Analysis of the intra- and intertumoral heterogeneity of hypoxia in pancreatic cancer patients receiving the nitroimidazole tracer pimonidazole.

BACKGROUND: Hypoxia is thought to be an adverse feature of pancreatic cancer, but direct measurement in patients is technically challenging. To address this, we characterised the intra/interpatient heterogeneity of hypoxia in surgical specimens from patients who received the 2-nitroimidazole tracer pimonidazole pre-operatively. METHODS: Pimondazole was given intravenously 16-20 h before pancreatectomy, and the extent and intratumoral heterogeneity of hypoxia determined by image analysis applied to multiple tissue blocks stained by immunohistochemistry. Intra/interpatient heterogeneity was estimated by variance component analysis. RESULTS: Pimonidazole staining was analysed in 10 tumours. The extent of labelling varied amongst patients (0-26%), with a broader range of hypoxia in the epithelial (1-39%) compared with the stromal (1-13%) compartments. Variance component analysis demonstrated greater inter- than intrapatient variability of hypoxia, and that multiple (4-5) tumour sections are required to provide a consistent evaluation of its extent in individual tumours. CONCLUSIONS: There is significant intra- and intertumoral heterogeneity of hypoxia in pancreatic cancers, and these do not appear to be generally more hypoxic than other cancer types. This study establishes the feasibility to assess hypoxia in pancreatic cancer patients using pimonidazole, but questions the reliability of measurements made using a single tissue section.

[Sudden cardiac death in a case of systemic sarcoidosis]. / Plötzlicher Herztod bei systemischer Sarkoidose.

CLINICAL PRESENTATION: A 55-year-old woman required emergency medical care because of sudden weakness. On arrival of the emergency physician the patient presented with bradycardia with a normal rhythm. The blood pressure was not measurable. The patient complained of recurrent dizziness for a few months. Subsequently, the patient presented with an asystole and required reanimation and insertion of a temporary cardiac pacemaker. On admission at the hospital myocardial infarction was suspected. CLINICAL AND LABORATORY TESTS: At the time of admission the patient presented in cardiogenic shock. The ECG revealed a 3rd atrioventricular block with idioventricular rhythm. Echocardiography showed reduced left ventricular function with global hypokinesia of the myocardium. Coronary artery disease was excluded by angiography. To exclude acute pulmonary embolism a CT-scan of the thorax was performed, revealing enlarged lymph nodes in the mediastinum. TREATMENT AND RESPONSE TO THERAPY: Despite the administration of high-dose catecholamines and before a left atrial-to-femoral arterial assist device could be completely implanted the patient died of cardiogenic shock. AUTOPSY: Autopsy revealed non-caseating epitheloid granulomas in the enlarged mediastinal lymph nodes as well as in the lung parenchyma, myocardium and several other organs. CONCLUSION: The cardiac involvement of previously undiagnosed systemic sarcoidosis was the cause of sudden death. In case of ECG changes of unknown cause in persons without a history of structural cardiac disease sarcoidosis should be considered in the differential diagnosis.