Outcomes of external and endonasal dacryocystorhinostomy according to a modified Lacrimal Symptom Questionnaire (Lac-Q)

Background: Nasolacrimal duct obstruction is usually treated using endoscopic or external dacryocystorhinostomy (DCR). The anatomic outcomes of both the endoscopic and external approaches are considered excellent. However, anatomic success does not translate into patient satisfaction. The current study assessed pre- and postoperative lacrimal problems using the symptom-based Lacrimal Symptom Questionnaire (Lac-Q) and investigated patient satisfaction depending on the choice of surgical technique. Methods: A total of 112 eligible patients with lacrimal problems treated using external or endonasal DCR at the ophthalmology and ear, nose, and throat clinics at Skane University Hospital, Sweden, over a four-year period, were enrolled in this retrospective study. Patients were considered eligible if they experienced preoperative epiphora and had lacrimal duct stenosis. They were offered treatment using either external or endonasal DCR and were allowed to freely choose the technique. Exclusion criteria consisted of previous ipsilateral DCR, congenital NLDO, age < 18 years, presence of cancer, previous orbital trauma, or noncompliance with postoperative follow-up. After surgery, the patients were sent the Lac-Q to evaluate their lacrimal symptoms pre- and postoperatively. Complementary questions were added pertaining to the operative scar and the patients’ overall satisfaction with the operation. Results: In total, 67 (60%) patients with ages ranging from 18 to 88 years completed the questionnaire, 33 (49%) of whom underwent external DCR and 34 (51%) endonasal DCR. Of the 67 respondents, 51 (76%) were women and 16 (24%) were men. Patients scored preoperative lacrimal problems highly on the Lac-Q, reporting both symptomatic and social problems due to epiphora. Following surgery, the group that underwent external DCR  remained home from work for 2 – 14 days (median, 3.5 days). However, 17 (52%) were retired. After the endonasal DCR, the patients remained home for 0 – 7 days (median, 2 days). Most patients were satisfied after DCR surgery, with both techniques significantly improving total, lacrimal symptom, and social impact scores (all P < 0.001). No differences in postoperative satisfaction were observed between the external DCR and endonasal DCR groups (P > 0.05). A small number of patients expressed scar-related concerns after external DCR. Conclusions: The patients perceived lacrimal problems as a significant symptomatic and social burden. Postoperative satisfaction and symptom relief were good regardless of the surgical approach. Further prospective studies assessing patient satisfaction and its correlation with anatomical and functional success rates after external and endonasal DCR could provide robust, practical, real-world implications

Does Helicobacter pylori infection per se cause gastric cancer or duodenal ulcer? Inadequate evidence in Mongolian gerbils and inbred mice

A role for Helicobacter pylori infection in the development of gastric cancer in humans is well established; however, evidence for its carcinogenicity in animals remains inadequate. Mongolian gerbils and mice are commonly used to investigate the carcinogenicity of H. pylori, yet it is unclear whether H. pylori infection per se causes gastric cancer or duodenal ulcers in these animal models. Gastric adenocarcinoma in the gerbils was reported over 10 years ago, but this species has proved an unreliable model for studying H. pylori infection-associated gastric cancer. Helicobacter pylori infection alone appears insufficient to induce gastric cancer in these animals; additional carcinogenic insult is required. The development of invasive adenocarcinoma in inbred mice is rare regardless of the mouse or bacterial strain, and many long-term studies have failed to induce gastric cancer in these animals. Helicobacter pylori infection is also an established causative factor for duodenal ulcer in humans. However, few studies have attempted to develop animal models of H. pylori infection-induced duodenal ulcer. We therefore conclude that both Mongolian gerbils and inbred mice may be inadequate models for studying H. pylori infection-associated gastric cancer and that there is no animal model of H. pylori infection-induced duodenal ulcer

Gastric bypass surgery does not increase susceptibility to Helicobacter pylori infection in the stomach of rat or mouse

Gastric bypass is a clinical option for obesity surgery. An increased susceptibility to Helicobacter pylori infection in the bypassed stomach has been speculated. The aim of the present study was to examine the susceptibility of the bypassed stomach to H. pylori infection in rats and mice. Adult Sprague-Dawley and Wistar rats and NMRI mice were subjected to either gastric bypass or laparotomy only as control. The animals were inoculated with the CagA- and VacA- positive H. pylori strain 67/21 (not mouse-adapted) in the first experiment and with 9 additional isolates in the second, by injection into the bypassed stomach or the control stomach during surgery. The stomach of each animal was collected for H. pylori culture 2-3 weeks later. While all the rats were H. pylori negative, 54% of gastric bypassed mice and 75% of controls were positive (P = 0.4). We conclude that susceptibility to H. pylori infection in the stomach is not increased by gastric bypass surgery

Ghrelin in the regulation of feeding and energy balance

Ghrelin, the first identified endogenous ligand for the growth hormone secretagogue receptor 1A, is a 28 amino acid peptide produced mainly by the stomach. Pharmacological studies indicate a role for ghrelin in the regulation of growth hormone secretion from the pituitary and also in the regulation of body weight, fat accumulation and food intake. Using a classical endocrine deletion/replacement approach we found support for the notion that endogenous ghrelin is required for the maintenance of normal body weight and adiposity. Gastrectomy (Gx) surgery, that depleted animals of ~80% of circulating ghrelin, caused a reduction in body weight, fat mass and lean mass in adult mice. Ghrelin replacement (at a dose that restores circulating ghrelin levels in Gx mice and that is without effect on body weight in sham animals) fully or partially reversed the decrease in body weight, fat mass and lean mass following Gx. To further investigate the central mechanism behind these effects on body weight and fat mass following Gx-surgery and ghrelin treatment key hypothalamic genes involved in energy homeostasis were analysed by in situ hybridisation. Surprisingly the marked changes in body composition following Gx did not effect expression of the hypothalamic genes studied, to any large extent. By contrast ghrelin treatment increased mRNA expression of NPY and AgRP and decreased POMC mRNA expression in accordance with ghrelin s effects to increase fat mass and body weight. Using growth hormone receptor (GHR) knockout animals we investigated the importance of a functional GHR signalling system for the acute effects of ghrelin on food intake. Ghrelin treatment increased food intake in wild type animals but not in GHR knockouts indicating that a functional GHR signalling system is needed for the acute effects of ghrelin on food intake. In addition to impacting upon the hypothalamic circuits controlling energy balance, ghrelin was found to interact with the mesolimbic reward circuits (reflected by increased locomotor activity and dopamine release after ghrelin injection to the brain ventricles). In conclusion, endogenous ghrelin from the stomach is important for maintaining normal body weight and body composition. Long term treatment with ghrelin increases body fat by a mechanism that appears to be independent of its acute affects on food intake. Long term ghrelin treatment still impacts upon hypothalamic genes regulating energy balance. Ghrelin s acute effect on food intake is dependant on a functional GHR signalling system. Moreover, this effect may be linked to dopamine release in areas of the brain intimately associated with reward-seeking activities

Human Barrett's Adenocarcinoma of the Esophagus, Associated Myofibroblasts, and Endothelium Can Arise from Bone Marrow-Derived Cells After Allogeneic Stem Cell Transplant

This study characterizes the contribution of bone marrow-derived cells (BMDCs) to Barrett's adenocarcinoma of the esophagus using a mouse surgical model of disease and human specimens. Transplantation of bone marrow expressing beta galactosidase into a wild-type mouse, followed by surgical esophagojejunostomy, allowed tracking of BMDCs into the surgical anastomosis and resulting Barrett's metaplasia. Human tissue from a male patient who had been transplanted with female bone marrow and later developed esophageal adenocarcinoma allowed us to tract donor-derived cells into the tumor. Using a combination of antibodies directed against beta-galactosidase (animal studies) and X/Y fluorescent in situ hybridization (FISH) (human studies), combined with specific lineage staining directed against epithelial, fibroblast, endothelial, and leukocyte markers, we show that bone marrow cells contribute to both the epithelial and stromal component of esophageal adenocarcinoma. These findings demonstrate that BMDCs can generate cancer-associated fibroblasts as well as contribute directly to epithelial cells in cancer of the esophagus

Swedish moist snuff accelerates gastric cancer development in Helicobacter pylori-infected wild-type and gastrin transgenic mice

The Swedish variant of moist oral smokeless tobacco (snus) is popular in Sweden and Norway, banned from sale within the European Union and is currently being introduced in USA. The aim of the present study was to determine if snus is carcinogenic to the stomach, particularly in Helicobacter pylori (H.P.)-infected hosts at increased risk for gastric cancer development. Snus (General (TM); Swedish Match, Sweden) was mixed with powdered standard mouse chow at a concentration of 5-9% (wt/wt) and given to wild-type (WT, FVB) and gastrin transgenic (INS-GAS, FVB) mice for 6 months with or without H.P. (strain 67:21, CagA(+), VacA(+)) infection. At necropsy, pathological evaluation of stomachs from uninfected snus-treated WT mice showed mild morphological changes, whereas 50% snus-treated INS-GAS mice developed carcinoma in situ (CIS), compared with 25% not exposed to snus. When snus was given to H.P.-infected mice, 9 of 17 WT mice developed CIS with intramucosal invasion, and the remaining 8 of 17 WT mice developed high-grade dysplasia (score > 1.5) that was associated with increased gastritis, epithelial defects, oxyntic atrophy, hyperplasia and intestinal metaplasia. Twelve of 12 H.P.-infected INS-GAS mice developed CIS with intramucosal invasion and submucosal herniation. We suggest that snus is a potential gastric carcinogen in mice. The development of CIS was associated with increased rates of the epithelial cell proliferation and apoptosis, common features of gastric carcinogenesis