Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) vs CRS alone for treatment of endometrial cancer with peritoneal metastases: a multi-institutional study from PSOGI and BIG RENAPE groups

Objective To investigate the benefit of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of endometrial peritoneal carcinomatosis compared to CRS alone. Methods We conducted a retrospective multicentre study of patients from experienced centres in treating peritoneal malignancies from 2002 to 2015. Patients who underwent surgery for peritoneal evolution of endometrial cancer (EC) were included. Two groups of 30 women were matched and compared: “CRS + HIPEC” which used HIPEC after CRS, and “CRS only” which did not use HIPEC. We analysed clinical, pathologic and treatment data for patients with peritoneal metastases from EC. The outcome measures were morbidity, overall survival (OS), and progression-free survival (PFS). Results In “CRS plus HIPEC” group, 96.7% of women were treated for recurrence, while in “CRS only” 83.3 were treated for primary disease. There was no significant difference between Peritoneal Carcinomatosis Index at laparotomy or Completeness of Cytoreduction score. Grade III and IV complications rates did not significantly differ between “CRS plus HIPEC” group and “CRS only” group (20.7% vs 20.7%, p = 0.739). Survival analysis showed no statistical difference between both groups. Median OS time was 19.2 months in “CRS plus HIPEC” group and 29.7 months in “CRS only” group (p = 0.606). Median PFS survival time was 10.7 months in “CRS plus HIPEC” group and 13.1 months in “CRS only” group (p = 0.511). Conclusion The use of HIPEC combined to CRS did not have any significance as regard the DFS and OS over CRS alone in patients with primary or recurrent peritoneal metastasis of endometrial cancer.

Safety and Clinical Value of Prophylactic Ureteral Stenting Before Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy

Background Prophylactic ureteral stents (PUS) are typically placed prior to complex abdominal or pelvic operations at the surgeon’s discretion to help facilitate detection of iatrogenic ureteral injury. However, its usefulness and safety in the setting of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) have not been examined. This study aims to evaluate the potential clinical value and risk profile of prophylactic ureteral stent placement prior to CRS-HIPEC. Methods We performed a single-institutional retrospective analysis of 145 patients who underwent CRS-HIPEC from 2013 to 2021. Demographic and operative characteristics were compared between patients who underwent PUS placement and those that did not. Ureteral stent–related complications were evaluated. Results Of the 145 patients included in the analysis, 124 underwent PUS placement. There were no significant differences in patient demographics, medical comorbidities, or tumor characteristics. Additionally, PUS placement did not significantly increase operative time and was not associated with increased pelvic organ resection. However, patients who underwent prophylactic ureteral stenting had significantly higher peritoneal carcinomatosis index score (15.1 vs 9.1, P =.002) and increased rate of ureteral complications (24.2% vs 14.3%, P =.04), which led to lengthened hospital stay (13.2 days vs 8.1 days, P = .03). Notably, the sole ureteral injury and three cases of hydronephrosis were seen in patients who underwent PUS. Conclusion Prophylactic ureteral stent placement in patients undergoing CRS-HIPEC may be useful, particularly in patients with predetermined extensive pelvic disease. However, PUS placement is not without potential morbidity and should be selectively considered in patients for whom benefits outweigh the risks.

Cytoreductive Surgery (CRS) Plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC) vs CRS Alone for Treatment of Endometrial Cancer with Peritoneal Metastases: A Multi-Institutional Study from PSOGI and BIG RENAPE Groups

ObjectiveTo investigate the benefit of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of endometrial peritoneal carcinomatosis compared to CRS alone.MethodsWe conducted a retrospective multicentre study of patients from experienced centres in treating peritoneal malignancies from 2002 to 2015. Patients who underwent surgery for peritoneal evolution of endometrial cancer (EC) where included. Two groups of 30 women were matched and compared: “CRS +HIPEC” which used HIPEC after CRS, and “CRS only” which did not used HIPEC. We analysed clinical, pathologic and treatment data for patients with peritoneal metastases from EC. The outcome measures were morbidity, overall survival (OS), and progression-free survival (PFS).ResultsIn “CRS plus HIPEC” group, 96,7% of women were treated for recurrence, while in “CRS only” 83,3 were treated for primary disease. There was no significant difference between Peritoneal Carcinomatosis Index at laparotomy or Completeness of Cytoreduction score. Grade III and IV complications rates did not significantly differ between “CRS plus HIPEC” group and “CRS only” group (20.7% vs 20.7%, p=0.739). Survival analysis showed no statistical difference between both groups. Median OS time was 19.2 months in “CRS plus HIPEC” group and 29.7 months in “CRS only” group (p=0.606). Median PFS survival time was 10.7 months in “CRS plus HIPEC” group and 13.1 months in “CRS only” group (p=0.511).ConclusionThe use of HIPEC combined to CRS appears to be as effective, well tolerated and feasible as CRS alone in patients with primary or recurrent peritoneal metastasis of endometrial cancer.

Blood Flow and Shear Stress Allow Monitoring of Progression and Prognosis of Tumor Diseases

In the presence of tumor angiogenesis, blood flow must increase, leading to an elevation of blood flow velocities (BFVels) and wall shear stress (WSS) in upstream native arteries. An adaptive arterial remodeling is stimulated, whose purpose lies in the enlargement of the arterial inner diameter, aiming for normalization of BFVels and WSS. Remodeling engages delayed processes that are efficient only several weeks/months after initiation, independent from those governing expansion of the neovascular network. Therefore, during tumor expansion, there is a time interval during which elevation of BFVels and WSS could reflect disease progression. Conversely, during the period of stability, BFVels and WSS drop back to normal values due to the achievement of remodeling processes. Ovarian peritoneal carcinomatosis (OPC), pseudomyxoma peritonei (PMP), and superficial arteriovenous malformations (AVMs) are diseases characterized by the development of abnormal vascular networks developed on native ones. In OPC and PMP, preoperative blood flow in the superior mesenteric artery (SMA) correlated with the per-operative peritoneal carcinomatosis index (OPC: n = 21, R = 0.79, p < 0.0001, PMP: n = 66, R = 0.63, p < 0.0001). Moreover, 1 year after surgery, WSS in the SMA helped in distinguishing patients with PMP from those without disease progression [ROC-curve analysis, AUC = 0.978 (0.902–0.999), p < 0.0001, sensitivity: 100.0%, specificity: 93.5%, cutoff: 12.1 dynes/cm2]. Similarly, WSS in the ipsilateral afferent arteries close to the lesion distinguished stable from progressive AVM [ROC-curve analysis, AUC: 0.988, (0.919–1.000), p < 0.0001, sensitivity: 93.5%, specificity: 95.7%; cutoff: 26.5 dynes/cm2]. Blood flow volume is indicative of the tumor burden in OPC and PMP, and WSS represents an early sensitive and specific vascular marker of disease progression in PMP and AVM.

44 Hipec Therapy-A New Development to Fight Cancer; Report Of 3 Cases

Introduction HIPEC is highly concentrated, heated chemotherapy treatment that is delivered directly to the abdomen during surgery. HIPEC delivers chemotherapy directly to cancer cells in abdomen. Cytoreductive surgery(CRS) combined with perioperative intraperitoneal chemotherapy is currently a valid treatment option for peritoneal dissemination of gastrointestinal, gynaecological cancers or primary peritoneal neoplasms. Method 3 patients with peritoneal surface malignancy were selected. PET scan was done for all the patients to assess metastasis and peritoneal carcinomatosis index(PCI) calculated was<20 for all 3 patients They were then treated with CRS+HIPEC therapy with disease-specific chemotherapeutic agents like Cisplatin, Mitomycin and Doxorubicin and Oxaliplatin . Aim was Results All the 3 patients had a good post-operative recovery with no recurrence in the follow-up period Conclusions HIPEC and CRS plays synergistic role. A complete CRS followed by HIPEC with the disease-specific chemotherapeutic agent at 41-43ºC constitutes optimal treatment for certain malignancies. High regional concentration with low systemic concentration of chemotherapy, increased tissue penetration and thermal enhancement of cytotoxicity are some of the advantages with HIPEC therapy

Validation of three predictive models for suboptimal cytoreductive surgery in advanced ovarian cancer

The standard treatment for advanced ovarian cancer (AOC) is cytoreduction surgery and adjuvant chemotherapy. Tumor volume after surgery is a major prognostic factor for these patients. The ability to perform complete cytoreduction depends on the extent of disease and the skills of the surgical team. Several predictive models have been proposed to evaluate the possibility of performing complete cytoreductive surgery (CCS). External validation of the prognostic value of three predictive models (Fagotti index and the R3 and R4 models) for predicting suboptimal cytoreductive surgery (SCS) in AOC was performed in this study. The scores of the 3 models were evaluated in one hundred and three consecutive patients diagnosed with AOC treated in a tertiary hospital were evaluated. Clinicopathological features were collected prospectively and analyzed retrospectively. The performance of the three models was evaluated, and calibration and discrimination were analyzed. The calibration of the Fagotti, R3 and R4 models showed odds ratios of obtaining SCSs of 1.5, 2.4 and 2.4, respectively, indicating good calibration. The discrimination of the Fagotti, R3 and R4 models showed an area under the ROC curve of 83%, 70% and 81%, respectively. The negative predictive values of the three models were higher than the positive predictive values for SCS. The three models were able to predict suboptimal cytoreductive surgery for advanced ovarian cancer, but they were more reliable for predicting CCS. The R4 model discriminated better because it includes the laparotomic evaluation of the peritoneal carcinomatosis index.

Neoadjuvant Chemotherapy Followed by Hyperthermic Intraperitoneal Chemotherapy for Patients with Colorectal Peritoneal Metastasis: A Retrospective Study of its Safety and Efficacy

Background Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are effective routine treatments for colorectal peritoneal metastases (PMs). However, the safety and efficacy of neoadjuvant chemotherapy (NAC) before CRS+HIPEC are poorly understood. Therefore, this study aimed to assess the perioperative safety and long-term efficacy for patients with synchronous colorectal PM who received NAC prior to CRS+HIPEC.Method Patients with synchronous colorectal PM who received NAC prior to CRS+HIPEC were systematically reviewed at the China National Cancer Center and Huanxing Cancer Hospital from June 2017 to June 2019. Clinicopathologic characteristics, perioperative parameters, and survival were compared between patients who underwent CRS+HIPEC with NAC (NAC group) and those who underwent CRS+HIPEC without NAC (non-NAC group).Results The study enrolled 52 patients, with 20 patients in the NAC group and 32 in the non-NAC group. In the NAC group, the proportion of patients with a peritoneal carcinomatosis index (PCI) score < 12 was significantly higher than that in the non-NAC group (80.0% vs 50.0%, P=0.031), and more patients received complete cyoreduction (80.0% vs 46.9%, P=0.018). The two groups had comparable grade III/IV complications and similar reoperation and mortality rates (P>0.05). However, patients who received NAC prior to CRS+HIPEC experienced lower platelet counts (151.9 vs 197.7 ×109/L, P=0.036) and neutrophil counts (4.7 vs 7.2×109/L, P=0.030) on postoperative day 1. Compared with the non-NAC group, more patients in the NAC group survived for two years (67.4% vs. 32.2%, respectively, P = 0.044). However, the CC score (HR, 2.99; 95% CI, 1.14-7.84; P=0.026), rather than NAC, was independently associated with OS in the multivariable analysis after controlling for confounding factors.Conclusion NAC administration before CRS+HIPEC can be regarded as a safe and feasible treatment for patients with colorectal PM with comparably low mortality and acceptable morbidity. Nevertheless, the administration of NAC before CRS+HIPEC conferred a greater survival benefit to patients, even though NAC was not identified as an independent factor for OS after controlling for confounding factors.

Survival advantage of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer: experience from a Western tertiary referral center

Background Selection criteria and prognostic factors for patients with advanced gastric cancer (AGC) undergoing cytoreductive surgery (CRS) plus hyperthermic intra-operative peritoneal chemotherapy (HIPEC) have not been well defined, and the literature data are not homogeneous. The aim of this study was to compare prognostic factors influencing overall (OS) and disease-free survival (DFS) in a population of patients affected by AGC with surgery alone and surgery plus HIPEC, both with curative (PCI, peritoneal carcinomatosis index > 1) and prophylactic (PCI = 0) intent. Methods A retrospective analysis of a prospectively collected database was conducted in patients affected by AGC from January 2006 to December 2015. Uni- and multivariate analyses of prognostic factors were performed. Results A total of 85 patients with AGC were analyzed. A 5-year OS for surgery alone, CRS plus curative HIPEC, and surgery plus prophylactic HIPEC groups was 9%, 27% and 33%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p = 0.05), curative HIPEC vs surgery alone group (p = 0.03), and curative vs prophylactic HIPEC (p = 0.04). A 5-year DFS for surgery alone, CRS + curative HIPEC, and surgery + prophylactic HIPEC groups was 9%, 20%, and 30%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p < 0.0001), curative HIPEC vs surgery alone group (p = 0.008), and curative vs prophylactic HIPEC (p = 0.05). Conclusions Patients with AGC undergoing surgery plus HIPEC had a better OS and DFS with respect to patients treated with surgery alone.

Two-step cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei with high peritoneal carcinomatosis index

Background Complete cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the only curative treatment for pseudomyxoma peritonei (PMP) arising from the appendix. High peritoneal carcinomatosis index (PCI) is associated with an increased risk of surgical complications. The objective of this study was to present the results of a planned two-step surgical strategy to decrease postoperative morbidity and improve resectability of patients with very high PCI. Methods All consecutive patients who underwent a planned two-step surgical approach for PMP between January 2012 and March 2020 were retrospectively included. This approach was offered for patients with low-grade PMP with PCI > 28 for which feasibility of a complete CRS in one operation was uncertain. The first surgery included a complete CRS of the inframesocolic compartment and omentectomy. HIPEC was delivered at the second surgery, after complete CRS of the supramesocolic compartment. Postoperative morbidity was assessed using the Clavien-Dindo classification and survival results were also collected. Results Eight patients underwent the two-step approach. The median PCI was 33 (29–39) and the median time between the two procedures was 111 days (90–212 days). One patient was deemed unresectable at the second surgery. The rate of major morbidity was 0% for the first step and 25% for the second step, with no mortality. Median follow-up was 53.8 months (3–73 months). Conclusion A two-step surgical management for low-grade PMP patients with very high PCI is safe and feasible, with acceptable postoperative morbidity and no compromise on oncological outcomes.

Survival advantage of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer: experience from a Western tertiary referral center

Background Selection criteria and prognostic factors for patients with advanced gastric cancer (AGC) undergoing cytoreductive surgery (CRS) plus hyperthermic intra-operative peritoneal chemotherapy (HIPEC) have not been well defined and the literature data are not homogeneous. The aim of this study was to compare prognostic factors influencing overall (OS) and disease-free survival (DFS) in a population of patients affected by AGC with surgery alone and surgery plus HIPEC, both with curative (PCI, Peritoneal Carcinomatosis Index >1) and prophylactic (PCI=0) intent. Methods A retrospective analysis of a prospectively collected database was conducted in patients affected by AGC from January 2006 to December 2015. Uni- and multivariate analyses of prognostic factors were performed. Results A total of 85 patients with AGC were analyzed. Five-year OS for surgery alone, CRS plus curative HIPEC, and surgery plus prophylactic HIPEC groups was 9%, 27%, and 33%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p = 0.05), curative HIPEC vs surgery alone group (p = 0.03), and curative vs prophylactic HIPEC (p = 0.04). Five-year DFS for surgery alone, CRS + curative HIPEC, and surgery + prophylactic HIPEC groups was 9%, 20%, and 30%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p < 0.0001), curative HIPEC vs surgery alone group (p = 0.008), and curative vs prophylactic HIPEC (p = 0.05). Conclusions Patients with AGC undergoing surgery plus HIPEC had a better OS and DFS with respect to patients treated with surgery alone.