization of the sinus tracts vs radical excision with primary wound closure in pilonidal sinus disease. DESIGN: Single-center, randomized controlled trial. SETTINGS: A primary teaching hospital in the Netherlands. PATIENTS: The study population included patients with primary pilonidal sinus disease presented between 2013 and 2017. INTERVENTIONS: Patients were randomly assigned to either pit excision with phenolization of the sinus tract(s) or excision with primary off-midline wound closure. MAIN OUTCOME MEASURES: The main outcomes included recurrence, quality of life (Short-Form 36), and patient's satisfaction. RESULTS: A total of 100 patients were randomized. Seventy-four patients (77.1%) were available for long-term follow-up. The mean (±SD) time to follow-up was 48.4 (±12.8) months for the phenolization group and 47.8 (±13.5) months for the excision group. No significant difference was found between both groups regarding quality of life. Two patients in the phenolization group (5.6%) and 1 in the excision group (2.6%) developed a recurrence ( p = 0.604). The impact of the whole treatment was significantly less after phenolization ( p = 0.010). LIMITATIONS: The response rate was almost 80% in this young patient population, patients and assessors were not blinded for the type of surgery, and the results are only applicable to primary pilonidal sinus disease. CONCLUSIONS: Because of the previously shown favorable short-term results and the currently reported comparable long-term recurrence rate and quality of life between phenolization and excision, phenolization should be considered the primary treatment option in patients with pilonidal sinus disease. See Video Abstract at http://links.lww.com/DCR/C27 .NTR4043. RESULTADO A LARGO PLAZO DE LA ESCISIN RADICAL FRENTE AL TRATAMIENTO CON FENOL DEL TRACTO SINUSAL EN LA ENFERMEDAD DEL SENO PILONIDAL SACRO COCCGEO PRIMARIO UN ENSAYO ALEATORIO CONTROLADO: ANTECEDENTES:El tratamiento con fenol de la enfermedad del seno pilonidal ha demostrado tener ventajas sobre la escisión radical con respecto al resultado a corto plazo; sin embargo, los resultados a largo plazo aún se encuentran escasos.OBJETIVO:El objetivo de este ensayo aleatorio controlado fue comparar el resultado a largo plazo de la escisión de la fosa del quiste y el tratamiento con fenol de los trayectos sinusales frente a la escisión radical con cierre primario de la herida en la enfermedad del seno pilonidal.DISEÑO:Ensayo aleatorio controlado de un solo centro.AJUSTES:Hospital de enseñanza primaria en los Países Bajos.PACIENTES:Pacientes con enfermedad primaria del seno pilonidal presentados entre 2013 y 2017.INTERVENCIONES:Los pacientes fueron asignados de manera aleatoria a la escisión de la fosa del quiste y posterior administración de fenol de los tractos sinusales o a la escisión con cierre primario de la herida fuera de la línea media.PRINCIPALES MEDIDAS DE RESULTADO:Recurrencia, calidad de vida (Short-Form 36) y satisfacción del paciente.RESULTADOS:Un total de 100 pacientes con enfermedad primaria del seno pilonidal fueron aleatorizados; 50 pacientes fueron sometidos al tratamiento con fenol y 50 a la escisión radical. Eventualmente, 74 pacientes (77,1%) estuvieron disponibles para seguimiento a largo plazo; 36 pacientes después del uso del fenol y 38 después de la escisión. El tiempo medio (± desviación estándar) de seguimiento fue de 48,4 (± 12,8) y 47,8 (± 13,5) meses, respectivamente. No hubo diferencia significativa entre ambos grupos con respecto a la calidad de vida. En el grupo tratado con fenal, dos pacientes (5,6%) desarrollaron recurrencia y un paciente (2,6%) en el grupo de escisión ( p = 0,604). El impacto de todo el tratamiento fue significativamente menor después del uso del fenol (p = 0,010).LIMITACIONES:La tasa de respuesta fue de casi el 80% en esta población de pacientes jóvenes, los pacientes y los evaluadores no estaban cegados por el tipo de cirugía, los resultados son solo aplicables a la enfermedad primaria del seno pilonidal.CONCLUSIONES:Debido a los resultados favorables a corto plazo descritos y a la tasa de recurrencia a largo plazo y la calidad de vida comparables actualmente informadas entre la administración de fenol y la escisión con cierre primario de la herida para la enfermedad primaria del seno pilonidal, la administración de fenol del tracto sinusal debe considerarse como opción de tratamiento primario en pacientes con enfermedad del seno pilonidal. Consulte Video Resumen en http://links.lww.com/DCR/C27 . (Traducción-Dr. Osvaldo Gauto )Registro de prueba holandés-ID:NTR4043

Sensitization to Apoptosis Underlies Kras(D12)-Dependent Oncolysis of Murine C26 Colorectal Carcinoma Cells by Reovirus T3D

Reovirus T3D is an oncolytic agent that preferentially targets tumor cells expressing an activated Ras oncogene. Ras signaling interferes with the cellular stress response that inhibits translation of reovirus RNAs. Murine C26 colorectal carcinoma cells express a mutant Kras(D12) gene. Reovirus T3D efficiently kills C26 cells, but not C26 cells in which the Kras(D12) mRNA is stably repressed by expression of Kras(D12)-directed short-hairpin RNAs. Surprisingly, neither reovirus T3D protein synthesis nor T3D virus yields were suppressed by deletion of Kras(D12). Rather, reovirus-induced tumor cell apoptosis was completely abrogated as a result of Kras knockdown. We conclude that sensitization of C26 tumor cells to reovirus-induced apoptosis underlies the Ras dependency of reovirus T3D oncolysis

Differential Notch and TGFβ Signaling in Primary Colorectal Tumors and Their Corresponding Metastases

Background: Loss of epithelial morphology and the acquisition of mesenchymal characteristics may contribute to metastasis formation during colorectal tumorigenesis. The Wnt, Notch and TGFβ signaling pathways control tissue homeostasis and tumor development in the gut. The relationship between the activity of these pathways and the expression of epithelial and mesenchymal markers was investigated in a series of primary colorectal tumors and their corresponding metastases

Male infertility after endoscopic Totally Extraperitoneal (Tep) hernia repair (Main): rationale and design of a prospective observational cohort study

Abstract Background To describe the rationale and design of an observational cohort study analyzing the effects of endoscopic Totally Extraperitoneal (TEP) hernia repair on male fertility (MAIN study). Methods and design The MAIN study is an observational cohort study designed to assess fertility after endoscopic TEP hernia repair. The setting is a high-volume single center hospital, specialized in TEP hernia repair. Male patients of 18-60 years of age, with primary, reducible, bilateral inguinal hernias and no contraindications for endoscopic TEP repair are eligible for inclusion in this study. Patients with an ASA-classification ≥ III and patients with recurrent and/or scrotal hernias and/or a medical history of pelvic surgery and/or radiotherapy, known fertility problems, diabetes and/or other diseases associated with a risk of fertility problems, will be excluded. The primary outcome is the testicular perfusion before and 6 months after TEP hernia repair (assessed by means of a scrotal ultrasonography). Secondary endpoints are the testicular volume (Ultrasound), semen quality and quantity and the endocrinological status, based on serum levels of the sexual hormones follicle-stimulating hormone (FSH), luteinizing hormone (LSH), testosterone and inhibin B before and 6 months after TEP hernia repair. Discussion The use of polypropylene mesh is associated with a strong foreign body reaction which could play a role in chronic groin pain development. Since the mesh in (endoscopic) inguinal hernia repair is placed in close contact to the vas deferens and spermatic vessels, the mesh-induced inflammatory reaction could lead to a dysfunction of these structures. Relevant large and prospective clinical studies on the problem are limited. This study will provide a complete assessment of fertility in male patients who undergo simultaneous bilateral endoscopic TEP hernia repair, by analyzing testicular perfusion and volume, semen quantity and quality and endocrinological status before and 6 months after TEP repair. Trial registration The MAIN study is registered in the Dutch Trial Register (NTR2208)</p