Quality of life in patients with short bowel syndrome treated with the new glucagon-like peptide-2 analogue teduglutide--analyses from a randomised, placebo-controlled study.

BACKGROUND & AIMS: Short bowel syndrome (SBS)-intestinal failure (IF) patients have impaired quality of life (QoL) and suffer from the burden of malabsorption and parenteral support (PS). A phase III study demonstrated that treatment with teduglutide, a glucagon-like peptide 2 analogue, reduces PS volumes by 32% while maintaining oral fluid intake constant; placebo-treated patients had reduced PS by 21%, but oral fluid intake increased accordingly. As effects of teduglutide on QoL are unknown, they were investigated here. METHODS: QoL analyses from a double-blind, randomised Phase III study in 86 SBS-IF patients receiving teduglutide (0.05 mg/kg/day s.c.) or placebo over 24 weeks. At baseline and every 4 weeks, QoL was assessed using the validated SBS-QoL™ scale. RESULTS: PS reductions were associated with QoL improvements (ANCOVA, p = 0.0194, SBS-QoL per-protocol). Compared to baseline, teduglutide significantly improved the SBS-QoL™ total score and the score of 9 of 17 items at week 24. These changes were not significant compared to placebo. Teduglutide-treated patients with remaining small intestine >100 cm experienced more gastrointestinal adverse events (GI-AE), unfavourably affecting QoL. CONCLUSIONS: Overall, PS volume reductions were associated with improvements in SBS-QoL™ scores. The short observation period, imbalances in oral fluid intake in relation to PS reductions, large patient and effect heterogeneity and occurrence of GI-AE in a subgroup of teduglutide-treated patients may account for the inability to show statistically significant effects of teduglutide on SBS-QoL™ scores compared to placebo.

Development and validation of the disease-specific Short Bowel Syndrome-Quality of Life (SBS-QoL™) scale.

BACKGROUND & AIMS: Subjects with short bowel syndrome (SBS) have impaired quality of life (QoL). No disease-specific instrument has been available to measure treatment-induced changes in QoL over time. Therefore, the aim was to develop and validate an SBS-specific QoL scale. METHODS: Classical test theory and Food and Drug Administration (FDA) guidance were applied for development and validation of the SBS-QoL™. Procedures included item generation and raw scale construction. Factor analysis, construct validity and internal consistency were assessed in a non-interventional observation, test re-test reliability and responsiveness in a randomised clinical study. RESULTS: The SBS-QoL™ comprises 17 items including two subscales. Subjects assessed the scale as easy to handle and comprehensible. Good construct validity was shown by comparison with the Home Parenteral Nutrition-Quality Of Life questionnaire as an external scale, which yielded moderately high correlation (r ≥ 0.7). High internal consistency was demonstrated (Cronbach's alpha: 0.94). Also the test re-test reliability was high (r ≥ 0.95), indicating reliable reproducibility of results. The Responsiveness Index (1.84) indicated the ability of the scale to detect changes in QoL over time. CONCLUSIONS: The SBS-QoL™ is an easy to handle and comprehensible SBS-specific subject-reported QoL scale. It is valid, reliable and sensitive with excellent psychometric characteristics to measure treatment-induced changes in QoL over time in subjects with SBS.

Randomised placebo-controlled trial of teduglutide in reducing parenteral nutrition and/or intravenous fluid requirements in patients with short bowel syndrome.

BACKGROUND AND AIMS: Teduglutide, a GLP-2 analogue, may restore intestinal structural and functional integrity by promoting repair and growth of the mucosa and reducing gastric emptying and secretion, thereby increasing fluid and nutrient absorption in patients with short bowel syndrome (SBS). This 24-week placebo-controlled study evaluated the ability of teduglutide to reduce parenteral support in patients with SBS with intestinal failure. METHODS: In 83 patients randomised to receive subcutaneous teduglutide 0.10 mg/kg/day (n = 32), 0.05 mg/kg/day (n = 35) or placebo (n = 16) once daily, parenteral fluids were reduced at 4-week intervals if intestinal fluid absorption (48 h urine volumes) increased ≥ 10%. Responders were subjects who demonstrated reductions of ≥ 20% in parenteral volumes from baseline at weeks 20 and 24. The primary efficacy end point, a graded response score (GRS), took into account higher levels and earlier onset of response, leading to longer duration of response. The intensity of the response was defined as a reduction from baseline in parenteral volume (from 20% to 100%), and the duration of the response was considered the response at weeks 16, 20 and 24. The results were tested according to a step-down procedure starting with the 0.10 mg/kg/day dose. RESULTS: Using the GRS criteria, teduglutide in a dose of 0.10 mg/kg/day did not have a statistically significant effect compared with placebo (8/32 vs 1/16, p=0.16), while teduglutide in a dose of 0.05 mg/kg/day had a significant effect (16/35, p = 0.007). Since parenteral volume reductions were equal (353 ± 475 and 354 ± 334 ml/day), the trend towards higher baseline parenteral volume (1816 ± 1008 vs 1374 ± 639 ml/day, p=0.11) in the 0.10 mg/kg/day group compared with the 0.05 mg/kg/day group may have accounted for this discrepancy. Three teduglutide-treated patients were completely weaned off parenteral support. Serious adverse events were distributed similarly between active treatment groups and placebo. Villus height, plasma citrulline concentration and lean body mass were significantly increased with teduglutide compared with placebo. CONCLUSIONS: Teduglutide was safe, well tolerated, intestinotrophic and suggested pro-absorptive effects facilitating reductions in parenteral support in patients with SBS with intestinal failure. ClinicalTrials.gov number NCT00172185.

Home enteral nutrition in adults: a European multicentre survey.

AIMS: This study was undertaken to report indications and practice of home enteral nutrition (HEN) in Europe. METHODS: A questionnaire on HEN practice was sent to 23 centres from Belgium (B), Denmark (D), France (F), Germany (G), Italy (I), Poland (P), Spain (S) and the United Kingdom (UK). This involved adult patients newly registered in HEN programme from 1 January 1998 to 31 December 1998. RESULTS: A total of 1397 patients (532 women, 865 men) were registered. The median incidence of HEN was 163 patients/million inhabitants/year (range: 62-457). Age distribution was 7.5%, 16-40 years; 37.1%, 41-65 years; 34.5%, 66-80 years and 20.9% >80 years. The chief underlying diseases were a neurological disorder (49.1%), or head and neck cancer (26.5%); the main reason for HEN was dysphagia (84.6%). A percutaneous endoscopic gastrostomy (58.2%) or a naso-gastric tube (29.3%) were used to infuse commercial standard or high energy diets (65.3%), or fibre diets (24.5%); infusion was cyclical (61.5%) or bolus (34.1%). Indications and feeds were quite similar throughout the different centres but some differences exist concerning the underlying disease. There was greater variation in the choice of tubes and mode of infusion. In F, G, I, S, and UK, costs of HEN are fully funded. In B, D, and P patients have to pay part or all of the charges. CONCLUSIONS: In Europe, HEN was utilised mainly in dysphagic patients with neurological disorders or cancer, using a standard feed via a PEG. However, there were important differences among the countries in the underlying diseases treated, the routes used, the mode of administration and the funding.

[Dynamic of IL-6 and IL-8 concentrations in patients after surgery treated with total parenteral nutrition]. / Dynamika zmian stezenia interleukin 6 i 8 u chorych po zabiegach chirurgicznych leczonych calkowitym zywieniem pozajelitowym.

Exaggerated cytokines productions and development of systemic inflammatory response (SIRS) is the most common cause of postoperative complications and death after major abdominal surgery. The present study was conducted to investigate alterations in systemic production of interleukin-6 (IL-6) and interleukin-8 (IL-8) after total parenteral nutrition (TPN) in surgical patients. Plasma concentrations of IL-6 and IL-8 were measured in 22 patients (10 treated with TPN and 12 without TPN) before major surgery and on the days 1, 3, 7, 10 and 14-16 after, by ELISA test (indications for surgery: stomach, pancreatic and colon carcinoma, complications of IBD and acute pancreatitis). There were no differences between preoperative levels of IL-6 and IL-8 in the examined groups of patients. The highest (on the days 1, 3, 7, 10: 268.3 (p = 0.002), 41.9 (p = 0.03), 122.6 (p = 0.009), 29.3 (p = 0.03) pg/ml respectively) and longer lasting significantly elevated level of IL-6 was observed in the group of patients after major surgery without TPN. In the group of patients received TPN (with glutamine) there was a significantly increased but in comparison with group of patients without TPN, significantly lower level of IL-6 on days 1 and 7 (103.4 and 34.7 pg/ml respectively, p = 0.01). There was no significant change in postoperative concentration of IL-8 after major surgery in the group of patients treated with TPN. The level of IL-8 was significantly elevated (p = 0.01) in the group of patients without TPN on day 1 and 3 following surgery. The IL-8 level in the TPN group vs. group of patients without TPN was significantly lower on day 1 after surgery. After TPN concentration of cholesterol was significantly higher and CRP level significantly lower. We conclude that TPN improved immunological response to major surgical trauma by reduction of the inflammatory response.

Home parenteral nutrition in adults: a european multicentre survey in 1997. ESPEN-Home Artificial Nutrition Working Group.

A retrospective survey on home parenteral nutrition (HPN) in Europe was performed from January to December 1997. Data were compared to a similar study performed in 1993. A questionnaire of HPN practice was designed by the members of the ESPEN-HAN group. This involved adult patients (older than 16 years) newly registered in an HPN program between 1 January and 31 December 1997 and included: number of patients, underlying diseases and a 6-12 month outcome. Incidence and prevalence (at 1.1.1998) of adult HPN were calculated according to the estimated total population in 1997 for the countries in which more than 80% of HPN patients were reported.A total of 494 patients were registered in 73 centres from nine countries (Belgium (B), Denmark (D), France (F), Poland (P), Spain (S), Sweden (Sw), United Kingdom (UK), The Netherlands (N) and Germany (G). The underlying diseases for HPN in 494 patients were cancer (39%), Crohn's (19%), vascular diseases (15%), radiation enteritis (7%), AIDS (2%), other diseases with intestinal failure (18%). Incidence (patients/million inhabitants/year) were in N (3), F. (2.9), D. (2.8), B. (2.6), UK (1. 2), S (0.7) and P (0.36), respectively. Prevalence were in D. (12.7). U.K. (3.7), N. (3.7), F (3.6), B (3.0), P (1.1), S (0.65). After this 6-12 months follow-up (n=284), the mortality was respectively 4% in Crohn's disease, 13% in vascular diseases, 16% in others, 21% in radiaton enteritis, 34% in AIDS, 74% in cancer. Incidences and prevalences modestly increased in these seven European countries in 1997 in comparison to 1993. The percentages of underlying diseases in these countries remained similar except for AIDS that significantly decreased (from 7% to 2%). Outcomes did not significantly differ in the 4-year period except for AIDS (34% instead of 88% mortality) and could have been related to newer, more efficacious therapy.

[Computer program "PANCREAS"]. / Program komputerowy "PANCREAS".

Contemporary computer technology allows precise and fast large database analysis. Widespread and common use depends on appropriate, user friendly software, usually lacking in special medical applications. The aim of this work was to develop an integrated system designed to store, explore and analyze data of patients treated for pancreatic cancer. For that purpose the database administration system MS Visual Fox Pro 3.0 was used and special application, according to ISO 9000 series has been developed. The system works under MS Windows 95 with possibility of easy adaptation to MS Windows 3.11 or MS Windows NT by graphic user's interface. The system stores personal data, laboratory results, visual and histological analyses and information on treatment course and complications. However the system archives them and enables the preparation reports of according to individual and statistical needs. Help and security settings allow to work also for one not familiar with computer science.

[Pancreatic fistulas]. / Przetoki trzustkowe.

The aim of our study was retrospective analysis of causes and treatment results of pancreatic fistula. In years 1989-1996, 40 patients aged 14-74 years were treated for pancreatic fistula in the Department of Gastroenterologic Surgery of Medical University in Warsaw. The majority of patients (36 adults) were treated conservatively, with the use of parenteral nutrition, drainage and somatostatin (in case of 4 patients). The healing of pancreatic fistula occurred in 27 medically treated patients after 26 days of therapy (mean value), the remaining patients were treated surgically. The applied treatment was effective in 38 out of 40 cases, 2 patients died (5.0%) due to the complications not connected with pancreatic fistula. In our opinion, in early stages of treatment of pancreatic fistula the conservative therapy with the use of parenteral nutrition is the treatment of choice and elective surgery should be used in patients, in whom conservative treatment fails.

Home parenteral nutrition in adults: a multicentre survey in Europe in 1993.

A retrospective survey was performed in 1994, involving 496 adult home parenteral nutrition (HPN) cases, newly enrolled in the year 1993 from 13 European countries from 75 centres. From the 8 countries having registered more than 80% of cases (423 patients), incidence and prevalence ranged from 0.2 to 4.6 and 0.3 to 12.2 patients/10(6) population/year. In the patients studied, the diagnosis was cancer (42%), Crohn's disease (15%), vascular diseases (13%), radiation enteritis (8%), AIDS (4%) and other nonmalignant non-AIDS diseases (18%). Short bowel syndrome and intestinal obstruction were the two major indications for HPN in 31% and 22%, respectively. Seventy-three percent of the centres had a nutrition team. HPN was administered through a tunnelled venous central catheter in 73%, cyclical nocturnal infusions were used in 90% of patients, and intravenous feeding was the sole source of nutrition in 33%. Only 44% undertook HPN unaided. The present report indicates that cancer has now become the main indication for HPN in Europe; there was, however, a heterogeneous distribution of diseases amongst the reporting countries. The observed 9 (6-12)-month probability of survival was poor in AIDS (n = 8; 12%) and cancer patients (n = 78; 29%) but better for the other HPN indications (n = 115; 92%).

[14-year experience with surgical treatment of chronic pancreatitis]. / 14-letnie doswiadczenia w chirurgicznym leczeniu przewleklego zapalenia trzustki.

The authors discuss their own 14-year experience with surgical treatment of the chronic pancreatitis. They treated 64 patients of a mean age of 43 years. An abdominal pain, persisting in all patients, constituted the main indication to surgery. Forty patients underwent pancreatic enterostomy with Puestow technique, 19 patients resections of various extension, and 5 patients underwent pancreatic duodenostomy. Mortality rate in pancreatic enterostomy and pancreatic duodenostomy was 2.5% whereas mortality rate in resections was 5.3%. Complications were noted in 27.5% and 36.8% of patients, respectively. Pain was completely abolished or markedly reduced in 90% of patients. Forty eight (77.4%) out of 62 patients were identified and followed up. According to commonly used criteria, positive late results were achieved in 56.2% of patients, moderate in 29.2%, and poor result in 14.6% of the treated patients.

[Renal biopsy in the aged]. / Biopsja nerki u osób w wieku podeszlym.

Pathological findings in urinalysis in the aged persons are usually thought to be caused by pathologic processes other than glomerulopathy. Histological evaluation of renal tissue in older patients is extremely difficult due to coexistence of involuntary changes-hyalinosis, increase in mesangial matrix content, and vascular changes. The aim of the study was to evaluate frequency of glomerulonephritis, both primary and secondary in persons older than 60. In this group, as compared to the younger people the secondary glomerulonephritis was more frequent, amyloidosis and vasculitis nodosa being the most frequent. In primary glomerulonephritis mesangiocapillary type dominate, quite often some tendency to hyalinization could be observed. Renal biopsy is useful as a diagnostic tool in both the aged and young. It should be performed regardless the patients age.