Background
Laparoscopic cholecystectomy is the standard treatment for symptomatic gallstones. The quality of the procedure frequently is included in quality improvement programs, but outcome values ...have not been described to define the standard of care for a general population. This study included 20,307 cholecystectomies from a national prospective database that combines administrative data with clinical data. This report states the quality of cholecystectomy in Denmark, establishes benchmarks, and identifies significant risk factors.
Methods
The Danish Cholecystectomy Database was queried for data from 2006 to 2009. The outcome measures included conversion rate, hospital length of stay (LOS), readmission, additional procedures, and 30-day mortality. Patient characteristics and operative findings were analyzed as risk factors using stepwise backward logistic regression.
Results
The study included 20,307 patients (82% of all cholecystectomies). The conversion rate was 7.6%. Male sex, acute cholecystitis, and previous upper abdominal surgery were risk factors for conversion, with respective odds ratios of 1.50, 4.61, and 3.54. The mean LOS was 1.5 days, and 37.3% of the patients had same-day surgery. The readmission rate was 9.6%. Nearly 70% had a LOS of 1 day or less and no readmission; 17.3% had a LOS longer than 3 days and/or readmission; 5.6% had an additional procedure within 30 days; and 0.2% had a bile duct injury requiring reconstructive surgery. The 30-day mortality rate was 0.27%. Age older than 60 years, American Society of Anesthesiology (ASA) score exceeding 1, and open procedure were significant risk factors for all the outcomes. Body mass index (BMI) was not a risk factor for any of the outcomes.
Conclusion
The quality of cholecystectomy is high in Denmark, with a low conversion rate and a high frequency of short admissions without readmission. Acute cholecystitis and open procedure are important risk factors for poorer outcomes.The results of this study analyzing a large, unbiased population can be used to benchmark outcomes of cholecystectomy.
Gastric cancer is the fourth most common cancer in the world and the second most prevalent cause of cancer related death. The development of gastric cancer is mainly associated with H. Pylori ...infection leading to a focus in pathology studies on bacterial and environmental factors, and to a lesser extent on the mechanistic development of the tumour. MicroRNAs are small non-coding RNA molecules involved in post-transcriptional gene regulation. They are found to regulate genes involved in diverse biological functions and alterations in microRNA expression have been linked to the pathogenesis of many malignancies. The current study is focused on identifying microRNAs involved in gastric carcinogenesis and to explore their mechanistic relevance by characterizing their targets.
Invitrogen NCode miRNA microarrays identified miR-449 to be decreased in 1-year-old Gastrin KO mice and in H. Pylori infected gastric tissues compared to tissues from wild type animals. Growth rate of gastric cell lines over-expressing miR-449 was inhibited by 60% compared to controls. FACS cell cycle analysis of miR-449 over-expressing cells showed a significant increase in the sub-G1 fraction indicative of apoptosis. ß-Gal assays indicated a senescent phenotype of gastric cell lines over-expressing miR-449. Affymetrix 133v2 arrays identified GMNN, MET, CCNE2, SIRT1 and CDK6 as miR-449 targets. Luciferase assays were used to confirm GMNN, MET, CCNE2 and SIRT1 as direct targets. We also show that miR-449 over-expression activated p53 and its downstream target p21 as well as the apoptosis markers cleaved CASP3 and PARP. Importantly, qPCR analyses showed a loss of miR-449 expression in human clinical gastric tumours compared to normal tissues.
In this study, we document a diminished expression of miR-449 in Gastrin KO mice and further confirmed its loss in human gastric tumours. We investigated the function of miR-449 by identifying its direct targets. Furthermore we show that miR-449 induces senescence and apoptosis by activating the p53 pathway.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A clinical syndrome of ulcers and diarrhea, which mimics the Zollinger–Ellison syndrome but with normal gastrin levels, was associated with a neuroendocrine tumor secreting cholecystokinin.
To the ...Editor:
Neuroendocrine tumors secrete hormones that may cause specific syndromes.
1
We describe a patient with an endocrine pancreas tumor and liver metastases that synthesized sufficient cholecystokinin (CCK) to cause symptoms that are explained by high levels of CCK. Such neuroendocrine tumors are called CCKomas, and we have termed the resulting condition the CCKoma syndrome.
The patient was a 58-year-old woman who in 1998 had frequent episodes of diarrhea, severe weight loss, and a bleeding peptic ulcer. Computed tomographic scanning revealed liver processes with cells that contained chromogranin A and synaptophysin but did not contain insulin, glucagon, somatostatin, gastrin, . . .
Gastric cancer is the second most common cause of cancer-related death in the world. Inflammatory signals originating from gastric cancer cells are important for recruiting inflammatory cells and ...regulation of metastasis of gastric cancer. Several microRNAs (miRNA) have been shown to be involved in development and progression of gastric cancer. miRNA-146a (miR-146a) is a modulator of inflammatory signals, but little is known about its importance in gastric cancer. We therefore wanted to identify targets of miR-146a in gastric cancer and examine its biological roles.
The expression of miR-146a was evaluated by quantitative PCR (qPCR) and found up-regulated in the gastrin knockout mice, a mouse model of gastric cancer, and in 73% of investigated human gastric adenocarcinomas. Expression of miR-146a by gastric cancer cells was confirmed by in situ hybridization. Global analysis of changes in mRNA levels after miR-146a transfection identified two transcripts, caspase recruitment domain-containing protein 10 (CARD10) and COP9 signalosome complex subunit 8 (COPS8), as new miR-146a targets. qPCR, Western blotting and luciferase assays confirmed these transcripts as direct miR-146a targets. CARD10 and COPS8 were shown to be part of the G protein-coupled receptor (GPCR) pathway of nuclear factor-kappaB (NF-kappaB) activation. Lysophosphatidic acid (LPA) induces NF-kappaB activation via this pathway and over-expression of miR-146a inhibited LPA-induced NF-kappaB activation, reduced LPA-induced expression of tumor-promoting cytokines and growth factors and inhibited monocyte attraction.
miR-146a expression is up-regulated in a majority of gastric cancers where it targets CARD10 and COPS8, inhibiting GPCR-mediated activation of NF-kappaB, thus reducing expression of NF-kappaB-regulated tumor-promoting cytokines and growth factors. By targeting components of several NF-kappaB-activating pathways, miR-146a is a key component in the regulation of NF-kappaB activity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The study was carried out to analyze the learning rate for laparoscopic skills on a virtual reality training system and to establish whether the simulator was able to differentiate between surgeons ...with different laparoscopic experience.
Forty-one surgeons were divided into three groups according to their experience in laparoscopic surgery: masters (group 1, performed more than 100 cholecystectomies), intermediates (group 2, between 15 and 80 cholecystectomies), and beginners (group 3, fewer than 10 cholecystectomies) were included in the study. The participants were tested on the Minimally Invasive Surgical Trainer–Virtual Reality (MIST-VR) 10 consecutive times within a 1-month period. Assessment of laparoscopic skills included time, errors, and economy of hand movement, measured by the simulator.
The learning curves regarding time reached plateau after the second repetition for group 1, the fifth repetition for group 2, and the seventh repetition for group 3 (Friedman’s tests
P <0.05). Experienced surgeons did not improve their error or economy of movement scores (Friedman’s tests,
P >0.2) indicating the absence of a learning curve for these parameters. Group 2 error scores reached plateau after the first repetition, and group 3 after the fifth repetition. Group 2 improved their economy of movement score up to the third repetition and group 3 up to the sixth repetition (Friedman’s tests,
P <0.05). Experienced surgeons (group 1) demonstrated best performance parameters, followed by group 2 and group 3 (Mann-Whitney test
P <0.05).
Different learning curves existed for surgeons with different laparoscopic background. The familiarization rate on the simulator was proportional to the operative experience of the surgeons. Experienced surgeons demonstrated best laparoscopic performance on the simulator, followed by those with intermediate experience and the beginners. These differences indicate that the scoring system of MIST-VR is sensitive and specific to measuring skills relevant for laparoscopic surgery.
Gastrin measurements are performed primarily for the diagnosis of gastrin-producing tumors, gastrinomas, which cause the Zollinger-Ellison syndrome (ZES). Gastrin circulates as several bioactive ...peptides, however, and the peptide pattern in gastrinoma patients often deviates from normal. Therefore, it is necessary to measure all forms of gastrin.
Only immunoassays are useful for measurement of gastrin in plasma. The original assays were RIAs developed in research laboratories that used antibodies directed against the C terminus of gastrin peptides. Because the C-terminal tetrapeptide amide sequence constitutes the active site of gastrin peptides, these assays were well suited for gastrinoma diagnosis. More recently, however, most clinical chemistry laboratories have switched to commercial kits. Because of recent cases of kit-measured normogastrinemia in patients with ZES symptoms, the diagnostic sensitivity and analytical specificity of the available kits have been examined. The results show that gastrin kits frequently measure falsely low concentrations because they measure only a single gastrin form. Falsely high concentrations were also encountered, owing to overreactivity with O-sulfated gastrins or plasma proteins. Thus, more than half of the gastrin kits on the market are unsuited for diagnostics.
Gastrinomas are neuroendocrine tumors, some of which become malignant. A delay in diagnosis leads to fulminant ZES, with major, even lethal, complications. Consequently, it is necessary that the diagnostic sensitivity of gastrin kits be adequate. This diagnostic sensitivity requires antibodies that bind the C-terminal epitope of bioactive gastrins without the influence of O-sulfation.
The value of chromogranin A (CgA) versus gastrin and progastrin in diagnosis and control of gastrinoma patients is not settled because the peptides circulate as variable mixtures. We have addressed ...this complexity using defined sequence-specific assays.
Six assays were applied to plasma from 40 gastrinoma patients to measure α-amidated gastrins, glycine-extended gastrins, the total progastrin product, and assays for CgA sequence (340-348) and the 'total' CgA product.
The gastrin/progastrin parameters did not add to the diagnosis beyond that of α-amidated gastrins, except in one patient. All gastrin parameters correlated otherwise closely. The CgA results differed. Thus, 11 patients had normal CgA concentrations. By contrast, all total CgA concentrations were elevated but correlated only moderately to gastrin.
Assays measuring α-amidated gastrins have high diagnostic value except for singular patients in whom only progastrin was elevated. By contrast, CgA measurements are not valid in diagnosis or control of gastrinomas.
Glucagon-like peptide 1 (GLP-1) analogs are increasingly being used in the treatment of type 2 diabetes. It is clear that these drugs lower blood glucose through an increase in insulin secretion and ...a lowering of glucagon secretion; in addition, they lower body weight and systolic blood pressure and increase heart rate. Using a new monoclonal antibody for immunohistochemistry, we detected GLP-1 receptor (GLP-1R) in important target organs in humans and monkeys. In the pancreas, GLP-1R was predominantly localized in β-cells with a markedly weaker expression in acinar cells. Pancreatic ductal epithelial cells did not express GLP-1R. In the kidney and lung, GLP-1R was exclusively expressed in smooth muscle cells in the walls of arteries and arterioles. In the heart, GLP-1R was localized in myocytes of the sinoatrial node. In the gastrointestinal tract, the highest GLP-1R expression was seen in the Brunner's gland in the duodenum, with lower level expression in parietal cells and smooth muscle cells in the muscularis externa in the stomach and in myenteric plexus neurons throughout the gut. No GLP-1R was seen in primate liver and thyroid. GLP-1R expression seen with immunohistochemistry was confirmed by functional expression using in situ ligand binding with 125I-GLP-1. In conclusion, these results give important new insight into the molecular mode of action of GLP-1 analogs by identifying the exact cellular localization of GLP-1R.
Abstract Background The aim of this retrospective study was to evaluate the perioperative and longterm outcome after early repair with a hepaticojejunostomy (HJ). Methods Between 1995 and 2010, a ...nationwide, retrospective multicentre study was conducted. All iatrogenic bile duct injury (BDI) sustained during a cholecystectomy and repaired with HJ in the five HepatoPancreaticoBiliary centres in Denmark were included. Results In total, 139 patients had an HJ repair. The median time from the BDI to reconstruction was 5 days. A concomitant vascular injury was identified in 26 cases (19%). Postoperative morbidity was 36% and mortality was 4%. Fortytwo patients (30%) had a stricture of the HJ. The median followup time without stricture was 102 months. Nineteen out of the 42 patients with postreconstruction biliary strictures had a reHJ. Twentythree patients were managed with percutaneous transhepatic cholangiography and dilation. The overall success rate of reestablishing the biliodigestive flow approached 93%. No association was found between timing of repair, concomitant vascular injury, level of injury and stricture formation. Conclusion In this national, unselected and consecutive cohort of patients with BDI repaired by early HJ we found a considerable risk of longterm complications (e.g. 30% stricture rate) and mortality in both the short and the longterm perspective.
Abstract Background An increase in the frequency of cholecystectomy in children has been described during the last decades. Part of the reason is that more cholecystectomies in children are performed ...for dyskinesia of the gallbladder and not only for gallstone disease. We conducted the first nationwide study to describe outcome of cholecystectomies performed in children in Denmark by using data from the national Danish Cholecystectomy Database (DCD). Methods In the DCD, two data sources were combined: administrative data from the National Patient Registry (NPR) and clinical data entered into the secure Web site by the surgeon immediately after the operation. In the present analysis, we have included children ≤ 15 years from the five year period January 1, 2006, to December 31, 2010. Results In the study period 35,444 patients were operated with a cholecystectomy. Of these, 196 (0.5%) were ≤ 15 years. The median age was 14 years, and 82% were girls. Predisposing medical factors for gallstones (despite obesity) were found in only 5%. More than 50% were overweight, and one third were obese. Ninety-seven percent of the operations were completed laparoscopically, and the conversion rate was 0. 5%. Nearly half of the operations (45%) were performed as same day surgery, and 80% of the children stayed in hospital 0–1 day without readmission. 91% were discharged within 3 days and not readmitted. Morbidity was low, and no bile duct lesions occurred. The 30 day mortality was zero. Conclusion Our nationwide outcome results indicate good quality with 91% of the patients discharged within 3 days without readmission, no bile duct injuries, and no mortality. All patients except two were operated for symptomatic gallstone disease in accordance to the Danish national guidelines. We have not experienced a demand or a need to expand the indications for cholecystectomy beyond gallstone disease.
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