Randomized phase-III study of low-dose cytarabine and etoposide + /- all-trans retinoic acid in older unfit patients with NPM1-mutated acute myeloid leukemia.

The aim of this randomized clinical trial was to evaluate the impact of all-trans retinoic acid (ATRA) in combination with non-intensive chemotherapy in older unfit patients (> 60 years) with newly diagnosed NPM1-mutated acute myeloid leukemia. Patients were randomized (1:1) to low-dose chemotherapy with or without open-label ATRA 45 mg/m2, days 8-28; the dose of ATRA was reduced to 45 mg/m2, days 8-10 and 15 mg/m2, days 11-28 after 75 patients due to toxicity. Up to 6 cycles of cytarabine 20 mg/day s.c., bid, days 1-7 and etoposide 100 mg/day, p.o. or i.v., days 1-3 with (ATRA) or without ATRA (CONTROL) were intended. The primary endpoint was overall survival (OS). Between May 2011 and September 2016, 144 patients (median age, 77 years; range, 64-92 years) were randomized (72, CONTROL; 72, ATRA). Baseline characteristics were balanced between the two study arms. The median number of treatment cycles was 2 in ATRA and 2.5 in CONTROL. OS was significantly shorter in the ATRA compared to the CONTROL arm (p = 0.023; median OS: 5 months versus 9.2 months, 2-years OS rate: 7% versus 10%, respectively). Rates of CR/CRi were not different between treatment arms; infections were more common in ATRA beyond treatment cycle one. The addition of ATRA to low-dose cytarabine plus etoposide in an older, unfit patient population was not beneficial, but rather led to an inferior outcome.The clinical trial is registered at clinicaltrialsregister.eu (EudraCT Number: 2010-023409-37, first posted 14/12/2010).

Prognostic and predictive value of CA 19-9 in locally advanced pancreatic cancer treated with multiagent induction chemotherapy: results from a prospective, multicenter phase II trial (NEOLAP-AIO-PAK-0113).

BACKGROUND: The prognostic and predictive value of carbohydrate antigen 19-9 (CA 19-9) in locally advanced pancreatic cancer (LAPC) has not yet been defined from prospective randomized controlled trials (RCTs). PATIENTS AND METHODS: A total of 165 LAPC patients were treated within the NEOLAP RCT for 16 weeks with multiagent induction chemotherapy [ICT; either nab-paclitaxel/gemcitabine alone or nab-paclitaxel/gemcitabine followed by FOLFIRINOX (combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin)] followed by surgical exploration of all patients without evidence of disease progression. CA 19-9 was determined at baseline and after ICT and correlated with overall survival (OS) and secondary R0 resection rate. RESULTS: From the NEOLAP study population (N = 165) 133 patients (81%) were evaluable for CA 19-9 at baseline and 81/88 patients (92%) for post-ICT CA 19-9 response. Median OS (mOS) in the CA 19-9 cohort (n = 133) was 16.2 months [95% confidence interval (CI) 13.0-19.4] and R0 resection (n = 31; 23%) was associated with a significant survival benefit [40.8 months (95% CI 21.7-59.8)], while R1 resected patients (n = 14; 11%) had no survival benefit [14.0 (95% CI 11.7-16.3) months, hazard ratio (HR) 0.27; P = 0.001]. After ICT most patients showed a CA 19-9 response (median change from baseline: -82%; relative decrease ≥55%: 83%; absolute decrease to ≤50 U/ml: 43%). Robust CA 19-9 response (decrease to ≤50U/ml) was significantly associated with mOS [27.8 (95% CI 18.4-37.2) versus 16.5 (95% CI 11.7-21.2) months, HR 0.49; P = 0.013], whereas CA 19-9 baseline levels were not prognostic for OS. Multivariate analysis demonstrated that a robust CA 19-9 response was an independent predictive factor for R0 resection. Using a CA 19-9 decrease to ≤61 U/ml as optimal cut-off (by receiver operating characteristic analysis) yielded 72% sensitivity and 62% specificity for successful R0 resection, whereas CA 19-9 nonresponders (<20% decrease or increase) had no chance for successful R0 resection. CONCLUSIONS: CA 19-9 response after multiagent ICT provides relevant prognostic and predictive information and is useful in selecting LAPC patients for explorative surgery. CLINICAL TRIAL NUMBER: ClinicalTrials.govNCT02125136; https://clinicaltrials.gov/ct2/show/NCT02125136; EudraCT 2013-004796-12; https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-004796-12/results.

Efficacy and safety of lipegfilgrastim versus pegfilgrastim in elderly patients with aggressive B cell non-Hodgkin lymphoma (B-NHL): results of the randomized, open-label, non-inferiority AVOID neutropenia study.

BACKGROUND: Lipegfilgrastim has been shown to be non-inferior to pegfilgrastim for reduction of the duration of severe neutropenia (DSN) in breast cancer patients. This open-label, non-inferiority study assessed the efficacy and safety of lipegfilgrastim versus pegfilgrastim in elderly patients with aggressive B cell non-Hodgkin lymphoma (NHL) at high risk for chemotherapy-induced neutropenia. PATIENT AND METHODS: One hundred and one patients (median age, 75 years) were randomized to lipegfilgrastim or pegfilgrastim (6 mg/cycle) during six cycles of R-CHOP21. RESULTS: Lipegfilgrastim was non-inferior to pegfilgrastim for the primary efficacy endpoint, reduction of DSN in cycle 1. In the per-protocol population, mean (standard deviation) DSN was 0.8 (0.92) and 0.9 (1.11) days in the two groups, respectively; the adjusted mean difference between groups was - 0.3 days (95% confidence interval, - 0.70 to 0.19). Non-inferiority was also demonstrated in the intent-to-treat population. The incidence of severe neutropenia in cycle 1 was 51% (21/41) in the lipegfilgrastim group and 52% (23/44) in the pegfilgrastim group. Very severe neutropenia (ANC < 0.1 × 109/L) in cycle 1 was reported by 5 (12%) patients in the lipegfilgrastim group and 8 (18%) patients in the pegfilgrastim group. However, over all cycles, febrile neutropenia (strict definition) was reported by only 1 (2%) patient in each treatment group (during cycle 1 in the lipegfilgrastim group and cycle 6 in the pegfilgrastim group). The mean time to absolute neutrophil count recovery (defined as ≥ 2.0 × 109/L) was 8.3 and 9.4 days in the two groups, respectively. Serious adverse events occurred in 46% of patients in each group; none were considered treatment-related. Eight patients died during the study (2 in the lipegfilgrastim group, 5 in the pegfilgrastim group, and 1 who died before starting study treatment). No deaths occurred during the treatment period, and all were considered to be related to the underlying disease. CONCLUSIONS: This study shows lipegfilgrastim to be non-inferior to pegfilgrastim for the reduction of DSN in elderly patients with aggressive B cell NHL receiving myelosuppressive chemotherapy, with a comparable safety profile. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT02044276; EudraCT number 2013-001284-23.

Dynamics in treatment response and disease progression of metastatic colorectal cancer (mCRC) patients with focus on BRAF status and primary tumor location: analysis of untreated RAS-wild-type mCRC patients receiving FOLFOXIRI either with or without panitumumab in the VOLFI trial (AIO KRK0109).

PURPOSE: In mCRC, disease dynamics may play a critical role in the understanding of long-term outcome. We evaluated depth of response (DpR), time to DpR, and post-DpR survival as relevant endpoints. METHODS: We analyzed DpR by central review of computer tomography images (change from baseline to smallest tumor diameter), early tumor shrinkage (≥ 20% reduction in tumor diameter at first reassessment), time to DpR (study randomization to DpR-image), post-DpR progression-free survival (pPFS = DpR-image to tumor progression or death), and post-DpR overall survival (pOS = DpR-image to death) with special focus on BRAF status in 66 patients and primary tumor site in 86 patients treated within the VOLFI-trial, respectively. RESULTS: BRAF wild-type (BRAF-WT) compared to BRAF mutant (BRAF-MT) patients had greater DpR (- 57.6% vs. - 40.8%, p = 0.013) with a comparable time to DpR [4.0 (95% CI 3.1-4.4) vs. 3.9 (95% CI 2.5-5.5) months; p = 0.8852]. pPFS was 6.5 (95% CI 4.9-8.0) versus 2.6 (95% CI 1.2-4.0) months in favor of BRAF-WT patients (HR 0.24 (95% CI 0.11-0.53); p < 0.001). This transferred into a significant difference in pOS [33.6 (95% CI 26.0-41.3) vs. 5.4 (95% CI 5.0-5.9) months; HR 0.27 (95% CI 0.13-0.55); p < 0.001]. Similar observations were made for patients stratified for primary tumor site. CONCLUSIONS: BRAF-MT patients derive a less profound treatment response compared to BRAF-WT patients. The difference in outcome according to BRAF status is evident after achievement of DpR with BRAF-MT patients hardly deriving any further disease control beyond DpR. Our observations hint towards an aggressive tumor evolution in BRAF-MT tumors, which may already be molecularly detectable at the time of DpR.

Randomized phase-II trial evaluating induction therapy with idarubicin and etoposide plus sequential or concurrent azacitidine and maintenance therapy with azacitidine.

The aim of this randomized phase-II study was to evaluate the effect of substituting cytarabine by azacitidine in intensive induction therapy of patients with acute myeloid leukemia (AML). Patients were randomized to four induction schedules for two cycles: STANDARD (idarubicin, cytarabine, etoposide); and azacitidine given prior (PRIOR), concurrently (CONCURRENT), or after (AFTER) therapy with idarubicin and etoposide. Consolidation therapy consisted of allogeneic hematopoietic-cell transplantation or three courses of high-dose cytarabine followed by 2-year maintenance therapy with azacitidine in the azacitidine-arms. AML with CBFB-MYH11, RUNX1-RUNX1T1, mutated NPM1, and FLT3-ITD were excluded and accrued to genotype-specific trials. The primary end point was response to induction therapy. The statistical design was based on an optimal two-stage design applied for each arm separately. During the first stage, 104 patients (median age 62.6, range 18-82 years) were randomized; the study arms PRIOR and CONCURRENT were terminated early due to inefficacy. After randomization of 268 patients, all azacitidine-containing arms showed inferior response rates compared to STANDARD. Event-free and overall survival were significantly inferior in the azacitidine-containing arms compared to the standard arm (p < 0.001 and p = 0.03, respectively). The data from this trial do not support the substitution of cytarabine by azacitidine in intensive induction therapy.

Small molecule PGC-1α1 protein stabilizers induce adipocyte Ucp1 expression and uncoupled mitochondrial respiration.

OBJECTIVE: The peroxisome proliferator-activated receptor-γ coactivator-1α1 (PGC-1α1) regulates genes involved in energy metabolism. Increasing adipose tissue energy expenditure through PGC-1α1 activation is potentially beneficial for systemic metabolism. Pharmacological PGC-1α1 activators could be valuable tools in the fight against obesity and metabolic disease. Finding such compounds has been challenging partly because PGC-1α1 is a transcriptional coactivator with no known ligand-binding properties. While, PGC-1α1 activation is regulated by several mechanisms, protein stabilization is a crucial limiting step due to its short half-life under unstimulated conditions. METHODS: We designed a cell-based high-throughput screening system to identify PGC-1α1 protein stabilizers. Positive hits were tested for their ability to induce endogenous PGC-1α1 protein accumulation and activate target gene expression in brown adipocytes. Select compounds were analyzed for their effects on global gene expression and cellular respiration in adipocytes. RESULTS: Among 7,040 compounds screened, we highlight four small molecules with high activity as measured by: PGC-1α1 protein accumulation, target gene expression, and uncoupled mitochondrial respiration in brown adipocytes. CONCLUSIONS: We identify compounds that induce PGC-1α1 protein accumulation and show that this increases uncoupled respiration in brown adipocytes. This screening platform establishes the foundation for a new class of therapeutics with potential use in obesity and associated disorders.

Analysis of the time-resolved magneto-optical Kerr effect for ultrafast magnetization dynamics in ferromagnetic thin films.

We discuss fundamental aspects of laser-induced ultrafast demagnetization probed by the time-resolved magneto-optical Kerr effect (MOKE). Studying thin Fe films on MgO substrate in the absence of electronic transport, we demonstrate how to disentangle pump-induced variations of magnetization and magneto-optical coefficients. We provide a mathematical formalism for retrieving genuine laser-induced magnetization dynamics and discuss its applicability in real experimental situations. We further stress the importance of temporal resolution achieved in the experiments and argue that measurements of both time-resolved MOKE rotation and ellipticity are needed for the correct assessment of magnetization dynamics on sub-picosecond timescales. The framework developed here sheds light onto the details of the time-resolved MOKE technique and contributes to the understanding of the interplay between ultrafast laser-induced optical and magnetic effects.

High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study).

To investigate immuno-chemotherapy for elderly immuno-competent patients (⩾65 years) with newly diagnosed primary central nervous system lymphoma, we conducted a multicentre single-arm trial. One cycle consisted of rituximab (375 mg/m2, days 1, 15, 29), high-dose methotrexate (3 g/m2 days 2, 16, 30), procarbazine (60 mg/m2 days 2-11) and lomustine (110 mg/m2, day 2)-R-MPL protocol. Owing to infectious complications, we omitted lomustine during the study and consecutive patients were treated with the R-MP protocol. Three cycles were scheduled and repeated on day 43. Subsequently, patients commenced 4 weekly maintenance treatment with procarbazine (100 mg for 5 days). Primary end point was complete remission (CR) after 3 cycles. We included 107 patients (69 treated with R-MPL and 38 with R-MP). In all, 38/107 patients achieved CR (35.5%) and 15 (14.0%) achieved partial remission. R-MP was associated with a lower CR rate (31.6%) compared with R-MPL (37.7%), but respective 2-year progression-free survival (All 37.3%; R-MP 34.9%; R-MPL 38.8%) and overall survival (All 47.0%; R-MP 47.7%; R-MPL 46.0%) rates were similar. R-MP was associated with less ⩾grade 3 toxicities compared with R-MPL (71.1% vs 87.0%). R-MP is more feasible while still associated with similar efficacy compared with R-MPL and warrants further improvement in future studies.

Pretransplant NPM1 MRD levels predict outcome after allogeneic hematopoietic stem cell transplantation in patients with acute myeloid leukemia.

The objective was to evaluate the prognostic impact of pre-transplant minimal residual disease (MRD) as determined by real-time quantitative polymerase chain reaction in 67 adult NPM1-mutated acute myeloid leukemia patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Twenty-eight of the 67 patients had a FLT3-ITD (42%). Median age at transplantation was 54.7 years, median follow-up for survival from time of allografting was 4.9 years. At transplantation, 31 patients were in first, 20 in second complete remission (CR) and 16 had refractory disease (RD). Pre-transplant NPM1 MRD levels were measured in 39 CR patients. Overall survival (OS) for patients transplanted in CR was significantly longer as compared to patients with RD (P=0.004), irrespective of whether the patients were transplanted in first or second CR (P=0.74). There was a highly significant difference in OS after allogeneic HSCT between pre-transplant MRD-positive and MRD-negative patients (estimated 5-year OS rates of 40 vs 89%; P=0.007). Multivariable analyses on time to relapse and OS revealed pre-transplant NPM1 MRD levels >1% as an independent prognostic factor for poor survival after allogeneic HSCT, whereas FLT3-ITD had no impact. Notably, outcome of patients with pre-transplant NPM1 MRD positivity >1% was as poor as that of patients transplanted with RD.

Abituzumab combined with cetuximab plus irinotecan versus cetuximab plus irinotecan alone for patients with KRAS wild-type metastatic colorectal cancer: the randomised phase I/II POSEIDON trial.

BACKGROUND: Integrins are involved in tumour progression and metastasis, and differentially expressed on colorectal cancer (CRC) cells. Abituzumab (EMD 525797), a humanised monoclonal antibody targeting integrin αν heterodimers, has demonstrated preclinical activity. This trial was designed to assess the tolerability of different doses of abituzumab in combination with cetuximab and irinotecan (phase I) and explore the efficacy and tolerability of the combination versus that of cetuximab and irinotecan in patients with metastatic CRC (mCRC) (phase II part). METHODS: Eligible patients had KRAS (exon 2) wild-type mCRC and had received prior oxaliplatin-containing therapy. The trial comprised an initial safety run-in using abituzumab doses up to 1000 mg combined with a standard of care (SoC: cetuximab plus irinotecan) and a phase II part in which patients were randomised 1 : 1 : 1 to receive abituzumab 500 mg (arm A) or 1000 mg (arm B) every 2 weeks combined with SoC, or SoC alone (arm C). The primary end point was investigator-assessed progression-free survival (PFS). Secondary end points included overall survival (OS), response rate (RR) and tolerability. Associations between tumour integrin expression and outcomes were also assessed. RESULTS: Phase I showed that abituzumab doses up to 1000 mg were well tolerated in combination with SoC. Seventy-three (arm A), 71 (arm B) and 72 (arm C) patients were randomised to the phase II part. Baseline characteristics were balanced. PFS was similar in the three arms: arm A versus SoC, hazard ratio (HR) 1.13 [95% confidence interval (CI) 0.78-1.64]; arm B versus SoC, HR 1.11 (95% CI 0.77-1.61). RRs were also similar. A trend toward improved OS was observed: arm A versus SoC, HR 0.83 (95% CI 0.54-1.28); arm B versus SoC, HR 0.80 (95% CI 0.52-1.25). Grade ≥3 treatment-emergent adverse events were observed in 72%, 78% and 67% of patients. High tumour integrin αvß6 expression was associated with longer OS in arms A [HR 0.55 (0.30-1.00)] and B [HR 0.41 (0.21-0.81)] than in arm C. CONCLUSION: The primary PFS end point was not met, although predefined exploratory biomarker analyses identified subgroups of patients in whom abituzumab may have benefit. The tolerability of abituzumab combined with cetuximab and irinotecan was acceptable. Further study is warranted. CLINICALTRIALS.GOV IDENTIFIER: NCT01008475.

[Probiotic therapy of the irritable bowel syndrome]. / Probiotische Behandlung des Reizdarmsyndroms.

The irritable bowel syndrome (IBS) is among the most common disorders in gastroenterological practice with a prevalence of approx. 12 % in Germany, and it is characterized by abdominal pain or discomfort, altered stool frequency and consistency, and meteorism and bloating. There is currently no agreement between those seeing patients with IBS (general practitioner, gastroenterologist, psychosomatics) on the criteria for clinical diagnosis. Metaanalyses of treatment studies in IBS have shown that probiotics have a high clinical efficacy in IBS, especially since development of novel pharmaceutical compounds have not reached the market or have been withdrawn. In addition to the actual status of probiotic efficacy in IBS studies conducted worldwide, we present 3 German clinical studies with probiotic E.COLI preparations that have proven their efficacy in IBS in adults and in children.

Probiotic treatment of irritable bowel syndrome in children.

UNLABELLED: Treatment of functional bowel disorders of irritable bowel-type (IBS) in children remains a difficult task because of a lack of drugs with low adverse event profile. We here report the results of a treatment study in 203 children (66 boys and 137 girls) age 4 to 18 years (mean: 10.5+/-4.5 years) with typical IBS symptoms with abdominal pain and either predominant diarrhea (n=50), constipation (n=56), alternating stool frequency (n=28) or unspecific pain (n=69). The average duration of symptoms prior to therapy was 175 days. Most (95%) patients up to age 11 were treated with a daily dose of 10 drops of Symbioflor 2 (SF2) (SymbioPharm, Herborn) (cells and autolysate of 1.5-4.5x10(7) CFU of bacteria of Escherichia coli type), in the elder children 77% received this dosage, while the remaining received a higher dose up to 30 drops/day. Treatment lasted 43 days on average. RESULTS: All patients tolerated the treatment well and without adverse events. The key IBS symptoms (abdominal pain, stool frequency) as well as the other symptoms (bloating, mucous and blood in stool, need for straining at stools, urge to defecate) improved significantly during treatment. Global assessment of therapy by parents and doctors was altogether positive. In summary these data confirm efficacy and tolerability of this probiotic compound in children and adolescents and supplement published data of probiotic IBS therapy in adults.

[Hypnotherapy for irritable bowel syndrome--a systematic review]. / Hypnotherapeutische Interventionen beim Reizdarmsyndrom - eine systematische Ubersicht.

The Irritable bowel syndrome (IBS) is a highly prevalent functional disorder with a remarkable clinical and economic impact. Several pathogenetic factors of IBS are discussed and summarised within a bio-psycho-social model. Data from published hypnotherapeutic interventions with approximately 800 patients show long-lasting symptom relief. The underlying mechanisms of action are not well understood. Nine mechanism studies show influences of hypnosis on colorectal sensitivity, colorectal motility and mental strain (anxiety, depression, maladaptive cognitions). Results are often contradictory and effects of hypnosis on several of the proposed pathogenetic factors are not examined at all. This paper reviews previous studies on hypnotherapy in IBS patients with a focus on symptom relief and mechanisms of action.

[Fear of allowing sugar into the cell--case 05/2009. Comorbidity of diabetes mellitus and eating disorders]. / Von der Angst, den Zucker in die Zelle zu lassen - Fall 05/2009. Komorbidität von Diabetes mellitus und Essstörungen.

HISTORY AND ADMISSION FINDINGS: An 19-year-old female patient was admitted to our department of psychosomatic medicine and psychotherapy for the treatment of her metabolically deranged type 1 diabetes mellitus. INVESTIGATIONS: Exploration and assessment revealed a typical eating disorder symptomatology. The body mass index at time of admission was 18.7 kg/m (2). Episodes of binge eating were followed by purging behaviour (insulin purging, vomiting). DIAGNOSIS, TREATMENT AND COURSE: After diagnosis of bulimia nervosa, the patient was treated with a structured dual treatment regime consisting of psychosomatic/psychotherapeutic interventions and endocrinological support. The existing complex bio-psycho-social conditions were considered carefully. In the treatment course typical eating disorder behaviour (i. e. insulin purging) decreased and mood stabilised. CONCLUSIONS: Adolescent women with diabetes mellitus are at an increased risk of developing an eating disorder. This comorbidity is associated with a markedly increased mortality. Therefore, diagnosis of an eating disorder should be made as soon as possible in order to provide adequate treatment not only for the metabolic disturbances but also for the coexisting psychosomatic disorder.

A mixture of Escherichia coli (DSM 17252) and Enterococcus faecalis (DSM 16440) for treatment of the irritable bowel syndrome--a randomized controlled trial with primary care physicians.

Therapy trials with bacterial compounds in irritable bowel syndrome (IBS) have produced conflicting results. This study was performed in 1988 and 1989, and was re-analysed according to current IBS standards. Two hundred ninety-seven patients with lower abdominal symptoms diagnosed as IBS were treated for 8 weeks by the compound ProSymbioflor((R)) (Symbiopharm GmbH, Herborn, Germany), an autolysate of cells and cell fragments of Enterococcus faecalis and Escherichia coli, or placebo in a double-blinded, randomized fashion. Patients were seen weekly by the physician, who assessed the presence of core IBS symptoms. Responders had at least a 50% decrease in global symptom score (GSS) and in abdominal pain score (APS) reports at >/=1 visit during treatment. The responder rate in GSS to the drug was 102/149 (68.5%) in comparison to placebo with 56/148 (37.8%) (P < 0.001), the improvement in APS was 108/149 (72.5%) and 66/148 (44.6%) respectively (P = 0.001). The number-needed-to-treat was 3.27 for GSS and 3.59 for the APS report. Kaplan-Meier analysis revealed a mean response time of 4-5 weeks for active treatment and more than 8 weeks for placebo (P < 0.0001). Treatment of IBS with the bacterial lysate ProSymbioflor is effective and superior to placebo in reducing typical symptoms of IBS patients seen by general practitioners.

[The next consensus for the irritable bowel syndrome has to be interdisciplinary]. / Der nächste Konsensus zum Reizdarmsyndrom muss interdisziplinär sein.

The publication of the Rome III consensus on functional bowel disorders one year ago has raised the question of whether a revision of the 1999 Celle consensus on the irritable bowel syndrome is necessary and who should be involved in this consensus. Therefore, the this review article attempts to reconstruct the history of the Rome criteria (and its predecessor, the Manning criteria) and contrasts this with the parallel history of the DSM/ICD classification in primary care and psychiatry/psychosomatics. The formulation of a common consensus between all medical societies (primary care, gastroenterology/neurogastroenterology, psychiatry/psychosomatics) is proposed instead of another consensus of gastroenterologists alone, in order to avoid the tendency--at both national and international levels--towards isolation between the medical subspecialties.

[Digestive and predigestive functions in patients with eating disorders]. / Digestive und prädigestive Funktionen bei Patienten mit Essstörungen.

Patients with eating disorders (anorexia nervosa, AN; bulimia nervosa, BN) frequently exhibit gastrointestinal symptoms and altered gastrointestinal functions, especially delayed gastric emptying. These symptoms are regarded as secondary to the disordered eating behaviour, vomiting or laxative misuse. They often improve during successful therapy. There are, however, studies showing that in addition predigestive functions (smell, taste, cephalic phase of digestion) and the hormonal regulation of digestion may be changed in eating disorders. This underlines the possibility that, in a subpopulation of patients with AN and BN, the disturbed digestive and predigestive functions may be involved in the pathogenesis of the eating disorders. The current literature is analysed and summarised in this context.