Programmed Death Ligand 1: Unveiling its Impact on Endometrial Carcinogenesis.

Endometrial cancer is a commonly diagnosed gynecological malignancy presenting an increasing incidence worldwide. The immune response plays a crucial role in the mechanisms underlying carcinogenesis and the progression of tumors. In recent times, there has been a discernible surge in the acknowledgment of the importance of programmed death ligand 1 (PDL1) in evading the immunological response of the host and promoting the growth of malignancies. The primary aim of this review is to consolidate the existing corpus of evidence pertaining to the role of PDL1 in the etiology and progression of endometrial cancer and investigate the molecular mechanisms involved in the expression of PDL1 in cells impacted by endometrial cancer. Finally, the association between PDL1 expression and clinical outcomes, as well as the potential therapeutic uses of targeting the PDL1 pathway are being analyzed.

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.

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.

The Expression Patterns and Implications of MALAT1, MANCR, PSMA3-AS1 and miR-101 in Esophageal Adenocarcinoma.

Esophageal adenocarcinoma (EAC) is a malignant tumor with poorly understood molecular mechanisms. This study endeavors to elucidate how the long non-coding RNAs (lncRNAs) MALAT1, MANCR and PSMA3-AS1, as well as the microRNA miR-101, exhibit specific expression patterns in the pathogenesis and prognosis of EAC. A total of 50 EAC tissue samples (tumors and lymph nodes) and a control group comprising 26 healthy individuals were recruited. The samples underwent quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analyses. The relative expression levels of MALAT1, MANCR, PSMA3-AS1, and miR-101 were ascertained and correlated with various clinicopathological parameters including TNM staging, tumor characteristics (size and grade of the tumor) lymphatic invasion, disease-free (DFS) and overall survival (OS) of EAC patients. Quantitative analyses revealed that MALAT1 and MANCR were significantly upregulated in EAC tumors and positive lymph nodes when compared to control tissues (p < 0.05). Such dysregulations correlated positively with advanced lymphatic metastases and a higher N stage. DFS in the subgroup of patients with negative lymph nodes was higher in the setting of low-MANCR-expression patients compared to patients with high MANCR expression (p = 0.02). Conversely, miR-101 displayed a significant downregulation in EAC tumors and positive lymph nodes (p < 0.05), and correlated negatively with advanced tumor stage, lymphatic invasion and the grade of the tumor (p = 0.006). Also, patients with low miR-101 expression showed a tendency towards inferior overall survival. PSMA3-AS1 did not demonstrate statistically significant alterations (p > 0.05). This study reveals MALAT1, MANCR, and miR-101 as putative molecular markers for prognostic evaluation in EAC and suggests their involvement in EAC progression.

Gastrectomy for Cancer: A 15-Year Analysis of Real-World Data from the University of Athens.

Background and Objectives: Encouraging data have been reported from referral centers following gastrointestinal cancer surgery. Our goal was to retrospectively review patient outcomes following gastrectomy for gastric or gastroesophageal junction (GEJ) cancer at a high-volume unit of the University of Athens. Methods: The enrollment period was from June 2003 to September 2018. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Cox proportional hazard models were constructed to identify variables independently associated with time-to-event outcomes. Results: A total of 205 patients were analyzed. R0 resection was achieved in 183 (89.3%) patients and was more likely to occur following neoadjuvant chemotherapy (p = 0.008). Recurrence developed in 46.6% of our cohort and the median disease-free survival was 31.2 months. On multivariate analysis, only staging (HR = 2.15; 95% CI: 1.06-4.36) was independently associated with increased risk of recurrence. All-cause mortality was 57.2% and the median time of death was 40.9 months. On multivariate regression, staging (HR: 1.35; 95% CI: 1.11-1.65) and recurrence (HR: 2.87; 95% CI: 1.32-6.22) predicted inferior prognosis. Conclusions: Gastrectomy at the University of Athens has yielded favorable outcomes for patients with GEJ cancer.

Cancer Treatment and Immunotherapy during Pregnancy.

BACKGROUND/AIM: Immunotherapy has, in recent years, witnessed an expansion in its indications for the treatment of cancer. Coupled with the fact that, nowadays, even more women choose to postpone parenthood, thus increasing their chances of having some kind of malignancy during pregnancy, more and more women are eligible for receiving immunotherapy during this period of their lives. The cases of cancer diagnosed during pregnancy is an ever-increasing trend nowadays. MATERIALS AND METHODS: The oncologists and clinicians treating women often face a range of ethical and therapeutic dilemmas due to the particularity of the patient's conditions. The primary concern is the protection of the mother, firstly, and then the fetus (through adjustments to the various treatment regimens) if possible. RESULTS AND CONCLUSIONS: Oncological drugs, radiation therapy, surgery, or a combination of all the above methods are selected, depending on the case. In this project, we studied the oncology drugs used for various types of gestational cancer, their appropriateness and timing, as well as their possible effects on the parent and embryo upon their administration. Various studies have shown that the administration of oncological drugs should be postponed until at least after the first trimester of pregnancy.

Primary Cervical Carcinosarcoma: Report of a Rare Case.

Background Carcinosarcomas are malignant mixed Müllerian tumors (MMMT), containing both epithelial and mesenchymal components. Carcinosarcomas of the uterine cervix comprise an extremely rare histopathological entity, with less than 150 cases reported in the literature to date. Materials and Methods A 79-year-old postmenopausal female patient was referred to our gynecological department due to a pelvic mass and vaginal bleeding. A cervical curettage was performed and the histological report revealed a malignant neoplasm with high cellularity consisting of two components; the first was a chondrosarcoma and the latter a adenocarcinoma. A diagnosis of MMMT was confirmed through immunohistochemical (IHC) staining. Neoadjuvant chemotherapy and radiotherapy were implemented, and a year later the patient underwent a radical hysterectomy and oncological pelvic lymph node dissection. She remains disease-free 12 months postoperatively. Conclusion Primary cervical carcinosarcomas are extremely rare tumors demonstrating a bipartite profile. Preoperative diagnosis with appropriate immunochemistry testing of this rare entity is crucial to decision making.

Radiation-Induced Esophageal Cancer: Investigating the Pathogenesis, Management, and Prognosis.

One of the most serious late side effects of irradiation is the promotion of tumorigenesis. Radiation-induced esophageal cancer (RIEC) can arise in a previously irradiated field, mostly in patients previously irradiated for thoracic malignancies such as breast cancer, Hodgkin and non-Hodgkin lymphomas, head and neck cancers, lung cancer, or previous esophageal cancer. RIEC is rare and accounts for less than 1% of all carcinomas of the esophagus. There are little data available in the current literature regarding pathogenesis, diagnosis, treatment, and outcome of esophageal cancer developed in a previously irradiated field. RIEC seems to represent a biologically aggressive disease with a poor prognosis. Although it is difficult to perform radical surgery on a previously irradiated field, R0 resection remains the mainstay of treatment. The use of neoadjuvant and adjuvant chemoradiotherapy remains very helpful in RIEC, similarly to conventional esophageal cancer protocols. The aim of this article is to elucidate this rare but challenging entity.

Oncologic outcomes of patients with resectable primary gastric squamous cell carcinoma: a systematic review.

Background: Primary gastric squamous cell carcinoma (PGSCC) is an uncommon type of gastric malignancy estimated to comprise around 0.04-0.5% of all gastric malignancies. PGSCC's long-term survival has been quoted to range from 17-50% depending on stage, with surgery arguably representing the most useful modality for prolonging oncologic survival. Nevertheless, reliable data on its effectiveness are still lacking in the literature. Method: A systematic literature search of the Medline, Cochrane library and Scopus databases was undertaken, to identify cases of surgically managed PGSCC reporting patient-related outcomes. Results: In total, 23 case reports and 1 case series incorporating 38 patients were identified. Mean patient age was 61.2 years and the male/female ratio was 18:1. Most tumors were high-stage at the time of diagnosis, with the T4 stage predominating in the patient pool (n=15, 50%) along with a high percentage of lymphatic spread (N positive tumors, n=15, 47%). All patients underwent curative-intent surgical resection and were subsequently followed for an average of 30.7±14 months. Extrapolated survival data revealed a projected 3- and 5-year overall survival of 62.2% and 51.9%, respectively, while the 3-year probability for being disease-free was calculated to be 30.8%. T4 stage and lymphatic spread were found to be predictors of poor survival in univariate but not in multivariate analysis. Conclusion: Notwithstanding the methodological limitations inherent to the present review, the obtained results, when superimposed on existing cross-sectional survival data, suggest significantly enhanced patient survival following surgery, solidifying its role in the management of patients with PGSCC.

The Role of SNHG15 in the Pathogenesis of Hepatocellular Carcinoma.

Long non-coding RNAs (lncRNAs) are transcripts of more than 200 nucleotides which cannot be translated into proteins. Small nucleolar RNA host gene 15 (SNHG15) is a lncRNA whose dysregulation has been found to have an important impact on carcinogenesis and affect the prognosis of cancer patients in various cancer types. Hepatocellular carcinoma (HCC) is one of the most common cancers with a poor long-term prognosis, while the best prognostic factor of the disease is its early diagnosis and surgery. Consequently, the investigation of the mechanisms of hepatocarcinogenesis, as well as the discovery of efficient molecular markers and therapeutic targets are of great significance. An extensive literature search was performed in MEDLINE in order to identify clinical studies that tried to reveal the role of SNHG15 in HCC. We used keywords such as 'HCC', 'hepatocellular carcinoma', 'SNHG15' and 'clinical study'. Finally, we included four studies written in English, published during the period 2016-2021. It was revealed that SNHG15 is related to the appearance of HCC via different routes and its over-expression affects the overall survival of the patients. More assays are required in order to clarify the potential role of SNHG15 as a prognostic tool and therapeutic target in HCC.

The Prognostic Role and Significance of Dll4 and Toll-like Receptors in Cancer Development.

The Notch signaling pathway regulates the development of embryonic and tissue homeostasis of various types of cells. It also controls cell proliferation, variation, fate and cell death because it emits short-range messages to nearby cells. The pathway plays an important role in the pathophysiology of various malignancies, controlling cancer creation. It also limits cancer development by adjusting preserved angiogenesis and cellular programs. One of the Notch signaling ligands (in mammals) is Delta-like ligand 4 (Dll4), which plays a significant role in the overall malignancies' advancement. Particularly, sequencing Notch gene mutations, including those of Dll4, have been detected in many types of cancers portraying information on the growth of particular gynecological types of tumors. The current research article examines the background theory that implies the ability of Dll4 in the development of endometrial and other cancer types, and the probable therapeutic results of Dll4 inhibition.

A Brief Overview of Oncogenes and Signal Transduction Pathways in Gynecological Cancer.

Gynecological cancer is the cancer that originates in the female reproductive system. According to the anatomical location of the cancer, it is distinguished into cervical, uterine, vaginal, ovarian, and vulvar cancer. Oncogenes and tumor catalytic genes play a key role in the genesis and development of gynecological cancer. This article presents the signaling pathways and expression of oncogenes that take place in the carcinogenesis of the female reproductive system.

Targeting the Endocannabinoid System: From the Need for New Therapies to the Development of a Promising Strategy. What About Pancreatic Cancer?

Pancreatic cancer is one of the most fatal malignancies, and therefore, new strategies, which aim at the improvement of the prognosis of this lethal disease, are needed. Many clinical trials have failed to improve overall survival. Nowadays, research is focused on advances provided by novel potential targets to efficiently enhance life expectancy. Cannabinoids, the active components of Cannabis sativa L., and their derivatives, have been reported as palliative adjuvants to conventional chemotherapeutic regimens. Cannabinoid effects are known to be mediated through the activation of cannabinoid receptors. To date, two cannabinoid receptors, cannabinoid receptor 1 and 2, have been cloned and identified from mammalian tissues. Cannabinoids exert a remarkable antitumoral effect on pancreatic cancer cells, due to their ability to selectively induce apoptosis of these cells. This review strengthens the perception that cannabinoid receptors might be useful in clinical testing to prognose and treat pancreatic cancer. Many studies have tried to describe the mechanism of cell death induced by cannabinoids. The aim of this review is to discuss the effects of cannabinoid receptors in pancreatic cancer in order to provide a brief insight into cannabinoids and their receptors as pancreatic cancer biomarkers and in therapeutic strategies.

The Impact of Nutritional and Functional Status on Postoperative Outcomes following Esophageal Cancer Surgery.

Malnourished patients undergoing esophagectomy have increased risk of postoperative complications. The aim of the current study was to identify nutritional and functional risk factors for postoperative complications in patients with esophageal and gastroesophageal junction cancer who underwent esophagectomy. Seventy patients who were admitted at the First Department of Surgery, Laikon General Hospital, Athens, Greece, were included in this study. Laboratory data and data regarding nutritional and functional status were recorded preoperatively. Postoperative complications were graded according to Clavien-Dindo classification. Thirty-seven patients (52.9%) developed postoperative complications. Albumin and Geriatric Nutritional Risk Index (GNRI) levels were lower in patients who developed major complications compared to patients who did not develop postoperative complications (3.90 ± 0.44 vs 4.18 ± 0.37 g/dL, p = 0.014 and 107.40 ± 15.76 vs 114.98 ± 12.26, p = 0.050 respectively). Major complications were associated with higher percentage of weight loss (12.1 ± 11.1 vs 6.2 ± 7.5%, p = 0.019) and with low handgrip strength (80 vs 16.9%, p = 0.006). Albumin (3.93 ± 0.18 vs 4.15 ± 0.41 g/dL, p = 0.019) and low muscle mass (22.6 vs 2.8%, p = 0.016) were significantly associated with anastomotic leakage occurence. The incorporation of patients' nutritional and functional status in the preoperative risk assessment might increase prognostic ability concerning postoperative complications of patients undergoing esophagectomy.

All that Glitters is not Cholecystitis. A Rare Presentation of Acute Pericarditis Mimicking Cholecystitis and Review of the Literature.

Acute pericarditis is the most common inflammatory disorder of the pericardium, responsible for approximately 5% of visits to the emergency departments, concerning chest pain without myocardial infarction. We report a case of a 41-year-old man who presented to our hospital, complaining about retrosternal and epigastrium pain. The transthoracic echocardiogram showed pericardial effusion while the electrocardiogram and laboratory findings revealed acute pericarditis. An abdominal ultrasound revealed gallbladder edema. The pericardial effusion was treated with pericardial catheter insertion, diuretics, and nonsteroidal anti-inflammatory drugs. This case shows that acute pericarditis can be clinically presented with many ways, one of them being gallbladder edema. Furthermore, in this case-based review we present all cases of simultaneous appearance of pericarditis and acalculous cholecystitis or gallbladder edema.

Histone Deacetylases and their Inhibitors in Colorectal Cancer Therapy: Current Evidence and Future Considerations.

Colorectal cancer (CRC) comprises a heterogeneous group of gastrointestinal tract tumors. It is a multifactorial disease, and a plethora of distinct factors are involved in its pathogenesis and pathophysiology. The development of CRC is not limited to genetic changes, but epigenetic and environmental factors are also involved. Among the epigenetic factors, histone deacetylases (HDACs), a group of epigenetic enzymes that regulate gene expression, have been reported to be over-expressed in CRC. HDACs and their inhibitors seem to play an important role in the molecular pathophysiology of CRC. The aim of this review was to define the role of HDAC inhibitors as potential anticancer agents against CRC.

Role of histone deacetylase inhibitors in diabetic cardiomyopathy in experimental models (Review).

In diabetes, metabolic dysregulation, caused by hyperglycemia, leads to both structural and functional changes in cardiomyocytes and subsequently leads to the development of cardiomyopathy. Histone deacetylases (HDAC) are enzymes that regulate gene transcription. Their actions have been examined in the development of multiple disorders, such as cardiovascular diseases and diabetes. The use of HDAC inhibitors (HDACIs), as potential therapeutic agents against disease progression has yielded promising results. The present review article reports preclinical trials identified in which HDACIs were administered to mice suffering from diabetic cardiomyopathy (DCM), and discusses the role and mechanisms of action of HDAC and HDACIs in DCM. A review of the literature was performed using the PubMed database, aiming to identify publications in the English language concerning the role of HDACIs in DCM. More specifically, key words, separately and in various combinations, such as HDACIs, HDAC, diabetes, cardiomyopathy, heart failure and ischemia/reperfusion injury, were used. Furthermore, the references from all the articles were cross-checked in order to include any other eligible studies. The full-text articles assessed for eligibility were eight, covering the period from 2015 to 2019; finally, all of them were included. The use of HDACIs exhibited encouraging results against DCM progression through various mechanisms, including the reduction of reactive oxygen species generation, inflammatory cytokine production and fibrosis, and an increase in autophagy and angiogenesis.

Comment on renal autotransplantation: A final option to preserve the kidney after an iatrogenic ureteral injury.

To the Editor, Autologous Renal Transplantation (ART) since firstly described in 1963 by Hardy, has been used in various cases. There are various reasons for the transplantation such as iatrogenic ureteral damage, chronic kidney pain, unresectable renal tumors or renovascular diseases. Indications concerning the suitable patients for this kind of procedure are gradually increasing. Nevertheless, each case is unique, and the treatment must be personalized [...].