Eugenol Reduced ΜPO, CD45 and HMGB1 Expression and Attenuated the Expression of Leukocyte Infiltration Markers in the Intestinal Tissue in Biliopancreatic Duct Ligation-Induced Pancreatitis in Rats.

Background and Objectives: Inflammation and dysregulation in the intestinal barrier function in acute pancreatitis (AP) trigger pancreatic lesions, systemic inflammatory response, and multiple organ dysfunction. Eugenol, as the main component of clove (Syzygium aromaticum), is known for its antioxidant and anti-inflammatory properties. We studied the potentially beneficial effect of eugenol in a rodent model of biliopancreatic duct ligation-induced AP. Materials and Methods: Rats were randomly divided into three groups: Sham, AP, and AP + eugenol (15 mg/kg/day). Serum TNFα, IL-6, IL-18, and resistin levels, as well as IL-6, TNFα, MPO, HMGB1, and CD45 tissue expression, were determined at various timepoints after the induction of AP. Results: Eugenol attenuated hyperemia and inflammatory cell infiltration in the intestinal mucosal, submucosal, and muscular layers. IL-6 and resistin serum levels were significantly reduced in the AP + eugenol group, while serum TNFα and IL-18 levels remained unaffected overall. TNFα pancreatic and intestinal expression was attenuated by eugenol at 72 h, while IL-6 expression was affected only in the pancreas. MPO, CD45, and HMGB1 intestinal expression was significantly reduced in eugenol-treated rats. Conclusions: Eugenol managed to attenuate the inflammatory response in the intestine in duct ligation-induced AP in rats.

Kallikrein-related peptidases in cancers of gastrointestinal tract: an inside view of their role and clinical significance.

Human tissue kallikrein (KLK1) and is related peptidases (KLK2-KLK15) are a family of 15 homologous serine proteases, participating in numerous processes of normal physiology. Considering the irreversible impact of proteases on substrates, the tissue-dependent regulation of KLKs activity becomes crucial for their beneficial role in normal homeostasis. Moreover, KLKs expression is strongly regulated at the transcriptional and post-transcriptional level by steroid hormones and miRNAs, respectively. Deregulation of KLKs expression, secretion and/or activation has been observed in most human malignancies and there is a trend to identify their role in the multi-complex process of cancer development. The identification of extracellular matrix (ECM) proteins, cell-surface receptors, cell-surface adhesion molecules and growth factors among substrates, clearly support the driving role of KLK abnormal expression and function during tumorigenesis and cancer progression. KLKs have also clinical utility in cancer diagnosis and monitoring like KLK 3 (PSA) in prostate cancer. In this review, we tried to summarize the existing literature about the role of KLKs in gastrointestinal cancers as well as to emphasize their clinical significance for patients' prognosis.

Saliva stress biomarkers in ERCP trainees before and after familiarisation with ERCP on a virtual simulator.

Background: Stress during the early ERCP learning curve may interfere with acquisition of skills during training. The purpose of this study was to compare stress biomarkers in the saliva of trainees before and after familiarisation with ERCP exercises on a virtual simulator. Methods: Altogether 26 endoscopists under training, 14 women and 12 men, completed the three phases of this study: Phase 1. Three different ERCP procedures were performed on the simulator. Saliva for α-amylase (sAA), Chromogranin A (sCgA), and Cortisol (sC) were collected before (baseline), halfway through the exercise (ex.), and 10 min after completion of the exercise (comp.); Phase 2. A three-week familiarisation period where at least 30 different cases were performed on the virtual ERCP simulator; and Phase 3. Identical to Phase 1 where saliva samples were once again collected at baseline, during, and after the exercise. Percentage differences in biomarker levels between baseline and exercise (Diffex) and between baseline and completion (Diffcomp) during Phase 1 and Phase 3 were calculated for each stress marker. Results: Mean % changes, Diffex and Diffcomp, were significantly positive (p < 0.05) for all markers in both Phase 1 and Phase 3. Diffex in Phase 1 was significantly greater than Diffex in Phase 3 (p < 0.05) for sAA and sCgA. Diffcomp for sAA in Phase 1 was significantly greater than Diffcomp in Phase 3 (p < 0.05). No significant differences were found in sC concentration between Phases 1 and 3. Conclusion: This study shows that familiarisation with the ERCP simulator greatly reduced stress as measured by the three saliva stress biomarkers used with sAA being the best. It also suggests that familiarisation with an ERCP simulator might reduce stress in the clinical setting.

CDKN2A copy number alteration in bladder cancer: Integrative analysis in patient-derived xenografts and cancer patients.

Bladder cancer (BlCa) is an extensively heterogeneous disease that leads to great variability in tumor evolution scenarios and lifelong patient surveillance, emphasizing the need for modern, minimally invasive precision medicine. Here, we explored the clinical significance of copy number alterations (CNAs) in BlCa. CNA profiling was performed in 15 patient-derived xenografts (PDXs) and validated in The Cancer Genome Atlas BlCa (TCGA-BLCA; n = 408) and Lindgren et al. (n = 143) cohorts. CDKN2A copy number loss was identified as the most frequent CNA in bladder tumors, associated with reduced CDKN2A expression, tumors of a papillary phenotype, and prolonged PDX survival. The study's screening cohort consisted of 243 BlCa patients, and CDKN2A copy number was assessed in genomic DNA and cell-free DNA (cfDNA) from 217 tumors and 189 pre-treatment serum samples, respectively. CDKN2A copy number loss was correlated with superior disease-free and progression-free survival of non-muscle-invasive BlCa (NMIBC) patients. Moreover, a higher CDKN2A index (CDKN2A/LEP ratio) in pre-treatment cfDNA was associated with advanced tumor stage and grade and short-term NMIBC progression to invasive disease, while multivariate models fitted for CDKN2A index in pre-treatment cfDNA offered superior risk stratification of T1/high-grade and EORTC high-risk patients, enhancing prediction of treatment outcome. CDKN2A copy number status could serve as a minimally invasive tool to improve risk stratification and support personalized prognosis in BlCa.

Colonic fibromatosis - a case report and review of the literature / Fibromatose colônica - relato de caso e revisão da literatura

ABSTRACT Intra-abdominal desmoids tumours are very rare and usually occur in patients with familiar adenomatous polyposis and previous surgery. They represent fibroepithelial growths with varied biologic behavior and therefore different prognosis. We report a case of a 60-year-old patient with a large right colonic mass who underwent right hemicolectomy. Histology proved morphological and immuno-histochemical features indicating fibromatosis. This desmoid tumour appeared growing from the colonic wall rather than the mesocolon, confirming a true colonic wall fibromatosis, a deep isolated form of intra-abdominal fibromatosis. Surgical resection is the treatment of choice in isolated well confirmed lesions. Multidisciplinary team approach is crucial for treatment and prognosis.

RESUMO Os tumores desmoides intra-abdominais são muito raros e geralmente ocorrem em pacientes com polipose adenomatosa familiar e cirurgia prévia. Eles representam crescimentos fibroepiteliais com comportamento biológico variado e, portanto, prognóstico diferente. Relatamos o caso de um paciente de 60 anos com grande massa colônica à direita, submetido a hemicolectomia direita. A histologia demonstrou características morfológicas e imuno-histoquímicas que indicavam fibromatose. Este tumor desmoide surgiu crescendo a partir da parede do cólon, e não do mesocólon, confirmando uma verdadeira fibromatose da parede do cólon, uma forma isolada profunda de fibromatose intra-abdominal. A ressecção cirúrgica é o tratamento de escolha em lesões isoladas bem confirmadas. A abordagem multidisciplinar é crucial para o tratamento e prognóstico.

Submucosal anoderm-preserving hemorrhoidectomy revisited: a modified technique for the surgical management of hemorrhoidal crisis.

Submucosal hemorrhoidectomy (Parks' procedure) is a recognized method for treating acute hemorrhoidal crisis. Anoderm preservation has been stressed in various techniques described for elective or emergency excisional hemorrhoidal management. Mucopexy techniques have been proven useful as an adjunct to minimally resectional techniques. A modified submucosal technique with anoderm preservation and mucopexy was applied to 45 patients who presented on an emergency basis with hemorrhoidal crisis. External piles were minimally removed, the minimum possible amount of diseased mucosa was excised, a linear incision was used at the anoderm to enter the subanodermal/mucosal plane to achieve the submucosal excision, and a mucopexy was added at the approximation of the mucosal flaps. Postoperative morbidity was minimal and pain after the procedure remained at acceptable levels. This technique allows for an excision limited to the pathology with important anatomic tissue preservation. This results in conservation of the sensitive and useful anoderm, a decreased risk of stenosis, and addresses the mucosal prolapse. The level of postoperative pain with this technique is acceptable and long-term follow-up reveals a high degree of patient satisfaction.

Routine abdominal drains after laparoscopic sleeve gastrectomy: a retrospective review of 353 patients.

Complications after laparoscopic sleeve gastrectomy (LSG) are usually silent and difficult to interpret. Our purpose was to evaluate the utility of routine placement of intraperitoneal drains at the end of LSG in detection and management of postoperative complications. This is a retrospective study of all patients that underwent LSG by a standard operative team in a 3-year period. Patients were enrolled in Group A when an intraperitoneal drain was placed and Group B when not. Three hundred and fifty-three patients underwent LSG with a median preoperative BMI of 46.4 k/m2. Two hundred and one patients were enrolled in group A and 152 in group B; the two groups were comparable in their characteristics. Staple line leak, bleeding, and abscess were observed in 4%, 2.9%, and 2.5% of group A and 2.6%, 1.9%, and 1.9% of group B and the differences did not reach statistical significance. In 50% of patients with drain and leak, per os blue de methylene test was negative and in another 50% leak took place after the fourth postoperative day when drain was already taken off. Abscesses were observed significantly more often in patients that had suffered postoperative bleeding (p < 0.001) or had undergone laparoscopic adjustable gastric banding (LAGB) in the past (p = 0.02). Placement of drains does not facilitate detection of leak, abscess, or bleeding. Furthermore, they don't seem to eliminate the reoperation rates for these complications. Maybe patients with previous LAGB and intraperitoneal bleeding could benefit from placement of a drain that will remain for more than 5 days.

Gastrointestinal stromal tumor causing small bowel intussusception in a patient with Crohn's disease.

We report a case of jejunoileal intussusception in a 42-year-old patient with Crohn's disease caused by a gastrointestinal stromal tumor. The patient complained of vague diffuse abdominal pain for a period of 4 mo. Intussusception was suspected at computer tomography and magnetic resonance imaging scans. Segmental resection of the small intestine was performed. Pathological examination of the surgical specimen revealed a gastrointestinal stromal tumor as well as aphthous ulcerations and areas of inflammation, which were characteristic of Crohn's disease. This is the first report of small bowel intussusception due to a gastrointestinal stromal tumor coexisting with Crohn's disease.