Juergen Bauditz

Thalidomide reduces tumour necrosis factor alpha and interleukin 12 production in patients with chronic active Crohn's disease.

Background: Thalidomide improves clinical symptoms in patients with therapy refractory Crohns disease, as shown in two recent studies. The mechanism of this effect however is still unknown. Suppression of tumour necrosis factor α (TNF-α) by thalidomide has been suggested as a possible mechanism. However, effects on other cytokines have not been adequately investigated. Aim: The aim of our study was to investigate the effects of thalidomide on cytokine production in patients with inflammatory bowel disease (IBD). Methods: Ten patients with therapy refractory IBD (nine Crohns disease, one ulcerative colitis) received thalidomide 300 mg daily in a 12 week open label study. Production of TNF-α, interleukin (IL)-1β, IL-6, and IL-12 was investigated in short term cultures of stimulated colonic lamina propria mononuclear cells (LPMC) and peripheral blood monocytes (PBMC) before and after 12 weeks of treatment. LPMC were also cultured with graded doses of thalidomide. Results: Three patients discontinued treatment because of sedative side effects. In the other patients, disease activity decreased significantly, with four patients achieving remission. Production of TNF-α and IL-12 decreased during treatment with thalidomide: LPMC (TNF-α: 42.3 (8.3) pg/ml v 16.4 (6.3); IL-12: 9.7 (3.3) v 5.0 (2.5); p<0.04) and PBMC (TNF-α: 62.8 (14.6) v 22.5 (9.2); p<0.02). Production of IL-1β and IL-6 did not change significantly. Culturing of LPMC with thalidomide showed a dose dependent decrease in TNF-α and IL-12 production. Conclusion: The clinical effects of thalidomide in Crohns disease may be mediated by reduction of both TNF-α and IL-12.

Thalidomide for treatment of severe intestinal bleeding

Apart from its anti-inflammatory activity, which has been used for the treatment of active Crohn’s disease, thalidomide is also a potent inhibitor of angiogenesis. We therefore studied the effect of thalidomide in six patients with severe recurrent intestinal bleeding refractory to standard treatment (three patients with Crohn’s disease (CD), three patients with obscure intestinal bleeding; mean of 56 blood transfusions within the last 24 months). Bleeding stopped within two weeks after the start of thalidomide in all patients. Haemoglobin normalised without further transfusions for the whole observation period (mean follow up 33 months) while patients needed a mean of 2.2 (CD) and 3.1 (obscure bleeding) blood units/month in the 12 months before treatment. After three months of thalidomide therapy, serum levels of vascular endothelial growth factor were strongly suppressed compared with pretreatment levels. (CD 818 (82) v 129 (86) pg/ml; obscure bleeding 264 (68) v 50 (25) pg/ml). All six patients reported transient fatigue. Peripheral neuropathy was observed in one patient with CD after nine months and was reversible after lowering the dose to 100 mg daily. These results indicate that thalidomide might be useful for patients with otherwise refractory intestinal bleeding.

Intestinal congestion and right ventricular dysfunction: a link with appetite loss, inflammation, and cachexia in chronic heart failure

AIMS Mechanisms leading to cachexia in heart failure (HF) are not fully understood. We evaluated signs of intestinal congestion in patients with chronic HF and their relationship with cachexia. METHODS AND RESULTS Of the 165 prospectively enrolled outpatients with left ventricular ejection fraction ≤40%, 29 (18%) were cachectic. Among echocardiographic parameters, the combination of right ventricular dysfunction and elevated right atrial pressure (RAP) provided the best discrimination between cachectic and non-cachectic patients [area under the curve 0.892, 95% confidence interval (CI): 0.832-0.936]. Cachectic patients, compared with non-cachectic, had higher prevalence of postprandial fullness, appetite loss, and abdominal discomfort. Abdominal ultrasound showed a larger bowel wall thickness (BWT) in the entire colon and terminal ileum in cachectic than in non-cachectic patients. Bowel wall thickness correlated positively with gastrointestinal symptoms, high-sensitivity C-reactive protein, RAP, and truncal fat-free mass, the latter serving as a marker of the fluid content. Logistic regression analysis showed that BWT was associated with cachexia, even after adjusting for cardiac function, inflammation, and stages of HF (odds ratio 1.4, 95% CI: 1.0-1.8; P-value = 0.03). Among the cardiac parameters, only RAP remained significantly associated with cachexia after multivariable adjustment. CONCLUSION Cardiac cachexia was associated with intestinal congestion irrespective of HF stage and cardiac function. Gastrointestinal discomfort, appetite loss, and pro-inflammatory activation provide probable mechanisms, by which intestinal congestion may trigger cardiac cachexia. However, our results are preliminary and larger studies are needed to clarify the intrinsic nature of this relationship.

Severe weight loss caused by chewing gum.

Sorbitol intake should be considered in patients with bowel problems, chronic diarrhoea, and weight loss

Non-alcohol induced steatohepatitis in non-obese patients: Treatment with ursodeoxycholic acid

Non-Alcohol Induced Steatohepatitis in Non-Obese Patients: Treatment With Ursodeoxycholic Acid

Primary Neuroendocrine Carcinoma of Inguinal Lymph Node

Ninety-seven percent of neuroendocrine carcinomas are located in the gastrointestinal tract or in the bronchopulmonary tree. Inguinal lymph nodes as the primary tumor site for neuroendocrine carcinoma represent a very unusual location, and have only been described in 2 patient series in the literature. A 64-year-old, previously healthy, Caucasian female presented with a 2-month history of an enlarged inguinal lymph node on the right side. The removed lymph node showed histological and immunohistochemical characteristics of neuroendocrine differentiation (positive for synaptophysin, cytokeratin 20, neuron-specific enolase and chromogranin A). Although extensive investigations including repeated CT and NMR scans, classical endoscopy, wireless capsule endoscopy of the small intestine, octreotide- and MIBG scintigraphy were performed, no other primary tumor was found. Furthermore, there was no evidence of Merkel cell carcinoma on dermatological examinations. A possible explanation for the presence of neuroendocrine carcinomas within the lymph nodes is malignant transformation of preexisting intranodal epithelial nests, which have previously been described in lymph nodes located close to the salivary glands, thyroid gland, breast tissue and pancreas. Since the surgical removal of the affected lymph node, the patient has now been disease-free for 42 months. We therefore consider our case to represent a primary undifferentiated neuroendocrine carcinoma in an inguinal lymph node.

Effective treatment of gastrointestinal bleeding with thalidomide - Chances and limitations

For more than 50 years bleeding from gastrointestinal angiodysplasias has been treated by hormonal therapy with estrogens and progesterons. After a randomized study finally demonstrated that hormones have no effect on bleeding events and transfusion requirements, therapy has switched to endoscopic coagulation. However, angiodysplasias tend to recur over months to years and endoscopy often has to be repeated for long time periods. Thalidomide, which caused severe deformities in newborn children in the 1960s, is now increasingly used after it was shown to suppress tumor necrosis factor alpha, inhibit angiogenesis and to be also effective for treatment of multiple myeloma. In 2011 thalidomide was proven to be highly effective for treatment of bleeding from gastrointestinal angiodysplasias in a randomized study. Further evidence by uncontrolled studies exists that thalidomide is also useful for treatment of bleeding in hereditary hemorrhagic telangiectasia. In spite of this data, endoscopic therapy remains the treatment of choice in many hospitals, as thalidomide is still notorious for its teratogenicity. However, patients with gastrointestinal bleeding related to angiodysplasias are generally at an age in which women have no child-bearing potential. Teratogenicity is therefore no issue for these elderly patients. Other side-effects of thalidomide like neurotoxicity may limit treatment options but can be monitored safely.

[Long-term follow-up of patients with suprasellar germinomas].

ZusammenfassungHintergrund:Supraselläre Germinome sind seltene Keimzelltumoren, die hauptsächlich bei Kindern und Jugendlichen auftreten und sich typischerweise mit endokrinen Störungen und/oder Kompressionserscheinungen manifestieren.Patienten und Methodik:Bei sieben Patienten (sechs männlich, einer weiblich) wurden die zur Diagnose führenden klinischen und hormonellen Befunde sowie der Langzeitverlauf nach Operation bzw. Radio-/Chemotherapie untersucht.Ergebnisse:Das mittlere Alter bei Diagnose betrug 19,7 Jahre (Bereich 15–32 Jahre). Als Erstsymptome zeigten sich ein Diabetes insipidus (drei Patienten), ein Libidoverlust (zwei Patienten), eine Pseudopubertas praecox (ein Patient) und ein Wachstumsstopp (ein Patient). Die zur Diagnose führenden Symptome waren hingegen Sehstörungen (fünf Patienten), Pseudopubertas tarda (ein Patient) und Hypogonadismus (ein Patient). Alle Patienten erhielten eine transkranielle Bestrahlung mit 40–54 Gy, in einem Fall wurde eine Radiochemotherapie mit Cisplatin, Etoposid und Ifosfamid (PEI) durchgeführt. Die Patienten wurden im Mittel über 14,6 Jahre (7–27 Jahre) nachbeobachtet. Bei zwei Patienten traten Rezidive auf (intrakranial bzw. pulmonal). Nach Therapie bestanden bei allen Patienten ein Panhypopituitarismus und ein Diabetes insipidus. Bei zwei Patienten kam es zur Erblindung, bei zwei weiteren zu einer einseitigen Amaurosis. Bei einem weiteren Patienten traten eine fokale Epilepsie und eine persistierende kognitive Funktionseinschränkung auf. Eine soziale Integration mit Ausübung einer beruflichen Tätigkeit gelang in einem Fall. Im weiteren Verlauf verstarben zwei Patienten an einem Rezidiv bzw. an einer dekompensierten Leberzirrhose bei starker Leberverfettung.Schlussfolgerung:Supraselläre Germinome verursachen frühzeitig endokrine Symptome, jedoch führen meist erst die in späteren Tumorstadien entstehenden Sehstörungen zur Diagnosestellung. Auch bei erfolgreicher Therapie ist der Langzeitverlauf durch einen substitutionspflichtigen Panhypopituitarismus, Diabetes insipidus und teilweise durch okuläre bzw. zerebrale Defekte gekennzeichnet.AbstractBackground:Suprasellar germinomas are rare intracranial neoplasms, which mainly occur in children and adolescents and manifest with endocrine symptoms and/or compression syndromes.Patients and Methods:The clinical, hormonal and morphological findings as well as treatment and complications were investigated in seven patients (six male, one female) with germinomas.Results:Mean age at diagnosis was 19.7 years (range 15–32 years). First disease-related symptoms were diabetes insipidus (three patients), loss of libido (two patients), pseudopubertas praecox (one patient), and dwarfism (one patient). However, decisive symptoms leading to final diagnosis were visual disturbances (five patients), pubertas tarda (one patient), and hypogonadism (one patient). All patients were treated by transcranial radiation with a dose of 40–54 Gy. One patient received additional chemotherapy with cisplatin, etoposide, and ifosfamide (PEI). Patients were followed up for 14.6 years (range 7–27 years). Intracranial and pulmonary relapses were observed in two patients. Panhypopituitarism and diabetes insipidus were seen in all patients after treatment. Two patients suffered from loss of vision, two further patients from unilateral amaurosis. One patient developed epilepsy and persistent cognitive impairment. Long-term follow-up shows that two patients died from recurrent disease and decompensated liver cirrhosis, respectively. The other patients are long-term survivors. Full social integration with employment was possible in one case.Conclusion:Suprasellar germinomas cause endocrine symptoms during early tumor stages, however, diagnosis is generally established when ocular symptoms related to tumor compression are already present. Long-term survival is characterized by panhypopituitarism, diabetes insipidus and, partly, ocular or cerebral defects.

Langzeitverlauf bei Patienten mit suprasellären Germinomen

ZusammenfassungHintergrund:Supraselläre Germinome sind seltene Keimzelltumoren, die hauptsächlich bei Kindern und Jugendlichen auftreten und sich typischerweise mit endokrinen Störungen und/oder Kompressionserscheinungen manifestieren.Patienten und Methodik:Bei sieben Patienten (sechs männlich, einer weiblich) wurden die zur Diagnose führenden klinischen und hormonellen Befunde sowie der Langzeitverlauf nach Operation bzw. Radio-/Chemotherapie untersucht.Ergebnisse:Das mittlere Alter bei Diagnose betrug 19,7 Jahre (Bereich 15–32 Jahre). Als Erstsymptome zeigten sich ein Diabetes insipidus (drei Patienten), ein Libidoverlust (zwei Patienten), eine Pseudopubertas praecox (ein Patient) und ein Wachstumsstopp (ein Patient). Die zur Diagnose führenden Symptome waren hingegen Sehstörungen (fünf Patienten), Pseudopubertas tarda (ein Patient) und Hypogonadismus (ein Patient). Alle Patienten erhielten eine transkranielle Bestrahlung mit 40–54 Gy, in einem Fall wurde eine Radiochemotherapie mit Cisplatin, Etoposid und Ifosfamid (PEI) durchgeführt. Die Patienten wurden im Mittel über 14,6 Jahre (7–27 Jahre) nachbeobachtet. Bei zwei Patienten traten Rezidive auf (intrakranial bzw. pulmonal). Nach Therapie bestanden bei allen Patienten ein Panhypopituitarismus und ein Diabetes insipidus. Bei zwei Patienten kam es zur Erblindung, bei zwei weiteren zu einer einseitigen Amaurosis. Bei einem weiteren Patienten traten eine fokale Epilepsie und eine persistierende kognitive Funktionseinschränkung auf. Eine soziale Integration mit Ausübung einer beruflichen Tätigkeit gelang in einem Fall. Im weiteren Verlauf verstarben zwei Patienten an einem Rezidiv bzw. an einer dekompensierten Leberzirrhose bei starker Leberverfettung.Schlussfolgerung:Supraselläre Germinome verursachen frühzeitig endokrine Symptome, jedoch führen meist erst die in späteren Tumorstadien entstehenden Sehstörungen zur Diagnosestellung. Auch bei erfolgreicher Therapie ist der Langzeitverlauf durch einen substitutionspflichtigen Panhypopituitarismus, Diabetes insipidus und teilweise durch okuläre bzw. zerebrale Defekte gekennzeichnet.AbstractBackground:Suprasellar germinomas are rare intracranial neoplasms, which mainly occur in children and adolescents and manifest with endocrine symptoms and/or compression syndromes.Patients and Methods:The clinical, hormonal and morphological findings as well as treatment and complications were investigated in seven patients (six male, one female) with germinomas.Results:Mean age at diagnosis was 19.7 years (range 15–32 years). First disease-related symptoms were diabetes insipidus (three patients), loss of libido (two patients), pseudopubertas praecox (one patient), and dwarfism (one patient). However, decisive symptoms leading to final diagnosis were visual disturbances (five patients), pubertas tarda (one patient), and hypogonadism (one patient). All patients were treated by transcranial radiation with a dose of 40–54 Gy. One patient received additional chemotherapy with cisplatin, etoposide, and ifosfamide (PEI). Patients were followed up for 14.6 years (range 7–27 years). Intracranial and pulmonary relapses were observed in two patients. Panhypopituitarism and diabetes insipidus were seen in all patients after treatment. Two patients suffered from loss of vision, two further patients from unilateral amaurosis. One patient developed epilepsy and persistent cognitive impairment. Long-term follow-up shows that two patients died from recurrent disease and decompensated liver cirrhosis, respectively. The other patients are long-term survivors. Full social integration with employment was possible in one case.Conclusion:Suprasellar germinomas cause endocrine symptoms during early tumor stages, however, diagnosis is generally established when ocular symptoms related to tumor compression are already present. Long-term survival is characterized by panhypopituitarism, diabetes insipidus and, partly, ocular or cerebral defects.

Langzeitverlauf bei Patienten mit suprasellären Germinomen@@@Long-Term Follow-Up of Patients with Suprasellar Germinomas

ZusammenfassungHintergrund:Supraselläre Germinome sind seltene Keimzelltumoren, die hauptsächlich bei Kindern und Jugendlichen auftreten und sich typischerweise mit endokrinen Störungen und/oder Kompressionserscheinungen manifestieren.Patienten und Methodik:Bei sieben Patienten (sechs männlich, einer weiblich) wurden die zur Diagnose führenden klinischen und hormonellen Befunde sowie der Langzeitverlauf nach Operation bzw. Radio-/Chemotherapie untersucht.Ergebnisse:Das mittlere Alter bei Diagnose betrug 19,7 Jahre (Bereich 15–32 Jahre). Als Erstsymptome zeigten sich ein Diabetes insipidus (drei Patienten), ein Libidoverlust (zwei Patienten), eine Pseudopubertas praecox (ein Patient) und ein Wachstumsstopp (ein Patient). Die zur Diagnose führenden Symptome waren hingegen Sehstörungen (fünf Patienten), Pseudopubertas tarda (ein Patient) und Hypogonadismus (ein Patient). Alle Patienten erhielten eine transkranielle Bestrahlung mit 40–54 Gy, in einem Fall wurde eine Radiochemotherapie mit Cisplatin, Etoposid und Ifosfamid (PEI) durchgeführt. Die Patienten wurden im Mittel über 14,6 Jahre (7–27 Jahre) nachbeobachtet. Bei zwei Patienten traten Rezidive auf (intrakranial bzw. pulmonal). Nach Therapie bestanden bei allen Patienten ein Panhypopituitarismus und ein Diabetes insipidus. Bei zwei Patienten kam es zur Erblindung, bei zwei weiteren zu einer einseitigen Amaurosis. Bei einem weiteren Patienten traten eine fokale Epilepsie und eine persistierende kognitive Funktionseinschränkung auf. Eine soziale Integration mit Ausübung einer beruflichen Tätigkeit gelang in einem Fall. Im weiteren Verlauf verstarben zwei Patienten an einem Rezidiv bzw. an einer dekompensierten Leberzirrhose bei starker Leberverfettung.Schlussfolgerung:Supraselläre Germinome verursachen frühzeitig endokrine Symptome, jedoch führen meist erst die in späteren Tumorstadien entstehenden Sehstörungen zur Diagnosestellung. Auch bei erfolgreicher Therapie ist der Langzeitverlauf durch einen substitutionspflichtigen Panhypopituitarismus, Diabetes insipidus und teilweise durch okuläre bzw. zerebrale Defekte gekennzeichnet.AbstractBackground:Suprasellar germinomas are rare intracranial neoplasms, which mainly occur in children and adolescents and manifest with endocrine symptoms and/or compression syndromes.Patients and Methods:The clinical, hormonal and morphological findings as well as treatment and complications were investigated in seven patients (six male, one female) with germinomas.Results:Mean age at diagnosis was 19.7 years (range 15–32 years). First disease-related symptoms were diabetes insipidus (three patients), loss of libido (two patients), pseudopubertas praecox (one patient), and dwarfism (one patient). However, decisive symptoms leading to final diagnosis were visual disturbances (five patients), pubertas tarda (one patient), and hypogonadism (one patient). All patients were treated by transcranial radiation with a dose of 40–54 Gy. One patient received additional chemotherapy with cisplatin, etoposide, and ifosfamide (PEI). Patients were followed up for 14.6 years (range 7–27 years). Intracranial and pulmonary relapses were observed in two patients. Panhypopituitarism and diabetes insipidus were seen in all patients after treatment. Two patients suffered from loss of vision, two further patients from unilateral amaurosis. One patient developed epilepsy and persistent cognitive impairment. Long-term follow-up shows that two patients died from recurrent disease and decompensated liver cirrhosis, respectively. The other patients are long-term survivors. Full social integration with employment was possible in one case.Conclusion:Suprasellar germinomas cause endocrine symptoms during early tumor stages, however, diagnosis is generally established when ocular symptoms related to tumor compression are already present. Long-term survival is characterized by panhypopituitarism, diabetes insipidus and, partly, ocular or cerebral defects.