Berberine Effects in Pre-Fibrotic Stages of Non-Alcoholic Fatty Liver Disease-Clinical and Pre-Clinical Overview and Systematic Review of the Literature.

Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver conditions, and its progression is marked by evolution to non-alcoholic steatosis, steatohepatitis, cirrhosis related to non-alcoholic steatohepatitis, and the potential occurrence of hepatocellular carcinoma. In our systematic review, we searched two databases, Medline (via Pubmed Central) and Scopus, from inception to 5 February 2024, and included 73 types of research (nine clinical studies and 64 pre-clinical studies) from 2854 published papers. Our extensive research highlights the impact of Berberine on NAFLD pathophysiology mechanisms, such as Adenosine Monophosphate-Activated Protein Kinase (AMPK), gut dysbiosis, peroxisome proliferator-activated receptor (PPAR), Sirtuins, and inflammasome. Studies involving human subjects showed a measurable reduction of liver fat in addition to improved profiles of serum lipids and hepatic enzymes. While current drugs for NAFLD treatment are either scarce or still in development or launch phases, Berberine presents a promising profile. However, improvements in its formulation are necessary to enhance the bioavailability of this natural substance.

Closure of gastrointestinal perforations using an endoloop system and a single-channel endoscope: description of a simple, reproducible, and standardized method.

BACKGROUND: Several endoscopic treatments for iatrogenic perforations are currently available, with some limitations in terms of size, location, complexity, or cost. Our aims were to introduce a novel technique for closure, using an endoloop and clips, to assess its rate of technical success and post-resection complications. METHODS: For closure of large perforations (diameter ≥ 10 mm), two similar techniques were implemented, using a single-channel endoscope. An endoloop was deployed through the operating channel or towed by an endoclip alongside the endoscope. Several clips were utilized to fix it on the muscular layer of defect's margins. The defect was closed, by fastening the loop either directly or after being reattached to the mobile hook. RESULTS: This analysis included eleven patients (72% women, median age 68 years). Eight colorectal, one appendiceal, and two gastric lesions were resected, with a median perforation size of 15 mm. As confirmed by computed tomography, closure of wall defects was achieved successfully in all cases, using a median of 6 clips. Pneumoperitoneum was evacuated in 4 cases. The median hospitalization duration was 4 days, prophylactic antibiotics being prescribed for a median of 7 days. One patient had a small abdominal collection, without requiring drainage, while another presented post-resection bleeding from the mucosal defect. CONCLUSION: The novel techniques, utilizing a single-channel endoscope, clips, and an endoloop, ensuring an edge-to-edge suture of muscular layer, proved to be safe, reproducible, and easy to implement. They exhibit an excellent technical success rate and a minimal incidence of non-severe complications.

Non eosinophilic chronic stricturing esophagitis: Lessons from thirty eight cases.

BACKGROUND AND AIMS: The endoscopic workup of dysphagia can lead to the diagnosis of atypical esophagitis, with thickened esophageal mucosa, strictures, mucosal exudates, furrows, and sloughing. While these aspects suggest eosinophilic esophagitis, pathology might not report the presence of eosinophils, but rather chronic inflammation, with spongiosis, parakeratosis, and lymphocytic infiltrate. We aimed to report the management of this disease and assess the prevalence of associated dermatological conditions. METHODS: We retrospectively evaluated the medical records of our patients with non-eosinophilic stricturing esophagitis for clinical, endoscopy, and pathology data. Patients were evaluated by a dermatologist. A blood immunoassay and skin biopsy were performed if needed. RESULTS: Thirty-eight patients (twenty-six women) were included in the study. The median age at onset of symptoms was 56.5 years, with a median duration of symptoms of two years. Thirty-five patients presented with dysphagia at diagnosis and eighteen with weight loss. At endoscopy, a single esophageal stenosis was diagnosed in 19 patients, localized in the upper third in 22 patients. Thirty patients received endoscopic treatment (dilatation in 29/38 and local triamcinolone injection in 11/38 patients). In 21 patients, oral, skin or vulvo-anal lesions were found on dermatological examination. Nineteen patients received systemic treatment, including corticosteroids, immunosuppressive drugs and plasmapheresis. Five patients developed esophageal squamous cell carcinoma. CONCLUSION: The management of non-eosinophilic chronic stricturing esophagitis is challenging, because of a low contribution of esophageal biopsies and the refractory nature of the strictures. In our experience, a dermatological evaluation helped in 55% of cases to introduce a systemic treatment, leading to limit the use of endoscopic dilatation. Endoscopic follow-up is needed, considering the significant risk of esophageal squamous cell carcinoma.

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.

"Transanal endoscopic microsurgery" with a flexible colonoscope (F-TEM): a new endoscopic treatment for suspicious deep submucosal invasion T1 rectal carcinoma.

BACKGROUND: Endoscopic techniques allow resections of deep submucosal invasion rectal carcinoma, but mostly are facing issues such as costs, follow-up care or size limit. Our aim was to design a new endoscopic technique, which retains the advantages over surgical resections while eliminating the disadvantages mentioned above. PATIENTS AND METHODS: We propose a technique for the resection of the superficial rectal tumours, with highly suspicious deep submucosal invasion. It combines steps of endoscopic submucosal dissection, muscular resection and edge-to-edge suture of the muscular layers, finally performing the equivalent of a "transanal endoscopic microsurgery" with a flexible colonoscope (F-TEM). RESULTS: A 60-year-old patient was referred to our unit, following the discovery of a 15 mm distal rectum adenocarcinoma. The computed tomography and the endoscopic ultrasound examination revealed a T1 tumour, without secondary lesions. Considering that the initial endoscopic evaluation highlighted a depressed central part of the lesion, with several avascular zones, an F-TEM was performed, without severe complication. The histopathological examination revealed negative resection margins, without risk factors for lymph node metastasis, no adjuvant therapy being proposed. CONCLUSION: F-TEM allows endoscopic resection of highly suspicious deep submucosal invasion T1 rectal carcinoma and it proves to be a feasible alternative to surgical resection or other endoscopic treatments as endoscopic submucosal dissection or intermuscular dissection.

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.