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1.
Ann Surg Oncol ; 29(12): 7553-7563, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35876926

ABSTRACT

BACKGROUND: Survival of patients affected by mucinous appendiceal neoplasms with peritoneal dissemination (PD) is mainly related to histopathological features. However, prognostic stratification is still a concern, as the clinical course of the disease is often unpredictable. The aim of this study is to construct and externally validate a nomogram predicting disease-free survival (DFS) in mucinous appendiceal neoplasms with PD treated by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). PATIENTS AND METHODS: Patients treated in two referral centers were included: Hospital General Universitario Gregorio Marañón, Madrid, Spain (derivation cohort) and Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy (validation cohort). Cox regression analysis identified factors associated with shorter DFS in the derivation cohort. The nomogram performance was externally evaluated in the validation cohort using concordance index and calibration plots. Histology was classified according to the Peritoneal Surface Oncology Group International (PSOGI). RESULTS: The derivation cohort included 95 patients, and the validation cohort 348. Five-year DFS rates were 51.5 and 62%, respectively. Cox regression analysis (derivation cohort) identified PSOGI histology of the peritoneal components, number of preoperative elevated tumor marker, and peritoneal disease extent, as assessed by peritoneal carcinomatosis index, to be predictors of DFS. The model's predictive capacity was higher than that of PSOGI classification alone, with respective concordance indexes of 0.702 ± 0.023 and 0.610 ± 0.018 (validation cohort). The nomogram approximated the perfect model in the calibration plots at 3- and 5-year DFS. CONCLUSIONS: An easy-to-use model that provides better prognostic stratification than histopathological features has been constructed. This nomogram may help clinicians in individualized survival predictions and informed clinical decision-making.


Subject(s)
Adenocarcinoma, Mucinous , Appendiceal Neoplasms , Appendix , Hyperthermia, Induced , Peritoneal Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Appendiceal Neoplasms/pathology , Appendix/pathology , Biomarkers, Tumor , Combined Modality Therapy , Cytoreduction Surgical Procedures/adverse effects , Humans , Hyperthermia, Induced/adverse effects , Hyperthermic Intraperitoneal Chemotherapy , Nomograms , Peritoneal Neoplasms/surgery , Retrospective Studies , Survival Rate
2.
Updates Surg ; 74(4): 1271-1279, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35606625

ABSTRACT

Despite operative benefit and oncological non-inferiority, videolaparoscopic (VLS) colorectal surgery is still relatively underutilized. This study analyzes the results of a program for the implementation of VLS colorectal surgery started in an Italian comprehensive cancer center shortly before COVID-19 outbreak. A prospective database was reviewed. The study period was divided in four phases: Phase-1 (Open surgery), Phase-2 (Discretional phase), Phase-3 (VLS implementation phase), and Phase-4 (VLS consolidation phase). Formal surgical and perioperative protocols were adopted from Phase-3. Postoperative complications were scored by the Clavien-Dindo classification. 414 surgical procedures were performed during Phase-1, 348 during Phase-2, 360 during Phase-3, and 325 during Phase-4. In the four phases, VLS primary colorectal resections increased from 11/214 (5.1%), to 55/163 (33.7%), 85/151 (57.0%), and 109/147 (74.1%), respectively. The difference was statistically significant (P < 0.001). All-type VLS procedures were 16 (3.5%), 61 (16.2%), 103 (27.0%), and 126 (38.6%) (P < 0.001). Conversions to open surgery of attempted laparoscopic colorectal resections were 17/278 in the overall series (6.1%), and 12/207 during Phase-3 and Phase-4 (4.3%). Severe (grades IIIb-to-V) postoperative complications of VLS colorectal resections were 9.1% in Phase-1, 12.7% in Phase-2, 12.8% in Phase-3, and 5.3% in Phase-4 (P = 0.677), with no significant differences with open resections in each of the four phases: 9.4% (P = 0.976), 11.1% (P = 0.799), 13.8% (P = 1.000), and 8.3% (P = 0.729). Despite the difficulties deriving from the COVID-19 outbreak, our experience suggests that volume of laparoscopic colorectal surgery can be significantly and safely increased in a specialized surgical unit by means of strict operative protocols.


Subject(s)
COVID-19 , Colorectal Neoplasms , Colorectal Surgery , Laparoscopy , COVID-19/epidemiology , Colorectal Neoplasms/complications , Humans , Laparoscopy/methods , Pandemics , Postoperative Complications/etiology , Retrospective Studies
3.
London; European Society of Surgical Oncology; Feb. 28, 2020. 25 p.
Non-conventional in English | BIGG | ID: biblio-1117236

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.


Subject(s)
Humans , Female , Pseudomyxoma Peritonei/prevention & control , Cytoreduction Surgical Procedures/instrumentation , Hyperthermia, Induced/instrumentation
4.
Ann Oncol ; 27(11): 2097-2103, 2016 11.
Article in English | MEDLINE | ID: mdl-27502722

ABSTRACT

BACKGROUND: Outcome of pseudomyxoma peritonei (PMP) after cytoreductive surgery (CRS) and hypertermic intraperitoneal chemotherapy (HIPEC) is heterogeneous even after adjusting for clinico-pathological prognostic variables. The identification of additional prognostic or even predictive biomarkers is an unmet clinical need. PATIENTS AND METHODS: Forty patients with mucinous appendiceal tumors and PMP were clinically eligible and had evaluable tumor samples obtained after CRS and HIPEC. We carried out next-generations sequencing (NGS) of 50 gene's hotspot regions contained in the Hotspot Cancer Panel v2 using the Ion Torrent Personal Genome Machine platform (Life Technologies). RESULTS: KRAS and GNAS mutations were found in 72% and 52%, and their allelic frequency was below 10% in 55% and 43% of samples, respectively. KRAS and GNAS mutations were associated with worse progression-free survival (PFS) at univariate analysis (P = 0.006 and 0.011, respectively). At multivariate analysis, only KRAS mutations were independently associated with PFS (P = 0.012); GNAS mutations were not-being significantly associated with other poor prognostic features such as incomplete cytoreduction or KRAS mutations. Validation of results was carried out in an independent bi-institutional cohort of 25 patients and the prognostic effect of KRAS mutations was again confirmed in the multivariate model (P = 0.029). NGS approach allowed the discovery of other potentially druggable mutations such as those in PI3K, AKT, LKB1, FGFR3 and PDGFRA. CONCLUSIONS: Given the homogeneity of this series and the sensitivity of NGS in this low-cellularity tumor, we demonstrated for the first time a poor prognostic role of KRAS mutations.


Subject(s)
Biomarkers, Tumor/genetics , Chromogranins/genetics , GTP-Binding Protein alpha Subunits, Gs/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Pseudomyxoma Peritonei/genetics , Adult , Aged , Cisplatin/administration & dosage , Combined Modality Therapy , Cytoreduction Surgical Procedures , Disease-Free Survival , Female , High-Throughput Nucleotide Sequencing , Humans , Hyperthermia, Induced , Male , Middle Aged , Mutation , Prognosis , Pseudomyxoma Peritonei/drug therapy , Pseudomyxoma Peritonei/pathology , Pseudomyxoma Peritonei/surgery
5.
Eur J Surg Oncol ; 41(8): 1097-105, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26026742

ABSTRACT

AIMS: Inflammation-based scores such as neutrophil-lymphocyte ratio (NLR) and Onodera nutritional index (ONI) have been identified as new prognosticators in several tumors. We conducted a prognostic analysis of these markers and performed a risk stratification of PMP patients submitted to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: 226 patients from two peritoneal surface malignancies centers participated in this study. Cox proportional modeling was used to select predictors of overall survival (OS) among baseline inflammation-based scores, serum tumor markers, clinical and surgical variables. Risk stratification was done using conditional inference tree model. RESULTS: One hundred eighty-two cases had diffuse peritoneal adenomucinosis subtype. Fifty-four cases had received previous systemic chemotherapy. The means of ONI and NLR were 51.4 (SD = 9.8) and 3.2 (SD = 2.3), respectively. Two hundred ten cases were optimally cytoreduced. Cox analysis identified completeness of cytoreduction, histological subtype, previous systemic chemotherapy, NLR, and CA 19-9 as independent prognosticators. Conditional inference tree method identified two poor prognostic subsets: NLR ≤2.7 and CA 19-9>336 (5yr-OS = 15%) and NLR >2.7 and ONI ≤42 (5yr-OS = 30%). CONCLUSIONS: NLR, ONI, and CA 19-9 are new prognosticators that contributed to improve prediction of OS in PMP patients treated by CRS and HIPEC. These markers allowed a risk stratification that could optimize therapeutic management of PMP patients.


Subject(s)
Antineoplastic Agents/administration & dosage , Biomarkers, Tumor/blood , Cytoreduction Surgical Procedures/methods , Hyperthermia, Induced/methods , Peritoneal Neoplasms/therapy , Pseudomyxoma Peritonei/therapy , Risk Assessment , Combined Modality Therapy , Female , Humans , Injections, Intraperitoneal , Italy/epidemiology , Male , Middle Aged , Peritoneal Neoplasms/blood , Peritoneal Neoplasms/mortality , Prognosis , Proportional Hazards Models , Pseudomyxoma Peritonei/blood , Pseudomyxoma Peritonei/mortality , Retrospective Studies , Survival Rate/trends
6.
Minerva Chir ; 70(3): 195-215, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25752673

ABSTRACT

Peritoneal surface malignancies (PSM) include peritoneal metastases from gastrointestinal and gynecological tumor and rare primary peritoneal malignancies. PSM have been historically considered as end-stage metastatic conditions only amenable to palliative options. Only in recent years, better knowledge of their natural history and pattern of disease-progression has evolved into the concept that PSM represent a local-regional disease stage. A novel treatment approach aiming at definitive disease eradication combines aggressive cytoreductive surgery (CRS) and perioperative local-regional chemotherapy, either in the form of hyperthermic intraperitoneal chemotherapy (HIPEC), or normothermic early postoperative chemotherapy. Such a combined treatment approach has reportedly resulted in a survival improvement over historical controls, and it is gaining an increasing acceptance as standard of care for selected patients with PSM. This article reviews the most recent literature data on the surgical and comprehensive management of PSM. Epidemiology and natural history of the different disease entities are briefly discussed. Cytoreductive surgical procedures and intraperitoneal chemotherapy administration techniques are described, focusing on the technical variants adopted in our institution. Indications for combined treatment, and outcomes following CRS/HIPEC, are addressed, including peritoneal metastases from appendiceal tumors (pseudomyxoma peritonei), colorectal cancer, gastric cancer, epithelial ovarian cancer, and rare primary peritoneum based neoplasms, such as diffuse malignant peritoneal mesothelioma, and primary peritoneal (extra-ovarian) serous papillary carcinoma.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant , Cytoreduction Surgical Procedures , Gastrointestinal Neoplasms/therapy , Hyperthermia, Induced , Neoplasms, Glandular and Epithelial/therapy , Ovarian Neoplasms/therapy , Peritoneal Neoplasms/therapy , Pseudomyxoma Peritonei/therapy , Carcinoma, Ovarian Epithelial , Chemotherapy, Adjuvant/methods , Evidence-Based Medicine , Gastrointestinal Neoplasms/mortality , Gastrointestinal Neoplasms/pathology , Humans , Infusions, Parenteral/methods , Meta-Analysis as Topic , Neoplasms, Glandular and Epithelial/mortality , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Patient Selection , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/secondary , Pseudomyxoma Peritonei/pathology , Randomized Controlled Trials as Topic , Risk Factors , Treatment Outcome
7.
Br J Surg ; 101(13): 1758-65, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25329419

ABSTRACT

BACKGROUND: The learning curves for cytoreductive surgery with intraperitoneal chemotherapy for treatment of pseudomyxoma peritonei (PMP) were explored between international centres/surgeons to identify institutional or other factors that might affect performance. METHODS: Data from patients with PMP treated with the combined procedure across 33 international centres between 1993 and 2012 were analysed retrospectively. A risk-adjusted sequential probability ratio test was conducted after defining the target outcome as early oncological failure (disease progression within 2 years of treatment), an acceptable risk for the target outcome (odds ratio) of 2, and type I/II error rates of 5 per cent. The risk prediction model was elaborated and patients were evaluated sequentially for each centre/surgeon. The learning curve was considered to be overcome and proficiency achieved when the odds ratio for early oncological failure became smaller than 2. RESULTS: Rates of optimal cytoreduction, severe postoperative morbidity and early oncological failure were 84·4, 25·7 and 29·0 per cent respectively. The median annual centre volume was 17 (range 6-66) peritoneal malignancies. Only eight of the 33 centres and six of 47 surgeons achieved proficiency after a median of 100 (range 78-284) and 96 (86-284) procedures respectively. The most important institutional factor affecting surgical performance was centre volume. CONCLUSION: The learning curve is extremely long, so centralization and/or networking of centres is necessary to assure quality of services. One centre for every 10-15 million inhabitants would be ideal.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Clinical Competence/standards , Cytoreduction Surgical Procedures/standards , Learning Curve , Peritoneal Neoplasms/surgery , Pseudomyxoma Peritonei/surgery , Chemotherapy, Cancer, Regional Perfusion/methods , Combined Modality Therapy/methods , Cytoreduction Surgical Procedures/education , Female , Humans , Hyperthermia, Induced/methods , Male , Middle Aged , Peritoneal Neoplasms/drug therapy , Pseudomyxoma Peritonei/drug therapy , Retrospective Studies
8.
Dis Colon Rectum ; 57(7): 858-68, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24901687

ABSTRACT

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is an effective but potentially morbid treatment for colorectal cancer peritoneal metastases. The impact of treatment-related morbidity on long-term survival has been reported in various malignancies, but it has never been assessed in this clinical setting. OBJECTIVE: The aim of this study was to assess the impact of major postoperative complications on oncological outcomes after cytoreduction and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases. DESIGN: Two prospective databases were reviewed. Major complications were defined as grade 3 to 5 according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. The extent of peritoneal involvement was scored by the use of the Peritoneal Cancer Index. SETTINGS: This study was conducted in 2 high-volume peritoneal malignancy management centers. PATIENTS: One hundred one consecutive patients with peritoneal metastases potentially amenable to macroscopically complete cytoreduction were selected. INTERVENTIONS: Peritonectomy procedures and multivisceral resections were used to remove all macroscopic tumor, and mitomycin-C plus cisplatin-based hyperthermic intraperitoneal chemotherapy was used to control microscopic residual disease. MAIN OUTCOME MEASURES: The primary outcomes measured were overall and disease-specific survival. RESULTS: Mortality and major morbidity were 3.0%, and 23.8%. Median follow-up was 44.9 months (95% CI, 24.1-65.7). Five-year disease-specific survival was 14.3% for patients who experienced major complications and 52.3% for those who did not (p = 0.001). Five-year overall survival was 11.7% for patients who experienced major complications, and 58.8% for those who did not (p = 0.003). At multivariate analysis, major morbidity correlated to both worse overall and disease-specific survival, along with a Peritoneal Cancer Index >19, and suboptimal cytoreduction. Poor performance status correlated only to worse disease-specific survival, and liver metastases correlated to worse overall survival. Longer operative time (OR, 4.1; 95% CI, 1.3-12.6; p = 0.01) and Peritoneal Cancer Index >19 (OR, 2.6; 95% CI, 1.1-6.0; p = 0.02) were independent risk factors for major morbidity. LIMITATIONS: This study is limited by its observational design. CONCLUSIONS: The prevention of major complications, by refining surgical technique and patient selection, is crucial because it affects oncologic outcome.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/pathology , Hyperthermia, Induced/methods , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/therapy , Peritoneum/surgery , Postoperative Complications/mortality , Adult , Aged , Cisplatin/administration & dosage , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Logistic Models , Male , Middle Aged , Mitomycin/administration & dosage , Multivariate Analysis , Patient Selection , Peritoneal Neoplasms/mortality , Postoperative Complications/etiology , Retrospective Studies , Risk Factors , Survival Analysis , Treatment Outcome
9.
BJOG ; 119(7): 800-9, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22571746

ABSTRACT

OBJECTIVE: To assess the efficacy and morbidity and mortality of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent epithelial ovarian cancer (EOC). DESIGN: A retrospective study conducted using information extracted from a multi-institutional prospective database on peritoneal surface malignancies (PSMs). Setting Four Italian centres specializing in locoregional treatment of PSM. POPULATION: Patients with recurrent EOC. METHODS: Fifty-six patients underwent 57 combined procedures. CRS was performed using peritonectomy procedures and HIPEC using the closed-abdomen technique with cisplatin and doxorubicin or cisplatin and mitomycin-C. MAIN OUTCOME MEASURES: Overall survival (OS), progression-free survival (PFS), morbidity and mortality rates. RESULTS: The median age of the patients was 55.2 years (range 30-75 years). The median peritoneal cancer index was 15.2 (range 4-30). Forty-seven patients had microscopic residual disease (completeness of cytoreduction, CC-0), seven had residual disease ≤2.5 mm (CC-1) and one had residual disease >2.5 mm (CC>2). Major complications occurred in 15 patients (26.3%), and procedure-related mortality occurred in three patients (5.3%). The median follow-up time was 23.1 months. The median OS and PFS were 25.7 (95% CI 20.3-31.0) and 10.8 (95% CI 5.4-16.2) months, respectively. The 5-year OS and PFS were 23% and 7%, respectively. Independent prognostic factors affecting OS according to the multivariate analysis were Eastern Cooperative Oncology Group performance status, preoperative serum albumin, and completeness of cytoreduction. CONCLUSIONS: Patients with recurrent EOC treated with CRS and HIPEC showed promising results in terms of outcome. The combined treatment strategy could benefit subsets of patients wider than that defined for conventional secondary debulking surgery without HIPEC. These data warrant further evaluation in randomised clinical trials.


Subject(s)
Antineoplastic Agents/therapeutic use , Hyperthermia, Induced , Neoplasm Recurrence, Local/therapy , Neoplasms, Glandular and Epithelial/therapy , Ovarian Neoplasms/therapy , Peritoneal Neoplasms/therapy , Peritoneum/surgery , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Ovarian Epithelial , Cisplatin/therapeutic use , Combined Modality Therapy , Doxorubicin/therapeutic use , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Infusions, Parenteral , Middle Aged , Mitomycin/therapeutic use , Multivariate Analysis , Neoplasm Recurrence, Local/mortality , Neoplasms, Glandular and Epithelial/mortality , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/secondary , Retrospective Studies , Survival Analysis , Treatment Outcome
10.
Eur J Surg Oncol ; 37(1): 4-9, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21112721

ABSTRACT

Favorable oncological outcomes have been reported in several trials with the introduction of Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in the treatment of Advanced Epithelial Ovarian Cancer (EOC). However most of the studies testing the combined approach are observational and have been conducted in inhomogeneous series so that the evidence supporting the performance of this combined treatment is still poor. Median Overall and Disease Free Survivals of up to 64 months and 57 months, respectively have been reported. Although a rate of morbidity of up to 40% has been observed in some series the CRS + HIPEC continues to gain an increased popularity. Several prospective randomized trials are ongoing using the procedure in various time points of the disease. In this review several issues such as the impact of cytoreduction and residual disease (RD) on outcomes as well as the role of HIPEC will be updated from the literature evidence. Some controversial points HIPEC related will also be discussed. Recent experiences regarding the introduction of a more aggressive surgical approach to upper abdomen to resect peritoneal carcinomatosis (PC) allowed increased rates of optimal cytoreduction and has demonstrated an apparent better outcome. This evidence associated with the positive results phase III trial testing normothermic intraperitoneal as first-line chemotherapy is guiding some investigators to propose the CRS + HIPEC in the primary setting. Several prospective phase II and III trials have recently been launched to validate the role of the combined treatment in various time points of disease natural evolution.


Subject(s)
Antineoplastic Agents/administration & dosage , Carcinoma, Ovarian Epithelial , Combined Modality Therapy , Female , Humans , Hyperthermia, Induced , Infusions, Parenteral , Neoplasms, Glandular and Epithelial/surgery , Ovarian Neoplasms/surgery , Standard of Care
11.
Eur J Surg Oncol ; 36(11): 1047-53, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20832234

ABSTRACT

AIM: This retrospective multi-institutional study addresses the role of surgical cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of multicystic peritoneal mesothelioma (MCPM). MCPM is an uncommon tumour with uncertain malignant potential and no current standard therapy. Additionally, poorly defined pathological and biological features of this disease were investigated. METHODS: Twelve patients with MCPM underwent 14 procedures of cytoreduction and HIPEC in two Italian referral centres. Nine patients had recurrent disease after previous debulking (one operation in six patients, two in two, four in one). Biological markers related to mesothelioma origin and clinical features were assessed by immunohistochemical studies. RESULTS: Median follow-up was 64 months (range 5-148). Optimal cytoreduction (residual tumour nodules ≤2.5 mm) was performed in all the procedures. One grade IV postoperative complication (NCI/CTCAE v.3.0) and no operative death occurred. All the patients are presently alive with no evidence of disease, including two patients who underwent the procedure twice, due to locoregional disease recurrence. Five- and ten-year progression-free survival was 90% and 72%, accounting for a. statistically significant difference (P = 0.0001) with progression-free survival following previous debulking surgery (median 11 months; range 2-31). All cases showed low proliferative activity assessed by mitotic rate and Ki-67 expression. CONCLUSIONS: MCPM is a borderline tumour with a high propensity to local-regional recurrence. Definitive tumour eradication by means of cytoreduction and HIPEC seems more effective than debulking surgery in preventing disease relapse. Low mitotic rate and poor Ki-67 expression might be related to the peculiar behaviour of MCMP.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Chemotherapy, Cancer, Regional Perfusion/methods , Hyperthermia, Induced , Mesothelioma/pathology , Mesothelioma/therapy , Peritoneal Neoplasms/pathology , Peritoneal Neoplasms/therapy , Adult , Chemotherapy, Adjuvant/methods , Disease-Free Survival , Female , Humans , Infusions, Parenteral , Kaplan-Meier Estimate , Length of Stay , Male , Mesothelioma/drug therapy , Mesothelioma/surgery , Middle Aged , Neoplasm, Residual/pathology , Patient Selection , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/surgery , Prognosis , Retrospective Studies , Surgical Procedures, Operative/methods , Treatment Outcome
12.
Eur J Surg Oncol ; 36(5): 463-9, 2010 May.
Article in English | MEDLINE | ID: mdl-20363094

ABSTRACT

AIM: The aim of the present study was to address the economic cost of the innovative comprehensive approach involving cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) to treat peritoneal surface malignancies, and to compare it with the financial support received by our centre. METHODS: A retrospective economic analysis was carried out on 382 consecutive procedures performed at a tertiary referral centre during the period 1995-2008. The costs of the combined therapy were estimated using the activity-based costing methodology. The financial support was assessed according to the current diagnosis-related group classification and reimbursement rates. RESULTS: The mean cost for one hospital stay was euro36,015.89 (range 28,435.24-82,189.08); mean length of stay was 24.3 days (range 9-108). In counterpart, our hospital received a total financial support of euro804,483.30, resulting in a deficit of euro1861,301.99 for the two years. CONCLUSION: The Italian current diagnosis-related groups classification does not include cytoreduction and HIPEC. This results in a relevant economic deficit for the hospitals offering this treatment option to their patients and a slow diffusion of the technique in our country. Two corrective measures are needed: to include this procedure in the official list of medical acts, and to determine its specific cost for reimbursing.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/economics , Hyperthermia, Induced/economics , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/surgery , Surgical Procedures, Operative/economics , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Combined Modality Therapy/economics , Costs and Cost Analysis , Female , Humans , Infusions, Parenteral , Insurance, Health, Reimbursement , Male , Middle Aged , Peritoneal Neoplasms/economics , Retrospective Studies , Young Adult
13.
Ann Surg Oncol ; 16(2): 463-72, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19082859

ABSTRACT

Improved survival has been reported for diffuse malignant peritoneal mesothelioma (DMPM) treated by cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC). The issue of treatment failure has never been extensively addressed. The present study assessed the failure pattern, management, and outcome of progressive DMPM following comprehensive treatment. Clinical data on 70 patients with DMPM undergoing cytoreduction and HIPEC were prospectively collected; after a median follow-up of 43 months, disease progression occurred in 38 patients. Progressive disease distribution in 13 abdominopelvic regions was analyzed. In 28 patients undergoing adequate cytoreduction (residual tumor < or =2.5 mm), clinicopathological factors correlating to disease progression in each region were investigated. Median time to progression was 9 months [95% confidence interval (CI) 1.6-35.9]. Median survival from progression was 8 months (95% CI 4-16.2). The failure pattern was categorized as peritoneal progression (n = 31), liver metastases (n = 1), abdominal lymph-node involvement (n = 2), pleural seeding (n = 4). Small bowel was the single site most commonly involved (n = 27). Residual tumor < or =2.5 mm (versus no visible) was the only independent risk factor for disease progression in epigastric region (P = 0.047), upper ileum (P = 0.029), upper jejunum (P = 0.034), and lower jejunum (P = 0.002). Progressive disease was treated with second HIPEC in 3 patients, debulking in 4, systemic chemotherapy in 16, and supportive care in 15. At multivariate analysis, time to progression <9 months (P = 0.009), poor performance status (P = 0.005), and supportive care (P = 0.003) correlated to reduced survival from progression. We conclude that minimal residual disease, compared with macroscopically complete cytoreduction, correlated to failure in critical anatomical areas, suggesting the need for maximal cytoreductive surgical efforts. In selected patients, aggressive management of progressive disease seems worthwhile.


Subject(s)
Antineoplastic Agents/therapeutic use , Chemotherapy, Cancer, Regional Perfusion , Hyperthermia, Induced , Mesothelioma/therapy , Neoplasm Recurrence, Local/diagnosis , Neoplasm, Residual/diagnosis , Peritoneal Neoplasms/therapy , Adult , Aged , Cisplatin/administration & dosage , Combined Modality Therapy , Disease Progression , Doxorubicin/administration & dosage , Female , Humans , Male , Mesothelioma/drug therapy , Mesothelioma/pathology , Mesothelioma/surgery , Middle Aged , Mitomycin/administration & dosage , Neoplasm Recurrence, Local/therapy , Neoplasm, Residual/therapy , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/surgery , Prognosis , Prospective Studies , Survival Rate , Treatment Failure , Young Adult
14.
In Vivo ; 22(1): 153-7, 2008.
Article in English | MEDLINE | ID: mdl-18396799

ABSTRACT

BACKGROUND: Multicystic peritoneal mesothelioma (MPM) is an extremely uncommon lesion with uncertain malignant potential. Multiple recurrences after surgical interventions and transition to aggressive malignancies have been reported. Here, we review our experience with cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) in the management of MPM. PATIENTS AND METHODS: Five women with MPM underwent 6 procedures of cytoreduction and close-abdomen HIPEC with cisplatin and doxorubicin. Three patients had recurrent disease after 1, 2 and 4 previous debulkings, respectively. RESULTS: Optimal cytoreduction (residual tumor nodules < or =2.5 mm) was performed in all the procedures. One grade 4 postoperative complication (NCI/CTCAE v.3.0) and no operative mortality occurred. Median follow-up was 31 months (range 3-102). MPM recurred in two patients: one is presently disease-free after a second cytoreduction with HIPEC and the other is alive with minimal stable disease. CONCLUSION: Definitive eradication by means of cytoreduction and HIPEC seems a safe and effective therapeutic option for MPM.


Subject(s)
Chemotherapy, Cancer, Regional Perfusion , Hyperthermia, Induced , Mesothelioma, Cystic/therapy , Peritoneal Neoplasms/therapy , Adult , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Mesothelioma, Cystic/mortality , Mesothelioma, Cystic/pathology , Middle Aged , Neoplasm Recurrence, Local , Neoplasm, Residual/pathology , Neoplasm, Residual/therapy , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/pathology , Reoperation , Survival Rate , Treatment Outcome
15.
Minerva Chir ; 62(6): 459-76, 2007 Dec.
Article in Italian | MEDLINE | ID: mdl-18091656

ABSTRACT

Peritoneal surface malignancy (PSM) is a clinical entity with an unfavourable prognosis, which characterizes the evolution of neoplastic diseases from the abdominal and/or pelvic organs and could also be the terminal stage of extra-abdominal tumors. Examples of diseases that can spread mainly within the peritoneal cavity are appendiceal tumors, ovarian cancer, colorectal cancer, abdominal sarcomatosis, gastric cancer and peritoneal mesothelioma. The locoregional therapy is defined as the combination of cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP). The rationale of this combined therapy for PSM is based on the natural history of this clinical entity that remains confined in the peritoneal cavity for most of its natural history. This pattern of spread would seem to indicate the potential usefulness of selectively increasing drug concentration in the tumour-bearing area by direct intraperitoneal chemotherapy instillation. This approach led to these outcomes: the median survival of colorectal carcinoma and ovarian cancer was 32 months; patients with peritoneal mesothelioma showed 57% survival at 5 years, while in patients with appendiceal mucinous tumors and pseudomyxoma peritonei (PMP) the 10 years overall survival was 78%. A significant improvement in survival was associated with hyperthermic intra-peritoneal chemotherapy (HIPEC) in patients with gastric cancer. Considering the constant increasing of diseases treatable with this procedure, more centres should be activated. The establishment of a clear policy and scientific guidelines is mandatory, in order to perform the CRS+HIPEC safely, minimizing treatment-related morbidity and mortality and maximizing the results in terms of survival and quality of life.


Subject(s)
Mesothelioma/surgery , Peritoneal Neoplasms/surgery , Pseudomyxoma Peritonei/surgery , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Combined Modality Therapy , Critical Care , Female , Humans , Hyperthermia, Induced , Infusions, Parenteral , Injections, Intraperitoneal , Male , Mesothelioma/mortality , Mesothelioma/therapy , Nutritional Support , Patient Selection , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/therapy , Postoperative Care , Postoperative Complications , Pseudomyxoma Peritonei/therapy , Quality of Life , Risk Factors , Survival Analysis , Time Factors , Treatment Outcome
17.
Ann Surg Oncol ; 14(10): 2790-7, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17661150

ABSTRACT

BACKGROUND: Multicystic peritoneal mesothelioma (MPM) and well-differentiated papillary peritoneal mesothelioma (WDPPM) are exceedingly uncommon lesions with uncertain malignant potential and no uniform treatment strategy. The aim of the current study was to review our experience with cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) in these clinical settings. METHODS: Four women with MPM and eight with WDPPM underwent 13 procedures of cytoreduction and close-abdomen HIPEC with cis-platin and doxorubicin. Seven patients had recurrent disease after previous debulking (one operation in five patients, two in one, four in one). Potential clinicopathological prognostic factors were assessed. RESULTS: Optimal cytoreduction (residual tumor nodules

Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Cancer, Regional Perfusion , Hyperthermia, Induced , Mesothelioma, Cystic/drug therapy , Mesothelioma, Cystic/surgery , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/surgery , Adult , Aged , Chemotherapy, Adjuvant , Cisplatin/administration & dosage , Combined Modality Therapy , Disease-Free Survival , Doxorubicin/administration & dosage , Female , Follow-Up Studies , Humans , Infusions, Parenteral , Mesothelioma, Cystic/mortality , Mesothelioma, Cystic/pathology , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/surgery , Neoplasm, Residual/drug therapy , Neoplasm, Residual/mortality , Neoplasm, Residual/pathology , Neoplasm, Residual/surgery , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/pathology , Reoperation
18.
Eur J Surg Oncol ; 32(6): 671-5, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16621425

ABSTRACT

AIMS: We report the effects of cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP) in the treatment of advanced/recurrent epithelial ovarian cancer (EOC) on survival, morbidity and mortality. PATIENTS: Forty EOC patients were studied. Median age was 52.5 years (range: 30-68) and median follow-up 26.1 months (range: 0.3-117.6). Most patients presented advanced disease (stage III/IV). Previous systemic chemotherapy included cisplatin-based, taxol-based or taxol/platinum containing regimens. RESULTS: After the CRS, 33 patients presented no macroscopic residual disease. Five-year overall survival was 15%; the mean overall and progression-free survivals were 41.4 and 23.9 months, respectively. The morbidity, toxicity and mortality rates were 5%, 15% and 0%, respectively. CONCLUSION: Our results suggest that CRS + IPHP merits further evaluation by a formal prospective trial.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hyperthermia, Induced , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/surgery , Adult , Aged , Cisplatin/administration & dosage , Combined Modality Therapy , Doxorubicin/administration & dosage , Female , Humans , Infusions, Parenteral , Middle Aged , Mitomycin/administration & dosage , Neoplasm Staging , Ovarian Neoplasms/pathology , Survival Rate , Treatment Outcome
19.
J Chemother ; 16 Suppl 5: 19-22, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15675470

ABSTRACT

The purpose of this study was to evaluate the feasibility and the outcome impact of cytoreductive surgery (CRS) followed by intraperitoneal hyperthermic perfusion (IPHP) in patients affected by uterine sarcoma (US). Ten US patients were treated with CRS+IPHP (closed technique, cisplatin+mitomycin C or cisplatin+doxorubicin). Median follow-up was 25 months (range: 2-61). Five patients received preoperative chemotherapy. Nine cases underwent optimal CRS. Five-year overall and progression-free survivals were 65% and 30%, respectively. There was no operative morbidity, nor mortality and nor toxicity. Six patients presented disease progression. CRS+IPHP proved feasible and safe, with encouraging outcome results, warranting confirmation by further prospective controlled trials.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Chemotherapy, Cancer, Regional Perfusion/methods , Hyperthermia, Induced/methods , Sarcoma/therapy , Uterine Neoplasms/therapy , Adult , Aged , Cisplatin/administration & dosage , Combined Modality Therapy , Doxorubicin/administration & dosage , Female , Humans , Middle Aged , Mitomycin/administration & dosage , Sarcoma/mortality , Survival Rate , Uterine Neoplasms/mortality
20.
Tumori ; 89(4 Suppl): 54-5, 2003.
Article in Italian | MEDLINE | ID: mdl-12903545

ABSTRACT

Pseudomyxoma peritonei is a rare disease characterized by a complete redistribution of mucin into the peritoneal cavity. Thirty three PMP patients referred to National Cancer Institute of Milan were submitted to 34 consecutive procedures of peritonectomy and intra peritoneal hyperthermic perfusion (IPHP). Five yrs overall survival has been 96% while 3 yrs PFS 68%. Morbility, mortality and toxicity were 18, 3 and 9% respectively. Peritonectomy associated with IPHP is the most indicated approach to cure patients with DPAM and IFG, subgroup of pseudomyxoma peritonei.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hyperthermia, Induced , Peritoneal Neoplasms/therapy , Pseudomyxoma Peritonei/therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Cisplatin/administration & dosage , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Infusions, Parenteral , Male , Middle Aged , Mitomycin/administration & dosage , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/surgery , Pseudomyxoma Peritonei/drug therapy , Pseudomyxoma Peritonei/mortality , Pseudomyxoma Peritonei/surgery , Recurrence , Survival Rate , Treatment Outcome
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