Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer.

The present review demonstrates the major tumor suppressor genes, including TP53, CDKN2A and SMAD4, associated with pancreatic cancer. Each gene's role, prevalence and impact on tumor development and progression are analyzed, focusing on the intricate molecular landscape of pancreatic cancer. In addition, this review underscores the prognostic significance of specific mutations, such as loss of TP53, and explores some potential targeted therapies tailored to these molecular signatures. The findings highlight the importance of genomic analyses for risk assessment, early detection and the design of personalized treatment approaches in pancreatic cancer. Overall, this review provides a comprehensive analysis of the molecular intricacies of pancreatic tumors, paving the way for more effective and tailored therapeutic interventions.

Efficacy of esophageal stents as a primary therapeutic option in spontaneous esophageal perforations: a systematic review and meta-analysis of observational studies.

Background: Spontaneous esophageal perforation traditionally mandates urgent surgical treatment. Lately, esophageal stents have been used to reduce the associated morbidity and mortality. The current systematic review aimed to assess the efficacy of stents as a primary treatment option in this scenario. Methods: A systematic search was conducted in PubMed/MEDLINE, Scopus and the Cochrane Library for studies published in the English language between 2000 and 2023. We included observational studies reporting on the use of stents, alongside conservative measures and drainage procedures, in patients with spontaneous esophageal perforations. Primary outcomes were sealing rate (persistent leak occlusion) and failure rate (mortality or conversion to a major surgical operation). Secondary outcomes included patients' presentation, sepsis, drainage procedures, and reinterventions. Results for primary outcomes were presented as pooled rates with 95% confidence intervals (CIs), using a random-effects model. Methodological quality was assessed using the MINORS score. Results: Eighteen studies involving 171 patients were included. Sealing rate was 86% (95%CI 77-93%) and failure rate was 14% (95%CI 7-22%). Weighted mortality rate was 6% (95%CI 2-13%), while conversion to surgical treatment was 2% (95%CI 0-9%). Late presentation was not related to a statistically significant increase in treatment failure (odds ratio 1.85, 95%CI 0.37-9.30; P=0.72). Drainage procedures were required for the majority of patients, with a high rate of surgical and endoscopic reinterventions. Conclusions: Our results imply that stents may offer an effective and safe alternative treatment for patients with spontaneous esophageal perforations. Additional endoscopic and surgical drainage procedures are frequently needed.

Development and internal validation of a clinical prediction model for serious complications after emergency laparotomy.

PURPOSE: Emergency laparotomy (EL) is a common operation with high risk for postoperative complications, thereby requiring accurate risk stratification to manage vulnerable patients optimally. We developed and internally validated a predictive model of serious complications after EL. METHODS: Data for eleven carefully selected candidate predictors of 30-day postoperative complications (Clavien-Dindo grade > = 3) were extracted from the HELAS cohort of EL patients in 11 centres in Greece and Cyprus. Logistic regression with Least Absolute Shrinkage and Selection Operator (LASSO) was applied for model development. Discrimination and calibration measures were estimated and clinical utility was explored with decision curve analysis (DCA). Reproducibility and heterogeneity were examined with Bootstrap-based internal validation and Internal-External Cross-Validation. The American College of Surgeons National Surgical Quality Improvement Program's (ACS-NSQIP) model was applied to the same cohort to establish a benchmark for the new model. RESULTS: From data on 633 eligible patients (175 complication events), the SErious complications After Laparotomy (SEAL) model was developed with 6 predictors (preoperative albumin, blood urea nitrogen, American Society of Anaesthesiology score, sepsis or septic shock, dependent functional status, and ascites). SEAL had good discriminative ability (optimism-corrected c-statistic: 0.80, 95% confidence interval [CI] 0.79-0.81), calibration (optimism-corrected calibration slope: 1.01, 95% CI 0.99-1.03) and overall fit (scaled Brier score: 25.1%, 95% CI 24.1-26.1%). SEAL compared favourably with ACS-NSQIP in all metrics, including DCA across multiple risk thresholds. CONCLUSION: SEAL is a simple and promising model for individualized risk predictions of serious complications after EL. Future external validations should appraise SEAL's transportability across diverse settings.

An Updated Review on the Emerging Role of Indocyanine Green (ICG) as a Sentinel Lymph Node Tracer in Breast Cancer.

Sentinel lymph node biopsy (SLNB) has become the standard of care for clinically node-negative breast cancer and has recently been shown by clinical trials to be also feasible for clinically node-positive patients treated with primary systemic therapy. The dual technique using both radioisotope (RI) and blue dye (BD) as tracers for the identification of sentinel lymph nodes is considered the gold standard. However, allergic reactions to blue dye as well as logistics issues related to the use of radioactive agents, have led to research on new sentinel lymph node (SLN) tracers and to the development and introduction of novel techniques in the clinical practice. Indocyanine green (ICG) is a water-soluble dye with fluorescent properties in the near-infrared (NIR) spectrum. ICG has been shown to be safe and effective as a tracer during SLNB for breast cancer and accumulating evidence suggests that ICG is superior to BD and at least comparable to RI alone and to RI combined with BD. Thus, ICG was recently proposed as a reliable SLN tracer in some breast cancer clinical practice guidelines. Nevertheless, there is lack of consensus regarding the optimal role of ICG for SLN mapping. Specifically, it is yet to be determined whether ICG should be used in addition to BD and/or RI, or if ICG could potentially replace these long-established traditional SLN tracers. This article is an updated overview of somerecent studies that compared ICG with BD and/or RI regarding their accuracy and effectiveness during SLNB for breast cancer.

Optical Imaging in Human Lymph Node Specimens for Detecting Breast Cancer Metastases: A Review.

Assessment of regional lymph node status in breast cancer is of important staging and prognostic value. Even though formal histological examination is the currently accepted standard of care, optical imaging techniques have shown promising results in disease diagnosis. In the present article, we review six spectroscopic techniques and focus on their use as alternative tools for breast cancer lymph node assessment. Elastic scattering spectroscopy (ESS) seems to offer a simple, cost-effective, and reproducible method for intraoperative diagnosis of breast cancer lymph node metastasis. Optical coherence tomography (OCT) provides high-resolution tissue scanning, along with a short data acquisition time. However, it is relatively costly and experimentally complex. Raman spectroscopy proves to be a highly accurate method for the identification of malignant axillary lymph nodes, and it has been further validated in the setting of head and neck cancers. Still, it remains time-consuming. Near-infrared fluorescence imaging (NIRF) and diffuse reflectance spectroscopy (DFS) are related to significant advantages, such as deep tissue penetration and efficiency. Fourier-transform infrared spectroscopy (FTIR) is a promising method but has significant drawbacks. Nonetheless, only anecdotal reports exist on their clinical use for cancerous lymph node detection. Our results indicate that optical imaging methods can create informative and rapid tools to effectively guide surgical decision-making.

High Intratumoral i-tRF-GlyGCC Expression Predicts Short-Term Relapse and Poor Overall Survival of Colorectal Cancer Patients, Independent of the TNM Stage.

Colorectal cancer (CRC), one of the most prevalent types of cancer, requires the discovery of new tumor biomarkers for accurate patient prognosis. In this work, the prognostic value of the tRNA fragment i-tRF-GlyGCC in CRC was examined. Total RNA extraction from 211 CRC patient cancer tissue specimens and 83 adjacent normal tissues was conducted. Each RNA extract was subjected to in vitro polyadenylation and reverse transcription. A real-time quantitative PCR assay was used to quantify i-tRF-GlyGCC in all samples. Extensive biostatics analysis showed that i-tRF-GlyGCC levels in CRC tissues were significantly lower than in matched normal colorectal tissues. Additionally, the disease-free survival (DFS) and overall survival (OS) time intervals were considerably shorter in CRC patients with high i-tRF-GlyGCC expression. i-tRF-GlyGCC expression maintained its prognostic value independently of other established prognostic factors, as shown by the multivariate Cox regression analysis. Additionally, survival analysis after TNM stage stratification revealed that higher i-tRF-GlyGCC levels were linked to shorter DFS time intervals in patients with TNM stage II tumors, as well as an increased probability of having a worse OS for patients in TNM stage II. In conclusion, i-tRF-GlyGCC has the potential to be a useful molecular tissue biomarker in CRC, independent of other clinicopathological variables.

Prospective multicenter external validation of postoperative mortality prediction tools in patients undergoing emergency laparotomy.

BACKGROUND: Accurate preoperative risk assessment in emergency laparotomy (EL) is valuable for informed decision making and rational use of resources. Available risk prediction tools have not been validated adequately across diverse health care settings. Herein, we report a comparative external validation of four widely cited prognostic models. METHODS: A multicenter cohort was prospectively composed of consecutive patients undergoing EL in 11 Greek hospitals from January 2020 to May 2021 using the National Emergency Laparotomy Audit (NELA) inclusion criteria. Thirty-day mortality risk predictions were calculated using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP), NELA, Portsmouth Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (P-POSSUM), and Predictive Optimal Trees in Emergency Surgery Risk tools. Surgeons' assessment of postoperative mortality using predefined cutoffs was recorded, and a surgeon-adjusted ACS-NSQIP prediction was calculated when the original model's prediction was relatively low. Predictive performances were compared using scaled Brier scores, discrimination and calibration measures and plots, and decision curve analysis. Heterogeneity across hospitals was assessed by random-effects meta-analysis. RESULTS: A total of 631 patients were included, and 30-day mortality was 16.3%. The ACS-NSQIP and its surgeon-adjusted version had the highest scaled Brier scores. All models presented high discriminative ability, with concordance statistics ranging from 0.79 for P-POSSUM to 0.85 for NELA. However, except the surgeon-adjusted ACS-NSQIP (Hosmer-Lemeshow test, p = 0.742), all other models were poorly calibrated ( p < 0.001). Decision curve analysis revealed superior clinical utility of the ACS-NSQIP. Following recalibrations, predictive accuracy improved for all models, but ACS-NSQIP retained the lead. Between-hospital heterogeneity was minimum for the ACS-NSQIP model and maximum for P-POSSUM. CONCLUSION: The ACS-NSQIP tool was most accurate for mortality predictions after EL in a broad external validation cohort, demonstrating utility for facilitating preoperative risk management in the Greek health care system. Subjective surgeon assessments of patient prognosis may optimize ACS-NSQIP predictions. LEVEL OF EVIDENCE: Diagnostic Test/Criteria; Level II.

The Hellenic Emergency Laparotomy Study (HELAS): A Prospective Multicentre Study on the Outcomes of Emergency Laparotomy in Greece.

BACKGROUND: Emergency laparotomy (EL) is accompanied by high post-operative morbidity and mortality which varies significantly between countries and populations. The aim of this study is to report outcomes of emergency laparotomy in Greece and to compare them with the results of the National Emergency Laparotomy Audit (NELA). METHODS: This is a multicentre prospective cohort study undertaken between 01.2019 and 05.2020 including consecutive patients subjected to EL in 11 Greek hospitals. EL was defined according to NELA criteria. Demographics, clinical variables, and post-operative outcomes were prospectively registered in an online database. Multivariable logistic regression analysis was used to identify independent predictors of post-operative mortality. RESULTS: There were 633 patients, 53.9% males, ASA class III/IV 43.6%, older than 65 years 58.6%. The most common operations were small bowel resection (20.5%), peptic ulcer repair (12.0%), adhesiolysis (11.8%) and Hartmann's procedure (11.5%). 30-day post-operative mortality reached 16.3% and serious complications occurred in 10.9%. Factors associated with post-operative mortality were increasing age and ASA class, dependent functional status, ascites, severe sepsis, septic shock, and diabetes. HELAS cohort showed similarities with NELA patients in terms of demographics and preoperative risk. Post-operative utilisation of ICU was significantly lower in the Greek cohort (25.8% vs 56.8%) whereas 30-day post-operative mortality was significantly higher (16.3% vs 8.7%). CONCLUSION: In this study, Greek patients experienced markedly worse mortality after emergency laparotomy compared with their British counterparts. This can be at least partly explained by underutilisation of critical care by surgical patients who are at high risk for death.

Circulating miRNA Expression Profiling in Breast Cancer Molecular Subtypes: Applying Machine Learning Analysis in Bioinformatics.

BACKGROUND/AIM: Breast cancer is a leading worldwide cause of female cancer-related morbidity and mortality. Since molecular characteristics increasingly guide disease management, demystifying breast tumor miRNA signature emerges as an essential step toward personalized care. This study aimed to investigate the variations in circulating miRNA expression profiles between breast cancer subtypes and healthy controls and to identify relevant target genes and molecular functions. MATERIALS AND METHODS: MiRNA expression was tested by miScript™ miRNA PCR Array Human Cancer Pathway Finder kit, and subsequently, a machine learning approach was applied for miRNA profiling of the various breast cancer molecular subtypes. RESULTS: Serum samples from patients with primary breast cancer (n=66) and healthy controls (n=16) were analyzed. MiR-21 was the single common molecule among all breast cancer subtypes. Furthermore, several miRNAs were found to be differentially expressed explicitly in the different subtypes; luminal A (miR-23b, miR-142, miR-29a, miR-181d, miR-16, miR-29b, miR-155, miR-181c), luminal B (miR-148a, let-7d, miR-92a, miR-34c, let-7b, miR-15a), HER2+ (miR-125b, miR-134, miR-98, miR-143, miR-138, miR-135b) and triple negative breast cancer (miR-17, miR-150, miR-210, miR-372, let-7f, miR-191, miR-133b, miR-146b, miR-7). Finally, miRNA-associated target genes and molecular functions were identified. CONCLUSION: Applying a machine learning approach to delineate miRNA signatures of various breast cancer molecular subtypes allows further understanding of molecular disease characteristics that can prove clinically relevant.

Breast Cancer and COVID-19: Challenges in Surgical Management.

The harsh healthcare reality imposed by the COVID-19 pandemic resulted in wide clinical practice alterations, postponements, and shortages, affecting both patients and caregivers. Breast-cancer management, from diagnosis to treatment and follow up, was a field that did not escape such changes, facing a challenging set of obstacles in order to maintain adequate cancer care services while diminishing viral spread among patients and personnel. In this review article, we discuss the impact of the COVID-19 pandemic on several aspects of breast-cancer management, and the subsequent modifications adopted by clinicians, scientific groups, and governments as a response to the novel conditions. Screening and diagnosis, as well as breast-cancer treatment paths-especially surgical interventions-were the most affected domains, while patients' psychological burden also emerged as a notable consequence. The aftermath of diagnostic and surgical delays is yet to be assessed, while the treatment alterations and the introduction of new therapeutic schemes might signify the opening of a novel era in breast-cancer management.

Complex refractive index of freshly excised human breast tissue as a marker of disease.

We report differences in the refractive index of healthy and tumorous freshly excised human breast tissue as determined from reflectance profile measurements at five wavelengths (432 nm, 532 nm, 633 nm, 964 nm, 1551 nm) in the visible and near-infrared using a standard prism-coupling refractometer. These refractive index differences, particularly in the near-infrared, can be used to distinguish fibroadenomas and cancerous growths not only from normal breast tissue but also from each other.

The Effect of Intraoperative Transversus Abdominis Plane Blocking on Postoperative Pain After Laparoscopic Transabdominal Pre-peritoneal (TAPP) Groin Hernia Repair.

BACKGROUND: Managing postoperative pain even after laparoscopic groin hernia repair still remains an interesting challenge for clinicians especially for patients of high risk. Plenty of operative techniques and analgesic methods have been proposed in order to minimize postoperative pain after laparoscopic groin hernia repair. The aim of the present study is to compare transverse abdominis plane (TAP)-block with local analgesic infiltration at trocar entry sites in the terms of reducing postoperative pain. METHODS: Patients that underwent laparoscopic trans-abdominal pre-peritoneal (TAPP) groin hernia repair in a high-volume university hospital were included. Patients were divided in two groups depending on the analgesic method used. Pain was assessed using Visual Numerical Scale (VNS) score. RESULTS: Thirty patients were included. Intraoperative TAP-block seemed to be superior in terms of decreasing pain at the hernia area and at the trocar insertion site (p < 0.05) compared to local analgesic infiltration at the trocar insertion site at 6, 12 and 24 h after surgery (p < 0.05). In addition, pain reduction was more effective in rest rather than in motion for both analgesic methods. CONCLUSION: Intraoperative TAP-block under direct vision seems to be an effective, fast and easy technique in order to reduce postoperative pain after laparoscopic groin hernia repair, but more studies are required to validate these results in a prospective and randomized context.

Exosomes in breast cancer management: Where do we stand? A literature review.

BACKGROUND: Exosomes constitute cellular molecular fingertips that participate in intercellular communication both in health and disease states. Hence, exosomes emerge as critical mediators of cancer development and progression, as well as potential biomarkers and novel therapeutic targets. OBJECTIVE: To review literature data regarding applications of circulating exosomes in breast cancer management. METHODS: This is a literature review of relevant published studies until April 2020 in PubMed and Google Scholar databases. Original papers in the English language concerning exosome related studies were included. RESULTS: Exosomes represent molecular miniatures of their parent cells. Several homeostatic mechanisms control exosomal secretion and synthesis. Exosomal exchange among cells creates an intricate intercellular crosstalk orchestrating almost every tissue process, as well as carcinogenesis. Available data highlight exosomes as major mediators of cancer development and progression. The secretion of specific exosomal molecules, particularly miRNAs, correlates with the underlying processes and can be used as a means of tumor detection and prognostic assessment. CONCLUSIONS: Exosomal miRNAs expression profiles and levels closely relate to cancer extent, type and prognosis. Deep comprehension of such correlations and systematization of experimental outcomes will offer a novel approach in cancer detection and management.

Implant infections after breast reconstruction surgery following mastectomy: Experience from a Greek breast unit.

BACKGROUND: Despite the dominance of implant-based breast reconstruction after mastectomy, during recent years, it has been correlated to some complications. The aim of this study is to present the Greek experience about management of implant infections after breast reconstructions and to investigate the relationship between possible risk factors and breast pocket fluid cultures. METHODS: In total, 260 patients underwent implant-based breast reconstruction due to breast cancer in our center from 2016 until 2020. 46 patients, that underwent implant or expander replacement after breast reconstruction due to mastectomy were included in the present study. RESULTS: 260 patients underwent breast reconstruction in our center and in 46 (18%) of them an implant replacement was required. 21 patients (8%) presented clinically with an implant infection, but 12 of them (5%) had positive cultures from the breast pocket fluid. On the contrary, 25 patients (10%) presented no clinical signs of implant infection, but 5 of them (2%) had a positive culture. In addition, we demonstrated a correlation between implant infection and positive cultures (p = 0.009), along with an association between chemotherapy before implant placements and negative cultures (p = 0.035). Finally, the most common pathogen was Staphylococcus epidermidis (29%), followed by Escherichia coli (24%) and Staphylococcus aureus (18%). CONCLUSION: Implant infection still remains a very serious complication after breast reconstruction surgery. The establishment of a therapeutic protocol, with specific antimicrobial and surgical targets seems as an effective strategy against implant infections.

mRNA coexpression patterns of Wnt pathway components and their clinicopathological associations in breast and colorectal cancer.

Aberrant Wnt signaling is implicated in carcinogenesis triggering efforts for the development of new therapeutic agents, many of which have entered clinical trials. We extend our previous analysis of WNT3, FZD7, LEF1 expression levels in breast and colorectal cancer including WNT2, FZD4 and ß-catenin expression, in an effort to delineate their relative expression levels along with concurrent expression patterns and possible prognostic value. We analyzed 82 breast and 102 colorectal carcinomas for relative mRNA expression levels of the investigated genes by RT-PCR relative quantification with the ΔΔCt method. Statistical analysis was performed in order to determine associations of relative mRNA expression and linear correlations. ß-catenin expression was determined by immunochemistry. Regarding breast carcinomas, decreased relative mRNA expression levels of WNT2, FZD4 were found frequently and WNT2 expression was correlated with ER/ PR status (p = 0.045/p = 0.028), whereas ß-catenin with grade (p = 0.026). In colorectal carcinomas, increased relative mRNA expression levels of WNT2 and FZD4 were found in 59% and 32% of cases respectively, whereas ß-catenin showed decreased mRNA expression levels in 57% of cases and a correlation with pN-category (p = 0.037). Linear correlations were observed between WNT2/FZD4 (R=0.542, p < 0.001), WNT2/ß-catenin (R=0.254, p = 0.010), FZD4/ß-catenin (R=0.406, p < 0.001) expression and a correlation between mRNA expression and membranous/cytoplasmic ß-catenin emerged (p = 0.039/0.046). Our results suggest a possible clinical significance for Wnt pathway gene expression levels in both tumour types. The concurrent expression of the investigated genes as well as the different expression profiles, underlines the complexity of this pathway and the necessity of patient selection in order to maximize the efficacy of drugs targeting Wnt pathway.

Severe anaphylactic reaction after blue dye injection for sentinel lymph node biopsy in breast surgery: Report of two cases and literature review.

Anaphylactic reactions, and especially the severe ones (types III and IV), should be kept in mind as considerable adverse effects while using blue dyes for SLNB.

Reliability and Concurrent Validity of the SARC-F and Its Modified Versions: A Systematic Review and Meta-Analysis.

OBJECTIVES: Sarcopenia, being prevalent in up to 40% of older adults, is associated with adverse health outcomes. The international sarcopenia guidelines recommend screening for sarcopenia using the SARC-F. A previous meta-analysis (2017) reported poor validity of the SARC-F among community-dwelling older adults. Since then, modified SARC-F versions were developed and new sarcopenia definitions were published, including the SARC-F for case-finding. This systematic review and meta-analysis aimed to assess the reliability of the SARC-F and its concurrent validity to identify sarcopenia. DESIGN: Systematic review and meta-analyses. SETTING AND PARTICIPANTS: Adults (all ages) from any study population. METHODS: A systematic search was conducted in MEDLINE, EMBASE, Cochrane, and CINAHL (January 1, 2013, to April 6, 2020). Articles were included if they reported on the reliability and/or concurrent validity of the (modified) SARC-F. No restrictions were applied for sex, age, study population, or sarcopenia definition. Reliability measures included inter-rater reliability, test-retest reliability, and internal consistency. Meta-analyses were performed for concurrent validity. RESULTS: The 29 included articles included 21,855 individuals (mean age of 63.3±14.6 years, 61.3% females) among community-dwelling (n = 16), geriatric inpatient (n = 5), geriatric outpatient (n = 2), nursing home (n = 2), and long-term care (n = 1) populations. The SARC-F had good (2/4 articles) to excellent (2/4 articles) inter-rater reliability, moderate (1/6 articles) to good (5/6 articles) test-retest reliability, and low (4/8 articles) to high (4/8 articles) internal consistency. The SARC-F had low to moderate sensitivity (28.9%-55.3%) and moderate to high specificity (68.9%-88.9%) according to the European Working Group on Sarcopenia in Older People (EWGSOP; n = 13), revised EWGSOP definition (EWGSOP2; n = 6), Asian Working Group for Sarcopenia (AWGS; n = 13), Foundation for the National Institutes of Health (FNIH; n = 8), International Working Group on Sarcopenia (IWGS; n = 9), and Society on Sarcopenia, Cachexia and Wasting Disorders (n = 2). The SARC-CalF had low to moderate sensitivity (45.9%-57.2%) and high specificity (87.7%-91.3%) according to the EWGSOP (n = 5), AWGS (n = 4), FNIH (n = 3), and IWGS (n = 3). CONCLUSIONS AND IMPLICATIONS: Despite the good reliability of the SARC-F, its low to moderate sensitivity and moderate to high specificity make it nonoptimal to use for sarcopenia screening. It is recommended to apply the diagnostic criteria for sarcopenia without screening.

The "misfortune" of being a COVID-19 negative patient during the coronavirus pandemic.

COVID-19 pandemic has obviously affected patients' behavior towards seeking medical help as well as physicians' decision in the management of emergencies. Our recent experience as surgeons at a COVID-19 referral hospital revealed cases which share an alerting characteristic: the delay in appropriate management. Unfortunately for COVID-19 negative patients a "coronacentric" health system has been adopted. In view of measures applied to avoid spread of the disease, a significant delay in patients' presentation as well as in their in-hospital management is observed. We present cases where delay in appropriate management affected the patients' outcome and underline the fact that balancing between COVID-19 safety measures and a patient who needs urgent treatment can be very challenging and stressful.