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Abstract Background Many chemotherapeutic agents have been used to treat pancreatic cancer without success. Apigenin, a naturally occurring flavonoid, has been shown to inhibit growth in some cancer cell lines but has not been studied in pancreatic cancer. We hypothesized that apigenin would inhibit pancreatic cancer cell growth in vitro. Results Apigenin caused both time- and concentration-dependent inhibition of DNA synthesis and cell proliferation in four pancreatic cancer cell lines. Apigenin induced G2/M phase cell cycle arrest. Apigenin reduced levels of cyclin A, cyclin B, phosphorylated forms of cdc2 and cdc25, which are all proteins required for G2/M transition. Conclusion Apigenin inhibits growth of pancreatic cancer cells through suppression of cyclin B-associated cdc2 activity and G2/M arrest, and may be a valuable drug for the treatment or prevention of pancreatic cancer.

Background and Aims: Females with Barrett's esophagus (BE) have a lower risk of neoplastic progression than males, but sufficiently powered risk analyses are lacking. This systematic review and meta-analysis of individual patient data (IPD) aims to provide more robust evidence on neoplastic progression risk in females., Methods: Systematic literature search of three electronic databases (Medline, Embase, Google Scholar) from inception until August 2023. Eligible studies (1) reported original data on progression from non-dysplastic BE (NDBE), indefinite for dysplasia (IND) or low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), and (2) included female and male patients. IPD were quality controlled by two independent reviewers. Primary outcome was the association between sex and neoplastic progression risk, adjusted for risk factors using multivariable Cox regression analysis. Secondary outcomes were sex differences in time to progression and annual progression rate., Results: IPD were obtained from 11/66 eligible studies, including 2.196 (31%) females. Neoplastic progression risk was lower in females (HR 1.44 for males vs females, 95%CI 1.13-1.82) after adjusting for age, smoking, medication use, hiatal hernia, BE length, and baseline pathology. Annual progression rate was 0.88% in females vs 1.29% in males. Time to progression was similar in both sexes; 3.7 years (IQR 2.1-7.7) in females, and 4.2 years (IQR 2.0-8.1) in males., Conclusion: Although females had a lower neoplastic progression risk, sex differences were smaller than previously reported and time to progression was similar for both sexes. Future research should focus on other factors than sex to identify low- and high-risk BE patients., (Copyright © 2024. Published by Elsevier Inc.)

Aim: To evaluate the efficacy and safety of the laparoscopic approaches for parastomal hernia repair reported in the literature., Methods: A systematic review of PubMed and MEDLINE databases was conducted using various combination of the following keywords: stoma repair, laparoscopic, parastomal, and hernia. Case reports, studies with less than 5 patients, and articles not written in English were excluded. Eligible studies were further scrutinized with the 2011 levels of evidence from the Oxford Centre for Evidence-Based Medicine. Two authors reviewed and analyzed each study. If there was any discrepancy between scores, the study in question was referred to another author. A meta -analysis was performed using both random and fixed-effect models. Publication bias was evaluated using Begg's funnel plot and Egger's regression test. The primary outcome analyzed was recurrence of parastomal hernia. Secondary outcomes were mesh infection, surgical site infection, obstruction requiring reoperation, death, and other complications. Studies were grouped by operative technique where indicated. Except for recurrence, most postoperative morbidities were reported for the overall cohort and not by approach so they were analyzed across approach., Results: Fifteen articles with a total of 469 patients were deemed eligible for review. Most postoperative morbidities were reported for the overall cohort, and not by approach. The overall postoperative morbidity rate was 1.8% (95%CI: 0.8-3.2), and there was no difference between techniques. The most common postoperative complication was surgical site infection, which was seen in 3.8% (95%CI: 2.3-5.7). Infected mesh was observed in 1.7% (95%CI: 0.7-3.1), and obstruction requiring reoperation also occurred in 1.7% (95%CI: 0.7-3.0). Other complications such as ileus, pneumonia, or urinary tract infection were noted in 16.6% (95%CI: 11.9-22.1). Eighty-one recurrences were reported overall for a recurrence rate of 17.4% (95%CI: 9.5-26.9). The recurrence rate was 10.2% (95%CI: 3.9-19.0) for the modified laparoscopic Sugarbaker approach, whereas the recurrence rate was 27.9% (95%CI: 12.3-46.9) for the keyhole approach. There were no intraoperative mortalities reported and six mortalities during the postoperative course., Conclusion: Laparoscopic intraperitoneal mesh repair is safe and effective for treating parastomal hernia. A modified Sugarbaker approach appears to provide the best outcomes.

Background and Study Aims: Type III achalasia is characterized by rapidly propagating pressurization attributable to spastic contractions. Although laparoscopic Heller myotomy (LHM) is the current gold standard management for type III achalasia, peroral endoscopic myotomy (POEM) is conceivably superior because it allows for a longer myotomy. Our aims were to compare the efficacy and safety of POEM with LHM for type III achalasia patients., Patients and Methods: A retrospective study of 49 patients who underwent POEM for type III achalasia across eight centers were compared to 26 patients who underwent LHM at a single institution. Procedural data were abstracted and pre- and post-procedural symptoms were recorded. Clinical response was defined by improvement of symptoms and decrease in Eckardt stage to ≤ 1. Secondary outcomes included length of myotomy, procedure duration, length of hospital stay, and rate of adverse events., Results: Clinical response was significantly more frequent in the POEM cohort (98.0 % vs 80.8 %; P = 0.01). POEM patients had significantly shorter mean procedure time than LHM patients (102 min vs 264 min; P < 0.01) despite longer length of myotomy (16 cm vs 8 cm; P < 0.01). There was no significant difference between POEM and LHM in the length of hospital stay (3.3 days vs 3.2 days; P = 0.68), respectively. Rate of adverse events was significantly less in the POEM group (6 % vs 27 %; P < 0.01)., Conclusions: POEM allows for a longer myotomy than LHM, which may result in improved clinical outcomes. POEM appears to be an effective and safe alternative to LHM in patients with type III achalasia.

Survival of patients with pancreatic cancer remains poor due to inadequate chemotherapeutic options. Sansalvamide A, a cyclic depsipeptide produced by a marine fungus, has demonstrated significant anticancer activity. We previously observed antiproliferative effects in a series of sansalvamide A analogs in pancreatic cancer cells, one of which was further evaluated in this study. Two human pancreatic cancer cell lines (AsPC-1 and CD18) were incubated with increasing concentrations (10-50 muM) of the sansalvamide analog. Cell proliferation was then measured by thymidine incorporation and cell counting, and cell cycle analysis was determined by flow cytometry. Western blot analysis was used to evaluate expression of cyclin D1, cdk4, cdk6, cyclin E, cyclin A, cdk2, and p21. Sansalvamide caused G(1) phase cell cycle arrest in both cell lines, and Western blot analyses demonstrated up-regulation of p21, down-regulation of cyclins D1, E, and A, and cdk4, consistent with G(0)/G(1) cell cycle arrest. Cumulatively the results show that Sansalvamide A attenuates pancreatic cancer cell growth and represents a potential anticancer therapy.

Pancreatic cancer is a disease carrying a dismal prognosis, with overall 5-year survival at around 4%. Recent clinical trials of adjuvant therapies have not found a dramatic increase in median survival. In the current review, we examine the available literature on flavonoids, a group of naturally occurring substances, for their effects on cancer cells and potential for therapy of pancreatic cancer in the future. With the available in vitro and in vivo data, it is likely that flavonoids will move into the clinical arena as therapeutic or preventive tools for cancer.