Establishment of a desirable dose using neutral argon plasma to eradicate miliary peritoneal implants: A phase I/II controlled trial.

INTRODUCTION: Neutral argon plasma (NAP) system could meet the requirements to achieve oncological cytoreduction of peritoneal carcinomatosis with miliary lesions, minimizing the associated morbidity. This phase I/II trial aims to establish the desirable dose that is safe and effective in eliminating tumor cells with lower penetration. METHODS: Patients diagnosed with different origins for peritoneal carcinomatosis and miliary implants were selected for the study. The safe and potentially effective dose (desirability) of NAP was evaluated according to three factors: distance (mm), application time (s) and power (%), to evaluate the response variables such as the presence of tumor cells (Y/N) and the depth of penetration. RESULTS: Ten patients and 120 samples were evaluated and treated with NAP. There was no vascular or organ injury intraoperative using a pre-established dose of 100% (coagulation mode) at a distance of 2-3 cm. The distance was found to be correlated with the presence of the tumor cells in ex-vivo analysis, with an OR of 15.4 (4.0-111.4). The time and energy used were protective factors to eliminate tumor cells with an OR of 0.4 (0.1-0.9) and 0.8 (0.8-0.9), respectively. The safest and most effective desirability results were as follows i) energy 80% during 2-4 s with a distance of 2 cm (0.89), and ii) energy 100% during 2-4 s with a distance of 3 cm (0.90). CONCLUSIONS: The use of NAP during a CRS and HIPEC is safe and effective for eradicating tumor cells on the peritoneal surface at suggested doses of energy, distance and duration. TRIAL IDENTIFICATION: ClinicalTrials.gov Identifier: NCT04904042.

Complete laparoscopic pelvic peritonectomy plus hyperthermic intraperitoneal chemotherapy.

BACKGROUND: The aim of our study was to present the technique for, and early results of complete laparoscopic pelvic peritonectomy (LPP) plus hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: We conducted a study on consecutive patients who had LPP for limited peritoneal carcinomatosis (peritoneal carcinomatosis index < 10) from ovarian cancer, colon cancer and benign multicystic mesothelioma, from January 2017 to November 2019 at 2 referral centers in Spain. Perioperative, pathologic, 30-day major morbidity and mortality characteristics were analyzed. The surgical technique is shown in the attached video. RESULTS: Twelve LPP + HIPEC were performed. Complete cytoreduction was achieved in 100% of the patients, the median duration of the operation was 450 min (range 360-600 min). There were 2 cases (16%) of IIIa morbidity (trocar hernia and pleural effusion), and no mortality. The median length of hospital stay was 5.5 days (range 4-10 days). The median length of follow-up was 10 months (range 2-30 months). There was a recurrence at the splenic hilum in 1 patient which was treated by laparoscopic splenectomy and one nodal recurrence at 13 months while all other patients are alive and free of disease at last follow-up. CONCLUSIONS: This is the first technical video of a minimally invasive approach for complete pelvic peritonectomy plus omentectomy associated with HIPEC. For highly selected patients, this procedure presents a feasible and safe alternative to the maximally invasive approach.

RAS Mutation Decreases Overall Survival After Optimal Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy of Colorectal Peritoneal Metastasis: A Modification Proposal of the Peritoneal Surface Disease Severity Score.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are currently the most accepted treatment for peritoneal metastases from colorectal cancer. Restrictive selection criteria are essential to obtain the best survival benefits for this complex procedure. The most widespread score for patient selection, the peritoneal surface disease severity score (PSDSS), does not include current biological factors that are known to influence on prognosis. We investigated the impact of including RAS mutational status in the selection criteria for these patients. METHODS: We studied the risk factors for survival by multivariate analysis using a prospective database of consecutive patients with carcinomatosis from colorectal origin treated by CRS and HIPEC in our unit from 2009 to 2017. The risk factors obtained were validated in a multicentre, international cohort, including a total of 520 patients from 15 different reference units. RESULTS: A total of 77 patients were selected for local análisis. Only RAS mutational status (HR: 2.024; p = 0.045) and PSDSS stage (HR: 2.90; p = 0.009) were shown to be independent factors for overall survival. Early PSDSS stages I and II associated to RAS mutations impaired their overall survival with no significant differences with PSDSS stage III overall survival (p > 0.05). These results were supported by the international multicentre validation. CONCLUSIONS: By including RAS mutational status, we propose an updated RAS-PSDSS score that outperforms PSDSS alone providing a quick and feasible preoperative assessment of the expected overall survival for patients with carcinomatosis from colorectal origin undergone to CRS + HIPEC.

Cytoreductive Surgery and Intraperitoneal Hyperthermic Chemotherapy (HIPEC) by Minimally Invasive Approach, an Initial Experience.

BACKGROUND: The cytoreductive surgery (CRS) associated with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the standard treatment in patients with carcinomatosis peritoneal from different origins. The use of a minimally invasive approach for this high complex procedure might be an alternative that provides them less morbidity and faster recovery with similar oncologic outcomes. METHODS: We describe the initial experience of CRS and HIPEC done via the laparoscopic route in patients with minimal peritoneal metastases in our Unit from March 2016 to January 2018. RESULTS: A total of eight patients were operated by this minimally invasive approach. The different diagnoses were low-grade pseudomyxoma peritonei (2), benign multicystic mesothelioma (2), primary epithelial ovarian carcinomatosis (2) and locally advanced colon carcinoma T4 (2). The median age was 54 (20-62) years, the median PCI was 3 (2-4), the median operative time was 287 min (240-360), complete cytoreduction CC0 was achieved in all the patients, and no major morbidity was observed. The median length of stay was 4.75 days (4-5). After a median follow-up of 9.5 months, no relapse has been observed. CONCLUSION: The results suggest that this minimally invasive approach for CRS and HIPEC is feasible and safe in a highly selected group of patients with peritoneal surface malignancies.

HIPECT4: multicentre, randomized clinical trial to evaluate safety and efficacy of Hyperthermic intra-peritoneal chemotherapy (HIPEC) with Mitomycin C used during surgery for treatment of locally advanced colorectal carcinoma.

BACKGROUND: Local relapse and peritoneal carcinomatosis (PC) for pT4 colon cancer is estimated in 15,6% and 36,7% for 12 months and 36 months from surgical resection respectively, achieving a 5 years overall survival of 6%. There are promising results using prophylactic HIPEC in this group of patients, and it is estimated that up to 26% of all T4 colon cancer could benefit from this treatment with a minimal morbidity. Adjuvant HIPEC is effective to avoid the possibility of peritoneal seeding after surgical resection. Taking into account these results and the cumulative experience in HIPEC use, we will lead a randomized controlled trial to determine the effectiveness and safety of adjuvant treatment with HIPEC vs. standard treatment in patients with colon cancer at high risk of peritoneal recurrence (pT4). METHODS/DESIGN: The aim of this study is to determine the effectiveness and safety of adjuvant HIPEC in preventing the development of PC in patients with colon cancer with a high risk of peritoneal recurrence (cT4). This study will be carried out in 15 Spanish HIPEC centres. Eligible for inclusion are patients who underwent curative resection for cT4NxM0 stage colon cancer. After resection of the primary tumour, 200 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously after the primary resection. Mitomycin C will be used as chemotherapeutic agent, for 60 min at 42-43 °C. Primary endpoint is loco-regional control (LC) in months and the rate of loco-regional control (%LC) at 12 months and 36 months after resection. DISCUSSION: We assumed that adjuvant HIPEC will reduce the expected absolute risk of peritoneal recurrence from 36% to 18% at 36 months for T4 colon-rectal carcinoma. TRIAL REGISTRATION: NCT02614534 ( clinicaltrial.gov ) Nov-2015.

"Assessment of RIFLE and AKIN criteria to define acute renal dysfunction for HIPEC procedures for ovarian and non ovarian peritoneal malignances".

BACKGROUND: The acute renal dysfunction (ARD) is a common complication in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Our aim is evaluate the ARD post-HIPEC procedures using the RIFLE and AKIN criteria. Evaluate the risk factors and analyze ARD's impact on postoperative course. METHODS: From 2011 to 2014, in a retrospective way using a prospective database were operated by HIPEC procedure. The ARD was analyzed by RIFLE and AKIN criteria. The perioperative features were analyzed and a multivariate analysis was performed to define the risk factors to develop the ARD. RESULTS: 141 patients were treated and analyzed. The ARD was detected in 30.5% (Injury 18.4% and Failure 12.1%) when RIFLE criteria were applied. The multivariate analysis detected that decrease of pH during HIPEC [OR = 29.39 (5.09-169.76)], PCI [OR = 1.07 (1.01-1.15)] and ureteral catheters [OR = 12.71 (1.44-111.85)] were associated to the development of acute renal injury (ARI) post-HIPEC. Decrease of Na during HIPEC [OR = 1.15 (1.01-1.30)], intraoperative inotrope use [OR = 3.83 (1.12-13.09)] and PCI [OR = 1.06 (1.0-1.14)] were associated to acute renal failure (ARF) post-HIPEC. The ARD was related to a higher length of stay hospital (17.2 ± 11 vs. 13.8 ± 8 days) (p = 0.05) but no impact in early survival was observed in ARD group. CONCLUSIONS: The widespread use of RIFLE criteria for ARD would have major benefits in terms of accurately diagnosing patients undergone HIPEC procedures. The ARD has a detrimental impact in length of stay hospital. The knowledge of risk factors helps us to prevent the ARD post-HIPEC by means of an aggressive and multidisciplinary perioperative management.

Peritonectomy procedures and HIPEC in the treatment of peritoneal carcinomatosis from ovarian cancer: Long-term outcomes and perspectives from a high-volume center.

BACKGROUND: Cytoreductive surgery with peritonectomy procedures and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) represents a radical therapeutic approach to achieve complete cytoreduction in ovarian peritoneal carcinomatosis. The aim of the present study was to analyze the outcomes obtained by the application of these procedures in a single center with extensive experience treating peritoneal carcinomatosis. PATIENTS AND METHODS: A series of 218 consecutive patients diagnosed with peritoneal carcinomatosis from primary or recurrent ovarian cancer (FIGO stage IIIC-IV) and treated with CRS + HIPEC between January 1996 and June 2012 were included in this observational study. RESULTS: Peritoneal carcinomatosis was treated primarily in 56% (124/218) of the cases and recurrently in 43% (94/218). A total of 42/218 patients (19%) presented with FIGO stage IV. Compared to recurrent cases, patients with primary ovarian carcinomatosis were older and presented higher Peritoneal Cancer Index (PCI) and percentage of FIGO stage IV; however, no significant differences in survival (5-year overall survival in patients with R0 cytoreduction, 63% and 56%, respectively) were observed. Cytoreduction score, PCI, lymphatic involvement and surgical morbidity ≥Grade III were statistically significant prognostic factors for survival in both univariate and multivariate analysis. CONCLUSIONS: CRS + HIPEC treating macroscopic and microscopic disease is currently an excellent surgical approach to achieve high rates of complete cytoreduction and improve survival in patients with peritoneal carcinomatosis from ovarian cancer. In order to minimize the high potential morbidity of these procedures, CRS + HIPEC should be performed in highly experienced centers.