Georgios Antonios Margonis

Memorial Sloan Kettering Cancer Center | MSKCC · Department of Surgery

Background There are several models that predict the risk of recurrence following resection of localised, primary gastrointestinal stromal tumour (GIST). However, assessment of calibration is not always feasible and when performed, calibration of current GIST models appears to be suboptimal. We aimed to develop a prognostic model to predict the rec...

Introduction: The role of visceral fat in disease development, particularly in Crohn´s disease (CD), is significant, yet its preoperative prognostic value for postoperative complications and CD relapse remains unknown. This study aims to assess the predictive potential of preoperatively measured visceral and subcutaneous fat in postoperative compli...

In patients presenting with colorectal cancer and synchronous liver metastases, the disease burden related to the liver metastasis is the driving cause of limited longevity and, eventually, risk of death. Surgical resection is the potentially curative treatment for colorectal cancer liver metastases. In the synchronous setting where both the liver...

Background/aim: Evidence of metastatic disease precludes oncological resection of pancreatic cancer. Near-infrared (NIR) fluorescent labels, such as indocyanine green (ICG), assist in the intraoperative detection of occult and micrometastatic liver disease. The present study aimed to analyse the role of NIR fluorescence imaging using ICG for pancr...

Purpose Interleukin 6 (IL-6), Oncostatin M (OSM), and downstream effector STAT3 are pro-tumorigenic agents in pancreatic ductal adenocarcinoma (PDAC). Glycoprotein 130 (gp130) is a compound of the IL-6 and OSM receptor complex that triggers STAT3 signaling. SC144 is a small molecule gp130 inhibitor with anticancer activity. This study examines the...

Objective: To investigate the clinical implications of BRAF mutated (mutBRAF) colorectal liver metastases (CRLM). Summary background data: The clinical implications of mutBRAF status in CRLM are largely unknown. Methods: Patients undergoing resection for mutBRAF CRLM were identified from prospectively maintained registries of the collaborating...

Background: Although primary tumor sidedness (PTS) has a known prognostic role in sporadic colorectal cancer (CRC), its role in Inflammatory Bowel Disease related CRC (IBD-CRC) is largely unknown. Thus, we aimed to evaluate the prognostic role of PTS in patients with IBD-CRC. Methods: All eligible patients with surgically treated, non-metastatic...

Surgery combined with chemotherapy and precision medicine is the only potential treatment for patients with colorectal cancer liver metastases (CRLM). The use of modern molecular biotechnology to identify suitable biomarkers is of great significance for predicting prognosis and formulating individualized treatment plans for these patients. BRAF mut...

In this Special Issue of Cells, we seek articles that focus on the study of tumor biology in order to guide the scalpel [...]

Precision surgery for colorectal liver metastases (CRLM) includes optimal selection of both the patient and surgery. Initial attempts of using clinical risk scores to identify patients for whom technically feasible surgery is oncologically futile failed. Since then, patient selection for single‐stage hepatectomy followed three distinct approaches,...

Importance: In patients with resectable colorectal cancer liver metastases (CRLM), the choice of surgical technique and resection margin are the only variables that are under the surgeon's direct control and may influence oncologic outcomes. There is currently no consensus on the optimal margin width. Objective: To determine the optimal margin w...

Importance: Intrahepatic cholangiocarcinoma (iCCA) is often multifocal (ie, satellites or intrahepatic metastases) at presentation. Objective: To compare the overall survival (OS) of patients with multifocal iCCA after hepatic arterial infusion pump (HAIP) floxuridine chemotherapy vs resection. Design, setting, and participants: In this cohort...

Although the natural history of recurrence/progression in patients with intraductal papillary mucinous neoplasms (IPMN) of the pancreas has not been studied thoroughly, the three principal mechanisms have been identified: (a) presence of residual disease at the transection margin, (b) presence of intraductal/intraparenchymal metastases and (c) deve...

Background: Interleukin-6 (IL-6), Oncostatin-M (OSM) and the major downstream effector STAT3 are pro-tumorigenic agents in many cancers, including pancreatic ductal adenocarcinoma (PDAC). Glycoprotein 130 (gp130) is a compound of the IL-6 and OSM receptor complex that triggers STAT3 signalling. Recently, a novel small molecule gp130 inhibitor named...

Purpose Myopenia and myosteatosis have been proposed to be prognostic factors of surgical outcomes for various diseases, but their exact role in Crohn’s disease (CD) is unknown. The aim of this study is to evaluate their impact on anastomotic leakage, CD recurrence, and postoperative complications after ileocecal resection in patients with CD. Met...

Background: It is debated whether primary tumor laterality (PTL) is prognostic in all patients with colorectal liver metastases (CRLM) or only those with KRAS wild-type or KRAS-mutated tumors; Methods: We systematically reviewed PubMed for studies reporting on resected CRLM originating from left-sided (LS) versus right-sided (RS) colon cancer stra...

Background Prognostic stratification of patients with colorectal cancer liver metastasis based solely on tumor-related factors has only moderate discriminatory ability. We hypothesized that the inclusion of nontumor related factors can improve prediction of long-term prognosis of patients with colorectal cancer liver metastasis. Methods Nontumor r...

Mechanisms of lymph node invasion seem to play a prognostic role in pancreatic ductal adenocarcinoma (PDAC) after resection. However, the 8th edition of the TNM classification of the American Joint Committee on Cancer (AJCC) does not consider this. The aim of this study was to analyse the prognostic role of different mechanisms of lymph node invasi...

Prognostic models allow clinicians to predict survival outcomes, facilitate patient–physician discussions, and identify subgroups with potentially distinct prognoses. Although such prognostic stratification cannot directly predict treatment benefit, it can help to inform clinical decision making. This editorial will discuss potential avenues for th...

Purpose Colorectal cancer revealed over the last decades a remarkable shift with an increasing proportion of a right- compared to a left-sided tumor location. In the current study, we aimed to disclose clinicopathological differences between right- and left-sided colon cancer (rCC and lCC) with respect to mortality and outcome predictors. Methods...

PURPOSE The American Joint Committee on Cancer (AJCC) eighth edition schema for pancreatic ductal adenocarcinoma treats T and N stage as independent factors and uses positive lymph nodes (PLNs) to define N stage, despite data favoring lymph node ratio (LNR). We used artificial intelligence–based techniques to compare PLN with LNR and investigate in...

Objective: To validate the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging system for patients with invasive carcinomas arising in association with IPMN (IPMN-associated PDAC). Background data: Although several studies have validated AJCC systems in patients with conventional PDAC, their applicability to IPMN-associ...

Despite the overall poor prognosis of pancreatic cancer there is heterogeneity in clinical courses of tumors not assessed by conventional risk stratification. This yields the need of additional markers for proper assessment of prognosis and multimodal clinical management. We provide a proof of concept study evaluating the feasibility of Matrix-assi...

Background: The prognostic implication of mutant KRAS (mKRAS) among patients with primary disease in the rectum remains unknown. Methods: From 2000 to 2018, patients undergoing hepatectomy for colorectal liver metastases at 10 collaborating international institutions with documented KRAS status were surveyed. Results: A total of 834 (65.8%) pa...

Introduction Mutations in the BRAF proto-oncogene have been shown to predict poor patient survival following curative-intent liver surgery for metastatic colorectal cancer. The aim of the present systematic review and meta-analysis is to evaluate the effect of mutated BRAF status (mutBRAF) on the overall (OS) and disease-free survival (DFS) in thes...

Background Although the value of RAS mutation status in predicting long-term outcomes in patients with colorectal liver metastases (CRLM) is widely accepted, the magnitude of its impact has recently been challenged by three large cohort studies. The aim of this meta-analysis is to reevaluate the impact of RAS mutations on Overall Survival (OS) and...

Introduction Two novel clinical risk scores (CRS) that incorporate KRAS mutation status (modified CRS (mCRS) and GAME score) were developed. However, they have not been tested in large national and international cohorts. The aim of this study was to validate the prognostic discrimination utility and determine the clinical usefulness of the two nove...

Background and Objectives Despite the long‐standing consensus on the importance of tumor size, tumor number and carcinoembryonic antigen (CEA) levels as predictors of long‐term outcomes among patients with colorectal liver metastases (CRLM), optimal prognostic cut‐offs for these variables have not been established. Methods Patients who underwent c...

Background Two-stage hepatectomy (TSH) is an important tool in the management of bilateral colorectal liver metastases (CRLM). This study sought to examine the presentation, management, and outcomes of patients completing TSH in major hepatobiliary centers in the United States (US).MethodsA retrospective review from five liver centers in the US ide...

Background Although the prognostic relevance of KRAS status in metastatic colorectal cancer (CRC) depends on tumor laterality, this relationship is largely unknown in non‐metastatic CRC. Methods Patients who underwent resection for non‐metastatic CRC between 2000 and 2018 were identified from institutional databases at six academic tertiary center...

Background: Although the prognostic relevance of KRAS status in metastatic colorectal cancer (CRC) depends on tumor laterality, this relationship is largely unknown in non-metastatic CRC. Methods: Patients who underwent resection for non-metastatic CRC between 2000 and 2018 were identified from institutional databases at six academic tertiary cent...

Importance: In patients who undergo surgery for colorectal cancer liver metastases (CRLM), a number of somatic mutations have been associated with worse overall (OS) and recurrence-free survival (RFS). Although useful, an association with prognosis does not necessarily equate to an impact on surgical management. Objective: The aim of this review...

Background: Lymph node staging of ductal adenocarcinoma of the pancreatic head (PDAC) by cross-sectional imaging is limited. The aim of this study was to determine the diagnostic accuracy of expanded criteria in nodal staging in PDAC patients. Methods: Sixty-six patients with histologically confirmed PDAC that underwent primary surgery were incl...

Background The value of liver resection (LR) for metachronous pancreatic ductal adenocarcinoma (PDAC) metastases remains controversial. However, in light of increasing safety of liver resections, surgery might be a valuable option for metastasized PDAC in selected patients. Methods We performed a retrospective, multicenter study including patients...

Background: Pancreatic cancer remains a fatal disease. Experimental systems are needed for personalized treatment strategies, drug testing and to further understand tumor biology. Cell cultures can serve as an excellent preclinical platform, but their generation remains challenging. Methods: Tumor cells from surgically removed pancreatic ductal...

Purpose To report outcomes of yttrium-90 (⁹⁰Y) radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC). Materials and Methods Retrospective review was performed of 115 patients at 6 tertiary care centers; 92 were treated with resin microspheres (80%), 22 were treated with glass microspheres (19%), and 1 was treated wi...

Purpose: In the era of biological therapy of ulcerative colitis (UC), surgical treatment frequently consists of colectomy, end ileostomy, and rectal stump closure before patients go on towards restorative proctocolectomy. We aimed to evaluate possible risk factors for the occurrence of postoperative complications and investigate those after initia...

Pancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive malignancies, and the majority of patients with PDAC present with metastatic disease, mainly in the liver, at the time of diagnosis. Surgical resection is the only treatment that can offer prolonged survival and possible cure. However, the indications for surgery for pati...

Two-stage hepatectomy (TSH) was introduced in 2000 and has since then been widely adopted, as it can offer a chance for cure in patients who are deemed otherwise unresectable. Over time, surgical strategy has evolved and in its current form, the future liver remnant (FLR) is first cleared of disease with minor (wedge or anatomical) resections or ab...

Objective: To evaluate the influence of consensus guidelines on the management of intraductal papillary mucinous neoplasms (IPMN) and the subsequent changes in pathologic outcomes. Background: Over time, multiple guidelines have been developed to identify high-risk IPMN. We hypothesized that the development and implementation of guidelines shoul...

Objective: To examine the prognostic impact of tumor laterality in colon cancer liver metastases (CLM) after stratifying by Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutational status. Background: Although some studies have demonstrated that patients with CLM from a right sided (RS) primary cancer fare worse, others have found equivoca...

Surgical resection is the mainstay of treatment for intrahepatic cholangiocarcinoma (ICC) and generally offers a 5-year overall survival probability of approximately 15–40%. However, approximately 70% of patients will recur, the majority of them within 2 years from surgery. As such, patient selection and the addition of adjuvant and/or neoadjuvant...

Background: FOLFIRINOX is a standard treatment for metastatic pancreatic cancer patients. The effectiveness of neoadjuvant FOLFIRINOX in patients with borderline resectable pancreatic cancer (BRPC) remains debated. Methods: We performed a systematic review and patient-level meta-analysis on neoadjuvant FOLFIRINOX in patients with BRPC. Studies w...

Enhanced recovery after surgery or 'fast-track' methods are evidence-based protocols designed to standardize post-operative medical care, improve patient outcomes, promote early recovery, and reduce healthcare expenditure. Fast-track surgery is a multifunctional concept involving pre-, peri- and post-operative measures aiming to reduce the length o...

Background: A major response to pre-hepatectomy chemotherapy has been associated with improved survival in patients who undergo resection of colorectal liver metastases (CRLM). However, the role of tumor biology, as exemplified by overall and codon-specific KRAS mutational status, in predicting response to chemotherapy is not well defined. Method...

Background Multiple tumor foci of intrahepatic cholangiocarcinoma (ICC) are often considered a contra-indication for resection. We sought to define long-term outcomes after resection of ICC in patients with multiple foci. Methods Patients who underwent resection for ICC between 1990 and 2017 were identified from 12 major HPB centers. Outcomes of p...

Current evidence cannot support denying metastasectomy in otherwise resectable patients solely based on their overall KRAS or BRAF mutational status. The combination of KRAS or BRAF mutational status with certain clinicopathologic characteristics has defined groups of patients who may not derive benefit from metastasectomy, but external validation...

Background: Progression of colorectal liver metastasis (CRLM) on preoperative chemotherapy has been associated with a worse prognosis compared with patients who have responsive disease. Defining response can be challenging as traditional criteria largely assess only tumor size. Methods: Patients who underwent hepatectomy between 2010 and 2017 we...

Objective: The purpose of this study is to determine preoperative factors that are predictive of malignancy in patients undergoing pancreatic resection for intraductal papillary mucinous neoplasms (IPMN). Summary background data: IPMN of the pancreas may be precursor lesions to pancreatic cancer (PC) and represent a target for early diagnosis or...

Objective The aim of this study was to examine if the prognostic significance of margin status in hepatectomy for colorectal cancer liver metastasis (CRLM) varies for different levels of tumor burden because hepatectomy indications for CRLM have been recently expanded to include patients with a higher tumor burden in whom achieving an R0 resection...

Background/aim: Radiofrequency ablation (RFA) is thought to result in inferior prognosis than hepatic resection among patients with colorectal liver metastasis (CRLM). However, resection plus RFA may be an option for patients with a large number of tumors (≥4 liver lesions) and borderline resectability. Materials and methods: A total of 717 pati...

Introduction: Investigation into right and left-sided primary colon liver metastasis (CLM) has revealed differences in the tumor biology and prognosis. This indicates that preoperative and operative factors may affect outcomes of right-sided primary CLM differently than left. This retrospective analysis investigated the effects of resection margin...

Background An azoxymethane/dextran sulfate sodium (AOM/DSS) protocol has been developed for the induction in an animal model of the precancerous stages of colitis-associated carcinogenesis, by modification of the established (AOM/DSS protocol for carcinogenesis. Methods Female C57BL6 mice were treated with a single intraperitoneal dose (10 mg/kg o...

Background and Objectives In contrast with sporadic colorectal cancer liver metastases (CRLM), inflammatory bowel disease (IBD)‐related CRLM have not been studied to date. Methods Patients who underwent resection for IBD‐related and sporadic CRLM from 2000 to 2015 were identified from an international registry and matched for pertinent prognostic...

In Reply We thank Moretto et al for their interest in our study.¹ As the authors correctly suspected, only a small fraction of the patient population (7 patients) received preoperative fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI); the introduction of this regimen is a fairly recent development that is not well represented in ou...

Objective: Minimally invasive techniques are the gold standard in surgery. Since conventional laparoscopic approach has been widely adopted, surgeons in their effort to further improve their skills passed to the era of the robotic assistance. The widespread adoption of robotics has led to the inevitable usage of robotic technology both in simple,...

Histone modification that occurs through the process of acetylation plays a key role in the epigenetic regulation of gene expression. The balance between histone deacetylases (HDACs) and histone acetyltransferases controls this process. Histone deacetylase inhibitors (HDACIs) can induce cancer cell cycle arrest, differentiation and cell death, redu...

Background: While several prognostic models have been developed to predict long-term outcomes in resectable intrahepatic cholangiocarcinoma (ICC), their prognostic discrimination remains limited. The addition of tumor markers might improve the prognostic power of the classification schemas proposed by the AJCC 8th edition and the Liver Cancer Stud...

Importance BRAF mutations are reportedly associated with aggressive tumor biology. However, in contrast with primary colorectal cancer, the association of V600E and non-V600E BRAF mutations with survival and recurrence after resection of colorectal liver metastases (CRLM) has not been well studied. Objective To investigate the prognostic associati...

Background: While previously believed to be mutually exclusive, concomitant mutation of Kirsten rat sarcoma viral oncogene homolog (KRAS)- and V-raf murine sarcoma b-viral oncogene homolog B1 (BRAF)-mutated colorectal carcinoma (CRC), has been described in rare instances and been associated with advanced-stage disease. The present case series is t...

Background: The role of CD40/CD40L in carcinogenesis is widely examined. The mechanisms linking the CD40/CD40L system and the soluble form of CD40 ligand (sCD40L) with neoplasia are nowadays a topic of intensive research. CD40L and sCD40L belong to the TNF superfamily and are molecules with a proinflammatory role. A variety of cells express CD40L...

Background This study sought to develop a clinical risk score for resectable colorectal liver metastasis (CRLM) by combining clinicopathological and clinically available biological indicators, including KRAS. Methods A cohort of patients who underwent resection for CRLM at the Johns Hopkins Hospital (JHH) was analysed to identify independent predi...

Prognostic significance of volumetric tumor burden: Compare with traditional morphologic characters.