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Taniguchi SH, Takahashi M, Chiu SW, Komine K, Wakayama S, Numakura R, Yoshida Y, Kasahara Y, Ouchi K, Imai H, Saijo K, Shirota H, Ishioka C. Impact of genetic mutations on prognosis and chemotherapy efficacy in advanced appendiceal carcinoma: insights from the nationwide Japanese comprehensive genomic profiling test database. Int J Clin Oncol 2025; 30:914-925. [PMID: 40019690 PMCID: PMC12014699 DOI: 10.1007/s10147-025-02724-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Accepted: 02/04/2025] [Indexed: 03/01/2025]
Abstract
BACKGROUND Appendiceal carcinoma (AC) is a rare malignancy and has distinct genomic features, but their impact on prognosis and chemotherapy efficacy requires further investigation. METHODS This retrospective study analyzed patients with advanced AC from the Japanese nationwide comprehensive genomic profiling test database, the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) database, focusing on genetic alterations and their associations with clinical outcomes. RESULTS Of the 314 patients, the histological types Queryincluded adenocarcinoma (Ad) (51.9%), mucinous adenocarcinoma (MAd) (30.3%), goblet cell adenocarcinoma (12.4%), and signet-ring cell adenocarcinoma (5.4%). The most common mutations were KRAS (52.5%), TP53 (49.4%), SMAD4 (18.8%), and GNAS (17.2%). KRAS mutations were most frequent in MAd (68.4%) and Ad (58.9%), whereas TP53 mutations were mostly prevalent in Ad (62.6%). We classified patients into molecular subtypes based on the presence of mutations and analyzed differences in overall survival (OS) by molecular subtype. Patients with TP53-mutant (mut) dominant tumors (all TP53-mut) and KRAS-mut focused tumors (TP53-wild-type (wt)/GNAS-wt/KRAS-mut/any SMAD4) showed a poorer median OS compared with those with GNAS-mut focused tumors (TP53-wt/GNAS-mut/any KRAS /any SMAD4) (median 47.4 and 37.5 months vs. not reached; p = 0.01 and p = 0.01, respectively). TP53 mutation was associated with poor time to treatment failure and OS with the oxaliplatin-based regimen for first-line chemotherapy. CONCLUSIONS This study suggested that the genetic mutations influenced the prognosis and chemotherapy efficacy in AC.
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Affiliation(s)
- Sakura Hiraide Taniguchi
- Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan
- Department of Clinical Oncology, Tohoku University Graduate School of Medicine, 4-1, Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan
| | - Masanobu Takahashi
- Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan.
- Department of Clinical Oncology, Tohoku University Graduate School of Medicine, 4-1, Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan.
| | - Shih-Wei Chiu
- Clinical Research Data Center, Tohoku University Hospital, Sendai, Japan
| | - Keigo Komine
- Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan
- Department of Clinical Oncology, Tohoku University Graduate School of Medicine, 4-1, Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan
| | - Shonosuke Wakayama
- Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan
- Department of Clinical Oncology, Tohoku University Graduate School of Medicine, 4-1, Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan
| | - Ryunosuke Numakura
- Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan
- Department of Clinical Oncology, Tohoku University Graduate School of Medicine, 4-1, Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan
| | - Yuya Yoshida
- Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan
- Department of Clinical Oncology, Tohoku University Graduate School of Medicine, 4-1, Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan
| | - Yuki Kasahara
- Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan
- Department of Clinical Oncology, Tohoku University Graduate School of Medicine, 4-1, Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan
| | - Kota Ouchi
- Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan
- Department of Clinical Oncology, Tohoku University Graduate School of Medicine, 4-1, Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan
| | - Hiroo Imai
- Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan
- Department of Clinical Oncology, Tohoku University Graduate School of Medicine, 4-1, Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan
| | - Ken Saijo
- Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan
- Department of Clinical Oncology, Tohoku University Graduate School of Medicine, 4-1, Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan
| | - Hidekazu Shirota
- Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan
- Department of Clinical Oncology, Tohoku University Graduate School of Medicine, 4-1, Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan
| | - Chikashi Ishioka
- Department of Medical Oncology, Tohoku University Hospital, Sendai, Japan
- Department of Clinical Oncology, Tohoku University Graduate School of Medicine, 4-1, Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980-8575, Japan
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Tang XW, Zhou Y. Signet ring cell carcinoma of the appendix and terminal ileum: A case report. World J Gastrointest Oncol 2025; 17:100526. [PMID: 40235885 PMCID: PMC11995356 DOI: 10.4251/wjgo.v17.i4.100526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 12/16/2024] [Accepted: 01/23/2025] [Indexed: 03/25/2025] Open
Abstract
BACKGROUND Appendiceal signet-ring cell carcinoma (SRCC) with terminal ileum metastasis is extremely rare. There have been no reported cases in domestic and foreign literature. CASE SUMMARY In this case report, we present an 88-year-old man with appendiceal SRCC with terminal ileum metastasis. The tumour stage was stage pT4bN2M1bG3 IVB, and the Tumour, Node, Metastasis staging system was used. The patient was admitted to our hospital on 12 July, 2022 and underwent laparoscopic appendectomy under general anaesthesia after the examination. The pathological examination that took place 1 week after the operation showed that SRCC of the appendix invaded the whole layer, vessels and nerves of the appendix wall. It was suggested that the primary appendix should be considered after excluding metastasis. Based on the postoperative pathology findings, the patient underwent a secondary surgery on 2 August, 2022. The second pathological examination showed residual SRCC in the appendiceal area of the ileocecal region, which infiltrated the serosal fibres and adipose tissue of the ileocecal region to the surface mesothelium. The tumour infiltrated the whole layer of the ileum wall, serosa fibres, adipose tissue and the surface mesothelium. Postoperative follow-up showed no signs of tumour recurrence or metastasis. CONCLUSION In clinical practice, a heightened awareness of rare diseases, coupled with thorough intraoperative exploration and rapid pathological examination, enables more accurate judgments, potentially sparing patients from unnecessary secondary surgery and ensuring optimal treatment.
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Affiliation(s)
- Xiao-Wen Tang
- Department of General Surgery, Jiading Hospital of Traditional Chinese Medicine, Shanghai 201800, China
| | - Yong Zhou
- Department of General Surgery, Jiading Hospital of Traditional Chinese Medicine, Shanghai 201800, China
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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.
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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
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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.
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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
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Hornstein NJ, Zeineddine MA, Gunes BB, Pellatt AJ, Knafl M, Zhu H, Willett AF, Yousef A, Liu S, Sun R, Futreal A, Woodman SE, Taggart MW, Overman MJ, Halperin DM, Raghav KP, Shen JP. Efficacy and Safety of Atezolizumab and Bevacizumab in Appendiceal Adenocarcinoma. CANCER RESEARCH COMMUNICATIONS 2024; 4:1363-1368. [PMID: 38709066 PMCID: PMC11135244 DOI: 10.1158/2767-9764.crc-24-0019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 03/27/2024] [Accepted: 04/30/2024] [Indexed: 05/07/2024]
Abstract
PURPOSE Appendiceal adenocarcinoma (AA) remains an orphan disease with limited treatment options for patients unable to undergo surgical resection. Evidence supporting the efficacy of combined VEGF and PD-1 inhibition in other tumor types provided a compelling rationale for investigating this combination in AA, where immune checkpoint inhibitors have not been explored previously. EXPERIMENTAL DESIGN We conducted a prospective, single-arm phase II study evaluating efficacy and safety of atezolizumab in conjunction with bevacizumab (Atezo+Bev) in advanced, unresectable AA. RESULTS Patients treated with the Atezo+Bev combination had 100% disease control rate (1 partial response, 15 stable disease) with progression-free survival (PFS) of 18.3 months and overall survival not-yet-reached with median duration of follow-up of 40 months. These survival intervals were significantly longer relative to a clinically and molecularly matched synthetic control cohort treated with cytotoxic chemotherapy designed for colorectal cancer (PFS of 4.4 months, P = 0.041). CONCLUSIONS In light of recent data demonstrating a lack of efficacy of 5-fluorouracil-based chemotherapy, Atezo+Bev is a promising treatment option for patients with low-grade unresectable AA; further study is warranted. SIGNIFICANCE AA remains an orphan disease with limited systemic therapy options for patients who are not candidates for surgical resection. These data suggest activity from combined VEGF and PD-L1 inhibition that warrants further study.
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Affiliation(s)
- Nicholas J. Hornstein
- Medical Oncology Fellowship, University of Texas MD Anderson Cancer Center, Houston, Texas
| | | | - Betul B. Gunes
- GI Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
- Faculty of Medicine, Biruni University, Zeytinburnu, Istanbul, Turkey
| | - Andrew J. Pellatt
- Medical Oncology Fellowship, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Mark Knafl
- Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Haifeng Zhu
- Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Anneleis F. Willett
- GI Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Abdelrahman Yousef
- GI Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Suyu Liu
- Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ryan Sun
- Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Andrew Futreal
- Genomic Medicine, University of Texas M. D. Anderson Cancer Center, Houston, Texas
| | - Scott E. Woodman
- Biostatistics, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Melissa W. Taggart
- Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Michael J. Overman
- GI Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Daniel M. Halperin
- GI Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Kanwal P. Raghav
- GI Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
| | - John Paul Shen
- GI Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas
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Li X, Liu G, Wu W. Progress in Biological Research and Treatment of Pseudomyxoma Peritonei. Cancers (Basel) 2024; 16:1406. [PMID: 38611084 PMCID: PMC11010892 DOI: 10.3390/cancers16071406] [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: 03/01/2024] [Revised: 03/28/2024] [Accepted: 03/30/2024] [Indexed: 04/14/2024] Open
Abstract
Pseudomyxoma peritonei (PMP) is a rare disease characterized by extensive peritoneal implantation and mass secretion of mucus after primary mucinous tumors of the appendix or other organ ruptures. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is currently the preferred treatment, with excellent efficacy and safety, and is associated with breakthrough progress in long-term disease control and prolonged survival. However, the high recurrence rate of PMP is the key challenge in its treatment, which limits the clinical application of multiple rounds of CRS-HIPEC and does not benefit from conventional systemic chemotherapy. Therefore, the development of alternative therapies for patients with refractory or relapsing PMP is critical. The literature related to PMP research progress and treatment was searched in the Web of Science, PubMed, and Google Scholar databases, and a literature review was conducted. The overview of the biological research, treatment status, potential therapeutic strategies, current research limitations, and future directions associated with PMP are presented, focuses on CRS-HIPEC therapy and alternative or combination therapy strategies, and emphasizes the clinical transformation prospects of potential therapeutic strategies such as mucolytic agents and targeted therapy. It provides a theoretical reference for the treatment of PMP and the main directions for future research.
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Affiliation(s)
- Xi Li
- Department of Geriatric Surgery, Xiangya Hospital, Central South University, Changsha 410008, China;
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Guodong Liu
- Department of Geriatric Surgery, Xiangya Hospital, Central South University, Changsha 410008, China;
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Wei Wu
- Department of Geriatric Surgery, Xiangya Hospital, Central South University, Changsha 410008, China;
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
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Bhutiani N, Grotz TE, Concors SJ, White MG, Helmink BA, Raghav KP, Taggart MW, Beaty KA, Royal RE, Overman MJ, Matamoros A, Scally CP, Rafeeq S, Mansfield PF, Fournier KF. Repeat Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Recurrent Mucinous Appendiceal Adenocarcinoma: A Viable Treatment Strategy with Demonstrable Benefit. Ann Surg Oncol 2024; 31:614-621. [PMID: 37872456 PMCID: PMC10695875 DOI: 10.1245/s10434-023-14422-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Accepted: 09/26/2023] [Indexed: 10/25/2023]
Abstract
INTRODUCTION Many patients with mucinous appendiceal adenocarcinoma experience peritoneal recurrence despite complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prior work has demonstrated that repeat CRS/HIPEC can prolong survival in select patients. We sought to validate these findings using outcomes from a high-volume center. PATIENTS AND METHODS Patients with mucinous appendiceal adenocarcinoma who underwent CRS/HIPEC at MD Anderson Cancer Center between 2004 and 2021 were stratified by whether they underwent CRS/HIPEC for recurrent disease or as part of initial treatment. Only patients who underwent complete CRS/HIPEC were included. Initial and recurrent groups were compared. RESULTS Of 437 CRS/HIPECs performed for mucinous appendiceal adenocarcinoma, 50 (11.4%) were for recurrent disease. Patients who underwent CRS/HIPEC for recurrent disease were more often treated with an oxaliplatin or cisplatin perfusion (35%/44% recurrent vs. 4%/1% initial, p < 0.001), had a longer operative time (median 629 min recurrent vs. 511 min initial, p = 0.002), and had a lower median length of stay (10 days repeat vs. 13 days initial, p < 0.001). Thirty-day complication and 90-day mortality rates did not differ between groups. Both cohorts enjoyed comparable recurrence free survival (p = 0.82). Compared with patients with recurrence treated with systemic chemotherapy alone, this select cohort of patients undergoing repeat CRS/HIPEC enjoyed better overall survival (p < 0.001). CONCLUSIONS In appropriately selected patients with recurrent appendiceal mucinous adenocarcinoma, CRS/HIPEC can provide survival benefit equivalent to primary CRS/HIPEC and that may be superior to that conferred by systemic therapy alone in select patients. These patients should receive care at a high-volume center in the context of a multidisciplinary team.
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Affiliation(s)
- Neal Bhutiani
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Travis E Grotz
- Division of Hepatobiliary and Pancreas Surgery, Department of Surgery, Mayo Clinic, Rochester, MN, USA
| | - Seth J Concors
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Michael G White
- Department of Colon and Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Beth A Helmink
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Kanwal P Raghav
- Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Melissa W Taggart
- Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Karen A Beaty
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Richard E Royal
- Division of Surgical Oncology, Department of Surgery, Maine Medical Center, Portland, ME, USA
| | - Michael J Overman
- Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Aurelio Matamoros
- Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Christopher P Scally
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Safia Rafeeq
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Paul F Mansfield
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Keith F Fournier
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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Zhang Y, Zhao X, Gao C, Lin LY, Li Y. Treatment outcome analysis of bevacizumab combined with cyclophosphamide and oxaliplatin in advanced pseudomyxoma peritonei. World J Gastrointest Surg 2023; 15:1149-1158. [PMID: 37405093 PMCID: PMC10315110 DOI: 10.4240/wjgs.v15.i6.1149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 03/18/2023] [Accepted: 04/14/2023] [Indexed: 06/15/2023] Open
Abstract
BACKGROUND Pseudomyxoma peritonei (PMP) is a rare peritoneal malignant tumor syndrome. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is its standard treatment. However, there are few studies and insufficient evidence regarding systemic chemotherapy of advanced PMP. Regimens for colorectal cancer are often used clinically, but there is no uniform standard for late-stage treatment.
AIM To determine if bevacizumab combined with cyclophosphamide and oxaliplatin (Bev+CTX+OXA) is effective for treatment of advanced PMP. The primary study endpoint was progression-free survival (PFS).
METHODS Retrospective analysis was conducted on the clinical data of patients with advanced PMP who received Bev+CTX+OXA regimen (bevacizumab 7.5 mg/kg ivgtt d1, oxaliplatin 130 mg/m2 ivgtt d1 and cyclophosphamide 500 mg/m2 ivgtt d1, q3w) in our center from December 2015 to December 2020. Objective response rate (ORR), disease control rate (DCR) and incidence of adverse events were evaluated. PFS was followed up. Kaplan-Meier method was used to draw survival curve, and log-rank test was used for comparison between groups. Multivariate Cox proportional hazards regression model was used to analyze the independent influencing factors of PFS.
RESULTS A total of 32 patients were enrolled. After 2 cycles, the ORR and DCR were 3.1% and 93.7%, respectively. The median follow-up time was 7.5 mo. During the follow-up period, 14 patients (43.8%) had disease progression, and the median PFS was 8.9 mo. Stratified analysis showed that the PFS of patients with a preoperative increase in CA125 (8.9 vs 2.1, P = 0.022) and a completeness of cytoreduction score of 2-3 (8.9 vs 5.0, P = 0.043) was significantly longer than that of the control group. Multivariate analysis showed that a preoperative increase in CA125 was an independent prognostic factor for PFS (HR = 0.245, 95%CI: 0.066-0.904, P = 0.035).
CONCLUSION Our retrospective assessment confirmed that the Bev+CTX+OXA regimen is effective in second- or posterior-line treatment of advanced PMP and that adverse reactions can be tolerated. A preoperative increase in CA125 is an independent prognostic factor of PFS.
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Affiliation(s)
- Ying Zhang
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
| | - Xin Zhao
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
| | - Chao Gao
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
| | - Lin-Yu Lin
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
| | - Yan Li
- Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
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Gül-Klein S, Arnold A, Oberender C, Kuzinska MZ, Alberto Vilchez ME, Mogl MT, Rau B. Appendixneoplasien. COLOPROCTOLOGY 2023. [DOI: 10.1007/s00053-023-00686-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/07/2023]
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10
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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.
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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
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11
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Banno F, Wiggins B, Knight KT, Peddi K, Alrammahi A, Landesman N. High-Grade Mucinous Adenocarcinoma of the Appendix With Signet Features and Omental Metastasis. Cureus 2022; 14:e31525. [DOI: 10.7759/cureus.31525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/14/2022] [Indexed: 11/16/2022] Open
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12
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Kepenekian V, Bhatt A, Péron J, Alyami M, Benzerdjeb N, Bakrin N, Falandry C, Passot G, Rousset P, Glehen O. Advances in the management of peritoneal malignancies. Nat Rev Clin Oncol 2022; 19:698-718. [PMID: 36071285 DOI: 10.1038/s41571-022-00675-5] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/29/2022] [Indexed: 11/09/2022]
Abstract
Peritoneal surface malignancies (PSMs) are usually associated with a poor prognosis. Nonetheless, in line with advances in the management of most abdominopelvic metastatic diseases, considerable progress has been made over the past decade. An improved understanding of disease biology has led to the more accurate prediction of neoplasia aggressiveness and the treatment response and has been reflected in the proposal of new classification systems. Achieving complete cytoreductive surgery remains the cornerstone of curative-intent treatment of PSMs. Alongside centralization in expert centres, enabling the delivery of multimodal and multidisciplinary strategies, preoperative management is a crucial step in order to select patients who are most likely to benefit from surgery. Depending on the specific PSM, the role of intraperitoneal chemotherapy and of perioperative systemic chemotherapy, in particular, in the neoadjuvant setting, is established in certain scenarios but questioned in several others, although more prospective data are required. In this Review, we describe advances in all aspects of the management of PSMs including disease biology, assessment and improvement of disease resectability, perioperative management, systemic therapy and pre-emptive management, and we speculate on future research directions.
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Affiliation(s)
- Vahan Kepenekian
- Surgical Oncology Department, Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France.,CICLY - EA3738, Université Claude Bernard Lyon I (UCBL1), Lyon, France
| | - Aditi Bhatt
- Department of Surgical Oncology, Zydus hospital, Ahmedabad, Gujarat, India
| | - Julien Péron
- Medical Oncology Department, Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France.,Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, UCBL1, Lyon, France
| | - Mohammad Alyami
- Department of General Surgery and Surgical Oncology, Oncology Center, King Khalid Hospital, Najran, Saudi Arabia
| | - Nazim Benzerdjeb
- CICLY - EA3738, Université Claude Bernard Lyon I (UCBL1), Lyon, France.,Department of Pathology, Institut de Pathologie Multisite, Hospices Civils de Lyon, UCBL1, Lyon, France
| | - Naoual Bakrin
- Surgical Oncology Department, Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France.,CICLY - EA3738, Université Claude Bernard Lyon I (UCBL1), Lyon, France
| | - Claire Falandry
- Department of Onco-Geriatry, Hôpital Lyon Sud, Hospices Civils de Lyon, Lyon, France
| | - Guillaume Passot
- Surgical Oncology Department, Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France.,CICLY - EA3738, Université Claude Bernard Lyon I (UCBL1), Lyon, France
| | - Pascal Rousset
- CICLY - EA3738, Université Claude Bernard Lyon I (UCBL1), Lyon, France.,Department of Radiology, Hôpital Lyon Sud, Hospices Civils de Lyon, UCBL1, Lyon, France
| | - Olivier Glehen
- Surgical Oncology Department, Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre Bénite, France. .,CICLY - EA3738, Université Claude Bernard Lyon I (UCBL1), Lyon, France.
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13
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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.
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Affiliation(s)
| | | | | | - Kate Mahon
- Chris O'Brien Lifehouse, 119-144 Missenden Road, Camperdown, NSW 2050, Australia
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14
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Wang Y, Geng Y, Hu W. Survival and prognostic factors for postoperative primary appendiceal cancer: a retrospective cohort study based on the Surveillance, Epidemiology, and End Results database. J Gastrointest Oncol 2022; 13:1433-1443. [PMID: 35837159 PMCID: PMC9274075 DOI: 10.21037/jgo-22-454] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Accepted: 06/14/2022] [Indexed: 12/21/2024] Open
Abstract
BACKGROUND The factors affecting the postoperative survival of patients with primary appendiceal cancer (PAC) have yet to be fully explored. And there are no clear guidelines for adjuvant treatment after appendectomy. Whether chemotherapy can prolong patient survival after appendectomy, is critical in guiding postoperative medications. The majority of studies on appendiceal cancer are single case reports, and they focused on the incidence of appendiceal cancer. The present study aimed to investigate the survival characteristics of patients with primary appendiceal cancer after surgery using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS The data of 2,891 cases of primary appendiceal cancer between 2004 to 2015 were obtained from the SEER database and subjected to survival analysis using the Kaplan-Meier method and Cox proportional-hazards model. The annual percentage change (APC) was calculated using the weighted least squares method. RESULTS The overall age-adjusted incidence rate per 100,000 population steadily increased from 0.58 in 2004 to 1.63 in 2015. For patients who received chemotherapy, the median overall survival (OS) was 65 months and the 5-year OS rate was 51.9%, and for patients who did not receive chemotherapy or whose chemotherapy status was unknown, the median OS was not reached and the 5-year OS rate was 78.9%. Age [35< age <69: hazard radio (HR) =2.147; 95% confidence interval (CI): 1.442-3.197, P<0.001; age >69: HR =5.259; 95% CI: 3.485-7.937, P<0.001], race (White race: HR =0.728; 95% CI: 0.590-0.899, P=0.003), histologic type (mucinous neoplasm: HR =0.690; 95% CI: 0.580-0.821, P<0.001; malignant carcinoid: HR =0.657; 95% CI: 0.536-0.806, P<0.001), grade (II: HR =1.794; 95% CI: 1.471-2.187, P<0.001; III: HR =2.905; 95% CI: 2.318-3.640, P<0.001; IV: HR =3.128; 95% CI: 2.159-4.533, P<0.001), and stage (localized: HR =0.236; 95% CI: 0.194-0.287, P<0.001; regional: HR =0.425; 95% CI: 0.362-0.499, P<0.001) were identified as independent predictors of survival. And after adjusting for known factors (age, sex, race, tumor size, marital status, histologic type, grade, stage), chemotherapy (HR =1.220; 95% CI: 1.050-1.417, P=0.009) was revealed to be an independent indicator of poor prognosis. CONCLUSIONS There was an increasing trend in the incidence of appendiceal cancer in the United States between 2004 and 2015. Chemotherapy was revealed to be an independent indicator of poor prognosis, which provide valuable insight into the therapy of primary appendiceal cancer. Large clinical trials of chemotherapy and targeted therapy for appendiceal cancer are urgently needed.
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Affiliation(s)
- Ying Wang
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Yiting Geng
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Wenwei Hu
- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, China
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15
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Hirose S, Enami C, Kawamatsu N, Ito Y, Onoda T, Sugiyama Y, Suzuki H, Nagafuchi M, Ikeda T, Niisato Y, Yamada T, Yamamoto Y, Moriwaki T, Suzuki H. Systemic chemotherapy combined with anti-epidermal growth factor receptor antibody therapy for RAS wild-type appendiceal signet-ring cell carcinoma: a series of three cases. Int Cancer Conf J 2022; 11:17-22. [PMID: 35127316 PMCID: PMC8787001 DOI: 10.1007/s13691-021-00507-w] [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: 05/22/2021] [Accepted: 08/23/2021] [Indexed: 11/30/2022] Open
Abstract
The effect of anti-epidermal growth factor receptor (EGFR) antibody-containing chemotherapy on appendiceal signet-ring cell carcinoma (SRCC) remains unknown. Herein, we report three patients, diagnosed as having synchronous metastases, who underwent this treatment for unresectable appendiceal SRCC with RAS wild type. Cases 1, 2, and 3 received FOLFOX with panitumumab, FOLFOX with cetuximab, and FOLFIRI with cetuximab, respectively, and their progression-free survival were 6.2, 7.2, and 18.7 months, respectively. The subsequent anti-vascular endothelial growth factor antibody-containing therapy was ineffective, and their overall survival was 8.2, 11.4, and 22.9 months, respectively. The anti-EGFR antibody-containing chemotherapy showed moderate efficacy for appendiceal SRCC. Further studies including molecular analysis should be needed.
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Affiliation(s)
- Suguru Hirose
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Chiaki Enami
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Natsumi Kawamatsu
- Department of Pathology, University of Tsukuba Hospital, Ibaraki, Japan
| | - Yoshimi Ito
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Tsubasa Onoda
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Yutaro Sugiyama
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Hirosumi Suzuki
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Miho Nagafuchi
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Takafumi Ikeda
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Yusuke Niisato
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Takeshi Yamada
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Yoshiyuki Yamamoto
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Toshikazu Moriwaki
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
| | - Hideo Suzuki
- Department of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575 Japan
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16
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Delhorme JB, Villeneuve L, Bouché O, Averous G, Dohan A, Gornet JM, You B, Bibeau F, Dartigues P, Eveno C, Fontaine J, Kepenekian V, Pocard M, Rousset P, Quenet F, Mariani P, Glehen O, Goéré D. Appendiceal tumors and pseudomyxoma peritonei: French Intergroup Clinical Practice Guidelines for diagnosis, treatments and follow-up (RENAPE, RENAPATH, SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, ACHBT, SFR). Dig Liver Dis 2022; 54:30-39. [PMID: 34815194 DOI: 10.1016/j.dld.2021.10.005] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 10/18/2021] [Accepted: 10/19/2021] [Indexed: 02/07/2023]
Abstract
INTRODUCTION This document is a summary of the French Intergroup guidelines regarding the management of appendicular epithelial tumors (AT) and pseudomyxoma peritonei (PMP) published in March 2020, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org). METHODS All French medical societies specialized in the management of AT and PMP collaboratively established these recommendations based on literature until December 2019 and the results of a Delphi vote carried out by the Peritoneal Surface Oncology Group International experts, and graded into 4 categories (A, B, C, Expert Agreement) according to their level of evidence. RESULTS AT and PMP are rare but represent a wide range of clinico-pathological entities with several pathological classification systems and different biological behaviors. Their treatment modalities may vary accordingly and range from simple surveillance or laparoscopic appendectomy to complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) and / or systemic chemotherapy. The prognosis of these neoplasms may also largely vary according to their pathological grade and spreading at diagnosis or during the follow-up. Given the rarity of certain situations, the therapeutic strategy adapted to each patient, must be discussed in a specialized multidisciplinary meeting after a specialized pathological and radiological pre-therapeutic assessment and a clinical examination by a surgeon specializing in the management of rare peritoneal malignancies. CONCLUSION These recommendations are proposed to achieve the most beneficial strategy in a daily practice as the wide range and the rareness of these entities renders their management challenging. These guidelines are permanently being reviewed.
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Affiliation(s)
- Jean-Baptiste Delhorme
- Department of general and digestive, Hautepierre Hospital, Strasbourg University Hospital, 1 avenue Molière, 67200 Strasbourg, France.
| | - Laurent Villeneuve
- Department of Public Health, Clinical Research and Epidemiology, Hospices Civils de Lyon, Lyon, France
| | - Olivier Bouché
- Department of Digestive Oncology, Reims University Hospital, Reims, France
| | - Gerlinde Averous
- Department of pathology, Hautepierre Hospital, Strasbourg University Hospital, Strasbourg, France
| | - Anthony Dohan
- Department of Abdominal Imaging, Hôpital Lariboisière-APHP, Paris, France
| | - Jean-Marc Gornet
- Department of hepato-gastroenteology, Hospital Saint-Louis, Paris, France
| | - Benoit You
- Department of Medical Oncology, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), Pierre-Bénite, France
| | - Frédéric Bibeau
- Department of pathology, Caen University Hospital, Caen, France
| | | | - Clarisse Eveno
- Department of general and digestive, Claude Huriez University Hospital, Lille, France
| | - Juliette Fontaine
- Depatement of pathology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France
| | - Vahan Kepenekian
- Department of General Surgery and Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France
| | - Marc Pocard
- Department of general and digestive, Hôpital Lariboisière-APHP, Paris, France
| | - Pascal Rousset
- Department of Radiology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Bénite, France
| | - Francois Quenet
- Department of Surgery, Institut du Cancer de Montpellier, Montpellier, France
| | | | - Olivier Glehen
- Department of General Surgery and Surgical Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Pierre-Bénite, France
| | - Diane Goéré
- Departement of general and digestive surgery, St Louis University Hospital, Paris, France
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Novel Perspectives in Pseudomyxoma Peritonei Treatment. Cancers (Basel) 2021; 13:cancers13235965. [PMID: 34885075 PMCID: PMC8656832 DOI: 10.3390/cancers13235965] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Revised: 11/11/2021] [Accepted: 11/23/2021] [Indexed: 12/15/2022] Open
Abstract
Simple Summary Pseudomyxoma Peritonei (PMP) represents a rare entity which greatly benefits from Cytoreductive Surgery (CRS) associated with Hyperthermic Intraperitoneal Chemotherapy (HIPEC). In fact, CRS-HIPEC represents the treatment with potential chances of cure and long-term disease control of patients affected by PMP. This therapeutic strategy should be performed in referral centers, where a consolidated know-how of this locoregional treatment and a multidisciplinary approach are available. CRS-HIPEC provides excellent results for PMP patients in terms of postoperative outcome, overall and disease-free survival, and quality of life. However, in patients with an extensive or recurrent disease, few therapeutic opportunities are available. This review is focused on the most recent clinical evidence and provides a better understanding of the molecular prognostic factors and potential therapeutic targets in this rare malignancy. Abstract Pseudomyxoma Peritonei (PMP) is an anatomo-clinical condition characterized by the implantation of neoplastic cells on peritoneal surfaces with the production of a large amount of mucin. The rarity of the disease precludes the evaluation of treatment strategies within randomized controlled trials. Cytoreductive Surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) has proven to be the only therapeutic option with potential chances of cure and long-term disease control. The present review discusses the epidemiology, pathogenesis, clinical presentation and treatment of PMP, focusing on the molecular factors involved in tumor progression and mucin production that could be used, in the upcoming future, to improve patient selection for surgery and to expand the therapeutic armamentarium.
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18
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Ceelen W, De Man M, Willaert W, van Ramshorst GH, Geboes K, Hoorens A. Incidentally found mucinous epithelial tumors of the appendix with or without pseudomyxoma peritonei: diagnostic and therapeutic algorithms based on current evidence. Acta Chir Belg 2021; 121:225-234. [PMID: 33904809 DOI: 10.1080/00015458.2021.1894734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Mucinous appendiceal tumors with or without the pseudomyxoma peritonei (PMP) syndrome are rare, but often present as an incidental finding. The confusing histology and lack of large prospective trials result in a considerable diagnostic and therapeutic challenge in these patients. We propose treatment algorithms in patients with incidentally found mucinous epithelial appendiceal tumors, with or without PMP, based on the currently available evidence. The therapeutic approach should take into account the histology and grade of the primary appendix tumor, as well as those of the associated peritoneal disease.
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Affiliation(s)
- Wim Ceelen
- Department ofGI Surgery, Ghent University Hospital, Ghent, Belgium
| | - Marc De Man
- Department of Digestive Oncology, Ghent University Hospital, Ghent, Belgium
| | - Wouter Willaert
- Department ofGI Surgery, Ghent University Hospital, Ghent, Belgium
| | | | - Karen Geboes
- Department of Digestive Oncology, Ghent University Hospital, Ghent, Belgium
| | - Anne Hoorens
- Department of Pathology, Ghent University Hospital, Ghent, Belgium
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19
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Anti-Angiogenic Treatment in Pseudomyxoma Peritonei-Still a Strong Preclinical Rationale. Cancers (Basel) 2021; 13:cancers13112819. [PMID: 34198773 PMCID: PMC8201024 DOI: 10.3390/cancers13112819] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 06/02/2021] [Accepted: 06/02/2021] [Indexed: 12/30/2022] Open
Abstract
Simple Summary Patients with pseudomyxoma peritonei that are not cured by the standard treatment (cytoreductive surgery and hyperthermic intraperitoneal chemotherapy) have no efficacious treatment options. Drugs that inhibit formation of new vessels (anti-angiogenic drugs) could be a therapeutic option for these patients. Using patient samples and animal models we show that angiogenesis is important in pseudomyxoma peritonei and that anti-angiogenic drugs may indeed have an effect. Our results support continued efforts to determine the role of anti-angiogenic treatment in pseudomyxoma peritonei. Abstract Pseudomyxoma peritonei (PMP) is a rare, slow-growing cancer characterized by progressive accumulation of intraperitoneal mucinous tumor deposits. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) cures approximately 50% of patients, but in unresectable and recurrent cases, treatment options are limited. Anti-angiogenic treatment is being explored as a potential therapeutic option. Using PMP patient samples, microvessel densities (immunostaining for CD31 and CD105) and pro-angiogenic factors were analyzed, and the proliferative response upon incubation with human umbilical cord vascular endothelial cells (HUVEC) was determined. Growth inhibition by anti-angiogenic drugs was analyzed in patient-derived xenograft models of PMP. PMP tumor tissues were found to be highly vascularized and contained key pro-angiogenic factors, in particular related to vascular endothelial growth factor (VEGF) signaling, but interestingly, high levels of fibroblast growth factor 2 were also detected. HUVEC proliferation was stimulated upon incubation with fresh tumor samples and the observed proliferation could be inhibited by VEGF pathway inhibitor bevacizumab. In xenograft models the two VEGF pathway inhibitors, bevacizumab and aflibercept, inhibited tumor growth. This work reemphasizes the importance of angiogenesis as a major driver in PMP and strengthens the preclinical rationale for continued exploration of angiogenesis inhibition in the hope of providing novel treatment to a group of patients that have few other treatment options.
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20
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Ahmadi N, Kostadinov D, Sakata S, Ball WR, Gandhi J, Carr NJ, Tzivanakis A, Dayal SP, Mohamed F, Cecil TD, Moran BJ. Managing Recurrent Pseudomyxoma Peritonei in 430 Patients After Complete Cytoreduction and HIPEC: A Dilemma for Patients and Surgeons. Ann Surg Oncol 2021; 28:7809-7820. [PMID: 34041626 DOI: 10.1245/s10434-021-10093-z] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 04/14/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Epithelial appendiceal neoplasms are uncommon peritoneal malignancies causing a spectrum of disease including pseudomyxoma peritonei (PMP). The optimal management is cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Despite complete CRS (CCRS), recurrence develops in almost 45% of patients. No consensus exists for the optimal treatment of recurrent disease, with treatment strategies including repeat CRS, watch-and-wait, and palliative chemotherapy. This report aims to describe evolving management strategies for a large cohort with recurrence after CCRS. METHODS This retrospective study analyzed a prospective database of patients with recurrence after CCRS for appendiceal neoplasms from 1994 to 2017 who had long-term follow-up evaluation with tumor markers and computed tomography (CT). RESULTS Overall, 430 (37.6%) of 1145 PMP patients experienced recurrence at a median of 19 months. Of these 430 patients 145 (33.7%) underwent repeat CRS, 119 (27.7%) had a watch-and-wait approach, and 119 (27.7%) had palliative chemotherapy. The patients with recurrence had a median overall survival (OS) of 39 months, a 3-year survival of 74.6%, a 5-year survival of 57.4%, and a 10-year survival of 36.5%. In the multivariate analysis, the patients who had recurrence within 1 year after primary CRS (hazard ratio [HR], 3.55), symptoms at recurrence (HR, 3.08), a high grade of disease or adenocarcinoma pathology (HR, 2.94), signet ring cells (HR, 1.91), extraperitoneal metastatic disease (HR, 1.71), or male gender (HR, 1.61) had worse OS. The OS was longer for the patients who had repeat CRS (HR, 0.41). The patients who underwent repeat CCRS had a 3-year OS of 87.5%, a 5-year OS of 78.1%, and a 10-year OS of 67.9%. CONCLUSIONS Dilemmas persist around the optimal management of patients with recurrence after CRS and HIPEC for appendiceal tumors. Selected patients benefit from repeat CRS, particularly those with favorable tumor biology and focal disease.
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Affiliation(s)
- Nima Ahmadi
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK.,Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | | | - Shinichiro Sakata
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK.,Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - William Robert Ball
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK.,Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - Jamish Gandhi
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK.,Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - Norman John Carr
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK.,Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - Alexios Tzivanakis
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK.,Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - Sanjeev Paul Dayal
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK.,Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - Faheez Mohamed
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK.,Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - Thomas Desmond Cecil
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK.,Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK
| | - Brendan John Moran
- Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK. .,Peritoneal Malignancy Institute, Basingstoke and North Hampshire Hospital, Basingstoke, UK.
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21
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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.
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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
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22
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Govaerts K, Lurvink RJ, De Hingh IHJT, Van der Speeten K, Villeneuve L, Kusamura S, Kepenekian V, Deraco M, Glehen O, Moran BJ. Appendiceal tumours and pseudomyxoma peritonei: Literature review with PSOGI/EURACAN clinical practice guidelines for diagnosis and treatment. Eur J Surg Oncol 2020; 47:11-35. [PMID: 32199769 DOI: 10.1016/j.ejso.2020.02.012] [Citation(s) in RCA: 146] [Impact Index Per Article: 29.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 02/12/2020] [Indexed: 12/20/2022] Open
Abstract
Pseudomyxoma Peritonei (PMP) is a rare peritoneal malignancy, most commonly originating from a perforated epithelial tumour of the appendix. Given its rarity, randomized controlled trials on treatment strategies are lacking, nor likely to be performed in the foreseeable future. However, many questions regarding the management of appendiceal tumours, especially when accompanied by PMP, remain unanswered. This consensus statement was initiated by members of the Peritoneal Surface Oncology Group International (PSOGI) Executive Committee as part of a global advisory role in the management of uncommon peritoneal malignancies. The manuscript concerns an overview and analysis of the literature on mucinous appendiceal tumours with, or without, PMP. Recommendations are provided based on three Delphi voting rounds with GRADE-based questions amongst a panel of 80 worldwide PMP experts.
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Affiliation(s)
- K Govaerts
- Department of Surgical Oncology, Hospital Oost-Limburg, Genk, Belgium.
| | - R J Lurvink
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - I H J T De Hingh
- Department of Surgery, Catharina Hospital, Eindhoven, the Netherlands
| | - K Van der Speeten
- Department of Surgical Oncology, Hospital Oost-Limburg, Genk, Belgium
| | - L Villeneuve
- Service de Recherche et Epidémiologie Cliniques, Pôle de Santé Publique, Hospices Civils de Lyon, Lyon, France, EMR 3738, Lyon 1 University, Lyon, France
| | - S Kusamura
- Department of Surgery, Peritoneal Surface Malignancy Unit, Fondazione IRCCS Instituto Nazionale Dei Tumori di Milano, Via Giacomo Venezian 1, Milano, Milan Cap, 20133, Italy
| | - V Kepenekian
- Service de Chirurgie Digestive et Endocrinienne, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Lyon, France, EMR 3738, Lyon 1 University, Lyon, France
| | - M Deraco
- Department of Surgery, Peritoneal Surface Malignancy Unit, Fondazione IRCCS Instituto Nazionale Dei Tumori di Milano, Via Giacomo Venezian 1, Milano, Milan Cap, 20133, Italy
| | - O Glehen
- Department of Digestive Surgery, Centre Hospitalier Lyon Sud, Lyon, France
| | - B J Moran
- Peritoneal Malignancy Institute, North-Hampshire Hospital, Basingstoke, UK
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23
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Hiraide S, Komine K, Sato Y, Ouchi K, Imai H, Saijo K, Takahashi M, Takahashi S, Shirota H, Takahashi M, Ishioka C. Efficacy of modified FOLFOX6 chemotherapy for patients with unresectable pseudomyxoma peritonei. Int J Clin Oncol 2019; 25:774-781. [PMID: 31823151 PMCID: PMC7118031 DOI: 10.1007/s10147-019-01592-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 11/29/2019] [Indexed: 01/02/2023]
Abstract
Background Pseudomyxoma peritonei (PMP) is a rare malignancy, and there is insufficient evidence about systemic chemotherapy for this disease. Methods We retrospectively evaluated the efficacy and safety of a chemotherapeutic regimen with 5-fluorouracil and oxaliplatin (modified FOLFOX6, mFOLFOX6) for patients with unresectable pseudomyxoma peritonei. Patients who received the therapy between April 2000 and February 2019 at the Department of Medical Oncology, Tohoku University Hospital, were enrolled in this study. Results Eight patients were treated with mFOLFOX6. The sites of primary tumor were appendix in six patients, ovary in a patient, and urachus in a patient. Six patients received surgery. Seven patients had histologically high-grade PMP, and one patient had low-grade PMP. The median follow-up duration was 27.2 months. All the patients had non-measurable regions as the targets of tumor response. Non-complete response or non-progressive disease was observed in seven patients, with a disease control rate of 87.5%. The median progression-free survival and overall survival were 13.0 months and 27.9 months, respectively. An obvious reduction in the symptoms was observed in two patients. Five patients experienced decline in the serum tumor markers, CEA or CA19-9. The grade 3/4 toxicity that was observed was grade 4 neutropenia in one patient and grade 3 neutropenia in two patients. Conclusions mFOLFOX6 might be an effective and tolerable treatment option for patients with unresectable PMP. To our knowledge, this is the first case series of mFOLFOX6 in patients with unresectable PMP and the first case series of systemic chemotherapy for Asian patients with unresectable PMP. Electronic supplementary material The online version of this article (10.1007/s10147-019-01592-x) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Sakura Hiraide
- Department of Medical Oncology, Tohoku University Hospital, Aoba-ku, Sendai, Miyagi, Japan
| | - Keigo Komine
- Department of Medical Oncology, Tohoku University Hospital, Aoba-ku, Sendai, Miyagi, Japan
| | - Yuko Sato
- Department of Medical Oncology, Tohoku University Hospital, Aoba-ku, Sendai, Miyagi, Japan
| | - Kota Ouchi
- Department of Medical Oncology, Tohoku University Hospital, Aoba-ku, Sendai, Miyagi, Japan
| | - Hiroo Imai
- Department of Medical Oncology, Tohoku University Hospital, Aoba-ku, Sendai, Miyagi, Japan
| | - Ken Saijo
- Department of Medical Oncology, Tohoku University Hospital, Aoba-ku, Sendai, Miyagi, Japan
| | - Masahiro Takahashi
- Department of Medical Oncology, Tohoku University Hospital, Aoba-ku, Sendai, Miyagi, Japan
- Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan
| | - Shin Takahashi
- Department of Medical Oncology, Tohoku University Hospital, Aoba-ku, Sendai, Miyagi, Japan
| | - Hidekazu Shirota
- Department of Medical Oncology, Tohoku University Hospital, Aoba-ku, Sendai, Miyagi, Japan
| | - Masanobu Takahashi
- Department of Medical Oncology, Tohoku University Hospital, Aoba-ku, Sendai, Miyagi, Japan
- Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan
| | - Chikashi Ishioka
- Department of Medical Oncology, Tohoku University Hospital, Aoba-ku, Sendai, Miyagi, Japan.
- Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, 4-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan.
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24
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The American Society of Colon and Rectal Surgeons, Clinical Practice Guidelines for the Management of Appendiceal Neoplasms. Dis Colon Rectum 2019; 62:1425-1438. [PMID: 31725580 DOI: 10.1097/dcr.0000000000001530] [Citation(s) in RCA: 84] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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25
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Review: Pathology and Its Clinical Relevance of Mucinous Appendiceal Neoplasms and Pseudomyxoma Peritonei. Clin Colorectal Cancer 2019; 18:1-7. [DOI: 10.1016/j.clcc.2018.11.007] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2018] [Accepted: 11/26/2018] [Indexed: 12/15/2022]
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26
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Liu W, Liu L, Wang R, Gong G, Ding X, Yang B, Bao Y, Wang Z, Zhang B, Zhao D, Wu F, Ding Y. Bevacizumab Combined With Oxaliplatin/Capecitabine in Patient With Refractory and Recurrent Mucinous Adenocarcinoma of the Appendix: A Case Report. Front Oncol 2019; 9:55. [PMID: 30792968 PMCID: PMC6374296 DOI: 10.3389/fonc.2019.00055] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Accepted: 01/21/2019] [Indexed: 12/31/2022] Open
Abstract
Primary appendiceal adenocarcinoma with peritoneal pseudomyxoma (PPM) has a high recurrence rate and refractory to medical interventions such as repetitive debulking surgery and systemic chemotherapy. Genome-based targeted therapy for such cases has not been well-documented. Here we present a 63-years-old women, who was diagnosed with recurrent mucinous adenocarcinoma of the appendix with local invasions and peritoneal carcinomatosis, was refractory to systemic chemotherapy after surgery. We used a regime developed using whole exome sequencing. Somatic mutations in the genes encoding VEGFR2, FGFR1, FGFR2, FGFR3, and KRAS were identified in the patient's tumor tissue. The patient was then treated with bevacizumab plus oxaliplatin. After 4 months of treatment, pelvic CT showed dramatic reduction of pseudomyoma and a decline of CA199 level from 5436.7 to 1121.4 U/ml. Continual treatment with bevacizumab-capecitabine remained effective and the patient's CA199 level further decreased to 401.26 U/ml according to the follow-up examination on Aug 15th, 2018. Results from this study show the evidence of gene mutations involving VEGF signal activation in the recurrence of appendiceal adenocarcinoma. Our results also suggest the association of these mutations with the effectiveness of anti-VEGF treatment using bevacizumab. Therefore, the screening of gene mutations involved in VEGF signaling and targeted therapy with anti-VEGF drugs may provide a new option to manage refractory/recurrent advanced-stage appendiceal adenocarcinoma.
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Affiliation(s)
- Wenzhi Liu
- The Institute for Translational Medicine, The Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - Lili Liu
- Department of Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Ruoyu Wang
- The Institute for Translational Medicine, The Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - Guanyu Gong
- The Institute for Translational Medicine, The Affiliated Zhongshan Hospital of Dalian University, Dalian, China.,Genomic Future Inc., Lexington, MA, United States
| | - Xinjia Ding
- Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Bin Yang
- Genomic Future Inc., Lexington, MA, United States.,Department of Pediatrics, Children's Hospital of Boston, Harvard Medical School, Boston, MA, United States
| | - Yun Bao
- The Institute for Translational Medicine, The Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - Zhiqiang Wang
- The Institute for Translational Medicine, The Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - Bo Zhang
- Department of Neurosurgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Dewei Zhao
- The Institute for Translational Medicine, The Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - Fei Wu
- The Institute for Translational Medicine, The Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - Yan Ding
- The Institute for Translational Medicine, The Affiliated Zhongshan Hospital of Dalian University, Dalian, China.,Department of Pediatrics, Children's Hospital of Boston, Harvard Medical School, Boston, MA, United States
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27
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Brandl A, Pratschke J, Rau B. Chirurgisch-onkologische Therapie primärer und sekundärer peritonealer Neoplasien. Eur Surg 2018. [DOI: 10.1007/s10353-018-0553-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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28
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Abstract
The peritoneal malignancies span the biologic spectrum of aggressiveness from the indolent growth pattern and superficial nature of well-differentiated mucinous appendiceal adenocarcinoma to the rapidly growing and invasive nature of poorly differentiated signet ring cell adenocarcinomas of the appendix, colon, and stomach. An understanding of the biology, distribution, and volume of disease is critical to appropriately selecting patients for cytoreduction and HIPEC with the goal of long-term survival. Herein the authors discuss appropriate the evaluation and selection of patients for with peritoneal surface malignancies for cytoreduction and HIPEC.
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Affiliation(s)
- Travis E Grotz
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA; Department of Surgical Oncology, MD Anderson Cancer Center, Houston, TX, USA.
| | - Keith F Fournier
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
| | - Paul F Mansfield
- Division of Hepatobiliary and Pancreas Surgery, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
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29
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Akin S, Dizdar Ö, Hayran M. Anti-VEGF Therapy in the Treatment of Unresectable Appendiceal Epithelial Neoplasms. Ann Surg Oncol 2017; 24:620. [PMID: 29168096 DOI: 10.1245/s10434-017-6147-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2017] [Indexed: 12/13/2022]
Affiliation(s)
- Serkan Akin
- Department of Preventive Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.
| | - Ömer Dizdar
- Department of Preventive Oncology, Hacettepe University Cancer Institute, Ankara, Turkey
| | - Mutlu Hayran
- Department of Preventive Oncology, Hacettepe University Cancer Institute, Ankara, Turkey
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30
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Grotz TE, Royal RE, Mansfield PF, Overman MJ, Mann GN, Robinson KA, Beaty KA, Rafeeq S, Matamoros A, Taggart MW, Fournier KF. Stratification of outcomes for mucinous appendiceal adenocarcinoma with peritoneal metastasis by histological grade. World J Gastrointest Oncol 2017; 9:354-362. [PMID: 28979717 PMCID: PMC5605335 DOI: 10.4251/wjgo.v9.i9.354] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Revised: 05/13/2017] [Accepted: 05/30/2017] [Indexed: 02/05/2023] Open
Abstract
AIM To investigate the importance of a three-tiered histologic grade on outcomes for patients with mucinous appendiceal adenocarcinoma (MAA). METHODS Two hundred and sixty-five patients with MAA undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were identified from a prospective database from 2004 through 2014. All pathology was reviewed by our gastrointestinal subspecialty pathologists and histological grade was classified as well-differentiated, moderately differentiated, and poorly differentiated. Survival analysis was performed using Cox proportional hazards regression. RESULTS There were 201 (75.8%) well-, 45 (16.9%) moderately- and 19 (7.2%) poorly-differentiated tumors. Histological grade significantly stratified the 5-year overall survival (OS), 94%, 71% and 30% respectively (P < 0.001) as well as the 5-year disease-free survival (DFS) 66%, 21% and 0%, respectively (P < 0.001). Independent predictors of DFS included tumor grade (HR = 1.78, 95%CI: 1.21-2.63, P = 0.008), lymph node involvement (HR = 0.33, 95%CI: 0.11-0.98, P < 0.02), previous surgical score (HR = 1.31, 95%CI: 1.1-1.65, P = 0.03) and peritoneal carcinomatosis index (PCI) (HR = 1.05, 95%CI: 1.02-1.08, P = 0.002). Independent predictors of OS include tumor grade (HR = 2.79, 95%CI: 1.26-6.21, P = 0.01), PCI (HR = 1.10, 95%CI: 1.03-1.16, P = 0.002), and complete cytoreduction (HR = 0.32, 95%CI: 0.11-0.92, P = 0.03). Tumor grade and PCI were the only independent predictors of both DFS and OS. Furthermore, histological grade and lymphovascular invasion stratified the risk of lymph node metastasis into a low (6%) and high (40%) risk groups. CONCLUSION Our data demonstrates that moderately differentiated MAA have a clinical behavior and outcome that is distinct from well- and poorly-differentiated MAA. The three-tier grade classification provides improved prognostic stratification and should be incorporated into patient selection and treatment algorithms.
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Affiliation(s)
- Travis Edward Grotz
- Department of Surgical Oncology at the University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Richard E Royal
- Department of Surgical Oncology at the University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Paul F Mansfield
- Department of Surgical Oncology at the University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Michael James Overman
- Department of Medical Oncology at the University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Gary N Mann
- Department of Surgical Oncology at the University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Kristen Ashlee Robinson
- Department of Surgical Oncology at the University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Karen A Beaty
- Department of Surgical Oncology at the University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Safiea Rafeeq
- Department of Surgical Oncology at the University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Auerlio Matamoros
- Department of Radiology at the University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Michelle W Taggart
- Department of Pathology at the University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
| | - Keith Francis Fournier
- Department of Surgical Oncology at the University of Texas MD Anderson Cancer Center, Houston, TX 77030, United States
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31
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Grotz TE, Overman MJ, Eng C, Raghav KP, Royal RE, Mansfield PF, Mann GN, Robinson KA, Beaty KA, Rafeeq S, Matamoros A, Taggart MW, Fournier KF. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Moderately and Poorly Differentiated Appendiceal Adenocarcinoma: Survival Outcomes and Patient Selection. Ann Surg Oncol 2017; 24:2646-2654. [PMID: 28695394 DOI: 10.1245/s10434-017-5938-8] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Indexed: 02/17/2025]
Abstract
BACKGROUND Moderately and poorly differentiated adenocarcinoma of the appendix represents an aggressive histological variant with a high risk of recurrence and death. METHODS Overall, 178 patients with moderately and poorly differentiated appendiceal adenocarcinoma were identified from a prospective database. Clinical, pathologic, and treatment factors were analyzed for outcomes. RESULTS Diagnostic laparoscopy (DL) identified radiographic occult peritoneal metastasis in 25 (42%) patients. These patients had a significantly lower peritoneal carcinomatosis index (PCI) and improved overall survival (OS) compared with those with radiographic disease. Twenty-seven (41%) patients were excluded from cytoreductive surgery (CRS) because of findings on DL, while 116 (65%) patients underwent CRS and hyperthermic intraperitoneal chemotherapy (HIPEC), with a median disease-free survival (DFS) of 23 months. Mucinous histology (hazard ratio [HR] 0.52, p = 0.04) and PCI (HR 1.054, p = 0.02) were independent predictors of DFS. The median OS following CRS and HIPEC was 48 months. Mucinous histology (HR 0.352, p = 0.018), signet ring cells (HR 3.34, p = 0.02), positive peritoneal cytology (HR 0.081, p = 0.04), and PCI (HR 1.076, p = 0.004) were independently associated with OS. Eight-five (73.3%) patients received neoadjuvant chemotherapy, and 40 (47.1%) patients achieved a radiographic response; 36 (42.3%) had stable disease, while 9 (10.6%) had progressive disease. Stable or responsive disease was associated with improved median OS of 44 months, compared with 21 months for those with progressive disease (p = 0.011). CONCLUSIONS In selected patients, long-term survival can be obtained. Mucinous histology, absence of signet ring cells, negative peritoneal cytology, PCI ≤ 20, and response/stable disease after neoadjuvant chemotherapy are important selection criteria for CRS and HIPEC.
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Affiliation(s)
- Travis E Grotz
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Michael J Overman
- Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Cathy Eng
- Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Kanwal P Raghav
- Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Richard E Royal
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Paul F Mansfield
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Gary N Mann
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Kristen A Robinson
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Karen A Beaty
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Safia Rafeeq
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Aurelio Matamoros
- Department of Radiology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Melissa W Taggart
- Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Keith F Fournier
- Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
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32
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Ehlerding EB, Lacognata S, Jiang D, Ferreira CA, Goel S, Hernandez R, Jeffery JJ, Theuer CP, Cai W. Targeting angiogenesis for radioimmunotherapy with a 177Lu-labeled antibody. Eur J Nucl Med Mol Imaging 2017; 45:123-131. [PMID: 28821931 DOI: 10.1007/s00259-017-3793-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Accepted: 07/25/2017] [Indexed: 12/26/2022]
Abstract
PURPOSE Increased angiogenesis is a marker of aggressiveness in many cancers. Targeted radionuclide therapy of these cancers with angiogenesis-targeting agents may curtail this increased blood vessel formation and slow the growth of tumors, both primary and metastatic. CD105, or endoglin, has a primary role in angiogenesis in a number of cancers, making this a widely applicable target for targeted radioimmunotherapy. METHODS The anti-CD105 antibody, TRC105 (TRACON Pharmaceuticals), was conjugated with DTPA for radiolabeling with 177Lu (t 1/2 6.65 days). Balb/c mice were implanted with 4T1 mammary carcinoma cells, and five study groups were used: 177Lu only, TRC105 only, 177Lu-DTPA-IgG (a nonspecific antibody), 177Lu-DTPA-TRC105 low-dose, and 177Lu-DTPA-TRC105 high-dose. Toxicity of the agent was monitored by body weight measurements and analysis of blood markers. Biodistribution studies of 177Lu-DTPA-TRC105 were also performed at 1 and 7 days after injection. Ex vivo histology studies of various tissues were conducted at 1, 7, and 30 days after injection of high-dose 177Lu-DTPA-TRC105. RESULTS Biodistribution studies indicated steady uptake of 177Lu-DTPA-TRC105 in 4T1 tumors between 1 and 7 days after injection (14.3 ± 2.3%ID/g and 11.6 ± 6.1%ID/g, respectively; n = 3) and gradual clearance from other organs. Significant inhibition of tumor growth was observed in the high-dose group, with a corresponding significant increase in survival (p < 0.001, all groups). In most study groups (all except the nonspecific IgG group), the body weights of the mice did not decrease by more than 10%, indicating the safety of the injected agents. Serum alanine transaminase levels remained nearly constant indicating no damage to the liver (a primary clearance organ of the agent), and this was confirmed by ex vivo histological analyses. CONCLUSION 177Lu-DTPA-TRC105, when administered at a sufficient dose, is able to curtail tumor growth and provide a significant survival benefit without off-target toxicity. Thus, this targeted agent could be used in combination with other treatment options to slow tumor growth allowing the other agents to be more effective.
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Affiliation(s)
- Emily B Ehlerding
- Department of Medical Physics, University of Wisconsin - Madison, 1111 Highland Avenue, Madison, WI, 53705, USA
| | - Saige Lacognata
- Department of Radiology, University of Wisconsin - Madison, Madison, WI, USA
| | - Dawei Jiang
- Department of Radiology, University of Wisconsin - Madison, Madison, WI, USA
| | - Carolina A Ferreira
- Department of Biomedical Engineering, University of Wisconsin - Madison, Madison, WI, USA
| | - Shreya Goel
- Department of Materials Science and Engineering, University of Wisconsin - Madison, Madison, WI, USA
| | - Reinier Hernandez
- Department of Medical Physics, University of Wisconsin - Madison, 1111 Highland Avenue, Madison, WI, 53705, USA
| | - Justin J Jeffery
- Small Animal Imaging Facility, University of Wisconsin - Madison, Madison, WI, USA
| | | | - Weibo Cai
- Department of Medical Physics, University of Wisconsin - Madison, 1111 Highland Avenue, Madison, WI, 53705, USA. .,Department of Radiology, University of Wisconsin - Madison, Madison, WI, USA. .,Department of Biomedical Engineering, University of Wisconsin - Madison, Madison, WI, USA. .,Department of Materials Science and Engineering, University of Wisconsin - Madison, Madison, WI, USA.
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Lemoine L, Sugarbaker P, Van der Speeten K. Drugs, doses, and durations of intraperitoneal chemotherapy: standardising HIPEC and EPIC for colorectal, appendiceal, gastric, ovarian peritoneal surface malignancies and peritoneal mesothelioma. Int J Hyperthermia 2017; 33:582-592. [PMID: 28540826 DOI: 10.1080/02656736.2017.1291999] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Affiliation(s)
- Lieselotte Lemoine
- Department of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium
- Department of Surgical Oncology, Ziekenhuis Oost-Limburg, Genk, Belgium
| | - Paul Sugarbaker
- Washington Cancer Institute, Washington Hospital Center, Washington DC, USA
| | - Kurt Van der Speeten
- Department of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium
- Department of Surgical Oncology, Ziekenhuis Oost-Limburg, Genk, Belgium
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Uemura M, Qiao W, Fournier K, Morris J, Mansfield P, Eng C, Royal RE, Wolff RA, Raghav K, Mann GN, Overman MJ. Retrospective study of nonmucinous appendiceal adenocarcinomas: role of systemic chemotherapy and cytoreductive surgery. BMC Cancer 2017; 17:331. [PMID: 28506255 PMCID: PMC5433007 DOI: 10.1186/s12885-017-3327-0] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Accepted: 05/05/2017] [Indexed: 01/23/2023] Open
Abstract
Background Mucinous appendiceal adenocarcinomas (AAs) are the most common histological subset of AAs. Nonmucinous AAs have been infrequently studied. We performed a single-center retrospective study to investigate this histological subtype. Methods We reviewed 172 patient records with nonmucinous AAs treated at MD Anderson Cancer Center from Jan, 1990 to Jun, 2015 and recorded patient demographics, tumor characteristics, treatment, and outcomes. Response rate (RR) was assessed semi-quantitatively (response/no response) according to the treating physician’s findings. Survival outcomes were calculated using the Kaplan-Meier product-limit method and compared using the log-rank test. Results Median age at diagnosis was 52.9 years. Most patients presented with advanced-stage disease: stage I-II (35%), stage III (15%), and stage IV (50%). Moderate and poorly differentiated histology was seen in 56% and 44% tumors, respectively. Median overall survival (OS) of all patients was stage-dependent and was 88.5, 39.2, and 28.3 months for stages I-II, stage III, and stage IV disease, respectively (p < 0.0001). In patients with metastatic disease, only 10% had extraperitoneal disease without peritoneal involvement. Cytoreductive surgery (CRS) was attempted in 31/69 (45%) patients with disease confined to the peritoneum. Complete CRS was achieved in 18. Median OS for patients receiving complete CRS was 48.6 months. Systemic chemotherapy was administered to 109 (86%) patients with metastatic disease; a large majority of patients received either an oxaliplatin-based (55%) or irinotecan-based (27%) regimen. Chemotherapy resulted in a semi-quantitative RR of 54% and median time to progression (TTP) of 9.4 months (95% CI, 8.03–11.50). Patients who received combination chemotherapy (either oxaliplatin or irinotecan-based) showed significantly longer median OS (p = 0.003), compared to those receiving fluoropyrimidine monotherapy. Conclusions This is one of the first studies to report specifically on nonmucinous AAs. Nonmucinous AAs presented with moderate or poorly differentiated histology with a predilection for peritoneal metastasis. Systemic chemotherapy is active in this AA subtype. Though CRS was infrequently used, complete CRS appears beneficial and warrants further investigation.
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Affiliation(s)
- Marc Uemura
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0426, Houston, TX, 77030, USA
| | - Wei Qiao
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Keith Fournier
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jeffrey Morris
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Paul Mansfield
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Cathy Eng
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0426, Houston, TX, 77030, USA
| | - Richard E Royal
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Robert A Wolff
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0426, Houston, TX, 77030, USA
| | - Kanwal Raghav
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0426, Houston, TX, 77030, USA
| | - Gary N Mann
- Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Michael J Overman
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 0426, Houston, TX, 77030, USA.
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