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Varvarousis DN, Marini AA, Ntritsos G, Barbouti A, Kitsoulis PV, Kanavaros PE. Relationship of lymphatic vessel invasion and density with clinicopathological parameters and survival in patients with gastric carcinoma: A systematic review and meta-analysis. Pathol Res Pract 2025; 269:155877. [PMID: 40024076 DOI: 10.1016/j.prp.2025.155877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2025] [Revised: 02/16/2025] [Accepted: 02/27/2025] [Indexed: 03/04/2025]
Abstract
The purpose of this study was to conduct a comprehensive review and meta-analysis to investigate the possible relationship of lymphatic vessel invasion (LVI) and lymphatic vessel density (LVD), evaluated using immunohistochemistry, with survival and clinicopathological parameters in patients with gastric carcinoma. The principal result of this meta-analysis was the statistically significant correlation between LVI and presence of lymph node metastasis. This finding, in view of previous data showing that lymph node metastasis is associated with decreased survival, suggests that LVI may be a negative prognostic factor in gastric carcinoma. In contrast, LVD, whether assessed overall, intratumorally, or peritumorally, showed no statistically significant correlation with survival. The major conclusion of this meta-analysis is that LVI is an important indicator of aggressiveness of gastric carcinomas and may be a negative prognostic factor because of the strong association between LVI and presence of lymph node metastasis.
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Affiliation(s)
| | - Aikaterini A Marini
- Laboratory of Anatomy-Histology-Embryology, Medical School, University of Ioannina, Greece
| | - Georgios Ntritsos
- Department of Economics, University of Ioannina, University Campus, Ioannina, Greece; Department of Informatics and Telecommunications, School of Informatics & Telecommunications, University of Ioannina, Arta, Greece
| | - Alexandra Barbouti
- Laboratory of Anatomy-Histology-Embryology, Medical School, University of Ioannina, Greece
| | - Panagiotis V Kitsoulis
- Laboratory of Anatomy-Histology-Embryology, Medical School, University of Ioannina, Greece
| | - Panagiotis E Kanavaros
- Laboratory of Anatomy-Histology-Embryology, Medical School, University of Ioannina, Greece
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Ren XC, Liang P. Preoperative prediction of microvascular/nerve invasion in locally advanced gastric cancer by differentiation and enhanced CT features. Medicine (Baltimore) 2024; 103:e40816. [PMID: 39686419 PMCID: PMC11651431 DOI: 10.1097/md.0000000000040816] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2023] [Accepted: 11/15/2024] [Indexed: 12/18/2024] Open
Abstract
The purpose of the article is to determine whether differentiation and enhanced CT features can preoperatively predict microvascular/nerve invasion in locally advanced gastric cancer. Retrospective analysis of the CT and pathological data of 325 patients with locally advanced gastric cancer confirmed by pathology in our hospital from July 2011 to August 2023. The patient's age, gender, tumor location, T stage, N stage, TNM stage, differentiation, Lauren classification, as well as tumor thickness, tumor longest diameter, plain CT value, arterial CT value, venous CT value, arterial phase enhancement rate, and venous phase enhancement rate were assessed. This study included a total of 325 patients with locally advanced gastric cancer and 189 patients (58.15%) with microvascular/nerve invasion. The results of the univariate analysis showed that gender, location, T stage, N stage, TNM stage, differentiation, Lauren classification, tumor thickness, and longest diameter of the tumor were associated with microvascular/nerve invasion (P < .05). Multivariate analysis suggested that TNM stage and differentiation were independent risk factors for microvascular/nerve invasion. The receiver operating characteristic analysis showed that the diagnostic efficacy of the combined parameter of TNM stage and differentiation was better than that of the single parameter, in which area under the curve, sensitivity, and specificity were 0.819 (95%CI: 0.770-0.867), 66.7%, and 83.8%, respectively. Differentiation and enhanced CT are helpful in predicting whether microvascular/nerve invasion occurs in locally advanced gastric cancer before operation, especially the combined parameters of TNM stage and differentiation.
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Affiliation(s)
- Xiu-Chun Ren
- Department of Ultrasonography, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China
| | - Pan Liang
- Department of Radiology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China
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Özcan P, Çarkman MS. The relationship between the Prognostic Nutritional Index and lymphovascular and perineural invasion of the tumor in patients diagnosed with gastric cancer, and its effect on overall survival. Medicine (Baltimore) 2024; 103:e40087. [PMID: 39432609 PMCID: PMC11495739 DOI: 10.1097/md.0000000000040087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Accepted: 09/26/2024] [Indexed: 10/23/2024] Open
Abstract
A low Prognostic Nutritional Index (PNI) value, lymphovascular invasion (LVI), and perineural invasion (PeNI) have been identified as indicators of poor prognosis for many malignancies. We aimed to evaluate the relationship between PNI and LVI/PeNI, their prognostic significance, and their effect on overall survival in gastric cancer patients who underwent curative gastrectomy. A cutoff value of 39.8 was taken for the PNI, and PNI < 39.8 was defined as moderate to severe malnutrition. Patients were grouped as PNI-low (PNI < 39.8) and PNI-high (PNI ≥ 39.8). Paraffin-embedded tissue sections of surgical specimens were used to evaluate PeNI as defined by previously reported criteria. The study included 270 patients with ages ranging from 23 to 90 years. The mean PNI was calculated as 39.8 ± 6.35. PeNI was detected in 232 patients (85.93%), and LVI was identified in 248 patients (91.85%). It was observed that the PNI value of patients with an expired status in the PNI < 39.8 group was lower compared to those who survived, and in patients with PNI > 39.8, those without PeNI had better survival. The presence of PeNI in patients with PNI > 39.8 increased the mortality risk by 2.088 units, while in patients with PNI > 39.8, it was found that those without LVI had better survival, and the presence of LVI increased the mortality risk by 3.171 units. Mortality developed in 166 patients (61.48%) during the five-year follow-up period. The five-year overall survival was found to be 31.02 ± 21.73 months. In patients with gastric cancer, the PNI, LVI, and PeNI are independent prognostic factors for overall survival in postoperative patients. A low PNI score is an inherently poor prognostic factor. In patients with a high PNI score, the presence of positive LVI and PeNI negatively impacts survival. We found that in patients with a low PNI, the rates of PeNI and LVI are higher compared to those with a high PNI, and this significantly affects mortality.
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Affiliation(s)
- Pırıltı Özcan
- Department of General Surgery, Istanbul University, Cerrahpaşa Faculty of Medicine, Istanbul, Turkey
| | - Mehmet Sinan Çarkman
- Department of General Surgery, Istanbul University, Cerrahpaşa Faculty of Medicine, Istanbul, Turkey
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Yue C, Xue H. Construction and validation of a nomogram model for lymph node metastasis of stage II-III gastric cancer based on machine learning algorithms. Front Oncol 2024; 14:1399970. [PMID: 39439953 PMCID: PMC11493538 DOI: 10.3389/fonc.2024.1399970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2024] [Accepted: 09/17/2024] [Indexed: 10/25/2024] Open
Abstract
Background Gastric cancer, a pervasive malignancy globally, often presents with regional lymph node metastasis (LNM), profoundly impacting prognosis and treatment options. Existing clinical methods for determining the presence of LNM are not precise enough, necessitating the development of an accurate risk prediction model. Objective Our primary objective was to employ machine learning algorithms to identify risk factors for LNM and establish a precise prediction model for stage II-III gastric cancer. Methods A study was conducted at Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine between May 2010 and December 2022. This retrospective study analyzed 1147 surgeries for gastric cancer and explored the clinicopathological differences between LNM and non-LNM cohorts. Utilizing univariate logistic regression and two machine learning methodologies-Least absolute shrinkage and selection operator (LASSO) and random forest (RF)-we identified vascular invasion, maximum tumor diameter, percentage of monocytes, hematocrit (HCT), and lymphocyte-monocyte ratio (LMR) as salient factors and consolidated them into a nomogram model. The area under the receiver operating characteristic (ROC) curve (AUC), calibration curves, and decision curves were used to evaluate the test efficacy of the nomogram. Shapley Additive Explanation (SHAP) values were utilized to illustrate the predictive impact of each feature on the model's output. Results Significant differences in tumor characteristics were discerned between LNM and non-LNM cohorts through appropriate statistical methods. A nomogram, incorporating vascular invasion, maximum tumor diameter, percentage of monocytes, HCT, and LMR, was developed and exhibited satisfactory predictive capabilities with an AUC of 0.787 (95% CI: 0.749-0.824) in the training set and 0.753 (95% CI: 0.694-0.812) in the validation set. Calibration curves and decision curves affirmed the nomogram's predictive accuracy. Conclusion In conclusion, leveraging machine learning algorithms, we devised a nomogram for precise LNM risk prognostication in stage II-III gastric cancer, offering a valuable tool for tailored risk assessment in clinical decision-making.
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Affiliation(s)
| | - Huiping Xue
- Department of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Gercek O, Senkol M, Yazar VM, Topal K. The Effect of Lymphovascular Invasion on Short-Term Tumor Recurrence and Progression in Stage T1 Bladder Cancer. Cureus 2024; 16:e54844. [PMID: 38533164 PMCID: PMC10964124 DOI: 10.7759/cureus.54844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/24/2024] [Indexed: 03/28/2024] Open
Abstract
Introduction Lymphovascular invasion (LVI) is the most important stage for tumor spread and metastasis. The role of LVI in transurethral resection is not yet clear. In this study, the progression and recurrences of patients who underwent transurethral resection bladder tumor (TUR-BT) and T1 high-grade tumor and concomitant LVI were detected in pathology results and were evaluated. Methods Our study included 58 patients, who underwent TUR-BT with the suspicion of bladder cancer and were pathologically diagnosed with T1 stage bladder cancer and who did not undergo radical surgery, in the Urology Clinic of Afyonkarahisar Health Sciences University, Turkey. The patient's age, gender, tumor size, tumor grade, presence of LVI, second resection, recurrence, and progression rates at three months and one year were compared. Results LVI was detected in the pathology specimens of nine (15.5%) of the 58 patients who were included in the study. When the one-year progression was evaluated, progression to T2 tumor was detected in six (66.7%) patients in the group with LVI and five (10.2%) patients in the group without LVI, and the progression was significantly higher in the group with LVI (p=0.001). In logistic regression analysis, the only significant predictor for one-year progression was the presence of LVI (p=0.001). Conclusion According to the results of our study, the presence of LVI in the pathology specimens of patients with T1 high grade significantly increases the progression. Suggesting radical cystectomy and neoadjuvant chemotherapy to patients with LVI in the early period seems to be a more accurate approach, considering the course of the disease.
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Affiliation(s)
- Osman Gercek
- Urology, Afyonkarahisar Health Sciences University, Afyonkarahisar, TUR
| | - Melih Senkol
- Urology, Afyonkarahisar Health Sciences University, Afyonkarahisar, TUR
| | - Veli Mert Yazar
- Urology, Afyonkarahisar Health Sciences University, Afyonkarahisar, TUR
| | - Kutay Topal
- Urology, Afyonkarahisar State Hospital, Afyonkarahisar, TUR
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Wang G, Otto CC, Heij LR, Al-Masri TM, Dahl E, Heise D, Olde Damink SWM, Luedde T, Lang SA, Ulmer TF, Neumann UP, Bednarsch J. Impact of Altered Body Composition on Clinical and Oncological Outcomes in Intrahepatic Cholangiocarcinoma. J Clin Med 2023; 12:7747. [PMID: 38137817 PMCID: PMC10744221 DOI: 10.3390/jcm12247747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 12/07/2023] [Accepted: 12/13/2023] [Indexed: 12/24/2023] Open
Abstract
Intrahepatic cholangiocarcinoma is a common primary liver tumor with limited treatment options and poor prognosis. Changes in body composition (BC) have been shown to affect the prognosis of various types of tumors. Therefore, our study aimed to investigate the correlation between BC and clinical and oncological outcomes in patients with iCCA. All patients with iCCA who had surgery from 2010 to 2022 at our institution were included. We used CT scans and 3D Slicer software to assess BC and conducted logistic regressions as well as Cox regressions and Kaplan-Meier analyses to investigate associations between BC and clinical variables with focus on postoperative complications and oncological outcomes. BC was frequently altered in iCCA (n = 162), with 53.1% of the patients showing obesity, 63.2% sarcopenia, 52.8% myosteatosis, 10.1% visceral obesity, and 15.3% sarcopenic obesity. The multivariate analysis showed no meaningful association between BC and perioperative complications. Myosteatosis was associated with reduced overall survival (OS) in iCCA patients (myosteatosis vs. non-myosteatosis, 7 vs. 18 months, p = 0.016 log rank). Further, the subgroup analysis revealed a notable effect in the subset of R0-resected patients (myosteatosis vs. non-myosteatosis, 18 vs. 32 months, p = 0.025) and patients with nodal metastases (myosteatosis vs. non-myosteatosis, 7 vs. 18 months, p = 0.016). While altered BC is not associated with perioperative outcomes in iCCA, myosteatosis emerges as a prognostic factor for reduced OS in the overall and sub-populations of resected patients.
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Affiliation(s)
- Guanwu Wang
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, 52074 Aachen, Germany; (G.W.); (C.C.O.); (L.R.H.); (T.M.A.-M.); (D.H.); (S.A.L.); (T.F.U.); (U.P.N.)
| | - Carlos C. Otto
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, 52074 Aachen, Germany; (G.W.); (C.C.O.); (L.R.H.); (T.M.A.-M.); (D.H.); (S.A.L.); (T.F.U.); (U.P.N.)
- Department of Surgery and Transplantation, University Hospital Essen, 45147 Essen, Germany
| | - Lara R. Heij
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, 52074 Aachen, Germany; (G.W.); (C.C.O.); (L.R.H.); (T.M.A.-M.); (D.H.); (S.A.L.); (T.F.U.); (U.P.N.)
- Department of Surgery and Transplantation, University Hospital Essen, 45147 Essen, Germany
| | - Tarick M. Al-Masri
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, 52074 Aachen, Germany; (G.W.); (C.C.O.); (L.R.H.); (T.M.A.-M.); (D.H.); (S.A.L.); (T.F.U.); (U.P.N.)
- University of Applied Science Aachen, 52066 Aachen, Germany
| | - Edgar Dahl
- Institute of Pathology, University Hospital RWTH Aachen, 52074 Aachen, Germany;
| | - Daniel Heise
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, 52074 Aachen, Germany; (G.W.); (C.C.O.); (L.R.H.); (T.M.A.-M.); (D.H.); (S.A.L.); (T.F.U.); (U.P.N.)
- Department of Surgery and Transplantation, University Hospital Essen, 45147 Essen, Germany
| | - Steven W. M. Olde Damink
- Department of Surgery, Maastricht University Medical Centre (MUMC), 6229 HX Maastricht, The Netherlands;
| | - Tom Luedde
- Department of Gastroenterology, Hepatology and Infectious Diseases, Heinrich Heine University Duesseldorf, 40225 Duesseldorf, Germany;
| | - Sven A. Lang
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, 52074 Aachen, Germany; (G.W.); (C.C.O.); (L.R.H.); (T.M.A.-M.); (D.H.); (S.A.L.); (T.F.U.); (U.P.N.)
- Department of Surgery and Transplantation, University Hospital Essen, 45147 Essen, Germany
| | - Tom F. Ulmer
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, 52074 Aachen, Germany; (G.W.); (C.C.O.); (L.R.H.); (T.M.A.-M.); (D.H.); (S.A.L.); (T.F.U.); (U.P.N.)
| | - Ulf P. Neumann
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, 52074 Aachen, Germany; (G.W.); (C.C.O.); (L.R.H.); (T.M.A.-M.); (D.H.); (S.A.L.); (T.F.U.); (U.P.N.)
- Department of Surgery and Transplantation, University Hospital Essen, 45147 Essen, Germany
- Department of Surgery, Maastricht University Medical Centre (MUMC), 6229 HX Maastricht, The Netherlands;
| | - Jan Bednarsch
- Department of Surgery and Transplantation, University Hospital RWTH Aachen, 52074 Aachen, Germany; (G.W.); (C.C.O.); (L.R.H.); (T.M.A.-M.); (D.H.); (S.A.L.); (T.F.U.); (U.P.N.)
- Department of Surgery and Transplantation, University Hospital Essen, 45147 Essen, Germany
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Rich BS, Dicken BJ, Billmire DF, Weil BR, Ross J, Fallahazad N, Krailo M, Shaikh F, Frazier AL, Hazard FK, Nuño MM. Characterizing Lymphovascular Invasion in Pediatric and Adolescent Malignant Ovarian Nongerminomatous Germ Cell Tumors: A Report from the Children's Oncology Group. J Pediatr Surg 2023; 58:2399-2404. [PMID: 37699777 PMCID: PMC10872999 DOI: 10.1016/j.jpedsurg.2023.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Revised: 08/11/2023] [Accepted: 08/15/2023] [Indexed: 09/14/2023]
Abstract
BACKGROUND Lymphovascular invasion (LVI) has been identified as a poor prognostic factor for a variety of tumors; however, its significance in malignant ovarian germ cell tumors (MOGCT) in pediatric and adolescent patients is not well described. We aim to clarify the significance of LVI in the subset of patients with nongerminomatous MOGCT. METHODS Records of patients 0-20 years of age with MOGCT enrolled on Children's Oncology Group study AGCT0132 were reviewed. Patients with documented presence or absence of LVI in either institutional or central review pathology reports were included. RESULTS Of 130 patients with MOGCTs, 83 patients had of the presence or absence of LVI documented in their pathology report. 42/83 patients (50.6%) were found to have LVI present. The estimated odds of having LVI was higher in patients with stage II and III disease, 11 years and older and with the presence of choriocarcinoma. Event-free survival (EFS) and overall survival (OS) remained high in patients with LVI. Approximately 50% of patients with a documented LVI status in either institutional pathology report or central review were found to have LVI. CONCLUSIONS The presence of LVI was higher in tumors with adverse risk factors including higher stage and age greater than 11 years. While LVI was not associated with EFS or OS in the intermediate risk group, further work is necessary to determine the effect of LVI on long-term disease-free survival. We, therefore, recommend routinely incorporating LVI status into institutional pathology reports for pediatric and adolescent patients with MOGCT. LEVEL OF EVIDENCE III.
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Affiliation(s)
- Barrie S Rich
- Division of Pediatric Surgery, Cohen Children's Medical Center, Zucker School of Medicine at Hofstra/Northwell, New Hyde Park, NY, USA.
| | - Bryan J Dicken
- Division of Pediatric Surgery, University of Alberta, Edmonton Canada
| | - Deborah F Billmire
- Division of Pediatric Surgery, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN, USA
| | - Brent R Weil
- Division of Pediatric Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Jonathan Ross
- Department of Urology, Department of Pediatrics, Rush Medical College, Chicago, IL, USA
| | - Negar Fallahazad
- Children's Oncology Group, Public Health Institute, Monrovia, CA, USA
| | - Mark Krailo
- Children's Oncology Group, Public Health Institute, Monrovia, CA, USA; Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA
| | - Furqan Shaikh
- Division of Haematology/Oncology, The Hospital for Sick Children, University of Toronto, Toronto, Canada
| | - A Lindsay Frazier
- Dana-Farber/Boston Children's Cancer and Blood Disorders Center Harvard Medical School, Boston, MA, USA
| | - Florette K Hazard
- Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA
| | - Michelle M Nuño
- Children's Oncology Group, Public Health Institute, Monrovia, CA, USA; Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA
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Wehrle CJ, Seavey CN, Chang J, Stackhouse K, Woo K, Augustin T, Joyce D, Simon R, Walsh RM, Naffouje SA. Neoadjuvant Gastric Score: How Response to Neoadjuvant Chemotherapy Affects Overall Survival and Adjuvant Benefit. Ann Surg Oncol 2023; 30:7240-7250. [PMID: 37659978 DOI: 10.1245/s10434-023-14259-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 08/22/2023] [Indexed: 09/04/2023]
Abstract
INTRODUCTION The Neoadjuvant Rectal score (NAR) was developed as a short-term surrogate for 5-year overall survival (OS) prediction in locally advanced rectal cancer on the basis of response to neoadjuvant therapy. We aim to assess whether this score can be repurposed for locally advanced gastric adenocarcinoma treated with neoadjuvant chemotherapy followed by surgical resection. METHODS Patients with gastric adenocarcinoma treated with neoadjuvant systemic therapy followed by surgical resection were extracted from the National Cancer Database. Neoadjuvant Gastric (NAG) scores were calculated, and patients were stratified into low-, intermediate-, and high-score categories, with low scores predicting longer survival. Patients were propensity-matched 1:1:1 between the groups for OS comparison. We also matched patients within each group 1:1 per receipt of adjuvant therapy and compared 5-year OS. RESULTS There were 2,970 patients identified. NAG classified patients into low- (n = 396, 13.3%), intermediate-(n = 756, 25.5%), and high (n = 1818, 61.2%) groups. After propensity matching, 5-year OS was significantly different between the matched groups (low-NAG 82%, intermediate-NAG 73%, and high-NAG 39%; p < 0.001). NAG score grouping also predicted OS benefit of adjuvant therapy; low- and intermediate-NAG patients had no OS benefit with adjuvant therapy (86% vs. 84%; p = 0.492, and 77% vs. 74%; p = 0.382, respectively), whereas patients with high-NAG score had a 5-year OS benefit with adjuvant therapy (39% vs. 29%; p = 0.024). CONCLUSION NAR score may be repurposed to generate a prognostic tool in gastric adenocarcinoma to predict 5-year OS and has the potential to guide decision-making regarding allocation of adjuvant therapy. Further studies should prospectively validate these findings to confirm clinical utility.
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Affiliation(s)
- Chase J Wehrle
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA.
| | - Caleb N Seavey
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Jenny Chang
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA
| | | | - Kimberly Woo
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Toms Augustin
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Daniel Joyce
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Robert Simon
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - R Matthew Walsh
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA
| | - Samer A Naffouje
- Department of General Surgery, Cleveland Clinic Foundation, Cleveland, OH, USA
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Guo Q, Sun Q, Bian X, Wang M, Dong H, Yin H, Dai X, Fan G, Chen G. Development and validation of a multiphase CT radiomics nomogram for the preoperative prediction of lymphovascular invasion in patients with gastric cancer. Clin Radiol 2023; 78:e552-e559. [PMID: 37117048 DOI: 10.1016/j.crad.2023.03.016] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 03/13/2023] [Accepted: 03/22/2023] [Indexed: 04/30/2023]
Abstract
AIM To develop a nomogram to predict lymphovascular invasion (LVI) in gastric cancer by integrating multiphase computed tomography (CT) radiomics and clinical risk factors. MATERIALS AND METHODS One hundred and seventy-two gastric cancer patients (121 training and 51 validation) with preoperative contrast-enhanced CT images and clinicopathological data were collected retrospectively. The clinical risk factors were selected by univariate and multivariate regression analysis. Radiomic features were extracted and selected from the arterial phase (AP), venous phase (VP), and delayed phase (DP) CT images of each patient. Clinical risk factors, radiomic features, and integration of both were used to develop the clinical model, radiomic models, and nomogram, respectively. RESULTS Radiomic features from AP (n=6), VP (n=6), DP (n=7) CT images and three selected clinical risk factors were used for model development. The nomogram showed better performance than the AP, VP, DP, and clinical models in the training and validation datasets, providing areas under the curves (AUCs) of 0.890 (95% CI: 0.820-0.940) and 0.885 (95% CI:0.765-0.957), respectively. All models indicated good calibration, and decision curve analysis proved that the net benefit of the nomogram was superior to that of the clinical and radiomic models throughout the vast majority of the threshold probabilities. CONCLUSIONS The nomogram integrating multiphase CT radiomics and clinical risk factors showed favourable performance in predicting LVI of gastric cancer, which may benefit clinical practice.
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Affiliation(s)
- Q Guo
- Department of Radiology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China
| | - Q Sun
- Department of Radiology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China
| | - X Bian
- Department of Radiology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China
| | - M Wang
- Department of Radiology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China
| | - H Dong
- Department of Radiology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China
| | - H Yin
- Institute of Advanced Research, Beijing Infervision Technology Co., Ltd, Beijing, China
| | - X Dai
- Department of Pathology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China
| | - G Fan
- Department of Radiology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China
| | - G Chen
- Department of Radiology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China.
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Miratashi Yazdi SA, Nazar E. Evaluation of Lymphovascular Invasion by CD31 Expression in Gastric Adenocarcinoma. IRANIAN JOURNAL OF PATHOLOGY 2023; 18:140-146. [PMID: 37600573 PMCID: PMC10439755 DOI: 10.30699/ijp.2023.562466.2977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 01/12/2023] [Indexed: 08/22/2023]
Abstract
Background & Objective Lymphovascular tumoral invasion is a typical histopathological feature of gastric carcinomas and supports the recognition of high-risk patients for the recurrence. We aimed to study CD31 expression in diverse subtypes of gastric carcinomas and to show its association with the histopathologic findings of the carcinoma to assess the prognosis. Methods This cross-sectional study was conducted on 40 established patients with gastric adenocarcinoma from radical gastrectomy. The patients were classified according to the pathology assessments. Tumoral tissues were assessed by immunohistochemical staining for CD31 expression. Malignant behavior was estimated by histopathological evaluations. Results CD31 positivity was described in 23 (57.5%) of all evaluated patients. In assessment of CD31 expression and tumor features presented, no significant association between the CD31 expression and patients' age, sex, tumor site, size, grade and stage, subtypes of carcinoma, perineural invasion, and also lymphovascular invasion was found. (P>0.05). Conclusion Lymphovascular invasion may make valuable additional evidence and may be useful to detect gastric carcinoma patients at high risk for recurrence, who could be candidates for more supplementary therapies. However, in our study, CD31 expression did not show any association with the aggressive histopathologic features of this tumor.
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Affiliation(s)
| | - Elham Nazar
- Department of Pathology, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
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11
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Zhang F, Chen H, Luo D, Xiong Z, Li X, Yin S, Jin L, Chen S, Peng J, Lian L. Lymphovascular or perineural invasion is associated with lymph node metastasis and survival outcomes in patients with gastric cancer. Cancer Med 2023; 12:9401-9408. [PMID: 36952439 PMCID: PMC10166947 DOI: 10.1002/cam4.5701] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 01/11/2023] [Accepted: 02/07/2023] [Indexed: 03/25/2023] Open
Abstract
BACKGROUND Lymphovascular invasion (LVI) and perineural invasion (PNI) are associated with poorer prognosis in several human malignancies, but their significance in gastric cancer (GC) remains to be clearly defined. Our study aimed to investigate the prognostic value of LVI/PNI in patients with curative resected GC. METHODS Records of 1488 patients with stage I--III GC and 3327 patients with stage I-III colorectal cancer (CRC) were reviewed retrospectively, and difference in the incidence of LVI/PNI between GC and CRC was compared. Univariate and multivariate analyses were used to evaluate whether LVI/PNI was an independent risk factor for lymph node metastasis (LNM) and overall survival (OS) in GC. RESULTS Patients with stage I-III GC had a significantly higher incidence of LVI/PNI than patients with stage I-III CRC (50.54% vs. 21.91%, p < 0.001). LVI/PNI was significantly associated with higher CEA, higher CA199, deeper tumor invasion, more lymph node metastasis, and advanced TNM stage in GC ( p < 0.05). Multivariate logistic regression analysis identified LVI/PNI (OR = 2.64, 95%CI: 2.05-3.40, p < 0.001) as an independent risk factor for LNM in GC. The OS rate was significantly lower in the LVI/PNI-positive GC group than that in the LVI/PNI-negative GC group ( p < 0.001). On multivariate Cox regression analysis, LVI/PNI (HR = 1.34, 95%CI: 1.04-1.71, p = 0.023) was an independent prognostic factor for OS in GC. CONCLUSION GC has a high incidence of LVI/PNI, which was closely associated with disease progression. LVI/PNI could serve as an independent risk factor for LNM and the prognosis of patients with curative resected GC. These findings will be helpful in predicting survival outcomes more accurately and establishing individualized treatment plans.
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Affiliation(s)
- Fengxiang Zhang
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Huaxian Chen
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Dandong Luo
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Zhizhong Xiong
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xianzhe Li
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shi Yin
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Longyang Jin
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Shi Chen
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Junsheng Peng
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Lei Lian
- Department of Gastrointestinal Surgery, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
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12
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Predictive Value of Inflammatory and Nutritional Indexes in the Pathology of Bladder Cancer Patients Treated with Radical Cystectomy. Curr Oncol 2023; 30:2582-2597. [PMID: 36975410 PMCID: PMC10047817 DOI: 10.3390/curroncol30030197] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 02/15/2023] [Accepted: 02/17/2023] [Indexed: 02/24/2023] Open
Abstract
In recent years, the focus of numerous studies has been the predictive value of inflammatory and nutritional parameters in oncology patients. The aim of our study was to examine the relationship between the inflammatory and nutritional parameters and the histopathological characteristics of patients with bladder cancer. A retrospective study included 491 patients who underwent radical cystectomy for bladder cancer between 2017 and 2021. We calculated the preoperative values of the neutrophil-to-lymphocyte ratio (NLR), the derived neutrophil-to-lymphocyte ratio (dNLR), the systemic immune-inflammation index (SII), the systemic inflammatory response index (SIRI), the platelet-to-lymphocyte ratio (PLR), the lymphocyte-to-monocyte ratio (LMR), the prognostic nutritional index (PNI), and the geriatric nutritional risk index (GNRI). Statistically significant positive correlations were observed between NLR, dNLR, SII, SIRI, and PLR and the pathological stage of the tumor. We observed statistically significant inverse correlations for LMR, PNI, and GNRI with the tumor stage. SIRI was identified as an independent predictor of the presence of LVI. dNLR was identified as an independent predictor of positive surgical margins. GNRI was identified as an independent predictor of the presence of metastases in the lymph nodes. We noticed the predictive value of SIRI, dNLR, and GNRI in the pathology of bladder cancer patients.
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Hao D, Li Q, Feng QX, Qi L, Liu XS, Arefan D, Zhang YD, Wu S. SurvivalCNN: A deep learning-based method for gastric cancer survival prediction using radiological imaging data and clinicopathological variables. Artif Intell Med 2022; 134:102424. [PMID: 36462894 DOI: 10.1016/j.artmed.2022.102424] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 09/15/2022] [Accepted: 10/07/2022] [Indexed: 12/13/2022]
Abstract
Radiological images have shown promising effects in patient prognostication. Deep learning provides a powerful approach for in-depth analysis of imaging data and integration of multi-modal data for modeling. In this work, we propose SurvivalCNN, a deep learning structure for cancer patient survival prediction using CT imaging data and non-imaging clinical data. In SurvivalCNN, a supervised convolutional neural network is designed to extract volumetric image features, and radiomics features are also integrated to provide potentially different imaging information. Within SurvivalCNN, a novel multi-thread multi-layer perceptron module, namely, SurvivalMLP, is proposed to perform survival prediction from censored survival data. We evaluate the proposed SurvivalCNN framework on a large clinical dataset of 1061 gastric cancer patients for both overall survival (OS) and progression-free survival (PFS) prediction. We compare SurvivalCNN to three different modeling methods and examine the effects of various sets of data/features when used individually or in combination. With five-fold cross validation, our experimental results show that SurvivalCNN achieves averaged concordance index 0.849 and 0.783 for predicting OS and PFS, respectively, outperforming the compared state-of-the-art methods and the clinical model. After future validation, the proposed SurvivalCNN model may serve as a clinical tool to improve gastric cancer patient survival estimation and prognosis analysis.
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Affiliation(s)
- Degan Hao
- Intelligent Systems Program, University of Pittsburgh, Pittsburgh, PA 15260, USA
| | - Qiong Li
- Department of Radiology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, PR China
| | - Qiu-Xia Feng
- Department of Radiology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, PR China
| | - Liang Qi
- Department of Radiology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, PR China
| | - Xi-Sheng Liu
- Department of Radiology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, PR China
| | - Dooman Arefan
- Department of Radiology, University of Pittsburgh, Pittsburgh, PA, 15260, USA
| | - Yu-Dong Zhang
- Department of Radiology, the First Affiliated Hospital with Nanjing Medical University, Nanjing, PR China.
| | - Shandong Wu
- Intelligent Systems Program, University of Pittsburgh, Pittsburgh, PA 15260, USA; Department of Radiology, University of Pittsburgh, Pittsburgh, PA, 15260, USA; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15260, USA; Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, 15260, USA.
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14
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A novel partial duplication in OPHN1, associated with vermis cerebellar hypoplasia, seizures and developmental delay. GENE REPORTS 2022. [DOI: 10.1016/j.genrep.2022.101590] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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15
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Li Q, Feng QX, Qi L, Liu C, Zhang J, Yang G, Zhang YD, Liu XS. Prognostic aspects of lymphovascular invasion in localized gastric cancer: new insights into the radiomics and deep transfer learning from contrast-enhanced CT imaging. Abdom Radiol (NY) 2022; 47:496-507. [PMID: 34766197 DOI: 10.1007/s00261-021-03309-z] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Revised: 10/03/2021] [Accepted: 10/04/2021] [Indexed: 12/24/2022]
Abstract
OBJECTIVES Lymphovascular invasion (LVI) is a factor significantly impacting treatment and outcome of patients with gastric cancer (GC). We aimed to investigate prognostic aspects of a preoperative LVI prediction in GC using radiomics and deep transfer learning (DTL) from contrast-enhanced CT (CECT) imaging. METHODS A total of 1062 GC patients (728 training and 334 testing) between Jan 2014 and Dec 2018 undergoing gastrectomy were retrospectively included. Based on CECT imaging, we built two gastric imaging (GI) markers, GI-marker-1 from radiomics and GI-marker-2 from DTL features, to decode LVI status. We then integrated demographics, clinical data, GI markers, radiologic interpretation, and biopsies into a Gastric Cancer Risk (GRISK) model for predicting LVI. The performance of GRISK model was tested and applied to predict survival outcomes in GC patients. Furthermore, the prognosis between LVI (+) and LVI (-) patients was compared in chemotherapy and non-chemotherapy cohorts, respectively. RESULTS GI-marker-1 and GI-marker-2 yield similar performance in predicting LVI in training and testing dataset. The GRISK model yields the diagnostic performance with AUC of 0.755 (95% CI 0.719-0.790) and 0.725 (95% CI 0.669-0.781) in training and testing dataset. Patients with LVI (+) trend toward lower progression-free survival (PFS) and overall survival (OS). The difference of prognosis between LVI (+) and LVI (-) was more noticeable in non-chemotherapy than that in chemotherapy group. CONCLUSION Radiomics and deep transfer learning features on CECT demonstrate potential power for predicting LVI in GC patients. Prospective use of a GRISK model can help to optimize individualized treatment decisions and predict survival outcomes.
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Affiliation(s)
- Qiong Li
- Department of Radiology, the First Affiliated Hospital With Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210000, Jiangsu, China
| | - Qiu-Xia Feng
- Department of Radiology, the First Affiliated Hospital With Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210000, Jiangsu, China
| | - Liang Qi
- Department of Radiology, the First Affiliated Hospital With Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210000, Jiangsu, China
| | - Chang Liu
- Department of Radiology, the First Affiliated Hospital With Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210000, Jiangsu, China
| | - Jing Zhang
- Shanghai Key Laboratory of Magnetic Resonance, East China Normal University, Shanghai, 200062, China
| | - Guang Yang
- Shanghai Key Laboratory of Magnetic Resonance, East China Normal University, Shanghai, 200062, China
| | - Yu-Dong Zhang
- Department of Radiology, the First Affiliated Hospital With Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210000, Jiangsu, China.
| | - Xi-Sheng Liu
- Department of Radiology, the First Affiliated Hospital With Nanjing Medical University, No. 300, Guangzhou Road, Nanjing, 210000, Jiangsu, China.
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16
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Fixing the GAP: the role of RhoGAPs in cancer. Eur J Cell Biol 2022; 101:151209. [DOI: 10.1016/j.ejcb.2022.151209] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 01/29/2022] [Accepted: 02/08/2022] [Indexed: 12/12/2022] Open
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Liu J, Zhang Y, Li S, Sun F, Wang G, Wei D, Yang T, Gu S. Androgen deprivation‑induced OPHN1 amplification promotes castration‑resistant prostate cancer. Oncol Rep 2021; 47:3. [PMID: 34738630 PMCID: PMC8600397 DOI: 10.3892/or.2021.8214] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 09/27/2021] [Indexed: 11/20/2022] Open
Abstract
Androgen deprivation therapy (ADT) is used to treat prostate cancer (PCa). However, ADT may increase the expression of androgen receptor (AR) through the amplification of chromosome X. The gene oligophrenin 1 (OPHN1) is located in the same region as the AR gene, which could be amplified by ADT. Thus, the role of OPHN1 in PCa pathology was investigated. The expression status of OPHN1 in PCa was searched in The Cancer Genome Atlas (TCGA) database. Androgen-sensitive cells LNCaP and 22RV1 were cultured under ADT conditions, and then the expression of OPHN1 was evaluated by northern blotting. The expression of OPHN1 was enhanced or knocked down in LNCaP and 22RV1 cells by transfection. Subsequently, the LNCaP and 22RV1 cells were cultured under ADT, and the viability rate, apoptosis, and migration of cells were assessed by MTT, flow cytometry, and Transwell assay respectively. The expression of OPHN1 was also enhanced or knocked down in androgen-insensitive PC3 cells, and then the effects of OPHN1 on the viability, apoptosis, and migration of PC3 cells were assessed. A mouse xenograft model was created by injecting LNCaP cells with OPHN1 overexpression subcutaneously, and the tumor growth rates were monitored. In TCGA database, amplification of the OPHN1 gene was observed in the PCa tumors. ADT increased the expression of OPHN1 in LNCaP and 22RV1 cells (P<0.05). OPHN1 could promote resistance of LNCaP and 22RV1 cells to ADT by promoting cell survival and preventing their apoptosis (P<0.05). In addition, OPHN1 contributed to cell viability (P<0.05) and enhanced the migration ability in LNCaP, 22RV1 and PC3 cells (P<0.05). In the mouse model, the PCa xenograft with OPHN1 overexpression had a higher growth rate and was more resistant to the ADT condition (P<0.05). In summary, ADT induced the overexpression of OPHN1 in PCa, which facilitated PCa cell survival and promoted PCa progression.
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Affiliation(s)
- Junjiang Liu
- Department of Urology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China
| | - Yunxia Zhang
- Department of Obstetrics and Gynecology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China
| | - Shoubin Li
- Department of Urology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China
| | - Fuzhen Sun
- Department of Urology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China
| | - Gang Wang
- Department of Urology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China
| | - Dong Wei
- Department of Urology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China
| | - Tao Yang
- Department of Urology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China
| | - Shouyi Gu
- Department of Urology, Hebei General Hospital, Shijiazhuang, Hebei 050051, P.R. China
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Lin JX, Wang ZK, Huang YQ, Xie JW, Wang JB, Lu J, Chen QY, Cao LL, Lin M, Tu RH, Huang ZN, Lin JL, Zheng HL, Zheng CH, Huang CM, Li P. Clinical Relevance of Splenic Hilar Lymph Node Dissection for Proximal Gastric Cancer: A Propensity Score-Matching Case-Control Study. Ann Surg Oncol 2021; 28:6649-6662. [PMID: 33768400 DOI: 10.1245/s10434-021-09830-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Accepted: 02/19/2021] [Indexed: 12/17/2022]
Abstract
BACKGROUND The application of splenic hilar lymph node (no. 10 LN) dissection (no. 10 LND) for proximal gastric cancer (PGC) remains controversial. This study aimed to investigate the clinical relevance of no. 10 LND from the perspective of long-term survival. METHODS The main study population included 995 previously untreated patients who underwent laparoscopic radical total gastrectomy between January 2008 and December 2014. Of these 995 patients, 564 underwent no. 10 LND (no. 10D+ group) and the remaining 431 patients did not (no. 10D- group). Propensity score-matching was applied to reduce the effects of confounding factors. The study end points were overall survival (OS) and disease-free survival (DFS). Additionally, 39 patients who received neoadjuvant chemotherapy during the same period also were included as a separate population for analysis. RESULTS The metastasis rate for no. 10 LN was 10.5 % (59/564). No significant differences were observed in intra- and postoperative complications nor in mortality between the no. 10D+ and no. 10D- groups (all P > 0.05). After 1:1 matching, the two groups were comparable in clinicopathologic characteristics. The no. 10D+ group had significantly better survival than the no. 10D- group (5-year OS: 63.3 % vs 52.2 %, P = 0.003; 5-year DFS: 60.4 % vs 48.1 %, P = 0.013). For the patients who received neoadjuvant chemotherapy, the 5-year OS rates in the no. 10D+ and no. 10D- groups were respectively 50.6 % and 31.3 % (P = 0.150) and the 5-year DFS rates were respectively 51.5 % and 31.3 % (P = 0.123). CONCLUSIONS Patients with untreated PGC may achieve the benefit of long-term survival from no. 10 LND. For patients with PGC who undergo neoadjuvant chemotherapy, no. 10 LND may not bring survival benefits. However, further validation with a large-sample study is needed.
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Affiliation(s)
- Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Zu-Kai Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Ying-Qi Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Jia-Bin Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
| | - Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Long-Long Cao
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Mi Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Ru-Hong Tu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Ze-Ning Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Ju-Li Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Hua-Long Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China.
- Key Laboratory of Ministry of Education of Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
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Ji XK, Madhurapantula SV, He G, Wang KY, Song CH, Zhang JY, Wang KJ. Genetic variant of cyclooxygenase-2 in gastric cancer: More inflammation and susceptibility. World J Gastroenterol 2021; 27:4653-4666. [PMID: 34366627 PMCID: PMC8326261 DOI: 10.3748/wjg.v27.i28.4653] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/17/2021] [Accepted: 07/02/2021] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer accounts for the majority cancer-related deaths worldwide. Although various methods have considerably improved the screening, diagnosis, and treatment of gastric cancer, its incidence is still high in Asia, and the 5-year survival rate of advanced gastric cancer patients is only 10%-20%. Therefore, more effective drugs and better screening strategies are needed for reducing the incidence and mortality of gastric cancer. Cyclooxygenase-2 (COX-2) is considered to be the key inducible enzyme in prostaglandins (PGs) synthesis, which is involved in multiple pathways in the inflammatory response. For example, inflammatory cytokines stimulate innate immune responses via Toll-like receptors and nuclear factor-kappa B to induce COX-2/PGE2 pathway. In these processes, the production of an inflammatory microenvironment promotes the occurrence of gastric cancer. Epidemiological studies have also indicated that non-steroidal anti-inflammatory drugs can reduce the risk of malignant tumors of the digestive system by blocking the effect of COX-2. However, clinical use of COX-2 inhibitors to prevent or treat gastric cancer may be limited because of potential side effects, especially in the cardiovascular system. Given these side effects and low treatment efficacy, new therapeutic approaches and early screening strategies are urgently needed. Some studies have shown that genetic variation in COX-2 also play an important role in carcinogenesis. However, the genetic variation analysis in these studies is incomplete and isolated, pointing out only a few single nucleotide polymorphisms (SNPs) and the risk of gastric cancer, and no comprehensive study covering the whole gene region has been carried out. In addition, copy number variation (CNV) is not mentioned. In this review, we summarize the SNPs in the whole COX-2 gene sequence, including exons, introns, and both the 5' and 3' untranslated regions. Results suggest that COX-2 does not increase its expression through the CNV and the SNPs in COX-2 may serve as the potential marker to establish risk stratification in the general population. This review synthesizes emerging insights of COX-2 as a biomarker in multiple studies, summarizes the association between whole COX-2 sequence variation and susceptibility to gastric cancer, and discusses the future prospect of therapeutic intervention, which will be helpful for early screening and further research to find new approaches to gastric cancer treatment.
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Affiliation(s)
- Xuan-Ke Ji
- College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Key Laboratory of Tumor Epidemiology of Henan Province, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Sailaja Vatsalya Madhurapantula
- College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Key Laboratory of Tumor Epidemiology of Henan Province, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Gui He
- College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Key Laboratory of Tumor Epidemiology of Henan Province, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Kun-Yan Wang
- College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Key Laboratory of Tumor Epidemiology of Henan Province, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Chun-Hua Song
- College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Key Laboratory of Tumor Epidemiology of Henan Province, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Jian-Ying Zhang
- College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Key Laboratory of Tumor Epidemiology of Henan Province, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Kai-Juan Wang
- College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Key Laboratory of Tumor Epidemiology of Henan Province, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou 450001, Henan Province, China
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Liu J, Li H, Zhou P, Cai T, Tang Z, Wang Y, Cui Y, Sun Y, Wang X. Reevaluation of lymphovascular invasion in gastric cancer using endothelial markers D2-40 and EVG: Enhanced detection, better predictor of lymph node metastasis and biological aggressiveness. J Surg Oncol 2021; 123:1736-1741. [PMID: 33772776 DOI: 10.1002/jso.26468] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Accepted: 03/12/2021] [Indexed: 11/09/2022]
Abstract
BACKGROUND AND OBJECTIVES The diagnosis of lymphovascular invasion (LVI) is often inaccurate with routine histology. This study aimed to evaluate the use of immunohistochemistry (IHC) in detecting LVI and reevaluate the clinical implications of LVI in gastric cancer. METHODS This prospective unrandomized cohort study analyzed the rates of LVI positivity and its relevance with other clinicopathologic features. RESULTS Between November 2017 and April 2018, 558 patients undergoing curative gastrectomy were enrolled and assigned to the IHC group (n = 285) and hematoxylin-eosin group (n = 273). The use of IHC increased the rates of LVI positivity (60.8% vs. 43.3%, p < .001) and decreased the rates of undetermined LVI subtype (7.7% vs. 27.1%, p < .001). The LVI-negative patients identified by IHC had fewer lymph node metastases (16.8% vs. 34.6%, p = .002) and earlier pathological stage (p = .004) than those identified by routine histology. The LVI-positive patients identified by IHC had a higher percentage of perineural invasion (p = .019). CONCLUSIONS The use of endothelial markers significantly enhanced the detection of LVI. The LVI detected by IHC could be a better predictor of lymph node metastasis and biological aggressiveness in gastric cancer.
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Affiliation(s)
- Jingdong Liu
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Haojie Li
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Peng Zhou
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Tianyi Cai
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Zhaoqing Tang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yan Wang
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yuehong Cui
- Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Yihong Sun
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Xuefei Wang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
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Tan E, Lam S, Han SP, Storey D, Sandroussi C. Perioperative outcomes and survival in elderly patients aged ≥ 75 years undergoing gastrectomy for gastric cancer: an 18-year retrospective analysis in a single Western centre. Langenbecks Arch Surg 2021; 406:1057-1069. [PMID: 33770264 DOI: 10.1007/s00423-021-02116-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Accepted: 02/03/2021] [Indexed: 11/25/2022]
Abstract
PURPOSE Surgical resection for elderly patients with gastric cancer is controversial. This study aims to evaluate the preoperative features and postoperative short- and long-term outcomes of elderly patients following surgical resection for gastric adenocarcinoma. METHODS Between January 2000 and May 2018, a total of 177 consecutive patients underwent curative gastrectomy for gastric adenocarcinoma was retrospectively reviewed. Propensity score matching (PSM) analysis was used to balance confounding covariates between the elderly and non-elderly groups. Clinicopathological characteristics, intraoperative characteristics, postoperative complications and long-term survival outcomes including overall survival (OS) and Disease Specific Survival (DSS) were compared and analysed using the Kaplan-Meier log-rank test. Multivariate cox proportional hazards regression analysis of clinicopathological factors influencing survival were evaluated. RESULTS There were 50 patients in the elderly group (age ≥ 75 years) and 127 patients in the non-elderly group (age < 75 years). Elderly patients had more comorbid conditions (p < 0.001), lower albumin concentration (p = 0.034), lower haemoglobin levels (p = 0.001), and poorer renal function (p = 0.043). TNM stage was similar between both groups (p = 0.174); however, lymphatic invasion (p = 0.006) and lymph node metastasis (p = 0.029) were higher in the elderly group. Elderly patients were much less likely to receive any chemo- (p < 0.001) or radiotherapy treatment (p = 0.007) with surgical treatment. After PSM, there were 50 patients in each group. Elderly patients were more likely to develop complications (Clavien Dindo ≥ 2: 50% vs. 26%, p = 0.003). The most common postoperative complications were pneumonia (12% vs. 6%, p = 0.498) and delirium (10% vs. 0%, p = 0.066). Elderly patients had a longer median length of hospital stay (median (IQR): 15.6(9.5) vs. 11.3 (9.9), p = 0.030). There were no differences in 30-day mortality (elderly vs. non-elderly: 1% vs. 1%, p = 0.988). Before and after PSM, age remains an independent predictor of postoperative complications. Before PSM, the estimated mean OS for the elderly and non-elderly patients were 108 months (95%CI, 72.5-143.5) and 143 months (95%CI, 123.0-163.8), respectively (p = 0.264). After PSM, the estimated mean OS for the elderly and non-elderly patients were 108 months (95%CI, 72.5-143.5) and 140 months (95%CI, 112.1-168.2), respectively, (p = 0.360). Before PSM, the estimated mean DSS for the elderly and non-elderly patients were 94 months (95%CI, 61.9-127.5) and 121 months (95%CI, 100.9-141.0), respectively (p = 0.405). After PSM, the estimated mean DSS for the elderly and non-elderly patients were 94 months (95%CI, 61.9-127.5) and 115 months (95%CI, 87.3-143.3), respectively (p = 0.721). Age was not an independent predictor of mortality following gastrectomy for gastric cancer in both PSM matched and unmatched cohort. CONCLUSION Chronological age alone is not a contraindication to curative resection of gastric adenocarcinoma in elderly patients with acceptable risk. Whilst age affects perioperative complications, the incidence of postoperative mortality and overall survival were not significantly different between elderly and non-elderly gastric cancer patients treated with curative surgery. Gastrectomy with D2 lymphadenectomy can also be performed in carefully selected elderly patients by surgeons with expertise in gastric resection along with appropriate perioperative management.
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Affiliation(s)
- Elinor Tan
- Department of Upper Gastrointestinal Surgery, Royal Prince Alfred Hospital, 50 Missenden Road, Camperdown, New South Wales, 2050, Australia.
- Surgical Outcomes Research Centre (SOuRCe), The University of Sydney, Sydney, New South Wales, 2006, Australia.
- Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, 2006, Australia.
| | - Susanna Lam
- Department of Upper Gastrointestinal Surgery, Royal Prince Alfred Hospital, 50 Missenden Road, Camperdown, New South Wales, 2050, Australia
- Surgical Outcomes Research Centre (SOuRCe), The University of Sydney, Sydney, New South Wales, 2006, Australia
| | - Shew Phyo Han
- Department of Upper Gastrointestinal Surgery, Royal Prince Alfred Hospital, 50 Missenden Road, Camperdown, New South Wales, 2050, Australia
| | - David Storey
- Department of Upper Gastrointestinal Surgery, Royal Prince Alfred Hospital, 50 Missenden Road, Camperdown, New South Wales, 2050, Australia
- Surgical Outcomes Research Centre (SOuRCe), The University of Sydney, Sydney, New South Wales, 2006, Australia
- Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, 2006, Australia
| | - Charbel Sandroussi
- Department of Upper Gastrointestinal Surgery, Royal Prince Alfred Hospital, 50 Missenden Road, Camperdown, New South Wales, 2050, Australia
- Surgical Outcomes Research Centre (SOuRCe), The University of Sydney, Sydney, New South Wales, 2006, Australia
- Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, 2006, Australia
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22
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Zhao B, Lu H, Luo R, Bao S, Mei D, Xu H, Huang B. Different clinicopathologic features and prognostic significance of signet ring cell histology in early and locally advanced gastric cancer patients. Clin Res Hepatol Gastroenterol 2021; 45:101454. [PMID: 32505731 DOI: 10.1016/j.clinre.2020.05.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 04/30/2020] [Accepted: 05/01/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Although many studies have evaluated the prognostic significance of signet ring cell (SRC) histology for gastric cancer (GC) patients, the results were conflicting. The objective of this study was to compare clinicopathologic characteristics between SRC type and other types, and evaluate its impact on survival outcome. METHODS We retrospectively reviewed clinicopathologic and survival data of 1891 patients who underwent curative resection for GC. All patients were divided into differentiated, undifferentiated and SRC type according to the histological classification. The prognostic differences between different types were compared and clinicopathologic factors were analyzed. RESULTS SRC histology type had a poorer disease-free survival (DFS) than differentiated type (5-year DFS, 37.7% vs 52.2%, P<0.001), but there was no prognostic difference between SRC type and undifferentiated type (37.7% vs 41.9%, P>0.05). For early GC patients, SRC type was more frequent in younger, female patients and T1a stage tumors; the 5-year DFS of SRC type was similar to that of any other histology type (P>0.05). SRC type showed more aggressive biological features, including extensive stomach involvement, large tumor size, advanced pTstage and pN stage, than other types for locally advanced GC patients; poorer DFS was observed in SRC type compared with differentiated type. Multivariate analysis indicated that SRC type (HR:1.71, 95%CI:1.10-1.68, P<0.01) and undifferentiated type (HR:1.21, 95%CI:1.04-1.40, P<0.05) were independently associated with poor DFS in locally advanced GC patients. CONCLUSION There was a significant difference between early and locally advanced GC patients with regard to clinicopathologic features and prognostic significance of SRC histology. SRC type was an independent prognostic factor for locally advanced GC patients, but not for early GC patients.
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Affiliation(s)
- Bochao Zhao
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, 110001 Shenyang, People's Republic of China
| | - Huiwen Lu
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, 110001 Shenyang, People's Republic of China
| | - Rui Luo
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, 110001 Shenyang, People's Republic of China
| | - Shiyang Bao
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, 110001 Shenyang, People's Republic of China
| | - Di Mei
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, 110001 Shenyang, People's Republic of China
| | - Huimian Xu
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, 110001 Shenyang, People's Republic of China
| | - Baojun Huang
- Department of Surgical Oncology, First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, 110001 Shenyang, People's Republic of China.
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Meng Y, Huang X, Liu J, Chen J, Bu Z, Wu G, Xie W, Jeen F, Huang L, Tian C, Mo X, Tang W. A Novel Nomogram for Individually Predicting of Vascular Invasion in Gastric Cancer. Technol Cancer Res Treat 2021; 20:15330338211004924. [PMID: 33929914 PMCID: PMC8111553 DOI: 10.1177/15330338211004924] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 01/22/2021] [Accepted: 02/25/2021] [Indexed: 02/03/2023] Open
Abstract
PURPOSE Vascular invasion (VI) is associated with recurrence and is an indicator of poor prognosis in gastric cancer (GC). Pre-operative identification of VI may guide the selection of the optimal surgical approach and assess the requirement for neoadjuvant therapy. METHODS A total of 271 patients were retrospectively collected and randomly allocated into the training and validation datasets. The least absolute shrinkage and selection operator regression model was used to select potentially relevant features, and multivariable logistic regression analysis was used to develop the nomogram. RESULTS The nomogram consisted of pre-operative serum complement C3 levels, duration of symptoms, pre-operative computed tomography stage, abdominal distension and undifferentiated carcinoma. The nomogram provided good calibration for both the training and the validation set, with area under the curve values of 0.792 and 0.774. Decision curve analysis revealed that the nomogram was clinically useful. CONCLUSION The present study constructed a nomogram for the pre-operative prediction of VI in patients with GC. The nomogram may aid the identification of high-risk patients and aid the optimization of pre-operative decision-making.
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Affiliation(s)
- Yongsheng Meng
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Xiaoliang Huang
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Jungang Liu
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Jianhong Chen
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Zhaoting Bu
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Guo Wu
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Weishun Xie
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Franco Jeen
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Lingxu Huang
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Chao Tian
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Xianwei Mo
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
| | - Weizhong Tang
- Division of Colorectal & Anal Surgery, Department of Gastrointestinal Surgery, Guangxi Medical University Cancer Hospital, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
- Guangxi Clinical Research Center for Colorectal Cancer, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China
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Jiang B, Zhou L, Lu J, Wang Y, Guo J. Predictors of lymph node metastasis and residual tumor in early gastric cancer patients after noncurative endoscopic resection: a systematic review and meta-analysis. Therap Adv Gastroenterol 2020; 13:1756284820935033. [PMID: 32636929 PMCID: PMC7313346 DOI: 10.1177/1756284820935033] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 05/25/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND It is challenging to identify the prevalence of lymph node metastasis (LNM) and residual tumor in patients with early gastric cancer (EGC) who underwent noncurative endoscopic resection (ER). This present meta-analysis was aimed to establish imperative potential predictive factors in order to select the optimal treatment method. METHODS A systematic literature search of PubMed, Embase, and Cochrane Library databases was performed through 1 February 2019 to identify relevant studies, which investigated risk factors for LNM and residual tumor in patients with EGC who underwent noncurative ER. Eligible data were systematically reviewed through a meta-analysis. RESULTS Overall, 12 studies investigating the risk factor of LNM were included, totaling 3015 patients, 7 of which also involved cancer residues. After the present meta-analysis, six predictors, including tumor size >30 mm, tumor invasion depth (⩾500 μm from the muscularis mucosae), macroscopic appearance, undifferentiated histopathological type, positive vertical margin, and presence of lymphovascular invasion (including lymphatic invasion and vascular invasion) were significantly associated with LNM, whereas tumor size >30 mm, positive horizontal margin, and positive vertical margin were identified as significant predictors for the risk of residual tumor. No evidence of publication bias was observed. CONCLUSIONS Six and three variables were established as significant risk factors for LNM and residual tumor in patients with EGC who underwent noncurative ER, respectively. Patients with EGC who present these risk factors after noncurative ER are strongly suggested to receive additional surgery, while others might be suitable for strict follow-up. This might shed some new light on the selection of follow-up treatment for noncurative ER.
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Affiliation(s)
- Bolun Jiang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Li Zhou
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Lu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yizhi Wang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Lymphatic Invasion Might Be Considered as an Upstaging Factor in N0 and N1 Gastric Cancer. J Clin Med 2020; 9:jcm9051275. [PMID: 32354156 PMCID: PMC7287765 DOI: 10.3390/jcm9051275] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 04/14/2020] [Accepted: 04/26/2020] [Indexed: 02/06/2023] Open
Abstract
(Background) The aim of this study was to investigate the prognostic impact of lymphatic invasion in gastric cancer, focusing on survival differences between N stage groups. (Methods) A total of 398 consecutive patients who underwent curative gastrectomy for primary gastric adenocarcinoma from January 2006 to December 2015 were analyzed retrospectively using data from a prospectively collected registry database. We compared various clinicopathological features and survival differences between lymphatic invasion-positive and -negative groups. (Results) Of the 398 patients, 141 (35.4%) showed lymphatic invasion. The lymphatic invasion-positive subgroup had poorer prognosis than the lymphatic invasion-negative subgroup in N0 (five-year survival rate: 87.8% vs. 73.6%, p = 0.048) and N1 (87.2% vs. 50%, p = 0.007) stage patients. The odds ratio (OR) of lymphatic invasion to five-year survival rate was 2.078 (95% confidence interval (CI), 1.103-3.916; p = 0.024). The presence of lymphatic invasion had worse effect on survival than age (OR, 1.807; 95% CI, 1.024-2.242; p = 0.029) or tumor depth (OR, 1.286; 95% CI, 1.078-1.897; p = 0.013) in N0 and N1 stage patients. The overall survival of patients with lymphatic invasion was not different from that of patients at a one-higher N stage without lymphatic invasion at any N stage. (Conclusions) The presence of lymphatic invasion may be the most important independent prognostic factor in N0 and N1 gastric cancer and might be an upstaging factor of N stage at any N stage. Therefore, in addition to the number of metastasized lymph nodes, the presence of lymphatic invasion should be included in N stage determination.
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Chen X, Yang Z, Yang J, Liao Y, Pang P, Fan W, Chen X. Radiomics analysis of contrast-enhanced CT predicts lymphovascular invasion and disease outcome in gastric cancer: a preliminary study. Cancer Imaging 2020; 20:24. [PMID: 32248822 PMCID: PMC7132895 DOI: 10.1186/s40644-020-00302-5] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Accepted: 03/06/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND To determine whether radiomics features based on contrast-enhanced CT (CECT) can preoperatively predict lymphovascular invasion (LVI) and clinical outcome in gastric cancer (GC) patients. METHODS In total, 160 surgically resected patients were retrospectively analyzed, and seven predictive models were constructed. Three radiomics predictive models were built from radiomics features based on arterial (A), venous (V) and combination of two phase (A + V) images. Then, three Radscores (A-Radscore, V-Radscore and A + V-Radscore) were obtained. Another four predictive models were constructed by the three Radscores and clinical risk factors through multivariate logistic regression. A nomogram was developed to predict LVI by incorporating A + V-Radscore and clinical risk factors. Kaplan-Meier curve and log-rank test were utilized to analyze the outcome of LVI. RESULTS Radiomics related to tumor size and intratumoral inhomogeneity were the top-ranked LVI predicting features. The related Radscores showed significant differences according to LVI status (P < 0.01). Univariate logistic analysis identified three clinical features (T stage, N stage and AJCC stage) and three Radscores as LVI predictive factors. The Clinical-Radscore (namely, A + V + C) model that used all these factors showed a higher performance (AUC = 0.856) than the clinical (namely, C, including T stage, N stage and AJCC stage) model (AUC = 0.810) and the A + V-Radscore model (AUC = 0.795) in the train cohort. For patients without LVI and with LVI, the median progression-free survival (PFS) was 11.5 and 8.0 months (P < 0.001),and the median OS was 20.2 and 17.0 months (P = 0.3), respectively. In the Clinical-Radscore-predicted LVI absent and LVI present groups, the median PFS was 11.0 and 8.0 months (P = 0.03), and the median OS was 20.0 and 18.0 months (P = 0.05), respectively. N stage, LVI status and Clinical-Radscore-predicted LVI status were associated with disease-specific recurrence or mortality. CONCLUSIONS Radiomics features based on CECT may serve as potential markers to successfully predict LVI and PFS, but no evidence was found that these features were related to OS. Considering that it is a single central study, multi-center validation studies will be required in the future to verify its clinical feasibility.
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Affiliation(s)
- Xiaofeng Chen
- Department of Radiology, Meizhou People's Hospital, Meizhou, Guangdong, 514031, People's Republic of China
| | - Zhiqi Yang
- Department of Radiology, Meizhou People's Hospital, Meizhou, Guangdong, 514031, People's Republic of China
| | - Jiada Yang
- Department of Radiology, Meizhou People's Hospital, Meizhou, Guangdong, 514031, People's Republic of China
| | - Yuting Liao
- GE Healthcare, Guangzhou, Guangdong, People's Republic of China, 510623
| | - Peipei Pang
- GE Healthcare, Hangzhou, Zhejiang, People's Republic of China, 311100
| | - Weixiong Fan
- Department of Radiology, Meizhou People's Hospital, Meizhou, Guangdong, 514031, People's Republic of China
| | - Xiangguang Chen
- Department of Radiology, Meizhou People's Hospital, Meizhou, Guangdong, 514031, People's Republic of China.
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Fujita K, Kanda M, Ito S, Mochizuki Y, Teramoto H, Ishigure K, Murai T, Asada T, Ishiyama A, Matsushita H, Tanaka C, Kobayashi D, Fujiwara M, Murotani K, Kodera Y. Association between Lymphovascular Invasion and Recurrence in Patients with pT1N+ or pT2–3N0 Gastric Cancer: a Multi-institutional Dataset Analysis. J Gastric Cancer 2020; 20:41-49. [PMID: 32269843 PMCID: PMC7105418 DOI: 10.5230/jgc.2020.20.e3] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Revised: 11/19/2019] [Accepted: 12/16/2019] [Indexed: 11/20/2022] Open
Abstract
Purpose Patients with pathological stage T1N+ or T2–3N0 gastric cancer may experience disease recurrence following curative gastrectomy. However, the current Japanese Gastric Cancer Treatment Guidelines do not recommend postoperative adjuvant chemotherapy for such patients. This study aimed to identify the prognostic factors for patients with pT1N+ or pT2–3N0 gastric cancer using a multi-institutional dataset. Materials and Methods We retrospectively analyzed the data obtained from 401 patients with pT1N+ or pT2–3N0 gastric cancer who underwent curative gastrectomy at 9 institutions between 2010 and 2014. Results Of the 401 patients assessed, 24 (6.0%) experienced postoperative disease recurrence. Multivariate analysis revealed that age ≥70 years (hazard ratio [HR], 2.62; 95% confidence interval [CI], 1.09–7.23; P=0.030) and lymphatic and/or venous invasion (lymphovascular invasion (LVI): HR, 7.88; 95% CI, 1.66–140.9; P=0.005) were independent prognostic factors for poor recurrence-free survival. There was no significant association between LVI and the site of initial recurrence. Conclusions LVI is an indicator of poor prognosis in patients with pT1N+ or pT2–3N0 gastric cancer.
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Affiliation(s)
- Keizo Fujita
- Department of Surgery, Ichinomiya Municipal Hospital, Ichinomiya, Japan
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Mitsuro Kanda
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Seiji Ito
- Department of Gastroenterological Surgery, Aichi Cancer Center, Nagoya, Japan
| | | | - Hitoshi Teramoto
- Department of Surgery, Yokkaichi Municipal Hospital, Yokkaichi, Japan
| | | | - Toshifumi Murai
- Department of Surgery, Ichinomiya Municipal Hospital, Ichinomiya, Japan
| | - Takahiro Asada
- Department of Surgery, Gifu Prefectural Tajimi Hospital, Tajimi, Japan
| | | | | | - Chie Tanaka
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Daisuke Kobayashi
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Michitaka Fujiwara
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Kenta Murotani
- Biostatistics Center, Graduate School of Medicine, Kurume University, Kurume, Japan
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan
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Lin JX, Wang ZK, Wang W, Desiderio J, Xie JW, Wang JB, Lu J, Chen QY, Cao LL, Lin M, Tu RH, Zheng CH, Li P, Parisi A, Zhou ZW, Huang CM. Risk factors of lymph node metastasis or lymphovascular invasion for early gastric cancer: a practical and effective predictive model based on international multicenter data. BMC Cancer 2019; 19:1048. [PMID: 31694573 PMCID: PMC6836519 DOI: 10.1186/s12885-019-6147-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2018] [Accepted: 09/10/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Most lymph node metastasis (LNM) models for early gastric cancer (EGC) include lymphovascular invasion (LVI) as a predictor. However, LVI must be confirmed by postoperative pathology. In this study, we aimed to develop a model for predicting the risk of LNM/LVI in EGC using preoperative factors. METHODS EGC patients who underwent radical gastrectomy at Fujian Medical University Union Hospital and Sun Yat-sen University Cancer Center (n = 1460) were selected as the training set. The risk factors of LNM/LVI were investigated. Data from the International study group on Minimally Invasive surgery for GASTRIc Cancer trial (n = 172) were selected as the validation set. RESULTS In the training set, the incidence of LNM/LVI was 21.6%. The 5-year cancer-specific survival rates of patients with and without LNM/LVI were 92.4 and 95.0%, respectively, with significant difference (P = 0.030). Multivariable logistic regression analysis showed that the four independent risk factors for LNM/LVI were female, tumor larger than 20 mm, submucosal invasion and undifferentiated tumor histological type (all P < 0.05); the area under the curve (AUC) was 0.694 (95% confidence interval [CI]: 0.659-0.730). Patients were divided into low-risk, intermediate-risk, high-risk and extremely high-risk groups by recursive partitioning analysis; the incidences of LNM/LVI were 5.4, 12.6, 24.2 and 37.8%, respectively (P < 0.001). The AUC of the validation set was 0.796 (95%CI, 0.662-0.851) and the predictive performance of the LNM/LVI risk in the validation set was consistent with that in the training set. CONCLUSIONS The risk of LNM/LVI in differentiated mucosal EGC is low, which indicated that endoscopic resection is a treatment option. The risk of LNM/LVI in undifferentiated mucosal EGC and submucosa EGC are high and gastrectomy with lymph node dissection is suggested.
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Affiliation(s)
- Jian-Xian Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, People's Republic of China
| | - Zu-Kai Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, People's Republic of China
| | - Wei Wang
- Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China
| | - Jacopo Desiderio
- Department of Digestive Surgery, St. Mary's Hospital, University of Perugia, 05100, Terni, Italy
| | - Jian-Wei Xie
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, People's Republic of China
| | - Jia-Bin Wang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, People's Republic of China
| | - Jun Lu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, People's Republic of China
| | - Qi-Yue Chen
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, People's Republic of China
| | - Long-Long Cao
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, People's Republic of China
| | - Mi Lin
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, People's Republic of China
| | - Ru-Hong Tu
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, People's Republic of China
| | - Chao-Hui Zheng
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, People's Republic of China
| | - Ping Li
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, People's Republic of China
| | - Amilcare Parisi
- Department of Digestive Surgery, St. Mary's Hospital, University of Perugia, 05100, Terni, Italy
| | - Zhi-Wei Zhou
- Department of Gastric and Pancreatic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China.
| | - Chang-Ming Huang
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, People's Republic of China.
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Wu ZS, Ding W, Cai J, Bashir G, Li YQ, Wu S. Communication Of Cancer Cells And Lymphatic Vessels In Cancer: Focus On Bladder Cancer. Onco Targets Ther 2019; 12:8161-8177. [PMID: 31632067 PMCID: PMC6781639 DOI: 10.2147/ott.s219111] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 08/07/2019] [Indexed: 12/16/2022] Open
Abstract
Bladder cancer is one of the most commonly diagnosed cancers worldwide and causes the highest lifetime treatment costs per patient. Bladder cancer is most likely to metastasize through lymphatic ducts, and once the lymph nodes are involved, the prognosis is poorly and finitely improved by current modalities. The underlying metastatic mechanism for bladder cancer is thus becoming a research focus to date. To identify relevant published data, an online search of the PubMed/Medline archives was performed to locate original articles and review articles regarding lymphangiogenesis and lymphatic metastasis in urinary bladder cancer (UBC), and was limited to articles in English published between 1998 and 2018. A further search of the clinical trials.gov search engine was conducted to identify both trials with results available and those with results not yet available. Herein, we summarized the unique mechanisms and biomarkers involved in the malignant progression of bladder cancer as well as their emerging roles in therapeutics, and that current data suggests that lymphangiogenesis and lymph node invasion are important prognostic factors for UBC. The growing knowledge about their roles in bladder cancers provides the basis for novel therapeutic strategies. In addition, more basic and clinical research needs to be conducted in order to identify further accurate predictive molecules and relevant mechanisms.
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Affiliation(s)
- Zhang-song Wu
- Medical College, Shenzhen University, Shenzhen518000, People’s Republic of China
- Department of Urological Surgery, The Third Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen518000, People’s Republic of China
- Shenzhen following Precision Medical Institute, The Third Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen518000, People’s Republic of China
| | - Wa Ding
- Medical College, Shenzhen University, Shenzhen518000, People’s Republic of China
- Shenzhen following Precision Medical Institute, The Third Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen518000, People’s Republic of China
| | - Jiajia Cai
- Shenzhen following Precision Medical Institute, The Third Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen518000, People’s Republic of China
- Medical College, Anhui University of Science and Technology, Huainan232001, People’s Republic of China
| | - Ghassan Bashir
- Shenzhen following Precision Medical Institute, The Third Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen518000, People’s Republic of China
| | - Yu-qing Li
- Department of Urological Surgery, The Third Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen518000, People’s Republic of China
- Shenzhen following Precision Medical Institute, The Third Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen518000, People’s Republic of China
| | - Song Wu
- Medical College, Shenzhen University, Shenzhen518000, People’s Republic of China
- Department of Urological Surgery, The Third Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen518000, People’s Republic of China
- Shenzhen following Precision Medical Institute, The Third Affiliated Hospital of Shenzhen University, Shenzhen University, Shenzhen518000, People’s Republic of China
- Medical College, Anhui University of Science and Technology, Huainan232001, People’s Republic of China
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Yang TS, Wang XF, Fairweather M, Sun YH, Mamon HJ, Wang JP. The Survival Benefit From the Addition of Radiation to Chemotherapy in Gastric Cancer Patients Following Surgical Resection. Clin Oncol (R Coll Radiol) 2019; 32:110-120. [PMID: 31570246 DOI: 10.1016/j.clon.2019.09.047] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 07/24/2019] [Accepted: 08/09/2019] [Indexed: 01/18/2023]
Abstract
AIMS The survival benefit of radiation therapy in gastric cancer patients who underwent curative resection remains contentious. MATERIALS AND METHODS Gastric cancer patients who underwent curative resection followed by adjuvant chemotherapy or chemoradiation therapy (CRT) between 2004 and 2014 were identified from the National Cancer Database. Survival analyses were carried out with the Kaplan-Meier method and the Cox regression model. RESULTS In total, 4347 patients were included in this study. Of these patients, 1185 patients received postoperative chemotherapy alone and 3162 patients received postoperative CRT. For all patients included in the analysis, patients who received CRT had significantly better overall survival than those who received chemotherapy alone (5-year overall survival: 54.8% versus 46.8%, P < 0.001). The survival benefit primarily occurred in patients with stage II (5-year overall survival: 58.7% versus 53.8%, P = 0.03), stage III (42.5% versus 30.3%, P < 0.001) and lymph node-positive (5-year overall survival: 52.2% versus 41.9%, P = 0.03) gastric cancer. Multivariable analysis confirmed the improvement in overall survival in patients who received postoperative CRT (hazard ratio = 0.78; 95% confidence interval, 0.661-0.926; P < 0.001) was independent of all known prognostic factors. For lymph node-positive patients with lymphovascular invasion (LVI), postoperative CRT significantly improved overall survival compared with chemotherapy alone (5-year overall survival: 49.0% versus 39.4%, P = 0.001). However, there was no survival difference between CRT and chemotherapy alone if lymph node-positive patients had no LVI (5-year overall survival: 54.5% versus 52.7%, P = 0.55). CONCLUSION The current study suggests that postoperative CRT provides a survival benefit in gastric cancer patients with concurrent lymph node-positive and LVI-positive disease. A randomised clinical trial may further evaluate the benefit of adjuvant CRT in this subgroup.
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Affiliation(s)
- T S Yang
- Department of General Surgery, Shanghai Tenth Peoples' Hospital, Tongji University, Shanghai, China
| | - X F Wang
- Gastric Cancer Center, Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - M Fairweather
- Division of Surgical Oncology, Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA; Gastrointestinal Surgical Center, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts, USA
| | - Y H Sun
- Gastric Cancer Center, Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - H J Mamon
- Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts, USA.
| | - J P Wang
- Division of Surgical Oncology, Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA; Gastrointestinal Surgical Center, Dana-Farber/Brigham and Women's Cancer Center, Boston, Massachusetts, USA.
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Jiang HH, Zhang ZY, Wang XY, Tang X, Liu HL, Wang AL, Li HG, Tang EJ, Lin MB. Prognostic significance of lymphovascular invasion in colorectal cancer and its association with genomic alterations. World J Gastroenterol 2019; 25:2489-2502. [PMID: 31171892 PMCID: PMC6543237 DOI: 10.3748/wjg.v25.i20.2489] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2019] [Revised: 03/27/2019] [Accepted: 04/20/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Lymphovascular invasion (LVI) is suggested to be an early and important step in tumor progression toward metastasis, but its prognostic value and genetic mechanisms in colorectal cancer (CRC) have not been well investigated.
AIM To investigate the prognostic value of LVI in CRC and identify the associated genomic alterations.
METHODS We performed a retrospective analysis of 1219 CRC patients and evaluated the prognostic value of LVI for overall survival by the Kaplan-Meier method and multivariate Cox regression analysis. We also performed an array-based comparative genomic hybridization analysis of 47 fresh CRC samples to examine the genomic alterations associated with LVI. A decision tree model was applied to identify special DNA copy number alterations (DCNAs) for differentiating between CRCs with and without LVI. Functional enrichment and protein-protein interaction network analyses were conducted to explore the potential molecular mechanisms of LVI.
RESULTS LVI was detected in 150 (12.3%) of 1219 CRCs, and the presence was positively associated with higher histological grade and advanced tumor stage (both P < 0.001). Compared with the non-LVI group, the LVI group showed a 1.77-fold (95% confidence interval: 1.40-2.25, P < 0.001) increased risk of death and a significantly lower 5-year overall survival rate (P < 0.001). Based on the comparative genomic hybridization data, 184 DCNAs (105 gains and 79 losses) were identified to be significantly related to LVI (P < 0.05), and the majority were located at 22q, 17q, 10q, and 6q. We further constructed a decision tree classifier including seven special DCNAs, which could distinguish CRCs with LVI from those without it at an accuracy of 95.7%. Functional enrichment and protein-protein interaction network analyses revealed that the genomic alterations related to LVI were correlated with inflammation, epithelial-mesenchymal transition, angiogenesis, and matrix remodeling.
CONCLUSION LVI is an independent predictor for survival in CRC, and its development may correlate with inflammation, epithelial-mesenchymal transition, angiogenesis, and matrix remodeling.
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Affiliation(s)
- Hui-Hong Jiang
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
- Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China
| | - Zhi-Yong Zhang
- Department of General Surgery, Zhuji People’s Hospital of Zhejiang Province, Zhuji 311800, Zhejiang Province, China
| | - Xiao-Yan Wang
- Department of Emergency Surgery, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
| | - Xuan Tang
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
- Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China
| | - Hai-Long Liu
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
| | - Ai-Li Wang
- Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
| | - Hua-Guang Li
- Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
| | - Er-Jiang Tang
- Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
| | - Mou-Bin Lin
- Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
- Institute of Gastrointestinal Surgery and Translational Medicine, Tongji University School of Medicine, Shanghai 200090, China
- Center for Clinical Research and Translational Medicine, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
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Wu L, Liang Y, Zhang C, Wang X, Ding X, Huang C, Liang H. Prognostic significance of lymphovascular infiltration in overall survival of gastric cancer patients after surgery with curative intent. Chin J Cancer Res 2019; 31:785-796. [PMID: 31814682 PMCID: PMC6856698 DOI: 10.21147/j.issn.1000-9604.2019.05.08] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Objective Lymphovascular infiltration (LVI) is frequently detected in gastric cancer (GC) specimens. Studies have revealed that GC patients with LVI have a poorer prognosis than those without LVI. Methods In total, 1,007 patients with curatively resected GC at Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital were retrospectively enrolled. The patients were categorized into two groups based on the LVI status: a positive group (PG; presence of LVI) and a negative group (NG; absence of LVI). The clinicopathological factors corrected with LVI and prognostic variables were analyzed. Additionally, a pathological lymphovascular-node (lvN) classification system was proposed to evaluate the superiority of its prognostic prediction of GC patients compared with that of the eighth edition of the N staging system. Results Two hundred twenty-four patients (22.2%) had LVI. The depth of invasion and lymph node metastasis were independently associated with the presence of LVI. GC patients with LVI demonstrated a significantly lower overall survival (OS) rate than those without LVI (42.8% vs. 68.9%, respectively; P<0.001). In multivariate analysis, LVI was identified as an independent prognostic factor for GC patients (hazard ratio: 1.370; 95% confidence interval: 1.094−1.717; P=0.006). Using strata analysis, significant prognostic differences between the groups were only observed in patients at stage I−IIIa or N0−2. The lvN classification was found to be more appropriate to predict the OS of GC patients after curative surgery than the pN staging system. The −2 log-likelihood of lvN classification (4,746.922) was smaller than the value of pN (4,765.196), and the difference was statistically significant (χ2=18.434, P<0.001).
Conclusions The presence of LVI influences the OS of GC patients at stage I−IIIa or N0−2. LVI should be incorporated into the pN staging system to enhance the accuracy of the prognostic prediction of GC patients.
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Affiliation(s)
- Liangliang Wu
- Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
| | - Yuexiang Liang
- Department of Gastrointestinal Oncology, the First Affiliated Hospital of Hainan Medical University, Haikou 570102, China
| | - Chen Zhang
- Nutritional Department, Tianjin Beichen Hospital, Tianjin 300000, China
| | - Xiaona Wang
- Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
| | - Xuewei Ding
- Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
| | - Chongbiao Huang
- Senior Ward, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
| | - Han Liang
- Department of Gastric Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China
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Arroyo-Martinez Q, Han WH, Eom BW, Yoon HM, Kim YI, Cho SJ, Lee JY, Kim CG, Morales-Conde S, Padillo-Ruiz J, Kook MC, Choi IJ, Kim YW, Ryu KW. The distribution pattern of metastatic lymph nodes after non-curative endoscopic resection in early gastric cancer. J Surg Oncol 2018; 118:1257-1263. [PMID: 30367687 DOI: 10.1002/jso.25279] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Accepted: 09/29/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND OBJECTIVES Additional surgery should be done after non-curative endoscopic resection (ER) in early gastric cancer (EGC) due to the risk of lymph node metastasis (LNM). However, the distribution pattern of LNM in these patients is complicated and unpredictable. The aim of this study is to identify any different distribution patterns of LNM in patients with EGC who underwent additional surgery after non-curative (ER) comparing to those without ER. METHODS Patients who underwent surgery for EGC between 2001 and 2016 were included. Enrolled patients were divided into two groups, those who underwent additional surgery after non-curative ER and those who underwent direct surgery without a history of ER. Demographics, tumor characteristics and LNM distribution pattern were analyzed. RESULTS Among 4295 patients with EGC, 404 patients had a history of preoperative ER, and 3891 patients did not. After the application of exclusion criteria, 23 (7.1%) of 322 patients undergoing additional surgery had LNM. The additional surgery group showed less LNM, fewer nodal stations and more restricted distribution pattern of LNM. CONCLUSIONS The distribution pattern of LNM in EGC is complicated. However, more restricted locoregional LNM could be expected in cases of additional surgery after non-curative ER than after direct surgery.
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Affiliation(s)
- Quetzalihuitl Arroyo-Martinez
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Korea.,Department of General and Digestive Surgery, University Hospital "Virgen del Rocio", Seville, Spain
| | - Won Ho Han
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Korea
| | - Bang Wool Eom
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Korea
| | - Hong Man Yoon
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Korea
| | - Young Il Kim
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Korea
| | - Soo Jeong Cho
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Korea
| | - Jong Yeul Lee
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Korea
| | - Chan Gyoo Kim
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Korea
| | - Salvador Morales-Conde
- Department of General and Digestive Surgery, University Hospital "Virgen del Rocio", Seville, Spain
| | - Javier Padillo-Ruiz
- Department of General and Digestive Surgery, University Hospital "Virgen del Rocio", Seville, Spain
| | - Myeong-Cherl Kook
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Korea
| | - Il Ju Choi
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Korea
| | - Young Woo Kim
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Korea
| | - Keun Won Ryu
- Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, Korea
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Xiao Y, Zhang B, Wu Y. Prognostic analysis and liver metastases relevant factors after gastric and hepatic surgical treatment in gastric cancer patients with metachronous liver metastases: a population-based study. Ir J Med Sci 2018; 188:415-424. [PMID: 30062399 DOI: 10.1007/s11845-018-1864-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 07/09/2018] [Indexed: 01/20/2023]
Abstract
BACKGROUND The prognosis for patients with liver metastases from gastric cancer is very poor. Nevertheless, standard therapeutic strategies have not been established yet. The impact of hepatic surgical treatment on survival of patients with metachronous liver metastases from gastric cancer still remains controversial. METHODS We conducted a retrospective analysis on records of 436 patients who received radical gastrectomy (with D2 lymphadenectomy, regardless of hepatic surgical treatment) for gastric cancer with metachronous (≥ 3 months after gastrectomy) liver metastases in our center between 2001 and 2016. All patients were followed until 2017/10/31 or withdrawn from the follow-up because of death. RESULTS The median interval for non-hepatic metastases of the 436 patients who underwent radical gastrectomy is 14 months. T (P = 0.041), N (P = 0.023) and lymphovascular invasion (P < 0.001) were independent predictors affecting liver metastases-free interval. The overall survival rates for the 436 patients were 44.5, 29.7, 16.3, and 16.3% at 1, 2, 3, and 5 years respectively since treatment of hepatic metastases, with a median survival time of 11 months. N (P = 0.025), extent of liver metastases (H) (H2 vs. H1, P = 0.036; H3 vs. H1, P < 0.001), and treatment of liver metastatic lesions (P < 0.001) were significant independent prognostic factors for survival after presence of liver metastases. Among H1 and H2 patients, median survival in hepatic surgical treatment group was significantly longer than that in systemic chemotherapy alone group (25 vs. 11 months, P = 0.015). CONCLUSIONS Liver examinations should be performed during the first 2 years after gastric surgery and continued for 5 years for high-risk patients. Active therapeutic strategies may prolong patients' survival compared with supportive treatment alone. Patients with H1, H2 metachronous liver metastases may be considered appropriate candidates for hepatic surgical treatment before embarking on systemic chemotherapy alone. TRIAL REGISTRATION ISRCTN Registry (Retrospectively registered; Reference number: 35067; Date: 02/04/2018).
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Affiliation(s)
- Yibin Xiao
- Department of Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China
| | - Bo Zhang
- Department of Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China
| | - Yulian Wu
- Department of Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.
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Zhang CD, Ning FL, Zeng XT, Dai DQ. Lymphovascular invasion as a predictor for lymph node metastasis and a prognostic factor in gastric cancer patients under 70 years of age: A retrospective analysis. Int J Surg 2018; 53:214-220. [PMID: 29609047 DOI: 10.1016/j.ijsu.2018.03.073] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Revised: 02/24/2018] [Accepted: 03/25/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND Accumulating evidence has confirmed the potential prognostic value of LVI in patients with cancers. This aim of the current study was to clarify the potential relationship between LVI and lymph node metastasis, establish predictive clinicopathologic prognostic factors for LVI and lymph node metastasis, and determine the prognostic significance of LVI for patients younger than 70 years with resected gastric cancer. METHODS Overall survival rates were calculated using Kaplan-Meier analysis. Differences in proportions of patients were tested with the χ2 test. Univariate and multivariate analyses were applied to identify independent prognostic factors. Logistic regression analysis was employed to identify the risk factors predicting the presence of LVI and LN metastasis. RESULTS Univariate analysis led to the identification of tumor size, LVI and pN stage as factors significantly correlated with prognosis. Multivariate analysis demonstrated that tumor size, LVI, pN stage, and number of LNs retrieved are independent prognostic factors for the entire population. Logistic regression analysis proved that LVI and pT stage were significantly associated with LN metastasis. CONCLUSION LVI is an independent prognostic factor predicting LN metastasis and a strongly independent predictor of survival for patients with resected gastric cancer. We recommend that LVI should be taken into account as an important adjuvant prognostic factor, specially for pN0 cases with inadequate LNs retrieved. And the maximum number of LNs possible should be retrieved for optimal staging, especially for patients with higher cT stage.
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Affiliation(s)
- Chun-Dong Zhang
- Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Fei-Long Ning
- Department of General Surgery, Xuzhou Hospital of Traditional Chinese Medicine, Xuzhou, Jiangsu, China
| | - Xian-Tao Zeng
- Department of Evidence-Based and Clinical Epidemiology, The Second Clinical College, Wuhan University, Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
| | - Dong-Qiu Dai
- Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China; Cancer Research Institute, China Medical University, Shenyang, Liaoning, China; Cancer Center, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
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Youn GJ, Chung WC. [Micrometastasis in Gastric Cancer]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2018; 69:270-277. [PMID: 28539031 DOI: 10.4166/kjg.2017.69.5.270] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Although the incidence and mortality rate of gastric cancer have been steadily declining, gastric cancer is still the fourth most common cancer in the world and more than 50% of cases occur in Eastern Asia. In Korea, gastric cancer is the second most common cancer and third cause of cancer related death. The standard surgical procedure for resectable advanced gastric cancer is D2 lymphadenectomy with radical gastrectomy. Even though R0 resection was completed, recurrence is relatively common, and contributes to the limited survival of the patients in gastric cancer. As a clinically relevant factor for detection of the recurrence, the presence of isolating tumor cells has been introduced and it is so called as 'micrometastasis'. Numerous immunohistochemistry and molecular studies have shown that micrometastasis can be demonstrated not only in lymph nodes but also in such body compartments as the bone marrow, peritoneal cavity and blood. Herein, we review the current knowledge and evidence of the prognostic significance of micrometastasis in peritoneal, lymph node, bone marrow. Also, we discuss the current state of research on the circulating tumor cell in peripheral blood.
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Affiliation(s)
- Gun Jung Youn
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Woo Chul Chung
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Mechanisms of angiogenesis in microbe-regulated inflammatory and neoplastic conditions. Angiogenesis 2017; 21:1-14. [PMID: 29110215 DOI: 10.1007/s10456-017-9583-4] [Citation(s) in RCA: 103] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2017] [Accepted: 10/24/2017] [Indexed: 12/19/2022]
Abstract
Commensal microbiota inhabit all the mucosal surfaces of the human body. It plays significant roles during homeostatic conditions, and perturbations in numbers and/or products are associated with several pathological disorders. Angiogenesis, the process of new vessel formation, promotes embryonic development and critically modulates several biological processes during adulthood. Indeed, deregulated angiogenesis can induce or augment several pathological conditions. Accumulating evidence has implicated the angiogenic process in various microbiota-associated human diseases. Herein, we critically review diseases that are regulated by microbiota and are affected by angiogenesis, aiming to provide a broad understanding of how angiogenesis is involved and how microbiota regulate angiogenesis in microbiota-associated human conditions.
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Burdelski C, Jakani-Karimi N, Jacobsen F, Möller-Koop C, Minner S, Simon R, Sauter G, Steurer S, Clauditz TS, Wilczak W. IMP3 overexpression occurs in various important cancer types and is linked to aggressive tumor features: A tissue microarray study on 8,877 human cancers and normal tissues. Oncol Rep 2017; 39:3-12. [PMID: 29115542 PMCID: PMC5783598 DOI: 10.3892/or.2017.6072] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2017] [Accepted: 09/24/2017] [Indexed: 12/11/2022] Open
Abstract
IMP3 is an RNA binding protein required for ribosomal RNA processing, which has been suggested to be a prognostic marker in a large variety of human types of cancer. However, available data on the prevalence of IMP3 expression are largely discrepant. To systematically investigate the epidemiology and clinical relevance of IMP3 expression in human cancers we employed a two-step tissue microarrays (TMAs) approach. First, a normal tissue TMA and a multi-tumor TMA were analyzed for immunohistochemically detectable expression of IMP3 in 76 different normal tissue types and 3889 cancer samples from 95 different tumor categories. In a second step, we searched for associations between IMP3 expression and tumor phenotype and patient prognosis in TMAs containing 697 urinary bladder cancers, 1711 colon cancers, 343 esophageal adenocarcinomas, 251 esophageal squamous cell cancers, 673 lung cancers), 275 pancreatic cancers and 230 stomach cancers. In normal tissues, unequivocal IMP3 expression was found in placenta, lymphocytes and some types of glandular epithelial cells. In cancers, at least one case with weak expression could be found in 76 out of 95 (80%) different tumor types and 64 entities (67%) had at least one tumor with strong positivity. IMP3 expression was most frequently found in testicular cancer (including 71% seminomas and 96% non-seminomas), neuroblastoma (88%), and squamous cell cancer of various origins. Significant associations were found between IMP3 and adverse tumor features in esophageal adenocarcinomas and cancers of the urinary bladder, lung, stomach, and pancreas. In summary, IMP3 was frequently expressed in many different tumor types, and was typically associated with aggressive tumor features.
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Affiliation(s)
- Christoph Burdelski
- General, Visceral and Thoracic Surgery Department and Clinic, University Medical Center Hamburg‑Eppendorf, Hamburg, Germany
| | - Nilofar Jakani-Karimi
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Frank Jacobsen
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Christina Möller-Koop
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Sarah Minner
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ronald Simon
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Guido Sauter
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Stefan Steurer
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Till S Clauditz
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Waldemar Wilczak
- Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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Kim JW, Lee HS, Nam KH, Ahn S, Kim JW, Ahn SH, Park DJ, Kim HH, Lee KW. PIK3CA mutations are associated with increased tumor aggressiveness and Akt activation in gastric cancer. Oncotarget 2017; 8:90948-90958. [PMID: 29207615 PMCID: PMC5710896 DOI: 10.18632/oncotarget.18770] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2016] [Accepted: 06/10/2017] [Indexed: 12/19/2022] Open
Abstract
PIK3CA mutations are frequent in gastric cancer. However, their pathological and clinical implications are still unclear. We analyzed the clinicopathological characteristics according to the PIK3CA mutation status of patients with stage IB–IV disease who underwent gastrectomy between May 2003 and Dec. 2005 (cohort 1; n = 302) and of those with stage IV disease who received gastrectomy between Jul. 2006 and Dec. 2012 (cohort 2; n = 120). PIK3CA mutations were detected in 40 patients (13.2%) in cohort 1. In these patients, PIK3CA-mutant tumors were more frequently located in the upper third of the stomach (p = 0.021) and significantly showed poorly differentiated histology (p = 0.018) and increased lymphatic (p = 0.015), vascular (p = 0.005), and perineural invasion (p = 0.026). In addition, these tumors showed significantly increased lymphocyte and neutrophil infiltration in cancer stroma (p < 0.001), Epstein–Barr virus positivity (p < 0.001), and microsatellite instability (p = 0.015). Cytoplasmic Akt expression was significantly increased in these tumors (p = 0.001). In cohort 2, PIK3CA mutations were identified in 15 patients (12.5%). PIK3CA-mutant tumors showed significantly increased vascular invasion (p = 0.019) and microsatellite instability (p = 0.041). In addition, cytoplasmic Akt expression was also significantly increased (p = 0.018). However, in both cohorts, PIK3CA mutations were not associated with the prognosis of patients. In conclusion, PIK3CA mutations were associated with increased tumor aggressiveness, especially in locoregional disease, and Akt activation in gastric cancer. Our data suggest that PIK3CA-mutated gastric cancer is a distinct disease entity, which might need a different therapeutic approach.
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Affiliation(s)
- Ji-Won Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea
| | - Hye Seung Lee
- Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea
| | - Kyung Han Nam
- Department of Pathology, Haeundae Paik Hospital, Inje University College of Medicine, Busan 48108, Korea
| | - Soyeon Ahn
- Medical Research Collaborating Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea
| | - Jin Won Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea
| | - Sang-Hoon Ahn
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea
| | - Do Joong Park
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea
| | - Hyung-Ho Kim
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea
| | - Keun-Wook Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam 13620, Korea
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Bozkaya Y, Demirci NS, Kurtipek A, Erdem GU, Ozdemir NY, Zengin N. Clinicopathological and prognostic characteristics in patients with AFP-secreting gastric carcinoma. Mol Clin Oncol 2017; 7:267-274. [PMID: 28781800 DOI: 10.3892/mco.2017.1288] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2016] [Accepted: 05/16/2017] [Indexed: 12/31/2022] Open
Abstract
The aim of the present study was to determine whether there are any clinicopathological or prognostic differences between patients with α-fetoprotein-secreting gastric carcinoma (AFP-SGC) and non-AFP-SGC. Pathological parameters, clinical parameters, and treatment efficacy were compared in patients with AFP-SGC and non-AFP-SGC. In total, 362 patients (53 with AFP-SGC and 309 with non-AFP-SGC) were included in the present study. Patients with AFP-SGC had significantly higher levels of lymphovascular invasion, perineural invasion (PNI), rate of liver metastasis, and stage IV cancer compared with patients with non-AFP-SGC (P<0.05). The median overall survival (OS) rate was 12.6 months in the AFP-SGC group, and 22.1 months in the non-AFP-SGC group (P<0.001). The median OS and disease free survival (DFS) of patients with stage I-III AFP-SGC were 28.1 and 13.4 months, respectively, whereas for patients with non-AFP-SGC, the OS and DFS were 45.3 and 38.0 months, respectively (P=0.01; P=0.02). The median OS for the stage IV AFP-SGC and non-AFP-SGC groups was 9.3 and 11.5 months, respectively (P=0.14). Multivariate analysis of the entire patient group revealed that the Eastern Cooperative Oncology Group (ECOG) performance score of ≥2, lymph node involvement, presence of PNI, high levels of carcinoembryonic antigen, and distant metastasis were significantly correlated with OS. The lymph node involvement, ECOG performance score of ≥2, AFP-SGC type, and weight loss at diagnosis were also significant factors influencing the DFS in the stage I-III group. In conclusion, patients with AFP-SGC had more aggressive clinicopathological features and biological behavior with an increased tendency of liver metastasis compared with patients with non-AFP-SGC. In the near future, AFP may become an important surrogate marker to manage therapies of patients with gastric cancer.
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Affiliation(s)
- Yakup Bozkaya
- Department of Medical Oncology, Ankara Numune Education and Research Hospital, Ankara, Turkey
| | - Nebi Serkan Demirci
- Department of Medical Oncology, Ankara Numune Education and Research Hospital, Ankara, Turkey
| | - Alican Kurtipek
- Department of Internal Medicine, Ankara Numune Education and Research Hospital, Ankara, Turkey
| | - Gökmen Umut Erdem
- Department of Medical Oncology, Ankara Numune Education and Research Hospital, Ankara, Turkey
| | - Nuriye Yildirim Ozdemir
- Department of Medical Oncology, Ankara Numune Education and Research Hospital, Ankara, Turkey
| | - Nurullah Zengin
- Department of Medical Oncology, Ankara Numune Education and Research Hospital, Ankara, Turkey
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Gao H, Lan X, Li S, Xue Y. Relationships of MMP-9, E-cadherin, and VEGF expression with clinicopathological features and response to chemosensitivity in gastric cancer. Tumour Biol 2017; 39:1010428317698368. [PMID: 28459196 DOI: 10.1177/1010428317698368] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
The matrix metalloproteinase-9, E-cadherin, and vascular endothelial growth factor play an important role in behavior of tumor cell growth, invasion, and metastasis. In this study, we investigated the relationships of matrix metalloproteinase-9, E-cadherin, and vascular endothelial growth factor expression with clinicopathological features and results of chemosensitivity tested by collagen gel droplet–embedded culture–drug sensitivity test in gastric cancer. Fresh specimens were used for collagen gel droplet–embedded culture–drug sensitivity test and paired fixed specimens were used for immunohistochemistry. Positive expression of matrix metalloproteinase-9 was associated with poorly differentiated carcinoma (p = 0.032), lymph node metastasis (p = 0.022), and tumor stage (p = 0.023). Negative expression of E-cadherin was associated with poorly differentiated carcinoma (p = 0.007), lymph node metastasis (p = 0.012), and tumor stage (p = 0.007). Positive expression of vascular endothelial growth factor was associated with tumor size (p = 0.040) and stage (p = 0.007). Collagen gel droplet–embedded culture–drug sensitivity test was successfully evaluated in 56 patients. Among them, 29 (51.7%) patients were resistant to TS-1 and 31 (55.3%) patients were resistant to L-OHP. The L-OHP resistance rate in vascular endothelial growth factor positive patients was significantly higher than that in negative patients (p = 0.031). The L-OHP resistance rate in E-cadherin negative patients was significantly higher than that in positive patients (p = 0.014). In conclusion, matrix metalloproteinase-9, E-cadherin, and vascular endothelial growth factor were involved in tumor invasion and metastasis. Positive expression of matrix metalloproteinase-9 and vascular endothelial growth factor and negative expression of E-cadherin were malignant markers for gastric cancer. Positive expression of vascular endothelial growth factor and negative expression of E-cadherin were associated with L-OHP resistance.
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Affiliation(s)
- Hongyu Gao
- Department of Gastroenterology Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China
| | - Xiuwen Lan
- Department of Gastroenterology Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China
| | - Sen Li
- Department of Gastroenterology Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China
| | - Yingwei Xue
- Department of Gastroenterology Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China
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Li C, Zhu Q, He Q, Wang J, Wang F, Zhang H. Plasma Levels of Cyclooxygenase-2 (COX-2) and Visfatin During Different Stages and Different Subtypes of Migraine Headaches. Med Sci Monit 2017; 23:24-28. [PMID: 28044053 PMCID: PMC5226301 DOI: 10.12659/msm.899269] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Background The aim of this study was to determine the plasma levels of cyclooxygenase-2 (COX-2) and visfatin in different stages and different subtypes of migraine headaches compared to a control group to elucidate the pathological mechanisms involved. Material/Methods We recruited a case-control cohort of 182 adult migraine patients and 80 age-matched and gender-matched healthy controls. The migraine patients were divided into two groups: the headache-attack-period group (Group A, n=77) and the headache-free-period group (Group B, n=105). The two groups were further divided into subgroups according to whether they had aura symptoms. Solid phase double antibody sandwich enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma levels of COX-2 and visfatin. Statistical analysis was performed using SPSS 17.0. Results The plasma levels of COX-2 and visfatin in the headache-attack-period group were significantly higher than in the headache-free-period group and the control group; there were no significant differences between the headache-free group and the control group. There were no significant differences in plasma levels of COX-2 and visfatin between the subgroups: headache-attack-period with aura subgroup and the headache-attack-period without aura sub group. Conclusions COX-2 and visfatin participated in the pathogenesis of migraine headaches. The presence of aura had no effect on the serum levels of COX-2 and visfatin.
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Affiliation(s)
- Chao Li
- Department of Neurology, The People's Hospital of Liaoning Province, Shenyang, Liaoning, China (mainland)
| | - Qiushi Zhu
- Department of Neurosurgery, Liaocheng Center Hospital, Liaocheng, Shandong, China (mainland)
| | - Qiu He
- Department of Neurology, The People's Hospital of Liaoning Province, Shenyang, Liaoning, China (mainland)
| | - Junwei Wang
- Department of Neurology, The Fourth Hospital of Chongqing, Chongqing, China (mainland)
| | - Fengzhi Wang
- Department of Neurology, The People's Hospital of Liaoning Province, Shenyang, Liaoning, China (mainland)
| | - Hemin Zhang
- Department of Neurology, The People's Hospital of Liaoning Province, Shenyang, Liaoning, China (mainland)
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Bozkaya Y, Erdem GU, Ozdemir NY, Demirci NS, Hocazade C, Yazıcı O, Zengin N. Comparison of clinicopathological and prognostic characteristics in patients with mucinous carcinoma and signet ring cell carcinoma of the stomach. Curr Med Res Opin 2017; 33:109-116. [PMID: 27646639 DOI: 10.1080/03007995.2016.1239192] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
AIM To determine whether there are any clinicopathological or prognostic differences between mucinous gastric carcinoma (MGC) and signet ring cell carcinoma (SRCC). METHODS Pathological parameters, clinical parameters, and treatment efficacy were compared in patients with MGC and SRCC. RESULTS In total, 193 patients (51 with MGC and 142 with SRCC) were included in this study. Patients with SRCC in particular had notably higher lymphovascular invasion, perineural invasion, rate of Borrmann types III and IV, and stage III-IV cancer (according to its TNM stage) compared with patients with MGC. However, tumor size was larger in patients with MGC (tumor size ≥5 cm). Median overall survival (OS) was 29.8 months in the MGC group and 16.6 months in the SRCC group (p = .04). The median OS in stage I-III patients was 59.9 and 42.5 months in the MGC and SRCC groups, respectively (p = .35). Comparing OS between MGC and SRCC stage IV patients revealed that the median OS was 10.1 and 8.8 months, respectively (p = .96). Multivariate analysis of the entire patient group revealed that the presence of weight loss at diagnosis, distant metastasis, and lymph node involvement were significantly related to OS. Multivariate analysis also revealed that weight loss at the diagnosis and T3-4 tumors were significant factors influencing OS in the stage I-III group. CONCLUSIONS Patients with SRCC had generally poorer prognosis and lower survival rates compared with patients with MGC. Further studies on the prognosis and treatment plan based on the pathological subtypes of SRCC and MGC are still needed.
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Affiliation(s)
- Yakup Bozkaya
- a Ankara Numune Education and Research Hospital, Department of Medical Oncology , Ankara , Turkey
| | - Gökmen Umut Erdem
- a Ankara Numune Education and Research Hospital, Department of Medical Oncology , Ankara , Turkey
| | - Nuriye Yıldırın Ozdemir
- a Ankara Numune Education and Research Hospital, Department of Medical Oncology , Ankara , Turkey
| | - Nebi Serkan Demirci
- a Ankara Numune Education and Research Hospital, Department of Medical Oncology , Ankara , Turkey
| | - Cemil Hocazade
- a Ankara Numune Education and Research Hospital, Department of Medical Oncology , Ankara , Turkey
| | - Ozan Yazıcı
- a Ankara Numune Education and Research Hospital, Department of Medical Oncology , Ankara , Turkey
| | - Nurullah Zengin
- a Ankara Numune Education and Research Hospital, Department of Medical Oncology , Ankara , Turkey
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Can lymphovascular invasion be predicted by preoperative multiphasic dynamic CT in patients with advanced gastric cancer? Eur Radiol 2016; 27:3383-3391. [PMID: 27999983 DOI: 10.1007/s00330-016-4695-6] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2016] [Revised: 11/21/2016] [Accepted: 12/05/2016] [Indexed: 12/26/2022]
Abstract
OBJECTIVES To determine whether multiphasic dynamic CT can preoperatively predict lymphovascular invasion (LVI) in advanced gastric cancer (AGC). METHODS 278 patients with AGC who underwent preoperative multiphasic dynamic CT were retrospectively recruited. Tumour CT attenuation difference between non-contrast and arterial (ΔAP), portal (ΔPP) and delayed phase (ΔDP), tumour-spleen attenuation difference in the portal phase (ΔT-S), tumour contrast enhancement ratios (CERs), tumour-to-spleen ratio (TSR) and tumour volumes were obtained. All CT-derived parameters and clinicopathological variables associated with LVI were analysed by univariate analysis, followed by multivariate and receiver operator characteristics (ROC) analysis. Associations between CT predictors for LVI and histopathological characteristics were evaluated by the chi-square test. RESULTS ΔPP (OR, 1.056; 95% CI: 1.032-1.080) and ΔT-S (OR, 1.043; 95% CI: 1.020-1.066) are independent predictors for LVI in AGC. ΔPP, ΔT-S and their combination correctly predicted LVI in 74.8% (AUC, 0.775; sensitivity, 88.6%; specificity, 54.1%), 68.7% (AUC, 0.747; sensitivity, 68.3%; specificity, 69.4%) and 71.7% (AUC, 0.800; sensitivity, 67.6%; specificity, 77.8%), respectively. There were significant associations between CT predictors for LVI with tumour histological differentiation and Lauren classification. CONCLUSION Multiphasic dynamic CT provides a non-invasive method to predict LVI in AGC through quantitative enhancement measurement. KEY POINTS • Lymphovascular invasion rarely can be evaluated preoperatively in advanced gastric cancer (AGC). • Δ PP and Δ T-S were independent predictors for LVI in patients with AGC. • Δ PP and Δ T-S showed acceptable predictive performance for LVI. • Combination of Δ PP and Δ T-S improved predictive performance for LVI. • Multiphasic dynamic CT may be a useful adjunct for detecting LVI preoperatively.
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Bracey TS, Keers LC, Adams SA, Smith MEF. Diffuse Gastric Carcinoma Undergoes Characteristic Phenotypic Changes in the Intravascular Environment: Evidence for a Reversal of the Epithelial-Mesenchymal Transition in Lymphovascular Metastasis. Int J Surg Pathol 2016; 25:222-229. [PMID: 27733664 DOI: 10.1177/1066896916672331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
This article reports differences between the properties of extravascular carcinoma, which generally forms the vast bulk of a tumor, and those of intravascular carcinoma, at both primary and metastatic lymph node sites. In a morphological and immunohistochemical study of 19 diffuse gastric adenocarcinomas, we report that in comparison to extravascular carcinoma, the intravascular tumor compartment showed frequent and profound phenotypic change, including increased tumor cell cohesion, differentiation and cadherin/catenin expression. For example, greatest cohesion was seen at the intravascular site in 78% ( P = .00006) of primary cancers and in 84% ( P = .000015) of their lymph node metastases. Pan cadherin showed a statistically significant increase at the intravascular metastatic site ( P = .031). We suggest that this change from an extravascular isolated cell phenotype to an intravascular cohesive phenotype represents reversal of the epithelial to mesenchymal transition. Since this proposed reversal of epithelial to mesenchymal transition in intravascular carcinoma is frequently conspicuous in routine histological sections of many types of cancer, as our previous publications have indicated, this process is likely to have widespread significance for the biology of metastasis.
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Lee EW, Lee WY, Koo HS. Prognostic Factors for Node-Negative Advanced Gastric Cancer after Curative Gastrectomy. J Gastric Cancer 2016; 16:161-166. [PMID: 27752393 PMCID: PMC5065945 DOI: 10.5230/jgc.2016.16.3.161] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Revised: 08/15/2016] [Accepted: 08/29/2016] [Indexed: 12/20/2022] Open
Abstract
PURPOSE Lymph node (LN) metastasis is the best prognostic indicator in non-distant metastatic advanced gastric cancer. This study aimed to assess the prognostic value of various clinicopathologic factors in node-negative advanced gastric cancer. MATERIALS AND METHODS We retrospectively analyzed the clinical records of 254 patients with primary node-negative stage T2~4 gastric cancer. These patients were selected from a pool of 1,890 patients who underwent radical resection at Memorial Jin-Pok Kim Korea Gastric Cancer Center, Inje University Seoul Paik Hospital between 1998 and 2008. RESULTS Of the 254 patients, 128 patients (50.4%), 88 patients (34.6%), 37 patients (14.6%), and 1 patient (0.4%) had T2, T3, T4a, and T4b tumors, respectively. In a univariate analysis, operation type, T-stage, venous invasion, tumor size, and less than 15 LNs significantly correlated with tumor recurrence and cumulative overall survival. In a multivariate logistic regression analysis, tumor size, venous invasion, and less than 15 LNs significantly and independently correlated with recurrence. In a multivariate Cox proportional hazards analysis, tumor size (hazard ratio [HR]: 2.926; 95% confidence interval [CI]: 1.173~7.300; P=0.021), venous invasion (HR: 3.985; 95% CI: 1.401~11.338; P=0.010), and less than 15 LNs (HR: 0.092; 95% CI: 0.029~0.290; P<0.001) significantly correlated with overall survival. CONCLUSIONS Node-negative gastric cancers recurred in 8.3% of the patients in our study. Tumor size, venous invasion, and less than 15 LNs reliably predicted recurrence as well as survival. Aggressive postoperative treatments and timely follow-ups should be considered in cases with these characteristics.
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Affiliation(s)
- Eun Woo Lee
- Department of Surgery, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
| | - Woo Yong Lee
- Department of Surgery, Inje University Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
| | - Ho-Seok Koo
- Department of Internal Medicine, Inje University Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea
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Abstract
Outcome prediction in patients with bladder cancer has improved through the development of nomograms and predictive models. However, integration of further characteristics such as lymphovascular invasion (LVI) might increase the accuracy and clinical utility of these instruments. Assessment and reporting of LVI in specimens from transurethral resection of the bladder tumour (TURBT) or biopsy in patients with non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer (MIBC) might enable improved staging, prognostication and clinical decision-making. In NMIBC, presence of LVI in TURBT and biopsy samples seems to be associated with understaging and increased risks of disease recurrence and progression. In MIBC, presence of LVI is associated with features of aggressive disease and predicts recurrence and survival. Integration of LVI status into predictive models might aid clinical decision-making regarding intravesical instillation schedules and regimens, early radical cystectomy in patients with high-grade T1 disease and perioperative chemotherapy. However, LVI assessment is hampered by insufficient reproducibility and reliability, lack of routine evaluation and limited concordance between findings in TURBT and radical cystectomy specimens. Standardization of the pathological criteria defining LVI is warranted to improve its reporting in routine clinical practice and its utility as a care-changing prognostic marker.
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Xue L, Chen XL, Lin PP, Xu YW, Zhang WH, Liu K, Chen XZ, Yang K, Zhang B, Chen ZX, Chen JP, Zhou ZG, Hu JK. Impact of capillary invasion on the prognosis of gastric adenocarcinoma patients: A retrospective cohort study. Oncotarget 2016; 7:31215-31225. [PMID: 27145279 PMCID: PMC5058751 DOI: 10.18632/oncotarget.9101] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2016] [Accepted: 04/11/2016] [Indexed: 02/05/2023] Open
Abstract
Capillary invasion (CI) has been found to play an important role in metastasis and recurrence of gastric adenocarcinoma (GAC). However, the prognostic significance of CI is still controversial. From January 2005 to December 2011, 1398 patients with GAC who underwent gastrectomy were retrospectively enrolled and divided into CI (+) and CI (-) groups. Clinicopathological features and survival outcomes were compared between these groups. In our study, 227 (16.2%) patients were CI (+). Patients with CI (+) had significantly more advanced tumors and worse prognosis than those with CI (-) (p < 0.001). CI was demonstrated as an independent prognostic factor (p = 0.023) in patients with GAC. When stratified by TNM stage, the prognosis of CI (+) group in stage III was remarkably worse than CI (-) group (p = 0.006), while the differences were not significant in stage I-II and stage IV (both p > 0.05). The nomograms indicated that CI was part of the individual prognostic prediction system. The predictive accuracy of CI and other characteristics was better than TNM alone (p < 0.001). Our finding suggested that CI was an independent prognostic factor in patients with GAC, and the nomogram based on CI and other clinicopathological factors was a valuable and accurate tool in individual prognostic prediction.
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Affiliation(s)
- Lian Xue
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, China
| | - Xiao-Long Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, China
| | - Pan-Pan Lin
- West China School of Medicine, Sichuan University, China
| | - Yuan-Wei Xu
- West China School of Medicine, Sichuan University, China
| | - Wei-Han Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, China
| | - Kai Liu
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, China
| | - Xin-Zu Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, China
| | - Kun Yang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, China
| | - Bo Zhang
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, China
| | - Zhi-Xin Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, China
| | - Jia-Ping Chen
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, China
| | - Zong-Guang Zhou
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, China
- Laboratory of Digestive Surgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center West China Hospital, Sichuan University, China
| | - Jian-Kun Hu
- Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, China
- Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, China
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Lymph vessels: the forgotten second circulation in health and disease. Virchows Arch 2016; 469:3-17. [PMID: 27173782 PMCID: PMC4923112 DOI: 10.1007/s00428-016-1945-6] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2015] [Revised: 04/06/2016] [Accepted: 04/18/2016] [Indexed: 12/19/2022]
Abstract
The lymphatic circulation is still a somewhat forgotten part of the circulatory system. Despite this, novel insights in lymph angiogenesis in health and disease, application of immune markers for lymphatic growth and differentiation and also the introduction of new imaging techniques to visualize the lymphatic circulation have improved our understanding of lymphatic function in both health and disease, especially in the last decade. These achievements yield better understanding of the various manifestations of lymph oedemas and malformations, and also the patterns of lymphovascular spread of cancers. Immune markers that recognize lymphatic endothelium antigens, such as podoplanin, LYVE-1 and Prox-1, can be successfully applied in diagnostic pathology and have revealed (at least partial) lymphatic differentiation in many types of vascular lesions.
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50
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Lin J, Kang M, Chen S, Deng F, Han Z, Lin J. Feasibility and strategy for left tracheobronchial lymph node dissection in thoracolaparoscopic esophageal cancer surgery. Thorac Cancer 2016; 7:199-206. [PMID: 27042222 PMCID: PMC4773297 DOI: 10.1111/1759-7714.12312] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2015] [Accepted: 08/09/2015] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND This study evaluates the feasibility and strategy of left tracheobronchial lymph node (LN) dissection in the surgical treatment of esophageal cancer, and its impact on surgical outcomes following thoracoscopic esophagectomy. METHODS Data of 265 patients with thoracic esophageal cancer who underwent thoracoscopic and laparoscopic esophagectomy was retrospectively reviewed. In 80 cases, thoracoscopic esophagectomy was performed without left tracheobronchial LN dissection (group non-4L), while 185 cases underwent thoracoscopic esophageal mobilization with routine left tracheobronchial node dissection (group 4L). We introduced a "mesoesophageal suspension" method in order to facilitate complete dissection of the left tracheobronchial nodes, along with left recurrent laryngeal nerve nodes. Both univariate and multivariate analyses were performed to evaluate risk factors correlated to left tracheobronchial node metastasis. RESULTS The non-4L group experienced less blood loss than the 4L group (P = 0.009). More mediastinal LNs were dissected in the 4L group (P < 0.001). There was no significant difference with regard to the incidence of major postoperative complications between the two groups. Compared with other LN metastases, the metastatic rate of the left tracheobronchial LNs was relatively lower. Based on multivariate analysis of six factors, lymphatic invasion and subcarinal node metastasis were shown to be strong independent predictors of left tracheobronchial metastasis. CONCLUSION Routine thoracoscopic extensive lymphadenectomy, including the left tracheobronchial LN, was technically feasible and safe in patients with esophageal cancer. Using a mesoesophagus suspension technique, we performed a meticulous LN dissection in the upper mediastinal space.
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Affiliation(s)
- Jiangbo Lin
- Department of Thoracic SurgeryAffiliated Union Hospital of Fujian Medical UniversityFuzhouFujianChina
| | - Mingqiang Kang
- Department of Thoracic SurgeryAffiliated Union Hospital of Fujian Medical UniversityFuzhouFujianChina
| | - Shuchen Chen
- Department of Thoracic SurgeryAffiliated Union Hospital of Fujian Medical UniversityFuzhouFujianChina
| | - Fan Deng
- Department of Thoracic SurgeryAffiliated Union Hospital of Fujian Medical UniversityFuzhouFujianChina
| | - Zhiyang Han
- Department of Thoracic SurgeryAffiliated Union Hospital of Fujian Medical UniversityFuzhouFujianChina
| | - Jihong Lin
- Department of Thoracic SurgeryAffiliated Union Hospital of Fujian Medical UniversityFuzhouFujianChina
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