Prognostic impact of the 8th edition of American Joint Committee on Cancer (AJCC) cancer staging system on clinically negative lymph nodes (cN0) breast cancer patients.

In 2017, the 8th edition of American Joint Committee on Cancer (AJCC) Staging Manual released the updating of TNM. The new edition introduces changes concerning tumor classification that could have a real innovative and useful clinical impact. The purpose of the study is to compare anatomic vs. prognostic stage group introduced in the new edition of AJCC staging system and its importance in clinical practice. We retrospectively analyzed the prognostic stage group introduced by the 8th edition of the AJCC staging system for breast cancer. We restaged a large series of patients with infiltrative breast cancer from 2004 to 2017 applying the AJCC 8th Edition prognostic stage group criteria. This study included 1575 patients with all molecular subtypes of breast cancer. Our follow-up included disease-free survival (DFS), disease-related survival (DRS), and overall survival (OS) data. Kaplan-Meier test was used for statistical analysis. The median follow-up was 7 years. The 5-year and 10-year OS were 96% and 90%, respectively. From our analysis, according to the 8th edition, the majority of patients included in the cohort had a down-staging to a better prognostic group except the triple-negative tumors. Most of the anatomic stage IIA turned into IA and IB. This new staging system seems to better relate to prognosis. Therefore, the prognostic stage represents an important support in breast cancer management since it could avoid unnecessary and ineffective therapies; in contrast, it could help realize the global evaluation of the risk of relapse/response to specific treatments, leading to a significant reduction in the national health cost.

Role of frozen section in sentinel lymph node biopsy for breast cancer in the era of the ACOSOG Z0011 and IBCSG 23-10 trials.

BACKGROUND: Intraoperative frozen sections (FS) of sentinel lymph nodes (SLN) were evaluated to avoid the need for deferred axillary lymph node dissection (ALND) in patients with early breast cancer (EBC). However, FS has low sensitivity for detecting micro-metastases (<2 mm), resulting in patients who later undergo deferred ALND. The aim of the study was to determine the best clinical approach for selecting patients who would derive real benefit from ALND, as well as to minimize the functional and psychological damage caused by delayed surgery, and the risk of undertreating EBC patients. METHODS: This study evaluated 1453 patients with early breast cancer (EBC) who underwent SLN biopsy, FS and definitive evaluation. Causes of discrepancies between SLN biopsy and FS results and the need for further surgery were evaluated. RESULTS: A total of 1226 (86%) patients underwent FS; of these patients, 146 (11.9%) were false negatives. The global sensitivity of FS in detecting both macro and micrometastases was 53.7%. Although ACOSOG Z0011 criteria found that ALND could be avoided in 236 patients, 40 (17%) of these had >3 positive axillary lymph nodes. In contrast, application of the IBCSG 23-10 trial criteria, found that only three patients (3.1%) had >3 positive axillary lymph nodes. CONCLUSIONS: FS has a low sensitivity in detecting micrometastases (19%), but a reasonable sensitivity for macrometastases (75%). Most false negatives were smaller metastases (mean 2.1 mm) and more likely in patients with infiltrating lobular carcinoma. Retrospective modelling of the IBCSG 23-10 criteria reduced the percentage of patients requiring deferred surgery from 12% to 4%. Guidelines recommend irradiation of lymph node drainage stations in patients with ≥4 axillary metastatic lymph nodes. Omission of ALND from 40% of patients who met Z0011 criteria would have resulted in their undertreatment. This risk decreases to 3% by omitting axillary clearing only in patients with micrometastases.

Emotional experiences and psychological well-being in 51 countries during the COVID-19 pandemic.

The COVID-19 pandemic presents challenges to psychological well-being, but how can we predict when people suffer or cope during sustained stress? Here, we test the prediction that specific types of momentary emotional experiences are differently linked to psychological well-being during the pandemic. Study 1 used survey data collected from 24,221 participants in 51 countries during the COVID-19 outbreak. We show that, across countries, well-being is linked to individuals' recent emotional experiences, including calm, hope, anxiety, loneliness, and sadness. Consistent results are found in two age, sex, and ethnicity-representative samples in the United Kingdom (n = 971) and the United States (n = 961) with preregistered analyses (Study 2). A prospective 30-day daily diary study conducted in the United Kingdom (n = 110) confirms the key role of these five emotions and demonstrates that emotional experiences precede changes in well-being (Study 3). Our findings highlight differential relationships between specific types of momentary emotional experiences and well-being and point to the cultivation of calm and hope as candidate routes for well-being interventions during periods of sustained stress. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Modified technique for performing STARR with Contour Transtar™.

Stapled Transanal Rectal Resection (STARR) performed using CCS-30 Contour Transtar™ despite its recent introduction seems to be an effective surgical procedure to treat obstructed defecation syndrome. The major constraint of this procedure is the need to open the prolapse longitudinally using the CCS-30. This is often difficult and can lead to an inadequate or spiralling resection. Our modified technique, presented in this paper, creates the prolapse opening with an electric scalpel between two Kocher clamps, placed to grab the whole prolapsed tissue at 2 and 4 o'clock, respectively. The results of the first 83 procedures confirm that this technique allows the surgeon to simplify the prolapse's longitudinal opening and especially the first loading of the tissue between the CCS-30 jaws, which is necessary to start the circular resection, as confirmed by the absence of spiralling and major complications in this series.

Laparoscopic cholecystectomy in day surgery: feasibility and outcomes of the first 400 patients.

BACKGROUND: The aim of this study was to evaluate the feasibility and safety of performing laparoscopic cholecystectomy (LC) in a day surgery setting in Italy. MATERIAL AND METHODS: Between March 2003 and June 2011, in our institution 439 patients were selected for day surgery LC. To evaluate the efficacy and safety of the procedure, postoperative complications, pain, nausea and vomiting were monitored at 4, 8, and 24 h after surgery. Patients admitted for an overnight stay or readmitted after discharging were also monitored. RESULTS: Over 8 years we performed 400 LC in day surgery setting and no conversion or major intraoperative complication were detected. A total of 387 patients (96.7%) were successfully discharged after 8-10 h of observation. Postoperative monitoring showed good pain control (mean VAS score 1.5) and only 3 (0.7%) of the 7 patients who experienced major pain were admitted. Twenty-seven patients (6.7%) experienced PONV and 9 (2.2%) of these required admission. None of the patients needed to be readmitted after discharging. The satisfaction questionnaire administered at 1 month office visit showed that 380 patients (95%) were satisfied with day surgery LC. CONCLUSIONS: Our success rate of 96.7% can be attributed to strict adherence to the patient selection criteria. The main reasons for hospital admission were pain and PONV; adequate control of these represents the key of success for day surgery LC. This study confirms the feasibility and safety of LC performed in day surgery setting.

The Proper Ki-67 Cut-Off in Hormone Responsive Breast Cancer: A Monoinstitutional Analysis with Long-Term Follow-Up.

INTRODUCTION: Breast cancer is a heterogeneous disease. Our study focuses on a monoinstitutional series of patients affected by Hormone Responsive carcinomas (luminal A and luminal B) and aims to define an optimal Ki-67 cut-off, to correctly stratify these patients into risk classes, using the ImmunoHistoChemical (IHC) surrogates of the Molecular Subtypes, according to the St. Gallen guidelines. METHODS: We analyzed 1685 patients. These patients underwent both radical and conservative surgeries with Sentinel Lymph Node Biopsy eventually followed by Axillary Dissection (AD). Furthermore, all the patients underwent adjuvant therapies according to the guidelines. A retrospective univariate analysis was performed and survival curves (Disease-Related Survival, DRS, and Disease-Free Survival, DFS) were carried out according to the following ki-67 risk classes: Low Risk (Ki-67 ≤ 14%); Intermediate Risk (Ki-67 15% ÷ 20%); High Risk (Ki-67 > 20%). RESULTS: 14 yy DRS was 98% in LA and 85% in LB with a ki-67 cut-off of 14% (p=0.037) vs 95% (LA) and 83% (LB) with a ki-67 cut-off of 20% (p=0.003). 14yy DFS was 85% in LA and 72% in LB with a ki-67 cut-off of 14% (p=0.017) vs 83% (LA) and 66% (LB) with a ki-67 cut-off of 20% (p<0.000). DISCUSSION: Our results confirmed that the 20% Ki-67 cut-off is more reliable in differentiating patients at low or high risk of recurrence and death, and stratifying patients eligible for adjuvant chemotherapy. Thus, despite its poor reproducibility, the identification of the most accurate ki-67 index assumes a pivotal relevance in guiding a tailored strategy among patients with this specific profile of breast cancer, as well as the molecular surrogates, in order to avoid harmful overtreatments.

Beyond BRCA1 and BRCA2: Deleterious Variants in DNA Repair Pathway Genes in Italian Families with Breast/Ovarian and Pancreatic Cancers.

The 5-10% of breast/ovarian cancers (BC and OC) are inherited, and germline pathogenic (P) variants in DNA damage repair (DDR) genes BRCA1 and BRCA2 explain only 10-20% of these cases. Currently, new DDR genes have been related to BC/OC and to pancreatic (PC) cancers, but the prevalence of P variants remains to be explored. The purpose of this study was to investigate the spectrum and the prevalence of pathogenic variants in DDR pathway genes other than BRCA1/2 and to correlate the genotype with the clinical phenotype. A cohort of 113 non-BRCA patients was analyzed by next-generation sequencing using a multigene panel of the 25 DDR pathways genes related to BC, OC, and PC. We found 43 unique variants in 18 of 25 analyzed genes, 14 classified as P/likely pathogenic (LP) and 28 as variants of uncertain significance (VUS). Deleterious variants were identified in 14% of index cases, whereas a VUS was identified in 20% of the probands. We observed a high incidence of deleterious variants in the CHEK2 gene, and a new pathogenic variant was detected in the RECQL gene. These results supported the clinical utility of multigene panel to increase the detection of P/LP carriers and to identify new actionable pathogenic gene variants useful for preventive and therapeutic approaches.

Buccal micronucleus assay in human populations from Sicily (Italy) exposed to petrochemical industry pollutants.

Petroleum refinery workers are potentially exposed to a wide range of petrochemical industry pollutants (PIP), such as benzene and 1,3-butadiene, cancer-related compounds classified as carcinogenic to humans. The aim of this study was to evaluate the cytogenetic effects of exposure to PIP from two industrialised areas in South/East Sicily (Italy) using a micronucleus (MN) assay and other nuclear anomalies (ONA) on exfoliated buccal cells. Results highlighted not only a statistically significant high level of increase of MN in petroleum refinery (PR) workers, but also in the subjects not working in PR but living in the industrialised area. The ONA analysis showed a highly significant increase in karyolytic cells in exposed vs unexposed subjects, in contrast to a decrease in differentiated cells. These results suggest the presence of a cytotoxic effect in the oral mucosa cells, probably related to the pollutant compounds present in the environment close to the petrochemical industries. Our data confirm that the analysis of exfoliated buccal cells is a useful and simple non-invasive method to evaluate the genotoxic/cytotoxic effects of pollutants in a specific area. To avoid confounding factors due to the different lifestyles of the human subjects, the above assays could be better applied on farm animals, which have a relatively consistent lifestyle and, in some cases, a very low genetic heterogeneity.

Positive margins (R1) risk factors in breast cancer conservative surgery.

BACKGROUND: The primary goal in conservative breast cancer surgery is the complete excision of the tumor, but at the same time attempting to obtain a satisfactory postoperative esthetic result. The notion of "No Ink on Tumor" that indicates exclusively the presence of tumor cells on the inked surface of the surgical specimen is now the gold standard; however, the problem of the free margin is still a fundamental topic of debate that has not yet found a definitive solution. METHODS: Our retrospective analysis takes into account 1440 patients undergoing breast conservative surgery, from October 2004 to November 2018, all treated at the breast unit of our institution. RESULTS: Positive margins (R1) rate was 10.2% (147 cases out of 1440). Overall survival was 95% at 5 years and 89% at 10 years. No differences in mortality and local recurrence rate between R0 and R1 patients were found. Half of the R1 patients underwent secondary surgery with enlargement of margins, while in the other half we performed direct mastectomy. Among the analyzed variables, age, histological size, histological type, grading, multifocality, lympho-vascular invasion and lymph node status were significantly correlated with the R1 status. The multivariate analysis shows  the association of age and surgical technique (oncoplastic) with R1 status. CONCLUSION: Further studies will allow the creation of a statistical model, for better pre-operative prediction of patients with higher risk of R1 and better selection of patients to be candidates for conservative surgery.

Alteration of neurotransmission and skeletogenesis in sea urchin Arbacia lixula embryos exposed to copper oxide nanoparticles.

The extensive use of copper oxide nanoparticles (CuO NPs) in many applications has raised concerns over their toxicity on environment and human health. Herein, the embryotoxicity of CuO NPs was assessed in the black sea urchin Arbacia lixula, an intertidal species commonly present in the Mediterranean. Fertilized eggs were exposed to 0.7, 10 and 20ppb of CuO NPs, until pluteus stage. Interferences with the normal neurotransmission pathways were observed in sea urchin embryos. In detail, evidence of cholinergic and serotoninergic systems affection was revealed by dose-dependent decreased levels of choline and N-acetyl serotonin, respectively, measured by nuclear magnetic resonance (NMR)-based metabolomics, applied for the first time to our knowledge on sea urchin embryos. The metabolic profile also highlighted a significant CuO NP dose-dependent increase of glycine, a component of matrix proteins involved in the biomineralization process, suggesting perturbed skeletogenesis accordingly to skeletal defects in spicule patterning observed previously in the same sea urchin embryos. However, the expression of skeletogenic genes, i.e. SM30 and msp130, did not differ among groups, and therefore altered primary mesenchyme cell (PMC) migration was hypothesized. Other unknown metabolites were detected from the NMR spectra, and their concentrations found to be reflective of the CuO NP exposure levels. Overall, these findings demonstrate the toxic potential of CuO NPs to interfere with neurotransmission and skeletogenesis of sea urchin embryos. The integrated use of embryotoxicity tests and metabolomics represents a highly sensitive and effective tool for assessing the impact of NPs on aquatic biota.

Effects of petrochemical contamination on caged marine mussels using a multi-biomarker approach: Histological changes, neurotoxicity and hypoxic stress.

This work was designed to evaluate the biological effects of petrochemical contamination on marine mussels. Mytilus galloprovincialis, widely used as sentinel organisms in biomonitoring studies, were caged at the "Augusta-Melilli-Priolo" industrial site (eastern Sicily, Italy), chosen as one of the largest petrochemical areas in Europe, and Brucoli, chosen as reference site. Chemical analyses of sediments at the polluted site revealed high levels of PAHs and mercury, exceeding the national and international guideline limits. In mussels from the polluted site, severe morphological alterations were observed in gills, mainly involved in nutrient uptake and gas exchange. Changes in serotonergic and cholinergic systems, investigated through immunohistochemical, metabolomics and enzymatic approaches, were highlighted in gills, as well as onset of hypoxic adaptive responses with up-regulation of hypoxia-inducible factor transcript. Overall, the application of a multi-biomarker panel results effective in assessing the biological effects of petrochemical contamination on the health of aquatic organisms.

Importance of perforating vessels in nipple-sparing mastectomy: an anatomical description.

BACKGROUND: Nipple-sparing mastectomy (NSM), understood as an oncologically valid procedure, is relatively new, and is an evolution of traditional mastectomy, particularly in relation to breast-conserving surgery. The anterior perforating branches are responsible for the cutaneous vascularization of the breast skin, and their preservation is a fundamental step to avoid possible postoperative necrosis. Therefore, evaluating the potential complications of cancer-related reconstructive surgical procedures such as NSM, both the distance of the tumoral lesion from the skin and the surgical incision site should be carefully considered. The preferred site of incision corresponds to the inframammary fold or possibly the periareolar area. METHODS: We retrospectively reviewed 113 patients who underwent NSM from January 2005 to October 2012 to evaluate skin complications. The anatomical study was performed by magnetic resonance imaging of the breast. RESULTS: Only one of the 113 women who had undergone a NSM procedure had total necrosis (0.9%) and six patients had partial necrosis (5.8%) of the nipple-areola complex.

Developmental abnormalities and neurotoxicological effects of CuO NPs on the black sea urchin Arbacia lixula by embryotoxicity assay.

The embryotoxicity of CuO NPs was evaluated in the black sea urchin Arbacia lixula embryos, by using 24-well plates. Fertilized eggs were exposed to five doses of CuO NPs ranging from 0.07 to 20 ppb, until pluteus stage. CuO NPs suspensions in artificial seawater formed agglomerates of 80-200 nm size, and copper uptake was 2.5-fold up in larvae exposed to high NP concentrations in respect to control. Developmental delay and morphological alteration, including skeletal abnormalities, were observed, as well as impairment in cholinergic and serotonergic nervous systems. These findings suggest the potential of CuO NPs to interfere with the normal neurotransmission pathways, thus affecting larval morphogenesis. Overall, the embryotoxicity tests are effective for evaluation of nanoparticle effects on the health of aquatic biota. Furthermore, as the black sea urchin A. lixula demonstrated to be vulnerable to NP exposure, it may be a valid bioindicator in marine biomonitoring and ecotoxicological programmes.

Can sequential 18F-FDG PET/CT replace WBC imaging in the diabetic foot?

UNLABELLED: White blood cell (WBC) scintigraphy is considered the nuclear medicine imaging gold standard for diagnosing osteomyelitis in the diabetic foot. Recent papers have suggested that the use of (18)F-FDG PET/CT produces similar diagnostic accuracy, but clear interpretation criteria have not yet been established. Our aim was to evaluate the role of sequential (18)F-FDG PET/CT in patients with a high suspicion of osteomyelitis to define objective interpretation criteria to be compared with WBC scintigraphy. METHODS: Thirteen patients whom clinicians considered positive for osteomyelitis (7 with ulcers, 6 with exposed bone) were enrolled. The patients underwent (99m)Tc-exametazime WBC scintigraphy with acquisition times of 30 min, 3 h, and 20 h and sequential (18)F-FDG PET/CT with acquisition times of 10 min, 1 h, and 2 h. A biopsy or tissue culture was performed for final diagnosis. Several interpretation criteria (qualitative and quantitative) were tested. RESULTS: At final biopsy, 7 patients had osteomyelitis, 2 had soft-tissue infection without osteomyelitis, and 4 had no infection. The best interpretation criterion for osteomyelitis with WBC scintigraphy was a target-to-background (T/B) ratio greater than 2.0 at 20 h and increasing with time. A T/B ratio greater than 2.0 at 20 h but stable or decreasing with time was suggestive of soft-tissue infection. A T/B ratio of no more than 2.0 at 20 h excluded an infection. Thus, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for osteomyelitis were 86%, 100%, 100%, 86%, and 92%, respectively. For (18)F-FDG PET/CT, the best interpretation criterion for osteomyelitis was a maximal standardized uptake value (SUVmax) greater than 2.0 at 1 and 2 h and increasing with time. A SUVmax greater than 2.0 after 1 and 2 h but stable or decreasing with time was suggestive of a soft-tissue infection. An SUVmax less than 2.0 excluded an infection. (18)F-FDG PET at 10 min was not useful. Using these criteria, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for osteomyelitis were 43%, 67%, 60%, 50%, and 54%, respectively. Combining visual assessment of PET at 1 h and CT was best for differentiating between osteomyelitis and soft-tissue infection, with a diagnostic accuracy of 62%. CONCLUSION: (18)F-FDG PET/CT, even with sequential imaging, has a low diagnostic accuracy for osteomyelitis and cannot replace WBC scintigraphy in patients with diabetic foot.

Large periampullary villous tumor of the duodenum.

A 67-year-old woman, who had symptoms of epigastric pain and abdominal distension, was found, on endoscopy, to have a large sessile villous adenoma of the periampullary duodenum. Despite the lack of evidence of malignancy, a pancreaticoduodenectomy procedure was performed, mainly because of the tumor size and site, involving the ampulla of Vater. The presence of the carcinoma was diagnosed only in the resected specimen by definitive histology. Because there is no general consensus on the optimal surgical procedure for the treatment of villous tumors of the duodenum, especially for the early stages, the indications for the operative procedure are discussed, based on a review of the literature.