Acute pancreatitis (AP) is one of the most common diseases in gastroenterology. However, neither the etiology nor the pathophysiology of the disease is fully understood and no specific or effective treatment has been developed. Heparanase is an endoglycosidase that cleaves heparan sulfate (HS) side chains of HS sulfate proteoglycans into shorter oligosaccharides, activity that is highly implicated in cellular invasion associated with cancer metastasis and inflammation. Given that AP involves a strong inflammatory aspect, we examined whether heparanase plays a role in AP. Here, we provide evidence that pancreatic heparanase expression and activity are significantly increased following cerulein treatment. Moreover, pancreas edema and inflammation, as well as the induction of cytokines and signaling molecules following cerulein treatment were attenuated markedly by heparanase inhibitors, implying that heparanase plays a significant role in AP. Notably, all the above features appear even more pronounced in transgenic mice over expressing heparanase, suggesting that these mice can be utilized as a sensitive model system to reveal the molecular mechanism by which heparanase functions in AP. Heparanase, therefore, emerges as a potential new target in AP, and heparanase inhibitors, now in phase I/II clinical trials in cancer patients, are hoped to prove beneficial also in AP.

Introduction. Thorough quality control (QC) study with systemic monitoring and evaluation is crucial to optimizing the effectiveness of EUS-FNA. Methods. Retrospective analysis was composed of investigating consecutive patient files that underwent EUS-FNA. QC specifically focused on diagnostic accuracy, impacts on preexisting diagnoses, and case management. Results. 268 patient files were evaluated. EUS-FNA cytology helped establish accurate diagnoses in 92.54% (248/268) of patients. Sensitivity, specificity, PPV, NPV, and accuracy were 83%, 100%, 100%, 91.6%, and 94%, respectively. The most common biopsy site was the pancreas (68%). The most accurate location for EUS-FNA was the esophagus, 13/13 (100%), followed by the pancreas (89.6%). EUS-FNA was least informative for abdominal lymph nodes (70.5%). After FNA and followup, eight false negatives for tumors were found (3%), while 7.5% of samples still lacked a definitive diagnosis. Discussion. QC suggests that the diagnostic accuracy of EUS-FNA might be improved further by (1) taking more FNA passes from suspected lesions, (2) optimizing needle selection (3) having an experienced echo-endoscopist available during the learning curve, and (4) having a cytologist present during the procedure. QC also identified remediable reporting errors. In conclusion, QC study is valuable in identifying weaknesses and thereby augmenting the effectiveness of EUS-FNA.

Purpose: Locally advanced pancreatic cancer (LAPC) accounts for 30% of pancreatic cancers. We assessed the efficacy and safety of a novel extended-release siRNA targeting KRASG12D/V mutations (siG12D-LODER) combined with chemotherapy in LAPC. Patients and Methods: This two-cohort, phase II multicenter, open-label study (NCT01676259) evaluated siG12D-LODER with chemotherapy in patients with LAPC, regardless of KRAS status. In cohort 1, patients were randomized to siG12D-LODER plus gemcitabine/nab-paclitaxel (arm 1) or gemcitabine/nab-paclitaxel alone (arm 2). In cohort 2, patients with LAPC or borderline resectable disease received siG12D-LODER plus standard chemotherapy (modified FOLFIRINOX or gemcitabine/nab-paclitaxel) in a single-arm, nonrandomized design. Primary endpoints were overall survival (OS) for cohort 1 and objective response rate (ORR) for cohort 2. Secondary endpoints included progression-free survival, duration of response, OS (cohort 2), and ORR (cohort 1). Results: Across two cohorts, 59 patients were enrolled. In cohort 1, the median OS in the modified intent-to-treat (mITT) population unselected for KRAS status was 22.7 months for siG12D-LODER + gemcitabine/nab-paclitaxel versus 21.9 months for chemotherapy alone (P > 0.05). Among patients with KRASG12D/V mutations, OS was 22.7 versus 13.5 months [HR, 0.59; 95% confidence interval (CI), 0.18–1.96; P = 0.39]. In cohort 2, ORR was 31.6% (95% CI, 0.13–0.57) in the mITT (unselected for KRAS); in the G12D/V subgroup, ORR was 57.1%, similar to 63.6% in cohort 1. Treatment-emergent adverse events were mainly procedure related, including grade 1/2 gastrointestinal events and higher infection rates in the intervention arm. Conclusions: siG12D-LODER plus chemotherapy is safe, tolerable, and warrants further investigation in KRASG12D/V-mutant LAPC.

Laparoscopic sleeve gastrectomy (LSG) is gaining popularity for the treatment of morbid obesity. It is a simple, low-cost procedure resulting in significant weight loss within a short period of time. LSG is a safe procedure with a low complication rate. The complications encountered nevertheless can result in morbidity and even mortality. The most significant complications are staple-line bleeding, stricture, and staple-line leak. The purpose of this paper is to present a patient who suffered from a staple-line leak presenting 16 months after LSG. Review of the current literature regarding this complication as well as outline of a strategy for the management of post-LSG gastric leaks is suggested.

The present in vitro and randomized, double‐blind, placebo‐controlled trial aims to determine the efficacy and safety of nine Mediterranean antiacne medicinal plants. The antimicrobial, antisebum, and anti‐inflammatory activities of the plant extracts were evaluated in cells from the immortalized human keratinocytes (HaCaT) and human monocytic cell line (THP‐1) as well as in a double‐blind, randomized, and placebo‐controlled trial. Most of the extracts showed no significant cytotoxic effects on HaCaT cells up to 250 μg/ml. Inula helenium (IH) and Saponaria officinalis (SO) inhibited sebum production at 90 μg/ml and 30 μg/ml, respectively. The inhibition effect of SO on the growth of Cutibacterium acnes was 1.2 times higher than that of chloramphenicol. IH and SO extracts significantly inhibited the lipopolysaccharide‐ (LPS‐) induced IL‐6 and TNF‐α production in THP‐1 cells reaching the control levels of untreated cells at a concentration of 250 μg/ml. SO, IH, and Solanum nigrum (SN) extracts inhibited the nitric oxide (NO) production in a dose‐dependent manner. Based on these results, an antiacne herbal cream (AHC) was prepared from different portions of extracts from SO, IH, and SN, and its efficacy was evaluated in a double‐blind, randomized, and controlled efficacy study with 41 acne patients, ages 18–24, who were asked to apply AHC (n = 27) or a placebo (n = 14) two to three times daily for six weeks. Results obtained indicate that the AHC has unique synergistic effects that halt sebum production, combined with highly antiseptic and anti‐inflammatory activity, in which 54.95% (t = 19.37 P < 0.001) of acne inflammatory and noninflammatory lesions disappeared after two weeks, 85.3%, after five weeks (t = 14.19 P < 0.001), and 91.4%, at the end of the sixth week of application (t = 5.7 P < 0.001). In conclusion, SO, IH, and SN as single extracts and in combination as AHC showed significant antimicrobial, antisebum, and anti‐inflammatory activities in vitro and in a double‐blind, randomized, and controlled antiacne efficacy. Therefore, AHC represents an interesting alternative treatment for acne.