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Havan N, Gülmez S, Senger AS, Uzun O, Dinçer M, Özduman Ö, Avan D, Polat A, Polat E, Duman M. Influence of the effectiveness of sarcopenia on postoperative major complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal surface malignancy: a retrospective cohort study. Int J Colorectal Dis 2025; 40:96. [PMID: 40257575 PMCID: PMC12011962 DOI: 10.1007/s00384-025-04863-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/09/2025] [Indexed: 04/22/2025]
Abstract
BACKGROUND AND PURPOSE Sarcopenia has recently been gaining importance due to its role on mortality and mobility in diseases and operations. In this study, we aimed to evaluate the effect of sarcopenia on major postoperative complications in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal surface malignancy. METHODS In this longitudinal cohort study included 202 patients treated between January 2018 and September 2023, with 52 undergoing prophylactic procedures. Peritoneal metastases originated from colorectal, gastric, and ovarian cancer; peritoneal mesothelioma; mucinous adenocarcinoma of the appendix; and endometrial cancer. Age, sex, body mass index (BMI), length of hospital stay (LOS), peritoneal cancer index (PCI), competency of cytoreduction (CC), operation time, and primary peritoneal carcinomatosis were recorded. All variables were analyzed according to the presence of major complications and sarcopenia. RESULTS Significant associations were found between major complications and sarcopenia (p = 0.002), PCI (p = 0.036), operation time (p = 0.015), and LOS (p < 0.001). In sarcopenic patients, significant associations were found with sex (p = 0.035), age (p = 0.025), and BMI (p = 0.001). Multivariate Cox regression analysis identified sarcopenia as an independent risk factor for major complications, tripling the likelihood (p = 0.005). Additionally, PCI score (p = 0.008) and LOS (p < 0.001) were independent risk factors. CONCLUSION This study underscores sarcopenia as an independent risk factor for major complications in CRS/HIPEC patients, with PCI and LOS as additional risk factors. In sarcopenic patients, pre-operative evaluation should be done carefully and post-operative risks should be kept in mind.
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Affiliation(s)
- Nuri Havan
- Department of Radiology, Istanbul Florence Nightingale Ataşehir Hospital, Atasehir, Istanbul, Turkey.
| | - Selçuk Gülmez
- Department of Gastroenterology Surgery, Istanbul KoşUyolu High Specialization Education and Research Hospital, Istanbul, Turkey
| | - Aziz Serkan Senger
- Department of Gastroenterology Surgery, Istanbul KoşUyolu High Specialization Education and Research Hospital, Istanbul, Turkey
| | - Orhan Uzun
- Department of Gastroenterology Surgery, Istanbul KoşUyolu High Specialization Education and Research Hospital, Istanbul, Turkey
| | - Mürşit Dinçer
- Department of Gastroenterology Surgery, Istanbul KoşUyolu High Specialization Education and Research Hospital, Istanbul, Turkey
| | - Ömer Özduman
- Department of Gastroenterology Surgery, Istanbul KoşUyolu High Specialization Education and Research Hospital, Istanbul, Turkey
| | - Deniz Avan
- Department of Anaesthesia and Reanimation, Istanbul KoşUyolu High Specialization Education and Research Hospital, Istanbul, Turkey
| | - Aytaç Polat
- Department of Anaesthesia and Reanimation, Istanbul KoşUyolu High Specialization Education and Research Hospital, Istanbul, Turkey
| | - Erdal Polat
- Department of Gastroenterology Surgery, Istanbul KoşUyolu High Specialization Education and Research Hospital, Istanbul, Turkey
| | - Mustafa Duman
- Department of Gastroenterology Surgery, Istanbul KoşUyolu High Specialization Education and Research Hospital, Istanbul, Turkey
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Hu Y, Gao T, Wang X, Zhang Q, Wang S, Liu P, Guan L. Effect of glucose-insulin-potassium on lactate levels at the end of surgery in patients undergoing cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: study protocol for a randomized controlled trial. Trials 2024; 25:708. [PMID: 39438970 PMCID: PMC11515742 DOI: 10.1186/s13063-024-08161-2] [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: 05/25/2023] [Accepted: 05/07/2024] [Indexed: 10/25/2024] Open
Abstract
INTRODUCTION Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been established as an effective treatment for peritoneal cancer (PC). However, this kind of combination therapy is associated with a high lactate level. Moreover, studies have suggested that the rate of complications early after surgery directly increased with elevated lactate levels. Glucose-insulin-potassium (GIP), a potent cardioprotective intervention, has been demonstrated to adjust blood glucose (BG) levels and reduce lactate levels. However, the insulin-glucose ratio should be adjusted according to the surgery performed. Here, we aimed to evaluate the advantages of using modified GIP during CRS/HIPEC to reduce the lactate level at the end of surgery and further reduce the incidence of early postoperative complications. METHODS AND ANALYSIS The modified GIP versus conventional management during surgery study is a single-center, randomized, single-blinded outcome assessment clinical trial of 80 patients with PC who are between 18 and 64 years old and undergoing CRS/HIPEC. Participants will be randomly allocated to receive modified GIP or conventional treatment (1:1). The primary outcome will be the plasma lactate level at the end of surgery. The secondary outcomes will include the highest levels and fluctuation ranges of lactate and BG during surgery, extubation time, APACHE-II score 24 h after surgery, postoperative defecation and exhaust time, postoperative lactate clearance time, postoperative liver and kidney function, incidence of complications within 7 days after surgery, length of intensive care unit stay (LIS), length of hospital stay (LHS), and total cost of hospitalization. ETHICS AND DISSEMINATION The trial protocol was approved by the Scientific Research Ethics Committee of Beijing Shijitan Hospital Affiliated with Capital Medical University, approval number sjtky11-1x-2022(118). The results will be published in international peer-reviewed journals. TRIAL REGISTRATION ChiCTR2200057258. Registered on March 5, 2022.
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Affiliation(s)
- Yanting Hu
- Department of Anaesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
| | - Teng Gao
- Department of Anaesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
- Peking University Health Science Center, Beijing, China
| | | | - Qing Zhang
- Department of Anaesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
| | - Shaoheng Wang
- Department of Anaesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
| | - Pengfei Liu
- Department of Anaesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China
| | - Lei Guan
- Department of Anaesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China.
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Gurusamy K, Leung J, Vale C, Roberts D, Linden A, Wei Tan X, Taribagil P, Patel S, Pizzo E, Davidson B, Mould T, Saunders M, Aziz O, O'Dwyer S. Hyperthermic intraoperative peritoneal chemotherapy and cytoreductive surgery for people with peritoneal metastases: a systematic review and cost-effectiveness analysis. Health Technol Assess 2024; 28:1-139. [PMID: 39254852 PMCID: PMC11417642 DOI: 10.3310/kwdg6338] [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: 09/11/2024] Open
Abstract
Background We compared the relative benefits, harms and cost-effectiveness of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery ± systemic chemotherapy versus cytoreductive surgery ± systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric or ovarian cancers by a systematic review, meta-analysis and model-based cost-utility analysis. Methods We searched MEDLINE, EMBASE, Cochrane Library and the Science Citation Index, ClinicalTrials.gov and WHO ICTRP trial registers until 14 April 2022. We included only randomised controlled trials addressing the research objectives. We used the Cochrane risk of bias tool version 2 to assess the risk of bias in randomised controlled trials. We used the random-effects model for data synthesis when applicable. For the cost-effectiveness analysis, we performed a model-based cost-utility analysis using methods recommended by The National Institute for Health and Care Excellence. Results The systematic review included a total of eight randomised controlled trials (seven randomised controlled trials, 955 participants included in the quantitative analysis). All comparisons other than those for stage III or greater epithelial ovarian cancer contained only one trial, indicating the paucity of randomised controlled trials that provided data. For colorectal cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably results in little to no difference in all-cause mortality (60.6% vs. 60.6%; hazard ratio 1.00, 95% confidence interval 0.63 to 1.58) and may increase the serious adverse event proportions compared to cytoreductive surgery ± systemic chemotherapy (25.6% vs. 15.2%; risk ratio 1.69, 95% confidence interval 1.03 to 2.77). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone (40.8% vs. 60.8%; hazard ratio 0.55, 95% confidence interval 0.32 to 0.95). For gastric cancer, there is high uncertainty about the effects of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy versus cytoreductive surgery + systemic chemotherapy or systemic chemotherapy alone on all-cause mortality. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to cytoreductive surgery + systemic chemotherapy (46.3% vs. 57.4%; hazard ratio 0.73, 95% confidence interval 0.57 to 0.93). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy may not be cost-effective versus cytoreductive surgery + systemic chemotherapy for colorectal cancer but may be cost-effective for the remaining comparisons. Limitations We were unable to obtain individual participant data as planned. The limited number of randomised controlled trials for each comparison and the paucity of data on health-related quality of life mean that the recommendations may change as new evidence (from trials with a low risk of bias) emerges. Conclusions In people with peritoneal metastases from colorectal cancer with limited peritoneal metastases and who are likely to withstand major surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should not be used in routine clinical practice (strong recommendation). There is considerable uncertainty as to whether hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy or cytoreductive surgery + systemic chemotherapy should be offered to patients with gastric cancer and peritoneal metastases (no recommendation). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should be offered routinely to women with stage III or greater epithelial ovarian cancer and metastases confined to the abdomen requiring and likely to withstand interval cytoreductive surgery after chemotherapy (strong recommendation). Future work More randomised controlled trials are necessary. Study registration This study is registered as PROSPERO CRD42019130504. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/135/02) and is published in full in Health Technology Assessment; Vol. 28, No. 51. See the NIHR Funding and Awards website for further award information.
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Affiliation(s)
- Kurinchi Gurusamy
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Jeffrey Leung
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Claire Vale
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Danielle Roberts
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Audrey Linden
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Xiao Wei Tan
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Priyal Taribagil
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Sonam Patel
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Elena Pizzo
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Brian Davidson
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Tim Mould
- Department of Gynaecological Oncology, University College London NHS Foundation Trust, London, UK
| | - Mark Saunders
- Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
| | - Omer Aziz
- Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
- Institute of Cancer Sciences, University of Manchester, Manchester, UK
| | - Sarah O'Dwyer
- Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
- Institute of Cancer Sciences, University of Manchester, Manchester, UK
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Gurusamy K, Leung J, Vale C, Roberts D, Linden A, Tan XW, Taribagil P, Patel S, Pizzo E, Davidson B, Saunders M, Aziz O, O’Dwyer ST. Cytoreductive surgery plus hyperthermic intraoperative peritoneal chemotherapy for people with peritoneal metastases from colorectal, ovarian or gastric origin: A systematic review of randomized controlled trials. World J Surg 2024; 48:1385-1403. [PMID: 38658171 PMCID: PMC7617159 DOI: 10.1002/wjs.12186] [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: 11/20/2023] [Accepted: 03/10/2024] [Indexed: 04/26/2024]
Abstract
BACKGROUND There is uncertainty in the relative benefits and harms of hyperthermic intraoperative peritoneal chemotherapy (HIPEC) when added to cytoreductive surgery (CRS) +/- systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric, or ovarian cancers. METHODS We searched randomized controlled trials (RCTs) in the medical literature until April 14, 2022 and applied methods used for high-quality systematic reviews. FINDINGS We included a total of eight RCTs (seven RCTs included in quantitative analysis as one RCT did not provide data in an analyzable format). All comparisons other than ovarian cancer contained only one trial. For gastric cancer, there is high uncertainty about the effect of CRS + HIPEC + systemic chemotherapy. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, CRS + HIPEC + systemic chemotherapy probably decreases all-cause mortality compared to CRS + systemic chemotherapy. For colorectal cancer, CRS + HIPEC + systemic chemotherapy probably results in little to no difference in all-cause mortality and may increase the serious adverse events proportions compared to CRS +/- systemic chemotherapy, but probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone. INTERPRETATION The role of CRS + HIPEC in gastric peritoneal metastases is uncertain. CRS + HIPEC should be standard of care in women with stage III or greater epithelial ovarian cancer undergoing interval CRS. CRS + systemic chemotherapy should be standard of care for people with colorectal peritoneal metastases, with HIPEC given only as part of a RCT focusing on subgroups and regimes. PROSPERO REGISTRATION CRD42019130504.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | - Mark Saunders
- The Colorectal and Peritoneal Oncology Centre, Christie NHS Foundation Trust, London, UK
| | - Omer Aziz
- The Colorectal and Peritoneal Oncology Centre, Christie NHS Foundation Trust, London, UK
- Division of Cancer Studies, University of Manchester, London, UK
| | - Sarah T. O’Dwyer
- The Colorectal and Peritoneal Oncology Centre, Christie NHS Foundation Trust, London, UK
- Division of Cancer Studies, University of Manchester, London, UK
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Sullivan KM, Whelan RL, DePeralta D, Merchea A, Dellinger T, Raoof M. Reply to Letter to the Editor Concerning "Safety and Efficacy of Oxaliplatin Pressurized Intraperitoneal Aerosolized Chemotherapy (PIPAC) in Colorectal and Appendiceal Cancer with Peritoneal Metastases: Results of a Multicenter Phase I Trial in the USA". Ann Surg Oncol 2024; 31:2408-2409. [PMID: 38245647 DOI: 10.1245/s10434-024-14934-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2023] [Accepted: 01/04/2024] [Indexed: 01/22/2024]
Affiliation(s)
- Kevin M Sullivan
- Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
| | | | | | - Amit Merchea
- Department of Surgery, Mayo Clinic, Jacksonville, FL, USA
| | - Thanh Dellinger
- Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
| | - Mustafa Raoof
- Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA.
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Sood A, Rudzinski JK, Labbate CV, Hensley PJ, Bree KK, Guo CC, Alhalabi O, Campbell MT, Siefker-Radtke AO, Navai N, Dinney CPN, Gao J, Kamat AM. Long-Term Oncological Outcomes in Patients Diagnosed With Nonmetastatic Plasmacytoid Variant of Bladder Cancer: A 20-Year University of Texas MD Anderson Cancer Center Experience. J Urol 2024; 211:241-255. [PMID: 37922370 DOI: 10.1097/ju.0000000000003778] [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: 01/02/2023] [Accepted: 10/30/2023] [Indexed: 11/05/2023]
Abstract
PURPOSE The treated natural history of nonmetastatic plasmacytoid variant of bladder cancer (PV-BCa) is poorly understood owing to its rarity. We sought to examine the disease recurrence and metastasis patterns in this select group of patients in order to identify opportunities for intervention. MATERIALS AND METHODS We conducted a natural language processing algorithm-augmented retrospective chart review of 56 consecutive patients who were treated with curative intent for nonmetastatic PV-BCa at our institution between 1998 and 2018. Kaplan-Meier and multivariable Cox regression methods were used for survival analyses. RESULTS The stage at presentation was: ≤ cT2N0 in 22 (39.3%), cT3N0 in 15 (26.8%), cT4N0 in 13 (23.2%), and ≥ cN1 in 6 patients (10.7%). Forty-nine patients (87.5%) received chemotherapy, and 42 (75%) were able to undergo the planned surgery. Notably, only 4 patients (7.2%) had pT0 stage, while 22 (52.4%) had pN+ disease at the time of surgery. At 36-month follow-up, 28.4% of patients (95% CI: 22.1%-34.5%) were alive and 22.2% (95% CI: 16.1%-28.5%) were free of metastatic disease. The benefit of surgical extirpation was stage specific: successful completion of surgery was associated with improved metastasis-free survival (at 36 months 32.4% vs 0%, log-rank P < .001) in patients with localized or locally advanced disease (≤cT2N0/cT3N0); however, in patients with regionally advanced disease (cT4N0/≥cN1), consolidative surgery following chemotherapy was not associated with improved metastasis-free survival (12.5% vs 10% at 36 months, log-rank P = .49). The median time to metastasis from primary treatment end was 6.5 months (IQR: 2.9-14.7). The predominant site of recurrence/metastasis was the peritoneum (76.1%), either in isolation or along with extraperitoneal lesions. Salvage immunotherapy in these patients significantly reduced the risk of death (HR = 0.11, P = .001). CONCLUSIONS PV-BCa is a disease with high lethality. Despite multimodal treatment, a vast majority of patients develop atypical intraperitoneal metastasis soon after therapy and rapidly succumb to it. Clinical trials evaluating utility of hyperthermic intraperitoneal chemotherapy and/or immunotherapy may be warranted in this high-risk population.
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Affiliation(s)
- Akshay Sood
- Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas
- Department of Urology, The James Cancer Hospital and Solove Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio
| | - Jan K Rudzinski
- Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Craig V Labbate
- Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Patrick J Hensley
- Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Kelly K Bree
- Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Charles C Guo
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Omar Alhalabi
- Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Matthew T Campbell
- Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Arlene O Siefker-Radtke
- Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Neema Navai
- Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Colin P N Dinney
- Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jianjun Gao
- Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ashish M Kamat
- Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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Kongsgaard UE, Menchini RJ, Larsen SG, Juul-Hansen KE. Skin conductance algesimeter is unreliable during sudden perioperative temperature increases. Scand J Pain 2024; 24:sjpain-2023-0106. [PMID: 38607365 DOI: 10.1515/sjpain-2023-0106] [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: 09/27/2023] [Accepted: 03/25/2024] [Indexed: 04/13/2024]
Abstract
OBJECTIVES Pain assessment in anesthetized and non-communicative patients remains a challenge. Clinical signs such as tachycardia, hypertension, sweat and tears, have a low specificity for pain and should therefore ideally be replaced by more specific monitoring techniques. Skin conductance variability has been demonstrated to establish a patients' sensitivity to pain, but may be influenced by temperature changes that leads to profuse sweating. The aim of this pilot study was to test skin conductance changes during sudden temperature changes due to hyperthermic intraperitoneal chemotherapy (HIPEC) perfusation. METHODS We investigated skin conductance algesimeter (SCA) in ten consecutive patients undergoing cytoreductive surgery and HIPEC. Results from the SCA was compared to other standard physiological variables at seven time points during the surgical procedure, in particular during the period with hyperthermic intraabdominal perfusion leading to an increase in the patients core temperature. RESULTS Nine out of ten patients had an increase in the SCA measurements during the HIPEC phase correlating the increase in temperature. CONCLUSION SCA is unreliable to detect increased pain sensation during sudden perioperative temperature changes in adult patients.
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Affiliation(s)
- Ulf E Kongsgaard
- Department of Anaesthesia, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
- Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Robin Johansen Menchini
- Department of Anaesthesia, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Stein Gunnar Larsen
- Department of Gastroenterological Surgery, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Knut Erling Juul-Hansen
- Department of Anaesthesia, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
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Mac Curtain BM, Qian W, Temperley HC, Simpkin AJ, Ng ZQ. Incisional hernias post cytoreductive surgery/peritonectomy and hyperthermic intraperitoneal chemotherapy: a systematic review and meta-analysis. Hernia 2023; 27:1067-1083. [PMID: 37653188 PMCID: PMC10533625 DOI: 10.1007/s10029-023-02859-z] [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: 06/18/2023] [Accepted: 08/07/2023] [Indexed: 09/02/2023]
Abstract
PURPOSE Cytoreductive surgery (CRS) is often combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal tumour deposits. Considering CRS, the evidence relating the large incisions, local chemotherapy and abdominal wall trauma to incisional hernias (IH) has not been synthesized. This systematic review and meta-analysis was conducted to examine the proportion of IH present in patients post CRS and the effect HIPEC had on these rates. METHODS PubMed, EMBASE, and Cochrane Central Registry of Trials were searched up to June 2023 to examine studies relating IH and CRS plus or minus HIPEC. The most up to date PRISMA guidelines were followed. Pertinent clinical information was synthesized in tabular form. A meta-analysis reporting the pooled proportions of IH post CRS plus or minus HIPEC, the odds of IH in HIPEC versus non-HIPEC CRS and the difference in follow-up time between groups was conducted. RESULTS Nine studies comprising 1416 patients were included. The pooled proportion of IH post CRS was 12% (95% confidence interval (CI) 8-16%) in HIPEC and 7% (95% CI 4-10%) in non-HIPEC patients and 11% (95% CI 7-14%) overall. Previously reported rates of IH in midline laparotomy range from 10 to 30%. The odds of IH in the HIPEC was 1.9 times higher compared to non-HIPEC cohorts however this was not statistically significant (odds ratio (OR) 1.9, 95% 0.7-5.2; p = 0.21). There was no significant difference in average follow-up times between HIPEC and non-HIPEC cohorts. CONCLUSIONS IH post CRS plus or minus HIPEC were in the expected range for midline laparotomies. IH in patients receiving HIPEC may occur at a greater proportion than in non-HIPEC patients, however, there were too few studies in our meta-analysis to determine this with statistical significance.
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Affiliation(s)
- B M Mac Curtain
- School of Medicine, University of Galway, Galway, Ireland.
- Department of Surgery, St John of God Subiaco Hospital, Subiaco, WA, Australia.
| | - W Qian
- Department of Surgery, St John of God Subiaco Hospital, Subiaco, WA, Australia
| | - H C Temperley
- Department of Surgery, St John of God Subiaco Hospital, Subiaco, WA, Australia
| | - A J Simpkin
- School of Mathematical and Statistical Sciences, University of Galway, Galway, Ireland
| | - Z Q Ng
- Department of General Surgery, Royal Perth Hospital, Perth, WA, Australia
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Khosrawipour C, Diakun A, Li S, Lau H, Kulas J, Khosrawipour V, Kielan W, Mikolajczyk-Martinez A. Triple-Therapy of Peritoneal Metastasis-Partial-Dehydration under Hyperthermic Condition Combined with Chemotherapy: The First Preliminary In-Vitro Results. Pharmaceuticals (Basel) 2023; 16:ph16050763. [PMID: 37242546 DOI: 10.3390/ph16050763] [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: 03/24/2023] [Revised: 05/14/2023] [Accepted: 05/16/2023] [Indexed: 05/28/2023] Open
Abstract
A newly introduced combination of intraperitoneal dehydration and hyperthermia has recently been shown to be feasible and cytotoxic for colon cancer cells in vivo. For the first time, our study now aims to evaluate dehydration under hyperthermic conditions combined with chemotherapy for potential use in the clinical setting. In this study, in vitro colon cancer cells (HT-29) were subjected to single or several cycles of partial dehydration under hyperthermic conditions (45 °C), followed by chemotherapy (triple exposure) with oxaliplatin or doxorubicin in various configurations. The viability, cytotoxicity, and proliferation of cells after the proposed protocols were assessed. Intracellular doxorubicin uptake was measured via flow cytometry. After one cycle of triple exposure, the viability of HT-29 cells was significantly reduced versus the untreated control (65.11 ± 5%, p < 0.0001) and versus only chemotherapy (61.2 ± 7%, p < 0.0001). An increased chemotherapeutic inflow into the cells after triple exposure was detected (53.4 ± 11%) when compared to cells treated with chemotherapy alone (34.23 ± 10%) (p < 0.001). Partial dehydration in a hyperthermic condition combined with chemotherapy increases the overall cytotoxicity of colon cancer cells significantly compared to chemotherapy alone. This could possibly be related to enhanced intracellular uptake of chemotherapeutic agents after partial dehydration. Further studies are required for the further evaluation of this new concept.
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Affiliation(s)
| | - Agata Diakun
- 2nd Department of General Surgery and Surgical Oncology, Wroclaw Medical University, 50-367 Wroclaw, Poland
| | - Shiri Li
- Division of Colon and Rectal Surgery, Department of Surgery, New York Presbyterian Hospital-Weill Cornell College of Medicine, New York, NY 10065, USA
| | - Hien Lau
- Department of Surgery, University of California Irvine (UCI)-Medical Center, Irvine, CA 92868, USA
| | - Joanna Kulas
- Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland
| | - Veria Khosrawipour
- 2nd Department of General Surgery and Surgical Oncology, Wroclaw Medical University, 50-367 Wroclaw, Poland
- Department of Surgery, Petrus-Hospital Wuppertal, 42283 Wuppertal, Germany
| | - Wojciech Kielan
- 2nd Department of General Surgery and Surgical Oncology, Wroclaw Medical University, 50-367 Wroclaw, Poland
| | - Agata Mikolajczyk-Martinez
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland
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10
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Overchuk M, Weersink RA, Wilson BC, Zheng G. Photodynamic and Photothermal Therapies: Synergy Opportunities for Nanomedicine. ACS NANO 2023; 17:7979-8003. [PMID: 37129253 PMCID: PMC10173698 DOI: 10.1021/acsnano.3c00891] [Citation(s) in RCA: 394] [Impact Index Per Article: 197.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 05/03/2023]
Abstract
Tumoricidal photodynamic (PDT) and photothermal (PTT) therapies harness light to eliminate cancer cells with spatiotemporal precision by either generating reactive oxygen species or increasing temperature. Great strides have been made in understanding biological effects of PDT and PTT at the cellular, vascular and tumor microenvironmental levels, as well as translating both modalities in the clinic. Emerging evidence suggests that PDT and PTT may synergize due to their different mechanisms of action, and their nonoverlapping toxicity profiles make such combination potentially efficacious. Moreover, PDT/PTT combinations have gained momentum in recent years due to the development of multimodal nanoplatforms that simultaneously incorporate photodynamically- and photothermally active agents. In this review, we discuss how combining PDT and PTT can address the limitations of each modality alone and enhance treatment safety and efficacy. We provide an overview of recent literature featuring dual PDT/PTT nanoparticles and analyze the strengths and limitations of various nanoparticle design strategies. We also detail how treatment sequence and dose may affect cellular states, tumor pathophysiology and drug delivery, ultimately shaping the treatment response. Lastly, we analyze common experimental design pitfalls that complicate preclinical assessment of PDT/PTT combinations and propose rational guidelines to elucidate the mechanisms underlying PDT/PTT interactions.
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Affiliation(s)
- Marta Overchuk
- Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 1L7, Canada
- Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, North Carolina 27599, United States
| | - Robert A Weersink
- Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 1L7, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5G 1L7, Canada
- Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5G 1L7, Canada
| | - Brian C Wilson
- Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 1L7, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada
| | - Gang Zheng
- Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario M5G 1L7, Canada
- Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5G 1L7, Canada
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11
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Rao JS, Ivkov R, Sharma A. Nanoparticle-Based Interventions for Liver Transplantation. Int J Mol Sci 2023; 24:7496. [PMID: 37108659 PMCID: PMC10144867 DOI: 10.3390/ijms24087496] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 03/29/2023] [Accepted: 04/13/2023] [Indexed: 04/29/2023] Open
Abstract
Liver transplantation is the only treatment for hepatic insufficiency as a result of acute and chronic liver injuries/pathologies that fail to recover. Unfortunately, there remains an enormous and growing gap between organ supply and demand. Although recipients on the liver transplantation waitlist have significantly higher mortality, livers are often not allocated because they are (i) classified as extended criteria or marginal livers and (ii) subjected to longer cold preservation time (>6 h) with a direct correlation of poor outcomes with longer cold ischemia. Downregulating the recipient's innate immune response to successfully tolerate a graft having longer cold ischemia times or ischemia-reperfusion injury through induction of immune tolerance in the graft and the host would significantly improve organ utilization and post-transplant outcomes. Broadly, technologies proposed for development aim to extend the life of the transplanted liver through post-transplant or recipient conditioning. In this review, we focus on the potential benefits of nanotechnology to provide unique pre-transplant grafting and recipient conditioning of extended criteria donor livers using immune tolerance induction and hyperthermic pre-conditioning.
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Affiliation(s)
- Joseph Sushil Rao
- Division of Solid Organ Transplantation, Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA
- Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN 55455, USA
| | - Robert Ivkov
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
- Department of Oncology, Sydney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- Department of Mechanical Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
- Department of Materials Science and Engineering, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Anirudh Sharma
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
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Khan S, Baumgartner JM. ASO Author Reflections: Routine Omentectomy During Cytoreductive Surgery and HIPEC. Ann Surg Oncol 2023; 30:774-775. [PMID: 36367628 PMCID: PMC9807545 DOI: 10.1245/s10434-022-12775-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 10/27/2022] [Indexed: 11/13/2022]
Affiliation(s)
- Sohini Khan
- Division of Surgical Oncology, Department of Surgery, University of California San Diego, 3855 Health Sciences Dr. #0987, La Jolla, CA 92093-0987 USA
| | - Joel M. Baumgartner
- Division of Surgical Oncology, Department of Surgery, University of California San Diego, 3855 Health Sciences Dr. #0987, La Jolla, CA 92093-0987 USA
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13
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Khan S, Doan NH, Hosseini M, Kelly K, Veerapong J, Lowy AM, Baumgartner J. Is Routine Omentectomy a Necessary Component of Cytoreductive Surgery and HIPEC? Ann Surg Oncol 2023; 30:768-773. [PMID: 36305990 PMCID: PMC9807473 DOI: 10.1245/s10434-022-12714-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 10/04/2022] [Indexed: 01/10/2023]
Abstract
BACKGROUND Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastases traditionally includes omentectomy, even in the absence of visible omental metastases. We sought to determine the rate of occult histologic omental metastasis (OHOM), evaluate morbidity with omentectomy, and examine the rate of omental recurrence among patients undergoing CRS-HIPEC. METHODS All CRS-HIPEC procedures from August 2007 to August 2020 were included in this single-center, retrospective, cohort study. Procedures were divided into those that included greater omentectomy (OM) and those that did not (NOM). The incidence of OHOM was evaluated specifically among the OM group with a grossly normal omentum. Multivariate regression analyses were performed to evaluate return of bowel function, ileus, and morbidity in the OM and NOM groups. RESULTS Among 683 CRS-HIPEC procedures, 578 (84.6%) included omentectomy and 105 (15.4%) did not. The OM group had higher operative time, blood loss, peritoneal cancer index, number of visceral resections, and length of stay. In the OM group, 72 (12.5%) patients had a grossly normal omentum, and 23 (31.9%) of these had OHOM. Risk-adjusted return of bowel function, ileus, and 60-day complications were no different in the OM and NOM groups. Among 43 patients with residual omentum, 24 (55.8%) recurred, including 9 (20.9%) with omental recurrence. CONCLUSIONS Histologically occult metastasis was present in one-third of patients undergoing omentectomy during CRS-HIPEC. Omentectomy did not increase the rate of overall morbidity, and one-fifth of patients with residual omentum later developed omental recurrence. Thus, omentectomy is warranted in the absence of gross metastases during CRS-HIPEC.
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Affiliation(s)
- Sohini Khan
- Division of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA USA
| | - Nguyen-Huong Doan
- Division of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA USA
| | - Mojgan Hosseini
- Department of Pathology, University of California San Diego, La Jolla, CA USA
| | - Kaitlyn Kelly
- Department of Surgery, University of Wisconsin, Madison, WI USA
| | - Jula Veerapong
- Division of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA USA
| | - Andrew M. Lowy
- Division of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA USA
| | - Joel Baumgartner
- Division of Surgical Oncology, Department of Surgery, University of California San Diego, La Jolla, CA USA
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14
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Ammerata G, Filippo R, Laface C, Memeo R, Solaini L, Cavaliere D, Navarra G, Ranieri G, Currò G, Ammendola M. Hyperthermic intraperitoneal chemotherapy and colorectal cancer: From physiology to surgery. World J Clin Cases 2022; 10:10852-10861. [PMID: 36338235 PMCID: PMC9631165 DOI: 10.12998/wjcc.v10.i30.10852] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 06/23/2022] [Accepted: 08/13/2022] [Indexed: 02/05/2023] Open
Abstract
The pursuit of this paper is to collect principal reviews and systematic reviews about hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) used in colorectal cancer (CRC). We focus on principal biological aspects of CRC, hyperthermia effects, and surgical procedures. We searched PubMed/MEDLINE for the principal reviews and systematic reviews published from 2010 to 2021 regarding the bimodal treatment (CRS + HIPEC) against local and advanced CRC. In the literature, from several studies, it seems that the efficacy of bimodal treatment with an accurate CRS can extend overall survival. Despite these studies, there are not still any straight guidelines more detailed and scheduled about the use of combined treatment in patients with CRC. Even if the concept is still not very clear and shared, after a careful evaluation of the published data, and after some technical and pathophysiological descriptions, we concluded that it is possible to improve the overall survival and quality of life and to reduce the tumor relapse in patients affected by locally advanced (pT4) CRC with peritoneal metastases.
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Affiliation(s)
- Giorgio Ammerata
- Science of Health Department, Digestive Surgery Unit, University “Magna Graecia” Medical School, Catanzaro 88100, Italy
| | - Rosalinda Filippo
- Science of Health Department, Digestive Surgery Unit, University “Magna Graecia” Medical School, Catanzaro 88100, Italy
| | - Carmelo Laface
- Interventional Oncology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre “Giovanni Paolo II”, Bari 70124, Italy
| | - Riccardo Memeo
- Hepato-Biliary and Pancreatic Surgical Unit, “F. Miulli” Hospital, Acquaviva delle Fonti, Bari 70124, Italy
| | - Leonardo Solaini
- Department of Medical and Surgical Sciences, University of Bologna, Forlì 40126, Italy
| | - Davide Cavaliere
- Department of General and Oncologic Surgery, Morgagni-Pierantoni Hospital, Forlì 47121, Italy
| | - Giuseppe Navarra
- Department of Human Pathology of Adult and Evolutive Age, Surgical Oncology Division, “G. Martino” Hospital, University of Messina, Messina 98122, Italy
| | - Girolamo Ranieri
- Interventional Oncology Unit with Integrated Section of Translational Medical Oncology, National Cancer Research Centre “Giovanni Paolo II”, Bari 70124, Italy
| | - Giuseppe Currò
- Science of Health Department, Digestive Surgery Unit, University “Magna Graecia” Medical School, Catanzaro 88100, Italy
| | - Michele Ammendola
- Science of Health Department, Digestive Surgery Unit, University “Magna Graecia” Medical School, Catanzaro 88100, Italy
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Uno K, Iyoshi S, Yoshihara M, Kitami K, Mogi K, Fujimoto H, Sugiyama M, Koya Y, Yamakita Y, Nawa A, Kanayama T, Tomita H, Enomoto A, Kajiyama H. Metastatic Voyage of Ovarian Cancer Cells in Ascites with the Assistance of Various Cellular Components. Int J Mol Sci 2022; 23:4383. [PMID: 35457198 PMCID: PMC9031612 DOI: 10.3390/ijms23084383] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Revised: 04/10/2022] [Accepted: 04/12/2022] [Indexed: 12/16/2022] Open
Abstract
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy and has a unique metastatic route using ascites, known as the transcoelomic root. However, studies on ascites and contained cellular components have not yet been sufficiently clarified. In this review, we focus on the significance of accumulating ascites, contained EOC cells in the form of spheroids, and interaction with non-malignant host cells. To become resistant against anoikis, EOC cells form spheroids in ascites, where epithelial-to-mesenchymal transition stimulated by transforming growth factor-β can be a key pathway. As spheroids form, EOC cells are also gaining the ability to attach and invade the peritoneum to induce intraperitoneal metastasis, as well as resistance to conventional chemotherapy. Recently, accumulating evidence suggests that EOC spheroids in ascites are composed of not only cancer cells, but also non-malignant cells existing with higher abundance than EOC cells in ascites, including macrophages, mesothelial cells, and lymphocytes. Moreover, hetero-cellular spheroids are demonstrated to form more aggregated spheroids and have higher adhesion ability for the mesothelial layer. To improve the poor prognosis, we need to elucidate the mechanisms of spheroid formation and interactions with non-malignant cells in ascites that are a unique tumor microenvironment for EOC.
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Affiliation(s)
- Kaname Uno
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, Nagoya 466-8560, Japan; (K.U.); (S.I.); (K.K.); (K.M.); (H.F.); (Y.Y.); (H.K.)
- Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, 223-62 Lund, Sweden
| | - Shohei Iyoshi
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, Nagoya 466-8560, Japan; (K.U.); (S.I.); (K.K.); (K.M.); (H.F.); (Y.Y.); (H.K.)
- Spemann Graduate School of Biology and Medicine, University of Freiburg, 79104 Freiburg, Germany
| | - Masato Yoshihara
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, Nagoya 466-8560, Japan; (K.U.); (S.I.); (K.K.); (K.M.); (H.F.); (Y.Y.); (H.K.)
| | - Kazuhisa Kitami
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, Nagoya 466-8560, Japan; (K.U.); (S.I.); (K.K.); (K.M.); (H.F.); (Y.Y.); (H.K.)
| | - Kazumasa Mogi
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, Nagoya 466-8560, Japan; (K.U.); (S.I.); (K.K.); (K.M.); (H.F.); (Y.Y.); (H.K.)
| | - Hiroki Fujimoto
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, Nagoya 466-8560, Japan; (K.U.); (S.I.); (K.K.); (K.M.); (H.F.); (Y.Y.); (H.K.)
- Discipline of Obstetrics and Gynecology, Adelaide Medical School, Robinson Research Institute, University of Adelaide, Adelaide 5005, Australia
| | - Mai Sugiyama
- Bell Research Center, Department of Obstetrics and Gynecology Collaborative Research, Graduate School of Medicine, Nagoya University, Nagoya 466-8560, Japan; (M.S.); (Y.K.); (A.N.)
| | - Yoshihiro Koya
- Bell Research Center, Department of Obstetrics and Gynecology Collaborative Research, Graduate School of Medicine, Nagoya University, Nagoya 466-8560, Japan; (M.S.); (Y.K.); (A.N.)
| | - Yoshihiko Yamakita
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, Nagoya 466-8560, Japan; (K.U.); (S.I.); (K.K.); (K.M.); (H.F.); (Y.Y.); (H.K.)
- Bell Research Center, Department of Obstetrics and Gynecology Collaborative Research, Graduate School of Medicine, Nagoya University, Nagoya 466-8560, Japan; (M.S.); (Y.K.); (A.N.)
| | - Akihiro Nawa
- Bell Research Center, Department of Obstetrics and Gynecology Collaborative Research, Graduate School of Medicine, Nagoya University, Nagoya 466-8560, Japan; (M.S.); (Y.K.); (A.N.)
| | - Tomohiro Kanayama
- Department of Tumor Pathology, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan; (T.K.); (H.T.)
| | - Hiroyuki Tomita
- Department of Tumor Pathology, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan; (T.K.); (H.T.)
| | - Atsushi Enomoto
- Department of Pathology, Graduate School of Medicine, Nagoya University, Nagoya 466-8560, Japan;
| | - Hiroaki Kajiyama
- Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, Nagoya 466-8560, Japan; (K.U.); (S.I.); (K.K.); (K.M.); (H.F.); (Y.Y.); (H.K.)
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Ponzini F, Kowal L, Ghafoor M, Goldberg A, Chan J, Lamm R, Cannaday SM, Richard SD, Nevler A, Lavu H, Bowne WB, Rosenblum NG. Rare occurrence of pseudomyxoma peritonei (PMP) syndrome arising from a malignant transformed ovarian primary mature cystic teratoma treated by cytoreductive surgery and HIPEC: a case report. World J Surg Oncol 2022; 20:78. [PMID: 35272690 PMCID: PMC8915470 DOI: 10.1186/s12957-022-02548-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 02/25/2022] [Indexed: 11/29/2022] Open
Abstract
Background Pseudomyxoma peritonei (PMP) syndrome is a disease process that typically occurs from ruptured appendiceal mucocele neoplasms. PMP syndrome arising from malignant transformation of an ovarian primary mature cystic teratoma (MCT) is a pathogenesis rarely encountered. Case Presentation Herein, we report a 28-year-old patient evaluated and treated for a right ovarian mass and large volume symptomatic abdominopelvic mucinous ascites. Molecular profiling and genetic analysis revealed mutations in ATM, GNAS, and KRAS proteins while IHC demonstrated gastrointestinal-specific staining for CK20, CDX2, CK7, and SATB2. Peritoneal cytology showed paucicellular mucin. Diffuse peritoneal adenomucinosis (DPAM) variant of PMP arising from a ruptured ovarian primary MCT after malignant transformation to a low-grade appendiceal-like mucinous neoplasm was ultimately confirmed. Treatment included staged therapeutic tumor debulking and right salpingo-oophorectomy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Conclusions Our report builds upon the existing literature supporting this aggressive treatment option reserved for advanced abdominal malignancies utilized in this patient with a rare clinical entity.
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Affiliation(s)
- Francesca Ponzini
- Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA
| | - Luke Kowal
- Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA
| | - Mariam Ghafoor
- Department of Pathology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Allison Goldberg
- Department of Pathology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Joanna Chan
- Department of Pathology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Ryan Lamm
- Department of Surgery, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Shawnna M Cannaday
- Department of Surgery, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Scott D Richard
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Avinoam Nevler
- Department of Surgery, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Harish Lavu
- Department of Surgery, Thomas Jefferson University Hospital, Philadelphia, PA, USA
| | - Wilbur B Bowne
- Department of Surgery, Thomas Jefferson University Hospital, Philadelphia, PA, USA.
| | - Norman G Rosenblum
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Thomas Jefferson University Hospital, Philadelphia, PA, USA.
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17
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Zhang C, Patel A, Hegeholz D, Brown K, Shostrom V, Pottebaum M, Foster JM. Cytoreductive Surgery with HIPEC is a Safe and Effective Palliative Option in Chemorefractory Symptomatic Peritoneal Metastasis. Ann Surg Oncol 2022; 29:3337-3346. [PMID: 35211861 DOI: 10.1245/s10434-022-11323-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Accepted: 12/23/2021] [Indexed: 01/16/2023]
Abstract
INTRODUCTION The safety and efficacy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in peritoneal metastasis in palliative settings remain poorly investigated and understood. Chemotherapy-refractory patients often present with symptomatic disease. This study investigated the safety and survival outcomes of optimal CRS/HIPEC performed primarily for palliation. METHODS Palliative CRS/HIPEC was defined as asymptomatic patients who did not respond to three or more lines of chemotherapy, progression on current chemotherapy, and/or any symptomatic disease progression, including ascites, bowel obstruction, and pain. Data collected included demographics, histology, length of stay (LOS), perioperative complications, perioperative mortality, adjuvant chemotherapy use, peritoneal recurrence, overall recurrence, and overall survival. RESULTS The median number of lines of chemotherapy received prior to CRS/HIPEC was 3.2, and 81% of patients were symptomatic. There were no postoperative deaths and the major complication rate was 22%. Ostomy creation and abdominal wall reconstruction were performed in 24% and 21% of patients, respectively. The median LOS was 11 days and successful palliation was achieved in 97% of patients. Overall survival was 13.5 months and factors associated with prolonged survival included optimal CRS (R1/R2a; p < 0.01) and the use of adjuvant chemotherapy (p < 0.001). Synchronous liver metastasis in the colon cancer subset did not negatively impact survival. CONCLUSION CRS/HIPEC was performed safely in the palliative setting in patients with symptomatic progressive disease receiving multiple lines of chemotherapy. Median survival exceeded 1 year and factors associated with longer survival were optimal CRS and adjuvant chemotherapy. Liver metastasis did not preclude survival benefit in colon cancer patients. CRS/HIPEC can be considered for palliation but should be performed at high-volume centers.
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Affiliation(s)
- Chunmeng Zhang
- Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA
| | - Asish Patel
- Department of Surgical Oncology, Nebraska Methodist Hospital, Omaha, NE, USA
| | - Dalton Hegeholz
- Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA
| | - Krista Brown
- Department of Epidemiology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Valerie Shostrom
- Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE, USA
| | - Mallory Pottebaum
- Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA
| | - Jason M Foster
- Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA.
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Mangieri CW, Moaven O, Valenzuela CD, Erali RA, Votanopoulos KI, Shen P, Levine EA. Utility of hyperthermic intraperitoneal chemotherapy in cases of incomplete cytoreductive surgery. J Surg Oncol 2021; 125:703-711. [PMID: 34841542 DOI: 10.1002/jso.26759] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 11/14/2021] [Accepted: 11/15/2021] [Indexed: 11/10/2022]
Abstract
INTRODUCTION Hyperthermic intraperitoneal chemotherapy (HIPEC) during cytoreductive surgery (CRS) is typically reserved for a complete or optimal cytoreduction. There is the potential for therapeutic effect of HIPEC with an incomplete cytoreduction, particularly for near optimal cytoreductions. METHODS Retrospective review of incomplete cytoreductions (R2b, R2c) for appendiceal and colorectal primaries. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Subgroup analysis for primary etiology and specific cytoreductive score. RESULTS A total of 121 cases of incomplete CRS, 74 CRS alone, and 47 CRS-HIPEC. For the entire study group there was a survival benefit with HIPEC. OS and PFS were 2.3 versus 1.4 (p = 0.001) and 1.6 versus 0.7 (p < 0.0001) respectively for cases with and without HIPEC. Subgroup analysis of appendiceal neoplasms, 43 CRS-HIPEC and 50 CRS alone, found HIPEC benefit persisted; OS and PFS were 2.4 versus 1.5 (p = 0.016) and 1.7 versus 0.8 (p < 0.0001), respectively for cases with and without HIPEC. Benefit most pronounced in low-grade cases with doubling of the OS and PFS (p = 0.004). With colorectal primary cases, 10 CRS-HIPEC and 18 CRS alone, no difference in OS and PFS. When stratifying out by cytoreduction scores, R2b and R2c, HIPEC only provided a benefit for R2b cases; OS and PFS for R2b cases were 2.28 versus 1.01 (p = 0.011) and 1.67 versus 0.75 (p = 0.001), respectively for cases with and without HIPEC. CONCLUSION HIPEC has utility for incomplete cytoreductions with appendiceal neoplasms, greatest effect with low-grade appendiceal neoplasms. HIPEC is only beneficial for near optimal cytoreductions (R2b).
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Affiliation(s)
- Christopher W Mangieri
- Division of Surgical Oncology, Surgical Oncology Section, Wake Forest Baptist Health Medical Center, Winston-Salem, North Carolina, USA
| | - Omeed Moaven
- Department of Surgery, Mayo Clinic Florida, Jacksonville, Florida, USA
| | - Cristian D Valenzuela
- Division of Surgical Oncology, Surgical Oncology Section, Wake Forest Baptist Health Medical Center, Winston-Salem, North Carolina, USA
| | - Richard A Erali
- Division of Surgical Oncology, Surgical Oncology Section, Wake Forest Baptist Health Medical Center, Winston-Salem, North Carolina, USA
| | - Konstantinos I Votanopoulos
- Division of Surgical Oncology, Surgical Oncology Section, Wake Forest Baptist Health Medical Center, Winston-Salem, North Carolina, USA
| | - Perry Shen
- Division of Surgical Oncology, Surgical Oncology Section, Wake Forest Baptist Health Medical Center, Winston-Salem, North Carolina, USA
| | - Edward A Levine
- Division of Surgical Oncology, Surgical Oncology Section, Wake Forest Baptist Health Medical Center, Winston-Salem, North Carolina, USA
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19
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Pelvic exenteration, cytoreductive surgery, and hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancy: experience and outcomes from an exenterative and peritonectomy unit. Langenbecks Arch Surg 2021; 406:2807-2815. [PMID: 34495403 DOI: 10.1007/s00423-021-02323-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 09/01/2021] [Indexed: 10/20/2022]
Abstract
PURPOSE Pelvic exenteration (PE) for locally advanced pelvic malignancy is well established, though high rates of morbidity and mortality exist. Such a complication profile has often deterred the surgical community from offering exenteration in combination with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). We aimed to evaluate the perioperative outcomes following pelvic exenteration when combined with CRS and HIPEC for peritoneal surface malignancy (PSM) in a tertiary referral centre. METHODS A review of a prospectively maintained PSM database from June 2015 to December 2020 at a tertiary referral institution was performed. Patients who underwent CRS, PE, and HIPEC were matched with patients who underwent PE alone. Primary endpoints were perioperative morbidity and mortality. RESULTS From June 2015 to December 2020, 20 patients required PE as part of their CRS and HIPEC for PSM. The majority of patients were female (n = 16, 80%) with a median age of 52 (range 21-70). Colorectal cancer was the predominant pathology (n = 12, 60%). Median PCI was 11.5 (range 3-39). CC0 and R0 resections were achieved in all patients. CRS, PE, and HIPEC and PE-alone groups were well matched for clinicopathological variables. There was no difference in perioperative major morbidity (HIPEC: 30% vs PE: 15% p = 0.256) and mortality (HIPEC: 0 vs PE: 5% p = 0.311) between groups. Median follow-up was 17.5 months (range 7-68). Eight patients (40%) died from disease-related issues during the study period. CONCLUSION An aggressive surgical strategy with complete resection is feasible and safe in select patients with complex PSM involving the pelvis.
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Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy Improves Survival with Acceptable Safety for Advanced Ovarian Cancer: A Clinical Study of 100 Patients. BIOMED RESEARCH INTERNATIONAL 2021; 2021:5533134. [PMID: 34258265 PMCID: PMC8245244 DOI: 10.1155/2021/5533134] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/24/2021] [Revised: 03/28/2021] [Accepted: 05/17/2021] [Indexed: 11/17/2022]
Abstract
Background The mainstay of treatment for advanced ovarian cancer is debulking surgery followed by chemotherapy that includes carboplatin and paclitaxel, but the prognosis is poor. This study is aimed at evaluating the efficacy and safety of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) as first-line surgical treatment in patients with advanced ovarian cancer (AOC). Methods FIGO stage III/IV AOC patients underwent CRS+HIPEC as first-line surgical treatment at our center from December 2007 to January 2020. The primary endpoint was survival, and the secondary endpoint was safety. Results Among 100 patients, the median Karnofsky performance status (KPS) score was 80 (50-100), median peritoneal cancer index (PCI) was 19 (1-39), median completeness of cytoreduction (CC) score was 1 (0-3), number of organ regions removed was 4 (3-9), number of peritoneal regions removed was 4 (1-9), and number of anastomoses was 1 (0-4). The median follow-up was 36.8 months; 75 (75.0%) patients were still alive, and 25 (25.0%) had died. The median overall survival (mOS) was 87.6 (95% CI: 72.1-103.0) months, and the 1-, 2-, 3-, 4-, and 5-year survival rates were 94.1%, 77.2%, 68.2%, 64.2%, and 64.2%, respectively. Univariate analysis showed that better mOS correlated with an age ≤, KPS ≥ 80, ascites ≤ 1000 ml, PCI < 19, and CC score 0-1. Multivariate Cox analysis showed that CC was an independent factor for OS; patients who underwent CRS with a CC score 0-1 had a mPFS of 67.8 (95% CI: 48.3-87.4) months. The perioperative serious adverse event and morbidity rates were 4.0% and 2.0%, respectively. Conclusions CRS+HIPEC improves survival for AOC patients with acceptable safety at experienced high-volume centers. Stringent patient selection and complete CRS are key factors for better survival.
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Marrelli D, Petrioli R, Cassetti D, D'Ignazio A, Marsili S, Mazzei MA, Lazzi S, Roviello F. A novel treatment protocol with 6 cycles of neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in stage III primary ovarian cancer. Surg Oncol 2021; 37:101523. [PMID: 33545658 DOI: 10.1016/j.suronc.2021.101523] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2020] [Revised: 11/24/2020] [Accepted: 01/25/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND Few prospective studies investigated neoadjuvant chemotherapy (NAC), interval cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced ovarian cancer. We report the results of a phase II study where 6 rather than 3 cycles of NAC, followed by CRS and HIPEC, were adopted (HIPEC_ovaio, EudraCT number 2007-005674-31). MATERIALS AND METHODS Between 2007 and 2014, 56 patients with stage III primary ovarian cancer and peritoneal carcinomatosis were assigned to 6 cycles of platinum and taxane-based NAC. Of these, two had progression, 8 underwent palliative surgery, and 46 had CRS and HIPEC. RESULTS A complete pathological response was observed in 9 patients. Of 46 patients who completed the treatment protocol, 29 had no macroscopic residual tumor. Postoperative grade III morbidity rate was 28.2%; no grade IV complications or mortality events were observed. Five-year overall survival (OS) of the entire series was 36 ± 7% (median: 36, 95% CI: 26-45 months). In 46 patients treated by CRS and HIPEC, 5-year OS was 42 ± 8% (median: 53, 95% CI: 29-76 months), and 5-year progression-free survival was 26 ± 7% (median: 23, 95% CI: 19-27 months). Completeness of cytoreduction, peritoneal cancer index and FIGO stage resulted as significant prognostic factors. CONCLUSIONS A novel protocol consisting of 6 cycles of NAC, followed by CRS and HIPEC, is associated with notable improvement in peritoneal carcinomatosis, limited postoperative morbidity risk and high survival rates in responders, and could deserve further investigations in randomized clinical trials.
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Affiliation(s)
- Daniele Marrelli
- Department of Medicine, Surgery and Neuroscience, Unit of General Surgery and Surgical Oncology, University of Siena, Italy.
| | - Roberto Petrioli
- Department of Oncology, Unit of Medical Oncology, Azienda Ospedaliera Universitaria Senese, Italy
| | - Dario Cassetti
- Department of Medicine, Surgery and Neuroscience, Unit of General Surgery and Surgical Oncology, University of Siena, Italy
| | - Alessia D'Ignazio
- Department of Medicine, Surgery and Neuroscience, Unit of General Surgery and Surgical Oncology, University of Siena, Italy
| | - Stefania Marsili
- Department of Oncology, Unit of Medical Oncology, Azienda Ospedaliera Universitaria Senese, Italy
| | - Maria Antonietta Mazzei
- Department of Medicine, Surgery and Neuroscience, Unit of Diagnostic Imaging, University of Siena, Italy
| | - Stefano Lazzi
- Department of Medical Biotechnologies, Unit of Pathology, University of Siena, Italy
| | - Franco Roviello
- Department of Medicine, Surgery and Neuroscience, Unit of General Surgery and Surgical Oncology, University of Siena, Italy
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22
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Taibi A, Sgarbura O, Hübner M. ASO Author Reflections: Developing Next-Generation Intraperitoneal Chemotherapy. Ann Surg Oncol 2020; 28:3861-3862. [PMID: 33216262 DOI: 10.1245/s10434-020-09377-7] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Accepted: 11/02/2020] [Indexed: 11/18/2022]
Affiliation(s)
- Abdelkader Taibi
- Digestive Surgery Department, Dupuytren Limoges University Hospital, Limoges, France. .,University Limoges, CNRS, XLIM, UMR 7252, 87000, Limoges, France.
| | - Olivia Sgarbura
- Surgical Oncology Department, Montpellier Cancer Institute (ICM), University of Montpellier, Montpellier, France
| | - Martin Hübner
- Department of Visceral Surgery, Lausanne University Hospital (CHUV), University of Lausanne (UNIL), Lausanne, Switzerland
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Wang S, Zhang Q, Chen L, Liu G, Liu PF. Thromboelastography-guided blood transfusion during cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy: study protocol for a prospective randomised controlled trial. BMJ Open 2020; 10:e042741. [PMID: 33184089 PMCID: PMC7662436 DOI: 10.1136/bmjopen-2020-042741] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 09/02/2020] [Accepted: 09/25/2020] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a well-established treatment for peritoneal cancer (PC). However, this kind of combination therapy is associated with a high incidence of complications. Moreover, relative studies have indicated that traditional laboratory testing is insufficient to demonstrate the overall haemostatic physiology of CRS/HIPEC. Thromboelastography (TEG), administered by monitoring dynamic changes in haemostasis, has been shown to contribute to reducing transfusion requirements and improving survival. However, there is no evidence to verify whether TEG can be applied to guide transfusion strategies during CRS/HIPEC. Therefore, we aim to investigate whether TEG-guided blood product transfusion (TEG-BT) therapy is superior to traditional blood product transfusion (T-BT) therapy for guiding perioperative blood transfusion treatment and improving the prognosis of patients undergoing CRS/HIPEC. METHODS AND ANALYSIS The TEG-BT versus T-BT study is a single-centre, randomised, blinded outcome assessment clinical trial of 162 patients with PC, aged 18-64 years and undergoing CRS/HIPEC. Participants will be randomly allocated to receive TEG-BT or T-BT. The primary outcome will be the evaluation of perioperative blood transfusion, which refers to the total amount of blood transfusion given from the time patients enter the operating room up to 72 hours postoperatively. The secondary outcomes will include the transfusion volume during surgery, total amount of intraoperative infusion, amount of blood lost during the operation, total blood transfusion between 0 and 72 hours after surgery, lowest haemoglobin level within 72 hours after surgery, intensive care unit duration, overall length of stay, total cost of hospitalisation and adverse events. Data will be analysed according to the intention-to-treat principle. ETHICS AND DISSEMINATION The study protocol has been approved by the Scientific Research Ethics Committee of Beijing Shijitan Hospital Affiliated with Capital Medical University (Approval Number: sjtkyll-lx-2020-3). The results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER Chinese Clinical Trial Registry (ChiCTR2000028835).
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Affiliation(s)
- Shaoheng Wang
- Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Qing Zhang
- Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Linfeng Chen
- Department of Blood Transfusion, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Gang Liu
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
| | - Peng Fei Liu
- Department of Anesthesiology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China
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24
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Martin D, Grass F, Deo SVS, Ashwin KR, Maheshwari A, Hübner M, Somashekhar SP. Current Opinion on Peritoneal Carcinomatosis Treatment: a Survey of the Indian Society of Peritoneal Surface Malignancies (ISPSM). J Gastrointest Cancer 2020; 52:1061-1066. [PMID: 33073299 PMCID: PMC8376720 DOI: 10.1007/s12029-020-00538-1] [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] [Accepted: 10/12/2020] [Indexed: 12/29/2022]
Abstract
Purpose Patients with peritoneal carcinomatosis (PC) are increasingly treated with multidisciplinary combined approaches. The study aim was to assess current practice and perceptions of treatment modalities of PC. Methods Indian Society of Peritoneal Surface Malignancies (ISPSM) members were invited to complete an online survey. Current practice and perceptions of treatment modalities were assessed through 19 closed questions. Scores were assessed using a Likert scale (0: not important, 5: very important). Treatment modality satisfaction was assessed using a semantic scale (frustrated: 0, perfectly happy: 10). Participants were sent 3 reminders at 4-week intervals. Results Fifty-seven out of 182 members completed the survey (31%). Forty percent of participants had an experience of at least 10 years, and 75% stated treating less than 20 PC patients per year. Main treatment goals for patients with PC were cure (5/5) and symptom relief (4/5). Participant’s satisfaction with treatment modalities for ovarian, colorectal, and gastric PC were 6/10, 5/10, and 2/10, respectively. Hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian (57%) and colorectal (44%) origins were considered to be useful. Clinical usefulness of chemotherapy for gastric PC was rated to be low (17%). Conclusions Current treatment modalities fall short to satisfy the needs (cure, symptom relief) of patients with PC. Alternative systemic and intraperitoneal treatment modalities should be assessed. Electronic supplementary material The online version of this article (10.1007/s12029-020-00538-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- David Martin
- Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne, Switzerland.
| | - F Grass
- Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne, Switzerland
| | - S V S Deo
- Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - K R Ashwin
- Department of Surgical Oncology, Manipal Hospital, Bangalore, India
| | - A Maheshwari
- Department of Gynecological Oncology, Tata Memorial Cancer Hospital, Mumbai, India
| | - M Hübner
- Department of Visceral Surgery, Lausanne University Hospital CHUV, Lausanne, Switzerland
| | - S P Somashekhar
- Department of Surgical Oncology, Manipal Hospital, Bangalore, India
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Lau H, Khosrawipour T, Mikolajczyk A, Frelkiewicz P, Nicpon J, Arafkas M, Pigazzi A, Knoefel WT, Khosrawipour V. Intraperitoneal chemotherapy of the peritoneal surface using high-intensity ultrasound (HIUS): investigation of technical feasibility, safety and possible limitations. J Cancer 2020; 11:7209-7215. [PMID: 33193884 PMCID: PMC7646163 DOI: 10.7150/jca.48519] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Accepted: 09/11/2020] [Indexed: 01/25/2023] Open
Abstract
Introduction: The penetration of chemotherapeutic drugs into peritoneal nodules remains at levels well below 1 mm, thus significantly limiting the antitumor effect of intraperitoneal chemotherapy (IPC). Recently, high-Intensity ultrasound (HIUS) has been discovered as a potential tool to significantly improve peritoneal diffusion rates. Despite promising preliminary data, basic aspects regarding its technical feasibility, safety and possible limitations remain unclear. This study aims to enhance our current understanding of HIUS and test its applicability using an ex-vivo swine model. Methods: Three postmortem swine were subject to laparotomy and consecutive lavage with 0.9%NaCl saline and HIUS application. For this purpose, a large HIUS radiating pen was introduced into the abdominal cavity and HIUS was applied on two of the four abdominal quadrants for 300 seconds each at an output power of 70 W, 50 % amplitude and 20 kHz frequency. Following the procedure, small intestinal tissue samples were retrieved for further analyses. Results: Peritoneal and subperitoneal layers showed structural changes only visible on a microscopic level. The peritoneal layer was transformed into a mesh-like structure while the subperitoneal layer (depth of 142 +/- 28 µm) exhibited microcavities and vascular detachment from surrounding tissues. No bowel rupture or vascular perforations were observed. Conclusions: Our data indicate that HIUS is a technically feasible and safe add-on procedure for intraperitoneal chemotherapy (IPC) with measurable microscopic changes on the peritoneal surface. Pretreatment of the abdominal cavity with HIUS could significantly improve IPC efficacy. Further studies are required to optimize and evaluate this novel approach.
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Affiliation(s)
- Hien Lau
- Division of Colorectal Surgery, Department of Surgery, University of California Irvine, Orange, USA
| | - Tanja Khosrawipour
- Division of Colorectal Surgery, Department of Surgery, University of California Irvine, Orange, USA.,Department of Surgery (A), University-Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Germany
| | - Agata Mikolajczyk
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland
| | - Piotr Frelkiewicz
- The Center of Experimental Diagnostics and Innovative Biomedical Technology, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland
| | - Jakub Nicpon
- The Center of Experimental Diagnostics and Innovative Biomedical Technology, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland
| | - Mohamed Arafkas
- Department of Plastic Surgery, Ortho-Clinic Dortmund, Dortmund, Germany
| | - Alessio Pigazzi
- Division of Colorectal Surgery, Department of Surgery, University of California Irvine, Orange, USA
| | - Wolfram Trudo Knoefel
- Department of Surgery (A), University-Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Germany
| | - Veria Khosrawipour
- Division of Colorectal Surgery, Department of Surgery, University of California Irvine, Orange, USA.,Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland
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26
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Mikkelsen MS, Blaakaer J, Petersen LK, Schleiss LG, Iversen LH. Pharmacokinetics and toxicity of carboplatin used for hyperthermic intraperitoneal chemotherapy (HIPEC) in treatment of epithelial ovarian cancer. Pleura Peritoneum 2020; 5:20200137. [PMID: 33575463 PMCID: PMC7829861 DOI: 10.1515/pp-2020-0137] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Accepted: 08/06/2020] [Indexed: 12/03/2022] Open
Abstract
Objectives Carboplatin is frequently used in various doses for hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of epithelial ovarian cancer (EOC) although its pharmacokinetics, including focus on the perfusion time, has not been evaluated when used in modern era cytoreductive surgery (CRS). The aim was to evaluate the pharmacokinetics and hematological toxicity of carboplatin used for HIPEC with a perfusion time of 90 min. Methods Fifteen patients with stage III–IV primary EOC received CRS and 90 min of HIPEC with carboplatin at dose 800 mg/m2. For the pharmacokinetic analysis, perfusate and blood samples were obtained during HIPEC and up to 48 h after HIPEC (blood only). Hematological toxicity within 30 days was graded according to Common Terminology Criteria for Adverse Events. Severe toxicity (grades 3–5) is reported. Results Mean maximum concentration of carboplatin was 12 times higher in perfusate than plasma (mean CmaxPF=348 µg/mL (range: 279–595 µg/mL) versus mean CmaxPL=29 µg/mL (range: 21–39 µg/mL)). Mean terminal half-life of carboplatin in perfusate was 104 min (range: 63–190 min) and mean intraperitoneal-to-plasma area under the concentration-time curve (AUC) ratio was 12.3 (range: 7.4–17.2). Two patients (13%) had grade 3 neutropenia within 30 days. No grade 4–5 hematological toxicities were identified. Conclusions Carboplatin has a favorable pharmacokinetic profile for 90 min HIPEC administration, and the hematological toxicity was acceptable at dose 800 mg/m2. Large interindividual differences were found in the pharmacokinetic parameters, making risk of systemic exposure difficult to predict.
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Affiliation(s)
- Mette Schou Mikkelsen
- Department of Gynecology and Obstetrics, Aarhus University Hospital, Aarhus, Denmark
| | - Jan Blaakaer
- Department of Clinical Research, University of Southern Denmark, Odense, Denmark.,Department of Gynecology and Obstetrics, Odense University Hospital, Odense, Denmark
| | - Lone Kjeld Petersen
- Open Patient Explorative Data Network, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.,Department of Gynecology and Obstetrics, Odense University Hospital, Odense, Denmark
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Somashekhar SP, Rohit KC, Deo SVS, Ashwin KR. Practice patterns, attitudes, and knowledge among clinicians regarding hyperthermic intraperitoneal chemotherapy and pressurized intraperitoneal aerosol chemotherapy: a national survey by Indian society of peritoneal surface malignancies (ISPSM). Pleura Peritoneum 2020; 5:20200120. [PMID: 33364340 PMCID: PMC7746887 DOI: 10.1515/pp-2020-0120] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Accepted: 07/29/2020] [Indexed: 11/15/2022] Open
Abstract
Objectives Perception of cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and pressurized intraperitoneal aerosol chemotherapy (PIPAC) for treating peritoneal surface malignancies (PSM) differ widely among physicians. Methods This on-site survey performed during a major oncology congress in 2019 evaluated the current opinion, perceptions, knowledge and practice of HIPEC and PIPAC among oncologists in India. Results There were 147 respondents (gynecologists (30%), surgical oncologists and gastrointestinal surgeons (64%), and medical oncologists (6%)). Whereas most respondents considered CRS and HIPEC an appropriate therapeutic option, 25% would not recommend CRS and HIPEC. The main barriers to referral to an expert center were inaccessibility to such a center (37.8%), non-inclusion of CRS and HIPEC in clinical practice guidelines (32.4%), and a high morbidity/mortality (21.6%). Variations were found in the various practice patterns of CRS/HIPEC like eligibility criteria, HIPEC protocols and safety measures. Although PIPAC awareness as a novel therapeutic option was high, only a limited number of centers offered PIPAC, mainly because of non-access to technology and missing training opportunities (76.2%). Conclusions Lack of widespread acceptance, poor accessibility and low utilization presents a significant challenge for HIPEC and PIPAC in India. There is a need to raise the awareness of curative and palliative therapeutic options for PSM. This might be achieved by the creation of expert centers, specialized training curricula and of a new sub-speciality in oncology.
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Affiliation(s)
| | - Kumar C Rohit
- Department of Surgical Oncology, Manipal Comprehensive Cancer Center, Manipal Hospital, Bangalore, India
| | - S V S Deo
- All India Institute of Medical Sciences, New Delhi, India
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Chokshi RJ, Kim JK, Patel J, Oliver JB, Mahmoud O. Impact of insurance status on overall survival after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Pleura Peritoneum 2020; 5:20200105. [PMID: 33364338 PMCID: PMC7746885 DOI: 10.1515/pp-2020-0105] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2020] [Accepted: 04/30/2020] [Indexed: 01/14/2023] Open
Abstract
Objectives The impact of insurance status on oncological outcome in patients undergoing cytoreduction and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is poorly understood. Methods Retrospective study on 31 patients having undergone 36 CRS-HIPEC at a single institution (safety-net hospital) between 2012 and 2018. Patients were categorized as insured or underinsured. Demographics and perioperative events were compared. Primary outcome was overall survival (OS). Results A total of 20 patients were underinsured and 11 were insured. There were less gynecologic malignancies in the underinsured (p=0.02). On univariate analysis, factors linked to poor survival included gastrointestinal (p=0.01) and gynecologic malignancies (p=0.046), treatment with neoadjuvant chemotherapy (p=0.03), CC1 (p=0.02), abdominal wall resection (p=0.01) and Clavien–Dindo 3-4 (p=0.01). Treatment with neoadjuvant chemotherapy and abdominal wall resections, but not insurance status, were independently associated with OS (p=0.01, p=0.02 respectively). However, at the end of follow-up, six patients were alive in the insured group vs. zero in the underinsured group. Conclusions In this small, exploratory study, there was no statistical difference in OS between insured and underinsured patients after CRS-HIPEC. However, long-term survivors were observed only in the insured group.
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Affiliation(s)
- Ravi J. Chokshi
- Division of Surgical Oncology, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Jin K. Kim
- Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Jimmy Patel
- Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Joseph B. Oliver
- Department of Surgery, Rutgers New Jersey Medical School, Newark, NJ, USA
| | - Omar Mahmoud
- Department of Radiation Oncology, Rutgers New Jersey Medical School, Newark, NJ, USA
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Schuitevoerder D, Sherman SK, Izquierdo FJ, Eng OS, Turaga KK. Assessment of the Surgical Workforce Pertaining to Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in the United States. Ann Surg Oncol 2020; 27:3097-3102. [DOI: 10.1245/s10434-020-08781-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Accepted: 06/22/2020] [Indexed: 12/16/2022]
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Fiorentini G, Sarti D, Patriti A, Eugeni E, Guerra F, Masedu F, Mackay AR, Guadagni S. Immune response activation following hyperthermic intraperitoneal chemotherapy for peritoneal metastases: A pilot study. World J Clin Oncol 2020; 11:397-404. [PMID: 32874953 PMCID: PMC7450817 DOI: 10.5306/wjco.v11.i6.397] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Revised: 04/13/2020] [Accepted: 05/12/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastases (PM) is considered to be feasible, safe and to improve survival. AIM To investigate whether an immune response is activated following HIPEC for PM. METHODS Six patients were enrolled in this study. Peripheral blood samples were obtained from each patient prior to (day 0) and post-procedure (day 30), and used to evaluate the number of CD3+ total, CD3+/CD4+ T-Helper, CD3+/CD8+ cytotoxic T, CD3+/CD56+ natural killer and CD19+ B lymphocyte numbers, and CD4+: CD8+ T lymphocyte ratios. RESULTS The total numbers of CD3+, CD3+/CD4+ T-Helper, CD3+/CD8+ cytotoxic T, CD3+/CD56+ natural killer and CD19+ B lymphocytes, and CD4+: CD8+ lymphocyte ratios were increased in all but one patient 30 d following the cytoreductive surgery-HIPEC procedure, and these increases were significant (P ≤ 0.05) for CD3+/CD4+ T Helper and CD3+/CD8+ cytotoxic T lymphocyte numbers. CONCLUSION This report provides the first evidence that HIPEC exhibits immunomodulating activity in PM patients, resulting in generalized activation of the adaptive immune response. Moreover, the majority of lymphocyte populations increased following HIPEC and continued to be elevated several weeks following the procedure, consistent with a potential authentic immunomodulating effect rather than a normal inflammatory response, to be fully characterised in future studies.
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Affiliation(s)
- Giammaria Fiorentini
- Department of Onco-Hematology, Azienda Ospedaliera “Ospedali Riuniti Marche Nord”, Pesaro 61122, Italy
| | - Donatella Sarti
- Department of Onco-Hematology, Azienda Ospedaliera “Ospedali Riuniti Marche Nord”, Pesaro 61122, Italy
| | - Alberto Patriti
- Department of General Surgery, Azienda Ospedaliera “Ospedali Riuniti Marche Nord”, Pesaro 61122, Italy
| | - Emilio Eugeni
- Department of General Surgery, Azienda Ospedaliera “Ospedali Riuniti Marche Nord”, Pesaro 61122, Italy
| | - Francesco Guerra
- Department of General Surgery, Azienda Ospedaliera “Ospedali Riuniti Marche Nord”, Pesaro 61122, Italy
| | - Francesco Masedu
- Department of Applied Clinical Sciences and Biotechnology, University of L’Aquila, L’Aquila 67100, Italy
| | - Andrew Reay Mackay
- Department of Applied Clinical Sciences and Biotechnology, University of L’Aquila, L’Aquila 67100, Italy
| | - Stefano Guadagni
- Department of Applied Clinical Sciences and Biotechnology, University of L’Aquila, L’Aquila 67100, Italy
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Gurusamy K, Vale CL, Pizzo E, Bhanot R, Davidson BR, Mould T, Mughal M, Saunders M, Aziz O, O'Dwyer S. Cytoreductive surgery (CRS) with hyperthermic intraoperative peritoneal chemotherapy (HIPEC) versus standard of care (SoC) in people with peritoneal metastases from colorectal, ovarian or gastric origin: protocol for a systematic review and individual participant data (IPD) meta-analyses of effectiveness and cost-effectiveness. BMJ Open 2020; 10:e039314. [PMID: 32404398 PMCID: PMC7228534 DOI: 10.1136/bmjopen-2020-039314] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Revised: 04/17/2020] [Accepted: 04/20/2020] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION There is uncertainty about whether cytoreductive surgery (CRS)+hyperthermic intraoperative peritoneal chemotherapy (HIPEC) improves survival and/or quality of life compared with standard of care (SoC) in people with peritoneal metastases who can withstand major surgery. PRIMARY OBJECTIVES To compare the relative benefits and harms of CRS+HIPEC versus SoC in people with peritoneal metastases from colorectal, ovarian or gastric cancers eligible to undergo CRS+HIPEC by a systematic review and individual participant data (IPD) meta-analysis. SECONDARY OBJECTIVES To compare the cost-effectiveness of CRS+HIPEC versus SoC from a National Health Service (NHS) and personal social services perspective using a model-based cost-utility analysis. METHODS AND ANALYSIS We will perform a systematic review of literature by updating the searches from MEDLINE, Embase, Cochrane library, Science Citation Index as well as trial registers. Two members of our team will independently screen the search results and identify randomised controlled trials comparing CRS+HIPEC versus SoC for inclusion based on full texts for articles shortlisted during screening. We will assess the risk of bias in the trials and obtain data related to baseline prognostic characteristics, details of intervention and control, and outcome data related to overall survival, disease progression, health-related quality of life, treatment related complications and resource utilisation data. Using IPD, we will perform a two-step IPD, that is, calculate the adjusted effect estimate from each included study and then perform a random-effects model meta-analysis. We will perform various subgroup analyses, meta-regression and sensitivity analyses. We will also perform a model-based cost-utility analysis to assess whether CRS+HIPEC is cost-effective in the NHS setting. ETHICS AND DISSEMINATION This project was approved by the UCL Research Ethics Committee (Ethics number: 16023/001). We aim to present the findings at appropriate international meetings and publish the review, irrespective of the findings, in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER CRD42019130504.
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Affiliation(s)
- Kurinchi Gurusamy
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Claire L Vale
- Meta-analysis Group, MRC Clinical Trials Unit at UCL, London, UK
| | - Elena Pizzo
- Department of Applied Health Research, University College London, London, UK
| | - R Bhanot
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Brian R Davidson
- Division of Surgery and Interventional Science, University College London, London, UK
- Department of HPB Surgery, Royal Free London NHS Foundation Trust, London, UK
| | - Tim Mould
- Gynaecological Oncology, University College London Hospitals NHS Trust, London, UK
| | - Muntzer Mughal
- Surgery, University College London Hospital NHS Foundation Trust, London, UK
| | - Mark Saunders
- Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
| | - Omer Aziz
- Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
| | - Sarah O'Dwyer
- Colorectal and Peritoneal Oncology Centre, The Christie NHS Foundation Trust, Manchester, UK
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Ceelen W, Braet H, van Ramshorst G, Willaert W, Remaut K. Intraperitoneal chemotherapy for peritoneal metastases: an expert opinion. Expert Opin Drug Deliv 2020; 17:511-522. [PMID: 32142389 DOI: 10.1080/17425247.2020.1736551] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Accepted: 02/26/2020] [Indexed: 12/13/2022]
Abstract
Introduction: The rationale for intraperitoneal (IP) drug delivery for patients with peritoneal metastases (PM) is based on the pharmacokinetic advantage resulting from the peritoneal-plasma barrier, and on the potential to adequately treat small, poorly vascularized PM. Despite a history of more than three decades, many aspects of IP drug delivery remain poorly studied.Areas covered: We outline the anatomy and physiology of the peritoneal cavity, including the pharmacokinetics of IP drug delivery. We discuss transport mechanisms governing tissue penetration of IP chemotherapy, and how these are affected by the biomechanical properties of the tumor stroma. We provide an overview of the current clinical evidence on IP chemotherapy in ovarian, colorectal, and gastric cancer. We discuss the current limitations of IP drug delivery and propose several potential areas of progress.Expert opinion: The potential of IP drug delivery is hampered by off-label use of drugs developed for systemic therapy. The efficacy of IP chemotherapy for PM depends on cancer type, disease extent, and mode of drug delivery. Results from ongoing randomized trials will allow to better delineate the potential of IP chemotherapy. Promising approaches include IP aerosol therapy, prolonged delivery platforms such as gels or biomaterials, and the use of nanomedicine.
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Affiliation(s)
- Wim Ceelen
- Department of GI Surgery, Ghent University Hospital, Ghent, Belgium
- Cancer Research Institute Ghent (CRIG), Belgium
| | - Helena Braet
- Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Ghent University, Ghent, Belgium
| | | | - Wouter Willaert
- Department of GI Surgery, Ghent University Hospital, Ghent, Belgium
| | - Katrien Remaut
- Cancer Research Institute Ghent (CRIG), Belgium
- Ghent Research Group on Nanomedicines, Laboratory of General Biochemistry and Physical Pharmacy, Ghent University, Ghent, Belgium
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Zaidi MY, Lee RM, Gamboa AC, Speegle S, Cloyd JM, Kimbrough C, Grotz T, Leiting J, Fournier K, Lee AJ, Dineen S, Dessureault S, Kelly KJ, Kotha NV, Clarke C, Gamblin TC, Patel SH, Lee TC, Hendrix RJ, Lambert L, Ronnekleiv-Kelly S, Pokrzywa C, Blakely AM, Lee B, Johnston FM, Fackche N, Russell MC, Maithel SK, Staley CA. Preoperative Risk Score for Predicting Incomplete Cytoreduction: A 12-Institution Study from the US HIPEC Collaborative. Ann Surg Oncol 2020; 27:156-164. [PMID: 31602579 PMCID: PMC7195626 DOI: 10.1245/s10434-019-07626-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND For patients with peritoneal carcinomatosis undergoing cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC), incomplete cytoreduction (CCR2/3) confers morbidity without survival benefit. The aim of this study is to identify preoperative factors which predict CCR2/3. METHODS All patients who underwent curative-intent CRS/HIPEC of low/high-grade appendiceal, colorectal, or peritoneal mesothelioma cancers in the 12-institution US HIPEC Collaborative from 2000 to 2017 were included (n = 2027). The primary aim is to create an incomplete-cytoreduction risk score (ICRS) to predict CCR2/3 CRS utilizing preoperative data. ICRS was created from a randomly selected cohort of 50% of patients (derivation cohort) and verified on the remaining patients (validation cohort). RESULTS Within our derivation cohort (n = 998), histology was low-grade appendiceal neoplasms in 30%, high-grade appendiceal tumor in 41%, colorectal tumor in 22%, and peritoneal mesothelioma in 8%. CCR0/1 was achieved in 816 patients and CCR 2/3 in 116 patients. On multivariable analysis, preoperative factors associated with incomplete cytoreduction were male gender [odds ratio (OR) 3.4, p = 0.007], presence of ascites (OR 2.8, p = 0.028), cancer antigen (CA)-125 ≥ 40 U/mL (OR 3.4, p = 0.012), and carcinoembryonic antigen (CEA) ≥ 4.2 ng/mL (OR 3.2, p = 0.029). Each preoperative factor was assigned a score of 0 or 1 to form an ICRS from 0 to 4. Scores were grouped as zero (0), low (1-2), or high (3-4). Incidence of CCR2/3 progressively increased by risk group from 1.6% in zero to 13% in low and 39% in high. When ICRS was applied to the validation cohort (n = 1029), this relationship was maintained. CONCLUSION The incomplete cytoreduction risk score incorporates preoperative factors to accurately stratify the risk of CCR2/3 resection in CRS/HIPEC. This score should not be used in isolation, however, to exclude patients from surgery.
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Affiliation(s)
- Mohammad Y Zaidi
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 1365C Clifton Road, NE; Building C, 2nd Floor, Atlanta, GA, 30322, USA
| | - Rachel M Lee
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 1365C Clifton Road, NE; Building C, 2nd Floor, Atlanta, GA, 30322, USA
| | - Adriana C Gamboa
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 1365C Clifton Road, NE; Building C, 2nd Floor, Atlanta, GA, 30322, USA
| | - Shelby Speegle
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 1365C Clifton Road, NE; Building C, 2nd Floor, Atlanta, GA, 30322, USA
| | - Jordan M Cloyd
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Charles Kimbrough
- Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| | - Travis Grotz
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA
| | - Jennifer Leiting
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, Rochester, MN, USA
| | - Keith Fournier
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Andrew J Lee
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Sean Dineen
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Department of Oncologic Sciences, Morsani College of Medicine, Tampa, FL, USA
| | - Sophie Dessureault
- Department of Gastrointestinal Oncology, Moffitt Cancer Center, Department of Oncologic Sciences, Morsani College of Medicine, Tampa, FL, USA
| | - Kaitlyn J Kelly
- Division of Surgical Oncology, Department of Surgery, University of California, San Diego, USA
| | - Nikhil V Kotha
- Division of Surgical Oncology, Department of Surgery, University of California, San Diego, USA
| | - Callisia Clarke
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, USA
| | - T Clark Gamblin
- Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, USA
| | - Sameer H Patel
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Tiffany C Lee
- Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Ryan J Hendrix
- Division of Surgical Oncology, Department of Surgery, University of Massachusetts Medical School, Worcester, MA, USA
| | - Laura Lambert
- Section of Surgical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
| | - Sean Ronnekleiv-Kelly
- Division of Surgical Oncology, Department of Surgery, University of Wisconsin, Madison, WI, USA
| | - Courtney Pokrzywa
- Division of Surgical Oncology, Department of Surgery, University of Wisconsin, Madison, WI, USA
| | - Andrew M Blakely
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
| | - Byrne Lee
- Division of Surgical Oncology, Department of Surgery, City of Hope National Medical Center, Duarte, CA, USA
| | | | - Nadege Fackche
- Department of Surgery, Johns Hopkins University, Baltimore, MD, USA
| | - Maria C Russell
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 1365C Clifton Road, NE; Building C, 2nd Floor, Atlanta, GA, 30322, USA
| | - Shishir K Maithel
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 1365C Clifton Road, NE; Building C, 2nd Floor, Atlanta, GA, 30322, USA
| | - Charles A Staley
- Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, 1365C Clifton Road, NE; Building C, 2nd Floor, Atlanta, GA, 30322, USA.
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Khosrawipour V, Reinhard S, Martino A, Khosrawipour T, Arafkas M, Mikolajczyk A. Increased Tissue Penetration of Doxorubicin in Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) after High-Intensity Ultrasound (HIUS). Int J Surg Oncol 2019; 2019:6185313. [PMID: 31915548 PMCID: PMC6930754 DOI: 10.1155/2019/6185313] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2019] [Accepted: 11/23/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND High-intensity ultrasound (HIUS) has been studied for the past two decades as a new therapeutic option for solid tumor direct treatment and a method for better chemotherapy delivery and perfusion. This treatment approach has not been tested to our knowledge in peritoneal metastatic therapy, where limited tissue penetration of intraperitoneal chemotherapy has been a main problem. Both liquid instillations and pressurized aerosols are affected by this limitation. This study was performed to evaluate whether HIUS improves chemotherapy penetration rates. METHODS High-intensity ultrasound (HIUS) was applied for 0, 5, 30, 60, 120, and 300 seconds on the peritoneal tissue samples from fresh postmortem swine. Samples were then treated with doxorubicin via pressurized intraperitoneal aerosol chemotherapy (PIPAC) under 12 mmHg and 37°C temperature. Tissue penetration of doxorubicin was measured using fluorescence microscopy on frozen thin sections. RESULTS Macroscopic structural changes, identified by swelling of the superficial layer of the peritoneal surface, were observed after 120 seconds of HIUS. Maximum doxorubicin penetration was significantly higher in peritoneum treated with HIUS for 300 seconds, with a depth of 962.88 ± 161.4 μm (p < 0.05). Samples without HIUS had a penetration depth of 252.25 ± 60.41. Tissue penetration was significantly increased with longer HIUS duration, with up to 3.8-fold increased penetration after 300 sec of HIUS treatment. CONCLUSION Our data indicate that HIUS may be used as a method to prepare the peritoneal tissue for intraperitoneal chemotherapy. Higher tissue penetration rates can be achieved without increasing chemotherapy concentrations and preventing structural damage to tissue using short time intervals. More studies need to be performed to analyze the effect of HIUS in combination with intraperitoneal chemotherapy.
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Affiliation(s)
- Veria Khosrawipour
- Division of Colorectal Surgery, Department of Surgery, University of California Irvine (UCI), Irvine, CA, USA
| | - Sören Reinhard
- Department of Bioengineering, University of California, Berkeley (UC Berkeley), Oakland, CA, USA
| | - Alice Martino
- Division of Colorectal Surgery, Department of Surgery, University of California Irvine (UCI), Irvine, CA, USA
| | - Tanja Khosrawipour
- Division of Colorectal Surgery, Department of Surgery, University of California Irvine (UCI), Irvine, CA, USA
- Department of Surgery, University-Hospital Düsseldorf, Düsseldorf, North-Rhein Westfalia, Germany
| | - Mohamed Arafkas
- Department of Plastic Surgery, Ortho-Klinik Dortmund, Dortmund, North-Rhein Westfalia, Germany
| | - Agata Mikolajczyk
- Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Wroclaw, Lower Silesia, Poland
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Demontoux L, Derangère V, Pilot T, Thinselin C, Chevriaux A, Chalmin F, Bouyer F, Ghiringhelli F, Rébé C. Hypotonic stress enhances colon cancer cell death induced by platinum derivatives and immunologically improves antitumor efficacy of intraperitoneal chemotherapy. Int J Cancer 2019; 145:3101-3111. [PMID: 31344262 DOI: 10.1002/ijc.32590] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Revised: 07/01/2019] [Accepted: 07/19/2019] [Indexed: 12/24/2022]
Abstract
Colorectal cancer is a highly metastatic disease that could invade various distal organs and also the peritoneal cavity leading to peritoneal carcinomatosis. This is a terminal condition with poor prognosis and only palliative treatments such as cytoreductive surgery and intraperitoneal chemotherapy are proposed to some patients. However, clinicians use different parameters of treatments without any consensus. Here we decided to evaluate the effect of osmolarity in the efficacy of this procedure to kill colon cancer cells. We first show that a short exposure of platinum derivatives in hypotonic conditions is more efficient to decrease cell viability of human and murine colon cancer cells in vitro as compared to isotonic conditions. This is related to more important incorporation of platinum and the capacity of hypotonic stress to induce the copper transporter CTR1 oligomerization. Oxaliplatin in hypotonic conditions induces caspase-dependent cell death of colon cancer cells. Moreover, hypotonic conditions also modulate the capacity of oxaliplatin and cisplatin (but not carboplatin) to induce immunogenic cell death (ICD). In vivo, oxaliplatin in hypotonic conditions increases CD8+ T cell tumor infiltration and activation. Finally, in a murine peritoneal carcinomatosis model, oxaliplatin in hypotonic conditions is the only tested protocol which is able to slow down the appearance of tumor nodules and increase mice survival, while showing no effect in CD8+ T cells depleted mice or in immunodeficient mice. Altogether, our study provides new information both in vitro and in a preclinical model of peritoneal carcinomatosis, which highlights the importance of hypoosmolarity in intraperitoneal chemotherapy.
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Affiliation(s)
- Lucie Demontoux
- INSERM LNC-UMR1231, Dijon, France.,University of Bourgogne Franche-Comté, Dijon, France
| | - Valentin Derangère
- INSERM LNC-UMR1231, Dijon, France.,University of Bourgogne Franche-Comté, Dijon, France.,Platform of Transfer in Cancer Biology, Centre Georges François Leclerc, Dijon, France
| | - Thomas Pilot
- INSERM LNC-UMR1231, Dijon, France.,University of Bourgogne Franche-Comté, Dijon, France
| | | | - Angélique Chevriaux
- INSERM LNC-UMR1231, Dijon, France.,Platform of Transfer in Cancer Biology, Centre Georges François Leclerc, Dijon, France
| | - Fanny Chalmin
- INSERM LNC-UMR1231, Dijon, France.,University of Bourgogne Franche-Comté, Dijon, France
| | | | - François Ghiringhelli
- INSERM LNC-UMR1231, Dijon, France.,University of Bourgogne Franche-Comté, Dijon, France.,Platform of Transfer in Cancer Biology, Centre Georges François Leclerc, Dijon, France
| | - Cédric Rébé
- INSERM LNC-UMR1231, Dijon, France.,University of Bourgogne Franche-Comté, Dijon, France.,Platform of Transfer in Cancer Biology, Centre Georges François Leclerc, Dijon, France
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Liu YW, Du Y, Chen BA. Effect of hyperthermic intraperitoneal chemotherapy for gastric cancer patients: a meta-analysis of the randomized controlled trials. J Int Med Res 2019; 47:5926-5936. [PMID: 31741406 PMCID: PMC7045644 DOI: 10.1177/0300060519882545] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Objective To determine the effectiveness and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced gastric cancer and peritoneal metastases. Methods PubMed®, CNKI, Web of Science, VIP and WANFANG databases were searched to identify randomized controlled trials (RCTs) that examined the effect of HIPEC on survival, clinical response and adverse events. Patients with advanced gastric cancer and peritoneal metastases were divided into an experimental group and a control group. The statistical results are presented as relative ratio (RR), mean difference (MD) and 95% confidence interval (CI). Results Twenty-one RCTs met the inclusion criteria (n = 1674 patients). Meta-analysis showed that the 3-year survival rate was significantly higher in the HIPEC group than in the control group (RR 1.61; 95% CI 1.43, 1.82) and the complete response rate was significantly higher in the HIPEC group than in the control group (RR 2.35; 95% CI 1.67, 3.31). HIPEC was also beneficial in terms of decreased CEA (MD −1.79; 95% CI −2.22, −1.35). There was no significant difference in the rate of adverse reactions (RR 1.00; 95% CI 0.87, 1.14). Conclusions HIPEC had a beneficial effect on 3-year survival rate and complete response in patients with advanced gastric cancer and peritoneal metastases.
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Affiliation(s)
- Yan-Wen Liu
- Department of Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu Province, China
| | - Ying Du
- Department of Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu Province, China
| | - Bao-An Chen
- Department of Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu Province, China
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Bartlett DJ, Thacker PG, Grotz TE, Graham RP, Fletcher JG, VanBuren WM, Iyer VR, Fidler JL, Menias CO, Wasif N, Sheedy SP. Mucinous appendiceal neoplasms: classification, imaging, and HIPEC. Abdom Radiol (NY) 2019; 44:1686-1702. [PMID: 30610247 DOI: 10.1007/s00261-018-01888-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Recent advances, specifically cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), offer advantages compared to the traditional therapeutic approach of systemic chemotherapy in the treatment of peritoneal carcinomatosis from mucinous appendiceal neoplasms (MAN). This review provides an up-to-date, comprehensive summary of the histologic classification of MAN, reviews common imaging findings of mucoceles and pseudomyxoma peritonei, and describes the radiologist's role in the multidisciplinary care team in quantifying disease and in helping select patients for definitive surgery.
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Affiliation(s)
- David J Bartlett
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Paul G Thacker
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Travis E Grotz
- Department of Hepatobiliary and Pancreatic Surgery, Mayo Clinic, Rochester, MN, USA
| | - Rondell P Graham
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Joel G Fletcher
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Wendaline M VanBuren
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Veena R Iyer
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | - Jeff L Fidler
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA
| | | | - Nabil Wasif
- Department of General Surgery, Mayo Clinic, Scottsdale, AZ, USA
| | - Shannon P Sheedy
- Department of Radiology, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
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