Investigating the Role of Minimally Invasive Surgery in Patients with Chronic Pulmonary Disease.

In the recent years, the role of minimally invasive surgery (e.g., laparoscopic or robotic assisted surgery) has emerged for the treatments of several benign and malignant conditions [1–4]. Growing..

Sentinel node mapping in endometrial cancer

Nodal status is one of the most important prognostic factors for patients with apparent early stage endometrial cancer. The role of retroperitoneal staging in endometrial cancer is controversial. Nodal status provides useful prognostic data, and allows to tailor the need of postoperative treatments. However, two independent randomized trials showed that the execution of (pelvic) lymphadenectomy increases the risk of having surgery-related complication without improving patients' outcomes. Sentinel node mapping aims to achieve data regarding nodal status without increasing morbidity. Sentinel node mapping is the removal of first (clinically negative) lymph nodes draining the uterus. Several studies suggested that sentinel node mapping is not inferior to lymphadenectomy in identifying patients with nodal disease. More importantly, thorough ultrastaging sentinel node mapping allows the detection of low volume disease (micrometastases and isolated tumor cells), that are not always detectable via conventional pathological examination. Therefore, the adoption of sentinel node mapping guarantees a higher identification of patients with nodal disease than lymphadenectomy. Further evidence is needed to assess the value of various adjuvant strategies in patients with low volume disease and to tailor those treatments also on the basis of the molecular and genomic characterization of endometrial tumors

A randomized phase 2 study of sapanisertib in combination with paclitaxel versus paclitaxel alone in women with advanced, recurrent, or persistent endometrial cancer

Endometrial cancer; Metastatic; RecurrentCàncer d'endometri; Metastàtic; RecurrentCáncer endometrial; Metastásico; RecurrenteObjective This phase 2 study investigated sapanisertib (selective dual inhibitor of mTORC1/2) alone, or in combination with paclitaxel or TAK-117 (a selective small molecule inhibitor of PI3K), versus paclitaxel alone in advanced, recurrent, or persistent endometrial cancer. Methods Patients with histologic diagnosis of endometrial cancer (1–2 prior regimens) were randomized to 28-day cycles on four treatment arms: 1) weekly paclitaxel 80 mg/m2 (days 1, 8, and 15); 2) weekly paclitaxel 80 mg/m2 + oral sapanisertib 4 mg on days 2–4, 9–11, 16–18, and 23–25; 3) weekly sapanisertib 30 mg, or 4) sapanisertib 4 mg + TAK-117 200 mg on days 1–3, 8–10, 15–17, and 22–24. Results Of 241 patients randomized, 234 received treatment (paclitaxel, n = 87 [3 ongoing]; paclitaxel+sapanisertib, n = 86 [3 ongoing]; sapanisertib, n = 41; sapanisertib+TAK-117, n = 20). The sapanisertib and sapanisertib+TAK-117 arms were closed to enrollment after futility analyses. After a median follow-up of 14.4 (paclitaxel) versus 17.2 (paclitaxel+sapanisertib) months, median progression-free survival (PFS; primary endpoint) was 3.7 versus 5.6 months (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.58–1.15; p = 0.139); in patients with endometrioid histology (n = 116), median PFS was 3.3 versus 5.7 months (HR 0.66; 95% CI 0.43–1.03). Grade ≥ 3 treatment-emergent adverse event rates were 54.0% with paclitaxel versus 89.5% paclitaxel+sapanisertib. Conclusions Our findings support inclusion of chemotherapy combinations with investigational agents for advanced or metastatic disease. The primary endpoint was not met and toxicity was manageable. Trial registration: ClinicalTrials.gov number, NCT02725268Takeda Development Center Americas, Inc., Lexington, MA, USA. This work was supported by funding from Takeda Development Center Americas, Inc. The study was designed by the authors in conjunction with the sponsors. Data were gathered and analyzed by the investigator and the sponsor; all the authors had access to the data. The authors received medical writing support for drafting the manuscript, which was funded by Takeda Pharmaceuticals USA, Inc. Manuscript drafts were reviewed by all authors and the sponsor and all the authors made the decision to submit the manuscript for publication

Ultrasounds induce blood-brain barrier opening across a sonolucent polyolefin plate in an in vitro isolated brain preparation

The blood-brain barrier (BBB) represents a major obstacle to the delivery of drugs to the central nervous system. The combined use of low-intensity pulsed ultrasound waves and intravascular microbubbles (MB) represents a promising solution to this issue, allowing reversible disruption of the barrier. In this study, we evaluate the feasibility of BBB opening through a biocompatible, polyolefin-based plate in an in vitro whole brain model. Twelve in vitro guinea pig brains were employed; brains were insonated using a planar transducer with or without interposing the polyolefin plate during arterial infusion of MB. Circulating MBs were visualized with an ultrasonographic device with a linear probe. BBB permeabilization was assessed by quantifying at confocal microscopy the extravasation of FITC-albumin perfused after each treatment. US-treated brains displayed BBB permeabilization exclusively in the volume under the US beam; no significant differences were observed between brains insonated with or without the polyolefin plate. Control brains not perfused with MB did not show signs of FITC-albumin extravasation. Our preclinical study suggests that polyolefin cranial plate could be implanted as a skull replacement to maintain craniotomic windows and perform post-surgical repeated BBB opening with ultrasound guidance to deliver therapeutic agents to the central nervous system

Primary or Interval Debulking Surgery for Advanced Endometrial Cancer with Carcinosis: A Systematic Review and Individual Patient Data Meta-Analysis of Survival Outcomes

Objective: To compare the survival outcomes of primary debulking surgery and platinum-based adjuvant chemotherapy versus interval debulking surgery after platinum-based neoadjuvant chemotherapy in patients with stage IVb endometrial cancer and peritoneal carcinosis. Methods: The online search included the following data sources: PubMed, Scopus, WOS, and the Cochrane Library from 1990 to 2024 (PROSPERO registration code: CRD42023438602). A total of 3230 studies were identified, with the inclusion of 16. Individual patient data on survival outcomes, disease distribution, and residual tumors, as well as details of neoadjuvant chemotherapy and adjuvant treatment, were extracted. Results: A total of 285 patients were included: 197 (69%) underwent primary debulking surgery and 88 (31%) underwent interval debulking surgery. The pooled analysis revealed a median progression-free survival in the primary debulking surgery group of 18.0 months compared to 12.0 months in the interval debulking surgery group (p = 0.028; log-rank test), and a median overall survival of 30.92 months versus 28.73 months (p = 0.400; log-rank test). Among the 134 patients with available information on the residual tumor after primary debulking surgery or interval debulking surgery, 110 (82%) had no macroscopic residual tumor (residual tumor = 0). The median progression-free survival was 18.9 months in the residual tumor = 0 group compared to 6.19 months in the residual tumor > 0 group (p < 0.001; log-rank test); the median overall survival was 40.6 months versus 21 months (p = 0.028; log-rank test). Conclusions: These results indicate that primary debulking surgery should be considered the preferred treatment approach for advanced endometrial cancer with carcinosis, especially in carefully selected patients where complete cytoreduction is achievable. Further prospective studies are warranted to confirm these results and to establish standardized criteria for patient selection, incorporating molecular-integrated risk profiles for endometrial cancer

Oncologic effectiveness of nerve-sparing radical hysterectomy in cervical cancer

Objective: Nerve-sparing radical hysterectomy (NSRH) was introduced with the aim to reduce pelvic dysfunctions related to conventional radical hysterectomy (RH). Here, we sought to assess the effectiveness and safety of NSRH in a relatively large number of the patients of cervical cancer (CC) patients undergoing either primary surgery or neoadjuvant chemotherapy (NACT) followed by surgery. Methods: Outcomes of consecutive patients undergoing NSRH and of a historical cohort of patients undergoing conventional RH were retrospectively reviewed. Results: This study included 325 (49.8%) and 327 (50.2%) undergoing NSRH and RH, respectively. Via a multivariable model, nodal status was the only factor predicting for DFS (hazard ratio [HR]=2.09; 95% confidence interval [CI]=1.17\u20133.73; p=0.01). A trend towards high risk of recurrence was observed for patients affected by locally advanced cervical cancer (LACC) undergoing NACT followed by surgery (HR=2.57; 95% CI=0.95\u20136.96; p=0.06). Type of surgical procedures (NSRH vs. RH) did not influence risk of recurrence (p=0.47). Similarly, we observed that the execution of NSRH rather than RH had not a detrimental effect on OS (HR=1.19; 95% CI=0.16\u20139.01; p=0.87). Via multivariable model, no factor directly correlated with OS. No difference in early complication rates was observed between the study groups. Conversely, a significant higher number of late complications was reported in RH versus NSRH groups (p=0.02). Conclusion: Our data suggested that NSRH upholds effectiveness of conventional RH, without increasing recurrence and complication rates but improving pelvic dysfunction rate

Targeting BRAF pathway in low-grade serous ovarian cancer

: Mutations in genes encoding for proteins along the RAS-RAF-MEK-ERK pathway have been detected in a variety of tumor entities including ovarian carcinomas. In the recent years, several inhibitors of this pathway have been developed, whose antitumor potential is currently being assessed in different clinical trials. Low grade serous ovarian carcinoma, is a rare gynecological tumor which shows favorable overall survival, compared to the general ovarian cancer population, but worrying resistance to conventional chemotherapies. The clinical behavior of low grade serous ovarian carcinoma reflects the different gene profile compared to high-grade serous carcinoma: KRAS/BRAF mutations. BRAF inhibitors as single agents were approved for the treatment of BRAF mutated tumors. Nevertheless, many patients face progressive disease. The understanding of the mechanisms of resistance to BRAF inhibitors therapy and preclinical studies showing that BRAF and mitogen-activated protein kinase kinase (MEK) inhibitors combined therapy delays the onset of resistance compared to BRAF inhibitor single agent, led to the clinical investigation of combined therapy. The aim of this paper is to review the efficacy and safety of the combination of BRAF plus MEK inhibitors on ovarian carcinomas, in particularly focusing on low grade serous ovarian carcinoma

A score system for complete cytoreduction in selected recurrent ovarian cancer patients undergoing secondary cytoreductive surgery: predictors- and nomogram-based analyses

Objective: To test the applicability of the Arbeitsgemeinschaft Gyn\ue4kologische Onkologie (AGO) and Memorial Sloan Kettering (MSK) criteria in predicting complete cytoreduction (CC) in patients undergoing secondary cytoreductive surgery (SCS) for recurrent ovarian cancer (ROC). Methods: Data of consecutive patients undergoing SCS were reviewed. The Arbeitsgemeinschaft Gyn\ue4kologische Onkologie OVARian cancer study group (AGO-OVAR) and MSK criteria were retrospectively applied. Nomograms, based on AGO criteria, MSK criteria and both AGO and MSK criteria were built in order to assess the probability to achieve CC at SCS. Results: Overall, 194 patients met the inclusion criteria. CC was achieved in 161 (82.9%) patients. According to the AGO-OVAR criteria, we observed that CC was achieved in 87.0% of patients with positive AGO score. However, 45 out of 71 (63.4%) patients who did not fulfilled the AGO score had CC. Similarly, CC was achieved in 87.1%, 61.9% and 66.7% of patients for whom SCS was recommended, had to be considered and was not recommended, respectively. In order to evaluate the predictive value of the AGO-OVAR and MSK criteria we built 2 separate nomograms (c-index: 0.5900 and 0.5989, respectively) to test the probability to achieve CC at SCS. Additionally, we built a nomogram using both the aforementioned criteria (c-index: 0.5857). Conclusion: The AGO and MSK criteria help identifying patients deserving SCS. However, these criteria might be strict, thus prohibiting a beneficial treatment in patients who do not met these criteria. Further studies are needed to clarify factors predicting CC at SC

Robotic-assisted, laparoscopic, and vaginal hysterectomy in morbidly obese patients with endometrial hyperplasia and endometrial cancer

Background: Hysterectomy for endometrial hyperplasia and endometrial cancer in morbidly obese patients is challenging. Here, we reported data regarding three minimally invasive approaches. Method: This is a multicenter retrospective study evaluating 30-day and 90-day surgery-related outcomes of morbidly obese patients (those with BMI > 40kg/m2) undergoing robotic-assisted, laparoscopic, and vaginal hysterectomy. Results: Charts of 95 morbidly obese patients who underwent surgery for endometrial cancer were retrieved. Overall, robotic-assisted, laparoscopic, and vaginal surgeries were performed in 35 (36.8%), 38 (40%), and 22 (23.2%) patients, respectively. Patients having robotic-assisted surgery experienced longer operative time than patients having vaginal and laparoscopic approaches (p < 0.001). Surgical approaches did not influence the risk of having intraoperative and severe (Clavien-Dindo grade 3 or more) postoperative complications. No 90-day mortality occurred. Conclusions: Robotic-assisted, laparoscopic, and vaginal surgery represent three safe and feasible minimally invasive approaches to manage morbidly obese patients with endometrial hyperplasia and endometrial cancer