Treatment of Gastric Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (15 December 2021) | Viewed by 21594

Special Issue Editors


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Guest Editor
General Surgery Unit, Department of Surgery, Cittiglio-Angera Hospital, ASST SetteLaghi, 21100 Varese, Italy
Interests: surgical oncology; gastric cancer; colon cancer; minimally invasive surgery; emergency surgery
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Guest Editor
Department of Surgery, University of Ioannina, Ioannina, Greece
Interests: surgical oncology; gastric cancer; colon cancer; minimally invasive surgery; emergency surgery

Special Issue Information

Dear Colleagues,

The treatment of gastric cancer has evolved with the recognition of the prognostic value of extended lymphadenectomy and use of multimodal strategies. At the same time, the potential roles of minimally invasive (endoscopic as well as laparoscopic) approaches and enhanced post-operative recovery protocols have been shown. Oncologists routinely participate in preoperative phase with surgeries conducted in curable cases, sometimes more surgery in incurable ones, and a longer term perspective on the quantity and quality of life of patients with durable responses. This Special Issue aims to explore the areas remodeled or reconsidered in the management of gastric cancer in the 2000s.

Dr. Stefano Rausei
Dr. Georgios D. Lianos
Guest Editors

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Keywords

  • gastric cancer
  • lymphadenectomy
  • laparoscopy
  • enhanced recovery after surgery
  • chemotherapy
  • translational therapy
  • conversion surgery
  • survival
  • quality of life

Published Papers (10 papers)

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Editorial

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5 pages, 169 KiB  
Editorial
Treatment of Gastric Cancer Means Surgery, but Not Surgery Alone
by Manrica Fabbi, Christina D. Bali, Georgios D. Lianos and Stefano Rausei
Cancers 2024, 16(8), 1601; https://doi.org/10.3390/cancers16081601 - 22 Apr 2024
Viewed by 565
Abstract
Despite numerous studies, gastric cancer (GC) still presents a high mortality rate in Eastern and Western countries, increasing attention for new therapeutic strategies [...] Full article
(This article belongs to the Special Issue Treatment of Gastric Cancer)
3 pages, 174 KiB  
Editorial
Treatment of Gastric Cancer
by Stefano Rausei and Georgios D. Lianos
Cancers 2020, 12(9), 2627; https://doi.org/10.3390/cancers12092627 - 15 Sep 2020
Cited by 14 | Viewed by 2016
Abstract
Surgery represents the only method for potentially curative intent for gastric cancer (GC) [...] Full article
(This article belongs to the Special Issue Treatment of Gastric Cancer)

Research

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15 pages, 6076 KiB  
Article
Gastric Cancer-Derived Extracellular Vesicles (EVs) Promote Angiogenesis via Angiopoietin-2
by Talya Kalfon, Shelly Loewenstein, Fabian Gerstenhaber, Stav Leibou, Hen Geller, Osnat Sher, Eran Nizri and Guy Lahat
Cancers 2022, 14(12), 2953; https://doi.org/10.3390/cancers14122953 - 15 Jun 2022
Cited by 6 | Viewed by 2122
Abstract
Angiogenesis is an important control point of gastric cancer (GC) progression and metastasis. Angiopoietin-2 (ANG2) is a key driver of tumor angiogenesis and metastasis, and it has been identified in primary GC tissues. Extracellular vesicles (EVs) play an important role in mediating intercellular [...] Read more.
Angiogenesis is an important control point of gastric cancer (GC) progression and metastasis. Angiopoietin-2 (ANG2) is a key driver of tumor angiogenesis and metastasis, and it has been identified in primary GC tissues. Extracellular vesicles (EVs) play an important role in mediating intercellular communication through the transfer of proteins between cells. However, the expression of ANG2 in GC-EVs has never been reported. Here, we characterized the EV-mediated crosstalk between GC and endothelial cells (ECs), with particular focus on the role of ANG2. We first demonstrate that ANG2 is expressed in GC primary and metastatic tissues. We then isolated EVs from two different GC cell lines and showed that these EVs enhance EC proliferation, migration, invasion, and tube formation in vitro and in vivo. Using an angiogenesis protein array, we showed that GC-EVs contain high levels of proangiogenic proteins, including ANG2. Lastly, using Lenti viral ANG2-shRNA, we demonstrated that the proangiogenic effects of the GC-EVs were mediated by ANG2 through the activation of the PI3K/Akt signal transduction pathway. Our data suggest a new mechanism via which GC cells induce angiogenesis. This knowledge may be utilized to develop new therapies in gastric cancer. Full article
(This article belongs to the Special Issue Treatment of Gastric Cancer)
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19 pages, 1418 KiB  
Article
Surgeon–Pathologist Team Approach Dramatically Affects Lymph Nodes Detection and Improves Patients’ Short-Term Outcome
by Maria Raffaella Ambrosio, Bruno Perotti, Alda Battini, Caterina Fattorini, Andrea Cavazzana, Rocco Pasqua, Piergaspare Palumbo, Liano Gia and Marco Arganini
Cancers 2022, 14(4), 1034; https://doi.org/10.3390/cancers14041034 - 18 Feb 2022
Cited by 2 | Viewed by 2015
Abstract
The downstaging of gastric cancer has recently gained particular attention in the field of gastric cancer surgery. The phenomenon is mainly due to an inappropriate sampling of lymph nodes during standard lymphadenectomy. Hence, collection of the maximum number of lymph nodes is a [...] Read more.
The downstaging of gastric cancer has recently gained particular attention in the field of gastric cancer surgery. The phenomenon is mainly due to an inappropriate sampling of lymph nodes during standard lymphadenectomy. Hence, collection of the maximum number of lymph nodes is a critical factor affecting the outcome of patients. None of the techniques proposed so far have demonstrated a real efficiency in increasing the number of identified lymph nodes. To harvest the maximum number of lymph nodes, we designed a protocol for on-site macroscopic evaluation and sampling of lymph nodes according to the Japanese Gastric Cancer Association protocol. The procedure was carried out by a surgeon/pathologist team in the operating room. We enrolled one hundred patients, 50 of whom belonged to the study group and 50 to a control group. The study group included patients who underwent lymph node dissection following the proposed protocol; the control group encompassed patients undergoing standard procedures for sampling. We compared the number and maximum diameter of lymph nodes collected in both groups, as well as some postoperative variables, the 30-day mortality and the overall survival. In the study group, the mean number of lymph nodes harvested was higher than the control one (p = 0.001). Moreover, by applying the proposed technique, we sampled lymph nodes with a very small diameter, some of which were metastatic. Noticeably, no difference in terms of postoperative course was identified between the two groups, again supporting the feasibility of an extended lymphadenectomy. By comparing the prognosis of patients, a better overall survival (p = 0.03) was detected in the study group; however, to date, no long-term follow-up is available. Interestingly, patients with metastasis in node stations number 8, 9, 11 or with skip metastasis, experienced a worse outcome and died. Based on our preliminary results, the pathologist/surgeon team approach seems to be a reliable option, despite of a slight increase in sfaff workload and technical cost. It allows for the harvesting of a larger number of lymph nodes and improves the outcome of the patients thanks to more precise staging and therapy. Nevertheless, since a higher number of patients are necessary to confirm our findings and assess the impact of this technique on oncological outcome, our study could serve as a proof-of-concept for a larger, multicentric collaboration. Full article
(This article belongs to the Special Issue Treatment of Gastric Cancer)
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12 pages, 2884 KiB  
Article
Feasibility and Short-Term Outcomes of Three-Dimensional Hand-Sewn Esophago-Jejunal Anastomosis in Completely Laparoscopic Total Gastrectomy for Cancer
by Alexandros Charalabopoulos, Spyridon Davakis, Panorea Paraskeva, Nikolaos Machairas, Alkistis Kapelouzou, Ali Kordzadeh, Panagiotis Sakarellos, Michail Vailas, Efstratia Baili, Christos Bakoyiannis and Evangelos Felekouras
Cancers 2021, 13(18), 4709; https://doi.org/10.3390/cancers13184709 - 20 Sep 2021
Cited by 4 | Viewed by 2336
Abstract
Laparoscopic total gastrectomy is on the rise. One of the most technically demanding steps of the approach is the construction of esophago-jejunal anastomosis. Several laparoscopic anastomotic techniques have been described, like linear stapler side-to-side or circular stapler end-to-side anastomosis; limited data exist regarding [...] Read more.
Laparoscopic total gastrectomy is on the rise. One of the most technically demanding steps of the approach is the construction of esophago-jejunal anastomosis. Several laparoscopic anastomotic techniques have been described, like linear stapler side-to-side or circular stapler end-to-side anastomosis; limited data exist regarding hand-sewn esophago-jejunal anastomosis. The study took place between January 2018 and June 2021. Patients enrolled in this study were adults with proximal gastric or esophago-gastric junction Siewert type III tumors that underwent 3D-assisted laparoscopic total gastrectomy. A hand-sewn esophago-jejunal anastomosis was performed in all cases laparoscopically. Forty consecutive cases were performed during the study period. Median anastomotic suturing time was 55 min, with intra-operative methylene blue leak test being negative in all cases. Median operating time was 240 min, and there were no conversions to open. The anastomotic leak rate and postoperative stricture rate were zero. The 30- and 90-day mortality rates were zero. Laparoscopic manual esophago-jejunal anastomosis utilizing a 3D platform in total gastrectomy for cancer can be performed with excellent outcomes regarding anastomotic leak and stricture rate. This anastomotic approach, although technically challenging, is safe and reproducible, with prominent results that can be disseminated in the surgical community. Full article
(This article belongs to the Special Issue Treatment of Gastric Cancer)
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12 pages, 1613 KiB  
Article
Does Pathological Stage and Nodal Involvement Influence Long Term Oncological Outcomes after CROSS Regimen for Adenocarcinoma of the Esophagogastric Junction? A Multicenter Retrospective Analysis
by Stefano de Pascale, Paolo Parise, Michele Valmasoni, Jacopo Weindelmayer, Fabrizia Terraneo, Chiara Alessandra Cella, Simone Giacopuzzi, Andrea Cossu, Simonetta Massaron, Ugo Elmore, Stefano Merigliano, Uberto Fumagalli Romario and on behalf of the Italian Society for the Study of Esophageal Diseases (SISME)
Cancers 2021, 13(4), 666; https://doi.org/10.3390/cancers13040666 - 7 Feb 2021
Cited by 1 | Viewed by 1634
Abstract
Background:After the results reported by the “Chemoradiotherapy for esophageal Cancer Followed by Surgery Study” (CROSS) trial, neo-adjuvant chemoradiotherapy became the standard treatment for locally advanced cancers of esophagus and gastroesophageal junction (GEJ). Excellent results were reported for squamocellular carcinomas (SCCs). Since the [...] Read more.
Background:After the results reported by the “Chemoradiotherapy for esophageal Cancer Followed by Surgery Study” (CROSS) trial, neo-adjuvant chemoradiotherapy became the standard treatment for locally advanced cancers of esophagus and gastroesophageal junction (GEJ). Excellent results were reported for squamocellular carcinomas (SCCs). Since the advent of the CROSS regimen, the results of surgery for esophageal adenocarcinomas (EAC) have cast some doubts about its efficacy on overall survival (OS) even in the presence of local response. This study evaluated the relation between pathological (yp) stage after CROSS regimen followed by surgery for adenocarcinoma of cardia and overall (OS) and disease-free survival (DFS). Sites of relapse after surgery were also analyzed. Methods: Patients submitted to the CROSS regimen for locally advanced EAC of the cardia followed by transthoracic esophagectomy were analyzed. Actuarial OS and DFS were analyzed and stratified according to yp stage. The site of relapse, distal and local, was also analyzed. Results: The study included 132 patients. The 50-month OS and DFS were 45% and 6.7%, respectively. No differences emerged analyzing OS according to yp stage. Time to relapse was significantly longer for yp Stage I and II, and for yp N0, compared with yp N+. Recurrence occurred in 48 cases (36.3%) with a 9 months median time to relapse. Local and distal relapse were 10 (7.5%) and 38 (28.7%) cases, respectively (p ≦ 0.001). Conclusions: Pathological stage after CROSS regimen does not relate to OS and DFS. Time to recurrence is significantly longer for yp Stages I and II and ypN0. Chemoradiotherapy in a neoadjuvant setting may influence the site of relapse, significantly reducing local recurrences. Full article
(This article belongs to the Special Issue Treatment of Gastric Cancer)
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12 pages, 312 KiB  
Article
Survival Outcomes Following Combination of First-Line Platinum-Based Chemotherapy with S-1 in Patients with Advanced Gastric Cancer
by Anna Koumarianou, Anastasios Ntavatzikos, Christos Vallilas, Katerina Kampoli, Zoi Kakoseou and Michalis V. Karamouzis
Cancers 2020, 12(12), 3780; https://doi.org/10.3390/cancers12123780 - 15 Dec 2020
Cited by 2 | Viewed by 1585
Abstract
The efficacy of S-1 combined with a platinum agent in the first-line setting and in patients with advanced gastric adenocarcinoma has been previously demonstrated in randomized clinical trials. However, real-world data regarding S-1 efficacy in European patients remains limited. In the present study, [...] Read more.
The efficacy of S-1 combined with a platinum agent in the first-line setting and in patients with advanced gastric adenocarcinoma has been previously demonstrated in randomized clinical trials. However, real-world data regarding S-1 efficacy in European patients remains limited. In the present study, we reviewed the data of a European cohort of patients with advanced gastric cancer treated with first-line therapy consisting of S-1 in combination with a platinum agent. Forty-eight patients (29 with locally advanced/inoperable and 19 with metastatic disease) were treated with S-1 plus oxaliplatin (33 patients) or S1 plus cisplatin (15 patients). The Cox regression analysis, adjusted with propensity score, indicated that the use of cisplatin as compared to oxaliplatin was associated with increased risk of death (HR 9.634, p = 0.000). Four SAEs (serious adverse events) GIII were recorded (1 fatigue, 1 neutropenia, 1 anemia, 1 diarrhea) in 3 patients. S-1 combination with a platinum agent in the first-line setting in European patients with advanced gastric cancer results to similar survival outcomes and toxicity with previously reported data from Asian populations. S-1 combination with oxaliplatin seems to be associated with superior efficacy as compared to cisplatin. Full article
(This article belongs to the Special Issue Treatment of Gastric Cancer)
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Review

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17 pages, 890 KiB  
Review
The Implication of Gastric Microbiome in the Treatment of Gastric Cancer
by George Pappas-Gogos, Kostas Tepelenis, Fotis Fousekis, Konstantinos Katsanos, Michail Pitiakoudis and Konstantinos Vlachos
Cancers 2022, 14(8), 2039; https://doi.org/10.3390/cancers14082039 - 18 Apr 2022
Cited by 12 | Viewed by 3154
Abstract
Gastric cancer (GC) is one of the most common and deadly malignancies worldwide. Helicobacter pylori have been documented as a risk factor for GC. The development of sequencing technology has broadened the knowledge of the gastric microbiome, which is essential in maintaining homeostasis. [...] Read more.
Gastric cancer (GC) is one of the most common and deadly malignancies worldwide. Helicobacter pylori have been documented as a risk factor for GC. The development of sequencing technology has broadened the knowledge of the gastric microbiome, which is essential in maintaining homeostasis. Recent studies have demonstrated the involvement of the gastric microbiome in the development of GC. Therefore, the elucidation of the mechanism by which the gastric microbiome contributes to the development and progression of GC may improve GC’s prevention, diagnosis, and treatment. In this review, we discuss the current knowledge about changes in gastric microbial composition in GC patients, their role in carcinogenesis, the possible therapeutic role of the gastric microbiome, and its implications for current GC therapy. Full article
(This article belongs to the Special Issue Treatment of Gastric Cancer)
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Other

13 pages, 963 KiB  
Systematic Review
Health-Related Quality of Life in Locally Advanced Gastric Cancer: A Systematic Review
by Romy M. van Amelsfoort, Karen van der Sluis, Winnie Schats, Edwin P. M. Jansen, Johanna W. van Sandick, Marcel Verheij and Iris Walraven
Cancers 2021, 13(23), 5934; https://doi.org/10.3390/cancers13235934 - 25 Nov 2021
Cited by 9 | Viewed by 1883
Abstract
Background: Current treatment strategies have been designed to improve survival in locally advanced gastric cancer patients. Besides its impact on survival, treatment also affects health-related quality of life (HRQOL), but an overview of reported studies is currently lacking. The aim of this systematic [...] Read more.
Background: Current treatment strategies have been designed to improve survival in locally advanced gastric cancer patients. Besides its impact on survival, treatment also affects health-related quality of life (HRQOL), but an overview of reported studies is currently lacking. The aim of this systematic review was therefore to determine the short- and long-term impact of chemotherapy, surgery, and (chemo)radiotherapy on HRQOL in locally advanced, non-metastatic gastric cancer patients. Methods: A systematic review was performed including studies published between January 2000 and February 2021. We extracted studies published in Medline, Embase, and Scopus databases that assessed HRQOL in patients with locally advanced, non-metastatic gastric cancer treated with curative intent. Studies using non-validated HRQOL questionnaires were excluded. Short-term and long-term HRQOL were defined as HRQOL scores within and beyond 6 months after treatment, respectively. Results: Initially, we identified 8705 articles (4037 of which were duplicates, i.e., 46%) and ultimately included 10 articles. Most studies reported that short-term HRQOL worsened in the follow-up period from 6 weeks to 3 months after surgery. However, recovery of HRQOL to preoperative levels occurred after 6 months. After completion of chemoradiotherapy, the same pattern was seen with worse HRQOL after treatment and a recovery of HRQOL after 6–12 months. Conclusions: In patients with locally advanced, non-metastatic gastric cancer, HRQOL deteriorated during the first 3 months after surgery and chemoradiotherapy. However, the long-term data showed a recovery of HRQOL after 6–12 months. To implement HRQOL in clinical decision making in current clinical practice, more research is needed. Full article
(This article belongs to the Special Issue Treatment of Gastric Cancer)
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13 pages, 1515 KiB  
Systematic Review
Partial Versus Total Omentectomy in Patients with Gastric Cancer: A Systemic Review and Meta-Analysis
by Shion Wei Chai, Suo-Hsien Wang, Chih-Yuan Wang, Yi-Chan Chen, Ruey-Shyang Soong and Ting-Shuo Huang
Cancers 2021, 13(19), 4971; https://doi.org/10.3390/cancers13194971 - 3 Oct 2021
Cited by 5 | Viewed by 2386
Abstract
Background: Surgical treatment is the key to cure localized gastric cancer. There is no strong evidence that supports the value of omentectomy. Thus, a meta-analysis was conducted to compare the safety and efficiency of partial and total omentectomy in patients with gastric cancer. [...] Read more.
Background: Surgical treatment is the key to cure localized gastric cancer. There is no strong evidence that supports the value of omentectomy. Thus, a meta-analysis was conducted to compare the safety and efficiency of partial and total omentectomy in patients with gastric cancer. Methods: PubMed, Embase, and Cochrane Library databases were searched. All studies that compared total and partial omentectomy as treatments for gastric cancer were included. The primary outcomes were patients’ overall survival and disease-free survival, while the secondary outcomes were perioperative outcome and postoperative complications. Results: A total of nine studies were examined, wherein 1043 patients were included in the partial omentectomy group, and 1995 in the total omentectomy group. The partial omentectomy group was associated with better overall survival (hazard ratio: 0.80, 95% CI: 0.66 to 0.98, p = 0.04, I2 = 0%), shorter operative time, and lesser blood loss than the total omentectomy group. In addition, no statistically significant difference was observed in the number of dissected lymph nodes, length of hospital stays, complication rate, and disease-free survival. Conclusions: Our results show that, compared with total omentectomy in gastric cancer surgery, partial omentectomy had non-inferior oncological outcomes and comparable safety outcomes. Full article
(This article belongs to the Special Issue Treatment of Gastric Cancer)
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