José Pinhata Otoch

Biliary drainage in patients with unresectable, malignant obstruction where ERCP fails: endoscopic ultrasonography-guided choledochoduodenostomy versus percutaneous drainage.

Background: Endoscopic retrograde cholangiopancreatography may fail because of malignant involvement of the second portion of the duodenum and the major papilla. Alternatives include percutaneous transhepatic biliary drainage (PTBD) or surgical bypass. Endoscopic ultrasonography-guided choledochoduodenostomy (EUS-CD) has been reported as an alternative. Objective: To prospectively compare EUS-CD and PTBD in patients with unresectable malignant biliary obstruction. Design: Prospective and randomized study. Setting: Tertiary center. Main Outcome Measurements: Success and efficacy comparison EUS-CD with PTBD. Results: Twenty-five subjects were randomized (13 EUS-CD and 12 PTBD). Mean age was 67 years (SD, 11.9). The 2 groups were similar before intervention in terms of quality of life [EUS-CD (58.3) vs. PTBD (57.8); P=0.78], total bilirubin (16.4 vs. 17.2; P=0.7), alkaline phosphatase (539 vs. 518; P=0.7), and gamma-glutamyl transferase (554.3 vs. 743.5; P=0.56). All procedures were technically and clinically successful in both groups. At 7-day follow-up there was a significant reduction in total bilirubin in both the groups (EUS-CD, 16.4 to 3.3; P=0.002 and PTBD, 17.2 to 3.8; P=0.01), although no difference was noted comparing the 2 groups (EUS-CD to PTBD; 3.3 vs. 3.8; P=0.2). There was no difference between the complication rates in the 2 groups (P=0.44), EUS-CD (2/13; 15.3%) and PTBD (3/12; 25%). Costs were similar in the 2 groups also (

Adipose tissue inflammation and cancer cachexia: Possible role of nuclear transcription factors

5673—EUS-CD vs.

EUS-Guided Antegrade Transhepatic Placement of a Self-Expandable Metal Stent in Hepatico-Jejunal Anastomosis

7570—PTBD; P=0.39). Limitations: Small sample size and single center study. Conclusions: EUS-CD can be an effective and safe alternative to PTBD with similar success, complication rate, cost, and quality of life.

Cachexia-associated adipose tissue morphological rearrangement in gastrointestinal cancer patients.

Cancer cachexia is a multifaceted syndrome whose aetiology is extremely complex and is directly related to poor patient prognosis and survival. Changes in lipid metabolism in cancer cachexia result in marked reduction of total fat mass, increased lipolysis, total oxidation of fatty acids, hyperlipidaemia, hypertriglyceridaemia, and hypercholesterolaemia. These changes are believed to be induced by inflammatory mediators, such as tumour necrosis factor-α (TNF-α) and other factors. Attention has recently been drawn to the current theory that cachexia is a chronic inflammatory state, mainly caused by the hosts reaction to the tumour. Changes in expression of numerous inflammatory mediators, notably in white adipose tissue (WAT), may trigger several changes in WAT homeostasis. The inhibition of adipocyte differentiation by PPARγ is paralleled by the appearance of smaller adipocytes, which may partially account for the inhibitory effect of PPARγ on inflammatory gene expression. Furthermore, inflammatory modulation and/or inhibition seems to be dependent on the IKK/NF-κB pathway, suggesting that a possible interaction between NF-κB and PPARγ is required to modulate WAT inflammation induced by cancer cachexia. In this article, current literature on the possible mechanisms of NF-κB and PPARγ regulation of WAT cells during cancer cachexia are discussed. This review aims to assess the role of a possible interaction between NF-κB and PPARγ in the setting of cancer cachexia as well as its significant role as a potential modulator of chronic inflammation that could be explored therapeutically.

Histologic, histochemical, and biomechanical properties of fragments isolated from the anterior wall of abdominal aortic aneurysms

CONTEXT To demonstrate an EUS-guided biliary drainage in patient with gastrointestinal tract modified surgically. CASE REPORT An EUS guided access to the left intra hepatic duct, followed by an antegrade passage of a partially self-expandable metal stent that was removed by using an enteroscope, in one patient with hepatico-jejunal anastomosis. There were no early or delayed complications and the procedure was effective in relieving jaundice until the self-expandable metal stent was removed, 3 months later. A cholangiogram was obtained via enteroscopy, after removal of self-expandable metal stent, and found to be normal. The patient had an uneventful evaluation afterwards. CONCLUSION The indication of these procedures must be made under a multidisciplinary view while sharing information with the patient or legal guardian. EUS-guided biliary drainage is feasible when performed by professionals with expertise in biliopancreatic endoscopy and advanced echo-endoscopy and should be performed currently under rigorous protocol in educational institutions.

EUS-Guided Biliary Drainage: A Review Article

Cachexia is a syndrome characterized by marked involuntary loss of body weight. Recently, adipose tissue (AT) wasting has been shown to occur before the appearance of other classical cachexia markers. We investigated the composition and rearrangement of the extracellular matrix, adipocyte morphology and inflammation in the subcutaneous AT (scAT) pad of gastrointestinal cancer patients.

Cancer as a Proinflammatory Environment: Metastasis and Cachexia

OBJECTIVE To analyze biomechanical, histologic, and histochemical properties of anterior fragments of abdominal aortic aneurysms (AAA) and to correlate them with the maximum transverse diameter (MTD) and symptoms associated to the aneurysms. METHODS Fragments of the anterior aneurysm wall were obtained from 90 patients submitted to open repair of AAA of degenerative etiology from 2004 to 2009 in the Clinics Hospital of São Paulo University Medical School. Two specimens were produced from the fragments: one for histologic analysis for quantification of collagen fibers, elastic fibers, smooth muscle cells, and degree of inflammatory activity and the other for uniaxial tensile test to assess biomechanical failure properties of the material, such as strength, tension, and stress. Cases were classified according to symptoms and to the AAA MTD. RESULTS Fragments from AAA with MTD < 5.5 cm showed higher values for biomechanical failure properties than those of AAA with MTD < 5.5 cm (strength, 5.32 ± 2.07 × 4.1 ± 2.41 N; tension, 13.83 ± 5.58 × 10.82 ± 6.48 N/cm; stress, 103.02 × 77.03 N/cm(2); P < .05). No differences were observed between the groups in relation to failure strain (0.41 ± 0.12 × 0.37 ± 0.14; P = .260) and thickness of the fragments (1.58 ± 0.41 × 1.53 ± 0.42 mm; P = .662). The average values of fiber compositions of all the fragments were as follows: collagen fibers, 44.34 ± 0.48% and 61.85 ± 10.14% (Masson trichrome staining and Picrosirius red staining, respectively); smooth muscle cells, 3.46 ± 2.23% (immunohistochemistry/alpha-actin); and elastic fibers, less than 1% (traces) (Verhoeff-van Gieson staining). No differences in fiber percentages (collagen, elastic, and smooth muscle) were observed in fragments from AAA with MTD <5.5 cm and <5.5 cm, but more intense inflammatory activity was seen in larger AAA (grade 3; 70% × 28.6%; P = .011). Compared with asymptomatic aneurysms, symptomatic aneurysms showed no differences in the biomechanical failure properties (strength, 5.32 ± 2.36 × 4.65 ± 2.05 N; P = .155; tension, 14.08 ± 6.11 × 12.81 ± 5.77 N/cm; P = .154; stress, 103.02 × 84.76 N/cm(2); P = .144), strain (0.38 ± 0.12 × 0.41 ± 0.13; P = .287), thickness of the fragments (1.56 ± 0.41 × 1.57 ± 0.41 mm; P = .848), and histologic composition (collagen fibers, 44.67 ± 11.17 × 44.02 ± 13.79%; P = .808; smooth muscle fibers, 2.52 × 2.35%; P = .751; elastic fibers, <1%) CONCLUSIONS Fragments of the anterior wall from larger aneurysms were more resistant than those from smaller AAA, with no tissue properties that could explain this phenomenon in the histologic or histochemical analyses utilized. CLINICAL RELEVANCE The fragments of the anterior midsection from larger aneurysms were more resistant than those from smaller abdominal aortic aneurysms, with no tissue properties that could explain this phenomenon in the histologic or histochemical analyses. Larger aneurysms, at least in this place may be stronger than smaller aneurysms. It could point toward regional differences (heterogeneity, localized pathologies) as an important player in aneurysm rupture. Uniaxial strain tests are an important tool for the comprehension of a complex behavior such as that from an aneurysmal aortic wall. However, these tests still have limitations in providing information that would allow the calculation of the risk of rupture for abdominal aortic aneurysms.

Systemic Inflammation in Cachexia – Is Tumor Cytokine Expression Profile the Culprit?

CONTEXT To demonstrate a comprehensive review of published articles regarding EUS-guided biliary drainage. METHODS Review of studies regarding EUS-guided biliary drainage including case reports, case series and previous reviews. RESULTS EUS-guided hepaticogastrostomy, choledochoduodenostomy and choledochoantrostomy are advanced procedures on biliary and pancreatic endoscopy and together make up the echo-guided biliary drainage. Hepaticogastrostomy is indicated in cases of hilar obstruction, while the procedure of choice is choledochoduodenostomy in distal lesions. Both procedures must be done only after unsuccessful ERCP. The indication of these procedures must be made under a multidisciplinary view while sharing information with the patient or legal guardian. CONCLUSION Hepaticogastrostomy and choledochoduodenostomy are feasible when performed by endoscopists with expertise in biliopancreatic endoscopy and advanced echo-endoscopy and should be performed currently under rigorous protocol in educational institutions.

NF-κBp65 and Expression of Its Pro-Inflammatory Target Genes Are Upregulated in the Subcutaneous Adipose Tissue of Cachectic Cancer Patients

The development of the syndrome of cancer cachexia and that of metastasis are related with a poor prognostic for cancer patients. They are considered multifactorial processes associated with a proinflammatory environment, to which tumour microenvironment and other tissues from the tumour bearing individuals contribute. The aim of the present review is to address the role of ghrelin, myostatin, leptin, HIF, IL-6, TNF-α, and ANGPTL-4 in the regulation of energy balance, tumour development, and tumoural cell invasion. Hypoxia induced factor plays a prominent role in tumour macro- and microenvironment, by modulating the release of proinflammatory cytokines.

Adipose tissue fibrosis in human cancer cachexia: the role of TGFβ pathway

Cachexia affects about 80% of gastrointestinal cancer patients. This multifactorial syndrome resulting in involuntary and continuous weight loss is accompanied by systemic inflammation and immune cell infiltration in various tissues. Understanding the interactions among tumor, immune cells, and peripheral tissues could help attenuating systemic inflammation. Therefore, we investigated inflammation in the subcutaneous adipose tissue and in the tumor, in weight stable and cachectic cancer patients with same diagnosis, in order to establish correlations between tumor microenvironment and secretory pattern with adipose tissue and systemic inflammation. Infiltrating monocyte phenotypes of subcutaneous and tumor vascular-stromal fraction were identified by flow cytometry. Gene and protein expression of inflammatory and chemotactic factors was measured with qRT-PCR and Multiplex Magpix® system, respectively. Subcutaneous vascular-stromal fraction exhibited no differences in regard to macrophage subtypes, while in the tumor, the percentage of M2 macrophages was decreased in the cachectic patients, in comparison to weight-stable counterparts. CCL3, CCL4, and IL-1β expression was higher in the adipose tissue and tumor tissue in the cachectic group. In both tissues, chemotactic factors were positively correlated with IL-1β. Furthermore, positive correlations were found for the content of chemoattractants and cytokines in the tumor and adipose tissue. The results strongly suggest that the crosstalk between the tumor and peripheral tissues is more pronounced in cachectic patients, compared to weight-stable patients with the same tumor diagnosis.