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1
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Song S, Fan Y, Zou G, Huo L, Kumar J, Li Y, Wang R, Dai E, Jin J, Scott AW, Shao S, Pizzi MP, Vykoukal JV, Katayama H, Hanash S, Calin GA, Zhang X, Lee MG, Wang Z, Lo YH, Gan Q, Waters RE, Yin F, Wang L, Cheng X, Ajani JA, Dhar SS. KAP1 promotes gastric adenocarcinoma progression by activating Hippo/YAP1 signaling via binding to HNRNPAB. Cancer Lett 2025; 621:217695. [PMID: 40189014 DOI: 10.1016/j.canlet.2025.217695] [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: 12/19/2024] [Revised: 03/31/2025] [Accepted: 04/03/2025] [Indexed: 04/15/2025]
Abstract
Gastric adenocarcinoma (GAC) remains a significant global health challenge, with over a million new cases annually. Peritoneal carcinomatosis (PC), detected in ∼20 % of cases at diagnosis and ∼45 % later, is uniformly fatal, with limited treatment options. This study investigated the role of KAP1 in GAC progression, focusing on its interaction with YAP1 and cancer stemness traits. Analysis of over 596 primary GACs and 72 PC samples revealed that high nuclear KAP1 expression correlates with poor prognosis. KAP1 knockdown reduced oncogenic activity and stemness traits in GAC cells. Mechanistically, KAP1 positively regulates YAP1 transcription by binding to its promoter and reducing H3K27ac levels. Mass spectrometry identified an interaction between KAP1 and HNRNPAB, further modulating YAP1 signaling. Expression of the KRAB domain of ZFP568 without its DNA-binding zinc fingers inhibited both KAP1 and YAP1 expression, significantly reducing colony formation and tumor growth in vivo. Additionally, emerging antisense oligonucleotides (ASOs) targeting KAP1 or YAP1 effectively suppressed mouse tumor progression. These findings establish KAP1 as a critical driver of tumor progression in GAC through YAP1 regulation and HNRNPAB interaction, highlighting its potential therapeutic target. This study advances our understanding and offers a preclinical framework to improve outcomes for GAC.
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Affiliation(s)
- Shumei Song
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yibo Fan
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Gengyi Zou
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Longfei Huo
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Janani Kumar
- Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Yuan Li
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, 110001, PR China
| | - Ruiping Wang
- Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Enyu Dai
- Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jiankang Jin
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ailing W Scott
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Shan Shao
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Melissa Pool Pizzi
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jody V Vykoukal
- Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Hiroyuki Katayama
- Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Samir Hanash
- Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - George A Calin
- Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Xing Zhang
- Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Min Gyu Lee
- Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Zhenning Wang
- Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang, 110001, PR China
| | - Yuan-Hung Lo
- Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Qiong Gan
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Rebecca E Waters
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Feng Yin
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Linghua Wang
- Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Xiaodong Cheng
- Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jaffer A Ajani
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
| | - Shilpa S Dhar
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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Lewis KA, Diggs LP, Badgwell BD. Educational Review: Updates on Therapeutic Strategies for Gastric Cancer with Peritoneal Metastasis. Ann Surg Oncol 2025; 32:3672-3687. [PMID: 40016614 DOI: 10.1245/s10434-025-17069-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Accepted: 02/09/2025] [Indexed: 03/01/2025]
Abstract
Gastric cancer (GC) commonly presents in advanced stages with metastatic spread to the peritoneal cavity, and outcomes associated with gastric cancer with peritoneal metastasis (GCPM) continue to carry a dismal prognosis. Persistent challenges in the detection of peritoneal metastasis (PM) have resulted in a relative paucity of high-quality data to inform management decisions. Several consensus groups have published recommendations to guide management, including most recently the National Comprehensive Cancer Network guidelines, which now include cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as a potential treatment modality in select patients with GCPM. Multiple clinical trials have investigated the use of CRS/HIPEC and other peritoneal-directed therapies, such as intraperitoneal chemotherapy (IPC) and pressurized intraperitoneal aerosolized chemotherapy (PIPAC). As high-volume centers work to incorporate such therapies into their practice, ongoing clinical trials are aimed at understanding their efficacy. Recent findings have improved understanding of the mechanisms and pathophysiology underlying GCPM while the discovery of novel targets offers potential for drug development and therapeutic strategies to overcome treatment resistance. This review highlights recent advancements and addresses the persistent challenges in managing GCPM while also offering a comprehensive summary of current guidelines and treatment strategies.
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Affiliation(s)
- Kever A Lewis
- Division of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
| | - Laurence P Diggs
- Division of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Brian D Badgwell
- Division of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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3
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Angerilli V, Callegarin M, Govoni I, De Lisi G, Paudice M, Fugazzola P, Vanoli A, Parente P, Bergamo F, Luchini C, Dei Tos AP, Grillo F, Lonardi S, Mastracci L, Spolverato G, Fassan M. Heterogeneity of predictive biomarker expression in gastric and esophago-gastric junction carcinoma with peritoneal dissemination. Gastric Cancer 2025:10.1007/s10120-025-01609-7. [PMID: 40205072 DOI: 10.1007/s10120-025-01609-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2025] [Accepted: 03/20/2025] [Indexed: 04/11/2025]
Abstract
BACKGROUND Temporal and spatial molecular heterogeneity contributes to resistance to targeted and immune therapies in gastric and esophagogastric junction carcinoma (G/EGJ). This study evaluates differences in biomarker expression between primary G/EGJ and paired peritoneal metastases (PM). METHODS We analyzed 74 cases of primary G/EGJ and paired PM using immunohistochemistry for HER2, PD-L1, Claudin18 (CLDN18), DNA mismatch repair (MMR) proteins, p53, E-cadherin, and in situ hybridization for EBER. Biomarker concordance between primary and metastatic tumors was assessed. RESULTS Primary G/EGJ were predominantly poorly cohesive (45.9%) or mixed-type (37.8%). Regarding predictive biomarkers, low rates of HER2 overexpression (5.4%), MMR deficiency (4.1%), and EBER positivity (1.4%) were observed, while PD-L1 CPS ≥ 1 occurred in 79.7% of cases and CLDN18 positivity was observed in 31.1% of cases. Concordance was perfect for MMR and EBER, while PD-L1 showed the highest discordance (32.4%). HER2 had a low discordance rate (2.7%). CLDN18 exhibited good concordance (86.5%) and showed consistent positivity in PD-L1- and HER2-negative primary tumors (28.6%). CONCLUSION G/EGJ with PM show distinct molecular features and spatial heterogeneity, with MMR, EBER, and HER2 demonstrating strong concordance, while PD-L1 showed greater variability. As for novel biomarkers, CLDN18.2 shows substantial concordance between primary G/EGJ and PM and could be a promising target in HER2/PD-L1-negative G/EGJ with PM.
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Affiliation(s)
- Valentina Angerilli
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, via Gabelli 61, 35121, Padua, Italy
- ULSS2 Marca Trevigiana, Treviso, Italy
- Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Matilde Callegarin
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, via Gabelli 61, 35121, Padua, Italy
| | - Ilaria Govoni
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy
| | - Giuseppe De Lisi
- IRCCS San Matteo Hospital, Pavia, Italy
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Michele Paudice
- Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Paola Fugazzola
- General Surgery Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Alessandro Vanoli
- IRCCS San Matteo Hospital, Pavia, Italy
- Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia, Pavia, Italy
| | - Paola Parente
- Unit of Pathology, Fondazione IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy
| | | | - Claudio Luchini
- Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy
| | - Angelo Paolo Dei Tos
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, via Gabelli 61, 35121, Padua, Italy
| | - Federica Grillo
- Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Sara Lonardi
- Veneto Institute of Oncology IOV-IRCCS, Padua, Italy
| | - Luca Mastracci
- Anatomic Pathology, Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genova, Genoa, Italy
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy
| | - Gaya Spolverato
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), University of Padua, Padua, Italy
| | - Matteo Fassan
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padua, via Gabelli 61, 35121, Padua, Italy.
- IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
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Nogueira Marques G, Marti-Garcia B, Oliveira Leal M, da Silva NUR, Flanagan CA, Suárez-Bonnet A. Metastatic gastric adenocarcinoma in a grey seal Halichoerus grypus: clinicopathological and immunohistochemical characterization. DISEASES OF AQUATIC ORGANISMS 2025; 161:125-131. [PMID: 40110738 DOI: 10.3354/dao03845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/22/2025]
Abstract
A 33 yr old female grey seal Halichoerus grypus presented with inappetence and progressive weight loss. Medical management included blood analysis, imaging, and fecal evaluation, along with multimodal supportive therapy, which periodically improved the overall medical condition. Six months after the initial presentation, the clinical condition deteriorated significantly, including severe hyporexia, hematemesis, and marked neutrophilic leukocytosis, which led to the decision to euthanise based on welfare grounds. Necropsy findings included severe thickening of the distal esophagus, cardia, and proximal gastric fundus, as well as multiple nodular to cystic structures over the stomach's serosa, omentum, and mesentery. Histologically, a mucinous gastric adenocarcinoma was diagnosed, with metastasis to the gastric lymph nodes and prominent carcinomatosis involving the omentum, mesentery, and diaphragm. Immunohistochemically, the gastric adenocarcinoma was positive for cytokeratin AE1/AE3, weakly positive for COX-2 and E-cadherin, and negative for vimentin. The Ki-67 proliferative index was low (0.8). Although rare, this case offers further insights into the clinical presentation, histopathology, and immunohistochemical profile of gastric tumors in pinnipeds.
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Affiliation(s)
| | - Bernat Marti-Garcia
- Department of Pathobiology and Population Sciences, The Royal Veterinary College, Hatfield AL9 7TA, UK
| | - Miriam Oliveira Leal
- Zoomarine Portugal, 8201-864 Guia, Portugal
- MARE-ISPA - Marine and Environmental Sciences Centre / ARNET - Aquatic Sciences Network, 1149-041 Lisbon, Portugal
| | | | | | - Alejandro Suárez-Bonnet
- Department of Pathobiology and Population Sciences, The Royal Veterinary College, Hatfield AL9 7TA, UK
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5
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Gingrich A, Manguso N, Zuckerman R. Treatment of Gastric Cancer Carcinomatosis. Surg Clin North Am 2025; 105:95-107. [PMID: 39523079 DOI: 10.1016/j.suc.2024.06.008] [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] [Indexed: 11/16/2024]
Abstract
Patients with gastric cancer peritoneal metastases (GCPM) have Stage IV disease. Systemic therapy is a crucial aspect of their care. Patients with GCPM should have their tumors tested for HER2 and PD-L1 expression and microsatellite instability for potential targeted therapies. If patients with synchronous GCPM have stable disease following neoadjuvant therapy, surgical intervention can be considered. Patients with positive cytology or low-volume peritoneal disease (peritoneal carcinomatosis index [PCI] < 7) may "convert" to negative cytology or resolution of peritoneal metastases following intraperitoneal therapy and may be candidates for subsequent gastrectomy.
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Affiliation(s)
- Alicia Gingrich
- Division of Surgery, Department of Surgical Oncology, MD Anderson Cancer Center, Houston, TX 77025, USA
| | - Nicholas Manguso
- Division of Surgical Oncology, Department of Surgery, University of Nevada Reno/Renown Integrated Health System, 1500 East 2nd Street, Suite 300, Reno, NV 89502, USA
| | - Randall Zuckerman
- Division of Surgical Oncology, Department of Surgery, University of Nevada Reno/Renown Integrated Health System, 1500 East 2nd Street, Suite 300, Reno, NV 89502, USA.
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6
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Krell M, Ranjbar S, Gitlin S, Alvarez Vega DR, Wilson R, Thrasher K, Brown ZJ. Evolution in the Surgical Management of Gastric Cancer Peritoneal Metastases. Cancers (Basel) 2024; 17:100. [PMID: 39796727 PMCID: PMC11719528 DOI: 10.3390/cancers17010100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 12/26/2024] [Accepted: 12/27/2024] [Indexed: 01/13/2025] Open
Abstract
Despite therapeutic treatments and the growing utilization of multimodal therapies, gastric cancer (GC) remains a highly aggressive malignancy with high mortality worldwide. Much of the complexity in treating GC is due to the high incidence of peritoneal metastasis (PM), with mean overall survival typically ranging from 4 to 10 months. With current systemic therapy, targeted therapies, and immunotherapies continuing to remain ineffective for GC/PM, there has been a significant growing interest in intraperitoneal (IP) therapies for the treatment of GC/PM. In this review, we summarize the development of PM and evolving treatment strategies for GC/PM. Furthermore, we explore the various advancements and outcomes of IP therapies, including heated intraperitoneal chemotherapy (HIPEC), neoadjuvant HIPEC, and pressurized intraperitoneal aerosolized chemotherapy (PIPAC).
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Affiliation(s)
| | | | | | | | | | | | - Zachary J. Brown
- Department of Surgery, Division of Surgical Oncology, NYU Langone Health, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA; (M.K.); (S.G.); (D.R.A.V.); (R.W.); (K.T.)
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7
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Khomiak A, Ghaffar S, Rodriguez Franco S, Ziogas IA, Yee EJ, Franklin O, Cumbler E, Chauhan A, McCarter MD, Gleisner AL, Ahrendt S, Del Chiaro M, Schulick RD, Mungo B. Survival Outcomes of Cytoreductive Surgery with HIPEC in Gastric Adenocarcinoma: A National Cancer Database Study. Ann Surg Oncol 2024; 31:8549-8559. [PMID: 39237827 DOI: 10.1245/s10434-024-16142-7] [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: 06/04/2024] [Accepted: 08/19/2024] [Indexed: 09/07/2024]
Abstract
BACKGROUND This study aimed to assess the impact of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) on the survival outcomes for patients with gastric cancer and peritoneal carcinomatosis (PC). METHODS A retrospective analysis of the National Cancer Database from 2004 to 2020 identified patients with topography and histology codes consistent with gastric adenocarcinoma who underwent CRS/HIPEC. The exclusion criteria ruled out known other distant metastasis and missing key data. The study compared the CRS/HIPEC group with patients who had stage IV disease (with the same exclusions for distant metastases) and received systemic chemotherapy but no surgery to the primary site. RESULTS The study included 148 patients who underwent CRS/HIPEC. Their median age was 57 years (interquartile range [IQR], 47-66 years), with 57.4% of the patients identifying as male and 73.6% identifying as white. Most of the CRS/HIPEC patients had locally advanced disease, with 33.8% having pT4 disease and 23% patients having pN3 status. The Charlson-Deyo scores were 0 for 77% and 1 for 16.9% of the patients. The overall survival (OS) among the stage IV patients managed with CRS/HIPEC was significantly longer than for the patients receiving only systemic chemotherapy (median survival, 18.1 vs 9.3 months; p < 0.001), and the 1-year OS was 72.6% versus 38.8% (p < 0.05)). Among the stage IV patients, CRS/HIPEC showed better survival than systemic chemotherapy (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.44-0.73; p < .001) when control was used for the Charlson Deyo score, histology, age, and sex. CONCLUSIONS These results suggest the association of CRS/HIPEC with improved survival for selected patients with gastric adenocarcinoma and peritoneal disease. Some of this difference may have been due to selection bias, but the differences in the survival curves are robust.
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Affiliation(s)
- Andrii Khomiak
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Sumaya Ghaffar
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Salvador Rodriguez Franco
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Ioannis A Ziogas
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Elliott J Yee
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Oskar Franklin
- Department of Diagnostics and Intervention, Surgery, Umeå University, Umeå, Sweden
| | - Ethan Cumbler
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Akshay Chauhan
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Martin D McCarter
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Ana L Gleisner
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Steven Ahrendt
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Marco Del Chiaro
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Richard D Schulick
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Benedetto Mungo
- Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
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8
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Jin S, Wang Q, Wei Y, Ju Y, Wang K. Patients With Gastric Cancer Who Undergo HIPEC Treatment and Have a Peritoneal Cancer Index of Less Than 12 Can Benefit From Surgery. Am J Ther 2024:00045391-990000000-00208. [PMID: 39167429 DOI: 10.1097/mjt.0000000000001798] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/23/2024]
Affiliation(s)
- Shiyang Jin
- Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital, Harbin, China
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9
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Mogal H, Shen P. Top Peritoneal Surface Malignancy Articles from 2022 to Inform your Cancer Practice. Ann Surg Oncol 2024; 31:5361-5369. [PMID: 38700798 DOI: 10.1245/s10434-024-15304-x] [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: 11/13/2023] [Accepted: 04/01/2024] [Indexed: 07/13/2024]
Abstract
Over the last few decades, the role of cytoreductive surgery (CRS) with or without regional-based peritoneal therapies such as hyperthermic intraperitoneal chemotherapy (HIPEC) has evolved in the management of patients with peritoneal surface malignances (PSMs). Despite the benefit of CRS in improving oncologic outcomes, significant challenges remain in the treatment of patients with advanced PSMs, and the role of HIPEC continues to be questioned. Additionally, while there has been improvement in perioperative outcomes, long-term survival remains poor. As a result, there is much need to improve our understanding of the processes that drive tumor biology, thereby improving patient selection for various treatment approaches. Additionally, newer therapies are needed for patients who remain poor surgical candidates and who progress on systemic therapy. This article highlights recently published studies that we consider impactful in the care of patients with PSMs.
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Affiliation(s)
- Harveshp Mogal
- Department of Surgery, Division of General Surgery, University of Washington/Fred Hutch Cancer Center, Seattle, WA, USA.
| | - Perry Shen
- Department of Surgery, Division of Surgical Oncology, Atrium Health Wake Forest Baptist, Winston Salem, NC, USA
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10
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Pelc Z, Sędłak K, Leśniewska M, Mielniczek K, Chawrylak K, Skórzewska M, Ciszewski T, Czechowska J, Kiszczyńska A, Wijnhoven BPL, Van Sandick JW, Gockel I, Gisbertz SS, Piessen G, Eveno C, Bencivenga M, De Manzoni G, Baiocchi GL, Morgagni P, Rosati R, Fumagalli Romario U, Davies A, Endo Y, Pawlik TM, Roviello F, Bruns C, Polkowski WP, Rawicz-Pruszyński K. Textbook Neoadjuvant Outcome-Novel Composite Measure of Oncological Outcomes among Gastric Cancer Patients Undergoing Multimodal Treatment. Cancers (Basel) 2024; 16:1721. [PMID: 38730672 PMCID: PMC11083243 DOI: 10.3390/cancers16091721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 04/26/2024] [Accepted: 04/26/2024] [Indexed: 05/13/2024] Open
Abstract
The incidence of gastric cancer (GC) is expected to increase to 1.77 million cases by 2040. To improve treatment outcomes, GC patients are increasingly treated with neoadjuvant chemotherapy (NAC) prior to curative-intent resection. Although NAC enhances locoregional control and comprehensive patient care, survival rates remain poor, and further investigations should establish outcomes assessment of current clinical pathways. Individually assessed parameters have served as benchmarks for treatment quality in the past decades. The Outcome4Medicine Consensus Conference underscores the inadequacy of isolated metrics, leading to increased recognition and adoption of composite measures. One of the most simple and comprehensive is the "All or None" method, which refers to an approach where a specific set of criteria must be fulfilled for an individual to achieve the overall measure. This narrative review aims to present the rationale for the implementation of a novel composite measure, Textbook Neoadjuvant Outcome (TNO). TNO integrates five objective and well-established components: Treatment Toxicity, Laboratory Tests, Imaging, Time to Surgery, and Nutrition. It represents a desired, multidisciplinary care and hospitalization of GC patients undergoing NAC to identify the treatment- and patient-related data required to establish high-quality oncological care further. A key strength of this narrative review is the clinical feasibility and research background supporting the implementation of the first and novel composite measure representing the "ideal" and holistic care among patients with locally advanced esophago-gastric junction (EGJ) and GC in the preoperative period after NAC. Further analysis will correlate clinical outcomes with the prognostic factors evaluated within the TNO framework.
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Affiliation(s)
- Zuzanna Pelc
- Department of Surgical Oncology, Medical University of Lublin, 20079 Lublin, Poland; (Z.P.); (K.S.); (M.L.); (K.M.); (K.C.); (M.S.); (T.C.); (J.C.); (A.K.); (W.P.P.)
| | - Katarzyna Sędłak
- Department of Surgical Oncology, Medical University of Lublin, 20079 Lublin, Poland; (Z.P.); (K.S.); (M.L.); (K.M.); (K.C.); (M.S.); (T.C.); (J.C.); (A.K.); (W.P.P.)
| | - Magdalena Leśniewska
- Department of Surgical Oncology, Medical University of Lublin, 20079 Lublin, Poland; (Z.P.); (K.S.); (M.L.); (K.M.); (K.C.); (M.S.); (T.C.); (J.C.); (A.K.); (W.P.P.)
| | - Katarzyna Mielniczek
- Department of Surgical Oncology, Medical University of Lublin, 20079 Lublin, Poland; (Z.P.); (K.S.); (M.L.); (K.M.); (K.C.); (M.S.); (T.C.); (J.C.); (A.K.); (W.P.P.)
| | - Katarzyna Chawrylak
- Department of Surgical Oncology, Medical University of Lublin, 20079 Lublin, Poland; (Z.P.); (K.S.); (M.L.); (K.M.); (K.C.); (M.S.); (T.C.); (J.C.); (A.K.); (W.P.P.)
| | - Magdalena Skórzewska
- Department of Surgical Oncology, Medical University of Lublin, 20079 Lublin, Poland; (Z.P.); (K.S.); (M.L.); (K.M.); (K.C.); (M.S.); (T.C.); (J.C.); (A.K.); (W.P.P.)
| | - Tomasz Ciszewski
- Department of Surgical Oncology, Medical University of Lublin, 20079 Lublin, Poland; (Z.P.); (K.S.); (M.L.); (K.M.); (K.C.); (M.S.); (T.C.); (J.C.); (A.K.); (W.P.P.)
| | - Joanna Czechowska
- Department of Surgical Oncology, Medical University of Lublin, 20079 Lublin, Poland; (Z.P.); (K.S.); (M.L.); (K.M.); (K.C.); (M.S.); (T.C.); (J.C.); (A.K.); (W.P.P.)
| | - Agata Kiszczyńska
- Department of Surgical Oncology, Medical University of Lublin, 20079 Lublin, Poland; (Z.P.); (K.S.); (M.L.); (K.M.); (K.C.); (M.S.); (T.C.); (J.C.); (A.K.); (W.P.P.)
| | - Bas P. L. Wijnhoven
- Department of General Surgery, Erasmus Medical Center, 3015 GD Rotterdam, The Netherlands;
| | - Johanna W. Van Sandick
- Department of Surgical Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands;
| | - Ines Gockel
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital Leipzig, 04103 Leipzig, Germany;
| | - Suzanne S. Gisbertz
- Department of Surgery, Amsterdam UMC location University of Amsterdam, 1007 MB Amsterdam, The Netherlands;
- Cancer Treatment and Quality of Life, Cancer Center Amsterdam, 1081 HV Amsterdam, The Netherlands
| | - Guillaume Piessen
- Department of Digestive and Oncological Surgery, University Lille, and Claude Huriez University Hospital, 59000 Lille, France; (G.P.); (C.E.)
| | - Clarisse Eveno
- Department of Digestive and Oncological Surgery, University Lille, and Claude Huriez University Hospital, 59000 Lille, France; (G.P.); (C.E.)
| | - Maria Bencivenga
- Upper G.I. Surgery Division, University of Verona, 37126 Verona, Italy; (M.B.); (G.D.M.)
| | - Giovanni De Manzoni
- Upper G.I. Surgery Division, University of Verona, 37126 Verona, Italy; (M.B.); (G.D.M.)
| | - Gian Luca Baiocchi
- Department of Clinical and Experimental Sciences, Surgical Clinic, University of Brescia, and Third Division of General Surgery, Spedali Civili di Brescia, 25123 Brescia, Italy;
| | - Paolo Morgagni
- Department of General Surgery, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy;
| | - Riccardo Rosati
- Department of Gastrointestinal Surgery, IRCCS San Raffaele Hospital, Vita Salute University, 20132 Milan, Italy;
| | | | - Andrew Davies
- Department of Upper Gastrointestinal and General Surgery, Guy’s and St Thomas’ Hospital, London SE1 7EH, UK;
| | - Yutaka Endo
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH 43210, USA; (Y.E.); (T.M.P.)
| | - Timothy M. Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH 43210, USA; (Y.E.); (T.M.P.)
| | - Franco Roviello
- Department of Medicine, Surgery, and Neurosciences, University of Siena, 53100 Siena, Italy;
| | - Christiane Bruns
- Department of General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, 50937 Cologne, Germany;
| | - Wojciech P. Polkowski
- Department of Surgical Oncology, Medical University of Lublin, 20079 Lublin, Poland; (Z.P.); (K.S.); (M.L.); (K.M.); (K.C.); (M.S.); (T.C.); (J.C.); (A.K.); (W.P.P.)
| | - Karol Rawicz-Pruszyński
- Department of Surgical Oncology, Medical University of Lublin, 20079 Lublin, Poland; (Z.P.); (K.S.); (M.L.); (K.M.); (K.C.); (M.S.); (T.C.); (J.C.); (A.K.); (W.P.P.)
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11
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van Hootegem SJM, Chmelo J, van der Sluis PC, Lagarde SM, Phillips AW, Wijnhoven BPL. The yield of diagnostic laparoscopy with peritoneal lavage in gastric adenocarcinoma: A retrospective cohort study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108233. [PMID: 38428107 DOI: 10.1016/j.ejso.2024.108233] [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: 10/20/2023] [Revised: 01/24/2024] [Accepted: 02/25/2024] [Indexed: 03/03/2024]
Abstract
INTRODUCTION Diagnostic laparoscopy (DL) with peritoneal lavage has been adopted as a standard staging procedure for patients with gastric cancer (GC). Evaluation of the value of DL is important given ongoing improvements in diagnostic imaging and treatment. As contemporary data from European centres are sparse, this retrospective cohort study aimed to assess the yield of DL in patients with potentially curable gastric cancer, and to identify predictive factors for peritoneal metastases. METHODS Patients with adenocarcinoma of the stomach, treated between January 2016 and December 2018, were identified from institutional databases of two high volume European Upper-GI centres. Patients who underwent a DL with peritoneal lavage for potentially curable disease after clinical staging with imaging (cT1-4N0-3M0) were included. The primary outcome was the proportion of patients with a positive DL, defined as macroscopic metastatic disease, positive peritoneal cytology washings (PC+) or locally irresectable disease. RESULTS Some 80 of 327 included patients (24.5%) had a positive DL, excluding these patients from neoadjuvant treatment (66 of 327; 20.2%) and/or surgical resection (76 of 327; 23.2%). In 34 of 327 patients (10.3%), macroscopic metastatic disease was seen, with peritoneal deposits in 30 of these patients. Only 16 of 30 patients with peritoneal disease had positive cytology. Some 41 of 327 patients (12.5%) that underwent DL had PC+ in the absence of macroscopic metastases and five patients (1.5%) had an irresectable primary tumour. Diffuse type carcinoma had the highest risk of peritoneal dissemination, irrespective of cT and cN categories. CONCLUSION The diagnostic yield of staging laparoscopy is high, changing the management in approximately one quarter of patients. DL should be considered in patients with diffuse type carcinoma irrespective of cT and cN categories.
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Affiliation(s)
- S J M van Hootegem
- Department of Surgery, Erasmus MC University, Rotterdam, the Netherlands.
| | - J Chmelo
- Northern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle-Upon-Tyne, UK
| | - P C van der Sluis
- Department of Surgery, Erasmus MC University, Rotterdam, the Netherlands
| | - S M Lagarde
- Department of Surgery, Erasmus MC University, Rotterdam, the Netherlands
| | - A W Phillips
- Northern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle-Upon-Tyne, UK; School of Medical Education, Newcastle University, UK
| | - B P L Wijnhoven
- Department of Surgery, Erasmus MC University, Rotterdam, the Netherlands
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12
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Halle-Smith JM, Bage T, Kamarajah SK, Siddaiah-Subramanya M, Pande R, Whiting JL, Griffiths EA. A preoperative predictive tool to assess the need for staging laparoscopy in oesophagogastric cancer patients. Ann R Coll Surg Engl 2024; 106:369-376. [PMID: 37642164 PMCID: PMC10981985 DOI: 10.1308/rcsann.2022.0140] [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] [Accepted: 10/26/2022] [Indexed: 08/31/2023] Open
Abstract
INTRODUCTION Staging laparoscopy (SL) has become commonplace in the preoperative staging pathway for oesophagogastric (OG) cancer. SL is often performed before curative treatment to examine for macroscopic peritoneal metastases (PM) or positive peritoneal cytology (PPC). The aim of this study was to develop an objective risk scoring system to predict both PM and PPC at SL. METHODS A prospectively collected and maintained database of all OG cancer patients treated between 2006 and 2020 was reviewed. Univariate and multivariate analyses were performed to identify risk factors for both PM and PPC at SL. A risk score was produced for both PM and PPC, and then validated internally. RESULTS Among 968 patients who underwent SL, 96 (9.9%) had PM and 81 (8.4%) had PPC at SL. Tumour site (p < 0.001), computed tomography (CT) T stage (p < 0.001) and N stage (p = 0.029) were significantly associated with PM at SL (p < 0.001). Tumour site (p < 0.001), biopsy histology (p = 0.041), CT T stage (p < 0.001) and N stage (p < 0.001) were significantly associated with PPC. The risk scoring model for PM included cancer site and CT T stage. This was successfully tested on the validation set (area under the receiver operating characteristic [AUROC] = 0.730). The risk scoring model for PPC included cancer site, CT T and N stage. This was successfully tested on the validation set (AUROC = 0.773). CONCLUSIONS The current risk scores are valid tools with which to predict the risk PM and PPC in patients undergoing SL for OG cancer and may help to avoid subjecting patients to unnecessary SL.
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Affiliation(s)
| | - T Bage
- Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, UK
| | | | | | - R Pande
- Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, UK
| | - JL Whiting
- Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, UK
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13
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Mitchell KG, Bayley EM, Ikoma N, Antonoff MB, Mehran RJ, Rajaram R, Rice DC, Roth JA, Sepesi B, Swisher SG, Vaporciyan AA, Walsh GL, Maru DM, Erasmus JJ, Weston BR, Ajani JA, Badgwell BD, Hofstetter WL. Gastric Extent of Tumor Predicts Peritoneal Metastasis in Siewert II Adenocarcinoma. Ann Thorac Surg 2024; 117:320-326. [PMID: 37080372 DOI: 10.1016/j.athoracsur.2023.04.014] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2022] [Revised: 03/14/2023] [Accepted: 04/10/2023] [Indexed: 04/22/2023]
Abstract
BACKGROUND Whereas current guidelines recommend staging laparoscopy for most patients with potentially resectable gastric cancer, such a recommendation for patients with adenocarcinoma of the gastroesophageal junction (AEG) is lacking. This study sought to identify baseline clinicopathologic characteristics associated with peritoneal metastasis (PM) among patients with Siewert II AEG. METHODS Trimodality therapy-eligible patients with Siewert II AEG (2000-2015, single institution) were retrospectively identified. A composite PM outcome was defined as follows: (1) PM at staging laparoscopy; (2) PM diagnosed during neoadjuvant chemoradiation; or (3) PM ≤6 months postoperatively. Logistic regression was used to identify features associated with PM; bootstrapped analysis (Youden J) identified the distal tumor extension that best discriminated the composite outcome. RESULTS Of 188 patients, a composite PM outcome was observed in 26 of 188 (13.8%); 12 of 26 had positive staging laparoscopy, 10 of 26 experienced PM during chemoradiation, and 4 of 26 had PM ≤6 months postoperatively. Tumor extension below the GEJ was greater in patients with PM (median, 4.0 cm [interquartile range, 3.0-5.0] vs 3.0 cm [interquartile range, 2.0-3.0]; P < .001). All patients with PM had cT3 to cT4 tumors. Among patients with cT3 to cT4 tumors (n = 168 of 188; 89.4%), distal tumor extent (odds ratio, 1.67/cm; 95% CI, 1.23-2.28; P = .001) was independently associated with increased odds of PM. Gastric tumor extension ≥4 cm remained independently associated with PM (OR, 5.14; 95% CI, 2.11-12.53; P < .001) after adjustment for signet ring cell status. CONCLUSIONS Distal tumor extent beyond the GEJ is independently associated with increased odds of PM in patients with Siewert II AEG. Patients with extensive gastric involvement should therefore be considered for staging laparoscopy before trimodality therapy.
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Affiliation(s)
- Kyle G Mitchell
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Erin M Bayley
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Naruhiko Ikoma
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Mara B Antonoff
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Reza J Mehran
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ravi Rajaram
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - David C Rice
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jack A Roth
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Boris Sepesi
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Stephen G Swisher
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ara A Vaporciyan
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Garrett L Walsh
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Dipen M Maru
- Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jeremy J Erasmus
- Department of Thoracic Imaging, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Brian R Weston
- Department of Gastroenterology Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jaffer A Ajani
- Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Brian D Badgwell
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Wayne L Hofstetter
- Department of Thoracic and Cardiovascular Surgery, University of Texas MD Anderson Cancer Center, Houston, Texas.
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14
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Buckarma E, Thiels CA, Jin Z, Grotz TE. Cytoreduction and Hyperthermic Intraperitoneal Paclitaxel and Cisplatin for Gastric Cancer with Peritoneal Metastasis. Ann Surg Oncol 2024; 31:622-629. [PMID: 37880514 DOI: 10.1245/s10434-023-14379-2] [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: 07/28/2023] [Accepted: 09/15/2023] [Indexed: 10/27/2023]
Abstract
BACKGROUND Peritoneal metastasis (PM) is the most common site of dissemination of gastric cancer (GC) and is associated with a poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for GC with PM remains controversial due to modest survival and significant morbidity. METHODS We conducted a retrospective analysis of patients with GC and PM treated with CRS and HIPEC with cisplatin and paclitaxel for 90 min from June 2019 to December 2022. RESULTS Twenty-two patients were included and received a median of 7 (interquartile range [IQR] 4-8) cycles of neoadjuvant systemic therapy. Seventeen patients (77%) underwent a single neoadjuvant laparoscopic HIPEC, and six (27%) patients received chemoradiation. The median Peritoneal Carcinomatosis Index at the time of CRS was 1 (IQR 0-4), and 21 patients (95%) underwent complete cytoreduction (CC-0). An R0 resection was achieved in 20 (91%) patients, and the median length of stay was 5.5 (IQR 4-7.5) days. There were six (27%) 90-day major complications (Clavien-Dindo grade ≥ 3), one (4%) Common Terminology Classification for Adverse Events (CTCAE) grade 4 cytopenia, and one (4%) acute kidney injury. The rate of anastomotic leak (all grades) was 14%, the 30-day readmission rate was 18%, and the 90-day mortality rate was 0%. At a median follow-up of 24 months, the median progression-free survival (PFS) and overall survival (OS) were not reached. The 1-, 2-, and 3-year PFS rates were 65%, 56%, and 40%, respectively, and the 1-, 2-, and 3-year OS rates were 96%, 78%, and 55%, respectively. CONCLUSIONS CRS and HIPEC with paclitaxel and cisplatin is well tolerated and is associated with favorable oncologic and perioperative outcomes.
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Affiliation(s)
- EeeLN Buckarma
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Cornelius A Thiels
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Zhaohui Jin
- GI Care Team, Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA
| | - Travis E Grotz
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA.
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15
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Jain AJ, Badgwell BD. Current Evidence for the Use of HIPEC and Cytoreductive Surgery in Gastric Cancer Metastatic to the Peritoneum. J Clin Med 2023; 12:6527. [PMID: 37892663 PMCID: PMC10607605 DOI: 10.3390/jcm12206527] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 10/11/2023] [Accepted: 10/12/2023] [Indexed: 10/29/2023] Open
Abstract
Gastric cancer (GCa) is an aggressive malignancy, representing the third leading cause of cancer mortality worldwide. The poor prognosis of GCa can be associated with the prevalence of peritoneal metastasis (PM). Current international and national GCa treatment guidelines only recommend palliative treatment options for patients with PM. Since the 1980s there have been multiple single arm trials, randomized controlled trials, and metanalysis investigating the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced GCa, with or without PM. Results from these studies have been encouraging, with some large-volume centers even incorporating HIPEC into their treatment algorithms for patients with advanced GCa. Additionally, there are several ongoing trials that, when completed, will increase our understanding of the efficacy of CRS & HIPEC in patients with GCa metastatic to the peritoneum. Herein we review the current evidence, ongoing trials, consensus guidelines, and future considerations regarding the use of CRS & HIPEC in patients suffering from GCa with PM.
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Affiliation(s)
- Anish J. Jain
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Brian D. Badgwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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16
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Lim ZY, Mohan S, Balasubramaniam S, Ahmed S, Siew CCH, Shelat VG. Indocyanine green dye and its application in gastrointestinal surgery: The future is bright green. World J Gastrointest Surg 2023; 15:1841-1857. [PMID: 37901741 PMCID: PMC10600780 DOI: 10.4240/wjgs.v15.i9.1841] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2023] [Revised: 07/17/2023] [Accepted: 07/31/2023] [Indexed: 09/21/2023] Open
Abstract
Indocyanine green (ICG) is a water-soluble fluorescent dye that is minimally toxic and widely used in gastrointestinal surgery. ICG facilitates anatomical identification of structures (e.g., ureters), assessment of lymph nodes, biliary mapping, organ perfusion and anastomosis assessment, and aids in determining the adequacy of oncological margins. In addition, ICG can be conjugated to artificially created antibodies for tumour markers, such as carcinoembryonic antigen for colorectal, breast, lung, and gastric cancer, prostate-specific antigen for prostate cancer, and cancer antigen 125 for ovarian cancer. Although ICG has shown promising results, the optimization of patient factors, dye factors, equipment, and the method of assessing fluorescence intensity could further enhance its utility. This review summarizes the clinical application of ICG in gastrointestinal surgery and discusses the emergence of novel dyes such as ZW-800 and VM678 that have demonstrated appropriate pharmacokinetic properties and improved target-to-background ratios in animal studies. With the emergence of robotic technology and the increasing reporting of ICG utility, a comprehensive review of clinical application of ICG in gastrointestinal surgery is timely and this review serves that aim.
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Affiliation(s)
- Zavier Yongxuan Lim
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
| | - Swetha Mohan
- Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
| | | | - Saleem Ahmed
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
| | | | - Vishal G Shelat
- Department of General Surgery, Tan Tock Seng Hospital, Singapore 308433, Singapore
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17
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Yang S, Li J, Cai X. The high expression of glial cell line-derived neurotrophic factor receptor alpha Ⅱ ( GFRA2) as a predictor of poor prognosis in gastric cancer patients: A survival and regression analysis approach. Heliyon 2023; 9:e18291. [PMID: 37519699 PMCID: PMC10372394 DOI: 10.1016/j.heliyon.2023.e18291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 07/09/2023] [Accepted: 07/13/2023] [Indexed: 08/01/2023] Open
Abstract
Gastric cancer has high mortality rates worldwide. Therefore, there is a need to identify prognostic biomarkers. This study evaluated the association between GFRA2 expression levels with clinicopathological features and prognosis in gastric cancer using data extracted from The Cancer Genome Atlas (TCGA) database and a series of algorithms. Survival analysis was performed using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were used to analyze the association between different clinical features and survival. Single-sample gene set enrichment analysis (GSEA) was used to examine the correlation between GFRA2 expression and immune infiltration. The results showed that the expression of GFRA2 in tumor samples was significantly lower than that in normal samples. High expression of GFRA2 was significantly associated with histological type, histologic grade, and worse overall survival, disease-specific survival, and progression-free survival. The univariate Cox analysis showed that the expression of GFRA2 was significantly correlated with T stage, N stage, M stage, and age. The multivariate analysis identified GFRA2 expression as an independent prognostic factor for gastric cancer. GSEA showed that GFRA2 might regulate the calcium signaling pathway, focus adhesion, olfactory conduction, the extracellular matrix glycoproteins, and response to the Leishmania parasitic infection. GFRA2 showed a significant moderate positive correlation with the infiltration of mast cells. In summary, a high expression of GFRA2 may contribute to poor survival in gastric cancer patients and could be used as a potential prognostic biomarker.
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Affiliation(s)
- Shaoyu Yang
- College of Marine Sciences, Guangxi Key Laboratory of Beibu Gulf Marine Biodiversity Conservation, Beibu Gulf University, Qinzhou 535011, China
- Nanchang Institute of Technology, Nanchang, 330044, China
| | - Juan Li
- School of Basic Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China
| | - Xiaohui Cai
- College of Marine Sciences, Guangxi Key Laboratory of Beibu Gulf Marine Biodiversity Conservation, Beibu Gulf University, Qinzhou 535011, China
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18
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Schena CA, Laterza V, De Sio D, Quero G, Fiorillo C, Gunawardena G, Strippoli A, Tondolo V, de'Angelis N, Alfieri S, Rosa F. The Role of Staging Laparoscopy for Gastric Cancer Patients: Current Evidence and Future Perspectives. Cancers (Basel) 2023; 15:3425. [PMID: 37444535 DOI: 10.3390/cancers15133425] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Revised: 06/18/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023] Open
Abstract
A significant proportion of patients diagnosed with gastric cancer is discovered with peritoneal metastases at laparotomy. Despite the continuous improvement in the performance of radiological imaging, the preoperative recognition of such an advanced disease is still challenging during the diagnostic work-up, since the sensitivity of CT scans to peritoneal carcinomatosis is not always adequate. Staging laparoscopy offers the chance to significantly increase the rate of promptly diagnosed peritoneal metastases, thus reducing the number of unnecessary laparotomies and modifying the initial treatment strategy of gastric cancer. The aim of this review was to provide a comprehensive summary of the current literature regarding the role of staging laparoscopy in the management of gastric cancer. Indications, techniques, accuracy, advantages, and limitations of staging laparoscopy and peritoneal cytology were discussed. Furthermore, a focus on current evidence regarding the application of artificial intelligence and image-guided surgery in staging laparoscopy was included in order to provide a picture of the future perspectives of this technique and its integration with modern tools in the preoperative management of gastric cancer.
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Affiliation(s)
- Carlo Alberto Schena
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Unit of Colorectal and Digestive Surgery, DIGEST Department, Beaujon University Hospital, AP-HP, University of Paris Cité, Clichy, 92110 Paris, France
| | - Vito Laterza
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Davide De Sio
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Giuseppe Quero
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Digestive Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Claudio Fiorillo
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Gayani Gunawardena
- Department of Digestive Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Antonia Strippoli
- Medical Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Vincenzo Tondolo
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
| | - Nicola de'Angelis
- Unit of Colorectal and Digestive Surgery, DIGEST Department, Beaujon University Hospital, AP-HP, University of Paris Cité, Clichy, 92110 Paris, France
| | - Sergio Alfieri
- Digestive Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Digestive Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Fausto Rosa
- Department of Digestive Surgery, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Emergency and Trauma Surgery Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
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19
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Racz K, Legner A, Böhme F, Sebesta C. [Gastric cancer]. Wien Med Wochenschr 2023; 173:227-231. [PMID: 37071301 DOI: 10.1007/s10354-023-01011-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 03/06/2023] [Indexed: 04/19/2023]
Abstract
Gastric cancers are relativ commonly cancer types. The therapy options have changed in the last years as well in the surgery as in the oncology, it is worth to look at the etiology, diagnosis and therapy.
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Affiliation(s)
- Krisztina Racz
- 2. Medizinische Abteilung, Klinik Donaustadt, Donaustadt, Österreich.
| | - Andras Legner
- Chirurgische Abteilung, Klinik Donaustadt, Donaustadt, Österreich
| | - Felix Böhme
- 2. Medizinische Abteilung, Klinik Donaustadt, Donaustadt, Österreich
| | - Christian Sebesta
- 2. Medizinische Abteilung, Klinik Donaustadt, Donaustadt, Österreich
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20
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Rawicz-Pruszyński K, Sędłak K, Pelc Z, Mlak R, Litwiński J, Mańko P, Zinkiewicz K, Paśnik I, Cięszczyk K, Pawlik T, Märkl B, Erodotou M, Polkowski WP. Staging LaParoscopy to Assess Lymph NOde InvoLvement in Advanced GAstric Cancer (POLA)-Study protocol for a single-arm prospective observational multicenter study. PLoS One 2023; 18:e0285758. [PMID: 37205666 DOI: 10.1371/journal.pone.0285758] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 04/25/2023] [Indexed: 05/21/2023] Open
Abstract
INTRODUCTION In the era of neoadjuvant chemotherapy in advanced gastric cancer (GC), the role of staging laparoscopy (SL) will become more established. However, despite guidelines recommendations, SL for optimal preoperative staging remains underutilized. Diagnostic value of near-infrared (NIR) / indocyanine green (ICG) guided sentinel node (SN) mapping in GC confirmed its technical feasibility, however no data exist regarding its potential role in pathological nodal staging. To the best of our knowledge, current study is the first to evaluate the role of ICG in nodal staging of advanced GC patients undergoing SL. MATERIALS AND METHODS This single-arm prospective observational multicenter study was approved by the Bioethical Committee of Medical University of Lublin (Ethic Code: KE-0254/331/2018). The protocol is registered at clinicaltrial.gov (NCT05720598), and the study results will be reported according to the Strengthening of Reporting of Observational Studies in Epidemiology (STROBE) statement. The primary endpoint of this study is the identification rate of ICG-guided SN in advanced GC patients. The secondary endpoints include pathological and molecular assessment of retrieved SNs and other pretreatment clinical variables potentially associated with SL: pattern of perigastric ICG distribution according to patients' pathological and clinical characteristics, neoadjuvant chemotherapy compliance, 30-day morbidity, and mortality. CONCLUSION POLA study is the first to investigate the clinical value of ICG-enhanced sentinel node biopsy during staging laparoscopy in advanced GC patients in a Western cohort. Identifying pN status before multimodal treatment will improve GC staging process.
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Affiliation(s)
| | - Katarzyna Sędłak
- Department of Surgical Oncology, Medical University of Lublin, Lublin, Poland
| | - Zuzanna Pelc
- Department of Surgical Oncology, Medical University of Lublin, Lublin, Poland
| | - Radosław Mlak
- Body Composition Research Laboratory, Department of Preclinical Sciences, Medical University of Lublin, Lublin, Poland
| | - Jakub Litwiński
- Department of Surgical Oncology, Medical University of Lublin, Lublin, Poland
| | - Paweł Mańko
- Department of Surgical Oncology, Medical University of Lublin, Lublin, Poland
| | | | - Iwona Paśnik
- Department of Clinical Pathomorphology, Medical University of Lublin, Lublin, Poland
| | - Katarzyna Cięszczyk
- Department of Clinical Pathomorphology, Medical University of Lublin, Lublin, Poland
| | - Timothy Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center and James Cancer Center, Columbus, Ohio, United States of America
| | - Bruno Märkl
- Institute of Pathology, Klinikum Augsburg, Augsburg, Germany
| | - Maria Erodotou
- Department of Surgery, Erasmus MC, Rotterdam, The Netherlands
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21
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Allievi N, Bianco F, Pisano M, Montori G, Fugazzola P, Coccolini F, Lotti M, Mosconi S, Merelli B, Campanati L, Lucianetti A, Ansaloni L, Magnone S. Hyperthermic intraperitoneal chemotherapy (HIPEC) as adjuvant and therapeutic options for patients with advanced gastric cancer at high risk of recurrence or established peritoneal metastases: a single-centre experience. Updates Surg 2023; 75:159-167. [PMID: 36371549 DOI: 10.1007/s13304-022-01399-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 10/04/2022] [Indexed: 11/13/2022]
Abstract
Peritoneal metastases from gastric cancer (PM-GC) have a detrimental prognostic impact on survival and there is a lack of consensus regarding treatment. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may offer a chance for prolonged survival as compared to standard chemotherapy. This study aims to present our experience in the management of GC with CRS and HIPEC. This is a single-centre retrospective study. Patients were divided into two groups: patients with GC at high risk for developing PM-GC (adjuvant HIPEC group) and patients with PM-GC or positive peritoneal cytology (therapeutic CRS and HIPEC group). Overall survival (OS) and disease-free survival (DFS) were considered as outcome measures. A total of 41 patients with a GC primary received surgery and HIPEC: 14 patients (34.1%) were in the adjuvant HIPEC group, while 27 patients (65.9%) were in the therapeutic CRS and HIPEC group. In the adjuvant HIPEC group, the 1- and 3-year OS were 85.7% and 71.4%, while 1- and 3-year DFS were 71.4% and 64.3%, respectively. In the therapeutic CRS and HIPEC group, OS was 60.3% and 35.1% at 1 and 3 years, whereas 1- and 3-year DFS were 38% and 32.6%, respectively. Univariate survival analysis of patients in the therapeutic CRS and HIPEC group showed that the presence of lymph node metastasis and signet ring cell histology predicted worse OS, while PCI > 12 and lymph node metastasis were associated with decreased DFS. Treatment of highly selected patients with GC at high risk of peritoneal recurrence or established PM with CRS and HIPEC showed satisfactory results in terms of OS and DFS.
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Affiliation(s)
- Niccolò Allievi
- First Department of General Surgery, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127, Bergamo, Italy
| | - Federica Bianco
- First Department of General Surgery, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127, Bergamo, Italy
| | - Michele Pisano
- First Department of General Surgery, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127, Bergamo, Italy
| | | | - Paola Fugazzola
- Unit of General Surgery, IRCCS San Matteo Foundation Hospital, Pavia, Italy
| | - Federico Coccolini
- General, Emergency and Trauma Surgery, Pisa University Hospital, Pisa, Italy
| | - Marco Lotti
- Division of General Surgery, Fatebenefratelli Oftalmico Hospital, Milan, Italy
| | | | - Barbara Merelli
- Medical Oncology Unit, Giovanni XXIII Hospital, Bergamo, Italy
| | - Luca Campanati
- First Department of General Surgery, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127, Bergamo, Italy
| | - Alessandro Lucianetti
- First Department of General Surgery, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127, Bergamo, Italy
| | - Luca Ansaloni
- Unit of General Surgery, IRCCS San Matteo Foundation Hospital, Pavia, Italy
| | - Stefano Magnone
- First Department of General Surgery, Papa Giovanni XXIII Hospital, Piazza OMS 1, 24127, Bergamo, Italy.
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22
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Guan G, Li Z, Wang Q, Ying X, Shan F, Li Z. Risk factors associated with peritoneal carcinomatosis of gastric cancer in staging laparoscopy: A systematic review and meta-analysis. Front Oncol 2022; 12:955181. [PMID: 36387230 PMCID: PMC9650136 DOI: 10.3389/fonc.2022.955181] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Accepted: 09/26/2022] [Indexed: 11/30/2022] Open
Abstract
Background The optimal indications of staging laparoscopy in gastric cancer to detect peritoneal carcinomatosis are still controversial. We performed this systematic review and meta-analysis to quantify the relevance of the preoperative factors with peritoneal carcinomatosis to explore the indications of staging laparoscopy. Materials and methods Systematic searches were conducted using Medline, Embase, and the Cochrane Library in December 2021. On the basis of calculating the odds ratio (OR) of each factor, we quantified the association between the risk factors and peritoneal carcinomatosis such as clinical T/N stage, Borrmann type, and tumor markers, using meta-analysis with a random-effects model. Results A total of 21 case-control studies and one cohort study were obtained. T stage, N stage, and differentiation degree were most widely studied, with OR values of 2.96 (95% CI: 1.87–4.69), 1.22 (95% CI: 0.86–1.73), and 1.91 (95% CI: 1.42–2.56), respectively. Among all the factors, elevated CA125 (OR = 19.45, 95% CI: 4.71–80.30), Borrmann type IV (OR = 7.68, 95% CI: 3.62–16.27), and large tumor diameter (OR = 5.12, 95% CI: 2.55–10.31) had the highest OR. In particular, CA125 had the best predictability for peritoneal carcinomatosis but was only mentioned by three articles. Conclusions There was a cognitive gap between the awareness and importance of risk factors for peritoneal carcinomatosis. In addition to T4 stage, patients with factors with high OR, such as Borrmann type IV, large tumor diameter, and elevated CA125, should undergo staging laparoscopy.
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23
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Gronnier C. Feature Review Papers on Gastroesophageal Junction and Gastric Cancers. Cancers (Basel) 2022; 14:cancers14163979. [PMID: 36010970 PMCID: PMC9406375 DOI: 10.3390/cancers14163979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 08/16/2022] [Indexed: 11/16/2022] Open
Affiliation(s)
- Caroline Gronnier
- Eso-Gastric Surgery Unit, Department of Digestive Surgery, Magellan Center, Bordeaux University Hospital, 33600 Pessac, France; ; Tel.: +33-(5)-5765-6005; Fax: +33-(5)-5765-6003
- Faculty of Medicine, Bordeaux Ségalen University, 33076 Bordeaux, France
- U1312 BRIC—BoRdeaux Institute in Oncology Inserm/Team 4 “Helicobacter-Associated Digestive Cancers, Cancer Stem Cells and Therapeutic Strategies”, 33076 Bordeaux, France
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24
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Solaini L, Bencivenga M, D'ignazio A, Milone M, Marino E, De Pascale S, Rosa F, Sacco M, Fumagalli Romario U, Graziosi L, De Palma G, Marrelli D, Morgagni P, Ercolani G. Which gastric cancer patients could benefit from staging laparoscopy? A GIRCG multicenter cohort study. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:1778-1784. [PMID: 35101316 DOI: 10.1016/j.ejso.2022.01.020] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 11/29/2021] [Accepted: 01/19/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND This study aimed to investigate which gastric cancer patients could benefit the most from staging laparoscopy. METHODS A retrospective cohort study was carried out, including 316 (216 cM- and 100 cM+) gastric cancer patients who had undergone staging laparoscopy between 2010 and 2020 in seven GIRCG centers. A model including easily-accessible clinical, biochemical and pathological markers was constructed to predict the risk of carcinomatosis. ROC curve and decision curve analyses were used to verify its accuracy and net benefit. RESULTS In the cM-population staging laparoscopy could detect 67 cases who had peritoneal carcinomatosis or positive cytology, for a yield of 30.5%. In cM-patients, intestinal type tumors (0.25, 0.12-0.51; p = 0.002), cT4 tumors (2.18, 1.11-4.28; p = 0.023) and cancers of the lower third (0.31, 0.14-0.70; p = 0.004) were associated with the presence of peritoneal carcinomatosis and/or positive cytology. The ROC curve analysis of the model including the three variables showed an AUC of 0.75 (0.68-0.81, p < 0.001). The decision curve analyses showed that the model had a higher net benefit than the treating all strategy between threshold probabilities of 15 and 50%. CONCLUSIONS Staging laparoscopy is a useful tool to address the patient with gastric cancer to the most adequate treatment. In cM-patients the assessment of the location of the tumor, the Lauren's histotype and the cT status may help in providing additional elements in indicating or not the use of staging laparoscopy.
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Affiliation(s)
- Leonardo Solaini
- Department of Medical and Surgical Sciences, University of Bologna, Morgagni-Pierantoni Hospital, Forlì, Italy.
| | - Maria Bencivenga
- University of Verona, General and Upper GI Surgery Division, Verona, Italy
| | - Alessia D'ignazio
- Policlinico le Scotte- University of Siena, Department of Surgery, Siena, Italy
| | - Marco Milone
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", Italy
| | - Elisabetta Marino
- Santa Maria della Misericordia Hospital University of Perugia, Department of Surgery, Perugia, Italy
| | | | - Fausto Rosa
- Digestive Surgery, Fondazione Policlinico Universitario "A. Gemelli", Università Cattolica del Sacro Cuore, Rome, Italy
| | - Michele Sacco
- University of Verona, General and Upper GI Surgery Division, Verona, Italy
| | | | - Luigina Graziosi
- Santa Maria della Misericordia Hospital University of Perugia, Department of Surgery, Perugia, Italy
| | - Giovanni De Palma
- Department of Clinical Medicine and Surgery, University of Naples "Federico II", Italy
| | - Daniele Marrelli
- Policlinico le Scotte- University of Siena, Department of Surgery, Siena, Italy
| | - Paolo Morgagni
- Department of Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy
| | - Giorgio Ercolani
- Department of Medical and Surgical Sciences, University of Bologna, Morgagni-Pierantoni Hospital, Forlì, Italy
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25
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Vatandoust S, Bright T, Roy AC, Abbas MN, Watson DI, Gan S, Bull J, Sorich M, Scott-Hoy A, Luu LJ, Karapetis CS. Phase 1 trial of intraperitoneal paclitaxel in combination with intravenous cisplatin and oral capecitabine in patients with advanced gastric cancer and peritoneal metastases (IPGP study). Asia Pac J Clin Oncol 2022; 18:404-409. [PMID: 34811896 DOI: 10.1111/ajco.13659] [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: 07/16/2021] [Accepted: 08/04/2021] [Indexed: 12/24/2022]
Abstract
AIMS Gastric cancer with peritoneal involvement has a poor prognosis. Intraperitoneal (IP) paclitaxel has shown promising results in these patients. However, this approach has only been studied in the Asian population, and in combination with S-1. We investigated the maximum tolerated dose of IP paclitaxel, with a standard chemotherapy combination, in the Australian population. METHODS The study of the population included metastatic human epidermal growth factor receptor 2 (HER2) negative gastric adenocarcinoma with peritoneal involvement. Treatment included six 21-day cycles of cisplatin (80 mg/m2 IV, day 1) plus capecitabine (1000 mg/m2 PO BD, days 1-14) plus IP paclitaxel (days 1 and 8). IP paclitaxel doses for cohort 1-3 were 10, 20, and 30 mg/m2 , respectively, in a 3 + 3 standard dose-escalation design. RESULTS Fifteen patients were enrolled of which 6 were female and the median age was 63. Two patients developed dose-limiting toxicities. No grade 4/5 toxicities were recorded. The maximum tolerated dose was not reached. Therefore, as defined by the study protocol, the recommended phase-2 dose for IP paclitaxel was determined to be 30 mg/m2 . The 12-month survival rate was 46.7%, and the median survival was 11.5 months (interquartile range [IQR]: 15.3-6.9). CONCLUSIONS IP paclitaxel is safe in combination with cisplatin and capecitabine and the recommended phase-2 dose is 30 mg/m2 .
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Affiliation(s)
- Sina Vatandoust
- Department of Medical Oncology, Flinders Medical Centre, Bedford Park, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Tim Bright
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
- Oesophago-Gastric Surgical Unit, Flinders Medical Centre, Bedford Park, Australia
| | - Amitesh Chandra Roy
- Department of Medical Oncology, Flinders Medical Centre, Bedford Park, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Muhammad Nazim Abbas
- Department of Medical Oncology, Flinders Medical Centre, Bedford Park, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - David Ian Watson
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
- Oesophago-Gastric Surgical Unit, Flinders Medical Centre, Bedford Park, Australia
| | - Susan Gan
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
- Oesophago-Gastric Surgical Unit, Flinders Medical Centre, Bedford Park, Australia
| | - Jeff Bull
- Oesophago-Gastric Surgical Unit, Flinders Medical Centre, Bedford Park, Australia
| | - Michael Sorich
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Alex Scott-Hoy
- Department of Medical Oncology, Flinders Medical Centre, Bedford Park, Australia
| | - Lee-Jen Luu
- Department of Medical Oncology, Flinders Medical Centre, Bedford Park, Australia
| | - Christos Stelios Karapetis
- Department of Medical Oncology, Flinders Medical Centre, Bedford Park, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
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26
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Li Z, Guan G, Liu Z, Li J, Ying X, Shan F, Li Z. Predicting peritoneal carcinomatosis of gastric cancer: A simple model to exempt low-risk patients from unnecessary staging laparoscopy. Front Surg 2022; 9:916001. [PMID: 35937608 PMCID: PMC9349356 DOI: 10.3389/fsurg.2022.916001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 06/28/2022] [Indexed: 11/21/2022] Open
Abstract
Background Peritoneal carcinomatosis (PC) of gastric cancer indicates a poor outcome and is mainly diagnosed by staging laparoscopy (SL). This study was designed to develop a risk stratification model based on the number of risk factors to exempt low-risk patients from unnecessary SL. Methods This was a retrospective cohort study based on a single institution between January 2015 and December 2019. SL is indicated for patients of advanced locoregional stage, and clinicopathologic characteristics of 535 consecutive patients were included. PC-associated variables were identified by logistic regression analysis. A risk stratification model based on the number of risk factors was constructed, and we defined its predictive value with a receiver operating characteristic (ROC) curve and negative predictive value. Results In total, 15.9% of included patients were found to have PC during SL. Borrmann type IV, elevated CA125, and tumour diameter ≥5 cm were independent risk factors of PC. These three factors combined with cT4 were selected as predictive factors, and the number of predictive variables was significantly related to the possibility of PC (2.0%, 12.8%, 20.0%, 54.2%, and 100%, respectively). When the cutoff value is more than one predictive factor, the negative predictive value is 98.0%, with an area under the curve of 0.780. This model could exempt 29.8% of unnecessary SL compared to the indication of the current NCCN guideline. Conclusions We constructed a simple model to predict the probability of PC using the number of predictive factors. It is recommended that patients without any of these factors should be exempt from SL.
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27
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Zhu X, Wang J, Jin X, Chen Y, Hu L, Zhao J. Construction and evaluation of a prognostic risk assessment model of gastric cancer by using hypoxia features. Mutat Res 2022; 825:111795. [PMID: 36049301 DOI: 10.1016/j.mrfmmm.2022.111795] [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: 04/07/2022] [Revised: 07/15/2022] [Accepted: 08/08/2022] [Indexed: 06/15/2023]
Abstract
In this study, mRNA expression of gastric cancer tissue and clinical data of patients in TCGA-STAD dataset were used, together with the hypoxia-related gene sets in the MsigDB database, to screen hypoxia-related differentially expressed genes (DEGs) in GC. Thereafter, univariate and multivariate Cox regression analyses were carried out on hypoxia-related DEGs. The optimal feature genes related to prognosis were obtained to construct a prognostic risk assessment model. According to the model, the riskScore of GC patients was measured, and GC samples were assigned into high- and low-risk groups in accordance with the median riskScore. Based on the Kaplan-Meier curve and Receiver operating characteristic curve, validity of the prognostic risk assessment model was measured. Gene set enrichment analysis was performed on the two risk groups through Gene set enrichment analysis software. The results revealed that in the high-risk group, 9 signaling pathways were remarkably activated in several terms, like focal adhesion, extracellular matrix receptor interaction, Cell adhesion molecules cams, Cytokine-cytokine receptor interaction, TGF-beta signaling pathway, NOD-like receptor signaling pathway, JAK-STAT signaling pathway, Toll-like receptor signaling pathway and MAPK signaling pathway. In combination with riskScore and clinical factors, univariate and multivariate Cox regression analyses verified the independence of the model. Meanwhile, a nomogram was constructed to predict the 1-, 3- and 5-year survival of GC patients. The calibration curve indicated that the survival status predicted by the nomogram fitted better with actual survival status. On the whole, the prognostic risk model of GC on the basis of hypoxia-related genes demonstrated good predictive ability. It can provide more powerful technical support for clinicians to make prognostic determination and therapeutic plans.
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Affiliation(s)
- Xiaoling Zhu
- Department of Oncology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing 312000, China
| | - Jianfang Wang
- Department of Oncology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing 312000, China
| | - Xueying Jin
- Department of Oncology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing 312000, China
| | - Yiyi Chen
- Department of Clinical Medicine, Wenzhou Medical University, Wenzhou 325035, China
| | - Liang Hu
- Assistant Researcher, Shanghai Engineering Research Center of Pharmaceutical Translation, Shanghai 200231, China
| | - Jianguo Zhao
- Department of Oncology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing 312000, China.
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28
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Guo Z, Guo H, Tian Y, Zhang Z, Zhao Q. Nomograms for Predicting Disease-Free Survival in Patients With Siewert Type II/III Adenocarcinoma of the Esophagogastric Junction Receiving Neoadjuvant Therapy and Radical Surgery. Front Oncol 2022; 12:908229. [PMID: 35756688 PMCID: PMC9213656 DOI: 10.3389/fonc.2022.908229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 05/19/2022] [Indexed: 11/15/2022] Open
Abstract
Objective This study aimed to develop prognostic prediction models for patients with Siewert type II/III adenocarcinoma of the esophagogastric junction (AEG) who received neoadjuvant therapy (neoadjuvant chemoradiotherapy or neoadjuvant chemotherapy) and radical surgery. A baseline nomogram and a post-operative nomogram were constructed before neoadjuvant therapy and after surgery. The predictive performance of the constructed nomograms was internally validated and compared to the TNM staging system. Materials and Methods A total of 245 patients diagnosed with Siewert type II/III AEG and treated with neoadjuvant therapy followed by radical surgery at The Fourth Hospital of Hebei Medical University between January 2011 and December 2017 were enrolled. The variables before neoadjuvant therapy were defined as baseline factors, while the variables of baseline factors along with the variables of treatment and postoperative pathology were defined as post-operative factors. To construct the corresponding nomograms, independent predictors of baseline and post-operative factors were identified. The C-index and a time-dependent receiver operating characteristic curve were used to evaluate the model’s discrimination ability. The calibration ability of the model was determined by comparing the probability of predicted free-recurrence to the actual free-recurrence. Decision curve analysis (DCA) was used to determine the clinical usefulness of the nomogram. Results Among the baseline factors, age, cT stage, cN stage, Borrmann type, and staging laparoscopy were independent prognostic predictors. In contrast, among the post-operative factors, age, cN stage, staging laparoscopy, ypT stage, clinical response, number of positive lymph nodes, number of negative lymph nodes, laurén classification, and lymphatic, or perineural invasion (VELPI) were independent prognostic predictors. The two nomograms were constructed using the independent predictors of prognosis. The C-indexes for the baseline and post-operative nomograms were 0.690 (95% CI, 0.644-0.736) and 0.817 (95% CI, 0.782-0.853), respectively. The AUCs of the baseline nomogram at 3 and 5 years were both greater than cTNM (73.1 vs 58.8, 76.1 vs 55.7). Similarly, the AUCs of the post-operative nomogram were both greater than ypTNM (85.2 vs 69.1, 88.2 vs 71.3) at 3 and 5 years. The calibration curves indicated that both models had a high degree of calibration ability. By comparing the DCA at 3 and 5 years, we determined that the two nomograms constructed had better clinical utility than the TNM staging system. Conclusions The constructed nomograms have a more accurate predictive ability than the eighth edition TNM staging system, which can be useful for treatment selection and follow-up monitoring of patients.
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Affiliation(s)
- Zhenjiang Guo
- Third Surgery Department, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.,Department of Gastrointestinal Surgery, Hengshui People's Hospital, Hengshui, China
| | - Honghai Guo
- Third Surgery Department, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yuan Tian
- Third Surgery Department, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Ze Zhang
- Third Surgery Department, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Qun Zhao
- Third Surgery Department, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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Young S, Ou R, Dehal A, O'Connor VV, DiFronzo LA. Peritoneal Lavage Cytology Following Neoadjuvant Chemotherapy for Gastric Adenocarcinoma: Low Yield in Detecting Peritoneal Metastases. Am Surg 2022; 88:1084-1089. [PMID: 33382351 DOI: 10.1177/0003134820984867] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Peritoneal lavage cytology (PLC) can detect advanced disease in gastric adenocarcinoma (GC); however, routine practice remains controversial. Furthermore, the effect of neoadjuvant chemotherapy (NAC) on cytological detection of carcinomatosis is unknown. METHODS Using a 2012-2020 prospective database, we retrospectively reviewed patients with GC who underwent NAC followed by a staging laparoscopic peritoneal lavage with or without biopsy of suspicious peritoneal nodules. PLC results were considered discordant if they did not align with the peritoneal biopsy results. Patients with benign peritoneal cytology (Cyt-) or biopsy results who had postoperative time to carcinomatosis of <6 months were considered to have diagnostic failure of peritoneal lavage. RESULTS Fifty-five patients with GC who underwent NAC followed by staging diagnostic laparoscopy with peritoneal lavage were identified. The majority of the patients in the cohort had Cyt- lavage (89.1%). Of the patients who underwent resection, 76.1% had T3 or greater disease on final pathology and 66% had nodal metastases. In 23 patients (41.8%) who had both peritoneal lavage and biopsy, four cases (17.4%) had discordant results. Diagnostic failure rate was 20% at 6 months and 42.2% at 12 months. The median time to carcinomatosis in patients who were Cyt- or biopsy negative was 7.9 months. CONCLUSION PLC after NAC has a high diagnostic failure rate and inaccurately predicts carcinomatosis in 20% of patients with GC. Novel methods for identifying cytology positive GC after NAC should also be developed and evaluated, since the risk of peritoneal dissemination is high.
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Affiliation(s)
- Stephanie Young
- Department of Surgery, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, USA
| | - Ryan Ou
- Department of Surgery, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, USA
| | - Ahmed Dehal
- Department of Surgery, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, USA
| | - Victoria V O'Connor
- Department of Surgery, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, USA
| | - L Andrew DiFronzo
- Department of Surgery, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA, USA
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Agnes A, Biondi A, Persiani R, Laurino A, Reddavid R, De Giuli M, Sicoli F, Cananzi F, De Pascale S, Fumagalli U, Galli F, Rausei S, Lorenzon L, D'Ugo D. Development of the PERI-Gastric (PEritoneal Recurrence Index) and PERI-Gram (Peritoneal Recurrence Index NomoGRAM) for predicting the risk of metachronous peritoneal carcinomatosis after gastrectomy with curative intent for gastric cancer. Gastric Cancer 2022; 25:629-639. [PMID: 34811622 DOI: 10.1007/s10120-021-01268-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2021] [Accepted: 11/13/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND A model that quantifies the risk of peritoneal recurrence would be a useful tool for improving decision-making in patients undergoing curative-aim gastrectomy for gastric cancer (GC). METHODS Five Italian centers participated in this study. Two risk scores were created according to the two most widely used pathologic classifications of GC (the Lauren classification and the presence of signet-ring-cell features). The risk scores (the PERI-Gastric 1 and 2) were based on the results of multivariable logistic regressions and presented as nomograms (the PERI-Gram 1 and 2). Discrimination was assessed with the area under the curve (AUC) of receiver operating curves. Calibration graphs were constructed by plotting the actual versus the predicted rate of peritoneal recurrence. Internal validation was performed with a bootstrap resampling method (1000 iterations). RESULTS The models were developed based on a population of 645 patients (selected from 1580 patients treated from 1998 to 2018). In the PERI-Gastric 1, significant variables were linitis plastica, stump GC, pT3-4, pN2-3 and the Lauren diffuse histotype, while in the PERI-Gastric 2, significant variables were linitis plastica, stump GC, pT3-4, pN2-3 and the presence of signet-ring cells. The AUC was 0,828 (0.778-0.877) for the PERI-Gastric 1 and 0,805 (0.755-0.855) for the PERI-Gastric 2. After bootstrap resampling, the PERI-Gastric 1 had a mean AUC of 0.775 (0.721-0.830) and a 95%CI estimate for the calibration slope of 0.852-1.505 and the PERI-Gastric 2 a mean AUC of 0.749 (0.693-0.805) and a 95%CI estimate for the slope of 0.777-1.351. The models are available at www.perigastric.org . CONCLUSIONS We developed the PERI-Gastric and the PERI-Gram as instruments to determine the risk of peritoneal recurrence after curative-aim gastrectomy. These models could direct the administration of prophylactic intraperitoneal treatments.
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Affiliation(s)
- Annamaria Agnes
- Università Cattolica del Sacro Cuore, Largo F. Vito n.1, 00168, Rome, Italy
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli n. 8, 00168, Rome, Italy
| | - Alberto Biondi
- Università Cattolica del Sacro Cuore, Largo F. Vito n.1, 00168, Rome, Italy.
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli n. 8, 00168, Rome, Italy.
| | - Roberto Persiani
- Università Cattolica del Sacro Cuore, Largo F. Vito n.1, 00168, Rome, Italy
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli n. 8, 00168, Rome, Italy
| | - Antonio Laurino
- Università Cattolica del Sacro Cuore, Largo F. Vito n.1, 00168, Rome, Italy
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli n. 8, 00168, Rome, Italy
| | - Rossella Reddavid
- Department of Oncology, Surgical Oncology and Digestive Surgery Unit, San Luigi University Hospital, University of Turin, Orbassano, Turin, Italy
| | - Maurizio De Giuli
- Department of Oncology, Surgical Oncology and Digestive Surgery Unit, San Luigi University Hospital, University of Turin, Orbassano, Turin, Italy
| | - Federico Sicoli
- IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Italy
| | - Ferdinando Cananzi
- IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089, Rozzano, Italy
| | - Stefano De Pascale
- Digestive Surgery, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy
| | - Uberto Fumagalli
- Digestive Surgery, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy
| | - Federica Galli
- ASST Sette Laghi, Presidio Ospedaliero Gallarate, Corso Leonardo da Vinci, 1, 21013, Gallarate, Italy
| | - Stefano Rausei
- ASST Sette Laghi, Presidio Ospedaliero Gallarate, Corso Leonardo da Vinci, 1, 21013, Gallarate, Italy
| | - Laura Lorenzon
- Università Cattolica del Sacro Cuore, Largo F. Vito n.1, 00168, Rome, Italy
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli n. 8, 00168, Rome, Italy
| | - Domenico D'Ugo
- Università Cattolica del Sacro Cuore, Largo F. Vito n.1, 00168, Rome, Italy
- Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli n. 8, 00168, Rome, Italy
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Khan H, Johnston FM. Current role for cytoreduction and HIPEC for gastric cancer with peritoneal disease. J Surg Oncol 2022; 125:1176-1182. [PMID: 35481913 PMCID: PMC9322542 DOI: 10.1002/jso.26894] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 03/25/2022] [Accepted: 03/25/2022] [Indexed: 12/12/2022]
Abstract
Gastric cancer (GC) is an aggressive malignancy with a high burden of peritoneal disease. Evidence regarding the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) to improve outcomes has been growing. However, given multiple limitations, there remains a lack of international consensus regarding the optimal treatment paradigm. This review article discusses the burden of peritoneal disease in GC patients and the role of CRS + HIPEC in all treatment intents—curative, prophylactic, and palliative.
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Affiliation(s)
- Hamza Khan
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland, USA
| | - Fabian M Johnston
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland, USA
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32
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AKÇAKAYA A. Staging Laparoscopy in Stomach Cancer. BEZMIALEM SCIENCE 2022. [DOI: 10.14235/bas.galenos.2021.04696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022]
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33
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Kobayashi H, Honda M, Kawamura H, Takiguchi K, Muto A, Yamazaki S, Teranishi Y, Shiraso S, Kono K, Hori S, Kamiga T, Iwao T, Yamashita N. Clinical impact of gastrectomy for gastric cancer patients with positive lavage cytology without gross peritoneal dissemination. J Surg Oncol 2022; 125:615-620. [PMID: 34985764 DOI: 10.1002/jso.26770] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 11/29/2021] [Accepted: 12/05/2021] [Indexed: 12/27/2022]
Abstract
BACKGROUND The prognosis of gastric cancer patients with positive lavage cytology without gross peritoneal dissemination (P0CY1) is poor. The survival benefit of gastrectomy for these patients has not been established. PATIENTS AND METHODS In this population-based cohort study, we investigated the impact of radical gastrectomy with lymph node dissection for P0CY1 patients. Patients who were diagnosed with Stage IV gastric cancer from 2008 to 2015 in all nine cancer-designated hospitals in a tertiary medical area were listed. Patients who were diagnosed with histologically proven adenocarcinoma in both the primary lesion and lavage cytology during the operation or a diagnostic laparoscopic examination were enrolled. Patients with a gross peritoneal lesion or other metastatic lesions were excluded. The primary outcome was the adjusted hazard ratio (aHR) of gastrectomy for overall survival. We also evaluated the survival time in patients who underwent gastrectomy or chemotherapy in comparison to patients managed without primary surgery or with best supportive care. RESULTS One hundred patients were enrolled. The aHR (95% confidence interval) of gastrectomy was 0.677 (0.411-1.114, p = 0.125). The median survival time in patients who received gastrectomy (n = 74) was 21.7, while that in patients managed without primary surgery (n = 30) was 20.5 months (p = 0.155). The median survival time in patients who received chemotherapy (n = 76) was 23.0 months, while that in patients managed without chemotherapy was 8.6 months (p < 0.001). CONCLUSION Gastrectomy was not effective for improving the survival time in patients with P0CY1 gastric cancer. Surgeons should prioritize the performance of chemotherapy over surgery as the initial treatment.
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Affiliation(s)
- Hiroshi Kobayashi
- Department of Minimally Invasive Surgical and Medical Oncology, Fukushima Medical University, Fukushima, Japan.,Department of Surgery, Southern TOHOKU General Hospital, Koriyama, Japan
| | - Michitaka Honda
- Department of Minimally Invasive Surgical and Medical Oncology, Fukushima Medical University, Fukushima, Japan.,Department of Surgery, Southern TOHOKU General Hospital, Koriyama, Japan
| | - Hidetaka Kawamura
- Department of Minimally Invasive Surgical and Medical Oncology, Fukushima Medical University, Fukushima, Japan.,Department of Surgery, Southern TOHOKU General Hospital, Koriyama, Japan
| | - Koichi Takiguchi
- Department of Surgery, The Takeda Healthcare Foundation Takeda General Hospital, Aizuwakamatsu, Japan
| | - Atsushi Muto
- Department of Surgery, Fukushima Rosai Hospital, Iwaki, Japan
| | - Shigeru Yamazaki
- Department of Surgery, Ohta Nishinouchi Hospital, Koriyama, Japan
| | - Yasushi Teranishi
- Department of Surgery, Southern TOHOKU General Hospital, Koriyama, Japan
| | - Satoru Shiraso
- Department of Surgery, Iwaki City Medical Center, Iwaki, Japan
| | - Koji Kono
- Department of Gastrointestinal Tract Surgery, Fukushima Medical University, Fukushima, Japan
| | - Soshi Hori
- Department of Minimally Invasive Surgical and Medical Oncology, Fukushima Medical University, Fukushima, Japan.,Department of Surgery, Southern TOHOKU General Hospital, Koriyama, Japan
| | - Takahiro Kamiga
- Department of Surgery, Shirakawa Kosei General Hospital, Shirakawa, Japan
| | - Toshiyasu Iwao
- Department of Internal Medicine, Aidu Chuo Hospital, Aizuwakamatsu, Japan
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Liu D, Zhang W, Hu F, Yu P, Zhang X, Yin H, Yang L, Fang X, Song B, Wu B, Hu J, Huang Z. A Bounding Box-Based Radiomics Model for Detecting Occult Peritoneal Metastasis in Advanced Gastric Cancer: A Multicenter Study. Front Oncol 2021; 11:777760. [PMID: 34926287 PMCID: PMC8678129 DOI: 10.3389/fonc.2021.777760] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 11/09/2021] [Indexed: 02/05/2023] Open
Abstract
Purpose To develop a bounding box (BBOX)-based radiomics model for the preoperative diagnosis of occult peritoneal metastasis (OPM) in advanced gastric cancer (AGC) patients. Materials and Methods 599 AGC patients from 3 centers were retrospectively enrolled and were divided into training, validation, and testing cohorts. The minimum circumscribed rectangle of the ROIs for the largest tumor area (R_BBOX), the nonoverlapping area between the tumor and R_BBOX (peritumoral area; PERI) and the smallest rectangle that could completely contain the tumor determined by a radiologist (M_BBOX) were used as inputs to extract radiomic features. Multivariate logistic regression was used to construct a radiomics model to estimate the preoperative probability of OPM in AGC patients. Results The M_BBOX model was not significantly different from R_BBOX in the validation cohort [AUC: M_BBOX model 0.871 (95% CI, 0.814–0.940) vs. R_BBOX model 0.873 (95% CI, 0.820–0.940); p = 0.937]. M_BBOX was selected as the final radiomics model because of its extremely low annotation cost and superior OPM discrimination performance (sensitivity of 85.7% and specificity of 82.8%) over the clinical model, and this radiomics model showed comparable diagnostic efficacy in the testing cohort. Conclusions The BBOX-based radiomics could serve as a simpler reliable and powerful tool for the preoperative diagnosis of OPM in AGC patients. And M_BBOX-based radiomics is simpler and less time consuming.
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Affiliation(s)
- Dan Liu
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Weihan Zhang
- Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Fubi Hu
- Department of Radiology, First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Pengxin Yu
- Institute of Advanced Research, Infervision, Beijing, China
| | - Xiao Zhang
- Department of Radiology, People's Hospital of Leshan, Leshan, China
| | - Hongkun Yin
- Institute of Advanced Research, Infervision, Beijing, China
| | - Lanqing Yang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Xin Fang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Bin Song
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Bing Wu
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
| | - Jiankun Hu
- Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
| | - Zixing Huang
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
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35
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Badgwell B. Regional therapy trials in peritoneal metastases: The path to standardization of care for gastric cancer. J Surg Oncol 2021; 125:64-68. [PMID: 34897716 DOI: 10.1002/jso.26718] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 10/07/2021] [Indexed: 11/08/2022]
Abstract
As the peritoneum is the most common site of metastatic disease at diagnosis, disease identified at staging laparoscopy, and site of recurrence for patients with gastric cancer, intraperitoneal therapy has been an area of interest for many investigators. There are several ways to categorize the existing trials and studies. One is by indication, which includes palliative, neoadjuvant, adjuvant, and prophylactic. Another is by treatment modality which includes approaches such as hyperthermic intraperitoneal chemotherapy, pressurized intraperitoneal aerosol chemotherapy, intraperitoneal normothermic chemotherapy, and bidirectional combinations of systemic and intraperitoneal therapy. Recently completed and ongoing trials of peritoneal therapy in gastric cancer may be improving on the historically dismal survival rates for patients with carcinomatosis or disease at high risk of peritoneal recurrence. All completed randomized trials are from outside the United States, and additional studies of peritoneal therapy in Western populations are needed to clarify survival outcomes. Cooperative group trials and multi-institutional registry study efforts are ongoing to help address this clear area of unmet need.
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Affiliation(s)
- Brian Badgwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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36
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Davis CH, Ikoma N, Mansfield PF, Das P, Minsky BD, Blum MA, Ajani JA, Bass BL, Badgwell BD. Comparison of laparoscopy versus mini-laparotomy for jejunostomy placement in patients with gastric adenocarcinoma. Surg Endosc 2021; 35:6577-6582. [PMID: 33170336 DOI: 10.1007/s00464-020-08155-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2020] [Accepted: 11/04/2020] [Indexed: 01/18/2023]
Abstract
BACKGROUND Optimal nutrition is challenging for patients with gastric and gastroesophageal adenocarcinoma and often requires feeding tube placement prior to preoperative therapy. Feeding jejunostomy (FJ) placement via mini-laparotomy is technically easier to perform than laparoscopic FJ. The purpose of this study was to compare outcomes in patients with gastric adenocarcinoma undergoing laparoscopic versus mini-laparotomy FJ placement. METHODS A retrospective cohort study was performed of patients with gastric adenocarcinoma receiving laparoscopic versus mini-laparotomy FJ at a single tertiary referral center from 2000 to 2018. 30-day outcomes included complications, conversion to laparotomy, reoperation, length of stay, and readmission. RESULTS A total of 656 patients met the inclusion criteria and were studied. The majority of patients were male (68.1%) with a mean age of 60.6 years. The difference in surgical approach remained relatively stable over time. Overall, 82 (12.5%) patients experienced complications, and three (0.5%) patients died postoperatively. While readmission and conversion to open laparotomy did not differ between groups, overall complications (10.5% vs. 20.8%, p = 0.002), Clavien-Dindo ≥ 3 complications (4.0% vs. 8.9%, p = 0.021), length of stay (4.1 vs. 5.6 days, p < 0.001), and reoperation (0.9% vs. 4.0%, p = 0.002) favored the laparoscopic over mini-laparotomy group. CONCLUSION The current study helps clarify the risk of FJ placement in patients with gastric adenocarcinoma requiring nutritional support. Laparoscopic FJ placement has lower overall morbidity and length of stay compared to mini-laparotomy. However, caution is needed in preventing and identifying the rare causes of postoperative mortality that may be associated with laparoscopic FJ placement.
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Affiliation(s)
| | - Naruhiko Ikoma
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Herman Pressler, Unit 1484, Houston, TX, 77030, USA
| | - Paul F Mansfield
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Herman Pressler, Unit 1484, Houston, TX, 77030, USA
| | - Prajnan Das
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Bruce D Minsky
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Mariela A Blum
- Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jaffer A Ajani
- Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Barbara L Bass
- Department of Surgery, Houston Methodist Hospital, Houston, TX, USA
| | - Brian D Badgwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1400 Herman Pressler, Unit 1484, Houston, TX, 77030, USA.
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Gertsen EC, Brenkman HJF, van Hillegersberg R, van Sandick JW, van Berge Henegouwen MI, Gisbertz SS, Luyer MDP, Nieuwenhuijzen GAP, van Lanschot JJB, Lagarde SM, Wijnhoven BPL, de Steur WO, Hartgrink HH, Stoot JHMB, Hulsewe KWE, Spillenaar Bilgen EJ, van Det MJ, Kouwenhoven EA, van der Peet DL, Daams F, van Grieken NCT, Heisterkamp J, van Etten B, van den Berg JW, Pierie JP, Eker HH, Thijssen AY, Belt EJT, van Duijvendijk P, Wassenaar E, van Laarhoven HWM, Wevers KP, Hol L, Wessels FJ, Haj Mohammad N, van der Meulen MP, Frederix GWJ, Vegt E, Siersema PD, Ruurda JP. 18F-Fludeoxyglucose-Positron Emission Tomography/Computed Tomography and Laparoscopy for Staging of Locally Advanced Gastric Cancer: A Multicenter Prospective Dutch Cohort Study (PLASTIC). JAMA Surg 2021; 156:e215340. [PMID: 34705049 PMCID: PMC8552113 DOI: 10.1001/jamasurg.2021.5340] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 08/13/2021] [Indexed: 12/24/2022]
Abstract
IMPORTANCE The optimal staging for gastric cancer remains a matter of debate. OBJECTIVE To evaluate the value of 18F-fludeoxyglucose-positron emission tomography with computed tomography (FDG-PET/CT) and staging laparoscopy (SL) in addition to initial staging by means of gastroscopy and CT in patients with locally advanced gastric cancer. DESIGN, SETTING, AND PARTICIPANTS This multicenter prospective, observational cohort study included 394 patients with locally advanced, clinically curable gastric adenocarcinoma (≥cT3 and/or N+, M0 category based on CT) between August 1, 2017, and February 1, 2020. EXPOSURES All patients underwent an FDG-PET/CT and/or SL in addition to initial staging. MAIN OUTCOMES AND MEASURES The primary outcome was the number of patients in whom the intent of treatment changed based on the results of these 2 investigations. Secondary outcomes included diagnostic performance, number of incidental findings on FDG-PET/CT, morbidity and mortality after SL, and diagnostic delay. RESULTS Of the 394 patients included, 256 (65%) were men and mean (SD) age was 67.6 (10.7) years. A total of 382 patients underwent FDG-PET/CT and 357 underwent SL. Treatment intent changed from curative to palliative in 65 patients (16%) based on the additional FDG-PET/CT and SL findings. FDG-PET/CT detected distant metastases in 12 patients (3%), and SL detected peritoneal or locally nonresectable disease in 73 patients (19%), with an overlap of 7 patients (2%). FDG-PET/CT had a sensitivity of 33% (95% CI, 17%-53%) and specificity of 97% (95% CI, 94%-99%) in detecting distant metastases. Secondary findings on FDG/PET were found in 83 of 382 patients (22%), which led to additional examinations in 65 of 394 patients (16%). Staging laparoscopy resulted in a complication requiring reintervention in 3 patients (0.8%) without postoperative mortality. The mean (SD) diagnostic delay was 19 (14) days. CONCLUSIONS AND RELEVANCE This study's findings suggest an apparently limited additional value of FDG-PET/CT; however, SL added considerably to the staging process of locally advanced gastric cancer by detection of peritoneal and nonresectable disease. Therefore, it may be useful to include SL in guidelines for staging advanced gastric cancer, but not FDG-PET/CT.
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Affiliation(s)
- Emma C. Gertsen
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Hylke J. F. Brenkman
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Richard van Hillegersberg
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Johanna W. van Sandick
- Department of Surgery, the Netherlands Cancer Institute–Antoni van Leeuwenhoek, Amsterdam, the Netherlands
| | - Mark I. van Berge Henegouwen
- Department of Surgery, Amsterdam University Medical Center, location AMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Suzanne S. Gisbertz
- Department of Surgery, Amsterdam University Medical Center, location AMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Misha D. P. Luyer
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | | | | | - Sjoerd M. Lagarde
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, the Netherlands
| | - Bas P. L. Wijnhoven
- Department of Surgery, Erasmus MC University Medical Center Rotterdam, the Netherlands
| | - Wobbe O. de Steur
- Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
| | - Henk H. Hartgrink
- Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands
| | | | | | | | - Marc J. van Det
- Department of Surgery, ZGT hospital, Almelo, the Netherlands
| | | | - Donald L. van der Peet
- Department of Surgery, Amsterdam University Medical Center, location VUmc, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Freek Daams
- Department of Surgery, Amsterdam University Medical Center, location VUmc, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Nicole C. T. van Grieken
- Department of Pathology, Amsterdam University Medical Center, location VUmc, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Joos Heisterkamp
- Department of Surgery, Elisabeth Twee-Steden Hospital, Tilburg, the Netherlands
| | - Boudewijn van Etten
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Jan Willem van den Berg
- Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Jean Pierre Pierie
- Department of Surgery, Medical Center Leeuwarden, Leeuwarden, the Netherlands
| | - Hasan H. Eker
- Department of Surgery, Medical Center Leeuwarden, Leeuwarden, the Netherlands
| | - Annemieke Y. Thijssen
- Department of Gastroenterology, Albert Schweitzer Hospital, Dordrecht, the Netherlands
| | - Eric J. T. Belt
- Department of Surgery, Albert Schweitzer Hospital, Dordrecht, the Netherlands
| | | | - Eelco Wassenaar
- Department of Surgery, Gelre Ziekenhuizen, Apeldoorn, the Netherlands
| | - Hanneke W. M. van Laarhoven
- Prospective Observational Cohort Study of Oesophageal-Gastric Cancer Patients (POCOP) of the Dutch Upper GI Cancer Group, Amsterdam, the Netherlands
- Department of Medical Oncology, Amsterdam University Medical Center, location AMC, Cancer Center Amsterdam, Amsterdam, the Netherlands
| | - Kevin P. Wevers
- Department of Surgery, Isala Ziekenhuis, Zwolle, the Netherlands
| | - Lieke Hol
- Department of Gastroenterology, Maasstad Ziekenhuis, Rotterdam, the Netherlands
| | - Frank J. Wessels
- Department of Radiology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Nadia Haj Mohammad
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
| | - Miriam P. van der Meulen
- Julius Center for Health Sciences and Primary Care, Utrecht University, Utrecht, the Netherlands
| | - Geert W. J. Frederix
- Julius Center for Health Sciences and Primary Care, Utrecht University, Utrecht, the Netherlands
| | - Erik Vegt
- Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands
| | - Peter D. Siersema
- Department of Gastroenterology, Radboud University Medical Center, Nijmegen, the Netherlands
| | - Jelle P. Ruurda
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
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Marano L, Marrelli D, Sammartino P, Biacchi D, Graziosi L, Marino E, Coccolini F, Fugazzola P, Valle M, Federici O, Baratti D, Deraco M, Di Giorgio A, Macrì A, Pasqual EM, Framarini M, Vaira M, Roviello F. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer with Synchronous Peritoneal Metastases: Multicenter Study of 'Italian Peritoneal Surface Malignancies Oncoteam-S.I.C.O.'. Ann Surg Oncol 2021; 28:9060-9070. [PMID: 34057569 PMCID: PMC8590997 DOI: 10.1245/s10434-021-10157-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 04/29/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND The development of multimodality treatment, including cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC), has led to promising results in selected patients with peritoneal disease of gastric origin. The aim of this study was to investigate the short- and long-term outcomes of CRS/HIPEC in the treatment of synchronous peritoneal metastasis in gastric cancer. METHODS The Italian Peritoneal Surface Malignancies Oncoteam-S.I.C.O. retrospective registry included patients with synchronous peritoneal malignancy from gastric cancer submitted to gastrectomy with CRS and HIPEC between 2005 and 2018 from 11 high-volume, specialized centers. RESULTS A total of 91 patients with a median age of 58 years (range 26-75) were enrolled. The median overall survival (OS) time for the whole group of patients was 20.2 months (95% confidence interval [CI] 11.8-28.5] and the median recurrence-free survival (RFS) was 7.3 months (95% CI 4-10.6). The completeness of cytoreduction score (CCS) of 0 and Peritoneal Cancer Index (PCI) score of ≤ 6 groups showed a significantly better long-term survival (median OS 40.7 and 44.3 months, respectively) compared with the incomplete resected groups (median OS 10.7 months, p = 0.003) and PCI score of > 6 group (median OS 13.4 months, p = 0.005). A significant difference was observed in the survival rate according to neoadjuvant treatment (untreated patients: 10.7 months, 95% CI 5.1-16.2; treated patients: 35.3 months, 95% CI 2.8-67.8; p = 0.022). CONCLUSIONS In referral centers, CRS and HIPEC after neoadjuvant treatment significantly improved survival in selected patients. Patients with a PCI score ≤ 6, complete cytoreduction, negative nodal involvements, and negative cytology had encouraging results, showing a clinically meaningful survival.
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Affiliation(s)
- Luigi Marano
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Siena, Italy.
| | - Daniele Marrelli
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Siena, Italy
| | - Paolo Sammartino
- Cytoreductive Surgery and HIPEC Unit, Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Rome, Italy
| | - Daniele Biacchi
- Cytoreductive Surgery and HIPEC Unit, Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Rome, Italy
| | - Luigina Graziosi
- General and Emergency Surgery, University of Perugia, Perugia, Italy
| | - Elisabetta Marino
- General and Emergency Surgery, University of Perugia, Perugia, Italy
| | - Federico Coccolini
- General, Emergency and Trauma Surgery Department, Bufalini Hospital, Cesena, Italy
- General, Emergency and Trauma Surgery Department, Pisa University Hospital, Pisa, Italy
| | - Paola Fugazzola
- General, Emergency and Trauma Surgery Department, Bufalini Hospital, Cesena, Italy
| | - Mario Valle
- Department of Digestive Surgery, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Orietta Federici
- Department of Digestive Surgery, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Dario Baratti
- Fondazione IRCCS Istituto Nazionale Dei Tumori di Milano, Peritoneal Surface Malignancies Unit, Milan, Italy
| | - Marcello Deraco
- Fondazione IRCCS Istituto Nazionale Dei Tumori di Milano, Peritoneal Surface Malignancies Unit, Milan, Italy
| | - Andrea Di Giorgio
- Surgical Unit of Peritoneum and Retroperitoneum, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Antonio Macrì
- Peritoneal Surface Malignancy and Soft Tissue Sarcoma Program, Messina University Medical School Hospital, Messina, Italy
| | - Enrico Maria Pasqual
- Department of Medical Area, University of Udine, Santa Maria della Misericordia University Hospital Udine, Udine, Italy
| | | | - Marco Vaira
- Candiolo Cancer Institute, Unit of Surgical Oncology, FPO-IRCCS, Candiolo, Italy
| | - Franco Roviello
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Siena, Italy
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Hashimoto Y, Ajiki T, Yanagimoto H, Tsugawa D, Shinozaki K, Toyama H, Kido M, Fukumoto T. Risk factors for occult metastasis detected by inflammation-based prognostic scores and tumor markers in biliary tract cancer. World J Clin Cases 2021; 9:9770-9782. [PMID: 34877316 PMCID: PMC8610912 DOI: 10.12998/wjcc.v9.i32.9770] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 07/13/2021] [Accepted: 09/23/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Radiological detection of small liver metastasis or peritoneal metastasis is still difficult, and some patients with biliary tract cancer (BTC) are unresectable after laparotomy. Staging laparoscopy may help avoid unnecessary laparotomy. However, which category of BTC is amenable with staging laparoscopy remains unclear.
AIM To clarify the risk factors for occult metastasis in patients with BTC.
METHODS Medical records of patients with BTC who underwent surgery at our institution between January 2008 and June 2014 were retrospectively reviewed. The patients were divided into two groups, according to resection or exploratory laparotomy (EL). Preoperative laboratory data, including inflammation-based prognostic scores and tumor markers, were compared between the two groups. Prognostic importance of detected risk factors was also evaluated.
RESULTS A total of 236 patients were enrolled in this study. Twenty-six (11%) patients underwent EL. Among the EL patients, there were 16 cases of occult metastasis (7 liver metastases and 9 abdominal disseminations). Serum carcinoembryonic antigen level, carbohydrate antigen 19-9 level, neutrophil-lymphocyte ratio and modified Glasgow prognostic score were significantly higher in the EL group than in the resected group, and these factors were prognostic. Among these factors, carcinoembryonic antigen > 7 ng/mL was the most useful to predict occult metastasis in BTC. When patients have more than three of these positive factors, the rate of occult metastasis increases.
CONCLUSION Inflammation-based prognostic scores and tumor markers are useful in detecting occult metastasis in BTC; based on these factors, staging laparoscopy may reduce the rate of EL.
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Affiliation(s)
- Yu Hashimoto
- Department of Surgery, Division of Hepato-Biliary-Pancreatic SurgeryKobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
| | - Tetsuo Ajiki
- Department of Surgery, Division of Hepato-Biliary-Pancreatic SurgeryKobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
| | - Hiroaki Yanagimoto
- Department of Surgery, Division of Hepato-Biliary-Pancreatic SurgeryKobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
| | - Daisuke Tsugawa
- Department of Surgery, Division of Hepato-Biliary-Pancreatic SurgeryKobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
| | - Kenta Shinozaki
- Department of Surgery, Division of Hepato-Biliary-Pancreatic SurgeryKobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
| | - Hirochika Toyama
- Department of Surgery, Division of Hepato-Biliary-Pancreatic SurgeryKobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
| | - Masahiro Kido
- Department of Surgery, Division of Hepato-Biliary-Pancreatic SurgeryKobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
| | - Takumi Fukumoto
- Department of Surgery, Division of Hepato-Biliary-Pancreatic SurgeryKobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
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Bonnot PE, Lintis A, Mercier F, Benzerdjeb N, Passot G, Pocard M, Meunier B, Bereder JM, Abboud K, Marchal F, Quenet F, Goere D, Msika S, Arvieux C, Pirro N, Wernert R, Rat P, Gagnière J, Lefevre JH, Courvoisier T, Kianmanesh R, Vaudoyer D, Rivoire M, Meeus P, Villeneuve L, Piessen G, Glehen O. Prognosis of poorly cohesive gastric cancer after complete cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy (CYTO-CHIP study). Br J Surg 2021; 108:1225-1235. [PMID: 34498666 DOI: 10.1093/bjs/znab200] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 05/07/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND The incidence of gastric poorly cohesive carcinoma (PCC) is increasing. The prognosis for patients with peritoneal metastases remains poor and the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The aim was to clarify the impact of gastric PCC with peritoneal metastases treated by CRS with or without HIPEC. METHODS All patients with peritoneal metastases from gastric cancer treated with CRS with or without HIPEC, in 19 French centres, between 1989 and 2014, were identified from institutional databases. Clinicopathological characteristics and outcomes were compared between PCC and non-PCC subtypes, and the possible benefit of HIPEC was assessed. RESULTS In total, 277 patients were included (188 PCC, 89 non-PCC). HIPEC was performed in 180 of 277 patients (65 per cent), including 124 of 188 with PCC (66 per cent). Median overall survival (OS) was 14.7 (95 per cent c.i. 12.7 to 17.3) months in the PCC group versus 21.2 (14.7 to 36.4) months in the non-PCC group (P < 0.001). In multivariable analyses, PCC (hazard ratio (HR) 1.51, 95 per cent c.i. 1.01 to 2.25; P = 0.044) was associated with poorer OS, as were pN3, Peritoneal Cancer Index (PCI), and resection with a completeness of cytoreduction score of 1, whereas HIPEC was associated with improved OS (HR 0.52; P < 0.001). The benefit of CRS-HIPEC over CRS alone was consistent, irrespective of histology, with a median OS of 16.7 versus 11.3 months (HR 0.60, 0.39 to 0.92; P = 0.018) in the PCC group, and 34.5 versus 14.3 months (HR 0.43, 0.25 to 0.75; P = 0.003) in the non-PCC group. Non-PCC and HIPEC were independently associated with improved recurrence-free survival and fewer peritoneal recurrences. In patients who underwent HIPEC, PCI values of below 7 and less than 13 were predictive of OS in PCC and non-PCC populations respectively. CONCLUSION In selected patients, CRS-HIPEC offers acceptable outcomes among those with gastric PCC and long survival for patients without PCC.
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Affiliation(s)
- P E Bonnot
- Department of Surgical Oncology, Centre Georges Francois Leclerc, Dijon, France.,Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France
| | - A Lintis
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France.,Department of General Surgery, CHU Lille, Lille, France
| | - F Mercier
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France.,Department of Surgical Oncology, Centre Hospitalier Universitaire de Montreal, Montreal, Quebec, Canada
| | - N Benzerdjeb
- Pathology Department, CHU Lyon Sud, Hospices Civils de Lyon, University of Lyon, Lyon, France
| | - G Passot
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France
| | - M Pocard
- Department of Surgical Oncology, Hôpital Lariboisière, Paris, France
| | - B Meunier
- Department of Surgical Oncology, CHU Pontchaillou, Rennes, France
| | - J M Bereder
- Department of Surgical Oncology, CHU L'Archet, Nice, France
| | - K Abboud
- Department of Surgical Oncology, CHU St Etienne, St Etienne, France
| | - F Marchal
- Department of Surgical Oncology, Institut de Cancérologie de Lorraine, Université de Lorraine, Nancy, France
| | - F Quenet
- Department of Surgical Oncology, Centre Val D'Aurelle, Montpellier, France
| | - D Goere
- Department of Surgical Oncology, Institut Gustave Roussy, Villejuif, France
| | - S Msika
- Department of Surgical Oncology, CHU Louis Mourier, Paris, France
| | - C Arvieux
- Department of Surgical Oncology, CHU La Tronche, Grenoble, France
| | - N Pirro
- Department of Surgical Oncology, CHU La Timone, Marseille, France
| | - R Wernert
- Department of Surgical Oncology, Institut Paul Papin, Angers, France
| | - P Rat
- Department of Surgical Oncology, CHU Le Bocage, Dijon, France
| | - J Gagnière
- Department of Surgical Oncology, CHU Clermont-Ferrand, Clermont Ferrand, France
| | - J H Lefevre
- Department of Surgical Oncology, Hôpital Saint-Antoine, AP-HP, Paris, Sorbonne Université, Paris, France
| | - T Courvoisier
- Department of Surgical Oncology, CHU Poitiers, Poitiers, France
| | - R Kianmanesh
- Department of Surgical Oncology, CHU Reims, Reims, France
| | - D Vaudoyer
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France
| | - M Rivoire
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - P Meeus
- Department of Surgical Oncology, Centre Léon Bérard, Lyon, France
| | - L Villeneuve
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France.,Unité de Recherche Clinique, Pôle Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon, France
| | - G Piessen
- Department of General Surgery, CHU Lille, Lille, France
| | - O Glehen
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, Lyon, France
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Bacalbasa N, Diaconu C, Socea B, Gherghiceanu F, Savu C, Dimitriu M, Balescu I, Cordos I. Neoadjuvant intraperitoneal chemotherapy for advanced stage gastric cancer (Review). Exp Ther Med 2021; 22:1314. [PMID: 34630668 DOI: 10.3892/etm.2021.10749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 07/08/2021] [Indexed: 11/05/2022] Open
Abstract
Gastric cancer remains one of the most lethal malignancies especially when diagnosed in advanced stages of the disease; most often patients diagnosed later during the progression of their disease will present a certain degree of peritoneal contamination such as positive peritoneal cytology or peritoneal metastatic nodules. In such cases most often they then progress to peritoneal carcinomatosis and succumb to the disease within one year. In order to increase the lifespan in such cases multiple therapeutic strategies have been proposed such as radical surgery and intraperitoneal heated chemotherapy or direct intraperitoneal chemotherapy followed by radical surgery. To date, the benefits of intraperitoneal heated chemotherapy at the time of resection have been widely investigated; however the method is still associated with increased rates of perioperative complications. Therefore, attention was focused on investigating the benefits of such procedures as neoadjuvant therapies followed by radical surgery. The aim of the present review was to examine the most efficient therapeutic strategies in advanced-stage gastric cancer such as neoadjuvant laparoscopic heated intraperitoneal chemotherapy, perioperative heated intraperitoneal chemotherapy and neoadjuvant systemic and peritoneal chemotherapy.
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Affiliation(s)
- Nicolae Bacalbasa
- Department of Obstetrics and Gynecology, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania.,Department of Visceral Surgery, Center of Excellence in Translational Medicine 'Fundeni' Clinical Institute, 022328 Bucharest, Romania
| | - Camelia Diaconu
- Department of Internal Medicine, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania.,Department of Internal Medicine, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Bogdan Socea
- Department of Surgery, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania.,Department of Surgery, 'Sf. Pantelimon' Emergency Hospital, 33094 Bucharest, Romania
| | - Florentina Gherghiceanu
- Department of Marketing and Medical Technology, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Cornel Savu
- Department of Thoracic Surgery, 'Marius Nasta' National Institute of Pneumology, 050159 Bucharest, Romania.,Department of Thoracic Surgery, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | - Mihai Dimitriu
- Department of Obstetrics and Gynecology, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania.,Department of Obstetrics and Gynecology, 'Sf. Pantelimon' Emergency Hospital, 33094 Bucharest, Romania
| | - Irina Balescu
- Department of Surgery, 'Ponderas' Academic Hospital, 021188 Bucharest, Romania
| | - Ioan Cordos
- Department of Thoracic Surgery, 'Marius Nasta' National Institute of Pneumology, 050159 Bucharest, Romania.,Department of Thoracic Surgery, 'Carol Davila' University of Medicine and Pharmacy, 020021 Bucharest, Romania
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Martínez-López E, Martínez-Pérez A, Navarro-Martínez S, Sebastián-Tomás JC, de'Angelis N, García-Granero E. Real-time fluorescence image-guided gastrointestinal oncologic surgery: Towards a new era. World J Gastrointest Oncol 2021; 13:1029-1042. [PMID: 34616510 PMCID: PMC8465438 DOI: 10.4251/wjgo.v13.i9.1029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 06/14/2021] [Accepted: 07/27/2021] [Indexed: 02/06/2023] Open
Abstract
Technological improvements are crucial in the evolution of surgery. Real-time fluorescence-guided surgery (FGS) has spread worldwide, mainly because of its usefulness during the intraoperative decision-making processes. The success of any gastrointestinal oncologic resection is based on the anatomical identification of the primary tumor and its regional lymph nodes. FGS allows also to evaluate the blood perfusion at the gastrointestinal stumps after colorectal or esophageal resections. Therefore, a reduction on the anastomotic leak rates has been postulated as one of the foreseeable benefits provided by the use of FGS in these procedures. Although the use of fluorescence in lymph node detection was initially described in breast cancer surgery, the technique is currently applied in gastric or splenic flexure cancers, as they both present complex and variable lymphatic drainages. FGS allows also to perform intraoperative lymphograms or sentinel lymph node biopsies. New applications of FGS are being developed to assist in the detection of peritoneal metastases or in the evaluation of the tumor resection margins. The present review aims to provide a general overview of the current status of real-time FGS in gastrointestinal oncologic surgery. We put a special focus on the different applications of FGS, discussing the main findings and limitations found in the contemporary literature and also the promising near future applications.
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Affiliation(s)
- Elías Martínez-López
- Department of Surgery, University of Valencia, Valencia 46010, Spain
- Department of General and Digestive Surgery, Hospital Universitario Doctor Peset, Valencia 46017, Spain
| | - Aleix Martínez-Pérez
- Faculty of Health Sciences, Valencian International University, Valencia 46002, Spain
- Minimally Invasive and Robotic Digestive Surgery Unit, Miulli Hospital, Acquaviva delle Fonti 70021, Italy
| | - Sergio Navarro-Martínez
- Department of General and Digestive Surgery, Hospital Universitario Doctor Peset, Valencia 46017, Spain
| | - Juan Carlos Sebastián-Tomás
- Department of Surgery, University of Valencia, Valencia 46010, Spain
- Department of General and Digestive Surgery, Hospital Universitario Doctor Peset, Valencia 46017, Spain
| | - Nicola de'Angelis
- Minimally Invasive and Robotic Digestive Surgery Unit, Miulli Hospital, Acquaviva delle Fonti 70021, Italy
| | - Eduardo García-Granero
- Department of Surgery, University of Valencia, Valencia 46010, Spain
- Department of General and Digestive Surgery, Hospital Universitario y Politécnico La Fe, Valencia 46026, Spain
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Yoshikawa K, Shimada M, Higashijima J, Tokunaga T, Nishi M, Takasu C, Kashihara H, Eto S, Yoshimoto T. Usefulness of Diagnostic Staging Laparoscopy for Advanced Gastric Cancer. Am Surg 2021:31348211038554. [PMID: 34382447 DOI: 10.1177/00031348211038554] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
BACKGROUND For advanced gastric cancer (AGC), peritoneal metastasis is the most common determinant of unresectability, but accurate preoperative diagnosis for peritoneal metastasis is challenging. Staging laparoscopy (SL) can detect unsuspected peritoneal metastasis. This study retrospectively evaluated the utility of SL and its indication in patients with AGC. METHODS In this study, we enrolled 114 patients with pathologically diagnosed gastric adenocarcinoma who underwent SL. RESULTS Of the 114 patients, 43 (37.7%) had peritoneal metastasis (P1 or CY1). Higher age, larger tumor size, type 4 GC, deeper tumor depth, elevated CA125, and ascites findings in preoperative CT were found to be significant predictors of peritoneal metastasis. In multivariate analysis, peritoneal metastasis was associated with type 4 GC (odds ratio [OR]: 6.11; 95% confidence interval [CI]: 1.87-19.8; P < .01) and ascites in CT (OR: 4.25; 95% CI: 1.48-12.1; P < .01). CONCLUSIONS Staging laparoscopy is an effective tool to detect peritoneal metastasis from AGC. It can increase the curative resection rate and decrease unnecessary laparotomies.
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Affiliation(s)
- Kozo Yoshikawa
- The Department of Surgery, 163647The University of Tokushima, Tokushima, Japan
| | - Mitsuo Shimada
- The Department of Surgery, 163647The University of Tokushima, Tokushima, Japan
| | - Jun Higashijima
- The Department of Surgery, 163647The University of Tokushima, Tokushima, Japan
| | - Takuya Tokunaga
- The Department of Surgery, 163647The University of Tokushima, Tokushima, Japan
| | - Masaaki Nishi
- The Department of Surgery, 163647The University of Tokushima, Tokushima, Japan
| | - Chie Takasu
- The Department of Surgery, 163647The University of Tokushima, Tokushima, Japan
| | - Hideya Kashihara
- The Department of Surgery, 163647The University of Tokushima, Tokushima, Japan
| | - Shohei Eto
- The Department of Surgery, 163647The University of Tokushima, Tokushima, Japan
| | - Toshiaki Yoshimoto
- The Department of Surgery, 163647The University of Tokushima, Tokushima, Japan
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Shimada H, Fukagawa T, Haga Y, Okazumi S, Oba K. Clinical TNM staging for esophageal, gastric, and colorectal cancers in the era of neoadjuvant therapy: A systematic review of the literature. Ann Gastroenterol Surg 2021; 5:404-418. [PMID: 34337289 PMCID: PMC8316742 DOI: 10.1002/ags3.12444] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 01/06/2021] [Accepted: 01/26/2021] [Indexed: 12/12/2022] Open
Abstract
AIM Clinical staging is vital for selecting appropriate candidates and designing neoadjuvant treatment strategies for advanced tumors. The aim of this review was to evaluate diagnostic abilities of clinical TNM staging for gastrointestinal, gastrointestinal cancers. METHODS We conducted a systematic review of recent publications to evaluate the accuracy of diagnostic modalities on gastrointestinal cancers. A systematic literature search was performed in PubMed/MEDLINE using the keywords "TNM staging," "T4 staging," "distant metastases," "esophageal cancer," "gastric cancer," and "colorectal cancer," and the search terms used in Cochrane Reviews between January 2005 to July 2020. Articles focusing on preoperative diagnosis of: (a) depth of invasion; (b) lymph node metastases; and (c) distant metastases were selected. RESULTS After a full-text search, a final set of 55 studies (17 esophageal cancer studies, 26 gastric cancer studies, and 12 colorectal cancer studies) were used to evaluate the accuracy of clinical TNM staging. Positron emission tomography-computed tomography (PET-CT) and/or magnetic resonance imaging (MRI) were the best modalities to assess distant metastases. Fat and fiber mode of CT may be useful for T4 staging of esophageal cancer, CT was a partially reliable modality for lymph node staging in gastric cancer, and CT combined with MRI was the most reliable modality for liver metastases from colorectal cancer. CONCLUSION The most reliable diagnostic modality differed among gastrointestinal cancers depending on the type of cancer. Therefore, we propose diagnostic algorithms for clinical staging for each type of cancer.
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Affiliation(s)
- Hideaki Shimada
- Department of Gastroenterological SurgeryToho University Graduate School of MedicineTokyoJapan
| | - Takeo Fukagawa
- Department of SurgeryTeikyo University School of MedicineTokyoJapan
| | - Yoshio Haga
- Department of SurgeryJapan Community Healthcare Organization Amakusa Central General HospitalAmakusaJapan
| | - Shin‐ichi Okazumi
- Department of Gastroenterological SurgeryToho University Graduate School of MedicineTokyoJapan
- Department of SurgeryToho University Sakura Medical CenterSakuraJapan
| | - Koji Oba
- Department of BiostatisticsSchool of Public HealthGraduate School of MedicineThe University of TokyoTokyoJapan
- Interfaculty Initiative in Information StudiesGraduate School of Interdisciplinary Information StudiesThe University of TokyoTokyoJapan
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Harris MC, Cockbain AJ, McQuillan PW, Kanhere HA. Survey and literature review on the importance of peritoneal cytology in staging and treatment of gastric cancer: always wash it before you treat it. ANZ J Surg 2021; 91:13-18. [PMID: 33590628 DOI: 10.1111/ans.16295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 08/12/2020] [Accepted: 08/13/2020] [Indexed: 11/28/2022]
Affiliation(s)
- Mark C Harris
- Division of Surgery, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia.,School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia
| | - Andrew J Cockbain
- Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Patrick W McQuillan
- Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Harsh A Kanhere
- Division of Surgery, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia.,School of Medicine, The University of Adelaide, Adelaide, South Australia, Australia.,Department of Surgery, Royal Adelaide Hospital, Adelaide, South Australia, Australia
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Kohli P, Penumadu P, Srinivas BH, M S, Dubashi B, Kate V, Kumar H, R K, Balasubramanian A. Clinicopathological profile and its association with peritoneal disease among gastric cancer patients. Surg Oncol 2021; 38:101595. [PMID: 33991942 DOI: 10.1016/j.suronc.2021.101595] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 03/30/2021] [Accepted: 04/26/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND There are no clinicopathological criteria or test to predict peritoneal metastasis either in primary or recurrent gastric cancer. The early prediction will help in altering or adding other adjuvant potential therapy modalities like HIPEC and maintenance chemotherapy. METHODS Paraffin based blocks of 110 gastric tumor specimens were subjected to IHC staining to assess VEGF, Her 2 neu, E cadherin, bcl 2 and p 53 expression and its association with peritoneal disease evaluated. RESULTS Her 2 neu uptake was present in 17.3%, bcl-2 expression in 19.1%, P53 expression in 40.9%, VEGF in 41.8% and E cadherin expression in 49.1% patients. On univariate analysis, a younger age(p = .029), female sex(p = .026), positive VEGF expression (p = .001) and p53 expression(p = .015) were significantly associated with peritoneal disease. A binomial logistic regression was performed to ascertain the effects of independent variables evaluated on univariate analysis. Of the 10 predictors variables, only three were statistically significant: tumor type, P53, and VEGF. Positive VEGF expression had 48.7, E cadherin 2.6 and Her2neu 1.5 times higher odds of exhibiting peritoneal disease. CONCLUSION A younger age, female sex, distal 2/3rd, diffuse variant, VEGF staining in >10% cells and decrease p53 expression were associated with peritoneal disease.
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Affiliation(s)
- Pavneet Kohli
- Department of Surgical Oncology, JIPMER, Puducherry, 6050006, India
| | - Prasanth Penumadu
- Department of Surgical Oncology, JIPMER, Puducherry, 6050006, India.
| | - B H Srinivas
- Department of Pathology, JIPMER, Puducherry, 605006, India
| | - Sivasanker M
- HPB Unit, Department of Surgery, Royal Liverpool University Hospitals NHS Trust, Merseyside, UK
| | - Biswajit Dubashi
- Department of Medical Oncology, JIPMER, Puducherry, 605006, India
| | - Vikram Kate
- Department of General Surgery, JIPMER, Puducherry, 605006, India
| | | | - Kalayarasan R
- Department of Surgical Gastroenterology, JIPMER, Puducherry, 605006, India
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Joshi SS, Badgwell BD. Current treatment and recent progress in gastric cancer. CA Cancer J Clin 2021; 71:264-279. [PMID: 33592120 PMCID: PMC9927927 DOI: 10.3322/caac.21657] [Citation(s) in RCA: 1041] [Impact Index Per Article: 260.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Revised: 12/08/2020] [Accepted: 12/09/2020] [Indexed: 12/15/2022] Open
Abstract
Gastric cancer is not a top-10 malignancy in the United States but represents one of the most common causes of cancer death worldwide. Biological differences between tumors from Eastern and Western countries add to the complexity of identifying standard-of-care therapy based on international trials. Systemic chemotherapy, radiotherapy, surgery, immunotherapy, and targeted therapy all have proven efficacy in gastric adenocarcinoma; therefore, multidisciplinary treatment is paramount to treatment selection. Triplet chemotherapy for resectable gastric cancer is now accepted and could represent a plateau of standard cytotoxic chemotherapy for localized disease. Classification of gastric cancer based on molecular subtypes is providing an opportunity for personalized therapy. Biomarkers, in particular microsatellite instability (MSI), programmed cell death ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2), tumor mutation burden, and Epstein-Barr virus, are increasingly driving systemic therapy approaches and allowing for the identification of populations most likely to benefit from immunotherapy and targeted therapy. Significant research opportunities remain for the less differentiated histologic subtypes of gastric adenocarcinoma and those without markers of immunotherapy activity.
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Affiliation(s)
- Smita S Joshi
- Gastrointestinal Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Brian D Badgwell
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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Dineen SP, Pimiento JM. The Landmark Series: Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC) for Treatment of Gastric Cancer Metastatic to Peritoneum. Ann Surg Oncol 2021; 28:4130-4137. [PMID: 33856601 DOI: 10.1245/s10434-021-09927-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Accepted: 03/11/2021] [Indexed: 12/24/2022]
Abstract
Gastric cancer (GC) is a common cancer worldwide, with patients developing isolated peritoneal metastases (PM) in approximately 30% of cases. In patients with PM, prognosis is quite poor, and long-term survival is almost zero. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been demonstrated to be an effective treatment in many peritoneal malignancies, including appendiceal and ovarian cancers and in peritoneal mesothelioma. In this educational review, we summarize many of the seminal studies addressing the potential benefit of CRS/HIPEC for patients with gastric cancer and peritoneal metastases (GC/PM).
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Affiliation(s)
- Sean P Dineen
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA. .,Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
| | - Jose M Pimiento
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA.,Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, Tampa, FL, USA
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Gertsen EC, Borggreve AS, Brenkman HJF, Verhoeven RHA, Vegt E, van Hillegersberg R, Siersema PD, Ruurda JP. Evaluation of the Implementation of FDG-PET/CT and Staging Laparoscopy for Gastric Cancer in The Netherlands. Ann Surg Oncol 2021; 28:2384-2393. [PMID: 32901312 PMCID: PMC7940330 DOI: 10.1245/s10434-020-09096-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2020] [Accepted: 08/15/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND The role of 18F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG-PET/CT) and staging laparoscopy (SL) has increased in the preoperative staging of gastric cancer. Dutch national guidelines have recommended the use of FDG-PET/CT and SL for patients with locally advanced tumors since July 2016. OBJECTIVE The aim of this study was to evaluate the implementation of FDG-PET/CT and SL in The Netherlands. METHODS Between 2011 and 2018, all patients who underwent surgery for gastric cancer were included from the Dutch Upper GI Cancer Audit. The use of FDG-PET/CT and SL was evaluated before and after revision of the Dutch guidelines. Outcomes included the number of non-curative procedures (e.g. palliative and futile procedures) and the association of FDG-PET/CT and SL, with waiting times from diagnosis to the start of treatment. RESULTS A total of 3310 patients were analyzed. After July 2016, the use of FDG-PET/CT (23% vs. 61%; p < 0.001) and SL (21% vs. 58%; p < 0.001) increased. FDG-PET/CT was associated with additional waiting time to neoadjuvant therapy (4 days), as well as primary surgical treatment (20 days), and SL was associated with 8 additional days of waiting time to neoadjuvant therapy. Performing SL or both modalities consecutively in patients in whom it was indicated was not associated with the number of non-curative procedures. CONCLUSION During implementation of FDG-PET/CT and SL after revision of the guidelines, both have increasingly been used in The Netherlands. The addition of these staging methods was associated with increased waiting time to treatment. The number of non-curative procedures did not differ after performing none, solely one, or both staging modalities.
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Affiliation(s)
- Emma C Gertsen
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Alicia S Borggreve
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Hylke J F Brenkman
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Rob H A Verhoeven
- Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, The Netherlands
- Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Erik Vegt
- Department of Radiology and Nuclear Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
- Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Richard van Hillegersberg
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands
| | - Peter D Siersema
- Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Jelle P Ruurda
- Department of Surgery, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
- Department of Surgery, Division Cancer Center, University Medical Center Utrecht, Utrecht, The Netherlands.
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50
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Gronau F, Jara M, Feldbrügge L, Wolf V, Oeff A, Rau B. [Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer]. Chirurg 2021; 92:522-527. [PMID: 33620502 DOI: 10.1007/s00104-021-01371-3] [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: 01/26/2021] [Indexed: 10/22/2022]
Abstract
BACKGROUND Gastric cancer with peritoneal metastases is associated with an extremely poor prognosis. Developed multimodal treatment concepts, which include a combination of perioperative systemic treatment and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), show promising results with respect to improvement of the long-term survival. METHODS This article contains a review of the literature of published studies on the topic of gastric cancer and peritoneal metastasis. RESULTS The prognosis of patients with gastric cancer peritoneal carcinomatosis shows an extremely limited median survival of 7 months under palliative second-line systemic treatment. The median survival time increased to 12 months with cytoreductive surgery and in combination with HIPEC showed a positive effect on survival in individual studies. EXPERT OPINION Treatment recommendations for patients with peritoneal metastases of gastric cancer should be carried out by experts in surgical reference centers.
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Affiliation(s)
- Felix Gronau
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Deutschland
| | - Maximilian Jara
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Deutschland
| | - Linda Feldbrügge
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Deutschland
| | - Vincent Wolf
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Deutschland
| | - Alan Oeff
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Deutschland
| | - Beate Rau
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Deutschland. .,Klinik für Chirurgie, Universitätsmedizin Berlin, Charité Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Deutschland.
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