|
1
|
Ruff SM. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer Peritoneal Metastases. Surg Oncol Clin N Am 2025; 34:241-251. [PMID: 40015802 DOI: 10.1016/j.soc.2024.12.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2025]
Abstract
Gastric cancer with peritoneal metastases (GC-PM) carries a poor prognosis and estimated survival is less than 6 to 12 months. One potential treatment of GC-PM is cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Success of this treatment largely relies on tumor biology and patient selection. These operations carry a high risk of morbidity and mortality and their efficacy in GC-PM remains controversial. This study will review the updated literature for CRS ± HIPEC in patients with GC-PM.
Collapse
Affiliation(s)
- Samantha M Ruff
- Department of Surgery, University of Virginia, 1215 Lee Street, Charlottesville, VA 22903, USA.
| |
Collapse
|
|
2
|
Sparkman BK, Freudenberger DC, Vudatha V, Trevino JG, Khader A, Fernandez LJ. Robotic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: is there a benefit? Surg Endosc 2025; 39:513-521. [PMID: 39414669 PMCID: PMC11666753 DOI: 10.1007/s00464-024-11199-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2024] [Accepted: 08/17/2024] [Indexed: 10/18/2024]
Abstract
BACKGROUND Open cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a therapeutic option for the management of malignancies with peritoneal carcinomatosis and of peritoneal origin. Robotic surgery shows promise as a minimally invasive approach for select patients. We aimed to evaluate the differences in outcomes between robotic versus open CRS/HIPEC and hypothesized less morbidity and faster recovery in the robotic approach group. METHODS We conducted a retrospective cohort study from our HIPEC database including all tumor origins. We included patients aged 18-89 years who underwent CRS/HIPEC for curative intent at a single institution between January 1, 2017, and December 31, 2023. Patients were stratified by open versus robotic-assisted surgery. Mann-Whitney U and Fisher Exact tests were used to compare differences in patient characteristics and outcomes. RESULTS A total of 111 patients underwent CRS/HIPEC for curative intent, with 95 (85.6%) cases performed open and 16 (14.4%) robotically. The groups were demographically similar, except patients undergoing robotic CRS/HIPEC had a significantly higher median income ($83,845 vs. $70,519, p < 0.001). Rate of comorbidities and cancer type, including appendiceal, colorectal, and ovarian, were the same. The peritoneal carcinomatosis index and completion of cytoreduction score were similar between groups. Robotic approach was associated with statistically significant lower estimated blood loss (113 vs. 400 mL, p < 0.001) and postoperative transfusions (6.3% vs. 23.2%, p = 0.036). Total complications, readmission rates, and 30-day mortality were similar among groups, but the robotic group had a significantly shorter length of stay (5.5 vs. 9 d., p < 0.001). CONCLUSION Robotic CRS/HIPEC holds promise to decrease intraoperative blood loss, blood transfusions, and hospital stay while providing similar immediate postoperative outcomes in select patients. These results should be validated in the setting of a prospective trial and effects on long-term oncologic outcomes should be investigated.
Collapse
Affiliation(s)
- Brian K Sparkman
- Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, 1200 E Broad St, PO Box 980011, Richmond, VA, 23219, USA
| | - Devon C Freudenberger
- Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, 1200 E Broad St, PO Box 980011, Richmond, VA, 23219, USA
| | - Vignesh Vudatha
- Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, 1200 E Broad St, PO Box 980011, Richmond, VA, 23219, USA
| | - Jose G Trevino
- Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, 1200 E Broad St, PO Box 980011, Richmond, VA, 23219, USA
| | - Adam Khader
- Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, 1200 E Broad St, PO Box 980011, Richmond, VA, 23219, USA
- Department of Surgery, Richmond Veteran Affairs Medical Center, 1201 Broad Rock Blvd, Richmond, VA, USA
| | - Leopoldo J Fernandez
- Division of Surgical Oncology, Department of Surgery, Virginia Commonwealth University School of Medicine, 1200 E Broad St, PO Box 980011, Richmond, VA, 23219, USA.
- Department of Surgery, Richmond Veteran Affairs Medical Center, 1201 Broad Rock Blvd, Richmond, VA, USA.
| |
Collapse
|
|
3
|
Dong FH, Shan YQ, Kong WC, Wei HR, Zhou LP, Yang YB, Shi J, Ji CH, Zhang YJ. Hyperthermic intraperitoneal chemotherapy: Ideal and reality. Asian J Surg 2024:S1015-9584(24)02488-6. [PMID: 39567292 DOI: 10.1016/j.asjsur.2024.10.155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2024] [Revised: 09/24/2024] [Accepted: 10/10/2024] [Indexed: 11/22/2024] Open
Abstract
Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) is a new adjuvant therapy for the treatment of abdominal malignant tumors and metastases, which has shown great potential. The HIPEC technique can effectively kill residual lesions in the abdominal cavity through the synergistic sensitization effect of thermal chemotherapy and the circulating perfusion and washing effect of large volume perfusion fluid, thereby reducing the occurrence of malignant ascites and reducing the risk of postoperative recurrence and metastasis. However, there are still many problems in the practical operation of HIPEC, such as non-uniform distribution of perfusate temperature, inadequate perfusion due to the presence of 'dead space', incomplete cytoreductive surgery (CRS), instances of catheter obstruction during perfusate circulation, the lack of a uniform standard for selecting appropriate HIPEC techniques, occupational exposure of medical personnel during the HIPEC procedure, and the selection of HIPEC chemotherapy regimens for patients with various types of tumors. This article aims to summarize the problems encountered in the clinical practice of HIPEC, explore the problems that can be improved, and put forward some suggestions, so as to promote the further standardization and normalization of HIPEC technology.
Collapse
Affiliation(s)
- Fan-He Dong
- Zhejiang Chinese Medical University, Hangzhou, China.
| | - Yu-Qiang Shan
- Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, China.
| | - Wen-Cheng Kong
- Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, China.
| | - Hao-Ran Wei
- Zhejiang Chinese Medical University, Hangzhou, China.
| | - Lin-Po Zhou
- Zhejiang Chinese Medical University, Hangzhou, China.
| | - Ye-Bin Yang
- Zhejiang Chinese Medical University, Hangzhou, China.
| | - Jing Shi
- Zhejiang Chinese Medical University, Hangzhou, China.
| | - Cheng-Hao Ji
- Zhejiang Chinese Medical University, Hangzhou, China.
| | - Yi-Jia Zhang
- Zhejiang Chinese Medical University, Hangzhou, China.
| |
Collapse
|
|
4
|
Wang T, Ma S, Zhang S, Aizezi Y, Wang Q. Optimal hyperthermic intraperitoneal chemotherapy regimen for advanced and peritoneal metastatic gastric cancer: a systematic review and Bayesian network meta-analysis. Front Oncol 2024; 14:1466473. [PMID: 39600651 PMCID: PMC11588639 DOI: 10.3389/fonc.2024.1466473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 10/28/2024] [Indexed: 11/29/2024] Open
Abstract
Background Peritoneal metastasis is one of the most common modes of spread of gastric cancer. Currently, surgical treatment combined with hyperthermic intraperitoneal chemotherapy (HIPEC) and systemic chemotherapy has demonstrated promising outcomes in both the treatment and prevention of peritoneal metastasis in gastric cancer. However, various HIPEC drug regimens are in clinical use, and their efficacy remains unclear. This study aims to evaluate the effectiveness of different HIPEC drug regimens in patients with advanced gastric cancer to determine the optimal therapeutic approach. Methods This study conducted a systematic review and Bayesian network meta-analysis. Patients in the experimental group underwent surgery combined with HIPEC and chemotherapy. The search period covered literature from database inception to June 1, 2024. Hazard ratios (HRs) with 95% confidence intervals (CIs) were used to evaluate overall survival (OS) as the primary outcome. Odds ratios (ORs) with 95% CIs were used to assess overall disease recurrence, peritoneal recurrence, and postoperative morbidity as secondary outcomes. To ensure scientific rigor and transparency, this study has been registered with PROSPERO (CRD42024533948). Results A total of 11 randomized controlled trials (RCTs) involving 1092 patients were included. Compared to surgery combined with chemotherapy, the regimens of cisplatin (HRs = 0.52, 95% CI: 0.38-0.73), mitomycin C (HRs = 0.99, 95% CI: 0.55-1.79), cisplatin plus fluorouracil (HRs = 0.60, 95% CI: 0.38-0.95), and oxaliplatin plus 5-fluorouracil (HRs = 0.53, 95% CI: 0.36-0.78) all demonstrated benefits in OS. The cisplatin (ORs = 0.16, 95% CI: 0.03-0.60) and mitomycin C (ORs = 0.03, 95% CI: 0-0.71) regimens also showed advantages in reducing peritoneal recurrence, with no impact on postoperative morbidity. Importantly, the cisplatin regimen was superior to other regimens in terms of OS and overall disease recurrence, achieving a balance between efficacy and safety. Conclusions Compared to chemotherapy alone, HIPEC treatment shows significant benefits in OS without a notable disadvantage in postoperative morbidity. Although no single HIPEC regimen demonstrated clear benefits across all outcomes, the cisplatin regimen performed well in multiple aspects, indicating its potential for further research and clinical application. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=533948, identifier CRD42024533948.
Collapse
Affiliation(s)
| | | | | | | | - Quan Wang
- Department of Gastric and Colorectal Surgery, General Surgery Center, The First Hospital of Jilin University, Changchun, China
| |
Collapse
|
|
5
|
Yue TM, Sun BJ, Xu N, Ohkuma R, Fowler C, Lee B. Improved Postoperative Pain Management Outcomes After Implementation of Enhanced Recovery After Surgery (ERAS) Protocol for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC). Ann Surg Oncol 2024; 31:3769-3777. [PMID: 38466484 DOI: 10.1245/s10434-024-15120-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Accepted: 02/14/2024] [Indexed: 03/13/2024]
Abstract
BACKGROUND Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for patients with peritoneal carcinomatosis is promising but has potential for significant morbidity and prolonged hospitalization. Enhanced Recovery After Surgery (ERAS) is a standardized protocol designed to optimize perioperative care. This study describes trends in epidural and opioid use after implementing ERAS for CRS-HIPEC at a tertiary academic center. METHODS A retrospective analysis of patients undergoing CRS-HIPEC from January 2020 to September 2023 was conducted. ERAS was implemented in February 2022. Medication and outcomes data were compared before and after ERAS initiation. All opioids were converted to morphine milligram equivalents (MMEs). RESULTS A total of 136 patients underwent CRS-HIPEC: 73 (54%) pre- and 63 (46%) post-ERAS. Epidural usage increased from 63% pre-ERAS to 87% post-ERAS (p = 0.001). Compared with those without epidurals, patients with epidurals had decreased total 7-day oral and intravenous (IV) opioid requirements (45 MME vs. 316 MME; p < 0.001). There was no difference in 7-day opioid totals between pre- and post-ERAS groups. After ERAS, more patients achieved early ambulation (83% vs. 53%; p < 0.001), early diet initiation (81% vs. 25%; p < 0.001), and early return of bowel function (86% vs. 67%; p = 0.012). CONCLUSIONS ERAS implementation for CRS-HIPEC was associated with increased epidural use, decreased oral and IV opioid use, and earlier bowel function return. Our study demonstrates that epidural analgesia provides adequate pain control while significantly decreasing oral and IV opioid use, which may promote gastrointestinal recovery postoperatively. These findings support the implementation of an ERAS protocol for effective pain management in patients undergoing CRS-HIPEC.
Collapse
Affiliation(s)
- Tiffany M Yue
- Stanford University School of Medicine, Stanford, USA
| | - Beatrice J Sun
- Section of Surgical Oncology, Department of Surgery, Stanford University School of Medicine, Stanford, USA
| | - Nova Xu
- Stanford University School of Medicine, Stanford, USA
| | - Rika Ohkuma
- Section of Surgical Oncology, Department of Surgery, Stanford University School of Medicine, Stanford, USA
| | - Cedar Fowler
- Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, USA
| | - Byrne Lee
- Section of Surgical Oncology, Department of Surgery, Stanford University School of Medicine, Stanford, USA.
| |
Collapse
|
|
6
|
Reese M, Eichelmann AK, Nowacki TM, Pascher A, Sporn JC. The role of cytoreductive surgery and HIPEC for the treatment of primary and secondary peritoneal malignancies-experience from a tertiary care center in Germany. Langenbecks Arch Surg 2024; 409:113. [PMID: 38589714 DOI: 10.1007/s00423-024-03309-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Accepted: 04/03/2024] [Indexed: 04/10/2024]
Abstract
PURPOSE Peritoneal surface malignancies (PSM) are commonly known to have a dismal prognosis. Over the past decades, novel techniques such as cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC) have been introduced for the treatment of PSM which could improve the overall survival and quality of life of patients with PSM. The decision to proceed with CRS and HIPEC is often challenging due the complexity of the disease, the extent of the procedure, associated side effects, and potential risks. Here, we present our experience with CRS and HIPEC to add to the ongoing discussion about eligibility criteria, technical approach, and expected outcomes and contribute to the evolution of this powerful and promising tool in the multidisciplinary treatment of patients with primary and secondary PSM. METHODS A single-center retrospective chart review was conducted and included a total of 40 patients treated with CRS and HIPEC from April 2020 to September 2022 at the University Hospital Münster Department of Surgery. All patients had histologically confirmed primary or secondary peritoneal malignancies of various primary origins. RESULTS Our study included 22 patients with peritoneal metastases from gastric cancer (55%), 8 with pseudomyxoma peritonei (20%), 4 with mesothelioma of the peritoneum (10%), and 6 patients with PSM originating from other primary tumor locations. Median PCI at time of cytoreduction was 4 (0-25). Completeness of cytoreduction score was 0 in 37 patients (92.5%), 1 in two patients (5%), and 2 in one patient (2.5%). Median overall survival across all patients was 3.69 years. CONCLUSION Complete cytoreduction during CRS and HIPEC can be achieved for patients with low PCI, for patients with high PCI in low-grade malignancies, and even for patients with initially high PCI in high-grade malignancies following a significant reduction of cancer burden due to extensive preoperative treatment with PIPAC and systemic chemotherapy.
Collapse
Affiliation(s)
- Mikko Reese
- Department of General, Visceral and Transplant Surgery, University Hospital Münster, Waldeyerstraße 1, 48149, Münster, Germany
| | - Ann-Kathrin Eichelmann
- Department of General, Visceral and Transplant Surgery, University Hospital Münster, Waldeyerstraße 1, 48149, Münster, Germany
| | - Tobias M Nowacki
- Department of Medicine B for Gastroenterology, Hepatology, Endocrinology and Clinical Infectiology, University Hospital Münster, Albert-Schweitzer-Campus 1, Münster, 48149, Germany
- Department of Gastroenterology, UKM Marienhospital Steinfurt, Mauritiusstr. 5, Steinfurt, 48565, Germany
| | - Andreas Pascher
- Department of General, Visceral and Transplant Surgery, University Hospital Münster, Waldeyerstraße 1, 48149, Münster, Germany
| | - Judith C Sporn
- Department of General, Visceral and Transplant Surgery, University Hospital Münster, Waldeyerstraße 1, 48149, Münster, Germany.
| |
Collapse
|
|
7
|
Rijken A, Pape M, Simkens GA, de Hingh IHJT, Luyer MDP, van Sandick JW, van Laarhoven HWM, Verhoeven RHA, van Erning FN. Peritoneal metastases from gastric cancer in a nationwide cohort: Incidence, treatment and survival. Int J Cancer 2024; 154:992-1002. [PMID: 37916797 DOI: 10.1002/ijc.34780] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Revised: 09/28/2023] [Accepted: 10/06/2023] [Indexed: 11/03/2023]
Abstract
The aims of this study were to investigate incidence, risk factors and treatment of synchronous or metachronous peritoneal metastases (PM) from gastric cancer and to estimate survival of these patients using population-based data. Patients diagnosed with gastric cancer in 2015 to 2016 were selected from the Netherlands Cancer Registry. The incidence of synchronous and metachronous PM were calculated. Multivariable regression analyses were performed to identify factors associated with the occurrence of PM. Treatment and survival were compared between patients with synchronous and metachronous PM. Of 2206 patients with gastric cancer, 741 (34%) were diagnosed with PM. Of these, 498 (23%) had synchronous PM. The cumulative incidence of metachronous PM in patients who underwent potentially curative treatment (n = 675) was 22.8% at 3 years. A factor associated with synchronous and metachronous PM was diffuse type histology. Patients diagnosed with synchronous PM more often received systemic treatment than patients with metachronous PM (35% vs 18%, respectively, P < .001). Median overall survival was comparable between synchronous and metachronous PM (3.2 vs 2.3 months, respectively, P = .731). Approximately one third of all patients with gastric cancer are diagnosed with PM, either at primary diagnosis or during 3-year follow-up after potentially curative treatment. Patients with metachronous PM less often received systemic treatment than those with synchronous PM but survival was comparable between both groups. Future trials are warranted to detect gastric cancer at an earlier stage and to examine strategies that lower the risk of peritoneal dissemination. Also, specific treatment options for patients with gastric PM should be further investigated.
Collapse
Affiliation(s)
- Anouk Rijken
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
- Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands
| | - Marieke Pape
- Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands
- Amsterdam UMC location University of Amsterdam, Medical Oncology, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands
| | - Geert A Simkens
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
- Department of Surgery and Cancer, Imperial College London, London, UK
| | - Ignace H J T de Hingh
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
- Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands
- GROW-School for Oncology and Development Biology, Maastricht University, Maastricht, the Netherlands
| | - Misha D P Luyer
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - Johanna W van Sandick
- Department of Surgery, Antoni van Leeuwenhoek - Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Hanneke W M van Laarhoven
- Amsterdam UMC location University of Amsterdam, Medical Oncology, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands
| | - Rob H A Verhoeven
- Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands
- Amsterdam UMC location University of Amsterdam, Medical Oncology, Amsterdam, the Netherlands
- Cancer Center Amsterdam, Cancer Treatment and Quality of Life, Amsterdam, the Netherlands
| | - Felice N van Erning
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
- Department of Research and Development, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, the Netherlands
| |
Collapse
|
|
8
|
Pugaev DM, Lyubchenko LN, Ryabov AB, Kaprin AD. Early-onset gasrtric cancer (review). SIBERIAN JOURNAL OF ONCOLOGY 2024; 22:153-171. [DOI: 10.21294/1814-4861-2023-22-6-153-171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
Abstract
Objective. Early-onset gastric cancer (EOGC) constitutes a serious medical and social problem. Early-onset gastric cancer accounts for approximately 6% of all malignant epithelial neoplasms.Material and Methods. We reviewed retrospective and prospective randomized trials using Medline and Elibrary databases.Results. The applied significance of the molecular genetic classifications consist in the formation of groups for evaluating prognosis of the disease using multifactorial analysis. This classification indicates that EOGC diagnosed at a locally advanced stage and primary dissemination is most often caused by GS (TCGA) and MSS/EMT(ACRG) subtypes and is characterized by mutations in CDH1, RhoA, CLDN18-ARHGAP genes. These changes are accompanied by the prevalence of diffuse histological type of gastric cancer according to the Lauren classification and ulcerated or infiltrative type according to the Borrmann classification (type III and IV) with the presence of high-grade adenocarcinoma with a signet ring cell component.Conclusion. Considering the aggressiveness of gastric cancer in young patients, who more frequently present with locally advanced and metastatic disease at the time of diagnosis, there is a need for increased cancer alertness among physicians of other specialties, early endoscopic controls to detect cancer at early stages and benefit from both surgical and multimodal treatment.
Collapse
Affiliation(s)
- D. M. Pugaev
- Kommunarka Moscow Multidisciplinary Clinical Center, Moscow City Health Department
| | - L. N. Lyubchenko
- N.A. Lopatkin Research Institute of Urology and Interventional Radiology – branch National Medical Research Radiological Centre of the Ministry of Health of the Russia;
National Medical Research Radiological Centre of the Ministry of Health of the Russia
| | - A. B. Ryabov
- P.A. Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russia;
National Medical Research Radiological Centre of the Ministry of Health of the Russia
| | - A. D. Kaprin
- RUDN University;
P.A. Hertsen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russia;
National Medical Research Radiological Centre of the Ministry of Health of the Russia
| |
Collapse
|
|
9
|
Fernández-Candela A, Bretcha-Boix P, Ruíz Ramírez JC, Paz A, Munoz P, Ortega MA, Álvarez-Mon M, Farré-Alegre J. Follow-up for More than 10 Years of Patients with Peritoneal Metastases Treated with Cytoreductive Surgery + Hyperthermic Intraperitoneal Chemotherapy in a Specialized Unit. J Clin Med 2024; 13:297. [PMID: 38202304 PMCID: PMC10779703 DOI: 10.3390/jcm13010297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 11/23/2023] [Accepted: 12/29/2023] [Indexed: 01/12/2024] Open
Abstract
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have demonstrated their impact on disease-free survival (DFS) and overall survival (OS) of patients with peritoneal metastases (PM). However, prior literature lacks evidence regarding any follow-up beyond 5 years. In this study, we analyse long-term OS and DFS (more than 10 years of follow-up) of patients undergoing CRS + HIPEC in a specialized unit. We conducted a retrospective study that included only patients who underwent CRS + HIPEC from January 2001 to May 2012. Data collection was conducted by reviewing medical records and telephone calls to patients or relatives. A total of 86 patients were included. The mean PCI was nine (range 0-39) and complete cytoreduction (CC-0) was reached in 80% of patients. Postoperative complications Clavien-Dindo III-IV occurred in 27.9% of patients and the 30-day mortality rate was 2.3%. After 10 years of actual follow-up, OS was 33.7% and DFS was 31.4%. Considering the historical context in which the standard of care for patients with PM was palliation, the results obtained show that CRS + HIPEC was a valid option, with morbimortality comparable to other major abdominal surgeries and encouraging survival results, since, after 10 years of follow-up, almost one-third of patients are still alive and disease-free.
Collapse
Affiliation(s)
- Alba Fernández-Candela
- Peritoneal Carcinomatosis Unit, General Surgery Department, Hospital Quironsalud Torrevieja, 03184 Torrevieja, Spain; (A.F.-C.); (A.P.); (P.M.); (J.F.-A.)
| | - Pedro Bretcha-Boix
- Peritoneal Carcinomatosis Unit, General Surgery Department, Hospital Quironsalud Torrevieja, 03184 Torrevieja, Spain; (A.F.-C.); (A.P.); (P.M.); (J.F.-A.)
| | | | - Alejandro Paz
- Peritoneal Carcinomatosis Unit, General Surgery Department, Hospital Quironsalud Torrevieja, 03184 Torrevieja, Spain; (A.F.-C.); (A.P.); (P.M.); (J.F.-A.)
| | - Paula Munoz
- Peritoneal Carcinomatosis Unit, General Surgery Department, Hospital Quironsalud Torrevieja, 03184 Torrevieja, Spain; (A.F.-C.); (A.P.); (P.M.); (J.F.-A.)
| | - Miguel A. Ortega
- Department of Medicine and Medical Specialties, Faculty of Medicine and Health Sciences, University of Alcalá, 28801 Alcalá de Henares, Spain;
- Ramón y Cajal Institute of Sanitary Research, 28034 Madrid, Spain;
| | | | - José Farré-Alegre
- Peritoneal Carcinomatosis Unit, General Surgery Department, Hospital Quironsalud Torrevieja, 03184 Torrevieja, Spain; (A.F.-C.); (A.P.); (P.M.); (J.F.-A.)
| |
Collapse
|
|
10
|
Balachandran R, Sørensen MM, Funder JA, Knudsen AR, Iversen LH. Outcomes after curatively intended treatment of limited peritoneal metastases and thermal ablation for liver metastases from colorectal cancer. Pleura Peritoneum 2023; 8:167-174. [PMID: 38144219 PMCID: PMC10739284 DOI: 10.1515/pp-2023-0015] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 06/08/2023] [Indexed: 12/26/2023] Open
Abstract
Objectives Peritoneal metastases (PM) and liver metastases (LM) are present simultaneously in up to 2 % of patients at the time of their colorectal cancer (CRC) diagnosis. Curatively intended treatment includes cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) combined with LM resection. A less invasive treatment for LM is ablation. We aimed to estimate overall survival (OS), disease-free survival (DFS) and postoperative data in patients managed simultaneously with CRS, HIPEC and radiofrequency ablation (RFA) as first choice. Methods This was a retrospective national cohort study. All patients were treated at Aarhus University Hospital; the only CRS+HIPEC centre in Denmark. We included CRC patients managed with curative intent for simultaneously diagnosed PM and LM in the period January 2016 - December 2021. LM was treated with RFA as first choice, if possible. Survival was calculated by the Kaplan-Meier method. Results A total of 25 patients were included, the median age was 60 years (range 43-75 years) and 15 (60 %) were females. The median peritoneal cancer index was 7 (range 0-12), the median number of LM was 1 (range 1-3). Ablation was performed as the only treatment for LM in 18 (72 %) patients. After a median follow-up time of 17.1 months (range 4-36 months), the median OS was 28.6 months (95 % confidence interval (Cl) 15.8;36.1), 1-year OS was 84.0 % (95 % Cl 62.8;93.7). Median DFS was 6.1 months (95 % Cl 4.0;10.3). Median LOS was ten days (range 5-26 days). Both 30-day and 90-day mortality were 0 %. Conclusions The selected treatment modality (RFA) for CRC patients with both LM and PM was safe. However, DFS was low. Further research is warranted to investigate if RFA is as effective as LM resection.
Collapse
Affiliation(s)
- Rogini Balachandran
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | | | | | | | - Lene Hjerrild Iversen
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| |
Collapse
|
|
11
|
Chidambaram S, Guiral DC, Markar SR. Novel Multi-Modal Therapies and Their Prognostic Potential in Gastric Cancer. Cancers (Basel) 2023; 15:3113. [PMID: 37370723 DOI: 10.3390/cancers15123113] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Revised: 05/22/2023] [Accepted: 06/06/2023] [Indexed: 06/29/2023] Open
Abstract
BACKGROUND Gastric cancer has a poor prognosis and involves metastasis to the peritoneum in over 40% of patients. The optimal treatment modalities have not been established for gastric cancer patients with peritoneal carcinomatosis (GC/PC). Although studies have reported favourable prognostic factors, these have yet to be incorporated into treatment guidelines. Hence, our review aims to appraise the latest diagnostic and treatment developments in managing GC/PC. METHODS A systematic review of the literature was performed using MEDLINE, EMBASE, the Cochrane Review, and Scopus databases. Articles were evaluated for the use of hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurised intraperitoneal aerosolised chemotherapy (PIPAC) in GC/PC. A meta-analysis of studies reporting on overall survival (OS) in HIPEC and comparing the extent of cytoreduction as a prognostic factor was also carried out. RESULTS The database search yielded a total of 2297 studies. Seventeen studies were included in the qualitative and quantitative analyses. Eight studies reported the short-term OS at 1 year as the primary outcome measure, and our analysis showed a significantly higher OS for the HIPEC/CRS cohort compared to the CRS cohort (pooled OR = 0.53; p = 0.0005). This effect persisted longer term at five years as well (pooled OR = 0.52; p < 0.0001). HIPEC and CRS also showed a longer median OS compared to CRS (pooled SMD = 0.61; p < 0.00001). Three studies reporting on PIPAC demonstrated a pooled OS of 10.3 (2.2) months. Prognostic factors for longer OS include a more complete cytoreduction (pooled OR = 5.35; p < 0.00001), which correlated with a peritoneal carcinomatosis index below 7. CONCLUSIONS Novel treatment strategies, such as HIPEC and PIPAC, are promising in the management of GC/PC. Further work is necessary to define their role within the treatment algorithm and identify relevant prognostic factors that will assist patient selection.
Collapse
Affiliation(s)
| | - Delia Cortés Guiral
- Surgical Oncology and General Surgery Department, King Khaled Hospital, Najran 66262, Saudi Arabia
| | - Sheraz Rehan Markar
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 17176 Stockholm, Sweden
- Nuffield Department of Surgery, University of Oxford, Oxford OX3 9DU, UK
| |
Collapse
|
|
12
|
Surgical Options for Peritoneal Surface Metastases from Digestive Malignancies-A Comprehensive Review. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59020255. [PMID: 36837456 PMCID: PMC9960111 DOI: 10.3390/medicina59020255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 01/25/2023] [Accepted: 01/25/2023] [Indexed: 01/31/2023]
Abstract
The peritoneum is a common site for the dissemination of digestive malignancies, particularly gastric, colorectal, appendix, or pancreatic cancer. Other tumors such as cholangiocarcinomas, digestive neuroendocrine tumors, or gastrointestinal stromal tumors (GIST) may also associate with peritoneal surface metastases (PSM). Peritoneal dissemination is proven to worsen the prognosis of these patients. Cytoreductive surgery (CRS), along with systemic chemotherapy, have been shown to constitute a survival benefit in selected patients with PSM. Furthermore, the association of CRS with hyperthermic intraperitoneal chemotherapy (HIPEC) seems to significantly improve the prognosis of patients with certain types of digestive malignancies associated with PSM. However, the benefit of CRS with HIPEC is still controversial, especially due to the significant morbidity associated with this procedure. According to the results of the PRODIGE 7 trial, CRS for PSM from colorectal cancer (CRC) achieved overall survival (OS) rates higher than 40 months, but the addition of oxaliplatin-based HIPEC failed to improve the long-term outcomes. Furthermore, the PROPHYLOCHIP and COLOPEC trials failed to demonstrate the effectiveness of oxaliplatin-based HIPEC for preventing peritoneal metastases development in high-risk patients operated for CRC. In this review, we discuss the limitations of these studies and the reasons why these results are not sufficient to refute this technique, until future well-designed trials evaluate the impact of different HIPEC regimens. In contrast, in pseudomyxoma peritonei, CRS plus HIPEC represents the gold standard therapy, which is able to achieve 10-year OS rates ranging between 70 and 80%. For patients with PSM from gastric carcinoma, CRS plus HIPEC achieved median OS rates higher than 40 months after complete cytoreduction in patients with a peritoneal cancer index (PCI) ≤6. However, the data have not yet been validated in randomized clinical trials. In this review, we discuss the controversies regarding the most efficient drugs that should be used for HIPEC and the duration of the procedure. We also discuss the current evidence and controversies related to the benefit of CRS (and HIPEC) in patients with PSM from other digestive malignancies. Although it is a palliative treatment, pressurized intraperitoneal aerosolized chemotherapy (PIPAC) significantly increases OS in patients with unresectable PSM from gastric cancer and represents a promising approach for patients with PSM from other digestive cancers.
Collapse
|
|
13
|
Kang D, Kim IH. Molecular Mechanisms and Potential Rationale of Immunotherapy in Peritoneal Metastasis of Advanced Gastric Cancer. Biomedicines 2022; 10:biomedicines10061376. [PMID: 35740397 PMCID: PMC9220323 DOI: 10.3390/biomedicines10061376] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2022] [Revised: 06/03/2022] [Accepted: 06/08/2022] [Indexed: 11/16/2022] Open
Abstract
Peritoneal metastasis (PM) is one of the most frequent metastasis patterns of gastric cancer (GC), and the prognosis of patients with PM is very dismal. According to Paget’s theory, disseminated free cancer cells are seeded and survive in the abdominal cavity, adhere to the peritoneum, invade the subperitoneal tissue, and proliferate through angiogenesis. In these sequential processes, several key molecules are involved. From a therapeutic point of view, immunotherapy with chemotherapy combination has become the standard of care for advanced GC. Several clinical trials of newer immunotherapy agents are ongoing. Understanding of the molecular process of PM and the potential rationale of immunotherapy for PM treatment is necessary. Beyond understanding of the molecular aspect of PM, many studies have been conducted on the modality of treatment of PM. Notably, intraperitoneal approaches, including chemotherapy or immunotherapy, have been conducted, because systemic treatment of PM has limitations. In this study, we reviewed the molecular mechanisms and immunologic aspects of PM, and intraperitoneal approaches under investigation for treating PM.
Collapse
Affiliation(s)
- Donghoon Kang
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea;
| | - In-Ho Kim
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, Korea
- Correspondence:
| |
Collapse
|
|
14
|
Prabhu A, Mishra D, Brandl A, Yonemura Y. Gastric Cancer With Peritoneal Metastasis-A Comprehensive Review of Current Intraperitoneal Treatment Modalities. Front Oncol 2022; 12:864647. [PMID: 35719946 PMCID: PMC9204320 DOI: 10.3389/fonc.2022.864647] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 04/22/2022] [Indexed: 12/24/2022] Open
Abstract
The treatment of patients with peritoneal metastasis from gastric cancer continues to evolve. With various forms of intraperitoneal drug delivery available, it is now possible to reach the sites of peritoneal metastases, which were otherwise sub-optimally covered by systemic chemotherapy, owing to the blood peritoneal barrier. We conducted a narrative review based on an extensive literature research, highlighting the current available intraperitoneal treatment options, which resulted in improved survival in well-selected patients of peritoneally metastasized gastric cancer. Intraperitoneal chemotherapy showed promising results in four different treatment modalities: prophylactic, neoadjuvant, adjuvant, and palliative. It is now possible to choose the type of intraperitoneal treatment/s in combination with systemic treatment/s, depending on patients' general condition and peritoneal disease burden, thus providing individualized treatment to these patients. Randomized controlled trials for the different treatment modalities were mainly conducted in Asia and lack further validation in the other parts of the world. Most recent application tools, such as pressurized intraperitoneal aerosol chemotherapy, seem promising and need to pass the ongoing clinical trials.
Collapse
Affiliation(s)
- Aruna Prabhu
- Department of Surgical Oncology, Thangam Cancer Center, Namakkal, India
| | - Deepti Mishra
- Department of Surgical Oncology, Thangam Cancer Center, Namakkal, India
| | - Andreas Brandl
- Digestive Unit, Champalimaud Foundation, Lisbon, Portugal
- Department of Surgery, Campus Virchow-Klinikum, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Yutaka Yonemura
- Department of Regional Cancer therapy, Peritoneal Surface Malignancy Centee, Kishiwada Tokushukai Hospital, Kishiwada, Japan
- Japanese/Asian School of Peritoneal Surface Oncology, Osaka, Japan
- Department of Regional Cancer therapy, Peritoneal Surface Malignancy Center, Kusatsu General Hospital, Shiga, Japan
| |
Collapse
|
|
15
|
Khan H, Johnston FM. Current role for cytoreduction and HIPEC for gastric cancer with peritoneal disease. J Surg Oncol 2022; 125:1176-1182. [PMID: 35481913 PMCID: PMC9322542 DOI: 10.1002/jso.26894] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Revised: 03/25/2022] [Accepted: 03/25/2022] [Indexed: 12/12/2022]
Abstract
Gastric cancer (GC) is an aggressive malignancy with a high burden of peritoneal disease. Evidence regarding the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) to improve outcomes has been growing. However, given multiple limitations, there remains a lack of international consensus regarding the optimal treatment paradigm. This review article discusses the burden of peritoneal disease in GC patients and the role of CRS + HIPEC in all treatment intents—curative, prophylactic, and palliative.
Collapse
Affiliation(s)
- Hamza Khan
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland, USA
| | - Fabian M Johnston
- Department of Surgery, Johns Hopkins University, Baltimore, Maryland, USA
| |
Collapse
|
|
16
|
Gronau F, Feldbruegge L, Oberwittler F, Gonzalez-Moreno S, Villeneuve L, Eveno C, Glehen O, Kusamura S, Rau B. HIPEC in Peritoneal Metastasis of Gastric Origin: A Systematic Review of Regimens and Techniques. J Clin Med 2022; 11:jcm11051456. [PMID: 35268546 PMCID: PMC8911234 DOI: 10.3390/jcm11051456] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 03/04/2022] [Accepted: 03/04/2022] [Indexed: 02/06/2023] Open
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 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.
Collapse
Affiliation(s)
- Felix Gronau
- Department of Surgery, Chirurgische Klinik Campus Charité Mitte|Campus Virchow Klinikum, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany; (F.G.); (L.F.); (F.O.)
| | - Linda Feldbruegge
- Department of Surgery, Chirurgische Klinik Campus Charité Mitte|Campus Virchow Klinikum, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany; (F.G.); (L.F.); (F.O.)
| | - Frauke Oberwittler
- Department of Surgery, Chirurgische Klinik Campus Charité Mitte|Campus Virchow Klinikum, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany; (F.G.); (L.F.); (F.O.)
| | | | - Laurent Villeneuve
- Réseau National de Prise en Charge des Tumeurs Rares du Péritoine, French National Registry of Rare Peritoneal Surface Malignancies, 69002 Lyon, France;
| | - Clarisse Eveno
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, 69495 Pierre-Bénite, France; (C.E.); (O.G.)
| | - Olivier Glehen
- Department of Surgical Oncology, CHU Lyon Sud, Hospices Civils de Lyon, 69495 Pierre-Bénite, France; (C.E.); (O.G.)
| | - Shigeki Kusamura
- Peritoneal Surface Malignancies Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Nazionale Tumori dei Tumori di Milano, 20133 Milano, Italy;
| | - Beate Rau
- Department of Surgery, Chirurgische Klinik Campus Charité Mitte|Campus Virchow Klinikum, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 13353 Berlin, Germany; (F.G.); (L.F.); (F.O.)
- Correspondence: ; Tel.: +49-30-450-622-214
| |
Collapse
|
|
17
|
Mazurek M, Szlendak M, Forma A, Baj J, Maciejewski R, Roviello G, Marano L, Roviello F, Polom K, Sitarz R. Hyperthermic Intraperitoneal Chemotherapy in the Management of Gastric Cancer: A Narrative Review. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:681. [PMID: 35055500 PMCID: PMC8776178 DOI: 10.3390/ijerph19020681] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 01/02/2022] [Accepted: 01/04/2022] [Indexed: 02/05/2023]
Abstract
Gastric cancer (GC) patients with peritoneal metastasis tend to achieve poor clinical outcomes. Until recently, the treatment options were limited mainly to either palliative chemotherapy or radiation therapy in exceptional cases. Currently, these patients benefit from multimodal treatment, such as cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Despite good overall results, this treatment modality is still widely debated. The following study is designed to assess the papers about the possible application and utility of HIPEC in GC. A search in the PubMed, Web of Science, and Scopus databases was performed to assess the papers devoted to the role of HIPEC in GC treatment; a literature search was performed until March 21st; and, finally, 50 studies with a total number of 3946 patients were analyzed. According to the most recent data, it seems to be reasonable to limit the duration of HIPEC to the shortest effective time. Moreover, the drugs used in HIPEC need to have equal concentrations and the same solvent. Perioperative chemotherapy needs to be reported in detail and, furthermore, the term "morbidity" should be defined more clearly by the authors.
Collapse
Affiliation(s)
- Marek Mazurek
- Department of Surgical Oncology, Voivodship Hospital in Siedlce, 08-110 Siedlce, Poland;
| | - Małgorzata Szlendak
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (M.S.); (J.B.); (R.M.)
- Department of Oncology, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Alicja Forma
- Department of Forensic Medicine, Medical University of Lublin, 20-090 Lublin, Poland;
| | - Jacek Baj
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (M.S.); (J.B.); (R.M.)
| | - Ryszard Maciejewski
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (M.S.); (J.B.); (R.M.)
| | | | - Luigi Marano
- Department of General Surgery and Surgical Oncology, University of Siena, 53100 Siena, Italy; (L.M.); (F.R.)
| | - Franco Roviello
- Department of General Surgery and Surgical Oncology, University of Siena, 53100 Siena, Italy; (L.M.); (F.R.)
| | - Karol Polom
- Department of Surgical Oncology, Medical University of Gdansk, 80-070 Gdansk, Poland;
| | - Robert Sitarz
- Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland; (M.S.); (J.B.); (R.M.)
- Department of Surgical Oncology, St. John’s Cancer Center, 20-090 Lublin, Poland
| |
Collapse
|
|
18
|
Marano L, Marrelli D, Sammartino P, Biacchi D, Graziosi L, Marino E, Coccolini F, Fugazzola P, Valle M, Federici O, Baratti D, Deraco M, Di Giorgio A, Macrì A, Pasqual EM, Framarini M, Vaira M, Roviello F. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer with Synchronous Peritoneal Metastases: Multicenter Study of 'Italian Peritoneal Surface Malignancies Oncoteam-S.I.C.O.'. Ann Surg Oncol 2021; 28:9060-9070. [PMID: 34057569 PMCID: PMC8590997 DOI: 10.1245/s10434-021-10157-0] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 04/29/2021] [Indexed: 12/20/2022]
Abstract
Background The development of multimodality treatment, including cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC), has led to promising results in selected patients with peritoneal disease of gastric origin. The aim of this study was to investigate the short- and long-term outcomes of CRS/HIPEC in the treatment of synchronous peritoneal metastasis in gastric cancer. Methods The Italian Peritoneal Surface Malignancies Oncoteam—S.I.C.O. retrospective registry included patients with synchronous peritoneal malignancy from gastric cancer submitted to gastrectomy with CRS and HIPEC between 2005 and 2018 from 11 high-volume, specialized centers. Results A total of 91 patients with a median age of 58 years (range 26–75) were enrolled. The median overall survival (OS) time for the whole group of patients was 20.2 months (95% confidence interval [CI] 11.8–28.5] and the median recurrence-free survival (RFS) was 7.3 months (95% CI 4–10.6). The completeness of cytoreduction score (CCS) of 0 and Peritoneal Cancer Index (PCI) score of ≤ 6 groups showed a significantly better long-term survival (median OS 40.7 and 44.3 months, respectively) compared with the incomplete resected groups (median OS 10.7 months, p = 0.003) and PCI score of > 6 group (median OS 13.4 months, p = 0.005). A significant difference was observed in the survival rate according to neoadjuvant treatment (untreated patients: 10.7 months, 95% CI 5.1–16.2; treated patients: 35.3 months, 95% CI 2.8–67.8; p = 0.022). Conclusions In referral centers, CRS and HIPEC after neoadjuvant treatment significantly improved survival in selected patients. Patients with a PCI score ≤ 6, complete cytoreduction, negative nodal involvements, and negative cytology had encouraging results, showing a clinically meaningful survival.
Collapse
Affiliation(s)
- Luigi Marano
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Siena, Italy.
| | - Daniele Marrelli
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Siena, Italy
| | - Paolo Sammartino
- Cytoreductive Surgery and HIPEC Unit, Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Rome, Italy
| | - Daniele Biacchi
- Cytoreductive Surgery and HIPEC Unit, Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Rome, Italy
| | - Luigina Graziosi
- General and Emergency Surgery, University of Perugia, Perugia, Italy
| | - Elisabetta Marino
- General and Emergency Surgery, University of Perugia, Perugia, Italy
| | - Federico Coccolini
- General, Emergency and Trauma Surgery Department, Bufalini Hospital, Cesena, Italy.,General, Emergency and Trauma Surgery Department, Pisa University Hospital, Pisa, Italy
| | - Paola Fugazzola
- General, Emergency and Trauma Surgery Department, Bufalini Hospital, Cesena, Italy
| | - Mario Valle
- Department of Digestive Surgery, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Orietta Federici
- Department of Digestive Surgery, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Dario Baratti
- Fondazione IRCCS Istituto Nazionale Dei Tumori di Milano, Peritoneal Surface Malignancies Unit, Milan, Italy
| | - Marcello Deraco
- Fondazione IRCCS Istituto Nazionale Dei Tumori di Milano, Peritoneal Surface Malignancies Unit, Milan, Italy
| | - Andrea Di Giorgio
- Surgical Unit of Peritoneum and Retroperitoneum, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Antonio Macrì
- Peritoneal Surface Malignancy and Soft Tissue Sarcoma Program, Messina University Medical School Hospital, Messina, Italy
| | - Enrico Maria Pasqual
- Department of Medical Area, University of Udine, Santa Maria della Misericordia University Hospital Udine, Udine, Italy
| | | | - Marco Vaira
- Candiolo Cancer Institute, Unit of Surgical Oncology, FPO-IRCCS, Candiolo, Italy
| | - Franco Roviello
- Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Siena, Italy
| | | |
Collapse
|
|
19
|
Granieri S, Bonomi A, Frassini S, Chierici AP, Bruno F, Paleino S, Kusamura S, Germini A, Facciorusso A, Deraco M, Cotsoglou C. Prognostic impact of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer patients: A meta-analysis of randomized controlled trials. Eur J Surg Oncol 2021; 47:2757-2767. [PMID: 34001385 DOI: 10.1016/j.ejso.2021.05.016] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/25/2021] [Accepted: 05/07/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND gastric cancer patients frequently develop peritoneal metastases (PM) with a poor long-term prognosis. A solid body of evidence underlines the beneficial role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on survival, but to date, there is a lack of consensus regarding the optimal strategy in the treatment of locally advanced primary tumors with or without peritoneal metastasis. The present meta-analysis aims to assess the impact of CRS + HIPEC on survival analyzing the results of randomized studies only. METHODS A systematic review of articles was conducted according to PRISMA guidelines. Twelve studies were included in qualitative and quantitative analysis. RESULTS A survival benefit for patients treated with CRS + HIPEC at all time points was highlighted. However, difference in survival was significant at all time points for patients treated for prophylaxis of PM, but no difference was found when considering resection with a curative intent. The 1, 2, 3 and 5-year survival rates (SR) for patients undergoing CRS + HIPEC were 86.9%, 70.5%, 63.7% and 55.7% respectively. CRS + HIPEC for the treatment rather than prophylaxis of PM was the only predictor of a reduced 3y SR. CONCLUSIONS CRS + HIPEC may lead to improved prognosis for patients suffering from locally advanced gastric cancer in both prophylactic and curative settings. However, due to far from negligible postoperative morbidity and mortality rates, a strict patient selection is crucial to achieve the best results. The presence of extraperitoneal disease strongly limits the indication of this kind of surgery.
Collapse
Affiliation(s)
- Stefano Granieri
- General Surgery Unit, ASST Vimercate, Via Santi Cosma e Damiano, 10, 20871, Vimercate, Italy.
| | - Alessandro Bonomi
- University of Milan, Via Festa del Perdono, 7, 20122, Milan, Italy; General Surgery Unit, ASST Fatebenefratelli-Sacco, Via Giovanni Battista Grassi, 74, 20157, Milan, Italy.
| | - Simone Frassini
- University of Pavia, Corso Str. Nuova, 65, 27100, Pavia, Italy; General Surgery Unit, Department of Surgery, Fondazione I.R.C.C.S. Policlinico San Matteo, Viale Camillo Golgi, 19, 27100, Pavia, Italy.
| | - Andrea Piero Chierici
- University of Milan, Via Festa del Perdono, 7, 20122, Milan, Italy; General Surgery Unit, ASST Vimercate, Via Santi Cosma e Damiano, 10, 20871, Vimercate, Italy.
| | - Federica Bruno
- General Surgery Unit, ASST Vimercate, Via Santi Cosma e Damiano, 10, 20871, Vimercate, Italy.
| | - Sissi Paleino
- University of Milan, Via Festa del Perdono, 7, 20122, Milan, Italy; General Surgery Unit, ASST Vimercate, Via Santi Cosma e Damiano, 10, 20871, Vimercate, Italy.
| | - Shigeki Kusamura
- Peritoneal Surface Malignancies Unit, Fondazione I.R.C.C.S., Istituto Nazionale Tumori, Via Venezian 1, 20133, Milan, Italy.
| | - Alessandro Germini
- General Surgery Unit, ASST Vimercate, Via Santi Cosma e Damiano, 10, 20871, Vimercate, Italy.
| | - Antonio Facciorusso
- Department of Medical Sciences, Gastroenterology Unit, Ospedali Riuniti di Foggia, Viale Luigi Pinto, 1, 71122, Foggia, Italy.
| | - Marcello Deraco
- Peritoneal Surface Malignancies Unit, Fondazione I.R.C.C.S., Istituto Nazionale Tumori, Via Venezian 1, 20133, Milan, Italy.
| | - Christian Cotsoglou
- General Surgery Unit, ASST Vimercate, Via Santi Cosma e Damiano, 10, 20871, Vimercate, Italy.
| |
Collapse
|
|
20
|
Ji ZH, Zhang Y, Li Y. Intra-operative hyperthermic intraperitoneal chemotherapy for prevention and treatment of peritoneal metastases from gastric cancer: a narrative review. J Gastrointest Oncol 2021; 12:S70-S78. [PMID: 33968427 DOI: 10.21037/jgo-20-262] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Peritoneal metastasis (PM) from gastric cancer (GC) has long been regarded as the terminal disease, lacking of effective treatments. In recent 40 years, cytoreductive surgery (CRS) plus perioperative intraperitoneal chemotherapy, including hyperthermic intraperitoneal chemotherapy (HIPEC), neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), and early post-operative intraperitoneal chemotherapy (EPIC), has been recommended as a preferred treatment option for some selected patients with GCPM. Intraperitoneal free cancer cells were recognized as the pathological cause of PM and the primary target for intraperitoneal chemotherapy. There were a lot of evidence demonstrating that HIPEC could effectively eradiate intraperitoneal free cancer cells and prolong overall survival in GCPM. However, there are still no standard HIPEC protocols. This review summarized the current HIPEC regimens used in GCPM from a literature search, trying to conclude the optimal HIPEC in GCPM, and indicate the future direction of HIPEC study. Moreover, the new data on the exploration of HIPEC in GCPM at Shijitan Hospital, Capital Medical University was shared. In conclusion, there was not enough evidence from publications and our own experience to conclude a recommended HIPEC regimen for GCPM. There is urgent need for standardizing HIPEC protocols worldwide. Accordingly, more international collaborations focusing on pharmacology and HIPEC-related parameters to generate high level evidence are essential.
Collapse
Affiliation(s)
- Zhong-He Ji
- Department of Peritoneal Cancer Surgery, Cancer Center of Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Ying Zhang
- Department of Pathology, Cancer Center of Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Yan Li
- Department of Peritoneal Cancer Surgery, Cancer Center of Beijing Shijitan Hospital, Capital Medical University, Beijing, China.,Department of Pathology, Cancer Center of Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| |
Collapse
|
|
21
|
Parray A, Gupta V, Chaudhari VA, Shrikhande SV, Bhandare MS. Role of intraperitoneal chemotherapy in gastric cancer. SURGERY IN PRACTICE AND SCIENCE 2021. [DOI: 10.1016/j.sipas.2020.100025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
|
|
22
|
Gronau F, Jara M, Feldbrügge L, Wolf V, Oeff A, Rau B. [Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer]. Chirurg 2021; 92:522-527. [PMID: 33620502 DOI: 10.1007/s00104-021-01371-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/26/2021] [Indexed: 10/22/2022]
Abstract
BACKGROUND Gastric cancer with peritoneal metastases is associated with an extremely poor prognosis. Developed multimodal treatment concepts, which include a combination of perioperative systemic treatment and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), show promising results with respect to improvement of the long-term survival. METHODS This article contains a review of the literature of published studies on the topic of gastric cancer and peritoneal metastasis. RESULTS The prognosis of patients with gastric cancer peritoneal carcinomatosis shows an extremely limited median survival of 7 months under palliative second-line systemic treatment. The median survival time increased to 12 months with cytoreductive surgery and in combination with HIPEC showed a positive effect on survival in individual studies. EXPERT OPINION Treatment recommendations for patients with peritoneal metastases of gastric cancer should be carried out by experts in surgical reference centers.
Collapse
Affiliation(s)
- Felix Gronau
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Deutschland
| | - Maximilian Jara
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Deutschland
| | - Linda Feldbrügge
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Deutschland
| | - Vincent Wolf
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Deutschland
| | - Alan Oeff
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Deutschland
| | - Beate Rau
- Chirurgische Klinik Campus Charité Mitte
- Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Deutschland. .,Klinik für Chirurgie, Universitätsmedizin Berlin, Charité Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Deutschland.
| |
Collapse
|
|
23
|
Yin Z, Wei M, Xie S, Zhou S, Zhang B, Gao P, Wu T, Qiao Q, Wang N, He X. Laparoscopic distal gastrectomy and hyperthermic intraperitoneal chemotherapy in the treatment of advanced gastric cancer: a retrospective case-matched study on perioperative outcomes. J Gastrointest Oncol 2021; 12:133-141. [PMID: 33708431 DOI: 10.21037/jgo-21-20] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Background This study aimed to assess the safety and efficacy of laparoscopic distal gastrectomy (LDG) with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer (AGC). Methods In this case-matched study, we retrospectively reviewed the database of 223 patients with AGC who underwent LDG in Tangdu Hospital from April 2016 to February 2019. Among all participants, 177 patients underwent LDG alone and 46 underwent LDG with HIPEC. We matched total of 138 (1:2) patients from the LDG + HIPEC group (n 46) and the LDG group (n 92) for gender, age, date of operation, and tumor-node-metastasis (TNM) stage of tumor. Results There was no significant difference in the Clavien-Dindo classification of complications between LDG alone and LDG + HIPEC patients. Further analysis showed the morbidity of gastroparesis to be significantly increased in LDG + HIPEC patients. At the same time, we found that the operation time, the time to 1st flatus, and hospital stay were longer in LDG + HIPEC patients and the incidence of abdominal recurrence 2 years after operation was significantly higher in the LDG group than the LDG + HIPEC group. Conclusions The combination of LDG with intraoperative HIPEC is a safe and feasible method for AGC and HIPEC will limit the recovery of gastrointestinal functions. In addition, during the follow-up of our study, although there was no statistical difference between the two groups in abdominal recurrence at 2 years after surgery, a decreasing trend of abdominal recurrence in LDG + HIPEC patients could be seen in comparison to LDG patients.
Collapse
Affiliation(s)
- Zhiyuan Yin
- Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Mingguang Wei
- Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Shuang Xie
- Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Shuai Zhou
- Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Bo Zhang
- Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Peng Gao
- Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Tao Wu
- Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Qing Qiao
- Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Nan Wang
- Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Xianli He
- Department of General Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| |
Collapse
|
|
24
|
Laparoscopic Hyperthermic Intraperitoneal Perfusion Chemotherapy for Patients With Malignant Ascites Secondary to Unresectable Gastric Cancer. Surg Laparosc Endosc Percutan Tech 2020; 30:55-61. [PMID: 32004214 DOI: 10.1097/sle.0000000000000380] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND To compare the efficacy of 3 chemotherapeutic combinations for laparoscopic hyperthermic intraperitoneal perfusion chemotherapy (HIPPC) in the treatment of malignant ascites secondary to unresectable gastric cancer (GC). MATERIALS AND METHODS From January 2010 to December 2013, 38 GC patients were randomly divided into 3 groups and treated by laparoscopic HIPPC with 1 of the 3 following chemotherapy combinations: raltitrexed (Ra) with oxaliplatin (L-OHP), Ra with cisplatin (DDP), and Ra with mitomycin C (MMC). Perioperative complications, patients' quality of life, and survival were recorded and compared among the 3 groups. RESULTS The intraoperative course was successful in all patients, and no perioperative death or complication related to laparoscopic HIPPC was documented. The median follow-up period was 9 months and the median survival was 7.5 months for all patients. Patients in the Ra/L-OHP group had a median survival of 8.7 months, the Ra/DDP group had a median survival of 5.6 months, and the Ra/MMC group had a median survival of 7.5 months. Patients' median survival in the Ra/L-OHP group and Ra/MMC group is significantly longer than Ra/DDP group (P<0.05). No significant difference was found in total remission rate of ascites, increase in the Karnofsky performance scale, and incidence rate of port-site metastases among the 3 groups. CONCLUSIONS Laparoscopy-assisted HIPPC provide modest yet encouraging efficacy for malignant ascites secondary to disseminated GC. Our preliminary data indicate that the chemotherapeutical combination of Ra/L-OHP and Ra/MMC might be more beneficial compared with Ra/DDP in terms of patients' survival.
Collapse
|
|
25
|
Ji ZH, Yu Y, Liu G, Zhang YB, An SL, Li B, Li XB, Yan GJ, Li Y. Peritoneal cancer index (PCI) based patient selecting strategy for complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy in gastric cancer with peritoneal metastasis: A single-center retrospective analysis of 125 patients. Eur J Surg Oncol 2020; 47:1411-1419. [PMID: 33293213 DOI: 10.1016/j.ejso.2020.11.139] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2020] [Revised: 11/04/2020] [Accepted: 11/21/2020] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE The role of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer with peritoneal metastasis (GCPM) is still controversial, mainly due to the limited survival benefit and uncertain patient selection. This study aims to construct a selecting strategy in GCPM for CRS + HIPEC. METHODS From a prospective established database, 125 patients were enrolled. All these patients were pathologically confirmed as GCPM and treated with CRS + HIPEC with or without preoperative or postoperative chemotherapy. The clinical documents and follow-up results were collected and analyzed with the primary endpoint of overall survival (OS) and the secondary endpoint of perioperative serious adverse events (SAEs). RESULTS The median OS of 125 GCPM patients treated with CRS + HIPEC was 10.7 months, with 1-, 2-, 3-, and 5-year survival rates of 43.8%, 24.7%, 18.6%, and 15.7%, respectively. The multivariate analysis identified completeness of cytoreduction (CC), SAEs, HIPEC drugs, and adjuvant chemotherapy as independent prognostic factors on OS. The median OS was 30.0 (95%CI: 16.8-43.3) months in CC-0 group, significantly better than 7.3 (95%CI: 5.8-8.8) months in CC1-3 group (P < 0.001). The median OS showed no significant difference among CC-1 (8.5, 95%CI: 6.7-10.2, months), CC-2 (5.6, 95%CI: 3.0-8.2, months) and CC-3 (6.5, 95%CI: 5.2-7.7, months) groups (P > 0.05 for all pairwise comparations). The nomogram based on peritoneal metastasis timing, preoperative tumor marker (TM), and peritoneal cancer index (PCI), with AUC of 0.985, showed a good accuracy and consistency between actual observation and prediction of the probability of complete CRS. The cutoffs of PCI were 16 for synchronous GCPM with normal TM, 12 for synchronous GCPM with abnormal TM, 10 for metachronous GCPM with normal TM, and 5 for metachronous GCPM with abnormal TM, setting the probability to achieve complete CRS as 50%. CONCLUSIONS Only complete CRS + HIPEC (CC-0) could improve survival for high selected GCPM patients with acceptable safety. An incomplete CRS (CC1-3) should be avoided for GCPM patients. Synchronous GCPM with PCI ≤16 and normal TM, synchronous GCPM with PCI ≤12 and abnormal TM, metachronous GCPM with PCI ≤10 and normal TM, or metachronous GCPM with PCI ≤5 and abnormal TM maybe potential indications for complete CRS + HIPEC treatment.
Collapse
Affiliation(s)
- Zhong-He Ji
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, PR China
| | - Yang Yu
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, PR China
| | - Gang Liu
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, PR China
| | - Yan-Bin Zhang
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, PR China
| | - Song-Lin An
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, PR China
| | - Bing Li
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, PR China
| | - Xin-Bao Li
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, PR China
| | - Guo-Jun Yan
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, PR China
| | - Yan Li
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, PR China.
| |
Collapse
|
|
26
|
Brandl A, Yonemura Y, Glehen O, Sugarbaker P, Rau B. Long term survival in patients with peritoneal metastasised gastric cancer treated with cytoreductive surgery and HIPEC: A multi-institutional cohort from PSOGI. Eur J Surg Oncol 2020; 47:172-180. [PMID: 33071173 DOI: 10.1016/j.ejso.2020.10.006] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Revised: 08/21/2020] [Accepted: 10/05/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Peritoneal metastasis (PM) of gastric cancer (GC) is relatively common (17%) and is associated with poor survival. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is still controversially discussed, as it has proven an increase in survival in selected patients, but only a small subgroup reached long-term survival. The aim of this study was to collect and analyse a worldwide cohort of patients treated with CRS and HIPEC with long-term survival in order to explore relevant patient characteristics. METHODS We conducted a questionnaire, which was distributed to all collaborators of the Peritoneal Surface Oncology Group International (PSOGI). Inclusion criteria were: histopathologic proven PM of GC, treated with CRS and HIPEC, and overall survival >5 years. Patient, tumour, and therapeutic details were collected and analysed. RESULTS From an analysis of 448 patients treated between 1994 and 2014, a total of 28 patients with a mean age of 53.0 years and mean PCI of 3.3 were included. The overall median survival was 11.0 years (min 5.0; max 27.9). The predictors completeness of cytoreduction (CC-0) and PCI<6 were present in 22/28 patients. 12/28 patients developed at a median of 9.6 years tumour recurrence, and was associated with inferior median overall survival compared to patients without recurrence (8.8 years vs. not reached; p = 0.002). CONCLUSIONS Long-term survival and even cure are possible in patients with PM of GC treated with CRS and HIPEC. Completeness of cytoreduction and low PCI seemed to be crucial. Further studies are needed in order to improve existing selection criteria.
Collapse
Affiliation(s)
- Andreas Brandl
- Department of Surgery, Campus Virchow-Klinikum and Charité Campus Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany; Digestive Unit, Champalimaud Foundation, Lisbon, Portugal
| | - Yutaka Yonemura
- Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kishiwada, Japan
| | - Olivier Glehen
- Department of Surgical Oncology, Centre Hospitalier Lyon-Sud, Lyon, France
| | - Paul Sugarbaker
- Program in Peritoneal Surface Oncology, Washington Cancer Institute, Washington, DC, USA
| | - Beate Rau
- Department of Surgery, Campus Virchow-Klinikum and Charité Campus Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany.
| |
Collapse
|
|
27
|
Lo Dico R, Gornet JM, Guglielmo N, Zaanan A, Taieb J, Pocard M. Bidirectional chemotherapy combining intraperitoneal docetaxel with intravenous 5-fluorouracil and oxaliplatin for patients with unresectable peritoneal metastasis from gastric cancer: the first study in Western countries. Pleura Peritoneum 2020; 5:20190035. [PMID: 32566725 PMCID: PMC7292234 DOI: 10.1515/pp-2019-0035] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 03/03/2020] [Indexed: 12/18/2022] Open
Abstract
Background A new treatment using bidirectional intraperitoneal (IP) and intravenous (IV) chemotherapy developed by Asiatic surgeons improves outcomes in patients with synchronous peritoneal metastasis (PM) from gastric cancer (GC). Methods We enrolled six consecutive patients with unresectable PM from GC who underwent bidirectional chemotherapy using IP docetaxel and IV FOLFOX or LV5FU2. In one course, IP docetaxel 30 mg/m2 was administrated on days 1, 8 and 15, and IV FOLFOX or LV5FU2 was administered on days 1 and 15, followed by 7 days of rest. Before and after a complete bidirectional cycle of three courses, the peritoneal cancer index (PCI) was evaluated by laparoscopy. The primary endpoint was to evaluate the feasibility and safety of bidirectional chemotherapy. Secondary endpoints were overall survival (OS), and the success of the therapeutic strategy was reflected by a decrease of 25% of the initial PCI. Results All patients completed one bidirectional cycle. The regimen was well tolerated. The median OS was 13 months [range 5–18], and the 1-year OS rate was 67%. After the first bidirectional cycle, the PCI decrease ≥25% of the initial value in four patients. A major histological response was observed in four patients. Conclusions This is the first Western study and confirms the feasibility and safety of bidirectional treatment using IP and IV chemotherapy for patients with unresectable PM from GC, resulting in a 13-month median OS with limited morbidity. The decrease in PCI after one bidirectional cycle is promising.
Collapse
Affiliation(s)
- Rea Lo Dico
- University of Paris, UMR 1275 CAP Paris-Tech, Department of Digestive Surgery, Lariboisière Hospital, AP-HP, F-75010Paris, France
| | - Jean Marc Gornet
- Department of Hepatology, Gastroenterology and Digestive Oncology, Saint-Louis Hospital, AP-HP, Paris, France
| | - Nicola Guglielmo
- Department of Digestive Surgery, Lariboisiere Hospital, AP-HP, Paris, France
| | - Aziz Zaanan
- Department of Hepatology, Gastroenterology and Digestive Oncology, Georges Pompiodou European Hospital, AP-HP, Paris, University of Paris, France
| | - Julien Taieb
- Department of Hepatology, Gastroenterology and Digestive Oncology, Georges Pompiodou European Hospital, AP-HP, Paris, University of Paris, France
| | - Marc Pocard
- University of Paris, UMR 1275 CAP Paris-Tech, Department of Digestive Surgery, Lariboisière Hospital, AP-HP, F-75010Paris, France
| |
Collapse
|
|
28
|
Long Term Survival after Cytoreductive Surgery Combined with Perioperative Chemotherapy in Gastric Cancer Patients with Peritoneal Metastasis. Cancers (Basel) 2020; 12:cancers12010116. [PMID: 31906405 PMCID: PMC7016959 DOI: 10.3390/cancers12010116] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2019] [Revised: 12/24/2019] [Accepted: 12/29/2019] [Indexed: 12/18/2022] Open
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.
Collapse
|
|
29
|
Lei Z, Wang J, Li Z, Li B, Luo J, Wang X, Wang J, Ba M, Tang H, He Q, Liao Q, Yang X, Guan T, Liang H, Cui S, On Behalf Of The Chinese Peritoneal Oncology Study Group. Hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis: A multicenter propensity score-matched cohort study. Chin J Cancer Res 2020; 32:794-803. [PMID: 33447001 PMCID: PMC7797229 DOI: 10.21147/j.issn.1000-9604.2020.06.12] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Objective Systemic chemotherapy has limited efficacy in the treatment of peritoneal metastasis (PM) in gastric cancer (GC). Hyperthermic intraperitoneal chemotherapy (HIPEC) combined with complete cytoreductive surgery (CRS) has shown promising outcomes but remains controversial. The present study aimed to evaluate the safety and efficacy of HIPEC without CRS in GC patients with PM. Methods This retrospective propensity score-matched multicenter cohort study included GC patients with PM treated with either chemotherapy alone (Cx group) or with HIPEC combined with chemotherapy (HIPEC-Cx group) in four Chinese high-volume gastric medical centers between 2010 and 2017. The primary outcomes were median survival time (MST) and 3-year overall survival (OS). Propensity score matching was performed to compensate for controlling potential confounding effects and selection bias. Results Of 663 eligible patients, 498 were matched. The MST in the Cx and HIPEC-Cx groups was 10.8 and 15.9 months, respectively [hazard ratio (HR)=0.71, 95% confidence interval (95% CI), 0.58−0.88; P=0.002]. The 3-year OS rate was 10.1% (95% CI, 5.4%−14.8%) and 18.4% (95% CI, 12.3%−24.5%) in the Cx and HIPEC-Cx groups, respectively (P=0.017). The complication rates were comparable. The time to first flatus and length of hospital stay for patients undergoing HIPEC combined with chemotherapy was longer than that of chemotherapy alone (4.6±2.4 dvs. 2.7±1.8 d, P<0.001; 14.2±5.8 dvs. 11.4±7.7 d, P<0.001), respectively. The median follow-up period was 33.2 months.
Conclusions Compared with standard systemic chemotherapy, HIPEC combined with chemotherapy revealed a statistically significant survival benefit for GC patients with PM, without compromising patient safety.
Collapse
Affiliation(s)
- Ziying Lei
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Jiahong Wang
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Zhi Li
- Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Tumor Hospital of Henan Province, Zhengzhou 450008, China
| | - Baozhong Li
- Department of Surgery, Anyang Tumor Hospital, Anyang 455000, China
| | - Jiali Luo
- Department of Oncology, Guangzhou Medical University, Guangzhou 510095, China
| | - Xuejun Wang
- Department of Gastrointestinal Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Jin Wang
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Mingchen Ba
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Hongsheng Tang
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Qingjun He
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Quanxing Liao
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Xiansheng Yang
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Tianpei Guan
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - Han Liang
- Department of Gastrointestinal Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Shuzhong Cui
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China
| | - On Behalf Of The Chinese Peritoneal Oncology Study Group
- Department of Abdominal Surgery, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou 510095, China.,Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Tumor Hospital of Henan Province, Zhengzhou 450008, China.,Department of Surgery, Anyang Tumor Hospital, Anyang 455000, China.,Department of Oncology, Guangzhou Medical University, Guangzhou 510095, China.,Department of Gastrointestinal Cancer, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| |
Collapse
|
|
30
|
Gamboa AC, Winer JH. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer. Cancers (Basel) 2019; 11:E1662. [PMID: 31717799 PMCID: PMC6896138 DOI: 10.3390/cancers11111662] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2019] [Revised: 10/21/2019] [Accepted: 10/24/2019] [Indexed: 12/24/2022] Open
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.
Collapse
Affiliation(s)
- Adriana C. Gamboa
- Division of Surgical Oncology, 1365B Clifton Road NE, Suite B4000, Atlanta, GA 30322, USA;
| | | |
Collapse
|
|
31
|
Zheng LN, Wen F, Xu P, Zhang S. Prognostic significance of malignant ascites in gastric cancer patients with peritoneal metastasis: A systemic review and meta-analysis. World J Clin Cases 2019; 7:3247-3258. [PMID: 31667175 PMCID: PMC6819285 DOI: 10.12998/wjcc.v7.i20.3247] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Revised: 08/16/2019] [Accepted: 09/09/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Recent evidence indicates that malignant ascites may be associated with the high malignancy and poor prognosis of gastric cancer (GC) with peritoneal metastasis (PM), but no robust consensus has been reached until now.
AIM To evaluate the prognostic significance of malignant ascites in GC patients with PM.
METHODS Two independent authors conducted database searches. The searches were performed in the EMBASE, PubMed, and Cochrane Library databases, and the terms used to search included stomach neoplasms, GC, ascites, peritoneal effusion, survival, and survival analysis. Outcomes included overall survival and hazard ratios with 95% confidence intervals (CIs). Three pairs of comparisons for measuring survival were made: (1) Patients with ascites vs those without ascites; (2) Patients with massive ascites vs those with mild to moderate ascites; and (3) Patients with massive ascites vs those with no to moderate ascites.
RESULTS Fourteen articles including fifteen studies were considered in the final analysis. Among them, nine studies assessed the difference in prognosis between patients with and without malignant ascites. A pooled HR of 1.63 (95%CI: 1.47-1.82, P < 0.00001) indicated that GC patients with malignant ascites had a relatively poor prognosis compared to patients without ascites. We also found that the prognosis of GC patients with malignant ascites was related to the volume of ascites in the six other studies.
CONCLUSION GC patients with malignant ascites tend to have a worse prognosis, and the volume of ascites has an impact on GC outcomes.
Collapse
Affiliation(s)
- Ling-Nan Zheng
- Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Feng Wen
- Department of Abdominal Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ping Xu
- Sichuan University Library, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Shuang Zhang
- Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| |
Collapse
|
|
32
|
Macrì A, Morabito F. The use of intraperitoneal chemotherapy for gastric malignancies. Expert Rev Anticancer Ther 2019; 19:879-888. [PMID: 31544548 DOI: 10.1080/14737140.2019.1671189] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Introduction: Gastric cancer is the fourth/fifth most common malignancy worldwide, with only a quarter of patients achieving a 5-year survival rate. It has been estimated that 15-50% or more of patients have peritoneal disease upon surgical exploration. Until the early 1990s, peritoneal metastasis was considered as terminal stage of the disease; in the late 1990s, selected patients with peritoneal metastasis were recategorized as local disease. Over the past two decades, the treatment of peritoneal involvement has transformed, and cytoreductive surgery plus intraperitoneal therapy have drastically altered the natural course of several malignancies. Areas covered: We performed a review of studies available on PubMed from 1 January 2014 to 31 July 2019 and the analysis of their reference citations. We describe the most current intraperitoneal chemotherapy opportunities in the treatment of gastric cancer: hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC), laparoscopic hyperthermic intraperitoneal chemotherapy (LHIPEC), neoadjuvant intraperitoneal and systemic chemotherapy (NIPS), LHIPEC + NIPS, extensive intraoperative peritoneal lavage (EIPL), early postoperative intraperitoneal chemotherapy (EPIC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC). Expert opinion: Comprehensive treatment consisting of CRS combined with perioperative intraperitoneal/systemic chemotherapy can, today, be considered an effective strategy to improve the long-term survival of gastric cancer patients with peritoneal metastasis.
Collapse
Affiliation(s)
- Antonio Macrì
- Peritoneal Surface Malignancy and Soft Tissue Sarcoma Program, Messina University Medical School Hospital , Messina , Italy
| | - Federico Morabito
- Peritoneal Surface Malignancy and Soft Tissue Sarcoma Program, Messina University Medical School Hospital , Messina , Italy
| |
Collapse
|
|
33
|
Guner A, Yildirim R. Surgical management of metastatic gastric cancer: moving beyond the guidelines. Transl Gastroenterol Hepatol 2019; 4:58. [PMID: 31559339 DOI: 10.21037/tgh.2019.08.03] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Accepted: 08/05/2019] [Indexed: 01/27/2023] Open
Abstract
Despite decreasing incidence, gastric cancer remains a major health problem worldwide and is associated with poor survival. The poor survival is mainly attributed to delayed presentation which may cause local or systemic metastases. The standard of care for patients with metastatic gastric cancer (MGC) is palliative chemotherapy with best supportive care. Although the survival has improved owing to advances in chemotherapeutic agents, it is still unsatisfactory, and some perspective changes are needed in the management of MGC to improve the outcomes. Therefore, various alternative treatment strategies for MGC have formed the most important research topics. Liver-directed treatment (LDT) options such as liver resection, radiofrequency ablation (RFA), microwave ablation (MWA), and hepatic artery infusion chemotherapy (HAIC) have been studied in the management of liver metastasis from gastric cancer (LMGC). Intraperitoneal chemotherapy (IPC) in addition to cytoreductive surgery (CRS) aiming to remove all macroscopic tumor focus resulting from peritoneal dissemination is the treatment option for peritoneal metastasis, while para-aortic lymph node dissection is the treatment option for para-aortic lymph node metastasis which is considered to be M1 disease. Conversion surgery is a novel concept aiming at R0 resection for originally unresectable or marginally resectable tumors after a remarkably good response to the chemotherapy. Large amounts of data in the literature have demonstrated the benefits of individualized approaches such as the combination of systemic and local treatment options in selected patient groups. In this review, we aimed to explore the current and future treatment options by reviewing the literature on this controversial topic.
Collapse
Affiliation(s)
- Ali Guner
- Department of General Surgery, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey.,Department of Biostatistics and Medical Informatics, Institute of Medical Science, Karadeniz Technical University, Trabzon, Turkey
| | - Reyyan Yildirim
- Department of General Surgery, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey
| |
Collapse
|
|
34
|
Bonnot PE, Piessen G, Kepenekian V, Decullier E, Pocard M, Meunier B, Bereder JM, Abboud K, Marchal F, Quenet F, Goere D, Msika S, Arvieux C, Pirro N, Wernert R, Rat P, Gagnière J, Lefevre JH, Courvoisier T, Kianmanesh R, Vaudoyer D, Rivoire M, Meeus P, Passot G, Glehen O. Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer With Peritoneal Metastases (CYTO-CHIP study): A Propensity Score Analysis. J Clin Oncol 2019; 37:2028-2040. [DOI: 10.1200/jco.18.01688] [Citation(s) in RCA: 152] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
PURPOSE Gastric cancer (GC) with peritoneal metastases (PMs) is a poor prognostic evolution. Cytoreductive surgery (CRS) yields promising results, but the impact of hyperthermic intraperitoneal chemotherapy (HIPEC) remains controversial. Here we aimed to compare outcomes between CRS-HIPEC versus CRS alone (CRSa) among patients with PMs from GC. PATIENTS AND METHODS From prospective databases, we identified 277 patients with PMs from GC who were treated with complete CRS with curative intent (no residual nodules > 2.5 mm) at 19 French centers from 1989 to 2014. Of these patients, 180 underwent CRS-HIPEC and 97 CRSa. Tumor burden was assessed using the peritoneal cancer index. A Cox proportional hazards regression model with inverse probability of treatment weighting (IPTW) based on propensity score was used to assess the effect of HIPEC and account for confounding factors. RESULTS After IPTW adjustment, the groups were similar, except that median peritoneal cancer index remained higher in the CRS-HIPEC group (6 v 2; P = .003). CRS-HIPEC improved overall survival (OS) in both crude and IPTW models. Upon IPTW analysis, in CRS-HIPEC and CRSa groups, median OS was 18.8 versus 12.1 months, 3- and 5-year OS rates were 26.21% and 19.87% versus 10.82% and 6.43% (adjusted hazard ratio, 0.60; 95% CI, 0.42 to 0.86; P = .005), and 3- and 5-year recurrence-free survival rates were 20.40% and 17.05% versus 5.87% and 3.76% ( P = .001), respectively; the groups did not differ regarding 90-day mortality (7.4% v 10.1%, respectively; P = .820) or major complication rate (53.7% v 55.3%, respectively; P = .496). CONCLUSION Compared with CRSa, CRS-HIPEC improved OS and recurrence-free survival, without additional morbidity or mortality. When complete CRS is possible, CRS-HIPEC may be considered a valuable therapy for strictly selected patients with limited PMs from GC.
Collapse
Affiliation(s)
- Pierre-Emmanuel Bonnot
- Centre Hospitalier Universitaire (CHU) Lyon Sud, Lyon, France
- University of Lyon 1, Lyon, France
| | | | - Vahan Kepenekian
- Centre Hospitalier Universitaire (CHU) Lyon Sud, Lyon, France
- University of Lyon 1, Lyon, France
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | - Delphine Vaudoyer
- Centre Hospitalier Universitaire (CHU) Lyon Sud, Lyon, France
- University of Lyon 1, Lyon, France
| | | | | | - Guillaume Passot
- Centre Hospitalier Universitaire (CHU) Lyon Sud, Lyon, France
- University of Lyon 1, Lyon, France
| | - Olivier Glehen
- Centre Hospitalier Universitaire (CHU) Lyon Sud, Lyon, France
- University of Lyon 1, Lyon, France
| | | |
Collapse
|
|
35
|
Chiu CC, Tsao CJ, Wang JJ, Yonemura Y. Can hyperthermic intraperitoneal chemotherapy effectively control gastric cancer-associated peritoneal carcinomatosis? World J Surg Proced 2019; 9:7-11. [DOI: 10.5412/wjsp.v9.i1.7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2018] [Revised: 03/11/2019] [Accepted: 04/19/2019] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer-associated peritoneal carcinomatosis leads to a poor prognosis and low quality of life. The current systemic chemotherapy processes cannot effectively improve survival. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been used as an alternative treatment to control this disease through recurrence prevention, definitive therapeutic modality, and symptom palliation. Although HIPEC has been demonstrated to yield favorable results mainly in some Asian studies, widespread adoption of this treatment is still debatable before larger prospective randomized controlled clinical trials confirm its effectiveness.
Collapse
Affiliation(s)
- Chong-Chi Chiu
- Department of General Surgery, Chi Mei Medical Center, Liouying 73657 and Tainan 71004, Taiwan
- Department of Electrical Engineering, Southern Taiwan University of Science and Technology, Tainan 71005, Taiwan
| | - Chao-Jung Tsao
- Department of Oncology, Chi Mei Medical Center, Liouying 73657, Taiwan
| | - Jhi-Joung Wang
- Department of Medical Research, Chi Mei Medical Center, Tainan 71004, Taiwan
- AI Biomed Center, Southern Taiwan University of Science and Technology, Tainan 71005, Taiwan
| | - Yutaka Yonemura
- Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kishiwada, Osaka 596-8522, Japan
| |
Collapse
|
|
36
|
Zhu BY, Yuan SQ, Nie RC, Li SM, Yang LR, Duan JL, Chen YB, Zhang XS. Prognostic Factors and Recurrence Patterns in T4 Gastric Cancer Patients after Curative Resection. J Cancer 2019; 10:1181-1188. [PMID: 30854127 PMCID: PMC6400673 DOI: 10.7150/jca.28993] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2018] [Accepted: 01/04/2019] [Indexed: 12/26/2022] Open
Abstract
Background: To investigate prognostic factors and recurrence patterns in T4 gastric cancer (GC) patients after curative resection. Methods: Between January 2004 and December 2014, 249 patients with T4 gastric cancer undergoing curative resection were recruited. Patient characteristics, survival, prognostic factors and recurrence patterns were analyzed. Results: Our results showed that the median survival time (MST) for T4 gastric cancer after curative resection was 55.47 months, with 59.47 months for T4a (tumor perforating serosa) and 25.90 months for T4b (tumor invasion of the adjacent structure). Multivariate analysis indicated that age (hazard ratio [HR], 1.86; P = 0.006), location of tumor (HR, 1.25, 0.90 - 5.64; P < 0.001) and intraoperative blood loss (HR, 1.85; P = 0.010) were independent prognostic factors for overall survival (OS). After a median follow-up of 25.87 months, a total of 109 (43.8%) patients suffered from recurrence, and 90 patients had been observed specific recurrence sites, among which peritoneal metastasis was the most common recurrence pattern, 59.0% for T4a and 88.3% for T4b, respectively. Conclusions: For T4 gastric cancer patients after curative resection, older age, gastric cancer of the entire stomach and more intraoperative blood loss were associated with poor OS. The recurrence rate after curative resection for T4 was high, and the most common recurrence pattern was peritoneal metastasis.
Collapse
Affiliation(s)
- Bao-Yan Zhu
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Shu-Qiang Yuan
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Run-Cong Nie
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Shu-Man Li
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Li-Rong Yang
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Jin-Ling Duan
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ying-Bo Chen
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Xiao-Shi Zhang
- Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| |
Collapse
|
|
37
|
Abstract
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is an evolving strategy in the locoregional management of peritoneal surface malignancies, and the role of laparoscopy is expanding. Staging laparoscopy is routinely used to obtain tissue for diagnosis and assess extent of tumor burden. Laparoscopic CRS and HIPEC with curative intent is safe and effective in patients with a low disease burden. In patients with refractory malignant ascites, complete resolution of ascites and improvement in quality of life have been demonstrated with palliative laparoscopic HIPEC. Laparoscopic CRS and HIPEC has an expanding role in the treatment of peritoneal surface disease.
Collapse
|
|
38
|
Abstract
Peritoneal malignancies may result in a widespread disease process, peritoneal carcinomatosis (PC), which has significant morbidity and mortality for patients afflicted by this disease. Dissemination into the peritoneum and throughout the abdomen can be due to a primary peritoneal cancer or other primary malignancies that have metastasized, including (but not limited to) colorectal cancer, gastric cancer, pancreatic cancer, appendiceal cancer, ovarian cancer, and mesothelioma. Patients with gastrointestinal (GI) or gynecologic malignancies with peritoneal carcinomatosis may have dismal survival due to a high disease burden within the abdominal cavity. Some studies suggest the average survival for patients with peritoneal carcinomatosis of colorectal origin is 18–48 months, for high-grade appendiceal adenocarcinoma 12–36 months, and for low-grade appendiceal neoplasms >60 months. As the understanding of peritoneal malignancies and peritoneal carcinomatosis evolved, it may now be acceptable to treat this as locoregional disease.
Collapse
Affiliation(s)
- Suayib Yalcin
- Department of Medical Oncology, Hacettepe University Institute of Cancer, Sihhiye, Ankara Turkey
| | - Philip A. Philip
- Department of Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI USA
| |
Collapse
|
|
39
|
Dahdaleh FS, Turaga KK. Evolving Treatment Strategies and Outcomes in Advanced Gastric Cancer with Peritoneal Metastasis. Surg Oncol Clin N Am 2018; 27:519-537. [PMID: 29935687 DOI: 10.1016/j.soc.2018.02.006] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Gastric cancer (GC) has a predilection to metastasize to the peritoneum, denoting a poor prognosis. Treatment strategies available for advanced GC have significantly evolved over time and can be categorized into systemic, regional, and surgical. Although systemic therapies have been the mainstay for the treatment of advanced GC, their ability in achieving long-term survival in patients with peritoneal involvement is modest at best. This article describes advances in combined modality treatment of peritoneal metastases, specifically with an emphasis on peritoneal-directed therapies.
Collapse
Affiliation(s)
- Fadi S Dahdaleh
- Complex General Surgical Oncology, Section of General Surgery/Surgical Oncology, The University of Chicago Medicine, 5841 South Maryland Avenue, Room S214, MC 5094, Chicago, IL 60637, USA
| | - Kiran K Turaga
- The University of Chicago Medicine, Section of General Surgery/Surgical Oncology, 5841 South Maryland Avenue, Room G207, MC 5094, Chicago, IL 60637, USA.
| |
Collapse
|
|
40
|
Leiting JL, Grotz TE. Optimizing outcomes for patients with gastric cancer peritoneal carcinomatosis. World J Gastrointest Oncol 2018; 10:282-289. [PMID: 30364780 PMCID: PMC6198298 DOI: 10.4251/wjgo.v10.i10.282] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 08/07/2018] [Accepted: 08/12/2018] [Indexed: 02/05/2023] Open
Abstract
Peritoneal carcinomatosis (PC) from gastric cancer has traditionally been considered a terminal progression of the disease and is associated with poor survival outcomes. Positive peritoneal cytology similarly worsens the survival of patients with gastric cancer and treatment options for these patients have been limited. Recent advances in multimodality treatment regimens have led to innovative ways to care for and treat patients with this disease burden. One of these advances has been to use neoadjuvant therapy to try and convert patients with positive cytology or low-volume PC to negative cytology with no evidence of active peritoneal disease. These strategies include the use of neoadjuvant systemic chemotherapy alone, using neoadjuvant laparoscopic heated intraperitoneal chemotherapy (NLHIPEC) after systemic chemotherapy, or using neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) in a bidirectional manner. For patients with higher volume PC, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been mainstays of treatment. When used together, CRS and HIPEC can improve overall outcomes in properly selected patients, but overall survival outcomes remain unacceptably low. The extent of peritoneal disease, commonly measured by the peritoneal carcinomatosis index (PCI), and the completeness of cytoreduction, has been shown to greatly impact outcomes in patients undergoing CRS and HIPEC. The uses of NLHIPEC and NLHIPEC plus NIPS have both been shown to decrease the PCI and thus increase the opportunity for complete cytoreduction. Newer therapies like pressurized intraperitoneal aerosol chemotherapy and immunotherapy, such as catumaxomab, along with improved systemic chemotherapeutic regimens, are being explored with great interest. There is exciting progress being made in the management of PC from gastric cancer and its' treatment is no longer futile.
Collapse
Affiliation(s)
- Jennifer L Leiting
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN 55905, United States
| | - Travis E Grotz
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN 55905, United States
| |
Collapse
|
|
41
|
Kodera Y. Surgery with curative intent for stage IV gastric cancer: Is it a reality of illusion? Ann Gastroenterol Surg 2018; 2:339-347. [PMID: 30238074 PMCID: PMC6139716 DOI: 10.1002/ags3.12191] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2018] [Accepted: 06/13/2018] [Indexed: 12/22/2022] Open
Abstract
Gastric cancer with metastases outside of the regional lymph nodes is deemed oncologically unresectable. Nevertheless, some metastatic lesions are technically resectable by applying established surgical techniques such as para-aortic lymphadenectomy and hepatectomy. At the time of compilation of the Japanese gastric cancer treatment guidelines version 4, systematic reviews were conducted to see whether it is feasible to make any recommendation to dissect both the primary and metastatic lesions with intent to cure, possibly as part of multimodality treatment. Long-term survivors were found among carefully selected groups of patients both in prospective and retrospective studies. In addition, there is a growing list of publications reporting encouraging outcomes of gastrectomy conducted after exceptionally good response to chemotherapy, usually among patients who underwent R0 resection. This type of surgery is often referred to as conversion surgery. It is sometimes difficult to define a clear borderline between curative surgery scheduled after neoadjuvant chemotherapy and the conversion surgery. This review summarizes what we knew after the literature reviews conducted at the time of compiling the Japanese guidelines and in addition reflects some new findings obtained thereafter through clinical trials and retrospective studies. Metastases were divided into three categories based on the major metastatic pathways: lymphatic, hematogenous, and peritoneal. In each of these categories, there were findings that could provide hope for patients with metastatic disease. These findings implied that the surgical technique that we already use could become more useful upon further developments in antineoplastic agents and drug delivery.
Collapse
Affiliation(s)
- Yasuhiro Kodera
- Department of Gastroenterological SurgeryNagoya University Graduate School of MedicineNagoyaAichiJapan
| |
Collapse
|
|
42
|
Knödler M, Körfer J, Kunzmann V, Trojan J, Daum S, Schenk M, Kullmann F, Schroll S, Behringer D, Stahl M, Al-Batran SE, Hacker U, Ibach S, Lindhofer H, Lordick F. Randomised phase II trial to investigate catumaxomab (anti-EpCAM × anti-CD3) for treatment of peritoneal carcinomatosis in patients with gastric cancer. Br J Cancer 2018; 119:296-302. [PMID: 29988111 PMCID: PMC6070920 DOI: 10.1038/s41416-018-0150-6] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Revised: 05/12/2018] [Accepted: 05/21/2018] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Peritoneal carcinomatosis (PC) represents an unfavourable prognostic factor for patients with gastric cancer (GC). Intraperitoneal treatment with the bispecific and trifunctional antibody catumaxomab (EpCAM, CD3), in addition to systemic chemotherapy, could improve elimination of PC. METHODS This prospective, randomised, phase II study investigated the efficacy of catumaxomab followed by chemotherapy (arm A, 5-fluorouracil, leucovorin, oxaliplatin, docetaxel, FLOT) or FLOT alone (arm B) in patients with GC and PC. Primary endpoint was the rate of macroscopic complete remission (mCR) of PC at the time of second diagnostic laparoscopy/laparotomy prior to optional surgery. RESULTS Median follow-up was 52 months. Out of 35 patients screened, 15 were allocated to arm A and 16 to arm B. mCR rate was 27% in arm A and 19% in arm B (p = 0.69). Severe side effects associated with catumaxomab were nausea, infection, abdominal pain, and elevated liver enzymes. Median progression-free (6.7 vs. 5.4 months, p = 0.71) and overall survival (13.2 vs. 13.0 months, p = 0.97) were not significantly different in both treatment arms. CONCLUSIONS Addition of catumaxomab to systemic chemotherapy was feasible and tolerable in advanced GC. Although the primary endpoint could not be demonstrated, results are promising for future investigations integrating intraperitoneal immunotherapy into a multimodal treatment strategy.
Collapse
Affiliation(s)
- Maren Knödler
- University Cancer Center Leipzig (UCCL), University Hospital Leipzig, Leipzig, Germany.
| | - Justus Körfer
- University Cancer Center Leipzig (UCCL), University Hospital Leipzig, Leipzig, Germany
| | - Volker Kunzmann
- Department of Internal Medicine II, University Hospital Würzburg, Würzburg, Germany
| | - Jörg Trojan
- Department of Internal Medicine I, University Hospital Frankfurt, Frankfurt am Main, Germany
| | - Severin Daum
- Medical Department, Division of Gastroenterology, Infectiology and Rheumatology, University Hospital Berlin (Charite), Campus Benjamin Franklin, Berlin, Germany
| | - Michael Schenk
- Department of Clinical Oncology and Hematology, Hospital Barmherzige Brüder Regensburg, Regensburg, Germany
| | - Frank Kullmann
- Department of Internal Medicine I, Hospital Weiden, Weiden, Germany
| | - Sebastian Schroll
- Department of Internal Medicine III, Hospital Braunschweig, Braunschweig, Germany
| | - Dirk Behringer
- Department of Hematology, Oncology and Palliative Medicine, Augusta-Kranken-Anstalt, Bochum, Germany
| | - Michael Stahl
- Department of Clinical Oncology and Hematology, Hospital Essen-Mitte Essen, Essen, Germany
| | - Salah-Eddin Al-Batran
- Department of Clinical Oncology and Hematology, Hospital Nordwest GmbH, Frankfurt, Germany
| | - Ulrich Hacker
- University Cancer Center Leipzig (UCCL), University Hospital Leipzig, Leipzig, Germany
| | - Stefan Ibach
- WiSP Scientific Service Pharma GmbH, Langenfeld, Germany
| | | | - Florian Lordick
- University Cancer Center Leipzig (UCCL), University Hospital Leipzig, Leipzig, Germany
| |
Collapse
|
|
43
|
Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with gastric cancer and peritoneal carcinomatosis. Eur J Surg Oncol 2018; 44:1805-1810. [PMID: 30087071 DOI: 10.1016/j.ejso.2018.06.036] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Revised: 05/23/2018] [Accepted: 06/27/2018] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Gastric Cancer (GC) with Peritoneal Carcinomatosis (PC) has long been regarded as a terminal disease. Over the past two decades, cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has changed the traditional concept of peritoneal metastases from being a systemic disease, to being considered a locoregional dissemination. PATIENTS AND METHODS A prospective study was performed at a high-volume Carcinomatosis Center to evaluate survival, morbi-mortality and prognostic factors for survival in a cohort of patients with GC and PC treated with CRS + HIPEC between June 2006 and December 2016. RESULTS Thirty-five patients were included in the study. Median follow-up was 54 months. Postoperative major complications (>grade IIIa) occurred in 25.7% of patients, including 2 deaths (mortality 5.7%). The median overall survival (OS) was 16 months and the 1-, 3- and 5-year OS rates were 70.8%, 21.3% and 21.3% %, respectively. The median OS for patients with PCI ≤6 was 19 months, in contrast to 12 months for the 19 patients with PCI >6. Three patients were included with only a positive cytology and their median OS was not reached. Perineural invasion was the only factor that had a negative influence in prognosis (HR 18.8) in multivariate analysis. CONCLUSION Although GC with PC still has a poor prognosis, survival has improved in selected patients with CRS + HIPEC and perioperative systemic chemotherapy. Patients with isolated positive cytology or peritoneal carcinomatosis with PCI less than 6 had encouraging survival rates.
Collapse
|
|
44
|
Efficacy of a docetaxel-5FU-oxaliplatin regimen (TEFOX) in first-line treatment of advanced gastric signet ring cell carcinoma: an AGEO multicentre study. Br J Cancer 2018; 119:424-428. [PMID: 29872148 PMCID: PMC6133962 DOI: 10.1038/s41416-018-0133-7] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2018] [Revised: 05/02/2018] [Accepted: 05/08/2018] [Indexed: 02/08/2023] Open
Abstract
Background Triplet chemotherapy, with docetaxel-5FU-oxaliplatin (TEFOX), has
yielded promising results in patients with advanced and operable gastric
adenocarcinoma. This may prove useful in treating signet ring cell carcinoma
(SRCC), which is known to be chemoresistant and has a poor prognosis. We therefore
evaluated TEFOX in patients with untreated advanced SRCC. Methods Patients with metastatic or locally advanced non-resectable SRCC
were treated with TEFOX. Chemotherapy was administered every 14 days, with
combined docetaxel (50 mg/m2) and oxaliplatin
(85 mg/m2) followed by 5FU
(2400 mg/m2). Results Among 65 patients enrolled, including 17 with linitis plastica, ORR
and DCR were 66.1% and 87.6%, respectively. Median PFS and OS were 9.7 months (95%
CI [6.9–11.4]) and 14.3 months (95% CI [11.6–21.6]) respectively. Twenty-six
patients (40%) initially considered as unresectable had secondary resection
(n = 24) or radiotherapy (n = 2) with curative intent, with median PFS and OS of
12.4 and 26.2 months, respectively. Conclusions TEFOX appears to be effective as first-line treatment in advanced
gastric SRCC and has an acceptable safety profile. It allowed a curative intent
approach in 40% of patients. Considering the low chemosensitivity of SRCC reported
with other chemotherapy regimens and pending for randomised studies, TEFOX might
be an option in advanced gastric SRCC.
Collapse
|
|
45
|
Ji ZH, Peng KW, Yu Y, Li XB, Yonemura Y, Liu Y, Sugarbaker PH, Li Y. Current status and future prospects of clinical trials on CRS + HIPEC for gastric cancer peritoneal metastases. Int J Hyperthermia 2018; 33:562-570. [PMID: 28124576 DOI: 10.1080/02656736.2017.1283065] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
PURPOSE There is no standard treatment for peritoneal metastases (PM) from gastric cancer (GC). The aim of this review is to evaluate the clinical trials on cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for GC PM. MATERIALS AND METHODS The published clinical trials on CRS + HIPEC for GC PM are critically evaluated, and survival and safety are the primary endpoints. In addition, the registered ongoing clinical trials are summarised. RESULTS The natural course of GC PM is <5 months. CRS + HIPEC could improve the overall survival (OS). In prospective studies, the median OS was 11.0 months in the CRS + HIPEC group vs. 5.4 months in the CRS alone group. In case-control studies, the median OS was 13.3 months in the CRS + HIPEC group vs. 7.9 months in the CRS alone group. In cohort studies, the median OS after CRS + HIPEC was 13.3. The median 1-, 2- and 5-year survival rates after CRS + HIPEC were 50.0%, 35.8% and 13.0%, respectively. There is no statistically significant increase in serious adverse events that are directly attributed to CRS + HIPEC. CONCLUSIONS The combination of CRS and HIPEC is a promising integrated treatment strategy for GC PM that has encouraging initial results, calling for urgent further evaluation of this strategy in randomised control trials (RCTs).
Collapse
Affiliation(s)
- Zhong-He Ji
- a Department of Peritoneal Cancer Surgery , Beijing Shijitan Hospital, Capital Medical University , Beijing , China
| | - Kai-Wen Peng
- b Department of Oncology , Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center , Wuhan , China
| | - Yang Yu
- a Department of Peritoneal Cancer Surgery , Beijing Shijitan Hospital, Capital Medical University , Beijing , China
| | - Xin-Bao Li
- a Department of Peritoneal Cancer Surgery , Beijing Shijitan Hospital, Capital Medical University , Beijing , China
| | - Yutaka Yonemura
- c NPO Organization to Support Peritoneal Dissemination Treatment , Kishiwada, Osaka , Japan
| | - Yang Liu
- c NPO Organization to Support Peritoneal Dissemination Treatment , Kishiwada, Osaka , Japan
| | | | - Yan Li
- a Department of Peritoneal Cancer Surgery , Beijing Shijitan Hospital, Capital Medical University , Beijing , China.,b Department of Oncology , Zhongnan Hospital of Wuhan University, Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center , Wuhan , China
| |
Collapse
|
|
46
|
Seshadri RA, Mehta AM. Role of HIPEC in the Prevention of Peritoneal Metastasis from Colorectal, Gastric and Appendiceal Cancer. MANAGEMENT OF PERITONEAL METASTASES- CYTOREDUCTIVE SURGERY, HIPEC AND BEYOND 2018:15-30. [DOI: 10.1007/978-981-10-7053-2_2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
47
|
Management of peritoneal surface malignancies in laparoscopic era: a concise review. INTERNATIONAL JOURNAL OF SURGERY-ONCOLOGY 2017; 1:e05. [PMID: 29177208 PMCID: PMC5673112 DOI: 10.1097/ij9.0000000000000005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 10/10/2016] [Accepted: 10/10/2016] [Indexed: 11/28/2022]
Abstract
Peritoneal carcinomatosis is seldom curable. Maximal cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy has been used in efforts to improve survival. There has been a recent explosion of interest in this modality of treatment with various centers employing its use throughout the world. This is a complex procedure associated with significant morbidity and mortality. This makes patient selection very critical and hence there has been immense interest in the evaluation of various prognostic indicators being evaluated. In addition, with the advent of minimally invasive surgery, laparoscopy is being increasingly utilized in different capacity. Newer indications for treatment and possible prevention of peritoneal carcinomatosis are being evaluated especially in colorectal cancer. The aim of this brief review is to synthesize and present the recent data available regarding the outcomes and evolving trends associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
Collapse
|
|
48
|
Ni X, Wu P, Wu J, Ji M, Tian B, Jiang Z, Sun Y, Xing X, Jiang J, Wu C. Hyperthermic intraperitoneal perfusion chemotherapy and response evaluation in patients with gastric cancer and malignant ascites. Oncol Lett 2017; 14:1691-1696. [PMID: 28789396 DOI: 10.3892/ol.2017.6342] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2015] [Accepted: 03/03/2017] [Indexed: 12/11/2022] Open
Abstract
The present study describes the use of bidirectional chemotherapy in the treatment of patients with gastric cancer and peritoneal carcinomatosis (PC), using newly developed response criteria for the treatment of malignant ascites. In addition, the association between effusion response and survival was analyzed. Between June 2010 and May 2014, patients affected by malignant ascites secondary to unresectable PC of gastric origin were treated with a combination of systemic and loco-regional chemotherapy. Cisplatin (75 mg/m2) at an inflow temperature of 43°C was infused intraperitoneally, and docetaxel (75 mg/m2) was infused simultaneously via a peripheral vein, on day 1 every 3 weeks. The primary endpoint was overall survival rate, and the secondary endpoint was efficacy against malignant ascites using new response criteria. In total, 41 patients were enrolled, the majority of whom received 6 cycles of intraperitoneal chemotherapy in combination with hyperthermia. The majority of patients exhibited clinical regression of ascites and relief of associated symptoms. Malignant ascites disappeared [complete response (CR)] or decreased by 50% [partial response (PR)] in 73.2% of patients. No mortalities associated with the procedures occurred. The median survival time was 8.6 months, and the 1-year survival rate was 24.4%. As these new response criteria for the treatment of malignant ascites were found to be feasible, bidirectional chemotherapy may be the preferred strategy for the treatment of gastric cancer with PC. The CR, PR and non-PR groups showed significant differences in overall survival, indicating that decreased effusion was associated with improved patient survival.
Collapse
Affiliation(s)
- Xuefeng Ni
- Department of Oncology, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| | - Ping Wu
- Department of Pharmacology, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| | - Jun Wu
- Department of Oncology, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| | - Mei Ji
- Department of Oncology, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| | - Bo Tian
- Department of Pathology, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| | - Zhenxing Jiang
- Department of Radiology, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| | - Yue Sun
- Department of Ultrasonography, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| | - Xiaoxiao Xing
- Department of Ultrasonography, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| | - Jingting Jiang
- Department of Oncology, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| | - Changping Wu
- Department of Oncology, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu 213003, P.R. China
| |
Collapse
|
|
49
|
Tan HL, Chia CS, Tan GHC, Choo SP, Tai DWM, Chua CWL, Ng MCH, Soo KC, Teo MCC. Gastric peritoneal carcinomatosis - a retrospective review. World J Gastrointest Oncol 2017; 9:121-128. [PMID: 28344747 PMCID: PMC5348627 DOI: 10.4251/wjgo.v9.i3.121] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Revised: 12/13/2016] [Accepted: 01/03/2017] [Indexed: 02/05/2023] Open
Abstract
AIM To characterize patients with gastric peritoneal carcinomatosis (PC) and their typical clinical and treatment course with palliative systemic chemotherapy as the current standard of care.
METHODS We performed a retrospective electronic chart review of all patients with gastric adenocarcinoma with PC diagnosed at initial metastatic presentation between January 2010 and December 2014 in a single tertiary referral centre.
RESULTS We studied a total of 271 patients with a median age of 63.8 years and median follow-up duration of 5.1 mo. The majority (n = 217, 80.1%) had the peritoneum as the only site of metastasis at initial presentation. Palliative systemic chemotherapy was eventually planned for 175 (64.6%) of our patients at initial presentation, of which 171 were initiated on it. Choice of first-line regime was in accordance with the National Comprehensive Cancer Network Guidelines for Gastric Cancer Treatment. These patients underwent a median of one line of chemotherapy, completing a median of six cycles in total. Chemotherapy disruption due to unplanned hospitalizations occurred in 114 (66.7%), while cessation of chemotherapy occurred in 157 (91.8%), with 42 cessations primarily attributable to PC-related complications. Patients who had initiation of systemic chemotherapy had a significantly better median overall survival than those who did not (10.9 mo vs 1.6 mo, P < 0.001). Of patients who had initiation of systemic chemotherapy, those who experienced any disruptions to chemotherapy due to unplanned hospitalizations had a significantly worse median overall survival compared to those who did not (8.7 mo vs 14.6 mo, P < 0.001).
CONCLUSION Gastric PC carries a grim prognosis with a clinical course fraught with disease-related complications which may attenuate any survival benefit which palliative systemic chemotherapy may have to offer. As such, investigational use of regional therapies is warranted and required validation in patients with isolated PC to maximize their survival outcomes in the long run.
Collapse
|
|
50
|
Kobayashi D, Kodera Y. Intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis. Gastric Cancer 2017; 20:111-121. [PMID: 27803990 DOI: 10.1007/s10120-016-0662-9] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Accepted: 10/15/2016] [Indexed: 02/07/2023]
Abstract
Peritoneal metastasis is the most frequent pattern of gastric cancer recurrence or metastasis and is a definitive determinant of prognosis. However, an effective means of treating peritoneal disease has not yet been established. Systemic chemotherapy has only a limited effect on peritoneal metastasis, although some progress has been shown in terms of median survival time, especially among patients with a minimal or moderate disease burden. Clinical research related to intraperitoneal administration of anticancer drugs is currently underway. An advantage of intraperitoneal chemotherapy is the ability to achieve high concentrations of anticancer drugs in the peritoneal cavity and the direct exposure of peritoneal deposits and free cancer cells to those drugs. In addition, pharmacokinetic studies with taxanes have shown that these high intraperitoneal drug concentrations are sustained for a considerable length of time, allowing prolonged exposure. As taxanes are the most appropriate drugs for intraperitoneal administration, the development of repeated intraperitoneal chemotherapy using taxanes for gastric cancer peritoneal metastasis-either alone or in combination with systemic chemotherapy-has taken place over the past decade, mostly in Japan. Several phase II trials and a phase III trial have recently demonstrated the efficacy of this therapy, including median survival times of 14.4-24.6 months and one-year overall survival rates of 67-91%. These results may lead to the approval of intraperitoneal taxanes, especially paclitaxel, for official insurance coverage in the near future.
Collapse
Affiliation(s)
- Daisuke Kobayashi
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
| | - Yasuhiro Kodera
- Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan
| |
Collapse
|