Tauroursodeoxycholic acid reduces endoplasmic reticulum stress, trypsin activation, and acinar cell apoptosis while increasing secretion in rat pancreatic acini.

Endoplasmic reticulum (ER) stress leads to accumulation of un- or misfolded proteins inside the ER and initiates the unfolded protein response (UPR). Several UPR components are physiologically involved in pancreatic development and are pathophysiologically activated during acute pancreatitis. However, the exact role of ER stress in exocrine pancreatic acini is mainly unclear. The present study examined the effects of tauroursodeoxycholic acid (TUDCA), a known ER chaperone, on acinar function and UPR components. Isolated rat pancreatic acini were stimulated by increasing concentrations of cholecystokinin (CCK-8) with or without preincubation of TUDCA. UPR components were analyzed, including chaperone binding protein (BiP), protein kinase-like ER kinase (PERK), X-box binding protein (XBP)-1, c-Jun NH(2)-terminal kinase (JNK), CCAAT/enhancer binding protein homologues protein (CHOP), caspase 3 activation, and apoptosis. In addition, TUDCA effects were measured on amylase secretion, calcium signaling, trypsin, and cathepsin B activation. TUDCA preincubation led to a significant increase in amylase secretion after CCK-8 stimulation, a 50% reduction of intracellular trypsin activation, and reduced cathepsin B activity, although the effects for cathepsin B were not statistical significant. Furthermore, TUDCA prevented the CCK-8-induced BiP upregulation, diminished PERK and JNK phosphorylation, and prohibited the expression of CHOP, caspase 3 activation and apoptosis. XBP-1 splicing was not altered. ER stress response mechanisms are activated in pancreatic inflammation. Chemical chaperones enhance enzyme secretion of pancreatic acini, reduce ER stress responses, and attenuate ER stress-associated apoptosis. These data hint new perspectives for an employment of chemical chaperones in the therapy of acute pancreatitis.

Oesophageal ulceration after selective internal radiation therapy in a patient with carcinoma of unknown primary.

BACKGROUND: Cancer of unknown primary (CUP) is defined as histologically confirmed metastases in the absence of an identifiable primary tumor. Patients with solely liver metastases from adenocarinomas represent the most frequent subgroup with an unfavourable prognosis. The medium survival averages 6 to 9 months. No chemotherapheutic standard has been established. CASE: We present a patient with hepatic CUP. After cycles of chemotherapy and hemihepatectomy the tumor returned and showed hepatic progression. The patient was evaluated for selective internal radiation therapy (SIRT). Three years after diagnosis she is still alive and tumorfree. Despite a good result and disease control our patient suffered radiation-induced ulceration in the oesophagus, stomach, and duodenum. This side effect appears in up to 12 % of patients, often very late after treatment, is refractory to pharmacotherapy and persistent over a long time. CONCLUSIONS: SIRT is a new, effective treatment in patients with hepatic CUP. Because of the anticipated increase of this therapy, adverse side effects such as ulcerations in the upper-GI tract secondary to ectopic implantation of microspheres may be seen more commonly. Awareness of this and the recognition of microspheres in biopsies is cardinal for appropriate management and maintenance of the patient's quality of life.

Radiofrequency ablation after selective internal radiation therapy with Yttrium90 microspheres in metastatic liver disease-Is it feasible?

This retrospective study analyzes, whether patients suffering from extensive hepatic metastatic disease treated with SIRT can become suitable candidates for RFA.Within 38 months 46 patients (26 female, 20 male; age 32-75 years) bearing an extensive hepatic metastatic disease were treated with SIRT. Patients suffered from metastases of breast cancer (16/46), colorectal cancer (CRC) (21/46), neuroendocrine (3/46), and other primary carcinomas (6/46). The indication for SIRT was otherwise untreatable metastases confined to the liver. Forty-three patients received single-session whole-liver radioembolization treatment using Yttrium90 resin microspheres with a mean activity of 2.13GBq. In 1 patient SIRT was confined to the left and in 2 patients to the right liver lobe. In 3 patients major complications (2/3 gastric ulceration and 1/3 oedematous pancreatitis) and in 24 patients minor complications occurred (acute abdominal/epigastric pain and/or nausea). Follow-up CT and/or MRI were obtained in 44 of 46 patients. In 5 of 44 patients tumor load decreased substantially (3/5 breast cancer, 1/5 CRC and 1/5 pancreatic cancer) making RFA feasible. The patients were referred for RFA after the first 3-month follow-up. RFA of the liver was successful in all cases in terms of complete ablation. In selected patients radioembolization is able to downstage liver metastases to an extent making a subsequent RFA suitable and therefore allows increasing the number of patients with a "complete response" after a minimally invasive therapy.

[Incidentaloma of the pancreas]. / Inzidentalome des Pankreas.

The term incidentaloma refers to an asymptomatic mass detected accidentally during a technical examination, mostly by radiological methods, when performed in a patient examined for other conditions or situations. Surgery is the adequate therapy for adrenal incidentalomas with increasing size, a size bigger than 4 cm at detection, hormone-activity or malignant histology. Incidentalomas of the adrenal and thyroid gland are still often dismissed because they are common and mostly benign. Incidentalomas of the pancreas are distinct and less frequent. At present, no evidence-based guidelines exist for the management of asymptomatic pancreatic lesions. Only few clinical studies describe pancreatic incidentalomas, however these studies claim a malignant histology of up to 30 % and of up to 50 % for pre-malignant incidentalomas of the pancreas. Thus, we recommend an early resection of pancreatic incidentalomas with a size of > 2 cm, in younger patients without concomitant diseases or increased operative risk, with a malignant histology, and with mucinous cells and increased tumour markers in blood samples. Organ-saving procedures or radical pancreatectomy are possible while both methods are safe and have a very low complication risk. The surgical resection of pancreatic incidentalomas offers a significant advantage in survival when the total collective of affected individuals is taken into account.