The role of clitoral anatomy in female to male sex reassignment surgery.

INTRODUCTION: Controversies on clitoral anatomy and its role in female sexual function still make clitoral reconstructive surgery very challenging. We evaluated the role of clitoral anatomic features in female to male sex reassignment surgery. MATERIAL AND METHODS: The study included 97 female transsexuals, aged from 18 to 41 years, who underwent single stage metoidioplasty between March 2008 and January 2013. The operative technique involved vaginectomy, the release of clitoral ligaments and urethral plate, urethroplasty by combining buccal mucosa graft and genital flaps, and scrotoplasty with insertion of testicle prostheses. Postoperative questionnaire was used to evaluate aesthetic, functional, and sexual outcome. RESULTS: The mean followup was 30 months. The mean length of the neophallus was 7 cm, compared to mean preoperative length of the hypertrophied clitoris of 3.3 cm. Complications occurred in 27.84% of all patients, related mostly to urethroplasty. Voiding while standing was achieved in all cases. None of the patients had problems in sexual arousal, masturbation, or orgasms. CONCLUSION: Accurate knowledge of the clitoral anatomy, physiology, and neurovascular supply is crucial for a successful outcome of female to male sex reassignment surgery. Our approach appears to ensure overall satisfaction and high quality of sexual life.

An overview of neovaginal reconstruction options in male to female transsexuals.

Transsexualism is a complex condition in which the person experiences the inconsistency between the desired gender and their biological gender. Absence of the vagina is devastating in male to female transsexuals. Creation of the neovagina is the main surgical problem in these patients. Historically, beginnings of the neovaginal creation have their roots in the treatment of Mayer-Rokitansky syndrome and conditions such as cloacal anomalies, certain intersex disorders, vaginal malignancies, or severe vaginal trauma, but have more recently found great purpose in male to female sex reassignment surgery. Many operative procedures have been described but none is ideal. Therefore, the search for new, improved solutions continues. In neovaginoplasty reconstruction of the vulvovaginal complex is performed in its entity. The gold standard in neovaginal reconstruction in male to female sex reassignment surgery is penile skin inversion technique with or without scrotal flaps, which enables adequate sensation of the neovagina, good neovaginal depth, good erotic sensitivity of the neclitoris, and esthetically acceptable labia minora and maiora.

Impact of CT and MRI in the diagnostic workup of malignant triton tumour-a monocentric analysis and review of the literature.

OBJECTIVES: Malignant triton tumours (MTTs) are rare but aggressive subtypes of malignant peripheral nerve sheath tumours (MPNSTs) with a high recurrence rate and 5-year survival of 14%. Systematic imaging data on MTTs are scarce and mainly based on single case reports. Therefore, we aimed to identify typical CT and MRI features to improve early diagnosis rates of this uncommon entity. METHODS: A systematic review on literature published until December 2022 on imaging characteristics of MTTs was performed. Based on that, we conducted a retrospective, monocentric analysis of patients with histopathologically proven MTTs from our department. Explorative data analysis was performed. RESULTS: Initially, 29 studies on 34 patients (31.42 ± 22.6 years, 12 female) were evaluated: Literature described primary MTTs as huge, lobulated tumours (108 ± 99.3 mm) with central necrosis (56% [19/34]), low T1w (81% [17/21]), high T2w signal (90% [19/21]) and inhomogeneous enhancement on MRI (54% [7/13]). Analysis of 16 patients (48.9 ± 13.8 years; 9 female) from our institution revealed comparable results: primary MTTs showed large, lobulated masses (118 mm ± 64.9) with necrotic areas (92% [11/12]). MRI revealed low T1w (100% [7/7]), high T2w signal (100% [7/7]) and inhomogeneous enhancement (86% [6/7]). Local recurrences and soft-tissue metastases mimicked these features, while nonsoft-tissue metastases appeared unspecific. CONCLUSIONS: MTTs show characteristic features on CT and MRI. However, these do not allow a reliable differentiation between MTTs and other MPNSTs based on imaging alone. Therefore, additional histopathological analysis is required. ADVANCES IN KNOWLEDGE: This largest published systematic analysis on MTT imaging revealed typical but unspecific imaging features that do not allow a reliable, imaging-based differentiation between MTTs and other MPNSTs. Hence, additional histopathological analysis remains essential.

Correlation of the apparent diffusion coefficient with the standardized uptake value in meningioma of the skull plane using [68]Ga-DOTATOC PET/MRI.

PURPOSE: To evaluate a correlation between an MRI-specific marker for cellular density [apparent diffusion coefficient (ADC)] and the expression of Somatostatin Receptors (SSTR) in patients with meningioma of the skull plane and orbital space. METHODS: 68 Ga-DOTATOC PET/MR imaging was performed in 60 Patients with suspected or diagnosed meningiomas of the skull base and eye socket. Analysis of ADC values succeeded in 32 patients. ADC values (ADC mean and ADC min ) were analyzed using a polygonal region of interest. Tracer-uptake of target lesions was assessed according to corresponding maximal (SUV max ) and mean (SUV mean ) values. Correlations between assessed parameters were evaluated using the Pearson correlation coefficient. RESULTS: One out of 32 patients (3%) was diagnosed with lymphoma by histopathological examination and therefore excluded from further analysis. Median ADC mean amounted to 822 × 10 -5  mm²/s -1 (95% CI: 570-1497) and median ADC min was 493 × 10 -5 mm 2 /s -1 (95% CI: 162-783). There were no significant correlations between SUV max and ADC min (r = 0.60; P  = 0.76) or ADC mean (r = -0.52; P  = 0.79), respectively. However, Pearson's test showed a weak, inverse but insignificant correlation between ADC mean and SUV mean (r = -0.33; P  = 0.07). CONCLUSION: The presented data displays no relevant correlations between increased SSTR expression and cellularity in patients with meningioma of the skull base. SSTR-PET and DWI thus may offer complementary information on tumor characteristics of meningioma.

Evaluation of [68Ga]-DOTATOC PET/MRI in Patients with Meningioma of the Subcranial and Intraorbital Space.

Meningiomas are known to express somatostatin receptor (SSTR) type 2 to a high degree. Therefore, radiolabeled somatostatin analogs, such as DOTATOC, have been introduced for PET imaging of meningiomas. However, the benefit of hybrid SSTR PET/MRI is still debated. Here, we report our experience with [68Ga]-DOTATOC PET/MRI. Methods: PET/MRI was performed in 60 patients with suspected or diagnosed meningiomas of the skull plane and eye socket. Acquired datasets were reported by 2 independent readers regarding local tumor extent and signal characteristics. Histopathologic results and follow-up imaging served as the reference standard. SUVs of target lesions were analyzed according to the corresponding maximal tracer uptake. The diagnostic accuracy of PET/MRI and conventional MRI was determined independently and compared with the reference standard. Results: In total, 60 target lesions were identified, with 54 considered to be meningiomas according to the reference standard. Sensitivity and specificity of PET/MRI versus MRI alone were 95% versus 96% and 75% versus 66%, respectively. The McNemar test was not able to distinguish any differences between PET/MRI and the reference standard or MRI and the reference standard. No differences were found between the 2 modalities with respect to local infiltration. Conclusion: SSTR PET/MRI and MRI yielded similar accuracy for the detection of meningiomas of the skull base and intraorbital space. Here, sequential low-dose SSTR PET/CT might be helpful for the planning of radioligand therapy or radiotherapy.

Conventional Imaging, MRI and 18F-FDG PET/MRI for N and M Staging in Patients with Newly Diagnosed Breast Cancer.

Background: This study compares the diagnostic potential of conventional staging (computed tomography (CT), axillary sonography and bone scintigraphy), whole-body magnetic resonance imaging (MRI) and whole-body 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/)MRI for N and M staging in newly diagnosed breast cancer. Methods: A total of 208 patients with newly diagnosed breast cancer were prospectively included in this study and underwent contrast-enhanced thoracoabdominal CT, bone scintigraphy and axillary sonography as well as contrast-enhanced whole-body 18F-FDG PET/MRI. The datasets were analyzed with respect to lesion localization and characterization. Histopathology and follow-up imaging served as the reference standard. A McNemar test was used to compare the diagnostic performance of conventional staging, MRI and 18F-FDG PET/MRI and a Wilcoxon test was used to compare differences in true positive findings for nodal staging. Results: Conventional staging determined the N stage with a sensitivity of 80.9%, a specificity of 99.2%, a PPV (positive predictive value) of 98.6% and a NPV (negative predictive value) of 87.4%. The corresponding results for MRI were 79.6%, 100%, 100% and 87.0%, and were 86.5%, 94.1%, 91.7% and 90.3% for 18F-FDG PET/MRI. 18F-FDG PET/MRI was significantly more sensitive in determining malignant lymph nodes than conventional imaging and MRI (p < 0.0001 and p = 0.0005). Furthermore, 18F-FDG PET/MRI accurately estimated the clinical lymph node stage in significantly more cases than conventional imaging and MRI (each p < 0.05). Sensitivity, specificity, PPV and NPV for the M stage in conventional staging were 83.3%, 98.5%, 76.9% and 98.9%, respectively. The corresponding results for both MRI and 18F-FDG PET/MRI were 100.0%, 98.5%, 80.0% and 100.0%. No significant differences between the imaging modalities were seen for the staging of distant metastases. Conclusions:18F-FDG PET/MRI detects lymph node metastases in significantly more patients and estimates clinical lymph node stage more accurately than conventional imaging and MRI. No significant differences were found between imaging modalities with respect to the detection of distant metastases.

68Ga-Labeled Fibroblast Activation Protein Inhibitor (68Ga-FAPI) PET for Pancreatic Adenocarcinoma: Data from the 68Ga-FAPI PET Observational Trial.

The fibroblast activation protein (FAP) is highly expressed on carcinoma-associated fibroblasts in the stroma of pancreatic cancer and thus is a promising target for imaging and therapy. Preliminary data on PET imaging with radiolabeled FAP inhibitors (FAPIs) demonstrate superior tumor detection. Here we assess the accuracy of FAP-directed PET in patients with pancreatic cancer. Methods: Of 64 patients with suspected or proven pancreatic cancer, 62 (97%) were included in the data analysis of the 68Ga-FAPI PET observational trial (NCT04571086). All of these patients underwent contrast-enhanced CT, and 38 patients additionally underwent 18F-FDG PET. The primary study endpoint was the association of 68Ga-FAPI PET uptake intensity and histopathologic FAP expression. Secondary endpoints were detection rate, diagnostic performance, interreader reproducibility, and change in management. Datasets were interpreted by 2 masked readers. Results: The primary endpoint was met: The association between 68Ga-FAPI SUVmax and histopathologic FAP expression was significant (Spearman r, 0.48; P = 0.04). For histopathology-validated lesions, 68Ga-FAPI PET showed high sensitivity and positive predictive values (PPVs) on per-patient (sensitivity, 100%; PPV, 96.3%) and per-region (sensitivity, 100%; PPV, 97.0%) bases. In a head-to-head comparison versus 18F-FDG or contrast-enhanced CT, 68Ga-FAPI detected more tumor on a per-lesion (84.7% vs. 46.5% vs. 52.9%), per-patient (97.4% vs. 73.7% vs. 92.1%), or per-region (32.6% vs. 18.8% vs. 23.7%) basis, respectively. 68Ga-FAPI PET readers showed substantial overall agreement on the basis of the Fleiss κ: primary κ, 0.77 (range, 0.66-0.88). Minor and major changes in clinical management occurred in 5 patients (8.4%) after 68Ga-FAPI PET. Conclusion: We confirmed an association of 68Ga-FAPI PET SUVmax and histopathologic FAP expression in pancreatic cancer patients. Additionally, we found high detection rate and diagnostic accuracy, superior to those of 18F-FDG PET/CT. 68Ga-FAPI might become a powerful diagnostic tool for pancreatic cancer work-up.

Superior Tumor Detection for 68Ga-FAPI-46 Versus 18F-FDG PET/CT and Conventional CT in Patients with Cholangiocarcinoma.

Management of cholangiocarcinoma is among other factors critically determined by accurate staging. Here, we aimed to assess the accuracy of PET/CT with the novel cancer fibroblast-directed 68Ga-fibroblast activation protein (FAP) inhibitor (FAPI)-46 tracer for cholangiocarcinoma staging and management guidance. Methods: Patients with cholangiocarcinoma from a prospective observational trial were analyzed. 68Ga-FAPI-46 PET/CT detection efficacy was compared with 18F-FDG PET/CT and conventional CT. SUVmax/tumor-to-background ratio (Wilcoxon test) and separately uptake for tumor grade and location (Mann-Whitney U test) were compared. Immunohistochemical FAP and glucose transporter 1 (GLUT1) expression of stromal and cancer cells was analyzed. The impact on therapy management was investigated by pre- and post-PET/CT questionnaires sent to the treating physicians. Results: In total, 10 patients (6 with intrahepatic cholangiocarcinoma and 4 with extrahepatic cholangiocarcinoma; 6 with grade 2 tumor and 4 with grade 3 tumor) underwent 68Ga-FAPI-46 PET/CT and conventional CT; 9 patients underwent additional 18F-FDG PET/CT. Immunohistochemical analysis was performed on the entire central tumor plain in 6 patients. Completed questionnaires were returned in 8 cases. Detection rates for 68Ga-FAPI-46 PET/CT, 18F-FDG PET/CT, and CT were 5, 5, and 5, respectively, for primary tumor; 11, 10, and 3, respectively, for lymph nodes; and 6, 4, and 2, respectively, for distant metastases. 68Ga-FAPI-46 versus 18F-FDG PET/CT SUVmax for primary tumor, lymph nodes, and distant metastases was 14.5 versus 5.2 (P = 0.043), 4.7 versus 6.7 (P = 0.05), and 9.5 versus 5.3 (P = 0.046), respectively, and tumor-to-background ratio (liver) was 12.1 versus 1.9 (P = 0.043) for primary tumor. Grade 3 tumors demonstrated a significantly higher 68Ga-FAPI-46 uptake than grade 2 tumors (SUVmax, 12.6 vs. 6.4; P = 0.009). Immunohistochemical FAP expression was high on tumor stroma (∼90% of cells positive), whereas GLUT1 expression was high on tumor cells (∼80% of cells positive). Overall, average expression intensity was estimated as grade 3 for FAP and grade 2 for GLUT1. Positive 68Ga-FAPI-46 PET findings led to a consequent biopsy workup and diagnosis of cholangiocarcinoma in 1 patient. However, patient treatment was not adjusted on the basis of 68Ga-FAPI-46 PET. Conclusion: 68Ga-FAPI-46 demonstrated superior radiotracer uptake, especially in grade 3 tumors, and lesion detection in patients with cholangiocarcinoma. In line with this result, immunohistochemistry demonstrated high FAP expression on tumor stroma. Accuracy is under investigation in an ongoing investigator-initiated trial.

68Ga-FAPI as a Diagnostic Tool in Sarcoma: Data from the 68Ga-FAPI PET Prospective Observational Trial.

Bone and soft-tissue sarcomas express fibroblast activation protein (FAP) on tumor cells and associated fibroblasts. Therefore, FAP is a promising therapeutic and diagnostic target. Novel radiolabeled FAP inhibitors (e.g., 68Ga-FAPI-46) have shown high tumor uptake on PET in sarcoma patients. Here, we report the endpoints of the 68Ga-FAPI PET prospective observational trial. Methods: Forty-seven patients with bone or soft-tissue sarcomas undergoing clinical 68Ga-FAPI PET were eligible for enrollment into the 68Ga-FAPI PET observational trial. Of these patients, 43 also underwent 18F-FDG PET. The primary study endpoint was the association between 68Ga-FAPI PET uptake intensity and histopathologic FAP expression analyzed with Spearman r correlation. Secondary endpoints were detection rate, positive predictive value (PPV), interreader reproducibility, and change in management. Datasets were interpreted by 2 masked readers. Results: The primary endpoint was met, and the association between 68Ga-FAPI PET uptake intensity and histopathologic FAP expression was significant (Spearman r = 0.43; P = 0.03). By histopathologic validation, PPV was 1.00 (95% CI, 0.87-1.00) on a per-patient and 0.97 (95% CI, 0.84-1.00) on a per-region basis. In cases with histopathologic validation, 27 of 28 (96%) confirmed patients and 32 of 34 (94%) confirmed regions were PET-positive, resulting in an SE of 0.96 (95% CI, 0.82-1.00) on a per-patient and 0.94 (95% CI, 0.80-0.99) on a per-region basis. The detection rate on a per-patient basis in 68Ga-FAPI and 18F-FDG PET was 76.6% and 81.4%, respectively. In 8 (18.6%) patients, 68Ga-FAPI PET resulted in an upstaging compared with 18F-FDG PET. 68Ga-FAPI PET readers showed substantial to almost perfect agreement for the defined regions (Fleiss κ: primary κ = 0.78, local nodal κ = 0.54, distant nodal κ = 0.91, lung κ = 0.86, bone κ = 0.69, and other κ = 0.65). Clinical management changed in 13 (30%) patients after 68Ga-FAPI PET. Conclusion: We confirm an association between tumoral 68Ga-FAPI PET uptake intensity and histopathologic FAP expression in sarcoma patients. Further, with masked readings and independent histopathologic validation, 68Ga-FAPI PET had a high PPV and sensitivity for sarcoma staging.

[Acute and late toxicity in radical radiotherapy of prostate cancer].

INTRODUCTION: Although radical radiotherapy has proved to be a successful method in prostate cancer treatment, the conventional (box) technique can result in significant adverse events. OBJECTIVE: The objective of our study was to estimate the frequency, type and severity of acute and late toxicity in radical radiotherapy of prostate cancer. METHODS: In a clinical retrospective study, we included 283 patients with histologically confirmed prostate cancer. All our patients received radical, conventional radiotherapy using the four-field technique. The study was performed at the Radiotherapy Department of the institute for Oncology and Radiology of Serbia between January 1991 and December 2005. During regular follow-up, we analysed the frequency, type and severity of acute and late toxicity. RESULTS: Two thirds (71%) of our patients had acute toxicity of at least one organ within the radiation field. Most frequent complication was radiation dermatitis (10.5%), and enteritis (9%), cystitis (6%) and proctitis (2.5%). Acute adverse events were mostly low grade (I and II, 28-61%). Late complications were registered in 20.5% of patients. Skin fibrosis was most frequent (12%). Chronic proctitis was detected in 4% and urethral stricture in 4.5% of our patients. All late complications were low grade. CONCLUSION: Treatment tolerance of radical radiotherapy is relatively good. Although most patients develop acute toxicity, it is commonly low grade and requires the interruption of radiotherapy treatment in 20% of patients only. Late toxicity is rarer than acute and, in most cases, it does not affect the quality of life.

[Disease relapses after radical radiotherapy of prostate cancer--analysis of prognostic factors].

INTRODUCTION: Although there is no consensus on which is the best option in prostate cancer treatment, these patients could be successfully treated with radiotherapy. Regarding some prognostic factors, it is possible today to classify prostate cancer patients into several risk groups for clinical and biochemical relapse, and therefore to choose the right treatment modality. OBJECTIVE: The objective in our study was to analyze the impact of tumour stage and grade, previous transurethral resection of the prostate (TUR), initial prostate specific antigen (PSA) level and age on disease relapse after radical radiotherapy of the prostate cancer. METHOD: Between January 1991 and December 2005, a clinical, retrospective study was performed at the Radiotherapy Department of the Institute for Oncology and Radiology of Serbia, which included 283 patients with prostate cancer treated only with radical radiotherapy. During regular followup we analyzed response to treatment and disease relapse. RESULTS: After radical radiotherapy disease relapse more often occurred (with statistical significance) in patients with locally advanced tumour (stage C 35% vs. A 13% vs. B 19%), low tumour grade (grade III 38% vs. grade II 23% vs. grade I 17%), initial PSA level over 10 ng/ml (29%) and over 20 ng/ml (37%) compared to 11% in the patients with initial PSA level below 10 ng/ml, and patients of lower age (less than 55 years 50% vs. 16% in patients over 70 years). CONCLUSION: Tumour stage C, low tumour grade (grade II-III), initial PSA level over 10 ng/ml (over 20 ng/ml) and younger age are poor prognostic factors for disease relapse. In this case, radiotherapy as monotherapy is not an adequate approach, and it needs to be combined with other therapeutic modalities.

Sacrospinous ligament fixation for neovaginal prolapse prevention in male-to-female surgery.

OBJECTIVES: To report our experiences of vaginal sacrospinous ligament fixation after vaginoplasty in male transsexual patients with the aim of preventing its postoperative prolapse. METHODS: From August 1997 through November 2005, a total of 62 male transsexual patients (mean age 26 years, range 18 to 58) underwent sacrospinous ligament fixation for neovaginal prolapse during male-to-female sex reassignment surgery. The neovagina was created from a penile skin tube flap combined with a urethral flap. A deep and wide perineal cavity between the urethra, bladder, and rectum was created by dissection of the tendineous center and rectourethral muscle. The right pararectal space was opened by penetrating the right pararectal fascia (rectal pillar) and right ischial spine was palpated. Using the ischial spine as a prominent landmark, the sacrospinous ligament was palpated. Long-handled Deschamps ligature was used to pierce the ligament medially to the ischial spine. Vaginopexy to the sacrospinous ligament was performed, and the neovagina was placed deep in the perineal cavity. RESULTS: The median follow-up was 32 months (range 7 to 102). Sacrospinous ligament fixation was successfully performed in all patients. The mean vaginal length was 10.7 cm (range 9.5 to 16). Of the 62 patients, 42 (76%) were able to have normal sexual intercourse. The appearance of the neovagina was aesthetically acceptable in 52 patients. In 3 cases, a minor bulge of the anterior vaginal wall was easily resolved by simple excision. CONCLUSIONS: Vaginal sacrospinous fixation is feasible in male transsexuals for neovaginal prolapse prevention. However, extensive experience with male pelvic surgery is required to avoid possible complications.