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Advances in Peritoneal Carcinomatosis from Gastric Cancer
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Advances in Peritoneal Carcinomatosis from Gastric Cancer

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (10 October 2021) | Viewed by 31534

Special Issue Editors

Prof. Dr. Santiago Gonzalez-Moreno

E-Mail Website
Guest Editor
1. Department of Surgical Oncology, MD Anderson Cancer Center, Madrid, Spain
2. Department of Surgical Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
3. Executive Committee Member, Peritoneal Surface Oncology Group International (PSOGI)
Interests: gastric adenocarcinoma; peritoneal neoplasms; peritoneal carcinomatosis; cytoreductive surgery; intraperitoneal chemotherapy; diagnostic imaging; research; immunotherapy; cell therapy
Dr. Gloria Ortega-Perez

E-Mail Website
Guest Editor
Department of Surgical Oncology, MD Anderson Cancer Center, Madrid, Spain
Interests: gastric adenocarcinoma; peritoneal neoplasms; peritoneal carcinomatosis; cytoreductive surgery; intraperitoneal chemotherapy; diagnostic imaging; research; immunotherapy; cell therapy

Special Issue Information

Dear Colleagues,

Advanced gastric adenocarcinoma remains nowadays a deadly disease despite our best clinical care and research efforts. In the era of systemic perioperative chemotherapy with improved regimens such as FLOT, and high-quality gastric resections with D2 lymphadenectomy, cancer recurrence still happens, leading to the partient´s eventual demise. There is no doubt in those of us treating this disease, either surgical, medical or radiation oncologists, that peritoneal recurrence is one of the main, if not the main cause of treatment failure. We have already stated in the past that gastric cancer is a peritoneal disease, meaning that it is by nature avid for the peritoneum (more so in diffuse-type cancers). We have also made the reflection, valid today, that any further progress in gastric cancer treatment and research can only come from the deep understanding and control of peritoneal dissemination, which constitutes the limit that prevents this progress from happening.

We are currently working in this Special Issue of the Journal of Clinical Medicine devoted to peritoneal dissemination from gastric cancer. We are constructing an issue that will compile the foremost knowledge in this topic, brought to you by top scholarly leaders in the field, with the hope that showing it all together will help us all find further clues to beat gastric cancer by preventing and treating its spread to the peritoneal surfaces. The support and scientifc sponsoring of the renowned Peritoneal Surface Oncology Group Internatonal (PSOGI), a global leader in the field, adds interest and promimence to this work. With contributions ranging from the pathophysiology of peritoneal dissemination and the meaning of peritoneal free cancer cells to its elusive radiological appearance, along with the current approach to curative-intent treatment, the role of surgically-directed intraperitoneal chemotherapy in the curative and palliative settings, the current status of new treatments such as immunotherapy or cell therapy with CAR-T cells, and the latest advances in the molecular and genetic profiling of peritoneal metastases and primary tumors, we sincerely hope that this trip will be interesting to you all, and will fulfil the above-mentioned ultimate goal to get a step closer to beat gastric cancer one day.

Prof. Dr. Santiago Gonzalez-Moreno
Dr. Gloria Ortega-Perez
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. Journal of Clinical Medicine 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 2600 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

  • Gastric adenocarcinoma
  • Peritoneal neoplasms
  • Peritoneal carcinomatosis
  • Cytoreductive surgery
  • Intraperitoneal chemotherapy
  • Diagnostic imaging
  • Research
  • Immunotherapy
  • Cell therapy

Published Papers (12 papers)

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Editorial

Jump to: Research, Review, Other

2 pages, 155 KiB  
Editorial
Prevention and Treatment of Peritoneal Metastases from Gastric Cancer
by Paul H. Sugarbaker
J. Clin. Med. 2021, 10(9), 1899; https://doi.org/10.3390/jcm10091899 - 28 Apr 2021
Cited by 9 | Viewed by 1483
Abstract
Common knowledge would suggest that regional treatments for peritoneal metastases from gastric cancer would not be successful [...] Full article
(This article belongs to the Special Issue Advances in Peritoneal Carcinomatosis from Gastric Cancer)

Research

Jump to: Editorial, Review, Other

9 pages, 904 KiB  
Article
Intraperitoneal Chemotherapy as Adjuvant or Perioperative Chemotherapy for Patients with Type 4 Scirrhous Gastric Cancer: PHOENIX-GC2 Trial
by Hironori Ishigami, Yasushi Tsuji, Hisashi Shinohara, Yasuhiro Kodera, Mitsuro Kanda, Hiroshi Yabusaki, Seiji Ito, Motohiro Imano, Hiroharu Yamashita, Akio Hidemura, Hironori Yamaguchi, Takeo Fukagawa, Koji Oba, Joji Kitayama and Yasuyuki Seto
J. Clin. Med. 2021, 10(23), 5666; https://doi.org/10.3390/jcm10235666 - 30 Nov 2021
Cited by 11 | Viewed by 2578
Abstract
The prognosis of patients with type 4 scirrhous gastric cancer remains poor due to a high risk of peritoneal metastasis. We have previously developed combined chemotherapy regimens of intraperitoneal (IP) paclitaxel (PTX) and systemic chemotherapy, and promising clinical efficacy was reported in gastric [...] Read more.
The prognosis of patients with type 4 scirrhous gastric cancer remains poor due to a high risk of peritoneal metastasis. We have previously developed combined chemotherapy regimens of intraperitoneal (IP) paclitaxel (PTX) and systemic chemotherapy, and promising clinical efficacy was reported in gastric cancer with peritoneal metastasis. Herein, a randomized, phase III study is proposed to verify the efficacy of IP PTX to prevent peritoneal recurrence. Gastric cancer patients with type 4 tumors and without apparent distant metastasis, including peritoneal metastasis, will be randomized for standard systemic chemotherapy or combined IP and systemic chemotherapy based on peritoneal lavage cytology findings. Those with negative peritoneal cytology will receive radical gastrectomy and adjuvant chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). Those with positive peritoneal cytology will receive three courses of S-1 plus oxaliplatin (control arm), or S-1 plus oxaliplatin and IP PTX (experimental arm). Subsequently, they undergo gastrectomy and receive postoperative chemotherapy of S-1 plus docetaxel (control arm), or S-1 plus intravenous and IP PTX (experimental arm). The primary endpoint is disease free survival after a 3-year follow-up period. Secondary endpoints are overall survival, survival without peritoneal metastasis, safety, completion rate, curative resection rate, and histological response of preoperative chemotherapy. A total of 300 patients are to be enrolled. Full article
(This article belongs to the Special Issue Advances in Peritoneal Carcinomatosis from Gastric Cancer)
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9 pages, 1077 KiB  
Article
Efficacy of Regional Chemotherapy Approach in Peritoneal Metastatic Gastric Cancer
by Kornelia Aigner, Yogesh Kumar Vashist, Emir Selak, Sabine Gailhofer and Karl Reinhard Aigner
J. Clin. Med. 2021, 10(22), 5322; https://doi.org/10.3390/jcm10225322 - 15 Nov 2021
Cited by 3 | Viewed by 1995
Abstract
Peritoneal spread is frequent in gastric cancer (GC) and a palliative condition. After failure to systemic chemotherapy (sCTx) remaining therapeutic options are very limited. We evaluated the feasibility and efficacy of locoregional chemotherapy (RegCTx) in peritoneal metastatic GC. In total, 38 (23 male [...] Read more.
Peritoneal spread is frequent in gastric cancer (GC) and a palliative condition. After failure to systemic chemotherapy (sCTx) remaining therapeutic options are very limited. We evaluated the feasibility and efficacy of locoregional chemotherapy (RegCTx) in peritoneal metastatic GC. In total, 38 (23 male and 15 female) patients with peritoneal metastatic GC after failure of previous sCTx and unresectable disease were enrolled in this study. Using the hypoxic abdominal stop-flow perfusion, upper abdominal perfusion and intraarterial infusion technique in total 114 cycles with Cisplatin, Adriamycin and Mitomycin C were applied. No significant procedure related toxicity was noticed- especially no Grade 3 or 4 toxicity occurred. With the RegCTx approach a median overall survival of 17.4 months was achieved. Patients who had undergone previously resection of the GC the median overall survival was even better with 23.5 months. RegCTx is a promising, safe and efficient approach in diffuse metastatic GC. The evaluation of RegCTx in the setting of multimodal treatment approach at less advanced stages is also warranted. Full article
(This article belongs to the Special Issue Advances in Peritoneal Carcinomatosis from Gastric Cancer)
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21 pages, 6190 KiB  
Article
Imaging of Gastric Carcinomatosis
by Raquel Saiz Martínez, Clarisse Dromain and Naik Vietti Violi
J. Clin. Med. 2021, 10(22), 5294; https://doi.org/10.3390/jcm10225294 - 14 Nov 2021
Cited by 10 | Viewed by 4731
Abstract
Diagnosing the absence or presence of peritoneal carcinomatosis in patients with gastric cancer, including its extent and distribution, is an essential step in patients’ therapeutic management. Such diagnosis still remains a radiological challenge. In this article, we review the strengths and weaknesses of [...] Read more.
Diagnosing the absence or presence of peritoneal carcinomatosis in patients with gastric cancer, including its extent and distribution, is an essential step in patients’ therapeutic management. Such diagnosis still remains a radiological challenge. In this article, we review the strengths and weaknesses of the different imaging techniques for the diagnosis of peritoneal carcinomatosis of gastric origin as well as the techniques’ imaging features. We also discuss the assessment of response to treatment and present recommendations for the follow-up of patients with complete surgical resection according to the presence of risk factors of recurrence, as well as discussing future directions for imaging improvement. Full article
(This article belongs to the Special Issue Advances in Peritoneal Carcinomatosis from Gastric Cancer)
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10 pages, 533 KiB  
Article
Molecular Cytology by One-Step Nucleic Acid Amplification (OSNA) Assay of Peritoneal Washings during D2 Gastrectomy in Advanced Gastric Cancer Patients: Preliminary Results
by Katarzyna Gęca, Karol Rawicz-Pruszyński, Radosław Mlak, Katarzyna Sędłak, Magdalena Skórzewska, Zuzanna Pelc, Teresa Małecka-Massalska and Wojciech P. Polkowski
J. Clin. Med. 2021, 10(22), 5230; https://doi.org/10.3390/jcm10225230 - 10 Nov 2021
Cited by 2 | Viewed by 1613
Abstract
The presence of peritoneal free cancer cells (FCC) in gastric cancer (GC) patients is a poor prognostic factor. D2 gastrectomy may induce exfoliated FCC spread from the primary tumour or involved lymph nodes (LN). Conventional cytology for FCC detection has several limitations, whereas [...] Read more.
The presence of peritoneal free cancer cells (FCC) in gastric cancer (GC) patients is a poor prognostic factor. D2 gastrectomy may induce exfoliated FCC spread from the primary tumour or involved lymph nodes (LN). Conventional cytology for FCC detection has several limitations, whereas prophylactic use of extensive intraoperative peritoneal lavage (IPL) does not improve survival. A prospective single-arm observational study was conducted to verify whether D2 gastrectomy causes an intraoperative increase of FCC in peritoneal fluid. Twenty-seven GC patients underwent D2 gastrectomy, followed by objective quantitative measurements of CK19 mRNA level reflecting FCC with One-Step Nucleic Acid Amplification (OSNA) assay. The IPL with 3000 mL of saline was performed twice: (1) after gastrectomy with D2 lymphadenectomy and (2) after alimentary tract reconstruction. The IPL samples were analysed by initial cytology and four (1–4) consecutive OSNA assays. Initial OSNA measurement (1) revealed positive results (≥24.6 cCP/μL) in 7 (29.6%) patients. Subsequent OSNA measurements showed a significant decrease in the FCC level after D2 gastrectomy (1 vs. 2; p = 0.0012). The first IPL induced a non-significant increase in the FCCs (2 vs. 3, p = 0.3300), but the second IPL reversed it to normal levels (3 vs. 4, p = 0.0.0574). The OSNA assay indicates a temporal intraoperative increase in the peritoneal FCC in advanced GC patients undergoing D2 gastrectomy. Two consecutive IPLs are necessary to reverse the increase of CK19 mRNA level in peritoneal washings. Full article
(This article belongs to the Special Issue Advances in Peritoneal Carcinomatosis from Gastric Cancer)
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7 pages, 521 KiB  
Communication
Laparoscopic Heated Intraperitoneal Chemotherapy in the Treatment of Carcinomatosis of Gastric Adenocarcinoma Origin
by Michael G. White and Brian D. Badgwell
J. Clin. Med. 2021, 10(20), 4757; https://doi.org/10.3390/jcm10204757 - 17 Oct 2021
Cited by 2 | Viewed by 1774
Abstract
The use of heated intraperitoneal chemotherapy (HIPEC) in conjunction with cytoreductive surgery has been gaining increasing traction in treating gastric adenocarcinoma with metastasis to the peritoneum in recent years. The addition of laparoscopic HIPEC (LS-HIPEC) to these treatment algorithms has increased the flexibility [...] Read more.
The use of heated intraperitoneal chemotherapy (HIPEC) in conjunction with cytoreductive surgery has been gaining increasing traction in treating gastric adenocarcinoma with metastasis to the peritoneum in recent years. The addition of laparoscopic HIPEC (LS-HIPEC) to these treatment algorithms has increased the flexibility and adaptability of HIPEC integrating into treatment sequencing, allowing for iterative protocols of LS-HIPEC prior to cytoreduction as neoadjuvant treatment, as well as in the palliation of patients with unresectable disease and uncontrolled ascites. As the use of HIPEC in gastric adenocarcinoma continues to be refined, LS-HIPEC algorithms should continue to be considered and utilized both in curative treatment algorithms as well as in patients in the palliative setting. Given that LS-HIPEC remains a relatively nascent treatment modality, we advocate for its use in the setting of a clinical trial when feasible. Full article
(This article belongs to the Special Issue Advances in Peritoneal Carcinomatosis from Gastric Cancer)
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Review

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21 pages, 2207 KiB  
Review
HIPEC in Peritoneal Metastasis of Gastric Origin: A Systematic Review of Regimens and Techniques
by Felix Gronau, Linda Feldbruegge, Frauke Oberwittler, Santiago Gonzalez-Moreno, Laurent Villeneuve, Clarisse Eveno, Olivier Glehen, Shigeki Kusamura and Beate Rau
J. Clin. Med. 2022, 11(5), 1456; https://doi.org/10.3390/jcm11051456 - 7 Mar 2022
Cited by 11 | Viewed by 2784
Abstract
(1) Background: Peritoneal metastasis in gastric cancer is associated with a poor prognosis. Complete cytoreductive surgery including gastrectomy and complete removal of all peritoneal lesions followed by hyperthermic intraperitoneal chemotherapy (HIPEC) achieves promising results. There exists an immersive variety of approaches for HIPEC [...] Read more.
(1) Background: Peritoneal metastasis in gastric cancer is associated with a poor prognosis. Complete cytoreductive surgery including gastrectomy and complete removal of all peritoneal lesions followed by hyperthermic intraperitoneal chemotherapy (HIPEC) achieves promising results. There exists an immersive variety of approaches for HIPEC that makes it difficult to weigh different results obtained in the literature. In order to enable standardization and development of HIPEC, we here present a systematic review of different drug regimens and technical approaches. (2) Methods: PubMed, Embase, and the Cochrane Library were systematically searched on 26 May 2021 using the mesh terms “intraperitoneal chemotherapy AND gastric cancer”. Under consideration of systematic review guidelines, articles reporting on HIPEC in combination with CRS were selected. Data on duration, drugs, dosage, and other application parameters as well as morbidity and long term survival data were extracted for subsequent statistical analysis, tabulation, and descriptive synthesis. We assessed the risk of bias due to inhomogeneity of the patient cohort and incompleteness of report of HIPEC parameters. (3) Results: Out of 1421 screened publications, 42 publications presenting data from 1325 patients met the criteria. Most of the publications were single institutional retrospective cohort studies. The most common HIPEC regimen is performed after gastrointestinal anastomosis and consists of 50–200 mg/m2 cisplatinum and 30–40 mg/m2 mytomycin C at 42–43 °C for 60–90 min in a closed abdomen HIPEC system with three tubes. Almost every study reported incompletely on HIPEC parameters. Lower rates of anastomotic leakage were reported in studies that performed HIPEC after gastrointestinal anastomosis. Studies that performed open HIPEC and integrated a two-drug regimen indicated better overall survival rates. (4) Discussion: This is an exhaustive overview of the use of drug regimens and techniques for HIPEC after CRS for gastric cancer peritoneal metastasis. Other indications and application modes of intraperitoneal chemotherapy such as prophylactic or palliative HIPEC apart from CRS were not addressed. (5) Conclusion: Complete report of HIPEC parameters should be included in every publication. A consensus for dose expression either per BSA or as flat dose is desirable for comparison of the drug regimens. Despite numerous variations, we identified the most common regimens and techniques and their advantages and disadvantages according to the data in the literature. More phase I/II studies are needed to identify the best approach for HIPEC. (6) Other: This review was not supported by third parties. Full article
(This article belongs to the Special Issue Advances in Peritoneal Carcinomatosis from Gastric Cancer)
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7 pages, 39707 KiB  
Review
Cytoreductive Surgery for Peritoneal Carcinomatosis from Gastric Cancer: Technical Details
by Thomas Boerner and Pompiliu Piso
J. Clin. Med. 2021, 10(22), 5263; https://doi.org/10.3390/jcm10225263 - 12 Nov 2021
Cited by 2 | Viewed by 2000
Abstract
Due to limited systemic treatment options, peritoneal carcinomatosis of gastric origin is still associated with a dismal outcome and is claimed a terminal disease. In the past, surgery had not been considered as a potential treatment option. However, there is emerging evidence that [...] Read more.
Due to limited systemic treatment options, peritoneal carcinomatosis of gastric origin is still associated with a dismal outcome and is claimed a terminal disease. In the past, surgery had not been considered as a potential treatment option. However, there is emerging evidence that in selected patients, locoregional treatment modalities including cytoreductive surgery of peritoneal carcinomatosis can improve survival in patients with gastric cancer. These operative procedures are complex and challenging, and a high surgical expertise of the treating physician is necessary to prevent major postoperative morbidity and mortality with a delay of further systemic therapy. This review summarizes our current knowledge and personal experience regarding the techniques of cytoreductive surgery for peritoneal metastasis of gastric origin. Full article
(This article belongs to the Special Issue Advances in Peritoneal Carcinomatosis from Gastric Cancer)
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13 pages, 941 KiB  
Review
The Role of CAR-T Cells in Peritoneal Carcinomatosis from Gastric Cancer: Rationale, Experimental Work, and Clinical Applications
by Siyuan Qian, Pedro Villarejo-Campos and Damián García-Olmo
J. Clin. Med. 2021, 10(21), 5050; https://doi.org/10.3390/jcm10215050 - 28 Oct 2021
Cited by 5 | Viewed by 2372
Abstract
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have shown poor effectiveness in treating peritoneal carcinomatosis (PC) of gastric origin with a high tumor burden (high peritoneal cancer index), though there are scarce therapy alternatives that are able to improve survival. In experimental [...] Read more.
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have shown poor effectiveness in treating peritoneal carcinomatosis (PC) of gastric origin with a high tumor burden (high peritoneal cancer index), though there are scarce therapy alternatives that are able to improve survival. In experimental studies, chimeric antigen receptor-T (CAR-T) cell therapy has shown encouraging results in gastric cancer and is currently being evaluated in several clinical trials. Regarding PC, CAR-T cell therapy has also proven useful in experimental studies, especially when administered intraperitoneally, as this route improves cell distribution and lifespan. Although these results need to be supported by ongoing clinical trials, CAR-T cells are a promising new therapeutic approach to peritoneal metastases from gastric cancer. In this review, we summarize the current evidence of the use of CAR-T cells in gastric cancer and PC of gastric origin. Full article
(This article belongs to the Special Issue Advances in Peritoneal Carcinomatosis from Gastric Cancer)
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16 pages, 543 KiB  
Review
The Burden of Peritoneal Metastases from Gastric Cancer: A Systematic Review on the Incidence, Risk Factors and Survival
by Anouk Rijken, Robin J. Lurvink, Misha D. P. Luyer, Grard A. P. Nieuwenhuijzen, Felice N. van Erning, Johanna W. van Sandick and Ignace H. J. T. de Hingh
J. Clin. Med. 2021, 10(21), 4882; https://doi.org/10.3390/jcm10214882 - 23 Oct 2021
Cited by 32 | Viewed by 3064
Abstract
The peritoneum is a common metastatic site in gastric cancer. This systematic review provides an overview of the incidence, risk factors and survival of synchronous peritoneal metastases from gastric cancer. A systematic search was performed to identify studies wherein the incidence, risk factors [...] Read more.
The peritoneum is a common metastatic site in gastric cancer. This systematic review provides an overview of the incidence, risk factors and survival of synchronous peritoneal metastases from gastric cancer. A systematic search was performed to identify studies wherein the incidence, risk factors and survival of gastric cancer with peritoneal metastases were investigated. Of all 38 potentially eligible studies, 17 studies were included based on the eligibility criteria. The incidence of synchronous gastric peritoneal metastases was reviewed for population-based studies (10–21%), for observational cohort studies (2–15%) and for surgical cohort studies (13–40%). Potential risk factors for synchronous gastric peritoneal metastases were younger age, non-cardia gastric cancer, female sex, signet ring cell carcinoma, diffuse type histology or linitis plastica, T4 stage, Hispanic ethnicity and more than one metastatic location. Synchronous peritoneal metastases are commonly diagnosed in patients with gastric cancer with an incidence up to 21% in recent population-based studies. Furthermore, prognosis of patients with gastric peritoneal metastases is poor with median overall survival ranging from 2 to 9 months. The high incidence and poor prognosis require intensive research on diagnostic features and effective treatment options to improve survival. Full article
(This article belongs to the Special Issue Advances in Peritoneal Carcinomatosis from Gastric Cancer)
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9 pages, 264 KiB  
Review
Immunotherapy for Peritoneal Metastases from Gastric Cancer: Rationale, Current Practice and Ongoing Trials
by Eva Ruiz Hispán, Manuel Pedregal, Ion Cristobal, Jesús García-Foncillas and Cristina Caramés
J. Clin. Med. 2021, 10(20), 4649; https://doi.org/10.3390/jcm10204649 - 11 Oct 2021
Cited by 12 | Viewed by 2544
Abstract
Peritoneal metastases from gastric cancer play a key role in the fatal prognosis of the disease. The lack of efficacy of actual therapeutic approaches together with the outcomes achieved with checkpoint inhibitors in gastric cancer compel us to address the current state-of-the-art immunotherapy [...] Read more.
Peritoneal metastases from gastric cancer play a key role in the fatal prognosis of the disease. The lack of efficacy of actual therapeutic approaches together with the outcomes achieved with checkpoint inhibitors in gastric cancer compel us to address the current state-of-the-art immunotherapy treatment of peritoneal dissemination. The immunogenicity of the peritoneum has been described to be particularly active at omentum and peritoneal lymph nodes. Also, both innate and acquired immunity seems to be involved at different molecular levels. Recent works show PDL1 expression being less present at the peritoneal level; however, some clinical trials have begun to yield results. For example, the ATTRACTION-2 trial has demonstrated the activity of Nivolumab in heavily pretreated patients even though peritoneal metastases were diagnosed in a 30% of them. Despite positive results in the metastatic setting, peritoneal responses to systemic checkpoint inhibitors remains unclear, therefore, new strategies for intraperitoneal immunotherapy are being proposed for different ongoing clinical trials. Full article
(This article belongs to the Special Issue Advances in Peritoneal Carcinomatosis from Gastric Cancer)

Other

25 pages, 214611 KiB  
Commentary
The Development of Peritoneal Metastasis from Gastric Cancer and Rationale of Treatment According to the Mechanism
by Yutaka Yonemura, Haruaki Ishibashi, Akiyoshi Mizumoto, Gorou Tukiyama, Yang Liu, Satoshi Wakama, Shouzou Sako, Nobuyuki Takao, Toshiyuki Kitai, Kanji Katayama, Yasuyuki Kamada, Keizou Taniguchi, Daisuke Fujimoto, Yoshio Endou and Masahiro Miura
J. Clin. Med. 2022, 11(2), 458; https://doi.org/10.3390/jcm11020458 - 17 Jan 2022
Cited by 9 | Viewed by 2803
Abstract
In the present article, we describe the normal structure of the peritoneum and review the mechanisms of peritoneal metastasis (PM) from gastric cancer (GC). The structure of the peritoneum was studied by a double-enzyme staining method using alkaline-phosphatase and 5′-nucreotidase, scanning electron microscopy, [...] Read more.
In the present article, we describe the normal structure of the peritoneum and review the mechanisms of peritoneal metastasis (PM) from gastric cancer (GC). The structure of the peritoneum was studied by a double-enzyme staining method using alkaline-phosphatase and 5′-nucreotidase, scanning electron microscopy, and immunohistological methods. The fundamental structure consists of three layers, mesothelial cells and a basement membrane (layer 1), macula cribriformis (MC) (layer 2), and submesothelial connective tissue containing blood vessels and initial lymphatic vessels, attached to holes in the MC (layer 3). Macro molecules and macrophages migrate from mesothelial stomata to the initial lymphatic vessels through holes in the MC. These structures are characteristically found in the diaphragm, omentum, paracolic gutter, pelvic peritoneum, and falciform ligament. The first step of PM is spillage of cancer cells (peritoneal free cancer cells; PFCCs) into the peritoneal cavity from the serosal surface of the primary tumor or cancer cell contamination from lymphatic and blood vessels torn during surgical procedures. After PFCCs adhere to the peritoneal surface, PMs form by three processes, i.e., (1) trans-mesothelial metastasis, (2) trans-lymphatic metastasis, and (3) superficial growing metastasis. Because the intraperitoneal (IP) dose intensity is significantly higher when generated by IP chemotherapy than by systemic chemotherapy, IP chemotherapy has a great role in the treatment of PFCCs, superficial growing metastasis, trans-lymphatic metastasis and in the early stages of trans-mesothelial metastasis. However, an established trans-mesothelial metastasis has its own interstitial tissue and vasculature which generate high interstitial pressure. Accordingly, it is reasonable to treat established trans-mesothelial metastasis by bidirectional chemotherapy from both IP and systemic chemotherapy. Full article
(This article belongs to the Special Issue Advances in Peritoneal Carcinomatosis from Gastric Cancer)
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