[Prosthetics after construction of the outer genitalia for transmen]. / Prothetik nach Genitalaufbau bei Transmännern.

BACKGROUND: Growing awareness of gender identity issues and a rising prevalence of female-to-male transsexualism is increasing demand for surgical solutions that deliver both aesthetically and functionally satisfying outer genitalia for transmen. OBJECTIVE: This article summarizes the available prosthetic options, describes different surgical approaches and reviews the outcome of prosthetics for transmen with a focus on penile prosthesis in phalloplasty. METHODS: Current international standards of care, reviews and original publications are critically reviewed and correlated with our own experience with more than 400 transmen at two interdisciplinary referral centres in Frankfurt, Germany and London, UK. RESULTS: Despite of a wide range of different phalloplasty techniques and prosthetic types, the currently most used technique is implantation of a three-piece, inflatable penile prosthesis in a radial-free-flap phalloplasty. There is still an ongoing debate about the number of implanted penile prosthesis cylinders, the use of customised corporoplasty-windsocks for the cylinder(s), and the location for the placement of the reservoir. At present there is only one penile prosthesis design for use in phalloplasties and long-term results are still pending. CONCLUSION: There is still no ideal implant available for the use in phalloplasties. The current literature does not provide evidence-based treatment algorithms, which is also due to a lack of prospective randomised studies and validated measurement tools for the postoperative outcome. Initial data for the first transmen-specific penile prosthesis as well as an increase of transgender studies might lead to an improvement of treatment and the quality-of-life of the affected transmen.

Simultaneous correction of a pectus excavatum with tubular breast deformity using a custom-made silicone implant.

Pectus excavatum (PE) is one of the most common congenital deformities of the thorax and is characterized by a depressed sternum with reduction of the antero-posterior thoracic diameter. Although the majority of patients with PE have no physiologic limitations, it is often associated with psychological problems influencing the patients' quality of life. Surgical treatment options show particular variation with regard to invasiveness and morbidity of the respective procedures. Surgical treatment using a custom-made silicone implant represents a less invasive alternative for patients without further accompanying physical symptoms. This article describes the simultaneous correction of a PE combined with tubular breast deformity using this minimally invasive technique.

[Gender reassignment from female to male : Phalloplasty]. / Geschlechtsangleichung von Frau zu Mann : Phallusplastik.

BACKGROUND: The increasing prevalence of gender dysphoria necessitates an evaluation of the literature of phalloplasty techniques for female to male transgender individuals. OBJECTIVE: The following article provides an overview of the current surgical concepts and complications of phalloplasty, associated urethrogenitoplasty and the implantation of prostheses in phalloplasty. MATERIAL AND METHODS: Current international reviews and original publications from 2010 to 2020 were reviewed and correlated with our referral center experience with more than 350 female to male transgender patients over the last 25 years. RESULTS: Free radial forearm flap phalloplasty is the most widely used technique, followed by an anterolateral thigh flap (ALT flap) and pedicled or microsurgical transplantation. Hydraulic multicomponent prostheses are given preference and supplementary surgical techniques, such as scrotoplasty and glans sculpturing can make sense or be necessary. The complication rates after phalloplasty and after insertion of penile prostheses are substantial. Nevertheless, the overall patient reported satisfaction rate in the majority of studies is often over 80%. CONCLUSION: Due to the increasing prevalence of gender dysphoria there is currently a need for interdisciplinary referral centers for gender reassignment surgery. A certain standardization of surgical techniques and timing would be desirable but a review of the current literature shows a high heterogeneity so that this cannot be derived from the currently available literature. It is hoped that the recently founded S2K guideline committee on operative treatment of gender dysphoria under the auspices of the German Society for Urology and the Society for Plastic and Reconstructive Surgery can report an initial collection of experiences in 2021.

Innate immune response of human epidermal keratinocytes and dermal fibroblasts to in vitro incubation of Trichophyton benhamiae DSM 6916.

BACKGROUND: Superficial cutaneous infection caused by the zoophilic dermatophyte Trichophyton benhamiae is often associated with a highly inflammatory immune response. As non-professional immune cells, epidermal keratinocytes and dermal fibroblasts contribute to the first line of defence by producing pro-inflammatory cytokines and antimicrobial peptides (AMP). OBJECTIVE: Purpose of this study was to gain a deeper understanding of the pathogenesis and the fungal-host interaction as not much is known about the innate immune response of these cutaneous cells against T. benhamiae. METHODS: Using a dermatophytosis model of fibroblasts and keratinocytes incubated with T. benhamiae DSM 6916, analyses included determination of cell viability and cytotoxicity, effects on the innate immune response including expression and secretion of pro-inflammatory cytokines/chemokines and expression of AMP, as well as alterations of genes involved in cell adhesion. RESULTS: Trichophyton benhamiae DSM 6916 infection led to severe cell damage and direct induction of a broad spectrum of pro-inflammatory cytokines and chemokines in both cutaneous cells. Only keratinocytes differentially up-regulated AMP genes expression after T. benhamiae DSM 6916 infection. Expression of AMPs in fibroblasts was not inducible by fungal infection, whereas their absences potentially contributed to a continuous increase in the fungal biomass on fibroblasts, which in turn was reduced in keratinocytes possibly due to the antimicrobial actions of induced AMPs. On mRNA level, T. benhamiae DSM 6916 infection altered cell-cell contact proteins in keratinocytes, indicating that targeting specific cell-cell adhesion proteins might be part of dermatophytes' virulence strategy. CONCLUSION: This study showed that in addition to immune cells, keratinocytes and fibroblasts could participate in antimicrobial defence against an exemplary infection with T. benhamiae DSM 6916.

Fine-needle aspiration cytology for parotid lesions, can we avoid surgery?

OBJECTIVE: Salivary gland neoplasms are rare tumours, with most arising in the parotid gland. Fine-needle aspiration cytology (FNAC) is a common method for preoperative evaluation of parotid masses, although its usefulness is controversial. This study was designed to evaluate the accuracy of FNAC in a large cohort of patients, with emphasis on diagnosis of benign tumours and especially Warthin tumour which can be managed conservatively. STUDY DESIGN: Retrospective case series with chart review. SETTING: Tertiary medical centre. SUBJECTS AND METHODS: From 1991 to 2014, all patients 18 or older with both preoperative FNAC and postoperative pathology report were included. Patients with a history of head and neck malignancy or chronic sialoadenitis and patients who had undergone prior oncological treatment were excluded. RESULTS: 470 patients were available for analysis. Overall accuracy was 82.6%. Positive predictive value (PPV) varied between 88.6% and 94.3% for pleomorphic adenoma and 77.1%-100% for Warthin tumour, with values varying depending on different characteristics of patients (eg age, smoking status). For pathologically proven malignant tumours, the FNAC diagnosis was benign or non-diagnostic in 26% of the cases. CONCLUSION: Fine-needle aspiration cytology has limited utility in confirming a benign diagnosis of a parotid mass for most patients, although for some subpopulations, the PPV may be high enough to defer surgery.

Duodenal intraepithelial lymphocytosis is common in children without coeliac disease, and is not meaningfully influenced by Helicobacter pylori infection.

BACKGROUND: Increased numbers of duodenal intraepithelial lymphocytes (IELs) characterise coeliac disease (CD) but have also been described in noncoeliacs. Controversy exists regarding an association between increased IELs and infection with Helicobacter pylori, which is commonly found in children. AIM: To assess the relationship between H. pylori infection and duodenal IELs in a large cohort of children, with and without CD. METHODS: We reviewed gastric and duodenal biopsies of children who underwent esophagogastroduodenoscopy between January 2006 and February 2013 because of either recurrent abdominal pain (RAP) or suspected CD at Schneider Children's Medical Center of Israel, a referral centre for Israel's largest Health Maintenance Organization. The duodenal IEL count and H. pylori presence in antral biopsies were determined for each specimen. RESULTS: Children with RAP (n = 693) or CD (n = 306) were included. Among children with RAP, H. pylori was present in 33.8%. The mean IEL count in the H. pylori positive RAP group was 17.8(±8.8)/100 enterocytes, vs. 15.8(±8.3) in the H. pylori negative patients (P = 0.004). Increased IEL counts (≥25 IELs/100 enterocytes) were found in 15.7% of H. pylori negative, noncoeliac children. Among children with CD, there was no significant difference in IEL counts according to H. pylori status: 73.1(±26.1) vs. 72.6 (±26.5) in H. pylori positive and negative patients respectively. CONCLUSIONS: Our study suggests that slightly elevated duodenal intraepithelial lymphocyte counts are common in the paediatric population. Helicobacter pylori infection has no major influence on the intraepithelial lymphocyte counts in children with recurrent abdominal pain or children with coeliac disease.

Abdominal actinomycosis masquerading as colon cancer in a liver transplant recipient.

Infections in transplant recipients are associated with high morbidity and mortality, making their early recognition and treatment particularly important. Abdominal actinomycosis is a rare clinical entity and difficult to diagnose because of its various and nonspecific features. We describe a 57-year-old patient who presented with abdominal actinomycosis simulating colon cancer 6 years after liver transplantation. The main symptom was abdominal pain. Abdominal computed tomography and colonoscopy revealed an intraluminal 4.5 cm mass in the right colon, raising suspicions of a colonic malignancy and leading to surgical intervention. The postoperative pathologic study showed sulfur granules in the resected specimen compatible with abdominal actinomycosis. No signs of recurrence were seen throughout the 6-month follow-up. The literature on actinomycosis infections in immune-compromised hosts is reviewed. This presentation of actinomycosis in a liver transplant recipient has not been described previously, to our knowledge.

Carcinoma within solitary ductal papilloma of the breast.

BACKGROUND: Solitary ductal papilloma of the breast, traditionally considered a benign disorder, was recently found to have malignant potential, especially when associated with atypical ductal hyperplasia. METHODS: All patients diagnosed with solitary ductal papilloma at a tertiary medical center from 1994 to 2004 were identified by a database search. Background, clinical and pathological data were collected for those with a carcinoma within the papilloma, and their pathological specimens were revised. RESULTS: Of the 3849 breast biopsies performed in our medical center during the study period, 77 (2%) yielded a solitary ductal papilloma. In 12 cases (15.6% of all solitary ductal papillomas; 0.3% of all breast biopsies), a carcinoma was found within the papilloma. Ten were diagnosed as carcinoma in situ and 2 as microinvasive carcinoma. CONCLUSION: In the present series, the incidence of carcinoma within solitary ductal papilloma was 15.6%, indicating that solitary ductal papillomas have malignant potential. SUMMARY: Carcinoma within solitary ductal papilloma of the breast was found in 15.6% of all papillomas. This seems to indicate a malignant potential of papillomas and the need for surgical excision.

[Exercise testing by spiroergometry in a patient with sarcoidosis stage II. An unusual combination of functional impairments]. / Spiroergometrie bei einem Patienten mit Sarkoidose II. Eine aussergewöhnliche Kombination von Funktionsstörungen.

Sarcoidosis is a multisystem disease of unknown origin characterised by epitheloid cell granulomas in the lung and many other organs. The measurement of the alveolo-arterial O(2)-gradient (AaDO(2)) during exercise is the most sensitive method to detect the involvement of the lung with impairment of gas exchange. The method is suitable for follow-up observations to make the indication for a steroid therapy in the case of deterioration. In this case presentation using the 9-panel display proposed by Wasserman we diagnosed besides a slight impairment of the gas exchange a cardiocirculatory dysfunction with a reduction of the oxygen pulse and a reduced minute ventilation with a decrease of the alveolar ventilation. The hypoventilation could be explained by a weakness of the respiratory muscles or a reduction of the central respiratory drive. The functional disturbances could be diagnosed by spiroergometry without expensive or invasive methods. The findings should be examined more specifically with regard to therapeutic consequences.

Development of a large bladder calculus on sutures used for pubic bone closure following extrophy repair.

Bladder exstrophy is a rare congenital condition that occurs in 1 to 30,000 live births. Primary bladder closure is usually performed in the first days of life in conjunction with an iliac osteotomy in order to achieve a more secure bladder closure. We report a case of a large bladder stone with secondary right-sided hydronephrosis in a 3-year-old child who underwent exstrophy repair at the age of 7 months. During the exstrophy repair a no. 1 braided, polyester, non-absorbable suture was used to close the pubic bones and served as a nidus for intravesical stone formation. This case substantiates the lithogenic nature of non-absorbable sutures in contact with urine as well as the need for close post-operative follow-up in these patients.

Gastric corpus mucin expression after partial gastrectomy, in relation to colonization with Helicobacter pylori.

Twelve different genes for mucin have been described. MUC5AC and MUC6 encode the secreted apomucins of the stomach. A gradient from the surface epithelium (foveola) to the glands is typical for MUC5AC synthesis, whereas a gradient in the opposite direction was found for MUC6. Our goal was to determine the distribution of MUC5AC and MUC6 in the postoperative stomach, with relation to the H. pylori status. Gastric corpus biopsy specimens from patients who underwent partial gastrectomy were examined by immunohistochemistry for mucin gene (MUC5AC and MUC6) apoproteins. We used polyclonal antibodies for amino acid tandem repeats of both proteins. A scoring system (0-3) was used to assess staining intensity at four sites: the lumen, the foveola, the mucous neck cells, and the glands. Helicobacter pylori status was determined by histology and rapid urease test and was considered positive or negative when both tests were positive or negative, respectively. We studied 19 H. pylori-positive and 32 H. pylori-negative patients. No significant change in MUC5AC or MUC6 synthesis and secretion was demonstrated between H. pylori-positive or -negative patients. A gradient similar to that shown for the intact stomach (from the surface epithelium to the glands) for MUC5AC protein and an increase of MUC6 protein presentation from the mucous neck cell to the glands were demonstrated. The pattern of MUC5AC protein synthesis was not different between H. pylori-positive and -negative patients in the postoperative stomach. MUC6 expression was higher in the foveola in H. pylori-positive patients, whereas there was no difference in the other cell layers.

Does Helicobacter pylori affect gastric mucin expression? Relationship between gastric antral mucin expression and H. pylori colonization.

BACKGROUND/OBJECTIVE: Helicobacter pylori colonizes the gastric mucous gel layer, the surface epithelium and glands. It has been shown that H. pylori infection causes aberrant expression of gastric mucins MUC 5 and MUC 6. This study aimed to determine the distribution of MUC 5 and MUC 6 in the gastric antrum of dyspeptic patients, and to investigate changes in this pattern in the presence of H. pylori and after successful eradication. MATERIALS AND METHODS: Gastric antrum biopsy specimens were examined by immunohistochemistry for mucin gene (MUC 5 and MUC 6) expression. Polyclonal antibodies were used to detect amino acid tandem repeats of each protein. A scoring system (0-3) was used to assess staining intensity at three sites: foveola, mucous neck cells and glands. H. pylori status was determined by histology and rapid urease test, and considered positive or negative when both tests were positive or negative, respectively. The study included 49 patients positive for H. pylori, in 36 of whom successful eradication was performed, and 11 H. pylori-negative patients. RESULTS: There was a gradient of MUC 5 expression, higher to lower, from the surface to the glands, which was more pronounced before eradication. Increased MUC 5 synthesis in the mucous neck cells and in the glands was found after H. pylori eradication (P = 0.016). MUC 6 was synthesized in the glands more than in the mucous neck cells or foveola. MUC 6 was also secreted into the lumen and probably comprised the superficial part of the unstirred mucous layer. CONCLUSION: The change in MUC 5 synthesis may reflect H. pylori colonization.

Use of guanfacine to control self-injurious behavior in two rhesus macaques (Macaca mulatta) and one baboon (Papio anubis).

BACKGROUND AND PURPOSE: Self-injurious behavior (SIB) affects 0.8 to 10% of individually housed non-human primates, and is a substantial threat to their health and well being. The potential for SIB to involve multiple neurotransmitters and the complex variations in response to external stressors complicate case management. Modulation of the adrenergic system by use of guanfacine, an alpha2A-adrenergic receptor agonist, was assessed as a novel therapeutic strategy for SIB. METHODS: The efficacy of guanfacine against SIB was evaluated in 11 self-biting episodes among two rhesus macaques (Macaca mulatta) and one baboon (Papio cynocephalus anubis). Affected animals were given guanfacine IM or PO at 0.5 mg/kg of body weight twice daily (rhesus) or 0.3 mg/kg (baboon) for 5 to 10 days, followed by gradual reduction of the dose to 0.25 mg/kg (rhesus) or 0.15 mg/kg (baboon) once daily over an average of 33 days. RESULTS: The 0.5 mg/kg twice daily regimen of guanfacine halted all self-biting, whereas reducing the dose to 0.25 mg/kg given twice daily or 0.5 mg/kg given once daily resulted in reversion to self-biting in four of the 11 episodes. Recurrence was controlled by returning to twice daily 0.5 mg/kg dosing for one aggressive episode, and resolved in the three milder episodes without dose or frequency being increased. Self-biting after discontinuation of therapy recurred six times over five years in case 1, three times over 1.5 years in case 2, and three times over one year in case 3. Clinical assessment suggested that guanfacine therapy decreased agitation without overt side effects associated with alpha2-agonists, such as profound sedation. CONCLUSION: The mechanism for guanfacine inhibition of self-biting is unclear, but could result from strengthening of prefrontal cortex inhibitory functions. Guanfacine therapy provides an effective psychological stabilizing tool that alleviates self-biting, and provides time to assess and address external stressors and triggers.

Gastrointestinal anastomosis with the nickel-titanium double ring.

We used a dog model to test the safety and effectiveness of sutureless gastrointestinal anastomoses (n = 23) (end-to-end, end-to-side, or side-to-side) with the nickel-titanium double ring with temperature-dependent shape memory. Results were compared to conventional hand-sutured anastomoses (n = 5). Examination performed after 2 weeks' follow-up showed no leaks and no difference in return of bowel function between the experimental groups and the control group. Microscopic studies showed a complete epithelial lining and perfectly functioning anastomoses. We conclude that the nickel-titanium double-ring device may have an important place in the armamentarium of the gastrointestinal surgeon.

HLA-DR and beta 2 microglobulin expression in medullary and atypical medullary carcinoma of the breast: histopathologically similar but biologically distinct entities.

AIMS: To examine the expression of HLA-DR and beta 2 microglobulin in medullary carcinoma and atypical medullary carcinoma of the breast to determine if the effective presentation of tumour antigens to the immune system can differentiate between these two histopathologically similar entities. METHODS: Expression of HLA-DR and beta 2 microglobulin was examined by immunohistochemical methods in five samples of medullary carcinoma of the breast, which has a relatively favourable prognosis, six samples of atypical medullary carcinoma of the breast, which has a prognosis closer to that of regular invasive duct carcinoma, and 20 samples of invasive duct carcinomas, 10 with an accompanying lymphocytic infiltrate. RESULTS: A positive and significant correlation was found between tumour type and both HLA-DR and beta 2 microglobulin expression. Expression was most prominent in medullary carcinoma, followed by atypical medullary carcinoma and invasive duct carcinoma with and without lymphocytic infiltrates. The mean intensity and percentage of HLA-DR tumour immunostaining were significantly higher in medullary carcinoma than in the other three tumour groups, as was the mean intensity of beta 2 microglobulin immunostaining. Mean percentage of beta 2 microglobulin immunostaining was significantly higher in medullary carcinoma than in invasive duct carcinoma without lymphocytic infiltrates, and showed a trend to increase from invasive duct carcinoma with lymphocytic infiltrates to atypical medullary carcinoma and medullary carcinoma. CONCLUSIONS: Medullary carcinoma and atypical medullary carcinoma of the breast differ in their expression of HLA-DR and beta 2 microglobulin. The relatively favourable prognosis of medullary carcinoma of the breast may be related to effective tumour antigen presentation to the immune system through MHC-I and MHC-II expression. Immunotherapy aimed at MHC-I and MHC-II induction might have a beneficial effect in breast cancer.

Monoclonal anti-endothelial cell antibodies from a patient with Takayasu arteritis activate endothelial cells from large vessels.

OBJECTIVE: To create monoclonal anti-endothelial cell antibodies (mAECA) from a patient with Takayasu arteritis to evaluate their ability to activate human umbilical vein endothelial cells (HUVEC), and to characterize the mechanism of EC activation. METHODS: A panel of mAECA was generated from peripheral blood lymphocytes of a patient with Takayasu arteritis, using Epstein-Barr virus transformation. Activity against macrovascular EC (HUVEC) and microvascular EC (human bone marrow EC immortalized by SV40) antigens was detected by enzyme-linked immunosorbent assay. Inhibition studies were used to select the monoclonal antibodies (mAECA) which share the same EC epitope binding specificity as the total IgG-AECA from the Takayasu arteritis patient. The binding of the mAECA to human aortic EC was studied by immunohistochemistry. The secretion levels of interleukin-6 (IL-6) and von Willebrand factor (vWF) were determined, to serve as markers for EC activation. The activated EC were examined for the adherence of a monocytic cell line (U937), as well as for expression of vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and E-selectin. In addition, nuclear extracts of the mAECA-treated EC were analyzed for the induction of translocation of nuclear factor kappaB (NF-kappaB), using a specific NF-kappaB oligoprobe in an electrophoretic mobility shift assay. RESULTS: Six mAECA were selected, the mixture of which produced 100% inhibition of binding of the original IgG (from the patient with Takayasu arteritis) to HUVEC. All mAECA possessed high activity against macrovascular EC, but none had significant antimicrovascular EC activity. The mAECA, but not normal human IgG, had anti-human aortic EC activity. Four of the 6 mAECA activated EC, manifested by increased IL-6 and vWF secretion. The 4 mAECA induced EC expression of adhesion molecules and increased adhesion of U937 monocytic cells to EC. In addition, these mAECA stimulated the nuclear translocation of the NF-kappaB transcription factor. CONCLUSION: Our findings suggest that AECA may directly stimulate EC in Takayasu arteritis through elevation of adhesion molecule expression associated with NF-kappaB activation and adhesion of monocytes, and may therefore play a pathogenic role in the development of the vasculopathy in Takayasu arteritis.

Synchronous appearance of keratoacanthomas in burn scar and skin graft donor site shortly after injury.

Skin malignancies can originate in burn scars (Marjolin's ulcer). The most common is squamous cell carcinoma, usually appearing years after injury. Split-thickness skin graft donor sites as a source of malignant transformation are far less frequent and demonstrate a shorter interval between surgery and tumor onset. Keratoacanthomas have rarely been reported to arise in such scars. We describe the simultaneous occurrence of keratoacanthomas on a spontaneously healed second-degree burn on the flank and in the scar of a skin graft donor site on the thigh, 4 months after a 40% total body surface area burn.

Colonic adenocarcinoma in a rhesus macaque (Macaca mulatta).

A spontaneous colonic adenocarcinoma and endometriosis was diagnosed in a 34-year-old female rhesus macaque (Macaca mulatta). The tumor caused partial obstruction of the ascending colon and histologically resembled the commonly described napkin-ring tumors of the descending and sigmoid colon found in humans. Serum levels of CA 125, a high-molecular-weight glycoprotein antigen that has been reported elevated in a variety of pathological conditions of the pelvic cavity in humans, was severely elevated. Both the adenocarcinoma and the endometriosis may have contributed to this finding.