Philipp Kirchhoff

Assessment of a novel screening score for nutritional risk in predicting complications in gastro-intestinal surgery

BACKGROUND & AIMS Malnutrition is a recognized risk factor for perioperative morbidity, but there is currently no standardized definition of malnutrition. The Nutrition Risk Screening 2002 score was recently proposed to identify patients at nutritional risk who may benefit from nutritional support therapy, and has been officially adopted by the European Society of Parenteral and Enteral Nutrition. The aim of this study was to assess the value of the Nutrition Risk Screening 2002 score in predicting the incidence and severity of postoperative complications in gastrointestinal surgery. METHODS We prospectively evaluated 608 patients admitted for elective gastrointestinal surgery. Nutritional risk was defined by the Nutrition Risk Screening 2002 score and correlated to the incidence and severity of postoperative complications. Complications were classified using an established surgical complication classification. RESULTS The overall incidence of nutritional risk was 14%. We observed a significantly higher complication rate of 40% (35 out of 87) in patients at nutritional risk, compared to 15% (81 out of 521) in patients with a normal score (p<0.001). The incidence of severe complications was significantly higher in patients at nutritional risk (54% versus 15%; p<0.001). The odds ratio to develop a complication was 2.8 in patients at risk (p=0.001), and 3.0 in patients with malignant disease (p<0.001). The median length of stay in nutritional risk patients was significantly longer (10 versus 4 days, p<0.001). CONCLUSION The prevalence of nutritional risk patients in gastrointestinal surgery is high. We showed that nutritional risk screening using the NRS 2002 strongly predicts the incidence and severity of complications.

The correlation of nutrition risk index, nutrition risk score, and bioimpedance analysis with postoperative complications in patients undergoing gastrointestinal surgery.

BACKGROUND Malnutrition in gastrointestinal (GI) surgery is associated with increased morbidity. Therefore, careful screening remains crucial to identify patients at risk for malnutrition and consequently postoperative complications. The aim of this study was to evaluate the ability of 3 established score systems to identify patients at risk of developing postoperative complications in GI surgery and to assess the correlation among the score systems. METHODS We evaluated prospectively 200 patients admitted for elective GI surgery using (1) nutrition risk index, (2) nutrition risk score, and (3) bioelectrical impedance analysis. Complications were assessed using a standardized complication classification. The findings of the score systems were correlated with the incidence and severity of complications. Parametric and nonparametric correlation analysis was performed among the different score systems. RESULTS All 3 score systems correlated significantly with the incidence and severity of postoperative complications and the duration of hospital stay. Using multiple regression analysis, only nutrition risk score and malignancy remained prognostic factors for the development of complications with odds ratios of 4.2 (P = .024) and 5.6 (P < .001), respectively. The correlation between nutrition risk score and nutrition risk index was only moderate (Pearson coefficient = 0.54). Bioelectrical impedance analysis displayed only weak to trivial correlation to the nutrition risk index (0.32) and nutrition risk score (0.19), respectively. CONCLUSION The nutrition risk score, nutrition risk index, and bioimpedance analysis correlate with the incidence and severity of perioperative complications in GI surgery. The nutrition risk score was the best score in predicting patients who will develop complications in this study population. The correlation between the individual scores was only moderate, and therefore, they do not necessarily identify the same patients.

The KCNE2 Potassium Channel Ancillary Subunit Is Essential for Gastric Acid Secretion

Genes in the KCNE family encode single transmembrane domain ancillary subunits that co-assemble with voltage-gated potassium (Kv) channel α subunits to alter their function. KCNE2 (also known as MiRP1) is expressed in the heart, is associated with human cardiac arrhythmia, and modulates cardiac Kv α subunits hERG and KCNQ1 in vitro. KCNE2 and KCNQ1 are also expressed in parietal cells, leading to speculation they form a native channel complex there. Here, we disrupted the murine kcne2 gene and found that kcne2 (-/-) mice have a severe gastric phenotype with profoundly reduced parietal cell proton secretion, abnormal parietal cell morphology, achlorhydria, hypergastrinemia, and striking gastric glandular hyperplasia arising from an increase in the number of non-acid secretory cells. KCNQ1 exhibited abnormal distribution in gastric glands from kcne2 (-/-) mice, with increased expression in non-acid secretory cells. Parietal cells from kcne2 (+/-) mice exhibited normal architecture but reduced proton secretion, and kcne2 (+/-) mice were hypochlorhydric, indicating a gene-dose effect and a primary defect in gastric acid secretion. These data demonstrate that KCNE2 is essential for gastric acid secretion, the first genetic evidence that a member of the KCNE gene family is required for normal gastrointestinal function.

Complications in colorectal surgery: risk factors and preventive strategies.

BackroundOpen or laparoscopic colorectal surgery comprises of many different types of procedures for various diseases. Depending upon the operation and modifiable and non-modifiable risk factors the intra- and postoperative morbidity and mortality rate vary. In general, surgical complications can be divided into intraoperative and postoperative complications and usually occur while the patient is still in the hospital.MethodsA literature search (1980-2009) was carried out, using MEDLINE, PubMed and the Cochrane library.ResultsThis review provides an overview how to identify and minimize intra- and postoperative complications. The improvement of different treatment strategies and technical inventions in the recent decade has been enormous. This is mainly attributable to the increase in the laparoscopic approach, which is now well accepted for many procedures. Training of the surgeon, hospital volume and learning curves are becoming increasingly more important to maximize patient safety, surgeon expertise and cost effectiveness. In addition, standardization of perioperative care is essential to minimize postoperative complications.ConclusionThis review summarizes the main perioperative complications of colorectal surgery and influencable and non-influencable risk factors which are important to the general surgeon and the relevant specialist as well. In order to minimize or even avoid complications it is crucial to know these risk factors and strategies to prevent, treat or reduce intra- and postoperative complications.

ΔF508 mutation results in impaired gastric acid secretion

The cystic fibrosis transmembrane conductance regulator (CFTR) is recognized as a multifunctional protein that is involved in Cl– secretion, as well as acting as a regulatory protein. In order for acid secretion to take place a complex interaction of transport proteins and channels must occur at the apical pole of the parietal cell. Included in this process is at least one K+ and Cl– channel, allowing for both recycling of K+ for the H,K-ATPase, and Cl– secretion, necessary for the generation of concentrated HCl in the gastric gland lumen. We have previously shown that an ATP-sensitive potassium channel (KATP) is expressed in parietal cells. In the present study we measured secretagogue-induced acid secretion from wild-type and ΔF508-deficient mice in isolated gastric glands and whole stomach preparations. Secretagogue-induced acid secretion in wild-type mouse gastric glands could be significantly reduced with either glibenclamide or the specific inhibitor CFTR-inh172. In ΔF508-deficient mice, however, histamine-induced acid secretion was significantly less than in wild-type mice. Furthermore, immunofluorescent localization of sulfonylurea 1 and 2 failed to show expression of a sulfonylurea receptor in the parietal cell, thus further implicating CFTR as the ATP-binding cassette transporter associated with the KATP channels. These results demonstrate a regulatory role for the CFTR protein in normal gastric acid secretion.

Stimulatory pathways of the Calcium-sensing receptor on acid secretion in freshly isolated human gastric glands

Gastric acid secretion is not only stimulated via the classical known neuronal and hormonal pathways but also by the Ca²⁺-Sensing Receptor (CaSR) located at the basolateral membrane of the acid-secretory gastric parietal cell. Stimulation of CaSR with divalent cations or the potent agonist Gd³⁺ leads to activation of the H⁺/K⁺-ATPase and subsequently to gastric acid secretion. Here we investigated the intracellular mechanism(s) mediating the effects of the CaSR on H⁺/K⁺-ATPase activity in freshly isolated human gastric glands. Inhibition of heterotrimeric G-proteins (G_i and G_o) with pertussis toxin during stimulation of the CaSR with Gd³⁺ only partly reduced the observed stimulatory effect. A similar effect was observed with the PLC inhibitor U73122. The reduction of the H⁺/K⁺-ATPase activity measured after incubation of gastric glands with BAPTA-AM, a chelator of intracellular Ca²⁺, showed that intracellular Ca²⁺ plays an important role in the signalling cascade. TMB-8, a ER Ca²⁺store release inhibitor, prevented the stimulation of H⁺/K⁺-ATPase activity. Also verapamil, an inhibitor of L-type Ca²⁺-channels reduced stimulation suggesting that both the release of intracellular Ca²⁺ from the ER as well as Ca²⁺ influx into the cell are involved in CaSR-mediated H⁺/K⁺-ATPase activation. Chelerythrine, a general inhibitor of protein kinase C, and Gö 6976 which selectively inhibits Ca²⁺-dependent PKC_α and PKC_βI-isozymes completely abolished the stimulatory effect of Gd³⁺. In contrast, Ro 31-8220, a selective inhibitor of the Ca²⁺-independent PKCε and PKC-δ isoforms reduced the stimulatory effect of Gd³⁺ only about 60 %. On the other hand, activation of PKC with DOG led to an activation of H⁺/K⁺-ATPase activity which was only about 60 % of the effect observed with Gd³⁺. Incubation of the parietal cells with PD 098059 to inhibit ERK1/2 MAP-kinases showed a significant reduction of the Gd³⁺ effect. Thus, in the human gastric parietal cell the CaSR is coupled to pertussis toxin sensitive heterotrimeric G-Proteins and requires calcium to enhance the activity of the proton-pump. PLC, ERK 1/2 MAP-kinases as well as Ca²⁺ dependent and Ca²⁺-independent PKC isoforms are part of the down-stream signalling cascade.

AMP-activated protein kinase : a physiological off switch for murine gastric acid secretion

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) has been shown to be a metabolic energy regulator in various cells. Activation is a direct result of rising AMP concentration coupled with falling adenosine triphosphate (ATP). AMPK activation during metabolic stress consequently reduces cellular ATP consumption. The gastric parietal cell has a large abundance of mitochondria per cell volume due to the numerous energy-dependent transporters and channels responsible for acid secretion. We identified AMPK in the parietal cell as a metabolic energy regulator that can switch acid secretion off as cellular ATP levels fall. AMPK presence in murine gastric glands was evaluated by immunofluorescent localization. We used a digital imaging system to monitor acid secretion as observed by proton efflux from parietal cells in hand-dissected gastric glands loaded with the pH-sensitive dye 2′,7′-bis-(2-carboxyethyl)-5-(and 6)-carboxyfluorescein. Individual murine gastric glands were exposed to histamine, pentagastrin, or carbachol. AMPK was pharmacologically activated with 5-aminoimidazole-4-carboxamide-1-β-d-riboside (AICAR) monophosphate or inhibited with 6-[4-(2-piperidin-1-yl-ethoxy)-phenyl)]-3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine (compound C) or ATP. Acid secretion was evaluated under these conditions as the rate of intracellular pH recovery. In addition, whole-stomach pH measurements were performed. Immunofluorescent localization confirmed the presence of AMPK in gastric mucosa. Exposure to AICAR monophosphate significantly reduced secretagogue-induced acid secretion; addition of compound C or ATP restored acid secretion. Our results indicate that secretagogue-induced acid secretion could be significantly reduced with AMPK activation and restored with its deactivation. We therefore propose the AMPK as a cellular metabolic off switch for gastric acid secretion.

Zinc Salts Provide a Novel, Prolonged and Rapid Inhibition of Gastric Acid Secretion

OBJECTIVES:The overproduction of acid and the associated illnesses linked to hypersecretion have a lifetime prevalence of 25–35% in the United States. Although a variety of pharmaceutical agents have been used to reduce the production of acid, alarming new evidence questions the long-term efficacy and safety of the agents. These issues coupled with the delayed onset of action and the return of symptoms in over 60% of the patients is less than satisfactory. The purpose of this study was to determine whether administration of a zinc salt could lead to a rapid and sustained increase in gastric pH in both animals and in humans and provide a new rapid acid suppression therapy.METHODS:Intracellular pH was measured with 2′,7′-bis-(2-carboxyethyl)-5-and-6-carboxy-fluorescin in both human and rat gastric glands following an acid load±a secretagogue. In a separate series of studies, whole stomach acid secretion was monitored in rats. A final study used healthy human volunteers while monitoring with a gastric pH measurement received placebo, zinc salt, or a zinc salt and proton pump inhibitor (PPI).RESULTS:We demonstrate that exposure to ZnCl2 immediately abolished secretagogue-induced acid secretion in isolated human and rat gastric glands, and in intact rat stomachs. Chronic low-dose zinc exposure effectively inhibited acid secretion in whole stomachs and isolated glands. In a randomized cross-over study in 12 volunteers, exposure to a single dose of ZnCl2 raised intragastric pH for over 3 h, including a fast onset of effect.CONCLUSIONS:Our findings demonstrate that zinc offers a novel rapid and prolonged therapy to inhibit gastric acid secretion in human and rat models.

PI3 kinase dependent stimulation of gastric acid secretion by dexamethasone.

Excessive gastric acid secretion plays an important role in the pathogenesis of peptic ulcers. Dexamethasone, a widely used drug, is known to stimulate gastric acid secretion and increase the incidence of peptic ulcers. However little is known about the mechanism of the dexamethasone’s effect on parietal cells. The present study was performed to investigate the contribution of the phosphatidylinositol-3-kinase (PI3 kinase) to dexamethasone induced stimulation of gastric acid secretion. In vivo pretreatment with dexamethasone injections (150µg/100g for 3 days) or in vitro exposure to (10 µM for > 20 minutes) significantly increased acid secretion in isolated gastric glands ñ 2-3 fold. The dexamethasone induced stimulation of gastric acid secretion was concentration dependent and significantly blunted by the H2+/K2+ ATPase inhibitor omeprazole (200 µM), the PI3 kinase inhibitor Wortmannin (500 nM), the protein kinase inhibitor staurosporine (2.5 µM) and the Cl- channel blocker NPPB (100 µM); but not by the H2 antagonist cimetidine (100 µM). In conclusion, it was observed that dexamethasone’s effect on proton extrusion requires the activity of a PI3 kinase pathway, an apical Cl- channel and the H2+/K2+ ATPase.

Small Bowel Obstruction Caused by an Incarcerated Hernia after Iliac Crest Bone Harvest

The iliac crest has become an often used site for autogenous bone graft, because of the easy access it affords. One of the less common complications that can occur after removal is a graft-site hernia. It was first reported in 1945 (see the work by Oldfield, 1945). We report a case of iliac crest bone hernia in a 53-year-old male who was admitted for elective resection of a pseudarthrosis and reconstruction of the left femur with iliac crest bone from the right side. One and a half months after initial surgery, the patient presented with increasing abdominal pain and signs of bowel obstruction. A CT scan of the abdominal cavity showed an obstruction of the small bowel caused by the bone defect of the right iliac crest. A laparoscopy showed a herniation of the small bowel. Due to collateral vessels of the peritoneum caused by portal hypertension, an IPOM (intraperitoneal onlay-mesh) occlusion could not be performed. We performed a conventional ventral hernia repair with an onlay mesh. The recovery was uneventful.