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Simple Summary The reported incidence of low-volume metastases (LVM) in early-stage cervical cancer ranges from 4 to 20%. Given the conflicting results of prospective and retrospective studies, their prognostic value is still debated, especially for isolated tumor cells (ITC). This narrative review aims to highlight current evidence, controversies, and unanswered questions about the definition and prognostic role of LVM.Abstract The implementation of sentinel lymph node (SLN) biopsy is changing the scenario in the surgical treatment of early-stage cervical cancer, and the oncologic safety of replacing bilateral pelvic lymphadenectomy with SLN biopsy is currently under investigation. Part of the undisputed value of SLN biopsy is its diagnostic accuracy in detecting low-volume metastases (LVM) via pathologic ultrastaging. In early-stage cervical cancer, the reported incidence of LVM ranges from 4 to 20%. The prognostic impact and the role of adjuvant treatment in patients with LVM is still unclear. Some non-prespecified analyses in prospective studies showed no impact on the oncologic outcomes compared to node-negative disease. However, the heterogeneity of the studies, the differences in the disease stage and the use of adjuvant treatment, and the concomitant pelvic lymphadenectomy (PLND) make reaching any conclusions on this topic hard. Current guidelines suggest considering micrometastases (MIC) as a node-positive disease, while considering isolated tumor cells (ITC) as a node-negative disease with a low level of evidence. This review aims to highlight the unanswered questions about the definition, identification, and prognostic and therapeutic roles of LVM and to underline the present and future challenges we are facing. We hope that this review will guide further research, giving robust evidence on LVM and their impacts on clinical practice.

Objective: The standard surgical treatment of advanced ovarian carcinoma is primary debulking surgery (PDS) aiming to complete cytoreduction. The need to achieve complete cytoreduction has shifted the surgical paradigm to more complex procedures, whose impact on morbidity is controversial. The objective of this retrospective analysis is to explore the impact of extensive PDS on morbidity and oncologic outcomes in a real-world scenario. Methods: A retrospective single-center analysis was performed on 137 patients with advanced high-grade ovarian carcinoma (HGOC) who received PDS in 2015–2020. Patients treated in 2015–2017 (Group 1) were compared to patients treated in 2018–2020 (Group 2). The two periods were chosen according to the higher complexity of surgical procedures introduced in 2018. Results: The increase in complete cytoreduction observed in Group2 (RD 0: 33 % vs 61 %, p = 0,008) was related to a higher surgical complexity (Aletti Score: 4 vs 6, p = 0,003) and did not reflect an increase in peri-operative complications (CCI: 20,9 vs 20,9, p = 0,11). After a median FUP of 44 months, PFS and OS at 24 months were 33,60 % vs 47,33 % (p = 0,288) and 72,10 % vs 80,37 % (p = 0,022) in Group 1 and 2, respectively. Conclusions: An extensive surgical effort leads to a significant increase in complete cytoreduction with acceptable morbidity. Arm-in-arm with novel maintenance therapies, it contributes to increasing the outcomes of patients with advanced HGOC.

This publication presents a newly created map of the seafloor of Linosa, a volcanic island located in the Sicily Channel (Mediterranean Sea). The seafloor of Linosa was previously surveyed using geophysical and ground-truth data (in 2016 and 2017). Linosa is regarded as a "sentinel area" for alien species and worldwide environmental changes because of its geographical location, making it worthy of particular attention. The predominant habitats found in Linosa have been identified as three priority habitats: Posidonia oceanica meadows, rhodolith beds, and coralligenous habitats, which encompass extensive coral forests. Another crucial environmental indicator is the assemblages of benthic foraminifera, which were previously studied in this area to analyse their correlations with the topography of the seafloor. Hence, all the accessible data was gathered to create a novel comprehensive map of the seabed (at a scale of 1:15,000), with the objective of displaying and highlighting the abundant marine biodiversity of Linosa.

Objective To evaluate the impact of different volumes of indocyanine green (ICG) on the detection rate and bilateral mapping of sentinel lymph nodes in patients with apparent uterine-confined endometrial cancer. Methods All patients who underwent surgical staging with sentinel node mapping in six reference centers were included. Two different protocols of ICG intracervical injection were used: (1) 2 mL group: total volume of 2 mL injected superficially; (2) 4 mL group: total volume of 4 mL, 2 mL deeply and 2 mL superficially. Logistic regression was used to analyze factors that could influence dye migration and detection rates. A sensitivity analysis was carried out to determine how independent variables could affect the sentinel node detection rate. Results Of 442 eligible patients, 352 were analyzed (172 in the 2 mL group and 180 in the 4 mL group). The bilateral detection rates of the 2 mL and 4 mL groups were 84.9% and 86.1%, respectively (p=0.76). The overall detection rate was higher with a volume of 4 mL than with 2 mL (92.4% vs 97.8%, respectively; p=0.024). In the univariate analysis the rate of bilateral mapping fell from 87.5% to 73.5% when the International Federation of Gynecology and Obstetrics (FIGO) 2009 tumor stage was >IB (p=0.018). In the multivariate analysis, for both overall and bilateral detection rates a statistically significant difference emerged for the volume of ICG injected and FIGO 2009 stage >IB. Increasing body mass index was associated with worse overall detection rates on univariate analysis (p=0.0006), and significantly decreased from 97% to 91% when the body mass index exceeded 30 kg/m(2) (p=0.05). Conclusions In patients with early-stage endometrial cancer, a volume of 2 mL ICG does not seem to compromise the bilateral detection of sentinel lymph nodes. In women with obesity and FIGO 2009 stage >IB, a 4 mL injection should be preferred.

Background: The adjuvanted recombinant zoster vaccine (RZV), consisting of varicella-zoster virus glycoprotein E (gE) and the AS01B adjuvant system, effectively prevents herpes zoster (HZ). In the absence of a well-defined correlate of protection, it is important to monitor the RZV immune response, as a proxy of clinical effectiveness. Methods: This systematic review examined post-vaccination parameters: humoral and cell-mediated immunity, avidity index, geometric mean concentration of antibody (GMC), and immunity persistence. The meta-analysis used a random-effects model, and subgroup and meta-regression analyses were conducted. Results: Among 37 included articles, after one month from RZV-dose 2, the pooled response rate for anti-gE humoral immunity was 95.2% (95%CI 91.9–97.2), dropping to 77.6% (95%CI 64.7–86.8) during immunosuppression. The anti-gE cell-mediated immunity-specific response reached 84.6% (95%CI 75.2–90.9). Varying factors, such as age, sex, coadministration with other vaccines, prior HZ, or live-attenuated zoster vaccine, did not significantly affect response rates. RZV induced a substantial increase in gE avidity. Immunity persistence was confirmed, with more rapid waning in the very elderly. Conclusions: This systematic review indicates that RZV elicits robust immunogenicity and overcomes immunocompromising conditions. The findings underscore the need for further research, particularly on long-term immunity, and have the potential to support HZ vaccination policies and programs.

Two pillars in modern oncology are treatment personalization and the reduction in treatment-related morbidity. For decades, the one-fits-all concept of radical hysterectomy has been the cornerstone of early-stage cervical cancer surgical treatment. However, no agreement exists about the prevalent method of parametrial invasion, and the literature is conflicting regarding the extent of parametrectomy needed to achieve adequate surgical radicality. Therefore, authors started investigating if less radical surgery was feasible and oncologically safe in these patients. Two historical randomized controlled trials (RCTs) compared classical radical hysterectomy (RH) to modified RH and simple hysterectomy. Less radical surgery showed a drastic reduction in morbidity without jeopardizing oncological outcomes. However, given the high frequency of adjuvant radiotherapy, the real impact of reduced radicality could not be estimated. Subsequently, several retrospective studies investigated the chance of tailoring parametrectomy according to the tumor's characteristics. Parametrial involvement was shown to be negligible in early-stage low-risk cervical cancer. An observational prospective study and a phase II exploratory RCT have recently confirmed the feasibility and safety of simple hysterectomy in this subgroup of patients. The preliminary results of a large prospective RCT comparing simple vs. radical surgery for early-stage low-risk cervical cancer show strong probability of giving a final answer on this topic.

Background: To evaluate the impact of the Laparoscopic Approach to Cervical Cancer (LACC) Trial on patterns of care and surgery-related morbidity in early-stage cervical cancer. Methods: This is a retrospective, a multi-institutional study evaluating 90-day surgery-related outcomes of patients undergoing treatment for early-stage cervical cancer before (period I: 01/01/2016–06/01/2018) and after (period II: 01/01/2019–06/01/2021) the publication of the results of the LACC trial. Results: Charts of 1295 patients were evaluated: 581 (44.9%) and 714 (55.1%) before and after the publication of the LACC trial, respectively. After the publication of the LACC trial, the number of patients treated with minimally invasive radical hysterectomy decreased from 64.9% to 30.4% (p < 0.001). Overall, 90-day complications occurred in 110 (18.9%) and 119 (16.6%) patients in the period I and period II, respectively (p = 0.795). Similarly, the number of severe (grade 3 or worse) complications did not differ between the two periods (38 (6.5%) vs. 37 (5.1%); p = 0.297). Overall and severe 90-day complications were consistent between periods even evaluating stage IA (p = 0.471), IB1 (p = 0.929), and IB2 (p = 0.074), separately. Conclusions: The present investigation highlighted that in referral centers the shift from minimally invasive to open radical hysterectomy does not influence 90-day surgery-related morbidity.

Background: Low-grade serous ovarian cancer (LGSOC) is a rare entity with different behavior compared to high-grade serous (HGSOC). Because of its general low chemosensitivity, complete cytoreductive surgery with no residual disease is crucial in advanced stage LGSOC. We evaluated the impact of optimal cytoreduction on survival outcome both at first diagnosis and at recurrence. Methods: We retrospectively studied consecutive patients diagnosed with advanced LGSOCs who underwent cytoreductive surgery in two oncological centers from January 1994 to December 2018. Survival curves were estimated by the Kaplan–Meier method, and 95% confidence intervals (95% CI) were estimated using the Greenwood formula. Results: A total of 92 patients were included (median age was 47 years, IQR 35–64). The median overall survival (OS) was 142.3 months in patients with no residual disease (RD), 86.4 months for RD 1–10 mm and 35.2 months for RD >10 mm (p = 0.002). Progression-free survival (PFS) was inversely related to RD after primary cytoreductive surgery (RD = 0 vs RD = 1–10 mm vs RD >10 mm, p = 0.002). On multivariate analysis, RD 1–10 mm (HR = 2.30, 95% CI 1.30–4.06, p = 0.004), RD >10 mm (HR = 3.89, 95% CI 1.92–7.88, p = 0.0004), FIGO stage IV (p = 0.001), and neoadjuvant chemotherapy (NACT) (p = 0.010) were independent predictors of PFS. RD >10 mm (HR = 3.13, 95% CI 1.52–6.46, p = 0.004), FIGO stage IV (p <0.0001) and NACT (p = 0.030) were significantly associated with a lower OS. Conclusions: Optimal cytoreductive surgery improves survival outcomes in advanced stage LGSOCs. When complete debulking is impossible, a RD <10 mm confers better OS compared to an RD >10 mm in this setting of patients.

Inorganic nanoparticles of boron-rich compounds represent an attractive alternative to boron-containing molecules, such as boronophenylalanine or boranes, for BNCT applications. This work describes the synthesis and biological activity of multifunctional boron carbide nanoparticles stabilized with polyacrylic acid (PAA) and a gadolinium (Gd)-rich solid phase. A fluorophore (DiI) was included in the PAA functionalization, allowing the confocal microscopy imaging of the nanoparticles. Analysis of the interaction and activity of these fluorescent Gd-containing B4C nanoparticles (FGdBNPs) with cultured cells was appraised using an innovative correlative microscopy approach combining intracellular neutron autoradiography, confocal, and SEM imaging. This new approach allows visualizing the cells, the FGdBNP, and the events deriving from the nuclear process in the same image. Quantification of 10B by neutron autoradiography in cells treated with FGdBNPs confirmed a significant accumulation of NPs with low levels of cellular toxicity. These results suggest that these NPs might represent a valuable tool for achieving a high boron concentration in tumoral cells.

Objective: To investigate factors predicting the risk of developing 90-day postoperative complications and lymphatic-specific morbidity in patients undergoing surgical staging for high-risk endometrial cancer. Methods: This is a multi-institutional retrospective cohort study. Patients affected by apparent early-stage high-risk endometrial cancer (endometrioid FIGO grade 3 with deep myometrial invasion and non-endometrioid endometrial cancer) undergoing surgical staging between 2007 and 2019. Complications were graded according to the Clavien-Dindo classification system. Martin criteria were applied to improve quality of complications reporting. Results: Charts of 279 patients were evaluated. Lymphadenectomy, sentinel node mapping (SNM), and SNM followed by back-up lymphadenectomy were performed in 83 (29.7%), 50 (17.9%), and 146 (52.4%) patients, respectively. The former group of patients included 13 patients who had lymphadenectomy after the failure of the SNM technique. Thirteen (4.6%) patients developed severe postoperative events (grade 3 or worse). At multivariate analysis, body mass index (OR: 1.08 (95%CI: 1.01, 1.17)) and open abdominal surgery (OR: 2.27 (95%CI: 1.02, 5.32)) were the two independent factors predictive of surgery-related morbidity. Seven severe lymphatic complications occurred. The adoption of laparoscopic approach (p < 0.001, log-rank test) and SNM (p = 0.038, log-rank test) correlated with a lower risk of developing surgery-related events. Independently, open abdominal surgery was associated with an increased risk of developing lymphatic morbidity (OR: 37.4 (95%CI: 4.38, 319.5); p = 0.001). Conclusion: The adoption of the laparoscopic approach and SNM technique were associated with lower 90-day complication rates than open surgery in high-risk endometrial cancer undergoing staging surgery.

Objective Conization/simple trachelectomy is feasible in patients with early-stage cervical cancer. Retrospective data suggest that conization with negative lymph nodes could be a safe option for these patients. This study aims to provide oncologic and obstetric outcomes of a large series of patients with 2018 International Federation of Gynecology and Obstetrics (FIGO) stage IB1 cervical cancer managed by conization. Methods Patients with early cervical cancer and a desire to preserve fertility who underwent conization and pelvic lymphadenectomy from January 1993 to December 2019 in two Italian centers were included. Inclusion criteria were: age >18 years and ≤45 years, 2018 FIGO stage IB1, no prior irradiation or chemotherapy, absence of pre-operative radiologic evidence of nodal metastases, a strong desire to preserve fertility, and absence of concomitant malignancies. We excluded patients with confirmed infertility, neuroendocrine tumor, clear cell or mucinous carcinoma. Results A total of 42 patients were included. The median age was 32 years (range 19-44) and median tumor size was 11 mm (range 8-20). Squamous cell carcinoma was found in 27 (64.3%). Grade 3 tumor was present in 7 (16.7%) patients and lymphovascular space involvement was detected in 15 (35.7%). At a median follow-up of 54 months (range 1-185), all patients were alive without evidence of disease. In the entire series three patients experienced recurrence resulting in an overall recurrence rate of 7.1%. All the recurrences occurred in the pelvis (2 in the cervix and 1 in the lymph nodes), resulting in a 3-year disease-free survival of 91.6%. Twenty-two (52%) patients tried to conceive; 18 pregnancies occurred in 17 patients and 12 live births were reported (6 pre-term and 6 term pregnancies). Two miscarriages were recorded, one first trimester and one second trimester fetal loss. Conclusions Our study showed that conization is feasible for the conservative management of women with stage IB1 cer

Background/Aim: The role of neoadjuvant chemotherapy (NACT) is under investigation in locally advanced cervical cancer (LACC). Patients and Methods: A total of 49 patients with FIGO stage IB1-IIB cervical cancer who underwent two different regimens of weekly dose-dense NACT were included. The objective was to evaluate clinical/pathological response and toxicity profile. Results: A clinical complete response and partial response were obtained in 43 patients with a clinical overall response rate of 88%. Among the 42 surgically treated patients, 7 (17%) and 35 (83%) achieved a pathological overall optimal response and a suboptimal pathological response, respectively. G3-G4 neutropenia occurred in 16% of patients, whereas no cases of G3 thrombocytopenia, G3 anemia and febrile neutropenia were observed. Conclusion: Dose-dense NACT is safe, has acceptable toxicity, and obtains good clinical response, but is less effective in terms of pathological overall optimal response rates compared to other regimens.

Objective: Sentinel lymph node mapping (SNM) has gained popularity in managing apparent early-stage endometrial cancer (EC). Here, we evaluated the long-term survival of three different approaches of nodal assessment. Methods: This is a multi-institutional retrospective study evaluating long-term outcomes of EC patients having nodal assessment between 01/01/2006 and 12/31/2016. In order to reduce possible confounding factors, we applied a propensity-matched algorithm. Results: Overall, 940 patients meeting inclusion criteria were included in the study, of which 174 (18.5%), 187 (19.9%), and 579 (61.6%) underwent SNM, SNM followed by backup lymphadenectomy (LND) and LND alone, respectively. Applying a propensity score matching algorithm (1:1:2) we selected 500 patients, including 125 SNM, 125 SNM/backup LND, and 250 LND. Baseline characteristics of the study population were similar between groups. The prevalence of nodal disease was 14%, 16%, and 12% in patients having SNM, SNM/backup LND and LND, respectively. Overall, 19 (7.6%) patients were diagnosed with low volume nodal disease. The survival analysis comparing the three techniques did not show statistical differences in terms of disease-free (p = 0.750) and overall survival (p = 0.899). Similarly, the type of nodal assessment did not impact survival outcomes after stratification based on uterine risk factors. Conclusion: Our study highlighted that SNM provides similar long-term oncologic outcomes than LND.

The aim of our study was to evaluate the benefits of a low-pressure insufflation system (AirSeal) vs. a standard insufflation system in terms of anesthesiologists’ parameters and postoperative pain in patients undergoing laparoscopic surgery for early-stage endometrial cancer. This retrospective study involved five tertiary centers and included 152 patients with apparent early-stage disease who underwent laparoscopic surgical staging with either the low-pressure AirSeal system (8–10 mmHg, n = 84) or standard laparoscopic insufflation (10–12 mmHg, n = 68). All the intraoperative anesthesia variables evaluated (systolic blood pressure, end-tidal CO2, peak airway pressure) were significantly lower in the AirSeal group. We recorded a statistically significant difference between the two groups in the median NRS scores for global pain recorded at 4, 8, and 24 h, and for overall shoulder pain after surgery. Significantly more women in the AirSeal group were also discharged on day one compared to the standard group. All such results were confirmed when analyzing the subgroup of women with a BMI >30 kg/m2. In conclusion, according to our preliminary study, low-pressure laparoscopy represents a valid alternative to standard laparoscopy and could facilitate the development of outpatient surgery.

The aim of our study was to evaluate the benefits of a low-pressure insufflation system (AirSeal) vs. a standard insufflation system in terms of anesthesiologists’ parameters and postoperative pain in patients undergoing laparoscopic surgery for early-stage endometrial cancer. This retrospective study involved five tertiary centers and included 152 patients with apparent early-stage disease who underwent laparoscopic surgical staging with either the low-pressure AirSeal system (8–10 mmHg, n = 84) or standard laparoscopic insufflation (10–12 mmHg, n = 68). All the intraoperative anesthesia variables evaluated (systolic blood pressure, end-tidal CO2, peak airway pressure) were significantly lower in the AirSeal group. We recorded a statistically significant difference between the two groups in the median NRS scores for global pain recorded at 4, 8, and 24 h, and for overall shoulder pain after surgery. Significantly more women in the AirSeal group were also discharged on day one compared to the standard group. All such results were confirmed when analyzing the subgroup of women with a BMI >30 kg/m2. In conclusion, according to our preliminary study, low-pressure laparoscopy represents a valid alternative to standard laparoscopy and could facilitate the development of outpatient surgery.