Performance characteristics of molecular (DNA) analysis for the diagnosis of mucinous pancreatic cysts.

BACKGROUND: Diagnosis of mucinous pancreatic cysts (MPCs) is challenging due to the poor sensitivity of cytology provided by EUS-guided-FNA (EUS-FNA). OBJECTIVE: To quantify the test characteristics of molecular (DNA) analysis in suspected low-risk MPCs. DESIGN: A prospective cohort study performed in between 2008 and 2011. SETTING: Academic referral center. PATIENTS: Consecutive patients who underwent EUS-FNA of suspected MPCs. INTERVENTION: EUS-FNA and molecular (DNA) analysis of cyst fluid. MAIN OUTCOME MEASUREMENTS: The sensitivity and specificity of molecular analysis in the diagnosis of MPCs using the criterion standard of surgical pathology in resected cysts. RESULTS: Patients with suspected MPCs underwent EUS-FNA and cyst fluid DNA analysis. Surgical resection was performed in 48 patients (17%), confirming a mucinous pathology in 38 (79%). In this group, molecular analysis had a sensitivity of 50% and a specificity of 80% in identifying MPCs (accuracy of 56.3%). The combination of molecular analysis with cyst fluid carcinoembryonic antigen (CEA) and cytology resulted in higher MPC diagnostic performance than either one of its individual components, with a sensitivity, specificity, and accuracy of 73.7%, 70%, and 72.9%, respectively. There was no significant difference in accuracy between molecular analysis and CEA/cytology in this group. LIMITATIONS: Single-center experience. CONCLUSION: Molecular analysis aids in the diagnosis of MPCs when cytology is nondiagnostic or cyst fluid is insufficient for CEA or its level is indeterminate. Our results do not support the routine use of molecular analysis, which should be used selectively after review of imaging findings and cyst fluid studies. Further studies are needed to assess DNA's performance in malignant cysts.

Recalcitrant Gastric Actinomycosis Treated With Over-the-Scope Clip.

Actinomycosis is an infrequent infection caused by Actinomyces species bacteria. Gastric actinomycosis is extremely rare but has been identified on endoscopy, typically presenting as erythema or ulceration. Standard therapies include prolonged antibiotics, and when these fail, gastric actinomycosis often requires surgical resection. We present a case of recalcitrant gastric actinomycosis, which presented as a subepithelial lesion and the first demonstration of treatment with endoscopic resection through over-the-scope clip.

Nitinol biliary stent versus surgery for palliation of distal malignant biliary obstruction.

BACKGROUND: Curative resection of pancreatic and biliary malignancies is rare. Most tumors are inoperable at presentation, and palliation of jaundice often is the goal. Biliary decompression can be achieved by surgical diversion or endoscopic biliary stents. This study aimed to compare clinical outcomes between surgical bypass and endoscopic uncovered nitinol stents in the palliation of patients with malignant distal common bile duct obstruction. METHODS: A multicenter, retrospective, cohort study investigated 86 patients with inoperable malignant distal common bile duct strictures at tertiary referral centers in Medellín, Colombia. These patients had undergone surgery (group 1) or placement of an uncovered 30-Fr self-expandable nitinol stent produced locally in Medellín, Colombia (group 2). The main outcome measurements included cumulative biliary patency, hospital stay, and patient survival. RESULTS: The study enrolled 86 patients (mean age, 66 years; range, 43-78 years) including 40 patients in group 1 and 46 patients in group 2. Both groups were similar in terms of age, gender, liver metastasis, and diagnosis. Technical success was achieved for 38 patients in group 1 (95%) and 43 patients in group 2 (93%). Functional biliary decompression was obtained in for 35 of the surgical patients (88%) and 42 of the stented patients (91%). Group 2 had lower rates for procedure-related mortality (2 vs. 7.5%; p = 0.01), a lower frequency of early complications (8.7 vs. 45%; p = 0.02), and a shorter hospital stay (median, 6 vs. 12 days; p = 0.01). Recurrent jaundice occurred for three patients in group 1 (7.5%) and eight patients in group 2 (17.3%) (p = 0.198). Late gastric outlet obstruction occurred for 12.5% of the patients in group 1 and 13% of the patients in group 2 (p = 0.73). Despite the early benefits of stenting, no significant difference in the median overall survival between the two groups was found (group 1, 163 days; group 2, 178 days; p = 0.11). The limitations of this study included the small number of patients and the retrospective design. CONCLUSIONS: Endoscopic stenting and surgery are effective palliation. The former is associated with fewer early complications and the latter with fewer late complications. Patients who do not qualify for curative resection may be better managed by stent placement. Surgery should be reserved for patients more likely to survive longer.

Improvement of antimalarial activity of a 3-alkylpiridine alkaloid analog by replacing the pyridine ring to a thiazole-containing heterocycle: Mode of action, mutagenicity profile, and Caco-2 cell-based permeability.

The development of new antimalarial drugs is urgent to overcome the spread of resistance to the current treatment. Herein we synthesized the compound 3, a hit-to­lead optimization of a thiazole based on the most promising 3-alkylpyridine marine alkaloid analog. Compound 3 was tested against Plasmodium falciparum and has shown to be more potent than its precursor (IC50 values of 1.55 and 14.7 µM, respectively), with higher selectivity index (74.7) for noncancerous human cell line. This compound was not mutagenic and showed genotoxicity only at concentrations four-fold higher than its IC50. Compound 3 was tested in vivo against Plasmodium berghei NK65 strain and inhibited the development of parasite at 50 mg/kg. In silico and UV-vis approaches determined that compound 3 acts impairing hemozoin crystallization and confocal microscopy experiments corroborate these findings as the compound was capable of diminishing food vacuole acidity. The assay of uptake using human intestinal Caco-2 cell line showed that compound 3 is absorbed similarly to chloroquine, a standard antimalarial agent. Therefore, we present here compound 3 as a potent new lead antimalarial compound.

Pyomyositis mimicking leptospirosis: two cases in a Brazilian tertiary care hospital in a non-tropical area.

Pyomyositis is a subacute, deep suppurative bacterial infection of skeletal muscle not arising from contiguous infection. It is presumably haematogenous in origin, and characterized by muscle pain and swelling. We report on two patients who presented with pyomyositis in a tertiary care hospital in temperate region located in southern Brazil with a clinical presentation, which was initially suggestive of leptospirosis. This report discusses the pathogenesis, clinical presentation, diagnosis and management of pyomyositis. Physicians living in non-tropical areas should note that pyomyositis might occur in those areas, and its initial clinical presentation may be similar to leptospirosis.

Obstrucción intestinal secundaria a enteritis por radiación: reporte de un caso / Bowel obstruction secondary to radiation enteritis: A case report

La enteritis por radiación o enteritis actínica es una complicación secundaria al uso de radioterapia para tratamiento de tumores pélvicos, que puede afectar con mayor frecuencia al intestino delgado (principalmente íleon) y al colon. La cirugía en pacientes con enteritis por radiación crónica debe reservarse ante la presencia de complicaciones, ya que está relacionada con una alta morbilidad y estancia hospitalaria prolongadas, así como posibilidad de re operación. Exponemos el caso de una paciente con oclusión intestinal secundaria a enteritis por radiación que desarrolló años después de la conclusión de su tratamiento por cáncer de cuello uterino, con el objetivo de que esta enfermedad sea sospechada en pacientes con antecedentes de radiación.

Radiation enteritis or actinic enteritis is a complication secondary to the use of radiotherapy to treat pelvic tumors, which can more frequently affect the small intestine (mainly ileum) and the colon. Surgery in patients with chronic radiation enteritis should be reserved in the presence of complications, since it is related to high morbidity and prolonged hospital stay, as well as the possibility of reoperation. We present the case of a patient with intestinal occlusion secondary to radiation enteritis who developed years after the conclusion of her treatment due to cervical cancer, with the objective that this disease has to be suspected in patients with history of radiation.

Utility of EUS following endoscopic polypectomy of high-risk rectosigmoid lesions.

BACKGROUND: The utility of endoscopic ultrasound (EUS) compared with standard white light endoscopy (WLE) following recent polypectomy of high-risk colorectal polyps is unknown. OBJECTIVE: To assess the incremental yield of EUS after endoscopic polypectomy of a high-risk rectal lesion. DESIGN: Retrospective cohort. SETTING: Tertiary referral center. MATERIALS AND METHODS: Patients referred for EUS following attempted endoscopic resection of a high-risk rectal neoplasm, defined as a tubulovillous adenoma, tubular adenoma with high-grade dysplasia, carcinoid, carcinoma in-situ or adenocarcinoma (CA). INTERVENTIONS: Sigmoidoscopy ± mucosal biopsy and EUS ± fine-needle aspiration (FNA) to evaluate for: (1) Residual polyp/tumor in the rectal wall or (2) peritumoral adenopathy. MAIN OUTCOME: Sensitivity and specificity for detection of residual neoplasia for WLE ± biopsy (WLE/BX) and EUS ± FNA for cancer (CA group) or benign disease (non-CA group). The incremental yield of EUS defined as: (1) Residual intramural neoplasia not present on WLE ± BX and; (2) abnormal peritumoral adenopathy. RESULTS: A total of 70 patients (mean age 64 ± 11 years, 61% male) with a final diagnosis of CA (n = 38) and non-CA (n = 32) were identified. There was no difference between the sensitivity and specificity of WLE alone (65% and 84%), WLE with biopsy (71% and 95%), and EUS (59% and 84%), for the detection of residual neoplasia (P > 0.05 for all). EUS identified 3 masses missed by WLE, all in the CA group. A malignant (n = 2) or benign (n = 3) node was identified in 5 (13%) CA patients; EUS-FNA in two showed residual malignancy in one and a reactive lymph node (LN) in one. No LNs were identified in the non-CA patients. LIMITATIONS: Retrospective design, incomplete follow-up in some patients. CONCLUSION: Following endoscopic polypectomy of high-risk rectal neoplasia, the incremental yield of EUS compared with WLE/BX for evaluation of residual disease appears limited, especially in patients with benign disease.

Microscopy and polymerase chain reaction detection of Leishmania chagasi in the pleural and ascitic fluid of a patient with AIDS: Case report and review of diagnosis and therapy of visceral leishmaniasis.

Atypical visceral leishmaniasis is increasingly reported in immunocompromised patients, including patients with AIDS. A case of visceral leishmaniasis in an HIV-infected Brazilian patient with pulmonary and peritoneal involvement is reported. Histological evaluation of pleural fluid and ascites aspirate revealed macrophages with intracellular Leishmania. Polymerase chain reaction analysis was positive for Leishmania in the pleural and ascitic fluid with use of primers specific for Leishmania chagasi. In addition to classical methods for diagnosing leishmaniasis, such as microscopy and culture, polymerase chain reaction detection and identification of Leishmania species in pleural effusions and ascites are important diagnostic tools that should be considered by clinicians evaluating HIV-infected patients from endemic areas of visceral leishmaniasis. The authors review the clinical manifestations, diagnostic and therapeutic aspects of visceral leishmaniasis in immunocompetent and HIV-infected patients.

EUS-guided celiac plexus interventions in pancreatic cancer pain: An update and controversies for the endosonographer.

Patients with pancreatic cancer (pancreatic ductal adenocarcinoma [PDAC]) can develop abdominal pain that can be debilitating. Celiac plexus neurolysis (CPN) is a chemical ablation of the celiac plexus that can be used to treat pain caused by pancreatic malignancy. It can be performed by an anterior or posterior approach, and also can be done percutaneously or under guidance of transabdominal ultrasound, computed tomography, intra-operatively or most recently under linear endoscopic ultrasound (EUS) guidance (EUS-CPN). EUS is well-suited for identification of the celiac plexus due to the close proximity of the gastric wall to the origin of the celiac artery. EUS-CPN is now widely practiced, and different EUS approaches have been developed in order to improve the efficacy of this technique. Our objective is to review the use of EUS-CPN in PDAC, including a description of different techniques, review of its efficacy, predictors of pain response, and describe its limitations and safety, as well as new developments.

Applications of endoscopic ultrasound in pancreatic cancer.

Since the introduction of endoscopic ultrasound guided fine-needle aspiration (EUS-FNA), EUS has assumed a growing role in the diagnosis and management of pancreatic ductal adenocarcinoma (PDAC). The objective of this review is to discuss the various applications of EUS and EUS-FNA in PDAC. Initially, its use for detection, diagnosis and staging will be described. EUS and EUS-FNA are highly accurate modalities for detection and diagnosis of PDAC, this high accuracy, however, is decreased in specific situations particularly in the presence of chronic pancreatitis. Novel techniques such as contrast-enhanced EUS, elastography and analysis of DNA markers such as k-ras mutation analysis in FNA samples are in progress and might improve the accuracy of EUS in the detection of PDAC in this setting and will be addressed. EUS and EUS-FNA have recently evolved from a diagnostic to a therapeutic technique in the management of PDAC. Significant developments in therapeutic EUS have occurred including advances in celiac plexus interventions with direct injection of ganglia and improved pain control, EUS-guided fiducial and brachytherapy seed placement, fine-needle injection of intra-tumoral agents and advances in EUS-guided biliary drainage. The future role of EUS and EUS in management of PDAC is still emerging.

Can endoscopic ultrasound predict pancreatic intraepithelial neoplasia lesions in chronic pancreatitis?: a retrospective study of pathologic correlation.

OBJECTIVE: This study aimed to evaluate associations between endoscopic ultrasound (EUS) criteria for chronic pancreatitis (CP) and coexisting pancreatic intraepithelial neoplasia (PanIN) lesions. METHODS: Patients with known or suspected CP who underwent pancreatic resection within a year of EUS were selected. Histology slides and EUS images were reviewed for evidence of pancreatic fibrosis. RESULTS: Ninety-seven (51 men; mean age, 53 [12] years) underwent EUS within a 1 year or less of EUS. Pancreatic intraepithelial neoplasia lesions were found in 84 (87%) patients. Pancreatic intraepithelial neoplasia 1, 2, and 3 lesions were seen in 71 (83%), 10 (14%), and 1 (2%), respectively. Two patients had more than 1 PanIN grade (one had PanIN 1 and 2 and the other had PanIN 1 and 3). The mean number of EUS criteria for PanIN 1, 2, and 3 lesions were 3.9, 4.5, and 5.5, respectively. The odds ratio for the association between PanIN 2 and hyperechoic foci without shadowing in the pancreas head was 8.5 (P = 0.05). The odds ratio for the association between PanIN 2 and lobularity with honeycombing was 2.7 (P = ns). Advanced PanIN lesions had greater than or equal to 4 EUS criteria for CP. CONCLUSIONS: Pancreatic intraepithelial neoplasia lesions were highly prevalent in CP resections. Increasing PanIN grade is observed with increasing fibrosis score and increasing number of EUS criteria for CP.

Ratio of pancreatic duct caliber to width of pancreatic gland by endosonography is predictive of pancreatic cancer.

OBJECTIVES: This study aimed to determine whether (1) a pancreatic duct (PD) diameter to pancreatic gland width (G) ratio (PDG) by endoscopic ultrasonography (EUS) predicts pancreatic cancer (PC) and (2) whether this ratio better indicates PC compared to PD dilation alone. METHODS: Patients presenting for EUS were classified into the following 4 categories: (1) normal, (2) noncalcific chronic pancreatitis (NCCP), (3) calcific CP (CCP), and (4) PC. RESULTS: There were 198 patients enrolled. Final diagnoses were PC (n = 34), CCP (n = 16), and normal/NCCP (n = 148). The median PD diameter (8, 5, and 2 mm, respectively; P = <0.001), G (16, 20, and 17 mm, respectively; P = 0.002), and PDG ratio were significantly different among groups (0.54, 0.25, and 0.12, respectively; P < 0.001). Patients with PC were more likely to have a PDG ratio of greater than or equal to 0.34 compared to CCP, and normal/NCCP groups (94%, 19%, 1.3%, respectively; P < 0.001). The positive predictive value, negative predictive value, sensitivity, specificity, and accuracy of PDG greater than or equal to 0.34 for detecting cancer were 87%, 99%, 94%, 97%, and 97%, respectively. The accuracy and positive predictive value of PD dilation alone for diagnosing PC were 83% and 50%, respectively. CONCLUSIONS: A PDG ratio is a good predictor of PC and is better than PD dilation. This sign should be routinely used by endosonographers to improve EUS diagnostic capability of PC.