Search Results (147)

After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany, the retraction of phenformin (N-Phenethylbiguanide) and of Buformin in the USA (but not outside) because of the lethal complication of acidosis seemed to have put an end to the era of the biguanides as oral antidiabetics. The strongly hygroscopic metformin (1-1-dimethylbiguanide), first synthesized 1922 and resuscitated as an oral antidiabetic (type 2 of the elderly) compound first released in 1959 in France and in other European countries, was used in the first large multicenter prospective long-term trial in England in the UKPDS (1977–1997). It was then released in the USA after a short-term prospective trial in healthy overweight “young” type 2 diabetics (mean age 53 years) in 1995 for oral treatment of type 2 diabetes. It was, however, prescribed to mostly multimorbid older patients (above 60–65 years of age). Metformin is now the most used oral drug for type 2 diabetes worldwide. While intravenous administration of biguanides does not have any glucose-lowering effect, their oral administration leads to enormous increase in their intestinal concentration (up to 300-fold compared to that measured in the blood), to reduced absorption of glucose from the diet, to increased excretion of glucose through the stool, and to decrease in insulin serum level through increased hepatic uptake and decreased production. Intravenously injected F18-labeled glucose in metformin-treated type 2 diabetics accumulates in the small and even more in the large intestine. The densitometry picture observed in metformin-treated overweight diabetics is like that observed in patients after bowel-cleansing or chronically taking different types of laxatives, where the accumulated radioactivity can even reach values observed in colon cancer. The glucose-lowering mechanism of action of metformin is therefore not only due to inhibition of glucose uptake in the small intestine but also to “attraction” of glucose from the hepatocyte into the intestine, possibly through the insulin-mediated uptake in the hepatocyte and its secretion into the bile. Furthermore, these compounds have also a diuretic effect (loss of sodium and water in the urine) Acute gastrointestinal side effects accompanied by fluid loss often lead to the drugs’ dose reduction and strongly limit adherence to therapy. Main long-term consequences are “chronic” dehydration, deficiency of vitamin B12 and of iron, and, as observed for all the biguanides, to “chronic” increase in fasting and postprandial lactate plasma level as a laboratory marker of a clinical condition characterized by hypotension, oliguria, adynamia, and evident lactic acidosis. Metformin is not different from the other biguanides: synthalin B, buformin, and phenformin. The mechanism of action of the biguanides as antihyperglycemic substances and their side effects are comparable if not even stronger (abdominal pain, nausea, vomiting, diarrhea, fluid loss) to those of laxatives. Full article

Background: Prehabilitation programs improve postoperative outcomes in vulnerable patients undergoing major surgery. However, current screening tools such as the Malnutrition Universal Screening Tool (MUST) may lack the sensitivity needed to identify those who would benefit most. Muscle quality assessed by Computed Tomography (CT), specifically muscle radiodensity in Hounsfield Units (HUs), has emerged as a promising alternative for risk stratification. Objective: To evaluate the prognostic performance of CT-derived muscle radiodensity in predicting adverse postoperative outcomes in colorectal cancer patients, and to compare it with the performance of the MUST score. Methods: This single-center cross-sectional study included 201 patients with non-metastatic colon cancer undergoing elective laparoscopic resection. Patients were stratified based on enrollment in a multimodal prehabilitation program, either within an Enhanced Recovery After Surgery (ERAS) protocol or a non-ERAS pathway. Nutritional status was assessed using MUST, SARC-F questionnaire (strength, assistance with walking, rise from a chair, climb stairs, and falls), and the Global Leadership Initiative on Malnutrition (GLIM) criteria. CT scans at the L3 level were analyzed using automated segmentation to extract muscle area and radiodensity. Postoperative complications and hospital stay were compared across nutritional screening tools and CT-derived metrics. Results: MUST shows limited sensitivity (<27%) for predicting complications and prolonged hospitalization. In contrast, CT-derived muscle radiodensity demonstrates higher discriminative power (AUC 0.62–0.69), especially using a 37 HU threshold. In the non-ERAS group, patients with HU ≤ 37 had significantly more complications (33% vs. 15%, p = 0.036), longer surgeries, and more severe events (Clavien–Dindo ≥ 3). Conclusions: Opportunistic CT-based assessment of muscle radiodensity outperforms traditional screening tools in identifying patients at risk of poor postoperative outcomes, and may enhance patient selection for prehabilitation strategies like the ERAS program. Full article

There has been a well-documented increase in the incidence of colorectal cancer in patients under 50 years of age. Additionally, these patients present with later-stage cancer at diagnosis compared to their over-50 counterparts. However, there is limited consensus on how the impact of this evolving epidemiology should impact existing prevention and screening tools. Recently proposed strategies include increased genetic testing, improved young patient awareness through targeted media campaigns, and initiatives to increase clinical suspicion in primary care providers. Prevention is further complicated by nuances of treating colorectal cancer in the younger population, with underexplored concerns regarding fertility, sexual health, financial impact, and extended post-treatment surveillance. This review aims to summarize the changing epidemiology of colorectal cancer in young patients, overview existing screening guidelines, and discuss challenges and opportunities surrounding prevention of early-onset colon cancer. Full article

Background: Looking for anomalies and vascular control gains a central role in colon cancer surgery. Complete mesocolic excision (CME) presents technical challenges, primarily due to the considerable variability in the arterial configuration of the right colon. The importance of understanding colonic vascular anatomy has become more prominent with the adoption of this surgical technique. The aim of this study is to systematically review the vascular anatomical variations in the superior mesenteric artery (SMA) in the setting of extended lymphadenectomy for CME in right colon cancer and to show its impact in clinical practice. Methods: A systematic review of the literature on Medline (PubMed), Web of Science (WOS), and Scopus was performed according to PRISMA guidelines. The following criteria were set for inclusion: (1) studies reporting minimally invasive (robotic, laparoscopic, and hybrid techniques) or open CME/D3 lymphadenectomy; (2) studies reporting patients with right-sided colon cancer; (3) studies reporting the description or illustration of SMA variations. The methodological quality of all included studies was evaluated using the Newcastle–Ottawa Scale (NOS). Results: After the literature search, 800 studies were recorded, 31 studies underwent full-text reviews, and 9 studies met the inclusion criteria. All studies reported vascular variations in SMA, and the total number of patients was 813. No intraoperative complications were reported. In 6.4% of patients, post-operative bleeding occurred. Conclusions: Vascular anatomical variations are not a rare entity. In experienced centers, vascular anomalies are not associated with an increase in complications, both in traditional open and minimally invasive surgery (MIS). However, in MIS, full access to central vessels and intraoperative vascular control, moderate retraction, safety maneuvers, and accurate vascular dissection are mandatory. Full article

Objective: Early diagnosis and treatment of metastatic pericardial disease are crucial to prevent the life-threatening complication of cardiac tamponade. Thin Layer Cytology (TLC), a widely adopted technique in cytology, has gained significant acceptance for most specimens. Our study aimed to assess the utility of TLC in diagnosing metastatic neoplasms and their origins in pericardial effusions, as well as monitoring response to chemotherapy. Methods: We examined 184 pericardial fluids collected by pericardiocentesis and processed using the ThinPrep liquid-based technique. Various immunocytochemical markers were used to determine the site of metastatic neoplasms. We also evaluated the response to therapy in 53 patients with lung and breast cancer. Results: Out of 184 specimens, 113 pericardial fluids were diagnosed as positive for malignancy, while 71 were negative. Twenty-three cases of unknown primary site were included in the total positive cases. Ninety cases positive for malignancy had a known primary site of origin, including 31 lung carcinomas, 22 breast carcinomas, 10 ovarian carcinomas, 6 T-cell lymphomas, 3 urinary bladder carcinomas, 4 renal carcinomas, 5 adenocarcinomas of the colon, 5 prostate carcinomas, 2 parotid adenocarcinomas, and 2 melanomas. Regarding the 53 cases with chemotherapy treatment, the cytologic examination of pericardial fluid showed a remarkable reduction in neoplastic burden after the third dose of cisplatin or thiotepa instilled into the pericardial cavity. ThinPrep provided excellent preservation of cytomorphological features, high cellularity per slide, and a clear background. This comprehensive analysis provides crucial information about the types and distribution of cancerous cells present in the samples. Conclusions: Thin Layer Cytology (TLC) is a valuable diagnostic tool for detecting metastatic pericardial malignancy. It allows the examination of exfoliated cells from the pericardial fluid, providing crucial information for diagnosis, management, and monitoring the acute responsiveness to intrapericardial chemotherapy. Immunocytochemistry (IHC) can identify specific markers for various types of cancer, enabling a more accurate diagnosis and guiding further treatment decisions. Full article

Background/Objectives: Opinions concerning the role of obesity and changes in muscle mass in individuals with malignancies vary. It is believed that decreased fat tissue leads to a higher complication rate, while decreased muscle mass results in a poorer oncologic outcome. This study aimed to evaluate the impact of fat distribution and skeletal muscle mass on postoperative morbidity and long-term oncological outcomes in patients with non-metastatic colon cancer. Methods: Between 2012 and 2018, a total of 129 patients with stage I-III colon cancer were evaluated. Abdominal CT scans were used to assess muscle mass and fat tissue (subcutaneous and visceral). Differences in postoperative morbidity and long-term oncologic outcome were analyzed and compared. Results: No significant differences occurred concerning complication rate or anastomotic leakage. Individuals with altered body composition parameters had a shorter length of hospital stay (p = 0.046) and an increased duration of surgery (p = 0.029). In patients with an ASA III score, altered fat tissue distribution was associated with improvements in both overall and disease-free survival (p = 0.031 and p = 0.027, respectively) but also resulted in longer hospital stay. Conclusions: Changes in body composition parameters lead to alterations in economic factors as well as changes in oncologic survival, especially in patients with higher ASA scores. No differences in morbidity were observed. Full article

Radiation-induced intestinal injury (RIII) is a significant concern for cancer patients receiving radiation therapy, as it can lead to complications such as radiation enteropathy. Presently, there are limited options for preventing or treating RIII. Tea polyphenols (TP), found in tea, provide various health benefits, but their antiradiation mechanisms are not fully understood. C57BL/6 mice pre-treated with TP for five days showed a significant improvement in survival rates after being exposed to 10 Gy of ⁶⁰Co radiation. In the same way, abdominal exposure to 15 Gy of ⁶⁰Co radiation effectively mitigated radiation-induced colon shortening, damage to intestinal tissues, oxidative stress, the release of inflammatory factors, and disruptions in intestinal microbial balance. In addition, TP treatment lowered the elevation of reactive oxygen species (ROS), iron imbalance, mitochondrial damage, and ferroptosis in IEC-6 cells post-irradiation. Utilizing network pharmacology, molecular docking, and affinity testing, we identified that TP has the capability to target the Nrf2/HO-1/GPX4 signaling pathway, while EGCG, a principal constituent of TP, interacts with HSP90 and mitigates radiation-induced ferroptosis. These findings suggest that TP may serve as a promising therapeutic agent to alleviate radiation-induced intestinal injury (RII). Full article

Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is a rare congenital coronary anomaly, with an uncertain prevalence and often diagnosed incidentally. This case report presents a 62-year-old male with ARCAPA diagnosed during an evaluation for chest surgery. The patient had a history of colon cancer and active tuberculosis, complicating the clinical management. He reported chest pain, shortness of breath, and palpitations, with atrial fibrillation observed on a 24 h Holter ECG. Coronary angiography revealed robust collateral circulation and a suspected anomalous origin of the right coronary artery, confirmed by CT imaging. The patient’s stress MRI showed mildly reduced left and right ventricular ejection fractions and perfusion deficits in the apical segments (2/17) of the septal and inferior walls. Given the patient’s comorbidities, including active tuberculosis, the Heart team decided on a non-operative management approach, focusing on careful monitoring and pharmacological management rather than immediate surgery. This case emphasizes the complexity of managing ARCAPA in the context of significant comorbidities, highlighting the importance of individualized, multidisciplinary treatment strategies. Early diagnosis using advanced imaging techniques is crucial, and a non-operative approach can be considered in patients with preserved left ventricular function and no significant ischemia, as demonstrated in this case. Full article

Esophageal cancer (EC) is the eighth leading cause of cancer-related deaths globally, largely due to its late-stage diagnosis and aggressive progression. Esophagectomy remains the primary treatment, typically requiring organ-based reconstruction techniques such as gastric pull-up or colonic interposition. However, these reconstruction methods often lead to severe complications, significantly reducing the quality of life of patients. To address these limitations, tissue engineering has emerged as a promising alternative, offering bioengineered patch-type and tubular-type scaffolds designed to restore both structural integrity and functional regeneration. Recent advancements in three-dimensional (3D) biofabrication—including 3D bioprinting, electrospinning, and other cutting-edge techniques—have facilitated the development of patient-specific constructs with improved biocompatibility. Despite significant advancements, critical challenges persist in achieving mechanical durability, multilayered cellular organization, and physiological resilience post-transplantation. Ongoing research continues to address these limitations and enhance clinical applicability. Therefore, this review aims to examine recent advancements in esophageal tissue engineering, with a focus on key biofabrication techniques, preclinical animal models, and the major translational challenges that must be addressed for successful clinical application. Full article

Background: The incidence of external lymphatic fistula (ELF) represents a relatively rare complication after surgery for colorectal cancer, especially in Western countries. However, the rate of this complication is progressively increasing following the introduction of complete mesocolic excision and central vascular ligation with consequent extensive lymphadenectomy. There are no guidelines for the management of ELF, with therapeutic options varying from conservative procedures to more invasive surgeries. The aim of this study was to retrospectively quantify the rate of ELF after surgery for colorectal cancer, to describe its management, and to evaluate its clinical impact on early postoperative outcomes in a tertiary referral European centre. Methods: Data on all patients who underwent surgery for colorectal cancer at our institution between July 2022 and December 2024 were entered into a database. Preoperative, perioperative, and early (within 30 days) postoperative data were recorded. Results: A total of 279 patients underwent elective surgery for colorectal cancer (205 colon and 74 rectum). No postoperative deaths occurred within 30 days after surgery, and the rates of overall and major (grade ≥ 3) postoperative morbidity were 34.7% and 7.1%, respectively. The anastomotic leakage and reoperation rates were 2.8% and 5.3%, respectively. ELFs occurred in 15 patients (5.3%). In all patients, conservative treatment (based on fasting, total parenteral nutrition (TPN), and a prolonged medium-chain triglyceride (MCT) diet) was administered successfully. A recurrent ELF (after the first oral feeding resumption) occurred in four (26.6%) patients, but all were successfully treated with a conservative approach. The occurrence of an ELF prolonged the postoperative length of stay which was 12 days, a length higher than that recorded in patients without ELF. Conclusions: The occurrence of an ELF was found to be a relatively frequent complication after surgery for colorectal cancer and appears to negatively influence only the postoperative length of stay. Conservative management appeared to be a successful treatment. Full article

Surgery continues to be the primary therapeutic approach for patients diagnosed with colon cancer. Unfortunately, postoperative complications have been shown to negatively impact short-term patient outcomes, long-term oncological prognosis, and overall healthcare costs. The risk factors of postoperative complications are multiple, being linked to the patient’s general condition (lifestyle, comorbidities, etc.), the state of the neoplastic disease, as well as the drug and surgical treatments applied. If these factors are associated, the incidence of postoperative complications especially increases in the form of anastomotic leakage, bleeding, infections, postoperative ileus, and stoma-related complications. It is not surprising that these conditions are common causes of prolonged hospitalization in colon surgery, being associated with high rates of morbidity and mortality. Literature data show that the management of the oncological patient, especially if treated surgically and even more so when they develop postoperative complications, is difficult. It is a direct consequence of the fact that such cases can be quite different from each other, so that the development of a common therapeutic protocol is not possible. Therefore, the purpose of this review is to update and highlight the main risk factors for unfavorable outcomes in patients diagnosed and treated surgically for colon cancer, determine what are the most common postoperative complications, and how the course towards severe forms of evolution is influenced by various clinical and biological parameters. Data used for this review were collected from literature published between 2013 and 2025, using several parameters presented in the text. Consequently, the management strategy for these postoperative complications must be primarily based on an early, multidisciplinary and personalized approach, which appear to significantly improve the therapeutic results obtained. Full article

Gastric intestinal metaplasia (GIM) is a precancerous lesion and the key risk factor in the development of gastric cancer (GC), but early detection and treatment remain challenging. The traditional endoscopic diagnosis of metaplastic lesions is complicated by an increased rate of inappropriateness and false negativity. Although early interventions with H. pylori eradication, as well as endoscopic therapy results, were promising, there is still a significant unmet need to control GIM progression and recurrences. Molecular alterations, such as an increased DNA methylation index, have been identified as a crucial factor in the downregulation of tumor suppressor genes, such as the caudal-type homeobox (CDX2) gene, which regulates epithelial cell proliferation and GIM progression and is associated with treatment failure. CDX2 is downregulated by promoter hypermethylation in the colonic-type epithelium, in which the methylation was correlated with reduced intake of dietary folate sources. Tumor cells alter to dietary methionine sources in the biosynthesis of S-Adenosylmethionine, a universal methyl donor for transmethylation, under the conditions of limited folate and B12 availability. The gut microbiota also exhibited a shift in microbial composition, which could influence the host’s dietary methionine metabolism. Meanwhile, activated oncogenic signaling via the PI3K/Akt/mTORC1/c-MYC pathway could promotes rewiring dietary methionine and cellular proliferation. Tumor methionine dependence is a metabolic phenotype that could be helpful in predictive screening of tumorigenesis and as a target for preventive therapy to enhance precision oncology. This review aimed to discuss the molecular alterations in GIM to shed light on the alteration of methionine metabolism, with insight into new diagnostic and treatment approaches and future research directions. Full article

Ketogenesis, a mitochondrial metabolic pathway, occurs primarily in liver, but kidney, colon and retina are also capable of this pathway. It is activated during fasting and exercise, by “keto” diets, and in diabetes as well as during therapy with SGLT2 inhibitors. The principal ketone body is β-hydroxybutyrate, a widely recognized alternative energy source for extrahepatic tissues (brain, heart, muscle, and kidney) when blood glucose is sparse or when glucose transport/metabolism is impaired. Recent studies have identified new functions for β-hydroxybutyrate: it serves as an agonist for the G-protein-coupled receptor GPR109A and also works as an epigenetic modifier. Ketone bodies protect against inflammation, cancer, and neurodegeneration. HMGCS2, as the rate-limiting enzyme, controls ketogenesis. Its expression and activity are regulated by transcriptional and post-translational mechanisms with glucagon, insulin, and glucocorticoids as the principal participants. Loss-of-function mutations occur in HMGCS2 in humans, resulting in a severe metabolic disease. These patients typically present within a year after birth with metabolic acidosis, hypoketotic hypoglycemia, hepatomegaly, steatotic liver damage, hyperammonemia, and neurological complications. Nothing is known about the long-term consequences of this disease. This review provides an up-to-date summary of the biological functions of ketone bodies with a special focus on HMGCS2 in health and disease. Full article

Background: Endometrial cancer is the most common gynecologic malignancy in developed countries, with obesity recognized as a major risk factor contributing to its incidence. The rising prevalence of obesity has significant implications for treatment planning, particularly in radiation therapy approaches such as high-dose-rate (HDR) vaginal cuff brachytherapy, which is commonly used as adjuvant therapy in early-stage endometrial carcinoma. Body Mass Index (BMI) is a key factor in brachytherapy, as increased adiposity may alter dosimetric parameters, affecting radiation distribution and doses received by organs at risk (OARs). Understanding the correlation between BMI and radiation dose to OARs is essential for optimizing treatment planning and minimizing adverse effects. Identifying dose variations across different BMI categories may help refine patient-specific brachytherapy approaches to ensure both efficacy and safety. Objectives: This study aims to investigate the influence of Body Mass Index (BMI) on the doses received by organs at risk (OAR) during high-dose-rate (HDR) vaginal cuff brachytherapy in patients diagnosed with early-stage endometrial carcinoma. Understanding the relationship between BMI and OAR doses could enhance treatment planning and minimize complications. Methods: We collected brachytherapy data for 242 endometrial cancer patients treated with adjuvant HDR vaginal cuff brachytherapy. The patients were categorized based on their BMI into normal weight, overweight, and obese groups. Dosimetric data were collected for OARs, including the bladder, rectum, and sigmoid colon, and also for dose fractionation, D90%, and the active length of the brachytherapy cylinder. The analysis included comparing the doses received by each organ across different BMI categories using appropriate statistical methods. Results: Preliminary findings indicated a significant variation in the doses to OARs correlating with BMI classifications. Obese patients exhibited slightly higher mean doses to the rectum and sigmoid compared to those with a normal BMI. The statistical analysis demonstrated that as BMI increased, the dose to these organs at risk also tended to increase, suggesting a need for adjusted treatment planning strategies in this population. Conclusions: Obesity is a key concern in endometrial cancer patients, with higher BMI linked to slightly increased doses to the rectum and sigmoid, though treatment remained homogeneously delivered. Future prospective clinical studies are essential to explore the relationship between these dosimetric findings, specifically the correlation between higher BMI, increased doses to organs at risk (OARs), and late treatment-related toxicities. This research is needed to better understand the long-term implications and to optimize therapeutic outcomes. Full article

Lagunamide D is a structurally distinct 26-membered cytotoxic cyclic depsipeptide, originally isolated from a marine cyanobacterium. It exhibits potent antiproliferative activity in the low nanomolar range against A549 human lung adenocarcinoma cells and HCT116 colon cancer cells. A significant challenge associated with lagunamide D is its propensity for intramolecular acyl migration, which leads to the formation of a contracted 24-membered analog, lagunamide D′. This structural rearrangement complicates its isolation, characterization, and synthesis. In this study, the total synthesis of lagunamide D was achieved in a 14-step longest linear sequence, starting from the known intermediate 17, with an overall yield of 4.6%. The synthetic strategy involved several key transformations, including Ghosh’s TiCl₄-promoted anti-aldol reaction, Corey–Bakshi–Shibata reduction (CBS reduction), cross-metathesis, Pinnick oxidation, and Yamaguchi esterification. Furthermore, this synthetic effort unambiguously confirmed the stereochemistry of the natural product. Full article