[New S2k guideline "Surgical techniques for gender incongruence"]. / Neue S2k-Leitlinie "Chirurgische Maßnahmen bei Geschlechtsinkongruenz".

BACKGROUND: Various techniques for the surgical treatment of gender incongruence (GI) have been available for years. The spectrum is broad and covers various specialties. In recent years, there has been an increase in the number of clinics offering body-modifying procedures. This has led to a considerable variation in methods in some cases. Although the topic has recently found its way more and more into teaching and the relevant specialist literature, there are still no evidence-based recommendations on the various techniques. AIM: A compendium of established surgical techniques was to be compiled, containing recommendations on indication, performance and aftercare as well as complication management and subjecting them to a consensus-based evaluation. MATERIALS AND METHODS: In accordance with "Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften" (AWMF) regulations, the guideline was developed at level S2k, i.e., it is consensus based. The guideline group was founded in February 2019 in a formal constituent meeting. A total of 14 medical societies and 2 interest groups were recruited for the guideline work. In the end, two consensus meetings were held, which was due to the large number of recommendations and background texts to be adopted. RESULTS: The guideline focuses on the choice and applicability of surgical techniques as well as the wishes of those seeking treatment and protection of fertility. There is a wide variety of methods and treatment goals for each individual. Taking into account medical standards, recommendations, and contraindications, an optimal result that minimizes individual suffering can be achieved together with the person seeking treatment. CONCLUSION: The content of the guideline represents a unique compendium of surgical methods, recommendations for the selection of procedures, and common indications in the field of body-modifying surgery for gender incongruence.

Effect of Focal vs Extended Irreversible Electroporation for the Ablation of Localized Low- or Intermediate-Risk Prostate Cancer on Early Oncological Control: A Randomized Clinical Trial.

Importance: Focal ablative irreversible electroporation (IRE) is a therapy that treats only the area of the tumor with the aim of achieving oncological control while reducing treatment-related functional detriment. Objective: To evaluate the effect of focal vs extended IRE on early oncological control for patients with localized low- and intermediate-risk prostate cancer. Design, Setting, and Participants: In this randomized clinical trial conducted at 5 centers in Europe, men with localized low- to intermediate-risk prostate cancer were randomized to receive either focal or extended IRE ablation. Data were collected at baseline and at regular intervals after the procedure from June 2015 to January 2020, and data were analyzed from September 2021 to July 2022. Main Outcomes and Measures: Oncological outcome as indicated by presence of clinically significant prostate cancer (International Society of Urological Pathology grade ≥2) on transperineal template-mapping prostate biopsy at 6 months after IRE. Descriptive measures of results from that biopsy included the number and location of positive cores. Results: A total of 51 and 55 patients underwent focal and extended IRE, respectively. Median (IQR) age was 64 years (58-67) in the focal ablation group and 64 years (57-68) in the extended ablation group. Median (IQR) follow-up time was 30 months (24-48). Clinically significant prostate cancer was detected in 9 patients (18.8%) in the focal ablation group and 7 patients (13.2%) in the extended ablation group. There was no significant difference in presence of clinically significant prostate cancer between the 2 groups. In the focal ablation group, 17 patients (35.4%) had positive cores outside of the treated area, 3 patients (6.3%) had positive cores in the treated area, and 5 patients (10.4%) had positive cores both in and outside of the treated area. In the extended group, 10 patients (18.9%) had positive cores outside of the treated area, 9 patients (17.0%) had positive cores in the treated area, and 2 patients (3.8%) had positive cores both in and outside of the treated area. Clinically significant cancer was found in the treated area in 5 of 48 patients (10.4%) in the focal ablation group and 5 of 53 patients (9.4%) in the extended ablation group. Conclusions and Relevance: This study found that focal and extended IRE ablation achieved similar oncological outcomes in men with localized low- or intermediate-risk prostate cancer. Because some patients with intermediate-risk prostate cancer are still candidates for active surveillance, focal therapy may be a promising option for those patients with a high risk of cancer progression. Trial Registration: ClinicalTrials.gov Identifier: NCT01835977.

A Multicenter, Randomized, Single-blind, 2-Arm Intervention Study Evaluating the Adverse Events and Quality of Life After Irreversible Electroporation for the Ablation of Localized Low-intermediate Risk Prostate Cancer.

PURPOSE: Our goal was to evaluate the effect of focal vs extended irreversible electroporation on side effects, patient-reported quality of life, and early oncologic control for localized low-intermediate risk prostate cancer patients. MATERIALS AND METHODS: Men with localized low-intermediate risk prostate cancer were randomized to receive focal or extended irreversible electroporation ablation. Quality of life was measured by International Index of Erectile Function, Expanded Prostate Cancer Index Composite questionnaire, and International Prostate Symptom Score. RESULTS: A total of 51 and 55 patients underwent focal and extended irreversible electroporation, respectively. The median follow-up time was 30 months. Rates of erectile dysfunction and rates of adverse events were similar between the 2 groups at 3 months. The focal ablation group seemed to have better International Index of Erectile Function scores at 3 months; it also had a better Expanded Prostate Cancer Index Composite-sexual function score than the extended ablation group across time that was close to statistical significance (mean difference 1.4; 95% CI -0.13 to 2.9, P = .073). There were no significant differences between the 2 groups in other quality-of-life measures. Upon prostate biopsy at 6 months, the rate of residual clinically significant prostate cancer (Gleason ≥3 + 4) was 18.8% and 13.2% in the focal and extended irreversible electroporation groups, respectively, without significant differences. CONCLUSIONS: Focal and extended irreversible electroporation ablation had similar safety profile, urinary function, and oncologic outcomes in men with localized low-intermediate risk prostate cancer. In addition, focal ablation demonstrated superior erectile function outcome over extended irreversible electroporation in the first 3-6 months.

[Genital surgical procedures for feminization in gender dysphoria]. / Genitalchirurgische Maßnahmen zur Feminisierung bei Geschlechtsdysphorie.

The necessity and the benefits of genital approximating surgery in gender dysphoria are established, therefore the indications after careful diagnostics are indisputable. For vaginoplasty, the method of choice is penile inversion, in which the penile skin is inserted as a pedicled flap into the prepared vaginal space. Alternatively, free skin grafts or intestinal segments can be used. Lifelong bougienage of the vagina is obligatory for all methods. The spectrum of complications after vaginoplasty is broad. Of particular note, although rare, is injury to the anterior rectal wall, from which rectovaginal fistulas can result. During the course strictures of the urinary meatus or also the neovagina occur. Corrections must often be surgically undertaken but conservative measures, e.g. intensified bougienage and topical estrogen treatment, can also be successful. Neovaginal infections are treated analogously to infections of a native vagina. A special situation is inflammation of the intestinal neovagina, which must be treated with mesalazine.

Influence of hematopoietic stem cell-derived hepatocytes on liver regeneration after sex-mismatched liver transplantation in humans.

BACKGROUND: Presence of hematopoietic stem-cell-derived hepatocytes after clinical liver transplantation was demonstrated repeatedly. The relevance of this controversial mechanism of regeneration was discussed. Regarding frequency, the demonstrated results were divergent. In the present study, we propose to investigate the influence of growth and regeneration on the frequency of hematopoietic stem-cell-derived hepatocytes in transplanted organs. MATERIAL AND METHOD: Paraffin-embedded liver specimens, obtained as clinically indicated, from female grafts transplanted into male recipients were investigated. The presence of Y-chromosome in hepatocytes, detected by fluorescence in situ hybridization (FISH), was the indicator for recipient origin. Slides were evaluated by assessing the relative number of Y-chromosome containing hepatocytes within 50 images representing an average of 775 hepatocytes. RESULTS: In only 9 out of 81 specimens, single Y-chromosome positive hepatocytes were detected, resulting in a maximal frequency of 0.64%. Six positive specimens were obtained from full-size liver grafts and one from a partial liver graft. In the pediatric group, two positive samples were found. By staining additional sections from the nine positive specimens, no additional positive hepatocytes were detected suggesting an even lower frequency within the whole sample. We did not find any accumulation of Y-chromosome positive cells in any of the individually analyzed patient groups. CONCLUSION: Transdifferentiation of hematopoietic stem cells is an extremely rare event in liver growth and regeneration after transplantation. Due to the low number of positive events, the biological relevance seems questionable.

Probe production for in situ hybridization by PCR and subsequent covalent labeling with fluorescent dyes.

A simple procedure for fluorescent labeling of probes just before in situ hybridization is provided. Aminoallyl-dUTP is introduced during probe production by polymerase chain reaction (PCR). The aminoallyl-dUTP functions as a reactive site for subsequent labeling of the probe. Activated fluorescent dyes such as fluorescein are covalently attached to the probe through the formation of a stable amide bond. Labeled probes are purified by size-exclusion gel chromatography to remove unincorporated dye. Target genes used to demonstrate the efficacy of this technique with in situ hybridization are rat Y-chromosome and rat granulocyte colony-stimulating factor receptor. PCR amplicons containing aminoallyl-dUTP were produced in high yield. Probes obtained after labeling with activated fluorophores demonstrated high intrinsic activity within in situ hybridizations. The introduction of aminoallyl-dUTP into the PCR reaction enables the production of "unlabeled" probes by PCR having a shelf life, which is not limited by the storage and stability challenges of fluorophore-labeled probes. Subsequent labeling of the probes with activated fluorescent dyes just before use allows one step in situ hybridization with high activity and minimal background staining.