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.

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.

[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.

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.

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.

Hemodialysis improves endothelial venous function in end-stage renal disease

The objective of the present study was to determine the acute effect of hemodialysis on endothelial venous function and oxidative stress. We studied 9 patients with end-stage renal disease (ESRD), 36.8 ± 3.0 years old, arterial pressure 133.8 ± 6.8/80.0 ± 5.0 mmHg, time on dialysis 55.0 ± 16.6 months, immediately before and after a hemodialysis session, and 10 healthy controls matched for age and gender. Endothelial function was assessed by the dorsal hand vein technique using graded local infusion of acetylcholine (endothelium-dependent venodilation, EDV) and sodium nitroprusside (endothelium-independent venodilation). Oxidative stress was evaluated by measuring protein oxidative damage (carbonyls) and antioxidant defense (total radical trapping antioxidant potential - TRAP) in blood samples. All patients were receiving recombinant human erythropoietin for at least 3 months and were not taking nitrates or a-receptor antagonists. EDV was significantly lower in ESRD patients before hemodialysis (65.6 ± 10.5) vs controls (109.6 ± 10.8; P = 0.010) and after hemodialysis (106.6 ± 15.7; P = 0.045). Endothelium-independent venodilation was similar in all comparisons performed. The hemodialysis session significantly decreased TRAP (402.0 ± 53.5 vs 157.1 ± 28.3 U Trolox/µL plasma; P = 0.001). There was no difference in protein damage comparing ESRD patients before and after hemodialysis. The magnitude of change in the EDV was correlated negatively with the magnitude of change in TRAP (r = -0.70; P = 0.037). These results suggest that a hemodialysis session improves endothelial venous function, in association with an antioxidant effect.

Telomere shortening of epithelial cells characterises the adenoma-carcinoma transition of human colorectal cancer.

BACKGROUND: and aims: Chromosomal instability is one of the most consistent markers of sporadic colorectal cancer in humans. There is growing evidence that telomere shortening is one of the mechanisms leading to chromosomal instability and cancer initiation. METHODS: To test this hypothesis, the telomere length of colorectal epithelial cells and cells from connective tissue was determined at the adenoma-carcinoma transition at the cellular level by quantitative fluorescence in situ hybridisation. RESULTS: Our study showed that the telomere fluorescence intensity of epithelial cells was significantly weaker at the earliest morphologically definable stage of carcinoma-high grade dysplasia with minimal invasive growth-compared with the surrounding adenoma. In contrast, cells from connective tissue had a similar telomere signal intensity at the carcinoma stage compared with the adenoma, and in turn cells from connective tissue had overall significantly stronger telomere fluorescence signals compared with epithelial cells. CONCLUSIONS: These results demonstrate that short telomeres of epithelial cells characterise the adenoma-carcinoma transition during human colorectal carcinogenesis, suggesting that carcinomas arise from cells with critical short telomeres within the adenoma. Since the adenoma-carcinoma transition in colorectal cancer is characterised by an increase in chromosomal instability and anaphase bridges, our data support the hypothesis that short telomeres initiate colorectal cancer by induction of chromosomal instability.