Validation of Perioperative Troponin Levels for Predicting Postoperative Mortality and Long-Term Survival in Patients Undergoing Surgery for Hepatobiliary and Pancreatic Cancer.

Background: Hepatopancreato and biliary (HPB) tumors represent some of the leading cancer-related causes of death worldwide, with the majority of patients undergoing surgery in the context of a multimodal treatment strategy. Consequently, the implementation of an accurate risk stratification tool is crucial to facilitate informed consent, along with clinical decision making, and to compare surgical outcomes among different healthcare providers for either service evaluation or clinical audit. Perioperative troponin levels have been proposed as a feasible and easy-to-use tool in order to evaluate the risk of postoperative myocardial injury and 30-day mortality. The purpose of the present study is to validate the perioperative troponin levels as a prognostic factor regarding postoperative myocardial injury and 30-day mortality in Greek adult patients undergoing HPB surgery. Method: In total, 195 patients undergoing surgery performed by a single surgical team in a single tertiary hospital (2020-2022) were included. Perioperative levels of troponin before surgery and at 24 and 48 h postoperatively were assessed. Model accuracy was assessed by observed-to-expected (O:E) ratios, and area under the receiver operating characteristic curve (AUC). Survival at one year postoperatively was compared between patients with high and normal TnT levels at 24 h postoperatively. Results: Thirteen patients (6.6%) died within 30 days of surgery. TnT levels at 24 h postoperatively were associated with excellent discrimination and provided the best-performing calibration. Patients with normal TnT levels at 24 h postoperatively were associated with higher long-term survival compared to those with high TnT levels. Conclusions: TnT at 24 h postoperatively is an efficient risk assessment tool that should be implemented in the perioperative pathway of patients undergoing surgery for HPB cancer.

The Genomic Signatures of Linitis Plastica Signal the Entrance into a New Era: Novel Approaches for Diagnosis and Treatment.

Linitis Plastica (LP) is a rare and aggressive tumor with a distinctive development pattern, leading to the infiltration of the gastric wall, the thickening of the gastric folds and a "leather bottle appearance". LP is an extremely heterogeneous tumor caused by mutations in oncogenic and tumor suppressive genes, as well as molecular pathways, along with mutations in stromal cells and proteins related to tight junctions. Elucidating the molecular background of tumorigenesis and clarifying the correlation between cancerous cells and stromal cells are crucial steps toward discovering novel diagnostic methods, biomarkers and therapeutic targets/agents. Surgery plays a pivotal role in LP management, serving both as a palliative and curative procedure. In this comprehensive review, we aim to present all recent data on the molecular background of LP and the novel approaches to its management.

Validation of the Surgical Outcome Risk Tool (SORT) and SORT v2 for Predicting Postoperative Mortality in Patients with Pancreatic Cancer Undergoing Surgery.

BACKGROUND: Pancreatic cancer surgery is related to significant mortality, thus necessitating the accurate assessment of perioperative risk to enhance treatment decision making. A Surgical Outcome Risk Tool (SORT) and SORT v2 have been developed to provide enhanced risk stratification. Our aim was to validate the accuracy of SORT and SORT v2 in pancreatic cancer surgery. METHOD: Two hundred and twelve patients were included and underwent pancreatic surgery for cancer. The surgeries were performed by a single surgical team in a single tertiary hospital (2016-2022). We assessed a total of four risk models: SORT, SORT v2, POSSUM (Physiology and Operative Severity Score for the enumeration of Mortality and Morbidity), and P-POSSUM (Portsmouth-POSSUM). The accuracy of the model was evaluated using an observed-to-expected (O:E) ratio and the area under the curve (AUC). RESULTS: The 30-day mortality rate was 3.3% (7 patients). Both SORT and SORT v2 demonstrated excellent discrimination traits (AUC: 0.98 and AUC: 0.98, respectively) and provided the best-performing calibration in the total analysis. However, both tools underestimated the 30-day mortality. Furthermore, both reported a high level of calibration and discrimination in the subgroup of patients undergoing pancreaticoduodenectomy, with previous ERCP, and CA19-9 ≥ 500 U/mL. CONCLUSIONS: SORT and SORT v2 are efficient risk-assessment tools that should be adopted in the perioperative pathway, shared decision-making (SDM) process, and counseling of patients with pancreatic cancer undergoing surgery.

Bioinformatic Analysis of the BCL-xL/BCL2L1 Interactome in Patients with Pancreatic Cancer.

Objectives: The aim of the present study was to analyze the differential gene expression of BCL-xL/BCL2L and the associated genetic, molecular, and biologic functions in pancreatic ductal adenocarcinoma (PDAC) by employing advanced bioinformatics to investigate potential candidate genes implicated in the pathogenesis of PDAC. Materials and Methods: Bioinformatic techniques were employed to build the gene network of BCL-xL, to assess the translational profile of BCL-xL in PDAC, assess its role in predicting PDAC, and investigate the associated biologic functions and the regulating miRNA families. Results: Microarray data extracted from one dataset was incorporated, including 130 samples (PDAC: 69; Control: 61). In addition, the expression level of BCL-xL was higher in PDAC compared to control samples (p < 0.001). Furthermore, BCL-xL demonstrated excellent discrimination (AUC: 0.83 [95% Confidence Intervals: 0.76, 0.90]; p < 0.001) and calibration (R squared: 0.31) traits for PDAC. A gene set enrichment analysis (GSEA) demonstrated the molecular functions and miRNA families (hsa-miR-4804-5p, hsa-miR-4776-5p, hsa-miR-6770-3p, hsa-miR-3619-3p, and hsa-miR-7152-3p) related to BCL-xL. Conclusions: The current findings unveil the biological implications of BCL-xL in PDAC and the related molecular functions and miRNA families.

Meta-analysis of robot-assisted versus video-assisted McKeown esophagectomy for esophageal cancer.

We aim to review the available literature on patients with esophageal cancer treated with robot-assisted (RAME) or video-assisted McKeown's esophagectomy (VAME), to compare the efficacy and safety of the two approaches. Original research studies that evaluated perioperative and oncologic outcomes of RAME versus VAME were identified, from January 1990 to July 2022. The 90-day mortality, the R0 resection rate, the dissected lymph nodes, the perioperative parameters, and the complications were calculated according to a fixed and a random effect model. The Q statistics and I2 statistic were used to test for heterogeneity among the studies. Seven studies were included, incorporating a total of 1617 patients treated with RAME or VAME. The 90-day mortality was similar between the two groups. No difference was found regarding the R0 resection rate and the number of dissected lymph nodes. In addition, the perioperative parameters, along with the total complications were similar between RAME and VAME. Nonetheless, the incidence of postoperative pneumonia was higher in the VAME group (OR:0.67 [95% CI: 0.49, 0.93]; p = 0.02). Finally, our outcomes were further validated by sensitivity analysis including only studies performing propensity score-matched analysis. Our meta-analysis showed that RAME was equivalent to VAME in terms of safety, feasibility, and oncologic adequacy. These results should be interpreted with caution due to the small number of included studies. New Randomized Controlled trials, that are currently active, will provide further evidence with greater clarity to assess the effectiveness and safety of RAME for esophageal cancer.

Establishment of Patient-derived Orthotopic Xenografts (PDX) as Models for Pancreatic Ductal Adenocarcinoma.

BACKGROUND/AIM: Pancreatic cancer (PC) is one of the leading causes of cancer-related death. The purpose of the present study was to establish a patient-derived orthotopic xenograft model (PDOX) for pancreatic ductal adenocarcinoma (PDAC), thus providing a tumor microenvironment resembling that of the human pancreas to identify novel potential biomarkers and treatment regimens. MATERIALS AND METHODS: PDAC tissue samples were received from 35 patients, following informed consent, and three mouse strains were implemented. RESULTS: Successful PDOX engraftment was performed in nonobese diabetic/severe combined immunodeficient (NOD/SCID) and NOD/SCID gamma (NSG) mice. Nonetheless, we found a higher rate of successful engraftment and tumor growth in NSG compared to NOD/SCID mice, possibly owning to the different level of immunosuppression and more specifically of the natural killer cells presence. CONCLUSION: Our suggested PDOX model represents a preclinical cancer research model with a high affinity for the patient's tumor microenvironment, thus enabling the acceleration of PDAC research.

Surgical versus non-operative initial management of post-endoscopic retrograde cholangiopancreatography perforation: a systematic review and meta-analysis.

BACKGROUND: In the present study we performed a systematic review and meta-analysis regarding the initial management of perforations following endoscopic retrograde cholangiopancreatography (ERCP). METHOD: A systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. RESULT: In total, 10 comparative studies and 223 patients with post-ERCP perforations were included in the present study. In type I and II perforations, the success rate of initial surgical management was higher compared to the non-operative management (NOM) group (P=0.09 and P=0.02, respectively). There was no statistically significant difference in mortality rates or length of hospital stay between initial surgical and NOM management for any type of perforation. CONCLUSIONS: The current meta-analysis demonstrated the significance of the initial management of patients with post-ERCP perforations. Whether a surgical or an endoscopic approach is chosen, the patient should immediately be evaluated by an experienced surgeon or endoscopist.

Metastatic rectal cancer in the ampulla of Vater: A unique case.

BACKGROUND: A metastatic lesion located in the ampulla of Vater is considered extremely rare, with only 32 cases reported globally. CASE: A 65-year-old patient was primarily diagnosed with a rectal adenocarcinoma. Twenty-four months later as part of the oncological follow-up, the patient was diagnosed with a single secondary tumor in the ampulla of Vater. After undergoing a pancreaticoduodenectomy (Whipple procedure), the patient experienced an uneventful recovery and received adjuvant chemotherapy. Sixteen months later the patient remained disease-free. CONCLUSION: To the best of our knowledge, the present case represents the first reported metastatic tumor in the ampulla of Vater, originating from a rectal adenocarcinoma. This case underlines the critical role of immunohistochemistry in arriving at a correct diagnosis in order to guide clinical decision-making.

A meta-analysis evaluating the role of high-intensity focused ultrasound (HIFU) as a fourth treatment modality for patients with locally advanced pancreatic cancer.

BACKGROUND: This study aimed to evaluate the outcomes of high-intensity focused ultrasound (HIFU) on patients with advanced pancreatic cancer. METHODS: A literature search was performed in PubMed, Scopus and Cochrane databases, in accordance with the PRISMA guidelines. The Odds Ratio, Weighted Mean Difference, and 95% Confidence Interval were evaluated by means of the Random-Effects model. RESULTS: Nineteen articles met the inclusion criteria, incorporating 939 patients. This study reveals that patients in the HIFU group presented increased median overall survival (OS), along with higher OS at 6 and 12 months after treatment compared with the control group (p < 0.05). Furthermore, patients treated with HIFU in conjunction with chemotherapy presented reduced levels of pain (p < 0.05) compared to the traditional treatment group. In addition, HIFU contributed to significant tumor responsiveness, in terms of CA19-9 reduction (p < 0.05). Finally, HIFU was a considerably safe treatment modality with a low incidence of complications. CONCLUSION: These outcomes suggest that HIFU is a feasible and safe treatment modality for patients with advanced pancreatic cancer and provides enhanced outcomes regarding survival and quality of life. Given the lack of a significant number of randomized clinical trials, this meta-analysis represents the best currently available evidence. New randomized trials assessing HIFU are necessary to further evaluate their outcomes.

The surgical challenge of oligometastatic pancreatic cancer: A systemic review of the literature.

PURPOSE: We aim to review the available literature on surgical management of oligometastatic pancreatic ductal adenocarcinoma (PDAC), in order to assess the clinical outcomes and intraoperative parameters of the different strategies. METHODS: A systematic literature search was performed in PubMed database, in accordance with the PRISMA guidelines. Nine studies met the inclusion criteria incorporating 401 patients. RESULTS: Perioperative mortality was as low as 0%, regarding resection of pancreatic cancer combined with synchronous metastasectomy. CONCLUSIONS: Currently, postoperative overall survival and progression-free survival have increased compared to previous trials. Nevertheless, the lack of precise operative indications delays the enhancement of survival rates. Well-designed, randomized controlled studies, assessing pancreatic surgery combined with metastasectomy, are necessary to further assess their clinical outcomes.

MTL-CEBPA Combined with Immunotherapy or RFA Enhances Immunological Anti-Tumor Response in Preclinical Models.

The transcription factor CEBPA is a master regulator of liver homeostasis, myeloid cell differentiation and is downregulated in several oncogenic diseases. MTL-CEBPA is a small activating RNA drug which upregulates gene expression of CEBPA for treatment of hepatocellular carcinoma (HCC). We investigate whether MTL-CEBPA has immune modulatory effects by combining MTL-CEBPA with an anti-PD-1 checkpoint inhibitor (CPI) and/or radiofrequency ablation (RFA) in two preclinical models. First, mice with two flanks of HCC tumors (BNL) were treated with combinations of RFA (right flank), anti-PD-1 or MTL-CEBPA. The reduction of the left flank tumors was most pronounced in the group treated with RFA+anti-PD1+MTL-CEBPA and 7/8 animals responded. This was the only group with a significant increase in CD8+ and CD49b+/CD45+ tumor infiltrating lymphocytes (TIL). Second, a combination of anti-PD-1+MTL-CEBPA was tested in a CT26 colon cancer model and this treatment significantly reduced tumor size, modulated the tumor immune microenvironment and increased TILs. These data suggest a clinical role for combination treatment with CPIs, RFA and MTL-CEBPA through synergistic priming of the immune tumor response, enabling RFA and CPIs to have a pronounced anti-tumor effect including activity in non-treated tumors in the case of RFA.

Differences in surgical oncology practice in Greece and Cyprus between the first and second COVID-19 pandemic waves: Lessons from a paradigm shift.

The SARS-CoV-2 (COVID-19) pandemic has led to the implementation of certain restrictions and rearrangements regarding the surgical oncology operations, thus affecting the surgical lists, the availability of surgical time, along with the consultations of oncologic patients. The purpose of the present study was to identify the differences in surgical oncology practices in Greece and Cyprus between the first and second pandemic waves. We designed a questionnaire for surgeons treating surgical oncology patients. A total of 104 surgeons participated in the present study by answering our questionnaire. According to our outcomes, there was a significant shift between the two waves in patients' willingness to undergo surgery and to present to consultations. Nonetheless, the availability of surgical services remained limited. The consequent mismatch in patients' needs and the availability of healthcare services, we demonstrate herein, is alarming and should be taken into consideration by the policymakers.

How to tie dangerous surgical knots: easily. Can we avoid this?

OBJECTIVE: Secure knots are essential in all areas of surgical, medical and veterinary practice. Our hypothesis was that technique of formation of each layer of a surgical knot was important to its security. DESIGN: Equal numbers of knots were tied, by each of three groups, using three techniques, for each of four suture materials; a standard flat reef knot (FRK), knots tied under tension (TK) and knots laid without appropriate hand crossing (NHCK). Each knot technique was performed reproducibly, and tested by distraction with increasing force, till each material broke or the knot separated completely. SETTING: Temporary knot tying laboratory. MATERIALS: The suture materials were, 2/0 polyglactin 910 (Vicryl), 3/0 polydioxanone, 4/0 poliglecaprone 25 (Monocryl) and 1 nylon (Ethilon). PARTICIPANTS: Three groups comprised, a senior surgeon, a resident surgeon and three medical students. OUTCOME MEASURES: Proportion of each knot type that slipped, degree of slippage and length of suture held in loop secured by each knot type. RESULTS: 20% of FRK tied with all suture materials slipped; all knots tied with the other two techniques, with all materials, slipped, TK (100%) and NHCK (100%). The quantitative degree of slip was significantly less for FRK (mean 6.3%-, 95% CI 2.2% to 10.4%) than for TK (mean 312%, 95% CI 280.0% to 344.0%) and NHCK (mean 113.0%, -95% CI 94.3% to 131.0%).The mean length of suture in loops held within (FRK mean 25.1 mm 95% CI 24.2 to 26.0 mm) was significantly greater than mean lengths held by the other techniques (TK mean 17.0 mm, 95% CI 16.3 to 17.7 mm), (NHCK mean 16.3 mm, 95% CI 15.9 to 16.7 mm). The latter two types of knot may have tightened more than anticipated, in comparison to FRK, with potential undue tissue tension. CONCLUSION: Meticulous technique of knot tying is essential for secure knots, appropriate tissue tension and the security of anastomoses and haemostasis effected.

In Silico Transcriptomic Analysis of the Chloride Intracellular Channels (CLIC) Interactome Identifies a Molecular Panel of Seven Prognostic Markers in Patients with Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. In this context, the identification of biomarkers regarding the PDAC diagnosis, monitoring, and prognosis is crucial. OBJECTIVES: The purpose of the current study was to investigate the differential gene expression profile of the chloride intracellular channel (CLIC) gene family network in patients with PDAC, in order to suggest novel biomarkers. METHODS: In silico techniques were used to construct the interactome of the CLIC gene family, identify the differentially expressed genes (DEGs) in PDAC as compared to healthy controls, and evaluate their potential prognostic role. RESULTS: Transcriptomic data of three microarray datasets were included, incorporating 114 tumor and 59 normal pancreatic samples. Twenty DEGs were identified; eight were up-regulated and twelve were downregulated. A molecular signature of seven genes (Chloride Intracellular Channel 1 - CLIC1; Chloride Intracellular Channel 3 - CLIC3; Chloride Intracellular Channel 4 - CLIC4; Ganglioside Induced Differentiation Associated Protein 1 - GDAP1; Ganglioside Induced Differentiation Associated Protein 1 Like 1 - GDAP1L1; Glutathione S-Transferase Pi 1 - GSTP1; Prostaglandin E Synthase 2 - PTGES2) were identified as prognostic markers associated with overall survival. Positive correlations were reported regarding the expression of CLIC1-CLIC3, CLIC4-CLIC5, and CLIC5-CLIC6. Finally, gene set enrichment analysis demonstrated the molecular functions and miRNA families (hsa-miR-122, hsa-miR-618, hsa-miR-425, and hsa-miR-518) relevant to the seven prognostic markers. CONCLUSION: These outcomes demonstrate a seven-gene molecular panel that predicts the patients' prospective survival following pancreatic resection for PDAC.