Iyad Khamaysi

Supplementary Figure S1 from A Phase II Trial of an Extended-Release siRNA Implant Targeting KRASG12D/V in Locally Advanced Pancreatic Cancer

Study Representativeness Table

Anastomotic strictures and leaks are frequent complications following the surgical repair of esophageal atresia, with a subset of patients developing refractory disease despite repeated dilations. This case series evaluates the preliminary feasibility and the outcomes of using off-label, fully covered, self-expanding, metal biliary stents in infants with refractory anastomotic strictures or leaks. Six infants treated at a tertiary referral center between 2021 and 2025 underwent endoscopic placement of fully covered self-expanding metal biliary stents. Technical success in stent placement and removal was achieved in all patients (100%). Clinical success was observed in 83.3% of patients; specifically, complete sealing of leaks and perforations was achieved in 100% of cases, while sustained luminal patency was observed in half of the isolated refractory strictures. One patient with a long-segment stricture required subsequent surgical revision. No major adverse events were identified during a median follow-up of 2.75 years. These preliminary findings suggest that biliary stents may represent a feasible rescue option for managing complex postoperative esophageal atresia complications in infants when specialized pediatric devices are unavailable.

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.

Acute pancreatitis (AP) is a common gastrointestinal disease with high morbidity and mortality rate. Unfortunately, neither the etiology nor the pathophysiology of AP are fully understood and causal treatment options are not available. Recently we demonstrated that heparanase (Hpa) is adversely involved in the pathogenesis of AP and inhibition of this enzyme ameliorates the manifestation of the disease. Moreover, a pioneer study demonstrated that Aspirin has partial inhibitory effect on Hpa. Another compound, which possesses a mild pancreato‐protective effect against AP, is Trehalose, a common disaccharide. We hypothesized that combination of Aspirin, Trehalose, PG545 (Pixatimod) and SST0001 (Roneparstat), specific inhibitors of Hpa, may exert pancreato‐protective effect better than each drug alone. Thus, the current study examines the pancreato‐protective effects of Aspirin, Trehalose, PG545 and SST0001 in experimental model of AP induced by cerulein in wild‐type (WT) and Hpa over‐expressing (Hpa‐Tg) mice. Cerulein‐induced AP in WT mice was associated with significant rises in the serum levels of lipase (X4) and amylase (X3) with enhancement of pancreatic edema index, inflammatory response, and autophagy. Responses to cerulein were all more profound in Hpa‐Tg mice versus WT mice, evident by X7 and X5 folds increase in lipase and amylase levels, respectively. Treatment with Aspirin or Trehalose alone and even more so in combination with PG545 or SST0001 were highly effective, restoring the serum level of lipase back to the basal level. Importantly, a novel newly synthesized compound termed Aspirlose effectively ameliorated the pathogenesis of AP as a single agent. Collectively, the results strongly indicate that targeting Hpa by using anti‐Hpa drug combinations constitute a novel therapy for this common orphan disease.

Brush cytology is a sampling technique extensively used for mucosal surfaces, particularly to identify malignancies. A sample is obtained by rubbing the brush bristles over the stricture or lesion several times until cells are trapped. Brush cytology detection rate varies, with malignancy confirmed in 15-65% of cases of adenocarcinoma-associated biliary strictures and 44-80% of cases of cholangiocarcinoma. Despite the widespread use of brush cytology, there is no consensus to date defining the optimal biliary brushing parameters for the collection of suspicious lesions, such as the number of passes, brushing rate, and force applied. The aim of this work is to increase the brush cytology diagnostic yield by elucidating the underlying mechanical phenomena. First, the mechanical interactions between the brush bristles and sampled tissue are analyzed. During brushing, mucus and detached cells are transferred to the space between the bristles through the capillary rise and flow eddies. These mass transfer mechanisms and their dependence on mucus rheology as a function of pH, brush displacement rate, and bristle geometry and configuration are examined. Lastly, results from ex vivo brushing experiments performed on porcine stomachs are presented. Clinical practitioners from a variety of disciplines can apply the findings of this study to outline clear procedures for cytological brushing to increase the sensitivity and specificity of the brushings.

Nigella sativa, Conyza bonariensis, and Alchemilla vulgaris are highly recommended in Greco-Arab traditional medicine as anti-hemorrhoid medicinal plants. The efficacy and safety of a topical cream (HPC) consisting of water–ethanol extracts of these three plants were evaluated here in vitro and in a randomized, double-blind, placebo-controlled study (RDBPC). HPC showed no significant cytotoxic effects in fibroblast cell line 3T3 (LDH-release and MTT assay); it inhibited the nitric oxide production by cultured monocyte cell line THP-1 in a dose-dependent manner (reaching the control levels of untreated cells at a concentration of 100 μg/mL). HPC showed a dose-dependent antibacterial activity against Escherichia coli (60% inhibition compared to Ampicillin at 5 mg/disc) and a significant vasoconstriction effect on intestinal vein rings (40% increase compared to phenylephrine). In a RDBPC with 77 hemorrhoidal disease (patients ages 19–61 years with a median grade of hemorrhoids of 2.0), we determined the anti-hemorrhoid efficacy and safety of HPC. The patients were randomly assigned to the HPC group (54 patients) or the placebo group (23 patients). They were asked to apply 2–3 mL of HPC or placebo twice daily for 6 days. The degree of hemorrhoidal disease severity, hemorrhage severity, pain, and itching served as an evaluation of the HPC efficacy. Compared to the placebo group, the obtained results showed that 6 days of treatment with HPC reduced the indexes of hemorrhage severity, severity of pain, and severity of itching to 0–1, 1, and 1 after 6 days, respectively. In conclusion, patients treated with HPC had a significant clinical improvement in all disease severity parameters compared to placebo. In vitro evaluations proved HPC to have significant antimicrobial, anti-inflammatory, and vasoconstriction effects. Therefore, HPC represents an interesting alternative treatment for hemorrhoidal disease.

Cite this article as: Khamaysi I, Leiderman M, Hajj E, Yassin K. Ultrasound-guided percutaneous venting duodenostomy: New technique. Turk J Gastroenterol 2020; 31(12): 962-3.