Freek Groenman - Academia.edu (original) (raw)

Papers by Freek Groenman

International Journal of Transgender Health, Nov 16, 2023

International Journal of Surgery

Background: When a disorder causes absence of a healthy, full-size vagina, various neovaginal cre... more Background: When a disorder causes absence of a healthy, full-size vagina, various neovaginal creation methods are available. Sometimes dilation or stretching of the vaginal cavity is sufficient, but intestinal or dermal flap tissue is generally required. However, different inherent tissue properties cause complications. Therefore, a lost body part should be replaced with a similar material. The use of organ-specific acellular vaginal tissue carries great potential, as its similar architecture and matrix composition make it suitable for vaginal regeneration. Methods: We developed an optimized protocol for decellularization of healthy, human vaginal tissue. Resected colpectomy tissue from 12 healthy transgender patients was used. Successful decellularization was confirmed by applying acellular criteria from in vivo remodeling-reports. Suitability as tissue-mimicking scaffold for vaginal reconstruction was determined by visible structural features, biocompatibility during stretching a...

Human Reproduction Update, Sep 1, 2019

The results are in agreement with our hypothesis that increased angiogenesis is present in the en... more The results are in agreement with our hypothesis that increased angiogenesis is present in the endometrium of patients with adenomyosis compared with the endometrium of control patients. It is likely that increased angiogenesis leads to fragile and more permeable vessels resulting in adenomyosis-related AUB and possibly subfertility. While this association has not sufficiently been studied yet, our results encourage future studies to investigate the exact role of angiogenesis in the etiology of adenomyosis and related AUB or subfertility in women with adenomyosis in order to design curative or preventive therapeutic strategies.

BMJ Open, Jul 1, 2023

et al. Effectiveness of laparoscopic niche resection versus expectant management in patients with... more et al. Effectiveness of laparoscopic niche resection versus expectant management in patients with unexplained infertility and a large uterine caesarean scar defect (uterine niche): protocol for a randomised controlled trial (the LAPRES study). BMJ Open 2023;13:e070950.

Sexual Medicine, Aug 2, 2021

Introduction: Genital gender affirming surgery (gGAS) is usually the final stage in the medical t... more Introduction: Genital gender affirming surgery (gGAS) is usually the final stage in the medical transition for transgender men and consists of creating a neophallus and neo-scrotum, with or without urethral lengthening (UL). To reduce the complication risks of UL, a mandatory colpectomy is performed prior to UL. Colpectomy is considered a complex surgery, which may lead to various perioperative complications. There are few long-term complications reported. Aim: To describe the clinical presentation and management of 3 consecutive transgender men presenting with a perineal cyst following gGAS. Methods: After obtaining informed consent all clinical data was collected, including medical history, current symptoms, imaging, as well as surgery and histological outcomes. Furthermore, a literature search was performed. Main outcome measure: To hypothesize the aetiology of the perineal cyst based on current published literature. Results: Three otherwise healthy transgender men, ages 26−46 with a similar medical history, presented with a perineal cyst several months or years following colpectomy and gGAS with UL. All patients underwent surgery to remove the cyst. Several theories regarding aetiology of this perineal cyst are discussed in this report. Conclusion: There remain several gaps in our knowledge regarding the aetiology and management of this perineal cyst. Therefore, further research is necessary.

American Journal of Physiology-lung Cellular and Molecular Physiology, Apr 1, 2006

Neonatology, 2005

Our understanding of lung development in the past two decades has moved from an anatomical to a h... more Our understanding of lung development in the past two decades has moved from an anatomical to a histological basis and, most recently, to a molecular basis. Tissue interactions specify tracheal and lung primordia formation, program branching morphogenesis of the airway epithelium and regulate epithelial differentiation. In addition, lung development is influenced by mechanical and humoral factors. The regulatory molecules involved in morphogenetic signaling include growth and transcription factors and extracellular matrix molecules. These morphogenetic signals are responsible for lung patterning and differentiation. We will provide a brief overview of molecular signaling during early respiratory formation, airway branching, pulmonary vascularization and epithelial differentiation. We will then review aberrant morphogenetic signaling in human lung abnormalities, such as tracheoesophageal fistula, congenital diaphragmatic hernia, pulmonary hyperplasia, alveolar capillary dysplasia, congenital cystic adenomatoid malformation and bronchopulmonary dysplasia.

International journal of transgender health, Oct 30, 2022

Journal of Minimally Invasive Gynecology, Nov 1, 2007

Authorea (Authorea), Nov 23, 2022

BACKGROUND: About 8,800-34,200 Gender Dysphoria (GD)-and 39,000-650,800 Mayer-Rokitansky-Küster-H... more BACKGROUND: About 8,800-34,200 Gender Dysphoria (GD)-and 39,000-650,800 Mayer-Rokitansky-Küster-Hauser (MRKH)patients undergo vaginoplasty annually. Various procedures are available, but comparisons are lacking. OBJECTIVES: To highlight information gaps, weaknesses and strengths of vaginoplasty techniques, to aid well-informed decision making by patients and healthcare professionals. SEARCH STRATEGY: A systematic search in Medline, EMBASE, Web of Science and Scopus until October 6, 2022, by PICO method and PROSPERO registration. SELECTION CRITERIA: Original retrospective studies on complete neovaginal creation in adult GD-and MRKH-patients and discussing anatomy, Quality of Life (QoL), satisfaction, sexual function, complications or complaints. DATA COLLECTION AND ANALYSIS: The 95% confidence intervals were calculated with DerSimonian and Laird random-effects. Methodological quality and potential bias were assessed. MAIN RESULTS: In total, 35 GD-and 16 MRKH-studies were eligible. Vagina length was 11.6 and 9.5 cm, respectively. In GD-patients, Hemorrhage (6%), prolapse (1%), gastrointestinal complications (1%), revisions (26%), pain (6%), regret (1%), fecal-(11%) and urinary issues (17%) were reported. Necrosis, stenosis, dyspareunia and revisions decreased, while duration increased with higher graft quantity. Intestinal-vaginoplasty reported 100% sensation. MRKH-patients reported more necrosis (17%) [McIndoe] and average satisfaction with sexual function (91%) and vaginal discharge (32%). They were more sexually active (86%) and had 100% anatomical satisfaction. Only Intestinal-vaginoplasty reported overall dissatisfaction. CONCLUSIONS: For GD-and MRKH-patients, multiple safe vaginoplasty techniques demonstrated acceptable outcomes, with significantly improved QoL and self-image. However, standardized validation tools are needed for well-informed decision-making. Direct technique comparisons per patient-cohort and exploration of tissue-engineering methods are critical for future surgical advancements.

Journal of Histochemistry and Cytochemistry, Dec 12, 2006

Lung development takes place in a relatively low-oxygen environment, which is beneficial for lung... more Lung development takes place in a relatively low-oxygen environment, which is beneficial for lung organogenesis, including vascular development. Hypoxia-inducible factor (HIF)-1 plays an important role in mediating oxygen-regulated events. HIF-1 is stable and initiates gene transcription under hypoxia, whereas in normoxia, interaction with the von Hippel-Lindau (VHL) tumor suppressor protein leads to rapid degradation of the HIF-1a subunit. Interaction with VHL requires hydroxylation of HIF-1a proline residues by prolyl hydroxylases (PHDs). We investigated the expression of the various components regulating HIF-1a stability in first trimester (8-14 weeks) human lungs. Spatial expression was assessed by immunohistochemistry and temporal expression by quantitative PCR. Immunoreactivity for PHD1, PHD3, and seven in absentia homolog (SIAH)1 was noted in the pulmonary epithelium. PHD2 was not expressed in the airway epithelium, but in the lung parenchyma. HIF-1a and vascular endothelial growth factor (VEGF) immunoreactivity were primarily detected in the branching epithelium. HIF-2a and ARNT proteins localized to the developing epithelium as well as mesenchymal, most likely vascular, structures in the parenchyma. VEGF receptor 2 (VEGFR2) was found in the subepithelium as well as in vascular structures of the mesenchyme. All components of the VEC complex (VHL, NEDD8, and Cullin2) were found in the epithelium. Quantitative PCR analysis demonstrated that VEGF, VEGFR1, HIF-1a, HIF-2a, ARNT, PHD1, PHD2, PHD3, and SIAH1 gene expression was constant during early pulmonary organogenesis. Cumulatively, the data suggest that the lung develops in a low-oxygen environment that allows for proper vascular development through HIF-regulated pathways.

The Journal of Sexual Medicine, Apr 26, 2019

Background: Colpectomy, removal of the vaginal epithelium, may be performed in transgender men be... more Background: Colpectomy, removal of the vaginal epithelium, may be performed in transgender men because of a disturbed male self-image, to reduce vaginal discharge, or to reduce the risk of fistula formation at the urethraleneourethral junction in future phalloplasty or metaidoioplasty. Aim: To demonstrate that vaginal colpectomy in transgender men, either alone or in combination with, for example, laparoscopic hysterectomy, metaidoioplasty, scrotoplasty, or urethroplasty, is a feasible procedure. Methods: This single-center retrospective cohort study included 143 transgender men who underwent vaginal colpectomy between January 2006 and April 2018. Surgical details and clinical outcomes were collected from all patients. Outcomes: The primary outcome was the number of perioperative and postoperative complications, including intraoperative blood loss. Secondary outcomes were operating time, change in hemoglobin level, and duration of hospital stay. Results: In 109 patients (76%), the procedure consisted of colpectomy only, whereas in 34 patients (23%), colpectomy was combined with other procedures. In the whole group (combined procedures included), the median blood loss was 300 mL (interquartile range [IQR] ¼ 250 mL), the mean operating time was 132 ± 62 minutes, and the mean duration of hospital admission was 3.6 ± 1.9 days. In the colpectomy-only group, the median blood loss was 300 mL (IQR ¼ 250 mL), mean operating time was 112 ± 40 minutes, and mean duration of hospital admission was 3.2 ± 1.5 days. For the total group, 15 patients (10%) experienced a major perioperative complication (ie, bowel injury, ureter injury, urethra injury, bladder injury, hemorrhage requiring transfusion and/or intervention and conversion to laparoscopy), and 1 patient (0.7%) had a minor perioperative complication (hemorrhage). Major postoperative complications (hemorrhage, hematoma, fistula, wound infection and prolonged pain complaints) were reported in 17 patients (12%), and minor postoperative complications (urinary tract infection, urinary retention, hemorrhage, and hematoma) occurred in 50 patients (35%). Clinical Implications: This study provides a detailed description of our technique and comprehensive reporting on perioperative and postoperative complications and reintervention rate. Strengths & Limitations: Study strengths include the large number of patients included and the detailed reporting on the complications of vaginal colpectomy. The main limitation is the retrospective design, which can cause data to go missing during extraction and is prone to bias. Conclusion: Vaginal colpectomy is a procedure with a high complication rate, but its advantages seem to outweigh its disadvantages. In all but 1 case, no long-term sequelae were reported. However, the high complication rate and reintervention rate should be discussed with patients who are considering undergoing this

Pediatric and Developmental Pathology, Sep 1, 2004

Congenital diaphragmatic hernia (CDH) is a congenital disorder, complicated by pulmonary hypoplas... more Congenital diaphragmatic hernia (CDH) is a congenital disorder, complicated by pulmonary hypoplasia (PH) and pulmonary hypertension. Hypoplastic lungs have fewer and smaller airspaces than normal, with thicker interalveolar septa; the adventitia and media of pulmonary arteries are thickened, and the total size of the pulmonary vascular bed is decreased compared to normal. Although histological abnormalities in PH have been described, less is known about the underlying molecular mechanisms. Therefore, we have investigated a series of proteins, known to be involved in angiogenesis, including von Hippel-Lindau protein (pVHL), hypoxia-inducible factor-1a (HIF-1a), vascular endothelial growth factor (VEGF), fetal liver kinase 1 (Flk-1), and endothelial and inducible nitric oxide synthase (eNOS, iNOS) by immunohistochemistry on paraffin-embedded lung tissue of CDH patients (n = 13), patients with lung hypoplasia due to other causes (n = 20), and normal controls (n = 33). pVHL was expressed more frequently in the arterial smooth muscle cells of CDH lungs compared with both other groups. Furthermore, HIF-1a was expressed less frequently in the endothelium of arteries, veins, and capillaries of CDH lungs as compared with both other groups. No differences were observed in the expression patterns of VEGF, Flk-1, eNOS, and iNOS between the different groups. Our data suggest a role for pVHL and HIF-1a in normal and abnormal pulmonary angiogenesis. The differential expression of these proteins may provide a molecular basis for the histological differences observed in the lung vessels of patients with CDH.

BJA: British Journal of Anaesthesia, Aug 1, 2008

After an episode of apparent venous gas embolism in a patient undergoing surgical hysteroscopy, t... more After an episode of apparent venous gas embolism in a patient undergoing surgical hysteroscopy, transoesophageal echocardiography revealed air in the left but not in the right heart. Contrast echocardiography failed to demonstrate anatomical right-to-left shunts, making it likely that venous emboli overwhelmed the capacity of lungs to filter emboli, resulting in paradoxical embolization.

Surgical Endoscopy and Other Interventional Techniques, Nov 14, 2016

Background Gender-affirming surgeries in female-to-male (FtM) transgender patients include mostly... more Background Gender-affirming surgeries in female-to-male (FtM) transgender patients include mostly hysterectomy, bilateral salpingo-oophorectomy and mastectomy. Sometimes further surgery is performed, such as phalloplasty. Colpectomy may be performed to overcome gender dysphoria and disturbing vaginal discharge; furthermore, it may be important in reducing the risk of fistulas due to the phalloplasty procedure with urethral elongation. Colpectomy prior to the reconstruction of the neourethra seems to reduce fistula rates on the very first anastomosis. Therefore, at our center, colpectomy has become a standard procedure prior to phalloplasty and metoidioplasty with urethral elongation. Colpectomy is known as a procedure with potentially serious complications, e.g., extensive bloodloss, vesicovaginal fistula or rectovaginal fistula. Colpectomy performed via the vaginal route can be a challenging procedure due to lack of exposure of the surgical field, as many patients are virginal. Therefore, we investigated whether robot-assisted laparoscopic hysterectomy with bilateral salpingo-oophorectomy (TLH-BSO) followed by robot-assisted laparoscopic colpectomy (RaLC) is an alternative for the vaginal approach. Methods Robot TLH/BSO and RaLC as a single-step procedure was performed in 36 FtM patients in a prospective cohort study. Results Median length of the procedure was 230 min (197-278), which reduced in the second half of the patients, median blood loss was 75 mL (30-200), and median discharge was 3 days (2-3) postoperatively. One patient with a major complication (postoperative bleeding with readmission and transfusion) was reported. Conclusion To our knowledge, this is the first report of RaLC. Our results show that RaLC combined with robot TLH-BSO is feasible as a single-step surgical procedure in FtM transgender surgery. Future studies are needed to compare this technique to the two-step surgical approach and on its outcome and complication rates of subsequent phalloplasty.

Journal of Minimally Invasive Gynecology, Mar 1, 2008

Hysteroscopic surgery has gained in popularity and has become the method of choice for diagnostic... more Hysteroscopic surgery has gained in popularity and has become the method of choice for diagnostic and therapeutic interventions of intrauterine pathology. Advantages consist of short operating time, rapid postoperative recovery, and low morbidity. However, there are concerns about the potential serious complications that can occur, such as venous air and gas embolism. These are rare but hazardous complications, which can occur in all surgical procedures. In hysteroscopic surgery, large uterine veins may be exposed and are, therefore, a point of entry for gas or air. A number of fatal and nonfatal cases have been described as case reports. Although awareness for air and gas embolism is raised this way, proper guidelines as to how to reduce the risk of venous gas or air embolism are lacking. The pathophysiologic difference between gas and air embolism is described herein because composition of the gases differs as does their physiologic effects. A gas embolism is likely to be derived from electrosurgical vapors whereas air embolism seems to arise from improper purging of lines or reinsertion of hysteroscopic instruments. Treatment regimens must, therefore, be designed to address the specific gases involved. Signs and symptoms of these different embolisms are described, as early detection and intervention are crucial for survival. Furthermore, we provide guidelines for operating department personnel, surgeons, and anesthesiologists to reduce the risk of venous gas or air embolism during hysteroscopic procedures. Potential complications of these procedures may be prevented this way.

Journal of Pediatric Surgery, Jul 1, 2005

This is the case of a 13-day-old female infant delivered at 34 2/7 weeks to a 38-year-old G1P0 mo... more This is the case of a 13-day-old female infant delivered at 34 2/7 weeks to a 38-year-old G1P0 mother with spontaneous rupture of membranes, via cesarean section on 2/26. Prenatally, the infant was diagnosed with an omphalocele and a 17q12 duplication encompassing the HNF1B gene; the karyotype was normal female.

Human Reproduction, Aug 9, 2019

STUDY QUESTION: What is the X chromosomal content of oocytes and granulosa cells of primordial/pr... more STUDY QUESTION: What is the X chromosomal content of oocytes and granulosa cells of primordial/primary (small) follicles and stromal cells in ovaries of young patients with Turner's syndrome (TS)? SUMMARY ANSWER: Small ovarian follicles were detected in one-half of the patients studied, and X chromosome analysis revealed that most oocytes were normal, granulosa cells were largely monosomic, while stromal cells showed a high level of mosaicism. WHAT IS KNOWN ALREADY: Most women with TS experience a premature reduction or complete loss of fertility due to an accelerated loss of gametes. To determine whether fertility preservation in this group of patients is feasible, there is a strong need for information on the X chromosomal content of ovarian follicular and stromal cells. STUDY DESIGN, SIZE, DURATION: Small follicles (<50 μm) and stromal cells were isolated from ovarian tissue of young TS patients and analysed for their X chromosomal content. In addition to ovarian cells, several other cell types from the same patients were analysed. PARTICIPANTS/MATERIALS, SETTING, METHODS: After unilateral ovariectomy, ovarian cortex tissue was obtained from 10 TS patients (aged 2-18 years) with numerical abnormalities of the X chromosome. Ovarian cortex fragments were prepared and cryopreserved. One fragment from each patient was thawed and enzymatically digested to obtain stromal cells and primordial/primary follicles. Stromal cells, granulosa cells and oocytes were analysed by FISH using an X chromosome-specific probe. Extra-ovarian cells (lymphocytes, buccal cells and urine cells) of the same patients were also analysed by FISH. Ovarian tissue used as control was obtained from individuals undergoing oophorectomy as part of their gender affirming surgery. MAIN RESULTS AND THE ROLE OF CHANCE: Ovarian follicles were detected in 5 of the 10 patients studied. A method was developed to determine the X chromosomal content of meiosis I arrested oocytes from small follicles. This revealed that 42 of the 46 oocytes (91%) that were analysed had a normal X chromosomal content. Granulosa cells were largely 45,X but showed different levels of X chromosome mosaicism between patients and between follicles of the same patient. Despite the presence of a low percentage (10-45%) of 46,XX ovarian cortex stromal cells, normal macroscopic ovarian morphology was observed. The level of mosaicism in lymphocytes, buccal cells or urinederived cells was not predictive for mosaicism in ovarian cells. LIMITATIONS, REASONS FOR CAUTION: The results are based on a small number (n = 5) of TS patient samples but provide evidence that the majority of oocytes have a normal X chromosomal content and that follicles from the same patient can differ with respect to the level of mosaicism of their granulosa cells. The functional consequences of these observations require further investigation.