IMMUNOREACT 7: Regular aspirin use is associated with immune surveillance activation in colorectal cancer.

BACKGROUND: Long-term daily use of aspirin reduces incidence and mortality due to colorectal cancer (CRC). This study aimed to analyze the effect of aspirin on the tumor microenvironment, systemic immunity, and on the healthy mucosa surrounding cancer. METHODS: Patients with a diagnosis of CRC operated on from 2015 to 2019 were retrospectively analyzed (METACCRE cohort). Expression of mRNA of immune surveillance-related genes (PD-L1, CD80, CD86, HLA I, and HLA II) in CRC primary cells treated with aspirin were extracted from Gene Expression Omnibus-deposited public database (GSE76583). The experiment was replicated in cell lines. The mucosal immune microenvironment of a subgroup of patients participating in the IMMUNOREACT1 (ClinicalTrials.gov NCT04915326) project was analyzed with immunohistochemistry and flow cytometry. RESULTS: In the METACCRE Cohort, 12% of 238 patients analyzed were aspirin users. Nodal metastasis was significantly less frequent (p = .008) and tumor-infiltrating lymphocyte infiltration was higher (p = .02) among aspirin users. In the CRC primary cells and selected cell lines, CD80 mRNA expression was increased following aspirin treatment (p = .001). In the healthy mucosa surrounding rectal cancer, the ratio of CD8/CD3 and epithelial cells expressing CD80 was higher in aspirin users (p = .027 and p = .034, respectively). CONCLUSIONS: These data suggested that regular aspirin use may have an active role in enhancing immunosurveillance against CRC.

Perception of Gender Bias in Otolaryngology and Head & Neck Surgery - A Comparative Study.

Introduction: To investigate the differences in the professional and personal life and the perception of gender-bias, among Italian female surgeons working in Otolaryngology-Head and Neck Surgery (OHNS), as compared to those involved in other surgical fields (overall group [OG]). Materials and Methods: An online survey was administered to female medical doctors working in all surgical fields in Italian hospitals. Results: Of the 1963 responders included, 153 (7.8%) were part of the ONHS group and 1810 (92.3%) of the OG. In both cohorts, female represented approximately one-third of the surgical staff. At least one female in the staff did not regularly attend the operating room (OR), especially in the OHNSG group. OHNS responders had to abandon the surgical activities in favour of outpatient services more than OG. A higher proportion of OHNS surgeons encountered gender-related difficulties in the OR. Discussion: Several gender-related issues emerged among OHNS responders, the most relevant being involvement in surgical activities and number/complexity of surgical cases.

Status of Women in Neurosurgery: Results from a National Survey in Italy.

Background: Gender inequity in surgery has increasingly been a matter of debate. Contributions of female neurosurgeons to academic medicine and societies are poorly highlighted. The aim of this study was to evaluate several aspects of the professional and work-life balance of female neurosurgeons in Italy. Methods: Data of the female neurosurgical population were extracted from a general 83-item questionnaire administered to a total of 3242 respondents. The survey was composed of multiple-choice questions investigating demographics, surgical training and practice, satisfaction, mentorship, discrimination, and harassment. Results: A total of 98 female neurosurgeons were included. Most responders were married or cohabiting (49%). Thirty-nine (43%) were planning to have children, and 15 of them (44%) stated the reason they still didn't have any was because of professional constraints. Seventy (71%) women were neurosurgeons with an academic position (residents or academics) and 28 (29%) were full-time attendings. Most of the female neurosurgeons are satisfied with their work: sometimes (35%), often (20%), and always or almost always (20%). Most of them (45%) stated they are rarely victims of harassment, but 66% think that they are treated differently because they are women. A similar rate for a poor and fulfilling work-life balance (34% and 35%, respectively) was detected. The majority of participants (89%) had encountered a role model during their career, but in only 11% of cases was that person female. Conclusions: Even though the rate of satisfaction among female neurosurgeons in Italy is high, some of them experienced gender discrimination, including incidents of sexual harassment and microaggressions. Policies including job sharing paradigms, consistent and meaningful options for parental leave, mentorship programs, equal and fair remuneration for equal work, and zero tolerance for harassment should be encouraged.

Women in thoracic, cardiac and vascular surgery claim for a change in the working situation: an Italian national survey.

Background: Women's participation in the surgical workforce has increased. The aim of the study is to acquire objective data regarding practice, training, satisfaction, and discrimination of women surgeons working in cardiothoracic and vascular surgery in Italy. Methods: An 83-item questionnaire was distributed through social media and sent to e-mails of women surgeons from November through December 2020. A sub-analysis on women working in cardiac, thoracic, and vascular surgery was performed. Results: Overall, 222 respondents were included (48 cardiac, 62 thoracic, and 112 vascular surgeons). Thirty-six percent partially abandoned surgical activities in favor of other professional activities, not including the operating room. On average, our respondents took part in 33% of all surgical cases performed in their units; however, of 12 high complexity surgeries per month, less than one is performed by them. Only 7 female participants who answered the questionnaire were in leadership positions. Many respondents struggle with lack of mentorship and missing opportunities in operating room. A high percentage of women experienced discrimination due to their gender in their professional life, and 59% claimed to have been subject to sexual harassment. Conclusions: In Italy, women thoracic, cardiac, and vascular surgeons face lack of mentorship, opportunities in the operating room, and gender-related issues including some episodes of sexual harassment. Diversity, equity, and inclusion should become strategic priorities in all institutions. Among our respondents, surgical exposure is limited, which may deter a surgical career and play a crucial role in surgeons' dissatisfaction, that also include poor work-life-balance, and a large amount of administrative work. Surgical societies may address these issues by providing structured mentorship programs and networking opportunities. Societies' contributions might substantially impact supporting and retaining women at different stages of their careers.

Early Barriers to Career Progression of Women in Surgery and Solutions to Improve Them: A Systematic Scoping Review.

OBJECTIVE: This study aims to summarize the evidence concerning the barriers that exist to the career progression of women in surgery and to provide potential solutions to overcome these obstacles. BACKGROUND: Visible and invisible impediments can hinder female doctors' pursuit of a surgical career, from choosing a surgical specialty to training opportunities and all the way through career progression. METHODS: Database search of original studies about barriers for female surgeons during choice of surgical career, residency, and career progression. A query including possible solutions such as mentorship and network was included. RESULTS: Of 4618 total articles; 4497 were excluded as duplicates, having incorrect study focus, or not being original studies; leaving 120 studies meeting the inclusion criteria. Of the articles included, 22 (18%) focused on factors affecting the pursuit of a surgical career, such as surgical work hours and limited time for outside interests, 55 (46%) analyzed the main barriers that exist during surgical residency and fellowship training, such as discrimination and sexual harassment, 27 (23%) focused on barriers to career advancement, heavy workloads, ineffective mentorship, unclear expectations for advancement, inequality in pay or work-home conflicts. Among studies reporting on possible solutions, 8 (6.5%) articles reported on the role of effective mentorship to support career advancement and to provide moral support and 8 (6.5%) on the emerging role of social media for networking. Our analysis showed how different impediments hinder surgical career progression for women, with notable consequences on burnout and attrition. CONCLUSIONS: Identification and recognition of obstacles to career progression is the first step to addressing the gender gap in surgery. Active strategies should be improved to promote a culture of diversity and to create equal opportunity for women in surgery, while implementing structured mentoring programs and investing on an adequate communication on social media to engage the future generations.

Women in Surgery Italia: what are the opportunities in the operatory room? Results from a nationwide interdisciplinary survey.

Many studies documented the "glass ceiling" effect for women in surgery: achievements in academic and leadership positions are not consistent with the percentage of female surgeons in practice. A solid surgical case volume and expertise in high-complexity cases are required to pursue leadership positions. The aim of the study was to determine whether part of the difficulties encountered by female surgeons may lie in reduced surgical opportunities. This is the first study to investigate this issue in Italy. An online survey, conceived and promoted by Women in Surgery Italia, was administered through the RedCap platform, between November and December 2020, and female surgeons actively working in Italian academic and non-academic hospitals were invited to answer anonymously. A multivariate analysis was performed to evaluate the role of different factors on two main variables: overall procedures done and a sub-analysis of complex cases performed as first surgeon. 1810 respondents were included; the women who responded participated in 3% fewer cases on average, when compared to the mean staff case volume, and were significantly more often listed as the assistant surgeon and as primary surgeons in low-complexity cases. 36.5% of the respondents declared that at least one female physician on staff had to abandon the operatory room (OR) and does not regularly perform any surgical procedure. 73% female surgeons would like to spend more hours in the OR. While acquiring skills and surgical autonomy, many obstacles still exist for female surgeons. A portion of women are relegated to non-surgical activities, irrespective of their specialty, and these results confirm the theory that gender-biased underemployment still exists in surgical fields.

Women surgeons: How can we shape the future of new leaders? A celebration of the past with a glimpse of the future.

BACKGROUND: Sporadic women involvement in surgery has been recorded since ancient times. Nevertheless, the presence of women in surgical disciplines has been marginal until the last 2 decades, with several barriers still existing worldwide. The aim of the study was to explore the history of women in surgery, with a main focus in North America from until the foundation women surgical societies. METHODS: Database search of studies about the history of women in surgery. RESULTS: The 19th century registered an increased presence of women in medicine; during the 20th century, pioneer women surgeons opened the way to a more consistent involvement of women in surgical specialties. In the last 20 years, increased awareness of barriers limiting women progression in surgical career led to the development of women's surgical societies, with the aim to share common experiences and find solutions to common issues. CONCLUSION: The history of women in surgery has been paved with challenges: during the last centuries, several barriers limited the inclusion of women in surgical fields, from training to leadership positions. Nevertheless, some pioneers actually broke the rules imposed by a male-dominated field and opened the way to a more diverse and equal future for women surgeons. Nowadays, the existence of women's surgical societies in different countries and their interconnection represents a way to support women surgeons at different stages of their career.

Discrimination Toward Women in Surgery: A Systematic Scoping Review.

BACKGROUND: Over the past twenty years explicit gender bias toward women in surgery has been replaced by more subtle barriers, which represent indirect forms of discrimination and prevents equality. OBJECTIVE: The aim of our scoping review is to summarize the different forms of discrimination toward women in surgery. METHODS: The database search consisted of original studies regarding discrimination toward female surgeons. RESULTS: Of 3615 studies meeting research criteria, 63 were included. Of these articles, 11 (18%) were focused on gender-based discrimination, 14 (22%) on discrimination in authorship, research productivity, and research funding, 21 (33%) on discrimination in academic surgery, 7 (11%) on discrimination in surgical leadership positions and 10 (16%) on discrimination during conferences and in surgical societies. The majority (n = 53, 84%) of the included studies were conducted in the U.S.A. According to our analysis, female surgeons experience discrimination from male colleagues, healthcare workers, but also from patients and trainees. Possible solutions may include acknowledgment of the problem, increased education of diversity and integration for the younger generations, mentorship, coaching, and more active engagement by male and female partners to support women in the surgical field. CONCLUSIONS: Gender-based discrimination toward women in the field of surgery has evolved over the past twenty years, from an explicit to a more subtle attitude. A work-environment where diversity and flexibility are valued would allow female surgeons to better realize their full potential.

Women in Surgery Italia: National Survey Assessing Gender-Related Challenges.

BACKGROUND: In 2019, women accounted for 46% of surgical residents. Despite the international debate on gender disparities, no literature regarding the experience in Italy is available. The aim of this survey study was to assess satisfaction among female surgeons in Italy, and determine whether they encounter gender-based discrimination. STUDY DESIGN: An anonymous, 83-item web-based survey was distributed among female surgeons working in Italy, from November 18 to December 31, 2020. Gender equity, satisfaction, and factors associated with higher satisfaction and work-life balance were explored. RESULTS: There were 3,242 volunteer respondents, 1,833 of whom completed at least 50% of the specific questions and were included in the study. Approximately 54% of female Italian surgeons reported being satisfied with their job, but only 34% with their work-life balance. Among residents, 67% thought they were not adequately trained. The majority of respondents were responsible for most of the housekeeping (60%) and childcare duties (53%), regardless of their partner's workload, and 62% reported that gender affects the way they are treated at work, with most of them experiencing microaggressions. Sexual harassment was common (59%), but only 10% of women reported it. CONCLUSIONS: Most Italian female surgeons are satisfied with their professional choice. However, they face gender discrimination, including incidents of sexual harassment and microaggression. Due to the fact that half of surgeons working in Italian hospitals will be females in the next few years, actions are urgently required to build a culture that supports a gender-neutral environment.

Relationship between gastric pouch and weight loss after laparoscopic sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is considered safe and effective even as conversion procedure after primary bariatric operations. The correlation between gastric pouch volumes and patients weight loss remains unclear. METHODS: To assess a correlation between the gastric remnant size and the weight loss, we reviewed 49 consecutive barium swallow UGS performed at our institute from August 2012 through May 2014 in LSG patients with symptoms and/or unsatisfactory weight loss. The anteroposterior (AP), laterolateral (LL) and vertical (CC) diameters of the gastric pouch were measured to calculate the volume by the formula of the ellipsoid (AP × LL × CC × 0.5). Patients were divided in two groups: group 1 without gastric pouch (n = 36) and group 2 with gastric pouch (n = 13). Correlation between pouch volume and weight loss data was calculated with t Student's and Fisher tests to compare the percent excess body mass index (BMI) and percent excess body mass loss (EBL) between two groups, and P < 0.05 was considered statistically significant. RESULTS: The mean percent EBL was 26.54 ± 11.02 and 27.12 ± 12.35 kg/m(2) in groups with and without pouch, respectively. The mean volume of the pouch after LSG was 17.13 ± 21.56 mm(3). Pouch volume, when present, was not significantly correlated to weight loss (P = 0.88 95% CI, CL 19.88-33.20 group 2; CL 22.94-31.30 group 1). CONCLUSIONS: No statistical correlation was found between the volume of the gastric pouch and weight loss (percent EBL) after LSG in symptomatic or with unsatisfactory weight loss patients.

Laparoscopic Gastric Plication: An Emerging Bariatric Procedure with High Surgical Revision Rate.

Introduction: Laparoscopic gastric plication (LGCP) reduces gastric volume without resecting or implanting a foreign body. Although still considered investigational, it could be appropriate for young patients with a low body mass index (BMI) and for those unwilling to undergo sleeve gastrectomy, gastric banding, or bypass. Objectives: The aim of this study was to assess the mid-term results (2 years) of LGCP in terms of safety and efficacy. Methods: A total of 56 obese patients (47 female; mean age=30.5±11.7 years; mean BMI=40.31±4.7 kg/m2) were candidates for LGCP from January 2011 to October 2013. Early and late complications, BMI, and excess BMI loss (EBL) were prospectively recorded at 3, 6, 9, 12, 18, and 24 months follow-up. Results: Mean operative time was 72.4±15.6 minutes. No conversion was required. Mean hospital stay was 3 days. Mean %EBL was 34.3±18.40%, 40.1±24.5%, 47.4±30.2%, 46.5±34.6%, 47.8±43.2%, and 55.3±53.6% at 3, 6, 9, 12, 18, and 24 months, respectively. The overall complication rate was 32.14%. Perioperative mortality was zero. Surgical revision was needed in 30 patients: 12 for unsatisfactory weight loss and 18 for gastric prolapse (one acute within 30 days), respectively. Conclusion: LGCP showed high complication rates requiring surgical revision.

Genetic variation and gastric cancer risk: a field synopsis and meta-analysis.

BACKGROUND: Data on genetic susceptibility to sporadic gastric carcinoma have been published at a growing pace, but to date no comprehensive overview and quantitative summary has been available. METHODS: We conducted a systematic review and meta-analysis of the evidence on the association between DNA variation and risk of developing stomach cancer. To assess result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate result noteworthiness. Meta-analysis was also conducted for subgroups, which were defined by ethnicity (Asian vs Caucasian), tumour histology (intestinal vs diffuse), tumour site (cardia vs non-cardia) and Helicobacter pylori infection status (positive vs negative). RESULTS: Literature search identified 824 eligible studies comprising 2 530 706 subjects (cases: 261 386 (10.3%)) and investigating 2841 polymorphisms involving 952 distinct genes. Overall, we performed 456 primary and subgroup meta-analyses on 156 variants involving 101 genes. We identified 11 variants significantly associated with disease risk and assessed to have a high level of summary evidence: MUC1 rs2070803 at 1q22 (diffuse carcinoma subgroup), MTX1 rs2075570 at 1q22 (diffuse), PSCA rs2294008 at 8q24.2 (non-cardia), PRKAA1 rs13361707 5p13 (non-cardia), PLCE1 rs2274223 10q23 (cardia), TGFBR2 rs3087465 3p22 (Asian), PKLR rs3762272 1q22 (diffuse), PSCA rs2976392 (intestinal), GSTP1 rs1695 11q13 (Asian), CASP8 rs3834129 2q33 (mixed) and TNF rs1799724 6p21.3 (mixed), with the first nine variants characterised by a low FPRP. We also identified polymorphisms with lower quality significant associations (n=110). CONCLUSIONS: We have identified several high-quality biomarkers of gastric cancer susceptibility. These data will form the backbone of an annually updated online resource that will be integral to the study of gastric carcinoma genetics and may inform future screening programmes.

Laparoscopic Gastric Plication (LGCP) Vs Sleeve Gastrectomy (LSG): A Single Institution Experience.

BACKGROUND: Laparoscopic greater curvature plication (LGCP) and laparoscopic sleeve gastrectomy (LSG) both reduce gastric capacity, either by in-folding (LGCP) or removing (LSG) the greater curvature. While mid and long-term results of LSG are well known, LGCP is still considered investigational. The aim of this study was to compare the effectiveness of LGCP and LSG in terms of weight loss and safety. METHODS: Forty-five obese LGCP patients (6 males and 39 females) were matched with 45 LSG patients. The two groups were matched according to sex, age ± 10 years and BMI ± 1 kg/m(2). Surgical complication rate, redo surgery need, excess BMI loss (%EBL) and mean BMI at 3 and 6 months were compared. RESULTS: LGCP and LSG mean age was 37.8 and 40 years, while the mean preoperative BMI was 40.65 and 41 kg/m(2), respectively. There was no difference in operative time, complication rate, mean BMI and %EBL at 3 months. Redo surgery rate was higher in LGCP group (LGCP 60 % vs LSG 8.8 %, P < 0.0001). The mean time to redo surgery was longer in LSG group (23 ± 6.61 vs 17.3 ± 7.67 months, P = 0.0003). The mean BMI at 6 months was lower in LSG group (32 ± 5.7 vs 34.6 ± 5.3, P = 0.028). The mean %EBL at 6 months was higher in LSG group (57 ± 30.89 vs 40.2 ± 25, P = 0.0057). CONCLUSIONS: LGCP patients required more redo surgery. Weight loss was greater in LSG group at 6-month follow-up.

Telomerase reverse transcriptase locus polymorphisms and cancer risk: a field synopsis and meta-analysis.

BACKGROUND: Several recent studies have provided evidence that polymorphisms in the telomerase reverse transcriptase (TERT) gene sequence are associated with cancer development, but a comprehensive synopsis is not available. We conducted a systematic review and meta-analysis of the available molecular epidemiology data regarding the association between TERT locus polymorphisms and predisposition to cancer. METHODS: A systematic review of the English literature was conducted by searching PubMed, Embase, Cancerlit, Google Scholar, and ISI Web of Knowledge databases for studies on associations between TERT locus polymorphisms and cancer risk. Random-effects meta-analysis was performed to pool per-allele odds ratios for TERT locus polymorphisms and risk of cancer, and between-study heterogeneity and potential bias sources (eg, publication and chasing bias) were assessed. Because the TERT locus includes the cleft lip and palate transmembrane 1-like (CLPTM1L) gene, which is in linkage disequilibrium with TERT, CLPTM1L polymorphisms were also analyzed. Cumulative evidence for polymorphisms with statistically significant associations was graded as "strong," "moderate," and "weak" according to the Venice criteria. The joint population attributable risk was calculated for polymorphisms with strong evidence of association. RESULTS: Eighty-five studies enrolling 490 901 subjects and reporting on 494 allelic contrasts were retrieved. Data were available on 67 TERT locus polymorphisms and 24 tumor types, for a total of 221 unique combinations of polymorphisms and cancer types. Upon meta-analysis, a statistically significant association with the risk of any cancer type was found for 22 polymorphisms. Strong, moderate, and weak cumulative evidence for association with at least one tumor type was demonstrated for 11, 9, and 14 polymorphisms, respectively. For lung cancer, which was the most studied tumor type, the estimated joint population attributable risk for three polymorphisms (TERT rs2736100, intergenic rs4635969, and CLPTM1L rs402710) was 41%. Strong evidence for lack of association was identified for five polymorphisms in three tumor types. CONCLUSIONS: To our knowledge, this is the largest collection of data for associations between TERT locus polymorphisms and cancer risk. Our findings support the hypothesis that genetic variability in this genomic region can modulate cancer susceptibility in humans.

Solitary fibrous tumor of the thyroid gland: a report of two cases with an analysis of their clinical and pathological features.

Solitary fibrous tumors of the thyroid gland are rare soft-tissue neoplasms and only 24 cases have been reported in the literature to date. We describe two patients who underwent surgery for rapidly growing thyroid nodes of uncertain nature on cytology. At the final histological examination, they proved to be fibrous tumors of the thyroid gland that were CD-34, BCL2, CD-99, and Ki-67 positive, like other known cases. Neither of these two cases have recurred so far.

Targeted Therapy Database (TTD): a model to match patient's molecular profile with current knowledge on cancer biology.

BACKGROUND: The efficacy of current anticancer treatments is far from satisfactory and many patients still die of their disease. A general agreement exists on the urgency of developing molecularly targeted therapies, although their implementation in the clinical setting is in its infancy. In fact, despite the wealth of preclinical studies addressing these issues, the difficulty of testing each targeted therapy hypothesis in the clinical arena represents an intrinsic obstacle. As a consequence, we are witnessing a paradoxical situation where most hypotheses about the molecular and cellular biology of cancer remain clinically untested and therefore do not translate into a therapeutic benefit for patients. OBJECTIVE: To present a computational method aimed to comprehensively exploit the scientific knowledge in order to foster the development of personalized cancer treatment by matching the patient's molecular profile with the available evidence on targeted therapy. METHODS: To this aim we focused on melanoma, an increasingly diagnosed malignancy for which the need for novel therapeutic approaches is paradigmatic since no effective treatment is available in the advanced setting. Relevant data were manually extracted from peer-reviewed full-text original articles describing any type of anti-melanoma targeted therapy tested in any type of experimental or clinical model. To this purpose, Medline, Embase, Cancerlit and the Cochrane databases were searched. RESULTS AND CONCLUSIONS: We created a manually annotated database (Targeted Therapy Database, TTD) where the relevant data are gathered in a formal representation that can be computationally analyzed. Dedicated algorithms were set up for the identification of the prevalent therapeutic hypotheses based on the available evidence and for ranking treatments based on the molecular profile of individual patients. In this essay we describe the principles and computational algorithms of an original method developed to fully exploit the available knowledge on cancer biology with the ultimate goal of fruitfully driving both preclinical and clinical research on anticancer targeted therapy. In the light of its theoretical nature, the prediction performance of this model must be validated before it can be implemented in the clinical setting.

DNA repair gene polymorphisms and risk of cutaneous melanoma: a systematic review and meta-analysis.

Polymorphisms of DNA repair-related genes might modulate cancer predisposition. We performed a systematic review and meta-analysis of the available evidence regarding the relationship between these polymorphisms and the risk of developing cutaneous melanoma. Relevant studies were searched using PubMed, Medline, Embase, Cancerlit, Cochrane and ISI Web of Knowledge databases. Data were gathered according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. The model-free approach was adopted to perform the meta-analysis of the retrieved data. We identified 20 original reports that describe the relationship between melanoma risk and the single-nucleotide polymorphisms (SNPs) of 16 genes (cases = 4195). For seven SNPs considered in at least two studies, the findings were heterogeneous. Data were suitable for meta-analysis only in the case of the XPD/ERCC2 SNP rs13181 (cases = 2308, controls = 3698) and demonstrated that the variant C allele is associated with increased melanoma risk (odds ratio = 1.12, 95% confidence interval = 1.03-1.21, P = 0.01; population attributable risk = 9.6%). This is the first meta-analysis suggesting that XPD/ERCC2 might represent a low-penetrance melanoma susceptibility gene. Much work is still to be done before definitive conclusions can be drawn on the role of DNA repair alterations in melanomagenesis since for the other genes involved in this highly complex process, the available information is scarce or null.