Dopamine receptors D1 and D2 show prognostic significance and potential therapeutic applications for endometrial cancer patients.

OBJECTIVE: Catecholaminergic signaling has been a target for therapy in different type of cancers. In this work, we characterized the ADRß2, DRD1 and DRD2 expression in healthy tissue and endometrial tumors to evaluate their prognostic significance in endometrial cancer (EC), unraveling their possible application as an antitumor therapy. METHODS: 109 EC patients were included. The expression of the ADRß2, DRD1 and DRD2 proteins was evaluated by immunohistochemistry and univariate and multivariate analysis to assess their association with clinic-pathological and outcome variables. Finally, HEC1A and AN3CA EC cell lines were exposed to different concentrations of selective dopaminergic agents alone or in combination to study their effects on cellular viability. RESULTS: ADRß2 protein expression was not associated with clinico-pathological parameters or prognosis. DRD1 protein expression was reduced in tumors samples but showed a significant inverse association with tumor size and stage. DRD2 protein expression was significantly associated with non-endometrioid EC, high grade tumors, tumor size, worse disease-free survival (HR = 3.47 (95%CI:1.35-8.88)) and overall survival (HR = 2.98 (95%CI:1.40-6.34)). The DRD1 agonist fenoldopam showed a reduction of cellular viability in HEC1A and AN3CA cells. The exposure to domperidone, a DRD2 antagonist, significantly reduced cell viability compared to the control. Finally, DRD1 agonism and DRD2 antagonism combination induced a significant reduction in cell viability of the AN3CA cells compared to monotherapy, close to being an additive response than a synergistic effect (CI of 1.1 at 0.5% Fa). CONCLUSION: DRD1 and DRD2 expression levels showed a significant association with clinico-pathological parameters. Both the combined activation of DRD1 and blockage of DRD2 may form an innovative strategy to inhibit tumor growth in EC.

Prognostic Value and Therapeutic Implication of Laparoscopic Extraperitoneal Paraaortic Staging in Locally Advanced Cervical Cancer: A Spanish Multicenter Study.

PURPOSE: To assess the impact of laparoscopic extraperitoneal paraaortic staging in therapeutic planning and prognosis of patients with locally advanced cervical cancer (LACC) as compared with imaging staging. METHODS: Retrospective multicenter study of stage IB2 and IIA2 to IVA (FIGO 2009) LACC patients who were candidates for primary chemoradiotherapy. The study (surgical) group included 634 patients undergoing laparoscopic/robotic extraperitoneal paraaortic staging treated with extended-field radiotherapy (EFRT) if lymph node involvement was confirmed. The control (imaging) group included 288 patients treated with EFRT when lymph node involvement was suspected on positron emission tomography-computed tomography scans and/or magnetic resonance imaging. RESULTS: In the study group, a median of 13 (range 9-17) lymph nodes were removed, with a rate of positive paraaortic nodes of 18%, with metastatic size ≤ 5 mm in 20.4% of cases. Paraaortic EFRT was administered to 18% of patients in the study group and in 58% of controls. In 34% of patients from the surgical group, EFRT was modified according to surgical findings with respect to imaging staging. The median follow-up in the study and control groups was 3.7 and 4.8 years, respectively. In both groups, the overall survival and cancer-specific disease-free survival were similar. The time interval between diagnosis and starting EFRT was 18 days longer in the study group, without differences in overall survival as compared with controls (hazard ratio 1.00, 95% confidence interval 0.998-1.005; p = 0.307). CONCLUSIONS: Laparoscopic extraperitoneal paraaortic staging in LACC patients is safe and modified therapeutic planning, allowing better selection of candidates for EFRT.

Laparoscopic Extraperitoneal Pelvic Lymph Node Debulking in Locally Advanced Cervical Cancer.

STUDY OBJECTIVE: To show the feasibility of the laparoscopic extraperitoneal approach for pelvic metastatic lymph node debulking in locally advanced cervical cancer. DESIGN: A surgical video article (Canadian Task Force classification III). SETTING: A university hospital. PATIENT: A 52-year-old patient presented with stage IIA2 cervical adenocarcinoma according to Fédération Internationale de Gynécologie et d'Obstétrique classification. During the physical examination, a 45-mm tumor was discovered. Positron emission tomographic imaging was positive for hypermetabolic enlarged lymph nodes in the left external iliac region of 1.4-cm size and an standardized uptake value of 21 and in the right obturator region of 1.3-cm size and an standardized uptake value of 7.1; no aortic nodes were found using the imaging procedures. Before chemoradiation therapy, she underwent extraperitoneal aortic lymph node dissection for surgical staging at Vall d'Hebron University Hospital, Barcelona, Spain. Pelvic lymph node debulking was proposed to confirm positivity and, if so, to adjust the radiotherapy field and reduce lymph node radioresistance [1,2]. INTERVENTIONS: After a complete extraperitoneal aortic infrarenal lymph node dissection as described by Querleu et al [3], the presacral space is created to expose the iliac vessels. The enlarged lymph nodes are identified and dissected using blunt dissection, monopolar energy, and a vessel sealing device. MEASUREMENTS AND MAIN RESULTS: There were no intraoperative or postoperative complications. The anatomopathologic study confirmed positivity for adenocarcinoma metastasis in 3 pelvic nodes and 2 of 29 aortic nodes. CONCLUSION: Laparoscopic debulking of enlarged pelvic lymph nodes via the extraperitoneal approach is a feasible procedure. It can be performed as an extension of extraperitoneal aortic lymphadenectomy in selected patients with locally advanced cervical cancer.

Patterns of First Recurrence and Oncological Outcomes in Locally Advanced Cervical Cancer Patients: Does Surgical Staging Play a Role?

BACKGROUND: We aimed to determine whether surgical aortic staging by minimally invasive paraaortic lymphadenectomy (PALND) affects the pattern of first recurrence and survival in treated locally advanced cervical cancer (LACC) patients when compared to patients staged by imaging (noPALND). METHODS: This study was a multicenter observational retrospective cohort study of patients with LACC treated at tertiary care hospitals throughout Spain. The inclusion criteria were histological diagnosis of squamous carcinoma, adenosquamous carcinoma, and/or adenocarcinoma; FIGO stages IB2, IIA2-IVA (FIGO 2009); and planned treatment with primary chemoradiotherapy between 2000 and 2016. Propensity score matching (PSM) was performed before the analysis. RESULTS: After PSM and sample replacement, 1092 patients were included for analysis (noPALND n = 546, PALND n = 546). Twenty-one percent of patients recurred during follow-up, with the PALND group having almost double the recurrences of the noPALND group (noPALND: 15.0%, PALND: 28.0%, p < 0.001). Nodal (regional) recurrences were more frequently observed in PALND patients (noPALND:2.4%, PALND: 11.2%, p < 0.001). Among those who recurred regionally, 57.1% recurred at the pelvic nodes, 37.1% recurred at the aortic nodes, and 5.7% recurred simultaneously at both the pelvic and aortic nodes. Patients who underwent a staging PALND were more frequently diagnosed with a distant recurrence (noPALND: 7.0%, PALND: 15.6%, p < 0.001). PALND patients presented poorer overall, cancer-specific, and disease-free survival when compared to patients in the noPALND group. CONCLUSION: After treatment, surgically staged patients with LACC recurred more frequently and showed worse survival rates.

Surgical treatment in older patients with endometrial cancer: A retrospective study.

INTRODUCTION: Older patients (OP) diagnosed with endometrial cancer (EC) are less likely to receive an optimal surgical treatment compared with non-older patients (NOP). This undertreatment along with the presence of more aggressive tumours at diagnosis can explain the worse prognosis of EC in OP. There is limited evidence comparing perioperative outcomes between OP and NOP, and the benefit of applying complex procedures to OP is still controversial. The primary objective of the study was to compare intraoperative and postoperative complications between NOP and OP with EC that underwent primary surgery. Secondary objectives were to compare surgical management and survival rates. METHODS: This is a retrospective single-centre observational study including women undergoing surgery for EC between 2010 and 2019. Patients were classified according to age as NOP (younger than 75 years) or OP (75 years or older). Basal characteristics and surgical outcomes of groups were compared using Chi-square, Fisher's exact tests, student T-tests or Mann Whitney tests. Kaplan Meier analysis was used to evaluate survival. RESULTS: In total 281 patients underwent primary surgery for EC between 2010 and 2019 in our centre. At diagnosis, 184 patients were younger than 75 years while 97 were 75 and older. No differences were found in disease characteristics. Most of our patients (83,3%) underwent laparoscopic surgery. Pelvic (58,2% vs. 37,1%, p = 0,001) and para-aortic (46,7% vs. 23,7%, p < 0,001) lymphadenectomies were performed more frequently in NOP compared with OP. Rates of intra-operative (6,5% vs. 12,4%, p = 0,116) and post-operative (13,0% vs. 20,6%, p = 0,120) complications were not statistically different between NOP and OP, and neither was the rate of severe complications according to Clavien-Dindo classification (5,4% vs. 8,2% of complications grade III-V respectively, p = 0,387). The 5-year disease-specific survival (DSS) rate tended to be lower in the OP than in the NOP (74,8% vs. 82,5%, p = 0,071). Considering only patients in whom complete surgical staging was performed, OP presented similar DSS to NOP, with comparable complication rate. CONCLUSIONS: OP do not present a significantly higher rate of perioperative complications compared to NOP. However, they underwent fewer lymphadenectomies and tended to present poorer DSS. Further studies are needed to standardize the surgical management of these patients.

Laparoscopic approach for symptomatic pelvic and para-aortic lymphoceles

Description and demonstration of the feasibility of laparoscopic management of symptomatic pelvic lymphocele after surgical staging in gynecological cancer surgery. Step-by-step description of the surgical procedure using pictures and an educational video. Patient gave informed consent for the use of images and the full video article was approved by the Institutional Review Board of the Hospital of Sant Pau. Lymphocele is one of the most common complications of pelvic or lumbo-aortic lymphadenectomy. Although the incidence is variable at 1-58%, around 5-18% of cases are symptomatic. Only symptomatic lymphocele requires treatment, which can be medical or interventional. Drainage is usuallyperformed by guided radiology although a surgical approach has shown a lower rate of recurrence. A 64-years-old woman diagnosed withendometrial carcinosarcoma was staged laparoscopically by pelvic and para-aortic lymphadenectomy. Para-aortic lymphadenectomy wasperformed using an extraperitoneal approach. Three weeks later she presented with an intense and persistent burning pain, radiating towardsthe left leg. Computed tomography imaging suggested the presence of a 10x7.6 cm lymphocele adjacent to the left external iliac vessels.Laparoscopy was performed with four-port placement configuration, enabling the identification of a large, bilobed lymphocele, adjacent to theleft pelvic wall and left paracolic gutter. Adhesiolysis and identification of main landmarks in the left paracolic gutter and left paravesical fossawas performed as a first step. Peritoneum of each lymphocele was opened in the caudal region and the opening was broadened to facilitatelymph drainage. Owing to the low morbidity and excellent results, we suggest that laparoscopic drainage should be performed as a feasible anduseful treatment for pelvic symptomatic lymphoceles.