Asunto(s)
Hipertermia Inducida , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneales , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Mesotelioma Maligno/terapia , Mesotelioma/tratamiento farmacológico , Mesotelioma/patología , Neoplasias Peritoneales/patología , Procedimientos Quirúrgicos de Citorreducción , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Estudios RetrospectivosAsunto(s)
Neoplasias Colorrectales , Hipertermia Inducida , Neoplasias Peritoneales , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneales/terapia , Procedimientos Quirúrgicos de Citorreducción , Peritoneo/patología , Terapia Combinada , Neoplasias Colorrectales/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Tasa de Supervivencia , Estudios RetrospectivosRESUMEN
PURPOSE: Multimodal treatment of colorectal (CRC) peritoneal metastases (PM) includes systemic chemotherapy (SC) and surgical cytoreduction (CRS), eventually with hyperthermic intraperitoneal chemotherapy (HIPEC), in select patients. Considering lack of clear guidelines, this study was designed to analyze the role of chemotherapy and its timing in patients treated with CRS-HIPEC. METHODS: Data from 13 Italian centers with PM expertise were collected by a collaborative group of the Italian Society of Surgical Oncology (SICO). Clinicopathological variables, SC use, and timing of administration were correlated with overall survival (OS), disease-free survival (DFS), and local (peritoneal) DFS (LDFS) after propensity-score (PS) weighting to reduce confounding factors. RESULTS: A total of 367 patients treated with CRS-HIPEC were included in the propensity-score weighting. Of the total patients, 19.9% did not receive chemotherapy within 6 months of surgery, 32.4% received chemotherapy before surgery (pregroup), 28.9% after (post), and 18.8% received both pre- and post-CRS-HIPEC treatment (peri). SC was preferentially administered to younger (p = 0.02) and node-positive (p = 0.010) patients. Preoperative SC is associated with increased rate of major complications (26.9 vs. 11.3%, p = 0.0009). After PS weighting, there were no differences in OS, DFS, or LDFS (p = 0.56, 0.50, and 0.17) between chemotherapy-treated and untreated patients. Considering SC timing, the post CRS-HIPEC group had a longer DFS and LDFS than the pre-group (median DFS 15.4 vs. 9.8 m, p = 0.003; median LDFS 26.3 vs. 15.8 m, p = 0.026). CONCLUSIONS: In patients with CRC-PM treated with CRS-HIPEC, systemic chemotherapy was not associated with overall survival benefit. The adjuvant schedule was related to prolonged disease-free intervals. Additional, randomized studies are required to clarify the role and timing of systemic chemotherapy in this patient subset.
Asunto(s)
Neoplasias Colorrectales , Hipertermia Inducida , Neoplasias Peritoneales , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Procedimientos Quirúrgicos de Citorreducción , Neoplasias Colorrectales/patología , Neoplasias Peritoneales/secundario , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Tasa de Supervivencia , Estudios RetrospectivosRESUMEN
BACKGROUND: The available data on the role of perioperative systemic chemotherapy (SC) for diffuse malignant peritoneal mesothelioma (DMPM) patients undergoing (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is heterogeneous and unstandardized. This study aimed to evaluate the impact of SC on the survival outcomes of DMPM patients undergoing CRS-HIPEC and to identify prognostic factors that affect the decision to administer SC. METHODS: Patients who underwent CRS-HIPEC in the National Cancer Institute Milan (1995-2020) were retrospectively analyzed using propensity score-matching of known covariates. The patients were grouped into three groups: group A (neoadjuvant chemotherapy [NACT] and no-SC), group B (no-SC and adjuvant chemotherapy [ACT]), and group C (NACT and ACT). Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meir method, and prognostic factors were calculated using the Cox-regression method. RESULTS: After a median follow-up period of 45 months (95% confidence interval [CI], 6.348-83.652 months) for group A, 115 months (95% CI, 44.379-185.621 months) for group B, and 88 months (95% CI, 3.296-172.704 months) for group C, the study analyzed 154 DMPM patients consisting of matched group A (NACT: 60 + no-SC: 52 = 112), group B (ACT: 38 + no-SC: 38 = 76), and group C (NACT: 31 + ACT: 31 = 62). The patients undergoing ACT had better 5-year OS and PFS than the patients undergoing NACT. In the multivariate analysis, ACT was significantly associated with improved OS by 48% (hazard ratio [HR], 0.52; 95% CI, 0.280-0.965, p = 0.038). For PFS, the association of ACT did not reach statistical significance (HR, 0.531; 95% CI, 0.266-1.058; p = 0.072). CONCLUSION: The optimum treatment sequence for DMPM is CRS-HIPEC followed by adjuvant chemotherapy for high-risk patients. Upfront surgery appears preferable to NACT for patients amenable to complete CRS.
Asunto(s)
Hipertermia Inducida , Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Peritoneales , Humanos , Mesotelioma/patología , Quimioterapia Intraperitoneal Hipertérmica , Estudios Retrospectivos , Neoplasias Pulmonares/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Hipertermia Inducida/métodos , Mesotelioma Maligno/tratamiento farmacológico , Neoplasias Peritoneales/cirugía , Procedimientos Quirúrgicos de Citorreducción/métodos , Tasa de Supervivencia , Terapia CombinadaRESUMEN
INTRODUCTION: Pseudomyxoma peritonei (PMP) is a rare, slow growing tumor, traditionally considered chemoresistant. The only curative approach is cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC). At disease relapse, or in patients with inoperable disease at diagnosis, no standard treatment has been defined, though nonrandomized series showed promising results with fluoropyrimidine-based regimens. PATIENTS AND METHODS: We conducted a prospective study in patients with relapsed or unresectable PMP and confirmed disease progression at baseline. Patients received MMC (7 mg/m2 every 6 weeks, up to a maximum of 4 cycles) plus metronomic capecitabine (625 mg/sqm/day b.i.d.) and bevacizumab (7.5 mg/kg every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal. Primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), overall response rate according to RECIST v1.1 criteria, serum markers response and safety. RESULTS: Fifteen patients were included. At a median follow-up of 26.1 months (IQR, 17.7-49.6), median PFS was 17.9 months (95% CI, 11.0-NE), with 1-year PFS and OS rates of 73% and 87%. Safety profile was manageable, with only 13% G3/G4 treatment-related adverse events. CONCLUSION: Metronomic capecitabine, bevacizumab, and MMC are an active regimen in advanced and progressive PMP and favorably compares with historical series.
Asunto(s)
Neoplasias del Apéndice , Hipertermia Inducida , Neoplasias Peritoneales , Seudomixoma Peritoneal , Humanos , Seudomixoma Peritoneal/tratamiento farmacológico , Seudomixoma Peritoneal/patología , Mitomicina/uso terapéutico , Bevacizumab/efectos adversos , Capecitabina/efectos adversos , Neoplasias Peritoneales/tratamiento farmacológico , Estudios Prospectivos , Hipertermia Inducida/métodos , Progresión de la Enfermedad , Neoplasias del Apéndice/patologíaRESUMEN
BACKGROUND: Gastrointestinal leak is one of the most feared complications after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) and harbors significant postoperative morbidity and mortality. We aim to identify risk-factors for anastomotic leak (AL) and gastrointestinal perforation (GP) to optimize postoperative outcomes of this population. METHODS: We performed a retrospective analysis of 1043 consecutive patients submitted to CRS in a single institution. Potential risk factors for AL and GP, both related to patient overall condition, disease status and surgical technique were reviewed. RESULTS: Anastomotic leaks were identified in 5.2% of patients, and GPs in 7.0%. The independent risk-factors for AL were age at surgery (OR1.40; CI95% 1.10-1.79); peritoneal cancer index (PCI) (OR1.04, CI95% 1.01-1.07); Cisplatin dose >240 mg during HIPEC (OR3.53; CI95% 1.47-8.56) and the presence of colorectal (CR) or colo-colic (CC) anastomosis (OR5.09; CI95% 2.71-9.53, and 4.58; CI95% 1.22-17.24 respectively). Male gender and intraoperative red blood cell transfusions were the only independent risk factors for GP identified (OR1.70; CI95% 1.04-2.78 and 1.06; CI95% 1.01-1.12, respectively). Regarding 30-day and 90-day postoperative mortality, independent risk-factors were mainly related to patient's overall condition. CONCLUSION: Gastrointestinal leaks are a frequent source of postoperative morbidity, mainly at the expense of GP. A careful and systematic intraoperative revision of all potential gastrointestinal injuries is equally critical to perfecting anastomotic fashioning techniques to decrease gastrointestinal complication rates. We identified multiple risk-factors for AL and GP related to disease status and patient condition. Our study suggests that patient-related conditions are of paramount relevance, highlighting the importance of patient selection and preoperative patient optimization.
Asunto(s)
Hipertermia Inducida , Neoplasias Peritoneales , Humanos , Masculino , Fuga Anastomótica/epidemiología , Fuga Anastomótica/etiología , Quimioterapia Intraperitoneal Hipertérmica , Terapia Combinada , Neoplasias Peritoneales/terapia , Pronóstico , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Estudios Retrospectivos , Quimioterapia del Cáncer por Perfusión Regional/efectos adversos , Hipertermia Inducida/efectos adversos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
BACKGROUND: The metastasizing potential of pseudomyxoma peritonei (PMP) is largely unknown. We assessed incidence, impact on prognosis, treatments, and outcomes of systemic metastases after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). METHODS: A prospective database of 327 patients undergoing CRS/HIPEC for PMP of appendiceal origin was reviewed. PMP was graded according to the Peritoneal Surface Oncology Group International (PSOGI) classification. Haematogenous metastases, and non-regional lymph-node involvement were considered as systemic metastases. RESULTS: After a median follow-up of 74.8 months (95% confidence interval [CI] = 68.0-94.8), systemic metastases occurred in 21 patients. Eleven patients were affected by low-grade PMP, and ten by high-grade PMP. Metastatic disease involved the lung (n = 12), bone (n = 1), liver (n = 4), distant nodes (n = 3), both lung and distant nodes (n = 1). Systemic metastases independently correlated with PSOGI histological subtypes (P = 0.001), and incomplete cytoreduction (P = 0.026). Median OS was 139.0 months (95%CI = 56.6-161.9) for patients who experienced systemic metastases, and 213.8 months (95%CI = 148.7-not reached) for those who did not (P = 0.159). Eight of eleven patients who had curative-intent surgery are presently alive at a median of 52.5 months (range 2.0-112.7). Seven are disease-free at a median of 27.4 months (range 2.0-110.4). At multivariate analysis, PSOGI histological subtypes (P = 0.001), completeness of cytoreduction (P = 0.001), and preoperative systemic chemotherapy (P = 0.020) correlated with poorer survival. Systemic metastases did not (P = 0.861). CONCLUSIONS: After CRS/HIPEC, systemic metastases occur in a small but clinically relevant number of patients, and the risk increases with incomplete cytoreduction and aggressive histology. In selected patients, surgical resection of metastatic disease can result in long survival.
Asunto(s)
Neoplasias del Apéndice , Hipertermia Inducida , Neoplasias Peritoneales , Seudomixoma Peritoneal , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/terapia , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Humanos , Neoplasias Peritoneales/secundario , Seudomixoma Peritoneal/patología , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) leads to prolonged survival for selected patients with colorectal (CRC) peritoneal metastases (PM). This study aimed to analyze the prognostic role of micro-satellite (MS) status and RAS/RAF mutations for patients treated with CRS. METHODS: Data were collected from 13 Italian centers with PM expertise within a collaborative group of the Italian Society of Surgical Oncology. Clinical and pathologic variables and KRAS/NRAS/BRAF mutational and MS status were correlated with overall survival (OS) and disease-free survival (DFS). RESULTS: The study enrolled 437 patients treated with CRS-HIPEC. The median OS was 42.3 months [95% confidence interval (CI), 33.4-51.2 months], and the median DFS was 13.6 months (95% CI, 12.3-14.9 months). The local (peritoneal) DFS was 20.5 months (95% CI, 16.4-24.6 months). In addition to the known clinical factors, KRAS mutations (p = 0.005), BRAF mutations (p = 0.01), and MS status (p = 0.04) were related to survival. The KRAS- and BRAF-mutated patients had a shorter survival than the wild-type (WT) patients (5-year OS, 29.4% and 26.8% vs 51.5%, respectively). The patients with micro-satellite instability (MSI) had a longer survival than the patients with micro-satellite stability (MSS) (5-year OS, 58.3% vs 36.7%). The MSI/WT patients had the best prognosis. The MSS/WT and MSI/mutated patients had similar survivals, whereas the MSS/mutated patients showed the worst prognosis (5-year OS, 70.6%, 48.1%, 23.4%; p = 0.0001). In the multivariable analysis, OS was related to the Peritoneal Cancer Index [hazard ratio (HR), 1.05 per point], completeness of cytoreduction (CC) score (HR, 2.8), N status (HR, 1.6), signet-ring (HR, 2.4), MSI/WT (HR, 0.5), and MSS/WT-MSI/mutation (HR, 0.4). Similar results were obtained for DFS. CONCLUSION: For patients affected by CRC-PM who are eligible for CRS, clinical and pathologic criteria need to be integrated with molecular features (KRAS/BRAF mutation). Micro-satellite status should be strongly considered because MSI confers a survival advantage over MSS, even for mutated patients.
Asunto(s)
Neoplasias Colorrectales , Hipertermia Inducida , Neoplasias Peritoneales , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/terapia , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción/métodos , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Inestabilidad de Microsatélites , Repeticiones de Microsatélite , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/terapia , Pronóstico , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: The development of multimodality treatment, including cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC), has led to promising results in selected patients with peritoneal disease of gastric origin. The aim of this study was to investigate the short- and long-term outcomes of CRS/HIPEC in the treatment of synchronous peritoneal metastasis in gastric cancer. METHODS: The Italian Peritoneal Surface Malignancies Oncoteam-S.I.C.O. retrospective registry included patients with synchronous peritoneal malignancy from gastric cancer submitted to gastrectomy with CRS and HIPEC between 2005 and 2018 from 11 high-volume, specialized centers. RESULTS: A total of 91 patients with a median age of 58 years (range 26-75) were enrolled. The median overall survival (OS) time for the whole group of patients was 20.2 months (95% confidence interval [CI] 11.8-28.5] and the median recurrence-free survival (RFS) was 7.3 months (95% CI 4-10.6). The completeness of cytoreduction score (CCS) of 0 and Peritoneal Cancer Index (PCI) score of ≤ 6 groups showed a significantly better long-term survival (median OS 40.7 and 44.3 months, respectively) compared with the incomplete resected groups (median OS 10.7 months, p = 0.003) and PCI score of > 6 group (median OS 13.4 months, p = 0.005). A significant difference was observed in the survival rate according to neoadjuvant treatment (untreated patients: 10.7 months, 95% CI 5.1-16.2; treated patients: 35.3 months, 95% CI 2.8-67.8; p = 0.022). CONCLUSIONS: In referral centers, CRS and HIPEC after neoadjuvant treatment significantly improved survival in selected patients. Patients with a PCI score ≤ 6, complete cytoreduction, negative nodal involvements, and negative cytology had encouraging results, showing a clinically meaningful survival.
Asunto(s)
Hipertermia Inducida , Neoplasias Peritoneales , Neoplasias Gástricas , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Italia , Persona de Mediana Edad , Neoplasias Peritoneales/tratamiento farmacológico , Estudios Retrospectivos , Neoplasias Gástricas/terapia , Tasa de SupervivenciaRESUMEN
BACKGROUND: Non-gynecologic rare peritoneal surface malignancies (PSMs) often are misdiagnosed as disseminated ovarian cancer and initially treated by gynecologic surgeons. This study aimed to assess whether these previous maneuvers (i.e., full surgical staging and/or cytoreductive attempts) affect outcomes after the definitive surgery performed in a tertiary center. METHODS: The study reviewed 298 women affected by non-gynecologic PSM who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) after previous gynecologic surgery. Prior surgery was categorized as limited surgery (pLS: abdominal exploration with biopsy plus adnexectomy and/or appendectomy) or extended surgery (pES: full surgical staging or cytoreductive attempts including hysterectomy with bilateral salpingo-oophorectomy). RESULTS: Of the 298 patients, 143 had pLS and 153 had pES. Morbidity was similar between the groups (P = 0.143), but the pES group had more severe urinary tract injuries (19 vs. 3; P < 0.001), longer operating time (585.9 vs. 506.7; P = 0.027), and more patients needing more than two anastomoses (41 vs. 26; P = 0.033). Age older than 55 years (odds ratio [OR] 2.42; P = 0.009) and number of anastomoses (OR 3.17; P = 0.002) correlated with severe morbidity; pES correlated with urinary tract grades 3 and 4 injuries (OR 7.9; P = 0.001). The 5-year cumulative incidence of locoregional relapse was significantly higher in the pES group (0.41 vs. 0.27; P = 0.012; median follow-up period, 69 months). The multivariate analysis identified a Peritoneal Carcinomatosis Index (PCI) higher than 20 and pES as independent risk factors. CONCLUSION: For women undergoing CRS±HIPEC for non-gynecologic PSM, the risk for locoregional relapse and severe postsurgical urinary tract complications is increased by pES. Therefore, prior full surgical staging or cytoreductive attempts without definitive gynecologic histology should be avoided. Prophylactic ureteral stenting and stricter oncologic follow-up assessment must be considered in this scenario.
Asunto(s)
Hipertermia Inducida , Neoplasias Ováricas , Neoplasias Peritoneales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia del Cáncer por Perfusión Regional , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Femenino , Procedimientos Quirúrgicos Ginecológicos , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/cirugía , Neoplasias Peritoneales/diagnóstico , Neoplasias Peritoneales/terapia , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: The Prodige-7 trial has questioned the role of hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal metastases from colorectal cancer (CRC-PM). PATIENTS AND METHODS: We compared a prospectively collected group of 48 patients undergoing oxaliplatin/irinotecan-based perioperative systemic chemotherapy (s-CT) with targeted agents, and cytoreductive surgery (CRS) (no-HIPEC group) with 48 controls undergoing the same perioperative s-CT and CRS/HIPEC (HIPEC group). Patients were matched (1:1) according to the Peritoneal Surface Disease Severity Score, completeness of cytoreduction, history of extraperitoneal disease (EPD), and Peritoneal Cancer Index. RESULTS: The groups were comparable, except for a higher number of patients in the HIPEC group with World Health Organization performance status 0, pN2 stage primary tumor, and treated with preoperative s-CT. Forty-one patients in the no-HIPEC group and 43 patients in the HIPEC group had optimal comprehensive treatment (P = 0.759), defined as complete cytoreduction of PM and margin-negative EPD resection. Median follow-up was 31.6 months in the no-HIPEC group and 39.9 months in the HIPEC group. Median overall survival was 39.3 months in the no-HIPEC group and 34.8 months in the HIPEC group (P = 0.702). In the two groups, severe morbidity occurred in 14 (29.2%) and 13 (27.1%) patients, respectively (P = 1.000), with no operative deaths. On multivariate analysis, left-sided primary and curative treatment independently correlated with better survival while HIPEC did not (hazard ratio 0.73; 95% confidence interval 0.47-1.15; P = 0.178). CONCLUSIONS: Our results confirmed that, in selected patients, perioperative s-CT and surgical treatment of CRC-PM resulted in unexpectedly high survival rates. Mitomycin C-based HIPEC did not increase morbidity but did not impact prognosis.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia del Cáncer por Perfusión Regional/mortalidad , Neoplasias Colorrectales/terapia , Procedimientos Quirúrgicos de Citorreducción/mortalidad , Hipertermia Inducida/mortalidad , Recurrencia Local de Neoplasia/terapia , Neoplasias Peritoneales/terapia , Estudios de Casos y Controles , Quimioterapia Adyuvante , Neoplasias Colorrectales/patología , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Irinotecán/administración & dosificación , Metástasis Linfática , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Recurrencia Local de Neoplasia/patología , Oxaliplatino/administración & dosificación , Neoplasias Peritoneales/secundario , Pronóstico , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Tasa de SupervivenciaRESUMEN
INTRODUCTION: Serous papillary peritoneal carcinoma (SPPC) is a rare clinical entity. Based on the understanding of the pattern of spread, its multifocality, polyclonality and the high frequency of diffuse, widespread peritoneal metastasis, a robust rationale for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for SPPC exists. Herein we report the clinical outcomes of SPPC patients treated with neoadjuvant systemic chemotherapy (NACT) followed by CRS including total parietal peritonectomy and HIPEC. METHODS: Clinico-pathological data of 22 patients of serous papillary peritoneal carcinoma (SPPC) was retrospectively analyzed from a prospectively maintained database from June 2000 to July 2017. Patients were treated with CRS, total parietal peritonectomy and HIPEC with cisplatin (42â¯mg/L of perfusate) and doxorubicin (15â¯mg/L of perfusate) after NACT. Survival curves were calculated from the date of surgery. RESULTS: 22 patients underwent CRS, total parietal peritonectomy and HIPEC. The median age was 62 years (Range 47-72). On histological evaluation, 18/30 (60%) parietal peritonectomy specimens showed microscopic disease, when no disease was evident macroscopically at surgical exploration. Grade III-IV surgical complications were recorded in 4/22 (18%) patients. There was no postoperative mortality. At a median follow up of 12 months, the five-year overall survival (OS) was 64.9%. The median OS was not reached. Median progression-free survival was 32.9 months and progression-free survival at 5 years was 33.2%. CONCLUSION: CRS with total peritonectomy + HIPEC after NACT, presents as a promising treatment modality for SPPC, and could be associated with good survival results in patients with SPPC.
Asunto(s)
Adenocarcinoma Papilar/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Procedimientos Quirúrgicos de Citorreducción , Hipertermia Inducida , Terapia Neoadyuvante , Neoplasias Quísticas, Mucinosas y Serosas/terapia , Neoplasias Peritoneales/terapia , Peritoneo/cirugía , Adenocarcinoma Papilar/patología , Anciano , Carboplatino/administración & dosificación , Cisplatino/administración & dosificación , Doxorrubicina/administración & dosificación , Femenino , Humanos , Infusiones Parenterales , Tiempo de Internación , Persona de Mediana Edad , Neoplasias Quísticas, Mucinosas y Serosas/patología , Paclitaxel/administración & dosificación , Neoplasias Peritoneales/patología , Complicaciones Posoperatorias/epidemiología , Supervivencia sin Progresión , Estudios RetrospectivosRESUMEN
BACKGROUND AND OBJECTIVES: The aims of this multi-institutional study were to assess the feasibility of iterative cytoreductive surgery (iCRS)/hyperthermic intraperitoneal chemotherapy, iCRS in colorectal peritoneal carcinomatosis (CRPC), evaluate survival, recurrence, morbidity and mortality outcomes, and identify prognostic factors for overall survival. METHODS: Patients with CRPC that underwent an iCRS, with or without intraperitoneal chemotherapy, from June 1993 to July 2016 at 13 institutions were retrospectively analyzed from prospectively maintained databases. RESULTS: The study comprised of 231 patients, including 126 females (54.5%) with a mean age at iCRS of 51.3 years. The iterative high-grade (3/4) morbidity and mortality rates were 23.4% and 1.7%, respectively. The median recurrence-free survival was 15.0 and 10.1 months after initial and iCRS, respectively. The median and 5-year survivals were 49.1 months and 43% and 26.4 months and 26% from the initial and iCRS, respectively. Independent negative predictors of survival from the initial CRS included peritoneal carcinomatosis index (PCI) > 20 ( P = 0.02) and lymph node positivity ( P = 0.04), and from iCRS, PCI > 10 ( P = 0.03 for PCI 11-20; P < 0.001 for PCI > 20), high-grade complications ( P = 0.012), and incomplete cytoreduction ( P < 0.001). CONCLUSION: iCRS can provide long-term survival benefits to highly selected colorectal peritoneal carcinomatosis patients with comparable mortality and morbidity rates to the initial CRS procedure. Careful patient selection is necessary to improve overall outcomes.
Asunto(s)
Quimioterapia del Cáncer por Perfusión Regional/mortalidad , Neoplasias Colorrectales/mortalidad , Procedimientos Quirúrgicos de Citorreducción/mortalidad , Hipertermia Inducida/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Neoplasias Peritoneales/mortalidad , Adolescente , Adulto , Anciano , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/terapia , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Well differentiated papillary peritoneal mesothelioma (WDPPM) is a rare variant of mesothelioma which affects mainly women in the reproductive age. The disease may present multifocally and recur after primary resection. Our aim was to describe the outcomes of cytoreduction (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in this disease. METHODS: Patients with histological diagnosis of WDPPM were retrieved from the PSOGI registry. Demographical and clinical data were extracted as well as outcomes data (overall survival (OS) and recurrence free survival (RFS)). RESULTS: We analyzed 45 patients for whom complete data was available. The majority of patients were women (nâ¯=â¯33, 73%) with a median age of 44 years. Preoperative chemotherapy (CT) was administered in 8 patients (18%). Median peritoneal carcinomatosis index was 9 (1-30), and complete cytoreduction was achieved in 69% of patients. There was one case (2%) of postoperative mortality, and 24% rate of severe morbidity. Overall, there were 4 deaths and 5 years OS was 80%. 8 patients (18%) had disease recurrence, all within 5 years from operation. On univariate analysis preoperative CT, high PCI and severe morbidity were associated with reduced RFS. On multivariate analysis, only preoperative CT (HRâ¯=â¯32.6, 95% CI: 2.39-446.2, pâ¯=â¯0.009) and high PCI (HRâ¯=â¯21.7, 95% CI: 1.11-425.7, pâ¯=â¯0.04) remained significant risk factors. CONCLUSIONS: WDPPM can be a lethal disease with substantial recurrence even after aggressive treatment. Patients presenting with extensive disease or disease recurrence after surgical excision are at increased risk for relapse. CRS + HIPEC can be safely applied to WDPPM in specialized centers.
Asunto(s)
Antineoplásicos/uso terapéutico , Procedimientos Quirúrgicos de Citorreducción/métodos , Hipertermia Inducida/métodos , Mesotelioma/terapia , Neoplasias Peritoneales/terapia , Sistema de Registros , Adulto , Australia/epidemiología , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Mesotelioma/diagnóstico , Mesotelioma/mortalidad , Persona de Mediana Edad , América del Norte/epidemiología , Neoplasias Peritoneales/diagnóstico , Neoplasias Peritoneales/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Resultado del TratamientoRESUMEN
BACKGROUND: Survival improvements have been reported in selected patients affected by colorectal peritoneal metastases who were undergoing cytoreductive surgery with intraperitoneal hyperthermic chemotherapy. Treatment of peritoneal metastases associated with extraperitoneal disease is still controversial. OBJECTIVE: We assessed the prognostic impact of a history of extraperitoneal disease that was curatively treated either at the same time as or before the onset of peritoneal metastases. DESIGN: We reviewed 2 prospective databases. Peritoneal involvement was scored by Peritoneal Cancer Index. SETTINGS: Our study was conducted in 2 high-volume peritoneal malignancy management institutions. PATIENTS: A total of 148 patients with peritoneal metastases were included. In 27 patients, extraperitoneal disease involving the liver (n = 23), lung (n = 1), both lung and liver (n = 2), or inguinal lymph nodes and liver (n = 1) was curatively treated either simultaneously with peritoneal metastases (n = 22) or before their onset (n = 5). INTERVENTIONS: All of the macroscopic tumors were removed by means of peritonectomy procedures and visceral resections. Microscopic residual disease was treated by mitomycin C/cisplatin-based hyperthermic intraperitoneal chemotherapy. MAIN OUTCOME MEASURES: Overall survival was the primary outcome measure. RESULTS: After a median follow-up of 34.6 months (95% CI, 22.6-65.7 mo), 5-year survival of patients treated for both peritoneal and extraperitoneal disease versus peritoneal metastases alone was 16.5% versus 52.0% (p = 0.019). After multivariate analysis, reduced survival correlated with extraperitoneal disease (p = 0.001), Peritoneal Cancer Index >19 (p = 0.004), and peritoneal residual disease >2.5 mm (p = 0.018). Three prognostic groups were defined, and median survival was not reached for group 1 (Peritoneal Cancer Index ≤19 and no extraperitoneal disease), reached in 27.0 months for group 2 (Peritoneal Cancer Index ≤9 and extraperitoneal disease), and reached in 11.6 months for group 3 (Peritoneal Cancer Index >19 and no extraperitoneal disease or Peritoneal Cancer Index >9 and extraperitoneal disease). LIMITATIONS: The main study limitation is its observational nature. CONCLUSIONS: A history of extraperitoneal disease is associated with poorer prognosis. However, survival benefit may be obtained in selected patients with limited peritoneal involvement. See Video Abstract at http://links.lww.com/DCR/A655.
Asunto(s)
Neoplasias Colorrectales/patología , Procedimientos Quirúrgicos de Citorreducción/efectos adversos , Hipertermia Inducida/efectos adversos , Neoplasias Peritoneales/secundario , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/terapia , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción/métodos , Femenino , Humanos , Hipertermia Inducida/métodos , Masculino , Persona de Mediana Edad , Neoplasias Peritoneales/mortalidad , Neoplasias Peritoneales/terapia , Peritoneo/patología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are associated with increased red blood cell transfusion (RBT) demand. Although the deleterious effects of RBT are documented in various settings, its effect in this setting is obscure. In this study, we evaluated the effects of different-grade RBT on the short- and long-term outcomes of CRS and HIPEC. METHODS: We analyzed 231 patients with diffuse malignant peritoneal mesothelioma (DMPM) and 273 patients with pseudomyxoma peritonei (PMP) operated in our unit. RBT was categorized according to the amount of packed red blood cell units (PRBCs) administered (0, 1-2, 3-5, > 6). The effects of RBT on long-term oncological outcomes [progression-free survival (PFS) and overall survival (OS)] were assessed by using multivariate analysis. RESULTS: Overall, 74% of the patients were transfused with a median of 2 PRBCs (range 0-37). Transfusion level correlated with operative time, surgical extent (as measured by the peritoneal carcinomatosis index), and age. Postoperatively, patients with major transfusion (> 6 PRBCs) had increased mortality rate (11.1%, p = 0.01) and length of hospital stay (31.2 ± 16.8 days, p = 0.01) compared with other levels of RBT. RBT was dose-dependently associated with oncological outcomes in both DMPM and PMP for both PFS [hazard ratio (HR) = 1.40, 95% confidence interval (CI) 1.12-1.74, p = 0.003; HR = 1.44, 95% CI 1.15-1.81, p = 0.001, respectively] and OS (HR = 1.57, 95% CI 1.21-2.03, p = 0.001; HR = 1.43, 95% CI 1.15-1.90, p = 0.01, respectively). CONCLUSIONS: Our data show a dose-dependent relationship between RBT and oncological outcomes. Further research to develop transfusion sparing protocols is needed in this extensive surgical procedure.
Asunto(s)
Quimioterapia del Cáncer por Perfusión Regional/mortalidad , Transfusión de Eritrocitos/mortalidad , Hipertermia Inducida/mortalidad , Neoplasias Peritoneales/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/terapia , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
INTRODUCTION: Peritoneal metastasis (PM) of hepatocellular carcinoma (HCC) without distant spread are rare. The related prognosis is poor without standard treatment available. The role of cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is poorly documented. METHODS: An international multicentric cohort was constituted by retrospective analysis of 21 patients undergoing CRS/HIPEC for PM of HCC between 1992 and 2016 from 10 reference centers of PSOGI. Data on clinical features, treatment strategies, and survival outcomes were analyzed. RESULTS: The median time interval from the diagnosis of PM to the procedure was 4.5 months. The median peritoneal cancer index was 14. Sixteen patients had complete cytoreduction (CCR0-1). Ten patients had grades 3 to 4 complications. The median duration of follow-up was 52.2 months. The median OS was 46.7 months. The projected 3y-OS and 5y-OS were 88.9 and 49.4% respectively. The median OS for patients with CCR0-1 resection was not reached whereas it was 5.9 months for those with CCR2-3 resection after CRS (p = 0.0005). The median RFS was 26.3 months and projected RFS at 3 years of 36.5 months Three prognostic factors were associated with improved RFS in the univariate analysis: preoperative chemotherapy (p = 0.0156), PCI >15 (p = 0.009), Number of chemotherapy agents used for HIPEC (p = 0.005). CONCLUSION: CRS/HIPEC is a safe and effective approach in selected patients with PM of HCC. CRS/HIPEC gives the patient a chance for a good relapse free and overall survival and should be considered as an option.
Asunto(s)
Carcinoma Hepatocelular/secundario , Carcinoma Hepatocelular/terapia , Procedimientos Quirúrgicos de Citorreducción/métodos , Hipertermia Inducida/métodos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/terapia , Adolescente , Adulto , Anciano , Terapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Multicystic peritoneal mesothelioma (MCPM) is an extremely rare disease with 40-50% rate of recurrence after surgical debulking. Due to the recurrent nature of the disease, the option of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) was offered for this condition. In the present study we aimed to describe the outcomes of this strategy in a single center cohort. METHODS: We retrospectively reviewed a prospectively collected database of all patients with MCPM that underwent the combined procedure in our center. Clinical presentation, operative procedures and outcomes were reviewed. RESULTS: Between August 1997 and October 2017, 19 patients with MCPM underwent 20 cytoreduction and HIPEC procedures in our center. The majority of the patients were females (n = 17, 89%), and mean age was 42, as reported in other series. Disease extent, as measured by mean peritoneal carcinomatosis index (PCI) was 15.5 ± 9.9 and total number of procedures performed 6.7 ± 2.6. Major complications occurred in 3 (15%) patients, with no perioperative mortality. After a median of follow-up of 69 months (range 4-220) all patients were alive and 4 patients had recurrence (21%). Patients with high PCI (defined by median PCI) had shorter recurrence free survival (RFS) than patient with low PCI (mean RFS = 106.4 ± 6.6 for high PCI vs. 125.6 ± 34.1 for low PCI, p = 0.03). CONCLUSION: Cytoreduction and HIPEC offer low recurrence rate and prolonged mean RFS for patients with MCPM. The combined procedure can be offered with acceptable morbidity in specialized centers.
Asunto(s)
Antineoplásicos/administración & dosificación , Procedimientos Quirúrgicos de Citorreducción/métodos , Hipertermia Inducida/métodos , Mesotelioma Quístico/terapia , Neoplasias Peritoneales/terapia , Complicaciones Posoperatorias/epidemiología , Absceso Abdominal/epidemiología , Lesión Renal Aguda/epidemiología , Adulto , Anastomosis Quirúrgica , Fuga Anastomótica/epidemiología , Anemia/epidemiología , Apendicectomía , Colecistectomía , Colectomía , Procedimientos Quirúrgicos del Sistema Digestivo , Supervivencia sin Enfermedad , Femenino , Humanos , Histerectomía , Infusiones Parenterales , Tiempo de Internación , Masculino , Mesotelioma Quístico/patología , Persona de Mediana Edad , Ovariectomía , Neoplasias Peritoneales/patología , Peritoneo/cirugía , Estudios Retrospectivos , Salpingectomía , Esplenectomía , Infección de la Herida Quirúrgica/epidemiología , Resultado del TratamientoRESUMEN
BACKGROUND: The differential diagnosis between diffuse malignant peritoneal mesothelioma (DMPM) and other peritoneal surface malignancies (PSM) is still challenging. Serum mesothelin and osteopontin are increasingly used as markers of pleural mesothelioma, but their role in DMPM is unclear. We assessed the diagnostic and prognostic values of mesothelin, osteopontin, CEA, CA19.9, CA125, and CA15.3 in DMPM patients. METHODS: Markers were dosed before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) by enzyme-linked immunosorbent assay (ELISA) in 30 DMPM patients and 14 controls with other PSMs. Receiver-operating characteristics (ROC) curve were plotted. The performance of each marker was assessed by the area under the ROC curve (AUC-ROC). RESULTS: Mean mesothelin levels were 7.84 ng/dl (SD = 5.14) in DMPM group and 3.00 ng/dl (SD = 1.25) in controls (P = 0.001). Mean CEA levels were 5.3 ng/dl (SD = 4.7), and 61.96 ng/dl (SD = 112.5) in the two groups (P = 0.008). No statistical difference was seen for osteopontin (P = 0.738), CA19.9 (P = 0.081), CA125 (P = 0.600), and CA15.3 (P = 0.365). AUC-ROC was 0.836 for CA19.9, 0.812 for mesothelin, 0.793 for CEA, and lower for CA125 (0.652), osteopontin (0.531), and CA15.3 (0.481). Using diagnostic cut-offs selected by ROC methodology, sensitivity, specificity, positive and negative predictive values were 70.0%, 100.0%, 100.0%, and 60.9% for mesothelin >5.21 ng/dl, and 90.0%, 85.7%, 93.1%, and 80.0% for CA19.9 < 8.8 U/dl. At multivariate analysis, osteopontin correlated with survival (hazard rate 6.46; 95%CI 1.81-23.05; P = 0.004). CONCLUSION: When assessing PSMs of unknown origin, elevated mesothelin with low CA19.9 may increase the suspicion index for DMPM. Ospeopontin warrants further investigations as a prognostic marker for DMPM.