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Recent Updates on Hyperthermic Intraperitoneal Chemotherapy and Cytoreductive Surgery
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Recent Updates on Hyperthermic Intraperitoneal Chemotherapy and Cytoreductive Surgery

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

Deadline for manuscript submissions: closed (24 December 2023) | Viewed by 7160

Special Issue Editors

Prof. Dr. Joseph Kim

E-Mail Website
Guest Editor
Division of Surgical Oncology, Department of Surgery, University of Kentucky, Lexington, KY 40536, USA
Interests: surgical oncology; robotic surgery; pancreatic cancer; gastric cancer; HIPEC
Special Issues, Collections and Topics in MDPI journals
Dr. Prakash Pandalai

E-Mail Website
Guest Editor
Division of Surgical Oncology, Department of Surgery, University of Kentucky, Lexington, KY 40536, USA
Interests: surgical oncology; HIPEC; pancreatic cancer
Special Issues, Collections and Topics in MDPI journals
Dr. Hannah G. McDonald

E-Mail Website
Guest Editor Assistant
Division of Surgical Oncology, Department of Surgery, University of Kentucky, Lexington, KY 40536, USA
Interests: surgical oncology

Special Issue Information

Dear Colleagues,

It is our pleasure to welcome you to participate in a Journal of Clinical Medicine Special Issue featuring heated intraperitoneal chemotherapy (HIPEC) in the setting of peritoneal surface malignancy. 

Originally championed as an aggressive surgical approach for peritoneal mesothelioma and appendiceal mucinous disease, cytoreductive surgery (CRS) with HIPEC has expanded to a wide range of gastrointestinal and gynecologic malignancies worldwide. While the exact incidence of de novo peritoneal carcinomatosis (PC) varies by histology, it is estimated that up to 50% of patients will develop peritoneal-based recurrence following curative intent surgery for gastric, colorectal, and appendix cancer, and a 20-40% rate of recurrence for ovarian cancer. The historic 5-year survival rate for these patients is less than 20%. As a clinical entity, peritoneal surface malignancy (PSM) continues to result in significant morbidity and uniform mortality for affected patients without therapeutic intervention. 

This is an important and timely topic with ongoing clinical and translational science in the field of PSM, but with tempered enthusiasm, following the publication of the PRODIGE-7 trial (Quenet et al., 2021). In this trial, a remarkable increase in the median overall survival of 40 months was observed with CRS in patients with colorectal PC. The addition of Oxaliplatin-based HIPEC did not improve overall survival in the study.   

Since this landmark publication, numerous discussions regarding the limitations of the trial have shifted the attention back to unanswered questions and gaps in knowledge in the application of intraperitoneal chemotherapy and the types of chemotherapeutic agents.

In this Special Issue, our objective is to highlight important advances in the field of PSM, such as the application of immunotherapy in peritoneal mesothelioma, the increased adoption of HIPEC in ovarian cancer, the potential of personalized chemo-profiling through the use of organoids, and many other advances that continue to revitalize this field. We look forward to receiving original work from leaders in the field, exploring the most up-to-date advances in drug development, in-vivo modeling and personalized tumor profiling; expanding techniques for drug delivery; and providing updates on clinical pathways to improve patient outcomes. We recognize that PSM affects patients globally and anticipate that leaders from around the world will contribute to the success of this Special Issue. It is our wish for this collection to promote future research and collaboration.

We hope you will enjoy this Special Issue.

Prof. Dr. Joseph Kim
Dr. Prakash Pandalai
Guest Editors
Dr. Hannah G. McDonald
Guest Editor Assistant

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.

Prof. Dr. Joseph Kim
Dr. Prakash Pandalai
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

  • peritoneal carcinomatosis
  • cytoreductive surgery
  • intraperitoneal chemotherapy
  • surgical oncology
  • robotic surgery

Published Papers (6 papers)

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Research

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10 pages, 1867 KiB  
Article
Circulating Tumor DNA (ctDNA) Clearance May Predict Treatment Response in Neoadjuvant Colorectal Cancer Management
by Britney Niemann, John Moise, Michael Sestito, Midhun Malla, Kevin Train, Douglas Murken, Keri Mayers, Emily Groves and Mary Garland-Kledzik
J. Clin. Med. 2024, 13(6), 1684; https://doi.org/10.3390/jcm13061684 - 14 Mar 2024
Viewed by 590
Abstract
Background: Circulating tumor DNA (ctDNA) is extracellular DNA released by tumors and has been proposed as a marker of residual disease as well as a predictor of disease recurrence in the adjuvant setting. However, data are lacking on the utility of this biomarker [...] Read more.
Background: Circulating tumor DNA (ctDNA) is extracellular DNA released by tumors and has been proposed as a marker of residual disease as well as a predictor of disease recurrence in the adjuvant setting. However, data are lacking on the utility of this biomarker in the neoadjuvant setting. Methods: We performed a retrospective study of stage III and IV colorectal cancer patients receiving neoadjuvant treatment at a single institution. Results: Seventeen patients converted from a positive pre-neoadjuvant ctDNA to a negative ctDNA prior to surgery. Five patients remained persistently positive despite systemic treatment. ctDNA conversion was found to be associated with a higher incidence of favorable treatment effect scores on final surgical pathology. There was no difference in recurrence-free survival in this small population. Furthermore, no added benefit was identified for patients receiving additional neoadjuvant therapy after the time of positive to negative ctDNA conversion. Conclusions: This study highlights the potential utility of ctDNA and the need for prospective trials in the neoadjuvant setting to monitor treatment response and guide decisions on treatment duration. Full article
(This article belongs to the Special Issue Recent Updates on Hyperthermic Intraperitoneal Chemotherapy and Cytoreductive Surgery)
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Review

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11 pages, 2821 KiB  
Review
Prophylactic Hyperthermic Intraperitoneal Chemotherapy for Patients at High Risk of Developing Gallbladder Cancer Peritoneal Metastases: Case Report and Rationale for a Prospective Clinical Trial
by Alexander E. Crum, Michael Sestito, Mary Garland-Kledzik and Brian A. Boone
J. Clin. Med. 2024, 13(3), 768; https://doi.org/10.3390/jcm13030768 - 29 Jan 2024
Viewed by 781
Abstract
Gallbladder cancer is a devastating disease with a 5-year survival of only 18%. The majority of gallbladder cancers are discovered incidentally in patients undergoing cholecystectomy. During non-oncologic laparoscopic cholecystectomy for gallbladder disease, gallbladder perforation occurs in 29% of cases and spillage of gallstones [...] Read more.
Gallbladder cancer is a devastating disease with a 5-year survival of only 18%. The majority of gallbladder cancers are discovered incidentally in patients undergoing cholecystectomy. During non-oncologic laparoscopic cholecystectomy for gallbladder disease, gallbladder perforation occurs in 29% of cases and spillage of gallstones occurs in 9% of cases. Patients with gallbladder cancer frequently develop peritoneal recurrence, particularly after intra-operative bile spillage during cholecystectomy for incidental gallbladder cancer. The high likelihood of spillage and peritoneal seeding during cholecystectomy for incidental gallbladder cancer suggests the need for prophylactic strategies to prevent peritoneal carcinomatosis. Hyperthermic intraperitoneal chemotherapy (HIPEC) has efficacy in gallbladder cancer patients with macroscopic peritoneal disease undergoing cytoreductive surgery and has been associated with a survival advantage in a multi-institutional retrospective case series. However, the utilization of HIPEC with a prophylactic intent against the development of peritoneal disease following resection of gallbladder cancer has not yet been prospectively studied. Here, we review the literature surrounding gallbladder cancer and HIPEC, report an institutional experience utilizing prophylactic HIPEC, and discuss a recently proposed prospective clinical trial evaluating the efficacy of prophylactic HIPEC in the prevention of gallbladder peritoneal metastasis. Full article
(This article belongs to the Special Issue Recent Updates on Hyperthermic Intraperitoneal Chemotherapy and Cytoreductive Surgery)
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19 pages, 715 KiB  
Review
PIPAC for Gastrointestinal Malignancies
by Sara K. Daniel, Beatrice J. Sun and Byrne Lee
J. Clin. Med. 2023, 12(21), 6799; https://doi.org/10.3390/jcm12216799 - 27 Oct 2023
Cited by 1 | Viewed by 2084
Abstract
The peritoneum is a common site of metastases for gastrointestinal tumors that predicts a poor outcome. In addition to decreased survival, peritoneal metastases (PMs) can significantly impact quality of life from the resulting ascites and bowel obstructions. The peritoneum has been a target [...] Read more.
The peritoneum is a common site of metastases for gastrointestinal tumors that predicts a poor outcome. In addition to decreased survival, peritoneal metastases (PMs) can significantly impact quality of life from the resulting ascites and bowel obstructions. The peritoneum has been a target for regional therapies due to the unique properties of the blood–peritoneum barrier. Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) have become accepted treatments for limited-volume peritoneal disease in appendiceal, ovarian, and colorectal malignancies, but there are limitations. Pressurized intraperitoneal aerosolized chemotherapy (PIPAC) improves drug distribution and tissue penetration, allowing for a minimally invasive application for patients who are not CRS/HIPEC candidates based on high disease burden. PIPAC is an emerging treatment that may convert the patient to resectable disease, and may increase survival without major morbidity, as indicated by many small studies. In this review, we discuss the rationale and benefits of PIPAC, as well as sentinel papers describing its application for gastric, colorectal, appendiceal, and pancreatobiliary PMs. While no PIPAC device has yet met FDA approval, we discuss next steps needed to incorporate PIPAC into neoadjuvant/adjuvant treatment paradigms, as well as palliative settings. Data on active clinical trials using PIPAC are provided. Full article
(This article belongs to the Special Issue Recent Updates on Hyperthermic Intraperitoneal Chemotherapy and Cytoreductive Surgery)
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12 pages, 762 KiB  
Review
Current Evidence for the Use of HIPEC and Cytoreductive Surgery in Gastric Cancer Metastatic to the Peritoneum
by Anish J. Jain and Brian D. Badgwell
J. Clin. Med. 2023, 12(20), 6527; https://doi.org/10.3390/jcm12206527 - 14 Oct 2023
Cited by 3 | Viewed by 1648
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Recent Updates on Hyperthermic Intraperitoneal Chemotherapy and Cytoreductive Surgery)
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Graphical abstract

15 pages, 1153 KiB  
Review
The Role of Prophylactic and Adjuvant Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Prevention of Peritoneal Metastases in Advanced Colorectal Cancer
by Beatrice J. Sun, Sara K. Daniel and Byrne Lee
J. Clin. Med. 2023, 12(20), 6443; https://doi.org/10.3390/jcm12206443 - 10 Oct 2023
Cited by 1 | Viewed by 1159
Abstract
Hyperthermic intraperitoneal chemotherapy (HIPEC) is a locoregional therapy that may be combined with cytoreductive surgery (CRS) to treat patients with colorectal cancer and peritoneal metastases (PM). In recent years, three randomized controlled trials (RCTs) have investigated the role of prophylactic or adjuvant HIPEC [...] Read more.
Hyperthermic intraperitoneal chemotherapy (HIPEC) is a locoregional therapy that may be combined with cytoreductive surgery (CRS) to treat patients with colorectal cancer and peritoneal metastases (PM). In recent years, three randomized controlled trials (RCTs) have investigated the role of prophylactic or adjuvant HIPEC in preventing the development of PM in patients with high-risk colorectal cancer: PROPHYLOCHIP and COLOPEC evaluated adjuvant HIPEC, and HIPECT4 studied concurrent HIPEC and CRS. Although PROPHYLOCHIP and COLOPEC were negative trials, a great deal may be learned from their methodology, outcome measures, and patient selection criteria. HIPECT4 is the first RCT to show a clinical benefit of HIPEC in high-risk T4 colorectal cancer, demonstrating improved locoregional disease control with the addition of HIPEC to CRS with no increase in the rate of complications. This review critically examines the strengths and limitations of each major trial and discusses their potential impact on the practice of HIPEC. Several additional ongoing clinical trials also seek to investigate the role of HIPEC in preventing PM in advanced colorectal cancer. Full article
(This article belongs to the Special Issue Recent Updates on Hyperthermic Intraperitoneal Chemotherapy and Cytoreductive Surgery)
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Other

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8 pages, 1011 KiB  
Brief Report
Data-Driven Surveillance Protocol for Patients at Risk for Peritoneal Recurrence of Primary Colon Cancer: Surveillance for Peritoneal Carcinomatosis
by Meloria A. Hoskins, Adam Finkelstein, Aisha Rashid, Olivia Ziegler, Marc M. Mankarious, Jorge V. Benavides and Colette R. Pameijer
J. Clin. Med. 2024, 13(8), 2358; https://doi.org/10.3390/jcm13082358 - 18 Apr 2024
Viewed by 405
Abstract
Peritoneal carcinomatosis (PC) is rarely discovered early due to low sensitivity of screening imaging and tumor markers, however, earlier identification may improve outcomes. This study assesses risk factors and time to recurrence of PC and implementation of a surveillance system. Patients with stage [...] Read more.
Peritoneal carcinomatosis (PC) is rarely discovered early due to low sensitivity of screening imaging and tumor markers, however, earlier identification may improve outcomes. This study assesses risk factors and time to recurrence of PC and implementation of a surveillance system. Patients with stage II–III colon adenocarcinoma undergoing curative colectomy between 2005–2022 were retrospectively reviewed at a single tertiary care institution. Patients were divided into three cohorts: no recurrence (NR), PC, and other types of recurrence (OTR). Baseline characteristics between cohorts were compared with univariate analysis. Overall survival and PC risk were assessed using multivariate analysis with Cox’s proportional-hazard modelling. 412 patients were included; 78.4% had NR, 7.8% had PC, and 13.8% had OTR. Patient demographics, comorbidities, tumor side, and histologic features were similar between cohorts. Patients with PC were more likely to have microscopic tumor perforation (25% vs. 8.8% vs. 6.8%, p = 0.002), margin involvement (25% vs. 8.8% vs. 4.6%, p < 0.001), lymphovascular invasion (56.2% vs. 33.3%, vs. 24.5%, p < 0.001), perineural invasion (28.1% vs. 15.8% vs. 11.5%, p = 0.026) compared to OTR or NR. Median time to PC after colectomy was 11 months. Tumor characteristics of stage II–III colon cancer define a high-risk profile for PC. An early surveillance program sensitive for peritoneal disease should be adopted for these patients. Full article
(This article belongs to the Special Issue Recent Updates on Hyperthermic Intraperitoneal Chemotherapy and Cytoreductive Surgery)
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