scholarly journals Peritoneal Metastases From Colorectal Cancer: Defining and Addressing the Challenges

2021 ◽  
Vol 11 ◽  
Author(s):  
Onno Kranenburg ◽  
Kurt van der Speeten ◽  
Ignace de Hingh
Keyword(s):  
Colorectal Cancer ◽  
Treatment Strategies ◽  
Clinical Trial Design ◽  
Peritoneal Metastases ◽  
Proof Of Concept ◽  
Diffusion Weighted Mri ◽  
True Incidence ◽  
Recent Developments ◽  
To Come ◽  
New Treatment

The presence of peritoneal metastases (PM) in patients with colorectal cancer (CRC) is associated with an extremely poor prognosis. The diagnosis of PM is challenging, resulting in an underestimation of their true incidence. While surgery can be curative in a small percentage of patients, effective treatment for non-operable PM is lacking, and clinical and pre-clinical studies are relatively sparse. Here we have defined the major clinical challenges in the areas of risk assessment, detection, and treatment. Recent developments in the field include the application of organoid technology, which has generated highly relevant pre-clinical PM models, the application of diffusion-weighted MRI, which has greatly improved PM detection, and the design of small clinical proof-of-concept studies, which allows the efficient testing of new treatment strategies. Together, these developments set the stage for starting to address the clinical challenges. To help structure these efforts, a translational research framework is presented, in which clinical trial design is based on the insight gained from direct tissue analyses and pre-clinical (organoid) models derived from CRC patients with PM. This feed-forward approach, in which a thorough understanding of the disease drives innovation in its clinical management, has the potential to improve outcome in the years to come.

scholarly journals Peritoneal Mesothelioma: Clinical and Therapeutic Aspects

Mesothelioma ◽  
2020 ◽  
Author(s):  
Cristian Mesina ◽  
Mihaela-Iustina Mesina-Botoran ◽  
Theodor Viorel Dumitrescu ◽  
Mihai Calin Ciorbagiu ◽  
Cosmin Vasile Obleaga
Keyword(s):  
Colorectal Cancer ◽  
Differential Diagnosis ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Therapeutic Option ◽  
Peritoneal Metastases ◽  
Peritoneal Mesothelioma ◽  
Malignant Peritoneal Mesothelioma ◽  
Advanced Stages ◽  
Crs And Hipec ◽  
New Treatment

Mesothelioma is a very rare malignant disease that originates from mesothelial cells that line the serosa: pleura, peritoneum, pericardium, or testicular vaginal tunic. Peritoneal mesothelioma accounts for 7–10% of all mesotheliomas diagnosed, and ranks second after pleural localization of mesothelioma. The incidence of peritoneal mesothelioma is 0.5–3 cases per million in men and 0.2–2 cases per million in women. Diagnosis of peritoneal mesothelioma is difficult due to nonspecific symptoms and because of this patients present in advanced stages of the disease. Histologically there are three major categories of malignant peritoneal mesothelioma: epithelioid, sarcomatoid, and biphasic. The differential diagnosis of peritoneal mesothelioma is made with peritoneal pseudomyxoma, ovarian tumors, and peritoneal metastases from colorectal cancer. An important role in differential diagnosis, in addition to immunohistochemistry, is played by various tumor markers and genetic tests. The treatment of peritoneal mesothelioma is performed by cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), with good results for patients in the early stages of the disease. For patients with advanced disease, a new treatment has been proposed: pressurized intraperitoneal aerosol chemotherapy (PIPAC). For patients who cannot use CRS and HIPEC, the only therapeutic option remains chemotherapy (systemic + intraperitoneal).

scholarly journals Aggressive Treatment of Patients with Metastatic Colorectal Cancer Increases Survival: A Scandinavian Single-Center Experience

HPB Surgery ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Kristoffer Watten Brudvik ◽  
Simer Jit Bains ◽  
Lars Thomas Seeberg ◽  
Knut Jørgen Labori ◽  
Anne Waage ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Biology ◽  
Treatment Strategies ◽  
Disease Free Survival ◽  
Single Center ◽  
Single Center Experience ◽  
New Treatment ◽  
Disease Free

Background. We examined overall and disease-free survivals in a cohort of patients subjected to resection of liver metastasis from colorectal cancer (CRLM) in a 10-year period when new treatment strategies were implemented. Methods. Data from 239 consecutive patients selected for liver resection of CRLM during the period from 2002 to 2011 at a single center were used to estimate overall and disease-free survival. The results were assessed against new treatment strategies and established risk factors. Results. The 5-year cumulative overall and disease-free survivals were 46 and 24%. The overall survival was the same after reresection, independently of the number of prior resections and irrespectively of the location of the recurrent disease. The time intervals between each recurrence were similar (11 ± 1 months). Patients with high tumor load given neoadjuvant chemotherapy had comparable survival to those with less extensive disease without neoadjuvant chemotherapy. Positive resection margin or resectable extrahepatic disease did not affect overall survival. Conclusion. Our data support that one still, and perhaps to an even greater extent, should seek an aggressive therapeutic strategy to achieve resectable status for recurrent hepatic and extrahepatic metastases. The data should be viewed in the context of recent advances in the understanding of cancer biology and the metastatic process.

scholarly journals Whole-body diffusion-weighted MRI for operability assessment in patients with colorectal cancer and peritoneal metastases

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Raphaëla Carmen Dresen ◽  
Sofie De Vuysere ◽  
Frederik De Keyzer ◽  
Eric Van Cutsem ◽  
Hans Prenen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Peritoneal Metastases ◽  
Whole Body ◽  
Diffusion Weighted Mri ◽  
Diffusion Weighted ◽  
Operability Assessment

scholarly journals Evolving treatment paradigms for PCV

Eye ◽  
2021 ◽  
Author(s):  
Beau J. Fenner ◽  
Chui Ming Gemmy Cheung ◽  
Shaun S. Sim ◽  
Won Ki Lee ◽  
Giovanni Staurenghi ◽  
...  
Keyword(s):  
Significant Proportion ◽  
Treatment Strategies ◽  
Disease Process ◽  
Clinical Trial Data ◽  
Treatment Burden ◽  
Spectral Domain Oct ◽  
Anti Vegf ◽  
Recent Developments ◽  
New Treatment ◽  
Therapeutic Research

AbstractPolypoidal choroidal vasculopathy (PCV) is a subtype of neovascular AMD (nAMD) that accounts for a significant proportion of nAMD cases worldwide, and particularly in Asia. Contemporary PCV treatment strategies have closely followed those used in typical nAMD, though there are significant gaps in knowledge on PCV management and it remains unclear if these strategies are appropriate. Current clinical trial data suggest intravitreal anti-vascular endothelial growth factor (VEGF) therapy alone or in combination with photodynamic therapy is effective in managing haemorrhage and exudation in PCV, although the optimal treatment interval, including as-needed and treat-and-extend approaches, is unclear. Newer imaging modalities, including OCT angiography and high-resolution spectral domain OCT have enabled characterisation of unique PCV biomarkers that may provide guidance on how and when treatment and re-treatment should be initiated. Treatment burden for PCV is a major focus of future therapeutic research and several newly developed anti-VEGF agents, including brolucizumab, faricimab, and new modes of drug delivery like the port delivery system, offer hope for dramatically reduced treatment burden for PCV patients. Beyond anti-VEGF therapy, recent developments in our understanding of PCV pathophysiology, in particular the role of choroidal anatomy and lipid mediators in PCV pathogenesis, offer new treatment avenues that may become clinically relevant in the future. This article explores the current management of PCV and more recent approaches to PCV treatment based on an improved understanding of this unique disease process.

scholarly journals Deep brain stimulation for severe autism: from pathophysiology to procedure

2015 ◽  
Vol 38 (6) ◽  
pp. E3 ◽  
Author(s):  
Saurabh Sinha ◽  
Robert A. McGovern ◽  
Sameer A. Sheth
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Neurodevelopmental Disorder ◽  
Clinical Manifestations ◽  
Treatment Strategies ◽  
Basolateral Nucleus ◽  
Recent Developments ◽  
New Treatment ◽  
Severe Autism ◽  
Deep Brain

Autism is a heterogeneous neurodevelopmental disorder characterized by early-onset impairment in social interaction and communication and by repetitive, restricted behaviors and interests. Because the degree of impairment may vary, a spectrum of clinical manifestations exists. Severe autism is characterized by complete lack of language development and potentially life-threatening self-injurious behavior, the latter of which may be refractory to medical therapy and devastating for affected individuals and their caretakers. New treatment strategies are therefore needed. Here, the authors propose deep brain stimulation (DBS) of the basolateral nucleus of the amygdala (BLA) as a therapeutic intervention to treat severe autism. The authors review recent developments in the understanding of the pathophysiology of autism. Specifically, they describe the genetic and environmental alterations that affect neurodevelopment. The authors also highlight the resultant microstructural, macrostructural, and functional abnormalities that emerge during brain development, which create a pattern of dysfunctional neural networks involved in socioemotional processing. They then discuss how these findings implicate the BLA as a key node in the pathophysiology of autism and review a reported case of BLA DBS for treatment of severe autism. Much progress has been made in recent years in understanding the pathophysiology of autism. The BLA represents a logical neurosurgical target for treating severe autism. Further study is needed that considers mechanistic and operative challenges.

scholarly journals Multidisciplinary Treatment for Colorectal Peritoneal Metastases: Review of the Literature

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Shaobo Mo ◽  
Guoxiang Cai
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Multidisciplinary Treatment ◽  
Surgical Techniques ◽  
Treatment Strategies ◽  
Peritoneal Metastases ◽  
Term Survival ◽  
Peritoneal Carcinomatosis Index ◽  
Multimodality Approach ◽  
Colorectal Cancer Patients

Peritoneum is one of the common sites of metastasis in advanced stage colorectal cancer patients. Colorectal cancer patients with peritoneal metastases (PM) are traditionally believed to have poor prognosis, which indicates it is of no value to adopt surgical treatment. With the advancement of surgical techniques, hyperthermic intraperitoneal chemotherapy (HIPEC), and multidisciplinary treatment in recent years, the cognition and treatment strategies of colorectal peritoneal metastases (CPM) have changed dramatically. In terms of prognosis, CPM under the palliative systemic treatment shows an inferior outcome compared with nonperitoneal metastasis. Nevertheless, some CPM patients amenable to the complete peritoneal cytoreductive surgery (CRS) combined with HIPEC may achieve long-term survival. The prognostic factors of CPM comprise peritoneal carcinomatosis index (PCI), completeness of cytoreduction score (CC score), the presence of extraperitoneal metastasis (liver, etc.), Peritoneal Surface Disease Severity Score (PSDSS), Japanese peritoneal staging, and so forth. Taken together, literature data suggest that a multimodality approach combining complete peritoneal CRS plus HIPEC, systemic chemotherapy, and targeted therapy may be the best treatment option for PM from colorectal cancer.

scholarly journals Redefining colorectal cancer classification and clinical stratification through a single-cell atlas

2021 ◽  
Author(s):  
Ateeq M. Khaliq ◽  
Zeyneb Kurt ◽  
Miles W. Grunvald ◽  
Cihat Erdogan ◽  
Sevgi S. Turgut ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Single Cell ◽  
Molecular Subtypes ◽  
Tumor Biology ◽  
Treatment Strategies ◽  
Clinical Trial Design ◽  
Large Degree ◽  
Classification Systems ◽  
Primary Resistance ◽  
Incidence And Mortality

ABSTRACTColorectal cancer (CRC), a disease of high incidence and mortality, has had few treatment advances owing to a large degree of inter- and intratumoral heterogeneity. Attempts to classify subtypes of colorectal cancer to develop treatment strategies has been attempted by Consensus Molecular Subtypes (CMS) classification. However, the cellular etiology of CMS classification is incompletely understood and controversial. Here, we generated and analyzed a single-cell transcriptome atlas of 49,859 CRC cells from 16 patients, validated with an additional 31,383 cells from an independent CRC patient cohort. We describe subclonal transcriptomic heterogeneity of CRC tumor epithelial cells, as well as discrete stromal populations of cancer-associated fibroblasts (CAFs). Within CRC CAFs, we identify the transcriptional signature of specific subtypes (CAF-S1 and CAF-S4) in more than 1,500 CRC patients using bulk transcriptomic data that significantly stratifies overall survival in multiple independent cohorts. We also uncovered two CAF-S1 subpopulations, ecm-myCAF and TGFß-myCAF, known to be associated with primary resistance to immunotherapies. We demonstrate that scRNA analysis of malignant, stromal, and immune cells exhibit a more complex picture than portrayed by bulk transcriptomic-based Consensus Molecular Subtypes (CMS) classification. By demonstrating an abundant degree of heterogeneity amongst these cell types, our work shows that CRC is best represented in a transcriptomic continuum crossing traditional classification systems boundaries. Overall, this CRC cell map provides a framework to re-evaluate CRC tumor biology with implications for clinical trial design and therapeutic development.

Radiotherapy for Brain Tumors: Current Practice and Future Directions

2020 ◽  
Vol 16 (3) ◽  
pp. 182-195
Author(s):  
Sarah Baker ◽  
Natalie Logie ◽  
Kim Paulson ◽  
Adele Duimering ◽  
Albert Murtha
Keyword(s):  
Brain Tumors ◽  
Treatment Strategies ◽  
Brain Parenchyma ◽  
Benign Tumors ◽  
Tumor Control ◽  
Normal Brain ◽  
Neurocognitive Deficits ◽  
Close Proximity ◽  
Recent Developments ◽  
High Level

Radiotherapy is an important component of the treatment for primary and metastatic brain tumors. Due to the close proximity of critical structures and normal brain parenchyma, Central Nervous System (CNS) radiotherapy is associated with adverse effects such as neurocognitive deficits, which must be weighed against the benefit of improved tumor control. Advanced radiotherapy technology may help to mitigate toxicity risks, although there is a paucity of high-level evidence to support its use. Recent advances have been made in the treatment for gliomas, meningiomas, benign tumors, and metastases, although outcomes remain poor for many high grade tumors. This review highlights recent developments in CNS radiotherapy, discusses common treatment toxicities, critically reviews advanced radiotherapy technologies, and highlights promising treatment strategies to improve clinical outcomes in the future.

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