intraperitoneal chemotherapy

腹腔化疗
  • 文章类型: Case Reports
    腹膜假粘液瘤(PMP)是一种罕见的腹腔内恶性肿瘤,其特征是粘液性肿瘤细胞的弥漫性扩散。导致黏液性腹水.准确的诊断对于适当的管理至关重要。本报告介绍了一例55岁的黎巴嫩男性农民,最初被误诊为肝硬化,他表现为利尿剂和饮食调整难以治疗的进行性腹胀。穿刺术显示有粘液样渗出物,随后的临床和组织病理学检查证实了PMP。患者被转诊至配备细胞减灭术(CRS)和腹腔热化疗(HIPEC)的专门中心进行进一步评估。由于PMP的非特异性表现,该病例突出了PMP的诊断挑战,强调及时准确诊断以促进最佳治疗干预的重要性。
    Pseudomyxoma peritonei (PMP) is a rare intra-abdominal malignancy characterized by diffuse dissemination of mucinous tumor cells, leading to mucinous ascites. Accurate diagnosis is crucial for appropriate management. This report presents a case of a 55-year-old Lebanese male farmer initially misdiagnosed with liver cirrhosis who presented with progressive abdominal distension refractory to diuretics and dietary modifications. Paracentesis revealed a mucinous exudate, with subsequent clinical and histopathological examination confirming PMP. The patient was referred for further evaluation at a specialized center equipped for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). This case highlights the diagnostic challenges of PMP due to its non-specific presentation, emphasizing the importance of prompt and accurate diagnosis to facilitate optimal therapeutic intervention.
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  • 文章类型: Journal Article
    背景:在胃癌中,腹膜转移是最常见的转移形式,并导致预后不良。我们旨在评估围手术期腹膜内(IP)联合全身化疗的安全性和有效性,细胞减灭术(CRS),和腹腔热化疗(HIPEC)的胃癌患者腹膜转移,甚至在通过预先IP化疗减轻腹膜肿瘤负担之后。
    方法:Ib期患者接受3+3剂量递增的IP紫杉醇加固定剂量的IP顺铂和口服S-1。在第二阶段,根据腹膜癌指数(PCI)通过诊断性腹腔镜检查对患者进行治疗.对于PCI>12的患者,给予预先IP和全身化疗。PCI≤12或在前期化疗后降低至≤12的患者接受HIPECCRS。主要终点是安全性和Ib期的推荐II期剂量(RP2D)确认以及II期的一年总生存率。
    结果:RP2D定义为IP175mg/m2紫杉醇和60mg/m2顺铂,口服70mg/m2/天S-1,持续14天。共纳入22例患者。在使用HIPEC的CRS之后,无3级或更高的并发症.中位住院时间为7天(范围,6-11).中位总生存期和无进展生存期为27.3个月(95%置信区间[CI],14.4-不可估计)和12.6个月(95%CI,7.7-14.5),分别。一年总生存率和无进展生存率分别为81.0%(95%CI,65.8-99.6)和54.5%(95%CI,37.2-79.9),分别。
    结论:IP联合全身化疗,CRS,和HIPEC是安全的,并导致良好的生存结局。
    BACKGROUND: In gastric cancer, peritoneal metastasis is the most common form of metastasis and leads to dismal prognosis. We aimed to evaluate the safety and efficacy of combining perioperative intraperitoneal (IP) plus systemic chemotherapy, cytoreductive surgery (CRS), and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with gastric cancer with limited peritoneal metastasis or even after reducing peritoneal tumor burden by upfront IP chemotherapy.
    METHODS: Patients were enrolled in phase Ib in a 3 + 3 dose escalation of IP paclitaxel plus a fixed dose of IP cisplatin and oral S-1. In phase II, patients were managed according to the peritoneal cancer index (PCI) by diagnostic laparoscopy. For patients with a PCI of >12, upfront IP and systemic chemotherapy were given. Patients with a PCI of ≤12 or reduced to ≤12 after upfront chemotherapy underwent CRS with HIPEC. The primary endpoints were safety and the recommended phase II dose (RP2D) confirmation for phase Ib and the 1-year overall survival rate for phase II.
    RESULTS: The RP2D was defined as IP 175 mg/m2 paclitaxel and 60 mg/m2 cisplatin and oral 70 mg/m2/day S-1 for 14 days. A total of 22 patients were included. After CRS with HIPEC, there were no grade 3 or higher complications. The median hospital stay was 7 days (range, 6-11). The median overall and progression-free survival were 27.3 months (95% CI, 14.4 to not estimable) and 12.6 months (95% CI, 7.7-14.5), respectively. One-year overall and progression-free survival rates were 81.0% (95% CI, 65.8-99.6) and 54.5% (95% CI, 37.2-79.9), respectively.
    CONCLUSIONS: A combination of IP plus systemic chemotherapy, CRS, and HIPEC was safe and resulted in good survival outcomes.
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  • 文章类型: Journal Article
    卵巢癌,以其在妇科癌症中的严重预后而著称,最近在治疗方法上取得了实质性进展。增强的化疗方案和引入聚(ADP-核糖)聚合酶(PARP)抑制剂用于维持治疗,对于具有特定遗传特征的患者,显着改善了预后。例如BRCA突变阳性或表现出同源重组缺陷(HRD)的那些。此外,腹膜内化疗的方法已成为传统经静脉途径的一种有价值的替代方法,显示出更广泛的临床采用的希望。外科领域也有所发展,随着越来越多地探索腹腔镜方法相对于更具侵入性的传统手术的益处和可行性,旨在完全切除肿瘤,但减少患者的影响。卵巢癌的遗传性突出了基因检测的重要性,这已经成为定制治疗策略不可或缺的一部分,特别是在确定PARP抑制剂的适用性。东亚妇科肿瘤试验组(EAGOT)的成立旨在优化整个日本的治疗,韩国,中国,和台湾。EAGOT的卵巢癌委员会分享了当前的政策,重点关注5个主题:1)初次手术和化疗后的维持治疗策略,2)铂敏感和铂耐药复发的药物方案,3)腹腔化疗,4)腹腔镜手术作为开腹手术的替代方法,5)基因检测的现状(BRCA,HRD,和小组测试)卵巢癌及其前景。EAGOT的跨国试验旨在协调这些不断发展的治疗策略,确保最新和最有效的协议可以在整个地区访问,从而显著影响东亚患者的预后。
    Ovarian cancer, notable for its severe prognosis among gynecologic cancers, has seen substantial progress in treatment approaches recently. Enhanced protocols in chemotherapy and the introduction of poly (ADP-ribose) polymerase (PARP) inhibitors for maintenance therapy have markedly improved outcomes for patients with specific genetic profiles, such as those positive for BRCA mutations or exhibiting homologous recombination deficiency (HRD). Additionally, the method of intraperitoneal chemotherapy administration has emerged as a valuable alternative to traditional transvenous routes, showing promise for wider clinical adoption. The field of surgery has also evolved, with increasing exploration into the benefits and feasibility of laparoscopic methods over more invasive traditional surgeries, aiming for complete tumor removal but with reduced patient impact. The hereditary nature of ovarian cancer underscores the importance of genetic testing, which has become integral in tailoring treatment strategies, particularly in determining suitability for PARP inhibitors. The formation of the East Asian Gynecologic Oncology Trial Group (EAGOT) aims to optimize treatment across Japan, Korea, China, and Taiwan. The ovarian cancer committee of EAGOT shared the current policies, focusing on 5 topics: 1) strategies for maintenance therapy after initial surgery and chemotherapy, 2) drug regimens for platinum-sensitive and platinum-resistant recurrence, 3) intraperitoneal chemotherapy, 4) laparoscopic surgery as an alternative to laparotomy, and 5) current status of genetic testing (BRCA, HRD, and panel tests) for ovarian cancer and its prospects. EAGOT\'s multi-national trials aim to harmonize these evolving treatment strategies, ensuring that the latest and most effective protocols are accessible across the region, thereby significantly impacting patient outcomes in East Asia.
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  • 文章类型: Journal Article
    腹膜转移是晚期胃癌患者的常见病。除了全身化疗,对于部分腹膜转移性胃癌患者,细胞减灭术和腹腔化疗等加性局部治疗被认为是不同多模式治疗方案的固有部分.本文综述了细胞减灭术(CRS)和腹腔化疗的作用,包括HIPEC,NIPS,和PIPAC,作为具有治愈和姑息意图的添加剂治疗选择。
    Peritoneal metastasis is a common finding in patients with advanced gastric cancer. Beyond systemic chemotherapy, additive local treatments such as cytoreductive surgery and intraperitoneal chemotherapy are considered an inherent part of different multimodal treatment concepts for selected patients with peritoneal metastatic gastric cancer. This review article discusses the role of cytoreductive surgery (CRS) and intraperitoneal chemotherapy, including HIPEC, NIPS, and PIPAC, as additive therapeutic options with curative and palliative intent.
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  • 文章类型: Multicenter Study
    背景:BRCA状态的知识为评估腹膜内途径在晚期卵巢癌原发性细胞减灭术后通过生物分子谱选择的患者中的作用提供了机会。
    方法:我们进行了回顾性研究,多中心研究根据辅助治疗(腹膜内[IP]与静脉内[IV])和BRCA状态(BRCA1/2突变与BRCA野生型[WT])。主要终点是确定无进展生存期。次要目标是总生存期和毒性。
    结果:共包括来自八个中心的288名女性:IP臂177名,IV臂111名,根据BRCA1/2状态分为四组。在接受IP化疗的BRCA1/2突变患者中观察到明显更好的PFS(HR:0.35;95%CI,0.16-0.75,p=0.007),在进行静脉化疗的BRCA1/2突变患者中不存在(HR:0.65;95%CI,0.37-1.12,p=0.14)。在IP化疗中也观察到显著更好的OS(HR:0.17;95%CI,0.06-043,p<0.0001),但与BRCA突变相关的静脉化疗中不存在(HR:0.52;95%CI,0.22-1.27,p=0.15).对于BRCAWT患者,无论使用何种佐剂途径,均观察到更差的生存率.与IV路线相比,IP路线毒性更大,但长期随访时毒性相当.
    结论:这项回顾性研究表明,BRCA状态可以帮助提供个性化,晚期卵巢癌最佳初级手术后的系统治疗,但受到样本量小的限制。前瞻性试验对于证实这些结果至关重要。
    BACKGROUND: The knowledge of BRCA status offers a chance to evaluate the role of the intraperitoneal route in patients selected by biomolecular profiles after primary cytoreduction surgery in advanced ovarian cancer.
    METHODS: We performed a retrospective, multicenter study to assess oncological outcomes depending on adjuvant treatment (intraperitoneal [IP] vs intravenous [IV]) and BRCA status (BRCA1/2 mutated vs. BRCA wild type [WT]). The primary endpoint was to determine progression-free survival. The secondary objectives were overall survival and toxicity.
    RESULTS: A total of 288 women from eight centers were included: 177 in the IP arm and 111 in the IV arm, grouped into four arms according to BRCA1/2 status. Significantly better PFS was observed in BRCA1/2-mutated patients with IP chemotherapy (HR: 0.35; 95% CI, 0.16-0.75, p = 0.007), which was not present in BRCA1/2-mutated patients with IV chemotherapy (HR: 0.65; 95% CI, 0.37-1.12, p = 0.14). Significantly better OS was also observed in IP chemotherapy (HR: 0.17; 95% CI, 0.06-043, p < 0.0001), but was not present in IV chemotherapy in relation with BRCA mutation (HR: 0.52; 95% CI, 0.22-1.27, p = 0.15). For BRCA WT patients, worse survival was observed regardless of the adjuvant route used. The IP route was more toxic compared to the IV route, but toxicity was equivalent at the long-term follow-up.
    CONCLUSIONS: This retrospective study suggests that BRCA status can help to offer an individualized, systematic treatment after optimal primary surgery for advanced ovarian cancer, but is limited by the small sample size. Prospective trials are essential to confirm these results.
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  • 文章类型: Journal Article
    目的:尽管全身治疗取得了进展,胃癌(GC)腹膜癌(PC)患者的预后仍然很差,部分原因是由于血浆-腹膜屏障和肿瘤内循环无政府状态导致的全身治疗对腹膜转移的渗透性差。因此,局部治疗方法,将化疗直接注入腹膜腔(腹膜内,IP)在各种条件下,联合或不联合细胞减灭术(CRS)仍然是一个值得关注的研究领域.这篇综述的目的是为局限性腹膜疾病的GCPC的区域治疗方法提供高水平的证据。
    方法:对目前文献和正在进行的GCPC区域IP治疗的临床试验进行综述。本综述中包括的研究包括III期随机对照试验,非随机II期研究,高影响力的回顾性研究,以及每种可用IP模式的正在进行的积极临床试验。
    结果:三种常见的IP方法是加热腹膜内化疗(HIPEC),常温腹腔化疗(NIPEC)和最近推出的,加压腹膜内雾化化疗(PIPAC)。这些IP方法已与全身性治疗和/或CRS相结合,取得了不同程度的有希望的结果。证明生存率和腹膜疾病控制改善的证据。患者选择,系统治疗的优化,和细胞减灭术的完整性已成为影响当代和正在进行的试验设计的主要因素。
    结论:IP化疗在GCPC患者的治疗中具有明确的作用,在适当选择的患者中,当与CRS联合使用时,有可能显着提高生存率。正在进行和即将进行的IP疗法临床试验有望为GCPC塑造治疗范式。
    OBJECTIVE: Despite advances in systemic therapy, outcomes of patients with gastric cancer (GC) peritoneal carcinomatosis (PC) remain poor, in part because of poor penetrance of systemic therapy into peritoneal metastasis due to the plasma-peritoneal barrier and anarchic intra-tumoral circulation. Hence, regional treatment approach with administration of chemotherapy directly into the peritoneal cavity (intraperitoneal, IP) under various conditions, combined with or without cytoreductive surgery (CRS) has remained an area of significant research interest. The purpose of this review is to provide high-level evidence for regional treatment approaches in the management of GCPC with limited peritoneal disease.
    METHODS: A review of the current literature and ongoing clinical trials for regional IP therapies for GCPC was performed. Studies included in this review comprise of phase III randomized controlled trials, non-randomized phase II studies, high-impact retrospective studies, and active ongoing clinical trials for each available IP modality.
    RESULTS: The three common IP approaches are heated intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal chemotherapy (NIPEC) and more recently introduced, pressurized intraperitoneal aerosolized chemotherapy (PIPAC). These IP approaches have been combined with systemic therapy and/or CRS with varying degrees of promising results, demonstrating evidence of improvements in survival rates and peritoneal disease control. Patient selection, optimization of systemic therapy, and completeness of cytoreduction have emerged as major factors influencing the design of contemporary and ongoing trials.
    CONCLUSIONS: IP chemotherapy has a clear role in the management of patients with GCPC, and when combined with CRS in appropriately selected patients has the potential to significantly improve survival. Ongoing and upcoming IP therapy clinical trials hold great promise to shape the treatment paradigm for GCPC.
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  • 文章类型: Journal Article
    在我们的临床实践中,我们已经不再使用辅助的常温腹膜内(IP)化疗,特别是在GOG252发布之后。我们的决定植根于越来越多的证据表明缺乏明显的优越性,以及与其管理相关的公认毒性和后勤挑战。这一战略偏离也受到贝伐单抗和PARP抑制剂等维持疗法利用率上升的影响。这为改善患者预后提供了可行的替代方案。我们对IP热化疗(HIPEC)的使用目前只针对特定的患者队列,反映了OVHIPEC-1试验中研究的患者群体。具体来说,我们的HIPEC方案适用于新诊断的IIIC期高级别上皮性卵巢癌患者,这些患者被认为不适合进行原发性减积手术.患者必须表现出至少稳定的疾病与新辅助铂为基础的化疗,保持良好的表现状态(ECOG评分0-1),拥有良好的营养储备(没有证据表明蛋白质-热量营养不良和白蛋白水平超过3.5),也没有慢性肾病.当计划HIPEC时,它是在间隔减积手术时施用的,取决于获得最佳的手术结果(<1cm的残留疾病)。我们的HIPEC协议遵循原始的OVHIPEC-1试验指南,使用剂量为100mg/m2的顺铂。我们至少使用两种止吐药,抗组胺药,和硫代硫酸钠来减轻已知的副作用。术后,病人被送入普通外科,为处于危急状态的人保留重症监护室。我们遵循手术后加速恢复的原则,将早期下床和进食纳入我们的术后护理策略。我们用这种方法取得了令人鼓舞的结果,大多数患者的术后病程基本不复杂,并在手术后3至4周内恢复辅助化疗。
    In our clinical practice, we have shifted away from the use of adjuvant normothermic intraperitoneal (IP) chemotherapy, particularly following the publication of GOG 252. Our decision is rooted in the accumulating evidence indicating a lack of demonstrable superiority, alongside the recognized toxicities and logistical challenges associated with its administration. This strategic departure is also influenced by the rising utilization of maintenance therapies such as bevacizumab and PARP inhibitors, which present viable alternatives for improving patient outcomes. Our utilization of hyperthermic IP chemotherapy (HIPEC) is currently reserved for a specific cohort of patients, mirroring the patient population studied in the OVHIPEC-1 trial. Specifically, our HIPEC protocol applies to patients presenting with newly diagnosed stage IIIC high-grade epithelial ovarian cancer who are deemed ineligible for primary debulking surgery. Patients must exhibit at least stable disease with neoadjuvant platinum-based chemotherapy, maintain a favorable performance status (ECOG score 0-1), possess good nutritional reserves (with no evidence of protein-calorie malnutrition and an albumin level exceeding 3.5), and not have chronic kidney disease. When HIPEC is planned, it is administered at the time of interval debulking surgery, contingent upon the attainment of optimal surgical outcomes (< 1 cm of residual disease). Our HIPEC protocol adheres to the original OVHIPEC-1 trial guidelines, employing cisplatin at a dosage of 100 mg/m2. We administer at least two antiemetics, antihistamines, and sodium thiosulfate to mitigate known side effects. Postoperatively, patients are admitted to the general surgical floor, reserving the intensive care unit for those in critical condition. We follow Enhanced Recovery After Surgery principles, incorporating early ambulation and feeding into our postoperative care strategy. We have encountered encouraging results with this approach, with most patients having largely uncomplicated postoperative courses and resuming adjuvant chemotherapy within 3 to 4 weeks of surgery.
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  • 文章类型: Meta-Analysis
    自从韩国妇科肿瘤学会(KSGO)于2021年制定了最新的卵巢癌实践指南以来,许多研究已经检查了上皮性卵巢癌(EOC)各种治疗方法的有效性和安全性。因此,提出了为EOC治疗制定建议的必要性.本研究使用4个关键项目和人口,干预,比较,和结果:多聚ADP核糖聚合酶抑制剂在新诊断的晚期EOC中的疗效和安全性;在最佳减损的晚期EOC中,腹腔内联合静脉化疗的疗效和安全性;在铂类敏感的复发性卵巢癌中,二次细胞减灭术的疗效和安全性;在首次接受贝伐单抗治疗的铂类复发敏感的EOC患者中,在铂类化疗中加入贝伐单抗的疗效和安全性.这些建议的证据,根据每个关键问题,采用系统评价和荟萃分析进行评估。KSGO的卵巢癌委员会制定了EOC治疗的最新指南。
    Since the latest practice guidelines for ovarian cancer were developed by the Korean Society of Gynecologic Oncology (KSGO) in 2021, many studies have examined the efficacy and safety of various treatments for epithelial ovarian cancer (EOC). Therefore, the need to develop recommendations for EOC treatments has been raised. This study searched the literature using 4 key items and the Population, Intervention, Comparison, and Outcome: the efficacy and safety of poly-ADP ribose polymerase inhibitors in newly diagnosed advanced EOC; the efficacy and safety of intraperitoneal plus intravenous chemotherapy in optimally debulked advanced EOC; the efficacy and safety of secondary cytoreductive surgery in platinum-sensitive recurrent ovarian cancer; and the efficacy and safety of the addition of bevacizumab to platinum-based chemotherapy in first platinum-sensitive recurrent EOC patients who received prior bevacizumab. The evidence for these recommendations, according to each key question, was evaluated using a systematic review and meta-analysis. The committee of ovarian cancer of the KSGO developed updated guidelines for treatments of EOC.
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  • 文章类型: Journal Article
    背景:卵巢癌是死亡率最高的妇科恶性肿瘤,诊断通常发生在晚期。在这些情况下,标准治疗基于完整的细胞减灭术和辅助静脉化疗。正在评估其他类型的治疗方法,以改善这些患者的预后,包括腹膜内化疗和抗血管生成治疗。除静脉化疗外,这些药物还可以改善生存率或复发时间。
    目的:本荟萃分析的目的是确定静脉化疗治疗是否仍然是金标准,或增加腹腔内化疗是否对总生存期(OS)和无病间期(DFS)有益处。
    方法:在Pubmed和Cochrane进行了文献检索,选择最近10年发表的临床研究和系统评价。使用RevMan工具中的风险比度量进行统计分析。
    结果:与标准静脉化疗相比,腹膜内化疗显示出OS和DFS的益处。OS(HR:0.81CI95%0.74-0.88)和DFS(HR:0.81CI95%0.75-0.87)的显著差异有统计学意义(p<0.00001)。在毒性和副作用方面没有临床差异。
    结论:腹膜内化疗是一种改善OS和DFS的选择,对于单独使用静脉化疗没有显著毒性。然而,需要进行前瞻性研究,以确定最佳剂量和治疗方案,以保持获益,同时最大限度地减少副作用和毒性,以及从这种治疗中获益最多的患者的情况.
    BACKGROUND: Ovarian cancer is the gynaecological malignancy with the highest mortality and diagnosis often occurs in its advanced stages. Standard treatment in these cases is based on complete cytoreductive surgery with adjuvant intravenous chemotherapy. Other types of treatment are being evaluated to improve the prognosis of these patients, including intraperitoneal chemotherapy and antiangiogenic therapy. These may improve survival or time to relapse in addition to intravenous chemotherapy.
    OBJECTIVE: The aim of this meta-analysis is to determine whether treatment with intravenous chemotherapy remains the gold standard, or whether the addition of intraperitoneal chemotherapy has a benefit in overall survival (OS) and disease-free interval (DFS).
    METHODS: A literature search was carried out in Pubmed and Cochrane, selecting clinical studies and systematic reviews published in the last 10 years. Statistical analysis was performed using the hazard ratio measure in the RevMan tool.
    RESULTS: Intraperitoneal chemotherapy shows a benefit in OS and DFS compared with standard intravenous chemotherapy. The significant differences in OS (HR: 0.81 CI 95% 0.74-0.88) and in DFS (HR: 0.81 CI 95% 0.75-0.87) are statistically significant (p < 0.00001). There were no clinical differences in toxicity and side-effects.
    CONCLUSIONS: Intraperitoneal chemotherapy is an option that improves OS and DFS without significant toxicity regarding the use of intravenous chemotherapy alone. However, prospective studies are needed to determine the optimal dose and treatment regimen that will maintain the benefits while minimising side effects and toxicity and the profile of patients who will benefit most from this treatment.
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  • 文章类型: Journal Article
    Cytoreductive surgery (CRS), combined with hyperthermic intraperitoneal chemotherapy, has significantly improved survival outcomes in patients with peritoneal carcinomatosis from colorectal cancer (CRC). Regorafenib is an oral agent administered in patients with refractory metastatic CRC. Our aim was to investigate the outcomes of intraperitoneal administration of regorafenib for intraperitoneal chemotherapy (IPEC) or/and CRS in a rat model of colorectal peritoneal metastases regarding immunology and peritoneal cytology. A total of 24 rats were included. Twenty-eight days after carcinogenesis induction, rats were randomized into following groups: group A: control group; group B: CRS only; group C: IPEC only; and group D: CRS + IPEC. On day 56 after carcinogenesis, euthanasia and laparotomy were performed. Serum levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) as well as peritoneal cytology were investigated. Groups B and D had statistically significant lower mean levels of IL-6 and TNF-α compared to groups A and C, but there was no significant difference between them. Both B and D groups presented a statistically significant difference regarding the rate of negative peritoneal cytology, when compared to the control group, but not to group C. In conclusion, regorafenib-based IPEC, combined with CRS, may constitute a promising tool against peritoneal carcinomatosis by altering the tumor microenvironment.
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