Advanced Non-linear Modeling and Explainable Artificial Intelligence Techniques for Predicting 30-Day Complications in Bariatric Surgery: A Single-Center Study.

PURPOSE: Metabolic bariatric surgery (MBS) became integral to managing severe obesity. Understanding surgical risks associated with MBS is crucial. Different scores, such as the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP), aid in patient selection and outcome prediction. This study aims to evaluate machine learning (ML) models performance in predicting 30-day post-operative complications and compare them with the MBSAQIP risk score. MATERIALS AND METHODS: We retrospectively evaluated 424 consecutive patients (2006-2020) who underwent MBS, analyzing 30-day surgical complications according to Clavien-Dindo Classification. ML models, including logistic regression, support vector machine, random forest, k-nearest neighbors, multi-layer perceptron, and extreme gradient boosting, were analyzed and compared to MBSAQIP risk score. Performance was measured by area under receiver operating characteristic curve (AUROC) analysis. RESULTS: Random forest showed the highest AUROC in the training (AUROC = 0.94) and the validation set (AUROC = 0.88). ML algorithms, particularly random forest, outperformed MBSAQIP in predicting negative 30-day outcomes in both the training and validation sets (AUROC = 0.64, DeLong's Test p < 0.001). The five features that were more relevant for the prediction of the random forest model were serum alkaline phosphatase, platelet count, triglycerides, glycated hemoglobin, and albumin. CONCLUSION: We developed several ML model that identifies patients at risk for 30-day complications after MBS. Among these, random forest is the most performing one and outperforms the already established MBSAQIP score. This model could increase the identification of high-risk patients before MBS.

Next-generation sequencing-based evaluation of the actionable landscape of genomic alterations in solid tumors: the "MOZART" prospective observational study.

BACKGROUND: The identification of the most appropriate targeted therapies for advanced cancers is challenging. We performed a molecular profiling of metastatic solid tumors utilizing a comprehensive next-generation sequencing (NGS) assay to determine genomic alterations' type, frequency, actionability, and potential correlations with PD-L1 expression. METHODS: A total of 304 adult patients with heavily pretreated metastatic cancers treated between January 2019 and March 2021 were recruited. The CLIA-/UKAS-accredit Oncofocus assay targeting 505 genes was used on newly obtained or archived biopsies. Chi-square, Kruskal-Wallis, and Wilcoxon rank-sum tests were used where appropriate. Results were significant for P < .05. RESULTS: A total of 237 tumors (78%) harbored potentially actionable genomic alterations. Tumors were positive for PD-L1 in 68.9% of cases. The median number of mutant genes/tumor was 2.0 (IQR: 1.0-3.0). Only 34.5% were actionable ESCAT Tier I-II with different prevalence according to cancer type. The DNA damage repair (14%), the PI3K/AKT/mTOR (14%), and the RAS/RAF/MAPK (12%) pathways were the most frequently altered. No association was found among PD-L1, ESCAT, age, sex, and tumor mutational status. Overall, 62 patients underwent targeted treatment, with 37.1% obtaining objective responses. The same molecular-driven treatment for different cancer types could be associated with opposite clinical outcomes. CONCLUSIONS: We highlight the clinical value of molecular profiling in metastatic solid tumors using comprehensive NGS-based panels to improve treatment algorithms in situations of uncertainty and facilitate clinical trial recruitment. However, interpreting genomic alterations in a tumor type-specific manner is critical.

Near-infrared indocyanine green fluorescent cholangiography in urgent and emergency laparoscopic cholecystectomy: a preliminary study after propensity score-matched study.

INTRODUCTION: Bile duct injury is a major complication of laparoscopic cholecystectomy (LC). Indocyanine green near-infrared fluorescence cholangiography (ICG-NIFC) is a well-recognized technique who provides an intraoperative mapping of the biliary system. METHODS: All patients underwent urgent LC and randomly divided into two groups: in one group, only white light imaging was used and, in the ICG group, ICG was used. Due to the heterogeneity of our groups, a PSM was performed with a 1:1 PSM cohort. RESULTS: The use of ICG clearly decreases the operation time (p value 0.002). The overall rate of intra- and post- operative complications was 4.17% and 15.8% respectively. Post-operative biliary duct injury trend decreases in ICG group and after the homogenization of the 2 cohorts, the intra- and post- operative complications (including vascular and biliary duct injury) results changed with a highest rate of complication in the cohort with no-ICG administration. The use of NIFC demonstrated a protective effect against intra- and post- operative complications and biliary duct injury (HR 0.037, p value 0.337 and HR 0.039, p value 0.647; HR 0.288; p value 0.05 and HR 0.635; p value 0.687, respectively). CONCLUSIONS: The intra-operative use of NIFC showed a trend in the reduction of the rate of intra- and post-operative complications, the duration of surgery, and the length of hospital stay. ICG is a highly safe approach to urgent and emergency LC, as for elective LC, and could lead the surgeon to conduct the procedure more efficiently.

Liver Bacterial Colonization in Patients with Obesity and Gut Dysbiosis.

PURPOSE: Recently, the link between gut microbiota, liver inflammation, and obesity has become an interesting focus of research. The aim of this study is to show the possible relation between gut microbiota dysbiosis in patients with obesity and the presence of bacterial genomes in their liver biopsies. MATERIALS AND METHODS: A prospective study on patients undergoing bariatric surgery was carried out. Anthropometric and metabolic data, comorbidities, stool samples, and hepatic biopsies were collected and analyzed at the time of surgery. The V3-16S rRNA region was sequenced using the Ion Torrent new-generation sequencing platform. RESULTS: In each of the 23 patients enrolled, the bacterial population was analyzed both in the stools and liver. In eight patients (34.7%), Prevotella (62.5%), Bacteroides (50%), Streptococcus (12.5%), and Dalister (12.5%) were found in both samples, simultaneously; in 15 cases, the liver was free from colonization. The statistically significant difference between groups was a Roseburia intestinalis reduction in fecal samples of patients with liver biopsies colonized by bacteria (1% vs 3%; p = 0.0339). CONCLUSION: To the best of our knowledge, this is the first study reporting the presence of bacterial genome in a liver biopsy on bariatric patients, instead of the microbe-associated molecular patterns. Notably, in literature, the presence of Roseburia intestinalis in stool samples has been shown to prevent intestinal inflammation playing its role in the gut barrier integrity. In our population, the Roseburia reduction was associated with the presence of bacterial genome in the liver, probably related to a greater permeability of the gut and vascular barriers.

The potential role of omentin-1 in obesity-related metabolic dysfunction-associated steatotic liver disease: evidence from translational studies.

BACKGROUND: Obesity, characterized by visceral adipose tissue (VAT) expansion, is closely associated with metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). Recent research has highlighted the crucial role of the adipose tissue-liver axis in the development of MASLD. In this study, we investigated the potential role of omentin-1, a novel adipokine expressed by VAT, in obesity-related MASLD pathogenesis. METHODS: Through in silico analysis of differentially expressed genes in VAT from obese patients with and without MASH, we identified omentin-1 as a significant candidate. To validate our findings, we measured omentin-1 levels in VAT and plasma of lean controls and obese patients with biopsy-proven MASLD. Additionally, we assessed omentin-1 expression in the VAT of diet-induced mice MASLD model. In vitro and ex vivo studies were conducted to investigate the effects of omentin-1 on MASLD-related mechanisms, including steatosis, inflammation, endoplasmic reticulum (ER) stress, and oxidative stress. We also analyzed the impact of D-glucose and insulin on VAT omentin-1 levels ex vivo. RESULTS: Compared to the lean group, the obese groups exhibited significantly lower VAT and plasma levels of omentin-1. Interestingly, within the obese groups, omentin-1 is further decreased in MASH groups, independent of fibrosis. Likewise, VAT of mice fed with high-fat diet, showing histological signs of MASH showed decreased omentin-1 levels as compared to their control diet counterpart. In vitro experiments on fat-laden human hepatocytes revealed that omentin-1 did not affect steatosis but significantly reduced TNF-α levels, ER stress, and oxidative stress. Similar results were obtained using ex vivo VAT explants from obese patients upon omentin-1 supplementation. Furthermore, omentin-1 decreased the mRNA expression of NF-κB and mitogen-activated protein kinases (ERK and JNK). Ex vivo VAT explants showed that D-glucose and insulin significantly reduced omentin-1 mRNA expression and protein levels. CONCLUSIONS: Collectively, our findings suggest that reduced omentin-1 levels contribute to the development of MASLD. Omentin-1 supplementation likely exerts its beneficial effects through the inhibition of the NF-κB and MAPK signaling pathways, and it may additionally play a role in the regulation of glucose and insulin metabolism. Further research is warranted to explore omentin-1 as a potential therapeutic target and/or biomarker for MASLD.

Predictive value of preoperative albumin-bilirubin score and other risk factors for short-term outcomes after open pancreatoduodenectomy.

BACKGROUND: Pancreatoduodenectomy represents a complex procedure involving extensive organ resection and multiple alimentary reconstructions. It is still associated with high morbidity, even in high-volume centres. Prediction tools including preoperative patient-related factors to preoperatively identify patients at high risk for postoperative complications could enable tailored perioperative management and improve patient outcomes. AIM: To evaluate the clinical significance of preoperative albumin-bilirubin score and other risk factors in relation to short-term postoperative outcomes in patients after open pancreatoduodenectomy. METHODS: This retrospective study included all patients who underwent open pancreatic head resection (pylorus-preserving pancreatoduodenectomy or Whipple resection) for various pathologies during a five-year period (2017-2021) in a tertiary care setting at University Medical Centre Ljubljana, Slovenia and Cattinara Hospital, Trieste, Italy. Short-term postoperative outcomes, namely, postoperative complications, postoperative pancreatic fistula, reoperation, and mortality, were evaluated in association with albumin-bilirubin score and other risk factors. Multiple logistic regression models were built to identify risk factors associated with these short-term postoperative outcomes. RESULTS: Data from 347 patients were collected. Postoperative complications, major postoperative complications, postoperative pancreatic fistula, reoperation, and mortality were observed in 52.7%, 22.2%, 23.9%, 21.3%, and 5.2% of patients, respectively. There was no statistically significant association between the albumin-bilirubin score and any of these short-term postoperative complications based on univariate analysis. When controlling for other predictor variables in a logistic regression model, soft pancreatic texture was statistically significantly associated with postoperative complications [odds ratio (OR): 2.09; 95% confidence interval (95%CI): 1.19-3.67]; male gender (OR: 2.12; 95%CI: 1.15-3.93), soft pancreatic texture (OR: 3.06; 95%CI: 1.56-5.97), and blood loss (OR: 1.07; 95%CI: 1.00-1.14) were statistically significantly associated with major postoperative complications; soft pancreatic texture was statistically significantly associated with the development of postoperative pancreatic fistula (OR: 5.11; 95%CI: 2.38-10.95); male gender (OR: 1.97; 95%CI: 1.01-3.83), soft pancreatic texture (OR: 2.95; 95%CI: 1.42-6.11), blood loss (OR: 1.08; 95%CI: 1.01-1.16), and resection due to duodenal carcinoma (OR: 6.58; 95%CI: 1.20-36.15) were statistically significantly associated with reoperation. CONCLUSION: The albumin-bilirubin score failed to predict short-term postoperative outcomes in patients undergoing pancreatoduodenectomy. However, other risk factors seem to influence postoperative outcomes, including male sex, soft pancreatic texture, blood loss, and resection due to duodenal carcinoma.

Evaluation of the ACS-NSQIP Surgical Risk Calculator in Patients with Hepatic Metastases from Colorectal Cancer Undergoing Liver Resection.

BACKGROUND: The American College of Surgeons National Surgical Quality Improvement Program surgical risk calculator (ACS-NSQIP SRC) has been designed to predict morbidity and mortality and help stratify surgical patients. This study evaluates the performance of the SRC for patients undergoing surgery for colorectal liver metastases (CRLM). METHODS: SRC was retrospectively computed for patients undergoing liver or simultaneous colon and liver surgery for colorectal cancer (CRC) in two high tertiary referral centres from 2011 to 2020. C-statistics and Brier score were calculated as a mean of discrimination and calibration respectively, for both group and for every level of surgeon adjustment score (SAS) for liver resections in case of simultaneous liver-colon surgery. An AUC ≥ 0.7 shows acceptable discrimination; a Brier score next to 0 means the prediction tool has good calibration. RESULTS: Four hundred ten patients were included, 153 underwent simultaneous resection, and 257 underwent liver-only resections. For simultaneous surgery, the ACS-NSQIP SRC showed good calibration and discrimination only for cardiac complication (AUC = 0.720, 0.740, and 0.702 for liver resection unadjusted, SAS-2, and SAS-3 respectively; 0.714 for colon resection; and Brier score = 0.04 in every case). For liver-only surgery, it only showed good calibration for cardiac complications (Brier score = 0.03). The SRC underestimated the incidence of overall complications, pneumonia, cardiac complications, and the length of hospital stay. CONCLUSIONS: ACS-NSQIP SRC showed good predicting capabilities only for 1 out of 5 evaluated outcomes; therefore, it is not a reliable tool for patients undergoing liver surgery for CRLM, both in the simultaneous and staged resections.

Effect of the COVID-19 pandemic on surgery for indeterminate thyroid nodules (THYCOVID): a retrospective, international, multicentre, cross-sectional study.

BACKGROUND: Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. METHODS: In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. FINDINGS: Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6-3·4]) compared with the prepandemic phase (2·0 [0·9-3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0-5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0-1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2-1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1-1·7]; p=0·0039). INTERPRETATION: Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. FUNDING: None.

Ischemic wound revascularization by the stromal vascular fraction relies on host-donor hybrid vessels.

Nonhealing wounds place a significant burden on both quality of life of affected patients and health systems. Skin substitutes are applied to promote the closure of nonhealing wounds, although their efficacy is limited by inadequate vascularization. The stromal vascular fraction (SVF) from the adipose tissue is a promising therapy to overcome this limitation. Despite a few successful clinical trials, its incorporation in the clinical routine has been hampered by their inconsistent results. All these studies concluded by warranting pre-clinical work aimed at both characterizing the cell types composing the SVF and shedding light on their mechanism of action. Here, we established a model of nonhealing wound, in which we applied the SVF in combination with a clinical-grade skin substitute. We purified the SVF cells from transgenic animals to trace their fate after transplantation and observed that it gave rise to a mature vascular network composed of arteries, capillaries, veins, as well as lymphatics, structurally and functionally connected with the host circulation. Then we moved to a human-in-mouse model and confirmed that SVF-derived endothelial cells formed hybrid human-mouse vessels, that were stabilized by perivascular cells. Mechanistically, SVF-derived endothelial cells engrafted and expanded, directly contributing to the formation of new vessels, while a population of fibro-adipogenic progenitors stimulated the expansion of the host vasculature in a paracrine manner. These data have important clinical implications, as they provide a steppingstone toward the reproducible and effective adoption of the SVF as a standard care for nonhealing wounds.

Can the American College of Surgeons NSQIP Surgical Risk Calculator Accurately Predict Adverse Postoperative Outcomes in Emergency Abdominal Surgery? An Italian Multicenter Analysis.

BACKGROUND: The American College of Surgeons NSQIP surgical risk calculator provides an estimation of 30-day postoperative adverse outcomes. It is useful in the identification of high-risk patients needing clinical optimization and supports the informed consent process. The purpose of this study is to validate its predictive value in the Italian emergency setting. STUDY DESIGN: Six Italian institutions were included. Inclusion diagnoses were acute cholecystitis, appendicitis, gastrointestinal perforation or obstruction. Areas under the receiving operating characteristic curves, Brier score, Hosmer-Lemeshow index, and observed-to-expected event ratio were measured to assess both discrimination and calibration. Effect of the Surgeon Adjustment Score on calibration was then tested. A patient's personal risk ratio was obtained, and a cutoff was chosen to predict mortality with a high negative predicted value. RESULTS: A total of 2,749 emergency procedures were considered for the analysis. The areas under the receiving operating characteristic curve were 0.932 for death (0.921 to 0.941, p < 0.0001; Brier 0.041) and 0.918 for discharge to nursing or rehabilitation facility (0.907 to 0.929, p < 0.0001; 0.070). Discrimination was also strong (area under the receiving operating characteristic curve >0.8) for renal failure, cardiac complication, pneumonia, venous thromboembolism, serious complication, and any complication. Brier score was informative (<0.25) for all the presented variables. The observed-to-expected event ratios were 1.0 for death and 0.8 for discharge to facility. For almost all other variables, there was a general risk underestimation, but the use of the Surgeon Adjustment Score permitted a better calibration of the model. A risk ratio >3.00 predicted the onset of death with sensitivity = 86%, specificity = 77%, and negative predicted value = 99%. CONCLUSIONS: The American College of Surgeons NSQIP surgical risk calculator has proved to be a reliable predictor of adverse postoperative outcomes also in Italian emergency settings, with particular regard to mortality. We therefore recommend the use of the surgical risk calculator in the multidisciplinary care of patients undergoing emergency abdominal surgery.

microRNAs combined to radiomic features as a predictor of complete clinical response after neoadjuvant radio-chemotherapy for locally advanced rectal cancer: a preliminary study.

OBJECTIVE: To define a predictive Artificial Intelligence (AI) algorithm based on the integration of a set of biopsy-based microRNAs expression data and radiomic features to understand their potential impact in predicting clinical response (CR) to neoadjuvant radio-chemotherapy (nRCT). The identification of patients who would truly benefit from nRCT for Locally Advanced Rectal Cancer (LARC) could be crucial for an improvement in a tailored therapy. METHODS: Forty patients with LARC were retrospectively analyzed. An MRI of the pelvis before and after nRCT was performed. In the diagnostic biopsy, the expression levels of 7 miRNAs were measured and correlated with the tumor response rate (TRG), assessed on the surgical sample. The accuracy of complete CR (cCR) prediction was compared for i) clinical predictors; ii) radiomic features; iii) miRNAs levels; and iv) combination of radiomics and miRNAs. RESULTS: Clinical predictors showed the lowest accuracy. The best performing model was based on the integration of radiomic features with miR-145 expression level (AUC-ROC = 0.90). AI algorithm, based on radiomics features and the overexpression of miR-145, showed an association with the TRG class and demonstrated a significant impact on the outcome. CONCLUSION: The pre-treatment identification of responders/NON-responders to nRCT could address patients to a personalized strategy, such as total neoadjuvant therapy (TNT) for responders and upfront surgery for non-responders. The combination of radiomic features and miRNAs expression data from images and biopsy obtained through standard of care has the potential to accelerate the discovery of a noninvasive multimodal approach to predict the cCR after nRCT for LARC.

Inflammatory-nutritional scores in the diagnosis of NASH and liver fibrosis.

BACKGROUND: The aim of the present study was to investigate the possible correlation between various inflammation-nutritional scores to histological determined nonalcoholic steatohepatitis (NASH) and other liver injury suggestive for non-alcoholic fatty liver disease (NAFLD) in a bariatric population. METHODS: We consecutively and retrospectively evaluated all the patients referred to the Department of Bariatric Surgery in Trieste, Italy. Inflammation-nutritional scores were calculated starting from preoperative hematologic data. Liver biopsy was performed at the time of bariatric surgery (sleeve gastrectomy or gastric bypass) and pathological assessment was performed using Kleiner-Brunt staging system (NAS score). RESULTS: Glasgow Prognostic Score/modified Glasgow Prognostic Score (GPS/ mGPS) and Prognostic Index (PI) were associated to the diagnosis of NASH (P=0.024 and P=0.03 respectively). The presence of perisinusoidal and/or periportal fibrosis was correlated to Prognostic Nutritional Index (PNI) and platelet-to-lymphocyte ratio (PLR) values (P=0.02 and P=0.009 respectively). CONCLUSIONS: GPS/mGPS and PI are statistically associated to the histological diagnosis of NASH. Further studies on large series are needed to better understand the relationship between these serum markers and liver injury in obese patients.

Indications for upper gastrointestinal endoscopy before bariatric surgery: a multicenter study.

BACKGROUND: The role of preoperative upper gastrointestinal endoscopy before bariatric surgery is still debated, and a consensus among the international scientific community is lacking. The aims of this study, conducted in three different geographic areas, were to analyze data regarding the pathological endoscopic findings and report their impact on the decision-making process and surgical management, in terms of delay in surgical operation, modification of the intended bariatric procedure, or contraindication to surgery. METHODS: This is a multicenter cross-sectional study using data obtained from three prospective databases. The preoperative endoscopic reports, patient demographics, Body Mass Index, type of surgery, and Helicobacter pylori status were collected. Endoscopic findings were categorized into four groups: (1) normal endoscopy, (2) abnormal findings not requiring a change in the surgical approach, (3) clinically important lesions that required a change in surgical management or further investigations or therapy prior to surgery, and (4) findings that contraindicated surgery. RESULTS: Between 2006 and 2020, data on 643 patients were analyzed. In all of the enrolled bariatric institutions, preoperative endoscopy was performed routinely. A total of 76.2% patients had normal and/or abnormal findings that did not required a change in surgical management; in 23.8% cases a change or a delay in surgical approach occurred. Helicobacter pylori infection was detected in 15.2% patients. No patient had an endoscopic finding contraindicating surgery. CONCLUSIONS: The role of preoperative UGE is to identify a wide range of pathological findings in patients with obesity that could influence the therapeutic approach, including the choice of the proper bariatric procedure. Considering the anatomical modifications, the incidence of asymptomatic pathologies, and the risk of malignancy, we support the decision of performing preoperative endoscopy for all patients eligible for bariatric operation.

Potential Application of Small Interfering RNA in Gastro-Intestinal Tumors.

Despite the progress made in the diagnoses and therapy of gastrointestinal cancers, these diseases are still plagued by a high mortality. Thus, novel therapeutic approaches are urgently required. In this regard, small interfering RNA (siRNA), double-stranded RNA molecules able to specifically target the mRNA of pathological genes, have the potential to be of therapeutic value. To be effective in the human body, siRNAs need to be protected against degradation. Additionally, they need to target the tumor, leaving the normal tissue untouched in an effort to preserve organ function. To accomplish these tasks, siRNAs have been formulated with smart delivery systems such has polymers and lipids. While siRNA protection is not particularly difficult to achieve, their targeting of tumor cells remains problematic. Here, after introducing the general features of gastrointestinal cancers, we describe siRNA characteristics together with representative delivery systems developed for gastrointestinal cancers. Afterward, we present a selection of research papers employing siRNAs against upper- and lower- gastrointestinal cancers. For the liver, we also consider papers using siRNAs to combat liver cirrhosis, a relevant risk factor for liver cancer development. Finally, we present a brief description of clinical trials employing siRNAs for gastrointestinal cancers.

Survival and long-term surgical outcomes after colorectal surgery: are there any gender-related differences?

Colorectal cancer (CRC) incidence and mortality seems to be lower in women than in men. The present study aims to evaluate the impact of gender on CRC diagnosis, treatment, and survival. This is a retrospective cohort study based on a single-center dataset of CRC patients from the University Hospital of Trieste (Italy). Data of 1796 consecutive CRC patients referred to our center from November 11th, 2004, to December 31st, 2017, were analyzed. Right-sided carcinomas are more frequent in women than in men; furthermore, women had a lower surgical complication rate. Men showed a higher 5- and 10-year mortality. This survival benefit for women was observed independently of the tumor localization. The 5-year hazard ratio (HR) for women vs men was 0.776 (p 0.003), and after 10-year 0.816 (p 0.017). Regarding the disease-free survival (DFS), 5 and 10-year HR was 0.759 (p 0.034) and 0.788 (p 0.07), respectively. On multivariable analysis, respecting tumor localization, the odds of female gender were higher than man with right colon disease. Male gender was more independently associated with age at the surgery time. Women survival advantage was higher than men, except for patients older than 80. Surgical outcome and survival after CRC surgical treatment seem to be gender related. For this reason, gender could play an important role in CRC diagnosis and therapy, allowing an earlier diagnosis in women.

SCL-90 empirical factors predict post-surgery weight loss in bariatric patients over longer time periods.

PURPOSE: This longitudinal study examined how pre-intervention psychological health helps predict bariatric surgery (BS) success as percentage of expected body mass index loss (%EBMIL) over shorter to longer periods. METHODS: Adult candidates for BS (N = 334, 67.4% females) completed the Symptoms Checklist 90 (SCL-90) questionnaire; on average, 11 months occurred between the pre-surgery psychological evaluations and the bariatric intervention. We explored the factor structure of the SCL-90 items and inspected how SCL-90 empirical factors compared with SCL-90 scales and general indices predicted %EBMIL at 3-6-month, 1-year, and 2-year follow-up occasions, adjusting for gender, pre-intervention use of antidepressants and actual and ideal BMIs. RESULTS: Factor analysis combined the 90 items into 8 factors, which partially replicated the expected item structure. The SCL-90 empirical factors (but not the SCL-90 scales and indices) contributed to predict BS success. In fact, the Relational Distress factor directly protected from weight regain at 1-year follow-up, indirectly via 1-year %EBMIL at the 2-year follow-up, when it further strengthened the impact of the empirical factor of Generalized Anxiety on the 2-year BS outcome. The results also evidenced a cascade effect of the pre-surgery actual BMI across time as well as unique and direct effects of pre-surgery use of antidepressants and perceived ideal BMI on the 2-year outcome. CONCLUSIONS: SCL-90 empirical factor scores for obese patients are more efficient in anticipating BS success compared with original scale scores. They reveal that relational distress and anxiety are risk factors for postoperative weight loss, in addition to pre-intervention actual BMI, antidepressant therapy, and perceived ideal BMI. LEVEL OF EVIDENCE: III, well-designed cohort.

Is the Adrenal Incidentaloma Functionally Active? An Approach-To-The-Patient-Based Review.

Adrenal incidentalomas are a common occurrence. Most of them are adrenocortical adenomas that do not cause harm and do not require surgery, but a non-negligible proportion of incidentalomas is represented by functionally active masses, including cortisol-secreting adenomas (12%), pheochromocytomas (3-6%), aldosterone-secreting adenomas (2-3%), as well as malignant nodules, such as adrenocortical carcinomas (2-5%), which can be either functioning or non-functioning. All patients with an adrenal incidentaloma should undergo a few biochemical screening and confirmatory tests to exclude the presence of a functionally active mass. In this approach-to-the-patient-based review, we will summarize current recommendations on biochemical evaluation and management of functionally active adrenal incidentalomas. For this purpose, we will present four case vignettes, whereby we will describe how patients were managed, then we will review and discuss additional considerations tied to the diagnostic approach, and conclude with practical aspects of patient perioperative management. To improve the perioperative management of patients with functional adrenal incidentalomas, multidisciplinary meetings are advocated.

Safety and efficacy of totally minimally invasive right colectomy in the obese patients: a multicenter propensity score-matched analysis.

Despite the well-known benefits of the minimally invasive approach for the right colon cancer treatment, less is known about its feasibility and advantages in morbid obese patients. The aim of this study is to compare the postoperative outcomes after totally minimally invasive right colectomy between the obese and non-obese population. Data derived from a prospectively maintained multicenter colorectal database were analysed, dividing the enrolled patients into two groups: obese (BMI > 29.99) patient group and non-obese patient group. Data about gender, age, American Society of Anesthesiologists (ASA) Score, tumor characteristics, operative time, anastomosis time, extraction site, incision length, intraoperative complications, postoperative complications, postoperative recovery, specimen length and retrieved nodes were taken to assess the achievement of the oncologic standards. After a propensity score matching, a total of 184 patients was included, 92 in each group. No differences were found in terms of demographic data and tumor characteristics. Intraoperative data showed a significant difference in terms of anastomosis time in favour of non-obese group (p < 0.0001). No intraoperative complications were recorded and no conversion was needed in both groups. No differences were found in terms of postoperative complications. There were no differences in terms of first mobilization (p = 0.745), time to first flatus (p = 0.241) time to tolerance to liquid and solid diet (p = 0.241 and p = 0.06) and length of hospital stay (p = 0.817). The analysis of oncologic outcomes demonstrated adequate results in both groups. The results obtained by our study confirmed the feasibility and safety of the totally minimally invasive approach even in obese population.

Ficolin-2 Plasma Level Assesses Liver Fibrosis in Non-Alcoholic Fatty Liver Disease.

Fibrosis is the strongest predictor for disease-specific mortality in non-alcoholic fatty liver diseases (NAFLD), but the need for liver biopsy limits its diagnosis. We assessed the performance of plasma ficolin-2 (FCN-2) as a biomarker of fibrosis identified by an in silico discovery strategy. Two hundred and thirty-five morbidly obese (MO) subjects with biopsy-proven NAFLD stratified by fibrosis stage (F0, n = 44; F1, n = 134; F2, n = 46; F3/F4, n = 11) and 40 cirrhotic patients were enrolled. The cohort was subdivided into discovery (n = 76) and validation groups (n = 159). The plasma level of FCN-2 and other candidate markers was determined. FCN-2 was inversely correlated with the stage of liver fibrosis (ρ = −0.49, p < 0.001) independently of steatosis (p = 0.90), inflammation (p = 0.57), and ballooning (p = 0.59). In the global cohort, FCN-2 level decreased significantly in a stepwise fashion from F0/F1 (median 4753 ng/mL) to F2−F3−F4 (2760 ng/mL) and in cirrhotic subjects (1418 ng/mL). The diagnostic performance of FCN-2 in detecting F ≥ 2 was higher than other indexes (APRI, FIB-4) (AUROC 0.82, 0.68, and 0.6, respectively). The accuracy improved when combined with APRI score and HDL values (FCNscore, AUROC 0.85). Overall, the FCN-2 plasma level can accurately discriminate liver fibrosis status (minimal vs. moderate/advanced) significantly improving the fibrosis diagnostic algorithms.

Impact of COVID-19 on the oncological outcomes of colorectal cancer surgery in northern Italy in 2019 and 2020: multicentre comparative cohort study.

BACKGROUND: This study compared patients undergoing colorectal cancer surgery in 20 hospitals of northern Italy in 2019 versus 2020, in order to evaluate whether COVID-19-related delays of colorectal cancer screening resulted in more advanced cancers at diagnosis and worse clinical outcomes. METHOD: This was a retrospective multicentre cohort analysis of patients undergoing colorectal cancer surgery in March to December 2019 versus March to December 2020. Independent predictors of disease stage (oncological stage, associated symptoms, clinical T4 stage, metastasis) and outcome (surgical complications, palliative surgery, 30-day death) were evaluated using logistic regression. RESULTS: The sample consisted of 1755 patients operated in 2019, and 1481 in 2020 (both mean age 69.6 years). The proportion of cancers with symptoms, clinical T4 stage, liver and lung metastases in 2019 and 2020 were respectively: 80.8 versus 84.5 per cent; 6.2 versus 8.7 per cent; 10.2 versus 10.3 per cent; and 3.0 versus 4.4 per cent. The proportions of surgical complications, palliative surgery and death in 2019 and 2020 were, respectively: 34.4 versus 31.9 per cent; 5.0 versus 7.5 per cent; and 1.7 versus 2.4 per cent. Cancers in 2020 (versus 2019) were more likely to be symptomatic (odds ratio 1.36 (95 per cent c.i. 1.09 to 1.69)), clinical T4 stage (odds ratio 1.38 (95 per cent c.i. 1.03 to 1.85)) and have multiple liver metastases (odds ratio 2.21 (95 per cent c.i. 1.24 to 3.94)), but were not more likely to be associated with surgical complications (odds ratio 0.79 (95 per cent c.i. 0.68 to 0.93)). CONCLUSION: Colorectal cancer patients who had surgery between March and December 2020 had an increased risk of advanced disease in terms of associated symptoms, cancer location, clinical T4 stage and number of liver metastases.