Anatomical-based classification of dorsolateral parametrectomy for deep endometriosis. Correlation with surgical complications and functional outcomes: A single- center prospective study.

OBJECTIVE: To evaluate complication rate and functional outcomes of nerve-sparing parametrectomy for deep endometriosis in relation to the extension of the surgical procedure, based on recognizable anatomical landmarks. METHODS: This was a prospective single-center study including all patients undergoing parametrectomy for deep endometriosis from September 2020 to June 2023 at our tertiary center. Dorsolateral parametrectomies were divided into parametrectomies medial to the presacral fascia and cranial to the medial rectal artery (superficial parametrectomy), and parametrectomies in which one of the two landmarks was overcome during the surgical procedure, leading to the excision of tissue lateral to the presacral fascia (deep parametrectomy type 1, or DP1) or caudal to the medial rectal artery (DP2). Finally, we used the hypogastric fascia as landmark to define type 3 deep parametrectomy (DP3), when the procedure was deeply lateral to the fascia. RESULTS: Bladder voiding deficit occurred in 9.7% of cases, with higher rates in DP2 (20.8%) and DP3 (30%) groups. Regarding postoperative gastrointestinal function, our data showed a significant improvement over time in all groups, with the exception of DP2; instead an improvement in postoperative bladder function was only shown in DP3. Parametrectomy was not associated with a simultaneous improvement in sexual function expressed with the female sexual function index, in any of the four groups. CONCLUSION: Our classification constitutes a concrete approach for comparing, in a standardized way, the complications and functional outcomes of parametrectomy, which, even if carried out by expert surgeons, demonstrates a non-negligible rate of bladder voiding deficit.

Robotic assisted versus laparoscopic surgery for deep endometriosis: a meta-analysis of current evidence.

Endometriosis is a benign inflammatory onco-mimetic disease affecting 10-15% of women in the world. When it is refractory to medical treatments, surgery may be required. Usually, laparoscopy is the preferred approach, but robotic surgery has gained popularity in the last 15 years. This study aims to evaluate the safety and efficacy of robotic-assisted laparoscopic surgery (RAS) versus conventional laparoscopic surgery (LPS) in the treatment of endometriosis. This study adheres to PRISMA guidelines and is registered with PROSPERO. Studies reporting perioperative data comparing RAS and LPS surgery in patients with endometriosis querying PubMed, Google Scholar and ClinicalTrials.gov were included in the analysis. The Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2) was used for the quality assessment of the selected articles. Fourteen studies were identified, including 2709 patients with endometriosis stage I-IV for the meta-analysis. There were no significant differences between RAS and LPS in terms of intraoperative and postoperative complications, conversion rate and estimated blood loss. However, patients in the RAS group have a longer operative time (p < 0.0001) and longer hospital stay (p = 0.020) than those in the laparoscopic group. Robotic surgery is not inferior to laparoscopy in patients with endometriosis in terms of surgical outcomes; however, RAS requires longer operative times and longer hospital stay. The benefits of robotic surgery should be sought in the easiest potential integration of robotic platforms with new technologies. Prospective studies comparing laparoscopy to the new robotic systems are desirable for greater robustness of scientific evidence.

Efficacy of Lamivudine Plus Dolutegravir vs Dolutegravir-Based 3-Drug Regimens in People With HIV Who Are Virologically Suppressed.

Background: Lamivudine + dolutegravir maintenance dual therapy (DT) could be less effective than 3-drug therapy (TT) in the context of resistance-associated mutations to nucleoside reverse transcriptase inhibitors (NRTIs). The ARCA database was queried to test this hypothesis with a trial emulation strategy. Methods: People with HIV taking 2 NRTIs plus a protease inhibitor or a non-NRTI who switched to DT or dolutegravir-based TT were followed up from the first HIV RNA <50 copies/mL (baseline) to virologic failure (VF; ie, 2 consecutive HIV RNA ≥50 copies/mL or 1 HIV RNA ≥200 copies/mL). Those switching to DT within 6 months were assigned to the treatment arm and all other patients to the control arm. Each participant was also cloned, assigned to the opposite strategy, and censored at the time of deviation from that strategy. Using inverse probability of censoring weight Cox regression models, we calculated hazard ratios of VF for DT vs TT stratified for the presence of resistance-associated mutations. Results: Overall 626 people were analyzed: 204 with DT and 422 with TT (73% men; mean age, 44 years). Ten and 31 VFs occurred with DT and TT, respectively, over a median 5.8 years. When compared with a fully active TT, the DT had similar efficacy (adjusted hazard ratio, 0.88; 95% CI, .29-2.61; P = .812) when full susceptibility was confirmed at historical genotype. When previous M184V/I was present in both groups, the risk of VF was higher for DT vs TT but was not statistically significant (adjusted hazard ratio, 3.06; 95% CI, .45-20.84; P = .252). Conclusions: DT was not associated with a significantly higher risk of VF than dolutegravir-based TT.

Totally intracorporeal colorectal anastomosis (TICA) versus classical mini-laparotomy for specimen extraction, after segmental bowel resection for deep endometriosis: a single-center experience.

PURPOSE: The surgical approach to bowel endometriosis is still unclear. The aim of the study is to compare TICA to conventional specimen extractions and extra-abdominal insertion of the anvil in terms of both complications and functional outcomes. METHODS: This is a single-center, observational, retrospective study conducted enrolling symptomatic women underwent laparoscopic excision of deep endometriosis with segmental bowel resection between September 2019 and June 2022. Women who underwent TICA were compared to classical technique (CT) in terms of intra- and postoperative complications, moreover, functional outcomes relating to the pelvic organs were assessed using validated questionnaires [Knowles-Eccersley-Scott-Symptom (KESS) questionnaire and Gastro-Intestinal Quality of Life Index (GIQLI)] for bowel function. Pain symptoms were assessed using Visual Analogue Scale (VAS) scores. RESULTS: The sample included 64 women. TICA was performed on 31.2% (n = 20) of the women, whereas CT was used on 68.8% (n = 44). None of the patients experienced rectovaginal, vesicovaginal, ureteral or vesical fistula, or ureteral stenosis and uroperitoneum, and in no cases was it necessary to reoperate. Regarding the two surgical approaches, no significant difference was observed in terms of complications. As concerns pain symptoms at 6-month follow-up evaluations on stratified data, except for dysuria, all VAS scales reported showed significant reductions between median values, for both surgery interventions. As well, significant improvements were further observed in KESS scores and overall GIQLI. Only the GIQLI evaluation was significantly smaller in the TICA group compared to CT after the 6-month follow-up. CONCLUSIONS: We did not find any significant differences in terms of intra- or post-operative complications compared TICA and CT, but only a slight improvement in the Gastro-Intestinal Quality of Life Index in patients who underwent the CT compared to the TICA technique.

Cytoreductive surgery for advanced epithelial ovarian cancer in the poly(ADP-ribose) polymerase inhibitors era-Is it time for a new paradigm shift? A systematic review and meta-analysis.

INTRODUCTION: In patients with newly diagnosed advanced high-grade serous and endometrioid epithelial ovarian cancer (EOC) first-line maintenance therapy with poly(ADP-ribose) polymerase inhibitors (PARPi) tremendously improved progression-free survival (PFS). Yet, data on the effect of PARPi in proportion to postoperative residual disease status were lacking. MATERIAL AND METHODS: A systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items of Systematic reviews and Meta-Analysis (PRISMA) guidelines. We searched Medline/Pubmed, Embase and Cochrane databases as well as meeting abstracts until 18th March 2023. Hazard ratios (HRs) alongside their 95% confidence intervals (CIs) for PFS were extracted from the studies. A subgroup analysis was conducted to examine the effect of PARPi according to postoperative residual disease. RESULTS: A total of six phase III randomised controlled trials were included and comprised SOLO 1, PAOLA 1, PRIMA, PRIME, ATHENA-MONO and VELIA. Patients who received PARPi following complete gross resection showed greatest PFS benefit. Compared with placebo, maintenance with PARPi significantly improved PFS in patients with macroscopic residual disease (pooled HR 0.55; 95% CI 0.44-0.68). This magnitude was comparable to that found in patients with complete gross resection (pooled HR 0.53; 95% CI 0.41-0.67). CONCLUSIONS: Patients with macroscopic residual disease benefit from PARPi at the same extent as cases with complete gross resection. However, patients with complete gross resection who were treated with PARPi show the most favourable PFS rates. Hence, the pursuit of achieving complete cytoreduction remains valid in the PARPi era.

Efficacy and safety of antiemetic regimens for highly emetogenic chemotherapy-induced nausea and vomiting: A systematic review and network meta-analysis.

BACKGROUND: Several regimens have been introduced in clinical practice in the last twenty years to treat chemotherapy-induced nausea and vomiting (CINV). However, direct comparative data remain insufficient, as many new regimes lack head-to-head comparisons. In this study, through an indirect comparison, we overcome this limit by providing the most up-to-date estimate of the efficacy and safety of all combinations used for HEC-induced nausea and vomiting. PATIENTS AND METHODS: We retrieved randomized controlled trials (RCTs) published in Pubmed, Embase, and Cochrane Library until June, 30th 2022. We included phase II-III RCTs, including adults with any cancer receiving HEC, and compared different antiemetic regimes to prevent CINV. The primary outcome was the overall complete response (defined as the absence of vomiting and of the use of rescue drugs from 0 to 120 hrs since chemotherapy); secondary outcomes were acute (absence of vomiting and use of rescue medicine 0-24 hrs after chemotherapy) and delayed (24-120 hrs) response and adverse events. RESULTS: A total of 53 RCTs enrolling 22 228 patients were included. We classified the different antiemetic regimes into 21 different groups. Overall, 3- or 4-drug regimens containing a combination of dexamethasone, 5HT3 antagonists, mirtazapine or olanzapine with or without NK antagonists, yielded the highest probability to be the most effective regimen in terms of complete response. Regimens containing a combination of dexamethasone and 5-HT3 antagonist have the lowest probability of being the most effective regimen in terms of complete, acute, and delayed response. CONCLUSION: In our network meta-analysis, 4-drug regimens with olanzapine displayed the highest probability of efficacy in terms of complete response. A 3-drug regimen with olanzapine represents a valid option in a limited resource context.

Resection versus biopsy for management of primary central nervous system lymphoma: a meta-analysis.

The role of surgery in the management of primary central nervous system lymphomas (PCNSL) is currently confined to diagnosis. However, over recent years, an increasing number of papers have suggested a possible positive prognostic impact of surgery in selected cases. The present work aims to perform a meta-analysis of the available literature evidence. A meta-analysis with meta-regression on the role of surgical resection compared to biopsy in the management of PCNSL was conducted according to the PRISMA statement, searching MEDLINE via PubMed and Embase. The random effect model was used. The quality of evidence was assessed using the GRADE framework. After screening 1395 records, we included 11 papers in our analysis. Patients who underwent surgical resection harbored superficial and single-lesion tumors. At 1-, 2-, and 5-year follow-up, progression-free survival did not differ between the two groups, while overall survival favored resection, even if in a non-significant fashion. Meta-regression analysis showed that the overall survival rate at 2 years, but not at 1 or 5 years, was significantly influenced by tumor location. There were no differences in terms of age, sex, Karnofsky performance status, adjuvant therapy, or procedure-related complications. Overall, the quality of evidence is low. The results of the present meta-analysis do not change the current standard of care for PCNSL. However, surgery could be non-inferior to biopsy with an acceptable risk profile in selected patients harboring single and superficial lesions. The low quality of evidence prompts future randomized studies.

Comparing efficacy and safety of upfront treatment strategies for anaplastic lymphoma kinase-positive non-small cell lung cancer: a network meta-analysis.

Aim: This article is based on our previous research, which was presented as a post at the Congress Aiom 2022 Congress and published in Tumori Journal as Conference Abstract (Tumori J. 2022;108:1-194. doi: 10.1177/03008916221114500). In this paper, a comprehensive presentation of all the achieved results is provided. Several tyrosine kinase inhibitors (TKIs) have been investigated to treat patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). However, direct comparisons between these TKIs are lacking, with many only being compared to crizotinib. To address this gap, a network meta-analysis was conducted to compare the efficacy and safety of various first-line systemic therapies for ALK-positive NSCLC. Methods: A thorough search of PubMed, Embase, and Cochrane Library was performed to identify randomized controlled trials (RCTs) published between January 01, 2000 and April 01, 2022, and included trials that investigated upfront treatments for this molecular subgroup and reported overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) of grade 3 or higher (grade ≥ 3 AEs). Results: The analysis included 9 RCTs with 2,443 patients receiving eight different treatments: alectinib (at two different dosages), brigatinib, ceritinib, crizotinib, ensartinib, lorlatinib, and chemotherapy. Second and third-generation TKIs significantly prolonged PFS compared to crizotinib, with lorlatinib having the highest probability of yielding the most favorable PFS, followed by alectinib (300 mg or 600 mg). However, only alectinib has been shown to significantly prolong OS compared to crizotinib to date. Lorlatinib appears superior in reducing the risk of central nervous system (CNS) progression, followed by alectinib 600 mg. Ceritinib had the highest rate of AEs, followed by lorlatinib and brigatinib. Conclusions: Based on the network meta-analysis, alectinib and lorlatinib emerged as the most promising upfront treatment options. These treatments provide prolonged disease control while maintaining an acceptable safety profile.

Visual fixation in disorders of consciousness: Development of predictive models to support differential diagnosis.

The visual fixation represents a doubtful behavioral sign to discriminate Vegetative from Minimally Conscious State (MCS). To disentangle its meaning, we fitted univariate and multivariable logistic regression models matching different neurophysiological and neuroimaging data of 54 patients with Disorders of Consciousness to select the best model predicting which visual performance (visual blink or pursuit) was shown by patients and the best predictors set. The best models found highlighted the importance of the structural MRI and the visual evoked potentials data in predicting visual pursuit. Then, a qualitative pilot test was made on four patients showing visual fixation revealing that the obtained models correctly predict whether the patients' visual performance could support/correlate to a cognitively mediated behavior. The present pilot models could help clinicians to evaluate if the visual fixation response can support the MCS diagnosis.

An Italian population-based case-control study on the association between farming and cancer: Are pesticides a plausible risk factor?

This population-based case-control study investigated the association between farming (a proxy for pesticide exposure) and cancer in the Vercelli suburban area (northwest Italy). The residents, aged 25 to 79 years, in the above-mentioned area during the period 2002-2009 were considered. Cases were all the first hospital admissions for cancer. Controls were all the subjects not included in the cases and not excluded from the study. Cases and controls were classified according to whether they occupationally resulted farmers or nonfarmers during the period 1965-2009. Cancer odds ratios (ORs) between farmers and nonfarmers were calculated with generalized linear mixed models adjusted by gender and age. Farmers showed higher odds for all cancers (OR=1.459; p < .001), nonmelanoma skin cancer, colorectal cancer, and breast cancer. The results suggest a plausible association between pesticide exposure and cancer occurrence.