PGE2 inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function.

Expansion of antigen-experienced CD8+ T cells is critical for the success of tumour-infiltrating lymphocyte (TIL)-adoptive cell therapy (ACT) in patients with cancer1. Interleukin-2 (IL-2) acts as a key regulator of CD8+ cytotoxic T lymphocyte functions by promoting expansion and cytotoxic capability2,3. Therefore, it is essential to comprehend mechanistic barriers to IL-2 sensing in the tumour microenvironment to implement strategies to reinvigorate IL-2 responsiveness and T cell antitumour responses. Here we report that prostaglandin E2 (PGE2), a known negative regulator of immune response in the tumour microenvironment4,5, is present at high concentrations in tumour tissue from patients and leads to impaired IL-2 sensing in human CD8+ TILs via the PGE2 receptors EP2 and EP4. Mechanistically, PGE2 inhibits IL-2 sensing in TILs by downregulating the IL-2Rγc chain, resulting in defective assembly of IL-2Rß-IL2Rγc membrane dimers. This results in impaired IL-2-mTOR adaptation and PGC1α transcriptional repression, causing oxidative stress and ferroptotic cell death in tumour-reactive TILs. Inhibition of PGE2 signalling to EP2 and EP4 during TIL expansion for ACT resulted in increased IL-2 sensing, leading to enhanced proliferation of tumour-reactive TILs and enhanced tumour control once the cells were transferred in vivo. Our study reveals fundamental features that underlie impairment of human TILs mediated by PGE2 in the tumour microenvironment. These findings have therapeutic implications for cancer immunotherapy and cell therapy, and enable the development of targeted strategies to enhance IL-2 sensing and amplify the IL-2 response in TILs, thereby promoting the expansion of effector T cells with enhanced therapeutic potential.

Contribution of preoperative ultrasound-guided implantation of a magnetic seed for optimal localization and resection of vulvar angiosarcoma: A case report.

INTRODUCTION: Vulvar cancer is a rare cause of malignancy among women. It is key for surgeons to achieve negative resection margins, as it greatly impacts patient's prognosis. Unfortunately, additional surgical procedures are often performed due to the regional anatomical complexity. Based on non-palpable breast tumors, where image-guided preoperative localization tools have enhanced the complete resection rates, we aimed at evaluating the feasibility of magnetic seed technique for localizing perineal lesions. PRESENTATION OF THE CASE: We present the case of a 40-year-old female patient, who underwent iterative resections for a recurrent epithelioid angiosarcoma of the left labia major. Imaging revealed a suspicious regional involvement at 3 months of follow-up, for which another surgery was planned. We decided to target this non-palpable lesion with the Magnetic Seed technique to guide the intervention. A seed was inserted into the nodule under ultrasound guidance. Resection was then performed, with negative margins and no recurrence on last follow-up. DISCUSSION: Surgical procedures with minimal extension are recommended in vulvar cancer, to limit the aesthetic and functional complication. Unfortunately, recurrences and residual tumors remain frequent, even higher when surgical margin safety is not achieved. Many studies have suggested the benefit of image-guided localization tools in non-palpable breast tumors. By reducing the excising volume and focusing on the lesions, relapse and complications are rarer. We considered Magnetic Seed to be the most appropriated technique for perineal lesions. CONCLUSION: As for breast cancer, Magnetic Seed technique could be appropriate for non-palpable perineal lesions, optimizing resection margins with minimal procedures.

Association of Axillary Dissection With Systemic Therapy in Patients With Clinically Node-Positive Breast Cancer.

Importance: The role of axillary lymph node dissection (ALND) to determine nodal burden to inform systemic therapy recommendations in patients with clinically node (cN)-positive breast cancer (BC) is currently unknown. Objective: To address the association of ALND with systemic therapy in cN-positive BC in the upfront surgery setting and after neoadjuvant chemotherapy (NACT). Design, Setting, and Participants: This was a prospective, observational, cohort study conducted from August 2018 to June 2022. This was a preplanned study within the phase 3 randomized clinical OPBC-03/TAXIS trial. Included were patients with confirmed cN-positive BC from 44 private, public, and academic breast centers in 6 European countries. After NACT, residual nodal disease was mandatory, and a minimum follow-up of 2 months was required. Exposures: All patients underwent tailored axillary surgery (TAS) followed by ALND or axillary radiotherapy (ART) according to TAXIS randomization. TAS removed suspicious palpable and sentinel nodes, whereas imaging-guidance was optional. Systemic therapy recommendations were at the discretion of the local investigators. Results: A total of 500 patients (median [IQR] age, 57 [48-69] years; 487 female [97.4%]) were included in the study. In the upfront surgery setting, 296 of 335 patients (88.4%) had hormone receptor (HR)-positive and Erb-B2 receptor tyrosine kinase 2 (ERBB2; formerly HER2 or HER2/neu)-negative disease: 145 (49.0%) underwent ART, and 151 (51.0%) underwent ALND. The median (IQR) number of removed positive lymph nodes without ALND was 3 (1-4) nodes compared with 4 (2-9) nodes with ALND. There was no association of ALND with the proportion of patients undergoing adjuvant chemotherapy (81 of 145 [55.9%] vs 91 of 151 [60.3%]; adjusted odds ratio [aOR], 0.72; 95% CI, 0.19-2.67) and type of systemic therapy. Of 151 patients with NACT, 74 (51.0%) underwent ART, and 77 (49.0%) underwent ALND. The ratio of removed to positive nodes was a median (IQR) of 4 (3-7) nodes to 2 (1-3) nodes and 15 (12-19) nodes to 2 (1-5) nodes in the ART and ALND groups, respectively. There was no observed association of ALND with the proportion of patients undergoing postneoadjuvant systemic therapy (57 of 74 [77.0%] vs 55 of 77 [71.4%]; aOR, 0.86; 95% CI, 0.43-1.70), type of postneoadjuvant chemotherapy (eg, capecitabine: 10 of 74 [13.5%] vs 10 of 77 [13.0%]; trastuzumab emtansine-DM1: 9 of 74 [12.2%] vs 11 of 77 [14.3%]), or endocrine therapy (eg, aromatase inhibitors: 41 of 74 [55.4%] vs 36 of 77 [46.8%]; tamoxifen: 8 of 74 [10.8%] vs 6 of 77 [7.8%]). Conclusion: Results of this cohort study suggest that patients without ALND were significantly understaged. However, ALND did not inform systemic therapy recommendations.

Para-aortic Lymphadenectomy for Gynecologic Cancers: Introducing the "Trans-Retro-Peritoneal (TRP) Single-Port Access".

BACKGROUND: In gynecological surgery to date, two distinct types of endoscopic accesses have been used to perform para-aortic lymphadenectomies: transperitoneal and extraperitoneal, each with advantages and disadvantages.1 We propose to develop a new mini-invasive access to perform an endoscopic extraperitoneal para-aortic lymphadenectomy via a single-port umbilical device that, to our knowledge, has never been described. METHODS: This innovative approach combines both an extraperitoneal and intraperitoneal procedure via the same umbilical incision using one single trocar. A 3-4 cm trans-umbilical incision is performed and a three-channel single-port device (Gelpoint Mini°; Applied Medical, Rancho Santa Margarita, CA, USA) is introduced in the peritoneal cavity. After peritoneal exploration, the peritoneum overlying the aorta bifurcation is grabbed, raised to the umbilicus, opened, and the single-port device is then re-introduced into the retroperitoneal space. RESULTS: The intervention has been successful in three patients with locally advanced cervical cancer (two International Federation of Gynecology and Obstetrics [FIGO] stage IB2, and one FIGO stage IVA) scheduled for concomitant radiochemotherapy after exclusion of any suspicious lymph nodes by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET), according to our standards of practice based on the European Society of Gynaecological Oncology (ESGO) and National Comprehensive Cancer Network (NCCN) guidelines.2,3 Due to the type of cancer, lymphadenectomy was limited to the infra-mesenteric nodes,2,4 although the dissection went up to the left renal vein in each case. We retrieved 13, 20, and 25 lymph nodes. No complications occurred. CONCLUSIONS: We describe a promising technique that combines all the advantages of the two previously described accesses without their disadvantages, and with the cosmetic benefit of one almost invisible single trans-umbilical scar.

[Use of mammaplasties in oncology: a 20­year evolution]. / Usage des plasties mammaires en oncologie : 20 ans d'évolution.

The use of mammaplasties to remove breast tumors was first described more than 20 years ago. They were initially indicated for tumors located in the lower quadrants and in large breasts, in order to mimic breast reductions used in aesthetic surgery. These techniques have been subsequently conformed to tumors located in every breast quadrant, including the central part. In some circumstances, some adaptations even allow the removal of skin areas outside the traditional Wise pattern. We report two cases illustrating some of these developments.Therefore, oncoplastic surgery has evolved according to the constraints induced by the disease, becoming a full discipline on its own.

L'usage des plasties mammaires pour réaliser l'exérèse de tumeurs cancéreuses a été décrit il y a plus de 20 ans. Celles-ci étaient initialement réservées aux tumeurs des quadrants inférieurs et pour des seins de gros volume afin de coller aux techniques de chirurgie plastique, utilisées en situation bénigne (réductions mammaires). Ces techniques ont été modifiées au fil des années afin de pouvoir réséquer des tumeurs situées dans tous les quadrants du sein, y compris en région centrale. Des adaptations des schémas de plastie permettent même, dans certains cas, la résection de peau située en dehors des tracés traditionnels. Nous rapportons deux cas cliniques illustrant ces avancées. La chirurgie oncoplastique a ainsi évolué selon les contraintes liées à la maladie traitée, devenant une discipline à part entière.

Comparative Study of Neoadjuvant Chemotherapy With and Without Zometa for Management of Locally Advanced Breast Cancer With Serum VEGF as Primary Endpoint: The NEOZOL Study.

INTRODUCTION: Neoadjuvant chemotherapy has become the treatment of choice for locally advanced breast cancer. Zoledronic acid (ZA) is a bisphosphonate initially used in the treatment of bone metastases because of its antibone resorption effect. Antitumor effects of ZA, including the inhibition of cell adhesion to mineralized bone or the antiangiogenic effect, have been demonstrated. However, the clinical significance of these effects remains to be determined. MATERIALS AND METHODS: We undertook a multicenter open-label randomized trial to analyze the value of adding ZA to neoadjuvant chemotherapy for TNM clinical stage T2/T3 breast cancer. The primary endpoint was the evolution of serum VEGF. RESULTS: The data from 24 patients were included in the ZA group and 26 in the control group. The evolution of serum VEGF was slightly in favor of ZA at 5.5 months (-0.7% vs. +7.5%), without reaching statistical significance (P = .52). The secondary endpoints were the breast conservation rate (higher with ZA; 83.3% vs. 65.4%; P = NS), pathologic complete response (no effect), and circulating tumor cells (odds ratio, 0.68 in favor of ZA; 95% confidence interval, 0.02-24.36). No cases of jaw necrosis or severe renal failure were observed in either group. CONCLUSION: ZA is an antitumor drug of interest because of its multiple effects on tumor biology. Larger trials with longer follow-up that include additional endpoints such as relapse and survival rates would be of interest.

Impact of a Surgical Sealing Patch on Lymphatic Drainage After Axillary Dissection for Breast Cancer: The SAKK 23/13 Multicenter Randomized Phase III Trial.

BACKGROUND: Several studies and a meta-analysis showed that fibrin sealant patches reduced lymphatic drainage after various lymphadenectomy procedures. Our goal was to investigate the impact of these patches on drainage after axillary dissection for breast cancer. METHODS: In a phase III superiority trial, we randomized patients undergoing breast-conserving surgery at 14 Swiss sites to receive versus not receive three large TachoSil® patches in the dissected axilla. Axillary drains were inserted in all patients. Patients and investigators assessing outcomes were blinded to group assignment. The primary endpoint was total volume of drainage. RESULTS: Between March 2015 and December 2016, 142 patients were randomized (72 with TachoSil® and 70 without). Mean total volume of drainage in the control group was 703 ml [95% confidence interval (CI) 512-895 ml]. Application of TachoSil® did not significantly reduce the total volume of axillary drainage [mean difference (MD) -110 ml, 95% CI -316 to 94, p = 0.30]. A total of eight secondary endpoints related to drainage, morbidity, and quality of life were not improved by use of TachoSil®. The mean total cost per patient did not differ significantly between the groups [34,253 Swiss Francs (95% CI 32,625-35,880) with TachoSil® and 33,365 Swiss Francs (95% CI 31,771-34,961) without, p = 0.584]. In the TachoSil® group, length of stay was longer (MD 1 day, 95% CI 0.3-1.7, p = 0.009), and improvement of pain was faster, although the latter difference was not significant [2 days (95% CI 1-4) vs. 5.5 days (95% CI 2-11); p = 0.2]. CONCLUSIONS: TachoSil® reduced drainage after axillary dissection for breast cancer neither significantly nor relevantly.

[Selective therapeutic de-escalation in early stage breast cancer]. / Cancer du sein de stade précoce : la désescalade thérapeutique sélective.

The survival of patients with breast cancer has improved considerably thanks to adjuvant radiotherapy and systemic treatments. Due to the potential adverse events associated with these treatments, a de-escalation effort was undertaken concerning surgery and more recently the adjuvant treatments. Conservative breast surgery and the avoidance of axillary dissection were possible for the majority of the patients without detrimental effect on survival. New radiotherapy techniques and the consideration of cancer biology allowed to better protect the peripheral organs and even to avoid treatment in certain low-risk patients. The refinement of prognostic and predictive criteria helped reducing the use of chemotherapy and adapting the duration of endocrine therapy to the risk.

La survie des patientes ayant présenté un cancer du sein s'est considérablement améliorée grâce à la radiothérapie et aux traitements systémiques adjuvants. Au vu des effets adverses liés à ces traitements, un effort de désescalade thérapeutique a été entrepris en ce qui concerne la chirurgie et plus récemment les traitements adjuvants. La chirurgie conservatrice du sein et l'abandon du curage axillaire sont possibles pour la majorité des patientes sans altérer leur survie. Les nouvelles techniques de radiothérapie et la prise en compte de la biologie tumorale ont permis de mieux protéger les organes périphériques, voire éviter le traitement chez certaines patientes à bas risque. L'affinement des critères pronostiques et prédictifs a aidé à diminuer le recours à la chimiothérapie et adapter la durée de l'hormonothérapie au risque.

Value of the sentinel lymph node procedure in patients with large size breast cancer.

BACKGROUND: Widely used in routine for small breast cancers, the sentinel lymph node (SN) biopsy is still discussed in tumors >or= 3 cm. METHODS: From 2000 to 2005, 152 patients with invasive breast tumor pT >or= 3 cm had a SN biopsy systematically followed by complete level I/II axillary dissection. Surgery was always the first stage of the treatment. Detection was done after injection of radioisotope followed by a lymphoscintigraphy and injection of Patent Blue. The SN procedure systematically included palpation of the axilla with removal of any enlarged (>1 cm) and/or abnormally firm node even if neither blue nor radioactive. The sentinel lymph node status was compared with the final axillary status. RESULTS: Tumor size ranged from 30 to 200 mm (median 42 mm). Lymphoscintigraphy was positive in 98% of the cases. At least one labeled sentinel node was retrieved in 97.4% of the patients. The median number of SN cleared out was 2 (range 1-9). The false negative risk was 4% (4/99). The false negative risk was not related to the tumor size and not related to the number of SN removed. CONCLUSIONS: This study shows that the SN procedure is feasible in patients with breast tumors >or= 3 cm with an acceptable false negative risk <5%, similar to false negatives reported for smaller tumors.

Residual pelvic lymph node involvement after concomitant chemoradiation for locally advanced cervical cancer.

OBJECTIVE: Concomitant chemoradiation (and brachytherapy) has become the standard treatment for locally advanced cervical cancers (FIGO stage IB2 to IVA). Adjuvant surgery is optional. The aim of this study was to evaluate the rate of residual positive pelvic lymph nodes after chemoradiation. METHODS: From February 1988 to August 2004, 113 patients with locally advanced cervical cancer have been treated by chemoradiation followed by an adjuvant surgery with a pelvic lymphadenectomy performed (study group). A para-aortic lymphadenectomy had also been performed in 85 of them. RESULTS: The mean age of the patients was 48.4 years (27-74). FIGO stage was: IB2 in 17.7% (20/113), II in 44.2% (50/113), III in 21.2% (24/113) and IVA in 16.8% of the patients (19/113). The mean number of removed nodes was 11.5 (median 11) in pelvic, and 7.5 (median 7) in para-aortic basins. A pelvic lymph node involvement was present in 15.9% (18/113) of the patients after chemoradiation. In 11 patients, only one node was positive. 11.7% (10/85) of the patients had a para-aortic lymph node involvement. A residual pelvic lymph node disease has been observed in 6.3% (4/63) of the cases with no residual cervical disease (or microscopic) versus 26.5% (13/49) of the cases with macroscopic residual cervical tumor (P = 0.003). CONCLUSIONS: Our experience shows that a pelvic lymph node involvement persists in about 16% of the patients after chemoradiation. We can make the assumption that performing a pelvic lymphadenectomy along with the removal of the primary tumor after chemoradiation could reduce the rate of latero-pelvic recurrences, whatever the para-aortic lymph node status.

Long-term survival after concomitant chemoradiotherapy prior to surgery in advanced cervical carcinoma.

OBJECTIVE: To report the long-term survival of 35 patients who underwent surgery after concomitant chemoradiation for locally advanced cervical cancers. METHODS: From 1988 to 1992, 20 bulky IB-IIB patients and 15 stage III-IVA patients underwent surgery after concurrent chemotherapy (CDDP and 5-FU) and radiotherapy. 26 had a hysterectomy, 8 had an exenteration, 1 had no tumor resection. 21 had a para-aortic lymphadenectomy. Endpoints were recurrence and distant metastasis rates, overall survival (OS) and disease-free survival (DFS) at 5 and 10 years. Analysis included FIGO stage, type of surgery (palliative or curative), response to chemoradiation or para-aortic lymphatic status. RESULTS: Surgery had been only palliative in 6 cases (17.1%). A pelvic control has been achieved in 31 patients (88.6%). Pelvic recurrences occurred after a median interval of 7 months. Distant metastases occurred in 10 patients (28.6%), after a median interval of 20 months. So far, 16 patients have died (45.7%). The 10-year DFS is 56.7% in the whole series. Only the type of surgery significantly affected the OS. Only the para-aortic lymphatic status significantly affected the DFS. CONCLUSION: Associating chemoradiation with curative surgery, we obtained a 10-year DFS of 66.4% (OS 57.7%). Adjuvant surgery may increase the survival as it reduces the risk of local relapse.

Previous abdominal surgery and closed entry for gynaecological laparoscopy: a prospective study.

OBJECTIVES: To assess the morbidity from closed laparoscopic access and define the role of previous surgery on the occurrence of these complications. DESIGN AND METHODS: We prospectively recorded data on all laparoscopic procedures between January 2000 and January 2001. We compared results from patients without previous abdominal surgery (group I) with patients with prior abdominal surgery (group II). The insertion site for the Verres needle was trans-umbilical for patients in group I and in the left upper quadrant for patients in group II. SETTING: Gynaecology department of a University Hospital. POPULATION: All laparoscopic procedures between January 2000 and January 2001. MAIN OUTCOME MEASURES: We compared results from patients without previous abdominal surgery (group I) with patients with prior abdominal surgery (group II). The insertion site for the Verres needle was trans-umbilical for patients in group I and the left upper quadrant for patients in group II. RESULTS: Four hundred and seventy-seven laparoscopies were carried out during the study period, 368 women without previous surgery were included in group I, and 109 women were included in group II. We recorded 1 complication (overall complication rate of 0.2% and 31 incidents (6.4%). One complication (small bowel injury) was related to the insertion of the Verres needle (0.2%). The incidents and complications occurred only in group II (P < 0.05). All the complications were treated by laparoscopy. CONCLUSION: The complication rate of the entry step is low in gynaecological laparoscopy. A previous history of laparotomy increases the risk of these complications and incidents. Safety rules and other access method should be investigated for these patients.

Endometriosis with FDG uptake on PET.

BACKGROUND: The value of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) uptake in endometriosis has not yet been extensively reported. CASE REPORT: A 32-year-old woman was examined to find an explanation for right pelvic pain associated with right subcostal pain. A computerised tomography (CT) scan was compatible with a haemangioma or a focus of endometriosis in the liver. Transvaginal sonography and magnetic resonance imaging (MRI) showed a complex ovarian cyst on the left. Blood CA125 levels were elevated. FDG-PET revealed a focus of uptake in the right paravesical area. Laparoscopy showed a left endometrioma associated with diffuse inflammatory pelvic adhesions. After surgery and 3 months GnRH agonist treatment the pain had disappeared and neither MRI nor FDG-PET showed any pelvic abnormality. The patient subsequently presented with dyspareunia and rectal pain resulting from a right uterosacral nodule and a rectal nodule. These were resected laparoscopically. After a 1-year follow-up, the patient is doing well. CONCLUSION: Endometriosis can give rise to false-positive results on FDG-PET. However, the FDG uptake in this particular case of endometriosis seems to have been due to inflammation rather than to a cyst. This report highlights the relationship between some of the biological features of endometriosis and some observed in neoplastic lesions.

[Sentinel lymph node biopsy in cervical and endometrial cancers: a feasibility study]. / Technique du ganglion sentinelle appliquée aux cancers de l'utérus: étude préliminaire.

The sentinel lymph node (SLN) biopsy has been proposed for the cancers of the uterus in order to optimize the diagnosis of lymphatic metastases and micrometastases in early stage tumors. Patients with early invasive cervical (n = 8) or endometrial (n = 15) cancers were enrolled. A lymphoscintigraphy was carried out before the intervention. Intraoperative SLN identification was performed with blue dye combined to a handheld gamma probe detection. Non-sentinel pelvic nodes were separately cleared out. SLNs were examined with frozen sections, permanent sections with hematoxylin-eosin staining and further serial sections with immunohistochemistry if negative. Six cervical cancer patients and 13 endometrial cancer patients had a positive lymphoscintigraphy, showing in 5 patients extra-iliac SLN(s). The intraoperative detection was successful in 6 cervical cancer patients and 14 endometrial cancer patients. The higher detection rate was obtained with the isotopic method. Most of the SLNs were ilio-obturator. Four endometrial cancer patients had a lymphatic spread, only involving the SLN in each case. No false negative SLN has been noted. SLN biopsy appears feasible in cervical and endometrial cancers. This procedure could improve the lymphatic evaluation of these cancers.

Sono-guided endometrial biopsy: comparison with hysteroscopy biopsy. Sono-guided endometrial biopsy using the Bernard catheter had no impact on endometrial assessment by sonohysterography.

OBJECTIVE: To assess the feasibility, tolerance and diagnostic accuracy of endometrial biopsy (EB) during sonohysterography (SH) compared to EB after hysteroscopy (HSC) in endometrial disorders. METHODS: 105 consecutive patients with irregular uterine bleeding were included prospectively in the calendar year 2001. SH and flexible HSC were performed in an office setting, subsequently and in a random order, by two different practitioners blind to the former experiment. SH-EB was performed using a 3.1-mm ultrasound-guided Bernard catheter in the uterine cavity still partly distended and with a gentle 20-ml syringe vacuum aspiration. The biopsy was directed on focal lesions or else randomly when no targets had previously been found. A Cornier Pipelle was used to perform EB after HSC. We investigated all patients by biopsy, independent of the endometrial thickness. HSC-EB was the gold standard. RESULTS: For both methods, cervical catheterism was impossible in 20 patients, 75 of them successfully underwent both exams. Duration and tolerance were similar. SH was effective in the distinction between normal and pathologic cavities, as well as in the diagnosis of polyps. Endometrium appeared significantly thinner with HSC (1.8 mm) when compared to SH (2.9 mm, p < 0.05). Histological endometrial assessment failed in 30 cases of SH-EB and in 22 cases in HSC-EB (NS). There was a poor correlation of the histological results of both techniques. Hyperplasia has never been diagnosed by SH-EB, whereas 3 EB issued from HSC-EB brought up this diagnosis. CONCLUSION: SH-EB with our technique did not improve the diagnostic potential of SH and severe diagnosis was missed. Histological assessment should fail less when we exclude endometrial atrophy. The diameter of the catheter and the aspiration technique must be revised and the learning curve must be considered. Our technique cannot replace EB by HSC.

Comparison between bisection/morcellation and myometrial coring for reducing large uteri during vaginal hysterectomy or laparoscopically assisted vaginal hysterectomy: results of a randomized prospective study.

BACKGROUND: Vaginal hysterectomy (VH) is being performed increasingly by gynecologic surgeons. Thus, enlarged uteri are more frequently removed vaginally, requiring reducing techniques to allow vaginal extraction. MATERIAL AND METHODS: We designed a randomized prospective study to compare bisection-morcellation and myometrial coring. Patients scheduled for VH or laparoscopically assisted vaginal hysterectomy (LAVH) were offered entry into the study. Endometrial cancer was an exclusion criterion. Uterine size was not a contraindication for vaginal surgery. We compared data from preoperative workup as well as from the operative and the postoperative course. Data were recorded prospectively. Results were analyzed with nonparametric tests and logistic regression models. RESULTS: Thirty patients were included in the study. Patients were similar in both groups. No severe peroperative complication occurred in this series. Operating time was comparable in both groups. Uteri weighed more than 280 g in more than 70% of patients in both groups. Myometrial coring failed more often than bisection-morcellation (25% vs. 0%, p = 0.06). Patients and uteri characteristics had no influence on the risk of failure, except for narrow uteri, which were associated with an increased risk of failure in the myometrial coring group only (68.3 vs. 83.9 mm, p = 0.01). Postoperative courses were similar for the two techniques, except for an increased rate of fever in the myometrial coring group (28%, p = 0.03). CONCLUSION: Both techniques appeared safe in this trial. Myometrial coring failed more frequently than bisection-morcellation, especially in the case of a narrow uterus. Postoperative fever was significantly more common after myometrial coring. Both techniques should be taught to resident surgeons.