[Thrombus in all four heart chambers in a 67-year-old female patient with pulmonary artery embolism and open foramen ovale]. / Thrombus in allen vier Herzkammern bei einer 67-jährigen Patientin mit Lungenarterienembolie und offenem Foramen ovale.

A 67-year-old woman presented to the emergency department due to acute dyspnea. Computed tomography of the chest showed a pronounced bilateral pulmonary artery embolism. Echocardiography demonstrated a large floating thrombus in the right atrium and right ventricle, which extended through a persistent foramen ovale via the left atrium into the left ventricle. A thrombectomy was later successfully performed.

Acute ingestion of a high-fructose drink impairs vascular autonomic modulation and reflex control of blood pressure in first-degree relatives of diabetic patients.

First-degree relatives of diabetes patients, despite being euglycemic, presented impaired BRS and exacerbation of sympathetic modulation after ingestion of a high fructose drink when challenged to orthostatic stress. This finding alerts the importance of early autonomic dysfunction even in clinically healthy people, especially in face of a stressful situation.

[Right upper abdominal pain, vomiting, weight loss and icterus in a 20-year-old male refugee]. / Rechtsseitiger Oberbauchschmerz, Erbrechen, Gewichtsverlust und Ikterus bei einem 20-jährigen Flüchtling.

Tuberculosis (TB) is one of the most common infectious diseases worldwide. The case of a 20-year old male refugee from Somalia, who initially presented with right-sided upper abdominal pain, vomiting, weight loss and jaundice with suspected cholecystitis is reported. In the course of further diagnostics, pyloric stenosis surprisingly appeared, which, like the cholestasis, was caused by compressing peripancreatic lymph nodes. Lymph node cytology finally showed evidence of caseating necrosis with evidence of TB pathogens.

Biomarkers Apo10 and TKTL1: Epitope-detection in monocytes (EDIM) as a new diagnostic approach for cholangiocellular, pancreatic and colorectal carcinoma.

OBJECTIVE: The EDIM (Epitope detection in monocytes) blood test is based on two biomarkers Apo10 and TKTL1. Apo10 is responsible for cell proliferation and resistance to apoptosis. TKTL1 plays a major role in anaerobic glycolysis of tumor cells, leading to destruction of the basal membrane and metastasis as well as in controlling cell cycle. For the first time we analyzed Apo10 and TKLT1 in patients with cholangiocellular (CCC), pancreatic (PC), and colorectal carcinoma (CRC). METHODS: Blood samples of 62 patients with CCC, PC, and CRC were measured and compared to 29 control patients. We also investigated 13 patients with inflammatory conditions, because elevated TKTL1 and Apo10 have been previously described in affected individuals. Flow cytometry was used to detect surface antigens CD14+/CD16+ (activated monocytes/macrophages). Percentages of macrophages harboring TKTL1 and Apo10 were determined. A combined EDIM score (EDIM-CS: TKTL1 plus Apo10) was calculated. Results were correlated with serum tumor markers CEA and CA19-9. RESULTS: Patients with CCC had 100% positive EDIM-CS but CEA and CA19-9 were positive in only 22.2% and 70%, respectively. Patients with PC had 100% positive EDIM-CS but positive tumor markers in only 37.5% (CEA) and 72.7% (CA19-9). Patients with CRC had 100% positive EDIM-CS but only 50% positive CEA. EDIM-CS was positive in 100% (62/62) of all cancer patients and in 0% of healthy individuals. Of the individuals with inflammation, 7.7% had a positive EDIM-CS. CONCLUSION: The sensitivity of the EDIM blood test and the comparison with traditional tumor markers indicate that this new test might improve the detection of carcinomas (CCC, PC and, CRC) and might be relevant for the diagnosis of all tumor entities.

Comparison of the effects of 1MHz and 3MHz therapeutic ultrasound on endothelium-dependent vasodilation of humans: a randomised clinical trial.

OBJECTIVE: To compare the effects of different waveforms of 1MHz and 3MHz therapeutic ultrasound on endothelial function in healthy subjects. DESIGN: Randomised placebo-controlled, crossover study with concealed allocation and assessor blinding. SETTING: Imaging Centre of the University Hospital. PARTICIPANTS: Thirty volunteers aged between 18 and 35 years were divided into two homogeneous groups (1MHz and 3MHz). INTERVENTIONS: Continuous (CUT; 0.4W/cm2SATA), pulsed (PUT; 20% duty cycle, 0.08W/cm2SATA) and placebo waveforms (equipment off) of ultrasound (1MHz and 3MHz) were randomized and applied over the brachial artery for 5minutes. MAIN OUTCOME MEASURES: Endothelial function was evaluated using the flow-mediated dilation (FMD) technique. RESULTS: Both 1MHz [CUT: mean difference 4%, 95% confidence interval (CI) 2 to 6%, P<0.001; PUT: mean difference 4%, 95% CI 2 to 6%, P<0.001] and 3MHz (CUT: mean difference 4%, 95% CI 2 to 6%, P<0.001; PUT: mean difference 4%, 95% CI 2 to 6%, P<0.001) of therapeutic ultrasound increased %FMD by approximately 4% compared with the placebo waveforms. The endothelium-dependent vasodilator responses were the same for both types of waves and frequencies. No differences in baseline diameter, hyperaemic flow, and nitroglycerin-mediated diameter and vasodilation were observed between groups. CONCLUSION: Both CUT and PUT ultrasound waveforms improved endothelial function. The 1MHz and 3MHz frequencies of therapeutic ultrasound led to similar improvement in endothelial function in healthy volunteers. Clinical trial registration number RBR-4z5z3t.

AFP-producing adenocarcinoma of the esophagogastric junction: report of a case with atypical immunohistochemical findings responding to palliative chemotherapy with 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT regime).

AFP-producing adenocarcinoma of the esophagus and esophagogastric junction are rare tumor diseases. These tumors show an aggressive behavior characterized by early occurrence of liver metastases and mimic hepatocellular carcinoma (HCC). A general recommendation for palliative therapy is not established for these special tumors.Here we report about a 61-year-old man with multiple liver metastases and high serum alpha-fetoprotein (AFP) level. First, HCC was suspected, but further evaluation showed an AFP-producing adenocarcinoma of the esophagogastric junction with unusual findings on further immunohistochemical analysis. Palliative chemotherapy with FLOT (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel) regime showed a 9 month duration of partial response.

Recurrent pyogenic cholangitis as a differential diagnosis in biliary tract diseases.

Recurrent Pyogenic Cholangitis (RPC) or Primary Hepatolithiasis is a common disease of the biliary tract in Asia, whereas it is usually not seen in Europeans. With increasing global mobility, the disease will be encountered in Europe more frequently, too. It should therefore be considered as a differential diagnosis in patients from endemic countries with recurrent symptoms of cholestasis/cholangitis and bile duct dilations, strictures and hepatolithiasis. In this case report, we present the history of a 37-year old patient from Sri Lanka and describe typical aspects of RPC. The patient presented at our hospital with scleral jaundice and pruritus. In the past she had been treated for septic cholangitis. Diagnosis in our patient was made after laboratory tests, MRT/MRCP and ERC. She was treated interventionally by ERC and is now monitored on a regular basis.

[OTSC-assisted resection of a duodenal neuroendocrine tumor: a case report]. / OTSC-assistierte Resektion eines neuroendokrinen Tumors im Duodenum: Ein Fallbericht.

The over the scope clip (OTSC) is mainly used for closure of gastrointestinal endoluminal defects and treatment of gastrointestinal bleeding. Its use for resection of subepithelial tumors or full-thickness resection is still under investigation. Duodenal neuroendocrine tumors (NET) are rare neoplasms. Endoscopic resection is appropriate up to a size of 20  mm, however positive deep margins are a frequent challenge in these subepithelial tumors. We report on a 60-year-old male patient who had undergone endoscopic mucosal resection with R1 deep margins of a NET (G1) in the duodenal bulb. To avoid local surgical resection in this multimorbid patient, we performed OTSC-assisted deep resection. Complete resection (R0) was achieved, and no complications occurred. Our report suggests that OTSC-assisted resection of subepithelial tumors is a possible and safe option, especially for patient's and in locations with a high perioperative risk.

[Guideline compliant diagnostics of hepatocellular carcinoma]. / Leitliniengerechte Diagnostik des hepatozellulären Karzinoms.

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer death worldwide. The incidence continues to rise and only a detailed surveillance of patients with chronic liver disease can allow an early assessment. Diagnosis is made by imaging techniques, such as contrast-enhanced ultrasound (CEUS), computed tomography (CT), magnetic resonance imaging (MRI) and also histopathological examination of biopsy material. The determination of the tumor marker alpha fetoprotein (AFP) is no longer established for early detection but can be used as a supplement in addition in HCC history progressio.

Effects of different frequencies of transcutaneous electrical nerve stimulation on venous vascular reactivity.

Transcutaneous electrical nerve stimulation (TENS) is a type of therapy used primarily for analgesia, but also presents changes in the cardiovascular system responses; its effects are dependent upon application parameters. Alterations to the cardiovascular system suggest that TENS may modify venous vascular response. The objective of this study was to evaluate the effects of TENS at different frequencies (10 and 100 Hz) on venous vascular reactivity in healthy subjects. Twenty-nine healthy male volunteers were randomized into three groups: placebo (n=10), low-frequency TENS (10 Hz, n=9) and high-frequency TENS (100 Hz, n=10). TENS was applied for 30 min in the nervous plexus trajectory from the superior member (from cervical to dorsal region of the fist) at low (10 Hz/200 µs) and high frequency (100 Hz/200 µs) with its intensity adjusted below the motor threshold and intensified every 5 min, intending to avoid accommodation. Venous vascular reactivity in response to phenylephrine, acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) was assessed by the dorsal hand vein technique. The phenylephrine effective dose to achieve 70% vasoconstriction was reduced 53% (P<0.01) using low-frequency TENS (10 Hz), while in high-frequency stimulation (100 Hz), a 47% increased dose was needed (P<0.01). The endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) responses were not modified by TENS, which modifies venous responsiveness, and increases the low-frequency sensitivity of α1-adrenergic receptors and shows high-frequency opposite effects. These changes represent an important vascular effect caused by TENS with implications for hemodynamics, inflammation and analgesia.

Effects of different frequencies of transcutaneous electrical nerve stimulation on venous vascular reactivity

Transcutaneous electrical nerve stimulation (TENS) is a type of therapy used primarily for analgesia, but also presents changes in the cardiovascular system responses; its effects are dependent upon application parameters. Alterations to the cardiovascular system suggest that TENS may modify venous vascular response. The objective of this study was to evaluate the effects of TENS at different frequencies (10 and 100 Hz) on venous vascular reactivity in healthy subjects. Twenty-nine healthy male volunteers were randomized into three groups: placebo (n=10), low-frequency TENS (10 Hz, n=9) and high-frequency TENS (100 Hz, n=10). TENS was applied for 30 min in the nervous plexus trajectory from the superior member (from cervical to dorsal region of the fist) at low (10 Hz/200 μs) and high frequency (100 Hz/200 μs) with its intensity adjusted below the motor threshold and intensified every 5 min, intending to avoid accommodation. Venous vascular reactivity in response to phenylephrine, acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) was assessed by the dorsal hand vein technique. The phenylephrine effective dose to achieve 70% vasoconstriction was reduced 53% (P<0.01) using low-frequency TENS (10 Hz), while in high-frequency stimulation (100 Hz), a 47% increased dose was needed (P<0.01). The endothelium-dependent (acetylcholine) and independent (sodium nitroprusside) responses were not modified by TENS, which modifies venous responsiveness, and increases the low-frequency sensitivity of α1-adrenergic receptors and shows high-frequency opposite effects. These changes represent an important vascular effect caused by TENS with implications for hemodynamics, inflammation and analgesia.

FOLFIRINOX as first-line treatment for unresectable acinar cell carcinoma of the pancreas: a case report.

Pancreatic acinar cell carcinoma (ACC) is a rare, aggressive variant of pancreatic ductal adenocarcinoma. Surgery is the only curative treatment option and protocols for palliative chemotherapies in this context are not standardized yet. We reported a 63-year-old white male patient who had painless jaundice, weight loss, elevated bilirubin, and a mass of the pancreatic head as well as liver metastasis. Core biopsy revealed the diagnosis of ACC. Therapy with FOLFIRINOX resulted in a significant decrease of the primary tumor and regressiveness of a liver metastasis after chemotherapy. Our report suggests that pancreatic ACC treated by FOLFIRINOX is well tolerated and might be superior to other single chemotherapies in this rare tumor disease.

Measurement of IgG4 in bile: a new approach for the diagnosis of IgG4-associated cholangiopathy.

BACKGROUND AND STUDY AIMS: Immunoglobulin G4 (IgG4)-associated cholangitis (IAC) is difficult to diagnose because on cholangiography the associated biliary tract strictures cannot be differentiated from cholangiocarcinoma or primary sclerosing cholangitis (PSC). Serum IgG4 levels show a low sensitivity and specificity and are unreliable, particularly in patients with related diseases such as PSC. As IAC takes place at the biliary epithelium, we hypothesized that IgG4 measurement in bile may have higher sensitivity compared with serum. METHODS: Bile and serum samples were collected during cholangiography in 67 patients, including 23 patients with PSC, 25 with cholangiocarcinoma, 14 with choledocholithiasis, and five with IAC. IgG4 was measured in both bile and serum. RESULTS: Bile IgG4 levels were markedly elevated in patients with IAC compared with patients with other biliary disorders. Whereas elevated serum IgG4 levels were found both in patients with PSC and IAC, biliary IgG4 levels were only increased in patients with IAC. CONCLUSIONS: The study demonstrates that bile IgG4 measurement is possible and may help to distinguish IAC from other diseases.

Molecular therapy of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of mortality and morbidity. The 5-year survival rate remains less than 5% and in contrast to other solid tumors, survial has changed only little in the last decade. Overall PDAC treatment shows only limited response to conventional chemotherapeutic agents. Several trials on therapy are ongoing and new targeted agents are in development to improve the treatment outcome of this deadly disease. However, our review presents the current developments of molecular therapies, supports the translational PDAC research and encourage you to take part in further clinical studies.

Microalbuminuria is associated with impaired arterial and venous endothelium-dependent vasodilation in patients with Type 2 diabetes.

BACKGROUND: Microalbuminuria in Type 2 diabetes is associated with arterial endothelial dysfunction, but the venous bed was never evaluated. AIM: To study the endothelial function in the venous and arterial bed in patients with Type 2 diabetes with normoalbuminuria or microalbuminuria. MATERIAL AND METHODS: We evaluated 28 patients with Type 2 diabetes, glycated hemoglobin (HbA(1c)) <7.5%, who were classified as normo- (albuminuria <30 mg/24 h; no.=16) or microalbuminuric (albuminuria 30-300 mg/24 h; no.=12). Venous and arterial endothelial function were assessed by the dorsal hand vein technique (venodilation by acetylcholine) and brachial artery flow-mediated vasodilation, respectively. RESULTS: Patients were normotensive (systolic arterial pressure: 131.1±10.6 mmHg) and on good metabolic control (HbA(1c): 6.6±0.6%). Microalbuminuric patients presented impaired venous (32.9±17.4 vs 59.3±26.5%; p=0.004) and arterial vasodilation (1.8±0.9 vs 5.1±2.4; p<0.001), as compared to normoalbuminuric patients. There was a negative correlation between acetylcholine-induced venodilation and albuminuria (r=-0.62; p<0.001) and HbA(1c) (r=-0.41; p=0.032). The same was observed between flow mediated arterial vasodilation and albuminuria (r=-0.49; p=0.007) and HbA(1c) (r=-0.44; p=0.019). Venous and arterial vasodilation was positively correlated (r=0.50; p=0.007). CONCLUSIONS: Both venous and arterial endothelial function are impaired in Type 2 microalbuminuric diabetics, in spite of good metabolic control, suggesting that other factors are involved in its pathogenesis.

Alterações hematológicas provocadas pelo ultra-som de 1MHz na forma contínua aplicadas no tratamento da fase aguda de lesão muscular iatrogênica em ratos / Hematological changes produced by 1MHz continuous ultrasound, applied during the acute phase of iatrogenic muscle injury in rats

CONTEXTUALIZAÇÃO: A literatura demonstra o efeito benéfico da terapia ultra-sônica de baixa intensidade sobre o processo de cicatrização de vários tecidos. OBJETIVO: Avaliar o efeito do ultra-som contínuo (USC) sobre a dinâmica hematológica do processo inflamatório agudo de lesão muscular iatrogênica. MÉTODOS: Foram utilizados 16 ratos da raça Wistar (350 a 400g), divididos em grupo controle (GC=8) e grupo experimental (G1=8), submetidos à incisão cirúrgica na face lateral do membro posterior direito, onde o músculo bíceps femoral foi lesionado transversalmente. O USC (1MHz) foi aplicado sobre o local da lesão a uma intensidade de 0,4W/cm², durante três minutos, na 1ª, 8ª e 24ª hora após a lesão. Nestes períodos, foram realizadas as coletas de sangue por punção venosa do plexo retroorbital para as análises sangüíneas das séries brancas e vermelhas. RESULTADOS: O USC diminui 8 por cento dos eritrócitos na primeira coleta (9,9±0,1 versus 7,8±0,1; x10(5)/mm³, p<0,001); dobrou os neutrófilos segmentados na segunda coleta (3.166,8±161,4 versus 6.426,2±306,0; x10³/mm³ p=0,008) e os eosinófilos na terceira coleta (2.883,6±99,0 versus 4.714,4±275,2; x10³/mm³ p=0,011) em relação ao GC. Não se observaram diferenças entre os grupos no hematócrito, leucócitos totais, neutrófilos bastonetes, monócitos e linfócitos, nos três momentos estudados. CONCLUSÕES: A aplicação do USC no tratamento agudo de lesão muscular é contra-indicada nesta condição, pois promove a redução dos eritrócitos, aumento dos neutrófilos segmentados e dos eosinófilos, favorecendo a hemorragia e o aumento do processo inflamatório.

BACKGROUND: The literature shows the beneficial effects of low-intensity ultrasound therapy on the healing process of several biological tissues. OBJECTIVE: To evaluate the effects of continuous ultrasound (CUS) on the hematological dynamics of an acute inflammatory process in iatrogenic muscle injuries. METHODS: Sixteen Wistar rats (350 to 400g) were divided into a control group (CG=8) and an experimental group (G1=8). The rats were submitted to a surgical incision on the lateral aspect of the right hind limb, in which the biceps femoris muscle was transversally injured. The CUS (1MHz) was applied to the injury site at an intensity of 0.4W/cm², for three minutes, in 1, 8 and 24 hour after the injury. At these times, blood was drawn by venipuncture of the retroorbital plexus, for analysis of red and white blood cells. RESULTS: The CUS reduced erythrocytes in 8 percent at the first blood collection (9.9±0.1 versus 7.8±0.1; x10(5)/mm³; p<0.001); it doubled the number of segmented neutrophils at the second collection (3,166.8±161.4 versus 6,426.2±306.0; x10³/mm³; p=0.008) and the eosinophils at the third collection (2,883.6±99.0 versus 4,714.4±275.2; x10³/mm³; p=0.011), in relation to the CG. No differences between the groups were seen with regard to hematocrit, total leukocytes, rod neutrophils, monocytes or lymphocytes at the three times studied. CONCLUSIONS: Application of CUS for acute treatment of muscle injuries is contraindicated under this condition, because it promotes reductions in erythrocytes and increases in segmented neutrophils and eosinophils, thus favoring hemorrhage and increasing inflammatory process.