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This study aims to estimate long-term survival, cancer prevalence, and several cure indicators for Italian women with gynecological cancers. Thirty-one cancer registries, representing 47% of the Italian female population, were included. Mixture cure models were used to estimate net survival, cure fraction, time to cure (when 5-year conditional net survival becomes > 95%), cure prevalence (women who will not die of cancer), and already cured (living longer than time to cure). In 2018, 0.4% (121 704) of Italian women were alive after diagnosis of corpus uteri cancer, 0.2% (52 551) after cervical cancer, and 0.2% (52 153) after ovarian cancer. More than 90% of patients with uterine cancers and 83% with ovarian cancer will not die from their neoplasm (cure prevalence). Women with gynecological cancers have a residual excess risk of death <5% at 5 years after diagnosis. The cure fraction was 69% for corpus uteri, 32% for ovarian, and 58% for cervical cancer patients. Time to cure was ≤10 years for women with gynecological cancers aged <55 years; 74% of patients with cervical cancer, 63% with corpus uteri cancer, and 55% with ovarian cancer were already cured. These results can contribute to improving follow-up programs for women with gynecological cancers and supporting efforts against discrimination of already cured ones. This article is part of a Special Collection on Gynecological Cancers. [ABSTRACT FROM AUTHOR]

Purpose: The choice of surgical approach for floor of the mouth (FOM) cancer, particularly for intermediate-stage tumors (cT2–cT3), remains controversial. This study aims to evaluate a method considering mylohyoid muscle (MM) invasion as a determinant for surgical approach selection, utilizing magnetic resonance imaging (MRI) preoperatively and frozen section (FS) analysis intraoperatively. Methods: This observational retrospective cohort study analyzed patients undergoing surgical resection of cT2 and cT3 FOM squamous cell carcinoma (SCC) between January 2013 and June 2023. MM infiltration assessed by preoperative MRI determined the surgical approach: clear infiltration led to compartmental surgery (CS), while doubtful or absent infiltration led to transoral surgery (TOS). Conversion from TOS to CS occurred intraoperatively based on macroscopic evidence or positive FS. Data collected included demographic, clinical, surgical, and pathological variables. Survival analysis was conducted using Kaplan–Meier method. Results: Among 44 patients included, majority had cT2 tumors (59.1%). MM resection was necessary in 22.7% of cases. Overall survival (OS) and progression-free survival (PFS) did not significantly differ between TOS and CS groups. Radiological depth of invasion (rDOI) < 10 mm is correlated with MM preservation in 89% of cases, while rDOI > 10 mm is correlated with MM resection only in 23.8% of cases. Pathological depth of invasion (pDOI) discrepancies were observed in the two groups: in CS group is shown a higher pDOI (> 10 mm) confirmation (90%). Surgical complications and functional outcomes differed between TOS and CS groups. Conclusion: Considering MM invasion for surgical approach selection in cT2–cT3 FOM tumors appears oncologically safe, with better functional outcomes in muscle preservation. Preoperative MRI for MM assessment combined with intraoperative FS analysis provides reliable guidance for surgical decision-making. [ABSTRACT FROM AUTHOR]

People alive many years after breast (BC) or colorectal cancer (CRC) diagnoses are increasing. This paper aimed to estimate the indicators of cancer cure and complete prevalence for Italian patients with BC and CRC by stage and age. A total of 31 Italian Cancer Registries (47% of the population) data until 2017 were included. Mixture cure models allowed estimation of net survival (NS); cure fraction (CF); time to cure (TTC, 5‐year conditional NS >95%); cure prevalence (who will not die of cancer); and already cured (prevalent patients living longer than TTC). 2.6% of all Italian women (806,410) were alive in 2018 after BC and 88% will not die of BC. For those diagnosed in 2010, CF was 73%, 99% when diagnosed at stage I, 81% at stage II, and 36% at stages III–IV. For all stages combined, TTC was >10 years under 45 and over 65 years and for women with advanced stages, but ≤1 year for all BC patients at stage I. The proportion of already cured prevalent BC women was 75% (94% at stage I). Prevalent CRC cases were 422,407 (0.7% of the Italian population), 90% will not die of CRC. For CRC patients, CF was 56%, 92% at stage I, 71% at stage II, and 35% at stages III–IV. TTC was ≤10 years for all age groups and stages. Already cured were 59% of all prevalent CRC patients (93% at stage I). Cancer cure indicators by stage may contribute to appropriate follow‐up in the years after diagnosis, thus avoiding patients' discrimination. [ABSTRACT FROM AUTHOR]

Glioblastoma is the most frequent and aggressive brain tumor in adults. This study aims to evaluate the expression and prognostic impact of CD99, a membrane glycoprotein involved in cellular migration and invasion. In a cohort of patients with glioblastoma treated with surgery, radiotherapy and temozolomide, we retrospectively analyzed tumor expression of CD99 by immunohistochemistry (IHC) and by quantitative real-time polymerase chain reaction (qRT-PCR) for both the wild type (CD99wt) and the truncated (CD99sh) isoforms. The impact on overall survival (OS) was assessed with the Kaplan–Meier method and log-rank test and by multivariable Cox regression. Forty-six patients with glioblastoma entered this study. Immunohistochemical expression of CD99 was present in 83%. Only the CD99wt isoform was detected by qRT-PCR and was significantly correlated with CD99 expression evaluated by IHC (rho = 0.309, p = 0.037). CD99 expression was not associated with OS, regardless of the assessment methodology used (p = 0.61 for qRT-PCR and p = 0.73 for IHC). In an exploratory analysis of The Cancer Genome Atlas, casuistry of glioblastomas CD99 expression was not associated with OS nor with progression-free survival. This study confirms a high expression of CD99 in glioblastoma but does not show any significant impact on survival. Further preclinical studies are needed to define its role as a therapeutic target in glioblastoma. [ABSTRACT FROM AUTHOR]

Next-generation sequencing (NGS) assays based on plasma cell-free DNA (cfDNA) are increasingly used for clinical trials inclusion. Their optimized limit of detection applied to a large number of genes leads to the identification of mutations not confirmed in tissue. It becomes essential to describe the characteristics and consequences of these liquid biopsy-only mutations. In the STING protocol (Gustave Roussy, NCT04932525), 542 patients with advanced solid cancer had cfDNA-based and tissue-based NGS analysis (performed by FoundationOne® Liquid CDx and FoundationOne CDx™, respectively). Mutations identified in the liquid biopsy but not in the paired tissue were considered as liquid biopsy-only mutations irrespective of their variant allelic frequency (VAF). Out of 542 patients, 281 (51.8%) harbored at least one liquid biopsy-only mutation. These patients were significantly older, and more heavily pretreated. Liquid biopsy-only mutations occurring in TP53, and in DDR genes (ATM, CHEK2, ATR, BRCA2, and BRCA1) accounted for 90.8% of all the mutations. The median VAF of these mutations was generally low (0.37% and 0.40% for TP53 and DDR genes respectively). The variant type repartition depended on the gene. Liquid biopsy-only mutations affected hotspot in TP53 codon 273, 125, 195, 176, 237 or 280 and ATM codon 2891 and 3008. In a subset of 37 patients, 75.0%, 53.5% and 83.3% of the liquid biopsy-only mutations occurring respectively in ATM, TP53, and CHEK2 were confirmed in the matching whole blood sample. Although liquid biopsy-only mutations makes the interpretation of liquid biopsy results more complex, they have distinct characteristics making them more easily identifiable. [ABSTRACT FROM AUTHOR]

Introduction: The presence of cervical lymph node metastases is an unfavorable prognostic factor in head and neck squamous cell carcinoma (HNSCC) and a potential cause of treatment failure. Occult lymph node metastasis occurs in approximately 15–20% of HNSCC patients with a clinically negative neck (cN0), greatly impacting on their prognosis. The present study aimed to investigate the role of pre-treatment peripheral blood markers in predicting clinically occult cervical lymph node metastasis. Methods: This multicenter, retrospective study was performed in a cohort of 472 patients diagnosed with cN0 HNSCC who underwent up-front surgery. Baseline neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammatory marker (SIM), and systemic immune-inflammation index (SII) were calculated from available blood parameters. Results: Oro-hypopharyngeal and oral cancers, locally advanced stage, moderately (G2), and poorly (G3) differentiated grade were associated with an increased risk of pathological lymph node involvement. NLR, LMR, PLR, SIM, and SII were significantly associated at multivariable analysis. NLR >2.12 was the most reliable at predicting occult lymph node metastasis (OR = 5.22; 95% CI: 2.14–12.75). We describe a predictive score integrating cancer site, local stage, and NLR which is effective at predicting positive lymph node pathological status. Conclusions: The present study provides evidence that pre-treatment peripheral blood markers, in particular NLR, represent reliable predictors of clinically occult cervical lymph node metastasis in cN0 HNSCC. Therefore, the present study provides a novel useful predictive score for directing the elective management of the neck in patients with cN0 HNSCC. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to determine the impact of the involvement of the superior pharyngeal constrictor muscle (SPCM) evaluated by magnetic resonance imaging (MRI) on outcome in oropharyngeal squamous cell carcinomas (OPSCCs). Methods: A retrospective study including consecutive patients with OPSCC treated with curative intent. Results: A total of 82 consecutive patients with OPSCC met inclusion criteria. At multivariate analysis, patients with SPCM infiltration were at significantly higher risk of death (HR: 3.37, CI: 1.21–9.38) and progression (HR: 3.39, CI: 1.38–8.32). In a multivariate model conditioned on HPV status, a significantly higher risk of death and progression was observed by combining both SPCM and HPV status with patients harboring an HPV‐negative OPSCC with SPCM infiltration showing the poorest outcome. Conclusion: MRI evidence of SPCM involvement significantly and independently increases the risk of death and progression in subjects with OPSCC. Considering both MRI‐assessed SPCM infiltration and HPV status significantly improved risk stratification in these malignancies. [ABSTRACT FROM AUTHOR]

Background: Primary human papillomaviruses (HPV) cervical cancer screening can be strengthened by offering home-collection of biological specimen as a valuable option to increase screening coverage. As recommended by World Health Organization (WHO), screening programs should consider whether the inclusion of HPV self-sampling as a complementary option within their existing screening algorithms could address the gaps in current coverage. However, few HPV screening tests are validated for self-sampling according to international guidelines. This study aimed to test a self-sampling-based screening strategy, complementary to the main screening program based on clinician-collected cervical samples. The study took place in Trieste, Italy, and it aimed to evaluate the feasibility of self-testing at home under an opt-in system during COVID-19 pandemic in order to exploit self-sampling to reduce the screening delay generated by the lockdown. Methods: 500 women, who should have received the screening call in 2020, were asked, via phone call, to participate in the study. To whom agreed, a home-collection kit, including a vaginal dry swab for specimen collection, was sent. The recipients performed the sample self-collection and sent back the swab through traditional mail using a prepaid envelope. Once received by the hospital, the samples were analyzed with HPV Selfy (Ulisse BioMed, Italy), a CE-IVD HPV screening test specifically validated for self-collection. Results were further compared using cobas® 4800 HPV (Roche, Switzerland). Results: 80% women sent back their swab, showing one of the highest return rate obtained in comparable studies. 34 HPV-positive women were followed up and underwent the Pap test, that revealed 8 low squamous intraepithelial lesions (LSIL) cases, later triaged to colposcopy. HPV Selfy was confirmed to be an adequate test for self-sampling-based screening. Conclusions: This study further confirmed the feasibility of self-test at home screening strategy based on self-sampling with an opt-in system as a support method to enhance cervical cancer screening coverage in Italy. Enrolled women showed a high appreciation for this approach. HPV Selfy test demonstrated to be a valuable assay for cervical cancer screening based on home self-collection. Trial registration: ASUGI Trieste n. 16008/2018 and amendment 02-11/09/2020. [ABSTRACT FROM AUTHOR]

Background: Several randomized clinical trials provide evidence of the survival benefit of extended adjuvant tamoxifen in women with estrogen receptor (ER)-positive early breast cancer (BC). However, non-adherence may lead to underestimate treatment effects using intention to treat (ITT) methods. We reanalyzed a randomized trial using contemporary statistical methods adjusting for non-adherence. Methods: The TAM01 study was a phase 3 trial including women with early BC, who had completed 2–3 years of adjuvant tamoxifen between 1986 and 1995. Participants were randomly assigned to continue tamoxifen up to 10 years or to discontinue the treatment at randomization. Invasive disease-free survival (iDFS) and overall survival (OS) were estimated using marginal structural models (MSM) and rank preserving structural failure time model (RPSFTM). Results: Of 3830 patients enrolled, 2485 were randomized to extended tamoxifen, and 1345 to treatment discontinuation. The 10-year non-adherence rate in the extended group was 27.2%. Among women with ER-positive BC (n = 2402), extended tamoxifen was associated with a 45% and 21% relative improvement in iDFS by MSM and RPSFTM, respectively (Hazard Ratio (HR), 0.55; 95% Confidence Interval (CI), 0.48–0.64 and HR, 0.79; 95%CI, 0.67–0.95, respectively), a considerable greater benefit than in the ITT analysis (HR, 0.90; 95%CI, 0.81–0.99). The OS reanalysis revealed a substantial benefit of extended tamoxifen (MSM: HR, 0.70; 95%CI, 0.59–0.83; RPSFTM: HR, 0.85; 95%CI, 0.67–1.04), compared to the ITT analyses (HR, 0.94; 95%CI, 0.84–1.07). Conclusion: This analysis emphasizes both the importance of adherence to hormonotherapy in hormone-receptor positive early BC and the usefulness of more complex statistical analyses. [ABSTRACT FROM AUTHOR]

Background: Anaplastic thyroid carcinoma (ATC) is a rare and frequently fatal type of thyroid cancer. The degree of heterogeneity in survival rates for ATC is incompletely studied. This study evaluated the factors associated with overall survival (OS) of patients with ATC using multicenter real-world data from a national tertiary care center network in France. Methods: In this multicenter, retrospective cohort study, all patients with ATC diagnosed between 2010 and 2020 were identified from the national database of the French ENDOCAN-TUTHYREF network. Factors associated with OS were examined in multivariable analyses using Cox proportional hazards models. Results: The study included 360 patients. Of these, 220 (61%) were female and the median age was 72 years (interquartile range: 62–80). The percentages of patients with pure and mixed (synchronously-transformed) ATC (p-ATC and st-ATC) were 62.5% and 26.7%, respectively. The median OS was 6.8 months [confidence interval, CI: 5.5–8.1]: not reached for stage IVa, 11.4 months [8.2–17.8] for IVb, and 4.6 months [3.5–5.7] for IVc. Surgery, radiation therapy to the neck, chemotherapy, and best supportive care were administered to 69 (19.2%), 214 (59.4%), 254 (70.6%), and 66 (18.3%) patients, respectively. In a multivariable analysis, including stage IVb–IVc patients, significantly higher OS was observed in patients with Eastern Cooperative Oncology Group performance-status of 0–1 (hazard ratio [HR], 0.6; [CI, 0.4–0.9], p < 0.02), stage IVb [HR, 0.5; CI, 0.4–0.8, p < 0.001], and multimodal treatment (surgery and chemoradiotherapy) [HR, 0.07; CI, 0.04–0.1, p < 0.001]. Variables associated with significantly worse OS included: p-ATC (vs. st-ATC) [HR, 1.83; CI, 1.33–2.51, p = 0.001] and a neutrophil-to-lymphocyte ratio (NLR) >5.05 [HR, 2.05, CI, 1.39–3.05, p < 0.001]. Conclusions: Factors independently associated with improved OS in ATC included: European Cooperative Oncology Group performance status, disease stage, multimodality treatment, synchronously transformed ATC, and lower NLR. Long-term OS was observed in selected patients with ATC who underwent multimodal treatment. [ABSTRACT FROM AUTHOR]

(1) Background: Oral semaglutide represents the first oral GLP-1 RA approved for the treatment of type 2 diabetes mellitus (T2DM). This real-world retrospective study aimed at evaluating its effectiveness and tolerability in the treatment of patients with T2DM when patients switched from a glucose-lowering agent to it and when it was added to the usual therapy. (2) Methods: Adult patients with T2DM taking oral semaglutide and followed in the ASUGI Diabetes Center were identified with the use of electronic medical records between October 2022 and May 2023. (3) Results: A total of 129 patients were recruited. The median follow-up was 6 months. Be it as a switchover or as an add-on therapy, oral semaglutide significantly reduced HbA1c and BMI. Switching from DPPIV inhibitors to oral semaglutide was associated with a significant reduction in HbA1c and BMI, switching from SGLT2 inhibitors was associated with a significant reduction in HbA1c, and switching from sulphonylureas was associated with a significant reduction in BMI. The median HbA1c change was associated with baseline HbA1c. SBP significantly decreased in the add-on group. Oral semaglutide was well tolerated. (4) Conclusions: This study shows that in the real-world setting, oral semaglutide is effective and safe as a switchover or as an add-on therapy for the treatment of T2DM. [ABSTRACT FROM AUTHOR]

Night shift work has been found to be associated with a higher risk of cardiovascular and cerebrovascular disease. One of the underlying mechanisms seems to be that shift work promotes hypertension, but results have been variable. This cross-sectional study was carried out in a group of internists with the aim of performing a paired analysis of 24 h blood pressure in the same physicians working a day shift and then a night shift, and a paired analysis of clock gene expression after a night of rest and a night of work. Each participant wore an ambulatory blood pressure monitor (ABPM) twice. The first time was for a 24 h period that included a 12 h day shift (08.00–20.00) and a night of rest. The second time was for a 30 h period that included a day of rest, a night shift (20.00–08.00), and a subsequent period of rest (08.00–14.00). Subjects underwent fasting blood sampling twice: after the night of rest and after the night shift. Night shift work significantly increased night systolic blood pressure (SBP), night diastolic blood pressure (DBP), and heart rate (HR) and decreased their respective nocturnal decline. Clock gene expression increased after the night shift. There was a direct association between night blood pressure and clock gene expression. Night shifts lead to an increase in blood pressure, non-dipping status, and circadian rhythm misalignment. Blood pressure is associated with clock genes and circadian rhythm misalignement. [ABSTRACT FROM AUTHOR]

Introduction: Obstructive sleep apnea syndrome (OSAS) and asthma are two diseases with a high epidemiological impact that may often coexist. Both diseases have underlying pathogenic mechanisms (chronic inflammation, genetic predisposition, etc.); it is still unclear whether or not their coexistence is due to a specific pathophysiological factor. In the literature, the pathogenesis of OSAS has four pathophysiological traits: one or more anatomical predisposing factors, a low arousal threshold (low AT), high loop gain, and poor muscle responsiveness. In this study, we hypothesized that a low AT is a common pathophysiological factor in OSAS and asthma. Methods: A retrospective study of patients attending the Pulmonology Unit of the University Hospital of Trieste was carried out. Low AT was predicted on the bases of the following polysomnography features, as previously shown by Edwards et al.: an AHI of < 30 events/h, a nadir SpO2 of > 82.5%, and a hypopnea fraction of total respiratory events of > 58.3%. Results: Thirty-five patients with asthma and OSAS and 36 with OSAS alone were included in the study. Low AT was present in 71% of patients affected by asthma and OSAS (25 patients out of 35) versus 31% (11 patients out of 36) of patients affected by OSAS alone with a statistically significant difference (p = 0.002) between the two groups. Stratifying for BMI and OSAS severity, the difference between groups remained statistically significant. Conclusions: This is the first study to describe specific polysomnographic characteristics of patients affected by asthma and OSAS. A low AT may well be the pathophysiological factor common to the two diseases. If confirmed by other studies, this finding could lead to the presence of asthma and OSAS in the same individual being considered a syndrome with a common pathophysiological factor. [ABSTRACT FROM AUTHOR]

Background: In Western countries, breast cancer (BC) is the most common cancer in women. Early detection has a positive impact on survival, quality of life, and public health costs. Mammography screening programs have increased early detection rates, but new approaches to more personalized surveillance could further improve diagnosis. Circulating cell-free DNA (cfDNA) in blood could provide a potential tool for early diagnosis by analyzing cfDNA quantity, circulating tumor DNA mutations, or cfDNA integrity (cfDI). Methods: Plasma was obtained from the blood of 106 breast cancer patients (cases) and 103 healthy women (controls). Digital droplet PCR was used for the determination of ALU 260/111 bp and LINE-1 266/97 bp copy number ratio and cfDI. cfDNA abundance was calculated using copies of the EEF1A2 gene. The accuracy of biomarker discrimination was analyzed with receiver operating characteristic curve (ROC). Sensitivity analyses were performed to account for age as a potential confounder. Results: Cases had significantly lower ALU 260/111 or LINE-1 266/97 copy number ratios (median; ALU 260/111 = 0.08, LINE-1 266/97 = 0.20), compared with control (median; ALU 260/111 = 0.10, LINE-1 266/97 = 0.28) (p < 0.001). ROC analysis showed that copy number ratio discriminated cases from controls (area under the curve, AUC = 0.69, 95% CI: 0.62–0.76 for ALU and 0.80, 95% CI: 0.73–0.86 for LINE-1). ROC from cfDI confirmed the better diagnostic performance of LINE-1 compared with ALU. Conclusions: Analysis of LINE-1 266/97 copy number ratio or cfDI by ddPCR appears to be a useful noninvasive test that could aid in early BC detection. Further studies in a large cohort are needed to validate the biomarker. [ABSTRACT FROM AUTHOR]

Purpose. Thermal ablations (TA) are gaining ground as alternative options to conventional therapies for symptomatic benign thyroid nodules. Little is known about the impact of nodule biology on the outcomes of TA. The aim of our study was to evaluate the baseline immunocytochemistry profile of thyroid nodules that were poorly responsive to TA in order to identify potential predictors of the treatment response. Methods. From a cohort of 406 patients with benign thyroid nodules treated with TA and followed for 5 years, we retrospectively selected two groups of patients: NONRESPONDERS (patients who did not respond to TA and were later surgically treated) and RESPONDERS (patients who responded to TA). The fine-needle aspiration cytology (FNAC) slides obtained before TA were stained for Galectin-3, HBME-1, CK-19, and Ki-67. Results. Benign nodules of NONRESPONDERS (n = 19) did not express CK-19 (p = 0.03), as compared to RESPONDERS (n = 26). We combined the absence of CK-19 and the presence of Ki-67 to obtain a composite biomarker of resistance to TA, which discriminated between likelihood of retreatment and no retreatment with an AUC of 0.68 (95%CI: 0.55-0.81) and a sensitivity, specificity, PPV, and NPV of 29%, 91%, 71%, and 64%, respectively. Conclusion. In benign thyroid nodules, the absence of CK-19 was associated with resistance to TA, while the presence of CK-19 was predictive of response to TA. If confirmed, this finding could provide rapid and inexpensive information about the potential outcome of TA on benign thyroid nodules. In addition, as CK-19 can be expressed in adenomatous hyperplasia, it could be speculated that these nodules, rather than follicular adenomas, might be better candidates for TA. [ABSTRACT FROM AUTHOR]

With the advent of immunotherapies, the field of cancer therapy has been revived with new hope, especially for cancers with dismal prognoses, such as the glioblastoma multiforme (GBM). Currently, immunotherapies should potentiate the host's own antitumor immune response against cancer cells, but it has been documented that they are effective only in small subsets of patients. Therefore, accurate predictors of response are urgently needed to identify who will benefit from immune-modulatory therapies. Brain tumors are challenging in terms of treatments. The immune response in the brain is highly regulated, and the immune microenvironment in brain metastases is active with a high density of tumor-infiltrating lymphocytes (TILs, CD3+ T cells) in certain patients and, therefore, may serve as a potential treatment target. In our study, we performed immunohistochemistry for CD3 and PD-L1 along the routine assessment of the O6-methylguanine-methyltransferase (MGMT) promoter methylation status and the IDH1 and 2 status in a single center cohort of 69 patients with GBM (58 primary tumors and 11 recurrences) who underwent standard multimodal therapies (surgery/radiotherapy/adjuvant temozolamide). We analyzed the association of PD-L1 tumor expression and TILs with overall survival (OS). The PD-L1 expression was observed in 25 of 58 (43%) newly diagnosed primary glioblastoma specimens. The sparse-to-moderate density of TILs, identified with CD3+ expression, was found in 48 of 58 (83%) specimens. Neither PD-L1 expression nor TILs were associated with overall survival. In conclusion, TILs and/or PD-L1 expression are detectable in the majority of glioblastoma samples, and even if they slightly relate to the outcome, they do not show a statistically significant correlation. [ABSTRACT FROM AUTHOR]

Objectives: Preoperative anterior commissure (AC) evaluation in glottic cancer is crucial for therapeutic decisions. Endoscopy is often inadequate to precisely detect the presence of cancer in the AC; thus, computed tomography (CT) scan could help. We investigated the relation between AC thickness on CT scan (in mm), AC involvement by cancer at histology, and radiologic signs of anterior paraglottic space (PGS) infiltration. Study Design: Retrospective observational study. Methods: An experienced radiologist retrospectively measured AC thickness and identified signs of anterior PGS infiltration on pretreatment contrast-enhanced CT scans of 80 patients with primary glottic cancer. The gold standard to define the presence of cancer in the AC was histology. The receiver operating characteristic (ROC) curves were used to determine the potential cut-off values of AC thickness (Youden index method) able to maximize both sensitivity and specificity in identifying the presence of cancer in the AC at histology and PGS infiltration on CT scan. Results: AC was significantly thicker in patients with cancer in the AC at histology (P < .001) and in patients with PGS infiltration on CT scan (P < .001). The cut-off values to discriminate the presence of cancer at histology and PGS infiltration on CT scan were 3.62 and 2.6 mm, respectively. We found a substantial agreement between anterior PGS infiltration on CT scan and the presence of cancer in the AC at histology (Cohen Kappa: P = .70). Conclusion: AC thickness and radiologic signs of PGS infiltration on pretreatment CT scan could represent a method to predict the presence of cancer in the AC at histology. [ABSTRACT FROM AUTHOR]

Bile duct injury is a major complication of laparoscopic cholecystectomy (LC). Intraoperative cholangiogram is useful, but faster techniques are available to assist the surgeon, like near-infrared fluorescent cholangiography (NIFC) with indocyanine green (ICG). The aim of our study is to evaluate the usefulness of NIFC during LC. This is a retrospective study conducted on prospectively recorded data of the General Surgery department of Trieste Academic Hospital, Italy. All patients underwent elective LC from January 2016 to January 2020. Patients were randomly divided in 2 groups: in one group, only white light imaging was used (n = 98 patients), in the NIFC group (n = 63) ICG was used. NIFC has been chosen more frequently by residents than consultants (P = .002). Operative time and length of stay resulted shorter in ICG group (P = .002 and .006), and this group showed also fewer intraoperative complications (P = .007). NIFC does not require any learning curve and makes surgery faster and safer. [ABSTRACT FROM AUTHOR]

Introduction: The treatment of choice for obstructive sleep apnea syndrome (OSAS) is continuous positive airway pressure (CPAP). However, CPAP is usually poorly tolerated and mandibular advancement devices (MADs) are an alternative innovative therapeutic approach. Uncertainty still remains as to the most suitable candidates for MAD. Herein, it is hypothesized that the presence of low arousal threshold (low ArTH) could be predictive of MAD treatment failure. Methods: A total of 32 consecutive patients, with OSAS of any severity, who preferred an alternate therapy to CPAP, were treated with a tailored MAD aimed at obtaining 50% of their maximal mandibular advancement. Treatment response after 6 months of therapy was defined as AHI < 5 events per hour or a reduction of AHI ≥ 50% from baseline. Low ArTH was predicted based on the following polysomnography features, as previously shown by Edwards et al.: an AHI of 82.5% and a hypopnea fraction of total respiratory events of >58.3%. Results: There were 25 (78.1%) responders (p-value < 0.01) at 6 months. Thirteen patients (40.6%) in the non-severe group reached AHI lower than 5 events per hour. MAD treatment significantly reduced the median AHI in all patients from a median value of 22.5 to 6.5 (74.7% of reduction, p-value < 0.001). The mandibular advancement device reduced AHI, whatever the disease severity. A significant higher reduction of Delta AHI, after 6 months of treatment, was found for patients without low ArTH. Conclusions: Low ArTH at baseline was associated with a poorer response to MAD treatment and a lower AHI reduction at 6 months. A non-invasive assessment of Low ArTH can be performed through the Edwards' score, which could help to identify an endotype with a lower predicted response to oral appliances in a clinical setting. [ABSTRACT FROM AUTHOR]

Anastomotic leakage (AL) represents one of the most relevant complications of colorectal cancer surgery. The aim of this study was to evaluate the utility of intraoperative indocyanine green (ICG) fluorescence imaging in the prevention of AL during laparoscopic colorectal surgery. Methods. We retrospectively analyzed 272 patients who underwent rectal and left colon surgery, consecutively enrolled between 2015 and 2019. Due to the heterogeneity of our groups, a propensity score matching (PSM) was performed with a 1:1 PSM cohort. Results. AL occurred in 36 (13.2%) patients. One hundred seventy-seven (65%) of them underwent an intraoperatory ICG test (ICG-group), whereas 95 patients (35%) did not receive the intraoperatory ICG test (no-ICG group). AL occurred in 10.8% of ICG group patients and in 17.8% of no-ICG group patients (P = 0.07). The ICG group registered significantly less type B and type C fistulas than the no-ICG group (57.9 vs 88.2%; P =.043). After PSM, the overall AL rate was less in the ICG group than the no-ICG group (9.3% vs 16%; P = 0.058), while type B and type C fistulas occurred in 5.48% in the ICG group vs 13.70% in the no-ICG group (P = 0.09). Univariate analysis demonstrated a protective effect of intraoperative ICG imaging against AL occurrence (odds ratio (OR: 0.66)). Conclusions. Hypoperfusion is a well-recognized cause of AL. The ICG assessment of colic vascularization is a simple, inexpensive, and side effects free method, which can sensibly reduce both overall AL and type B and type C fistulas when routinely used. [ABSTRACT FROM AUTHOR]

Background: The cause of short stature remains often unknown. The renin-angiotensin system contributes to growth regulation. Several groups reported that angiotensinconverting enzyme 2 (ACE2)-knockout mice weighed less than controls. Our casecontrol study aimed to investigate if children with short stature had reduced ACE2 expression as compared to controls, and its significance. Materials and Methods: children aged between 2 and 14 years were consecutively recruited in a University Hospital pediatric tertiary care center. Cases were children with short stature defined as height SD ≤ -2 diagnosed with growth hormone deficiency (GHD) or idiopathic short stature (ISS), before any treatment. Exclusion criteria were: acute diseases, kidney disease, endocrine or autoimmune disorders, precocious puberty, genetic syndromes, SGA history. ACE and ACE2 expression were measured in peripheral blood mononuclear cells, angiotensins were measured by ELISA. Results: Children with short stature displayed significantly lower ACE2 expression, being 0.40 fold induction (0.01-2.27) as compared to controls, and higher ACE/ACE2, with no differences between GHD and ISS. ACE2 expression was significantly and inversely associated with the risk of short stature, OR 0.26 (0.07-0.82), and it had a moderate accuracy to predict it, with an AUC of 0.73 (0.61-0.84). The cutoff of 0.45 fold induction of ACE2 expression was the value best predicting short stature, identifying correctly 70% of the children. Conclusions: Our study confirms the association between the reduction of ACE2 expression and growth retardation. Further studies are needed to determine its diagnostic implications. [ABSTRACT FROM AUTHOR]

The postponing of screening and the health care system reorganization, due to the Covid-19 pandemic and lockdown, could led to a concerning decline in breast and colorectal cancer diagnoses. This monocentric retrospective analysis has compared the pre-Covid period (March 2019 to March 2020) to the Covid period (April 2020 to April 2021) in terms of screening programs, clinical, surgical and pathological. A total of 799 patients diagnosed with Breast Cancer (BC) and Colorectal Cancer (CRC) underwent surgery during the two periods. In FVG in 2020 a decrease in mammography screening of 17.1% has been registered compared to 2019; this reduction has been higher for CRC screening, which summed up to 24.5%. As far as BC is concerned, screening-detected tumours rose significantly from 18 to 28%, mastectomies decreased from 40 to 31% and advanced tumours treated surgically decreased from 12 to 6%. Concerning CRC, a significant increase in admissions through the Emergency Department has been registered in spite of a stable percentage of urgent surgery performed, proving that severely symptomatic patients have been treated adequately. Open surgery has significantly decreased, whereas the tumoral stage and complications have remained constant in the two periods. This study has proved that maintaining standards of care and validated protocols during emergency is the most adequate and winning strategy: impact on BC and CRC has been less important than expected. These results support the recommendations for immediate and rapid screening program resumption at operating speed, using prioritization strategies to make up for the diagnostic delays. [ABSTRACT FROM AUTHOR]

Background: According to international guidelines, Human Papillomavirus (HPV) DNA tests represent a valid alternative to Pap Test for primary cervical cancer screening, provided that they guarantee balanced clinical sensitivity and specificity for cervical intraepithelial neoplasia grade 2 or more (CIN2+) lesions. The study aimed to assess whether HPV Selfy (Ulisse BioMed - Trieste, Italy), a full-genotyping HPV DNA test that detects and differentiates 14 high-risk HPV (HR-HPV) types, meets the criteria for primary cervical cancer screening described in the international guidelines, on clinician-collected as well as on self-collected samples.Methods: For each participant woman, consecutively referring to Azienda Sanitaria Universitaria Giuliano Isontina (Trieste, Italy) and CRO-National Cancer Institute (Aviano, Italy) for the cervical cancer screening program, the following samples were tested: (a) a clinician-collected cervical specimen, analyzed with the reference test (Hybrid Capture®2 test, HC2) and HPV Selfy; and (b) a self-collected vaginal sample, analyzed with HPV Selfy. Enrolled women were also asked to fulfill a questionnaire about self-sampling acceptability. As required by guidelines, a non-inferiority test was conducted to compare the clinical performance of the test under evaluation with its reference test.Results: HPV Selfy clinical sensitivity and specificity resulted non-inferior to those of HC2. By analysis of a total of 889 cervical liquid-based cytology samples from a screening population, of which 98 were from women with CIN2+, HPV Selfy showed relative sensitivity and specificity for CIN2+ of 0.98 and 1.00 respectively (non-inferiority score test: P = 0.01747 and P = 0.00414, respectively); the test reached adequate intra- and inter-laboratory reproducibility. Moreover, we demonstrated that the performance of HPV Selfy on self-collected vaginal samples was non-inferior to the performance obtained on clinician-collected cervical specimen (0.92 relative sensitivity and 0.97 relative specificity). Finally, through HPV Selfy genotyping, we were able to describe HPV types prevalence in the study population.Conclusions: HPV Selfy fulfills all the requirements of the international Meijer's guidelines and has been clinically validated for primary cervical cancer screening purposes. Moreover, HPV Selfy has also been validated for self-sampling according to VALHUDES guidelines. Therefore, at date, HPV Selfy is the only full-genotyping test validated both for screening purposes and for self-sampling. Trial registration ASUGI Trieste n. 16008/2018; CRO Aviano n.17149/2018. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate the feasibility of adequacy, accuracy, and safety of ultrasound-guided tru-cut biopsy in managing malignant and benign abdominopelvic masses in a selected population and critically discuss some issues in different situations, which deserve some reflections on those practices. Materials and Methods: This is a retrospective study involving 42 patients who underwent transvaginal or transabdominal tru-cut biopsy between August 2017 and November 2021. The inclusion criteria were poor health status or primary inoperable advanced tumor, suspicion of recurrence or metastasis to the ovaries or peritoneum in gynecological and non-gynecological pelvic malignancies. Tissue samples were considered adequate if it was possible to determine the origin of the tumor, and immunohistochemistry could be performed. Diagnostic accuracy was assessed considering the agreement between tru-cut biopsy histology and final postoperative histology. Results: It total, 44 biopsies were obtained from 42 patients (2 patients had repeat biopsies). The pathologist considered all pathological samples adequate (adequacy 100%). The final histology was consistent with tru-cut biopsy diagnosis in all but 2 cases (diagnostic accuracy 88.2%). If we consider only the cases that have carried out at least two diagnostic samples, accuracy rose to 94.1%. Pathological examinations from tru-cut samples showed 2 benign lesions (4.8%) and 40 malignant tumors (95.2%), divided into 19 advanced primary inoperable ovarian cancers, 7 primary advanced cervical cancers, 4 recurrent endometrial cancers, 3 recurrent cervical cancers, 3 recurrent ovarian cancers, 1 case of primitive peritoneal malignancy (leiomyosarcoma), and 3 non-gynecological cancers with a strong suspicion of metastases at ultrasound (2 cases of ovarian, colorectal cancer metastasis, and 1 case of pelvic site type B lymphoma metastasis). However, one case of minor complication related to the procedure was reported but not significant. Conclusions: The diagnostic adequacy, accuracy of the tru-cut biopsy, and safety were high. Pathological samples are representative of the disease and suitable for histological and immunohistochemical analysis. [ABSTRACT FROM AUTHOR]

Purpose. Obesity is a risk factor for severe coronavirus disease 2019 (COVID-19). Circulating adipokines have been associated with inflammatory burden and amplified or dysregulated immune responses. This study aimed to evaluate the discriminatory ability of adipokines to identify COVID-19 pneumonia and to assess disease severity. Methods. We conducted an observational case-control study, with a prospective design, and recruited patients with diagnosis of COVID-19 pneumonia (n = 48) and healthy controls (n = 36), who were matched by age, sex, and BMI. Leptin, adiponectin, IL-6, and TNF-α were measured by ELISA. Results. Patients with COVID-19 pneumonia had higher levels of leptin, lower adiponectin/leptin (Adpn/Lep) ratio, and higher expression of IL-6. Leptin had an acceptable discriminatory accuracy for COVID-19 pneumonia in patients with BMI >30 (AUC 0.74 [0.58, 0.90]) with a cutoff of 7852 pg/mL and it was associated with maximum respiratory support. By contrast, Adpn/Lep had an excellent discriminatory accuracy for COVID-19 pneumonia in patients with BMI <25 (AUC 0.9 [0.74, 1.06]) with a cutoff of 2.23. Conclusion. Our data indicate that high Adpn/Lep (>2.23) in lean patients is consistent with a state of good health, which decreases in case of inflammatory states, ranging from adipose tissue dysfunction with low-grade inflammation to COVID-19 pneumonia. [ABSTRACT FROM AUTHOR]

Although the eukaryotic elongation factor eEF1A1 plays a role in various tumours, there is little information on its prognosis/therapeutic value in prostate carcinoma. In high-grade and castration-resistant prostate carcinoma (CRPC), the identification of novel therapeutic markers/targets remains a priority. The expression of eEF1A1 protein was determined in formalin-fixed, paraffin-embedded prostate cancer and hyperplasia tissue by IHC. The role of eEF1A1 was investigated in a cellular model using a DNA aptamer (GT75) we previously developed. We used the aggressive CRPC cancer PC-3 and non-tumourigenic PZHPV-7 lines. Cytotoxicity was measured by the MTS assay and eEF1A1 protein levels by in-cell Western assays. The mRNA levels of eEF1A1 were measured by qPCR and ddPCR. Higher expression of eEF1A1 was found in Gleason 7–8 compared with 4–6 tissues (Gleason ≥ 7, 87% versus Gleason ≤ 6, 54%; p = 0.033). Patients with a high expression of eEF1A1 had a worse clinical outcome. In PC-3, but not in PZHPV-7, GT75 decreased cell viability and increased autophagy and cell detachment. In PC-3 cells, but not in PZHPV-7, GT75 mainly co-localised with the fraction of eEF1A1 bound to actin. Overexpression of the eEF1A1 protein can identify aggressive forms of prostate cancer. The targeting of eEF1A1 by GT75 impaired cell viability in PC-3 cancer cells but not in PZHPV-7 non-tumourigenic cells, indicating a specific role for the protein in cancer survival. The eEF1A1–actin complexes appear to be critical for the viability of PC-3 cancer cells, suggesting that eEF1A1 may be an attractive target for therapeutic strategies in advanced forms of prostate cancer. [ABSTRACT FROM AUTHOR]

Context Aortic stiffness is an emerging predictor of cardiovascular morbidity and mortality. Current data about the effect of subclinical and overt thyroid hormone disorders on aortic stiffness are often conflicting. Objective Primary outcome was to investigate if subclinical and overt thyroid hormone disorders were associated with aortic stiffness. Secondary outcome was to identify disease effect modifiers. Methods Data sources were PubMed, Google Scholar, SCOPUS, Web of Sciences, and the Cochrane Library. Eligible studies included reports of pulse wave velocity (PWV), which is the gold standard method for measuring aortic stiffness, in patients with subclinical and overt thyroid disorders. Two investigators independently identified eligible studies and extracted data. Pooled mean difference was the summary effect measure. Data were presented in forest plots with outlier and influential case diagnostics. Univariate meta-regression analysis was used to identify effect modifiers. Results Eleven observational studies were selected, including 1239 patients with subclinical hypothyroidism, 81 patients with overt hypothyroidism, 338 patients with thyrotoxicosis, and 12 715 controls. PWV was significantly higher in subclinical (P  < .001) and overt hypothyroidism (P  < .001), as well as in patients with thyrotoxicosis (P  = .027) compared with controls. Age was an effect modifier in hypothyroid patients. Conclusion This study shows that both overt and subclinical hypothyroidism as well as thyrotoxicosis were associated with an increase of aortic stiffness. The impact of treatment of these conditions on aortic stiffness should be assessed in clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: Narrow band imaging (NBI) enhances mucosal vasculature and could help in the identification of recurrences. We assessed the effectiveness of NBI with flexible video-endoscope in the early detection of recurrence after treatment of head and neck squamous cell carcinoma, its diagnostic advantage over high-definition white-light (HD WL) endoscopy, also in relation to recurrence site, and the influence of previous radiotherapy (RT) or chemotherapy (CT). Moreover, we investigated the association between index tumor site and the risk of developing recurrence, and the relation between index tumor site and recurrence site. Methods: From January 2018 to November 2020, 160 patients previously treated with surgery and/or RT ± CT were evaluated using NBI with flexible video-endoscope. Sensitivity, specificity, positive/negative predictive value, and accuracy were calculated for NBI and HD WL, and compared using the McNemar test. The Fisher exact test was used to compare the other associations investigated. Results: The difference between NBI and HD WL sensitivity was statistically significant (p < 0.001). The NBI diagnostic advantage was 62.5%, highest in the hypopharynx (p = 0.05), and was not influenced by previous RT or CT (p = 0.49). Index tumor site statistically related with recurrence site (p < 0.001), but not with the risk of developing recurrence (p = 0.81). Conclusion: NBI with flexible video-endoscope could represent a valid option to detect recurrence early during the follow-up, especially in a difficult-to-visualize site such as the hypopharynx. [ABSTRACT FROM AUTHOR]

Thus, HPV Selfy assay fulfills VALHUDES requirements for use of HR-HPV DNA tests on self-collected samples according to non-inferiority analysis (relative sensitivity > 0.90 with T = B I 1.70 i b , p = B I 0.044 i b ; relative specificity > 0.95 with T = B I 1.87 i b , p = B I 0.031 i b ). B Clinical validation of HPV Selfy on self-collected vaginal samples (VALHUDES) b Next, we aimed at evaluating HPV Selfy performance on self-collected samples, as indicated by VALHUDES protocol. [Extracted from the article]

Purpose: To retrospectively investigate long-term outcomes of renal cryoablation from a multicenter database. Methods: 338 patients with 363 renal tumors underwent cryoablation in 4 centers in North-Eastern Italy. 340/363 tumors (93.7%) were percutaneously treated with CT guidance. 234 (68.8%) were treated after conscious sedation, 76 (22.3%) under local lidocaine anesthesia only and 30 (8.8%) under general anesthesia. Treatment efficacy and complication rate considered all procedures. Oncologic outcomes considered a subset of 159 patients with 159 biopsy proven renal cell carcinoma. Results: Mean tumor size was 2.53 cm. Technical success was achieved in 355/363 (97.8%) treatments. Treatment efficacy after the first treatment was achieved in 348/363 (95.9%) tumors. Statistical analysis revealed a significant lower treatment efficacy for ASA score >3, Padua score >8, tumor size >2.5 cm, use of >2 cryoprobes, presence of one single kidney. In the subset of 159 patients, recurrence-free survival rates were 90.5% (95% CI 83.0%, 94.9%) at 3 years and 82.4% (95% CI 72.0%, 89.4%) at 5 years; overall survival rates were 96.0% (95% CI 90.6%, 98.3%) at 3 years and 91.0% (95% CI 81.7%, 95.7%) at 5 years; no patient in this subset developed metastatic disease. Clavien-Dindo >1 complications were recorded in 14/369 procedures (3.8%) and were related to age >70 years, tumor size >4 cm and use of >2 cryoprobes. Conclusion: Cryoablation performed across four different centers in a large cohort of predominantly small renal tumors showed that this technique provides good recurrence-free survival rates and overall survival rates at three- and five-year with very low major complications rate. [ABSTRACT FROM AUTHOR]

Breast intraoperative electron radiation therapy (B-IOERT) can be used in clinical practice both as elective irradiation (partial breast irradiation – APBI) in low risk breast cancer patients, and as an anticipated boost. The procedure generally includes the use of a shielding disk between the residual breast and the pectoralis fascia for the protection of the tissues underneath the target volume. The aim of the study was to evaluate the role of intraoperative ultrasound (IOUS) in improving the quality of B-IOERT. B-IOERT was introduced in Trieste in 2012 and its technique was improved in 2014 with IOUS. Both, needle and IOUS were used to measure target thickness and the latter was used even to check the correct position of the shielding disk. The primary endpoint of the study was the evaluation of the effectiveness of IOUS in reducing the risk of a disk misalignment related to B-IOERT and the secondary endpoint was the analysis of acute and late toxicity, by comparing two groups of patients treated with IOERT as a boost, either measured with IOUS and needle (Group 1) or with needle alone (Group 2). Acute and late toxicity were evaluated by validated scoring systems. From the institutional patients who were treated between June 2012 and October 2019, 109 were eligible for this study (corresponding to 110 cases, as one patients underwent bilateral conservative surgery and bilateral B-IOERT). Of these, 38 were allocated to group 1 and 72 to group 2. The target thickness measured with the IOUS probe and with the needle were similar (mean difference of 0.1 mm, p = 0.38). The percentage of patients in which the shield was perfectly aligned after IOUS introduction increased from 23% to more than 70%. Moreover, patients treated after IOUS guidance had less acute toxicity (36.8% vs. 48.6%, p = 0.33) from radiation therapy, which reached no statistical significance. Late toxicity turned out to be similar regardless of the use of IOUS guidance: 39.5% vs. 37.5% (p = 0.99). IOUS showed to be accurate in measuring the target depth and decrease the misalignment between collimator and disk. Furthermore there was an absolute decrease in acute toxicity, even though not statistically significant, in the group of women who underwent B-IOERT with IOUS guidance. [ABSTRACT FROM AUTHOR]

Objective: Recently, a novel host‐related index, the Host‐index (H‐index), including both inflammatory and nutritional markers, has been described and observed to stratify prognosis in patients with squamous cell carcinoma (SCC) of the oral cavity more accurately than other host‐related indexes This study aimed to investigate the prognostic performance of the H‐index using pretreatment blood tests in patients receiving up‐front surgery for SCC of the larynx. Methods: This retrospective observational study included a multicenter series of consecutive patients with SCC of the larynx diagnosed between 1 January 2009 and 31 July 2018, whose pretreatment blood tests were available and included the parameters necessary for the calculation of neutrophil to lymphocyte ratio (NLR) and the H‐index. Their association with disease‐free survival (DFS) and overall survival (OS) was measured. Results: A total of 231 patients were eligible for the present analysis (median [range] age, 68 [37‐96] years; 191 [82.7%] men). The median follow‐up was 73 months. In multivariable Cox proportional hazards regression models, increasing age (adjusted hazard ratio [aHR], 1.07 per year; 95% CI, 1.04‐1.09), advanced pT stage (aHR = 1.71 95% CI: 1.07‐2.71), and having close or positive surgical margins (aHR = 2.01; 95% CI: 1.21‐3.33) were significantly associated with poor OS. Among blood parameters, a higher neutrophil count was a strong predictor of both worse DFS (aHR for recurrence/death = 2.34; 95% CI: 1.24‐4.40) and OS (aHR for death = 2.67; 95% CI: 1.51‐4.71). Among inflammatory blood indexes, while NLR was not significantly associated with DFS or OS, patients with H‐index ≥8.37 showed a higher aHR for both recurrence/death (2.82; 95% CI: 1.65‐4.79) and death (2.22; 95% CI: 1.26‐3.89). Conclusion: In conclusion, the present study confirms the prognostic value of pretreatment H‐index, an easily measurable inflammatory and nutritional index, in patients with SCC of the larynx. Level of Evidence: III [ABSTRACT FROM AUTHOR]

Introduction: Olaparib is effective in metastatic triple negative breast cancer (TNBC) carrying germline mutations in DNA damage repair (DDR) genes BRCA1/2 (g BRCA -mut). The OLTRE window-of-opportunity trial preliminarily investigated potential pathologic, radiometabolic and immune biomarkers of early-response to olaparib in g BRCA -wild-type (wt) TNBC and, as proof-of-concept in g BRCA -mut HER2-negative BC. Methods: Patients received olaparib for 3 weeks (3w) before standard neoadjuvant chemotherapy and underwent multiple FDG18-PET/CT scan (basal, after olaparib), clinical assessments (basal, every 3w), tumor biopsies and blood samplings (baseline, after olaparib). Clinical and radiometabolic responses were evaluated according to RECIST1.1 and PERCIST criteria. Results: 27 patients with g BRCA -wt TNBC and 8 with g BRCA -mut BC (6 TNBC, 2 HR+/HER2-negative) were enrolled. Three (11.1%) patients showed mutations in non- BRCA 1/2 DDR genes and 4 (14.8%) in other genes. 3w olaparib induced 16/35 and 15/27 partial clinical and radiometabolic responses, including in 40.7% and 50.0% g BRCA -wt patients. g BRCA -mut tumors presented numerically higher tumor-infiltrating lymphocytes (TILs) levels and PD-L1 positive tumors. Clinical responders experienced a reduction in T-regs/T-eff ratio (p=0.05), B and NK lymphocytes (p=0.003 both), with an average increase in T-helpers rate (p<0.001) and CD4/CD8 ratio (p=0.02). Ki67% and TILs did not vary significantly (p=0.67 and p=0.77). A numerical increase in PD-L1 positive cases after olaparib was observed, though non-significant (p=0.134). No differences were observed according to g BRCA status and type of response. Conclusions: Early-stage TNBC might be a target population for olaparib, irrespective of g BRCA mutations. Future trials should combine TILs, PD-L1 and g BRCA status to better identify candidates for escalated/de-escalated treatment strategies including olaparib. [ABSTRACT FROM AUTHOR]

Purpose: Prediction algorithms estimating survival rates for breast cancer (BC) based upon risk factors and treatment could give a help to the clinicians during multidisciplinary meetings. The aim of this study was to evaluate accuracy and clinical utility of three different scores: the Clinical Treatment Score Post-5 Years (CTS5), the PREDICT Score, and the Nottingham Prognostic Index (NPI). Methods: This is a retrospective cohort analysis conducted on prospectively recorded databases of two EUSOMA certified centers (Breast Unit of Trieste Academic Hospital and of Cremona Hospital, Italy). We included patients with Luminal BC undergone to breast surgery between 2010 and 2015, and subsequent endocrine therapy for 5 years for curative intent. Results: A total of 473 patients were enrolled in this study. ROC analysis showed fair accuracy for NPI, good accuracy for PREDICT, and optimal accuracy for CTS5 (AUC 0.7, 0.76, and 0.83, respectively). The three scores seemed strongly correlated in Spearman's rank correlation coefficient analysis. PREDICT partially overestimated OS in patients undergone to mastectomy, and in pT3-4, G3 tumors. Considering DRFS as a surrogate of OS, CTS5 showed women in intermediate and high risk class had shorter OS too (respectively p = 0.001 and p < 0.001). Combining scores does not improve prognostication power. Conclusion: Mathematical models may help clinicians in decision making (adjuvant therapies, CDK4/6i, genomic test's gray zones). CTS5 has the higher prognostic accuracy in predicting recurrence, while score predicting OS did not show substantial advances, proving that pN, G, and pT are still the most important variables in predicting OS. [ABSTRACT FROM AUTHOR]

Male breast cancer (MBC) is a rare disease. The few studies on MBC reported conflicting data regarding survival outcomes compared to women. This study has two objectives: to describe the characteristics of a single-cohort of MBC and to compare overall survival (OS) and disease-free survival (DFS) between men and women using the propensity score matching (PSM) analysis. We considered MBC patients (n = 40) diagnosed between January 2004 and May 2019. Clinical, pathological, oncological and follow-up data were analyzed. Univariate analysis was performed to determine the prognostic factors on OS and DFS for MBC. We selected female patients with BC (n = 2678). To minimize the effect of the imbalance of the prognostic factors between the two cohorts, the PSM method (1:3 ratio) was applied and differences in survival between the two groups were assessed. The average age of MBC patients was 73 years. The 5-year OS and DFS rates were 76.7% and 72.2% respectively. The prognostic factors that significantly influenced OS and DFS were tumor size and lymph node status. After the PSM, 5 year-OS was similar between MBC and FBC (72.9% vs 72.3%, p = 0.70) while we found a worse DFS for MBC (72.2% vs 91.4%, p = 0.03). Our data confirmed previous reported MBC characteristics: we found a higher risk of recurrence in MBC compared to FMC but similar OS. MBC and FMC are different entities and studies are needed to understand its epidemiology and guide its management. [ABSTRACT FROM AUTHOR]

Background: Biomarkers may play a role as predictive and prognostic factors in colorectal cancer patients. The aims of the study were to verify the prognostic role of pre‐operative serum carcinoembryonic antigen (CEA) level in predicting overall survival and risk of recurrence in a cohort of colorectal cancer patients and to evaluate optimal cut‐off values. Methods: A retrospective cohort analysis was performed on colorectal cancer patients undergoing elective curative surgery between 2004 and 2019 at an Italian Academic Hospital. Main outcomes were overall survival, disease‐free survival at 3‐years and risk of local, loco‐regional and distant recurrence during follow‐up. A receiver operating characteristic (ROC) curve analysis was plotted using CEA pre‐operative values and follow‐up data in order to estimate the optimal cut‐off values. Results: A total of 559 patients were considered. The mean CEA value was 12.1 ± 54.1 ng/mL, and the median 29.3 (0–4995) ng/mL. The ROC curve analysis identified 12.5 ng/mL as the best CEA cut‐off value to predict the risk of metastatic development after surgery in stage I–III colorectal cancer patients, and 10 ng/mL as the best CEA cut‐off value to predict overall survival and disease‐free survival in stage III–IV patients. These data suggest a stratification of colorectal cancer patients in three classes of risk: a low risk class (CEA <10 ng/mL), a moderate risk class (CEA 10–12.5 ng/mL) and a high risk class (CEA >12.5 ng/mL). Conclusion: In conclusion, pre‐operative serum CEA measurements could integrate information to enhance patient risk stratification and tailored therapy. [ABSTRACT FROM AUTHOR]

Context: Current data about the cardiovascular manifestations of mild primary hyperparathyroidism (pHPT) are often conflicting. Pulse wave velocity (PWV) is the gold standard for assessing aortic stiffness, and it predicts cardiovascular morbidity and mortality.Objective: Primary outcomes were to investigate if mild pHPT was associated with higher PWV and if parathyroidectomy (PTX) reduced PWV in mild pHPT. Secondary outcome was to investigate blood pressure changes after PTX.Methods: Sources were PubMed, Google Scholar, SCOPUS, Web of Science, and the Cochrane Library. Eligible studies included reports of PWV in patients with mild pHPT and controls, or in patients with mild pHPT before and after PTX. Two investigators independently identified eligible studies and extracted data. Pooled mean difference (MD) was the summary effect measure. Data were presented in forest plots with outlier and influential case diagnostics. Nine observational studies and one randomized clinical trial were selected, including 433 patients with mild pHPT, 171 of whom underwent PTX, and 407 controls. PWV was significantly higher in mild pHPT than in controls (MD = 1.18, 0.67 to 1.68, P < .0001). Seven studies evaluated the effect of PTX on PWV. PTX significantly reduced PWV (MD = -0.48, -0.88 to -0.07, P = .022).Conclusion: Aortic stiffness is increased in patients with mild pHPT, supporting the notion that mild pHPT is also associated with adverse cardiovascular manifestations. PTX significantly reduced arterial stiffness in mild pHPT, indicating that the benefit of PTX over cardiovascular manifestations should not be dismissed but it deserves further studies. [ABSTRACT FROM AUTHOR]

Patients undergoing colon resection are often concerned about their functional outcomes after surgery. The primary aim of this prospective, multicentric study was to assess the intestinal activity and health-related quality-of-life (HRQL) after ileocecal valve removal. The secondary aim was to evaluate any vitamin B12 deficiency. The study included patients undergoing right colectomy, extended right colectomy and ileocecal resection for either neoplastic or benign disease. Selected items of GIQLI and EORTC QLQ-CR29 questionnaires were used to investigate intestinal activity and HRQL before and after surgery. Blood samples for vitamin B12 level were collected before and during the follow-up period. The empirical rule effect size (ERES) method was used to explain the clinical effect of statistical results. Linear mixed effect (LME) model for longitudinal data was applied to detect the most important parameters affecting the total score. A total of 158 patients were considered. Applying the ERES method, the analysis of both questionnaires showed clinically and statistically significant improvement of HRQL at the end of the follow-up period. Applying the LME model, worsening of HRQL was correlated with female gender and ileum length when using GIQLI questionnaire, and with female gender, open approach, and advanced cancer stage when using the EORTC QLQ-CR29 questionnaire. No significant deficiency in vitamin B12 levels was observed regardless of the length of surgical specimen. In our series, no deterioration of HRQL and no vitamin B12 deficiency were found during the follow-up period. Nevertheless, warning patients about potential changes in bowel habits is mandatory. In our series, no deterioration of HRQL and no vitamin B12 deficiency were found during the follow-up period. Nevertheless, warning patients about potential changes in bowel habits is mandatory. [ABSTRACT FROM AUTHOR]

Background: Radiofrequency ablation (RFA) has gained ground as an effective and well-tolerated technique to treat benign thyroid nodules. Most of the available studies have described the short-term outcomes of RFA, whereas there is a limited number of studies evaluating long-term issues, such as regrowth and the likelihood of retreatments. In addition, risk markers of regrowth and retreatment remain to be defined. The initial ablation ratio (IAR) is an index that measures the amount of ablation after RFA, which has been associated with technique efficacy (i.e. volume reduction >50% after 1 year from the procedure). This study aimed at evaluating i) IAR reproducibility and ii) IAR predictive value for RFA 5-year outcomes. Materials and Methods: This is a retrospective single center study on patients with benign thyroid nodules treated with RFA and followed for 5 years after initial treatment. IAR interobserver reproducibility was evaluated with Bland-Altman method and Lin's concordance correlation coefficient (ρc). IAR predictive value for RFA 5-year outcomes was evaluated with linear and logistic regression models, as well as with Cox models, while receiver operating characteristic (ROC) analyses were used for cut-offs. Results: We selected 78 patients with 82 benign thyroid nodules. The procedure significantly reduced nodule volume and this reduction was generally maintained over time. Technique efficacy was achieved in 92% of patients, while 23% of nodules regrew and 12% of nodules were retreated. Median IAR was 83%. Lin's concordance and Pearson's correlation coefficients suggested a good interobserver reproducibility of this index, consistent with the limits of agreement of the Bland-Altman plot. IAR was significantly associated with technique efficacy, 1- and 5-year volume reduction ratio, and with the likelihood of a retreatment, but not with nodule regrowth. ROC analyses showed that IAR cut-off was 49% for technique efficacy and 73% for retreatment. Conclusions: Our results show for the first time that IAR is reproducible and that it predicts the volume reduction and the likelihood of a retreatment after 5 years from RFA. [ABSTRACT FROM AUTHOR]

Background: Radiofrequency ablation (RFA) and laser ablation (LA) are effective treatments for benign thyroid nodules. Due to their relatively recent introduction into clinical practice, there are limited long-term follow-up studies. This study aimed to evaluate technique efficacy, rate of regrowth, and retreatment over 5 years after RFA or LA and to identify predictive factors of outcome. Methods: In this multicenter retrospective study, the rates of technique efficacy, regrowth, and retreatment were evaluated in 406 patients treated with either RFA or LA, and followed for 5 years after initial treatment. Propensity score matching was used to compare treatments. Cumulative incidence studies with hazard models were used to describe regrowth and retreatment trends, and to identify prognostic factors. Logistic regression models and receiver operating characteristic analyses were used for risk factors and their cutoffs. Results: RFA and LA significantly reduced benign thyroid nodule volume, and this reduction was generally maintained for 5 years. Technique efficacy (defined as a reduction ≥50% after 1 year from the treatment) was achieved in 74% of patients (85% in the RFA and 63% in the LA group). Regrowth occurred in 28% of patients (20% in the RFA and 38% in the LA group). In the majority of cases, further treatment was not required as only 18% of patients were retreated (12% in the RFA and 24% in the LA group). These data were confirmed by propensity score matching. Cumulative incidence studies showed that RFA was associated with a lower risk of regrowth and a lower risk of requiring retreatment over time. Overall, technique inefficacy and regrowth were associated with low-energy delivery. Retreatments were more frequent in young patients, in large nodules, in patients with lower volume reduction at 1 year, and in cases of low-energy delivery (optimal cutoff was 918 J/mL for RFA). Conclusions: Both thermal ablation techniques result in a clinically significant and long-lasting volume reduction of benign thyroid nodules. The risk of regrowth and needing retreatment was lower after RFA. The need for retreatment was associated with young age, large baseline volume, and treatment with low-energy delivery. [ABSTRACT FROM AUTHOR]

Purpose: mTOR inhibitor everolimus is used for hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (mBC). No reliable predictive biomarker of response is available. Following evidences from other solid tumors, we aimed to assess the association between treatment-associated immune system features and everolimus activity. Methods: We retrospectively explored a correlation with the therapeutic activity of everolimus and tumor-associated immune pathways with ingenuity pathway analysis (IPA), neutrophil-to-lymphocyte ratio (NLR), circulating lymphocytes, and endothelial cells (CECs) in 3 different HR+ mBC studies, including the BALLET phase IIIb study. Results: The circulating levels of CD3+/CD8+, CD3+/CD4+, and overall T lymphocytes were higher in responders versus non-responders at baseline (p = 0.017, p < 0.001, p = 0.034) and after treatment (p = 0.01, p = 0.003, p = 0.023). Reduced CECs, a tumor neoangiogenesis marker, were observed in responders after treatment (p < 0.001). Patients with low NLR (≤ 4.4) showed a better progression-free survival compared to patients with high NLR (> 4.4) (p = 0.01). IPA showed that the majority of immunity-related genes were found upregulated in responders compared to non-responders before treatment, but not after. Conclusions: Lymphocytes subpopulations, CECs and NLR could be interesting biomarkers predictive of response to everolimus-based regimens, potentially useful in daily clinical practice to select/monitor everolimus-based treatment in mBC. Further studies to confirm such hypotheses are warranted. [ABSTRACT FROM AUTHOR]