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Recent Advances in Gastric Cancer

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A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (19 December 2019) | Viewed by 51999

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Dr. Saowanee Ngamruengphong

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Division of Gastroenterology & Hepatology. Johns Hopkins Medicine 4940 Eastern Avenue, A Building, 5th Floor. A-501 Baltimore,MD 21224
Interests: diagnosis and detection of premalignant and malignant gastric lesions; early gastric cancer; roles of endoscopy in gastric cancer; therapy of gastric cancer
Special Issues, Collections and Topics in MDPI journals

Assoc. Prof. Dr. Fabian M. Johnston

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Division of Surgical Oncology, Johns Hopkins University, 600 N. Wolfe Street / Blalock 606, Baltimore, MD 21287, USA
Interests: incorporating highly innovative patient-centered models to improve the utilization of palliative care amongst patients with advanced gastrointestinal malignancies; improving the quality of life for patient populations when they are most severely ill and vulnerable
Special Issues, Collections and Topics in MDPI journals

Assoc. Prof. Dr. Lei Zheng

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Department of Oncology, Johns Hopkins University School of Medicine, 600 N. Wolfe Street CRB I Room 351, Baltimore, MD 21287, USA
Interests: pancreatic cancer biology and translational research; translational immunology and cancer immunotherapy; tumor microenvironment; cancer invasion and metastasis; clinical and translation research of gastrointestinal malignancies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Gastric cancer remains a prevalent disease worldwide, with high mortality rates. Recent advances in early detection and mprovements in cancer management have led to decreased incidences and increased survival of patients with gastric cancer.

This Special Issue will discuss the recent discovery of the cellular and molecular bases underlying gastric cancer development and progression, recent advances in endoscopic diagnosis and the early detection of precancerous lesions and early gastric cancer, endoscopic therapy of these lesions, surgical management including techniques and considerations in minimally invasive surgery, innovations in neoadjuvant and adjuvant chemotherapy, immunotherapy, and radiation treatment in gastric cancer.

Dr. Saowanee Ngamruengphong
Assoc. Prof. Dr. Fabian M. Johnston
Assoc. Prof. Dr. Lei Zheng
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Advances in early detection of gastric lesions
Biomarkers for assessing gastric cancer
Endoscopic therapy for gastric cancer
Gastric carcinogenesis and metastasis
Cancer therapy
Epigenetics of gastric cancer
Genetics and genomics of gastric cancer
Imaging of gastric lesions
Immunotherapy for gastric cancer
Molecular targeted therapies for gastric cancer
Therapeutic approaches to gastric cancer

Published Papers (13 papers)

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Research

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19 pages, 2821 KiB

Open AccessArticle

Molecular Classification of Gastric Cancer among Alaska Native People

by Holly A. Martinson, Dominic Mallari, Christine Richter, Tsung-Teh Wu, James Tiesinga, Steven R. Alberts and Matthew J. Olnes

Cancers 2020, 12(1), 198; https://doi.org/10.3390/cancers12010198 - 13 Jan 2020

Cited by 19 | Viewed by 3819

Abstract

Gastric cancer is an aggressive and heterogeneous malignancy that often varies in presentation and disease among racial and ethnic groups. The Alaska Native (AN) people have the highest incidence and mortality rates of gastric cancer in North America. This study examines molecular markers in solid tumor samples from eighty-five AN gastric adenocarcinoma patients using next-generation sequencing, immunohistochemistry, and in situ hybridization analysis. AN patients have a low mutation burden with fewer somatic gene mutations in their tumors compared to other populations, with the most common mutation being TP53. Epstein-Barr virus (EBV) was associated with 20% of AN gastric cancers, which is higher than the world average of 10%. The inflammation marker, cyclooxygenase-2 (COX-2), is highly expressed in patients with the lowest survival rates. Mismatch repair deficiency was present in 10% of AN patients and was associated with patients who were female, 50 years or older, gene mutations, and tumors in the distal stomach. Program death-ligand 1 (PD-L1) was expressed in 14% of AN patients who were more likely to have MMR deficiency, EBV-associated gastric cancers, and mutations in the PIK3CA gene, all of which have been linked to clinical response to PD-1 inhibitors. These studies suggest a portion of AN gastric cancer patients could be candidates for immunotherapy. Overall, this study highlights future avenues of investigation for clinical and translational studies, so that we can improve early detection and develop more effective treatments for AN patients. Full article

(This article belongs to the Special Issue Recent Advances in Gastric Cancer)

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10 pages, 550 KiB

Open AccessArticle

Socio-Demographic Disparities in Gastric Adenocarcinoma: A Population-Based Study

by Navpreet Rana, Rohit Gosain, Riccardo Lemini, Chong Wang, Emmanuel Gabriel, Turab Mohammed, Beas Siromoni and Sarbajit Mukherjee

Cancers 2020, 12(1), 157; https://doi.org/10.3390/cancers12010157 - 09 Jan 2020

Cited by 28 | Viewed by 3208

Abstract

Background: Gastric cancer is one of the leading causes of cancer-related mortality worldwide, accounting for 8.2% of cancer-related deaths. The purpose of this study was to investigate the geographic and sociodemographic disparities in gastric adenocarcinoma patients. Methods: We conducted a retrospective study in gastric adenocarcinoma patients between 2004 and 2013. Data were obtained from the National Cancer Data Base (NCDB). Univariate and multivariable analyses were performed to evaluate overall survival (OS). Socio-demographic factors, including the location of residence [metro area (MA) or rural area (RA)], gender, race, insurance status, and marital status, were analyzed. Results: A total of 88,246 [RA, N = 12,365; MA, N = 75,881] patients were included. Univariate and multivariable analysis showed that RA had worse OS (univariate HR = 1.08, p < 0.01; multivariate HR = 1.04; p < 0.01) compared to MA. When comparing different racial backgrounds, Native American and African American populations had poorer OS when compared to the white population; however, Asian patients had a better OS (multivariable HR = 0.68, p < 0.01). From a quality of care standpoint, MA patients had fewer median days to surgery (28 vs. 33; p < 0.01) with fewer positive margins (6.3% vs. 6.9%; p < 0.01) when compared to RA patients. When comparing the extent of lymph node dissection, 19.6% of MA patients underwent an extensive dissection (more than or equal to 15 lymph nodes) in comparison to 18.7% patients in RA (p = 0.03). Discussion: This study identifies socio-demographic disparities in gastric adenocarcinoma. Future health policy initiatives should focus on equitable allocation of resources to improve the outcomes. Full article

(This article belongs to the Special Issue Recent Advances in Gastric Cancer)

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11 pages, 356 KiB

Open AccessArticle

Long Term Survival after Cytoreductive Surgery Combined with Perioperative Chemotherapy in Gastric Cancer Patients with Peritoneal Metastasis

by Yutaka Yonemura, Aruna Prabhu, Shouzou Sako, Haruaki Ishibashi, Akiyoshi Mizumoto, Nobuyuki Takao, Masumi Ichinose, Shunsuke Motoi, Yang Liu, Kazurou Nishihara, Andreas Brandl and Sachio Fushida

Cancers 2020, 12(1), 116; https://doi.org/10.3390/cancers12010116 - 01 Jan 2020

Cited by 28 | Viewed by 4072

Abstract

The present study demonstrated prognostic factors for long-term survival in patients after a comprehensive treatment (CHT) for peritoneal metastasis (PM) from gastric cancer (GC). Materials and Methods: Among 419 patients treated with neoadjuvant intraperitoneal/systemic chemotherapy (NIPS), 266 (63.5%) patients received complete resection (CC-0) of the macroscopic tumors. In total, 184 (43.9%) patients were treated with postoperative systemic chemotherapy. Results: All patients treated who received incomplete cytoreduction (CC-1) died of GC within 6 years. In contrast, 10- year survival rates (-YSR) of CC-0 resection were 8.3% with median survival time (MST) of 20.5 months. Post-NIPS peritoneal cancer index (PCI) ≤11, and pre-NIPS PCI ≤13 were the significant favorable prognostic factors. Patients with numbers of involved peritoneal sectors ≤5 survived significant longer than those with ≥6. Both negative pre- and post-NIPS cytology was associated with significant favorable prognosis. Multivariate analyses identified pre-PCI (≤13 vs. ≥14), and cytology after NIPS (negative cytology vs. positive cytology) as independent prognostic factors. Ten year-survivors were found in patients with involvement of the greater omentum (9%), pelvic peritoneum (3%), para-colic gutter (13.9%), upper jejunum (5.6%), lower jejunum (5.5%), spermatic cord (21.9%), rectum (9.5%), ureter (6.3%), ovary (6.7%), and diaphragm (7.0%) at the time of cytoreduction. Twenty-one patients survived longer than 5 years, and 17 patients are still alive without recurrence. Conclusions: GC-PM should be removed aggressively, in patients with PCI after NIPS ≤11, PCI before NIPS ≤13, mall bowel PCI ≤2, and complete cytoreduction should be performed for metastasis in ≤5 peritoneal sectors. Full article

(This article belongs to the Special Issue Recent Advances in Gastric Cancer)

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16 pages, 6435 KiB

Open AccessArticle

PI3K/AKT/β-Catenin Signaling Regulates Vestigial-Like 1 Which Predicts Poor Prognosis and Enhances Malignant Phenotype in Gastric Cancer

by Bo-Kyung Kim, Jae-Ho Cheong, Joo-Young Im, Hyun Seung Ban, Seon-Kyu Kim, Mi-Jung Kang, Jungwoon Lee, Seon-Young Kim, Kyung-Chan Park, Soonmyung Paik and Misun Won

Cancers 2019, 11(12), 1923; https://doi.org/10.3390/cancers11121923 - 03 Dec 2019

Cited by 22 | Viewed by 4203

Abstract

Although gastric cancer is a common cause of cancer mortality worldwide, its biological heterogeneity limits the available therapeutic options. Therefore, identifying novel therapeutic targets for developing effective targeted therapy of gastric cancer is a pressing need. Here, we investigate molecular function and regulatory mechanisms of Vestigial-like 1 (VGLL1) in gastric cancer. Microarray analysis of 556 gastric cancer tissues revealed that VGLL1 was a prognostic biomarker that correlated with PI3KCA and PI3KCB. VGLL1 regulates the proliferation of gastric cancer cells, as shown in live cell imaging, sphere formation, and in vivo xenograft model. Tail vein injection of NUGC3 cells expressing shVGLL1 resulted in less lung metastasis occurring when compared to the control. In contrast, larger metastatic lesions in lung and liver were detected in the VGLL1-overexpressing NUGC3 cell xenograft excision mouse model. Importantly, VGLL1 expression is transcriptionally regulated by the PI3K-AKT-β-catenin pathway. Subsequently, MMP9, a key molecule in gastric cancer, was explored as one of target genes that were transcribed by VGLL1-TEAD4 complex, a component of the transcription factor. Taken together, PI3K/AKT/β-catenin signaling regulates the transcription of VGLL1, which promotes the proliferation and metastasis in gastric cancer. This finding suggests VGLL1 as a novel prognostic biomarker and a potential therapeutic target. Full article

(This article belongs to the Special Issue Recent Advances in Gastric Cancer)

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12 pages, 1960 KiB

Open AccessArticle

Conversion Surgery with HIPEC for Peritoneal Oli-gometastatic Gastric Cancer

by Jerzy Mielko, Karol Rawicz-Pruszyński, Magdalena Skórzewska, Bogumiła Ciseł, Agnieszka Pikuła, Magdalena Kwietniewska, Katarzyna Gęca, Katarzyna Sędłak, Andrzej Kurylcio and Wojciech P. Polkowski

Cancers 2019, 11(11), 1715; https://doi.org/10.3390/cancers11111715 - 02 Nov 2019

Cited by 14 | Viewed by 3836

Abstract

Peritoneal metastases (PM) of gastric cancer (GC) are characterized by a particularly poor prognosis, with median survival time of 6 months, and virtually no 5-year survival reported. Conversion therapy for GC is defined as a surgical treatment aiming at an R0 resection after systemic chemotherapy for tumours that were originally unresectable (or marginally resectable) for technical and/or oncological reasons. The aim of the present study was to evaluate early and late outcomes in GC patients with PM who underwent the cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) after neoadjuvant (conversion) chemotherapy. Thirty patients with stage IV GC underwent CRS plus HIPEC. Severe grade III/IV (Clavien-Dindo classification) complications occurred in 13 (43%) patients. The Comprehensive Complication Index (CCI) ranged from 8.7 to 100 (median, 42.4). In the multivariate survival analysis, ypT2 and P3 (according to the Japanese classification of the PM severity) were favourable and adverse prognostic factors p = 0.031 and o = 0.035, respectively. Estimated 1- and 3-year survival was 73.9% and 36.6%, respectively. The median survival was 19.3 months. Conclusion: Conversion surgery, including extended gastrectomy and multi-organ resections followed by HIPEC performed after systemic chemotherapy therapy for GC with PM is justified in downstaged patients with ypT2 and limited (less than P3) PM. Full article

(This article belongs to the Special Issue Recent Advances in Gastric Cancer)

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18 pages, 5565 KiB

Open AccessArticle

Mutation in DNA Polymerase Beta Causes Spontaneous Chromosomal Instability and Inflammation-Associated Carcinogenesis in Mice

by Shengyuan Zhao, Alex W. Klattenhoff, Megha Thakur, Manu Sebastian and Dawit Kidane

Cancers 2019, 11(8), 1160; https://doi.org/10.3390/cancers11081160 - 13 Aug 2019

Cited by 16 | Viewed by 3847

Abstract

DNA polymerase beta (Pol β) is a key enzyme in the base excision repair (BER) pathway. Pol β is mutated in approximately 40% of human tumors in small-scale studies. The 5´-deoxyribose-5-phosphate (dRP) lyase domain of Pol β is responsible for DNA end tailoring to remove the 5’ phosphate group. We previously reported that the dRP lyase activity of Pol β is critical to maintain DNA replication fork stability and prevent cellular transformation. In this study, we tested the hypothesis that the human gastric cancer associated variant of Pol β (L22P) has the ability to promote spontaneous chromosomal instability and carcinogenesis in mice. We constructed a Pol β L22P conditional knock-in mouse model and found that L22P enhances hyperproliferation and DNA double strand breaks (DSBs) in stomach cells. Moreover, mouse embryonic fibroblasts (MEFs) derived from L22P mice frequently induce abnormal numbers of chromosomes and centrosome amplification, leading to chromosome segregation errors. Importantly, L22P mice exhibit chronic inflammation accompanied by stomach tumors. These data demonstrate that the human cancer-associated variant of Pol β can contribute to chromosomal instability and cancer development. Full article

(This article belongs to the Special Issue Recent Advances in Gastric Cancer)

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14 pages, 4158 KiB

Open AccessArticle

Aberrant DNA Polymerase Beta Enhances H. pylori Infection Induced Genomic Instability and Gastric Carcinogenesis in Mice

by Shengyuan Zhao, Megha Thakur, Alex W. Klattenhoff and Dawit Kidane

Cancers 2019, 11(6), 843; https://doi.org/10.3390/cancers11060843 - 18 Jun 2019

Cited by 7 | Viewed by 2851

Abstract

H. pylori is a significant risk factor of gastric cancer that induces chronic inflammation and oxidative DNA damage to promote gastric carcinoma. Base excision repair (BER) is required to maintain the genome integrity and prevent oxidative DNA damage. Mutation in DNA polymerase beta (Pol β) impacts BER efficiency and has been reported in approximately 30–40% of gastric carcinoma tumors. In this study, we examined whether reduced BER capacity associated with mutation in the POLB gene, along with increased DNA damage generated by H. pylori infection, accelerates gastric cancer development. By infecting a Pol β mutant mouse model that lacks dRP lyase with H. pylori, we show that reactive oxygen and nitrogen species (RONS) mediated DNA damage is accumulated in Pol β mutant mice (L22P). In addition, H. pylori infection in Leu22Pro (L22P) mice significantly increases inducible nitric oxide synthesis (iNOS) mediated chronic inflammation. Our data show that L22P mice exhibited accelerated H. pylori induced carcinogenesis and increased tumor incidence. This work shows that Pol β mediated DNA repair under chronic inflammation conditions is an important suppressor of H. pylori induced stomach carcinogenesis. Full article

(This article belongs to the Special Issue Recent Advances in Gastric Cancer)

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15 pages, 3019 KiB

Open AccessArticle

Acute Tumor Transition Angle on Computed Tomography Predicts Chromosomal Instability Status of Primary Gastric Cancer: Radiogenomics Analysis from TCGA and Independent Validation

by Ying-Chieh Lai, Ta-Sen Yeh, Ren-Chin Wu, Cheng-Kun Tsai, Lan-Yan Yang, Gigin Lin and Michael D. Kuo

Cancers 2019, 11(5), 641; https://doi.org/10.3390/cancers11050641 - 09 May 2019

Cited by 9 | Viewed by 3775

Abstract

Chromosomal instability (CIN) of gastric cancer is correlated with distinct outcomes. This study aimed to investigate the role of computed tomography (CT) imaging traits in predicting the CIN status of gastric cancer. We screened 443 patients in the Cancer Genome Atlas gastric cancer cohort to filter 40 patients with complete CT imaging and genomic data as the training cohort. CT imaging traits were subjected to logistic regression to select independent predictors for the CIN status. For the validation cohort, we prospectively enrolled 18 gastric cancer patients for CT and tumor genomic analysis. The imaging predictors were tested in the validation cohort using receiver operating characteristic curve (ROC) analysis. Thirty patients (75%) in the training cohort and 9 patients (50%) in the validation cohort had CIN subtype gastric cancers. Smaller tumor diameter (p = 0.017) and acute tumor transition angle (p = 0.045) independently predict CIN status in the training cohort. In the validation cohort, acute tumor transition angle demonstrated the highest accuracy, sensitivity, and specificity of 88.9%, 88.9%, and 88.9%, respectively, and areas under ROC curve of 0.89. In conclusion, this pilot study showed acute tumor transition angle on CT images may predict the CIN status of gastric cancer. Full article

(This article belongs to the Special Issue Recent Advances in Gastric Cancer)

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Review

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30 pages, 963 KiB

Open AccessReview

Recent Developments of Systemic Chemotherapy for Gastric Cancer

by Hiroyuki Arai and Takako Eguchi Nakajima

Cancers 2020, 12(5), 1100; https://doi.org/10.3390/cancers12051100 - 28 Apr 2020

Cited by 31 | Viewed by 6179

Abstract

Gastric cancer (GC) is a molecularly heterogeneous disease. Its molecular background, epidemiology, and standard of care are quite different between Eastern and Western countries. Many efforts have been made in developing more effective surgeries and adjuvant chemotherapies for resectable GC in each region. Recently, an intensive combination of cytotoxic agents has been established as a new standard of adjuvant treatment. Meanwhile, palliative chemotherapy is a uniform standard treatment for unresectable GC worldwide. Recently, one of the most remarkable advances in therapy for unresectable GC has been the approval of immune checkpoint inhibitors (ICIs). The use of ICIs as frontline treatment is currently being investigated. In addition, novel combinations of ICIs and targeted drugs are being evaluated in clinical trials. Despite these advances, the complex biology of GC has resulted in the failure of targeted therapies, with the exceptions of HER2-targeted trastuzumab and VEGFR2-targeted ramucirumab. GC harbors many redundant oncogenic pathways, and small subsets of tumors are driven by different specific pathways. Therefore, a combination strategy simultaneously inhibiting several pathways and/or stricter patient selection for better response to targeted drugs are needed to improve clinical outcomes in this field. Full article

(This article belongs to the Special Issue Recent Advances in Gastric Cancer)

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13 pages, 224 KiB

Open AccessReview

Gastric Cancer with Radiographically Occult Metastatic Disease: Biology, Challenges, and Diagnostic Approaches

by Aravind Sanjeevaiah, Haeseong Park, Benjamin Fangman and Matthew Porembka

Cancers 2020, 12(3), 592; https://doi.org/10.3390/cancers12030592 - 05 Mar 2020

Cited by 3 | Viewed by 2287

Abstract

Gastric adenocarcinoma is an aggressive cancer that demonstrates heterogeneous biology depending on patient ethnicity, tumor location, tumor type, and genetic profile. It remains the third leading cause of cancer deaths worldwide and was estimated to result in 782,000 deaths in 2018. Challenges exist in accurately assessing the disease burden, as available radiological staging often underestimates metastatic disease. This diagnostic handicap, along with the poor understanding of the heterogeneous biology of gastric cancer, has hindered the development of effective therapeutic solutions and thus halted improvement in patient outcomes over the last few decades. The management of occult peritoneal disease is complicated, as most patients are understaged by standard imaging studies and therefore thought to have local diseases. In this article, we systematically review recent literature on the limitations that are associated with standard radiographic staging, discuss recent molecular biology advances to better identify and diagnose occult peritoneal disease, and propose possible management strategies to approach this complicated clinical problem. Full article

(This article belongs to the Special Issue Recent Advances in Gastric Cancer)

14 pages, 679 KiB

Open AccessReview

Emerging Targeted Therapies for HER2 Positive Gastric Cancer That Can Overcome Trastuzumab Resistance

by Seiichiro Mitani and Hisato Kawakami

Cancers 2020, 12(2), 400; https://doi.org/10.3390/cancers12020400 - 10 Feb 2020

Cited by 50 | Viewed by 6134

Abstract

Trastuzumab, a monoclonal antibody to human epidermal growth factor receptor 2 (HER2), has improved survival in patients with HER2-positive advanced gastric or gastroesophageal junction cancer (AGC). The inevitable development of resistance to trastuzumab remains a problem, however, with several treatment strategies that have proven effective in breast cancer having failed to show clinical benefit in AGC. In this review, we summarize the mechanisms underlying resistance to HER2-targeted therapy and outline past and current challenges in the treatment of HER2-positive AGC refractory to trastuzumab. We further describe novel agents such as HER2 antibody–drug conjugates that are under development and have shown promising antitumor activity in early studies. Full article

(This article belongs to the Special Issue Recent Advances in Gastric Cancer)

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25 pages, 338 KiB

Open AccessReview

New Treatment Options for Advanced Gastroesophageal Tumours: Mature for the Current Practice?

by Hannah Christina Puhr, Matthias Preusser, Gerald Prager and Aysegül Ilhan-Mutlu

Cancers 2020, 12(2), 301; https://doi.org/10.3390/cancers12020301 - 28 Jan 2020

Cited by 7 | Viewed by 2295

Abstract

Several clinical trials attempted to identify novel treatment options for advanced gastroesophageal tumours in first, second and further lines. Although results of targeted therapy regimens were mainly disappointing, novel immunotherapy agents showed promising activity, which led to their approval in second and third lines in many countries. This review focuses on the results of recent clinical trials investigating novel agents including targeted therapies, immunotherapy components and chemotherapies and discuss their current impact as well as current approval status on the treatment armamentarium of advanced gastroesophageal tumours. Full article

(This article belongs to the Special Issue Recent Advances in Gastric Cancer)

19 pages, 274 KiB

Open AccessReview

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer

by Adriana C. Gamboa and Joshua H. Winer

Cancers 2019, 11(11), 1662; https://doi.org/10.3390/cancers11111662 - 26 Oct 2019

Cited by 37 | Viewed by 4020

Abstract

The management of peritoneal metastases from gastric cancer origin has evolved considerably over the last three decades with the establishment of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as efficacious therapies in carefully selected patients. Other approaches such as the use of prophylactic/adjuvant HIPEC in patients who are considered high-risk and those with positive peritoneal cytology will benefit from additional data before being adopted into routine clinical practice. Lastly, there are new and emerging intraperitoneal chemotherapy techniques such as early post-operative intraperitoneal chemotherapy (EPIC) for residual microscopic disease, and pressurized intraperitoneal aerosolized chemotherapy (PIPAC) for patients with advanced unresectable peritoneal carcinomatosis, which are currently under evaluation in clinical trials. The following review outlines the natural history of gastric cancer, currently available neoadjuvant and adjuvant therapies for resectable disease, and existing evidence supporting various approaches to CRS and intraperitoneal chemotherapy. Full article

(This article belongs to the Special Issue Recent Advances in Gastric Cancer)

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