Liquid Biopsy Transcriptomics of Extracellular Vesicles (EV) in Plasma of Pancreatic Ductal Adenocarcinoma (PDAC)

https://openworks.mdanderson.org/sumexp22/1089/thumbnail.jp

Abdominal tuberculosis mimicking Crohn’s disease’s exacerbation: a clinical, diagnostic and surgical dilemma. A case report

INTRODUCTION: Tuberculosis in Europe is a health public problem, which has increased constantly over the last few decades. The most common clinical manifestation of tuberculosis is pulmonary. The diagnosis of extrapulmonary tuberculosis can be challenging and clinical manifestations of gastrointestinal tuberculosis are unspecific and can mimic other pathologies. PRESENTATION OF CASE: A young Chinese man, who had recently been diagnosed with Crohn’s disease, was admitted to the emergency room of our hospital with a one-month history of diffuse abdominal pain and weight loss. The patient initially presented with epigastric pain, which had been constantly increasing over the last 48 h. Other symptoms included diarrhea, nausea, and fever. The patient was then admitted with the diagnosis of Crohn’s disease exacerbation, and a treatment with corticosteroids, azathioprine, mesalazine, adalimumab, and antibiotic therapy was started. The symptoms were due to an initially misdiagnosed case of abdominal tuberculosis. DISCUSSION: Intestinal tuberculosis is mainly localized at the ileocecal level in 85% of patients. Medical therapy is the treatment of choice and surgery is not required if it is diagnosed at an early stage.’ CONCLUSION: The diagnosis of abdominal tuberculosis still remains a challenge for both internists and surgeons. Before starting a therapy with adalimumab, every patient should be tested for latent tuberculosis infection

Identifying Differences in Spatial Transcriptomics Between Subtypes of Pancreatic Ductal Adenocarcinoma

https://openworks.mdanderson.org/sumexp22/1072/thumbnail.jp

A Combined TLR7/TLR9/GATA3 Score Can Predict Prognosis in Biliary Tract Cancer

Biliary tract cancer (BTC) refers to a heterogenous group of epithelial malignancies arising along the biliary tree. The highly aggressive nature combined with its silent presentation contribute to the dismal prognosis of this tumor. Tumor-infiltrating immune cells (TIICs) are frequently present in BTC and there is growing evidence regarding their role as therapeutic targets. In this study, we analyzed the immune cell infiltration in BTC and developed a promising immune signature score to predict prognosis in BTC. Immunohistochemistry (IHC) was carried out on tissue microarray sections from 45 patients with resectable cholangiocarcinoma for the detection of 6-sulfoLacNAc+ monocytes (slanMo), BDCA-2+ plasmacytoid dendritic cells (pDC), CD8+ or CD4+T-lymphocytes, CD103+ cells, GATA3+ cells, Toll-like receptor (TLR) 3, 7 and 9-expressing cells as well as programmed cell death protein 1 and programmed cell death ligand 1 positive cells. Data from the IHC staining were analyzed and correlated with clinicopathological and survival data. High expression of TLR7, TLR9, and GATA3 was associated with improved overall survival (OS, Log-rank p < 0.05). In addition, TLR9 was associated with better disease-free survival (Log-rank p < 0.05). In the multivariate Cox proportional-hazards model for OS, the TLR/TLR9/GATA3 score was found to be an independent prognostic factor for OS (“Score 2” vs. “Score 0”: HR 11.17 95% CI 2.27–54.95, p < 0.01)

Differential in vitro neurotoxicity of the flame retardant PBDE-99 and of the PCB Aroclor 1254 in human astrocytoma cells

Polybrominated diphenyl ethers (PBDEs) are an important class of flame retardants. Because of their presence in maternal milk and their structural similarity to polychlorinated biphenyls (PCBs), concern has been raised on their possible developmental neurotoxicity. Aim of the present study was to investigate the in vitro effects of PBDE-99 (2,2', 4,4',5-pentabromodiphenyl ether) on astroglial cells (human 132-1N1 astrocytoma cells) and comparing it with those of the PCB mixture Aroclor 1254. Both PBDE99 and Aroclor 1254 caused a concentration-dependent inhibition of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) reduction, however, only the latter increased lactate dehydrogenase (LDH) release or cell death, assessed by the trypan blue assay. PBDE-99 caused translocation of the three protein kinase C (PKC) isozymes (alpha, epsilon, zeta) present in 132 astrocytoma cells, while Aroclor 1254 affected only PKCalpha and epsilon translocation. However, pre-incubation with the PKC inhibitor GF109203X or PKC down-regulation by the phorbol ester PMA, had minimal or no effect on PBDE-99 or Aroclor 1254-induced cytotoxicity. Similarly, the calcium chelator BAPTA-AM, the tyrosine kinase inhibitor genistein, and the MEK (mitogen activated protein kinase kinase) inhibitor PD98059 had no effect on PBDE-99 and Aroclor 1254 cytoxicity. On the other hand, the phosphatidylinositol 3 kinase (PI-3K) inhibitor LY290042 enhanced PBDE-99 toxicity, but did not affect Aroclor 1254. Because of the involvement of PI-3K in apoptotic cell death, the ability of PBDE-99 and Aroclor 1254 to induce apoptosis in astrocytoma cells was investigated. PBDE-99, but not Aroclor 1254, caused apoptotic cell death in astrocytoma cells, assessed by the TUNEL method and by Hoechst 33258 staining, via a p53 dependent mechanism. These results suggest that PBDE-99 and Aroclor 1254 exert differential cytotoxic effects on human astroglial cells. (C) 2004 Elsevier Ireland Ltd. All rights reserved

Visceral artery aneurysms: evolving interdisciplinary management and future role of the abdominal surgeon

Abstract Background Visceral artery aneurysms (VAA) are rare vascular lesions. Clinically silent VAA are increasingly detected by cross-sectional imaging but some lesions are at risk for rupture with severe bleeding. The aim of the present study was to evaluate the trends in the interdisciplinary management at a tertiary center. Methods Patients who underwent treatment for VAA at University Hospital of Bonn between 2005 and 2018 were enrolled in this retrospective study. Demographic, clinical, VAA-specific data as well as information on therapy, early and long-term outcome were collected and statistically analyzed. Results Forty-two consecutive patients, 19 females and 23 males with a median age of 59 years (range 30–91 years), were diagnosed with 56 VAA. The majority were true aneurysms (N = 32; 57%), whereas 43% (N = 24) were pseudoaneurysms. The most common localization was the splenic artery (N = 18; 32%) and the average diameter was 3 cm (range 1–5 cm). Twenty-five patients (59.5%) had VAA-related symptoms such as chronic abdominal pain and hemorrhage at primary diagnosis, while the diagnosis was incidental in 17 patients (40.5%). Eleven patients (26%) underwent open surgery whereas 29 patients (69%) received an endovascular treatment. Patients with pseudoaneurysms were significantly older (P = 0.003), suffered more often from associated symptoms (P < 0.001) and required more emergency interventions (P < 0.0001) compared to those with true VAA. In the last years, the number and proportion of true VAA increased significantly (P < 0.001) while a significantly larger proportion could be managed interventionally (P = 0.017). Conclusions VAA are increasingly detected on imaging with lesions presenting very heterogeneously. Due to the risk of lethal rupture and in the absence of reliable prognostic markers, all the patients with VAA should be offered definite treatment. Localization, anatomy and the end-organ perfusion after intervention or operation are the most important aspects to consider when planning a treatment for VAA. For this reason, a multidisciplinary evaluation of every individual patient is necessary for an optimized outcome

DNA Methylation of PITX2 and PANCR Is Prognostic for Overall Survival in Patients with Resected Adenocarcinomas of the Biliary Tract.

Biliary tract cancers (BTC) are rare but highly aggressive malignant epithelial tumors. In order to improve the outcome in this lethal disease, novel biomarkers for diagnosis, prognosis, and therapy response prediction are urgently needed. DNA promoter methylation of PITX2 variants (PITX2ab, PITX2c) and intragenic methylation of the PITX2 adjacent non-coding RNA (PANCR) were investigated by methylations-specific qPCR assays in formalin-fixed paraffin-embedded tissue from 80 patients after resection for BTC. Results were correlated with clinicopathologic data and outcome. PITX2 variants and PANCR showed significant hypermethylation in tumor vs. normal adjacent tissue (p < 0.001 and p = 0.015), respectively. In survival analysis, dichotomized DNA methylation of variant PITX2c and PANCR were significantly associated with overall survival (OS). Patients with high tumor methylation levels of PITX2c had a shorter OS compared to patients with low methylation (12 vs. 40 months OS; HR 2.48 [1.38-4.48], p = 0.002). In contrast, PANCR hypermethylation was associated with prolonged survival (25 vs. 19 months OS; HR 0.54 [0.30-0.94], p = 0.015) and qualified as an independent prognostic factor on multivariate analysis. The biomarkers investigated in this study may help to identify BTC subpopulations at risk for worse survival. Further studies are needed to evaluate if PITX2 might be a clinically useful biomarker for an optimized and individualized treatment

Management of post-operative pancreatic fistulas following Longmire–Traverso pylorus-preserving pancreatoduodenectomy by endoscopic vacuum-assisted closure therapy

Background!#!Pylorus-preserving pancreatoduodenectomy (PPPD) with pancreatogastrostomy is a standard surgical procedure for pancreatic head tumors, duodenal tumors and distal cholangiocarcinomas. Post-operative pancreatic fistulas (POPF) are a major complication causing relevant morbidity and mortality. Endoscopic vacuum therapy (EVT) has become a widely used method for the treatment of intestinal perforations and leakages. Here we report on a pilot single center series of 8 POPF cases specifically caused by dehiscences of the pancreatogastric anastomosis (PGD), successfully managed by EVT.!##!Methods!#!We included all patients with PGD after PPPD, who were treated with EVT between 07/2017 and 08/2020. For EVT a vacuum drainage film (EVT film) or open-pore polyurethane foam sponge (EVT sponge) was fixed to a 14Fr or 16Fr suction catheter and placed endoscopically within the PGD for intracavitary EVT with continuous suction between - 100 and - 150 mmHg. The EVT film/sponge was exchanged twice per week. EVT was discontinued when the PGD was sufficiently healed.!##!Results!#!PGD closure was achieved in 7 of 8 patients after a mean EVT time of 16 days (range 8-38) and 3 EVT film/sponge exchanges (range 1-9). One patient died on day 18 after PPPD from acute hemorrhagic shock, unlikely related to EVT, before effectiveness of EVT could be fully achieved. There were no adverse events directly attributable to EVT.!##!Conclusions!#!EVT could be an effective and safe addition to our therapeutic armamentarium in the management of POPF with PGD. Unless prospective comparative studies are available, EVT as minimally invasive therapeutic alternative should be considered individually by an interdisciplinary team involving endoscopists, surgeons and radiologists