Spontaneous duodenal wall hematoma.

59-year-old man, smoker, diabetic and hypertensive. He went to the ER due to fixed abdominal pain in the epigastrium, diaphoresis, dizziness, nausea, and "coffee grounds" vomiting. On examination he presented abdominal distension and pain on palpation in the epigastrium, without peritonism. He had a BP of 235/100 mmHg and in the blood-tests, leukocytosis with neutrophilia and normal hemoglobin. An urgent abdominal CT scan was performed, identifying a 5x6 cm nodular lesion of homogeneous density attached to the wall of the second and third duodenal portions that compressed the lumen, with two vessels with active bleeding within it. Therefore, percutaneous embolization of the gastroduodenal artery was performed. Subsequently, the patient suffered an episode of severe acute pancreatitis that required ICU admission. Finally, he presented a good clinical evolution with ceasing of pain, complete reabsorption of the hematoma and resolution of the obstructive symptoms.

Applied diagnostics in liver cancer. Efficient combinations of sorafenib with targeted inhibitors blocking AKT/mTOR.

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. There is increasing interest in developing specific markers to serve as predictors of response to sorafenib and to guide targeted therapy. Using a sequencing platform designed to study somatic mutations in a selection of 112 genes (HepatoExome), we aimed to characterize lesions from HCC patients and cell lines, and to use the data to study the biological and mechanistic effects of case-specific targeted therapies used alone or in combination with sorafenib. We characterized 331 HCC cases in silico and 32 paired samples obtained prospectively from primary tumors of HCC patients. Each case was analyzed in a time compatible with the requirements of the clinic (within 15 days). In 53% of the discovery cohort cases, we detected unique mutational signatures, with up to 34% of them carrying mutated genes with the potential to guide therapy. In a panel of HCC cell lines, each characterized by a specific mutational signature, sorafenib elicited heterogeneous mechanistic and biological responses, whereas targeted therapy provoked the robust inhibition of cell proliferation and DNA synthesis along with the blockage of AKT/mTOR signaling. The combination of sorafenib with targeted therapies exhibited synergistic anti-HCC biological activity concomitantly with highly effective inhibition of MAPK and AKT/mTOR signaling. Thus, somatic mutations may lead to identify case-specific mechanisms of disease in HCC lesions arising from multiple etiologies. Moreover, targeted therapies guided by molecular characterization, used alone or in combination with sorafenib, can effectively block important HCC disease mechanisms.