Incidence of postoperative complications is underestimated if outcome data are recorded by interns and first year residents in a low volume hospital setting.

The aim of this study is to evaluate the accuracy of outcome reporting after elective visceral surgery in a low volume district hospital. Outcome measurement as well as transparent reporting of surgical complications becomes more and more important. In the future, financial and personal resources may be distributed due to reported quality and thus, it is in the main interest of healthcare providers that outcome data are accurately collected. Between 10/2020 and 09/2021 postoperative complications during the hospitalisation were recorded using the Clavien-Dindo classification (CDC) and comprehensive complication index by residents of a surgical department in a district hospital. After one year of prospective data collection, data were retrospectively analyzed and re-evaluated for accuracy by senior consultant surgeons. In 575 patients undergoing elective general or visceral surgery interns and residents reported an overall rate of patients with complications of 7.3% (n = 42) during the hospitalization phase, whereas a rate of 18.3% (n = 105) was revealed after retrospective analysis by senior consultant surgeons. Thus, residents failed to report patients with postoperative complications in 60% of cases (63/105). In the 42 cases, in which complications were initially reported, the grading of complications was correct only in 33.3% of cases (n = 14). Complication grades that were most missed were CDC grade I and II. Quality of outcome measurement in a district hospital is poor if done by unexperienced residents and significantly underestimates the true complication rate. Outcome measurement must be done or supervised by experienced surgeons to ensure correct and reliable outcome data.

Comparative analysis of linear- and circular-stapled gastrojejunostomies in Roux-en-Y gastric bypass: a focus on postoperative morbidity using the comprehensive complication index.

PURPOSE: The linear-stapled (LSA) and the circular-stapled anastomosis (CSA) are the two most commonly performed techniques for the gastrojejunostomy (GJ) during laparoscopic Roux-en-Y gastric bypass (RYGB). This study compared the outcome after both techniques with special focus on postoperative morbidity using the comprehensive complication index (CCI). METHODS: Five hundred eighty-eight patients operated between 01/2010 and 12/2019 were included in the final analysis and divided in two cohorts according to the surgical technique of the GJ (LSA (n = 290) or CSA (n = 298)). Before 09/2016, the CSA was exclusively performed for the GJ, while after 09/2016, the LSA was solely used. RESULTS: The mean CCI for patients with Clavien-Dindo complication grade ≥ 2 within the first 90 days after RYGB was 31 ± 9.1 in the CSA and 25.7 ± 6.8 in the LSA group (p < 0.001), both values still below the previously published benchmark cutoff (≤ 33.73). The C-reactive Protein (CRP)-levels on postoperative days (POD) 1 and 3 as well as the use of opioids on POD 1 were significantly higher in the CSA- than in the LSA-group (all p < 0.001). There were significantly more internal herniations in the CSA group during the first 24 postoperative months (p < 0.001). CONCLUSION: Patients after RYGB with CSA were found to have higher CCI values during the first 90 PODs compared to patients in which the LSA was applied. To achieve optimal outcomes in terms of patient morbidity, the LSA seems to be the superior technique for GJ in RYGB.

Assessing daily energy intake in adult women: validity of a food-recognition mobile application compared to doubly labelled water.

Accurate dietary assessment is crucial for nutrition and health research. Traditional methods, such as food records, food frequency questionnaires, and 24-hour dietary recalls (24HR), have limitations, such as the need for trained interviewers, time-consuming procedures, and inaccuracies in estimations. Novel technologies, such as image-based dietary assessment apps, have been developed to overcome these limitations. SNAQ is a novel image-based food-recognition app which, based on computer vision, assesses food type and volume, and provides nutritional information about dietary intake. This cross-sectional observational study aimed to investigate the validity of SNAQ as a dietary assessment tool for measuring energy and macronutrient intake in adult women with normal body weight (n = 30), compared to doubly labeled water (DLW), a reference method for total daily energy expenditure (TDEE). Energy intake was also estimated using a one-day 24HR for direct comparison. Bland-Altman plots, paired difference tests, and Pearson's correlation coefficient were used to assess agreement and relationships between the methods. SNAQ showed a slightly higher agreement (bias = -329.6 kcal/day) with DLW for total daily energy intake (TDEI) compared to 24HR (bias = -543.0 kcal/day). While both SNAQ and 24HR tended to underestimate TDEI, only 24HR significantly differed from DLW in this regard (p < 0.001). There was no significant relationship between estimated TDEI and TDEE using SNAQ (R2 = 27%, p = 0.50) or 24HR (R2 = 34%, p = 0.20) and there were no significant differences in energy and macronutrient intake estimates between SNAQ and 24HR (Δ = 213.4 kcal/day). In conclusion, these results indicate that SNAQ provides a closer representation of energy intake in adult women with normal body weight than 24HR when compared to DLW, but no relationship was found between the energy estimates of DLW and of the two dietary assessment tools. Further research is needed to determine the clinical relevance and support the implementation of SNAQ in research and clinical settings. Clinical trial registration: This study is registered on ClinicalTrials.gov with the unique identifier NCT04600596 (https://clinicaltrials.gov/ct2/show/NCT04600596).

Attitudes of primary care physicians toward bariatric surgery: a free word association networks analysis.

BACKGROUND: Primary care physicians (PCPs) hold major responsibility in referring patients with obesity eligible for bariatric surgery (BS). OBJECTIVE: The aim was to explore PCPs' mental representation of BS in order to identify barriers and catalysts of BS referral practices. SETTING: Switzerland. METHODS: A total of 3526 PCPs were invited to participate in an online survey. PCPs were asked to write the first 5 words that came to their mind about the term "bariatric surgery." Additionally, they had to pick 2 emotions that best described each provided association. Demographic data and obesity-related referral patterns were collected. Mental representation network was constructed based on co-occurrence of associations, using validated data-driven methodology. RESULTS: In all, 216 PCPs completed the study (response rate: 6.13%). Respondents were aged 55 ± 9.8 years, had an equal sex distribution, and practiced mainly in urban settings. Three mental representations of BS emerged: indication-focused (most frequent associations: "obesity," "diabetes"), treatment-focused ("gastric bypass," "weight loss"), and outcome-focused ("complications," "challenging follow-up"). The emotional label "interested" was used significantly more frequently in the treatment-focused group. Comparison of PCPs among mental modules showed that those with a treatment-focused mindset referred patients for BS most frequently and were significantly more willing to follow up with postbariatric patients (χ2 = 17.8, P = .022). CONCLUSIONS: PCPs think about BS along 3 mental representations, and the treatment-focused attitude was coupled with the highest willingness to refer eligible patients for BS. Confidence in performing postbariatric follow-up was identified as catalyst of BS referral. Access to optimal care for patients with obesity may be improved accordingly.

The Effect of a Multifaceted Intervention Including Classroom Education and Bariatric Weight Suit Use on Medical Students' Attitudes toward Patients with Obesity.

INTRODUCTION: Weight bias refers to negative attitudes toward individuals because of their weight. Evidence-based strategies to successfully reduce weight bias in medical students are lacking. The purpose of this study was to investigate the impact of a multifaceted intervention on medical students' attitudes toward patients with obesity. METHODS: Third and fourth year medical students (n = 79), who enrolled in an 8-week graduate course focusing on the various epidemiologic, physiological, and clinical aspects of obesity, including a gamification task with bariatric weight suits (BWSs), were asked to complete the Nutrition, Exercise and Weight Management (NEW) Attitudes Scale questionnaire pre- and post-course. The inclusion period was between September 2018 and June 2021 and covered 4 consecutive groups of students. RESULTS: The overall NEW Attitudes Scale scores did not change significantly pre- versus post-intervention (pre-course: 19.59, post-course: 24.21, p value = 0.24). However, the subgroup of 4th year medical students showed a significant improvement in their attitudes (pre-course: 16.4, post-course: 26.16, p value = 0.02). The Thurstone rating of 9 out of 31 individual survey items changed significantly from pre- to post-course with a moderate strength (Cramer's V >0.2), including 5 items showing weight bias reduction. The disagreement with the statement "overweight/obese individuals lack willpower" increased from 37 to 68%. CONCLUSION: These findings suggest that in medical students with a low level of weight bias at baseline, a semester course on obesity combined with BWS use affects only a limited number of items of the NEW Attitudes Scale questionnaire. The sensitization of medical students to weight stigma has the potential to improve quality of healthcare for patients with obesity.

[Healthcare cost reimbursement without application-Experiences of a German bariatric service]. / Kostenübernahme bariatrischer Operationen ohne Antragstellung ­ Erfahrungen in einem deutschen Adipositaszentrum.

BACKGROUND: Only a small proportion of patients with morbid obesity in Germany have access to the currently most effective treatment, bariatric surgery. A major reason for this is the restrictive attitude of health insurance companies regarding the reimbursement of costs. OBJECTIVE: To record the postoperative rate of cost coverage by health insurance companies without the currently common preoperative application for morbidly obese patients who received a guideline-indicated bariatric surgery. METHODS: The process of postoperative reimbursement was evaluated through a prospective database over a 2-year period. Cases of primary reimbursement were correlated with respect to age, BMI, comorbidities and membership of a specific health insurance company. Rejected coverage cases were followed up for further advocacy and social court process. RESULTS: A total of 188 patients underwent bariatric surgery as indicated in the guidelines without prior application. Primary cost coverage was achieved in 76.6% (n = 144). There was no correlation with BMI, comorbidities or health insurance affiliation. Patients over 40 years of age were significantly more likely to be covered for costs. For patients without postoperative cost coverage, an out of court settlement was reached in 7 cases, 8 cases were heard by the social courts and 29 cases were still being processed by lawyers. CONCLUSION: Despite the relatively high rate of primary cost coverage, this analysis also shows the restrictive attitude of the health insurance companies regarding bariatric surgery with corresponding economic pressure on the service providers. The consistent implementation of application-free surgery seems necessary to increase the political pressure on health insurers and social courts.

Burst-pause criterion derivation for drinkometer measurements of ingestive behavior.

The drinkometer is a promising device for the study of ingestive behavior of liquid meals in humans. It can be used to investigate behavior in different target populations. However, ingestive behavior has a great variability across study participants. Therefore, a new analytical approach is required for the extraction and analysis of drinkometer-derived data that could account for this variability. We developed an optimized protocol to predict an optimal burst-pause criterion (PC) for the extraction of PC-dependent microstructural parameters of ingestive behavior. These describe the microstructure of bursts, while PC-independent parameters describe the microstructure of sucks. Therefore, a PC is required to analyze separately two physiologically different parts of behavior. To accomplish this burst-pause criterion derivation (BPCD), a Gaussian Mixture Model (GMM) was built for estimation of two probability density functions (PDFs). These model the distribution of inter-suck intervals (ISIs) and inter-burst intervals (IBIs), respectively. The PC is defined at the intersection point of the two density functions. A Kaplan-Meier (KM) survival analysis was performed for post-hoc verification of the fit of the predicted optimal PC to the ISI distribution. In this protocol paper, we present a walkthrough of the data analysis of drinkometer-derived data for the measurement of microstructure of ingestive behavior based on previous results published by our group [1].•Standardization of the burst-pause criterion derivation for drinkometer measurements of ingestive behavior.•All codes are publicly available in a repository.•The method can be easily adapted to studies with larger sample size or more than one study stimulus.

Results of robotic TAPP and conventional laparoscopic TAPP in an outpatient setting: a cohort study in Switzerland.

PURPOSE: Recently, robotic surgery has been increasingly performed in hernia surgery. Although feasibility and safety of robot-assisted inguinal hernia repair in an inpatient setting have been already shown, its role in outpatient hernia surgery has not yet been investigated. Thus, this study aimed to compare robot-assisted TAPP (r-TAPP) and conventional laparoscopic TAPP (l-TAPP) in an outpatient setting. METHODS: A prospective database of patients with inguinal hernia treated by l-TAPP or r-TAPP in an outpatient setting during a 1-year period was analyzed in a comparative cohort study. All patients underwent a check-up appointment with their surgeon within 3 days and 6 weeks postoperatively. Data on surgical time, perioperative complications, and postoperative pain were collected. Pain was recorded by using a Verbal Rating Scale (VRS). RESULTS: Overall, outpatient laparoendoscopic inguinal hernia repair was performed in 58 patients (29 l-TAPP; 29 r-TAPP). Mean age was 57 years (21-81), mean BMI 24.5 kg/m2 (19-33) with no differences between both groups. Most patients reported none or only a low postoperative pain level in both groups (89.6% in l-TAPP group; 100% in r-TAPP), while there was a trend for less pain after r-TAPP. In both groups, there was one case of postoperative hematoma, which was successfully treated by conservative means. No other complications occurred during follow-up in either group and there was no 30-day-readmission, no unplanned overstay or any 30-day mortality in the cohort. CONCLUSION: Robot-assisted inguinal hernia surgery can be safely performed in an outpatient setting with a tendency to less pain when compared to the conventional laparoscopic technique. Cost-effectiveness and cost-coverage of outpatient robot-assisted inguinal hernia surgery must be further investigated in times of limited health cost resources and diagnosis-related medical reimbursements.

Two cases of an internal hernia after laparoscopic sigmoid resection.

Two patients with a laparoscopic resection of the sigmoid colon in their surgical history were diagnosed with an internal hernia because of a mesenteric gap underneath the descending neocolon. While the first case demonstrated a strongly symptomatic patient with a closed-loop obstruction of the small bowel, the second case was less obvious and correct diagnosis was achieved after a few weeks by finally performing a diagnostic laparoscopy. Since internal hernias after laparoscopic sigmoid resection are a rare complication and as presented in the second case can display very unspecific symptoms, the surgeon's awareness is not immediately raised towards it. Therefore, an asymptomatic internal hernia bears a constant risk of a life-threatening outcome allowing to recommend an initial closure of the mesenteric gap. In both cases, successful treatment was achieved by surgery and intraoperatively closing the remaining mesenteric gap. Subsequently recovery and follow-up were uneventful.

Association between microstructure of ingestive behavior and body weight loss in patients one year after Roux-en-Y gastric bypass.

Roux-en-Y gastric bypass (RYGB) is one of the most effective procedures in the treatment of obesity. However, the predictive value of the microstructure of ingestion has not been widely investigated in this context. Here, we applied a recently developed drinkometer device to analyze the microstructure of ingestive behavior during a liquid meal in women and investigate whether it correlated with measures of weight loss after RYGB. Macro- and microstructural parameters of ingestive behavior of female patients (n = 24) one year after RYGB were measured in two different test sessions within a period of two weeks using the drinkometer. A Pearson correlation analysis was performed to compare the macro- and microstructural parameters of ingestive behavior with the percentage of total weight loss (%TWL), percentage excess BMI loss (%EBMIL), and body mass index (BMI) one year after RYGB, as well as age. A Bonferroni adjusted p < 0.003 was considered significant for the correlation analysis. For all other statistical tests, a p < 0.05 was considered significant. One year after surgery, a significant body weight loss was achieved in our study population (111.2 ± 15.6 kg vs 73.4 ± 11.7 kg; ***p < 0.001), with a mean%TWL of 33.8% (range: 20.4-48.6%). At the first test session,%TWL correlated with suck duration (r = 0.41, 0.05 > p > 0.003);%EBMIL correlated with both suck duration (r = 0.64, *p < 0.003) and inter-suck intervals (ISIs, r = -0.47, *p < 0.003), and, finally, BMI correlated with suck duration (r = 0.62, *p < 0.003) and ISIs (r = 0.48, *p < 0.003). However, at the second test session, no correlation was found between the body weight loss and the recorded ingestive parameters. Furthermore, no statistically significant difference was found in microstructural parameters of ingestive behavior between the two test sessions even though meal size decreased by 20% on the second visit (342.6.6 ± 167 kcal vs. 271.8 ± 142.8 kcal). A greater body weight loss of patients one year after surgery seems to be associated with longer suck duration and shorter ISIs, but only when the stimulus is tested for the first time by the study participants. This study contributes to the current knowledge about the ingestive behavior of bariatric patients one year after RYGB in terms of its association with the achieved weight loss. The use of the drinkometer device for the measurement of microstructure of ingestive behavior should be further expanded to different research questions and patient subgroups other than good responders. Its possible applications in clinical and behavioral research need to be included in the agenda of bariatric research.

Online survey on factors influencing patients' motivation to undergo bariatric surgery.

Given the worldwide increasing prevalence of severe obesity and considering the amount of scientific evidence demonstrating the beneficial effects of bariatric surgery (BS), it is surprising that only a fraction of patients with obesity undergo BS. We therefore conducted an anonymized online survey among individuals with a history of BS to understand factors influencing the deciding process leading to BS. Respondents were recruited on a voluntary basis from obesity-related social media groups between April and June 2020. The self-designed, non-validated questionnaire consisted of 20 questions and was open to any participants with a history of BS. Of 851 participants who started the survey, 665 completed the questionnaire (completion rate of 78.1%). Five years after BS, still 70% of the survey-participants were very satisfied or satisfied with the surgical result. However, the majority (73.3%) would have undergone BS earlier. The main motivation to choose BS was related to health status or quality of life. Important characteristics for a bariatric surgeon to obtain patients' trust are "taking time and listen" (74.7%), empathy (64%) and sympathy (56%). Post-operative satisfaction with the surgical outcome was high and long-lasting in this large cohort of BS patients. However, most participants would retrospectively have undergone BS earlier. The main reason to choose BS as treatment for their obesity were impaired physical health or reduced quality of life. Nearby location to patients' residence and availability of surgeons with empathy were decisive motives for bariatric centre selection.

Mind the gap - Small bowel obstruction due to preperitoneal herniation following laparoscopic inguinal hernia repair - A case report.

INTRODUCTION AND IMPORTANCE: Inguinal hernia repair is a very frequent operation in general and visceral surgery worldwide. The laparo-endoscopic approaches such as TAPP have gained increasing acceptance among specialists and many consider them as standard of care due to perioperative safety and excellent postoperative results. Knowledge of specific complications after minimally invasive inguinal hernia surgery, however, is important for the successful management of these patients. CASE PRESENTATION: We herein present the case of a 75-year-old female patient who electively underwent laparoscopic repair of combined inguinal and femoral hernia. During the postoperative course a small bowel obstruction occurred requiring emergency re-laparoscopy revealing a preperitoneal herniation of small bowel through a peritoneal defect. CLINICAL DISCUSSION: Small bowel obstruction due to preperitoneal herniation of small bowel through a peritoneal defect after laparoscopic hernia repair is extremely rare. In such cases, emergency laparoscopic revision is necessary to avoid bowel ischaemia. Adequate closure of the peritoneum during the primary procedure along with the necessary attention to detail seems mandatory to avoid preperitoneal herniation after TAPP. CONCLUSION: Inadequate peritoneal closure after TAPP may lead to preperitoneal herniation of the small bowel leading to postoperative intestinal obstruction. All hernia surgeons should be aware of this rare, but potentially life-threatening complication and should close all peritoneal defects with greatest care and accuracy.

Excess Body Weight and Gastroesophageal Reflux Disease.

BACKGROUND: Gastroesophageal reflux disease (GERD) is strongly associated with excess body weight. SUMMARY: GERD is characterized by typical symptoms with or without mucosal damage because of retrograde flow of gastric content into the esophagus. An ineffective esophagogastric junction (EGJ) combined with anatomical abnormalities is considered to be causative. The incidence of GERD is strongly associated with excess body weight, reflecting the pathophysiological relevance of the abdominothoracic pressure gradient. KEY MESSAGE: Weight loss has been demonstrated to be an effective therapy for GERD combined with obesity. In cases in which surgical therapy is indicated, traditional antireflux surgery has led to equivocal results, advocating a proximal Roux-en-Y gastric bypass in these patients to correct both GERD and excess body weight.

Defining Global Benchmarks in Elective Secondary Bariatric Surgery Comprising Conversional, Revisional, and Reversal Procedures.

OBJECTIVE: To define "best possible" outcomes for secondary bariatric surgery (BS). BACKGROUND: Management of poor response and of long-term complications after BS is complex and under-investigated. Indications and types of reoperations vary widely and postoperative complication rates are higher compared to primary BS. METHODS: Out of 44,884 BS performed in 18 high-volume centers from 4 continents between 06/2013-05/2019, 5,349 (12%) secondary BS cases were identified. Twenty-one outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of centers. Benchmark cases had no previous laparotomy, diabetes, sleep apnea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, thromboembolic events, BMI> 50 kg/m2 or age> 65 years. RESULTS: The benchmark cohort included 3143 cases, mainly females (85%), aged 43.8 ±â€Š10 years, 8.4 ±â€Š5.3 years after primary BS, with a BMI 35.2 ±â€Š7 kg/m2. Main indications were insufficient weight loss (43%) and gastro-esophageal reflux disease/dysphagia (25%). 90-days postoperatively, 14.6% of benchmark patients presented ≥1 complication, mortality was 0.06% (n = 2). Significantly higher morbidity was observed in non-benchmark cases (OR 1.37) and after conversional/reversal or revisional procedures with gastrointestinal suture/stapling (OR 1.84). Benchmark cutoffs for conversional BS were ≤4.5% re-intervention, ≤8.3% re-operation 90-days postoperatively. At 2-years (IQR 1-3) 15.6% of benchmark patients required a reoperation. CONCLUSION: Secondary BS is safe, although postoperative morbidity exceeds the established benchmarks for primary BS. The excess morbidity is due to an increased risk of gastrointestinal leakage and higher need for intensive care. The considerable rate of tertiary BS warrants expertise and future research to optimize the management of non-success after BS.

Pitfalls of laparoscopic Re-TAPP in recurrent inguinal hernia repair-a plea for extended preoperative diagnostic.

According to international guidelines, recurrent inguinal hernia should be treated by a surgical approach opposing of the primary strategy (anterior-posterior or posterior-anterior). However, recent evidence demonstrates feasibility and safety of re-laparoscopic repair of recurrent inguinal hernia after primary laparoscopy. For such a strategy, correct identification of anatomical structures is challenging, but absolutely crucial for a satisfactory postoperative result. This case of an unrecognized sliding hernia of the sigmoid colon during re-laparoscopy highlights that a precise physical examination as well as an extended preoperative radiological workup (ultrasound, computed tomography and/or magnetic resonance imaging of the abdomen and pelvis) should be considered prior to re-laparoscopy of recurrent inguinal hernia.

An unusual reason for an inguinal swelling: De Garengeot's hernia.

We present the case of a 71-year-old female with an inguinal swelling. Intra-abdominally the appendix was found in a femoral hernia sac (De Garengeot's hernia). A laparoscopic transabdominal preperitoneal hernia repair procedure was performed with uneventful post-operative course. Clinical presentation of this type of hernia is unspecific and often not to be distinguished from a common incarcerated hernia. Computed tomography can be helpful in obtaining a diagnosis, although the definite diagnosis is mostly found intraoperatively. As surgical options are numerous, there is no consensus on the most suitable one. A laparoscopic approach incorporates the benefit of a total abdominal overview and the possibility of standard procedures. If the appendix appears normal, the use of synthetic mesh is considered safe and an incidental appendectomy is not necessarily required.

E7080 (lenvatinib), a multi-targeted tyrosine kinase inhibitor, demonstrates antitumor activities against colorectal cancer xenografts.

Clinical prognosis of metastasized colorectal carcinoma (CRC) is still not at desired levels and novel drugs are needed. Here, we focused on the multi-tyrosine kinase inhibitor E7080 (Lenvatinib) and assessed its therapeutic efficacy against human CRC cell lines in vitro and human CRC xenografts in vivo. The effect of E7080 on cell viability was examined on 10 human CRC cell lines and human endothelial cells (HUVEC). The inhibitory effect of E7080 on VEGF-induced angiogenesis was studied in an ex vivo mouse aortic ring angiogenesis assay. In addition, the efficacy of E7080 against xenografts derived from CRC cell lines and CRC patient resection specimens with mutated KRAS was investigated in vivo. A relatively low cytotoxic effect of E7080 on CRC cell viability was observed in vitro. Endothelial cells (HUVEC) were more susceptible to the incubation with E7080. This is in line with the observation that E7080 demonstrated an anti-angiogenic effect in a three-dimensional ex vivo mouse aortic ring angiogenesis assay. E7080 effectively disrupted CRC cell-mediated VEGF-stimulated growth of HUVEC in vitro. Daily in vivo treatment with E7080 (5 mg/kg) significantly delayed the growth of KRAS mutated CRC xenografts with decreased density of tumor-associated vessel formations and without tumor regression. This observation is in line with results that E7080 did not significantly reduce the number of Ki67-positive cells in CRC xenografts. The results suggest antiangiogenic activity of E7080 at a dosage that was well tolerated by nude mice. E7080 may provide therapeutic benefits in the treatment of CRC with mutated KRAS.

The impact of pyrvinium pamoate on colon cancer cell viability.

PURPOSE: The in vitro and in vivo effects of pyrvinium pamoate (PP), a newly identified WNT signaling inhibitor, were evaluated against colon cancer cell lines and primary colon cancer samples. EXPERIMENTAL DESIGN: Antiproliferative activity of PP and its effects on protein and RNA levels of WNT targets were evaluated on adenomatous polyposis coli (APC (mut)) and ß-catenin(mut) cell lines, one WNT(wt) colon cancer cell line, as well as six primary colon cancer samples with mutant APC in vitro. In addition, the effect of PP on the growth of liver metastasis was examined. RESULTS: PP blocked colon cancer cell growth in vitro in a dose-dependent manner with great differences in the inhibitory concentration (IC(50)), ranging from 0.6 × 10(-6) to 65 × 10(-6) mol/L for colon cancer cells with mutations in WNT signaling. In addition, PP demonstrated a cytotoxic effect on primary colon cancer samples. A combined cytotoxic effect of PP with 5-fluorouracil (5-FU) was observed for two cell lines. PP decreased messenger RNA (mRNA) and protein levels of known WNT target genes as c-MYC and thereby led to the induction of p21. PP inhibited the migration of HCT116 colon cancer cells in vitro and decreased tumor growth in vivo after intraportal injection of HCT116 cells in nude mice. CONCLUSIONS: PP displays promising anticancer activity against a broad panel of human colon cancer cell lines, as well as primary colon cancer samples. However, our findings do not demonstrate a predominant cytotoxic effect of PP on colon cancer cells with mutations in WNT signaling.

Does bariatric surgery change olfactory perception? Results of the early postoperative course.

PURPOSE: Changes of food preference toward foods with low caloric density have been demonstrated after bariatric surgery and may contribute to sustained body weight loss. It has been hypothesized that olfactory perception as an integral part of food selection might be altered after bariatric surgery. METHODS: Sniffin' Sticks® were used to investigate the olfactory perception of morbidly obese patients undergoing either Roux-en-Y gastric bypass (RYGB, n = 15) or sleeve gastrectomy (SG, n = 15) before 1, 6, 12, and 24 weeks after surgery. Obese patients without surgical intervention served as controls (CG, n = 12). Results are presented using the testing odor threshold, discrimination, and identification score (TDI; higher scores indicate better olfactory perception). Body weight loss was recorded. RESULTS: Initial BMI of the SG group (56.04 ± 7.096 kg m(-2)) was higher compared to the BMI of the RYGB (48.71 ± 6.49 kg m(-2)) and CG (50.35 ± 6.78 kg m(-2)); p = 0.011. Body weight loss among the surgical groups was not different (p = 0.011) while controls did not lose weight. Mean baseline TDI scores were significantly lower in the SG group 27.1 ± 3.9 vs. 32.6 ± 3.6 (RYGB) and 32.1 ± 5.3 (CG), respectively, whereas there were after 24 weeks no changes in RYGB and CG patients; the TDI score in the SG group increased significantly to 31.1 ± 3.5 (p < 0.01). CONCLUSIONS: Our data suggest that a substantial body weight loss per se does not affect olfactory perception. However, our results point towards improved olfactory perception after sleeve gastrectomy but not Roux-en-Y gastric bypass.

Noninvasive visualization of tumor growth in a human colorectal liver metastases xenograft model using bioluminescence in vivo imaging.

BACKGROUND: Bioluminescence imaging (BLI) is an ideal tool for noninvasive, quantitative monitoring of tumor progression/regression in animal models. The effectiveness of different treatment strategies is displayed by an altered intensity of bioluminescence, demonstrating a change of the tumor burden. The aim of this study was to establish a reliable, reproducible colorectal hepatic metastases cancer animal model. METHODS: Cells of the human colon carcinoma cell line HCT-116 Luc(pos) expressing the firefly luciferase enzyme gene were used. HCT-116 Luc(pos) cells (2.5 × 10(6)) were injected through the portal vein into the liver of immunoincompetent nude mice. BLI was used to analyze intrahepatic tumor burden and growth kinetic. RESULTS: HCT-116 Luc(pos) cells demonstrated a progressive and reproducible growth in the liver after intraportal injection. Four days after injection, the animals were analyzed for tumor growth by BLI, and mice without or too low bioluminescence signals were excluded (between 10% and 20% animals). HCT-116 Luc(pos) intrahepatic tumors responded successfully to different dosages (5 and 10 mg/kg) of 5-fluorouracil. CONCLUSIONS: BLI is an important tool with many potential advantages for investigators. The measurement of intrahepatic tumor growth by imaging luciferase activity noninvasively provides valuable information on tumor burden and effectiveness of therapy. Thus, the presented intrahepatic metastases model based on the growth of HCT-116 Luc(pos) cells is suitable for in vivo testing of different cancer therapy strategies.