Efficacy of sofosbuvir and ledipasvir in an HCV+ gastro-resected patient

2017 ◽  
Vol 42 (5) ◽  
pp. 621-623 ◽  
Author(s):  
C. Taibi ◽  
M. Tempestilli ◽  
A. D'Avolio ◽  
A. R. Garbuglia ◽  
A. De Nicolò ◽  
...  
Keyword(s):  
Resected Patient

scholarly journals Comparing Glioblastoma Surgery Decisions Between Teams Using Brain Maps of Tumor Locations, Biopsies, and Resections

2019 ◽  
pp. 1-12 ◽  
Author(s):  
Domenique M.J. Müller ◽  
Pierre A.J.T. Robe ◽  
Roelant S. Eijgelaar ◽  
Marnix G. Witte ◽  
Martin Visser ◽  
...  
Keyword(s):  
Tumor Location ◽  
Three Dimensions ◽  
Multidisciplinary Teams ◽  
Surgical Removal ◽  
Treatment Variation ◽  
Probability Maps ◽  
Resected Patient ◽  
The Right ◽  
Referral Bias ◽  
The Brain

Purpose The aim of glioblastoma surgery is to maximize the extent of resection while preserving functional integrity, which depends on the location within the brain. A standard to compare these decisions is lacking. We present a volumetric voxel-wise method for direct comparison between two multidisciplinary teams of glioblastoma surgery decisions throughout the brain. Methods Adults undergoing first-time glioblastoma surgery from 2012 to 2013 performed by two neuro-oncologic teams were included. Patients had had a diagnostic biopsy or resection. Preoperative tumors and postoperative residues were segmented on magnetic resonance imaging in three dimensions and registered to standard brain space. Voxel-wise probability maps of tumor location, biopsy, and resection were constructed for each team to compare patient referral bias, indication variation, and treatment variation. To evaluate the quality of care, subgroups of differentially resected brain regions were analyzed for survival and functional outcome. Results One team included 101 patients, and the other included 174; 91 tumors were biopsied, and 181 were resected. Patient characteristics were largely comparable between teams. Distributions of tumor locations were dissimilar, suggesting referral bias. Distributions of biopsies were similar, suggesting absence of indication variation. Differentially resected regions were identified in the anterior limb of the right internal capsule and the right caudate nucleus, indicating treatment variation. Patients with (n = 12) and without (n = 6) surgical removal in these regions had similar overall survival and similar permanent neurologic deficits. Conclusion Probability maps of tumor location, biopsy, and resection provide additional information that can inform surgical decision making across multidisciplinary teams for patients with glioblastoma.

scholarly journals Systematic Generation of Patient-Derived Tumor Models in Pancreatic Cancer

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 142 ◽  
Author(s):  
Karl Roland Ehrenberg ◽  
Jianpeng Gao ◽  
Felix Oppel ◽  
Stephanie Frank ◽  
Na Kang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Decision Making ◽  
Primary Cultures ◽  
Ductal Adenocarcinoma ◽  
In Vitro Cultivation ◽  
Tumor Models ◽  
Primary Tumors ◽  
Immunodeficient Mice ◽  
Resected Patient

In highly aggressive malignancies like pancreatic cancer (PC), patient-derived tumor models can serve as disease-relevant models to understand disease-related biology as well as to guide clinical decision-making. In this study, we describe a two-step protocol allowing systematic establishment of patient-derived primary cultures from PC patient tumors. Initial xenotransplantation of surgically resected patient tumors (n = 134) into immunodeficient mice allows for efficient in vivo expansion of vital tumor cells and successful tumor expansion in 38% of patient tumors (51/134). Expansion xenografts closely recapitulate the histoarchitecture of their matching patients’ primary tumors. Digestion of xenograft tumors and subsequent in vitro cultivation resulted in the successful generation of semi-adherent PC cultures of pure epithelial cell origin in 43.1% of the cases. The established primary cultures include diverse pathological types of PC: Pancreatic ductal adenocarcinoma (86.3%, 19/22), adenosquamous carcinoma (9.1%, 2/22) and ductal adenocarcinoma with oncocytic IPMN (4.5%, 1/22). We here provide a protocol to establish quality-controlled PC patient-derived primary cell cultures from heterogeneous PC patient tumors. In vitro preclinical models provide the basis for the identification and preclinical assessment of novel therapeutic opportunities targeting pancreatic cancer.

scholarly journals Patient-derived organoids reflect the genetic profile of endometrial tumors and predict patient prognosis

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Hege F. Berg ◽  
Marta Espevold Hjelmeland ◽  
Hilde Lien ◽  
Heidi Espedal ◽  
Tina Fonnes ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Tumor Heterogeneity ◽  
Treatment Strategies ◽  
Gene Signature ◽  
Model Systems ◽  
Rank Test ◽  
Genetic Profile ◽  
Resected Patient

Abstract Background A major hurdle in translational endometrial cancer (EC) research is the lack of robust preclinical models that capture both inter- and intra-tumor heterogeneity. This has hampered the development of new treatment strategies for people with EC. Methods EC organoids were derived from resected patient tumor tissue and expanded in a chemically defined medium. Established EC organoids were orthotopically implanted into female NSG mice. Patient tissue and corresponding models were characterized by morphological evaluation, biomarker and gene expression and by whole exome sequencing. A gene signature was defined and its prognostic value was assessed in multiple EC cohorts using Mantel-Cox (log-rank) test. Response to carboplatin and/or paclitaxel was measured in vitro and evaluated in vivo. Statistical difference between groups was calculated using paired t-test. Results We report EC organoids established from EC patient tissue, and orthotopic organoid-based patient-derived xenograft models (O-PDXs). The EC organoids and O-PDX models mimic the tissue architecture, protein biomarker expression and genetic profile of the original tissue. Organoids show heterogenous sensitivity to conventional chemotherapy, and drug response is reproduced in vivo. The relevance of these models is further supported by the identification of an organoid-derived prognostic gene signature. This signature is validated as prognostic both in our local patient cohorts and in the TCGA endometrial cancer cohort. Conclusions We establish robust model systems that capture both the diversity of endometrial tumors and intra-tumor heterogeneity. These models are highly relevant preclinical tools for the elucidation of the molecular pathogenesis of EC and identification of potential treatment strategies.

scholarly journals Pes Anserinus Syndrome Caused by Osteochondroma in Paediatrics: A Case Series Study

2017 ◽  
Vol 11 (1) ◽  
pp. 397-403 ◽  
Author(s):  
Akio Sakamoto ◽  
Shuichi Matsuda
Keyword(s):  
Case Series ◽  
Paediatric Population ◽  
Current Case ◽  
Painful Condition ◽  
Hereditary Multiple Exostoses ◽  
Medial Side ◽  
Pes Anserinus ◽  
Resected Patient ◽  
Multiple Exostoses ◽  
Case Series Study

Introduction: Osteochondroma is a common benign bone tumor, protruding from the underlying normal bone. Osteochondromas can cause pain depending on their location and size. The pes anserinus is located at the proximal medial side of the tibia, where the tendinous insertions of the sartorius, gracilis and semitendinosus muscles collectively attach. Pes anserinus syndrome, or anserine bursitis, is a painful condition of the pes anserinus, and is more common in adults typically with overweight females. The occurrence of pes anserinus syndrome is rare in the paediatric population. Results: In the current case series, five patients with pes anserinus syndrome due to proximal tibial osteochondroma are reported. Pain was present in all cases, with snapping in one case. The average age of the patients was 13 ± 1.2 years, ranging from 12 to 15 years. Three patients had a single osteochondroma, and two patients had hereditary multiple exostoses. The sizes of the osteochondromas on plain radiographs varied from 0.5 to 2.5 cm, with an average of 1.46 ± 0.83 cm. All lesions characteristically were located at the medial-posterior edge of the proximal tibia. The symptoms resolved in four cases with surgical resection, and persisted in one non-resected patient. Conclusion: The characteristic location of the osteochondroma causes pes anserinus syndrome, even though the lesion is small. The diagnosis of osteochondroma or pes anserinus syndrome may be overlooked when it occurs in a paediatric population. The symptoms seem to be consistent, and resection of the osteochondroma is necessary for treatment.

Obessive-Compulsive Disorder After Streptococcal Infection in a Frontal Lobe-Resected Patient

CNS Spectrums ◽  
2008 ◽  
Vol 13 (8) ◽  
pp. 645-646
Author(s):  
Lucas C. Quarantini ◽  
Marielza F. Veiga ◽  
Aline Santos Sampaio ◽  
Alberto Junqueira-Pinto ◽  
Maria Conceiçāo do Rosario
Keyword(s):  
Frontal Lobe ◽  
Streptococcal Infection ◽  
Compulsive Disorder ◽  
Resected Patient

scholarly journals High-Throughput Mechanistic Screening of Epigenetic Compounds for the Potential Treatment of Meningiomas

2021 ◽  
Vol 10 (14) ◽  
pp. 3150
Author(s):  
Philip D. Tatman ◽  
Tadeusz H. Wroblewski ◽  
Anthony R. Fringuello ◽  
Samuel R. Scherer ◽  
William B. Foreman ◽  
...  
Keyword(s):  
Hdac Inhibitors ◽  
Tumor Grade ◽  
Potential Treatment ◽  
Target Class ◽  
Recurrence Rates ◽  
Average Cell ◽  
Patient Gender ◽  
Resected Patient ◽  
Meningioma Cell ◽  
Hc Toxin

Background: Meningiomas are the most common primary central nervous system tumors. 20–30% of these tumors are considered high-grade and associated with poor prognosis and high recurrence rates. Despite the high occurrence of meningiomas, there are no FDA-approved compounds for the treatment of these tumors. Methods: In this study, we screened patient-cultured meningiomas with an epigenetic compound library to identify targetable mechanisms for the potential treatment of these tumors. Meningioma cell cultures were generated directly from surgically resected patient tumors and were cultured on a neural matrix. Cells were treated with a library of compounds meant to target epigenetic functions. Results: Although each tumor displayed a unique compound sensitivity profile, Panobinostat, LAQ824, and HC toxin were broadly effective across most tumors. These three compounds are broad-spectrum Histone Deacetylase (HDAC) inhibitors which target class I, IIa, and IIb HDACs. Panobinostat was identified as the most broadly effective compound, capable of significantly decreasing the average cell viability of the sample cohort, regardless of tumor grade, recurrence, radiation, and patient gender. Conclusions: These findings strongly suggest an important role of HDACs in meningioma biology and as a targetable mechanism. Additional validation studies are necessary to confirm these promising findings, as well to identify an ideal HDAC inhibitor candidate to develop for clinical use.

scholarly journals Alveolar Echinococcosis—A Challenging Task for the Hepatobiliary Surgeon

Pathogens ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 40
Author(s):  
Jens Strohaeker ◽  
Mihaly Sulyok ◽  
Alfred Koenigsrainer ◽  
Silvio Nadalin
Keyword(s):  
Liver Resection ◽  
Alveolar Echinococcosis ◽  
Extrahepatic Bile Duct ◽  
High Volume ◽  
Late Presentation ◽  
Long Term Outcomes ◽  
Single Center Experience ◽  
Resected Patient

(1) Background: Alveolar echinococcosis (AE) is an ultimately fatal disease, whose only curative treatment is surgery. Due to its late presentation extended liver resections are often necessary. The true benefit of extensive surgery has yet to be established; (2) Methods: We present a single center experience of 33 cases of Echinococcus multilocularis that have been treated at a high-volume hepatobiliary surgery center between 2004 and 2021. (3) Results: Of the 33 patients 24 patients underwent major liver resection (73%). In addition to the liver resection patients frequently underwent complex extrahepatic procedures such as lymphadenectomy (n = 21, 61%), vascular resections and reconstructions (n = 9, 27%) or resections and reconstruction of the extrahepatic bile duct (n = 11, 33%). Seven patients suffered from ≥ grade III complications (21%). Complete resection was achieved in 17 patients. Fourteen patients had R1 resections and two had macroscopic parasitic remnant (R2). Progressive disease was reported in three patients (The two R2 patients and one R1 resected patient). At a median follow-up of 54 months no mortality has occurred in our cohort; (4) Conclusions: Liver resection remains the gold standard for AE. Even in extensive disease the combination of complex resection and perioperative benzimidazoles can achieve favorable long-term outcomes.

Establishment of primary human esophageal xenografts: Rationale for selection and cancer model.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 45-45
Author(s):  
L. Dodbiba ◽  
J. Teichman ◽  
A. Ramjaun ◽  
M. Li ◽  
B. Sun ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Barrett’S Esophagus ◽  
Cell Lines ◽  
Barrett's Esophagus ◽  
Drug Testing ◽  
Treatment Strategies ◽  
Operative Therapy ◽  
Predictive Biomarkers ◽  
Disease Stage ◽  
Resected Patient

45 Background: New animal models of esophageal cancer are required to accelerate research into novel treatment strategies. Mouse xenografts used in pre-clinical drug testing are typically derived from cell lines, but several esophageal cancer cell lines have been contaminated (PMID 20075370). Xenografts implanted from surgically resected human tumors are a potentially viable model, and may better recapitulate the characteristics of the original tumor. We describe the feasibility of such an approach. Methods: 2-10 mm esophageal carcinoma fragments obtained from resected patient tumors were implanted directly into NOD/SCID mice. Tumors that grew beyond 1.5 cm in diameter were passaged serially. Pathologic properties were assessed from passage to passage. Potential clinicopathological predictors of engraftment were evaluated. Results: Of the 63 patients with tumors used for implantation, 67% were male; median age 66 (range 31-89); 31% node negative disease; 69% node positive disease; 12% metastatic; 55% received neoadjuvant therapy; 12% had prior Barrett's esophagus; 46% had pre-existing heartburn; 88% were distal esophageal/GE junction cancers. Engraftment occurred in 14/43 (33%) adeno-, 1/14 (7%) squamous, and 1/1 adenosquamous carcinomas (p=0.05; 5 others were rare tumors e.g. granular or small cell). Engraftment occurred in 6/31 well/moderately vs 7/18 poorly differentiated tumors (p=0.08). Because we amended our implantation procedures, we compared engraftment rates pre- (7/39; 18%) and post-amendment (8/23; 35%; p=0.13). The primary architecture of the xenografted tissue remained similar pathologically for up to 5+ passages. None of the following variables predicted for engraftment (p>0.20 each comparison): cancer location, age, gender, history of heartburn, pre-operative therapy, presence of Barrett's esophagus, disease stage, or recurrence of primary cancer. Conclusions: Creation of esophageal cancer xenografts from primary human resected specimens is feasible. Adenocarcinomas, higher tumor grade, and newer implantation strategies were associated with improved engraftment. We are treating these models with chemotherapy to discover new pharmacogenomic predictive biomarkers. No significant financial relationships to disclose.

scholarly journals A Human Organoid Model of Aggressive Hepatoblastoma for Disease Modeling and Drug Testing

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2668
Author(s):  
James A. Saltsman ◽  
William J. Hammond ◽  
Nicole J. C. Narayan ◽  
David Requena ◽  
Helmuth Gehart ◽  
...  
Keyword(s):  
Drug Testing ◽  
Disease Modeling ◽  
Treatment Options ◽  
Expression Patterns ◽  
Current Treatment ◽  
Treatment Regimens ◽  
Resected Patient ◽  
Liver Organoids ◽  
New Treatments ◽  
Tumor Organoids

Hepatoblastoma is the most common childhood liver cancer. Although survival has improved significantly over the past few decades, there remains a group of children with aggressive disease who do not respond to current treatment regimens. There is a critical need for novel models to study aggressive hepatoblastoma as research to find new treatments is hampered by the small number of laboratory models of the disease. Organoids have emerged as robust models for many diseases, including cancer. We have generated and characterized a novel organoid model of aggressive hepatoblastoma directly from freshly resected patient tumors as a proof of concept for this approach. Hepatoblastoma tumor organoids recapitulate the key elements of patient tumors, including tumor architecture, mutational profile, gene expression patterns, and features of Wnt/β-catenin signaling that are hallmarks of hepatoblastoma pathophysiology. Tumor organoids were successfully used alongside non-tumor liver organoids from the same patient to perform a drug screen using twelve candidate compounds. One drug, JQ1, demonstrated increased destruction of liver organoids from hepatoblastoma tumor tissue relative to organoids from the adjacent non-tumor liver. Our findings suggest that hepatoblastoma organoids could be used for a variety of applications and have the potential to improve treatment options for the subset of hepatoblastoma patients who do not respond to existing treatments.

scholarly journals A patient-designed tissue-engineered model of the infiltrative glioblastoma microenvironment

2020 ◽  
Author(s):  
R. C. Cornelison ◽  
J. X. Yuan ◽  
K. M. Tate ◽  
A. Petrosky ◽  
G. F. Beeghly ◽  
...  
Keyword(s):  
Fluid Flow ◽  
Interstitial Fluid ◽  
Tumor Model ◽  
Drug Efficacy ◽  
Interstitial Fluid Flow ◽  
Diffuse Infiltration ◽  
Human Astrocytes ◽  
Resected Patient ◽  
The Brain

AbstractGlioblastoma is an aggressive brain cancer characterized by diffuse infiltration. Infiltrated glioma cells persist in the brain post-resection where they interact with glial cells and experience interstitial fluid flow. We recreate this infiltrative microenvironment in vitro based on resected patient tumors and examine malignancy metrics (invasion, proliferation, and stemness) in the context of cellular and biophysical factors and therapies. Our 3D tissue-engineered model comprises patient-derived glioma stem cells, human astrocytes and microglia, and interstitial fluid flow. We found flow contributes to all outcomes across seven patient-derived lines, and glial effects are driven by CCL2 and differential glial activation. We conducted a six-drug screen using four outcomes and find expression of putative stemness marker CD71, opposed to viability IC50, significantly predicts murine xenograft survival. Our results dispute the paradigm of viability as predictive of drug efficacy. We posit this patient-centric, infiltrative tumor model is a novel advance towards translational personalized medicine.

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