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Background: The increased number of cancer survivors and the recognition of physical and psychosocial challenges, present from cancer diagnosis through active treatment and beyond, led to the discipline of cancer survivorship. Design and methods: Herein, we reflected on the different components of survivorship care, existing models and priorities, in order to facilitate the promotion of high-quality European survivorship care and research. Results: We identified five main components of survivorship care: (i) physical effects of cancer and chronic medical conditions; (ii) psychological effects of cancer; (iii) social, work and financial effects of cancer; (iv) surveillance for recurrences and second cancers; and (v) cancer prevention and overall health and well-being promotion. Survivorship care can be delivered by structured care models including but not limited to shared models integrating primary care and oncology services. The choice of the care model to be implemented has to be adapted to local realities. High-quality care should be expedited by the generation of: (i) focused and shared European recommendations, (ii) creation of tools to facilitate implementation of coordinated care and (iii) survivorship educational programs for health care teams and patients. The research agenda should be defined with the participation of health care providers, researchers, policy makers, patients and caregivers. The following patient-centered survivorship research areas were highlighted: (i) generation of a big data platform to collect long-term real-world data in survivors and healthy controls to (a) understand the resources, needs and preferences of patients with cancer, and (b) understand biological determinants of survivorship issues, and (ii) develop innovative effective interventions focused on the main components of survivorship care. Conclusions: The European Society for Medical Oncology (ESMO) can actively contribute in the efforts of the oncology community toward (a) promoting the development of high-quality survivorship care programs, (b) providing educational material and (c) aiding groundbreaking research by reflecting on priorities and by supporting research networking.

Objectives: Martini et al. developed a nomogram to predict significant (>25%) renal function loss after robot-assisted partial nephrectomy and identified four risk categories. We aimed to externally validate Martini’s nomogram on a large, national, multi-institutional data set including open, laparoscopic, and robot-assisted partial nephrectomy. Methods: Data of 2584 patients treated with partial nephrectomy for renal masses at 26 urological Italian centers (RECORD2 project) were collected. Renal function was assessed at baseline, on third postoperative day, and then at 6, 12, 24, and 48 months postoperatively. Multivariable models accounting for variables included in the Martini’s nomogram were applied to each approach predicting renal function loss at all the specific timeframes. Results: Multivariable models showed high area under the curve for robot-assisted partial nephrectomy at 6- and 12-month (87.3% and 83.6%) and for laparoscopic partial nephrectomy (83.2% and 75.4%), whereas area under the curves were lower in open partial nephrectomy (78.4% and 75.2%). The predictive ability of the model decreased in all the surgical approaches at 48 months from surgery. Each Martini risk group showed an increasing percentage of patients developing a significant renal function reduction in the open, laparoscopic and robot-assisted partial nephrectomy group, as well as an increased probability to develop a significant estimated glomerular filtration rate reduction in the considered time cutoffs, although the predictive ability of the classes was

Immunotherapy; PARP inhibitors; Pembrolizumab Immunoteràpia; Inhibidors de PARP; Pembrolizumab Inmunoterapia; Inhibidores de PARP; Pembrolizumab Metastatic triple-negative breast cancer (mTNBC) is a poor prognostic disease with limited treatments and uncertain therapeutic algorithms. We performed a systematic review and multiple Bayesian network meta-analyses according to treatment line to establish an optimal therapeutic sequencing strategy for this lethal disease. We included 125 first-line trials (37,812 patients) and 33 s/further-lines trials (11,321 patients). The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall response rates (ORR), overall survival (OS) and safety, for first and further lines, separately. We also estimated separate treatment rankings for the first and subsequent lines according to each endpoint, based on (surface under the cumulative ranking curve) SUCRA values. No first-line treatment was associated with superior PFS and OS than paclitaxel ± bevacizumab. Platinum-based polychemotherapies were generally superior in terms of ORR, at the cost of higher toxicity.. PARP-inhibitors in germline-BRCA1/2-mutant patients, and immunotherapy + chemotherapy in PD-L1-positive mTNBC, performed similar to paclitaxel ± bevacizumab. In PD-L1-positive mTNBC, pembrolizumab + chemotherapy was better than atezolizumab + nab-paclitaxel in terms of OS according to SUCRA values. In second/further-lines, sacituzumab govitecan outperformed all other treatments on all endpoints, followed by PARP-inhibitors in germline-BRCA1/2-mutant tumors. Trastuzumab deruxtecan in HER2-low mTNBC performed similarly and was the best advanced-line treatment in terms of PFS and OS after sacituzumab govitecan, according to SUCRA values. Moreover, comparisons with sacituzumab govitecan, talazoparib and olaparib were not statistically significant. The most effective alternatives or candidates for subsequent lines were represented by nab-paclitaxel (in ORR), capecitabine (in PFS) and eribulin (in PFS and OS).

Summary Background A number of mutations related to malignant melanoma (MM) have been identified, and of the mutated genes, BRAF has been found to be altered in > 50% of cases. Most of these have been BRAF V600E mutations, whereas the incidence of BRAF V600K may vary from 10% to 30%. Little is known about the clinical prognostic correlations of BRAF V600K MMs. We evaluated the clinical and dermoscopic features, incidence, therapy response and outcomes in the medium to long term. Aim To compare the clinical and dermoscopic characteristics, the response to systemic therapies and the prognosis among MMs with BRAF V600E and BRAF V600K mutations. Methods We retrieved the data of patients tested in our centre for MM from 2012 to 2015, including clinical features, dermoscopic pictures, clinical history and tumour mutations. Only patients with BRAF V600E and BRAF V600K mutations were included. Any MMs positive for BRAF V600K mutation were collected, and the number of V600K cases and their features were used to extract the same number of patients with BRAF V600E from our database using a matching method. The clinical and dermoscopic presentation, therapy response and disease progression of the two groups were then evaluated. Results In total, 132 cases of BRAF V600E-mutated MMs were identified, and then randomized with a propensity-score method to match the 10 retrieved cases of BRAF V600K mutation. Both groups had a nodular appearance to the tumours and an advanced disease stage, and no significant differences in dermoscopic features were highlighted. During the follow-up period, four patients with BRAF V600K died of disease-specific causes. Moreover, we found a higher frequency of metastasis, a faster disease progression and more rapid mortality in patients with BRAF V600K. Conclusion Despite the small size of this study, the results show similar clinical and dermoscopic characteristics between V600E and V600K mutations, but compared with BRAF V600E MMs, BRAF V600K MMs seem to be less responsive to therapy and have a worse prognosis.

Breast cancer risk associated with germline likely pathogenic/pathogenic variants (PV) varies by gene, often by penetrance (high50% or moderate 20-50%), and specific locus. Germline PVs in BRCA1 and BRCA2 play important roles in the development of breast and ovarian cancer in particular, as well as in other cancers such as pancreatic and prostate cancers and melanoma. Recent studies suggest that other cancer susceptibility genes, including ATM, CHEK2, PALB2, RAD51C and RAD51D confer differential risks of breast and other specific cancers. In the era of multigene panel testing, advances in next-generation sequencing technologies have notably reduced costs in the United States (US) and enabled sequencing of BRCA1/2 concomitantly with additional genes. The use of multigene-panel testing is beginning to expand in Europe as well. Further research into the clinical implications of variants in moderate penetrance genes, particularly in unaffected carriers, is needed for appropriate counselling and risk management with data-driven plans for surveillance and/or risk reduction. For individuals at high risk without any pathogenic or likely pathogenic variant in cancer susceptibility genes or some carriers of pathogenic variants in moderate-risk genes such as ATM and CHEK2, polygenic risk scores offer promise to help stratify breast cancer risk and guide appropriate risk management options. Cancer patients whose tumours are driven by the loss of function of both copies of a predisposition gene may benefit from therapies targeting the biological alterations induced by the dysfunctional gene e.g. poly ADP ribose polymerase (PARP) inhibitors and other novel pathway agents in cancers with DNA repair deficiencies. A better understanding of mechanisms by which germline variants drive various malignancies may lead to improvements in both therapeutic and preventive management options.

To investigate the clinical and surgical predictors of urinary tract endometriosis (UTE) relapse.Retrospective single institutional study.Italian multidisciplinary referral center for endometriosis.Consecutive patients affected by UTE and surgically treated between January 2016 and March 2020.Surgical excision for UTE. Uni- and multivariate logistic regression analyses were fitted to evaluate clinical and surgical predictors of recurrence.A total of 105 female age-reproductive patients were enrolled. Median age was 32 years (interquartile range, 24-37). Ureteral involvement was recorded in 53 patients (50.5%), being unilateral and bilateral in 46 patients (43.8%) and 7 patients (6.7%), respectively. Bladder involvement occurred in 52 patients (49.5%). Open surgical approach was performed in 24 cases (22.9%), whereas 30 patients (28.5%) and 51 patients (48.6%) were treated with laparoscopic and robot-assisted approach, respectively. Overall, 53 patients (50.5%) received adjuvant hormonal therapy. At a median follow-up of 39 months (interquartile range, 22-51), 30 patients (28.6%) experienced disease relapse, with 14 recurrences (13.3%) recorded at the level of the urinary tract. At multivariable analysis, age at first surgery25 years (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.10-1.84; p = .02) and the presence of a concomitant autoimmune disease (OR, 1.45; 95% CI, 1.24-2.17; p = .02) were found as predictors of deep infiltrating endometriosis recurrence, whereas adjuvant postsurgical therapy showed a protective role (OR, 0.83; 95% CI, 0.53-0.98; p = .01).Young age (25 years) and the presence of autoimmune diseases were significant predictors for the development of disease recurrence, whereas adjuvant hormonal therapy showed a protective role.

PURPOSE Combining standard of care (pertuzumab-trastuzumab [PH], chemotherapy) with cancer immunotherapy may potentiate antitumor immunity, cytotoxic activity, and patient outcomes in high-risk, human epidermal growth factor receptor 2 (HER2)–positive early breast cancer. We report the phase III IMpassion050 primary analysis of neoadjuvant atezolizumab, PH, and chemotherapy in these patients. METHODS Patients with a primary tumor of > 2 cm and histologically confirmed, positive lymph node status (T2-4, N1-3, M0) were randomly assigned 1:1 to atezolizumab/placebo with dose-dense doxorubicin/cyclophosphamide, followed by paclitaxel, and PH. After surgery, patients were to continue atezolizumab/placebo and PH (total: 1 year of HER2-targeted therapy); those with residual disease could switch to ado-trastuzumab emtansine with atezolizumab/placebo. Coprimary efficacy end points were pathologic complete response (pCR; ypT0/is ypN0) rates in intention-to-treat (ITT) and programmed cell death-ligand 1 (PD-L1)–positive populations. RESULTS At clinical cutoff (February 5, 2021), pCR rates in the placebo and atezolizumab groups in the ITT populations were 62.7% (n = 143/228) and 62.4% (n = 141/226), respectively (difference –0.33%; 95% CI, –9.2 to 8.6; P = .9551). The pCR rates in the placebo and atezolizumab groups in patients with PD-L1–positive tumors were 72.5% (n = 79/109) and 64.2% (n = 70/109), respectively (difference –8.26%; 95% CI, –20.6 to 4.0; P = .1846). Grade 3-4 and serious adverse events were more frequent in the atezolizumab versus placebo group. Five grade 5 adverse events occurred (four neoadjuvant, one adjuvant; two assigned to study treatment), all with atezolizumab. Overall, the safety profile was consistent with that of atezolizumab in other combination studies. CONCLUSION Atezolizumab with neoadjuvant dose-dense doxorubicin/cyclophosphamide–paclitaxel and PH for high-risk, HER2-positive early breast cancer did not increase pCR rates versus placebo in the ITT or PD-L1–positive populations. PH and chemotherapy remains standard of care; longer follow-up may help to inform the long-term impact of atezolizumab.

Patients with cancer are at an increased risk of venous (VTE) and arterial thromboembolism (ATE), and thromboembolic events (TEs) represent the second-leading cause of death in cancer patients. The risk of cancer-associated thromboembolism is multifactorial. In addition to patient risk factors, anticancer treatments have been found to increase the risk of both VTE and ATE. Immune checkpoint blockade (ICB) has become a mainstay of treatment in various types of cancers. Their use is associated with the occurrence of a new spectrum of side effects called immune-related adverse events. Meta-analyses-including data from prospective and retrospective studies-and case reports both reported VTE and ATE as adverse events associated with ICB, with a cumulative incidence equaling around 3% and 1%, respectively. The exact mechanism underlying a TE after ICB use is currently unclear, as well as its associated risk factors. Considering their potential life-threatening impact, it is important for clinicians to be aware of the potential thrombotic complications, to educate patients and recognize early signs and symptoms of VTE and ATE, in order to allow prompt treatment (if needed) and avoid complications.

FloRIN reconfiguration technique was introduced in 2016 according to the IDEAL-Collaboration Guidelines, with the attempt to conjugate the advantages of both intracorporeal neobladder and robotic assistance. Herein we report functional outcomes of FloRIN reservoir, specifically focusing on urodynamic features.Consecutive patients treated with RARC and FloRIN reconstruction were prospectively collected from February 2016 to June 2020. Only patients with a minimum 6-month follow up were analyzed to obtain a stable grade of neobladder maturation before performing the urodynamic study (UDS). The FACT-BL and the QLQ-C30 EORTC questionnaires were used to evaluate urinary function and health-related QoL. Results were compared with a contemporary series of patients treated at the same Institution with open radical cystectomy (ORC) and Vescica Ileale Padovana (VIP).One hundred patients entered the study and 69 patients had complete functional data. Overall, 52 (75.4%) patients reached the daytime continence. Among these, 28 (40.6%) were dry (no pads during daytime), while 24 (34.8%) used one pad/12 h. Night-time continence was achieved by 45 (65.2%) patients. Complete UDS findings were available for 28 patients. No statistically significant differences were found with the VIP-ORC group except for neobladder compliance, being higher in the FloRIN group (p = 0.03). When evaluating QoL scores, RARC with FloRIN reconfiguration showed a better continence recovery, as well as a higher improvement in urgency domain (p = 0.01), psychological status (0.02) and physical self-acceptance (p = 0.02), compared to the VIP-ORC group.The FloRIN technique showed excellent functional outcomes when compared to the referral VIP-ORC procedure.

Adolescent and young adult cancer survivors may experience various forms of social difficulties years or even decades after completing their cancer treatments. This article will hopefully help the Italian national project dedicated to adolescents and young adults with cancer promoting political and legal solutions to stop discrimination and supporting the right to be forgotten.

Foodborne diseases are a significant cause of illness in low- and middle-income countries (LMICs). Poor infrastructure, lack of regulatory oversight, and environmental conditions can increase food safety risks, particularly in traditional markets. Food vendors in traditional markets shoulder a heavy responsibility to keep food safe under often challenging conditions. The ability of these vendors to ensure food is safe is shaped by their knowledge, attitudes, and practices (KAP). Hence, understanding vendor KAP is important when designing interventions to improve food safety. To date most research on food vendors in LMICs has focused on vendors of ready-to-eat street foods and not on vendors of fresh food commodities. To fill this gap, a scoping review was undertaken to compile existing research on food safety KAP of vendors of food commodities in LMICs. PubMed, Google Scholar, Ovid Medline, and institutional Web sites of major research organizations were searched for original research articles and reports. Of 17,483 titles screened, 84 relevant studies were identified. Of the studies included, most were conducted after 2014 and focused on urban and periurban Africa. Most studies had a cross-sectional design with mixed methods (e.g., quantitative and qualitative analyses of vendor KAP through interviews and observations) and had small sample sizes (50 participants). Common food value chains studied were dairy, meat, and fruits and vegetables. Very few studies included more than one type of commodity or value chain. Food vendor knowledge typically ranged from little to none, which was evident from observations of vendors operating under unsafe and unhygienic conditions, such as poor food handling and storage practices. Poor compliance with existing food safety policies, laws, and regulations was evident in some cases primarily due to either limited awareness of their existence or limited knowledge of how to implement them. However, vendors generally had positive attitudes toward food safety. No significant gaps were found between food safety knowledge and actual practices, although this correlation was not always examined rigorously in the reviewed studies. KAP and gaps between food safety behavior did not differ with vendor age or gender, type of product sold, or geography. Local government staff were identified as key enabling actors, interacting with food market vendors to foster improved food safety practices.

Introduction: A significant proportion of patients with cancer who recover from Coronavirus Disease 2019 (COVID-19) may experience COVID-19 sequelae in the early post-infection phase, which negatively affect their continuity of care and oncological outcome. The long-term prevalence and clinical impact of the post-COVID-19 syndrome in patients with cancer are largely unknown. Methods: In this study, we describe the time course of COVID-19 sequelae in patients with non-advanced cancers enrolled in the OnCovid registry. Results: Overall, 186 patients were included, with a median observation period of 9.9 months (95%CI:8,8–11.3) post-COVID-19 resolution. After a median interval of 2.3 months post-COVID-19 (interquartile range: 1.4–3.7), 31 patients (16.6%) reported ≥1 sequelae, including respiratory complications (14, 7.6%), fatigue (13, 7.1%), neuro-cognitive sequelae (7, 3.8%). The vast majority of the patients were not vaccinated prior to COVID-19. COVID-19-related sequelae persisted in 9.8% and 8% of patients 6 and 12 months after COVID-19 resolution. Persistence of sequelae at first oncological follow-up was associated with history of complicated COVID-19 (45.2% vs 24.8%, p = 0.0223), irrespective of oncological features at COVID-19 diagnosis. Conclusion: This study confirms for the first time that, in a largely unvaccinated population, post-COVID-19 syndrome can affect a significant proportion of patients with non-advanced cancer who recovered from the acute illness. COVID-19 sequelae may persist up to 12 months in some patients, highlighting the need for dedicated prevention and supportive strategies.

Background: Scalp melanomas are usually thicker and show worse prognosis than other sites and other head and neck melanomas. One hypothesis to explain this aggressive behavior could be diagnosis delay attributed to hair concealment of lesions. Methods: Primary melanomas of the scalp diagnosed over two decades at four reference centers in Australia and Italy were included. Hair coverage and visibility of the lesions were assessed on preoperative photographic documentation by two investigators and correlated with some prognostic factors (Breslow thickness, mitotic rate, and ulceration). Patients records and pathology reports provided clinical and histological data. Results: The majority of 113 melanomas included were located on easily visible areas of the scalp – hairless scalp (49%) or hairline (15%). The remaining ones (36%), considered to be hair-covered, showed more frequently thinning of hair (63%) than a dense hair coverage (37%). Melanomas of “hairy scalps” were more frequently invasive (81%) and had higher median Breslow (0.8±1.3mm) than those arising on bald scalps or areas with thinning of hair (43%; 0±0.6mm), P=0.004. However, when considering only the invasive cases (n=55), Breslow thickness and mitotic rate were not statistically different between concealed and easily visible areas. Melanomas detected by a doctor were thinner than those first noticed by the patient, relatives, or a hairdresser (P&nbsp

BackgroundAs management and prevention strategies against COVID-19 evolve, it is still uncertain whether prior exposure to immune checkpoint inhibitors (ICIs) affects COVID-19 severity in patients with cancer.MethodsIn a joint analysis of ICI recipients from OnCovid (NCT04393974) and European Society for Medical Oncology (ESMO) CoCARE registries, we assessed severity and mortality from SARS-CoV-2 in vaccinated and unvaccinated patients with cancer and explored whether prior immune-related adverse events (irAEs) influenced outcome from COVID-19.FindingsThe study population consisted of 240 patients diagnosed with COVID-19 between January 2020 and February 2022 exposed to ICI within 3 months prior to COVID-19 diagnosis, with a 30-day case fatality rate (CFR30) of 23.6% (95% CI 17.8 to 30.7%). Overall, 42 (17.5%) were fully vaccinated prior to COVID-19 and experienced decreased CFR30(4.8% vs 28.1%, p=0.0009), hospitalization rate (27.5% vs 63.2%, pOverall, 38 patients (15.8%) experienced at least one irAE of any grade at any time prior to COVID-19, at a median time of 3.2 months (range 0.13–48.7) from COVID-19 diagnosis. IrAEs occurred independently of baseline characteristics except for primary tumor (p=0.0373) and were associated with a significantly decreased CFR30(10.8% vs 26.0%, p=0.0462) additionally confirmed by the IPTW-fitted multivariable analysis (aOR 0.47, 95% CI 0.33 to 0.67). Patients who experienced irAEs also presented a higher median absolute lymphocyte count at COVID-19 (1.4 vs 0.8 109 cells/L, p=0.0098).ConclusionAnti-SARS-CoV-2 vaccination reduces morbidity and mortality from COVID-19 in ICI recipients. History of irAEs might identify patients with pre-existing protection from COVID-19, warranting further investigation of adaptive immune determinants of protection from SARS-CoV-2.

Previous analyses of the GIM (Gruppo Italiano Mammella) 2 study showed that addition of fluorouracil to epirubicin, cyclophosphamide, and paclitaxel in patients with node-positive early breast cancer does not improve outcome, whereas dose-dense chemotherapy induces a significant improvement in both disease-free survival and overall survival as compared with a standard schedule. Here, we present long-term results of the study.In this 2 × 2 factorial, open-label, randomised, phase 3 trial, we enrolled patients aged 18-70 years with operable, node-positive, breast cancer with Eastern Cooperative Oncology Group performance status of 0-1 from 81 hospitals in Italy. Eligible patients were randomly allocated (1:1:1:1) to one of the four following study groups: four cycles of standard-interval intravenous EC (epirubicin 90 mg/mBetween April 24, 2003, and July 3, 2006, 2091 patients were randomly assigned to treatment: 545 to q3EC-P, 544 to q3FEC-P, 502 to q2EC-P, and 500 to q2FEC-P. 88 patients were enrolled in centres providing only standard interval schedule and were assigned only to q3FEC-P and q3EC-P; thus, 2091 patients were included in the intention-to-treat analysis for the comparison of EC-P (1047 patients) versus FEC-P (1044 patients) and 2003 patients were included in the intention-to-treat analysis for the comparison of dose-dense (1002 patients) versus standard interval analysis (1001 patients). After a median follow-up of 15·1 years (IQR 8·4-16·3), median disease-free survival was not significantly different between FEC-P and EC-P groups (17·09 years [95% CI 15·51-not reached] vs not reached [17·54-not reached]; unadjusted hazard ratio 1·12 [95% CI 0·98-1·29]; log-rank p=0·11). Median disease-free survival was significantly higher in the dose-dense interval group than the standard-interval group (not reached [95% CI 17·45-not reached] vs 16·52 [14·24-17·54]; 0·77 [95% CI 0·67-0·89]; p=0·0004). The most common grade 3-4 adverse events were neutropenia (200 [37%] of 536 patients in the q3EC-P group vs 257 [48%] of 533 in the q3FEC-P group vs 50 [10%] of 496 q2EC-P vs 97 [20%] of 492) and alopecia (238 [44%] vs 249 [47%] vs 228 [46%] vs 235 [48%]). During extended follow-up, no further grade 3-4 adverse events or deaths related to toxic-effects were reported. Treatment-related serious adverse events were reported in nine (2%) patients in the q3EC-P group, seven (1%) in the q3FEC-P group, nine (2%) in the q2EC-P group, and nine (2%) in the q2FEC-P group. No treatment-related deaths occurred.Updated results from the GIM2 study support that optimal adjuvant chemotherapy for patients with high-risk early breast cancer should not include fluorouracil and should use a dose-dense schedule.Bristol-Myers Squibb, Pharmacia, Dompè Biotec Italy, Italian Ministry of Health, Fondazione Italiana per la Ricerca sul Cancro, and Alliance Against Cancer.

Malignant cutaneous melanoma (CM) is a potentially lethal form of skin cancer whose worldwide incidence has been constantly increasing over the past decades. During their lifetime, about 8% of CM patients will develop multiple primary melanomas (MPMs), usually at a young age and within 3 years from the first tumor/diagnosis. With the aim of improving our knowledge on MPM biology and pathogenesis, we explored the miRNome of 24 single and multiple primary melanomas, including multiple tumors from the same patient, using a small RNA-sequencing approach. From a supervised analysis, 22 miRNAs were differentially expressed in MPM compared to single CM, including key miRNAs involved in epithelial–mesenchymal transition. The first and second melanoma from the same patient presented a different miRNA profile. Ten miRNAs, including miR-25-3p, 149-5p, 92b-3p, 211-5p, 125a-5p, 125b-5p, 205-5p, 200b-3p, 21-5p, and 146a-5p, were further validated in 47 single and multiple melanoma samples. Pathway enrichment analysis of miRNA target genes revealed a more differentiated and less invasive status of MPMs compared to CMs. Bioinformatic analyses at the miRNA isoform (isomiR) level detected a panel of highly expressed isomiRs belonging to miRNA families implicated in human tumorigenesis, including miR-200, miR-30, and miR-10 family. Moreover, we identified hsa-miR-125a-5p|0|−2 isoform as tenfold over-represented in melanoma than the canonical form and differentially expressed in MPMs arising in the same patient. Target prediction analysis revealed that the miRNA shortening could change the pattern of target gene regulation, specifically in genes implicated in cell adhesion and neuronal differentiation. Overall, we provided a putative and comprehensive characterization of the miRNA/isomiR regulatory network of MPMs, highlighting mechanisms of tumor development and molecular features differentiating this subtype from single melanomas.

Foodborne illnesses are a global public health issue. Responsibility to prevent foodborne disease is shared by many actors along the food supply chain, including consumers. However, consumers often lack knowledge about food safety and behaviors that can reduce risk. Consumers are often targeted for interventions to address these gaps, but a current comprehensive analysis of such interventions globally by type, geography, and outcome is lacking in the literature. In addition, there is a need to understand how individual interventions could be broadened to include the relationships between consumers and other actors in the food system, and how targeted communication strategies can affect behavior. We conducted a rigorous scoping review to assess consumer-facing food safety interventions carried out globally over the past 20 years, and categorized and analyzed them by type of intervention, methods, and outcomes to understand which interventions might be effective in changing consumer behavior, knowledge, attitudes, beliefs, and perceptions on food safety. Ninety-two interventions were reviewed, the majority of which were published in the last 10 years in North America. Most target adults, and 25% are directed at women and mothers. Health or risk communication interventions are becoming increasingly common to move beyond skill-based education and address risk perceptions of food safety that might motivate consumers. Only two studies addressed risk perception in consumers to potentially change food handlers' behavior outside of the home. This review suggests that focusing on risk perception combined with strategies that leverage emotion and trusted sources, such as respected peers or family members, might be useful strategies for interventions.

Background/Aim: Clinicopathological features of patients undergoing margin enlargement after lumpectomy for early breast cancer with positive/close excision margins were analyzed in order to define whether a re-operative procedure could have been avoided. Furthermore, a standardized protocol of specimen orientation was adopted in order to optimize both the widening procedure as well as the oncologic outcome. Patients and Methods: A retrospective analysis was performed including pre-, peri-, and post-operative parameters, and a predictive score by means of a multivariate model was developed using all clinically and statistically significant variables associated with residual disease (RD). Results: RD was significantly related to positive tumor margins, hormone receptor negative, HER2-positive, and tumors with high Ki67 proliferation index (p3, only 2 patients (2.0%) had RD, while in 81 patients with a score ≤3, 55 patients (67.9%) had RD (p

Epidemiologic data highlight sex differences in melanoma outcome. A putative role of sex hormones is still under investigation. Very few laboratory investigations have focused on the level of expression of estrogen receptors in melanoma. We evaluated the presence of estrogen receptors alpha (ERα) and beta (ERβ) in melanoma specimens from female patients with a previous history of breast carcinoma (BC). Moreover, another group of female patients undergoing ovarian stimulation (OS) were also compared to two control groups matched for age and melanoma staging. The study was performed at the IRCCS Policlinico di Sant'Orsola Hospital's Melanoma Unit from January 2017 to December 2019. The nuclear and cytoplasmatic immunohistochemical staining was evaluated and scored by the percentage of stained tumour cells: 0 (≤20%), 1 (21-50%) or 2 (≥50%). Twenty-eight specimens were analysed. ERβ nuclear presence was detected in all cases of women with a history of breast cancer. Cytoplasmatic ERβ was clearly expressed with a score of 2 in seven cases. In the respective control group, nuclear and cytoplasmatic ERβ expression was much lower. A cytoplasmatic ERα positivity was also detected in almost all cases. In the second group of women who experienced ovarian stimulation for Assisted Reproductive Technology (ART), a lower abundance of nuclear ERs was detected. Conversely, cytoplasmatic ERβ and α expression ranged widely. Melanoma of women treated with anti-estrogen therapy is generally more prone to express estrogen receptors compared with women of the same age and CM staging but also compared with women in fertile age with and without a history of OS.

Immunotherapy has greatly improved outcomes for subgroups of patients with cancer. As indications keep expanding, there is an unmet need to gain a better understanding of the effect of these therapies on pregnancy and fertility. During pregnancy, substantial adaptations occur in the maternal immune system to maintain protection against pathogens while avoiding detrimental reactions to the semi-allogeneic fetus. The pathways involved in the establishment of this fetomaternal tolerance can be hijacked by cancers. Immunotherapies that target these inhibitory pathways, or that directly interact with the regulatory immune cells involved in tolerance mechanisms, might therefore result in complications during pregnancy. Similarly, by activating the patient's immune system with immunotherapy, a broad range of immune-related adverse events can occur that could negatively affect the fetus or impede a future desired pregnancy. This Review summarises preclinical and clinical data related to the use of immunotherapy during pregnancy, including all approved immune checkpoint inhibitors, recombinant cytokines, cell therapies, vaccines, and immunomodulatory drugs.

Symptoms of treatment-induced menopause negatively affect quality of life and adherence to endocrine therapy of breast cancer (BC) survivors. Nevertheless, the use of systemic hormone replacement therapy (HRT) to mitigate these symptoms may be associated with an increased risk of disease recurrence in these patients. This systematic review and meta-analysis aimed to assess the safety of systemic HRT on risk of disease recurrence in BC survivors. A systematic search of PubMed up to April 20, 2021 was conducted to identify randomized controlled trials (RCTs) that investigated the risk of disease recurrence with the use of HRT in BC survivors. A random-effect model was applied to calculate the risk of recurrence, reported as pooled hazard ratio (HR) with 95% confidence intervals (CI). A subgroup analysis was performed to estimate the risk of recurrence according to hormone receptor status. Four RCTs were included in the meta-analysis (n = 4050 patients). Overall, 2022 patients were randomized to receive HRT (estrogen/progestogen combination or tibolone) and 2023 to the control group with placebo or no HRT. HRT significantly increased the risk of BC recurrence compared to placebo (HR 1.46, 95% CI 1.12–1.91, p = 0.006). At the subgroup analysis, the risk of BC recurrence with the use of HRT was significantly increased in patients with hormone receptor-positive disease (HR 1.8, 95% CI 1.15–2.82, p = 0.010) but not in those with hormone receptor-negative tumors (HR 1.19, 95% CI 0.80–1.77, p = 0.390). Use of HRT was associated with a detrimental prognostic effect in BC survivors, particularly in those with hormone receptor-positive disease. Alternative interventions to mitigate menopause-related symptoms should be proposed.

Background KRISTINE is an open-label, phase III study of trastuzumab emtansine + pertuzumab (T-DM1 + P) versus docetaxel + carboplatin + trastuzumab + pertuzumab (TCH + P) in patients with HER2-positive, stage II–III breast cancer. We investigated the association of biomarkers with clinical outcomes in KRISTINE. Methods Patients were randomized to receive neoadjuvant T-DM1 + P or TCH + P and assessed for pathologic complete response (pCR; ypT0/is, ypN0). HER2 status (per central assessment), hormone receptor status, PIK3CA mutation status, HER2/HER3 mRNA levels, tumor-infiltrating lymphocyte levels, PD-L1 status, and NanoString data were analyzed. pCR rates by treatment arm were compared across biomarker subgroups. Analyses were descriptive. Results Biomarker analyses included data from all 444 patients (T-DM1 + P, n = 223; TCH + P, n = 221) enrolled in KRISTINE. Biomarker distribution was balanced across treatment arms. All subgroups with higher HER2 amplification/expression and immune marker levels showed numerically higher pCR rates in both arms. Mutated versus non-mutated PIK3CA tumors were associated with numerically lower pCR rates in the T-DM1 + P arm but not in the TCH + P arm. In a multivariate analysis, Prediction Analysis of Microarray with the 50-gene classifier (PAM50) HER2-enriched subtype, HER2 gene ratio ≥ 4, and PD-L1-positive status positively influenced the pCR rate. Biomarkers associated with lower pCR rates (e.g., low HER2 levels, positive hormone receptor status, mutated PIK3CA) were more likely to co-occur. Dynamic on-treatment biomarker changes were observed. Differences in the treatment effects for T-DM1 + P versus TCH + P were similar to those observed in the intent-to-treat population for the majority of the biomarker subgroups. Conclusions Although our biomarker analysis did not identify a subgroup of patients that benefited from neoadjuvant T-DM1 + P versus TCH + P, the data revealed that patients with higher HER2 amplification/expression and immune marker levels had improved response irrespective of treatment arm. These analyses confirm the role of HER2 tumor biology and the immune microenvironment in influencing pCR in the neoadjuvant setting and reaffirm the molecular diversity of HER2-positive breast cancer. Trial Registration: ClinicalTrials.gov NCT02131064. Registered 06 May 2014.

Immune checkpoint inhibitor (ICI)-induced cardiotoxicity is a rare immune-related adverse event (irAE) characterized by a high mortality rate. From a pathological point of view, this condition can result from a series of causes, including binding of ICIs to target molecules on nonlymphocytic cells, cross-reaction of T lymphocytes against tumor antigens with off-target tissues, generation of autoantibodies and production of proinflammatory cytokines. The diagnosis of ICI-induced cardiotoxicity can be challenging, and cardiac magnetic resonance (CMR) represents the diagnostic tool of choice in clinically stable patients with suspected myocarditis. CMR is gaining a central role in diagnosis and monitoring of cardiovascular damage in cancer patients, and it is entering international cardiology and oncology guidelines. In this narrative review, we summarized the clinical aspects of ICI-associated myocarditis, highlighting its radiological aspects and proposing a novel algorithm for the use of CMR.

There is a strong rationale for combining HER2-targeted therapies with cancer immunotherapy to increase efficacy in breast cancer, particularly in the early-stage setting, where the immune system has not been weakened by heavy pretreatment. ASTEFANIA aims to evaluate the efficacy of adjuvant atezolizumab in combination with ado-trastuzumab emtansine in patients with high-risk, HER2-positive early breast cancer and residual disease following HER2-based neoadjuvant therapy. Eligible patients will be randomized to receive ado-trastuzumab emtansine in combination with either atezolizumab or placebo for 14 cycles within 12 weeks of primary surgery. The primary outcome is invasive disease-free survival and secondary outcomes include additional efficacy end points, safety and pharmacokinetics. The study plans to enroll 1700 patients across 32 counties. Clinical Trial Registration: NCT04873362 ( ClinicalTrials.gov )

Background: Lymphovascular invasion (LVI) is considered an unfavorable prognostic factor in cutaneous melanoma (CM). However, its detection by hematoxylin and eosin (H&E) is challenging, with discordant data about its association with clinical-pathological features and no previous studies investigating the inter- (IrOA) and intra-observer (IaOA) agreement. Herein, we tested H&E and double staining (DS) for CD34/SOX10 to detect the LVI in a cohort of 92 CMs, evaluating the IrOA, the IaOA, and the association with the other clinical-pathological features. Methods: Five authors independently evaluated 92 consecutive and retrospectively enrolled cases of CMs. We assessed the IrOA (Fleiss's Kappa/FK and intraclass correlation coefficient/ICC) and the IaOA (Cohen's Kappa/CK) with both H&E and CD34/SOX10. Furthermore, we compared the LVI assessment with the two stains and analyzed the association with other clinical-pathological features [χ2 tests for dichotomous and categorical data; Student t-test (normal distribution) and Mann-Whitney U-test (non-normal distribution) for continuous data]. Results: The IrOA was almost identical with H&E (FK=0.446; ICC=0.805) and CD34/SOX10 (FK=0.454; ICC=0.810); by contrast, the IaOA was higher with H&E for one pathologist (CK: 0.809) and with CD34/SOX10 for the other one (CK: 0.563). Applying previously defined criteria, LVI was detected in 10 (9.2%) and 11 (10.1%) cases with H&E and CD34/SOX10, respectively (p = 1.000). Both H&E and CD34/SOX10 were significantly associated with vertical growth phase (H&E, p: 0.014; CD34/SOX10, p: 0.010), mitosis ≥ 1/mm2 (H&E, p: 0.000; CD34/SOX10, p: 0.004), pT (H&E, p: 0.000; CD34/SOX10, p: 0.001), Breslow thickness (H&E, p: 0.000; CD34/SOX10, p: 0.001), and lymph node and/or distant metastasis (H&E, p: 0.005; CD34/SOX10, p: 0.000); only H&E was associated with ulceration (p: 0.002) and distant metastasis (p: 0.000), conversely, only CD34/SOX10 was associated with lymph node metastasis (p: 0.003). Conclusions: CD34/SOX10 does not improve the IrOA and the IaOA of the LVI assessment in CM; furthermore, H&E and CD34/SOX10 show a similar profile of association with the other unfavorable clinical-pathological features of CM. As result, CD34/SOX10 could be a redundant diagnostic tool if applied for the prognostic characterization of not-selected CM in a routine diagnostic scenario.

s Introduction During the COVID-19 pandemic, teleconsultation was implemented in clinical practice to limit patient exposure to COVID-19 while monitoring their treatment and follow-up. We sought to examine the satisfaction of patients with breast cancer (BC) who underwent teleconsultations during this period. Methods Eighteen centres in France and Italy invited patients with BC who had at least one teleconsultation during the first wave of the COVID-19 pandemic to participate in a web-based survey that evaluated their satisfaction (EORTC OUT-PATSAT 35 and Telemedicine Satisfaction Questionnaire [TSQ] scores) with teleconsultation. Results Among the 1299 participants eligible for this analysis, 53% of participants were undergoing standard post-treatment follow-up while 22 and 17% were currently receiving active anticancer therapy for metastatic and localised cancers, respectively. The mean satisfaction scores were 77.4 and 73.3 for the EORTC OUT-PATSAT 35 and TSQ scores, respectively. In all, 52.6% of participants had low/no anxiety. Multivariable analysis showed that the EORTC OUT-PATSAT 35 score correlated to age, anxiety score and teleconsultation modality. The TSQ score correlated to disease status and anxiety score. Conclusion Patients with BC were satisfied with oncology teleconsultations during the COVID-19 pandemic. Teleconsultation may be an acceptable alternative follow-up modality in specific circumstances.

Background: The diagnosis of nodal nevi (NN) is challenging as they mimic melanoma metastases (MM), with a detection rate mostly ranging between 1% and 11% in sentinel lymph node biopsy (SLNB). Herein, we assessed the incidence of NN and the association with the clinical-pathological features of primary melanoma, adopting the updated European Organisation for Research and Treatment of Cancer (EORTC) protocol for SLNB. Methods: All cases of paired melanoma and SLNB were retrospectively evaluated (April 2019-May 2020). Appropriate statistical tests were adopted, with significant variables included in the logistic regression model. Results: 81 patients and a total of 186 lymph nodes (LNs) were included. Eleven patients had only NN and 4 had both NN and MM (18.5%); 29 LNs (15.6%) showed at least one NN and 12 (6.5%) showed more than one NN (a total amount of 43 NN was detected). All NN and none MM stained for p16. NN were associated with age < 60 years (p: 0.042), no ulceration (p: 0.025) and nevus-associated melanoma (NAM) (p: 0.018), with this latter being the only predictor at the logistic regression model (p: 0.022). Conclusions: The updated EORTC protocol shows a high number of NN and highlights a strong association with NAM.

Cutaneous melanoma (cM) is the deadliest of all primary skin cancers. Its prognosis is strongly influenced by the stage at diagnosis, with early stages having a good prognosis and being potentially treatable with surgery alone; advanced stages display a much worse prognosis, with a high rate of recurrence and metastasis. For this reason, the accurate and early diagnosis of cM is crucial—misdiagnosis may have extremely dangerous consequences for the patient and drastically reduce their chances of survival. Although the histological exam remains the “gold standard” for the diagnosis of cM, a continuously increasing number of immunohistochemical markers that could help in diagnosis, prognostic characterization, and appropriate therapeutical choices are identified every day, with some of them becoming part of routine practice. This review aims to discuss and summarize all the data related to the immunohistochemical analyses that are potentially useful for the diagnosis of cM, thus rendering it easier to appropriately applicate to routine practice. We will discuss these topics, as well as the role of these molecules in the biology of cM and potential impact on diagnosis and treatment, integrating the literature data with the experience of our surgical pathology department.

BACKGROUND BReast CAncer (BRCA) genes are extensively studied in the context of fertility and reproductive aging. BRCA proteins are part of the DNA repair Fanconi anemia (FA)/BRCA pathway, in which more than 20 proteins are implicated. According to which gene is mutated and which interactions are lost owing to the mutation, carriers and patients with monoallelic or biallelic FA/BRCA mutations exhibit very different phenotypes, from overt FA to cancer predisposition or no pathological implications. The effect of the so far neglected non-BRCA FA mutations on fertility also deserves consideration. OBJECTIVE AND RATIONALE As improved treatments allow a longer life expectancy in patients with biallelic FA mutations and overt FA, infertility is emerging as a predominant feature. We thus reviewed the mechanisms for such a manifestation, as well as whether they also occur in monoallelic carriers of FA non-BRCA mutations. SEARCH METHODS Electronic databases PUBMED, EMBASE and CENTRAL were searched using the following term: ‘fanconi’ OR ‘FANC’ OR ‘AND’ ‘fertility’ OR ‘pregnancy’ OR ‘ovarian reserve’ OR ‘spermatogenesis’ OR ‘hypogonadism’. All pertinent reports in the English-language literature were retrieved until May 2021 and the reference lists were systematically searched in order to identify any potential additional studies. OUTCOMES Biallelic FA mutations causing overt FA disease are associated with premature ovarian insufficiency (POI) occurring in the fourth decade in women and with primary non-obstructive azoospermia (NOA) in men. Hypogonadism in FA patients seems mainly associated with a defect in primordial germ cell proliferation in fetal life. In recent small, exploratory whole-exome sequencing studies, biallelic clinically occult mutations in the FA complementation group A (Fanca) and M (Fancm) genes were found in otherwise healthy patients with isolated NOA or POI, and also monoallelic carrier status for a loss-of-function mutation in Fanca has been implicated as a possible cause for POI. In those patients with known monoallelic FA mutations undergoing pre-implantation genetic testing, poor assisted reproduction outcomes are reported. However, the mechanisms underlying the repeated failures and the high miscarriage rates observed are not fully known. WIDER IMPLICATIONS The so far ‘neglected’ members of the FA/BRCA family will likely emerge as a relevant focus of investigation in the genetics of reproduction. Several (rather than a single) non-BRCA genes might be implicated. State-of-the-art methods, such as whole-genome/exome sequencing, and further exploratory studies are required to understand the prevalence and mechanisms for occult FA mutations in infertility and recurrent miscarriage.

IMPORTANCE Whether the severity and mortality of COVID-19 in patients with cancer have improved in terms of disease management and capacity is yet to be defined. OBJECTIVE To test whether severity and mortality from COVID-19 among patients with cancer have improved during the course of the pandemic. DESIGN, SETTING, AND PARTICIPANTS OnCovid is a European registry that collects data on consecutive patients with solid or hematologic cancer and COVID-19. This multicenter case series study included real-world data from 35 institutions across 6 countries (UK, Italy, Spain, France, Belgium, and Germany). This update included patients diagnosed between February 27, 2020, and February, 14, 2021. Inclusion criteria were confirmed diagnosis of SARS-CoV-2 infection and a history of solid or hematologic cancer. EXPOSURES SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES Deaths were differentiated at 14 days and 3 months as the 2 landmark end points. Patient characteristics and outcomes were compared by stratifying patients across 5 phases (February to March 2020, April to June 2020, July to September 2020, October to December 2020, and January to February 2021) and across 2 major outbreaks (February to June 2020 and July 2020 to February 2021). RESULTS At data cutoff, 2795 consecutive patients were included, with 2634 patients eligible for analysis (median [IQR] age, 68 [18-77] years ; 52.8% men). Eligible patients demonstrated significant time-dependent improvement in 14-day case-fatality rate (CFR) with estimates of 29.8% (95% CI, 0.26-0.33) for February to March 2020; 20.3% (95% CI, 0.17-0.23) for April to June 2020;12.5% (95% Cl, 0.06-22.90) for July to September 2020; 17.2% (95% CI, 0.15-0.21) for October to December 2020; and 14.5% (95% CI, 0.09-0.21) for January to February 2021(all P < .001) across the predefined phases. Compared with the second major outbreak, patients diagnosed in the first outbreak were more likely to be 65 years or older (974 of 1626 [60.3%] vs 564 of 1008 [56.1%]; P = .03), have at least 2 comorbidities (793 of 1626 [48.8%) vs 427 of 1008 [42.4%); P = .001), and have advanced tumors (708 of 1626 [46.4%) vs 536 of 1008 [56.1%]: P < .001). Complications of COVID-19 were more likely to be seen (738 of 1626 [45.4%) vs 342 of 1008 [33.9%]; P < .001) and require hospitalization (969 of 1626 [59.8%) vs 418 of 1008 [42.1%); P < .001) and anti-COVID-19 therapy (1004 of 1626 [61.7%) vs 501of 1008 [49.7%); P < .001) during the first major outbreak. The 14-day CFRs for the first and second major outbreaks were 25.6% (95% CI, 0.23-0.28) vs 16.2% (95% CI, 0.13-0.19; P < .001), respectively. After adjusting for country, sex, age, comorbidities, tumor stage and status, anti-COVID-19 and anticancer therapy, and COVID-19 complications, patients diagnosed in the first outbreak had an increased risk of death at 14 days (hazard ratio [HR], 1.85; 95% CI, 1.47-2.32) and 3 months (HR, 1.28; 95% CI, 1.08-1.51) compared with those diagnosed in the second outbreak. CONCLUSIONS AND RELEVANCE The findings of this registry-based study suggest that mortality in patients with cancer diagnosed with COVID-19 has improved in Europe; this improvement may be associated with earlier diagnosis, improved management, and dynamic changes in community transmission over time.

Squamous cell carcinoma (SCC) is the most common malignancy of the nail unit. Pathogenetic mechanisms are yet to be determined, and a deeper molecular characterization of this disease is still necessary. The aim was to obtain a molecular characterization of NU SCC samples using an NGS approach to identify the genetic drivers involved in this tumor. The presence of HPV infection was also assessed. Furthermore, the mutational status was correlated with specific clinical-pathological features for a better insight into the carcinogenesis of this uncommon tumor. We analysed twenty paraffin-embedded nail unit SCC samples from patients diagnosed with primary SCC of the nail unit by next genome sequencing. In the 20 tested samples, the neoplastic cells enrichment ranged from 10% to 50% (mean value: 25.7%). In 14/20 cases (70.0%), at least one mutation was detected; whereas in the other six cases (30.0%), no alterations were observed (‘wild-type/WT cases’). Overall, a total of 23 mutations were identified in the 20 specimens. TP53 was the most mutated gene (6/20 cases, 30.0%), while cKit, GNAS, EGFR, DICER1 and CTNNB1 were observed in one sample each (5.0%). No clinical-pathological parameters (age, sex, depth of invasion-DOI, histological subtype, grading and HPV) were significantly associated with the mutational status. The nail unit SCC mutational landscape appeared to be heterogeneous, favouring the hypothesis of a complex pathogenesis and an interaction of multiple elements, including HPV infections. This wealth of information undoubtedly improves our understanding of SCC biology.

Background: The medium-term and long-term impact of COVID-19 in patients with cancer is not yet known. In this study, we aimed to describe the prevalence of COVID-19 sequelae and their impact on the survival of patients with cancer. We also aimed to describe patterns of resumption and modifications of systemic anti-cancer therapy following recovery from SARS-CoV-2 infection. Methods: OnCovid is an active European registry study enrolling consecutive patients aged 18 years or older with a history of solid or haematological malignancy and who had a diagnosis of RT-PCR confirmed SARS-CoV-2 infection. For this retrospective study, patients were enrolled from 35 institutions across Belgium, France, Germany, Italy, Spain, and the UK. Patients who were diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, and entered into the registry at the point of data lock (March 1, 2021), were eligible for analysis. The present analysis was focused on COVID-19 survivors who underwent clinical reassessment at each participating institution. We documented prevalence of COVID-19 sequelae and described factors associated with their development and their association with post-COVID-19 survival, which was defined as the interval from post-COVID-19 reassessment to the patients’ death or last follow-up. We also evaluated resumption of systemic anti-cancer therapy in patients treated within 4 weeks of COVID-19 diagnosis. The OnCovid study is registered in ClinicalTrials.gov, NCT04393974. Findings: 2795 patients diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, were entered into the study by the time of the data lock on March 1, 2021. After the exclusion of ineligible patients, the final study population consisted of 2634 patients. 1557 COVID-19 survivors underwent a formal clinical reassessment after a median of 22·1 months (IQR 8·4–57·8) from cancer diagnosis and 44 days (28–329) from COVID-19 diagnosis. 234 (15·0%) patients reported COVID-19 sequelae, including respiratory symptoms (116 [49·6%]) and residual fatigue (96 [41·0%]). Sequelae were more common in men (vs women; p=0·041), patients aged 65 years or older (vs other age groups; p=0·048), patients with two or more comorbidities (vs one or none; p=0·0006), and patients with a history of smoking (vs no smoking history; p=0·0004). Sequelae were associated with hospitalisation for COVID-19 (p

Introduction how best to manage patients with colorectal cancer and synchronous liver metastasis is still controversial, with specific concerns of increased risk of postoperative complications following combined resection. We aimed at analyzing the influence of combined liver resection on the risk of anastomotic leak (AL) following colorectal resection. Methods we reviewed the iCral prospectively maintained database to compare the relative risk of AL of patients undergoing colorectal resection for cancer to that of patients receiving simultaneous liver and colorectal resection for cancer with isolated hepatic metastases. The incidence of AL was the primary outcome of the analysis. Perioperative details and postoperative complications were also appraised. Results out of a total of 996 patients who underwent colorectal resection for cancer, 206 receiving isolated colorectal resection were compared with a matched group of 53 patients undergoing simultaneous liver and colorectal resection. Combined surgery had greater operative time and resulted in longer postoperative hospitalization compared to colorectal resection alone. The proportion of overall morbidity following combined resection was significantly higher than after isolated colorectal resection (56.6% vs. 37.9%, p = 0.021). Overall, the two groups of patients did not differ neither on the rate of major postoperative complications, nor in terms of AL (9.4% vs. 6.3%, p = 0.381). At specific multivariate analysis, the duration of surgery was the only risk factor independently associated with the likelihood of AL. Conclusions combining hepatic with colorectal resection for the treatment of synchronous liver metastasis from colorectal cancer does not increase significantly the incidence of AL.

Preservation and expansion of β-cell mass is a therapeutic goal for diabetes. Here we show that the hyperactive isoform of carbohydrate response-element binding protein (ChREBPβ) is a nuclear effector of hyperglycemic stress occurring in β-cells in response to prolonged glucose exposure, high-fat diet, and diabetes. We show that transient positive feedback induction of ChREBPβ is necessary for adaptive β-cell expansion in response to metabolic challenges. Conversely, chronic excessive β-cell-specific overexpression of ChREBPβ results in loss of β-cell identity, apoptosis, loss of β-cell mass, and diabetes. Furthermore, β-cell “glucolipotoxicity” can be prevented by deletion of ChREBPβ. Moreover, ChREBPβ-mediated cell death is mitigated by overexpression of the alternate CHREBP gene product, ChREBPα, or by activation of the antioxidant Nrf2 pathway in rodent and human β-cells. We conclude that ChREBPβ, whether adaptive or maladaptive, is an important determinant of β-cell fate and a potential target for the preservation of β-cell mass in diabetes.

To assess whether socio-economic disparities exist on access to care, treatment options and outcomes among patients with renal mass amenable of surgical treatment within the universal healthcare system.Data of consecutive patients submitted to partial nephrectomy (PN) or radical nephrectomy (RN) at our Institution between 2017 and 2020 were retrospectively evaluated. Patients were grouped according to their income level (low, intermediate, and high) based on the Indicator of Equivalent Economic Situation national criterion. Survival analysis was performed. Cox regression models were employed to analyse the impact of socio-economic variables on survival outcomes.One thousand forty-two patients were included (841 PN and 201 RN). Patients at the lowest income level were found more likely symptomatic and with a higher pathological tumour stage in the RN cohort (p 0.05). The guidelines adherence on surgical indication rate as well as the access to minimally invasive surgery did not differ according to patient's income level in both cohorts (p 0.05). Survival curves were comparable among the groups. Cox regression analysis showed that none of the included socio-economic variables was associated with survival outcomes in our series.Universal healthcare system may increase the possibility to ensure egalitarian treatment modalities for patients with renal cancer.

Funding: This work was undertaken in part in the MRC Centre for Reproductive Health, (supported by MRC grant MR/N022556/1). ML acknowledges the Italian Association for Cancer Research (“Associazione Italiana per la Ricerca sul Cancro”, AIRC; MFAG 2020 ID 24698) and the Italian Ministry of Health (5 x 1000 funds 2017) for supporting his research in the field of breast cancer in young women and oncofertility. Background There remains a considerable concern among both patients and oncologists that having a live birth (LB) after breast cancer might adversely impact survival. Methods analysis of survival in a national cohort of women with breast cancer diagnosed at age 20–39 years between 1981 and 2017 (n = 5181), and subsequent LB using Scottish Cancer Registry and national maternity records. Cases had at least one subsequent LB, each was matched with up to six unexposed cases without subsequent LB, accounting for guaranteed time bias. Results In 290 women with a LB after diagnosis, overall survival was increased compared to those who did not have a subsequent LB, HR 0.65 (95%CI 0.50–0.85). Women with subsequent LB who had not had a pregnancy before breast cancer showed increased survival (HR 0.56, 0.38–0.82). There was a progressively greater interaction of subsequent LB with survival with younger age, thus for women aged 20–25 years, HR 0.30 (0.12–0.74) vs. those aged 36–39, HR 0.89 (0.42–1.87). In women with LB within five years of diagnosis, survival was also increased (HR 0.66; 0.49–0.89). Survival following LB was similar to unexposed women by ER status (both positive and negative) and in those known to have been exposed to chemotherapy. Conclusions This analysis provides further evidence that for the growing number of women who wish to have children after breast cancer, LB does not have a negative impact on overall survival. This finding was confirmed within subgroups, including the youngest women and those not previously pregnant. Publisher PDF

Survivorship has become a crucial component in breast cancer care. For women who have not completed their family planning, conceiving at the end of anticancer treatments should not be discouraged but might be challenging. Oncofertility counseling should be offered at the time of diagnosis to all patients, in order to inform them about the potential treatment-induced gonadotoxicity as well as the available strategies for fertility preservation, thus allowing to increase the chances of a future pregnancy. This article reports an updated overview on the current state of the art on pregnancy in women with prior breast cancer diagnosis and treatment, with a main focus on the issues faced by patients with history of hormone receptor-positive disease and BRCA carriers.

Oral (OP) and nail (NP) pigmentations may occur simultaneously in physiological or pathological conditions, and may be a sign of underlying syndromic conditions that necessitate further investigation and treatment. Interestingly, the nail unit and oral cavity show a clinical parallelism that may help the clinician to conduct a correct examination and reach a prompt diagnosis. Both OP and NP can manifest clinically with focal or diffuse involvement and are due to external factors (exogenous pigmentation, drug-induced pigmentation) or endogenous factors (racial pigmentation, post-inflammatory pigmentation, nevi, genetic conditions and other disorders). The most concerning differential diagnosis is melanoma. Here we report the pathogenetic basis of OP and NP, together with the description of similar clinical features. To the best of our knowledge this is the first paper to summarize and describe the causes of pigmentation of both the oral cavity and the nail unit.

Purpose: To evaluate the role of F-18-Fluorothymidine (FLT) PET/CT in lymphoma patients with suspected recurrent or residual disease. Methods: Adult lymphoma patients presenting with positive or equivocal F-18-FDG PET/CT at end-treatment or follow-up were prospectively addressed to an additional F-18-FLT-PET/CT. SUV max and tumour-to-background ratios (TBRs) were recorded for the most avid lesion. Biopsy or, when not available, clinical or imaging assessment were employed as standard of reference. Results: Overall 52 patients were recruited. Histology was available in 20/52 patients (38%), proliferation-index (Ki-67) in 14/20. Disease was excluded in 13/52 patients (25%) (one reactive follicular hyperplasia, five reactive-inflammatory tissues, four reactive nodes, two nodal sarcoid-like and one non-specific peri-caecal finding). FDG and FLT scans were concordant in disease restaging in 34/52 patients (65%), whereas in 18/52 cases (35%) relevant discrepancies were recorded. SUV max and TBR were significantly higher in the disease versus the disease-free group, with both tracers (p = 0.0231 and 0.0219 for FDG; p = 0.0008 and 0.0016 for FLT). FLT-SUVmax demonstrated slightly better performance in discriminating benign from malignant lesions (ROC-AUC: 0.8116 and 0.7949 for FLT-SUV max and TBR; 0.7120 and 0.7140 for FDG). Optimal FLT-SUV max cut-offs were searched: three would lead to 95% sensitivity, 81% accuracy, and 39% specificity, whereas seven led to 100%, 41%, and 56% respectively. No statistically significant correlation was observed between the two FLT indices and Ki-67. Conclusions: According to our results in a clinical setting of recurrent or residual lymphoma, FLT is not significantly superior to FDG and it is unlikely that it will be employed independently. FLT may be restricted to a few specific cases, as complementary to standard FDG imaging, to confirm a diagnosis or to define a better target to biopsy. However, due to FLT suboptimal performance, many findings would remain inconclusive, requiring further diagnostic procedures and reducing the effectiveness of performing an additional FLT scan.

Objectives: The extension of atypical melanocytes to the hair follicle, also termed melanoma folliculotropism, is poorly evaluated and its role is contradictory. We performed an observational study focusing on anatomical areas rich in follicles, such as the head and neck region. Methods: Primary head and neck melanomas diagnosed in the Melanoma Unit, Policlinic Sant'Orsola-Malpighi, University of Bologna were analyzed. Folliculotropism was evaluated with a quantitative and morphologic parameter. Statistical analyses were performed correlating patients' prognosis with folliculotropism and other clinical and histopathologic factors. Results: The study was carried out on a sample of 62 patients. The diffuse distribution (atypical melanocytes present in more than three contiguous follicular units) correlated with scalp localization, nodular subtype, higher Breslow thickness, and a poorer prognosis. Conclusions: We believe that folliculotropism should be further investigated and reported by pathologists during the histologic diagnosis of melanoma.