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.

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas: An individual participant data meta-analysis.

Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGCs) of the pancreas is a rare neoplasm that accounts for less than 1% of all pancreatic malignancies. The aim of this study was to review the literature regarding UC-OGC, and to highlight its biological behavior, clinicopathologic characteristics, prognosis, and therapeutic options. A systematic review of the literature in PubMed/Medline and Scopus databases was performed (last search October 31st, 2023) for articles concerning pancreatic UC-OGC in the adult population. Fifty-seven studies met the inclusion criteria, involving 69 patients with a male-to-female ratio of 1.1:1 and a mean age of 62.96. Main symptoms included abdominal pain (33.3%), jaundice (14.5%), weight loss (8.7%), while fourteen patients (20.3%) were asymptomatic. Surgical resection was performed in 88.4% of cases. Survival rates at one, three, and five years were 58%, 44.7%, and 37.3% respectively. Sex, age, size (cut-off of 4 cm), location, and adjuvant treatment did not significantly affect patient survival. UC-OGC of the pancreas is a rare subtype of undifferentiated pancreatic carcinoma with a better prognosis than conventional pancreatic ductal adenocarcinoma or undifferentiated carcinoma without giant cells. The establishment of a dedicated patient registry is imperative to further delineate the optimal treatment for this uncommon clinical entity.

The Impact of Mechanical Bowel Preparation and Oral Antibiotics in Colorectal Cancer Surgery (MECCA Study): A Prospective Randomized Clinical Trial.

Background: Colorectal cancer surgery has been associated with surgical site infections (SSIs), leading to an increase in postoperative morbidity, length of stay and total cost. The aim of the present randomized study was to investigate the relationship between the preoperative administration of oral antibiotic therapy and SSI rate, as well as other postoperative outcomes in patients undergoing colorectal cancer surgery. Material and Methods: Patients who underwent colorectal cancer surgery in a university surgical department were included in the present study. Patients were randomized into two groups using the "block randomization" method. The intervention group received three doses of 400 mg rifaximin and one dose of 500 mg metronidazole per os, as well as mechanical bowel preparation the day before surgery. The control group underwent only mechanical bowel preparation the day before surgery. The study has been registered in ClinicalTrials.gov (NCT03563586). Results: Two hundred and five patients were finally included in the present study, 97 of whom received preoperative antibiotic therapy per os (intervention group). Patients of this group demonstrated a significantly lower SSI rate compared with patients who did not receive preoperative antibiotic therapy (7% vs. 16%, p = 0.049). However, preoperative antibiotic administration was not correlated with any other postoperative outcome (anastomotic leak, overall complications, readmissions, length of stay). Conclusions: Preoperative antibiotic therapy in combination with mechanical bowel preparation seemed to be correlated with a lower SSI rate after colorectal cancer surgery.

Malignant Bowel Obstruction: A Retrospective Multicenter Cohort Study.

BACKGROUND: Malignant bowel obstruction (MBO) is a serious clinical entity that requires surgical intervention in almost 50% of cases. However, overall survival remains low even for operable cases. The aim of the present study was to investigate the correlation between patients' characteristics, perioperative details, histopathological results and postoperative outcomes of patients who were operated on due to MBO. METHODS: A retrospective search of patients who were operated on due to MBO in a university and a rural hospital was conducted. Patients' characteristics, perioperative details, histopathological results and postoperative outcomes were reported. Univariable and multivariable analysis was performed. RESULTS: Seventy patients were included with a mean age of 76.1 ± 10.6 years. The 30-day mortality rate was 18.6%, the Intensive Care Unit (ICU) admission rate was 17.1% and the mean length of stay (LOS) was 12.4 ± 5.7 days. Postoperative 30-day mortality was associated with increased age, known malignant recurrence, microscopically visible metastatic foci and defunctioning stoma creation. Colorectal malignancy type, sigmoid obstruction and primary anastomosis were correlated with decreased 30-day mortality. In addition, operation at the university hospital led to increased LOS, while stoma creation led to decreased LOS. Finally, ICU admission rates were increased for operations at university hospitals, at least one comorbidity, known malignant recurrence and longer preoperative waiting interval, whereas they were decreased for colorectal primary malignancy type. CONCLUSIONS: Surgery due to MBO leads to increased morbidity and mortality. Therefore, prospective studies are needed to highlight inter-patient differences regarding the best individualized therapeutic strategy.

Adherence to Oral Nutrition Supplementation in Gastrointestinal Cancer Patients: A Systematic Review of the Literature.

The prevalence of malnutrition is high in gastrointestinal (GI) cancer patients. The use of oral nutrition supplementation (ONS) as part of patients' nutritional therapy seems to be effective in the improvement of nutritional status. Nevertheless, oncology patients, experience several symptoms that negatively affect their compliance with ONS products. Τhe aim of this systematic review is to examine the factors affecting compliance with ONS in patients who underwent GI cancer surgery and/or adjuvant treatments. A systematic search was conducted to identify studies published until June 2023 that assessed compliance to ONS in GI cancer patients. Eleven studies fulfilled the eligibility criteria and were included in the analysis. Postoperative compliance with ONS among GI cancer surgery patients ranged between 26.2% and 71.1%, whereas in GI cancer patients receiving chemotherapy the average reported rate was 90.2%. The main reasons for noncompliance were the presence of GI symptoms, such as early satiety, bloating, and diarrhea after ONS consumption, as well as taste alterations that result in aversion to the provided ONS. Frequent monitoring of these patients is crucial in order to record adverse effects, identify patients that are in need of personalized guidance at an early stage and motivate them to follow their ONS plan.

Exploring the Impact of Cyanidin-3-Glucoside on Inflammatory Bowel Diseases: Investigating New Mechanisms for Emerging Interventions.

Cyanidin-3-O-glucoside (C3G), the most widely distributed anthocyanin (ACN) in edible fruits, has been proposed for several bioactivities, including anti-inflammatory, neuro-protective, antimicrobial, anti-viral, anti-thrombotic and epigenetic actions. However, habitual intake of ACNs and C3G may vary widely among populations, regions, and seasons, among individuals with different education and financial status. The main point of C3G absorption occurs in the small and large bowel. Therefore, it has been supposed that the treating properties of C3G might affect inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn's disease (CD). IBDs develop through complex inflammatory pathways and sometimes may be resistant to conventional treatment strategies. C3G presents antioxidative, anti-inflammatory, cytoprotective, and antimicrobial effects useful for IBD management. In particular, different studies have demonstrated that C3G inhibits NF-κB pathway activation. In addition, C3G activates the Nrf2 pathway. On the other hand, it modulates the expression of antioxidant enzymes and cytoprotective proteins, such as NAD(P)H, superoxide dismutase, heme-oxygenase (HO-1), thioredoxin, quinone reductase-oxide 1 (NQO1), catalase, glutathione S-transferase and glutathione peroxidase. Interferon I and II pathways are downregulated by C3G inhibiting interferon-mediating inflammatory cascades. Moreover, C3G reduces reactive species and pro-inflammatory cytokines, such as C reactive protein, interferon-γ, tumor necrosis factor-α, interleukin (IL)-5, IL-9, IL-10, IL-12p70, and IL-17A in UC and CD patients. Finally, C3G modulates gut microbiota by inducing an increase in beneficial gut bacteria and increasing microbial abundances, thus mitigating dysbiosis. Thus, C3G presents activities that may have potential therapeutic and protective actions against IBD. Still, in the future, clinical trials should be designed to investigate the bioavailability of C3G in IBD patients and the proper therapeutic doses through different sources, aiming to the standardization of the exact clinical outcome and efficacy of C3G.

Primary immature teratoma of the thigh: a review.

Teratomas are a subtype of germ cell tumors composed of a variety of somatic tissues derived from more than one of the three germinal layers (ectoderm, endoderm and mesoderm). They can be classified as mature tumors and immature tumors. Teratomas most commonly arise at the sacrococcygeal region and the gonads. The occurrence of a teratoma outside the common gonadal and midline locations is exceptional. This review article lists the reported primary and metastatic malignant teratomas in extragonadal locations and discusses the possible explanation for the atypical location, their treatment and prognosis.

The Prognostic Role of GLIM Criteria in Postoperative Outcomes after Upper Gastrointestinal Cancer Surgery: A Meta-Analysis of Observational Studies.

Oncologic patients often suffer from malnutrition, which might negatively affect treatment outcomes. Global Leadership Initiative on Malnutrition (GLIM)-based malnutrition is associated with short- and long-term outcomes in cancer patients. The aim of the current meta-analysis was to determine the impact of GLIM-defined malnutrition on postoperative complications and survival in esophageal and gastric cancer patients. A systematic search was conducted to identify studies published until February 2022 that assessed the association between GLIM criteria and short- and long-term outcomes in esophageal and gastric cancer patients. We included seven observational studies reporting on a total of 3662 patients with esophageal and gastric cancer. GLIM-defined malnutrition was associated with increased overall complications (pooled HR 2.58, 95% CI 1.45-4.59, p = 0.001). Malnutrition was significantly associated with decreased overall survival (pooled HR 1.63, 95% CI 1.18-1.84, p = 0.003) as well as with decreased disease-free survival (pooled HR 1.78, 95% CI 1.36-2.33, p < 0.0001). GLIM-based malnutrition was associated with an increased risk for developing postoperative complications and impaired survival of esophageal and gastric cancer patients. Our findings support the use of GLIM criteria in clinical practice as a relatively simple and reliable tool for assessing the nutritional status of oncologic patients.

Somatostatinoma of the Ampulla of Vater: A Systematic Review.

BACKGROUND AND AIMS: Somatostatinoma of the ampulla of Vater (SAV) is a rare neuroendocrine tumor that usually appears with atypical clinical manifestations and is associated with Von Recklinghausen's disease. The aims of this study were to systematically review the literature regarding SAV and to highlight the clinicopathological characteristics and optimal therapeutic management of this rare entity. METHODS: A systematic search of the literature in PubMed/Medline and Scopus databases was performed by two independent investigators, including all case reports and case series concerning SAVs from 1980 until September 2021. RESULTS: In total, 37 articles were retrieved, including 43 patients, with a male to female ratio of 1.8:1 and a mean age of 46.8 ± 11.3 years (mean, SD). For 23 out of 43 patients (53.5%), Von Recklinghausen's disease was proved. The main clinical manifestations were abdominal pain (41.9%), jaundice (27.9%), weight loss (20.9%) and bowel disorders (20.9%). Typical histological findings included psammoma bodies, nests or clusters of epithelial cells with eosinophilic cytoplasm, while somatostatin staining was positive in 35 patients (81.4%), chromogranin-A in 21 patients (48.8%) and synaptophysin in 18 patients (41.9%). Surgery was the initial therapeutic approach in 34 patients (79.1%), whereas Whipple's procedure was the preferred surgical approach in 23 patients (53.4%). The longest survival among included patients was 13 years and only two postoperative deaths (4.7%) were reported. CONCLUSIONS: Somatostatinomas of the ampulla of Vater are rare malignancies that require increased physicians' suspicion and accurate surgical approach in order to achieve optimal therapeutic results.

The impact of surgery delay on survival of resectable pancreatic cancer: A systematic review of observational studies.

BACKGROUND: Pancreatic cancer is considered a lethal disease and the only potentially curative option is R0 excision. The aim of this study was to investigate whether the waiting time interval from diagnosis to surgical treatment affects overall survival in patients who undergo curative-intent surgery for pancreatic cancer. METHODS: Search in Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases was conducted from inception until April 2022. RESULTS: Overall, 10 studies were included that enrolled 181,344 patients. The dominating cut-off time point was 4 weeks in studies which utilized a biphasic waiting time pattern. In addition, prolonged waiting time interval was associated with decreased overall survival in 3 studies, whereas it demonstrated a favorable effect on overall survival in 2 studies and no impact on survival in 5 studies. CONCLUSION: The great diversity that was observed regarding the impact of surgery delay on survival underlines the lack of knowledge about biologic pathways of pancreatic cancer. Novel imaging studies and molecular "fingerprints" in combination to time-to-treatment standardization in the design of future randomized trials could lead to the recognition of patients that could benefit from a timely resection.

PD-L1 Gene Polymorphisms rs822336 G>C and rs822337 T>A: Promising Prognostic Markers in Triple Negative Breast Cancer Patients

Background and Objectives: Triple-negative breast cancer (TNBC) is a highly heterogeneous subtype that is associated with unresponsiveness to therapy and hence with high mortality rates. In this study we aimed to investigate the prognostic role of the rs822336 G>C and rs822337 T>A polymorphisms of the PD-L1 (Programmed Death-Ligand 1) in TNBC patients. Materials and methods: Formalin-fixed paraffin-embedded tissues from 114 TNBC patients and blood samples from 124 healthy donors were genotyped, and subsequently extensive statistical analysis was performed in order to investigate the clinical value of these polymorphism in TNBC. Results: Regarding rs822336 G>C, we found that the CG genotype was the most common among women that harbored Stage IV breast tumors (81.8%; p = 0.022), recurred (38.9%; p = 0.02) and died (66.7%; p = 0.04). Similarly, the rs822337 T>A genotype AA is associated with worse prognosis, since it was the most common genotype among stage IV tumors (72.7%; p = 0.04) and in TNBC patients that relapsed (75%; p = 0.021) and died (81.5%; p = 0.004). Our statistical analysis revealed that the rs822336 G>C genotype CG and the rs822337 T>A allele AA are strongly associated with inferior DFS and OS intervals. Moreover, it was revealed that women harboring mutated genotypes of both SNPs had shorter disease-free (Kaplan−Meier; p = 0.037, Cox analysis; p = 0.04) and overall (Kaplan−Meier; p = 0.025, Cox analysis; p = 0.03) survival compared to patients having normal genotype of at least one SNP. Multivariate analysis also showed that the presence of mutated genotypes of both SNPs is a strong and independent marker for predicting shorter DFS (p = 0.02) and OS (p = 0.008). Conclusion: Our study revealed that PD-L1 rs822336 G>C and rs822337 T>A polymorphisms were differentially expressed in our cohort of TNBC patients, and that this distribution was associated with markers of unfavorable prognosis and worse survival.

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.

miRNAs expression pattern and machine learning models elucidate risk for gastric GIST.

BACKGROUND: Gatrointestinal stromal tumors (GISTs) are the main mesenchymal tumors found in the gastrointestinal system. GISTs clinical phenotypes differ significantly and their molecular basis is not yet completely known. microRNAs (miRNAs) have been involved in carcinogenesis pathways by regulating gene expression at post-transcriptional level. OBJECTIVE: The aim of the present study was to elucidate the expression profiles of miRNAs relevant to gastric GIST carcinogenesis, and to identify miRNA signatures that can discriminate the GIST from normal cases. METHODS: miRNA expression was tested by miScript™miRNA PCR Array Human Cancer PathwayFinder kit and then we used machine learning in order to find a miRNA profile that can predict the risk for GIST development. RESULTS: A number of miRNAs were found to be differentially expressed in GIST cases compared to healthy controls. Among them the hsa-miR-218-5p was found to be the best predictor for GIST development in our cohort. Additionally, hsa-miR-146a-5p, hsa-miR-222-3p, and hsa-miR-126-3p exhibit significantly lower expression in GIST cases compared to controls and were among the top predictors in all our predictive models. CONCLUSIONS: A machine learning classification approach may be accurate in determining the risk for GIST development in patients. Our findings indicate that a small number of miRNAs, with hsa-miR218-5p as a focus, may strongly affect the prognosis of GISTs.

The Effect of TISSEELTM on Confined Bowel Perforation: An Experimental Study.

OBJECTIVE: During the last decades, surgeons of several specialties presenting different levels of expertise in colon handling have been involved in laparoscopic procedures. The aim of the present experimental study was to investigate the feasibility of TISSEELTM versus the conventional suture placement technique on confined bowel lesions in rats. METHODS: Twenty-four Sprague-Dawley rats underwent confined bowel perforation and were divided into three groups: the SUTURE group (sutures were used), the SUTURE + TISSEELTM group (sutures and TISSEELTM were utilized), and the TISSEELTM group (only TISSEELTM was used). Blinded histopathologic analysis followed animal sacrifice. RESULTS: The median weight of the rats was 526 ± 50 g. A single animal had hematochezia on the first postoperative day. Cessation of bleeding at the perforation margin was indicated intraoperatively after TISSEELTM application. Animals in the TISSEELTM group presented less intraperitoneal adhesions and lower hemorrhagic infiltration compared to animals of the two other groups. In addition, animals in the TISSEELTM group showed thrombus formation at the bowel perforation site compared to animals of the two other groups (p = 0.042). Histopathologic analysis demonstrated reduced inflammatory reaction (p = 0.003), diminished fibrosis (p = 0.001), and better tissue regeneration (p = 0.000) in the TISSEELTM group compared to the other two groups. CONCLUSION: Application of TISSEELTM at the perforation site was associated with increased regeneration of the intestinal wall and less inflammatory and fibrotic reaction compared to suture placement. However, more experimental and clinical studies should be conducted before implementation in humans.

Place of hyperthermic intraperitoneal chemotherapy in the armament against pancreatic adenocarcinoma: A survival, mortality and morbidity systematic review.

Pancreatic adenocarcinoma is one of the deadliest types of cancer worldwide, with a 5-year survival rate of 8% despite recent treatment advancements. The present systematic review aimed to investigate the role of hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical resection for pancreatic adenocarcinoma, with or without peritoneal carcinomatosis. A systematic search of the MEDLINE and SCOPUS electronic databases was performed according to PRISMA guidelines. All possible relevant articles published between January 1980 and May 2019 were retrieved using multiple search terms associated with HIPEC and pancreatic adenocarcinoma. The initial search resulted in 1,244 reports, which condensed to 41 reports following screening of titles and abstracts, and subsequently to four reports following full-text thorough examination. The four reports included involved a prospective cohort study of HIPEC use in resectable pancreatic adenocarcinoma, and three retrospective studies of HIPEC use following cytoreductive surgery for peritoneal carcinomatosis due to pancreatic adenocarcinoma, resulting in a total of 47 patients. The overall survival ranged between 2 and 62 months, and the hospital mortality rate was 8.5%. Morbidity (34%) was mainly attributed to anastomotic leak or respiratory failure. Due to the small sample size and low quality of evidence of the included studies, no valid conclusions could be drawn. Therefore, further studies are required to justify the use of HIPEC as an adjuvant therapy in resectable pancreatic adenocarcinoma, while cytoreductive surgery and HIPEC in peritoneal carcinomatosis of pancreatic origin seems not only not useful but also unsafe at this level of evidence.

Presentation and surgical management of xanthogranulomatous cholecystitis.

BACKGROUND: Xanthogranulomatous cholecystitis (XGC) is a rare benign chronic inflammatory disease of the gallbladder that often presents as cholecystitis and most of the times requires surgical management. In addition, distinguishing XGC from gallbladder cancer preoperatively is still a challenge. The aim of the present systematic review was to outline the clinical presentation and surgical approach of XGC. DATA SOURCES: The present systematic review was designed using the PRISMA and AMSTAR guidelines. We searched MEDLINE, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and Google Scholar databases from inception until June 2020. RESULTS: The laparoscopic cholecystectomy rate (34%) was almost equal to the open cholecystectomy rate (47%) for XGC. An important conversion rate (35%) was observed as well. The XGC cases treated by surgery were associated with low mortality (0.3%), limited intraoperative blood loss (58-270 mL), low complication rates (2%-6%), along with extended operative time (82.6-120 minutes for laparoscopic and 59.6-240 minutes for open cholecystectomy) and hospital stay (3-9 days after laparoscopic and 8.3-18 days after open cholecystectomy). Intraoperative findings during cholecystectomies for XGC included empyema or Mirizzi syndrome. In addition, complex surgical procedures, like wedge hepatic resections and bile duct excision were required during operations for XGC. CONCLUSIONS: XGC seemed to be a rare, benign inflammatory disease that presents similar features as gallbladder cancer. The mortality and complication rates of XGC were low, despite the complex surgical procedures that might be required in some cases.