SUrgical Access and Pattern of Recurrence of Endometrial Cancer: The SUPeR Study, a Multicenter Retrospective Observational Study.

STUDY OBJECTIVE: To evaluate recurrence rate and pattern in apparently early-stage endometrial cancer (EC) treated with minimally invasive surgery (MIS) and compare it to the "historical" populations treated by laparotomy. Secondary outcomes were to establish if, among MIS recurrent patients, intermediate-high/high-risk patients presented the same recurrence pattern compared to those at low/intermediate-risk and to evaluate time to first recurrence (TTR) of the study population. DESIGN: Multicenter retrospective observational study. SETTING: Five Italian Gynecologic Oncology referral centers. PATIENTS: All patients with proven recurrence of apparently early-stage EC treated with MIS from January 2017 to June 2022 . The laparotomic historical cohort was obtained from Laparoscopy Compared With Laparotomy for Comprehensive Surgical Staging of Uterine Cancer: Gynecologic Oncology Group Study (LAP2) and Laparoscopic Approach to Cancer of the Endometrium trials. INTERVENTIONS: Evaluation of recurrence rate and pattern. MEASUREMENTS AND MAIN RESULTS: Seventy-seven recurrences occurred on the total of 1028 patients treated with MIS for apparently early-stage EC during a median follow-up time of 36 months. The rate of recurrence in our cohort did not differ significantly from the rate of the historical cohort (7.4% vs 7.9%, odds ratio 0.9395, 95% CI 0.6901-1.2792). No significant differences were noticed for local, abdominal, nodal, and multiple site recurrence patterns; distant site recurrence appeared more likely in patients from the historical cohort. Postoperative low/intermediate risk patients had a higher likelihood of local recurrence compared to intermediate-high/high risk patients. Mean TTR was 19 months. No significant difference of TTR was observed for each pattern of recurrence compared to others. CONCLUSION: MIS appears to be safe for the treatment of early-stage EC. We did not identify any recurrence pattern specifically associated with MIS in early-stage EC.

Automated Prediction of Photographic Wound Assessment Tool in Chronic Wound Images.

Many automated approaches have been proposed in literature to quantify clinically relevant wound features based on image processing analysis, aiming at removing human subjectivity and accelerate clinical practice. In this work we present a fully automated image processing pipeline leveraging deep learning and a large wound segmentation dataset to perform wound detection and following prediction of the Photographic Wound Assessment Tool (PWAT), automatizing the clinical judgement of the adequate wound healing. Starting from images acquired by smartphone cameras, a series of textural and morphological features are extracted from the wound areas, aiming to mimic the typical clinical considerations for wound assessment. The resulting extracted features can be easily interpreted by the clinician and allow a quantitative estimation of the PWAT scores. The features extracted from the region-of-interests detected by our pre-trained neural network model correctly predict the PWAT scale values with a Spearman's correlation coefficient of 0.85 on a set of unseen images. The obtained results agree with the current state-of-the-art and provide a benchmark for future artificial intelligence applications in this research field.

An Overview of PARP Resistance in Ovarian Cancer from a Molecular and Clinical Perspective.

Epithelial ovarian cancer (EOC), a primarily high-grade serous carcinoma (HGSOC), is one of the major causes of high death-to-incidence ratios of all gynecological cancers. Cytoreductive surgery and platinum-based chemotherapy represent the main treatments for this aggressive disease. Molecular characterization of HGSOC has revealed that up to 50% of cases have a deficiency in the homologous recombination repair (HRR) system, which makes these tumors sensitive to poly ADP-ribose inhibitors (PARP-is). However, drug resistance often occurs and overcoming it represents a big challenge. A number of strategies are under investigation, with the most promising being combinations of PARP-is with antiangiogenetic agents and immune checkpoint inhibitors. Moreover, new drugs targeting different pathways, including the ATR-CHK1-WEE1, the PI3K-AKT and the RAS/RAF/MEK, are under development both in phase I and II-III clinical trials. Nevertheless, there is still a long way to go, and the next few years promise to be exciting.

Management of malignant cutaneous wounds in oncologic patients.

PURPOSE: Neoplastic wounds may develop as a result of primary tumor growth in the skin, due to metastasis, or due to skin invasion by tumors emerging from deeper levels. Malignant wounds may present as a crater-like ulcer, or as raised nodules with a cauliflower-like appearance. They are associated with malodor, necrosis, pain, bleeding, and secondary infection. The aim of our study is to better characterize fungating wounds and their management. METHODS: We retrospectively reviewed the database of the Wound Care Unit of the University of Bologna in order to identify individuals affected by neoplastic wound, between January 2019 and February 2021. RESULTS: We identified 9 females and 2 males with a mean age of 63 years; all were referred by the Oncology Unit. Management differed depending on the characteristics of the patients and the ulcers. Complete healing of the wound, following the parallel complete remission of the lymphoproliferative neoplasia, was observed in one individual. Among the others, one died because of breast cancer, while cutaneous lesions in 2 individuals deteriorated after 1 year of follow-up. Remission/relapse of the ulcer following the treatment course administered for the lymphoma were observed in one patient. CONCLUSIONS: Treatment of malignant fungating wounds is challenging. Considering the neoplastic nature of the wounds, complete healing or improvement cannot be expected with the application of classically prescribed dressing for wounds. A mostly palliative treatment, focusing on maintaining the patient's quality of life, is a reasonable choice.

Hypericum and neem oil for dehisced post-surgical wounds: a randomised, controlled, single-blinded phase III study.

OBJECTIVE: To evaluate the clinical efficacy of a hypericum and neem oil dressing, Primary Wound Dressing [ONE] (1PWD) (Kerecis AG, Switzerland), in a patient population with dehiscence of surgical wounds with critical colonisation/infection. Efficacy was defined as resolution of inflammatory/infective symptoms. METHOD: A randomised, controlled, single-blinded, parallel-arms phase III study was conducted comparing the experimental medication to silver-based dressings. All patients were evaluated at enrolment, on days 7, 14, 21 and 28. Improvement of inflammatory/infective symptoms was measured by detecting seven items of the Bates-Jensen Wound Assessment Tool (BWAT). Pain was assessed using the Numeric Rating Scale (NRS). RESULTS: The study enrolled 99 patients. Follow-up was completed in 49 patients in the experimental group and 48 patients in the control group. Overall BWAT evaluation demonstrated similar outcomes between the groups: t=0.23, p-value=0.81, 95% confidence interval (CI): -13.3-10.8. Furthermore, when evaluating the seven items of the BWAT relating to inflammatory signs, there was not a significant difference between the groups: t=0.38, p=0.35, 95% CI: -2.8-2.7. However, when an analysis using the NRS pain scale was performed, a statistically significant pain reduction was demonstrated in favour of the experimental group: t=7.8, p<0.0001, 95% CI: 2.918-4.8819. CONCLUSION: This randomised controlled trial confirmed the efficacy of 1PWD, an investigational product, in the management of surgical dehiscence with critical colonisation or infection, with the added benefit of significant pain reduction when compared with a silver-based dressing.

Effectiveness of Semi-Supervised Active Learning in Automated Wound Image Segmentation.

Appropriate wound management shortens the healing times and reduces the management costs, benefiting the patient in physical terms and potentially reducing the healthcare system's economic burden. Among the instrumental measurement methods, the image analysis of a wound area is becoming one of the cornerstones of chronic ulcer management. Our study aim is to develop a solid AI method based on a convolutional neural network to segment the wounds efficiently to make the work of the physician more efficient, and subsequently, to lay the foundations for the further development of more in-depth analyses of ulcer characteristics. In this work, we introduce a fully automated model for identifying and segmenting wound areas which can completely automatize the clinical wound severity assessment starting from images acquired from smartphones. This method is based on an active semi-supervised learning training of a convolutional neural network model. In our work, we tested the robustness of our method against a wide range of natural images acquired in different light conditions and image expositions. We collected the images using an ad hoc developed app and saved them in a database which we then used for AI training. We then tested different CNN architectures to develop a balanced model, which we finally validated with a public dataset. We used a dataset of images acquired during clinical practice and built an annotated wound image dataset consisting of 1564 ulcer images from 474 patients. Only a small part of this large amount of data was manually annotated by experts (ground truth). A multi-step, active, semi-supervised training procedure was applied to improve the segmentation performances of the model. The developed training strategy mimics a continuous learning approach and provides a viable alternative for further medical applications. We tested the efficiency of our model against other public datasets, proving its robustness. The efficiency of the transfer learning showed that after less than 50 epochs, the model achieved a stable DSC that was greater than 0.95. The proposed active semi-supervised learning strategy could allow us to obtain an efficient segmentation method, thereby facilitating the work of the clinician by reducing their working times to achieve the measurements. Finally, the robustness of our pipeline confirms its possible usage in clinical practice as a reliable decision support system for clinicians.

Improving the quality of clinical research on chronic wound infection treatment: expert-based recommendations.

OBJECTIVE:: To produce recommendations for the design of reliable and informative clinical investigations in chronic wound infection. METHOD:: A multidisciplinary panel of international experts from four countries (Italy, UK, Ireland and the US) were involved in a detailed, semi-structured discussion on how to better select and describe a target population, interventions and outcomes, and which infection-related criteria to apply in order to achieve a high-quality trial. Consent among the experts was measured using the Delphi method and GRADE Working Group suggestions. The project was fully supported by AISLeC 2016 (Italian Nursing Society for Wound Care Study). RESULTS:: In total, 37 recommendations achieved substantial agreement among the experts; 10 concerned the most appropriate description and selection of a target population, four related to interventions and 15 to outcomes. A further eight statements about critical methodological points were approved. CONCLUSION:: Developing recommendations in a systematic manner through a representative group of experts could generate tools for improving the design of clinical trials in this challenging area.

Asbestos between science and myth. A 6,000-year story.

Asbestos was used in making pottery in Eastern Finland from around 4000 B.C. In the ancient era and in the Middle Ages, magic properties were frequently attributed to this mineral. In the first century A.D., the Latin encyclopaedist Pliny the Elder reported in his Historia Naturalis that asbestos protects against all poisonings, particularly that of magicians. Moreover, asbestos was often found in places of worship, in Rome as well as in Athens and in Jerusalem. In the Middle Ages asbestos was identified with some animals, such as the salamander and certain white rodents. With such appearance, the mineral  had a huge success in Western as well as in Eastern literature and the fine arts. Marco Polo (1254-1324) in the Milione tried to deny that asbestos was a salamander. Despite its noxious effects, asbestos continues to be used in much of the world. In the 21st century it seems to be maintaining its quality as a magic stone.

Low-Volume Metastases in Cervical Cancer: Does Size Matter?

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.

Radical Hysterectomy in Early-Stage Cervical Cancer: Abandoning the One-Fits-All Concept.

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.

Lymph node staging in grade 1-2 endometrioid ovarian carcinoma apparently confined to the ovary: Is it worth?

OBJECTIVE: The aim of this study was to assess the disease-free survival (DFS) and overall survival (OS) of patients with grade 1-2 endometrioid ovarian carcinoma apparently confined to the ovary, according to surgical staging. METHODS: Multicenter, retrospective, observational cohort study. Patients with endometrioid ovarian carcinoma, surgical procedure performed between May 1985 and December 2019, stage pT1 N0/N1/Nx, grade 1-2 were included. Patients were stratified according to lymphadenectomy (defined as removal of any lymph node versus no lymph node assessment), and subgroup analyses according to tumor grade were performed. Kaplan-Meier curves and cox regression analyses were used to perform survival analyses. RESULTS: 298 patients were included. 199 (66.8 %) patients underwent lymph node assessment. Of these, 166 (83.4 %) had unilateral/bilateral pelvic and para-aortic/caval lymphadenectomy. Eleven (5.5 %) patients of those who underwent lymph node assessment showed pathologic metastatic lymph nodes (FIGO stage IIIA1). Twenty-seven patients (9.1 %) had synchronous endometrioid endometrial cancer. After a median follow up of 45 months (95 %CI:37.5-52.5), 5-year DFS and OS of the entire cohort were 89.8 % and 96.2 %, respectively. Age ≤ 51 years (HR=0.24, 95 %CI:0.06-0.91; p = 0.036) and performance of lymphadenectomy (HR=0.25, 95 %CI: 0.07-0.82; p = 0.022) represented independent protective factors toward risk of death. Patients undergoing lymphadenectomy had better 5-year DFS and OS compared to those not receiving lymphadenectomy, 92.0 % versus 85.6 % (p = 0.016) and 97.7 % versus 92.8 % (p = 0.013), respectively. This result was confirmed after exclusion of node-positive patients. When stratifying according to tumor grade (node-positive excluded), patients with grade 2 who underwent lymphadenectomy had better 5-year DFS and OS than those without lymphadenectomy (93.0 % versus 83.1 %, p = 0.040 % and 96.5 % versus 90.6 %, p = 0.037, respectively). CONCLUSION: Staging lymphadenectomy in grade 2 endometrioid ovarian carcinoma patients was associated with improved DFS and OS. Grade 1 and grade 2 might be considered as two different entities, which could benefit from different approach in terms of surgical staging. Prospective studies, including molecular profiles are needed to confirm the survival drivers in this rare setting.

Copy number alterations in stage I epithelial ovarian cancer highlight three genomic patterns associated with prognosis.

BACKGROUND: Stage I epithelial ovarian cancer (EOC) encompasses five histologically different subtypes of tumors confined to the ovaries with a generally favorable prognosis. Despite the intrinsic heterogeneity, all stage I EOCs are treated with complete resection and adjuvant therapy in most of the cases. Owing to the lack of robust prognostic markers, this often leads to overtreatment. Therefore, a better molecular characterization of stage I EOCs could improve the assessment of the risk of relapse and the refinement of optimal treatment options. MATERIALS AND METHODS: 205 stage I EOCs tumor biopsies with a median follow-up of eight years were gathered from two independent Italian tumor tissue collections, and the genome distribution of somatic copy number alterations (SCNAs) was investigated by shallow whole genome sequencing (sWGS) approach. RESULTS: Despite the variability in SCNAs distribution both across and within the histotypes, we were able to define three common genomic instability patterns, namely stable, unstable, and highly unstable. These patterns were based on the percentage of the genome affected by SCNAs and on their length. The genomic instability pattern was strongly predictive of patients' prognosis also with multivariate models including currently used clinico-pathological variables. CONCLUSIONS: The results obtained in this study support the idea that novel molecular markers, in this case genomic instability patterns, can anticipate the behavior of stage I EOC regardless of tumor subtype and provide valuable prognostic information. Thus, it might be propitious to extend the study of these genomic instability patterns to improve rational management of this disease.

Advanced low grade serous ovarian cancer: A retrospective analysis of surgical and chemotherapeutic management in two high volume oncological centers.

Simple summary: Low-grade serous ovarian cancer (LGSOC) represents an uncommon histotype of serous ovarian cancer (accounting for approximately 5% of all ovarian cancer) with a distinct behavior compared to its high-grade serous counterpart, characterized by a better prognosis and low response rate to chemotherapeutic agents. Similar to high-grade serous ovarian cancer, cytoreductive surgery is considered crucial for patient survival. This retrospective study aimed to analyze the outcomes of women affected by advanced stages (III-IV FIGO) of LGSOC from two high-volume oncological centers for ovarian neoplasm. In particular, we sought to evaluate the impact on survival outcomes of optimal cytoreductive surgery [i.e., residual disease (RD) <10 mm at the end of surgery]. The results of our work confirm the role of complete cytoreduction (i.e., no evidence of disease after surgery) in the survival of patients and even the positive prognostic role of a minimal RD (i.e., <10 mm), whenever complete cytoreduction cannot be achieved. 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 LGSOC s . When complete debulking is impossible, a RD <10 mm confers better OS compared to an RD >10 mm in this setting of patients.

Malignant mesothelioma of the pleura in nonagenarian patients.

AIMS AND BACKGROUND: Malignant mesothelioma developing at very old ages is a rare event. The reasons for such late development were investigated. METHODS: A series of 811 malignant mesothelioma of the pleura, diagnosed at the Trieste and Monfalcone Hospitals, in northeastern Italy, in the period 1968-2008 were reviewed. Eight cases regarding patients aged 90 years or more were selected. In such cases, occupational histories were re-examined, and additional data could be obtained from the patients' relatives. Routine lung sections obtained at necropsy were examined for asbestos bodies. In 2 cases, asbestos bodies had been isolated after chemical digestion of lung tissue. RESULTS: The group included 7 men and one woman, aged between 90 and 93 years. All 8 patients had long-term histories of occupational exposure to asbestos, mostly in shipyards. Latency periods, elapsed between first exposure to asbestos and tumor manifestation, ranged between 64 and 75 years. Asbestos bodies were found on routine lung sections in 6 cases. Isolation of lung asbestos bodies showed 72,000 bodies per gram of dried tissue in a 90-year-old man, who had worked in the shipyards for 34 years, and 150 bodies per gram in a 93-year-old woman, who had worked in the shipyards for 23 years. CONCLUSIONS: In this group of cases, the late development of mesothelioma can not be attributed to mild exposure to asbestos or to unusually late exposures. Very long latency periods even in people heavily exposed suggest an individual resistance to the oncogenic effects of asbestos.

Adapting a Vacuum Assisted Closure dressing to challenging wounds: negative pressure treatment for perineal necrotizing fasciitis with rectal prolapse in a newborn affected by acute myeloid leukaemia.

We report the case of a newborn with acute myeloid leukaemia, who developed perineal necrotizing fasciitis due to Pseudomonas Aeruginosa, after twenty days of life. Following surgical debridement, she was effectively treated with topical negative pressure therapy (V.A.C.(R) device) with silver foam dressings, this achieved complete closure in thirteen days. Negative pressure therapy should be considered when conventional wound care fails to achieve complete wound closure, even in neonates.

Safety profile of chronic leg ulcer biopsy: a monocentric retrospective series.

BACKGROUND: Skin biopsy is an important tool for various skin conditions. However, in the case of leg ulcers, some Authors still consider it highly risky and mandatory only in selected cases. METHODS: The aim of this study was to evaluate the rate of adverse events after leg ulcers biopsy in 866 consecutive patients referring to our Wound Care Unit in Bologna from January 2008 to December 2016. Two biopsies were performed (from the border and the centre) by the same dermatologist following a standardized structured protocol. RESULTS: A total of 329 males and 537 females (ratio of 1:1.6), mean age 72 years (range 50-97 years) underwent a skin biopsy. Up to 70% of all analyses revealed a vascular ulcer (614 patients; 70.9%) while other conditions (252 patients; 29.1%) included inflammatory dermatitis, vasculitis, ulcerated neoplasms, infective lesions, post-traumatic and pressure sores, erosive pustular, dermatitis and pyoderma gangrenosum. Adverse events occurred in 322 patients (38.43% of all biopsies), mostly a dull pain (320 patients, 37%) that resolved within some hours. Five patients with vasculitis (0.6%) experienced a worsening of the lesion and another five patients (0.6%) developed erysipelas. Only two patients, on double antithrombotic therapy (0.23%), had intraoperative bleeding. No allergic reactions were detected. CONCLUSIONS: According to our experience, skin biopsy should be mandatory for non-healing wounds. It is safe and involves only a low rate of adverse events.