HRD related signature 3 predicts clinical outcome in advanced tubo-ovarian high-grade serous carcinoma.

OBJECTIVES: We evaluated usability of single base substitution signature 3 (Sig3) as a biomarker for homologous recombination deficiency (HRD) in tubo-ovarian high-grade serous carcinoma (HGSC). MATERIALS AND METHODS: This prospective observational trial includes 165 patients with advanced HGSC. Fresh tissue samples (n = 456) from multiple intra-abdominal areas at diagnosis and after neoadjuvant chemotherapy (NACT) were collected for whole-genome sequencing. Sig3 was assessed by fitting samples independently with COSMIC v3.2 reference signatures. An HR scar assay was applied for comparison. Progression-free survival (PFS) and overall survival (OS) were studied using Kaplan-Meier and Cox regression analysis. RESULTS: Sig3 has a bimodal distribution, eliminating the need for an arbitrary cutoff typical in HR scar tests. Sig3 could be assessed from samples with low (10%) cancer cell proportion and was consistent between multiple samples and stable during NACT. At diagnosis, 74 (45%) patients were HRD (Sig3+), while 91 (55%) were HR proficient (HRP, Sig3-). Sig3+ patients had longer PFS and OS than Sig3- patients (22 vs. 13 months and 51 vs. 34 months respectively, both p < 0.001). Sig3 successfully distinguished the poor prognostic HRP group among BRCAwt patients (PFS 19 months for Sig3+ and 13 months for Sig3- patients, p < 0.001). However, Sig3 at diagnosis did not predict chemoresponse anymore in the first relapse. The patient-level concordance between Sig3 and HR scar assay was 87%, and patients with HRD according to both tests had the longest median PFS. CONCLUSIONS: Sig3 is a prognostic marker in advanced HGSC and useful tool in patient stratification for HRD.

Impact of Assistant Experience on Perioperative Outcomes of Simple and Radical Laparoscopic Nephrectomy: Does It Really Matter?

Background and Objectives: While systematic reviews highlight the advantages of laparoscopic nephrectomy over traditional open surgery, the impact of an assistant's experience on surgical outcomes remains unclear. This study aims to evaluate whether the level of assistant expertise influences laparoscopic nephrectomy outcomes. Materials and Methods: Retrospective data from our institutional database were analyzed for patients who underwent laparoscopic nephrectomy between January 2018 and December 2022. Procedures were performed by a highly experienced surgeon, including postgraduate year (PGY)-3 to PGY-5 residents as assistants. Senior-level assistants had completed at least 10 procedures. Patient characteristics, surgical outcomes, and postoperative details were collected. Multivariable linear and logistic regression models were performed to test the effect of assistant experience (low vs. high) on estimated blood loss (EBL), length of stay (LOS), operative time (OT), and postoperative complications. Results: 105 patients were included, where 53% had highly experienced assistants and 47% had less experienced ones. Low assistant experience and higher BMI predicted longer operative time (OT), confirmed by multivariable regression (ß = 40.5, confidence interval [CI] 18.7-62.3, p < 0.001). Assistant experience did not significantly affect EBL or LOS after adjusting for covariates (ß = -14.2, CI -91.8-63.3, p = 0.7 and ß = -0.83, CI -2.7-1.02, p = 0.4, respectively). There was no correlation between assistant experience and postoperative complications. Conclusions: Assistant experience does not significantly impact complications, EBL, and LOS in laparoscopic nephrectomy. Surgeries with less experienced assistants had longer OT, but the overall clinical impact seems limited. Trainee involvement remains safe, guided by experienced surgeons.

Clonal mast cell disorders in patients with severe Hymenoptera venom allergy and normal serum tryptase levels.

BACKGROUND: Systemic mastocytosis is a clonal mast cell (MC) disease that can lead to potentially fatal anaphylactic reactions caused by excessive MC mediator release. The prevalence of mastocytosis in patients with Hymenoptera venom allergy is high, and thus the disease should be suspected in patients with severe reactions caused by Hymenoptera stings and increased serum basal tryptase (SBT) levels. OBJECTIVE: We sought to evaluate the presence of clonal MC disorders in patients seen at our mastocytosis center with Hymenoptera sting-induced anaphylaxis, documented hypotension, absence of urticaria pigmentosa, and normal SBT levels. METHODS: Twenty-two patients with Hymenoptera sting-induced anaphylaxis, without skin lesions, and with tryptase levels of less than 11.4 ng/mL underwent bone marrow evaluation. Bone mineral density was assessed in those patients with ascertained mastocytosis. RESULTS: In 16 of 22 patients, a diagnosis of indolent mastocytosis could be established, and 1 patient had a monoclonal MC activation syndrome. Patients with mastocytosis had higher SBT levels (P = .03) but only rarely had angioedema/urticaria associated with hypotension (P = .004). CONCLUSIONS: The absence of urticaria or angioedema in severe reactions to Hymenoptera stings with hypotension might represent the most relevant factor in identifying patients with mastocytosis, regardless of their serum tryptase levels.

The Lifetime History of the First Italian Public Extra-Corporeal Shock Wave Lithotripsy (ESWL) Lithotripter as a Mirror of the Evolution of Endourology over the Last Decade.

Extracorporeal shockwave lithotripsy (ESWL) is the only non-invasive treatment for kidney stones. It does not require an operating room, anesthesia, or hospital stay. Its role evolved over the years and nowadays ESWL is slowly disappearing from many stone centers and urologic departments. We present the history and the role of ESWL treatment since its birth in 1959 and its development through the following years. We also present details of its application and impact on the first Italian stone center in 1985. ESWL has had different roles over the centuries: in the early years it was a great alternative to open surgery and percutaneous nephrolithotripsy (PCNL), then it had its decline with the introduction of the miniscopes. Currently, although ESWL is not considered a treatment of excellence, newer models are emerging. With the application of new technologies and artificial intelligence, this technique can become a good option alongside endourologic treatments.

Evolutionary states and trajectories characterized by distinct pathways stratify patients with ovarian high grade serous carcinoma.

Ovarian high-grade serous carcinoma (HGSC) is typically diagnosed at an advanced stage, with multiple genetically heterogeneous clones existing in the tumors long before therapeutic intervention. Herein we integrate clonal composition and topology using whole-genome sequencing data from 510 samples of 148 patients with HGSC in the prospective, longitudinal, multiregion DECIDER study. Our results reveal three evolutionary states, which have distinct features in genomics, pathways, and morphological phenotypes, and significant association with treatment response. Nested pathway analysis suggests two evolutionary trajectories between the states. Experiments with five tumor organoids and three PI3K inhibitors support targeting tumors with enriched PI3K/AKT pathway with alpelisib. Heterogeneity analysis of samples from multiple anatomical sites shows that site-of-origin samples have 70% more unique clones than metastatic tumors or ascites. In conclusion, these analysis and visualization methods enable integrative tumor evolution analysis to identify patient subtypes using data from longitudinal, multiregion cohorts.

Peritoneal dialysis catheters in pediatric patients: 10 years of experience in a single centre.

Peritoneal Dialysis (PD) is one of the numerous options for chronic dialysis and in many cases when access for acute dialysis is required early in a hospital course, at any age. PD catheter can be inserted with an open or laparoscopic approach. The complication rate after catheter insertion is still high, as reported in published literature. We present the experience matured at our Centre in the last 10 years on implantation of peritoneal dialysis catheters in children, emphasising surgical complications. We conducted a retrospective study on patients who underwent PD at our Centre in a range period of 10 years. We analysed patients 'demographic data, past and present medical, perioperative and post-operative data, permanence of the catheter, duration of dialysis, the gap between placement and use, outcomes and complications. We compared the data, dividing patients in 2 groups: patients operated with a traditional open technique and patients operated laparoscopically. We retrospectively reviewed 29 children with an average age of 3years and 6 months. Mean age was 42 months (1 month; 8 years) for the VLS group, 18 months (11 days, 4 years) for the OT group. Mean operative time was 106 min for the VLS group; 44 min for the OT group. The Catheter permanence period was 17 days (12h-64 days). Duration of dialysis was between 48 hours and 23 days (average 8 days). In the total population, we registered 8 complications (5 minor, 3 major), the overall complication rate being 33 % (minor complication rate 21%, major complication rate 12,5 %). 6 complications occurred in patients operated laparoscopically (6/14 = 36 %); 2 complications in the OT group (2/10 = 20 %). The complication rate after PD catheter insertion is still high. Advantages and disadvantages of the open and laparoscopic approach must be known. Both minor and major complications, such as bowel perforations and occlusions, must be understood and differentiated.