Evolution and current trends in the management of colorectal cancer liver metastasis.

Metastatic colorectal cancer (mCRC) is a major cause of cancer-related death, with a 5-year relative overall survival of up to 20%. The liver is the most common site of distant metastasis in colorectal cancer (CRC), with about 50% of CRC patients metastasizing to their liver over the course of their disease. Complete liver resection is the primary modality of treatment for resectable colorectal cancer liver metastasis (CRLM), with an overall 5-year survival rate of up to 58%.

Incorporation of Simulation in Graduate Medical Education: Historical Perspectives, Current Status, and Future Directions.

Technological advancement and improved training strategies have transformed the healthcare practice environment in the last few decades. Simulation has evolved as one of the leading training models for the next generation of healthcare professionals. Simulation-based training enables healthcare professionals to acquire knowledge and skills in a safe and educationally oriented environment and can be a valuable tool for improving clinical practice and patient outcomes.

PI3K/Akt/mTOR Signaling Pathway as a Target for Colorectal Cancer Treatment.

In the last decade, pathway-specific targeted therapy has revolutionized colorectal cancer (CRC) treatment strategies. This type of therapy targets a tumor-vulnerable spot formed primarily due to an alteration in an oncogene and/or a tumor suppressor gene. However, tumor heterogeneity in CRC frequently results in treatment resistance, underscoring the need to understand the molecular mechanisms involved in CRC for the development of novel targeted therapies.

Intraperitoneal oxygen microbubble therapy: A novel approach to enhance systemic oxygenation in a smoke inhalation model of acute hypoxic respiratory failure.

Background: Patients suffering from severe acute respiratory distress syndrome (ARDS) face limited therapeutic options and alarmingly high mortality rates. Refractory hypoxemia, a hallmark of ARDS, often necessitates invasive and high-risk treatments. Oxygen microbubbles (OMB) present a promising approach for extrapulmonary oxygenation, potentially augmenting systemic oxygen levels without exposing patients to significant risks.

Competency-Based Medical Education (CBME): an Overview and Relevance to the Education of Future Surgical Oncologists.

In the next two decades, the global cancer burden is expected to rise by 47%, and the demand for global cancer surgery will increase by 52%. At present, only 25% of the estimated 80% of patients needing surgical intervention have access to timely surgical care. The shortage of a trained workforce of surgical oncologists is one of the main barriers to providing the optimal surgical intervention needed for cancer patients.

Colonic oxygen microbubbles augment systemic oxygenation and CO removal in a porcine smoke inhalation model of severe hypoxia.

Inhalation injury can lead to pulmonary complications resulting in the development of respiratory distress and severe hypoxia. Respiratory distress is one of the major causes of death in critically ill patients with a reported mortality rate of up to 45%. The present study focuses on the effect of oxygen microbubble (OMB) infusion via the colon in a porcine model of smoke inhalation-induced lung injury.

Colorectal cancer: Review of signaling pathways and associated therapeutic strategies.

Tumor profiling and targeted therapy revolutionized the treatment strategies of metastatic colorectal cancer (mCRC) in the last decade. The heterogeneity of CRC tumors plays a critical role in the development of treatment resistance, which underscores the need to understand the molecular mechanism involved in CRC to develop novel targeted therapeutic strategies. This review provides an overview of the signaling pathways driving CRC, the existing targeted agents, their limitations, and future trends.

Rat model of smoke inhalation-induced acute lung injury.

Background: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a lethal disease with limited therapeutic options and an unacceptably high mortality rate. Understanding the complex pathophysiological processes involved in the development of ALI/ARDS is critical for developing novel therapeutic strategies. Smoke inhalation (SI) injury is the leading cause of morbidity and mortality in patients with burn-associated ALI/ARDS; however, to our knowledge few reliable, reproducible models are available for pure SI animal model to investigate therapeutic options for ALI/ARDS without the confounding variables introduced by cutaneous burn or other pathology.

A novel large animal model of smoke inhalation-induced acute respiratory distress syndrome.

Background: Acute respiratory distress syndrome (ARDS) is multifactorial and can result from sepsis, trauma, or pneumonia, amongst other primary pathologies. It is one of the major causes of death in critically ill patients with a reported mortality rate up to 45%. The present study focuses on the development of a large animal model of smoke inhalation-induced ARDS in an effort to provide the scientific community with a reliable, reproducible large animal model of isolated toxic inhalation injury-induced ARDS.

Stathmin expression in metastatic colorectal cancer.

Objectives: To evaluate the relationship between stathmin expression and clinical outcome in colorectal cancer (CRC).

Background: Stathmin is a phosphoprotein involved in the regulation of microtubule dynamics and integration of intracellular signaling pathways. Stathmin has been implicated in the tumorigenesis of several cancers and is a potential therapeutic target.

Correlation of PRL3 expression with colorectal cancer progression.

Objectives: To evaluate the relationship between phosphatase of regenerating liver 3 (PRL3) expression and clinical outcome in colorectal cancer (CRC).

Background: PRL3, a protein tyrosine phosphatase functions as one of the key regulatory enzymes of various signal transduction pathways. PRL3 is highly expressed in a majority of cancers and is a novel potential therapeutic target.

Prognostic and therapeutic implications of NHERF1 expression and regulation in colorectal cancer.

Background: Na /H exchanger regulatory factor 1 (NHERF1) has been implicated in the tumorigenesis of several cancer types and is a potential therapeutic target. The current study evaluated the relationship between NHERF1 expression and clinical outcome in colorectal cancer (CRC).

Methods: NHERF1 expression was evaluated by immunohistochemistry in 167 patients with CRC primary tumors, 37 patients with no disease, and 27 patients with metastatic CRC (mCRC); and in the orthotopically implanted tumors in mice.

Role of keratan sulfate expression in human pancreatic cancer malignancy.

Keratan sulfate (KS) is a sulfated linear polymer of N-acetyllactosamine. Proteoglycans carrying keratan sulfate epitopes were majorly observed in cornea, cartilage and brain; and mainly involved in embryonic development, cornea transparency, and wound healing process. Recently, expression of KS in cancer has been shown to be highly associated with advanced tumor grade and poor prognosis.

TGFβ and IGF1R signaling activates protein kinase A through differential regulation of ezrin phosphorylation in colon cancer cells.

Aberrant cell survival plays a critical role in cancer progression and metastasis. We have previously shown that ezrin, a cAMP-dependent protein kinase A-anchoring protein (AKAP), is up-regulated in colorectal cancer (CRC) liver metastasis. Phosphorylation of ezrin at Thr-567 activates ezrin and plays an important role in CRC cell survival associated with XIAP and survivin up-regulation.

Akt inhibitor MK-2206 promotes anti-tumor activity and cell death by modulation of AIF and Ezrin in colorectal cancer.

Background: There is extensive evidence for the role of aberrant cell survival signaling mechanisms in cancer progression and metastasis. Akt is a major component of cell survival-signaling mechanisms in several types of cancer. It has been shown that activated Akt stabilizes XIAP by S87 phosphorylation leading to survivin/XIAP complex formation, caspase inhibition and cytoprotection of cancer cells.

Ezrin expression and cell survival regulation in colorectal cancer.

Colorectal cancer (CRC) is the second largest cause of cancer deaths in the United States. A key barrier that prevents better outcomes for this type of cancer as well as other solid tumors is the lack of effective therapies against the metastatic disease. Thus there is an urgent need to fill this gap in cancer therapy.

In vivo analysis of insulin-like growth factor type 1 receptor humanized monoclonal antibody MK-0646 and small molecule kinase inhibitor OSI-906 in colorectal cancer.

The development and characterization of effective anticancer drugs against colorectal cancer (CRC) is of urgent need since it is the second most common cause of cancer death. The study was designed to evaluate the effects of two IGF-1R antagonists, MK-0646, a recombinant fully humanized monoclonal antibody and OSI-906, a small molecule tyrosine kinase inhibitor on CRC cells. Xenograft study was performed on IGF-1R-dependent CRC cell lines for analyzing the antitumor activity of MK-0646 and OSI-906.

Differential PKA activation and AKAP association determines cell fate in cancer cells.

Background: The dependence of malignant properties of colorectal cancer (CRC) cells on IGF1R signaling has been demonstrated and several IGF1R antagonists are currently in clinical trials. Recently, we identified a novel pathway in which cAMP independent PKA activation by TGFβ signaling resulted in the destabilization of survivin/XIAP complex leading to increased cell death. In this study, we evaluated the effect of IGF1R inhibition or activation on PKA activation and its downstream cell survival signaling mechanisms.

Establishment and Validation of an Orthotopic Metastatic Mouse Model of Colorectal Cancer.

Metastases are largely responsible for cancer deaths in solid tumors due to the lack of effective therapies against disseminated disease, and there is an urgent need to fill this gap. This study demonstrates an orthotopic colorectal cancer (CRC) mouse model system to develop spontaneous metastasis in vivo and compare its reproducibility against human CRC. IGF1R-dependent GEO human CRC cells were used to study metastatic colonization using orthotopic transplantation procedures and demonstrated robust liver metastasis.

A preoperative nomogram to predict the risk of perioperative mortality following gastric resections for malignancy.

Introduction: Surgery remains one of the major treatment options available to patients with gastric cancer. The aim of this study was to develop a preoperative nomogram based on the presence of comorbidities to predict the risk of perioperative mortality following gastric resections for malignancy.

Methods: The Nationwide Inpatient Sample (NIS) database was used to create a nomogram using SAS software.

National trends in discharge disposition after hepatic resection for malignancy.

Background: There is a paucity of data on the trends in discharge disposition for patients undergoing hepatic resection for malignancy.

Aim: To analyse the national trends in discharge disposition after hepatic resection for malignancy.

Methods: The National Inpatient Sample (NIS) database was queried (1993 to 2005) to identify patients that underwent hepatic resection for malignancy and analyse the discharge status (home, home health or rehabilitation/skilled facility).

Pre-operative nomogram to predict risk of peri-operative mortality following liver resections for malignancy.

Introduction: The majority of liver resections for malignancy are performed in older patient with major co-morbidities. There is currently no pre-operative, patient-specific method to determine the likely peri-operative mortality for each individual patient. The aim of this study was to develop a pre-operative nomogram based on the presence of co-morbidities to predict risk of peri-operative mortality following liver resections for malignancy.