RESUMEN
Background: We compared the relative benefits, harms and cost-effectiveness of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery ± systemic chemotherapy versus cytoreductive surgery ± systemic chemotherapy or systemic chemotherapy alone in people with peritoneal metastases from colorectal, gastric or ovarian cancers by a systematic review, meta-analysis and model-based cost-utility analysis. Methods: We searched MEDLINE, EMBASE, Cochrane Library and the Science Citation Index, ClinicalTrials.gov and WHO ICTRP trial registers until 14 April 2022. We included only randomised controlled trials addressing the research objectives. We used the Cochrane risk of bias tool version 2 to assess the risk of bias in randomised controlled trials. We used the random-effects model for data synthesis when applicable. For the cost-effectiveness analysis, we performed a model-based cost-utility analysis using methods recommended by The National Institute for Health and Care Excellence. Results: The systematic review included a total of eight randomised controlled trials (seven randomised controlled trials, 955 participants included in the quantitative analysis). All comparisons other than those for stage III or greater epithelial ovarian cancer contained only one trial, indicating the paucity of randomised controlled trials that provided data. For colorectal cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably results in little to no difference in all-cause mortality (60.6% vs. 60.6%; hazard ratio 1.00, 95% confidence interval 0.63 to 1.58) and may increase the serious adverse event proportions compared to cytoreductive surgery ± systemic chemotherapy (25.6% vs. 15.2%; risk ratio 1.69, 95% confidence interval 1.03 to 2.77). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to fluorouracil-based systemic chemotherapy alone (40.8% vs. 60.8%; hazard ratio 0.55, 95% confidence interval 0.32 to 0.95). For gastric cancer, there is high uncertainty about the effects of hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy versus cytoreductive surgery + systemic chemotherapy or systemic chemotherapy alone on all-cause mortality. For stage III or greater epithelial ovarian cancer undergoing interval cytoreductive surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably decreases all-cause mortality compared to cytoreductive surgery + systemic chemotherapy (46.3% vs. 57.4%; hazard ratio 0.73, 95% confidence interval 0.57 to 0.93). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy may not be cost-effective versus cytoreductive surgery + systemic chemotherapy for colorectal cancer but may be cost-effective for the remaining comparisons. Limitations: We were unable to obtain individual participant data as planned. The limited number of randomised controlled trials for each comparison and the paucity of data on health-related quality of life mean that the recommendations may change as new evidence (from trials with a low risk of bias) emerges. Conclusions: In people with peritoneal metastases from colorectal cancer with limited peritoneal metastases and who are likely to withstand major surgery, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should not be used in routine clinical practice (strong recommendation). There is considerable uncertainty as to whether hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy or cytoreductive surgery + systemic chemotherapy should be offered to patients with gastric cancer and peritoneal metastases (no recommendation). Hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should be offered routinely to women with stage III or greater epithelial ovarian cancer and metastases confined to the abdomen requiring and likely to withstand interval cytoreductive surgery after chemotherapy (strong recommendation). Future work: More randomised controlled trials are necessary. Study registration: This study is registered as PROSPERO CRD42019130504. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/135/02) and is published in full in Health Technology Assessment; Vol. 28, No. 51. See the NIHR Funding and Awards website for further award information.
Cancers of the bowel, ovary or stomach can spread to the lining of the abdomen ('peritoneal metastases'). Chemotherapy (the use of drugs that aim to kill cancer cells) given by injection or tablets ('systemic chemotherapy') is one of the main treatment options. There is uncertainty about whether adding cytoreductive surgery (cytoreductive surgery; an operation to remove the cancer) and 'hyperthermic intraoperative peritoneal chemotherapy' (warm chemotherapy delivered into the lining of the abdomen during cytoreductive surgery) are beneficial. We reviewed all the information from medical literature published until 14 April 2022, to answer the above uncertainty. We found the following from eight trials, including about 1000 participants. In people with peritoneal metastases from bowel cancer, hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably does not provide any benefits and increases harm compared to cytoreductive surgery + systemic chemotherapy, while cytoreductive surgery + systemic chemotherapy appears to increase survival compared to systemic chemotherapy alone. There is uncertainty about the best treatment for people with peritoneal metastases from stomach cancer. In women with peritoneal metastases from ovarian cancer who require systemic chemotherapy before cytoreductive surgery to shrink the cancer to allow surgery ('advanced ovarian cancer'), hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy probably increases survival compared to cytoreductive surgery + systemic chemotherapy. In people who can withstand a major operation and in whom cancer can be removed, cytoreductive surgery + systemic chemotherapy should be offered to people with peritoneal metastases from bowel cancer, while hyperthermic intraoperative peritoneal chemotherapy + cytoreductive surgery + systemic chemotherapy should be offered to women with peritoneal metastases from 'advanced ovarian cancer'. Uncertainty in treatment continues for gastric cancer. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/135/02) and is published in full in Health Technology Assessment; Vol. 28, No. 51. See the NIHR Funding and Awards website for further award information.
Asunto(s)
Análisis Costo-Beneficio , Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneales , Humanos , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/tratamiento farmacológico , Procedimientos Quirúrgicos de Citorreducción/economía , Evaluación de la Tecnología Biomédica , Ensayos Clínicos Controlados Aleatorios como Asunto , Femenino , Años de Vida Ajustados por Calidad de Vida , Neoplasias Ováricas/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/terapia , Hipertermia Inducida/economía , Análisis de Costo-EfectividadRESUMEN
OBJECTIVES: Pancreatic cancer with peritoneal metastasis presents a challenging prognosis, with limited effective treatment options available. This study aims to evaluate the efficacy and safety of combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) as a treatment strategy for this patient group. METHODS: A retrospective analysis was conducted on patients with peritoneal metastasis of pancreatic cancer who underwent CRS + HIPEC treatment at Beijing Shijitan Hospital from March 2017 to December 2023. The study focused on assessing clinical features, the incidence of sever adverse events (SAEs), and overall survival (OS). RESULTS: A total of 10 patients were enrolled in this study. The median OS was 24.2 months, suggesting an improvement over traditional therapies. While SAEs were noted, including two cases of severe complications necessitating additional surgical interventions, no perioperative fatalities were recorded. The overall survival time for patients with CC0/1 was not significantly different from that of patients with CC2/3, and no prognostic predictors were identified. CONCLUSIONS: The combination of CRS and HIPEC appears to be a viable and promising treatment modality for patients with peritoneal metastasis of pancreatic cancer, offering an improved survival rate with manageable safety concerns. Further research is needed to refine patient selection criteria and to explore the long-term benefits of this approach.
Asunto(s)
Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Pancreáticas , Neoplasias Peritoneales , Humanos , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/mortalidad , Procedimientos Quirúrgicos de Citorreducción/métodos , Procedimientos Quirúrgicos de Citorreducción/mortalidad , Masculino , Femenino , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Quimioterapia Intraperitoneal Hipertérmica/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Tasa de Supervivencia , Terapia Combinada , Pronóstico , Anciano , Estudios de Seguimiento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , AdultoRESUMEN
BACKGROUND: Clinical T4 (cT4) stage gastric cancer presents with frequent postoperative recurrence and poor prognosis. This study is to evaluate the oncological efficacy of laparoscopic radical total gastrectomy combined with postoperative prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with cT4N + M0 gastric cancer who received neoadjuvant chemotherapy. METHODS: We reviewed the clinicopathological data of 174 patients with clinical T4 gastric cancer who underwent neoadjuvant chemotherapy followed by laparoscopic radical total gastrectomy between June 2017 and December 2021. Among them, 142 were included in the non-HIPEC group, and 32 in the HIPEC group. Patients in both groups were paired based on propensity score in a 2:1 ratio to assess disparities in tumor recurrence and long-term survival. RESULTS: After matching, there were no significant differences in the clinicopathological data between the two groups. The peritoneum (16.1%) and distant organs (10.9%) were the most frequent locations for recurrence. Prior to matching, the recurrence rates were similar at all sites for both groups. Compared with those in the non-HIPEC cohort, the recurrence rates at all sites, the lung, and the peritoneum were notably lower in the HIPEC cohort. Prior to matching, the 3-year overall survival and disease-free survival rates were similar between the two groups; following matching, the HIPEC group exhibited notably greater survival rates than did the non-HIPEC group. The disparities in survival rates between the groups became even more pronounced after conducting a stratified analysis among patients with stage III disease. CONCLUSIONS: Neoadjuvant chemotherapy combined with prophylactic HIPEC after laparoscopic radical gastrectomy can effectively reduce the rate of peritoneal metastasis in patients with cT4N + M0 advanced gastric cancer and significantly improve the prognosis of such patients, which is of great clinical value.
Asunto(s)
Gastrectomía , Quimioterapia Intraperitoneal Hipertérmica , Laparoscopía , Terapia Neoadyuvante , Recurrencia Local de Neoplasia , Puntaje de Propensión , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/terapia , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/mortalidad , Gastrectomía/métodos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Laparoscopía/métodos , Terapia Neoadyuvante/métodos , Tasa de Supervivencia , Pronóstico , Quimioterapia Intraperitoneal Hipertérmica/métodos , Estudios de Seguimiento , Recurrencia Local de Neoplasia/prevención & control , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estadificación de Neoplasias , Terapia Combinada , Anciano , Quimioterapia Adyuvante/métodos , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/mortalidad , AdultoRESUMEN
PURPOSE: High-grade appendiceal adenocarcinomas (HGAA) with peritoneal metastases (PMs) are associated with poor survival. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a novel treatment approach for unresectable HGAA-PM. However, its influence on immunogenomic profiles has not yet been fully explored. MATERIALS AND METHODS: We obtained 79 samples of metastatic peritoneal tumor deposits from patients diagnosed with HGAA and performed whole-exome sequencing, RNA sequencing, and immunoprofiling before and after HIPEC. Tumor biopsies were subjected to immunogenomic profiling to detect mutational signatures and immune populations associated with oncologic outcomes. RESULTS: Fifteen patients with HGAA-PMs were included in the study. The median progression-free survival (PFS) was 6.7 months (2.7-25.3) and the median overall survival was 11.4 months (4.7-42). Mucin-associated genes (MUC16, MUC3A, and MUC5AC) and titin (TTN) had the highest mutation frequencies. Mutational signatures such as single-base substitution 29 and doublet-base substitution 11 were present in >50% of single-base and double-base mutations. Higher PD-L1 coexpression on CD8+ T cells demonstrated a higher PFS both intratumorally (P = .019) and at the margin (P = .025). CONCLUSION: HIPEC-associated mutational signatures were identified in HGAA-PMs. Elevated PD-L1+ cytotoxic T-cell populations after HIPEC had better PFS, offering valuable insights for prognostication in the context of HIPEC treatment.
Asunto(s)
Neoplasias del Apéndice , Quimioterapia Intraperitoneal Hipertérmica , Mutación , Neoplasias Peritoneales , Microambiente Tumoral , Humanos , Masculino , Femenino , Neoplasias del Apéndice/genética , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/terapia , Persona de Mediana Edad , Anciano , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/terapia , Adulto , Adenocarcinoma/genética , Adenocarcinoma/terapia , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Clasificación del TumorRESUMEN
Diseases of the peritoneum are divided into benign and malignant, whereby malignant diseases are more frequent. The incidence of peritoneal metastases is difficult to determine as they are frequently not listed separately in cancer databases and registries. Peritoneal metastases can be caused by many primary tumors but are particularly frequent in gastric, ovarian and colorectal carcinomas. Systemic chemotherapy shows gender-specific differences in the tolerability, especially gastrointestinal side effects and hematological toxicity occur more often in women. Surgical treatment options in selected patients include cytoreductive surgery with or without hyperthermic intraperitoneal chemoperfusion (HIPEC). The treatment recommendations depend on the primary tumor entity and the stage of the disease. Hysterectomy and/or salpingo-oophorectomy is often necessary during cytoreductive surgery. As the incidence of cancerous diseases is increasing in younger patients, the aspect of fertility is becoming increasingly more important. The iatrogenically induced menopause is another aspect that needs to be addressed after these types of procedures. Women with gastric and colorectal cancer tend to have a slightly better survival rate, especially in localized tumors; however, in advanced tumor stages the survival rates are comparable. Even if gender-specific differences in incidence, treatment response and adverse events are conspicuous, there is so far no exact explanation for these differences. More studies are needed in order to treat both genders as adequately as possible, with low adverse events and to achieve the best possible outcome.
Asunto(s)
Neoplasias Peritoneales , Humanos , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/patología , Femenino , Masculino , Factores Sexuales , Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal HipertérmicaRESUMEN
INTRODUCTION & OBJECTIVES: Treatment of PMP consists of appendectomy, cytoreductive surgery (CRS) and HIPEC. Right-sided hemicolectomy is necessary only when PMP is high grade, given the lymphatic invasion risk. To date, no single preoperative factor was identified as predictive of PMP grade. MATERIALS & METHODS: Preoperative factors of a prospective cohort study on PMP were retrospectively analyzed, in order to identify situations linked with high or low grade appendiceal PMP. The main outcome was PMP grade on definitive histology after CRS. RESULTS: n = 105. In univariate analysis, the grade of the appendiceal tumor, systematically reviewed in an expert center, showed an OR of 25.00 (95 % CI: 3.30-189.27; p = 0.001) and an NPV of 93.75 [85.36, 100]. Peritoneal biopsy demonstrated an OR of 19.80 (95 % CI: 2.30-170.71; p = 0.002) and a PPV of 90 [71.41, 100]. In multivariate analysis, these two factors remained significantly associated with PMP grade. CONCLUSION: Whenever appendiceal tumor is low grade on preoperative histology, the colon has to be spared unless completeness of CRS is compromised, which is a high-grade feature in fact. In case of high grade appendiceal tumor and/or peritoneal biopsy, right-sided hemicolectomy is warranted. If no histology is available preoperatively, adapt to intraoperative lesions as no preoperative factors seem to be predictive.
Asunto(s)
Neoplasias del Apéndice , Colectomía , Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Clasificación del Tumor , Neoplasias Peritoneales , Seudomixoma Peritoneal , Humanos , Procedimientos Quirúrgicos de Citorreducción/métodos , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/cirugía , Neoplasias del Apéndice/terapia , Femenino , Masculino , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/cirugía , Persona de Mediana Edad , Quimioterapia Intraperitoneal Hipertérmica/métodos , Estudios Retrospectivos , Seudomixoma Peritoneal/patología , Seudomixoma Peritoneal/cirugía , Seudomixoma Peritoneal/terapia , Anciano , Estudios Prospectivos , Estudios de Seguimiento , Pronóstico , Adulto , Hipertermia Inducida/métodos , Cuidados Preoperatorios , Terapia CombinadaRESUMEN
The prevention of intraperitoneal spread is of utmost importance in the management of advanced ovarian cancer (OC), thus demanding the exploration of innovative treatment techniques. The propensity of OC to spread to the peritoneum has highlighted the potential of local therapy as a promising approach. Among the proposed treatments thus far are several local intraperitoneal therapies, with hyperthermic intraperitoneal chemotherapy (HIPEC) being one of them. The application of HIPEC may potentially enhance the survival rates of patients with OC, as indicated by a recent publication of high-quality prospective data. The incorporation of HIPEC in conjunction with primary cytoreductive surgery (CRS) does not have a significant impact on either overall survival (OS) or disease-free survival (DFS). However, the incorporation of HIPEC alongside interval CRS, followed by systemic chemotherapy (CTH), markedly enhances both OS and DFS. The most recent data also substantiates the effectiveness of HIPEC in recurrent ovarian cancer (ROC), resulting in an improvement of survival outcomes. Additional research will contribute to the improvement of the HIPEC regimen and technique, as well as the precise identification of patients who will gain the most advantage from this treatment approach. It is recommended to discuss and update (inter)national clinical guidelines for managing patients with advanced OC and peritoneal involvement.
Asunto(s)
Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/terapia , Neoplasias Ováricas/patología , Neoplasias Ováricas/tratamiento farmacológico , Quimioterapia Intraperitoneal Hipertérmica/métodos , Procedimientos Quirúrgicos de Citorreducción/métodos , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/secundario , Manejo de la Enfermedad , Terapia Combinada , PronósticoRESUMEN
Peritoneal involvement represents one of the major difficulties that arise during the treatment of pancreatic adenocarcinoma. In fact, currently, there is a growing interest in the administration of intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) as an adjunct to surgical pancreatic resection, both with prophylactic or therapeutic intent. With this video, we report a case of pancreatic body adenocarcinoma treated with fully laparoscopic distal splenic pancreatectomy with intraoperative HIPEC with gemcitabine, administered initially with a prophylactic intent, based on a preliminary negative peritoneal washing cytology result. In our case, the association of HIPEC and surgical resection did not affect the postoperative recovery, and after 15 months of follow-up, the patient remains alive and has no signs of disease recurrence.
Asunto(s)
Quimioterapia Intraperitoneal Hipertérmica , Laparoscopía , Pancreatectomía , Neoplasias Pancreáticas , Humanos , Pancreatectomía/métodos , Laparoscopía/métodos , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/terapia , Masculino , Adenocarcinoma/terapia , Adenocarcinoma/cirugía , Adenocarcinoma/patología , Gemcitabina , Persona de Mediana Edad , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/uso terapéutico , Terapia Combinada , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/uso terapéuticoRESUMEN
Colorectal cancer (CRC) with peritoneal metastases is a complex disease and its management presents significant clinical challenges. In well-selected patients at experienced centers, CRS/hyperthermic intraperitoneal chemotherapy (HIPEC) can be performed with acceptable morbidity and is associated with prolonged survival. Based on the results of recent randomized controlled trials, HIPEC using oxaliplatin after CRS with shortened perfusion periods (30 minutes) is no longer recommended. There is a movement toward utilizing mitomycin C as a first-line intraperitoneal agent with extended perfusion times (90-120 minutes); however, there is currently little prospective evidence to support its widespread use.
Asunto(s)
Neoplasias del Colon , Quimioterapia Intraperitoneal Hipertérmica , Mitomicina , Neoplasias Peritoneales , Humanos , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias del Colon/patología , Neoplasias del Colon/terapia , Mitomicina/administración & dosificación , Oxaliplatino/administración & dosificación , Antineoplásicos/administración & dosificación , Compuestos Organoplatinos/administración & dosificación , Compuestos Organoplatinos/uso terapéutico , Procedimientos Quirúrgicos de Citorreducción , Resultado del TratamientoRESUMEN
BACKGROUND: The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) constitutes the established standard of care for pseudomyxoma peritonei patients. However, the role of HIPEC lacks validation through randomized trials, leading to diverse proposed treatment protocols. This consensus seeks to standardize HIPEC regimens and identify research priorities for enhanced clarity. METHODS: The steering committee applied the patient, intervention, comparator, and outcome method to formulate crucial clinical questions. Evaluation of evidence followed the Grading of Recommendations, Assessment, Development, and Evaluation system. Consensus on HIPEC regimens and research priorities was sought through a two-round Delphi process involving international experts. RESULTS: Out of 90 eligible panelists, 71 (79%) participated in both Delphi rounds, resulting in a consensus on six out of seven questions related to HIPEC regimens. An overwhelming 84% positive consensus favored combining HIPEC with CRS, while a 70% weak positive consensus supported HIPEC after incomplete CRS. Specific HIPEC regimens also gained consensus, with 53% supporting Oxaliplatin 200 mg/m2 and 51% favoring the combination of cisplatin (CDDP) associated with mitomycin-C (MMC). High-dose MMC regimens received an 89% positive recommendation. In terms of research priorities, 61% of panelists highlighted the importance of studies comparing HIPEC regimens post CRS. The preferred regimens for such studies were the combination of CDDP/MMC and high-dose MMC. CONCLUSIONS: The consensus recommends the application of HIPEC following CRS based on the available evidence. The combination of CDDP/MMC and high-dose MMC regimens are endorsed for both current clinical practice and future research efforts.
Asunto(s)
Consenso , Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneales , Seudomixoma Peritoneal , Humanos , Neoplasias Peritoneales/terapia , Seudomixoma Peritoneal/terapia , Terapia Combinada , Técnica Delphi , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mitomicina/administración & dosificación , Pronóstico , Hipertermia Inducida/métodosRESUMEN
BACKGROUND: Obesity is a public health concern with an increasing occurrence worldwide. Literature regarding impact of obesity on results after management of peritoneal carcinomatosis is poor. Our aim was to compare postoperative and oncological outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for rare peritoneal malignancies according to the body mass index. METHODS: All the patients managed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for rare peritoneal malignancies (including mainly pseudomyxoma peritonei and peritoneal mesothelioma), between 1995 and 2020, were retrospectively included from the French national registry of rare peritoneal tumors. RESULTS: 1450 patients were retrospectively included (63.5 % female, mean age 54 ± 13 years). Patients were divided into two groups according to their body mass index: non-obese (n = 1248, 86 %) and obese (n = 202, 14 %). Overall morbidity was significantly lower in non-obese patients in comparison with obese patients (n = 532/1248, 43 % vs n = 106/202, 53 %, p = 0.009). Medical and surgical morbidities were significantly lower in non-obese patients in comparison with obese patients (423/1258, 34 % vs n = 86/202, 43 %, p = 0.02 and n = 321/1248, 26 % vs n = 67/202, 33 %, p = 0.003, respectively). One-, 5- and 10-year overall survivals were similar between non-obese and obese patients (95 %, 82 % and 70 % vs 94 %, 76 % and 63 %; p = 0.1). One-, 5- and 10-year disease free survivals were similar between non-obese and obese patients (84 %, 67 % and 61 % vs 79 %, 62 % and 56 %, p = 0.1). CONCLUSION: Obese patients have to be carefully managed after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for rare peritoneal malignancies. Some perioperative prophylactic treatments could be specifically implemented to reduce thromboembolic events, metabolic and wound complications.
Asunto(s)
Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Obesidad , Neoplasias Peritoneales , Humanos , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/secundario , Femenino , Persona de Mediana Edad , Masculino , Obesidad/complicaciones , Estudios Retrospectivos , Índice de Masa Corporal , Pronóstico , Adulto , Anciano , Seudomixoma Peritoneal/terapia , Tasa de Supervivencia , Francia/epidemiología , Mesotelioma Maligno/terapiaRESUMEN
BACKGROUND: Cytoreductive surgery (CRS) combined with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is a complex procedure that involves extensive peritoneal and visceral resections followed by intraperitoneal chemotherapy. The Enhanced Recovery After Surgery (ERAS) program aims to achieve faster recovery by maintaining pre-operative organ function and reducing the stress response following surgery. A recent publication introduced dedicated ERAS guidelines for CRS and HIPEC with the aim of extending the benefits to patients with peritoneal surface malignancies. METHODS: A survey was conducted among 21 Italian centers specializing in peritoneal surface malignancies (PSM) treatment to assess adherence to ERAS guidelines. The survey covered pre/intraoperative and postoperative ERAS items and explored attitudes towards ERAS implementation. RESULTS: All centers completed the survey, demonstrating expertise in PSM treatment. However, less than 30 % of centers adopted ERAS protocols despite being aware of dedicated guidelines. Preoperative optimization was common, with variations in bowel preparation methods and fasting periods. Intraoperative normothermia control was consistent, but fluid management practices varied. Postoperative practices, including routine abdominal drain placement and NGT management, varied greatly among centers. The majority of respondents expressed an intention to implement ERAS, citing concerns about feasibility and organizational challenges. CONCLUSIONS: The study concludes that Italian centers specialized in PSM treatment have limited adoption of ERAS protocols for CRS ± HIPEC, despite being aware of guidelines. The variability in practice highlights the need for standardized approaches and further evaluation of ERAS applicability in this complex surgical setting to optimize patient care.
Asunto(s)
Procedimientos Quirúrgicos de Citorreducción , Recuperación Mejorada Después de la Cirugía , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneales , Humanos , Procedimientos Quirúrgicos de Citorreducción/métodos , Neoplasias Peritoneales/terapia , Italia , Adhesión a Directriz , Encuestas y Cuestionarios , Guías de Práctica Clínica como AsuntoRESUMEN
BACKGROUND: The prognostic impact of genetic mutations for patients who undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) of colorectal origin (CRC) is not well defined. OBJECTIVE: We aimed to describe the genetic classifications in an unsupervised fashion, and the outcomes of this patient population. METHODS: A retrospective, bi-institutional study was performed on patients who underwent CRS-HIPEC with targeted mutation data with a median follow-up time of 61 months. Functional link analysis was performed using STRING v11.5. Genes with similar functional significance were clustered using unsupervised k-means clustering. Chi-square, Kaplan-Meier, and the log-rank test were used for comparative statistics. RESULTS: Sixty-four patients with peritoneal carcinomatosis from CRC origin underwent CRS-HIPEC between 2007 and 2022 and genetic mutation data were extracted. We identified 19 unique altered genes, with KRAS (56%), TP53 (33%), and APC (22%) being the most commonly altered; 12.5% had co-altered KRAS/TP53. After creating an interactome map, k-means clustering revealed three functional clusters. Reactome Pathway analysis on three clusters showed unique pathways (1): Ras/FGFR3 signaling; (2) p53 signaling; and (3): NOTCH signaling. Seventy-one percent of patients in cluster 1 had KRAS mutations and a median overall survival of 52.3 months (p < 0.05). CONCLUSIONS: Patients with peritoneal carcinomatosis (PC) of CRC origin who underwent CRS-HIPEC and with tumors that harbored mutations in cluster 1 (Ras/FGFR3 signaling) had worse outcomes. Pathway disruption and a cluster-centric perspective may affect prognosis more than individual genetic alterations in patients with PC of CRC origin.
Asunto(s)
Neoplasias Colorrectales , Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Mutación , Neoplasias Peritoneales , Proteínas Proto-Oncogénicas p21(ras) , Proteína p53 Supresora de Tumor , Humanos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia , Femenino , Masculino , Estudios Retrospectivos , Proteínas Proto-Oncogénicas p21(ras)/genética , Persona de Mediana Edad , Proteína p53 Supresora de Tumor/genética , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/genética , Pronóstico , Tasa de Supervivencia , Terapia Combinada , Estudios de Seguimiento , Anciano , Biomarcadores de Tumor/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , AdultoRESUMEN
PURPOSE: Peritoneal carcinomatosis (PC) presents a major challenge in the treatment of late-stage, solid tumors, with traditional therapies limited by poor drug penetration. We evaluated a novel hyperthermic pressurized intraperitoneal aerosol chemotherapy (HPIPAC) system using a human abdominal cavity model for its efficacy against AGS gastric cancer cells. MATERIALS AND METHODS: A model simulating the human abdominal cavity and AGS gastric cancer cell line cultured dishes were used to assess the efficacy of the HPIPAC system. Cell viability was measured to evaluate the impact of HPIPAC under 6 different conditions: heat alone, PIPAC with paclitaxel (PTX), PTX alone, normal saline (NS) alone, heat with NS, and HPIPAC with PTX. RESULTS: Results showed a significant reduction in cell viability with HPIPAC combined with PTX, indicating enhanced cytotoxic effects. Immediately after treatment, the average cell viability was 66.6%, which decreased to 49.2% after 48 hours and to a further 19.6% after 120 hours of incubation, demonstrating the sustained efficacy of the treatment. In contrast, control groups exhibited a recovery in cell viability; heat alone showed cell viability increasing from 90.8% to 94.4%, PIPAC with PTX from 82.7% to 89.7%, PTX only from 73.3% to 74.8%, NS only from 90.9% to 98.3%, and heat with NS from 74.4% to 84.7%. CONCLUSIONS: The HPIPAC system with PTX exhibits a promising approach in the treatment of PC in gastric cancer, significantly reducing cell viability. Despite certain limitations, this study highlights the system's potential to enhance treatment outcomes. Future efforts should focus on refining HPIPAC and validating its effectiveness in clinical settings.
Asunto(s)
Aerosoles , Supervivencia Celular , Quimioterapia Intraperitoneal Hipertérmica , Paclitaxel , Neoplasias Peritoneales , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/terapia , Paclitaxel/farmacología , Paclitaxel/administración & dosificación , Quimioterapia Intraperitoneal Hipertérmica/métodos , Supervivencia Celular/efectos de los fármacos , Línea Celular Tumoral , Hipertermia Inducida/métodos , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/farmacologíaAsunto(s)
Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneales , Neoplasias Gástricas , Humanos , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Gástricas/patología , Neoplasias Gástricas/terapia , Procedimientos Quirúrgicos de Citorreducción/métodos , Terapia CombinadaRESUMEN
OBJECTIVE: To investigate the factors contributing to the blockage of perfusion tubes during hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with appendiceal pseudomyxoma peritonei (PMP) undergoing combined cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy treatment, and to construct a nomogram for predicting the risk of tube occlusion. STUDY DESIGN: Observational study. Place and Duration of the Study: Department of Gastrointestinal Surgery, Central Hospital Affiliated to Shandong First Medical University, Jinan, China, from June 2017 to December 2023. METHODOLOGY: Tube occlusion was defined as the inability to achieve 30 minutes of continuous unobstructed perfusion. Statistical methods such as univariate analysis, multivariate analysis, and Lasso regression were employed for data analysis. RESULTS: The results revealed that 27% of the 383 hyperthermic intraperitoneal chemotherapy perfusion treatments resulted in the tube occlusion events. Multivariate logistic regression analysis identified age, CA-125, CA19-9, and pathological type as the independent risk factors. A nomogram predicting the tube occlusion was constructed and validated for its predictive accuracy and clinical utility. CONCLUSION: This study successfully developed a nomogram to predict the tube occlusion risk during cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy treatment for patients with pseudomyxoma peritonei, providing valuable guidance for clinical practice and aiding in personalised treatment decisions to improve patient prognosis. However, further research is needed to validate the reliability and clinical applicability of the model, as well as to investigate the impact of tube occlusion on treatment outcomes and corresponding management strategies. KEY WORDS: Pseudomyxoma peritonei, Cytoreductive surgery, Hyperthermic intraperitoneal chemotherapy treatment, Tube occlusion, Nomogram.
Asunto(s)
Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Nomogramas , Neoplasias Peritoneales , Seudomixoma Peritoneal , Humanos , Seudomixoma Peritoneal/terapia , Seudomixoma Peritoneal/tratamiento farmacológico , Femenino , Masculino , Persona de Mediana Edad , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/tratamiento farmacológico , Adulto , China , Neoplasias del Apéndice/terapia , Neoplasias del Apéndice/patología , Neoplasias del Apéndice/tratamiento farmacológico , Anciano , Factores de RiesgoRESUMEN
OBJECTIVE: This study evaluates the potential superiority of combining paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) with sequential intravenous neoadjuvant chemotherapy over intravenous neoadjuvant chemotherapy alone in Chinese patients with Federation of Gynecology and Obstetrics (FIGO) stage IIIC, IVA and IVB high-grade serous ovarian/fallopian tube carcinoma (HGSOC). This interim analysis focuses on the safety and immediate efficacy of both regimens to determine the feasibility of the planned trial (C-HOC Trial). METHODS: In a single-center, open-label, randomized control trial, FIGO stage IIIC, IVA, and IVB HGSOC patients (FAGOTTI score ≥ 8 during laparoscopic exploration) unsuitable for optimal cytoreduction in primary debulking surgery (PDS) were randomized 2:1 during laparoscopic exploration. The Experiment Group (HIPEC Group) received one cycle of intraperitoneal neoadjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (paclitaxel) followed by three cycles of intravenous chemotherapy (paclitaxel plus carboplatin), while the Control Group received only three cycles of intravenous chemotherapy. Both groups subsequently underwent interval debulking surgery (IDS). The adverse effects of chemotherapy, postoperative complications, and pathological chemotherapy response scores (CRS) after IDS were compared. RESULTS: Among 65 enrolled patients, 39 HIPEC Group and 21 Control Group patients underwent IDS. Grade 3-4 chemotherapy-related adverse effects were primarily hematological with no significant differences between the two groups. The HIPEC Group exhibited a higher proportion of CRS 3 (20.5% vs. 4.8%; P = 0.000). R0 resection rates in IDS were 69.2% (HIPEC Group) and 66.7% (Control Group). R2 resection occurred in 2.6% (HIPEC Group) and 14.3% (Control Group) cases. No reoperations or postoperative deaths were reported, and complications were managed conservatively. CONCLUSIONS: Combining HIPEC with IV NACT in treating ovarian cancer demonstrated safety and feasibility, with no increased chemotherapy-related adverse effects or postoperative complications. HIPEC improved tumor response to neoadjuvant chemotherapy, potentially enhancing progression-free survival (PFS). However, the final overall survival results are pending, determining if HIPEC combined with IV NACT is superior to IV NACT alone.
Asunto(s)
Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Ováricas , Paclitaxel , Humanos , Femenino , Paclitaxel/administración & dosificación , Paclitaxel/uso terapéutico , Quimioterapia Intraperitoneal Hipertérmica/métodos , Persona de Mediana Edad , Neoplasias Ováricas/terapia , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Adulto , Anciano , Resultado del Tratamiento , Terapia Neoadyuvante/métodos , Estadificación de Neoplasias , Clasificación del Tumor , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cistadenocarcinoma Seroso/terapia , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/patología , Terapia CombinadaRESUMEN
Peritoneal metastasis in gastric cancer is associated with rapid disease progression. Hyperthermic intraoperative peritoneal chemotherapy (HIPEC) done immediately after cytoreductive surgery (CRS) has become an important treatment for peritoneal metastasis in gastric cancer patients. However, different treatment options for HIPEC exist with potential influence on survival rates and prognosis in patients, exist. These treatment options include open or closed abdomen technique, perfusion solution, number of catheters, temperature, duration, and drug regimens. This paper aims to provide more evidence on standardization of HIPEC treatment options and technologies by systematically reviewing different drug regimens and technical approaches. The study included 2 randomized controlled trials, 3 phase I/II clinical trials, 2 prospective cohort studies, and 34 retrospective cohort studies, involving 1511 patients. The most common HIPEC option is to dissolve 50-75 mg/m2 of Cisplatin and 30-40 mg/m2 of Mitomycin C in 3-4 L saline solution at 42-43â. After gastrointestinal anastomosis, 2-3 catheters are used in the HIPEC system with a perfusion flow rate of 500 ml/min. The duration is 60-90 minutes. Anastomotic leakage was low in studies where HIPEC was performed after gastrointestinal anastomosis. The utilization of open HIPEC and a two-drug regimen resulted in improved overall survival rates. The future development of HIPEC aims to enhance tumor-specific therapy by optimizing various aspects, such as identifying the safest and most effective chemotherapy regimens, refining patient selection criteria, and improving perioperative care.
Asunto(s)
Procedimientos Quirúrgicos de Citorreducción , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneales , Neoplasias Gástricas , Humanos , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción/métodos , Hipertermia Inducida/métodos , Quimioterapia Intraperitoneal Hipertérmica/métodos , Mitomicina/administración & dosificación , Mitomicina/uso terapéutico , Neoplasias Peritoneales/secundario , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Gástricas/terapiaRESUMEN
Low-grade appendiceal mucinous neoplasm (LAMN) may culminate as a mucin-secreting disease known as pseudomyxoma peritonei (PMP). Once the diagnosis of LAMN and PMP is made, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) are indicated.Herein, we present a female patient in her 50s who was diagnosed with an ovarian mass for which she underwent laparoscopic oophorectomy. As the pathology of the ovary showed a tumour of gastrointestinal origin, she then underwent CRS and HIPEC with a final pathology of LAMN. Six weeks later, a mucinous lesion confined to the abdominal wall was detected on a postoperative CT. Suspected for port-site metastasis at the laparoscopic trocar site, we treated this lesion using the same principles of treatment as the intra-abdominal disease. The abdominal wall mass was surgically resected, and the cavity created was irrigated with mitomycin C. On 30 months of follow-up, the patient had no evidence of disease.