Ex-vivo 3D cellular models of pancreatic ductal adenocarcinoma: from embryonic development to precision oncology.

ABSTRACT: Pancreas is a vital gland of gastro-intestinal system with exocrine and endocrine secretory functions, interweaved into essential metabolic circuitries of the human body. Pancreatic ductal adenocarcinoma (PDAC) represents one of the most lethal malignancies, with a five-year survival rate of 11%. This poor prognosis is primarily attributed to the absence of early symptoms, rapid metastatic dissemination, and the limited efficacy of current therapeutic interventions. Despite recent advancements in understanding the etiopathogenesis and treatment of PDAC, there remains a pressing need for improved individualized models, the identification of novel molecular targets, and the development of unbiased predictors of disease progression. Here we aim to explore the concept of precision medicine utilizing three-dimensional, patient-specific cellular models of pancreatic tumors and discuss their potential applications in uncovering novel druggable molecular targets and predicting clinical parameters for individual patients.

The Use of Confocal Laser Endomicroscopy in Diagnosing Barrett's Esophagus and Esophageal Adenocarcinoma.

Confocal laser endomicroscopy (CLE) is a diagnostic technique that enables real-time microscopic imaging during microscopic examination and evaluation of epithelial structures with 1000-fold magnification. CLE can be used in the diagnosis of various pathologies, in pneumology, and in urology, and it is very widely utilized in gastroenterology, most importantly in the diagnosis of Barrett's esophagus (BE), esophageal adenocarcinoma (EAC), biliary strictures, and cystic pancreatic lesions. A literature search was made in MEDLINE/PubMed and Google Scholar databases while focusing on diagnostics using CLE of BE and EAC. We then examined randomized and observational studies, systematic reviews, and meta-analyses relating to the utilization of CLE in BE and EAC diagnostics. Here, we discuss whether CLE can be a suitable diagnostic method for surveillance of BE. Even though many studies have proven that CLE increases diagnostic accuracy in detecting neoplastic transformation of BE, CLE is still not used as a standard diagnostic tool in BE surveillance due to a deficiency of scientific evidence. More studies and data are needed if CLE is to find a place as a new technique in BE surveillance.

Confocal laser endomicroscopy in the diagnostics of esophageal diseases: a pilot study.

BACKGROUND: Probebased confocal laser endomicroscopy (pCLE) is a novel diagnostic technique for endoscopy which enables a microscopic view at a cellular resolution in realtime. Endoscopic detection of early neoplasia in the distal esophagus is difficult and often these lesions can be missed. The aim of the pilot study was to obtain characteristic pCLE figures in esophageal diseases for following studies, and to evaluate the possible future role of pCLE in the diagnostics of dysplastic Barretts esophagus (BE) or early esophageal adenocarcinoma (EAC). METHODS: A review of the current literature was performed and previously published pCLE images and classifications of esophageal diseases were searched and studied first. In phase two of the pilot study patients with esophageal diseases such as reflux esophagitis, BE and EAC were enrolled and scheduled for upper endoscopy with pCLE. A healthy cohort was also included. RESULTS: From January 2019 to July 2019, a total of 14 patients were enrolled in this prospective pilot study: 3 patients with reflux esophagitis, 4 with BE, 3 with EAC and 4 persons were included in the healthy cohort. The endoscopy with pCLE was performed and characteristic pCLE figures were obtained. The correct diagnoses based on realtime pCLE were evaluated by an endoscopist in 11 of the 14 cases (78.6 %). CONCLUSION: It was possible to obtain typical pCLE images of esophageal diseases during a standard capassisted endoscopic procedure. pCLE seems to be a feasible new technique in BE surveillance and early neoplastic lesion detection. However, more studies and data on larger number of patients are needed.

The Influence of Microscopic Inflammation at Resection Margins on Early Postoperative Endoscopic Recurrence After Ileocaecal Resection for Crohn's Disease.

BACKGROUND AND AIMS: The pathogenesis and risk factors for early postoperative endoscopic recurrence of Crohn's disease [CD] remain unclear. Thus, this study aimed to identify whether histological inflammation at the resection margins after an ileocaecal resection influences endoscopic recurrence. METHODS: We have prospectively followed up patients with CD who underwent ileocaecal resection at our hospital between January 2012 and January 2018. The specimens were histologically analysed for inflammation at both of the resection margins [ileal and colonic]. We evaluated whether histological results of the resection margins are correlated with endoscopic recurrence of CD based on colonoscopy 6 months after ileocaecal resection. Second, we assessed the influence of known risk factors and preoperative therapy on endoscopic recurrence of CD. RESULTS: A total of 107 patients were included in our study. Six months after ileocaecal resection, 23 patients [21.5%] had an endoscopic recurrence of CD. The histological signs of CD at the resection margins were associated with a higher endoscopic recurrence [56.5% versus 4.8%, p < 0.001]. Disease duration from diagnosis to surgery [p = 0.006] and the length of the resected bowel [p = 0.019] were significantly longer in patients with endoscopic recurrence. Smoking was also proved to be a risk factor for endoscopic recurrence [p = 0.028]. CONCLUSIONS: Histological inflammation at the resection margins was significantly associated with a higher risk of early postoperative endoscopic recurrence after an ileocaecal resection for CD.

Triple malignancy (NET, GIST and pheochromocytoma) as a first manifestation of neurofibromatosis type-1 in an adult patient.

BACKGROUND: Neurofibromatosis type-1 (NF1), also called von Recklinghausen disease, is a rare genetic disease which can lead to the development of benign or even malignant tumors. NF1 is mostly diagnosed in children or early adolescents who present with clinical symptoms. A curative therapy is still missing and the management of NF1 is based on careful surveillance. Concerning tumors which affect the gastrointestinal tract in patients with NF1, the most common is a gastrointestinal stromal tumor (GIST). CASE PRESENTATION: We present a case of a 58-year-old adult patient with dyspeptic symptoms who was incidentally diagnosed with triple malignancy (pheochromocytoma, multiple GISTs of small intestine and an ampullary NET) as a first manifestation of NF1. The patient underwent surgical treatment (adrenalectomy and pancreaticoduodenectomy) with no complications and after 2 years remains in oncological remission. CONCLUSION: NF1 is a rare genetic disease which can cause various benign or malignant tumors. The coincidence of GIST and NET is almost pathognomonic for NF1 and should raise a suspicion of this rare disorder in clinical practice.

Multiple neuroendocrine tumor of the small bowel: a case report and a review of literature.

Primary malignant tumors of small bowel constitute only about 1-2% of all gastrointestinal neoplasms. Although neuroendocrine tumors (NETs) are relatively rare, they still represent the second most common malignancy of the small bowel (after adenocarcinoma). Clinical manifestations include abdominal pain, bowel obstruction, diarrhea, weight loss and bleeding. The differential diagnosis of obscure gastrointestinal bleeding can sometimes be challenging for endoscopy as well as for radiology methods. We present the case of an 80-year-old man suffering from severe hypochromic anemia. Routine endoscopic methods did not show any appropriate pathology. Finally, a single ulcerative infiltration of the ileum was diagnosed by capsule endoscopy (CE). CT enterography did not reveal any other lesions. In accordance with a positive chromogranin A, endoscopic and radiologic methods, a suspicion of NET was expressed. During the surgery, 7 lesions were found and a resection of 120 cm of ileum was performed. The histology confirmed a diagnosis of NET grade 1, with a total number of 15 NET lesions in the specimen. The following octreotide scan did not show any residual infiltration. We present a patient with 15 NET lesions in the ileum diagnosed by CE and successfully cured by surgical resection of the ileum. Key words: capsule endoscopy - carcinoid syndrome - gastrointestinal carcinoids - neuroendocrine tumor - obscure gastrointestinal bleeding - small bowel - surgery.