Cure indicators and prevalence by stage at diagnosis for breast and colorectal cancer patients: A population-based study in Italy.

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.

Indicators of cure for women living after uterine and ovarian cancers: a population-based study.

This study aims to estimate long-term survival, cancer prevalence, and several cure indicators for Italian women with gynaecological cancers. Thirty-one cancer registries, representing 47% of the Italian female population, were included. Mixture cure models were used to estimate Net Survival (NS), Cure Fraction, Time To Cure (5-year conditional NS>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 corpus uteri cancer, 0.2% (52,551) after cervical, 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 gynaecological cancers have a residual excess risk of death <5% after 5 years since 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 gynaecological 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 will contribute to improving follow-up programs for women with gynaecological cancers and supporting efforts against discrimination of already cured ones.

MRI and frozen section evaluation of mylohyoid muscle in determining surgical approach for T2-T3 floor of the mouth cancer.

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.

Blood Markers Predicting Clinically Occult Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma.

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.

Insights adjusting for non-adherence in randomized clinical trials: a reanalysis of an adjuvant trial of tamoxifen duration in early breast cancer.

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.

Low arousal threshold: a common pathophysiological trait in patients with obstructive sleep apnea syndrome and asthma.

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.

Impact of time-to-surgery on survival and quality of life in oral cancer.

PURPOSE: To investigate the association between time-to-surgery (TTS) and overall survival (OS), disease specific survival (DSS) and quality of life (QoL) in patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: 116 patients with OSCC candidate to surgery were examined. TTS intervals starting from diagnosis (TTS-clinical-based) and from histological reports (TTS-biopsy-based) were calculated. The effects of TTS intervals and prognostic factors on 5-year OS and DSS were explored. RESULTS: In our cohort advanced T-categories OSCCs with TTS < 30 days showed a trend to have higher DSS rate (p = 0.049). Patients with TTS-clinical-based < 30 days showed better postoperative QoL. Positive surgical margins, nodal involvement (pN+), DOI >10 mm, invasive surgery and extra-capsular extension in pN+ were found to be significantly associated with a poor OS and DSS. CONCLUSIONS: TTS ≥ 30 days can adversely affect DSS, especially in the advanced T categories. Short TTS intervals resulted associated with a better postoperative QoL.

Is there a role for tumor volume in prediction of prognosis for oral cancer?

PURPOSE: New prognostic factors in oral squamous cell carcinoma (OSCC) (tumor-, host-, and environment-related) have been introduced recently to complete those traditionally considered. Among them, tumor volume (TV) could be the most interesting and applicable in clinical practice, considering the routine use of computed tomography in tumor staging. In this retrospective study we aimed to investigate whether a correlation exists among these new prognostic factors and survival outcomes. METERIALS AND METHODS: We collected data about 140 patients affected by OSCC who underwent primary surgery. Prognostic factors were collected and Overall Survival (OS), Disease Specific Survival (DSS) and Disease Free Survival (DFS) were estimated using Kaplan-Meier method; the Log-Rank test (Mantel-Cox) and Cox regression models were applied to investigate predictors of survival. RESULTS: The 5-year OS, DSS and DFS were 73.6 %, 89.2 % and 75.2 % respectively. Nodal metastasis (pN+), relapse and American Society of Anesthesiologists ASA-II were found independent prognostic factors for OS, and significantly associated to worst DSS (p < 0.001). TV significantly correlated with higher relapse occurrence (p = 0.03). CONCLUSIONS: In our experience, lymph-node status, ASA classification and relapse significantly influenced DSS on univariate analysis. TV could represent an interesting additional parameter, since it significantly influenced DFS. However, prospective studies with standardized TV measurements and a greater number of patients are needed to validate this result.

A Case-Control Study by ddPCR of ALU 260/111 and LINE-1 266/97 Copy Number Ratio in Circulating Cell-Free DNA in Plasma Revealed LINE-1 266/97 as a Potential Biomarker for Early Breast Cancer Detection.

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.

Preliminary Study on the Effect of a Night Shift on Blood Pressure and Clock Gene Expression.

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.

Clinico-Immunological Effects of a Single-Agent CDK4/6 Inhibitor in Advanced HR+/HER2- Breast Cancer Based on a Window of Opportunity Study.

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6 i), abemaciclib, palbociclib, and ribociclib, have been FDA-approved for the treatment of hormone receptor-positive (HR+), HER2−negative (HER2−) advanced breast cancer (aBC). This targeted therapy has revived hope in those aBC patients who did not respond to standard therapies. Interestingly, when administered as a single agent, CDK4/6 modulated several peripheral blood cells after a short-course treatment of 28 days. However, the impact of these immune effects has yet to be thoroughly investigated. Methods: We administered abemaciclib, palbociclib, and ribociclib monotherapy to 23 patients with HR+/HER2− metastatic breast cancer. The aim is to investigate the impact of on-treatment modifications on peripheral blood cells and their composite scores in patients after a 28-day course of CDK4/6 i alone. Results: In the current study, we observed a significant decrease in neutrophils (p-value < 0.001) for patients treated with abemaciclib, palbociclib, and ribociclib. An overall decrease of Tregs was observed and potentially linked to palbociclib treatment. The neutrophile to lymphocyte (N/L) ratio was also decreased overall and potentially linked to abemaciclib and palbociclib treatment. Platelets were decreased in patients administered with abemaciclib. Notably, the radiometabolic response was available only for those patients treated with ribociclib and abemaciclib, and only those lesions treated with ribociclib reached statistical relevance. Conclusions: Our study strongly supports the notion that CDK4/6 inhibitors induce tumour immune modulation. N/L ratio and platelet levels decreased due to treatment. Future studies should test whether patients would benefit from immunomodulators in association with CDK4/6 agents in a larger clinical trial. Moreover, the CDK4/6-induced immune modulation could also be considered a potential predictive clinical factor in HR+/HER2− advanced breast cancer.

Clinical validation of full HR-HPV genotyping HPV Selfy assay according to the international guidelines for HPV test requirements for cervical cancer screening on clinician-collected and self-collected samples.

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.

Dietary Beliefs in Children and Adolescents with Inflammatory Bowel Disease and their Parents.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) may have diet-related beliefs that lead to restrictive dietary behaviours. This study aimed to evaluate dietary beliefs in young patients with IBD and their parents and the presence of restrictive behaviours. METHODS: A questionnaire regarding dietary beliefs was administered to IBD patients aged 8-17 years and their parents. A Food Frequency Questionnaire was administered to patients with IBD and a peer control group. RESULTS: Seventy-five patients and 105 parents were interviewed. Twenty-seven (36%) patients and 39 (37.1%) parents believed that dietary modifications could control the IBD course.Twenty-five (33.0%) patients and 33 (33.0%) parents believe that some dietary components can prevent relapse or improve symptoms (mainly abdominal pain and diarrhoea), while 36 (48%) patients and 60 (60.0%) parents believe that some foods can induce or worsen symptoms during an IBD flare.Patients believe that milk, dairy, fried and spicy foods, sweets and carbonated drinks could have a negative effect on IBD while fruits, vegetables and rice could have a positive impact. Parents believe that fruits and vegetables have a negative effect.Responses did not differ among patients classified according to IBD phenotype, activity status, or current therapies.Compared to controls, young patients with IBD have reduced daily consumption of milk, lunch meat, raw and cooked vegetables. CONCLUSIONS: About one-third of paediatric patients with IBD and their parents have dietary beliefs that lead to restrictive dietary behaviours.

20-Year Follow-up Study of Celiac Patients Identified in a Mass School Screening: Compliance to Gluten-Free Diet and Autoimmunity.

OBJECTIVES: To investigate the compliance to the gluten-free diet in a cohort of adult celiac patients 20 years after the diagnosis, received in childhood through a mass screening. METHODS: This is an observational historic cohort follow-up study. It was carried out at the Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy. Two matched cohorts of adult celiac patients, diagnosed in childhood through a mass screening or for symptoms were enrolled. Adherence to the gluten free-diet and development of autoimmune diseases were investigated through a questionnaire administrated in the course of a phone interview.The primary study outcome was the adherence to the gluten-free diet, measured through the Biagi questionnaire, in the two cohorts of celiac patients. RESULTS: We contacted 25 patients (mean age 28 years, 19 females) diagnosed with screening and 34 patients (mean age 25 years, 26 females) diagnosed in the same period for symptoms. After 20 years, in the cohort diagnosed with screening and in the cohort diagnosed for symptoms the adherence to the gluten-free diet was optimal in 14 (56%) and 26 (81%), improvable in 5 (20%) and 3 (9%), inadequate in 6 (24%) and 3 (9%), respectively. In the two cohorts, four patients (16%) and six patients (18%) developed other autoimmune diseases. CONCLUSIONS: Twenty years after the diagnosis, near half of the patients diagnosed in a mass screening, does not have an optimal adherence to the gluten-free diet and a remarkable proportion of them have developed another autoimmune disease.

The role of NBI with flexible video-endoscope in the follow-up of head and neck cancer patients: a prospective study.

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.

The Added Value of Intraoperative Near-Infrared Fluorescence Imaging in Elective Laparoscopic Cholecystectomy.

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.

Anastomosis Leak: Is There Still a Place for Indocyanine Green Fluorescence Imaging in Colon-Rectal Surgery? A Retrospective, Propensity Score-Matched Cohort Study.

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.

High eEF1A1 Protein Levels Mark Aggressive Prostate Cancers and the In Vitro Targeting of eEF1A1 Reveals the eEF1A1-actin Complex as a New Potential Target for Therapy.

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.

Direct comparison of three different mathematical models in two independent datasets of EUSOMA certified centers to predict recurrence and survival in estrogen receptor-positive breast cancer: impact on clinical practice.

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.

Percutaneous CT-Guided Renal Cryoablation: Technical Aspects, Safety, and Long-Term Oncological Outcomes in a Single Center.

Background and objectives: Cryoablation is emerging as a safe and effective therapeutic option for treating renal cell carcinoma. This study analyzed the safety and long-term oncological outcomes of cryoablation in our center. Materials and methods: Patients who underwent computed tomography (CT)-guided percutaneous cryoablation between February 2011 and June 2020 for one or more clinically localized renal tumors were identified. Technical success and treatment efficacy were assessed. Post-procedural complications were classified according to the Clavien-Dindo system. Recurrence-free survival was determined for biopsy-proven malignant renal tumors. Results: A total of 174 renal tumors, 78 of which were biopsy-proven malignant carcinomas, were treated in 138 patients (97 males and 41 females, mean age: 73 years, range: 43-89 years). Mean tumor size was 2.25 cm and 54.6% of the lesions required a complex approach. Technical success was achieved in 171 out of 174 tumors (98.3%). Primary treatment efficacy was 95.3% and increased to 98.2% when retreats were taken into account. The overall complication rate was 29.8%. No complications of Clavien-Dindo grade III or more were encountered. Median follow-up was 21.92 months (range: 0.02-99.87). Recurrence-free survival was 100% at 1 year, 95.3% (95% CI: 82.1%-98.8%) at 3 years, and 88.6% (95% CI: 71.8%-95.7%) at 5 years. Conclusions: Cryoablation is a safe and effective technique for the treatment of small renal lesions, with no major complications when performed by expert interventional radiologists. The multidisciplinary discussion is essential, especially considering the high number of histologically undetermined lesions. Our long-term oncological outcomes are encouraging and in line with the literature.