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Patel S, Bhatt A, Mehta S, Ramakrishnan AS. Two-stage cytoreductive surgery for 'extensive' pseudomyxoma peritonei: A legitimate alternative or salvage strategy? EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108593. [PMID: 39121632 DOI: 10.1016/j.ejso.2024.108593] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 08/06/2024] [Accepted: 08/06/2024] [Indexed: 08/12/2024]
Abstract
BACKGROUND AND AIM Two-stage cytoreductive surgery (CRS) has been proposed as an alternative to one-stage surgery in patients who have 'extensive' pseudomyxoma peritonei (PMP) and/or are unfit for very extensive surgery, to reduce morbidity. We review current evidence on two-stage CRS focusing on patient selection, interval between procedures, extent of surgery, use of HIPEC, perioperative and oncological outcomes. METHODS This is a narrative review. A literature search on PubMed and Embase was performed using keywords- 'Two-stage cytoreductive surgery', 'pseudomyxoma peritonei', 'high-volume PMP', 'huge PMP', 'cytoreductive surgery', 'HIPEC', 'staged surgery' and 'extensive pseudomyxoma peritonei'. RESULTS Five studies reported outcomes in a total of 114 patients. The indications for two-stage CRS were: in two studies, patients undergoing an incomplete cytoreduction due to undue surgical risk were reevaluated for a second surgery during routine surveillance; severe comorbidities in one; extensive disease with PCI>28 in another and in one, only HIPEC was performed as a second procedure due to intraoperative hemodynamic instability (the two-stage procedure was performed in interest of patient's safety). Major morbidity ranged from 0 to 37.5 % (first-stage) and 25%-38.9 % (second-stage). Short term follow-up demonstrated equivalent short-term oncological outcomes compared to historical data. Long term follow-up and quality-of-life data were not available. CONCLUSIONS The published studies showed different interpretations and applications of the two-stage CRS concept. The reported morbidity was similar to that after single-stage CRS for extensive PMP. Though short-term survival outcomes are acceptable, long-term follow-up is needed. Planned two-stage CRS should currently be reserved for highly selected clinical situations.
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Affiliation(s)
- Swapnil Patel
- Dept of Surgical Oncology, MPMMCC & HBCH, Tata Memorial Centre, Varanasi, India
| | - Aditi Bhatt
- Dept of Surgical Oncology, KD Hospital, Ahmedabad, India.
| | - Sanket Mehta
- Dept of Surgical Oncology, Specialty Surgical Oncology, Mumbai, India
| | - A S Ramakrishnan
- Dept. of Surgical Oncology, Cancer Institute, WIA, Chennai, India
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Martínez-Quintanilla J, Cabot D, Sabia D, Arqués O, Vergés J, Chicote I, Bijelic L, Cabellos L, Alcántara AM, Ramos I, Barrios P, Crusellas O, Palacio LM, Cámara JA, Barriuso J, Jiménez JJ, Muñoz-Torres P, Nonell L, Flores R, Médico E, Guaglio M, Ros J, Élez E, Tabernero J, Aziz O, Deraco M, Palmer HG. Precision Oncology and Systemic Targeted Therapy in Pseudomyxoma Peritonei. Clin Cancer Res 2024; 30:4082-4099. [PMID: 39018564 PMCID: PMC11393541 DOI: 10.1158/1078-0432.ccr-23-4072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 04/18/2024] [Accepted: 07/10/2024] [Indexed: 07/19/2024]
Abstract
PURPOSE Pseudomyxoma peritonei (PMP) is a rare and poorly understood malignant condition characterized by the accumulation of intra-abdominal mucin produced from peritoneal metastases. Currently, cytoreductive surgery remains the mainstay of treatment but disease recurrence and death after relapse frequently occur in patients with PMP. New therapeutic strategies are therefore urgently needed for these patients. EXPERIMENTAL DESIGN A total of 120 PMP samples from 50 patients were processed to generate a collection of 50 patient-derived organoid (PDO) and xenograft (PDX) models. Whole exome sequencing, immunohistochemistry analyses, and in vitro and in vivo drug efficacy studies were performed. RESULTS In this study, we have generated a collection of PMP preclinical models and identified druggable targets, including BRAFV600E, KRASG12C, and KRASG12D, that could also be detected in intra-abdominal mucin biopsies of patients with PMP using droplet digital PCR. Preclinical models preserved the histopathological markers from the original patient sample. The BRAFV600E inhibitor encorafenib reduced cell viability of BRAFV600E PMP-PDO models. Proof-of-concept in vivo experiments showed that a systemic treatment with encorafenib significantly reduced tumor growth and prolonged survival in subcutaneous and orthotopic BRAFV600E-PMP-PDX mouse models. CONCLUSIONS Our study demonstrates for the first time that systemic targeted therapies can effectively control PMP tumors. BRAF signaling pathway inhibition represents a new therapeutic opportunity for patients with BRAFV600E PMP who have a poor prognosis. Importantly, our present data and collection of preclinical models pave the way for evaluating the efficacy of other systemic targeted therapies toward extending the promise of precision oncology to patients with PMP.
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Affiliation(s)
- Jordi Martínez-Quintanilla
- Translational Program, Stem Cells and Cancer Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Débora Cabot
- Translational Program, Stem Cells and Cancer Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Doménico Sabia
- Peritoneal Surface Malignancies Surgery Unit, Hospital Sant Joan Despí, Moises Broggi, Sant Joan Despí, Spain
| | - Oriol Arqués
- Translational Program, Stem Cells and Cancer Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Jordi Vergés
- Translational Program, Stem Cells and Cancer Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Irene Chicote
- Translational Program, Stem Cells and Cancer Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Lana Bijelic
- Peritoneal Surface Malignancies Surgery Unit, Hospital Sant Joan Despí, Moises Broggi, Sant Joan Despí, Spain
| | - Laia Cabellos
- Translational Program, Stem Cells and Cancer Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Anna M Alcántara
- Translational Program, Stem Cells and Cancer Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Isabel Ramos
- Department of General Surgery, Hospital Sant Joan Despí, Consorci Sanitari Integral, Sant Joan Despí, Spain
| | - Pedro Barrios
- Former Peritoneal Surface Malignancies Surgery Unit, Hospital Sant Joan Despí, Moises Broggi, Sant Joan Despí, Spain
| | - Oriol Crusellas
- Department of General Surgery, Hospital Sant Joan Despí, Consorci Sanitari Integral, Sant Joan Despí, Spain
- Department of General Surgery, Hospital de Barcelona, Assistència Sanitària Col·legial, Barcelona, Spain
| | - Lina M Palacio
- Peritoneal Surface Malignancies Surgery Unit, Hospital Sant Joan Despí, Moises Broggi, Sant Joan Despí, Spain
| | - Juan A Cámara
- Preclinical Therapeutics Core, University of California, San Francisco, California
| | - Jorge Barriuso
- Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom
- Colorectal and Peritoneal Oncology Centre, The Christie NHSFT, Manchester, United Kingdom
| | - Juan J Jiménez
- Preclinical Imaging Platform, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
| | - Pau Muñoz-Torres
- Bioinformatics Unit, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
| | - Lara Nonell
- Bioinformatics Unit, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain
| | - Raquel Flores
- Translational Program, Stem Cells and Cancer Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Enzo Médico
- Department of Oncology, University of Turin, Turin, Italy
- Candiolo Cancer Institute, FPO-IRCCS, Candiolo, Italy
| | - Marcello Guaglio
- Consultant Surgeon, Peritoneal Surface Malignancies Unit, Division of Colorectal Surgery, National Cancer Institute, Milan, Italy
| | - Javier Ros
- Medical Oncology Service, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Elena Élez
- Medical Oncology Service, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Josep Tabernero
- Medical Oncology Service, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- CIBERONC, Madrid, Spain
| | - Omer Aziz
- Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom
- Colorectal and Peritoneal Oncology Centre, The Christie NHSFT, Manchester, United Kingdom
| | - Marcello Deraco
- Peritoneal Surfaces Malignance Unit, Fondazione IRCCS Instituto Nazionale dei Tumori, Milan, Italy
| | - Héctor G Palmer
- Translational Program, Stem Cells and Cancer Laboratory, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain
- CIBERONC, Madrid, Spain
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3
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Ma R, Su Y, Yan F, Lin Y, Gao Y, Li Y. A nomogram prediction model of pseudomyxoma peritonei established based on new prognostic factors of HE stained pathological images analysis. Cancer Med 2024; 13:e7101. [PMID: 38506243 PMCID: PMC10952024 DOI: 10.1002/cam4.7101] [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: 08/04/2023] [Revised: 02/13/2024] [Accepted: 03/02/2024] [Indexed: 03/21/2024] Open
Abstract
BACKGROUND Pseudomyxoma peritonei (PMP) is a rare clinical malignant syndrome, and its rarity causes a lack of pathology research. This study aims to quantitatively analyze HE-stained pathological images (PIs), and develop a new predictive model integrating digital pathological parameters with clinical information. METHODS Ninety-two PMP patients with complete clinic-pathological information, were included. QuPath was used for PIs quantitative feature analysis at tissue-, cell-, and nucleus-level. The correlations between overall survival (OS) and general clinicopathological characteristics, and PIs features were analyzed. A nomogram was established based on independent prognostic factors and evaluated. RESULTS Among the 92 PMP patients, there were 34 (37.0%) females and 58 (63.0%) males, with a median age of 57 (range: 31-76). A total of 449 HE stained images were obtained for QuPath analysis, which extracted 40 pathological parameters at three levels. Kaplan-Meier survival analysis revealed eight clinicopathological characteristics and 20 PIs features significantly associated with OS (p < 0.05). Partial least squares regression was used to screen the multicollinearity features and synthesize four new features. Multivariate survival analysis identified the following five independent prognostic factors: preoperative CA199, completeness of cytoreduction, histopathological type, component one at tissue-level, and tumor nuclei circularity variance. A nomogram was established with internal validation C-index 0.795 and calibration plots indicating improved prediction performance. CONCLUSIONS The quantitative analysis of HE-stained PIs could extract the new prognostic information on PMP. A nomogram established by five independent prognosticators is the first model integrating digital pathological information with clinical data for improved clinical outcome prediction.
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Affiliation(s)
- Ru Ma
- Department of Peritoneal Cancer Surgery, Beijing Shijitan HospitalCapital Medical UniversityBeijingChina
| | - Yan‐Dong Su
- Department of Peritoneal Cancer Surgery, Beijing Shijitan HospitalCapital Medical UniversityBeijingChina
| | - Feng‐Cai Yan
- Department of Pathology, Beijing Shijitan HospitalCapital Medical UniversityBeijingChina
| | - Yu‐Lin Lin
- Department of Peritoneal Cancer Surgery, Beijing Shijitan HospitalCapital Medical UniversityBeijingChina
| | - Ying Gao
- Department of Pathology, Beijing Shijitan HospitalCapital Medical UniversityBeijingChina
| | - Yan Li
- Department of Peritoneal Cancer Surgery, Beijing Shijitan HospitalCapital Medical UniversityBeijingChina
- Department of Surgical OncologyBeijing Tsinghua Changgung Hospital Affiliated to Tsinghua UniversityBeijingChina
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Bangeas P, Kyziridis D, Kalakonas A, Tentes AA. Low-Grade Pseudomyxoma Peritonei Behaving as a High-Grade Disease: A Case Series and Literature Review. Curr Oncol 2023; 30:9996-10006. [PMID: 37999146 PMCID: PMC10670747 DOI: 10.3390/curroncol30110726] [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: 09/07/2023] [Revised: 10/18/2023] [Accepted: 10/25/2023] [Indexed: 11/25/2023] Open
Abstract
Patients with low-grade appendiceal mucinous carcinomas (LAMNs) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have a favorable prognosis. However, a subgroup of patients presents a clinically aggressive course with disease progression despite receiving treatment. The purpose of this study is to report the experience of clinically aggressive LAMN patients treated by the same team, and to present a review of the literature. The cases of four patients with clinically aggressive LAMNs were reviewed. Clinical and histopathological characteristics were re-examined. Recurrences and the time of recurrence, as well as the survival time, were recorded. These patients were four men with clinically aggressive LAMNs treated with CRS plus HIPEC. One of them underwent CC-0 surgery, two underwent CC-1 surgery, and one underwent CC-3 surgery. All patients received systemic chemotherapy after surgery. Recurrence was recorded in three of the patients within 4-23 months after the initial treatment. Two of the patients underwent secondary CRS. Three patients died of disease recurrence within 13-23 months, and one is alive with a disease relapse at 49 months after his initial surgery. LAMNs were identified in both the initial specimens and the specimens obtained during reoperation. The prognosis of LAMN patients treated with CRS plus HIPEC is favorable. A small number of patients present a clinically aggressive course that is unresponsive to any treatment. Molecular and genetic studies are required to identify this group of LAMN patients who have an unfavorable prognosis.
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Affiliation(s)
- Petros Bangeas
- University Surgery Department, Papageorgiou Hospital, Aristotle University of Thessaloniki, 54453 Thessaloniki, Greece
- Department of Surgical Oncology, Peritoneal Surface Malignancy Program, Euromedica Kyanos Stavros, 54454 Thessaloniki, Greece; (D.K.); (A.A.T.)
| | - Dimitrios Kyziridis
- Department of Surgical Oncology, Peritoneal Surface Malignancy Program, Euromedica Kyanos Stavros, 54454 Thessaloniki, Greece; (D.K.); (A.A.T.)
| | - Apostolos Kalakonas
- Department of Anaesthesiology, Euromedica Kyanos Stavros, 54454 Thessaloniki, Greece;
| | - Apostolis A. Tentes
- Department of Surgical Oncology, Peritoneal Surface Malignancy Program, Euromedica Kyanos Stavros, 54454 Thessaloniki, Greece; (D.K.); (A.A.T.)
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Villarejo-Campos P, García-Arranz M, Qian S, Jiménez de Los Galanes S, Domínguez-Prieto V, Vélez-Pinto JF, Guijo Castellano I, Jiménez-Fuertes M, Guadalajara H, García-Olmo D. Under the Hood: Understanding the Features of Mucin in Pseudomyxoma Peritonei. J Clin Med 2023; 12:4007. [PMID: 37373701 DOI: 10.3390/jcm12124007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 06/06/2023] [Accepted: 06/09/2023] [Indexed: 06/29/2023] Open
Abstract
Pseudomyxoma peritonei (PMP) is a rare malignant growth characterized by the production of mucin and the potential for peritoneal relapse. This study aimed to investigate the immunohistochemical and biological characteristics of mucin in patients with cellular and acellular PMP. We prospectively analyzed mucin specimens obtained from our patient cohort and described the composition and type of mucin present in each sample. A metagenomic analysis of the samples was performed to investigate the bacterial composition of the PMP microbiome. Secreted mucins 2 and 5AC and membrane-associated mucin-1 were the primary components of mucin in both cellular and acellular tumor specimens. The metagenomic study revealed a predominance of the phylum Proteobacteria and the genus Pseudomonas. Notably, Pseudomonas plecoglossicida, a species not previously reported in the human microbiome, was found to be the most abundant organism in the mucin of pseudomyxoma peritonei. Our findings suggest that the presence of MUC-2 and mucin colonization by Pseudomonas are characteristic features of both cellular and acellular disease. These results may have significant implications for the diagnosis and treatment of this rare entity.
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Affiliation(s)
- Pedro Villarejo-Campos
- Department of Surgery, Fundación Jiménez Díaz University Hospital, Avda. Reyes Católicos, 2, 28040 Madrid, Spain
- Department of Surgery, Universidad Autónoma de Madrid, C/Arzobispo Morcillo s/n, 28034 Madrid, Spain
| | - Mariano García-Arranz
- Department of Surgery, Universidad Autónoma de Madrid, C/Arzobispo Morcillo s/n, 28034 Madrid, Spain
- New Therapies Laboratory, Health Research Institute-Fundación Jiménez Díaz University Hospital (IIS-FJD), Avda. Reyes Católicos, 2, 28040 Madrid, Spain
| | - Siyuan Qian
- Department of Surgery, Fundación Jiménez Díaz University Hospital, Avda. Reyes Católicos, 2, 28040 Madrid, Spain
| | | | - Víctor Domínguez-Prieto
- Department of Surgery, Fundación Jiménez Díaz University Hospital, Avda. Reyes Católicos, 2, 28040 Madrid, Spain
| | - Juan Felipe Vélez-Pinto
- Department of Surgery, Fundación Jiménez Díaz University Hospital, Avda. Reyes Católicos, 2, 28040 Madrid, Spain
| | - Ismael Guijo Castellano
- Department of Surgery, Fundación Jiménez Díaz University Hospital, Avda. Reyes Católicos, 2, 28040 Madrid, Spain
| | - Montiel Jiménez-Fuertes
- Department of Surgery, Fundación Jiménez Díaz University Hospital, Avda. Reyes Católicos, 2, 28040 Madrid, Spain
| | - Héctor Guadalajara
- Department of Surgery, Fundación Jiménez Díaz University Hospital, Avda. Reyes Católicos, 2, 28040 Madrid, Spain
- Department of Surgery, Universidad Autónoma de Madrid, C/Arzobispo Morcillo s/n, 28034 Madrid, Spain
| | - Damián García-Olmo
- Department of Surgery, Fundación Jiménez Díaz University Hospital, Avda. Reyes Católicos, 2, 28040 Madrid, Spain
- Department of Surgery, Universidad Autónoma de Madrid, C/Arzobispo Morcillo s/n, 28034 Madrid, Spain
- New Therapies Laboratory, Health Research Institute-Fundación Jiménez Díaz University Hospital (IIS-FJD), Avda. Reyes Católicos, 2, 28040 Madrid, Spain
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Sugarbaker PH, Chang D, Liang J. Pathogenesis of histologic variations of appendiceal mucinous neoplasms. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:895-901. [PMID: 36863914 DOI: 10.1016/j.ejso.2023.02.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Revised: 01/18/2023] [Accepted: 02/23/2023] [Indexed: 03/03/2023]
Abstract
BACKGROUND In order for peritoneal metastases from a primary appendiceal mucinous neoplasm to occur, the wall of the appendix must perforate to allow mucus with tumor cells access to the peritoneal spaces. With progression the peritoneal metastases show a broad spectrum of tumor biology varying from indolent to aggressive activity. METHODS The histopathology of peritoneal tumor masses was determined from the clinical material resected at the time of cytoreductive surgery (CRS). All groups of patients were treated by a uniform strategy that involved complete CRS and perioperative intraperitoneal chemotherapy. Overall survival was determined. RESULTS From a database of 685 patients, four histologic subtypes were identified and long-term survival determined. Four hundred and fifty patients (66.0%) had low-grade appendiceal mucinous neoplasm (LAMN), 37 patients (5.4%) had mucinous appendiceal adenocarcinoma of intermediate subtype (MACA-Int), 159 patients (23.2%) had mucinous appendiceal adenocarcinoma (MACA), and 39 patients (5.4%) had a mucinous appendiceal adenocarcinoma with positive lymph nodes (MACA-LN). The mean survival of the four groups was 24.5, 14.8, 11.2 and 7.4 years, respectively (p < 0.0001). These four subtypes of mucinous appendiceal neoplasms were shown to have distinct survival estimates. CONCLUSIONS The estimated survival of these four histologic subtypes in patients having a complete CRS plus HIPEC is of value to the oncologist managing these patients. A mutations and perforations hypothesis was offered in an attempt to explain the broad spectrum of mucinous appendiceal neoplasms that exist. Inclusion of MACA-Int and MACA-LN as standalone subtypes was thought to be necessary.
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Affiliation(s)
- Paul H Sugarbaker
- Program in Peritoneal Surface Malignancy, Washington Cancer Institute, Washington, DC, USA.
| | | | - John Liang
- Department of Pathology, MedStar Washington Hospital Center, Washington, DC, USA
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Martín Román L, Lozano P, Baratti D, Kusamura S, Deraco M, Vásquez W, González Bayón L. Validation of a Nomogram to Predict Recurrence in Patients with Mucinous Neoplasms of the Appendix with Peritoneal Dissemination After Cytoreductive Surgery and HIPEC. Ann Surg Oncol 2022; 29:7553-7563. [PMID: 35876926 DOI: 10.1245/s10434-022-12060-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 06/04/2022] [Indexed: 12/24/2022]
Abstract
BACKGROUND Survival of patients affected by mucinous appendiceal neoplasms with peritoneal dissemination (PD) is mainly related to histopathological features. However, prognostic stratification is still a concern, as the clinical course of the disease is often unpredictable. The aim of this study is to construct and externally validate a nomogram predicting disease-free survival (DFS) in mucinous appendiceal neoplasms with PD treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). PATIENTS AND METHODS Patients treated in two referral centers were included: Hospital General Universitario Gregorio Marañón, Madrid, Spain (derivation cohort) and Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy (validation cohort). Cox regression analysis identified factors associated with shorter DFS in the derivation cohort. The nomogram performance was externally evaluated in the validation cohort using concordance index and calibration plots. Histology was classified according to the Peritoneal Surface Oncology Group International (PSOGI). RESULTS The derivation cohort included 95 patients, and the validation cohort 348. Five-year DFS rates were 51.5 and 62%, respectively. Cox regression analysis (derivation cohort) identified PSOGI histology of the peritoneal components, number of preoperative elevated tumor marker, and peritoneal disease extent, as assessed by peritoneal carcinomatosis index, to be predictors of DFS. The model's predictive capacity was higher than that of PSOGI classification alone, with respective concordance indexes of 0.702 ± 0.023 and 0.610 ± 0.018 (validation cohort). The nomogram approximated the perfect model in the calibration plots at 3- and 5-year DFS. CONCLUSIONS An easy-to-use model that provides better prognostic stratification than histopathological features has been constructed. This nomogram may help clinicians in individualized survival predictions and informed clinical decision-making.
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Affiliation(s)
- L Martín Román
- Peritoneal Carcinomatosis Unit, Department of General and Digestive Surgery, Hospital General Universitario Gregorio Marañón, Madrid, Spain.,Department of Surgery, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - P Lozano
- Peritoneal Carcinomatosis Unit, Department of General and Digestive Surgery, Hospital General Universitario Gregorio Marañón, Madrid, Spain.,Department of Surgery, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - D Baratti
- Peritoneal Malignancy Program, Department of Surgery, National Cancer Institute, Milan, Italy.
| | - S Kusamura
- Peritoneal Malignancy Program, Department of Surgery, National Cancer Institute, Milan, Italy
| | - M Deraco
- Peritoneal Malignancy Program, Department of Surgery, National Cancer Institute, Milan, Italy
| | - W Vásquez
- Peritoneal Carcinomatosis Unit, Department of General and Digestive Surgery, Hospital General Universitario Gregorio Marañón, Madrid, Spain.,Department of Surgery, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
| | - L González Bayón
- Peritoneal Carcinomatosis Unit, Department of General and Digestive Surgery, Hospital General Universitario Gregorio Marañón, Madrid, Spain.,Department of Surgery, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain
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8
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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
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Ma R, Lin YL, Li XB, Yan FC, Xu HB, Peng Z, Li Y. Tumor-stroma ratio as a new prognosticator for pseudomyxoma peritonei: a comprehensive clinicopathological and immunohistochemical study. Diagn Pathol 2021; 16:116. [PMID: 34895284 PMCID: PMC8667412 DOI: 10.1186/s13000-021-01177-1] [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: 09/15/2021] [Accepted: 11/28/2021] [Indexed: 12/20/2022] Open
Abstract
Background As a rare clinical tumor syndrome with an indolent clinical course and lack of pathognomonic symptoms, pseudomyxoma peritonei (PMP) is usually diagnosed at an advanced stage. In-depth pathological analysis is essential to assess tumor biological behaviors, assist treatment decision, and predict the clinical prognosis of PMP. The tumor-stroma ratio (TSR) is a promising prognostic parameter based on the tumor and stroma. This study explored the relationship between TSR and the pathological characteristics and prognosis of PMP. Methods PMP patients with complete data who underwent cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy were enrolled. The TSR of postoperative pathological images was quantitatively analyzed by Image-Pro Plus. Then the relationship between TSR and the clinicopathological characteristics, immunohistochemical characteristics and prognosis of PMP was analyzed. Results Among the 50 PMP patients included, there were 27 males (54.0%) and 23 females (46.0%), with a median age of 55 (range: 31–76) years. 25 (50.0%) patients were diagnosed with low-grade PMP (LG-PMP), and 25 (50.0%) were diagnosed with high-grade PMP (HG-PMP). There were 4 (8.0%) patients with vascular tumor emboli, 3 (6.0%) patients with nerve invasion, and 5 (10.0%) patients with lymph node metastasis. The immunohistochemical results showed that the Ki67 label index was < 25% in 18 cases (36.0%), 25 - 50% in 18 cases (36.0%) and > 50% in 14 cases (28.0%). The range of TSR was 2 - 24% (median: 8%). The cutoff value of TSR was 10% based on the receiver operating characteristic (ROC) curve and X-Tile analysis. There were 31 (62.0%) cases with TSR < 10% and 19 (38.0%) cases with TSR ≥ 10%. The TSR was closely related to histopathological type (P < 0.001) and Ki67 label index (P < 0.001). Univariate analysis showed that preoperative carcinoembryonic antigen (CEA), preoperative carbohydrate antigen 19–9, pathological type, vascular tumor emboli and TSR influenced the prognosis of PMP patients (P < 0.05). Multivariate analysis showed that preoperative CEA, vascular tumor emboli and the TSR were independent prognostic factors. Conclusions The TSR could be a new independent prognosticator for PMP.
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Affiliation(s)
- Ru Ma
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, 100038, Beijing, China
| | - Yu-Lin Lin
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, 100038, Beijing, China
| | - Xin-Bao Li
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, 100038, Beijing, China
| | - Feng-Cai Yan
- Department of Pathology, Beijing Shijitan Hospital, Capital Medical University, 100038, Beijing, China
| | - Hong-Bin Xu
- Department of Myxoma, Aero Space Central Hospital, Peking University, 100049, Beijing, China
| | - Zheng Peng
- Department of General Surgery, Chinese PLA General Hospital, 100853, Beijing, China
| | - Yan Li
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, 100038, Beijing, China. .,Department of Pathology, Beijing Shijitan Hospital, Capital Medical University, 100038, Beijing, China.
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Sugarbaker PH, Chang D. Treatment of advanced pseudomyxoma peritonei using cytoreductive surgery including total gastrectomy and perioperative chemotherapy. J Surg Oncol 2021; 124:378-389. [PMID: 33914912 DOI: 10.1002/jso.26506] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 03/23/2021] [Accepted: 03/24/2021] [Indexed: 11/10/2022]
Abstract
BACKGROUND Pseudomyxoma peritonei is a disease caused by the widespread distribution of mucinous tumor into the peritoneal space from a perforated appendiceal neoplasm. METHODS All patients in this study had cytoreductive surgery with total gastrectomy plus perioperative intraperitoneal chemotherapy. A high diverting jejunostomy was used on all patients. Patient characteristics, adverse events, and survival were accumulated prospectively. RESULTS Fifty-eight patients were available for long-term follow-up. In the univariate analysis, features associated with a less favorable outcome included female gender (p = 0.0127), intestinal obstruction before treatment (p = 0.00791), and prior surgical score (PSS) (p = 0.0054). In the multivariate analysis, the two significant variables were grade (p = 0.0458) and PSS (p = 0.0041). Median survival was 12 years with a 5-, 10-, and 20-year survival of 76%, 58%, and 37%, respectively. There were two postoperative deaths (3.4%) and Grades 3 and 4 adverse events in 20 (34.5%) patients. CONCLUSIONS A 10-year survival after cytoreductive surgery, total gastrectomy with temporary high diverting jejunostomy, and perioperative chemotherapy occurred in 58% of these patients with advanced pseudomyxoma peritonei. High-grade disease and extensive prior surgery with a high PSS were associated with reduced benefit.
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Affiliation(s)
- Paul H Sugarbaker
- Center for Gastrointestinal Malignancies, MedStar Washington Hospital Center, Washington, District Columbia, USA
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Calabrò ML, Lazzari N, Rigotto G, Tonello M, Sommariva A. Role of Epithelial-Mesenchymal Plasticity in Pseudomyxoma Peritonei: Implications for Locoregional Treatments. Int J Mol Sci 2020; 21:ijms21239120. [PMID: 33266161 PMCID: PMC7731245 DOI: 10.3390/ijms21239120] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2020] [Revised: 11/25/2020] [Accepted: 11/28/2020] [Indexed: 12/14/2022] Open
Abstract
The mechanisms by which neoplastic cells disseminate from the primary tumor to metastatic sites, so-called metastatic organotropism, remain poorly understood. Epithelial-mesenchymal transition (EMT) plays a role in cancer development and progression by converting static epithelial cells into the migratory and microenvironment-interacting mesenchymal cells, and by the modulation of chemoresistance and stemness of tumor cells. Several findings highlight that pathways involved in EMT and its reverse process (mesenchymal-epithelial transition, MET), now collectively called epithelial-mesenchymal plasticity (EMP), play a role in peritoneal metastases. So far, the relevance of factors linked to EMP in a unique peritoneal malignancy such as pseudomyxoma peritonei (PMP) has not been fully elucidated. In this review, we focus on the role of epithelial-mesenchymal dynamics in the metastatic process involving mucinous neoplastic dissemination in the peritoneum. In particular, we discuss the role of expression profiles and phenotypic transitions found in PMP in light of the recent concept of EMP. A better understanding of EMP-associated mechanisms driving peritoneal metastasis will help to provide a more targeted approach for PMP patients selected for locoregional interventions involving cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
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Affiliation(s)
- Maria Luisa Calabrò
- Immunology and Molecular Oncology, Veneto Institute of Oncology IOV-IRCCS, I-35128 Padua, Italy; (N.L.); (G.R.)
- Correspondence:
| | - Nayana Lazzari
- Immunology and Molecular Oncology, Veneto Institute of Oncology IOV-IRCCS, I-35128 Padua, Italy; (N.L.); (G.R.)
| | - Giulia Rigotto
- Immunology and Molecular Oncology, Veneto Institute of Oncology IOV-IRCCS, I-35128 Padua, Italy; (N.L.); (G.R.)
| | - Marco Tonello
- Surgical Oncology of the Esophagus and Digestive Tract, Veneto Institute of Oncology IOV-IRCCS, I-35128 Padua, Italy;
| | - Antonio Sommariva
- Advanced Surgical Oncology, Surgical Oncology of the Esophagus and Digestive Tract, Veneto Institute of Oncology IOV-IRCCS, I-35128 Padua, Italy;
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Azzam AZ, Al-Hamadah FH, Azzam KA, Amin TM. Mucinous Appendiceal Adenocarcinoma Penetrated the Quadratus Lumborum Muscle Posteriorly and Presented as Gluteal Abscess Managed Aggressively with Drainage Followed by Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Combined with Intraoperative Radiotherapy. a Case Report and Review of the Literature. Indian J Surg Oncol 2020; 11:128-130. [PMID: 33088148 PMCID: PMC7534762 DOI: 10.1007/s13193-020-01090-x] [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: 06/22/2019] [Accepted: 05/07/2020] [Indexed: 02/05/2023] Open
Abstract
Appendiceal mucinous adenocarcinoma is a term that was given for invasive appendiceal tumors. It is always present with pseudomyxoma peritonei which is a complex disease. These tumors have the tendency to surround the primary tumor then extend primarily and extensively all over the peritoneal cavity as the primary site of metastases. The invasion through the abdominal wall muscles is rare but the penetration and passing through these muscles to the subcutaneous tissue are extremely rare. A 62-year-old male patient known to have pseudomyxoma peritonei presented with gluteal abscess. After 2 weeks from the abscess drainage, the patient underwent cytoreductive surgery (CRS) combined with intraoperative radiotherapy (IORT) and hyperthermic intraperitoneal chemotherapy (HIPEC). He tolerated the operation well and discharged home in a good condition. Even with extensive appendiceal mucinous neoplasms presented with the penetration of the abdominal wall muscles, still aggressive management should be considered.
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Affiliation(s)
- Ayman Zaki Azzam
- General Surgery Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
- Surgical Oncology Department, Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Fatimah Hassan Al-Hamadah
- Surgical Oncology Department, Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | | | - Tarek Mahmoud Amin
- Surgical Oncology Department, Oncology Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
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Lin YL, Ma R, Li Y. The biological basis and function of GNAS mutation in pseudomyxoma peritonei: a review. J Cancer Res Clin Oncol 2020; 146:2179-2188. [PMID: 32700107 PMCID: PMC7382651 DOI: 10.1007/s00432-020-03321-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 07/10/2020] [Indexed: 12/16/2022]
Abstract
Purpose Pseudomyxoma peritonei (PMP) is a rare clinical malignancy syndrome characterized by the uncontrollable accumulation of copious mucinous ascites in the peritoneal cavity, resulting in “jelly belly”. The mechanism of tumor progression and mucin hypersecretion remains largely unknown, but GNAS mutation is a promising contributor. This review is to systemically summarize the biological background and variant features of GNAS, as well as the impacts of GNAS mutations on mucin expression, tumor cell proliferation, clinical-pathological characteristics, and prognosis of PMP. Methods NCBI PubMed database (in English) and WAN FANG DATA (in Chinese) were used for literature search. And NCBI Gene and Protein databases, Ensembl Genome Browser, COSMIC, UniProt, and RCSB PDB database were used for gene and protein review. Results GNAS encodes guanine nucleotide-binding protein α subunit (Gsα). The mutation sites of GNAS mutation in PMP are relatively stable, usually at Chr20: 57,484,420 (base pair: C-G) and Chr20: 57,484,421 (base pair: G-C). Typical GNAS mutation results in the reduction of GTP enzyme activity in Gsα, causing failure to hydrolyze GTP and release phosphoric acid, and eventually the continuous binding of GTP to Gsα. The activated Gsα could thus continuously promote mucin secretion through stimulating the cAMP-PKA signaling pathway, which is a possible mechanism leading to elevated mucin secretion in PMP. Conclusion GNAS mutation is one of the most important molecular biological features in PMP, with major functions to promote mucin hypersecretion.
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Affiliation(s)
- Yu-Lin Lin
- Department of Peritoneal Cancer Surgery and Pathology, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, Beijing, 100038, China
| | - Ru Ma
- Department of Peritoneal Cancer Surgery and Pathology, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, Beijing, 100038, China
| | - Yan Li
- Department of Peritoneal Cancer Surgery and Pathology, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Yangfangdian Street, Haidian District, Beijing, 100038, China.
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Bhatt A, Mishra S, Parikh L, Sheth S, Gorur I. Essentials for Pathological Evaluation of Peritoneal Surface Malignancies and Synoptic Reporting of Cytoreductive Surgery Specimens-A review and evidence-based guide. Indian J Surg Oncol 2020; 11:101-126. [PMID: 32205979 PMCID: PMC7064688 DOI: 10.1007/s13193-019-00897-7] [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: 11/20/2018] [Accepted: 02/18/2019] [Indexed: 12/14/2022] Open
Abstract
Peritoneal surface oncology has emerged as a subspecialty of surgical oncology, with the growing popularity of surgical treatment of peritoneal metastases comprising of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Pathological evaluation plays a key role in multidisciplinary management but there are still many areas where there are no guidelines or consensus on reporting. Some tumors presenting to a peritoneal surface oncology unit are rare and pathologists my not be familiar with diagnosing and classifying those. In this manuscript, we have reviewed the evidence regarding various aspects of histopathological evaluation of peritoneal tumors. It includes establishing a diagnosis, appropriate classification and staging of common and rare tumors and evaluation of pathological response to chemotherapy. In many instances, the information captured is of prognostic value alone with no direct therapeutic implications. But proper capturing of such information is vital for generating evidence that will guide future treatment trends and research. There are no guidelines/data set for reporting cytoreductive surgery specimens. Based on the authors' experience, a format for handling/grossing and synoptic reporting of these specimens is provided.
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Affiliation(s)
- Aditi Bhatt
- Department of Surgical Oncology, Zydus Hospital, Zydus hospital road, SG highway, Thaltej, Ahmedabad, 380054 India
| | - Suniti Mishra
- Department of Pathology, Fortis Hospital, Bangalore, India
| | - Loma Parikh
- Department of Pathology, Zydus Hospital, Ahmedabad, India
| | - Sandeep Sheth
- Department of Pathology, Zydus Hospital, Ahmedabad, India
| | - Imran Gorur
- Department of Pathology, Aster-CMI Hospital, Bangalore, India
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Sugarbaker PH. Psoas/iliacus muscle invasion from mucinous appendiceal neoplasm. Radiologic appearance and outcome of treatment in 3 patients. Surg Oncol 2018; 27:154-157. [PMID: 29937165 DOI: 10.1016/j.suronc.2018.02.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Accepted: 02/04/2018] [Indexed: 11/17/2022]
Abstract
BACKGROUND Mucinous appendiceal neoplasms have a pattern of metastases that is different from the other gastrointestinal cancers. The first site for cancer dissemination is the peritoneal space surrounding the primary tumor and this is followed by increasingly extensive peritoneal spread. Invasion of the psoas and iliacus muscle is an unusual phenomenon. METHOD From a prospective database of appendiceal mucinous neoplasms treated by cytoreductive surgery (CRS) and perioperative hyperthermic chemotherapy (HIPEC), patients with psoas muscle invasion were reviewed. Their clinical features and treatments were tabulated. RESULTS Three patients with ages 33, 60, and 63 were identified. Two patients had disease progression into the psoas muscle 33 and 95 months after CRS plus HIPEC. One had dissecting mucinous tumor into psoas, iliacus and quadratus lumborum muscle at the time of diagnosis of the appendiceal mucinous neoplasm. All three survived at least five years from their initial treatment. CONCLUSION Despite the fact that mucinous tumor invasion was outside the peritoneal cavity, long term benefit from psoas muscle resection with a mucinous appendiceal neoplasm is possible and resection possibly with HIPEC should be considered.
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Affiliation(s)
- Paul H Sugarbaker
- Program in Peritoneal Surface Oncology, MedStar Washington Cancer Institute, MedStar Washington Hospital Center, 106 Irving St., NW, Suite 3900, Washington, DC 20010, USA.
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Bhatt A, Mishra S, Prabhu R, Ramaswamy V, George A, Bhandare S, Shah M, Mehta S. Can low grade PMP be divided into prognostically distinct subgroups based on histological features? A retrospective study and the importance of using the appropriate classification. Eur J Surg Oncol 2018; 44:1105-1111. [PMID: 29685759 DOI: 10.1016/j.ejso.2018.03.032] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Revised: 03/14/2018] [Accepted: 03/31/2018] [Indexed: 02/04/2023] Open
Abstract
INTRODUCTION The pathological classification of PMP of appendiceal origin has prognostic and treatment implications. Our goals were to • Classify low grade mucinous carcinoma peritonei (LGMCP) into prognostically distinct subgroups based on histological features. • Compare the reproducibility of the WHO and the PSOGI classifications for both PMP and the appendiceal primary tumor. PATIENTS AND METHODS A retrospective analysis of patients undergoing CRS and HIPEC or debulking surgery was done. All the tumors were re-classified according to the PSOGI classification. LGMCP was further classified into three histological subgroups and the impact on survival was evaluated. RESULTS From Jun 2011 to June 2016, 101 patients underwent CRS with HIPEC (n = 89) or debulking surgery (n=12). The median PCI was 28 (3-39) and 74.1% patients had CC-0/1 resections. Of the 76.2% patients who had LGMCP, 4 patients (5.1%) were classified as group 1, 54 (70.1%) as group 2 and 19 patients (24.6%) as group 3. At a median follow up of 21 months, the disease free survival was not reached, 30 months and 14 months for groups 1, 2 and 3 respectively (p = 0.09). There was no difference in overall survival. Using the WHO classification, there was a discordance in the grade of the primary tumor and the peritoneal lesions in 19.8% and conflicting terminology was used in 62% of patients. CONCLUSIONS The subgroups of LGMCP described here are prognostically different though this needs further prospective evaluation in larger series. The PSOGI classification is more uniformly reproducible and should be preferred to the WHO classification.
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Affiliation(s)
- Aditi Bhatt
- Department of Surgical Oncology, Fortis Hospital, Bangalore, India.
| | - Suniti Mishra
- Department of Pathology, Fortis Hospital, Bangalore, India
| | - Robin Prabhu
- Department of Surgical Oncology, Fortis Hospital, Bangalore, India
| | | | - Antony George
- Department of Anesthesiology, Fortis Hospital, Bangalore, India
| | | | - Mita Shah
- Department of Pathology, Saifee Hospital, Mumbai, India
| | - Sanket Mehta
- Department of Peritoneal Surface Oncology, Saifeee Hospital, Mumbai, India
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A Consensus for Classification and Pathologic Reporting of Pseudomyxoma Peritonei and Associated Appendiceal Neoplasia: The Results of the Peritoneal Surface Oncology Group International (PSOGI) Modified Delphi Process. Am J Surg Pathol 2016; 40:14-26. [PMID: 26492181 DOI: 10.1097/pas.0000000000000535] [Citation(s) in RCA: 496] [Impact Index Per Article: 55.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Pseudomyxoma peritonei (PMP) is a complex disease with unique biological behavior that usually arises from appendiceal mucinous neoplasia. The classification of PMP and its primary appendiceal neoplasia is contentious, and an international modified Delphi consensus process was instigated to address terminology and definitions. A classification of mucinous appendiceal neoplasia was developed, and it was agreed that "mucinous adenocarcinoma" should be reserved for lesions with infiltrative invasion. The term "low-grade appendiceal mucinous neoplasm" was supported and it was agreed that "cystadenoma" should no longer be recommended. A new term of "high-grade appendiceal mucinous neoplasm" was proposed for lesions without infiltrative invasion but with high-grade cytologic atypia. Serrated polyp with or without dysplasia was preferred for tumors with serrated features confined to the mucosa with an intact muscularis mucosae. Consensus was achieved on the pathologic classification of PMP, defined as the intraperitoneal accumulation of mucus due to mucinous neoplasia characterized by the redistribution phenomenon. Three categories of PMP were agreed-low grade, high grade, and high grade with signet ring cells. Acellular mucin should be classified separately. It was agreed that low-grade and high-grade mucinous carcinoma peritonei should be considered synonymous with disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis, respectively. A checklist for the pathologic reporting of PMP and appendiceal mucinous neoplasms was also developed. By adopting the classifications and definitions that were agreed, different centers will be able to use uniform terminology that will allow meaningful comparison of their results.
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Bignell M, Carr NJ, Mohamed F. Pathophysiology and classification of pseudomyxoma peritonei. Pleura Peritoneum 2016; 1:3-13. [PMID: 30911604 PMCID: PMC6386305 DOI: 10.1515/pp-2016-0008] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2016] [Accepted: 03/15/2016] [Indexed: 12/23/2022] Open
Abstract
Background: The term pseudomyxoma peritonei (PMP) was first described in 1884 and there has been much debate since then over the term. A recent consensus of world experts agreed that PMP should be thought of as a clinical entity characterised by the presence of mucinous ascites, omental cake, peritoneal implants and possibly ovarian involvement. It generally originates from mucinous appendiceal tumours. Content: This review details the clinical presentation of this unusual condition, presents the new classification system and how this relates to outcome. The pathophysiology of this disease is also explored with a special reference to the relationship of the disease to tumour markers. Summary: A classification system has been agreed upon by the leading experts in PMP which is now divided into low and high grade mucinous carcinomatosis peritonei. This distinction correlates with clinical outcome as does the presence of raised tumour markers preoperatively. Outlook: Research needs to be focused on understanding the factors associated with poor prognosis through well designed multi-centred prospective studies. This will allow us to identify patients with bad tumour biology so that targeted treatment based on likely prognosis may then become a reality.
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Affiliation(s)
- Mark Bignell
- Peritoneal Malignancy Institute, Basingstoke, United Kingdom of Great Britain and Northern Ireland
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Affiliation(s)
- Dario Baratti
- Department of Surgical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Shigeki Kusamura
- Department of Surgical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Claudia Maggi
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Filippo de Braud
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Marcello Deraco
- Department of Surgical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Maria Di Bartolomeo
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Filippo Pietrantonio
- Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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Amini A, Masoumi-Moghaddam S, Morris DL. Pseudomyxoma peritonei: current chemotherapy and the need for mucin-directed strategies. Expert Opin Orphan Drugs 2015; 3:183-193. [DOI: 10.1517/21678707.2015.1006627] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
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Amini A, Masoumi-Moghaddam S, Ehteda A, Morris DL. Secreted mucins in pseudomyxoma peritonei: pathophysiological significance and potential therapeutic prospects. Orphanet J Rare Dis 2014; 9:71. [PMID: 24886459 PMCID: PMC4013295 DOI: 10.1186/1750-1172-9-71] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2014] [Accepted: 04/22/2014] [Indexed: 12/22/2022] Open
Abstract
Pseudomyxoma peritonei (PMP, ORPHA26790) is a clinical syndrome characterized by progressive dissemination of mucinous tumors and mucinous ascites in the abdomen and pelvis. PMP is a rare disease with an estimated incidence of 1-2 out of a million. Clinically, PMP usually presents with a variety of unspecific signs and symptoms, including abdominal pain and distention, ascites or even bowel obstruction. It is also diagnosed incidentally at surgical or non-surgical investigations of the abdominopelvic viscera. PMP is a neoplastic disease originating from a primary mucinous tumor of the appendix with a distinctive pattern of the peritoneal spread. Computed tomography and histopathology are the most reliable diagnostic modalities. The differential diagnosis of the disease includes secondary peritoneal carcinomatoses and some rare peritoneal conditions. Optimal elimination of mucin and the mucin-secreting tumor comprises the current standard of care for PMP offered in specialized centers as visceral resections and peritonectomy combined with intraperitoneal chemotherapy. This multidisciplinary approach has reportedly provided a median survival rate of 16.3 years, a median progression-free survival rate of 8.2 years and 10- and 15-year survival rates of 63% and 59%, respectively. Despite its indolent, bland nature as a neoplasm, PMP is a debilitating condition that severely impacts quality of life. It tends to be diagnosed at advanced stages and frequently recurs after treatment. Being ignored in research, however, PMP remains a challenging, enigmatic entity. Clinicopathological features of the PMP syndrome and its morbid complications closely correspond with the multifocal distribution of the secreted mucin collections and mucin-secreting implants. Novel strategies are thus required to facilitate macroscopic, as well as microscopic, elimination of mucin and its source as the key components of the disease. In this regard, MUC2, MUC5AC and MUC5B have been found as the secreted mucins of relevance in PMP. Development of mucin-targeted therapies could be a promising avenue for future research which is addressed in this article.
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Affiliation(s)
- Afshin Amini
- Department of Surgery, St George Hospital, The University of New South Wales, Level 3, Clinical Sciences (WR Pitney) Building, Gray Street, Kogarah, Sydney, NSW 2217, Australia
| | - Samar Masoumi-Moghaddam
- Department of Surgery, St George Hospital, The University of New South Wales, Level 3, Clinical Sciences (WR Pitney) Building, Gray Street, Kogarah, Sydney, NSW 2217, Australia
| | - Anahid Ehteda
- Department of Surgery, St George Hospital, The University of New South Wales, Level 3, Clinical Sciences (WR Pitney) Building, Gray Street, Kogarah, Sydney, NSW 2217, Australia
| | - David Lawson Morris
- Department of Surgery, St George Hospital, The University of New South Wales, Level 3, Clinical Sciences (WR Pitney) Building, Gray Street, Kogarah, Sydney, NSW 2217, Australia
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Kusamura S, Hutanu I, Baratti D, Deraco M. Circulating tumor markers: predictors of incomplete cytoreduction and powerful determinants of outcome in pseudomyxoma peritonei. J Surg Oncol 2013; 108:1-8. [PMID: 23720095 DOI: 10.1002/jso.23329] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2012] [Accepted: 02/05/2013] [Indexed: 12/13/2022]
Abstract
BACKGROUND Incomplete cytoreduction (IC) is one of the main prognostic factor in pseudomyxoma peritonei (PMP). We evaluated the ability of preoperative Ca125, CEA, and Ca19-9 to predict IC and prognosis in PMP. METHODS One hundred fifty-six cases elected candidate to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy from 1996 to 2011 were included in the study. We assessed the: (1) optimal cut-off values for circulating Tumor markers (CTM) in predicting IC (residual disease >2.5 mm) using receiver-operating characteristics (ROC); (2) discriminant power of CTM and risk prediction models for IC by calculating the area under ROC curve (AUC-ROC); (3) prognostic factors using Cox proportional-hazard model. RESULTS Optimal cut-offs were 125 U/ml for Ca125, 18 ng/ml for CEA, and 89 U/ml for Ca19-9. The AUCs-ROC were 0.76, 0.68, and 0.69 for Ca125, CEA, and Ca19-9, respectively. The addition of CTM to risk prediction model that considered preoperative clinicopathological factors increased marginally the AUC-ROC (0.80-0.84). Ca125 > 125 U/ml, Ca19-9 > 89 U/ml independently affected overall survival. CONCLUSIONS Preoperative CTMs were reasonable but not perfect discriminators of IC. Moreover, Ca125 and Ca19-9, using new cut-off values, were proven to be new strong prognostic factors that overcome the value of disease extension and histological subtype.
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Affiliation(s)
- Shigeki Kusamura
- Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumouri Milano, Milan, Italy
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Vlaeminck-Guillem V, Bienvenu J, Isaac S, Grangier B, Golfier F, Passot G, Bakrin N, Rodriguez-Lafrasse C, Gilly FN, Glehen O. Intraperitoneal cytokine level in patients with peritoneal surface malignancies. A study of the RENAPE (French Network for Rare Peritoneal Malignancies). Ann Surg Oncol 2013; 20:2655-62. [PMID: 23519518 DOI: 10.1245/s10434-013-2933-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2012] [Indexed: 12/11/2022]
Abstract
BACKGROUND Prognosis of peritoneal surface malignancies is influenced by the adequacy of surgical and chemotherapeutic treatment and by tumor spread at the time of diagnosis. By promoting morphological changes in the mesothelium, inflammatory cytokines reflect tumor biology and could be evaluated as biomarkers. Our objective was to evaluate intraperitoneal levels of IL-6, IL-8, IL-10, TNF-alpha, and sICAM in patients with pseudomyxoma peritonei and peritoneal mesothelioma. METHODS Serum and peritoneal fluid samples were prospectively collected in patients managed for peritoneal surface malignancies including pseudomyxoma peritonei (PMP), mesotheliomas, and other rare primitive peritoneal cancers (cancer group) and patients who underwent intraperitoneal laparoscopic surgical procedures for benign diseases (noncancer group). Samples were analyzed for IL-6, IL-8, IL-10, TNF-alpha, and sICAM concentrations. Correlations were assessed with tumor spread related clinical scores. RESULTS In both patient groups, intraperitoneal cytokine levels were higher than serum levels. Cancer patients had significantly higher intraperitoneal cytokine levels than noncancer patients. Peritoneal levels tended to increase in cancer patients with free tumor cells in peritoneal fluid. They were significantly higher in patients with tumor implants ≥2 cm and/or patients with peritoneal carcinomatosis index (PCI) >19. Furthermore, patients with malignant pseudomyxoma peritonei (grades II and III) had higher levels than patients with nonmalignant disease (grade I). CONCLUSIONS Assessment of intraperitoneal IL-6, IL-8, IL-10, TNF-alpha, and sICAM levels can be performed in patients with peritoneal surface malignancies. They can be considered as both diagnostic and prognostic biomarkers that could be used as useful adjuncts for therapeutic decision making.
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Affiliation(s)
- Virginie Vlaeminck-Guillem
- Molecular Oncology and Transfer Unit, Department of Biochemistry, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon, France.
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Guo AT, Li YM, Wei LX. Pseudomyxoma peritonei of 92 Chinese patients: Clinical characteristics, pathological classification and prognostic factors. World J Gastroenterol 2012; 18:3081-8. [PMID: 22791943 PMCID: PMC3386321 DOI: 10.3748/wjg.v18.i24.3081] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2011] [Revised: 04/16/2012] [Accepted: 05/26/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the clinicopathologic features and its relationship with prognosis of pseudomyxoma peritonei (PMP) in Chinese patients.
METHODS: The clinicopathologic features and follow-up data of 92 patients with PMP were reviewed and retrospectively analyzed. The cases were categorized into three groups: disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and peritoneal mucinous carcinomatosis with intermediate or discordant features (PMCA-I/D). The log-rank test was used to analyze survival for each group and various clinicopathological parameters. Multivariate Cox proportional-hazard models were constructed to determine the important factors associated with survival.
RESULTS: The median age at diagnosis was 51.9 years (range: 22-76 years). The median follow up was 124 mo. The 3-, 5- and 10-year survival rates were 74.0%, 67.4% and 49.1%, respectively. There were 49 (53.2%) patients with DPAM, 26 (28.3%) with PMCA-I and 17 (18.5%) with PMCA. Patients with DPAM, PMCA-I/D and PMCA exhibited statistically significant difference in survival (P = 0.001). The 3 year survival for DPAM, PMCAI/D and PMCA was 97.0%, 80.0% and 67.0%, respectively; the 5 year survival was 80.0%, 67.0% and 50.0%, respectively; and the 10 year survival was 65.0%, 28.0% and 14.0%, respectively. Survival rate was significantly lowest in patients < 40 age years of age (P = 0.011). Appendiceal tumor and extra-ovarian parenchymal organ involvement were significantly related to overall survival. Patients with appendiceal mucinous adenocarcinoma (MACA) showed the significantly poorer prognosis (P = 0.011). Multivariate analysis showed that pathological classification, age, appendiceal tumor were significant related to overall survival.
CONCLUSION: The clinical process “PMP” should be pathologically classified into DPAM, PMCA and PMCA-I/D. Pathological classification, age, appendiceal MACA are survival independent predictors in Chinese patients with PMP.
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Levine EA, Blazer DG, Kim MK, Shen P, Stewart JH, Guy C, Hsu DS. Gene expression profiling of peritoneal metastases from appendiceal and colon cancer demonstrates unique biologic signatures and predicts patient outcomes. J Am Coll Surg 2012; 214:599-606; discussion 606-7. [PMID: 22342786 DOI: 10.1016/j.jamcollsurg.2011.12.028] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2011] [Accepted: 12/15/2011] [Indexed: 01/31/2023]
Abstract
BACKGROUND Treatment of peritoneal metastases from appendiceal and colon cancer with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) shows great promise. Although long-term disease-free survival is achieved in some cases with this procedure, many patients have recurrence. Oncologists have treated such recurrences of appendiceal cancer similarly to colorectal carcinoma, which has been largely ineffective. This study uses gene expression analysis of peritoneal metastases to better understand these neoplasms. STUDY DESIGN From a prospectively maintained database and tissue bank, 41 snap frozen samples of peritoneal metastases (26 appendiceal, 15 colorectal) from patients undergoing HIPEC with complete cytoreduction and more than 3 years of follow-up underwent global gene expression analysis. Distinct phenotypes were identified using unsupervised hierarchical clustering based on differential gene expression. Survival curves restratified by genotype were generated. RESULTS Three distinct phenotypes were found, 2 consisting of predominantly low grade appendiceal samples (10 of 13 in Cluster 1 and 15 of 20 in Cluster 2) and 1 consisting of predominantly colorectal samples (7 of 8 in Cluster 3). Cluster 1 consisted of patients with good prognosis and Clusters 2 and 3 consisted of patients with poor prognosis (p = 0.006). Signatures predicted survival of low- (Cluster 1) vs high-risk (Cluster 2) appendiceal (p = 0.04) and low-risk appendiceal (Cluster 1) vs colon primary (Cluster 3) (p = 0.0002). CONCLUSIONS This study represents the first use of gene expression profiling for appendiceal cancer, and demonstrates genomic signatures quite distinct from colorectal cancer, confirming their unique biology. Consequently, therapy for appendiceal lesions extrapolated from colonic cancer regimens may be unfounded. These phenotypes may predict outcomes guiding patient management.
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Affiliation(s)
- Edward A Levine
- Surgical Oncology Service, Department of General Surgery, Wake Forest University, Winston-Salem, NC 27157, USA.
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Tanaka H, Kobayashi T, Yoshida K, Asakura T, Taniguchi H, Mikami Y. Low-grade appendiceal mucinous neoplasm with disseminated peritoneal adenomucinosis involving the uterus, mimicking primary mucinous endometrial adenocarcinoma: a case report. J Obstet Gynaecol Res 2011; 37:1726-30. [PMID: 21733040 DOI: 10.1111/j.1447-0756.2011.01585.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
We present a patient with a low-grade appendiceal mucinous neoplasm, resulting in disseminated peritoneal adenomucinosis (pseudomyxoma peritonei) with uterine involvement, and mimicking primary mucinous endometrial adenocarcinoma. On immunohistochemistry, neoplastic glands were cytokeratin 7-negative and cytokeratin 20-positive, indicating a gastrointestinal origin rather than a primary ovarian mucinous neoplasm. A diagnosis of uterine metastasis of appendiceal origin was made, based on the constellation of clinicopathological findings, that is, preceding appendiceal neoplasm, peritoneal involvement, absence of coexisting prototypical endometrioid adenocarcinoma or endometrial hyperplasia. The patient underwent hysterectomy and there was no evidence of disease progression at the 12-month follow up. This suggested the indolent nature of this particular neoplasm, despite its advanced stage.
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Affiliation(s)
- Hirohiko Tanaka
- Department of Obstetrics and Gynecology, Mie Prefectural General Medical Center, Yokkaichi, Mie, Japan.
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Bevan KE, Mohamed F, Moran BJ. Pseudomyxoma peritonei. World J Gastrointest Oncol 2010; 2:44-50. [PMID: 21160816 PMCID: PMC2999154 DOI: 10.4251/wjgo.v2.i1.44] [Citation(s) in RCA: 83] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2009] [Revised: 12/24/2009] [Accepted: 12/31/2009] [Indexed: 02/05/2023] Open
Abstract
Pseudomyxoma peritonei (PMP) is an uncommon “borderline malignancy” generally arising from a perforated appendiceal epithelial tumour. Optimal treatment involves a combination of cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC). Controversy persists regarding the pathological classification and its prognostic value. Computed tomography scanning is the optimal preoperative staging technique. Tumour marker elevations correlate with worse prognosis and increased recurrence rates. Following CRS with HIPEC, 5-year survival ranges from 62.5% to 100% for low grade, and 0%-65% for high grade disease. Treatment related morbidity and mortality ranges from 12 to 67.6%, and 0 to 9%, respectively. Surgery and HIPEC are the optimal treatment for PMP which is at best a “borderline” peritoneal malignancy.
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Affiliation(s)
- Katharine E Bevan
- Katharine E Bevan, Faheez Mohamed, Brendan J Moran, Pseudomyxoma Peritonei Centre, Basingstoke and North Hampshire Hospital Foundation Trust, Aldermaston Road, Basingstoke, Hampshire RG24 9NA, United Kingdom
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Stewart JH, Levine EA, Shen P. The Current Role of Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Dissemination of Appendiceal Tumors. Curr Probl Cancer 2009; 33:142-53. [DOI: 10.1016/j.currproblcancer.2009.06.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Appendiceal Epithelial Neoplasms and Pseudomyxoma Peritonei, A Distinct Clinical Entity With Distinct Treatments. POLISH JOURNAL OF SURGERY 2007. [DOI: 10.2478/v10035-007-0097-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Murphy EM, Sexton R, Moran BJ. Early results of surgery in 123 patients with pseudomyxoma peritonei from a perforated appendiceal neoplasm. Dis Colon Rectum 2007; 50:37-42. [PMID: 17115339 DOI: 10.1007/s10350-006-0741-9] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE Epithelial appendiceal tumors are uncommon but can present as an emergency simulating appendicitis, or unexpectedly at laparotomy, laparoscopy, or on cross-sectional imaging. Occult rupture with features of pseudomyxoma peritonei may be encountered. We report the operative findings, pathologic assessment, and early outcomes in 123 consecutive patients with a perforated appendiceal neoplasm presenting as pseudomyxoma peritonei. METHODS From March 1994 to March 2004, 292 patients were referred to a peritoneal malignancy surgical treatment center. Complete tumor removal (cytoreduction) was attempted in selected patients and, if achieved, surgery was combined with intraoperative, intraperitoneal mitomycin C (10 mg/m(2)). RESULTS In total, 123 patients (52 males; 41 percent) underwent laparotomy for a perforated appendiceal malignancy presenting as pseudomyxoma peritonei. The median age was 52 (range 30-77) years. Complete cytoreduction was achieved in 83 of 123 patients (67 percent), major palliative resection in 34 patients (28 percent), and 6 patients (5 percent) were inoperable. Postoperative mortality was 6 of 123 patients (5 percent). Kaplan-Meier analysis of the 83 patients who had complete tumor removal predicted 75 percent disease-free survival at five years. CONCLUSIONS A perforated appendiceal epithelial tumor most frequently presents as pseudomyxoma peritonei. This treatment strategy, involving surgery and intraperitoneal chemotherapy, can result in good outcomes in this rare and otherwise fatal disease.
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Affiliation(s)
- Elizabeth M Murphy
- Pseudomyxoma Peritonei Centre, Colorectal Research Unit, North Hampshire Hospital, Basingstoke, Hampshire, United Kingdom
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Yan TD, Black D, Savady R, Sugarbaker PH. A systematic review on the efficacy of cytoreductive surgery and perioperative intraperitoneal chemotherapy for pseudomyxoma peritonei. Ann Surg Oncol 2006; 14:484-92. [PMID: 17054002 DOI: 10.1245/s10434-006-9182-x] [Citation(s) in RCA: 224] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2006] [Revised: 06/10/2006] [Accepted: 06/14/2006] [Indexed: 12/17/2022]
Abstract
BACKGROUND The efficacy of cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) for patients with pseudomyxoma peritonei (PMP) remains to be established. METHODS Searches for all relevant studies prior to March 2006 were performed on six databases. Two reviewers independently appraised each study using a predetermined protocol. The quality of each study was assessed. Clinical effectiveness was synthesized through a narrative review with full tabulation of results of all included studies. RESULTS Ten most recent updates from each institution were included for appraisal and data extraction. There were no randomized controlled trials or comparative studies. All included articles were observational studies without control groups. Five studies were relatively large series (n>or=100). Two studies had relatively long-term follow-up (48 months and 52 months). The median follow-up in the remaining eight studies was shorter than 3 years (range 19-35 months). The median survival ranged from 51 to 156 months. The 1-, 2-, 3- and 5-year survival rates varied from 80 to 100%, 76 to 96%, 59 to 96% and 52 to 96%, respectively. The overall morbidity rate varied from 33 to 56%. The overall mortality rates ranged from 0 to 18%. CONCLUSIONS This study reviewed current evidence on CRS and PIC for PMP. Only observational studies were available for evaluation, which demonstrated some promising long-term results, as compared to historical controls. Due to the rarity of this disease, a well-designed prospective multi-institutional study would be meaningful.
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Affiliation(s)
- Tristan D Yan
- Peritoneal Surface Malignancy Program, Washington Cancer Institute, Washington Hospital Center, 106 Irving Street, NW, Suite 3900N, Washington, DC 20010, USA
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Bibi R, Pranesh N, Saunders MP, Wilson MS, O'Dwyer ST, Stern PL, Renehan AG. A specific cadherin phenotype may characterise the disseminating yet non-metastatic behaviour of pseudomyxoma peritonei. Br J Cancer 2006; 95:1258-64. [PMID: 17031402 PMCID: PMC2360585 DOI: 10.1038/sj.bjc.6603398] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Pseudomyxoma peritonei (PMP) is a rare neoplasm of mainly appendiceal origin, characterised by excess intra-abdominal mucin production leading to high morbidity and mortality. While histological features are frequently indolent, this tumour disseminates aggressively throughout the abdominal cavity, yet seldom metastasises. This study determined the expression of several markers of colorectal differentiation (carcinoembryonic antigen (CEA), cytokeratins (CK20 and CK7), epithelial membrane antigen), mucin production (MUC-2, interleukin-9 (IL-9), IL-9 receptor (IL-9Rα)), and cell adhesion (N- and E-cadherin, vimentin) in PMP tissue (n=26) compared with expressions in normal colonic mucosa (n=19) and colorectal adenocarcinoma (n=26). Expressions of CEA and cytokeratins were similar for PMP as those in colorectal adenocarcinomas with the exception that the CK20−/CK7− pattern was rare in PMP (Fisher's exact test: P=0.001). Similarly, expressions of mucin-related proteins were comparable for adenocarcinoma and PMP, with the exception that IL-9 expression was uncommon in adenocarcinoma (P=0.009). Pseudomyxoma peritonei demonstrated a specific pattern of adhesion-related protein expressions of increased N-cadherin, reduced E-cadherin, and increased vimentin (P=0.004), a phenotype suggesting a possible epithelial–mesenchymal transition state. Primary PMP cell cultures were successfully maintained and demonstrated marker expressions similar to those seen in in vivo tissues. These early characterisation studies demonstrate similarities between PMP and colorectal adenocarcinoma, but also reveal a specific cadherin phenotype that may characterise the distinct non-metastasising behaviour of PMP, and form the basis for future mechanistic and therapy-targeting research.
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Affiliation(s)
- R Bibi
- Cancer Research UK Immunology Group, Paterson Institute for Cancer Research, Manchester, UK
| | - N Pranesh
- Cancer Research UK Immunology Group, Paterson Institute for Cancer Research, Manchester, UK
- Department of Surgery, Christie Hospital NHS Trust, Manchester, UK
| | - M P Saunders
- Department of Clinical Oncology, Christie Hospital NHS Trust, Manchester, UK
| | - M S Wilson
- Department of Surgery, Christie Hospital NHS Trust, Manchester, UK
| | - S T O'Dwyer
- Department of Surgery, Christie Hospital NHS Trust, Manchester, UK
| | - P L Stern
- Cancer Research UK Immunology Group, Paterson Institute for Cancer Research, Manchester, UK
| | - A G Renehan
- Department of Surgery, Christie Hospital NHS Trust, Manchester, UK
- Department of Surgery, Christie Hospital NHS Trust, Wilmslow Road, Manchester
M20 4BX, UK; E-mail:
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Maheshwari V, Tsung A, Lin Y, Zeh HJ, Finkelstein SD, Bartlett DL. Analysis of loss of heterozygosity for tumor-suppressor genes can accurately classify and predict the clinical behavior of mucinous tumors arising from the appendix. Ann Surg Oncol 2006; 13:1610-6. [PMID: 17009159 DOI: 10.1245/s10434-006-9081-1] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2006] [Revised: 04/24/2006] [Accepted: 05/10/2006] [Indexed: 12/31/2022]
Abstract
BACKGROUND Pseudomyxoma peritonei is a rare heterogenous clinical syndrome with a variable clinical course. On the basis of the hypothesis that cumulative mutational damage can predict biological aggressiveness, we evaluated the utility of integrated histopathology and molecular analysis for patients with pseudomyxoma peritonei syndrome. METHODS Tissue specimens from 23 mucinous appendiceal tumors were analyzed. DNA samples from multiple sites were analyzed for loss of heterozygosity by using a panel of 15 allelic loss microsatellite markers and K-ras-2 point mutational damage. The fractional mutational rate (FMR), determined as the number of mutated markers divided by the total number of informative markers, was calculated by using the six most informative markers and the K-ras-2 gene. Kappa statistics were calculated to test the association between FMR and the histopathologic classification. RESULTS Our study included 6 female and 17 male patients with a mean age of 53.6 years and a mean survival of 43.9 months. We found an association between tumor loss of heterozygosity markers and histopathologic classification (P < .05). In addition, there was also an association between the FMR and pathological classification as well as between the FMR and survival (P < .05). An FMR less than .25 indicated low-grade disease, an FMR of .25 to .50 indicated intermediate grade, and an FMR greater than .5 indicated a high-grade tumor. CONCLUSIONS Mutational profiling of accumulated allelic loss and point mutational damage correlated strongly with histopathologic definitions of pseudomyxoma peritonei disease and helped to predict the prognosis of these patients. FMR, along with histopathology, offers a comprehensive classification of these rare tumors.
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Affiliation(s)
- Vivek Maheshwari
- Department of Surgery, Division of Surgical Oncology, UPMC Cancer Pavillion, 5150 Centre Avenue, Room 415, Pittsburgh, Pennsylvania 15232, USA
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Sugarbaker PH. The natural history, gross pathology, and histopathology of appendiceal epithelial neoplasms. Eur J Surg Oncol 2006; 32:644-7. [PMID: 16621426 DOI: 10.1016/j.ejso.2006.03.016] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2005] [Accepted: 03/02/2006] [Indexed: 10/24/2022] Open
Abstract
AIM To report the pathology of appendiceal epithelial neoplasms a review of the Washington Cancer Institute experience and a PubMed literature search was performed. FINDINGS Epithelial appendiceal neoplasms present a significant oncologic challenge. The clinical and pathologic features are unusually varied as compared to other gastrointestinal cancers and require expert clinical judgment for proper management. CONCLUSIONS Appendiceal epithelial neoplasms should be regarded as a distinct clinical entity with special clinical treatments used for optimal management.
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Affiliation(s)
- P H Sugarbaker
- Washington Cancer Institute, 106 Irving Street, NW, Suite 3900, Washington, DC 20010, USA.
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Stewart JH, Shen P, Russell GB, Bradley RF, Hundley JC, Loggie BL, Geisinger KR, Levine EA. Appendiceal neoplasms with peritoneal dissemination: outcomes after cytoreductive surgery and intraperitoneal hyperthermic chemotherapy. Ann Surg Oncol 2006; 13:624-34. [PMID: 16538401 DOI: 10.1007/s10434-006-9708-2] [Citation(s) in RCA: 118] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2005] [Accepted: 08/16/2005] [Indexed: 12/12/2022]
Abstract
BACKGROUND Appendiceal neoplasms frequently present with peritoneal dissemination (PD) and have a clinical course marked by bowel obstruction and subsequent death. Few data have correlated outcome with appendiceal histology after cytoreductive surgery and intraperitoneal hyperthermic chemotherapy (IPHC). We have reviewed our experience with cytoreductive surgery and IPHC for PD from the appendix. METHODS A total of 110 cases of PD from proven appendiceal neoplasms treated with IPHC were identified from a prospectively managed database. Tumor samples were classified on pathologic review as disseminated peritoneal adenomucinosis (n = 55), peritoneal mucinous carcinomatosis (PMCA) with intermediate features (n = 18), PMCA (n = 29), or high-grade nonmucinous lesions (n = 8). A retrospective review was performed with long-term survival as the primary outcome measure. RESULTS A total of 116 IPHCs were performed on 110 patients for appendiceal PD between 1993 and 2004. The 1-, 3-, and 5-year survival rates for all cases were 79.9% +/- 4.1%, 59.0% +/- 5.7%, and 53.4% +/- 6.5%, respectively. When stratified by histology, disseminated peritoneal adenomucinosis and intermediate tumors had better 3-year survival rates (77% +/- 7% and 81% +/- 10%) than PMCA and high-grade nonmucinous lesions (35% +/- 10% and 15% +/- 14%; P = .0032 for test of differences between groups). Age at presentation (P = .0134), performance status (P < .0001), time between diagnosis and IPHC (P = .0011), resection status (P = .0044), and length of hyperthermic chemoperfusion (P = .0193) were independently associated with survival. CONCLUSIONS The data show that long-term survival is anticipated in most patients who are treated with cytoreduction and IPHC for appendiceal PD. The findings presented herein underscore the important prognostic characteristics that predict outcome after IPHC in patients with PD. In all, this work establishes a framework for the consideration of IPHC in future trials for appendiceal PD.
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Affiliation(s)
- John H Stewart
- Department of General Surgery, Surgical Oncology Service, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA
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