Polarised epithelial monolayers of the gastric mucosa reveal insights into mucosal homeostasis and defence against infection.

OBJECTIVE: Helicobacter pylori causes life-long colonisation of the gastric mucosa, leading to chronic inflammation with increased risk of gastric cancer. Research on the pathogenesis of this infection would strongly benefit from an authentic human in vitro model. DESIGN: Antrum-derived gastric glands from surgery specimens served to establish polarised epithelial monolayers via a transient air-liquid interface culture stage to study cross-talk with H. pylori and the adjacent stroma. RESULTS: The resulting 'mucosoid cultures', so named because they recapitulate key characteristics of the gastric mucosa, represent normal stem cell-driven cultures that can be passaged for months. These highly polarised columnar epithelial layers encompass the various gastric antral cell types and secrete mucus at the apical surface. By default, they differentiate towards a foveolar, MUC5AC-producing phenotype, whereas Wnt signalling stimulates proliferation of MUC6-producing cells and preserves stemness-reminiscent of the gland base. Stromal cells from the lamina propria secrete Wnt inhibitors, antagonising stem-cell niche signalling and inducing differentiation. On infection with H. pylori, a strong inflammatory response is induced preferentially in the undifferentiated basal cell phenotype. Infection of cultures for several weeks produces foci of viable bacteria and a persistent inflammatory condition, while the secreted mucus establishes a barrier that only few bacteria manage to overcome. CONCLUSION: Gastric mucosoid cultures faithfully reproduce the features of normal human gastric epithelium, enabling new approaches for investigating the interaction of H. pylori with the epithelial surface and the cross-talk with the basolateral stromal compartment. Our observations provide striking insights in the regulatory circuits of inflammation and defence.

First surgical tumour reduction of peritoneal surface malignancy in a rat's model.

Surgical therapy of peritoneal surface malignancy from colorectal origin in combination with Hyperthermic Intraoperative Peritoneal Chemotherapy (HIPEC) has now become an established treatment approach in very few specialised centres. A peritonectomy procedure is possible to perform with additional HIPEC in patients. An experimental model to simulate peritonectomy procedure and HIPEC does not exist so far in rats. Nevertheless, animal models seem to be very important for evaluation of new therapeutic opportunities and toxicity of different multimodal therapies. In a first step we analysed the surgical tumour debulking of peritoneal surface malignancy in rats. A peritoneal surface malignancy from colonic origin was induced in 75 male BD IX rats. Twenty one days after induction of peritoneal surface malignancy rats were randomised and animals intend to create an operation with surgical tumour debulking. There was no tumour growth in two animals. The aim of the peritonectomy procedure was the complete tumour reduction. In this study the results of the surgical approach will be described. A complete tumour reduction (R0) was achieved in 34 animals. In 39 rats a macroscopic tumour deposit was left behind (R2). The intraoperative experimental Peritoneal Cancer Index (ePCI) was used to describe tumour weight and number of tumour inoculations. Both parameters were found to be dependent factors of complete tumour reduction. Six animals died due to therapeutical interventions. Surgical tumour debulking in rats with peritoneal surface malignancy is possible with high reliability and a low mortality rate. This animal model could be an important step for investigation of multimodal treatment options and toxicity in treatment regimens of peritoneal surface malignancy.

Olfactory and Gustatory Function After Bariatric Surgery.

BACKGROUND: Neither hormone levels nor malabsorption alone fully explains the distinct weight loss after bariatric surgery in morbidly obese patients. Postoperatively, patients regularly report a change in the sense of taste and the development of food aversions. Hedonic and sensory components like olfactory and gustatory stimuli significantly affect appetite and flavour. METHODS: We prospectively analysed the orthonasal olfactory and gustatory function with psychophysical testing in 44 patients undergoing laparoscopic Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG) or adjustable gastric banding (AGB) and in 23 healthy controls. RESULTS: About 22.7 % of morbidly obese patients were hyposmic, showing significantly lower threshold-discrimination-identification (TDI) scores (p = 0.009) with decreased discrimination and identification ability. In addition, 22.7 % of patients were tested to be limited in gustatory function, with significantly lower taste strip test (TST) scores (p = 0.003). Six months after surgery, olfactory and gustatory function was not different when compared to healthy controls. CONCLUSIONS: Due to obesity, patients frequently show impaired olfactory and gustatory function. Six months after laparoscopic bariatric surgery, both chemosensory functions improve. The TDI test is an appropriate tool to measure olfactory function in obese patients.

Associations of physical activity with depressiveness and coping in subjects with high-grade obesity aiming at bariatric surgery: a cross-sectional study.

BACKGROUND: Reduced physical activity is supposed to be associated with depressiveness and more passive coping patterns. For further evaluation of this assumed relation we studied energy expenditure due to physical activity - usually referred to as activity thermogenesis (AT) - together with depressiveness (clinical diagnosis, depression module of the Patient Health Questionnaire), and coping behaviours (Brief COPE Inventory) in 50 patients with high-grade obesity (42 ± 12 years; 9 with II° and 41 with III° obesity) aiming at bariatric surgery. METHODS: AT was assessed with a portable armband device (SenseWear™ armband). Depressiveness and coping were assessed using validated questionnaires. RESULTS: Weight-adjusted non-exercise AT and intensity of physical activity (metabolic equivalent) correlated inversely with body mass index (non-exercise AT: r = -0.32, P < 0.05; mean metabolic equivalent: r = -0.37, P < 0.01) but not with depressiveness. The coping strategies "support coping" and "active coping" showed significant inverse correlations to a) weight-adjusted non-exercise AT ("support coping": r = -0.34, P < 0.05; "active coping": r = -0.36, P < 0.05), b) weight-adjusted exercise-related AT ("support coping": r = -0.36, P < 0.05; "active coping": r = -0.38, P < 0.01) and c) intensity of physical activity (for mean metabolic equivalent: "support coping": r = -0.38, P < 0.01; "active coping": r = -0.40, P < 0.01; for duration of exercise-related AT: "support coping": r = -0.36, P < 0.05; "active coping": r = -0.38, P < 0.01). CONCLUSIONS: AT was not associated with depressiveness. Furthermore, supposed adaptive coping strategies of individuals aiming at bariatric surgery were negatively associated with AT.

Long-term results of quality of life after standard laparoscopic vs. robot-assisted laparoscopic fundoplications for gastro-oesophageal reflux disease. A comparative clinical trial.

BACKGROUND: The role of telematic surgical approach in gastro-oesophageal reflux disease (GERD) is still unclear. METHODS: The aim of the study is to assess disease specific symptoms and quality of life in patients with GERD treated with either traditional laparoscopic (TL) or robot-assisted fundoplication using the Da Vinci system (DV) in long-term follow-up. RESULTS: Eighty patients underwent a fundoplication in 2003. Four years later all patients were given a standardized questionnaire and 59 (74%) replied. The TL group included 44 patients (18 male/26 female) and the DV group 15 patients (9 male/6 female); the mean operating time was 116 min for the TL group and 207 min for the DV group (p < 0.001). The mean GIQLI score was 106 points for TL and 107 points in the DV (p > 0.05). CONCLUSIONS: Although a safe and feasible procedure, high functional costs of the Da Vinci system and longer operating time prevent this operation from being the standard surgical procedure for GERD.

The clear cell adenocarcinoma of the colon: case report and review of the literature.

BACKGROUND: Primary clear cell adenocarcinoma of the colon is a rare oncological entity. We report a case of such a tumor in the left colonic flexure of an 89-year-old patient who was treated surgically in our Department. We also review published cases which include primary colonic clear cell formations. CASE PRESENTATION: The patient sustained a segmental resection of the region [pT2 N0 (0/12) M0]. Histochemical examination indicated a primary clear cell colonic adenocarcinoma. The patient was discharged in good health but died from his disease 2 years later. RESULTS: Primary clear cell colonic adenocarcinoma is found exclusively in the left colon and generally in elderly men. From the few cases that have been published it is not possible to estimate the oncological impact of this tissue. CONCLUSION: Even in advanced age surgical resection is the mainstay of the recommended treatment.