|
1
|
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.
Collapse
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
| |
Collapse
|
|
2
|
Sigler GI, Murtha J, Varley PR. Diagnostic Advances and Novel Therapeutics in Peritoneal Metastasis. Surg Oncol Clin N Am 2025; 34:173-194. [PMID: 40015798 DOI: 10.1016/j.soc.2024.12.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2025]
Abstract
Appropriate assessment of disease burden in patients with peritoneal surface malignancy (PSM) is critical for treatment decision-making, and conventional cross-sectional imaging (computed tomography and/or MRI) often underestimates burden of disease. Advances in imaging for PSM include novel functional imaging modalities that target cells unique to the tumor microenvironment. Novel alternative methods of diagnosis and disease monitoring are also potentially applicable to management of PSM. These include forms of "liquid biopsy" targeting circulating tumor DNA. Novel regional therapies include both new therapeutic agents (immune-based and nanoparticle-based), as well as new methods of delivery such as pressurized intraperitoneal aerosolized chemotherapy.
Collapse
Affiliation(s)
- Gregory I Sigler
- Division of Surgical Oncology, Department of General Surgery, Complex General Surgical Oncology, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Mail Code 7375, Madison, WI 53792, USA
| | - Jacqueline Murtha
- Department of General Surgery, General Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Mail Code 7375, Madison, WI 53792, USA
| | - Patrick R Varley
- Division of Surgical Oncology, Department of General Surgery, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Mail Code 7375, Madison, WI 53792, USA; William S. Middleton Memorial Veterans Affairs Hospital, Madison, WI, USA.
| |
Collapse
|
|
3
|
Dinçer B, Gök AFK, İlhan M, Ercan LD, Kulle CB, Ercan CC, Berker N, Ertekin C. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy outcomes in peritoneal carcinomatosis: 11-year tertiary-center experience. BMC Cancer 2025; 25:479. [PMID: 40089698 PMCID: PMC11909872 DOI: 10.1186/s12885-025-13858-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 03/04/2025] [Indexed: 03/17/2025] Open
Abstract
BACKGROUND Cytoreductive Surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are techniques developed for curative treatment of peritoneal carcinomatosis (PC). Studies have shown that CRS + HIPEC provides a survival advantage in PC, and long-term survival can be achieved in selected cases. This study aimed to evaluate CRS + HIPEC cases performed for curative purposes and to examine the prognostic factors. METHODS PC patients who underwent CRS + HIPEC with curative intent between January 2011 and September 2022 were included. Demographic, clinical, and pathological findings, procedure-specific parameters, complications, mortality, progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS Optimal cytoreduction was achieved in 70% of the patients. The median PFS for the entire series was 9.2 months, while the median OS was 20.5 months, with a 3-year OS rate of 36%. Appendiceal origin, cytoreduction score, absence of lymph node metastasis, and absence of complications were factors associated with a positive impact on both PFS and OS. In multivariate analysis, cytoreduction score emerged as the sole independent factor influencing both PFS and OS. CONCLUSIONS Considering the results in our series, cases of PC in which complete cytoreduction can be achieved should be evaluated for CRS + HIPEC.
Collapse
Affiliation(s)
- Burak Dinçer
- Department of Surgical Oncology, Ankara Oncology Training and Research Hospital, University of Health Sciences, Ankara, Türkiye.
| | - Ali Fuat Kaan Gök
- Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Mehmet İlhan
- Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Leman Damla Ercan
- Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Cemil Burak Kulle
- Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Celal Caner Ercan
- Department of Radiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Neslihan Berker
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Cemalettin Ertekin
- Department of General Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| |
Collapse
|
|
4
|
Noguchi R, Yamaguchi K, Yano H, Gohda Y, Kiyomatsu T, Ota Y, Igari T, Takahashi N, Ohsugi T, Takane K, Ikenoue T, Niida A, Shimizu E, Yamaguchi R, Miyano S, Imoto S, Furukawa Y. Cell of origin and expression profiles of pseudomyxoma peritonei derived from the appendix. Pathol Res Pract 2025; 266:155776. [PMID: 39742833 DOI: 10.1016/j.prp.2024.155776] [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] [Received: 07/20/2024] [Revised: 12/10/2024] [Accepted: 12/16/2024] [Indexed: 01/04/2025]
Abstract
Pseudomyxoma peritonei (PMP) is a rare disease caused by mucin-producing tumors that develop most frequently from the appendix. The disease is characterized by the accumulation of mucin in the abdominal cavity. Although frequent mutations in the KRAS and GNAS genes have been reported in PMP, gene expression profiles of the tumors remain to be fully clarified because of its rarity and the difficulties in collecting pure cancerous cells scattered within the mucin. To disclose the molecular features of PMP cells, we performed RNA-seq analysis of ten PMPs and their matched non-tumorous colonic epithelium in combination with laser-microdissection. As a result, we identified a total of 32 differently expressed genes (DEGs) between the tumors and non-tumorous colonic epithelium. A cell-of-origin subtype analysis with the nearest template prediction algorithm corroborated that PMP tumor cells belonged to the goblet cell subtype, and tumorous cells of PMP appear to arise from goblet cells. Interestingly, over representation analysis (ORA) uncovered that the tumors were significantly associated with three ontology terms, namely epithelial mesenchymal transition (EMT), angiogenesis, and inflammatory response. Comparison of gene expression profiles between disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous adenocarcinomas (PMCA) identified a total of 687 DEGs. Additional gene set enrichment analysis (GSEA) revealed that ontology terms "G2M checkpoint" and "E2F targets" were significantly enriched in PMCA supporting the view that PMCA has more aggressive properties than DPAM. These data may be useful to further understand the molecular characteristics of PMP.
Collapse
Affiliation(s)
- Rei Noguchi
- Division of Clinical Genome Research, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Kiyoshi Yamaguchi
- Division of Clinical Genome Research, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Hideaki Yano
- Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Yoshimasa Gohda
- Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Tomomichi Kiyomatsu
- Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Yasunori Ota
- Department of Pathology, Research Hospital, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Toru Igari
- Pathology Division of Clinical Laboratory, National Center for Global Health and Medicine, Tokyo, Japan
| | - Norihiko Takahashi
- Division of Clinical Genome Research, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Tomoyuki Ohsugi
- Division of Clinical Genome Research, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Kiyoko Takane
- Division of Clinical Genome Research, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Tsuneo Ikenoue
- Division of Clinical Genome Research, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Atsushi Niida
- Division of Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Eigo Shimizu
- Division of Health Medical Intelligence, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Rui Yamaguchi
- Division of Health Medical Intelligence, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Division of Cancer Systems Biology, Aichi Cancer Center Research Institute, Aichi, Japan
| | - Satoru Miyano
- Division of Health Medical Intelligence, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan; Department of Integrated Analytics, Medical and Dental Data Science Center, Tokyo Medical and Dental University, Tokyo, Japan
| | - Seiya Imoto
- Division of Health Medical Intelligence, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Yoichi Furukawa
- Division of Clinical Genome Research, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
| |
Collapse
|
|
5
|
Stillman M, Somasundar P, Espat NJ, Calvino AS, Kwon S. Negative Impact of Systemic Therapy on Survival in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Low-Grade Metastatic Appendiceal Adenocarcinoma. Ann Surg Oncol 2025; 32:221-229. [PMID: 39500859 DOI: 10.1245/s10434-024-16443-x] [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: 08/26/2024] [Accepted: 10/20/2024] [Indexed: 12/22/2024]
Abstract
BACKGROUND Despite studies demonstrating that patients with peritoneal metastases from low-grade appendiceal adenocarcinoma (AA) do not respond well to systemic chemotherapy (SC), patients frequently undergo combination of SC with cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) regardless of grade. METHODS A nationwide retrospective analysis using the National Cancer Database evaluated patients with AA with peritoneal metastasis from 2016 to 2021. Cox proportional hazards model was used to evaluate the impact of SC in addition to CRS/HIPEC on overall survival (OS) stratified by tumor grade. RESULTS A total of 1,449 patients were included: 481 low-grade, 428 intermediate-grade, and 540 high-grade tumors. Clinical variables, such as age, sex, and comorbidity index, were similar across tumor grades. Cytoreductive surgery/hyperthermic intraperitoneal chemotherapy without SC was utilized in 65.73% of low-grade cases compared with 41.01% in intermediate-grade and 11.11% in high-grade cases. Systemic chemotherapy was utilized alone in 17.74% and with CRS/HIPEC in 16.53% of low-grade cases. In adjusted survival analysis, addition of SC to CRS/HIPEC was associated with worse OS for patients with low-grade AA (hazard ratio [HR] 2.77, 95% confidence interval [CI] 1.18-6.50) but not for intermediate (HR 1.65, 95% CI 0.82-3.35) and high-grade tumors (HR 1.18, 95% CI 0.67-2.45). The addition of time to definitive surgery variable nullified the negative impact of adding SC to CRS/HIPEC in low-grade AA (HR 1.76, 95% CI 0.68-4.53). CONCLUSIONS Negative OS impact of SC may be mediated by delays in effective surgical/intraoperative therapy. If CRS/HIPEC is planned for patients with metastatic low-grade AA, avoiding SC may facilitate earlier surgical intervention and improve survival.
Collapse
Affiliation(s)
- Mason Stillman
- Department of Surgery, Columbia University Irving Medical Center, New York, NY, USA
| | - Ponnandai Somasundar
- Department of Surgery, Division of Surgical Oncology, Roger Williams Medical Center, Providence, RI, USA
- Department of Surgery, Boston University Medical Center, Boston, MA, USA
- Roger Williams Surgery and Cancer Outcomes Research and Equity (RWSCORE) Center, Providence, RI, USA
| | - N Joseph Espat
- Department of Surgery, Division of Surgical Oncology, Roger Williams Medical Center, Providence, RI, USA
- Department of Surgery, Boston University Medical Center, Boston, MA, USA
- Roger Williams Surgery and Cancer Outcomes Research and Equity (RWSCORE) Center, Providence, RI, USA
| | - Abdul S Calvino
- Department of Surgery, Division of Surgical Oncology, Roger Williams Medical Center, Providence, RI, USA
- Department of Surgery, Boston University Medical Center, Boston, MA, USA
- Roger Williams Surgery and Cancer Outcomes Research and Equity (RWSCORE) Center, Providence, RI, USA
| | - Steve Kwon
- Department of Surgery, Division of Surgical Oncology, Roger Williams Medical Center, Providence, RI, USA.
- Department of Surgery, Boston University Medical Center, Boston, MA, USA.
- Roger Williams Surgery and Cancer Outcomes Research and Equity (RWSCORE) Center, Providence, RI, USA.
| |
Collapse
|
|
6
|
Pastier C, De Hingh IHJT, Goéré D. New insights in the management of pseudomyxoma peritonei. J Surg Oncol 2024; 130:1316-1325. [PMID: 39206531 PMCID: PMC11826005 DOI: 10.1002/jso.27842] [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: 07/01/2024] [Revised: 08/05/2024] [Accepted: 08/09/2024] [Indexed: 09/04/2024]
Abstract
While a rare entity, peritoneal pseudomyxoma treatment evolves. Decision-making criteria improve with imaging development and exploratory laparoscopy. Surgery remains at the core of the therapeutic strategy whatever disease progression. Complete cytoreduction plus hyperthermic intraperitoneal chemotherapy (HIPEC) is standard of care. Iterative cytoreduction or debulking is sometimes justified. Intraperitoneal chemotherapy modalities change with early postoperative HIPEC or pressurized intraperitoneal aerosol chemotherapy. Systemic or local treatment such as new chemo/immuno-therapies or BromAc should improve outcomes. Expertise and multicentric cooperation are more than ever needed.
Collapse
Affiliation(s)
- Clément Pastier
- Department of Digestive and Endocrine Surgery, Saint‐Louis Hospital AP‐HPUniversité Paris CitéParisFrance
| | | | - Diane Goéré
- Department of Digestive and Endocrine Surgery, Saint‐Louis Hospital AP‐HPUniversité Paris CitéParisFrance
| |
Collapse
|
|
7
|
Ward EP, Greenbaum A. Exploring the Patient Experience Through Qualitative Methods: The Missing Piece of Cytoreductive Surgery and HIPEC Research. Ann Surg Oncol 2024; 31:7679-7681. [PMID: 39103683 DOI: 10.1245/s10434-024-15997-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 07/23/2024] [Indexed: 08/07/2024]
Affiliation(s)
- Erin P Ward
- Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA
| | - Alissa Greenbaum
- Department of Surgery, Division of Surgical Oncology, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.
| |
Collapse
|
|
8
|
Ghandour R, Bardier A, Wagner M, Malgras B, Kaci R, Doat S, Pocard M. Association between preoperative appendiceal histology grade and Pseudomyxoma peritonei grade offers a solution to avoid right hemicolectomy during cytoreductive surgery and HIPEC. Surg Oncol 2024; 56:102123. [PMID: 39163796 DOI: 10.1016/j.suronc.2024.102123] [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: 03/14/2024] [Revised: 08/01/2024] [Accepted: 08/16/2024] [Indexed: 08/22/2024]
Abstract
INTRODUCTION & OBJECTIVES Treatment of PMP consists of appendectomy, cytoreductive surgery (CRS) and HIPEC. Right-sided hemicolectomy is necessary only when PMP is high grade, given the lymphatic invasion risk. To date, no single preoperative factor was identified as predictive of PMP grade. MATERIALS & METHODS Preoperative factors of a prospective cohort study on PMP were retrospectively analyzed, in order to identify situations linked with high or low grade appendiceal PMP. The main outcome was PMP grade on definitive histology after CRS. RESULTS n = 105. In univariate analysis, the grade of the appendiceal tumor, systematically reviewed in an expert center, showed an OR of 25.00 (95 % CI: 3.30-189.27; p = 0.001) and an NPV of 93.75 [85.36, 100]. Peritoneal biopsy demonstrated an OR of 19.80 (95 % CI: 2.30-170.71; p = 0.002) and a PPV of 90 [71.41, 100]. In multivariate analysis, these two factors remained significantly associated with PMP grade. CONCLUSION Whenever appendiceal tumor is low grade on preoperative histology, the colon has to be spared unless completeness of CRS is compromised, which is a high-grade feature in fact. In case of high grade appendiceal tumor and/or peritoneal biopsy, right-sided hemicolectomy is warranted. If no histology is available preoperatively, adapt to intraoperative lesions as no preoperative factors seem to be predictive.
Collapse
Affiliation(s)
- Richard Ghandour
- Department of Hepato-Biliary and Pancreatic Surgery, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière University Hospital, 47-83 Bd de l'Hôpital,Cedex 13, F-75651, Paris, France.
| | - Armelle Bardier
- Department of Anatomopathology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière University Hospital, 47-83 Bd de l'Hôpital,Cedex 13, F-75651, Paris, France
| | - Mathilde Wagner
- Department of Radiology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière University Hospital, 47-83 Bd de l'Hôpital,Cedex 13, F-75651, Paris, France
| | - Brice Malgras
- Department of Surgery, Bégin Army Instruction Hospital, 69, avenue de Paris, 94160, St Mandé, France; Paris Cité University, INSERM U1275, CArcinose Péritoine Paris-Technologies, F-75010, Paris, France
| | - Rachid Kaci
- Paris Cité University, INSERM U1275, CArcinose Péritoine Paris-Technologies, F-75010, Paris, France; Department of Anatomopathology, Lariboisière University Hospital, 2 rue Ambroise Paré, F-75010, Paris, France
| | - Solène Doat
- Department of Hepato-Gastro-Enterology, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière University Hospital, 47-83 Bd de l'Hôpital,Cedex 13, F-75651, Paris, France
| | - Marc Pocard
- Department of Hepato-Biliary and Pancreatic Surgery, Sorbonne Université, Assistance Publique-Hôpitaux de Paris (AP-HP), Pitié-Salpêtrière University Hospital, 47-83 Bd de l'Hôpital,Cedex 13, F-75651, Paris, France; Paris Cité University, INSERM U1275, CArcinose Péritoine Paris-Technologies, F-75010, Paris, France.
| |
Collapse
|
|
9
|
McClelland PH, Gregory SN, Nah SK, Hernandez JM, Davis JL, Blakely AM. Predicting Survival in Mucinous Adenocarcinoma of the Appendix: Demographics, Disease Presentation, and Treatment Methodology. Ann Surg Oncol 2024; 31:6237-6251. [PMID: 38874874 PMCID: PMC11300641 DOI: 10.1245/s10434-024-15526-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 05/13/2024] [Indexed: 06/15/2024]
Abstract
BACKGROUND Mucinous adenocarcinoma of the appendix (MACA) follows a complex disease course with variable survival. Large-scale predictive modeling may determine subtle yet important prognostic factors otherwise unseen in smaller cohort analyses. METHODS Patients with MACA were identified from the Surveillance, Epidemiology, and End Results (SEER) Research Plus database (2005-2019). Primary, secondary, and tertiary outcomes were disease-specific survival (DSS), overall survival (OS), and average annual percent change (AAPC) in incidence. RESULTS Among 4,258 included patients, MACA was most frequently diagnosed at 50 to 69 years (52.0%), with female preponderance (55.9%). MACA incidence AAPC was 3.8 (95% confidence interval [CI] 1.9-5.9). For patients with exclusive, first-diagnosis MACA included in survival analysis (3,222 patients), median DSS and OS were 118 and 88 months, respectively. In DSS-based multivariable analysis, worse prognosis was associated with non-Hispanic Black background (HR 1.36, 95% CI 1.02-1.82; p = 0.036), high grade (grade 3 HR 3.10, 95% CI 2.44-3.92; p < 0.001), lymphatic spread (HR 2.73, 95% CI 2.26-3.30; p < 0.001), and distant metastasis (HR 5.84, 95% CI 3.86-8.83; p < 0.001). In subcohort analysis of patients with rationale for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC, 2,387 patients), CRS-HIPEC was associated with survival benefit compared with surgery alone but only for moderate-grade tumors (median DSS/OS 138/138 vs. 116/87 months; p < 0.001). CONCLUSIONS Mucinous adenocarcinoma of the appendix incidence is increasing in the United States. Survival rates are affected by both demographics and classical risk factors, and CRS-HIPEC-associated survival benefit predominantly occurs in moderate-grade tumors. Further exploration of biologic and clinicopathologic features may enhance risk stratification for this disease.
Collapse
Affiliation(s)
- Paul H McClelland
- Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Stephanie N Gregory
- Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Shirley K Nah
- Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Jonathan M Hernandez
- Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Jeremy L Davis
- Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
| | - Andrew M Blakely
- Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
| |
Collapse
|
|
10
|
Yano H, Gohda Y, Moran BJ, Suda R, Kokudo N. Long-term outcomes and survival analysis of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy in patients with pseudomyxoma peritonei at a newly established peritoneal malignancy centre in Japan. Ann Gastroenterol Surg 2024; 8:701-710. [PMID: 38957568 PMCID: PMC11216784 DOI: 10.1002/ags3.12791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 12/20/2023] [Accepted: 02/26/2024] [Indexed: 07/04/2024] Open
Abstract
Background Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is established in the management of pseudomyxoma peritonei (PMP), selected cases of peritoneal mesothelioma, and resectable colorectal or ovarian peritoneal metastases in Western countries. However, the efficacy and feasibility of these techniques are not well established in the Asian population, and little has been reported on long-term survival outcomes for surgically resected PMP patients. Materials and Methods Retrospective analysis of a prospective database of short- and longer-term outcomes of consecutive patients who underwent CRS and HIPEC for PMP in a newly established peritoneal malignancy unit in Japan between 2010 and 2016. Results A total of 105 patients underwent CRS and HIPEC and 57 maximal tumor debulking (MTD) for pseudomyxoma peritonei. In the CRS group, the primary tumor was appendiceal in 94 patients (90%) followed by ovarian and colorectal. Major postoperative complications occurred in 22/105 patients (21%) with one in-hospital mortality (0.9%). The 5-year overall and disease-free survival rates for the CRS group were 74.2% and 50.1%, respectively. Multivariate analysis revealed unfavorable histology to be the significant predictor of reduced overall and disease-free survival. Completeness of cytoreduction, CA19-9, and CA125 were also associated with disease-free survival. Conclusions This is the first report on long-term outcomes and survival analysis of CRS and HIPEC for PMP in the Asian population. CRS and HIPEC can be conducted with reasonable safety and favorable survival in a new center. Complete tumor removal and histological type are the strongest prognostic factors for both overall and disease-free survival.
Collapse
Affiliation(s)
- Hideaki Yano
- Department of SurgeryNational Center for Global Health and MedicineTokyoJapan
- Division of Colorectal SurgeryUniversity Hospital SouthamptonSouthamptonUK
| | - Yoshimasa Gohda
- Department of SurgeryNational Center for Global Health and MedicineTokyoJapan
| | - Brendan J. Moran
- Peritoneal Malignancy Institute, North Hampshire HospitalBasingstokeUK
| | | | - Norihiro Kokudo
- Department of SurgeryNational Center for Global Health and MedicineTokyoJapan
| |
Collapse
|
|
11
|
Ayala-de Miguel C, Jiménez-Castro J, Sánchez-Vegas A, Díaz-López S, Chaves-Conde M. Neoplastic appendiceal mucinous lesions: a narrative review of the literature from an oncologist's perspective. Clin Transl Oncol 2024; 26:1287-1299. [PMID: 38070049 DOI: 10.1007/s12094-023-03356-6] [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: 08/19/2023] [Accepted: 11/14/2023] [Indexed: 05/22/2024]
Abstract
Appendiceal mucinous lesions' classification and nomenclature has been modified several times along the last decades, reflecting their great heterogeneity and making difficult to compare results and draw conclusions. Despite its nearby origin, appendiceal mucinous lesions have a distinctive behaviour compared to colorectal cancer, including their molecular and genetic markers. Due to their low frequency, their management is not well standardised. However, surgery is considered the cornerstone of treatment. Their indolent behaviour has encouraged surgeons to apply more aggressive treatments, such as cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC), that may extend overall survival. Chemotherapy is reserved for unresectable and/or disseminated disease and could play a role in the adjuvant and neoadjuvant setting. Pressurised intraperitoneal aerosol chemotherapy (PIPAC) is recently emerging as a possible alternative for treatment in advanced disease although its results in long-term survival are lacking Hereby, we review the available evidence in the management of appendiceal mucinous lesions, including localised and disseminated disease, with a special emphasis on the oncological perspective, focusing on the lights and shadows of the systemic treatments.
Collapse
Affiliation(s)
- Carlos Ayala-de Miguel
- Servicio Oncología Médica, Hospital Universitario Valme, Ctra. de Cádiz Km 548,9, C.P.: 41014, Seville, Spain
| | - Jerónimo Jiménez-Castro
- Servicio Oncología Médica, Hospital Universitario Valme, Ctra. de Cádiz Km 548,9, C.P.: 41014, Seville, Spain.
| | - Adrián Sánchez-Vegas
- Servicio Oncología Médica, Hospital Universitario Valme, Ctra. de Cádiz Km 548,9, C.P.: 41014, Seville, Spain
| | - Sebastián Díaz-López
- Servicio Oncología Médica, Hospital Universitario Valme, Ctra. de Cádiz Km 548,9, C.P.: 41014, Seville, Spain
| | - Manuel Chaves-Conde
- Servicio Oncología Médica, Hospital Universitario Valme, Ctra. de Cádiz Km 548,9, C.P.: 41014, Seville, Spain
| |
Collapse
|
|
12
|
Moran BJ. Appendicitis to multivisceral transplantation: a career experience with appendiceal malignancy. Ann R Coll Surg Engl 2024; 106:219-225. [PMID: 37367485 PMCID: PMC10904263 DOI: 10.1308/rcsann.2023.0013] [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] [Accepted: 02/17/2023] [Indexed: 06/28/2023] Open
Abstract
John Hunter is regarded as the father of scientific surgery. His principles involved reasoning, observation and experimentation. His most powerful saying was: "Why not try the experiment?" This manuscript charts a career in abdominal surgery ranging from the treatment of appendicitis to the development of the largest appendiceal tumour centre in the world. The journey has led to the first report of a successful multivisceral and abdominal wall transplant for patients with recurrent non-resectable pseudomyxoma peritonei. We all stand on the shoulders of giants and surgery progresses by learning from the past while being prepared to experiment into the future.
Collapse
Affiliation(s)
- BJ Moran
- Hampshire Hospitals NHS Foundation Trust, UK
| |
Collapse
|
|
13
|
Noguchi R, Yoshimatsu Y, Sin Y, Ono T, Tsuchiya R, Yoshida H, Kiyono T, Yonemura Y, Kondo T. Establishment and characterization of NCC-PMP2-C1: a novel patient-derived cell line of pseudomyxoma peritonei with signet ring cells. Hum Cell 2024; 37:511-522. [PMID: 38143259 DOI: 10.1007/s13577-023-01015-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Accepted: 11/23/2023] [Indexed: 12/26/2023]
Abstract
Pseudomyxoma peritonei (PMP) is a rare phenomenon, characterized by accumulation of mucus in the abdominal cavity due to a mucinous neoplasm. Histologically, PMP is divided into three prognostic classes, namely low-grade mucinous carcinoma peritonei (LGMCP), high-grade mucinous carcinoma peritonei (HGMCP), and high-grade mucinous carcinoma peritonei with signet ring cells (HGMCP-S); HGMCP-S exhibits the worst prognosis. Complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have been established as the standard therapy for PMP. However, 50% of patients with PMP experience a recurrence, and 30-40% are unable to receive the standard treatment due to invasive diseases. Therefore, novel therapies are required for their treatment. Although patient-derived cell lines are important tools for basic and pre-clinical research, PMP cell lines derived from patients with HGMCP-S have never been reported. Thus, we established a novel PMP cell line NCC-PMP2-C1, using surgically resected tumor tissue from a patient with HGMCP-S. NCC-PMP2-C1 cells were maintained for more than five months and passaged 30 times under culture conditions. NCC-PMP2-C1 cells exhibited multiple deletions and somatic mutations, slow growth, histological features, and dissemination of tumor cells in nude mice. Screening for the anti-proliferative effects of anti-cancer drugs on cells revealed that bortezomib, mubritinib, and romidepsin had a significant response against NCC-PMP2-C1 cells. Thus, the NCC-PMP2-C1 cell line is the first PMP cell line harboring signet ring cells and will be a valuable resource for basic and preclinical studies of HGMCP-S.
Collapse
Affiliation(s)
- Rei Noguchi
- Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Yuki Yoshimatsu
- Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Yooksil Sin
- Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Takuya Ono
- Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Ryuto Tsuchiya
- Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan
| | - Hiroshi Yoshida
- Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, Japan
| | - Tohru Kiyono
- Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan
| | - Yutaka Yonemura
- NPO to Support Peritoneal Surface Malignancy Treatment, Japanese/Asian School of Peritoneal Surface Oncology, Kyoto, Japan
- Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kishiwada Tokushukai Hospital, Kishiwada, Japan
- Department of Regional Cancer Therapy, Peritoneal Surface Malignancy Center, Kusatsu General Hospital, Shiga, Japan
| | - Tadashi Kondo
- Division of Rare Cancer Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-Ku, Tokyo, 104-0045, Japan.
| |
Collapse
|
|
14
|
Xia W, Geng Y, Hu W. Peritoneal Metastasis: A Dilemma and Challenge in the Treatment of Metastatic Colorectal Cancer. Cancers (Basel) 2023; 15:5641. [PMID: 38067347 PMCID: PMC10705712 DOI: 10.3390/cancers15235641] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 11/07/2023] [Accepted: 11/13/2023] [Indexed: 10/25/2024] Open
Abstract
Peritoneal metastasis (PM) is a common mode of distant metastasis in colorectal cancer (CRC) and has a poorer prognosis compared to other metastatic sites. The formation of PM foci depends on the synergistic effect of multiple molecules and the modulation of various components of the tumor microenvironment. The current treatment of CRC-PM is based on systemic chemotherapy. However, recent developments in local therapeutic modalities, such as cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC), have improved the survival of these patients. This article reviews the research progress on the mechanism, characteristics, diagnosis, and treatment strategies of CRC-PM, and discusses the current challenges, so as to deepen the understanding of CRC-PM among clinicians.
Collapse
Affiliation(s)
- Wei Xia
- Department of Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou 213003, China;
| | - Yiting Geng
- Department of Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou 213003, China;
| | - Wenwei Hu
- Department of Oncology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou 213003, China;
- Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou 213003, China
| |
Collapse
|
|
15
|
Wald AI, Pingpank JF, Ongchin M, Hall LB, Jones H, Altpeter S, Liebdzinski M, Hamed AB, Derby J, Nikiforova MN, Bell PD, Paniccia A, Zureikat AH, Gorantla VC, Rhee JC, Thomas R, Bartlett DL, Smith K, Henn P, Theisen BK, Shyu S, Shalaby A, Choudry MHA, Singhi AD. Targeted Next-Generation Sequencing Improves the Prognostication of Patients with Disseminated Appendiceal Mucinous Neoplasms (Pseudomyxoma Peritonei). Ann Surg Oncol 2023; 30:7517-7526. [PMID: 37314541 DOI: 10.1245/s10434-023-13721-y] [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: 08/18/2022] [Accepted: 04/19/2023] [Indexed: 06/15/2023]
Abstract
BACKGROUND Appendiceal mucinous neoplasms (AMNs) with disseminated disease (pseudomyxoma peritonei) are heterogeneous tumors with variable clinicopathologic behavior. Despite the development of prognostic systems, objective biomarkers are needed to stratify patients. With the advent of next-generation sequencing (NGS), it remains unclear if molecular testing can improve the evaluation of disseminated AMN patients. METHODS Targeted NGS was performed for 183 patients and correlated with clinicopathologic features to include American Joint Committee on Cancer/World Health Organization (AJCC/WHO) histologic grade, peritoneal cancer index (PCI), completeness of cytoreduction (CC) score, and overall survival (OS). RESULTS Genomic alterations were identified for 179 (98%) disseminated AMNs. Excluding mitogen-activated protein kinase genes and GNAS due to their ubiquitous nature, collective genomic alterations in TP53, SMAD4, CDKN2A, and the mTOR genes were associated with older mean age, higher AJCC/WHO histologic grade, lymphovascular invasion, perineural invasion, regional lymph node metastasis, and lower mean PCI (p < 0.040). Patients harboring TP53, SMAD4, ATM, CDKN2A, and/or mTOR gene alterations were found to have lower OS rates of 55% at 5 years and 14% at 10 years, compared with 88% at 5 years and 88% at 10 years for patients without the aforementioned alterations (p < 0.001). Based on univariate and multivariate analyses, genomic alterations in TP53, SMAD4, ATM, CDKN2A, and/or the mTOR genes in disseminated AMNs were a negative prognostic factor for OS and independent of AJCC/WHO histologic grade, PCI, CC score, and hyperthermic intraperitoneal chemotherapy treatment (p = 0.006). CONCLUSIONS Targeted NGS improves the prognostic assessment of patients with disseminated AMNs and identifies patients who may require increased surveillance and/or aggressive management.
Collapse
Affiliation(s)
- Abigail I Wald
- Department of Pathology, UPMC Presbyterian Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - James F Pingpank
- Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Melanie Ongchin
- Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Lauren B Hall
- Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Heather Jones
- Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Shannon Altpeter
- Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Michelle Liebdzinski
- Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Ahmed B Hamed
- Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Joshua Derby
- Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Marina N Nikiforova
- Department of Pathology, UPMC Presbyterian Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Phoenix D Bell
- Department of Pathology, UPMC Presbyterian Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Alessandro Paniccia
- Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Amer H Zureikat
- Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Vikram C Gorantla
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - John C Rhee
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Roby Thomas
- Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - David L Bartlett
- AHN Cancer Institute, Allegheny Health Network, Pittsburgh, PA, USA
| | - Katelyn Smith
- Department of Pathology, UPMC Presbyterian Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - Patrick Henn
- Department of Pathology, University of Colorado Hospital, Aurora, CO, USA
| | - Brian K Theisen
- Department of Pathology, Henry Ford Health System, Detroit, MI, USA
| | - Susan Shyu
- Department of Pathology, WellSpan York Hospital, York, PA, USA
| | - Akram Shalaby
- Department of Pathology, UPMC Presbyterian Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - M Haroon A Choudry
- Department of Surgery, UPMC Cancer Pavilion, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
| | - Aatur D Singhi
- Department of Pathology, UPMC Presbyterian Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
| |
Collapse
|
|
16
|
Chao A, Chen SJ, Chen HC, Tan KT, Hsiao W, Jung SM, Yang LY, Huang KG, Chou HH, Huang HJ, Chang TC, Chao AS, Lee YH, Wu RC, Lai CH. Mutations in circulating tumor DNA detected in the postoperative period predict poor survival in patients with ovarian cancer. Biomed J 2023; 46:100563. [PMID: 36208860 PMCID: PMC10498401 DOI: 10.1016/j.bj.2022.09.004] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 08/01/2022] [Accepted: 09/30/2022] [Indexed: 11/02/2022] Open
Abstract
BACKGROUND We investigated whether mutations in plasma circulating tumor DNA (ctDNA) can provide prognostic insight in patients with different histological types of ovarian carcinoma. We also examined the concordance of mutations detected in ctDNA samples with those identified in the corresponding formalin-fixed paraffin-embedded (FFPE) tumor specimens. METHODS Between July 2016 and December 2017, 29 patients with ovarian carcinoma were prospectively enrolled. FFPE tumor specimens were obtained from all participants. A total of 187 blood samples for ctDNA analysis were collected before surgery (C0), immediate after surgery before adjuvant chemotherapy (C1), and at six-month intervals. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS The study cohort consisted of 13 (44.8%) patients with high-grade serous carcinomas (HGSC), 9 (31.0%) with clear cell carcinoma, 2 (6.9%) with mucinous carcinomas, 4 (13.8%) with low-grade serous carcinomas, and 1 (3.4%) with endometrioid carcinoma. Twenty-four (82.8%) patients had at least one detectable ctDNA variant. The concordance rate between mutations identified in pretreatment ctDNA and corresponding FFPE tumor specimens was 92.3% for patients with HGSC and 58.6% for the entire cohort. The median follow-up time was 33.15 months (range: 0.79-46.13 months). Patients with an advanced stage disease more likely had detectable ctDNA mutations before surgery (C0) and after surgery at C1, while those with HGSC more likely had ctDNA mutations detected before surgery. The presence of ctDNA mutations at C1 was an independent predictor of worse OS with a hazard ratio of 6.56 (95% confidence interval, (1.07-40.17) for detectable versus undetectable C1 ctDNA variants, p = 0.042). CONCLUSIONS ctDNA mutations are common in patients with ovarian carcinoma. The presence of ctDNA mutations after surgery was an independent predictor of less favorable PFS and OS.
Collapse
Affiliation(s)
- Angel Chao
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Gynecologic Cancer Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | | | | | | | - Wen Hsiao
- ACT Genomics, Co. Ltd, Taipei, Taiwan
| | - Shih-Ming Jung
- College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Pathology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Lan-Yan Yang
- Biostatistics Unit, Clinical Trial Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Kuan-Gen Huang
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Gynecologic Cancer Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Hung-Hsueh Chou
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Gynecologic Cancer Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Huei-Jean Huang
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Gynecologic Cancer Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Ting-Chang Chang
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Gynecologic Cancer Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - An-Shine Chao
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Obstetrics and Gynecology, New Taipei City Municipal Tu Cheng Hospital, New Taipei, Taiwan
| | - Yun-Hsien Lee
- Department of Biotechnology, Ming-Chuan University, Taoyuan, Taiwan; Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan
| | - Ren-Chin Wu
- College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Pathology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
| | - Chyong-Huey Lai
- Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan; Gynecologic Cancer Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan.
| |
Collapse
|
|
17
|
Conley AB, Fournier KF, Sood AK, Frumovitz M. Secondary Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy for Advanced or Recurrent Mucinous Ovarian Cancer. Obstet Gynecol 2023; 141:1019-1023. [PMID: 37023452 DOI: 10.1097/aog.0000000000005154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 01/12/2023] [Indexed: 04/08/2023]
Abstract
BACKGROUND Advanced or recurrent primary mucinous ovarian cancer is typically incurable and associated with short progression-free and overall survival when treated with standard chemotherapy. Novel approaches are desperately needed for women with this disease. CASES Two patients with advanced or recurrent primary mucinous ovarian cancer were treated with secondary cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). No additional chemotherapy was administered postoperatively. Both patients achieved a complete and durable response, with no evidence of recurrence at 21 and 27 months, respectively, after CRS with HIPEC. CONCLUSION Secondary CRS with HIPEC represents a potential therapeutic option for women with recurrent primary mucinous ovarian cancer.
Collapse
Affiliation(s)
- Aliyah B Conley
- Department of Gynecologic Oncology and Reproductive Medicine and the Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | | | | | | |
Collapse
|
|
18
|
Taher R, Carr NJ, Vanderpuye N, Stanford S. Fear of Cancer Recurrence in peritoneal malignancy patients following treatment: a cross-sectional study. J Cancer Surviv 2023; 17:300-308. [PMID: 35900688 DOI: 10.1007/s11764-022-01238-4] [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: 02/16/2022] [Accepted: 07/19/2022] [Indexed: 02/07/2023]
Abstract
PURPOSE To assess Fear of Cancer Recurrence (FCR)-its prevalence, trajectory, and relationship to several demographic and clinical characteristics, and quality of life-in a sample of peritoneal malignancy survivors, up to 5 years post-surgery. METHODS The Fear of Cancer Recurrence Inventory-Short Form (FCRI-SF) and 36-Item Short-Form Health Survey (SF-36) were used to collect cross-sectional data from peritoneal malignancy survivors to assess their Fear of Cancer Recurrence and quality of life respectively as well as other demographic and clinical data. RESULTS The results show that more than two-thirds of the participants (N = 301) experience severe/clinical FCR. FCR is relatively stable over time. Younger patients who are struggling with anxiety or depression or receiving professional mental health support at the time of the surgery are at a higher risk of FCR. FCR is associated with a worse quality of life. CONCLUSIONS Peritoneal malignancy survivors are at a high risk of FCR, and it compromises their psychological, mental, and social well-being (quality of life). IMPLICATIONS FOR CANCER SURVIVORS Raise awareness about the high risk of FCR in this population and the demographic and clinical factors that are associated with it. Encourage peritoneal malignancy services and health professionals to address FCR in this population by normalizing it and providing support for those struggling with it.
Collapse
Affiliation(s)
- Rayan Taher
- Peritoneal Malignancy Institute, Hampshire Hospitals NHS Foundation Trust, Ground Floor, The Ark, Dinwoodie Drive, Basingstoke, RG24 9NN, UK.
| | - Norman John Carr
- Peritoneal Malignancy Institute, Hampshire Hospitals NHS Foundation Trust, Ground Floor, The Ark, Dinwoodie Drive, Basingstoke, RG24 9NN, UK
| | - Nancy Vanderpuye
- Peritoneal Malignancy Institute, Hampshire Hospitals NHS Foundation Trust, Ground Floor, The Ark, Dinwoodie Drive, Basingstoke, RG24 9NN, UK
| | - Sophia Stanford
- Peritoneal Malignancy Institute, Hampshire Hospitals NHS Foundation Trust, Ground Floor, The Ark, Dinwoodie Drive, Basingstoke, RG24 9NN, UK
| |
Collapse
|
|
19
|
Ihemelandu C. The Landmark Series: Scoring Systems for Primary Peritoneal Surface Malignancy. Ann Surg Oncol 2023; 30:1832-1837. [PMID: 36550329 DOI: 10.1245/s10434-022-12941-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 12/01/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) represents an innovative approach to treat or prevent peritoneal metastasis. However, given the morbidity that can be associated with this procedure, adequate patient selection facilitated by scoring systems for primary peritoneal surface malignancy (PSM) is paramount to ensure equitable morbidity as well as acceptable survival outcome. METHODS Seminal studies on scoring systems for PSM that have laid the foundation for adequate patient selection and prognostication are spotlighted. RESULTS Quantitative prognostic indicators have been defined for patients with PSM that enable the surgeon to make sound clinical judgements as to who may or may not benefit from CRS/HIPEC. These prognostic indicators include the histopathology of the tumor, findings on the preoperative abdominal and pelvic computerized axial tomography, the Peritoneal Cancer Index, completeness of cytoreduction score, and prior surgical score. CONCLUSIONS Scoring systems for primary peritoneal surface malignancy reviewed in this article highlight the utility of these systems for patient selection for CRS/HIPEC and prognostication.
Collapse
|
|
20
|
Vaira M, Robella M, Guaglio M, Berchialla P, Sommariva A, Valle M, Pasqual EM, Roviello F, Framarini M, Fiorentini G, Sammartino P, Ilari Civit A, Di Giorgio A, Ansaloni L, Deraco M. Diagnostic and Therapeutic Algorithm for Appendiceal Tumors and Pseudomyxoma Peritonei: A Consensus of the Peritoneal Malignancies Oncoteam of the Italian Society of Surgical Oncology (SICO). Cancers (Basel) 2023; 15:cancers15030728. [PMID: 36765686 PMCID: PMC9913318 DOI: 10.3390/cancers15030728] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Revised: 11/28/2022] [Accepted: 12/07/2022] [Indexed: 01/26/2023] Open
Abstract
Aim: Pseudomyxoma peritonei (PMP) is an uncommon pathology, and its rarity causes a lack of scientific evidence, precluding the design of a prospective trial. A diagnostic and therapeutic algorithm (DTA) is necessary in order to standardize the disease treatment while balancing optimal patient management and the correct use of resources. The Consensus of the Italian Society of Surgical Oncology (SICO) Oncoteam aims at defining a diagnostic and therapeutic pathway for PMP and appendiceal primary tumors applicable in Italian healthcare. Method: The consensus panel included 10 delegated representatives of oncological referral centers for Peritoneal Surface Malignancies (PSM) affiliated to the SICO PSM Oncoteam. A list of statements regarding the DTA of patients with PMP was prepared according to recommendations based on the review of the literature and expert opinion. Results: A consensus was obtained on 33 of the 34 statements linked to the DTA; two flowcharts regarding the management of primary appendiceal cancer and peritoneal disease were approved. Conclusion: Currently, consensus has been reached on pathological classification, preoperative evaluation, cytoreductive surgery technical detail, and systemic treatment; some controversies still exist regarding the exclusion criteria for HIPEC treatment. A shared Italian model of DTA is an essential tool to ensure the appropriateness and equity of treatment for these patients.
Collapse
Affiliation(s)
- Marco Vaira
- Unit of Surgical Oncology, Candiolo Cancer Institute, FPO—IRCCS, 10060 Candiolo, Italy
- Correspondence: authors: (M.V.); (M.R.)
| | - Manuela Robella
- Unit of Surgical Oncology, Candiolo Cancer Institute, FPO—IRCCS, 10060 Candiolo, Italy
- Correspondence: authors: (M.V.); (M.R.)
| | - Marcello Guaglio
- Peritoneal Surface Malignancies Unit, Fondazione Istituto Nazionale Tumori IRCCS Milano, 20133 Milano, Italy
| | - Paola Berchialla
- Department of Clinical and Biological Sciences, Centre for Biostatistics, Epidemiology and Public Health (C-BEPH), University of Torino, 10124 Torino, Italy
| | - Antonio Sommariva
- Advanced Surgical Oncology Unit, Surgical Oncology of the Esophagus and Digestive Tract, Veneto Institute of Oncology IOV-IRCCS, t, 35100 Padova, Italy
| | - Mario Valle
- Peritoneal Tumours Unit, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy
| | - Enrico Maria Pasqual
- AOUD Center Advanced Surgical Oncology, DAME University of Udine, 33100 Udine, Italy
| | - Franco Roviello
- Unit of General Surgery and Surgical Oncology, Department of Medicine, Surgery, and Neurosciences, University of Siena, 53100 Siena, Italy
| | - Massimo Framarini
- Surgery and Advanced Oncological Therapy Unit, Ospedale “GB.Morgagni-L.Pierantoni”—AUSL Forlì, 47122 Forlì, Italy
| | - Giammaria Fiorentini
- Italian Network of International Clinical Hyperthermia Society Coordinator, 48121 Ravenna, Italy
| | - Paolo Sammartino
- CRS and HIPEC Unit, Pietro Valdoni, Umberto I Policlinico di Roma, 00161 Roma, Italy
| | - Alba Ilari Civit
- Unit of Surgical Oncology, Candiolo Cancer Institute, FPO—IRCCS, 10060 Candiolo, Italy
| | - Andrea Di Giorgio
- Surgical Unit of Peritoneum and Retroperitoneum, Fondazione Policlinico Universitario A. Gemelli—IRCCS, 00168 Rome, Italy
| | - Luca Ansaloni
- Unit of General Surgery, San Matteo Hospital, 27100 Pavia, Italy
| | - Marcello Deraco
- Peritoneal Surface Malignancies Unit, Fondazione Istituto Nazionale Tumori IRCCS Milano, 20133 Milano, Italy
| |
Collapse
|
|
21
|
Acs M, Gerken M, Schmitt V, Piso P, Königsrainer A, Baransi S, Yurttas C, Häusler S, Horvath P. Role of HIPEC after Complete Cytoreductive Surgery (CRS) in Peritoneal Recurrence of Platinum-Sensitive Recurrent Ovarian Cancer (OC): The Aim for Standardization at Two Reference Centers for CRS. Cancers (Basel) 2023; 15:405. [PMID: 36672352 PMCID: PMC9856919 DOI: 10.3390/cancers15020405] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 12/17/2022] [Accepted: 12/28/2022] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND This bicentric study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for platinum-sensitive recurrent ovarian cancer patients. METHODS The data of 88 patients with the first peritoneal recurrence of platinum-sensitive epithelial ovarian cancer who underwent CRS and HIPEC from a prospective HIPEC registry were retrospectively investigated. Endpoints were feasibility, chemotherapeutic compound, time of exposure, complications, and overall survival. RESULTS The median follow-up was 4.7 years (95%-CI 4.6-5.5). The median age was 55.8 years (IQR: 50.3-66.2). Eighty-four patients (95.5%) had high-grade serous histology. The median peritoneal cancer index was 12.0 (IQR: 7.0-20.5). Sixty-five patients (73.9%) had complete cytoreduction (CCR 0). Thirty-eight patients (43.2%) received HIPEC for 60 min, and fifty patients (56.8%) for 90 min. Eighteen patients (20.5%) had grade III to IV complications. One patient (1.1%) died perioperatively. The overall median survival was 43.1 months (95%-CI 34.1-52.2), and the 5-year survival rate was 39.7%. Only 90 min HIPEC and cisplatin were associated with survival. CONCLUSION In well-selected patients with platinum-sensitive recurrent ovarian cancer, survival may correlate with complete CRS and 90 min cisplatin-based HIPEC. We confirmed the results of primary OC studies; therefore, this combination should be used for further analysis in the recurrent situation.
Collapse
Affiliation(s)
- Miklos Acs
- Department of General and Visceral Surgery, Hospital Barmherzige Brüder, 93049 Regensburg, Germany
| | - Michael Gerken
- Tumor Center—Institute for Quality Management and Health Services Research, University of Regensburg, 93049 Regensburg, Germany
| | - Vanessa Schmitt
- Department of General and Visceral Surgery, Hospital Barmherzige Brüder, 93049 Regensburg, Germany
| | - Pompiliu Piso
- Department of General and Visceral Surgery, Hospital Barmherzige Brüder, 93049 Regensburg, Germany
| | - Alfred Königsrainer
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, 72074 Tübingen, Germany
| | - Saher Baransi
- Department of Gynecology and Gynecological Oncology, Florence Nightingale Hospital, 40489 Düsseldorf, Germany
| | - Can Yurttas
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, 72074 Tübingen, Germany
| | - Sebastian Häusler
- Department of Gynecology and Gynecological Oncology, Hospital Barmherzige Brüder, 93049 Regensburg, Germany
| | - Philipp Horvath
- Department of General, Visceral and Transplant Surgery, University Hospital Tübingen, 72074 Tübingen, Germany
| |
Collapse
|
|
22
|
Baratti D, Kusamura S, Guaglio M, Milione M, Pietrantonio F, Cavalleri T, Morano F, Deraco M. Relapse of Pseudomyxoma Peritonei After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Pattern of Failure, Clinical Management and Outcomes. Ann Surg Oncol 2023; 30:404-414. [PMID: 36094689 DOI: 10.1245/s10434-022-12367-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Accepted: 07/25/2022] [Indexed: 12/13/2022]
Abstract
INTRODUCTION Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) have dramatically improved pseudomyxoma peritonei (PMP) prognosis, but treatment failures are still a concern. We investigated the pattern of failure, treatment and outcomes of progressing disease. METHODS A prospective database of 374 PMP patients was reviewed, and 152 patients relapsing after complete CRS/HIPEC were identified. PMP was graded according to the Peritoneal Surface Oncology Group International (PSOGI) classification. Hematogenous metastases and non-regional lymph node involvement were considered as systemic metastases. RESULTS Median follow-up was 78.3 months (95% confidence interval [CI] 66.7-90.4). PMP relapse involved the peritoneum in 112 patients, pleural cavity in 8, both peritoneum and pleura in 8, systemic sites in 11, and both peritoneum and systemic sites in 13 patients. Systemic metastases involved the lung (n = 14), liver (n = 4), distant nodes (n = 3), bone (n = 2), and both lung and distant nodes (n = 1). Survival after diagnosis of PMP relapse was independently associated with curative versus palliative treatment (hazard ratio [HR] 0.52, 95% CI 0.36-0.75; p = 0.001) and PSOGI histology (HR 1.80, 95% CI 1.19-2.74; p = 0.005), but was not influenced by site of failure (p = 0.444). Ten-year overall survival was 77.5% for 62 patients who had curative-intent surgery for PMP relapse, compared with 83.0% for 192 patients who had no recurrences (p = 0.154) and 26.1% for 90 patients who underwent palliative treatments (p = 0.001). CONCLUSIONS Relapse after CRS/HIPEC most commonly involves the peritoneum, but pleural recurrences and systemic metastases occur in a small but clinically relevant number of patients. In selected patients, surgical resection of recurrent disease can result in long survival, irrespective of sites of failure.
Collapse
Affiliation(s)
- Dario Baratti
- Peritoneal Malignancy Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
| | - Shigeki Kusamura
- Peritoneal Malignancy Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Marcello Guaglio
- Peritoneal Malignancy Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Massimo Milione
- Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Filippo Pietrantonio
- Department of Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Tommaso Cavalleri
- Peritoneal Malignancy Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Federica Morano
- Department of Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Marcello Deraco
- Peritoneal Malignancy Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| |
Collapse
|
|
23
|
Foster JM, Zhang C, Rehman S, Sharma P, Alexander HR. The contemporary management of peritoneal metastasis: A journey from the cold past of treatment futility to a warm present and a bright future. CA Cancer J Clin 2023; 73:49-71. [PMID: 35969103 DOI: 10.3322/caac.21749] [Citation(s) in RCA: 43] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 05/12/2022] [Accepted: 06/15/2022] [Indexed: 01/17/2023] Open
Abstract
Peritoneal metastasis (PM) is often regarded as a less frequent pattern of spread; however, collectively across all spectra of primary tumors, the consequences of PM impact a large population of patients annually. Unlike other modes of metastasis, symptoms at presentation or during the treatment course are common, representing an additional challenge in the management of PM. Early efforts with chemotherapy and incomplete surgical interventions transiently improved symptoms, but durable symptom control and survival extension were rare, which established a perspective of treatment futility for PM through most of the 20th century. Notably, the continued development of better systemic therapy combinations, optimization of cytoreductive surgery (CRS), and rigorous investigation of combining regional therapy-specifically hyperthermic intraperitoneal chemotherapy-with CRS, have resulted in more effective multimodal treatment options for patients with PM. In this article, the authors provide a comprehensive review of the data establishing the contemporary approach for tumors with a high frequency of PM, including appendix, colorectal, mesothelioma, and gastric cancers. The authors also explore the emerging role of adding hyperthermic intraperitoneal chemotherapy to the well established paradigm of CRS and systemic therapy for advanced ovarian cancer, as well as the recent clinical trials identifying the efficacy of poly(adenosine diphosphate ribose) polymerase maintenance therapy. Finally, recent data are included that explore the role of precision medicine technology in PM management that, in the future, may help further improve patient selection, identify the best systemic therapy regimens, detect actionable mutations, and identify new targets for drug development.
Collapse
Affiliation(s)
- Jason M Foster
- Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Chunmeng Zhang
- Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Shahyan Rehman
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey
| | - Prateek Sharma
- Division of Surgical Oncology, Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | | |
Collapse
|
|
24
|
Sipok A, Dort JM, Visioni A, Bijelic L. Retrospective Review of Outcomes in Non-Invasive Mucinous Appendiceal Neoplasms with and without Peritoneal Spread: A Cohort Study. Curr Oncol 2022; 29:9125-9134. [PMID: 36547128 PMCID: PMC9777109 DOI: 10.3390/curroncol29120714] [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: 09/30/2022] [Revised: 11/04/2022] [Accepted: 11/22/2022] [Indexed: 11/25/2022] Open
Abstract
Patients treated surgically for local non-invasive mucinous appendiceal neoplasm (NI-MAN) may recur with the development of peritoneal dissemination (PD). The risk of recurrence and predictive factors are not well studied. Patients with NI-MAN, with or without peritoneal dissemination at presentation, were included. Patients with limited disease underwent surgical resection only. Patients with peritoneal dissemination underwent cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC). Patients without PD (nPD) were compared to those who presented with PD. Thirty-nine patients were included, 25 in nPD and 14 in PD. LAMN was diagnosed in 96% and 93% of patients in nPD and PD, respectively. Acellular mucin on the peritoneal surface was seen in 16% of nPD patients vs. 50% of PD patients (p = 0.019). Two (8%) patients in the nPD group who had LAMN without wall rupture recurred, at 57 and 68 months, with a PCI of 9 and 22. The recurrence rate in the PD group was 36%. All recurred patients underwent CRS+HIPEC. A peritoneal recurrence is possible in NI-MANs confined to the appendix even with an intact wall at initial diagnosis. The peritoneal disease may occur with significant delay, which is longer than a conventional follow-up.
Collapse
Affiliation(s)
- Arkadii Sipok
- Department of Surgery, Inova Medical Campus, 3300 Gallows Rd, Falls Church, VA 22042, USA
| | - Jonathan M. Dort
- Department of Surgery, Inova Medical Campus, 3300 Gallows Rd, Falls Church, VA 22042, USA
- Correspondence: ; Tel.: +1-(703)-776-2126; Fax: +1-(703)-776-2146
| | - Anthony Visioni
- Department of General Surgery, Cleveland Clinic, Akron General Ave, Akron, OH 44307, USA
| | - Lana Bijelic
- Consorci Sanitari Integral, Hospital Sant Joan Despì, 90 Moises Broggi Calle Jacint Verdaguer, Sant Joan Despí, 08970 Barcelona, Spain
| |
Collapse
|
|
25
|
Hull NC, Granberg CF, Gargollo PC, Thacker PG. Imaging of pre- and post-cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pediatric intraperitoneal malignancy. Pediatr Radiol 2022; 52:2254-2266. [PMID: 36207454 DOI: 10.1007/s00247-022-05424-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2022] [Revised: 04/09/2022] [Accepted: 06/02/2022] [Indexed: 11/24/2022]
Abstract
Although rare, pediatric peritoneal carcinomatosis does occur in primary abdominopelvic tumors. Additionally, peritoneal carcinomatosis has been described to occur as metastatic disease where the primary tumor is outside the abdominopelvic cavity. Where amenable, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) can be beneficial in disease management. However, favorable outcomes are predicated on specific tumor histology as well as proper patient selection, which significantly relies on preoperative imaging. This review gives a comprehensive, up-to-date summary on pediatric peritoneal carcinomatosis pre-surgical evaluation; where imaging is beneficial and limited; pediatric radiologists' role in helping to quantify disease; and how we, as pediatric radiologists, can help the surgeons and oncologists in the selection of patients for cytoreductive surgery and HIPEC.
Collapse
Affiliation(s)
- Nathan C Hull
- Department of Radiology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA
| | | | | | - Paul G Thacker
- Department of Radiology, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.
| |
Collapse
|
|
26
|
Strach MC, Sutherland S, Horvath LG, Mahon K. The role of chemotherapy in the treatment of advanced appendiceal cancers: summary of the literature and future directions. Ther Adv Med Oncol 2022; 14:17588359221112478. [PMID: 35898968 PMCID: PMC9310237 DOI: 10.1177/17588359221112478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 06/20/2022] [Indexed: 11/16/2022] Open
Abstract
Appendiceal cancer is rare and encompasses a diverse group of tumours ranging from low-grade appendiceal mucinous neoplasms to high-grade adenocarcinomas. Appendiceal cancers often spread to the peritoneal cavity causing extensive mucinous dissemination and peritoneal metastases. Prognosis varies with histological subtype. Cytoreductive surgery and heated intraperitoneal chemotherapy is well-established as the most effective treatment achieving long-term survival in some patients. Chemotherapy regimens used to treat appendiceal cancer are extrapolated from the colorectal cancer setting, but disease biology differs and outcomes are inferior. The role of chemotherapy in the treatment of appendiceal cancer remains poorly defined. There is an urgent need to develop novel tailored treatment strategies in the perioperative and unresectable setting. This review aims to evaluate the literature for patients who received intraperitoneal and systemic chemotherapy for appendiceal cancers.
Collapse
Affiliation(s)
| | | | | | - Kate Mahon
- Chris O'Brien Lifehouse, 119-144 Missenden Road, Camperdown, NSW 2050, Australia
| |
Collapse
|
|
27
|
Ten-year single-center experience with treatment of primary diffuse malignant peritoneal mesothelioma (DMPM) by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Langenbecks Arch Surg 2022; 407:3057-3067. [PMID: 35732846 DOI: 10.1007/s00423-022-02594-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 06/15/2022] [Indexed: 11/27/2022]
Abstract
PURPOSE This single-center study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for diffuse malignant peritoneal mesothelioma (DMPM). METHODS Prospectively collected data from a single institution data registry was retrospectively investigated. Eighty-four patients with primary malignant peritoneal mesothelioma underwent CRS and HIPEC with cisplatin and doxorubicin either for 60 min or 90 min of duration from 2011 to 2021. The primary endpoint was overall survival. The secondary endpoint was the evaluation of prognostic factors for overall survival. The tertiary endpoint was to assess the effect of neoadjuvant chemotherapy on survival. RESULTS The median follow-up was 5.0 years (95%-CI 4.6-5.5). The median age was 59.2 years (IQR: 47-66). Eighty-two patients (97.6%) had epithelioid tumors. The median peritoneal cancer index was 18.0 (IQR: 13-27). Sixty-six patients (78.6%) had complete or near-complete cytoreduction (CCR 0 or CCR 1). Seventy patients (83.3%) received HIPEC for 60 min and 14 patients (16.7%) received it for 90 min. Twenty-two patients (26.2%) had grade 3 to 4 complications. Acute kidney injury (AKI) stage I-III occurred in 30 (35.7%) patients. Three patients (3.6%) died perioperatively. The overall median survival was 38.4 months (95%-CI 23.6-54.3), and the 5-year survival rate was 42%. Survival was independently associated with age, female gender, and thrombocytosis. Preoperative chemotherapy did not emerge as an adverse prognostic factor. CONCLUSION In well-selected patients with DMPM, prolonged survival is achievable with CRS and HIPEC in specialized centers.
Collapse
|
|
28
|
Roy SP, Al Zhahrani N, Barat S, Morris DL. Case series on high grade appendiceal cancer with peritoneal and liver carcinomatosis undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Int J Surg Case Rep 2022; 94:107027. [PMID: 35398783 PMCID: PMC9006324 DOI: 10.1016/j.ijscr.2022.107027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 03/28/2022] [Accepted: 03/31/2022] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Pseudomyxoma Peritonei (PMP) is a mucin producing cancer with appendix as primary site. Cytoreductive Surgery (CRS) combined with hyper-thermic intraperitoneal chemotherapy (HIPEC) is an established form of therapy known to prolong survival in patients with PMP and peritoneal carcinomatosis. Methods/patients In our case series, we present five cases of PMP with synchronous liver and peritoneal metastasis treated with CRS and HIPEC. It is a very rare condition which needs more research to be able to comment on overall survival. RESULTS However, in our study, we found lower age, female gender and complete cytoreduction in surgery to be favourable predictors for improved morbidity. CONCLUSION In our experience, CRS/HIPEC seem to be feasible for patients with PMP with synchronous liver and peritoneal metastasis.
Collapse
Affiliation(s)
- Susmit Prosun Roy
- General Surgery, John Hunter Hospital, University of Newcastle, Newcastle, Australia; Liver and Peritonectomy Unit, St George Hospital, Kogarah, Australia.
| | - Nayef Al Zhahrani
- Liver and Peritonectomy Unit, St George Hospital, Kogarah, Australia; College of Medicine, Al Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia.
| | - Shoma Barat
- Southeast Sydney Local Health District, Australia; University of New South Wales, Australia.
| | - David L Morris
- Liver and Peritonectomy Unit, St George Hospital, Kogarah, Australia; University of New South Wales, Australia; Liver and Peritonectomy Unit, St George Hospital, Kogarah, Australia; UNSW, St George and Sutherland Clinical School, NSW 2052, Australia; St George and Sutherland Clinical School, Kogarah, NSW 2217, Australia.
| |
Collapse
|
|
29
|
Noguchi R, Yoshimatsu Y, Sin Y, Ono T, Tsuchiya R, Yoshida H, Kiyono T, Yonemura Y, Kondo T. Establishment and Characterization of NCC-PMP1-C1: A Novel Patient-Derived Cell Line of Metastatic Pseudomyxoma Peritonei. J Pers Med 2022; 12:258. [PMID: 35207746 PMCID: PMC8877412 DOI: 10.3390/jpm12020258] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 01/20/2022] [Accepted: 02/07/2022] [Indexed: 02/06/2023] Open
Abstract
Pseudomyxoma peritonei (PMP) is the intraperitoneal accumulation of mucus due to a mucinous tumor. PMP predominantly occurs in low-grade carcinomas. The incidence rate of PMP is one to two cases per million people per year. The standard therapy of PMP comprises complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. PMP recurs in about 50% of patients, and 30-40% are unable to receive the standard treatment because of its invasiveness. Therefore, novel therapies are of the utmost necessity. For basic and pre-clinical research, patient-derived cell lines are essential resources. However, only two PMP cell lines have been reported. Thus, we established a novel PMP cell line from resected metastatic PMP tissue. The cell line, named NCC-PMP1-C1, was maintained for more than 5 months and was passaged 25 times. NCC-PMP1-C1 cells demonstrated multiple amplifications and deletions, slow growth, tumorigenic ability, and dissemination of tumor cells in nude mice. We also used NCC-PMP1-C1 cells to screen drugs, which demonstrated a significant response to daunorubicin HCl, homoharringtonine, mitomycin C, and ponatinib. The NCC-PMP1-C1 cell line is the first PMP cell line derived from metastasized tissue and will be a potential resource for basic and pre-clinical research of metastasized PMP.
Collapse
Affiliation(s)
- Rei Noguchi
- Division of Rare Cancer Research, National Cancer Center Research Institute, Tokyo 104-0045, Japan; (R.N.); (Y.Y.); (Y.S.); (T.O.); (R.T.)
| | - Yuki Yoshimatsu
- Division of Rare Cancer Research, National Cancer Center Research Institute, Tokyo 104-0045, Japan; (R.N.); (Y.Y.); (Y.S.); (T.O.); (R.T.)
| | - Yooksil Sin
- Division of Rare Cancer Research, National Cancer Center Research Institute, Tokyo 104-0045, Japan; (R.N.); (Y.Y.); (Y.S.); (T.O.); (R.T.)
| | - Takuya Ono
- Division of Rare Cancer Research, National Cancer Center Research Institute, Tokyo 104-0045, Japan; (R.N.); (Y.Y.); (Y.S.); (T.O.); (R.T.)
| | - Ryuto Tsuchiya
- Division of Rare Cancer Research, National Cancer Center Research Institute, Tokyo 104-0045, Japan; (R.N.); (Y.Y.); (Y.S.); (T.O.); (R.T.)
- Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, Chiba 263-8522, Japan
| | - Hiroshi Yoshida
- Department of Diagnostic Pathology, National Cancer Center Hospital, Tokyo 104-0045, Japan;
| | - Tohru Kiyono
- Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa 277-8577, Japan;
| | - Yutaka Yonemura
- NPO to Support Peritoneal Surface Malignancy Treatment, Japanese/Asian School of Peritoneal Surface Oncology, Kyoto 600-8189, Japan;
- Peritoneal Surface Malignancy Center, Department of Regional Cancer Therapy, Kishiwada Tokushukai Hospital, Kishiwada 596-8522, Japan
- Peritoneal Surface Malignancy Center, Department of Regional Cancer Therapy, Kusatsu General Hospital, Shiga 525-8585, Japan
| | - Tadashi Kondo
- Division of Rare Cancer Research, National Cancer Center Research Institute, Tokyo 104-0045, Japan; (R.N.); (Y.Y.); (Y.S.); (T.O.); (R.T.)
| |
Collapse
|
|
30
|
Lopes A, de Mello ES, Mendoza Lopez RV, Leonardi PC, Ribeiro U. Prognostic Impact of Pathology, Cytoreduction, and Tumor Markers in Pseudomyxoma Peritonei. J Surg Res 2022; 274:68-76. [PMID: 35123285 DOI: 10.1016/j.jss.2022.01.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 10/08/2021] [Accepted: 01/01/2022] [Indexed: 11/28/2022]
Abstract
INTRODUCTION The pathologic classification of pseudomyxoma peritonei is controversial. This study aimed to standardize the histopathological evaluation of pseudomyxoma peritonei and identify the clinicopathological factors associated with survival. METHODS A pathologic review was performed to systematize the pathology report and verify the relationship between clinical features and survival. Terminology was based on the World Health Organization and Peritoneal Surface Oncology Group International definitions. Preoperative serum levels of carcinoembryonic antigen, CA19-9, and CA-125 were evaluated to determine their association with overall survival (OS) and ability to predict CC0-1 cytoreduction. RESULTS Among 109 patients with carcinomas resulting from primary appendiceal neoplasms, 72 had pseudomyxoma peritonei of appendiceal origin and underwent debulking surgery. CC0-1 cytoreduction and CC2-3 cytoreduction were achieved in 61% and 39% of patients, respectively. Patients in the CC0-1 and CC2-3 groups had an OS of 122.80 and 32.92 mo, respectively. The histologic grade was associated with CC0-1 cytoreduction; however, it did not influence OS. Patients with CC0-1 cytoreduction, acellular mucin, and low-grade lesions had better disease-free survival. Higher preoperative CA19-9 levels were associated with poor OS. Normal carcinoembryonic antigen values were associated with 100% sensitivity for predicting CC0-1. CA19-9 levels of 625 U/mL were associated with a low possibility of predicting CC0-1. CONCLUSIONS Histologic grades are associated with disease-free survival when CC0-1 cytoreduction is achieved. Normal preoperative CA19-9 levels were associated with a better OS. CC0-1 cytoreduction is the main determinant of longer survival.
Collapse
Affiliation(s)
- Andre Lopes
- Gastroenterology Department, Digestive Surgery Division, Instituto do Cancer do Estado de Sao Paulo ICESP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil.
| | - Evandro Sobroza de Mello
- Department of Pathology, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil
| | - Rossana Veronica Mendoza Lopez
- Center for Translational Research in Oncology, Instituto do Cancer do Estado de Sao Paulo ICESP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil
| | - Paulo Cesar Leonardi
- Gastroenterology Department, Digestive Surgery Division, Instituto do Cancer do Estado de Sao Paulo ICESP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil
| | - Ulysses Ribeiro
- Gastroenterology Department, Digestive Surgery Division, Instituto do Cancer do Estado de Sao Paulo ICESP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil
| |
Collapse
|
|
31
|
Floriano I, Silvinato A, Reis JC, Cafalli C, Bernardo WM. Efficacy and safety in the use of intraperitoneal hyperthermia chemotherapy and peritoneal cytoreductive surgery for pseudomyxoma peritonei from appendiceal neoplasm: A systematic review. Clinics (Sao Paulo) 2022; 77:100039. [PMID: 35576869 PMCID: PMC9118488 DOI: 10.1016/j.clinsp.2022.100039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Accepted: 01/10/2022] [Indexed: 11/25/2022] Open
Abstract
The objective of this systematic review is to provide efficacy and safety data in the application of Intra-Abdominal Hyperthermia Chemotherapy (HIPEC) and Cytoreductive Surgery (CRS) in patients with Peritoneal Pseudomyxoma (PMP) of origin in the cecal appendix. The databases Medline and Central Cochrane were consulted. Patients with PMP of origin in the cecal appendix, classified as low grade, high or indeterminate, submitted to HIPEC and CRS. The results were meta-analyzed using the Comprehensive Metanalysis software. Twenty-six studies were selected to support this review. For low-grade PMP outcome, 60-month risk of mortality, Disease-Free Survival (DFS), and adverse events was 28.8% (95% CI 25.9 to 32), 43% (95% CI 36.4 and 49.8), and 46.7% (95% CI 40.7 to 52.8); for high-grade PMP, 60-month risk of mortality, Disease-Free Survival (DFS) and adverse events was 55.9% (95% CI 51.9 to 59.6), 20.1% (95% CI 15.5 to 25.7) and 30% (95% CI 25.2 to 35.3); PMP indeterminate degree, 60-month risk of mortality, Disease-Free Survival (DFS) and adverse events was 32.6% (95% CI 30.5 to 34.7), 61.8% (95% CI 58.8 to 64.7) and 32.9% (95% CI 30.5 to 35.4). The authors conclude that the HIPEC technique and cytoreductive surgery can be applied to selected cases of patients with PMP of peritoneal origin with satisfactory results.
Collapse
Affiliation(s)
- Idevaldo Floriano
- Evidence Based Medicine Center, UNIMED Cooperative, Baixa Mogiana regional, Mogi-Guaçu, SP, Brazil; Evidence Based Medicine Center, UNIMED Fesp, São Paulo, SP, Brazil.
| | - Antônio Silvinato
- Evidence Based Medicine Center, UNIMED Cooperative, Baixa Mogiana regional, Mogi-Guaçu, SP, Brazil; Evidence Based Medicine Center, UNIMED Fesp, São Paulo, SP, Brazil
| | - João C Reis
- Guidelines Program of the Brazilian Medical Association, São Paulo, SP, Brazil
| | - Claudia Cafalli
- Evidence Based Medicine Center, UNIMED Fesp, São Paulo, SP, Brazil
| | - Wanderley Marques Bernardo
- Guidelines Program of the Brazilian Medical Association, São Paulo, SP, Brazil; Evidence Based Medicine Center, UNIMED Fesp, São Paulo, SP, Brazil
| |
Collapse
|
|
32
|
Systemic metastases from low-grade and high-grade pseudomyxoma peritonei: Treatments and outcomes. Eur J Surg Oncol 2022; 48:1590-1597. [DOI: 10.1016/j.ejso.2022.01.010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 12/30/2021] [Accepted: 01/08/2022] [Indexed: 12/17/2022] Open
|
|
33
|
Gangi A, Shah R. The Landmark Series: Appendiceal Primary Peritoneal Surface Malignancy. Ann Surg Oncol 2021; 29:2056-2068. [PMID: 34853944 DOI: 10.1245/s10434-021-10856-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Accepted: 09/09/2021] [Indexed: 12/24/2022]
Abstract
Appendiceal primary peritoneal surface malignancies are rare and include a broad spectrum of pathologies ranging from indolent disease to aggressive disease. As such, the data that drive the management of appendiceal peritoneal surface malignancies is generally not based on prospective clinical trial data, but rather consists of level 1 data based on retrospective studies and high-volume institutional experiences. Complete surgical debulking typically offers the best chance for long-term survival. This review highlights the landmark articles on which management of primary appendiceal peritoneal surface malignancies are based.
Collapse
Affiliation(s)
- Alexandra Gangi
- Division of Surgical Oncology, Cedars Sinai Medical Center, Los Angeles, CA, USA.
| | - Rupen Shah
- Division of Surgical Oncology, Henry Ford Cancer Institute/Henry Ford Health System, Detroit, MI, USA
| |
Collapse
|
|
34
|
Abdel Mageed H, Van Der Speeten K, Sugarbaker P. The many faces of intraperitoneal chemotherapy. Surg Oncol 2021; 40:101676. [PMID: 34875459 DOI: 10.1016/j.suronc.2021.101676] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2021] [Revised: 11/12/2021] [Accepted: 11/18/2021] [Indexed: 12/16/2022]
Abstract
Cytoreductive surgery and intraperitoneal chemotherapy may offer chance for cure for patients with peritoneal metastasis. Many variations emerged, causing uncertainty when choosing the most suitable variant. By reviewing variability encountered in the management of peritoneal metastasis, we aim to raise awareness about this issue and hopefully initiate efforts to solve it. We review variance encountered in all aspects of this complex field of surgical oncology, indications, patient selection criteria, definition and extent of cytoreductive surgery and the numerous variables of intraperitoneal chemotherapy. Best benefit was achieved with pseudomyxoma peritonei, and to lesser extent in colorectal, ovarian and gastric cancer, but Indications keep expanding to include other tumors pathologies. Selection of patients depends on numerous prognostic indicators and criteria, according to tumor extent and pathology. The standard definition of cytoreductive surgery remains the same, but the boundaries of resection expand. Numerous chemotherapy regimens and administration methods are used, in search for best possible benefit. This variance must be reduced, to make the best use of, and further spread this treatment combination. Practical simple guidelines are needed for surgical oncologists willing to utilize this treatment for their patients, to be considered a true standard of care.
Collapse
Affiliation(s)
- Hisham Abdel Mageed
- Surgical Oncology Department, National Cancer Institute, Cairo University, Cairo, Egypt. 27a Baghdad St., Korba, Heliopolis, Cairo, 11341, Egypt.
| | - Kurt Van Der Speeten
- Department of Surgical Oncology, Schiepse Bos 6, Ziekenhuis Oost-Limburg. Genk, Belgium; Hasselt University. Diepenbeek, Belgium.
| | - Paul Sugarbaker
- Program in Peritoneal Surface Malignancy, Washington Cancer Institute, Washington, DC, USA; Sugarbaker Oncology 3629 Fulton St. NW, Washington, DC, 20007, USA.
| |
Collapse
|
|
35
|
Garland-Kledzik M, Maithel S, Jafari MD, Dehkordi-Vakil F, Chaudhry H, Dinicu A, Chang I, Krasnoff C, Gambhir S, Sheehan B, Pigazzi A. Misdiagnosis of appendiceal neoplasms as ovarian tumors: Impact of prior gynecologic surgery on definitive cytoreduction and HIPEC. Eur J Surg Oncol 2021; 48:449-454. [PMID: 34454813 DOI: 10.1016/j.ejso.2021.08.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Accepted: 08/20/2021] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Female patients with pelvic/adnexal masses often undergo gynecologic operations due to presumed ovarian origin. The diagnosis of an appendiceal tumor is often only made postoperatively after suboptimal cytoreduction has been performed. We hypothesized that an index gynecological procedure increases the morbidity of definitive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) in patients with appendiceal mucinous tumors. METHODS A single-center retrospective review was performed to identify female patients undergoing CRS/HIPEC for appendiceal tumors from 2012 to 2020. RESULTS During the 8-year period, CRS/HIPEC was performed in 36 female patients with appendiceal mucinous tumors. Eighteen patients (50.0%) had received a prior pelvic operation by gynecologists (PPO Group) for presumed ovarian origin before referral for definitive CRS/HIPEC. The median peritoneal cancer index (PCI) was higher in the PPO group (21 vs. 9, p = 0.04). The median number of days from gynecologic procedure to definitive CRS/HIPEC was 169 days. Compared to patients who did not undergo a prior gynecologic operation, those in the PPO group had higher intraoperative blood loss (650 vs 100 mL, p < 0.01) during CRS/HIPEC as well as longer length of stay (12 vs 8 days, p = 0.02) and higher overall morbidity (72.3% vs 33.3%, p = 0.02). After controlling for PCI, prior gynecologic operation increased risk of 30-day morbidity after definitive CRS/HIPEC (OR 11.6, p < 0.01). CONCLUSION A multi-disciplinary approach is needed for the primary evaluation of patients with pelvic masses of undetermined origin. A gynecological resection is associated with increased morbidity during definitive cytoreduction and HIPEC for appendiceal mucinous tumors.
Collapse
Affiliation(s)
- Mary Garland-Kledzik
- Division of Surgical Oncology, West Virginia University, Morgantown, WV, 26508, USA
| | - Shelley Maithel
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA, 92868, USA
| | - Mehraneh D Jafari
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA, 92868, USA
| | | | - Haris Chaudhry
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA, 92868, USA
| | - Andreea Dinicu
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA, 92868, USA
| | - Irene Chang
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA, 92868, USA
| | - Chloe Krasnoff
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA, 92868, USA
| | - Sahil Gambhir
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA, 92868, USA
| | - Brian Sheehan
- Department of Surgery, University of California, Irvine Medical Center, Orange, CA, 92868, USA
| | - Alessio Pigazzi
- Colon and Rectal Surgery, Weill Cornell Medicine, New York-Presbyterian Hospital, NY, 10021, USA.
| |
Collapse
|
|
36
|
Ceelen W, Demuytere J, de Hingh I. Hyperthermic Intraperitoneal Chemotherapy: A Critical Review. Cancers (Basel) 2021; 13:cancers13133114. [PMID: 34206563 PMCID: PMC8268659 DOI: 10.3390/cancers13133114] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Revised: 06/14/2021] [Accepted: 06/16/2021] [Indexed: 12/15/2022] Open
Abstract
Simple Summary Patients with cancer of the digestive system or ovarian cancer are at risk of developing peritoneal metastases (PM). In some patients with PM, surgery followed by intraperitoneal (IP) chemotherapy has emerged as a valid treatment option. The addition of hyperthermia is thought to further enhance the efficacy of IP chemotherapy. However, the results of recent clinical trials in large bowel cancer have put into question the use of hyperthermic intraperitoneal chemotherapy (HIPEC). Here, we review the rationale and current results of HIPEC for PM and propose a roadmap to further progress. Abstract With increasing awareness amongst physicians and improved radiological imaging techniques, the peritoneal cavity is increasingly recognized as an important metastatic site in various malignancies. Prognosis of these patients is usually poor as traditional treatment including surgical resection or systemic treatment is relatively ineffective. Intraperitoneal delivery of chemotherapeutic agents is thought to be an attractive alternative as this results in high tumor tissue concentrations with limited systemic exposure. The addition of hyperthermia aims to potentiate the anti-tumor effects of chemotherapy, resulting in the concept of heated intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal metastases as it was developed about 3 decades ago. With increasing experience, HIPEC has become a safe and accepted treatment offered in many centers around the world. However, standardization of the technique has been poor and results from clinical trials have been equivocal. As a result, the true value of HIPEC in the treatment of peritoneal metastases remains a matter of debate. The current review aims to provide a critical overview of the theoretical concept and preclinical and clinical study results, to outline areas of persisting uncertainty, and to propose a framework to better define the role of HIPEC in the treatment of peritoneal malignancies.
Collapse
Affiliation(s)
- Wim Ceelen
- Department of GI Surgery, Ghent University Hospital, 9000 Ghent, Belgium;
- Cancer Research Institute Ghent (CRIG), 9000 Ghent, Belgium
- Correspondence: ; Tel.: +32-9332-6251
| | - Jesse Demuytere
- Department of GI Surgery, Ghent University Hospital, 9000 Ghent, Belgium;
- Cancer Research Institute Ghent (CRIG), 9000 Ghent, Belgium
| | - Ignace de Hingh
- Department of Surgery, Catharina Cancer Institute, PO Box 1350, 5602 ZA Eindhoven, The Netherlands;
- GROW—School for Oncology and Developmental Biology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands
| |
Collapse
|
|
37
|
The addition of sodium thiosulphate to hyperthermic intraperitoneal chemotherapy with cisplatin in ovarian cancer. Gynecol Oncol Rep 2021; 37:100796. [PMID: 34141848 PMCID: PMC8185237 DOI: 10.1016/j.gore.2021.100796] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 05/17/2021] [Accepted: 05/18/2021] [Indexed: 12/28/2022] Open
Abstract
Cisplatin chemotherapy is highly nephrotoxic and is a dose limiting side effect. The OVIHIPEC-1 trial employed sodium thiosulphate (ST) as a renal protectant. We analyse the implementation of HIPEC for EOC in a peritoneal malignancy centre. One acute kidney injury (AKI) event was noted when ST was not used with HIPEC. No AKI was observed when sodium thiosulphate was used with cisplatin at 100 mg/m2. Cisplatin based hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to prolong recurrence free and overall survival of women with ovarian cancer who have responded to neoadjuvant chemotherapy. The aim of this study was to assess the impact of cytoreductive surgery with or without the addition of HIPEC on renal function. Method This is a retrospective case-controlled study at a tertiary teaching hospital in Dublin, Ireland. All patients who had interval cytoreductive surgery (CRS) and HIPEC from October 2017 to October 2020 were included. A cohort of patients who had interval CRS without HIPEC were included as a control. Sodium thiosulphate (ST) was added to the HIPEC protocol in 2019. In order to assess the impact of ST as a renal protectant, renal function and post-operative outcomes were compared between the groups. Results Sixty patients who had interval CRS were included, thirty of whom received cisplatin-based HIPEC. Seven received cisplatin 50 mg/m2 without the addition of ST. Twenty three patients received cisplatin 100 mg/m2 and ST. There were no statistically differences in age, body mass index BMI, American society of anaesthesia score, estimated blood loss or peritoneal cancer index between the cohorts (p > 0.05). The only episode of acute kidney injury (AKI) was within the HIPEC cohort, after cisplatin 50 mg/m2 (without ST) and this was sustained at three months. In contrast, no patients within the CRS cohort or cisplatin 100 mg/m2 that received the addition of ST, sustained a renal injury and all had a creatinine within the normal range at three days post operatively. Conclusion The renal toxicity associated with cisplatin HIPEC and major abdominal surgery can be minimised with careful preoperative optimisation, intra operative fluid management and attention to renal function. The addition of sodium thiosulphate is a safe and effective method to minimise toxicity and should be added to any cisplatin HIPEC protocol.
Collapse
|
|
38
|
Rozich NS, Lewis SE, Chen S, Stewart KE, Stout MB, Dooley WC, Fischer LE, Morris KT. Women survive longer than men undergoing cytoreductive surgery and HIPEC for appendiceal cancer. PLoS One 2021; 16:e0250726. [PMID: 33930051 PMCID: PMC8087099 DOI: 10.1371/journal.pone.0250726] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 04/12/2021] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND We hypothesize that women undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis from appendiceal cancer will have a survival advantage compared to men. METHODS The National Cancer Database (NCDB) public user file (2004-2014) was used to select patients with PC undergoing CRS and HIPEC from appendiceal cancer. Univariate and multivariable analyses were performed. RESULTS 1,190 patients with PC from appendiceal cancer underwent HIPEC and CRS. OS was significantly longer for women than for men, with mean and median OS being 73.8 months and 98.2 months for women vs 58.7 months and 82.5 months for men, respectively (p = 0.0032). On multivariable analysis, male sex (HR: 1.444, 95% CI: 1.141-1.827, p = 0.0022) and increasing age (HR: 1.017, 95% CI: 1.006-1.027, p = 0.0017) were both found to be independent risk factors for worse OS. CONCLUSION Women undergoing CRS and HIPEC for PC from appendiceal origin live longer than men undergoing the same treatment. Increasing age was also found to be independent risk factors for worse survival.
Collapse
Affiliation(s)
- Noah S. Rozich
- Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
| | - Samara E. Lewis
- Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
| | - Sixia Chen
- Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
| | - Kenneth E. Stewart
- Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
| | - Michael B. Stout
- Department of Nutritional Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
| | - William C. Dooley
- Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
| | - Laura E. Fischer
- Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
| | - Katherine T. Morris
- Department of Surgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America
| |
Collapse
|
|
39
|
Ray MD, Dhall K. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the management of peritoneal surface malignancies - An evidence-based review. Curr Probl Cancer 2021; 45:100737. [PMID: 34116836 DOI: 10.1016/j.currproblcancer.2021.100737] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 02/27/2021] [Accepted: 03/15/2021] [Indexed: 12/23/2022]
Abstract
BACKGROUND Traditionally, peritoneal surface malignancies (PSM) were considered terminal diseases because of their advanced nature, therefore, systemic chemotherapy was given with palliative intent only. As a result, very poor survival outcomes were observed. But with the introduction of complete Cytoreductive surgery (CRS) and Hyperthermic intraperitoneal chemotherapy (HIPEC), the scenario has changed dramatically. METHODOLOGY An objective electronic database search was performed in Pubmed, NLM Catalog, Google scholar, Bookshelf, and Pubmed Central published in the time period from 2000 till 2020. All the randomized studies were included. In the absence of randomized studies, both prospective and retrospective studies were included. The outcomes of HIPEC were measured in terms of median survival, disease-free survival, overall survival, complications and drug toxicities. RESULTS CRS and HIPEC are considered the standard of care for PMP and MPM even in the absence of level 1 evidence due to lack of an effective alternative treatment. In colorectal and gastric cancer, several phase-three trials are showing overall survival benefit in selected cases while there is a prophylactic and palliative role of HIPEC in gastric cancer. Three reported phase 3 trials showed positive results in ovarian cancer. In peritoneal sarcomatosis, the role of HIPEC is yet to be proven. CONCLUSION The patient selection is the key to the successful outcomes after HIPEC. HIPEC should be performed by the experienced surgeons in specialized centres with a strong critical care and intensive care support to reduce the morbidity and mortality. Ongoing trials and future directions will prove to be an indispensable arm in the oncological armamentarium.
Collapse
Affiliation(s)
- Mukur Dipi Ray
- Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India
| | - Kunal Dhall
- Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, India.
| |
Collapse
|
|
40
|
Epidemiology, histopathology, clinical outcomes and survival of 50 cases of appendiceal mucinous neoplasms: Retrospective cross-sectional single academic tertiary care hospital experience. Ann Med Surg (Lond) 2021; 64:102199. [PMID: 33815784 PMCID: PMC8010208 DOI: 10.1016/j.amsu.2021.102199] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Accepted: 02/28/2021] [Indexed: 02/08/2023] Open
Abstract
Background Appendicular neoplasms are rare, most commonly as carcinoids followed by appendicular mucinous neoplasms (AMN). To date, there remains controversy regarding the best treatment of AMN and factors affecting its prognosis. Method Retrospective chart review of patients operated for appendicular pathology (January 2011–December 2018, follow up to December 2020) at our institution. For all AMN patients, data included pre-operative clinical presentation, and operative/post-operative findings. Results 12454 patients underwent appendectomy, of whom 50 (0.4%) had AMN histopathologically (mean age = 47.2). Most patients had laparoscopic appendectomy as primary surgery. Low grade AMN was the most common subtype (n = 41, 82%), and pseudomyxoma peritonei (PMP) was found in 8 (16%) patients. Based on histopathology and margin involvement, the 50 patients were categorized into 3 prognostic categories of recurrence risk (no risk, 24 patients; low risk, 8; high recurrence risk, 18 patients). Disease-free survival (DFS) was lowest for high recurrence risk group (P < 0.001). Eleven (22%) patients had AMN involving resection margin, of whom 3 had no completion surgery and had no recurrence. Higher tumor markers were associated with lower DFS, however it was not statistically significant. Conclusion AMNs are rare but serious due to the risk of PMP. Laparoscopic approach for AMN may be feasible. Prognostic categories were significantly inversely correlated with recurrence risk; hence useful in predicting prognosis. Contrary to previous proposals, AMNs with acellular mucin at margin or local acellular mucin spillage may not require secondary surgery, especially if the patient is in low recurrence risk group. Tumor markers may predict risk of recurrence.
Laparoscopic approach may be feasible for appendiceal mucinous neoplasms (AMN). AMN can be categorized into 3 risk recurrence groups (No risk, low, and high). AMN with acellular mucin at the margin may not require secondary surgery. Higher tumor markers may indicate high risk of AMN recurrence.
Collapse
|
|
41
|
Hoehn RS, Rieser CJ, Choudry MH, Melnitchouk N, Hechtman J, Bahary N. Current Management of Appendiceal Neoplasms. Am Soc Clin Oncol Educ Book 2021; 41:1-15. [PMID: 33770459 DOI: 10.1200/edbk_321009] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Appendiceal neoplasms include a heterogeneous group of epithelial and nonepithelial tumors that exhibit varying malignant potential. This review article summarizes current diagnostic criteria, classification systems, and optimal therapeutic strategies for the five main histopathologic subtypes of appendiceal neoplasms. In particular, the management of epithelial appendiceal neoplasms has evolved. Although their treatment has historically been extrapolated from colon cancer, improved understanding of their unique histopathologic and molecular characteristics and a growing body of published clinical data support a more nuanced approach to their management.
Collapse
Affiliation(s)
- Richard S Hoehn
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Caroline J Rieser
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - M Haroon Choudry
- Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA
| | - Nelya Melnitchouk
- Division of Surgical Oncology, Brigham and Women's Hospital, Boston, MA
| | - Jaclyn Hechtman
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Nathan Bahary
- Division of Medical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA
| |
Collapse
|
|
42
|
Guaglio M, Baratti D, Kusamura S, Reis ACV, Montenovo M, Bartolini V, Battaglia L, Deraco M. Impact of Previous Gynecologic Surgical Procedures on Outcomes of Non-Gynecologic Peritoneal Malignancies Mimicking Ovarian Cancer: Less Is More? Ann Surg Oncol 2021; 28:2899-2908. [PMID: 33641011 DOI: 10.1245/s10434-021-09587-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 01/02/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Non-gynecologic rare peritoneal surface malignancies (PSMs) often are misdiagnosed as disseminated ovarian cancer and initially treated by gynecologic surgeons. This study aimed to assess whether these previous maneuvers (i.e., full surgical staging and/or cytoreductive attempts) affect outcomes after the definitive surgery performed in a tertiary center. METHODS The study reviewed 298 women affected by non-gynecologic PSM who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) after previous gynecologic surgery. Prior surgery was categorized as limited surgery (pLS: abdominal exploration with biopsy plus adnexectomy and/or appendectomy) or extended surgery (pES: full surgical staging or cytoreductive attempts including hysterectomy with bilateral salpingo-oophorectomy). RESULTS Of the 298 patients, 143 had pLS and 153 had pES. Morbidity was similar between the groups (P = 0.143), but the pES group had more severe urinary tract injuries (19 vs. 3; P < 0.001), longer operating time (585.9 vs. 506.7; P = 0.027), and more patients needing more than two anastomoses (41 vs. 26; P = 0.033). Age older than 55 years (odds ratio [OR] 2.42; P = 0.009) and number of anastomoses (OR 3.17; P = 0.002) correlated with severe morbidity; pES correlated with urinary tract grades 3 and 4 injuries (OR 7.9; P = 0.001). The 5-year cumulative incidence of locoregional relapse was significantly higher in the pES group (0.41 vs. 0.27; P = 0.012; median follow-up period, 69 months). The multivariate analysis identified a Peritoneal Carcinomatosis Index (PCI) higher than 20 and pES as independent risk factors. CONCLUSION For women undergoing CRS±HIPEC for non-gynecologic PSM, the risk for locoregional relapse and severe postsurgical urinary tract complications is increased by pES. Therefore, prior full surgical staging or cytoreductive attempts without definitive gynecologic histology should be avoided. Prophylactic ureteral stenting and stricter oncologic follow-up assessment must be considered in this scenario.
Collapse
Affiliation(s)
- Marcello Guaglio
- Peritoneal Surface Malignancies Unit, Colorectal Surgical Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
| | - Dario Baratti
- Peritoneal Surface Malignancies Unit, Colorectal Surgical Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Shigeki Kusamura
- Peritoneal Surface Malignancies Unit, Colorectal Surgical Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Arthur C V Reis
- Peritoneal Surface Malignancies Unit, Colorectal Surgical Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.,Fellow of European School of PeritonealSurface Oncology (ESPSO), Department of Gastrointestinal Surgery, Irmandade Santa Casa de Misericórdia de São José Dos Campos, São Paulo, Brazil
| | - Matteo Montenovo
- Peritoneal Surface Malignancies Unit, Colorectal Surgical Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Valentina Bartolini
- Peritoneal Surface Malignancies Unit, Colorectal Surgical Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Luigi Battaglia
- Colorectal Surgical Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Marcello Deraco
- Peritoneal Surface Malignancies Unit, Colorectal Surgical Division, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| |
Collapse
|
|
43
|
Larentzakis A, Anagnostou E, Georgiou K, Vrakopoulou GZ, Zografos CG, Zografos GC, Toutouzas KG. Place of hyperthermic intraperitoneal chemotherapy in the armament against pancreatic adenocarcinoma: A survival, mortality and morbidity systematic review. Oncol Lett 2021; 21:246. [PMID: 33664810 PMCID: PMC7882886 DOI: 10.3892/ol.2021.12507] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2020] [Accepted: 01/25/2021] [Indexed: 12/20/2022] Open
Abstract
Pancreatic adenocarcinoma is one of the deadliest types of cancer worldwide, with a 5-year survival rate of 8% despite recent treatment advancements. The present systematic review aimed to investigate the role of hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical resection for pancreatic adenocarcinoma, with or without peritoneal carcinomatosis. A systematic search of the MEDLINE and SCOPUS electronic databases was performed according to PRISMA guidelines. All possible relevant articles published between January 1980 and May 2019 were retrieved using multiple search terms associated with HIPEC and pancreatic adenocarcinoma. The initial search resulted in 1,244 reports, which condensed to 41 reports following screening of titles and abstracts, and subsequently to four reports following full-text thorough examination. The four reports included involved a prospective cohort study of HIPEC use in resectable pancreatic adenocarcinoma, and three retrospective studies of HIPEC use following cytoreductive surgery for peritoneal carcinomatosis due to pancreatic adenocarcinoma, resulting in a total of 47 patients. The overall survival ranged between 2 and 62 months, and the hospital mortality rate was 8.5%. Morbidity (34%) was mainly attributed to anastomotic leak or respiratory failure. Due to the small sample size and low quality of evidence of the included studies, no valid conclusions could be drawn. Therefore, further studies are required to justify the use of HIPEC as an adjuvant therapy in resectable pancreatic adenocarcinoma, while cytoreductive surgery and HIPEC in peritoneal carcinomatosis of pancreatic origin seems not only not useful but also unsafe at this level of evidence.
Collapse
Affiliation(s)
- Andreas Larentzakis
- First Department of Propaedeutic Surgery, Athens Medical School, National and Kapodistrian University of Athens, Hippocration General Athens Hospital, Athens 11527, Greece
| | - Evangelos Anagnostou
- Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Whitechapel, E1 2AT London, UK
| | - Konstantinos Georgiou
- First Department of Propaedeutic Surgery, Athens Medical School, National and Kapodistrian University of Athens, Hippocration General Athens Hospital, Athens 11527, Greece
| | - Gavriella-Zoi Vrakopoulou
- First Department of Propaedeutic Surgery, Athens Medical School, National and Kapodistrian University of Athens, Hippocration General Athens Hospital, Athens 11527, Greece
| | - Constantinos G Zografos
- First Department of Surgery, Athens Medical School, National and Kapodistrian University of Athens, Laikon General Hospital, Goudi, Athens 11527, Greece
| | - Georgios C Zografos
- First Department of Propaedeutic Surgery, Athens Medical School, National and Kapodistrian University of Athens, Hippocration General Athens Hospital, Athens 11527, Greece
| | - Konstantinos G Toutouzas
- First Department of Propaedeutic Surgery, Athens Medical School, National and Kapodistrian University of Athens, Hippocration General Athens Hospital, Athens 11527, Greece
| |
Collapse
|
|
44
|
Rufián-Andujar B, Valenzuela-Molina F, Rufián-Peña S, Casado-Adam Á, Sánchez-Hidalgo JM, Rodríguez-Ortiz L, Medina-Fernández FJ, Díaz-López C, Ortega-Salas R, Martínez-López A, Briceño-Delgado J, Romero-Ruíz A, Arjona-Sánchez Á. From the Ronnett to the PSOGI Classification System for Pseudomyxoma Peritonei: A Validation Study. Ann Surg Oncol 2021; 28:2819-2827. [PMID: 33471266 DOI: 10.1245/s10434-020-09560-w] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 12/23/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Several classifications have been used for pseudomyxoma peritonei (PMP), and among these, the Ronnett classification is the most commonly used. However, a new consensual Peritoneal Surface Oncology Group International (PSOGI) classification has recently been proposed. Nonetheless, to date, the ability of the PSOGI classification to predict survival based on its different disease histologic categories has not been validated. METHODS This study enrolled 117 patients with PMP who had undergone cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) between 1997 and 2020. Cox proportional hazards regression models and time-dependent curve receiver operating characteristic (ROC) analyses were used to assess the predictive capacity of both classification systems for the overall survival (OS) and disease-free survival (DFS) of these patients. RESULTS Significant differences in the 5-year OS rate were found for the different histologic grades according to each of the classifications. The completeness of cytoreduction score (CCS) was identified as a factor that predicted patient OS prognosis (p = 0.006). According to the time-dependent ROC curves at the "100" time point, adjusted by the CCS and DFS, the capacity to predict OS was optimal and achieved an area under the curve (AUC) of about 69% for OS and approximately 62% for DFS. CONCLUSIONS Both the Ronnett and PSOGI classifications were able to predict survival optimally for this patient cohort. However, when the classifications were adjusted by the CCS, the predictive availability for OS was better with the PSOGI classification than with the Ronnett classification.
Collapse
Affiliation(s)
- Blanca Rufián-Andujar
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Av. Menendez Pidal, s/n, 14004, Cordoba, Spain.,GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical, Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain
| | - Francisca Valenzuela-Molina
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Av. Menendez Pidal, s/n, 14004, Cordoba, Spain.,GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical, Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain
| | - Sebastián Rufián-Peña
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Av. Menendez Pidal, s/n, 14004, Cordoba, Spain.,GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical, Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain
| | - Ángela Casado-Adam
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Av. Menendez Pidal, s/n, 14004, Cordoba, Spain.,GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical, Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain
| | - Juan Manuel Sánchez-Hidalgo
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Av. Menendez Pidal, s/n, 14004, Cordoba, Spain.,GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical, Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain
| | - Lidia Rodríguez-Ortiz
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Av. Menendez Pidal, s/n, 14004, Cordoba, Spain.,GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical, Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain
| | - Francisco Javier Medina-Fernández
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Av. Menendez Pidal, s/n, 14004, Cordoba, Spain.,GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical, Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain
| | - Cesar Díaz-López
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Av. Menendez Pidal, s/n, 14004, Cordoba, Spain.,GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical, Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain
| | - Rosa Ortega-Salas
- GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical, Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain.,Pathology Unit, Reina Sofia University Hospital, Cordoba, Spain
| | - Ana Martínez-López
- GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical, Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain.,Pathology Unit, Reina Sofia University Hospital, Cordoba, Spain
| | - Javier Briceño-Delgado
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Av. Menendez Pidal, s/n, 14004, Cordoba, Spain
| | - Antonio Romero-Ruíz
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Av. Menendez Pidal, s/n, 14004, Cordoba, Spain. .,GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical, Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain.
| | - Álvaro Arjona-Sánchez
- Unit of Surgical Oncology, Department of Surgery, Reina Sofia University Hospital, Av. Menendez Pidal, s/n, 14004, Cordoba, Spain. .,GE09 Research in Peritoneal and Retroperitoneal Oncological Surgery, Maimonides Biomedical, Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Cordoba, Spain.
| |
Collapse
|
|
45
|
The Role of Hyperthermic Intraperitoneal Chemotherapy for Non-colorectal Peritoneal Surface Malignancies. J Gastrointest Surg 2021; 25:303-318. [PMID: 32808135 DOI: 10.1007/s11605-020-04771-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Accepted: 08/03/2020] [Indexed: 01/31/2023]
Abstract
BACKGROUND Peritoneal carcinomatosis, from a variety of gastrointestinal and gynecological malignancies, has been historically challenging to treat and there remains a wide range of biologic aggressiveness in these patients. Malignancies commonly associated with PC include those of colorectal, appendiceal, gastric, ovarian, sarcoma, small intestinal, and primary peritoneal origin among others. Advances in our understanding of this unique disease process have led to significant interest in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) as an emerging treatment option. The goal of CRS-HIPEC is to remove all visible macroscopic disease while preserving organ function, and then treat microscopic disease through perfusion of the peritoneal cavity with heated chemotherapy. PURPOSE Although recent reviews have focused on the management of peritoneal carcinomatosis secondary to colorectal cancer given the publication of several recent randomized controlled trials, the purpose of the current review is to summarize the evidence on CRS-HIPEC for non-colorectal peritoneal surface malignancies, including appendiceal neoplasms, malignant peritoneal mesothelioma, gastric cancer, and ovarian cancer. RESULTS While retrospective studies have clarified the importance of prognostic factors such as the peritoneal carcinomatosis index, completeness of cytoreduction, histopathological characteristics, and lymph node positivity, the lack of convincing level 1 evidence for the use of CRS-HIPEC has led to it remaining a highly controversial topic. CONCLUSION The decision to utilize CRS-HIPEC should involve a multidisciplinary team approach and evaluation of prognostic factors to balance the short-term morbidity of the operation with maximum long-term benefits. Large, multi-institutional groups and ongoing trials hold promise for clarifying the role of CRS-HIPEC in peritoneal surface malignancies.
Collapse
|
|
46
|
Ray MD, Dhall K. Where Does HIPEC Stand: An Evidence Based Review. MULTIDISCIPLINARY APPROACH TO SURGICAL ONCOLOGY PATIENTS 2021:349-358. [DOI: 10.1007/978-981-15-7699-7_44] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
47
|
Outcomes in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for maximal volume (PCI 39) appendiceal tumours. Eur J Surg Oncol 2020; 47:1406-1410. [PMID: 33279358 DOI: 10.1016/j.ejso.2020.11.138] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 11/08/2020] [Accepted: 11/21/2020] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Higher Peritoneal Cancer Index (PCI) requires more extensive surgery and maybe associated with more limited outcomes. The aim of this study in a high-volume centre in Australia was to analyse the outcomes in PCI 39 patients regarding short and long term outcomes in appendiceal tumours. METHODS A retrospective analysis of prospectively maintained database of patients that underwent primary cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC) with PCI 39 at St George Hospital, Sydney from 1996 to 2018. Patients with appendiceal tumours (inclusive of high and low grade) were analysed. Factors contributing to high grade (III/IV Clavien-Dindo) morbidity and mortality were assessed. RESULTS Of the 1201 patients in the database, 58 patients had a PCI 39 from appendix tumours at their first operation. The overall survival rate at 1, 3 and 5 year was 91.2%, 79.5% and 62.9% respectively. The median survival was 87.2 months (96% CI 51.8-NR). The rate of major morbidity was 71%. The postoperative mortality incidence was 1.7%. The median hospital length of stay was 34 days (IQR:27-54 days). CONCLUSIONS In an experienced centre CRS + HIPEC is safe in selected patients with PCI 39. Despite the high morbidity, the overall survival for appendiceal tumours appear considerably better than debulking surgery.
Collapse
|
|
48
|
Swain D, Mason G, Yates A, Burke S, Cecil T, Mohamed F, Dayal S, Tzivanakis A, Moran B. Outcomes of home parenteral nutrition in 34 patients with intestinal failure from recurrent or progressive peritoneal malignancy of gastro-intestinal tract origin. Eur J Clin Nutr 2020; 75:856-858. [PMID: 33221816 DOI: 10.1038/s41430-020-00810-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Revised: 10/16/2020] [Accepted: 11/09/2020] [Indexed: 11/09/2022]
Abstract
OBJECTIVES To investigate the outcomes of 34 patients with intestinal failure secondary to advanced peritoneal malignancy on home parenteral nutrition (HPN). METHODS A retrospective analysis of all known patients receiving HPN at any time between January 2012 and the 31st March 2020 registered in a high volume peritoneal malignancy surgical centre database. RESULTS The median duration of HPN for all patients was 309.5 days (range 31-2198). Overall 11/34 went on to have multivisceral transplants. Of these 5/11 resumed normal oral intake off HPN, 3 died and 3 required ongoing HPN. Average time on HPN for patients with pseudomyxoma peritonei of appendix origin was 338 days (71-2198) compared with 90 days (31-260) in the group with more aggressive tumours. CONCLUSIONS HPN is feasible and effective in selected patients with pseudomyxoma peritonei as either a bridge to transplant or definitive treatment. As expected, patients with more aggressive tumours fare worse.
Collapse
Affiliation(s)
- David Swain
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Aldermaston Rd, Basingstoke, RG24 9NA, UK.
| | - Gemma Mason
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Aldermaston Rd, Basingstoke, RG24 9NA, UK
| | - Allison Yates
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Aldermaston Rd, Basingstoke, RG24 9NA, UK
| | - Sara Burke
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Aldermaston Rd, Basingstoke, RG24 9NA, UK
| | - Tom Cecil
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Aldermaston Rd, Basingstoke, RG24 9NA, UK
| | - Faheez Mohamed
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Aldermaston Rd, Basingstoke, RG24 9NA, UK
| | - Sanjeev Dayal
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Aldermaston Rd, Basingstoke, RG24 9NA, UK
| | - Alexios Tzivanakis
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Aldermaston Rd, Basingstoke, RG24 9NA, UK
| | - Brendan Moran
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Hampshire Hospitals NHS Foundation Trust, Aldermaston Rd, Basingstoke, RG24 9NA, UK
| |
Collapse
|
|
49
|
The role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis: a systematic review including evidence from Japan. Surg Today 2020; 51:1085-1098. [PMID: 33185798 DOI: 10.1007/s00595-020-02180-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Accepted: 09/29/2020] [Indexed: 02/07/2023]
Abstract
The prognosis of peritoneal carcinomatosis is poor. However, the emergence of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) as a treatment option has prolonged survival and it can even potentially cure patients with peritoneal carcinomatosis. Randomized controlled studies and other observational studies indicated that this combined therapy potentially improved the prognosis of patients with colon, gastric, and ovarian cancers with acceptable morbidity and mortality rates. Even in rarer diseases, such as pseudomyxoma peritonei and malignant peritoneal mesothelioma, CRS + HIPEC markedly improved the prognoses over those with conventional treatment. Based on the accumulated evidence, clinical guidelines recommend CRS + HIPEC for selected patients with peritoneal carcinomatosis. However, several issues still need to be overcome. A standard method for HIPEC has not yet been established. Furthermore, the criteria employed for patient selection need to be clarified to achieve real benefits. The peritoneal cancer index, chemo-sensitivity and several biological markers are considered to be key factors.
Collapse
|
|
50
|
Martin RC, Marshall BM, Philips P, Egger M, McMasters KM, Scoggins CR. Enhanced recovery after surgery is safe for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Am J Surg 2020; 220:1428-1432. [PMID: 32921403 DOI: 10.1016/j.amjsurg.2020.08.041] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 07/19/2020] [Accepted: 08/29/2020] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is an effective, aggressive approach to treating intraperitoneal carcinomatosis. This study aimed to test the efficacy/safety of an enhanced recovery (ERAS) program after CRS-HIPEC surgery. METHODS Review of an IRB-approved prospectively maintained HIPEC database from 2003 to 2019. Adverse events and outcomes related to the primary operation were noted. RESULTS 125 HIPEC procedures performed met inclusion criteria, with 20 treated through ERAS. There was an improvement in LOS (ERAS: 9, 6.0-28.0; non-ERAS: 11.0, 6.0-45.1, P = 0.5), a significant reduction in opioid use during hospitalization (ERAS Total Morphine Equivalents 156 vs Non-ERAS of 856, p < 0.001), and a significant reduction in discharge opioid requirements (ERAS 55% of patients, non-ERAS 97%, p < 0.02). CONCLUSION ERAS for CRS-HIPEC is safe, while maintaining quality outcomes, and leads to significant reductions in hospital opioid use and discharge narcotic usage. Our experience supports the full implementation of an ERAS protocol for HIPEC.
Collapse
Affiliation(s)
- Robert Cg Martin
- Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, USA.
| | - Bryce M Marshall
- Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, USA
| | - Prejesh Philips
- Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, USA
| | - Michael Egger
- Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, USA
| | - Kelly M McMasters
- Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, USA
| | - Charles R Scoggins
- Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, USA
| |
Collapse
|