Novel Insights into Postoperative Surveillance in Resected Pancreatic Cystic Neoplasms-A Review.

Pancreatic cystic lesions (PCL) are frequently encountered in clinical practice and some are referred to surgery due to their neoplastic risk or malignant transformation. The management of PCL involves complex decision-making, with postoperative surveillance being a key component for long-term outcomes, due to the potential for recurrence and postoperative morbidity. Unfortunately, the follow-up of resected patients is far from being optimal and there is a lack of consensus on recommendations with regard to timing and methods of surveillance. Here, we summarize the current knowledge on the postoperative surveillance of neoplastic pancreatic cysts, focusing on the mechanisms and risk factors for recurrence, the recurrence rates according to the initial indication for surgery, the final result of the surgical specimen and neoplastic risk in the remaining pancreas, as well as the postsurgical morbidity comprising pancreatic exocrine insufficiency, metabolic dysfunction and diabetes after resection, according to the type of surgery performed. We analyze postsurgical recurrence rates and morbidity profiles, as influenced by different surgical techniques, to better delineate at-risk patients, and highlight the need for tailored surveillance strategies adapted to preoperative and operative factors with an impact on outcomes.

Intersecting Pathways: Nonalcoholic Fatty Liver Disease and Psoriasis Duet-A Comprehensive Review.

Psoriasis is a chronic, immune-mediated, inflammatory disease that has a major impact on patients' quality of life. Common psoriasis-associated comorbidities include cardiovascular diseases, psoriatic arthritis, inflammatory bowel syndromes, type-2 diabetes, and metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is affecting a substantial portion of the population and is closely linked with psoriasis. The interplay involves low-grade chronic inflammation, insulin resistance, and genetic factors. The review presents the pathophysiological connections between psoriasis and nonalcoholic fatty liver disease, emphasizing the role of cytokines, adipokines, and inflammatory cascades. The "hepato-dermal axis" is introduced, highlighting how psoriatic inflammation potentiates hepatic inflammation and vice versa. According to the new guidelines, the preliminary examination for individuals with psoriasis should encompass evaluations of transaminase levels and ultrasound scans as part of the initial assessment for this cohort. Considering the interplay, recent guidelines recommend screening for NAFLD in moderate-to-severe psoriasis cases. Treatment implications arise, particularly with medications impacting liver function. Understanding the intricate relationship between psoriasis and NAFLD provides valuable insights into shared pathogenetic mechanisms. This knowledge has significant clinical implications, guiding screening practices, treatment decisions, and the development of future therapeutic approaches for these chronic conditions.

Ferritin and Ferritin-to-Hemoglobin Ratio as Promising Prognostic Biomarkers of Severity in Acute Pancreatitis-A Cohort Study.

BACKGROUND: Acute pancreatitis is an inflammation of the pancreas with variable outcomes depending on its severity. Multiple systems of prediction have been proposed, each with variable specificity and sensitivity and with uneven clinical use. Ferritin is a versatile protein associated with various acute and chronic conditions. AIMS: In our study, we aimed to assess the association of serum ferritin and the ferritin-to-hemoglobin ratio (FHR) with the severity of acute pancreatitis. METHODS: A retrospective study was conducted in our hospital from January 2020 to September 2022 and included 116 patients with acute pancreatitis (graded according to the revised Atlanta classification). Serum ferritin and FHR were determined next to established laboratory parameters in the first 24 h following admission (hematological parameters, amylase, lipase, C-reactive protein, D-dimers, lactate dehydrogenase). We performed a receiver operating characteristic curve analysis for potential predictors. Also, we made correlations and conducted univariate and multivariate analyses for all potential severity biomarkers. RESULTS: The median values of serum ferritin and FHR differed significantly between patients with severe acute pancreatitis and mild cases (serum ferritin: 352.40 vs. 197.35 ng/mL, p = 0.011; FHR: 23.73 vs. 13.74, p = 0.002) and between patients with organ failure and those without organ failure (serum ferritin: 613.45 vs. 279.65 ng/mL, p = 0.000; FHR: 48.12 vs. 18.64, p = 0.000). The medians of the serum ferritin and FHR levels were significantly higher in non-survivors compared with survivors (serum ferritin: 717.71 vs. 305.67 ng/mL, p = 0.013; FHR: 52.73 vs. 19.58, p = 0.016). Serum ferritin and FHR were good predictors for organ failure and mortality, next to D-dimers and procalcitonin (AUC > 0.753 for organ failure and AUC > 0.794 for mortality). In univariate regression analysis, serum ferritin and FHR were independent variables for moderate-severe forms of acute pancreatitis. Still, adjusting the multivariate analysis, only FHR remained a significant predictor. The cut-offs for serum ferritin and FHR for predicting organ failure were 437.81 ng/mL (sensitivity, 71%; specificity, 75%) and 45.63 (sensitivity, 61%; specificity, 88%), and those for mortality during hospitalization were 516 ng/mL (sensitivity, 83%; specificity, 74%) and 51.58 (sensitivity, 66%; specificity, 86%). CONCLUSIONS: Serum ferritin and the ferritin-to-hemoglobin ratio stood out in this study as valuable and accessible predictors of disease severity in the early assessment of acute pancreatitis, next to established severity serum markers (CRP, fibrinogen, D-dimers).

Hidradenitis suppurativa: Detangling phenotypes and identifying common denominators.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with a severe impact on patients' quality of life through its recurrent and painful nature, as well as its comorbidity burden. The shift in the pathogenic paradigm from a condition of the apocrine glands to an autoinflammatory disease associated with follicular destruction has rendered its understanding difficult, as there are still large gaps in pinpointing the underlying mechanisms, which cannot currently explain the existing clinical variation and as a result, translate into suboptimal therapy. Multifactorial involvement is hypothesized, with an implication of genetic mutations, microbiome dysbiosis, cytokine upregulation and environmental factors. Clinical observation is fundamental for diagnosis, however, the marked heterogeneity in presentation leads to delays in detection and challenges in treatment selection, showcasing clear limits in defining the link between genetic aspects of HS, the role of epigenetic factors and its pathogenic pathways. There have been attempts to formulate phenotypes that could aid in prognostication and management, however, current classification schemata show significant overlap and no validation through longitudinal studies. In this context, nomenclature poses a great challenge due to the lack of global agreement in the definition of lesions, which should be addressed by future research to enable simplified recognition and allow for more precise severity scoring. This could be complemented by the addition of extra dermatologic findings or paraclinical assessment in constructing phenotypes. The development of valid, predictive and reliable classifications of HS may lead to an improvement in comprehending its pathophysiology, favouring a more personalized approach in management. This could be achieved through consensus in the characterization of clinical features and data gathering, as well as validation attempts for described phenotypes. Ultimately, the genotype-endotype-phenotype correlation in HS requires targeted, systematic inquiries and should be addressed more largely to broaden the perspective on this debilitating entity.

Metastatic Renal Cell Carcinoma to Pancreas: Case Series and Review of the Literature.

Metastasis to the pancreas represents a small proportion of all pancreatic malignancies. Among primary tumors that metastasize to the pancreas, renal cell carcinoma (RCC) is one of the most common causes of metastatic pancreatic lesions. We herein report a case series of three patients with pancreatic metastasis from RCC. The first is a 54-year-old male with a history of left nephrectomy for RCC, in whom an isthmic pancreatic mass suggestive of a neuroendocrine lesion was found during oncological follow-up. Endoscopic ultrasound (EUS)-guided fine needle biopsy (FNB) identified pancreatic metastasis of RCC and the patient was referred for surgery. The second case is a 61-year-old male, hypertensive, diabetic, with left nephrectomy for RCC six years previously, who complained of weight loss and was found with a hyperenhancing mass in the head of the pancreas and a lesion with a similar pattern in the gallbladder. EUS-FNB from the pancreas proved to be a metastatic pancreatic lesion. Cholecystectomy and treatment with tyrosine kinase inhibitors were recommended. The third case is a 68-year-old dialysis patient referred for evaluation of a pancreatic mass, also confirmed by EUS-FNB, who was started on sunitinib treatment. We report a literature summary on epidemiology and clinical features, diagnosis and differential diagnosis and treatment and outcomes in pancreatic metastasis of RCC.

Skin Cancer Correlations in Psoriatic Patients.

Psoriasis is a common chronic, immune-mediated, inflammatory disease with associated comorbidities. Common psoriasis-associated comorbidities include psoriatic arthritis, cardiovascular disease, metabolic syndrome, inflammatory digestive syndromes, and depression. A less studied association is between psoriasis and specific-site cancers. A key cell in the pathophysiology of psoriasis is the myeloid dendritic cell, which links the innate and adaptive immune systems, and therefore is involved in the control of cancer-prevention mechanisms. The relationship between cancer and inflammation is not new, with inflammation being recognized as a key element in the development of neoplastic foci. Infection leads to the development of local chronic inflammation, which further leads to the accumulation of inflammatory cells. Various phagocytes produce reactive oxygen species that cause mutations in cellular DNA and lead to the perpetuation of cells with altered genomes. Therefore, in inflammatory sites, there will be a multiplication of cells with damaged DNA, leading to tumor cells. Over the years, scientists have tried to assess the extent to which psoriasis can increase the risk of developing skin cancer. Our aim is to review the available data and present some information that might help both the patients and the care providers in properly managing psoriatic patients to prevent skin cancer development.

Kaempferol: Antimicrobial Properties, Sources, Clinical, and Traditional Applications.

Flavonoids are a category of plant-derived compounds which exhibit a large number of health-related effects. One of the most well-known and studied flavonoids is kaempferol, which can be found in a wide variety of herbs and plant families. Apart from their anticarcinogenic and anti-inflammatory effects, kaempferol and its associated compounds also exhibit antibacterial, antifungal, and antiprotozoal activities. The development of drugs and treatment schemes based on these compounds is becoming increasingly important in the face of emerging resistance of numerous pathogens as well as complex molecular interactions between various drug therapies. In addition, many of the kaempferol-containing plants are used in traditional systems all over the world for centuries to treat numerous conditions. Due to its variety of sources and associated compounds, some molecular mechanisms of kaempferol antimicrobial activity are well known while others are still under analysis. This paper thoroughly documents the vegetal and food sources of kaempferol as well as the most recent and significant studies regarding its antimicrobial applications.

Clinical characteristics and outcomes in carbohydrate antigen 19-9 negative pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of death from cancer worldwide. Tumor markers like carbohydrate antigen 19-9 (CA 19-9) have been proven valuable as a diagnostic tool and a predictor for tumor staging and response to therapy. AIM: To delineate the phenotype of normal CA 19-9 PDAC according to clinical features, disease staging and prognosis as compared with high CA 19-9 PDAC cases. METHODS: We performed a retrospective single-center analysis of all PDAC cases admitted in our Gastroenterology department over a period of 30 mo that were diagnosed by endoscopic ultrasound-guided tissue acquisition. Patients were divided into two groups according to CA 19-9 levels over a threshold of 37 U/mL. We performed a comparison between the two groups with regard to demographic and clinical data, biomarkers, tumor staging and 6-mo survival. RESULTS: Altogether 111 patients were recruited with 29 having documented normal CA 19-9 (< 37 U/mL). In the CA 19-9 negative group of patients, 20.68% had elevated levels of both CEA and CA 125, 13.79% for CA 125 only whilst 17.24% for CEA only. The two groups had similar demographic characteristics. Abdominal pain was more frequently reported in positive vs negative CA 19-9 PDAC cases (76.83% vs 55.17%), while smoking was slightly more prevalent in the latter group (28.04% vs 31.03%). Tumors over 2 cm were more frequently seen in the positive CA 19-9 group, reflecting a higher proportion of locally advanced and metastatic neoplasia (87.7% vs 79.3%). Six-month survival was higher for the negative CA 19-9 group (58.62% vs 47.56%). CONCLUSION: Elevated CA 19-9 at diagnosis seems to be associated with a more pronounced symptomatology, high tumor burden and poor prognosis compared to negative CA 19-9 PDAC cases. CEA and CA 125 can be adjunctive useful markers for PDAC, especially in CA 19-9 negative cases.

A combination of two regional flaps for the complex reconstruction after head and neck cancer surgery as an alternative approach during the COVID-19 pandemic: A case report.

Since the COVID-19 pandemic outbreak, the medical systems were challenged by continuously increasing numbers of infections and faced critical issues when trying to find solutions for patients suffering from other diseases, including patients with head and neck cancers. Complex surgeries were delayed due to an acute deficit of specialized intensive care medical staff and equipment, which were redirected towards COVID-19 hospitalized cases, with irreversible consequences for the patients. In the present study, the case of locally advanced head and neck cancer was presented, which was treated radically during the heaviest wave of the COVID-19 pandemic in Romania using an alternative approach for immediate defect reconstruction. The case of locally advanced buccal carcinoma (staged T4aN0Mx) was reported, where radical tumor excision was followed by immediate reconstruction using a combination of two regional flaps, temporal and submental, in order to provide timely and optimal medical care. In the difficult context of the COVID-19 pandemic, the standard reconstructive technique, which is the free vascularized tissue transfer, could not be performed for this patient, due to the acute deficit of anesthetists and associated medical staff, as well as the lack of free beds in intensive care units. Combinations of local and regional flaps, such as temporal muscle flap and submental flap, are simple and accessible surgical techniques that require reduced surgical time, minimal equipment, and basic surgical training, advantages that become crucial in historically challenging times, such as a global pandemic. Individual cases, like elderly patients or patients with severe comorbidities, should be considered for these types of reconstructive techniques: simple solutions, single or in combination, which may be an improved therapeutic option for these patients.

Skin Inflammation Modulation via TNF-α, IL-17, and IL-12 Family Inhibitors Therapy and Cancer Control in Patients with Psoriasis.

The systemic inflammatory syndrome concept is one of the foundations that stand at the basis of revolutionary modern and future therapies, based on the in-depth understanding of the delicate mechanisms that govern the collaboration between the systems and organs of the human body and, at the same time, the fine balance that ensures a reproach-free operation. An interesting concept that we propose is that of the environment-inadequacy status, a concept that non-specifically incorporates all the situations of the organism's response disorders in the face of imprecisely defined situations of the environment. The correlation between these two concepts will define the future of modern medicine, along with the gene-adjustment mechanisms. Psoriasis is a clear example of an inadequate body response as a result of exposure to as of yet undefined triggers with an excessive systemic inflammatory reaction and hitherto insufficiently controllable. Modern biological therapies, such as TNF-α, IL-12 family, and IL-17 inhibitors, are intended to profoundly reshape the cytokine configuration of patients with inflammatory diseases such as psoriasis, with tremendous success in disease control. Yet, because of the important roles of cytokines in cancer promotion and control, concern was raised about the fact that the use of biologicals may alter immune surveillance and promote cancer progression. Both theoretical and practical data nevertheless showed that the treatment-induced control of cytokines may be beneficial for reducing the inflammatory milieu that promotes cancer and such have a beneficial role in maintaining health. We briefly present the intricate roles of those cytokine families on cancer control, with some debates on if their inhibition might or might not promote additional tumoral development.

Comparative effects of capsaicin in chronic obstructive pulmonary disease and asthma (Review).

Chronic obstructive pulmonary disease (COPD) and asthma are chronic respiratory diseases with high prevalence and mortality that significantly alter the quality of life in affected patients. While the cellular and molecular mechanisms engaged in the development and evolution of these two conditions are different, COPD and asthma share a wide array of symptoms and clinical signs that may impede differential diagnosis. However, the distinct signaling pathways regulating cough and airway hyperresponsiveness employ the interaction of different cells, molecules, and receptors. Transient receptor potential cation channel subfamily V member 1 (TRPV1) plays a major role in cough and airway inflammation. Consequently, its agonist, capsaicin, is of substantial interest in exploring the cellular effects and regulatory pathways that mediate these respiratory conditions. Increasingly more studies emphasize the use of capsaicin for the inhalation cough challenge, yet the involvement of TRPV1 in cough, bronchoconstriction, and the initiation of inflammation has not been entirely revealed. This review outlines a comparative perspective on the effects of capsaicin and its receptor in the pathophysiology of COPD and asthma, underlying the complex entanglement of molecular signals that bridge the alteration of cellular function with the multitude of clinical effects.

Impact of laparoscopic sleeve gastrectomy on esophageal physiology.

Introduction. Laparoscopic sleeve gastrectomy (LSG) is a popular weight loss surgery technique, but the impact on esophageal physiology and esophagogastric junction is still debatable. The aim of our study was to evaluate the manometric changes of the lower esophageal sphincter (LES) after LSG in order to indicate LES manometry pre- procedure. Methods. In a prospective study we evaluated clinically, with upper gastrointestinal endoscopy, and high-resolution esophageal manometry 45 morbidly obese patients before, and 6-12 months after LSG. Results. The BMI (body mass index) decreased from 46.28±5.79 kg/m2 to 32.28±4.65 kg/m2 postoperatively (p <0.01), with a reduction of ~14 kg/m2 of BMI, 39.9 (±11.9) kg body weight and 29.9 (± 6.2)% of the TWL (Total Weight Loss index), in a median interval of 7.9 months. Gastroesophageal reflux disease (GERD) prevalence increased from 17.8% to 31.1% postoperatively, with new GERD onset in 22.2%, but mild symptomatology (the median GERD-HRQL score increased from 1.56 to 2.84 points). Postoperatory reflux was associated with lower esophageal sphincter (LES) hypotonia, shortening of LES length and IIGP (increased intragastric pressure). Hiatal hernia repair rate was 17.8%, and proton pump inhibitor consumption 20%. After weight loss, the 10 cases of esophagitis discovered preoperatively cured, but 3 patients were diagnosed with de novo esophagitis. The prevalence of manometric dysmotility after LSG was 28.9%, lower than before surgery (44.4%). Conclusion. Even if GERD remains the main limitation of LSG, the high-resolution esophageal manometry has proved useful and should be implemented in morbidly obese evaluation protocol, to better select the bariatric procedure.

The Effects of Capsaicin on Gastrointestinal Cancers.

Gastrointestinal (GI) cancers are a group of diseases with very high positions in the ranking of cancer incidence and mortality. While they show common features regarding the molecular mechanisms involved in cancer development, organ-specific pathophysiological processes may trigger distinct signaling pathways and intricate interactions with inflammatory cells from the tumoral milieu and mediators involved in tumorigenesis. The treatment of GI cancers is a topic of increasing interest due to the severity of these diseases, their impact on the patients' survivability and quality of life, and the burden they set on the healthcare system. As the efficiency of existing drugs is hindered by chemoresistance and adverse reactions when administered in high doses, new therapies are sought, and emerging drugs, formulations, and substance synergies are the focus of a growing number of studies. A class of chemicals with great potential through anti-inflammatory, anti-oxidant, and anti-tumoral effects is phytochemicals, and capsaicin in particular is the subject of intensive research looking to validate its position in complementing cancer treatment. Our paper thoroughly reviews the available scientific evidence concerning the effects of capsaicin on major GI cancers and its interactions with the molecular pathways involved in the course of these diseases.

Early Diagnosis of Pancreatic Cancer: The Key for Survival.

Pancreatic cancer (PC) is one of the most aggressive forms of cancer. Negative prognosis is mainly due to the late diagnosis in advanced stages, when the disease is already therapeutically overcome. Studies in recent years have focused on identifying biomarkers that could play a role in early diagnosis, leading to the improvement of morbidity and mortality. Currently, the only biomarker widely used in the diagnosis of PC is carbohydrate antigen 19-9 (CA19.9), which has, however, more of a prognostic role in the follow-up of postoperative recurrence than a diagnostic role. Other biomarkers, recently identified as the methylation status of ADAMTS1 (A disintegrin and metalloproteinase with thrombospondin motifs 1) and BNC1 (zinc finger protein basonuclin-1) in cell-free deoxyribonucleic acid (DNA), may play a role in the early detection of PC. This review focuses on the diagnosis of PC in its early stages.

Use of prokinetics and other quality factors in capsule endoscopy - old and new insights (Review).

Despite the extensive recent development of different techniques for endoscopic evaluation for both diagnostic and therapeutic reasons, the small bowel remains quite difficult to visualize. Capsule endoscopy and device assisted enteroscopy are presently considered the best diagnostic tools for examination of small bowel disorders, assessing diverse pathologies such as obscure gastrointestinal bleeding, iron deficiency anemia, Crohn disease, small bowel tumors and polyposis syndromes. Like any other imagistic method, it has specific indications, and contraindications, and possibly it is more important to consider limitations. In order to obtain a better result, it is necessary to respect the procedural quality indicators. Among them the use of prokinetics - diverse pharmacological substances increasing the success rate of capsule endoscopy have raised debates. Capsule endoscopy small bowel evaluation is a reliable, non-invasive and safe with many advantages and minimum risks, with a proper selection of patients, and can be used as first line investigation.

Cannabinoids in the Pathophysiology of Skin Inflammation.

Cannabinoids are increasingly-used substances in the treatment of chronic pain, some neuropsychiatric disorders and more recently, skin disorders with an inflammatory component. However, various studies cite conflicting results concerning the cellular mechanisms involved, while others suggest that cannabinoids may even exert pro-inflammatory behaviors. This paper aims to detail and clarify the complex workings of cannabinoids in the molecular setting of the main dermatological inflammatory diseases, and their interactions with other substances with emerging applications in the treatment of these conditions. Also, the potential role of cannabinoids as antitumoral drugs is explored in relation to the inflammatory component of skin cancer. In vivo and in vitro studies that employed either phyto-, endo-, or synthetic cannabinoids were considered in this paper. Cannabinoids are regarded with growing interest as eligible drugs in the treatment of skin inflammatory conditions, with potential anticancer effects, and the readiness in monitoring of effects and the facility of topical application may contribute to the growing support of the use of these substances. Despite the promising early results, further controlled human studies are required to establish the definitive role of these products in the pathophysiology of skin inflammation and their usefulness in the clinical setting.

Ratio of spleen diameter to red blood cell distribution width: a novel indicator for celiac disease.

Celiac disease (CD) is currently considerably underdiagnosed, setting the need for developing tools to select patients with probability of CD, who warrant further testing. Red blood cell distribution width (RDW) has been shown in previous studies to be a sensitive predictor for CD, but it lacks specificity. Splenic hypotrophy is also noted frequently in celiac patients. Our aim was to evaluate if spleen diameter to RDW ratio can be used as an indicator for CD. We evaluated 15 newly diagnosed CD patients, 52 patients with inflammatory bowel disease, and 35 patients with irritable bowel syndrome (IBS). We evaluated the differences in spleen diameter, RDW, and their ratio among the four groups. Two-thirds of the CD patients had elevated RDW, compared to 9% in the IBS group. A small spleen was seen in 80% of the celiacs, compared to 21.9% in the ulcerative colitis group, 10% in the Crohn disease group, and 9% in the IBS group. A spleen diameter to RDW ratio under 6 had a sensitivity of 73.3% and specificity of 88.5% in predicting CD, with an AUROC of 0.737. Spleen diameter to RDW ratio is a simple, widely available score, which can be used to select adult patients with probability of CD.