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Purpose: Transduodenal surgical ampullectomy (tAMP) with papillary reimplantation is a valid alternative to pancreaticoduodenectomy for lesions of the periampullary region not amenable to endoscopic resection. As tAMP is burdened by high rates of biliopancreatic-enteric anastomotic leak, we tested preventive endoluminal vacuum therapy (eVAC) combined with post-operative continuous perianastomotic irrigation (CPI) to reduce such anastomotic leak., Methods: Between 10/2013 and 09/2023, 37 patients undergoing laparotomic tAMP (with or without jejunal transposition) and papillary reimplantation at Hirslanden Klinik Zurich were retrospectively analysed; of these, 16 received prophylactic eVAC combined with CPI, while the remaining represented the historical cohort., Results: The eVAC-CPI-group and the historical-cohort were homogeneous in demographic characteristics. Surgery in the prophylactic eVAC-CPI-group lasted about 30 min longer due to eVAC application (p = 0.008). The biliopancreatico-enteric anastomotic leak rates were 6.2% in the eVAC-CIP-group vs. 19.0% in the historical-cohort (p = 0.266). Along, a strong trend of less severe post-operative complications in general (p = 0.073), and borderline-significantly less cases of acute pancreatitis (p = 0.057) and tAMP-related re-operations or re-interventions (p = 0.057) in particular, were observed in the eVAC-CPI-group. The only anastomotic leak in the eVAC-CPI-group was successfully managed through repeated cycles of eVAC. The device was well tolerated by all patients; no vacuum/irrigation-related complications or malfunctioning occurred., Conclusion: Our study is the first to provide some technical insights demonstrating the safety and feasibility of a prophylactic approach with eVAC and perianastomotic irrigation to reduce anastomotic leak after tAMP. Increasing the number of subjects will confirm the benefit of our promising results., (© 2024. The Author(s).)

Rectal cancer typically necessitates a combination of radiotherapy (RT), chemotherapy, and surgery. The associated functional disorders and reduction in quality of life have led to an increasing interest in organ preservation strategies. Response strongly correlates with RT dose, but dose escalation with external beam remains limited even with modern external beam RT techniques because of toxicity of the surrounding tissues. This study reports on the use of Papillon, an endocavitary Radiotherapy device, in the treatment of rectal cancer. The device delivers low energy X-rays, allowing for safe dose escalation and better complete response rate. Between January 2015 and February 2024, 24 rectal cancer patients were treated with the addition of a boost delivered by Papillon to standard RT, with or without chemotherapy, in an upfront organ preservation strategy. After a median follow-up (FU) of 43 months, the organ preservation rate was 96% (23/24), and the local relapse rate was 8% (2/24). None of our patients developed grade 3 or more toxicities. Our results demonstrate that the addition of Papillon contact RT provides a high rate of local remission with sustained long-term organ preservation, offering a promising alternative to traditional surgical approaches in patients with rectal cancer.

Background: Worldwide population is ageing, but little is known regarding risk factors associated with increased mortality in subjectively healthy, community-dwelling older adults. We present the updated results of the longest follow-up carried out on Swiss pensioners and we provide results on potential risk factors associated with mortality before the onset of the COVID-19 pandemic., Materials and Methods: Within the SENIORLAB study, we collected demographic data, anthropometric measures, medical history, and laboratory parameters of 1467 subjectively healthy, community-dwelling, Swiss adults aged ≥ 60 years over a median follow-up of 8.79 years. The variables considered in the multivariable Cox-proportional hazard model for mortality during follow-up were selected based on prior knowledge. Two separate models for males and females were calculated; moreover, we fitted the old model obtained in 2018 to the complete follow-up data to highlight differences and similarities., Results: The population sample included 680 males and 787 females. Age of participants ranged between 60 and 99 years. We experienced 208 deaths throughout the entire follow-up period; no patients were lost at follow-up. The Cox-proportional hazard regression model included female gender, age, albumin levels, smoking status, hypertension, osteoporosis and history of cancer within predictors of mortality over the follow-up period. Consistent findings were obtained also after gender stratification. After fitting the old model, female gender, hypertension, and osteoporosis still showed statistically significant independent associations with all-cause mortality., Conclusions: Understanding the predictors of a healthy survival can improve the overall quality of life of the ageing population and simultaneously reduce their global economic burden., Trial Registration: The present study was registered in the International Standard Randomized Controlled Trial Number registry: https://www.isrctn.com/ISRCTN53778569 (registration date: 27/05/2015)., (© 2023. The Author(s).)

Objective: To assess whether prophylactic irrigation and passive drainage of pancreatico-jejunal anastomosis could reduce leak and mortality rates after high-risk pancreaticoduodenectomies., Background: Postoperative pancreatic fistula (POPF) is a life-threatening complication following pancreaticoduodenectomy. Several risk factors have been proposed likewise potential mitigation strategies. Regarding the latter, surgical drain policy remains a "hot topic." We propose an innovative approach to mitigate POPF and POPF-related mortality following high-risk pancreaticoduodenectomies., Methods: One hundred fifty-seven patients undergoing pancreaticoduodenectomy between January 2012 and November 2021 were included in the study. Subjects with main pancreatic duct ≤ 3 mm and soft parenchyma were classified as high-risk for POPF development. Since August 2015, high-risk patients received prophylactic irrigation and drainage of the perianastomotic area. These patients were compared with risk-matched historical controls., Results: We identified 73 high-risk patients. Of these, the 47 subjects receiving prophylactic perianastomotic irrigation showed significantly lower POPF rates (12.7% vs 69.2%, P < 0.001). Multivariate regression analysis confirmed the significant association between irrigation drainages and POPF (odds ratio 0.014, P = 0.01). Although not significant, mortality was lower in the irrigation group (4.2% vs 13.0%, P = 0.340). However, none of the fatalities in the irrigation-drainage group were POPF-related. No significant difference in length of hospital stay was observed between the 2 groups (18.0 vs 21.0 days, P = 0.091)., Conclusions: Irrigation and drainage of the perianastomotic area represents a powerful approach to reduce POPF and, potentially, mortality after high-risk pancreaticoduodenectomies., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Osteoporosis is an important morbidity factor for ageing populations in developed countries. However, compared to the amount of information available on diabetes and cardiovascular disease, little is known about the direct impact of osteoporosis on general mortality in older age., Methods: We obtained data from a prospective population-based cohort of pensioners from the SENIORLAB study who were subjectively healthy. The inclusion criteria were an age of at least 60 years and Swiss residence. We assessed and analysed clinical measures, voluntary reports, and laboratory values., Results: In total, 1467 subjects were included in the cohort. The mean follow-up time was 3.68 years (95% confidence interval, 3.64-3.71). The ages of the included participants ranged from 60 to 99 years. At follow-up, there were 1401 survivors, and 66 participants had died. According to the multivariate analysis (Cox regression), osteoporosis was the most important risk factor for all-cause mortality (hazard ratio, 4.46; 95% confidence interval, 1.82-10.91), followed by diabetes (hazard ratio, 2.17; 95% confidence interval, 1.04-4.52) and hypertension (hazard ratio, 1.81; 95% confidence interval, 1.09-3.03)., Conclusions: Osteoporosis is a major risk factor for all-cause mortality in a subjectively healthy senior population, followed by type 2 diabetes mellitus and hypertension. Osteoporosis should be more actively diagnosed in healthy pensioners before they develop osteoporosis-associated health incidents., Trial Registration: The present study was registered in the International Standard Randomized Controlled Trial Number registry: ISRCTN53778569 .

Objective: The role of gastrointestinal (GI) hormones in the pathophysiology of obesity is unclear, although they are involved in the regulation of satiation and glucose metabolism. To (i) examine glucagon-like peptide 1 (GLP-1), amylin, ghrelin, and glucagon responses to a meal in obese adolescents and to (ii) test which GI peptides are associated with insulin resistance are presented., Methods: A total of 16 obese (body mass index (BMI) ≥ 97th percentile for age and gender) and 14 control (BMI between 25th and 75th percentiles) adolescents were included. Subjects were instructed to eat a test meal (490 kcal). Plasma samples were collected for hormone and glucose analysis., Results: Obese adolescents were insulin resistant as expressed by the Homeostasis Model Assessment (HOMA) index and had significantly increased fasting glucagon and amylin levels compared to the control group (P = 0.003 and 0.044, respectively). In response to the meal, the increase in GLP-1 levels was reduced in obese adolescents (P < 0.001). In contrast, amylin secretion was significantly increased in the obese population compared to the control group (P < 0.005)., Conclusions: Obese adolescents have increased fasting glucagon and amylin levels and attenuated post-prandial GLP-1 concentrations compared with the control group. These factors could contribute to the metabolic syndrome., (© 2014 The Obesity Society.)

Background: Traditionally, emergency consultations have been done by a general practitioner (GP) in Switzerland. Over the last years, there seems to have been a shift between general practice to hospital emergency ward utilisation. There are several local initiatives of general practitioners and hospitals to change the organisation of emergency care. To plan a new organisation form of emergency care, delivery should be based on population based data., Objective: The aim of the study was to investigate the epidemiology and distribution of emergency consultations of primary care in a hospital and in a practice of general practitioners. In addition, factors of clinical performance in emergency consultations are of great public health interest., Methods: For this survey, all emergency patient contacts of general practitioners from the catchment area of Bülach, serving 27 088 inhabitants, were assessed by a questionnaire during the fourth quarter of 2006. Sex, age, time, duration of the contact and triage diagnosis were assessed. In addition, all patients seen by the emergency ward at the local hospital were assessed. Contact rates and hospitalisation rates per 100 000 inhabitants were determined. In addition, a multiple linear regression model was performed to determine factors associated with consultation time as a marker for clinical performance., Results: Between October 1th and December 31th 2006, 1001 patient contacts were registered at the same time period in the hospital and general practice. The patient contact rate was 94.8 contacts per 100 000 inhabitants per day, and the hospitalisation rate was 9.1 patient per 100 000 inhabitants. Patients seen at the hospital were older than in general practice (41.2 ± 22.8 vs. 32.6 ± 26.3 years) and consultation and waiting time was longer in the hospital than consultation time with the GP (144.8 ± 106.5 vs. 19.6 ± 17.6 minutes)., Conclusion: Nearly 1 out of 1000 inhabitants were looking for emergency primary care help, and 10% of the patients were seen urgently by general practitioners and hospital staff and were hospitalised. These numbers are important information for planning emergency primary care facilities. The most prevalent triage diagnoses in practice are infections, traumatological reasons and ENT-problems, whereas in hospital the most frequent triage diagnosis is a traumatological disorder, followed by thoracic pain and infections. In addition, GP's treat patients more rapidly than a hospital does and treat patients in shorter time intervals.

Glucagon-like peptide-1 (GLP-1) and CCK-33 were intravenously infused alone or in combination into normal weight men for 60 min before they were served a lunch of ham sandwiches, chocolate mousse, and orange juice. Infusion of GLP-1 (dose: 0.9 pmol x kg(-1) x min(-1)) or CCK-33 (dose: 0.2 pmol x kg(-1) x min(-1)) each reduced calorie intake of the test meal. However, simultaneous infusion of these peptide doses reduced calorie intake less than the sum of the peptides' individual effects. Infusions of the same doses of GLP-1 plus CCK-33 had neither individual nor interactive effects on meal size or calorie consumption. The combination of GLP-1 plus CCK-33 induced, however, a significant reduction in hunger feelings in the premeal period (P = 0.036 vs. all other treatments). In summary, intravenous infusion of near physiological doses of CCK-33 and GLP-1 produced specific inhibitions of hunger feeling in men; the simultaneous infusion resulted in an infra-additive reduction in calorie consumption, rejecting thereby the hypothesis that the two peptides exert a positive synergistic effect on food intake compared with the effects observed with infusion of individual peptides. In conclusion, CCK and GLP-1 are meal-related satiety signals that are released from the gastrointestinal tract during food intake.

Background: Half of the dialysis population suffers from hyperphosphataemia, which is now recognized as a major factor of haemodialysis (HD) morbidity and mortality. Current control is focussed on reducing dietary phosphate intake and diminishing absorption using phosphate binders, whereas control and quantification of phosphate removal by HD is undervalued. The aim of this prospective study was to develop a simple, bedside formula to estimate dialytic phosphate removal in stable HD patients., Methods: This was a prospective, randomized trial. Phosphate and urea elimination were assessed in a representative group of patients at two dialysis centres using randomly different dialysers (1.3-2.4 m(2)). Quantification was performed by partial dialysate collection, concentration measurements in blood and effluent dialysate spot samples, and Kt/V(urea) during standard high-flux HD. Multiple linear regression analyses were used in 77% of all data sets to generate an equation to predict phosphate removal. The formula was validated in the remaining 23% of data sets, in the same group of patients using a large capillary filter, and in diabetic patients treated with a small dialyser at different blood flows (200, 250, and 300 ml/min)., Results: A formula allowing quantification of phosphate removal within one HD session was developed in 18 of 74 patients during 41 treatments (137 out of 177 data sets) and was determined as: M(PO4pred)=0.1t -17+50c(ds60)+11c(b60), where t is treatment time in min, c(ds60) and c(b60) are phosphate concentrations in dialysate and plasma measured 60 min into HD in mmol/l, and M(PO4pred) is estimated phosphate removed in mmol. The precision was remarkable (r(2)=0.92-0.94). The comparison of phosphate and Kt/V(urea) showed a significant association (r(2)=0.28), albeit with remarkable scatter., Conclusions: We present the first approach to quantify phosphate removal during high-flux HD by a bedside formula. Only 28% of the variation in phosphate removal was explained by Kt/V(urea). It appears that other factors not adequately accounted for by Kt/V(urea) affect phosphate removal. Therefore, we propose an individual control and quantification of phosphate removal in HD.

Background: The influence of potassium (K) removal on dialysis efficiency as measured by urea elimination is not clear. In this prospective, randomized, cross-over study we investigated the magnitude of K removal and its effect on urea (u) elimination during high-flux haemodialysis (HD)., Methods: Twelve stable, non-diabetic HD patients were investigated during three one-week standardized HD periods (1.8 m(2) high-flux polysulphone dialyser, treatment time 240 min, Qb = 300 ml/min, Qd = 500 ml/min, dialysate without glucose, bicarbonate 40 mmol/l), using dialysates containing 0 (0K), 1 (1K), and 2 (2K) mmol/l of K. Mass removal of K (M(K)) and u (M(U)) were measured during the mid-week treatment by partial dialysate collection. Urea reduction rate (URR) and Kt/V were determined., Results: 0K, 1K and 2K treatments were perfectly comparable. Plasma K (PK) continuously declined reaching stable concentrations after 180 min. While 0K dialysate removed 117.1 mmol, 80.2 and 63.3 mmol (P < 0.001) were removed by 1K and 2K baths respectively. M(U) was not influenced by M(K) (r = 0.22) and amounted to 491.1 (0K), 508.6 (1K), and 506.2 (2K) mmol (NS) respectively. Accordingly, urea clearance, URR and Kt/V were constant during 0K, 1K and 2K treatments., Conclusions: Potassium-free dialysate significantly enhances potassium elimination. Potassium removal has no influence on urea elimination. High potassium removal, when needed, does not impair dialysis efficiency as measured by urea kinetics in high-flux, glucose-free, 40 mmol/l bicarbonate HD.

Cholecystokinin (CCK) interacts with neural signals to induce satiety in several species, but the mechanisms are unclear. We therefore tested the hypothesis that alimentary CCK (CCK-A) receptors mediate the interaction of CCK with an appetizer on food intake in humans. CCK octapeptide (CCK-8, 0.75 microgram infused over 10 min) or saline (placebo) with concomitant infusions of saline (placebo) or loxiglumide, a specific CCK-A antagonist, was infused into 16 healthy men with use of a double-blind, four-period design. All subjects received a standard 400-ml appetizer (amounting to 154 kcal) but were free to eat and drink thereafter as much as they wished. The effect of these infusions on feelings of hunger and satiety and on food intake was quantified. CCK-8 induced a reduction in calorie intake (P < 0.05) compared with saline. Furthermore, a decrease in hunger feelings (P < 0.05, saline-CCK-8 vs. all other treatments) and an increase in fullness were observed. These effects were antagonized for hunger and fullness by loxiglumide. We conclude that CCK-8 interacts with an appetizer to modulate satiety in humans. These effects are mediated by CCK-A receptors.

Background/aims: Studies in animals suggest a physiological role for glucagon-like peptide-1-(7-36)-amide (GLP-1) in regulating satiety. The role of GLP-1 in regulating food intake in man has, however, not been investigated. Subjects-Sixteen healthy male subjects were examined in a double blind placebo controlled fashion., Methods: The effect of graded intravenous doses (0, 0.375, 0.75, and 1.5 pmol/kg/min) of synthetic human GLP-1 on food intake and feelings of hunger and satiety was tested in healthy volunteers., Results: Graded GLP-1 infusions resulted in a dose dependent reduction in food intake (maximal inhibition 35%, p<0.001 v control) and a similar reduction in calorie intake (32%; p<0.001). Fluid ingestion was also reduced by GLP-1 (18% reduction, p<0.01). No overt side effects were produced by GLP-1, but subjects experienced less hunger and early fullness in the period before a meal during GLP-1 infusion at the highest dose (p<0.05)., Conclusions: Intravenous infusions of GLP-1 decrease spontaneous food intake even at physiological plasma concentrations, implying an important role for GLP-1 in the regulation of the early satiety response in humans.

Background/aims: Bombesin and gastrin-releasing peptide (GRP) are closely related peptides. Both have been proposed to serve as a satiety signal in animals., Methods: To explore further the role of GRP in humans, its effects on satiety and eating behavior were investigated by infusion of GRP into healthy men at three dosages (10, 40, and 160 pmol/kg per hour) and compared with saline infusions., Results: GRP produced a significant reduction in calorie intake (P < 0.05) but only a 19% (nonsignificant) reduction in food intake. Fluid ingestion was not affected by GRP. No overt side effects were produced by GRP, but subjects experienced d less hunger and early fullness in the premeal period during GRP infusion but not when receiving saline (P < 0.05-0.01)., Conclusions: This study shows that intravenous infusions of GRP can decrease spontaneous food intake at concentrations that produce physiological effects, such as stimulation of acid or pancreatic secretion or gallbladder contraction. The data imply that GRP-like peptides can act as satiety signals in humans, confirming data previously reported in animals.