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Most hospitals have a contingency plan, based on all-risks and all-hazards assessment principles. However, emerging threats and risks often necessitate a flexible approach to emergency management at several levels of a disaster response system, for example, in hospitals. Sweden, and possibly other countries, has limited possibilities of surge capacity in the management of large-scale disasters and emergencies, which necessitates a local/national partnership and a flexible local disaster and contingency plan. This study evaluates the opinions of a selected managerial group, both at operative and strategic levels, regarding possible changes in a major hospital’s contingency plan during the ongoing COVID-19 pandemic. Semistructured interviews were conducted to explore the elements of surge capacity and an operational tool, consisting of command and control, safety, communication, assessment, triage, treatment, and transport. The results show a need to create feasible management methods that can be evaluated, establish clear leadership, put preparedness as a constant point on the highest managerial agenda, improve external monitoring, and create a regional coordinating center. Furthermore, the results emphasize the significant role played by the incident command system and qualified leadership to facilitate competent and crucial medical decision making, as well as to provide reliable communication, collaboration, and coordination in a multi-agency response system during dynamic and unexpected emergencies. These steps enable a constant connection between reactive contingency plans and the proactivity in continuous risk assessment and enhance the flexibility of the contingency plans.

OBJECTIVES Pancreatic ductal adenocarcinomas (PDACs) are found in more than 85% of patients with pancreatic cancer and with 5-year survival of less than 10%. Effective treatment may be radical surgery, which is hampered by rapid relapse. Therefore, our aim was to compare DNA sequence alterations in patients with short and long survival to evaluate if confirmed DNA alterations predict short postoperative survival. METHODS DNA was extracted from tumor tissue from 59 PDAC patients, analyzed for KRAS mutations, and hybridized to 180 K CGH + SNP microarrays and 450 K methylation arrays. Analyses were based on postoperative survival where less than 12 months was considered to be short survival and more than 18 months was considered long survival. RESULTS Ninety-three percent of the patients had KRAS mutations in tumor DNA. Great heterogeneity of whole genome DNA sequence alterations were observed among chromosomes within the patient materials. Specific DNA sequence alterations did not directly predict postoperative survival, although short survivors had significantly more and larger DNA amplifications (P < 0.006). Amplifications on chromosome 11 and 21 and deletions on chromosome 2 predicted short postoperative survival (P < 0.03). DNA methylation was not related to survival. CONCLUSIONS Highly variable genetic differences among DNA regions in PDAC tumors were demonstrated. Postoperative short survival was related to tumor sequence DNA alterations on chromosome 2, 11, and 21.

We earlier reported cost-utility estimates in patients who undergo resection aimed at cure for pancreatic carcinoma. The present study describes similar information on patients with unresectable tumors who experienced palliative care only.A population-based cohort of patients with exocrine pancreatic adenocarcinoma during 1998-2005 was evaluated retrospectively (n = 444). Total direct health care costs at departments of surgery and oncology, for primary health care, and at hospice were achieved. Self-estimated health-related quality of life (HRQL) was assessed by the SF-36. A single preference-based utility index, SF-6D, was derived from SF-36 items to estimate quality-adjusted life years (QALYs). Results were compared to similar findings in a previously reported group of patients with pancreatic carcinoma resected for cure (n = 31).Palliative care patients (n = 305) had impaired HRQL particularly related to physical domains. The mean preference-based health utility index at diagnosis was 0.65 ± 0.02 [95 % confidence interval (CI) 0.61-0.69] compared to 0.77 ± 0.02 (95 % CI 0.75-0.79) in healthy reference individuals. Total direct health care costs were 50 % in patients on palliative care compared to costs for surgical R0 resections (23,701 and 50,950euro, respectively). QALYs for 1 year from diagnosis were 0.2 (95 % CI 0.17-0.23) in patients on palliative care and 0.48 (95 % CI 0.44-0.54) in resection patients. Costs per QALY were 118,418euroand 106,146euro, respectively (95 % CI 103,048-139,418euroand 94,352-115,795euro).Optimized palliative care of patients with exocrine pancreatic carcinoma had costs per achieved utility similar to those for surgical resections aimed at cure.

Summary Background & aims Nutritional therapy has traditionally been evaluated by changes in weight and in food intake, while body composition and function may be of greater clinical significance. We investigated relationships between total body skeletal muscle mass (TBSMM), energy balance and exercise capacity in 41 patients before, 6 and 12 months after curatively intended major upper gastrointestinal surgery. Methods TBSMM and body energy content were assessed by DXA. Exercise capacity was measured on a treadmill. Energy balance was defined as the difference in body energy content at two points in time. Results During the first postoperative year average weight loss was 7% although 1 our of 3 patients remained weight stable (WS). Average TBSMM decreased significantly at 6 months (0.9 kg, p Conclusions TBSMM and exercise capacity were clearly related in cancer patients after major upper gastrointestinal surgery, as were changes in TBSMM and exercise capacity. Energy balance was not directly correlated to exercise capacity, but more WS than WL patients increased their TBSMM indicating a possible influence by energy balance.

Virtual reality (VR) simulators have been demonstrated to improve basic psychomotor skills in endoscopic surgery. The exercise configuration settings used for validation in studies published so far are default settings or are based on the personal choice of the tutors. The purpose of this study was to establish consensus on exercise configurations and on a validated training program for a virtual reality simulator, based on the experience of international experts to set criterion levels to construct a proficiency-based training program. A consensus meeting was held with eight European teams, all extensively experienced in using the VR simulator. Construct validity of the training program was tested by 20 experts and 60 novices. The data were analyzed by using the t test for equality of means. Consensus was achieved on training designs, exercise configuration, and examination. Almost all exercises (7/8) showed construct validity. In total, 50 of 94 parameters (53%) showed significant difference. A European, multicenter, validated, training program was constructed according to the general consensus of a large international team with extended experience in virtual reality simulation. Therefore, a proficiency-based training program can be offered to training centers that use this simulator for training in basic psychomotor skills in endoscopic surgery.

The aim of this study was to investigate whether specialized supportive enteral and parenteral feeding have superior effects compared to oral nutrition on recovery during long-term postoperative treatment of cancer patients with preoperative weight loss and reduced maximum exercise capacity.One hundred twenty-six patients referred for resection of the esophagus (n = 48), stomach (n = 28), or pancreas (n = 50) were considered to be included before operation. Included patients (n = 80) received supportive enteral or parenteral nutrition postoperatively at home corresponding to 1000 kcal/d until the patients did not wish to continue with artificial nutrition for any reason. Patients randomized to oral nutrition only served as control subjects. Caloric intake, body composition (dual-energy x-ray absorptiometry), and respiratory gas exchanges at rest and during exercise were measured including health-related quality of life.Survival and hospital stay did not differ among the groups, whereas overall complications were higher on artificial nutrition (P.05). Changes in resting energy expenditure and biochemical tests did not differ during follow-up among the groups. Body weight and whole body fat declined similarly over time in all groups (P.005), whereas lean body mass was unchanged during follow-up compared to preoperative values. Maximum exercise capacity and maximum oxygen consumption were normalized within 6 months postoperatively in all groups. There was no difference in recovery of food intake among the groups. Parenteral feeding was associated with the highest rate of nutrition-related complications, whereas enteral feeding reduced quality of life most extensively.After major surgery, specialized supportive enteral and parenteral nutrition are not superior to oral nutrition only when guided by a dietitian.

Objective: To assess the feasibility, safety, and short-term functional outcome of a pancreas-sparing duodenectomy. Design: Prospective, uncontrolled study. Setting: University hospital, Sweden. Subjects: Four patients with extensive lesions in the duodenum (2 familial polyposis, 1 villous adenoma, and 1 giant multiple lipoma). Results: All 4 patients had a duodenectomy with sparing of 1-1.5 cm of the duodenal bulb and reinplantation of the biliary and pancreatic ducts into the jejunum. Except for one early postoperative bile leak the operative and postoperative courses were uneventful. The functional results have been promising with unaltered alimentary function in the 3 patients who had no preoperative outlet obstruction and complete resolution of symptoms in the patient with duodenal lipomas who had chronic incomplete obstruction preoperatively. Conclusions: Although the indications for pancreas-preserving duodenectomy are limited, the procedure can be done safely with gastrointestinal function maintained.

Background Pancreatic cystic lesions (PCLs) are increasingly frequent radiological incidentalomas, with a considerable proportion representing precursors of pancreatic cancer. Better diagnostic tools are required for patients to benefit from this development. Methods To evaluate whether cyst fluid mucin expression could predict malignant potential and/or transformation in PCLs, a proteomic method was devised and prospectively evaluated in consecutive patients referred to our tertiary center for endoscopic ultrasound-guided aspiration of cystic lesions from May 2007 through November 2008 (discovery cohort) and from December 2008 through October 2012 (validation cohort). Cytology and cyst fluid carcinoembryonic antigen (CEA; premalignancy > 192ng/mL, malignancy > 1000ng/mL) were routinely analyzed, and samples were further processed as follows: one-dimensional gel electrophoresis, excision of high-mass areas, tryptic digestion and nano-liquid chromatography–tandem mass spectrometry, with peptide identification by Mascot software and an in-house mucin database. All diagnostic evaluations were blinded to proteomics results. Histology was required to confirm the presence/absence of malignant transformation. All statistical tests were two-sided. Results Proteomic mucin profiling proved statistically significantly more accurate (97.5%; 95% confidence interval [CI] = 90.3% to 99.6%) than cytology (71.4%; 95% CI = 59.8% to 80.9%; P < .001) and cyst fluid CEA (78.0%; 95% CI = 65.0% to 87.3%; P < .001) in identifying the 37 (out of 79; 46.8%) lesions with malignant potential (ie, premalignant or malignant tumors). The accuracy of proteomics was nearly identical (96.6% vs 98.0%) between the discovery (n = 29) and validation (n = 50) cohorts. Furthermore, mucin profiling predicted malignant transformation, present in 16 out of 29 (discovery cohort: 9, validation cohort: 20) lesions with available histology, with 89.7% accuracy (95% CI = 71.5% to 97.3%) (for the validation cohort only: 95.0%; 95% CI = 73.1% to 99.7%). This markedly exceeded corresponding results for cytology (51.7%; 95% CI = 32.9% to 70.1%; P = .003) and CEA (57.1%; 95% CI = 34.4% to 77.4%; P = .02). Conclusions Proteomic cyst fluid mucin profiling robustly discriminates benign, premalignant, and malignant PCLs. Consequently, it may improve pancreatic cancer prevention and reduce the morbidity burden of unwarranted pancreatic surgery.

Background: Does profound acid inhibition by continuous infusion of omeprazole for 72 h reduce further bleeding in elderly patients with peptic ulcer bleeding (PUB)? Methods: Three hundred and thirty-three patients ≥60 years old with PUB were randomized to omeprazole (80 mg + 8 mg/h) or placebo as continuous infusion for 72 h. From day 4 to 21 all patients received 20 mg omeprazole orally once daily. Results: When evaluated on day 3, the primary variable ‘overall outcome’ (based on an ordinal ranking scale; see Study variables) (P = 0.017) and the secondary variables, surgery (P = 0.003), degree (P = 0.004) and duration of bleeding (P = 0.003) all favored the omeprazole group. Blood transfusions, need for endoscopic treatment, and mortality were not statistically different. On follow-up, by day 21, the mortality in the group initially receiving intravenous omeprazole was 6.9%, while the intravenous placebo group showed an extremely low mortality, 0.6%. Conclusion: Three days' infusion of omeprazole improv...

Major histocompatibility complex class I-related chain A and B (MICA/B) are two stress-inducible ligands that bind to the immunoreceptor NKG2D and play an important role in mediating cytotoxicity of NK and T cells. Release of MIC molecules from the cell surface is thought to constitute an immune escape mechanism of tumor cells and thus could be associated with more aggressive course of tumor growth. In this study, we investigated the expression of MICA/B in ductal pancreatic carcinoma and serum in relation to tumor stage, differentiation and survival. MICA/B expression in tumor tissues and sera from patients with pancreatic cancer were analyzed by immunohistochemical staining (IHC), western blotting and ELISA, respectively. MICA/B expression was present in 17 of 22 (77%) of the tumors but not in normal pancreatic ductal epithelial cells. Poorly differentiated tumors showed more pronounced MICA/B expression compared to differentiated tumors, but did not correlate significantly to other tumor characteristics. MICA/B-negative tumors displayed significantly lower incidence of lymph node metastases (p

This study has evaluated the effects of recombinant human insulin-like growth factor I (rhIGF-I) to moderately stressed post-operative patients provided with dextrose as the only exogeneous substrate. Thirty patients who underwent elective colorectal surgery were randomized to receive either rhIGF-I (80 micrograms kg-1 bw) subcutaneously twice daily or placebo injections in a double-blind parallel group design. Nitrogen balance, urinary 3-methyl-histidine excretion plasma growth hormone (GH), serum cortisol, IGF-I binding proteins (IGFBP-1,3), glomerular filtration rate, plasma amino acid concentrations and whole-body energy expenditures were measured as effector variables during days 1-5 post-operatively. Animal and isolated tissue experiments were performed as additional control experiments to confirm cellular effectiveness of the recombinant material. rhIGF-I increased significantly the glomerular filtration rate and prevented the adaptive decrease in whole-body energy expenditure in response to partial starvation in the postoperative period. Serum and plasma concentrations of IGFBP-1,3 cortisol, blood glucose and amino acids were not significantly influenced by rhIGF-I administration, while plasma GH levels decreased significantly as expected. rhIGF-I had no effect on either nitrogen balance or protein breakdown (3-methylhistidine excretion) in post-operative patients on dextrose supplementation only, although plasma concentrations of IGF-I increased from 130-140 ng mL-1 to a range of 300-450 ng mL-1. In contrast, IGF-I stimulated the synthesis of both globular and myofibrillar proteins (+50%, P < 0.01), when given as a single dose (100 micrograms kg-1) 2 h before measurements of protein synthesis in skeletal muscles of overnight fasted adult mice. This stimulatory effect by IGF-I (1 microgram mL-1) was also confirmed by measurements of skeletal muscle protein synthesis in vitro (+40%, P < 0.05). Orally re-fed mice had a normal transcription of IGF-I mRNA in skeletal muscle cells, while overnight fasted mice showed a trend to down-regulated transcription. Our results demonstrate that rhIGF-I has several significant physiological effects, without major side-effects, when supplied to partially starved patients in the post-operative phase. The lack of a whole-body nitrogen sparing effect by rhIGF-I alone to post-operative patients is not clear, but was most likely explained by subnormal plasma concentrations of amino acids.

The role of IV infusion kinetics to explain nutrition efficiency was investigated in patients after major surgical procedures.IV nutrition was provided as three different infusion kinetic regimens in a randomized fashion. All patients received nonprotein calories (100% of predicted preoperative REE, 60% D-glucose, 40% fat) and amino acid nitrogen (0.2 g N/d). Group A: Nutrition was provided by sequential infusion with combined fat and amino acids during daytime and glucose alone during nighttime ("sequential infusion"). Group B: Patients received 24-hour combined infusion with fat, amino acids, and glucose (all in one mixture) ("continuous infusion"). Group C: Nutrition was provided by bolus infusions during 1 hour followed by 2 hours without any infusion ("bolus infusion").The daily energy balance was negative in all groups (-318 +/- 25 kcal/d, sequential infusion; -368 +/- 25 kcal/d continuous infusion; -292 +/- 20 kcal/d, bolus infusion). Significantly different excretion patterns of nitrogen in urine occurred among the groups despite an almost identical provision of nitrogen. Continuously infused patients retained nitrogen significantly better (-0.2 +/- 0.6 g/d) compared with sequentially (-3.4 +/- 1.0 g/d) and bolus-infused patients (-2.8 +/- 0.3 g/d) (p.01), whereas their cumulative urinary glucose excretion was significantly larger. Continuously infused patients were in cumulative nitrogen balance during the entire postoperative period, whereas the other groups were in a significantly negative nitrogen balance. Urinary 3-methylhistidine excretion was similar in all groups.The breakdown of muscle proteins was not sensitive to alterations in nutrient and substrate supply. Thus improved nitrogen retention reflected entirely improved synthesis. "All-in-one" IV nutrition with prolonged infusion periods is at present the most favorable regimen considering both the nutritional efficiency and its metabolic load on the organism after major surgery.

This review considers the development of structured triglycerides as an IV nutrient source. The replacement of a portion of long-chain fatty acids in the conventional fat emulsion triglycerides confers favorable qualities on these lipids and renders them attractive as an energy source, particularly in critically ill patients. This report considers the features of structured triglycerides that may make them competitive or even more efficient as an energy source compared with conventional fat emulsions.

Various modes of intravenous nutrient administration may be associated with characteristic alterations in physiologic and metabolic host responses. Notably, cyclic parenteral nutrition produces greater short-term thermic effects than continuous nutrient infusion. This may increase the metabolic burden upon patients who exhibit cardiopulmonary insufficiency. On the other hand, nitrogen accretion seems to be more efficient with cyclic total parenteral nutrition, making it quite attractive as an intravenous form of nutrition support. This article details these aspects of cyclic intravenous feeding and considers its optimal applicability to different patient populations.

The aim of this study was to investigate the effect of a selective β2-adrenoceptor agonist, clenbuterol, on body composition in tumour-bearing adult and growing mice. Therefore, adult female C57/BL6 mice (n = 20) were inoculated subcutaneously with a 3-methylcholanthrene-induced sarcoma and divided into two identical groups. One group received injections twice a day of clenbuterol corresponding to 1 mg/kg body weight, the other group received sham injections. Growing mice (n = 20) were similarly divided after tumour inoculation into one study group with clenbuterol injections and one control group. The growing animals were sacrificed on day 11 after commencement of treatment, the adult mice on day 16.Clenbuterol treatment had no statistically significant effect on accumulated food intake or body composition in the adult mice. However, fooe intake in these animals increased numerically compared to control animals after day 12 of the study. Tumour growth was also unaffected. The growing animals displayed an increased carcass dry weight with borderline significance (p = 0.06) and an increased quadriceps muscle fat free dry weight after clenbuterol treatment. Tumour growth was not affected. Food intake measured on a daily basis was significantly increased in the growing clenbuterol treated animals and accumulated food intake was increased with a trend towards statistical significance (p = 0.06). The results support the suggestion that treatment with a selective β2-adrenoceptor agonist does not improve body composition in tumour-bearing adult mice relying on spontaneous food intake while growing animals may benefit from such treatment.

Three hundred patients undergoing major general surgical procedures were randomized by means of a computer-assisted algorithm to receive either total parenteral nutrition (TPN) from the first postoperative day or only prolonged glucose administration (250-300 g/day) up to 15 days after operation. All patients receiving TPN were treated individually based on daily measurements of energy and nitrogen balances. The treatment goal was to keep the patients in positive energy balance (+20%) and close to nitrogen balance. The effects of the two "nutrition regimens" on outcome such as mortality rate, complications, the need of additional medical support and patient-related functional disabilities were investigated. No selection of patients was made, that is, malnourished patients were also randomized. There were no differences among TPN versus glucose treatment when results were analyzed according to intent to treat. Approximately 60% of all patients were able to start eating within 8 to 9 days after operation. No differences were observed between such patients regardless of being treated with TPN or glucose only. Patients on glucose treatment during 14 days had a significantly higher mortality rate (p < 0.05) than patients on either continuous and uncomplicated TPN treatment or short-term glucose treatment. Similar results for mortality rates also were seen with regard to severe complications (cardiopulmonary problems, sepsis, and wound-healing insufficiencies), functional disturbances, the need of additional medical support, and abnormalities in nutritional state. Twenty per cent of the patients randomized to TPN treatment showed a statistical trend (p < 0.10) toward a higher mortality rate (36%) compared with patients randomized to prolonged glucose treatment (21% mortality rate). These patients could not be identified by evaluation of preoperative factors. Thus, the overall evaluation of the results makes it likely that a fraction of high-risk patients (approximately 20%) were not doing well on immediate postoperative intravenous feeding, and it is possible that TPN to such patients accentuated their morbidity rate. Although patients (20%) on prolonged semi-starvation (14 days glucose treatment) had increased mortality rate and severe complications, it was possible that undernutrition induced a slightly different complication scenario than induced by TPN in the high-risk patients. The results demonstrate that in most surgical patients (60%), postoperative semi-starvation is not a limiting factor for outcome. In remaining 40%, inadequate nutrition was associated with both increased morbidity and mortality rates. In this sense, inadequate nutrition represents both too much and too little, whereas overfeeding seemed to be a larger problem than underfeeding.(ABSTRACT TRUNCATED AT 400 WORDS)

The aim of this study was to demonstrate significant factors behind elevated resting energy expenditure in weight-losing cancer patients. Therefore, weight-losing cancer patients (n = 60), with normal liver and kidney function tests, were randomized to receive one of four drug treatments for 5 days: (a) Propranolol 80 mg x 2 (beta-adrenoceptor blockade); (b) Indomethacin 50 mg x 2 (prostaglandin synthesis inhibition); (c) Morphine 5 mg x 3 (pain relief) or (d) Placebo x 2. A reference group of healthy well-nourished individuals were examined outside the formal randomization protocol and they received Propranolol 80 mg x 2. The cancer patients were randomized by a computer based algorithm stratifying for measured resting energy expenditure (REE), body composition, biochemical tests, previous therapy, tumour type and tumour stage. Resting energy expenditure was measured by indirect calorimetry in the morning after an overnight fast before and after drug treatment. beta-blockade reduced REE significantly in cancer patients from 1416 +/- 95 kcal day-1 to 1160 +/- 63 kcal day-1 (P < 0.02) and from 1472 +/- 69 vs, 1398 +/- 63 kcal day-1 (P < 0.01) in the well-nourished reference individuals. The reduction found in cancer patients (10%) was significantly larger than that in the group of reference patients (5%), (P < 0.01). Indomethacin, morphine or placebo did not induce any significant alteration in energy expenditure in our cancer patients. Propranolol treatment was associated with a significant reduction in plasma concentrations of free fatty acids (FFA), but not in plasma glycerol.(ABSTRACT TRUNCATED AT 250 WORDS)

Little is reported on costs for radical tumor resections of pancreatic carcinoma in relationship to adjusted quality of life survival postoperatively. Therefore, the aim of the present study was to estimate the cost utility of surgical treatment aimed at cure.A population-based cohort of patients with exocrine or ampullary pancreatic adenocarcinoma resected for cure in Gothenburg University Hospitals during 1998-2005 were evaluated retrospectively (n = 139). Total inpatient and outpatient healthcare costs were available for 103 patients, and health-related quality of life (HRQL) (based on the SF-36 Health Survey) were assessed preoperatively and postoperataively in 119 patients. Survival and utility index (SF-36-6D) across 5 years of postoperative follow-up were used to achieve quality adjusted life years.Mean survival after resection was 977 days for patients with exocrine pancreatic carcinoma, with expected differences among subgroups as related to disease stage (p0.01), in agreement with international reports. The HRQL index was 0.65 ± 0.06 preoperatively, 0.63 ± 0.04 early postoperatively (1 year) and 0.69 ± 0.06 at long-term follow-up (1-5 years) compared to 0.77 ± 0.02 in age-matched healthy reference individuals from the Swedish population (p0.05). Total lifetime costs for treatments including surgery and adjuvant chemotherapy were 39,000 euro per patient, with a mean of 1.13 (95% Confidence Interval [CI] 0.93-1.40) QALYs across 5 years follow-up. The cost per QALY was 35,000 euro (95% CI 28,026 euro-41,947 euro).Resection aimed at cure of pancreatic exocrine ductal carcinoma provided costs for one quality adjusted year of survival comparable to other complex surgical treatments within cost limits regarded as reasonable to bear by the Swedish health care system, as well as in several other Western countries.

BACKGROUND: The short-term provision of ghrelin to patients with cancer indicates that there may be benefits from long-term provision of ghrelin for the palliative treatment of weight-losing cancer patients. This hypothesis was evaluated in a randomized, double-blind, phase 2 study. METHODS: Weight-losing cancer patients with solid gastrointestinal tumors were randomized to receive either high-dose ghrelin treatment (13 μg/kg daily; n = 17 patients) or low-dose ghrelin treatment (0.7 μg/kg daily; n = 14 patients) for 8 weeks as a once-daily, subcutaneous injections. Appetite was scored on a visual analog scale; and food intake, resting energy expenditure, and body composition (dual x-ray absorpitometry) were measured before the start of treatment and during follow-up. Serum levels of ghrelin, insulin, insulin-like growth factor 1, growth hormone (GH), triglycerides, free fatty acids, and glucose were measured. Health-related quality of life, anxiety, and depression were assessed by using standardized methods (the 36-item Short Form Health Survey and the Hospital Anxiety and Depression Scale). Physical activity, rest, and sleep were measured by using a multisensor body monitor. RESULTS: Treatment groups were comparable at inclusion. Appetite scores were increased significantly by high-dose ghrelin analyzed both on an intent-to-treat basis and according to the protocol. High-dose ghrelin reduced the loss of whole body fat (P < .04) and serum GH (P < .05). There was a trend for high-dose ghrelin to improve energy balance (P < .07; per protocol). Otherwise, no statistically significant differences in outcome variables were observed between the high-dose and low-dose groups. Adverse effects were not observed by high-dose ghrelin, such as serum levels of tumor markers (cancer antigen 125 [CA 125], carcinoembryonic antigen, and CA 19-9). CONCLUSIONS: The current results suggested that daily, long-term provision of ghrelin to weight-losing cancer patients with solid tumors supports host metabolism, improves appetite, and attenuates catabolism. Cancer 2010. © 2010 American Cancer Society.

The aim of this study was to evaluate to what extent secondary carnitine deficiency may exist based on the prevalence of subnormal carnitine status in patients with critical illness and abnormal nutritional state. Healthy control patients (n = 12) were investigated and compared with patients with possible secondary carnitine deficiency, ie, patients with overt severe protein-energy malnutrition (PEM, n = 28), postoperative long-term (greater than 14 days) parenteral glucose feeding (250 g glucose/d, n = 7), severe liver disease (n = 10), renal insufficiency (n = 7), and sustained septicemia with increased metabolic rate (n = 8). Nutritional status, energy expenditure, creatinine excretion, and blood biochemical tests were measured in relationship to free and total carnitine concentrations in plasma and skeletal muscle tissue, as well as urinary excretion of free and total carnitine. The overall mortality rate was 48% within 30 days of the investigation in study patients with the highest mortality in liver disease (90%). The hospitalization range was 14 to 129 days in study patients. Most study patients had lost weight (4% to 19%) and had abnormal body composition. Patients with liver disease, septicemia, renal insufficiency, and those on long-term glucose feeding had significantly higher than predicted metabolic rate (+25% +/- 3%), while patients with severe malnutrition had decreased metabolic rate compared with controls. Patients with liver disease had increased plasma concentrations of free (96 +/- 16 mumol/L) and total (144 +/- 27 mumol/L) carnitine compared with controls (45 +/- 3, 58 +/- 7 mumol/L, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Cancer patients (n = 106) and non-cancer subjects (n = 96) were classified as weight stable (n = 70) or weight-losing (n = 132). Cancer patients had elevated resting energy expenditure (REE) compared with either weight-losing (23.6 [0.4] vs. 20.5 [0.5] kcal/kg per day, P less than 0.001) or weight-stable controls (22.0 [0.6] vs. 17.9 [0.4], P less than 0.001). Cancer patients had increased fat oxidation irrespective of weight loss (1.24 [0.07] vs. 0.87 [0.04] mg/kg per min; 1.07 [0.04] vs. 0.78 [0.04], P less than 0.001). Elevated energy expenditure was counter-regulated by a decrease in thyroid hormones. Abnormal liver function had no impact on REE in either group. Heart rate was the most powerful factor for prediction of high energy expenditure in both patients and controls. Elevated energy expenditure was related to the increased heart rate in cancer patients in a significantly higher proportion than that in controls. Increased metabolic rate is a significant component behind weight loss in cancer disease, independent of malnutrition and an elevated adrenergic state may be a likely explanation.

Cancer and non-cancer patients received total parenteral nutrition (TPN) corresponding to either 120% or 200% non-protein energy resting energy expenditure. Whole-body tyrosine flux and leg exchange of various metabolites were measured in the fasted and fed state. Feeding with the moderate TPN rate did not stimulate whole-body protein synthesis in either group, but the high rate did. Both TPN rates switched an efflux of branched-chain aminoacids from the leg to an uptake in both groups, but this did not apply to tyrosine or phenylalanine. Only the high TPN rate stimulated glucose uptake across the leg in both groups. The leg exchanges of lactate, glycerol and free fatty acids were not significantly influenced by moderate or high TPN rates in either group, although changes in arterial concentrations indicated significant exchanges in compartments other than leg tissues. Thus standard TPN is insufficient to stimulate overall protein synthesis in both malnourished cancer and non-cancer patients, which may explain why previous studies have demonstrated insignificant functional effects with nutritional support to cancer patients.

BACKGROUND: Several investigations that yielded different results in terms of net changes in body composition of weight-losing cancer patients have been reported that employed a variety of methods based on fundamentally different technology. Most of those reports were cross-sectional, whereas to the authors' knowledge there is sparse information available on longitudinal follow-up measurements in relation to other independent methods for the assessment of metabolism and performance. METHODS: For the current report, the authors evaluated time course changes in body composition (dual-energy X-ray absorptiometry) with measurements of whole body and regional distribution of fat and lean tissue in relation to food and dietary intake, host metabolism (indirect calorimetry), maximum exercise capacity (walking test), and circulating hormones in cancer patients who were receiving palliative care during 4-62 months of follow-up. The entire cohort comprised 311 patients, ages 68 years +/- 3 years who were diagnosed with solid gastrointestinal tumors (84 colorectal tumors, 74 pancreatic tumors, 73 upper gastrointestinal tumors, 51 liver-biliary tumors, 3 breast tumors, 5 melanomas, and 21 other tumor types). RESULTS: Decreased body weight was explained by loss of body fat, preferentially from the trunk, followed by leg tissue and arm tissue, respectively. Lean tissue (fat-free mass) was lost from arm tissue, whereas trunk and leg tissue compartments increased, all concomitant with declines in serum albumin, increased systemic inflammation (C-reactive protein, erythrocyte sedimentation rate), increased serum insulin, and elevated daily caloric intake; whereas serum insulin-like growth factor 1 (IGF-1), resting energy expenditure, and maximum exercise capacity remained unchanged in the same patients. Serum albumin levels (P < 0.001), whole body fat (P < 0.02), and caloric intake (P < 0.001) predicted survival, whereas lean tissue mass did not. Daily intake of fat and carbohydrate was more important for predicting survival than protein intake. Survival also was predicted by serum IGF-1, insulin, leptin, and ghrelin levels (P < 0.02 - P < 0.001). Serum insulin, leptin, and ghrelin (total) levels predicted body fat (P < 0.001), whereas IGF-1 and thyroid hormone levels (T3, free T3) predicted lean tissue mass (P < 0.01). Systemic inflammation primarily explained variation in lean tissue and secondarily explained loss in body fat. Depletion of lean arm tissue was related most to short survival compared with the depletion of lean leg and trunk tissue. CONCLUSIONS: The current results demonstrated that body fat was lost more rapidly than lean tissue in progressive cancer cachexia, a phenomenon that was related highly to alterations in the levels of circulating classic hormones and food intake, including both caloric amount and diet composition. The results showed importance in the planning of efficient palliative treatment for cancer patients.

Purpose: The purpose is to evaluate relationships between objectively assessed exercise capacity and subjectively assessed scoring of physical functioning and well-being after erythropoietin treatment in cancer patients on palliative care. Experimental Design: Unselected cancer patients (n = 108) who experienced progressive cachexia were randomized to receive either anti-inflammatory treatment alone (indomethacin) or recombinant erythropoietin plus indomethacin to prevent the appearance of disease-induced anemia and thereby protect patients’ exercise capacity. Follow-up investigations of nutritional status, exercise capacity, and health-related quality of life assessed by SF-36 and the European Organization for Research and Treatment of Cancer QLQ-C30 were compared. Results: Effective treatment by erythropoietin on top of basal whole body anti-inflammatory treatment was confirmed and indicated by time course changes of biochemical, physiologic, and nutritional objectives, whereas individual self-reported scoring of physical functioning and general health did not indicate a clear-cut effectiveness, particularly at moderately subnormal hemoglobin levels. Conclusions: Discrepancies between objective and subjective self-reported measures may be either fundamental or indicate scoring limitations for evaluation of therapeutic results. Present results demonstrate a clinical benefit of erythropoietin treatment in cancer patients with subnormal to normal hemoglobin levels, whereas the patients’ own subjective scoring was insufficient to sense such improvements. The discrepancy may be either fundamental or methodological but emphasizes the importance to document therapeutic outcome in both subjective and objective perspectives in palliative care of cancer patients.

Cancer patients lose weight due to negative energy balance because of insufficient appetite and inappropriately high energy expenditure. Host and tumor derived cytokines and more recently eicosanoids have been held responsible as mediators. Accordingly, observations in animal experiments and short-term clinical trials in selected groups of cancer patients, have implied that cyclo-oxygenase (COX) blockade can improve host metabolism and well-being, and long-term COX-treatment of unselected groups have implied improved survival. The aim of this study was to search for evidence that long-term COX-treatment improves energy and cardiovascular homeostasis in unselected weight-losing cancer patients. A retrospective case control analysis was performed on a data-base material collected consecutively. Weight-losing untreated cancer patients had elevated resting energy expenditure compared to undernourished non-cancer patients (23.3+/-0.1, n=702 vs 20.9+/-0.3 kcal/kg/day, n=132, p

To evaluate an aggressive surgical strategy in patients with mediastinal sepsis as a result of oesophageal leakage.A prospective clinical study.University hospital, Sweden.11 consecutive patients who presented with mediastinal sepsis as a result of a damaged oesophagus caused by instrumental perforation in 4 cases and spontaneous rupture in 6 cases during a 6-year period.Ten patients were treated with oesophagectomy with a diverting proximal oesophagostomy and in one case a primary cervical oesophagogastrostomy was done after emergency resection.Mortality and morbidity.The median delay from onset of symptoms to admission to the unit was 3 days (range 0-6). All patients required artificial ventilation postoperatively and the stay in the ICU amounted to 12.5 days but only 1 patient died during the postoperative course. All patients have subsequently undergone substernal oesophageal replacement with either a gastric tube or a colonic graft.Emergency oesophagectomy and proximal deviating oesophagostomy is a salvage procedure for patients with severe fulminant mediastinal sepsis, and it can be done in selected cases with good results.

The aim of the study was to evaluate whether basic surgical skills achieved by training in LapSim, a computerbased laparoscopic simulator, could be transferred to the operating room.For this study, 24 medical students undergoing courses in surgery were randomly assigned to train with LapSim or to serve as control subjects. After they had undergone simulator training 2 h per week for 5 weeks, their basic skills in laparoscopic surgery were assessed in a porcine model. The time to perform each task was measured, and four senior surgeons independently graded the overall performance on a 9-step differential rating scale.The participants randomized to train with LapSim showed significantly better results for all tasks in both parts of the study than the untrained participants, according to the expert evaluation. Time consumption was accordingly lower in the training group in the control group.The results show that basic skills achieved by systematic training with a laparoscopic simulator such as LapSim can be transferred to the operating room.

With the objective of further optimizing the outcome of antireflux surgery, we have studied the importance of dividing the short gastric vessels when performing a laparoscopic total fundoplication. Ninety-nine consecutive patients with chronic gastroesophageal reflux disease (GERD) were enrolled in the trial. Forty-seven patients (25 men, age 52 +/- 1.6 years [mean +/- standard error]) were randomized to undergo a laparoscopic Nissen-Rossetti total fundic wrap with intact short gastric vessels, whereas 52 patients (29 men, 48 +/- 1.4 years) had complete division of these vessels. Quality of life was assessed by means of the psychological general well-being and gastrointestinal symptom rating scale indices. The 6- and 12-month follow-up data are reported. Two patients were converted to open surgery. Mobilization of the fundus significantly prolonged the operative time (120 vs. 104 minutes, P = 0.05); otherwise the complication rates were similar in the two groups. Both procedures were equally effective in controlling gastroesophageal reflux at 6 and 12 months' postoperatively. Division of the short gastric vessels had no significant impact on the point prevalence of postfundoplication complaints at the given follow-up time points. Quality of life was significantly improved by both operative procedures and remained "normal" throughout the follow-up period. Dividing all short gastric vessels had no impact on the functional outcome during the first year of recovery after a total laparoscopic fundoplication.

This study was aimed at comparing the blocking of beta-adrenoceptor activity to changes in the resting energy metabolism of 10 cancer patients with progressive weight loss due to solid malignant tumours. Resting energy expenditure (REE) as well as whole body carbohydrate and fat oxidation were investigated and related to plasma substrate levels (glucose, glycerol, free fatty acids (FFA)) before and after 5 days of oral administration of specific beta1 receptor blocker (atenolol, 50 mg/day) and non-specific beta1,beta2-adrenoceptor (propranolol, 80 mg/day) blockade. The administration order of the drugs was random, and a 3-day washout period was used in all individuals between the provision of the first and the second drug in order to minimise the risk of carry-over effects. Resting measurements in the morning after an overnight fast were performed by indirect calorimetry. Atenolol treatment reduced REE by 77+/-14 kcal/day and propranolol by 48+/-13 kcal/day, respectively (P