World Journal of Gastrointestinal Pharmacology and Therapeutics最新文献

Aim: To investigate the clinical impact of post-hyperthermic intraperitoneal chemotherapy (HIPEC) leukopenia, intraperitoneal and combined intravenous/intraperitoneal drug administrations were compared.

Methods: Two patient cohorts were retrospectively analyzed regarding the incidence of postoperative leukopenia. The first cohort (n = 32) received Mitomycin C (MMC)-based HIPEC intraperitoneally (35 mg/m² for 90 min) and the second cohort (n = 10) received a bi-directional therapy consisting of oxaliplatin (OX) (300 mg/m(2) for 30 min) intraperitoneally and 5-fluorouracil (5-FU) 400 mg/m² plus folinic acid 20 mg/m² intravenously. The following data were collected retrospectively: Age, sex, length of operation, length of hospital stay, amount of resection including extent of peritonectomy, peritoneal cancer index, CC (completeness of cytoreduction)-status and leukocyte-count before cytoreductive surgery (CRS) and HIPEC, on days 3, 7 and 14 after CRS and HIPEC. HIPEC leukopenia was defined as < 4000 cells/m³.

Results: Leukopenia occurred statistically more often in the MMC than in the OX/5-FU-group (10/32 vs 0/10; P = 0.042). Leukopenia set-on was on day 7 after CRS and MMC-HIPEC and lasted for two to three days. Three patients (33%) required medical treatment. Patients affected by leukopenia were predominantly female (7/10 patients) and older than 50 years (8/10 patients). The length of hospital stay tended to be higher in the MMC-group without reaching statistical significance (22.5 ± 11 vs 16.5 ± 3.5 d). Length of operation (08:54 ± 01:44 vs 09:48 ± 02:28 h) were comparable between patients with and without postoperative leukopenia. Prior history of systemic chemotherapy did not trigger post-HIPEC leukopenia. Occurrence of leucopenia did not trigger surgical site infections, intraabdominal abscess formations, hospital-acquired pneumonia or anastomotic insufficiencies.

Conclusion: Surgeons must be aware that there is a higher incidence of postoperative leukopenia in MMC-based HIPEC protocols primarily affecting females and older patients.

Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis are complex disorders with undetermined etiology. Several hypotheses suggest that IBDs result from an abnormal immune response against endogenous flora and luminal antigens in genetically susceptible individuals. The dysfunction of the mucosal immune response is implicated in the pathogenesis of IBD. The balance between pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, and IL-17A], anti-inflammatory cytokines (IL-4 and IL-13), and immunoregulatory cytokines (IL-10 and transforming growth factors β) is disturbed. Moreover, evidence from animal and clinical studies demonstrate a positive correlation between an increased concentration of nitric oxide (NO) and the severity of the disease. Interestingly, proinflammatory cytokines are involved in the up-regulation of inducible oxide synthase (iNOS) expression in IBD. However, anti-inflammatory and immunoregulatory cytokines are responsible for the negative regulation of iNOS. A positive correlation between NO production and increased pro-inflammatory cytokine levels (TNF-α, IL-6, IL-17, IL-12, and interferon-γ) were reported in patients with IBD. This review focuses on the role of cytokines in intestinal inflammation and their relationship with NO in IBD.

Barrett's esophagus (BE) is defined as the extension of salmon-colored mucosa into the tubular esophagus ≥ 1 cm proximal to the gastroesophageal junction with biopsy confirmation of intestinal metaplasia. Patients with BE are at increased risk of esophageal adenocarcinoma (EAC), and undergo endoscopic surveillance biopsies to detect dysplasia or early EAC. Dysplasia in BE is classified as no dysplasia, indefinite for dysplasia (IND), low grade dysplasia (LGD) or high grade dysplasia (HGD). Biopsies are diagnosed as IND when the epithelial abnormalities are not sufficient to diagnose dysplasia or the nature of the epithelial abnormalities is uncertain due to inflammation or technical issues. Specific diagnostic criteria for IND are not well established and its clinical significance and management has not been well studied. Previous studies have focused on HGD in BE and led to changes and improvement in the management of BE with HGD and early EAC. Only recently, IND and LGD in BE have become focus of intense study. This review summarizes the definition, neoplastic risk and clinical management of BE IND.

Aim: To evaluate the structural organization of the elastic and collagen fibers in the region of the ileocecal transition in 30 young and old male Wistar rats.

Methods: Histology, immunohistochemistry (IHC), transmission electron microscopy and scanning electron microscopy were employed in this study. The results demonstrated that there was a demarcation of the ileocecal region between the ileum and the cecum in both groups.

Results: The connective tissue fibers had different distribution patterns in the two groups. IHC revealed the presence of nitric oxide synthase, enteric neurons and smooth muscle fibers in the ileocecal junctions (ICJs) of both groups. Compared to the young group, the elderly group exhibited an increase in collagen type I fibers, a decrease in collagen type III fibers, a decreased linear density of oxytalan elastic fibers, and a greater linear density of elaunin and mature elastic fibers.

Conclusion: The results revealed changes in the patterns of distribution of collagen and elastic fibers that may lead to a possible decrease in ICJ functionality.

Inflammatory bowel disease (IBD) predominantly affects young adults. Fertility-related issues are therefore important in the management of patients with IBD. However, relatively modest attention has been paid to reproductive issues faced by men with IBD. To investigate the effects of IBD and its treatment on male fertility, we reviewed the current literature using a systematic search for published studies. A PubMed search were performed using the main search terms "IBD AND male infertility", "Crohn's disease AND male infertility", "ulcerative colitis AND male infertility". References in review articles were used if relevant. We noted that active inflammation, poor nutrition, alcohol use, smoking, medications, and surgery may cause infertility in men with IBD. In surgery such as proctocolectomy with ileal pouch-anal anastomosis, rectal incision seems to be associated with sexual dysfunction. Of the medications used for IBD, sulfasalazine reversibly reduces male fertility. No other medications appear to affect male fertility significantly, although small studies suggested some adverse effects. There are limited data on the effects of drugs for IBD on male fertility and pregnancy outcomes; however, patients should be informed of the possible effects of paternal drug exposure. This review provides information on fertility-related issues in men with IBD and discusses treatment options.

Aim: To classify changes over time in causes of lower gastrointestinal bleeding (LGIB) and to identify factors associated with changes in the incidence and characteristics of diverticular hemorrhage (DH).

Methods: A total of 1803 patients underwent colonoscopy for overt LGIB at our hospital from 1995 to 2013. Patients were divided into an early group (EG, 1995-2006, n = 828) and a late group (LG, 2007-2013, n = 975), and specific diseases were compared between groups. In addition, antithrombotic drug (ATD) use and nonsteroidal anti-inflammatory drug (NSAID) use were compared between patients with and without DH.

Results: Older patients (≥ 70 years old) and those with colonic DH were more frequent in LG than in EG (P < 0.01). Patients using ATDs as well as NSAIDs, male sex, obesity (body mass index ≥ 25 kg/m(2)), smoking, alcohol drinking, and arteriosclerotic diseases were more frequent in patients with DH than in those without.

Conclusion: Incidence of colonic DH seems to increase with aging of the population, and factors involved include use of ATDs and NSAIDs, male sex, obesity, smoking, alcohol drinking, and arteriosclerotic disease. These factors are of value in handling DH patients.

One of the most challenging issues arising in patients with chronic pancreatitis is the management of abdominal pain. Many competing theories exist to explain pancreatic pain including ductal hypertension from strictures and stones, increased interstitial pressure from glandular fibrosis, pancreatic neuritis, and ischemia. This clinical problem is superimposed on a background of reduced enzyme secretion and altered feedback mechanisms. Throughout history, investigators have used these theories to devise methods to combat chronic pancreatic pain including: Lifestyle measures, antioxidants, analgesics, administration of exogenous pancreatic enzymes, endoscopic drainage procedures, and surgical drainage and resection procedures. While the value of each modality has been debated over the years, pancreatic enzyme therapy remains a viable option. Enzyme therapy restores active enzymes to the small bowel and targets the altered feedback mechanism that lead to increased pancreatic ductal and tissue pressures, ischemia, and pain. Here, we review the mechanisms and treatments for chronic pancreatic pain with a specific focus on pancreatic enzyme replacement therapy. We also discuss different approaches to overcoming a lack of clinical response update ideas for studies needed to improve the clinical use of pancreatic enzymes to ameliorate pancreatic pain.

The use of biological agents and immunomodulators for inflammatory bowel disease (IBD) is associated with an increased risk of opportunistic infections, in particular of viral or bacterial etiology. Despite the existence of international guidelines, many gastroenterologists have not adopted routine screening and vaccination in those patients with IBD, which are candidate for biologic therapy. Available strategies to screen, diagnose and prevent bacterial and viral infections in patients with IBD prior to start biological therapy are discussed in this review.