Feasibility of targeted therapies in the adjuvant setting of early breast cancer in men: real-world data from a population-based registry.

BACKGROUND: Following the positive iDFS and OS results of the phase III clinical trials monarchE, NATALEE and OlympiA, new oral anticancer agents (the CDK4/6 inhibitors abemaciclib, ribociclib as well as the PARP inhibitor olaparib) have recently been introduced into the treatment of high-risk early breast cancer (eBC). However, only few male patients were included in these trials (0.4%, 0.6% and 0.3%, respectively). The objective of this real-world analysis was to determine the proportion of male patients with eBC fulfilling the clinical high-risk criteria of above-mentioned trials. PATIENTS AND METHODS: We conducted a data inquiry and analysis with the Cancer Registry of Baden-Württemberg of men with breast cancer diagnosed between January 1, 2015 and December 31, 2021. Men with eBC were identified and the number of patients at clinical high-risk according to the inclusion criteria of monarchE, NATALEE and OlympiA was assessed. RESULTS: Of 397 men with eBC, 354 (89.1%) had a HR + /Her2- and 4 (1.0%) a triple-negative subtype. 84 patients (21.2%) met the clinical high-risk criteria according to the monarchE, 189 (47.6%) those according to the NATALEE and 50 (12.6%) those according to the OlympiA trial. CONCLUSION: In a large real-world sample, more men with eBC are at clinical high risk according to the inclusion criteria of monarchE, NATALEE and OlympiA than would be expected in women. This is most likely due to more advanced stages at initial diagnosis in men. To evaluate whether CDK4/6 and PARP inhibitors improve prognosis also in men should be the topic of future real- world analyses.

Unexpected malignant uterine pathology: Incidence, characteristics and outcome in a large single-center series of hysterectomies for presumed benign uterine disease.

OBJECTIVE: Hysterectomy is a frequently used therapeutic option for benign gynecological conditions. The purpose of this study was to investigate the incidence and characteristics of unforeseen malignant pathologies of the uterine corpus in a large population-based, single center cohort. METHODS: Patients who underwent hysterectomy for presumed benign conditions between 2003 and 2016 were identified. In cases of unexpected malignancies of the uterine corpus (UUM), available tissue samples were collected and a specialized gynecopathological review was performed. RESULTS: A total of 10,756 patients underwent hysterectomy for benign indications. After chart and gynecopathological review, 45/10,756 (0.42%) cases of unexpected uterine malignancies were confirmed. 33/45 (73.3%) were endometrial carcinomas (UEC) and 12/45 (26.7%) were uterine sarcomas (UUS). 27/33 (81.8%) UEC were FIGO IA, 5/33 (15.2%) FIGO IB and 1/33 (3%) FIGO stage II disease. Endometrioid and serous histotype were present in 31/33 (93.9%) and in 2/33 (6.1%) cases, respectively. 8/12 (66.7%) USS were early stage (FIGO IA or IB); only 3/12 (25.0%) were diagnosed at an advanced stage (≥FIGO II). Fatal outcome was observed in 1 patient diagnosed with UEC and 3 patients diagnosed with UUS. CONCLUSION: Our study shows that diagnosis of UUM is rare (0.42%). The majority of UUM tend to be early stage, making preoperative diagnosis difficult. In case of UEC, patient outcome is generally favorable. Nevertheless, the appropriate surgical approach for hysterectomy for a benign indication should be chosen carefully, taking all preoperative findings into account. Patients should always be informed about the residual risk of UUM.

Neovagina creation methods and their potential impact on subsequent uterus transplantation: a review.

Congenital uterovaginal aplasia commonly occurs in Mayer-Rokitansky-Küster-Hauser syndrome. Various methods of neovagina creation exist, including nonsurgical self-dilation, surgical dilation, and surgical procedures involving skin or intestinal transplants. Subsequent uterus transplantation is necessary to enable pregnancy. We review the main characteristics, advantages, and disadvantages of established neovagina creation methods and discuss their suitability regarding subsequent uterus transplantation. Suitability criteria include sufficient vaginal length, absence of previous major intra-abdominal surgery, a natural vaginal axis, and a natural vaginal epithelium. In conclusion, Vecchietti-based laparoscopically assisted neovagina creation provides ideal functional conditions for uterus transplantation. Nonsurgical self-dilation and Wharton-Sheares-George vaginoplasty may also be suitable. TWEETABLE ABSTRACT: This review discusses the main advantages and disadvantages of neovagina creation methods with regard to subsequent uterus transplantation.

Vaginal prevalence of human papillomavirus infections in women with uterovaginal aplasia before and after laparoscopically assisted creation of a neovagina: a prospective epidemiological observational study.

OBJECTIVE: To study vaginal as opposed to cervical human papillomavirus (HPV) acquisition with regard to true prevalence, HPV types, and the role of co-factors in virgins and after their sexual debut. DESIGN: Prospective epidemiological observational study. SETTING: University hospital specialised in genital malformations. POPULATION: Women diagnosed with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) and undergoing neovaginoplasty between November 2011 and July 2017. METHODS: This is a prospective study including 186 women with MRKHS before and after sexual debut. MAIN OUTCOME MEASURES: Conventional vaginal cytology and different HPV tests were performed at surgery and during routine gynaecological follow-up 1, 3, 6 and ≥ 11 months after surgery and risk factors were documented. RESULTS: The mean age of all women at surgery was 20.1 years (SD 5.4), mean body mass index (BMI) was 22.1 kg/m2 (SD 4.6). In 83 vaginal samples from 41 different women at least one of the HPV tests was positive. Thirty-three different HPV types were detected. The prevalence of 41/186 = 22.0% as well as type distribution are comparable with those found in a young German female population. The overall rate of acquisition was clearly associated with sexual activity and smoking habits. Out of 367 Papanicolaou smears only six were abnormal with Pap IIID (MN II) and no obvious vaginal lesion was detected. CONCLUSIONS: Vaginal HPV prevalence and HPV types in previously virgin women after creation of a neovagina are not different from the acquisition of cervical infections in the general population and is clearly associated with sexual activity and with smoking habits. However, abnormal Papanicolaou smears are rarely seen. TWEETABLE ABSTRACT: Vaginal HPV prevalence after creation of a neovagina is similar to that on the cervix in the general population.

High intensity focused ultrasound (HIFU) for the treatment of symptomatic breast fibroadenoma.

PURPOSE: The aim of the study was to evaluate the efficacy of high intensity focused ultrasound (HIFU) in the treatment of symptomatic breast fibroadenomas (FA) after 6 and 12 months. MATERIALS AND METHODS: Between December 2013 and November 2014, 27 patients with histologically confirmed FA received one application of HIFU under local anesthesia (NCT02011919). Follow-up visits occurred after 6 and 12 months measuring the FA volume and clinical symptoms. A volume reduction of more than 65% was defined as success. Core needle biopsy (CNB) was offered after 12 months if indistinct residuals were visible on ultrasound (US). RESULTS: A successful reduction in FA volume after 12 months was achieved in 24/27 patients (89%). At baseline 16 patients (59%) had pain, which was resolved in 63% (10/16). All patients were satisfied with the cosmetic related outcome. Twenty-four patients (89%) would repeat the procedure. After 12 months 21 patients with sonographically indistinct residuals underwent a CNB. There were no vital cells in 86%. Three cases showed vital cells of FA. Retrospectively possible reasons in these three cases were an insufficient treatment due to bad visibility and insufficient fixation of the FA during HIFU and/or a too short follow-up time. CONCLUSION: US-guided HIFU is an effective procedure and a minimally invasive alternative for the treatment of breast FA.

Disseminated tumor cells from the bone marrow of patients with nonmetastatic primary breast cancer are predictive of locoregional relapse.

BACKGROUND: Disseminated tumor cells (DTCs) are detectable in the bone marrow (BM) of patients with primary breast cancer (PBC) and predictive of an impaired prognosis. This large trial aimed to analyze the impact of DTC detection on locoregional relapse (LR). PATIENTS AND METHODS: Patients with nonmetastatic PBC were eligible for this analysis. BM aspiration (BMA1) was carried out during primary surgery and DTCs were detected by using immunocytochemistry (A45-B/B3 antibody against pancytokeratin) and morphological criteria. At the time of LR, a subgroup of patients with nonmetastatic and operable LR received a secondary BM aspiration (BMA2). RESULTS: A total of 3072 patients were included into the analysis. Of these, 732 (24%) presented with DTCs at BMA1. One hundred thirty-nine patients experienced LR and 48 of these (35%) were initially DTC positive. DTC detection was significantly associated with an increased risk of LR in univariate (P = 0.002) and multivariate analysis (P = 0.009) with a hazard ratio of 1.65 (95% confidence interval 1.13-2.40). Of the patients with LR, 55 patients were available for BMA2 and 17 of these (32%) were DTC positive. DTC detection at the time of LR was indicative of impaired overall survival (univariate analysis, P = 0.037). CONCLUSIONS: DTC detection in patients with PBC is associated with an increased risk of LR, indicating that tumor cells may have the ability to recirculate from the BM to the site of the primary tumor. The impaired prognosis associated with DTC detection at the time of LR may help to identify patients that are in need for additional or more aggressive treatment.

Clinical characteristics, pathological reevaluation, surgical management and adjuvant therapy of patients with endometrial stromal tumors.

PURPOSE: To review a single-center experience over a 27-year period in the management of endometrial stromal sarcoma (ESS) and undifferentiated endometrial sarcoma (UES) for insight into clinical characteristics, pathological diagnosis, surgical practice, adjuvant therapy and clinical outcome. MATERIALS AND METHODS: This was a retrospective study of women with histologically proven ESS and UES who were treated at the Department of Obstetrics and Gynecology, University of Tuebingen, Germany, between 1983 and 2010. Available tumor tissue, as well as inpatient and ambulatory records were reviewed; follow-up and survival data were ascertained. RESULTS: The study sample comprised ten patients with ESS and seven patients with UES. Primary surgical treatment consisted of total hysterectomy in nine patients (90.0 %) with ESS and six patients (85.7 %) with UES; one patient (10.0 %) with ESS and one patient (14.3 %) with UES underwent debulking surgery. All patients (100 %) from the ESS group and six patients (85.7 %) from the UES group underwent bilateral salpingo-oophorectomy. Seven women (70.0 %) with ESS and six women (85.7 %) with UES underwent lymphadenectomy. Median DFS was 83.8 months (95 % CI 80.6-87.0) and median OS was 232.6 (95 % CI 49.3-415.9) for patients with ESS; median DFS was 12.9 months (95 % CI 0-284.1) and median OS was 17.6 (95 % CI 0-37.0) for patients with UES. There was no significant difference in DFS between patients with ESS as compared with patients with UES. However, patients with ESS had a significantly better OS when compared to patients with UES (p = 0.011). CONCLUSION: ESS and UES are very rare uterine neoplasms. Surgery consisting of total hysterectomy with or without bilateral salpingo-oophorectomy is the most important treatment-element in patients with ESS or UES.

The efficacy of sacituzumab govitecan and trastuzumab deruxtecan on stable and active brain metastases in metastatic breast cancer patients-a multicenter real-world analysis.

BACKGROUND: Fifteen to thirty percent of all patients with metastatic breast cancer (MBC) develop brain metastases (BCBMs). Recently, the antibody-drug conjugates (ADCs) sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) have shown to be highly effective in the treatment of MBC. However, there are only limited data whether these macromolecules are also effective in patients with BCBMs. We therefore aimed to examine the efficacy of SG and T-DXd in patients with stable and active BCBMs in a multicenter real-world analysis. PATIENTS AND METHODS: Female patients with stable or active BCBMs who were treated with either SG or T-DXd at three breast centers in Germany before 30 June 2023 were included. As per local clinical praxis, chemotherapy efficacy was evaluated by whole-body computed tomography and cranial magnetic resonance imaging at baseline and at least every 3 months according to local standards. Growth dynamics of BCBMs were assessed by board-certified neuroradiologists. RESULTS: Of 26 patients, with a median of 2.5 prior therapy lines in the metastatic setting (range 2-15), 12 (43%) and 16 (57%) patients received SG and T-DXd, respectively. Out of the 12 patients who received SG, 2 (17%) were subsequently treated with T-DXd. Five out of 12 (42%) and 5 out of 16 (31%) patients treated with SG and T-DXd, respectively, had active BCBMs at treatment initiation. The intracranial disease control rate was 42% [95% confidence interval (CI) 13% to 71%] for patients treated with SG and 88% (95% CI 72% to 100%) for patients treated with T-DXd. After a median follow-up of 12.7 months, median intracranial progression-free survival was 2.7 months (95% CI 1.6-10.5 months) for SG and 11.2 months (95% CI 7.5-23.7 months) for T-DXd. CONCLUSIONS: SG and T-DXd showed promising clinical activity in both stable and active BCBMs. Further prospective clinical studies designed to investigate the efficacy of modern ADCs on active and stable BCBMs are urgently needed.

The HER2 status of disseminated tumor cells in the bone marrow of early breast cancer patients is independent from primary tumor and predicts higher risk of relapse.

Overexpression of the HER2-receptor in early breast cancer (EBC) patients is associated with aggressive tumor behavior. However, women suffering from HER2-positive EBC benefit from trastuzumab treatment. As the HER2 status of the primary tumor may differ from that of disseminated tumor cells (DTC) in bone marrow (BM), the aim of this study was (1) to compare the HER2 status of the primary tumor (prim-HER2-status) with that of DTC (DTC-HER2-status) and (2) to analyze the influence of the DTC-HER2-status on patient survival. For this purpose, BM aspirates from 569 EBC patients were analyzed for the presence of DTC. The DTC-HER2-status was identified by a double-staining procedure against cytokeratin and the HER2-receptor. DTC were detected in 151 (27 %) patients. The concordance between the HER2 status of DTC and the primary tumor was 51 %. In patients with detectable DTC, mean disease-free survival was 77.44 (95 % CI 74.72-80.17) months for DTC-HER2-negative and 55.15 (95 % CI 48.57-61.79) months for DTC-HER2-positive patients (p = 0.044). The multivariate analysis showed that the DTC-HER2-status was an independent predictor of disease-free survival. In conclusion, the presence of HER2-positive DTC in EBC patients is associated with an increased risk of relapse. Due to the low concordance between the HER2 status of the primary tumor and DTC, only a minority (13 %) of the DTC-HER2-positive patients was treated with trastuzumab. These patients might, however, benefit from HER2-directed therapy.

Enhanced killing of ovarian carcinoma using oncolytic measles vaccine virus armed with a yeast cytosine deaminase and uracil phosphoribosyltransferase.

OBJECTIVE: To preclinical assess the feasibility of combining oncolytic measles vaccine virus (MeV) with suicide gene therapy for ovarian cancer treatment. METHODS: We genetically engineered a recombinant MeV armed with a yeast-derived bifunctional suicide gene that encodes for cytosine deaminase and uracil phosphoribosyltransferase (MeV-SCD). From this suicide gene, a chimeric protein is produced that converts the non-toxic prodrug 5-fluorocytosine (5-FC) into highly cytotoxic 5-fluorouracil (5-FU) and directly into 5-fluorouridine monophosphate (5-FUMP) thereby bypassing an important mechanism of chemoresistance to 5-FU. RESULTS: MeV-SCD was demonstrated to infect, replicate in and effectively lyse not only human ovarian cancer cell lines, but also primary tumor cells (albeit at lower efficiencies) that were derived from malignant ascites of ovarian cancer patients. Addition of the prodrug 5-FC significantly enhanced cell killing. Importantly, precision-cut tumor slices of human ovarian cancer patient specimens were efficiently infected with MeV-SCD. The prodrug-converting enzyme SCD was expressed by all infected tumor slices, thereby ensuring provision of the suicide gene arming function in patient-derived materials. CONCLUSIONS: With respect to safety and therapeutic impact, arming of oncolytic measles vaccine virus warrants further clinical investigation for ovarian cancer treatment.

Magnetic resonance-guided focused ultrasound (MRgFUS) compared with abdominal hysterectomy for treatment of uterine leiomyomas.

OBJECTIVES: To compare women undergoing magnetic resonance-guided focused ultrasound (MRgFUS) to a group of contemporaneously recruited women undergoing total abdominal hysterectomy. Patient demographics, safety parameters, quality of life outcomes and disability measures are reported. METHODS: One hundred and nine women were recruited in seven centers for MRgFUS treatment and 83 women who underwent abdominal hysterectomy were recruited in seven separate centers to provide contemporaneous assessment of safety. The adverse-event profile and disability parameters were prospectively assessed. Patients were also screened at baseline and at 1, 3 and 6 months using the SF-36 health survey questionnaire. RESULTS: There were no life-threatening adverse events in either group. Overall, the number of significant clinical complications and adverse events was lower in women in the MRgFUS group compared to women undergoing hysterectomy. MRgFUS was associated with significantly faster recovery, including resumption of usual activities. At 6 months of follow-up, there were four (4%) treatment failures in the MRgFUS arm. Regarding SF-36 subscale scores, at 6 months there was improvement in all SF-36 subscales for both treatment groups. However, most of the SF-36 subscale scores were significantly better at this stage in the hysterectomy group than in the MRgFUS group. Women undergoing MRgFUS had steady improvement in all parameters throughout the 6-month follow-up period, despite the fact that they continued to have myomatous uteri and menstruation, which at baseline had given them significant symptomatology. CONCLUSIONS: The results of this study show that MRgFUS treatment of uterine leiomyomas leads to clinical improvement with fewer significant clinical complications and adverse events compared to hysterectomy at 6 months' follow-up.

Experiences of a multistep process with medical and psychological interventions for patients with congenital uterine aplasia to achieve motherhood: the Gothenburg-Tübingen collaboration.

Congenital uterine aplasia, also known as Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a condition associated to a non-functional uterus in the presence of functional ovaries. In a setting where surrogacy is illegal (or not accepted) and adoption is the only alternative, neovaginoplasty and subsequent uterus transplantation (UTx) can provide a route to motherhood for women with MRKHS. This review article describes a multistep process by which patients with MRKHS can achieve motherhood with their own biological child. This process involving a careful clinical diagnosis, psychological counselling, assessment of eligibility for neovagina creation and UTx, the surgical treatment, fertility treatment, and long-term follow-up was developed at the Tübingen University Hospital and in close collaboration with Sahlgrenska Academy, University of Gothenburg, Sweden, where the basic experimental and clinical groundwork for UTx was laid and the first-ever UTx procedure was performed.

Clinical Characteristics, Surgical Management and Adjuvant Therapy of Patients with Uterine Carcinosarcoma: A Retrospective Case Series.

Purpose: To review a single-center experience over a 27-year period of managing uterine carcinosarcoma (UCS), focusing on surgical practice, adjuvant therapy and clinical outcome. Material and Methods: This was a retrospective study of women with histologically proven UCS treated at the Department of Obstetrics and Gynecology, University of Tübingen, Germany, between 1983 and 2010. Inpatient and outpatient records were reviewed; follow-up and survival data were ascertained. Results: The study population comprised 18 patients with UCS. Primary surgical treatment consisted of total abdominal hysterectomy in 12 patients (67 %) and laparoscopic total hysterectomy in 4 patients (22 %). Bilateral salpingo-oophorectomy was performed in 94 % of patients (17/18). Lymph nodes were evaluated in 15 patients (83 %). Positive pelvic lymph nodes were present in 2 patients (11 %). A total of 17 patients (94 %) received adjuvant therapy. Disease recurred in 7 (39 %) patients of our study group, with no recurrence noted in the 4 patients who underwent laparoscopic surgical staging. Median disease-free survival (DFS) was 48.7 months (95 % CI: 0.0-157.3) and median overall survival (OS) was 49.9 months (95 % CI: 0.0-108.2). The 5-year survival rate was 40 %. Conclusion: UCS is a rare and aggressive uterine neoplasm with high recurrence rates and metastatic potential. Surgical staging consisting of total hysterectomy with bilateral salpingo-oophorectomy and systematic lymphadenectomy is the most important treatment for patients with UCS. Adjuvant radiation therapy appears to decrease pelvic recurrence, but there is a high incidence of distant recurrence, indicating the need for additional systemic treatment.

A Case of Choroidal Melanoma Metastatic to the Breast.

A 61-year-old woman developed blurred vision in her left eye in December 2006. A clinical diagnosis of choroidal melanoma was made. The patient underwent excision of the left lens, followed by vitrectomy and stereotactic radiotherapy. She remained systemically healthy until 50 months later when, during a CT scan done for staging purposes, a newly visible lump was noted in the lower quadrant of her left breast. Core needle biopsy of the lesion in the left breast was performed, and histologic examination revealed metastasis from the choroidal melanoma. The patient underwent breast-conserving surgery of the left breast. Definitive histological examination showed clear tumor margins in the resected specimen and one sentinel lymph node without evidence of metastatic cells. Twenty-nine months after surgery, a similar nodule was detected in the upper quadrant of the left breast. Core biopsy again showed metastatic melanoma, and similar breast-conserving surgery was performed. Systemic examination, including magnetic resonance imaging of the head and computed tomography of the pelvis, abdomen, and chest, was done regularly and revealed no significant findings. Solitary breast metastases from choroidal melanoma are extremely rare. Nevertheless, clinicians should be aware of this rare form of metastasis when treating patients with suspicious breast lesions and a history of choroidal melanoma. If solitary metastasis is confirmed, then breast-conserving surgery may be recommended.

Adjuvant chemotherapy in elderly patients with primary breast cancer: are women ≥65 undertreated?

PURPOSE: To establish whether women over 65 years of age with newly diagnosed with breast cancer (BC) receive adjuvant chemotherapy less frequently than younger postmenopausal women and whether comorbidity influences this potential undertreatment. MATERIALS AND METHODS: In a single-site, retrospective, comparative study, postmenopausal early stage BC patients treated between 01/2001 and 12/2005 at a major German university hospital were analyzed in two age Groups A and B (≥65 vs. <65 years) for initiation and completion of guideline-recommended adjuvant chemotherapy. Risk stratification was based on the 2005 St. Gallen Consensus Conference criteria. Comorbidity was parametrized using the Charlson Comorbidity Index (CCI). RESULTS: Analysis included 634 patients, 380 in Group A and 254 in Group B. Mean age (range) was 73 (65-94) and 61 (55-64) years, respectively. The proportion of patients from Group A given ≥3 cycles of chemotherapy was significantly decreased as compared to Group B. 52 % of patients with CCI <3 but only 20 % with CCI ≥3 were recommended to undergo chemotherapy (p < 0.001). Median follow-up [95 % confidence interval (CI)] was 85 (82-88) months. DFS was significantly shorter in patients aged ≥65 years as compared to younger postmenopausal patients (HR, 0.598; 95 % CI, 0.358-0.963; p = 0.048). CONCLUSIONS: Despite being high-risk patients, older women with early stage BC were often not given guideline-recommended chemotherapy. Higher recurrence rates compared with younger postmenopausal women suggest that older patients are undertreated. Treatment needs to be adapted to general health and tumor biology rather than age. More trials in elderly BC patients are needed.

Radiofrequency Volumetric Thermal Ablation of Fibroids and Laparoscopic Myomectomy: Long-Term Follow-up From a Randomized Trial.

Aims: Laparoscopic myomectomy (LM) has been the gold standard treatment for uterine fibroids in women desiring uterine conservation. To evaluate a new fibroid treatment modality - radiofrequency volumetric thermal ablation (RFVTA) - we compare 12-month results in women who had symptomatic uterine fibroids and who were randomized to laparoscopic ultrasound-guided RFVTA or LM. Materials and Methods: Our study is a 1 : 1 parallel, randomized, prospective, single-center, longitudinal, comparative analysis of RFVTA to LM for fibroid treatment in women ≥ 18 years of age who desired uterine conservation. Fifty women were randomized intraoperatively to RFVTA (n = 25) or to LM (n = 25) after laparoscopic ultrasound mapping of the uterus. Results: Post surgery, ablation and myomectomy subjects took pain medications for 4 days (range: 1-46) and 7 days (range: 1-83 days) respectively (p = 0.60). Ablation and myomectomy subjects missed 10.0 workdays (range: 2-86 days) and 17.0 workdays (range: 7-30 days) (p = 0.28), resumed normal activities in 20.5 days (range: 5-103 days) versus 28.0 days (range: 10-42 days) (p = 0.86) respectively. Mean symptom severity scores decreased (improved) by - 7.8 for the ablation subjects and by - 17.9 for the myomectomy subjects (p = 0.16). Health-related quality of life improved (increased) by 7.5 and 13.1, respectively, for the two groups (p = 0.46). Two myomectomy subjects had pregnancies that ended in a Cesarean delivery and a vaginal delivery of healthy infants. Two pregnancies in the RFVTA group ended in full-term vaginal deliveries of healthy infants. Conclusions: Early postoperative recovery and twelve-month results attest to similar clinical benefits from RFVTA and LM.