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Tentes AAK, Korakianitis OS, Kakolyris S, Kyziridis D, Veliovits D, Karagiozoglou C, Sgouridou E, Moustakas K. Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy in Recurrent Ovarian Cancer. TUMORI JOURNAL 2018; 96:411-6. [DOI: 10.1177/030089161009600306] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background and aims Cytoreductive surgery with perioperative intraperitoneal chemotherapy is another approach for recurrent ovarian cancer. The purpose of the study was to assess the feasibility and the effect of cytoreduction and perioperative intraperitoneal chemotherapy in recurrent ovarian cancer. Patients and methods Twenty-nine women with recurrent ovarian cancer underwent cytoreductive surgery. Clinical variables were correlated to morbidity, hospital mortality, recurrences, and survival. Results Complete cytoreduction was possible in 58.6%. Extensive seeding of the small bowel and distant metastases excluded the possibility of performing complete cytoreduction. Perioperative intraperitoneal chemotherapy was given in 75.9%. Morbidity and hospital mortality rates were subsequently 24.1% and 3.4%. Recurrence was recorded in 48.3%. The extent of peritoneal dissemination was an independent variable of recurrence (P = 0.014). The 5-year survival rate was 30%. The extent of peritoneal dissemination and the completeness of cytoreduction were related to survival (P <05). The completeness of cytoreduction independently influenced survival (P = 0.013). Conclusions Secondary cytoreduction with intraperitoneal chemotherapy is feasible in most women with recurrent ovarian cancer with acceptable morbidity and mortality. Complete cytoreduction is not possible if distant and unresectable metastases are present or if the small bowel is extensively seeded. Long-term survivors are patients with limited peritoneal dissemination who may undergo complete cytoreduction.
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Affiliation(s)
| | - Odysseas S Korakianitis
- Anesthesiology Department, Didimotichon General Hospital Didimotichon, Democritus University of Thrace, Alexandroupolis, Greece
| | | | - Dimitrios Kyziridis
- Department of Surgery, Democritus University of Thrace, Alexandroupolis, Greece
| | - Dousan Veliovits
- Department of Surgery, Democritus University of Thrace, Alexandroupolis, Greece
| | - Chrysa Karagiozoglou
- Anesthesiology Department, Didimotichon General Hospital Didimotichon, Democritus University of Thrace, Alexandroupolis, Greece
| | - Evanthia Sgouridou
- Department of Surgery, Democritus University of Thrace, Alexandroupolis, Greece
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Bhat RA, Chia YN, Lim YK, Yam KL, Lim C, Teo M. Survival Impact of Secondary Cytoreductive Surgery for Recurrent Ovarian Cancer in an Asian Population. Oman Med J 2015; 30:344-52. [PMID: 26421115 DOI: 10.5001/omj.2015.70] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
OBJECTIVE The aim of this study was to evaluate the role of secondary cytoreductive surgery in Asian patients with recurrent ovarian cancer and to assess prognostic variables on overall post-recurrence survival time. METHODS We conducted a retrospective review of patients with recurrent ovarian cancer who underwent secondary cytoreduction at the Gynaecological Cancer Center at the KK Women's and Children's Hospital, Singapore, between 1999 and 2009. Eligible patients included those who had been firstly treated by primary cytoreductive surgery and followed by adjuvant chemotherapy and had a period of clinical remission of at least six months and subsequently underwent secondary cytoreductive surgery for recurrence. Univariate analysis was performed to evaluate various variables influencing the overall survival. RESULTS Twenty-five patients met our eligibility criteria. The median age was 52 years (range=31-78 years). The median time from completion of primary treatment to recurrence was 25.1 months (range=6.4-83.4). Secondary cytoreduction was optimal in 20 of 25 patients (80%). The median follow-up duration was 38.9 months (range=17.8-72.4) and median overall survival time was 33.1 months (95% confidence interval, 15.3-undefined.). Ten (40.0%) patients required bowel resection, but no end colostomy was performed. One (4.0%) patient had wedge resection of the liver, one (4.0%) had a distal pancreatectomy, one (4.0%) had a unilateral nephrectomy, and one (4.0%) had adrenalectomy. There were no operative deaths. The overall survival of patients who responded to secondary cytoreductive surgery and adjuvant chemotherapy was significantly longer than those patients who did not respond to the treatment. Of those patients who responded to the surgical management, patients with clear cell carcinoma fared well compared to those with the endometrioid, mucinous adenocarcinoma, and papillary serous type (p<0.001). Complete secondary cytoreductive surgery appeared to have some relationship to overall survival but was not statistically significant. CONCLUSION In carefully selected patients with recurrent ovarian cancer, optimal cytoreductive surgery is possible and in a subgroup of patients who respond to surgery and chemotherapy survival is significantly longer.
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Affiliation(s)
- Rani Akhil Bhat
- Department of Gynaecologic Oncology, BGS Global Hospitals, Bangalore, India
| | - Yin Nin Chia
- Department of Gynaecological Oncology, KK Women's and Children's Hospital, Singapore
| | - Yong Kuei Lim
- Department of Gynaecological Oncology, KK Women's and Children's Hospital, Singapore
| | - Kwai Lam Yam
- Department of Gynaecological Oncology, KK Women's and Children's Hospital, Singapore
| | - Cindy Lim
- Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore, Singapore
| | - Melissa Teo
- Department of Surgical Oncology, National Cancer Centre Singapore, Singapore
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Coccolini F, Catena F, Manfredi R, Montori G, Manegold JE, Ansaloni L. Value of neoadjuvant chemotherapy in advanced ovarian cancer. World J Obstet Gynecol 2015; 4:64-67. [DOI: 10.5317/wjog.v4.i3.64] [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: 02/10/2015] [Revised: 03/20/2015] [Accepted: 06/19/2015] [Indexed: 02/05/2023] Open
Abstract
Data regarding the role of neoadjuvant chemotherapy (NACT) are not definitive. Several randomized trials and meta-analyses demonstrate that this chemotherapy regimen decreases the morbidity and mortality rates and increases complete cytoreduction rates. If combined with hyperthermic intraperitoneal chemotherapy (HIPEC), NACT could potentially further improve upon these already promising results. Moreover the use of NACT could help in evaluating the chemo-sensitivity of the cancer, thus preventing unnecessary HIPEC procedures in chemo-resistant patients. NACT should definitely be considered as a preferred regimen in the management of advanced ovarian cancer, especially in association with cytoreductive surgery + HIPEC procedure in the context of a multidisciplinary team management in an experienced cancer centre.
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Yonemura Y, Canbay E, Endou Y, Ishibashi H, Mizumoto A, Miura M, Li Y, Liu Y, Takeshita K, Ichinose M, Takao N, Hirano M, Sako S, Tsukiyama G. Peritoneal cancer treatment. Expert Opin Pharmacother 2014; 15:623-36. [PMID: 24617975 DOI: 10.1517/14656566.2014.879571] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION In the past, peritoneal surface malignancy (PSM) was considered as a final stage of cancer, and patients were offered the best supportive care. Recently, a new therapeutic alternative approach based on the combination of surgery with chemotherapy was developed. In this curative intent, the macroscopic disease was treated with cytoreductive surgery (CRS) combined with perioperative chemotherapy, including neoadjuvant chemotherapy, hyperthermic intraoperative intraperitoneal chemotherapy, extensive intraoperative peritoneal lavage and early postoperative intraperitoneal chemotherapy AREAS COVERED This article reviews the mechanisms of the formation of PSM, quantitative estimation of PSM and residual disease, multimodal treatment, value of laparoscopy, prognostic factors and patients' selection for the multimodal therapy. EXPERT OPINION Recent studies show that CRS plus intraperitoneal chemotherapy applications confer prolonged survival in patients with PSM from colorectal, gastric, ovarian, appendiceal mucinous carcinoma and diffuse malignant peritoneal mesothelioma. The comprehensive treatment is now justified as state-of-the-art for patients with peritoneal metastasis.
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Affiliation(s)
- Yutaka Yonemura
- NPO Organization to Support Peritoneal Surface Malignancy Treatment , Oosaka , Japan
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Budker VG, Monahan SD, Subbotin VM. Loco-regional cancer drug therapy: present approaches and rapidly reversible hydrophobization (RRH) of therapeutic agents as the future direction. Drug Discov Today 2014; 19:1855-70. [PMID: 25173702 DOI: 10.1016/j.drudis.2014.08.009] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2014] [Revised: 07/10/2014] [Accepted: 08/21/2014] [Indexed: 01/01/2023]
Abstract
Insufficient drug uptake by solid tumors remains the major problem for systemic chemotherapy. Many studies have demonstrated anticancer drug effects to be dose-dependent, although dose-escalation studies have resulted in limited survival benefit with increased systemic toxicities. One solution to this has been the idea of loco-regional drug treatments, which offer dramatically higher drug concentrations in tumor tissues while minimizing systemic toxicity. Although loco-regional delivery has been most prominent in cancers of the liver, soft tissues and serosal peritoneal malignancies, survival benefits are very far from desirable. This review discusses the evolution of loco-regional treatments, the present approaches and offers rapidly reversible hydrophobization of drugs as the new future direction.
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Iimuro Y, Ohashi K, Suzumura K, Hai S, Tanaka S, Nakamura I, Kondo Y, Asano Y, Okada T, Hirano T, Kuroda N, Hirota S, Fujimoto J. Rare form of extraovarian primary peritoneal papillary serous carcinoma with solitary cystic lesion mimicking a liver tumor; report of a case. Clin J Gastroenterol 2013; 6:145-9. [PMID: 26181452 DOI: 10.1007/s12328-013-0361-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2012] [Accepted: 01/10/2013] [Indexed: 11/25/2022]
Abstract
Extraovarian primary peritoneal serous papillary carcinoma (EOPPC) has a similar clinical presentation to that of ovarian cancer in advanced stages, such as peritoneal dissemination and a large amount of ascites, while EOPPC with a solitary tumor is very rare. We report here a 47-year-old Japanese woman with solitary form of EOPPC mimicking a liver tumor. Ovaries of both sides had no malignant lesion, which was histologically confirmed. Histological examination revealed that the tumor was located at the right diaphragm and partially invaded into the liver, and papillary or ductal proliferation of the tumor cells with an occasional appearance of psammoma bodies was detected. Immunohistologically, the tumor cells were positive for CA 125 and Ber-EP4 and negative for D2-40 or calretinin, ruling out the possibility of mesothelioma, and the diagnosis of the tumor was EOPPC. After the operation, the patient received chemotherapy with carboplatin and paclitaxel, but died 10 months later due the progression of recurrence. The present case is very rare form of EOPPC without any ascites or peritoneal dissemination.
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Affiliation(s)
- Yuji Iimuro
- Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
| | - Koichiro Ohashi
- Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Kazuhiro Suzumura
- Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Seikan Hai
- Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Shogo Tanaka
- Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Ikuo Nakamura
- Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Yuichi Kondo
- Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Yasukane Asano
- Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Toshihiro Okada
- Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Tadamichi Hirano
- Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Nobukazu Kuroda
- Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
| | - Seiichi Hirota
- Department of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Japan
| | - Jiro Fujimoto
- Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan
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Coccolini F, Catena F, Manfredi R, Lotti M, Frigerio L, Ansaloni L. Advanced ovarian cancer: Neoadjuvant chemotherapy plus surgery and HIPEC as up-front treatment. World J Obstet Gynecol 2012; 1:55-59. [DOI: 10.5317/wjog.v1.i4.55] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Epithelial ovarian cancer (EOC) is one of the most common malignancies and one of the principal causes of death in gynecological neoplasms. The majority of EOC patients present with an advanced International Federation of Gynecology and Obstetrics stage disease. The current standard treatment for these patients consists of complete cytoreduction and combined systemic chemotherapy of a platinum agent and paclitaxel. Even if the majority of patients with EOC respond to first-line platinum based chemotherapy, almost 20% of them are resistant or refractory. According to these data, the main risk is for a certain number of patients to have undergone cytoreductive surgery (CRS) and subsequent hyperthermic intraoperative peritoneal chemotherapy (HIPEC) in a useful way. Radical surgery, especially in advanced cases, is associated with a high incidence of postoperative morbidity and mortality, which could be increased by the HIPEC. Every effort should be made for previously selected patients to improve outcome and optimize resources. Over the last decade, new options have been introduced to prolong survival. Improved long-term results can be achieved using CRS in combination with intraoperative HIPEC. This combination has also been used in an up-front setting. Controversial outcomes have been reported for neoadjuvant platinum-based chemotherapy. Different papers have been published reporting discordant results. Further studies are needed.
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Rafii A, Stoeckle E, Jean-Laurent M, Ferron G, Morice P, Houvenaeghel G, Lecuru F, Leblanc E, Querleu D. Multi-center evaluation of post-operative morbidity and mortality after optimal cytoreductive surgery for advanced ovarian cancer. PLoS One 2012; 7:e39415. [PMID: 22844394 PMCID: PMC3402488 DOI: 10.1371/journal.pone.0039415] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2011] [Accepted: 05/24/2012] [Indexed: 11/18/2022] Open
Abstract
PURPOSE While optimal cytoreduction is the standard of care for advanced ovarian cancer, the related post-operative morbidity has not been clearly documented outside pioneering centers. Indeed most of the studies are monocentric with inclusions over several years inducing heterogeneity in techniques and goals of surgery. We assessed the morbidity of optimal cytoreduction surgery for advanced ovarian cancer within a short inclusion period in 6 referral centers dedicated to achieve complete cytoreduction. PATIENTS AND METHODS The 30 last optimal debulking surgeries of 6 cancer centers were included. Inclusion criteria included: stage IIIc- IV ovarian cancer and optimal surgery performed at the site of inclusion. All post-operative complications within 30 days of surgery were recorded and graded using the Memorial secondary events grading system. Student-t, Chi2 and non-parametric statistical tests were performed. RESULTS 180 patients were included. There was no demographic differences between the centers. 63 patients underwent surgery including intestinal resections (58 recto-sigmoid resection), 24 diaphragmatic resections, 17 splenectomies. 61 patients presented complications; One patient died post-operatively. Major (grade 3-5) complications requiring subsequent surgeries occurred in 21 patients (11.5%). 76% of patients with a major complication had undergone an ultraradical surgery (P = 0.004). CONCLUSION While ultraradical surgery may result in complete resection of peritoneal disease in advanced ovarian cancer, the associated complication rate is not negligible. Patients should be carefully evaluated and the timing of their surgery optimized in order to avoid major complications.
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Ansaloni L, Agnoletti V, Amadori A, Catena F, Cavaliere D, Coccolini F, De Iaco P, Di Battista M, Framarini M, Gazzotti F, Ghermandi C, Kopf B, Saponara M, Tauceri F, Vallicelli C, Verdecchia GM, Pinna AD. Evaluation of extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced epithelial ovarian cancer. Int J Gynecol Cancer 2012; 22:778-85. [PMID: 22572845 DOI: 10.1097/igc.0b013e31824d836c] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE Although standard treatment for advanced epithelial ovarian cancer (EOC) consists of surgical debulking and intravenous platinum- and taxane-based chemotherapy, favorable oncological outcomes have been recently reported with the use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of the study was to analyze feasibility and results of CRS and HIPEC in patients with advanced EOC. MATERIALS/METHODS This is an open, prospective phase 2 study including patients with primary or recurrent peritoneal carcinomatosis due to EOC. Thirty-nine patients with a mean (SD) age of 57.3 (9.7) years (range, 34-74 years) were included between September 2005 and December 2009. Thirty patients (77%) had recurrent EOC and 9 (23%) had primary EOC. RESULTS For HIPEC, cisplatin and paclitaxel were used for 11 patients (28%), cisplatin and doxorubicin for 26 patients (66%), paclitaxel and doxorubicin for 1 patient (3%), and doxorubicin alone for 1 patient (3%). The median intra-abdominal outflow temperature was 41.5°C. The mean peritoneal cancer index (PCI) was 11.1 (range, 1-28); and according to the intraoperative tumor extent, the tumor volume was classified as low (PCI <15) or high (PCI ≥15) in 27 patients (69%) and 12 patients (31%), respectively. Microscopically complete cytoreduction was achieved for 35 patients (90%), macroscopic cytoreduction was achieved for 3 patients (7%), and a gross tumor debulking was performed for 1 patient (3%). Mean hospital stay was 23.8 days. Postoperative complications occurred in 7 patients (18%), and reoperations in 3 patients (8%). There was one postoperative death. Recurrence was seen in 23 patients (59%) with a mean recurrence time of 14.4 months (range, 1-49 months). CONCLUSIONS Hyperthermic intraperitoneal chemotherapy after extensive CRS for advanced EOC is feasible with acceptable morbidity and mortality. Complete cytoreduction may improve survival in highly selected patients. Additional follow-up and further studies are needed to determine the effects of HIPEC on survival.
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MESH Headings
- Adenocarcinoma, Mucinous/mortality
- Adenocarcinoma, Mucinous/pathology
- Adenocarcinoma, Mucinous/therapy
- Adult
- Aged
- Antineoplastic Combined Chemotherapy Protocols/therapeutic use
- Cisplatin/administration & dosage
- Combined Modality Therapy
- Cystadenocarcinoma, Serous/mortality
- Cystadenocarcinoma, Serous/pathology
- Cystadenocarcinoma, Serous/therapy
- Doxorubicin/administration & dosage
- Endometrial Neoplasms/mortality
- Endometrial Neoplasms/pathology
- Endometrial Neoplasms/therapy
- Feasibility Studies
- Female
- Follow-Up Studies
- Humans
- Hyperthermia, Induced
- Injections, Intraperitoneal
- Middle Aged
- Neoplasm Recurrence, Local/mortality
- Neoplasm Recurrence, Local/pathology
- Neoplasm Recurrence, Local/therapy
- Neoplasm Staging
- Ovarian Neoplasms/mortality
- Ovarian Neoplasms/pathology
- Ovarian Neoplasms/therapy
- Paclitaxel/administration & dosage
- Peritoneal Neoplasms/mortality
- Peritoneal Neoplasms/secondary
- Peritoneal Neoplasms/therapy
- Prognosis
- Prospective Studies
- Survival Rate
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Affiliation(s)
- Luca Ansaloni
- Unit of General Surgery I, Ospedali Riuniti of Bergamo, Bergamo, Italy.
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Brücher BLDM, Piso P, Verwaal V, Esquivel J, Derraco M, Yonemura Y, Gonzalez-Moreno S, Pelz J, Königsrainer A, Ströhlein M, Levine EA, Morris D, Bartlett D, Glehen O, Garofalo A, Nissan A. Peritoneal carcinomatosis: cytoreductive surgery and HIPEC--overview and basics. Cancer Invest 2012; 30:209-24. [PMID: 22360361 DOI: 10.3109/07357907.2012.654871] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Tumor involvement of the peritoneum-peritoneal carcinomatosis-is a heterogeneous form of cancer that had been generally regarded as a sign of systemic tumor disease and as a terminal condition. The multimodal treatment approach for patients with peritoneal carcinomatosis, which had been conceived and developed, consists of what is known as cytoreductive surgery, followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Depending on the tumor mass as assessed intraoperatively and the histopathological differentiation, patients who undergo cytoreductive surgery and HIPEC have a significant survival benefit. Mean increases in the survival period ranging from six months to up to four years have now been reported. In view of the substantial logistic effort and the extent of the surgery involved, this treatment approach represents a major challenge both for patients and for surgical oncologists, as well as for the members of the overall interdisciplinary structure required, which includes oncology, anesthesiology and intensive care, psycho-oncology, and patient management. The surgical procedures alone may take 8-14 hr. The present paper provides an overview of the basis for the approach and the use of specialized classifications and quantitative prognostic indicators.
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Affiliation(s)
- Björn L D M Brücher
- Surgical Oncology, Department of Surgery, Tübingen Comprehensive Cancer Center, University of Tübingen, Germany.
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Pili-Floury S, Royer B, Bartholin F, Crumiere N, Combe M, Chalopin JM, Pivot X, Heyd B, Chauffert B, Samain E. Protective effect of intra-peritoneal epinephrine on postoperative renal function after cisplatin-based intra-peritoneal intra-operative chemotherapy. Eur J Obstet Gynecol Reprod Biol 2011; 156:199-203. [PMID: 21306815 DOI: 10.1016/j.ejogrb.2011.01.006] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2010] [Revised: 12/15/2010] [Accepted: 01/08/2011] [Indexed: 11/24/2022]
Abstract
OBJECTIVES Intra-operative cisplatin-based intra-peritoneal chemotherapy (IPC) may alter renal function in patients with advanced ovarian cancer. The aim of this study was to describe postoperative alteration of renal function after cisplatin-based IPC and to identify risk factors for moderate to severe acute renal failure. STUDY DESIGN This prospective observational study was carried out on 77 consecutive patients who underwent cisplatin-based IPC procedures, with (n=23) or without (n=54) intra-peritoneal epinephrine, for advanced ovarian cancer. Postoperative renal function was assessed using serial serum creatinine measurements and was based on serum creatinine changes from pre-operative values, according to the risk, injury, failure, loss, end-stage kidney disease (RIFLE) classification. Patients were divided into two groups according to postoperative renal function: patients with renal injury or failure (IF group) or patients with no renal alteration or renal risk (NR group). Clinical variables were compared between the IF and NR groups using univariate and multivariate analysis. RESULTS Postoperative acute change in renal function was observed in 34 (44.2%) patients (unimodal distribution), among whom 23 patients (29.8%) constituted the IF group. In univariate analysis, the absence of epinephrine in the IPC bath, a higher duration of severe hypotension, a lower postoperative blood protein level, and a lower volume of intra-operative diuresis were significantly associated with the occurrence of renal injury or failure. In multivariate analysis, the absence of epinephrine was the only factor associated with the occurrence of moderate to severe acute renal failure (odds ratio [95% confidence interval]=4.49 [1.36-14.80]). CONCLUSIONS Transient acute renal dysfunction after cisplatin-based IPC associated with cytoreductive surgery is frequent and intra-peritoneal epinephrine plays a protective role.
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Abstract
Human epithelial ovarian cancer (EOC) is the most lethal neoplasm affecting the female genital tract, and is characterized by overexpression of vascular endothelial growth factor (VEGF) and growth as ascites. Anti-VEGF strategies are currently used in EOC therapy with promising results; however, molecular targeting of specific VEGF receptors on the cancer cells themselves has not been explored to date. We previously showed that activation of a VEGF/VEGFR2 signaling loop in EOC cells supports their survival in suspension, and short-term pharmacological inhibition of this loop increased EOC cell apoptosis in vitro. In this study, we stably knocked down VEGFR2 in OVCAR-3 and SKOV-3 EOC cells using short hairpin RNA (shRNA), an RNA interference strategy that could potentially overcome chemoresistance arising with angiogenic inhibitors. Unexpectedly, we observed an induction of more aggressive cellular behavior in transfected cells, leading to increased growth in mouse xenografts, enhanced accumulation of ascites, increased VEGF and neuropilin-1 (NRP-1) expression, and decreased expression of adhesion proteins, notably cadherins and integrins. Sonic hedgehog (SHH) pathways do not seem to be involved in the upregulation of NRP-1 message in VEGFR2 knockdown cells. Supporting our mouse model, we also found a significant increase in the ratio between NRP-1 and VEGFR2 with increasing tumor grade in 80 cases of human EOC. The change in EOC behavior that we report in this study occurred independent of the angiogenic response and shows the direct effect of VEGF blockade on the cancer cells themselves. Our findings highlight the possible confounding events that may affect the usefulness of RNAi in a therapeutic setting for disrupting EOC cell survival in ascites.
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Affiliation(s)
- Sirin A. I. Adham
- Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada N1G 2W1
| | | | - Brenda L. Coomber
- Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada N1G 2W1
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Cytoreductive surgery for recurrent ovarian cancer: a meta-analysis. Gynecol Oncol 2008; 112:265-74. [PMID: 18937969 DOI: 10.1016/j.ygyno.2008.08.033] [Citation(s) in RCA: 240] [Impact Index Per Article: 14.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2008] [Revised: 08/22/2008] [Accepted: 08/23/2008] [Indexed: 01/23/2023]
Abstract
OBJECTIVE To determine the relative effect of multiple prognostic variables on overall post-recurrence survival time among cohorts of patients with recurrent ovarian cancer undergoing cytoreductive surgery. METHODS Forty cohorts of patients with recurrent ovarian cancer (2019 patients) meeting study inclusion criteria were identified from the MEDLINE database (1983-2007). Simple and multiple linear regression analyses, with weighted correlation calculations, were used to assess the effect on median post-recurrence survival time of the following variables: year of publication, age, disease-free interval, localized disease, tumor grade and histology, the proportion of patients undergoing complete cytoreductive surgery, requirement for bowel resection, and the sequence of cytoreductive surgery and salvage chemotherapy. RESULTS The mean weighted median disease-free interval prior to cytoreductive surgery was 20.2 months, and the mean weighted median overall post-recurrence survival time was 30.3 months. The weighted mean proportion of patients in each cohort undergoing complete cytoreductive surgery was 52.2%. Median survival improved with increasing year of publication (p=0.009); however, the only statistically significant clinical variable independently associated with post-recurrence survival time was the proportion of patients undergoing complete cytoreductive surgery (p=0.019). After controlling for all other factors, each 10% increase in the proportion of patients undergoing complete cytoreductive surgery was associated with a 3.0 month increase in median cohort survival time. CONCLUSIONS Among patients undergoing operative intervention for recurrent ovarian cancer, the proportion of patients undergoing complete cytoreductive surgery is independently associated with overall post-recurrence survival time. For this select group of patients, the surgical objective should be resection of all macroscopic disease.
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Suh JH, Kim YH, Chang ED. Primary papillary serous carcinoma of the peritoneum diagnosed by video-assisted thoracoscopic surgery: Report of a case. Surg Today 2008; 38:743-6. [DOI: 10.1007/s00595-007-3709-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2007] [Accepted: 11/28/2007] [Indexed: 11/24/2022]
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Cotte E, Glehen O, Mohamed F, Lamy F, Falandry C, Golfier F, Gilly FN. Cytoreductive surgery and intraperitoneal chemo-hyperthermia for chemo-resistant and recurrent advanced epithelial ovarian cancer: prospective study of 81 patients. World J Surg 2007; 31:1813-1820. [PMID: 17629740 DOI: 10.1007/s00268-007-9146-8] [Citation(s) in RCA: 127] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE There is no standardized treatment for patients with chemo-resistant or recurrent advanced ovarian cancer. Locoregional treatments combining cytoreductive surgery and intraperitoneal chemohyperthermia (HIPEC) may improve survival for locoregional disease. PATIENTS AND METHODS A prospective single center study of 81 patients with recurrent or chemo-resistant peritoneal carcinomatosis from ovarian cancer was performed. Patients were treated by maximal cytoreductive surgery combined with HIPEC (with cisplatinum at 20 mg/m(2)/L). A total of 47 patients were included for their third, fourth, fifth, sixth, or seventh surgical look. Altogether, 54 patients presented with extensive carcinomatosis (malignant nodules of >5 mm). RESULTS Complete macroscopic resection (CCR-0) was achieved in 45 patients. Mortality and morbidity rates were 2.5% and 13.6%, respectively. With a median follow-up of 47.1 months, the overall and disease-free median survivals were 28.4 and 19.2 months, respectively. Carcinomatosis extent and completeness of cytoreduction (p = 0.02 and p <0.001, respectively) were identified as independent prognostic factors. For CCR-0 patients, overall and disease-free survivals were 54.9 and 26.9 months, respectively. CONCLUSION Salvage therapy combining optimal cytoreductive surgery and HIPEC may achieve long-term survival in selected patients with recurrent or chemo-resistant ovarian cancer. This strategy may be most effective in patients with limited carcinomatosis or when cytoreductive surgery provides sufficient downstaging.
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Affiliation(s)
- Eddy Cotte
- Department of Oncologic Surgery, Centre Hospitalo-Universitaire Lyon Sud, 69495, Pierre Bénite, Cedex, France
- EA 3738, UCBL, Faculté de Médicine Lyon Sud, BP 12, 69921, Oullins, Cedex, France
| | - Olivier Glehen
- Department of Oncologic Surgery, Centre Hospitalo-Universitaire Lyon Sud, 69495, Pierre Bénite, Cedex, France.
- EA 3738, UCBL, Faculté de Médicine Lyon Sud, BP 12, 69921, Oullins, Cedex, France.
| | - Faheez Mohamed
- School of Surgical and Reproductive Sciences, Newcastle upon Tyne, UK
| | - Franck Lamy
- Department of Oncologic Surgery, Centre Hospitalo-Universitaire Lyon Sud, 69495, Pierre Bénite, Cedex, France
- EA 3738, UCBL, Faculté de Médicine Lyon Sud, BP 12, 69921, Oullins, Cedex, France
| | - Claire Falandry
- EA 3738, UCBL, Faculté de Médicine Lyon Sud, BP 12, 69921, Oullins, Cedex, France
- Department of Medical Oncology, CHLS-HCL, 69495, Pierre Bénite, Cedex, France
| | - François Golfier
- EA 3738, UCBL, Faculté de Médicine Lyon Sud, BP 12, 69921, Oullins, Cedex, France
- Department of Gynecologic surgery, Centre Hospitalo-Universitaire Lyon Sud, 69495, Pierre Bénite, Cedex, France
| | - Francois Noel Gilly
- Department of Oncologic Surgery, Centre Hospitalo-Universitaire Lyon Sud, 69495, Pierre Bénite, Cedex, France
- EA 3738, UCBL, Faculté de Médicine Lyon Sud, BP 12, 69921, Oullins, Cedex, France
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Nam JH, Kim YM, Jung MH, Kim KR, Yoo HJ, Kim DY, Kim JH, Kim YT, Mok JE. Primary peritoneal carcinoma: experience with cytoreductive surgery and combination chemotherapy. Int J Gynecol Cancer 2006; 16:23-8. [PMID: 16445605 DOI: 10.1111/j.1525-1438.2006.00314.x] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
The objective of this study was to review the clinical outcome and prognosis of patients with primary peritoneal carcinoma (PPC) treated with cytoreductive surgery and combination chemotherapy. We retrospectively reviewed the charts of 27 patients with histologically confirmed PPC, treated between March 1990 and February 2004 at Asan Medical Center, South Korea. The review included demographic data, pathologic findings, treatments, and outcomes. The mean age of the 27 patients was 57.5 +/- 7.2 years, and the rate of optimal cytoreduction was 70.4%. Seven patients had stage IIIB, 17 had stage IIIC, and 3 had stage IV; all patients received adjuvant chemotherapy. There were 4 patients with progressive disease, 5 partial responders, and 15 complete responders; the remaining 3 patients were nonevaluable. At the time of the review, 10 patients were alive without evidence of disease, 3 were alive with disease, and 14 had died from disease. The median overall survival time was 41 months, and the overall 5-year survival rate was 18.1%. Patients who had optimal cytoreduction had a longer median survival (42 months) than those who had suboptimal cytoreduction (10 months; P < 0.05). Combination chemotherapy after optimal cytoreductive surgery may be effective in the treatment of patients with PPC.
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Affiliation(s)
- J H Nam
- Department of Obstetrics and Gynecology, Asan Medical Center, College of Medicine, University of Ulsan, 388-1 Pungnap-2-dong, Songpa-gu, Seoul 138-736, South Korea
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Piso P, Dahlke MH, Loss M, Schlitt HJ. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal carcinomatosis from ovarian cancer. World J Surg Oncol 2004; 2:21. [PMID: 15222884 PMCID: PMC446210 DOI: 10.1186/1477-7819-2-21] [Citation(s) in RCA: 96] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2004] [Accepted: 06/28/2004] [Indexed: 02/08/2023] Open
Abstract
Background In selected patients with peritoneal carcinomatosis from ovarian cancer prognosis can be improved by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Methods Between September 1995 and February 1999, 19 patients (mean age 52 years, range 30–72 years) with peritoneal carcinomatosis from primary or recurrent epithelial ovarian carcinoma were operated with the aim of complete macroscopical cytoreduction. Surgery was followed by intraoperative HIPEC. The data was analyzed retrospectively. Results Eleven patients had recurrent and 8 primary ovarian cancer. The median progression free interval was 18 months (range 6–36 months). Macroscopically complete cytoreduction was achieved in 9 patients. Cisplatin (n = 16) or mitoxantrone (n = 3) were used for the intraoperative chemotherapy. The median intraabdominal inflow temperature was 41.5°C. Complications occurred in seven patients. Most frequent complications were anastomotic leakage (2/19) and intraabdominal abscess formation (2/19). One patient died postoperatively. The mean (± SD) overall survival time was 33(± 6) months with a 5-year survival rate of 15%. The survival was found to be influenced by the completeness of cytoreduction (44 ± 11 vs. 25 ± 6 months, p = 0.40), tumor volume (54 ± 10 versus 16 ± 4, p = 0.002) and presence of lymph node (38 ± 8 vs. 20 ± 8 months, p= 0.2) or liver metastases (51 ± 9 vs. 21 ± 6 months, p = 0.06). Conclusions Cytoreductive surgery combined with HIPEC is feasible and is associated with a reasonable morbidity and mortality. Complete cytoreduction may improve survival in select group of patients with low tumor volume and no organ metastases.
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Affiliation(s)
- Pompiliu Piso
- Department for Visceral and Transplant Surgery, Medical School of Hannover, 30623 Hannover, Germany
| | | | - Martin Loss
- Department for Surgery, University of Regensburg, 93053 Regensburg, Germany
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