Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy Research Articles

Implementation of a Multidisciplinary Enhanced Recovery After Surgery (ERAS) Program for Cytoreductive Surgery (CRS) With Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) can be associated with prolonged hospital stays. A novel Enhanced Recovery After Surgery (ERAS) based on ERAS Society guidelines was designed and implemented. The primary outcome was ERAS compliance. Secondary outcomes included length of stay (LOS) and postoperative complications. A retrospective study on patients who underwent CRS/HIPEC between 2018 and 2022, with ERAS implementation in 2022. Health records were reviewed. Statistical analysis included descriptive statistics, Wilcoxon tests, Student t-test, and χ2 and binomial negative regression. Health Ethics Research Board approval was obtained. Eighty patients underwent CRS/HIPEC: 59 in the pre-ERAS group and 21 in the post-ERAS group. Groups were similar in age, comorbidities, and Peritoneal Carcinomatosis Index. ERAS compliance increased from 32.8% to 70.8% (p < 0.001). Median LOS decreased from 14 to 9 days (p < 0.001). Comparing pre-ERAS to post-ERAS showed no significant difference in the major morbidity rate (13.6% vs. 9.5%) or 30-day readmission (9.4% vs. 4.8%) and no mortalities. Controlling for patient characteristics, the mean LOS decreased by 6.94 days (p < 0.001). Implementation of an ERAS CRS/HIPEC program is safe and allows for improved compliance to ERAS protocols and a significant reduction in LOS.

Triphasic Learning Curve of Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is an effective but costly procedure for select patients with peritoneal malignancies. The impact of progression along a learning curve on the cost of these procedures is unknown. We performed a retrospective cohort study of patients undergoing CRS-HIPEC from 2016 to 2022 at a single quaternary center. Our study cohort was temporally divided into four equally sized volume quartiles (A, B, C, and D). We utilized cumulative sum plots and split-group analysis to characterize the institutional learning curve based on cost, operative time, length of stay, and morbidity. Multivariable linear regression was performed to estimate costs after adjusting for covariates. Bivariate analysis was performed using a Kruskal-Wallis test to compare continuous variables and a χ2 test to compare categorical variables. Of 201 patients, the median age [interquartile range (IQR)] was 57 (47-65) years, 113 (56%) patients were female, 143 (71%) were white, and 107 (53%) had private insurance. Median operating room charge [US$42,639 (US$32,477-54,872), p < 0.001] varied between volume quartiles, peaking in quartile C. Stabilization was achieved for 86 cases for operating room cost, 88 cases for routine cost, 96 cases for length of stay, 103 cases for operative time, 120 cases for intensive care unit length of stay, and 150 cases for overall and serious morbidity. The actual operating room and routine costs were similar to predicted costs at the end of the study period. The CRS-HIPEC learning curve is triphasic, with cost stability achieved relatively early compared with other markers of surgical proficiency.

Surgical management of peritoneal metastases from appendix and colon cancer in patients with inflammatory bowel disease

BackgroundInflammatory bowel disease (IBD) may compromise outcomes of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for peritoneal metastases (PM) from appendix/colon cancer. We evaluated CRS/HIPEC outcomes in patients with concurrent IBD. MethodsA matched cohort study using a prospective institutional CRS/HIPEC database (1998–2023) included appendix/colon cancer patients with PM. We matched IBD patients to IBD-free controls in a 1:5 ratio with nearest-neighbor propensity score for sex, age, and peritoneal cancer index (PCI), and exact matching for prior CRS/HIPEC and primary tumor. Perioperative variables, including Clavien-Dindo 90-day complications, were compared. Kaplan-Meier overall (OS) and progression-free survival (PFS) were compared using stratified Cox regression. ResultsOf 605 CRS/HIPECs for appendix/colon cancer, 14 (2.3%) had concurrent Crohn’s disease (n = 6) or ulcerative colitis (n = 8). Seventy IBD-free controls were matched. Nine (64.7%) IBD patients had an appendix primary. Complete cytoreduction (CC-0/1) was achieved in 10 (71.4%) IBD and 57 (81.4%) IBD-free patients (p = 0.468). IBD vs IBD-free patients tended to have more grade-III/IV complications (35.7% [n = 5] vs 15.7% [n = 11], p = 0.082) and had a higher rate of severe nausea/vomiting (35.7% vs 4.3 %, p < 0.001) and diarrhea (28.6% vs 8.6%, p = 0.035). Rates of anastomotic leak (7.1% [n = 1] vs 1.4% [n = 1], p = 0.200) and intraabdominal infections (7.1% [n = 1] vs 2.9% [n = 2], p = 0.430) were similar for IBD vs IBD-free, respectively. IBD did not affect OS (HR [95% CI]: 1.1 [0.4, 2.9]) or PFS (HR [95% CI]: 1.2 [0.4, 3.9]). ConclusionIBD is associated with a higher rate of gastrointestinal complications after CRS/HIPEC for appendix/colon cancer; however, it does not affect OS or PFS.

A machine learning approach for predicting textbook outcome after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Peritoneal carcinomatosis is considered a late-stage manifestation of neoplastic diseases. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) can be an effective treatment for these patients. However, the procedure is associated with significant morbidity. Our aim was to develop a machine learning model to predict the probability of achieving textbook outcome (TO) after CRS-HIPEC using only preoperatively known variables. Adult patients with peritoneal carcinomatosis and who underwent CRS-HIPEC were included from a large, single-center, prospectively maintained dataset (2001-2020). TO was defined as a hospital length of stay ≤14days and no postoperative adverse events including any complications, reoperation, readmission, and mortality within 90days. Four models (logistic regression, neural network, random forest, and XGBoost) were trained, validated, and a user-friendly risk calculator was then developed. A total of 1954 CRS-HIPEC procedures for peritoneal carcinomatosis were included. Overall, 13% (n=258) achieved TO following CRS-HIPEC procedure. XGBoost and logistic regression had the highest area under the curve (AUC) (0.76) after model optimization, followed by random forest (AUC 0.75) and neural network (AUC 0.74). The top preoperative variables associated with achieving a TO were lower peritoneal cancer index scores, not undergoing proctectomy, splenectomy, or partial colectomy and being asymptomatic from peritoneal metastases prior to surgery. This is a data-driven study to predict the probability of achieving TO after CRS-HIPEC. The proposed pipeline has the potential to not only identify patients for whom surgery is not associated with prohibitive risk, but also aid surgeons in communicating this risk to patients.

ASO Author Reflections: Addressing Hospital-Based Disparities in Access to Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) and Survival in Patients with Isolated Colorectal Peritoneal Metastases.

ASO Author Reflections: Addressing Hospital-Based Disparities in Access to Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC) and Survival in Patients with Isolated Colorectal Peritoneal Metastases.

Towards Equal Access to Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy and Survival in Patients with Isolated Colorectal Peritoneal Metastases: A Nationwide Population-Based Study

BackgroundBefore 2016, patients with isolated synchronous colorectal peritoneal metastases (PMCRC) diagnosed in expert centers had a higher odds of undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) and better overall survival (OS) than those diagnosed in referring centers. Nationwide efforts were initiated to increase awareness and improve referral networks.MethodsThis nationwide study aimed to evaluate whether the between-center differences in odds of undergoing CRS-HIPEC and OS have reduced since these national efforts were initiated. All patients with isolated synchronous PMCRC diagnosed between 2009 and 2021 were identified from the Netherlands Cancer Registry. Associations between hospital of diagnosis and the odds of undergoing CRS-HIPEC, as well as OS, were assessed using multilevel multivariable regression analyses for two periods (2009–2015 and 2016–2021).ResultsIn total, 3948 patients were included. The percentage of patients undergoing CRS-HIPEC increased from 17.2% in 2009–2015 (25.4% in expert centers, 16.5% in referring centers), to 23.4% in 2016–2021 (30.2% in expert centers, 22.6% in referring centers). In 2009–2015, compared with diagnosis in a referring center, diagnosis in a HIPEC center showed a higher odds of undergoing CRS-HIPEC (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.02–2.67) and better survival (hazard ratio [HR] 0.80, 95% CI 0.66–0.96). In 2016–2021, there were no differences in the odds of undergoing CRS-HIPEC between patients diagnosed in HIPEC centers versus referring centers (OR 1.27, 95% CI 0.76–2.13) and survival (HR 1.00, 95% CI 0.76–1.32).ConclusionPreviously observed differences in odds of undergoing CRS-HIPEC were no longer present. Increased awareness and the harmonization of treatment for PMCRC may have contributed to equal access to care and a similar chance of survival at a national level.

Continuous Wound Irrigation and Intraoperative Methadone Decreases Opioid Use and Shortens Length of Stay After CRS/HIPEC.

Epidural analgesia is resource and laborintense and may limit postoperative management options and delay discharge. This study compared postoperative outcomes after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) with epidural analgesia versus continuous wound infusion system (CWIS) with/without intraoperative methadone. A single-institution, retrospective chart review was performed including all patients undergoing open CRS/HIPEC from 2018 to 2021. Patient demographics, surgical characteristics, length of stay, and in-hospital analgesic use were reviewed. In-hospital opioid exposure in morphine milligram equivalents (MME) was calculated. Multivariate analysis (MVA) for mean total and daily opioid exposure was conducted. A total of 157 patients were included. Fifty-three (34%) had epidural analgesia, 96 (61%) had CWIS, and 79 (50%) received methadone. Length of stay was significantly shorter with CWIS + methadone versus epidural (7 vs. 8 days, p < 0.01). MVA showed significantly lower mean total and daily opioid exposure with CWIS+methadone versus epidural (total: 252.8 ± 17.7 MME vs. 486.8 ± 86.6 MME; odds ratio [OR] 0.72, 95% confidence interval [CI] 0.52-0.98, p = 0.04; Daily: 32.8 ± 2.0 MME vs. 51.9 ± 5.7 MME, OR 0.72, 95% CI 0.52-0.99, p ≤ 0.05). The CWIS-only group (n = 17) had a significantly lower median oral opioid exposure versus epidural (135 MME vs. 7.5 MME, p < 0.001) and longer length of stay versus CWIS + methadone (9 vs. 7 days, p = 0.04), There were no CWIS or methadone-associated complications and one epidural abscess. CWIS + methadone safely offers better pain control with less in-hospital opioid use, shorter length of stay, and decreased resource utilization compared with epidural analgesia in patients undergoing CRS-HIPEC.

Predictors of Financial Toxicity Risk Among Patients Undergoing Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy (CRS-HIPEC).

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the preferred treatment for select patients with peritoneal malignancies. However, the procedure is resource intensive and costly. This study aimed to determine the risk of financial toxicity for patients undergoing CRS-HIPEC. We performed a retrospective cohort study of patients undergoing CRS-HIPEC at a single institution from 2016 to 2022. We utilized insurance status, out-of-pocket expenditures, and estimated post-subsistence income to determine risk of financial toxicity. A multivariable logistic regression was used to determine risk factors for financial toxicity. Our final study cohort consisted of 163 patients. Average age was 58 [standard deviation 10] years, and 52.8% (n = 86) were male. A total of 52 patients (31.9%) were at risk of financial toxicity. A total of 36 patients (22.1%) were from the lower income quartiles (first or second) and 127 patients (77.9%) were from the higher income quartiles (third or fourth). A total of 47 patients (29%) were insured by Medicare, and 116 patients (71%) had private insurance. The median out-of-pocket expenditure across the study cohort was $3500, with a median of $5000 ($3341-$7350) for the at-risk group and $3341 ($2500-$4022) for the not at-risk group (p < 0.001). Risk factors for financial toxicity included high out-of-pocket expenditures and a lower income quartile. An estimated one-third of patients undergoing CRS-HIPEC at our institution were at risk for financial toxicity. Several preoperative factors were associated with an increased risk and could be utilized to identify patients who might benefit from interventions.

Handgrip strength, nutrition-related factors and postoperative outcome after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC)

Handgrip strength, nutrition-related factors and postoperative outcome after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC)

Early Cost-Effectiveness Analysis of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer Patients with Limited Peritoneal Carcinomatosis.

Gastric cancer patients with peritoneal carcinomatosis (PC) have a poor prognosis, with a median overall survival of 10 months when treated with systemic chemotherapy only. Cohort studies showed that cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) might improve the prognosis for gastric cancer patients with limited PC. Besides generating trial data on clinical effectiveness, it is crucial to timely collect information on economic aspects to guide the reimbursement decision-making process. No previous data have been published on the cost(-effectiveness) of CRS/HIPEC in this group of patients. Therefore, we performed an early model-based cost-effectiveness analysis of CRS/HIPEC for gastric cancer patients with limited PC in the Dutch setting. We constructed a two-state (alive-dead) Markov transition model to evaluate costs and clinical outcomes from a Dutch healthcare perspective. Clinical outcomes, transition probabilities and utilities were derived from literature and verified by clinical experts in the field. Costs were measured using two available representative cohorts (2010-2017): one 'systemic chemotherapy only' cohort and one 'CRS/HIPEC' cohort (n=10 each). Incremental cost-utility ratios (ICURs) were expressed as Euros per quality-adjusted life-year (QALY). We performed probabilistic and deterministic sensitivity, scenario, and value-of-information analyses using a willingness-to-pay (WTP) threshold of €80,000/QALY, which reflects the Dutch norm for severe diseases. In the base-case analysis, CRS/HIPEC yielded more QALYs (increment of 0.68) and more costs (increment of €34,706) compared with systemic chemotherapy only, resulting in an ICUR of €50,990/QALY. The probability that CRS/HIPEC was cost effective compared with systemic chemotherapy alone was 64%. To reduce uncertainty, the expected value of perfect information amounted to €4,021,468. The scenario analyses did not alter the results and showed that treatment costs, lifetime health-related quality of life and overall survival had the largest influence on the model. The presented early cost-effectiveness analysis suggests that adding CRS/HIPEC to systemic chemotherapy for gastric cancer patients with limited PC has a good chance of being cost-effectiveness compared with systemic chemotherapy alone when using a WTP of €80,000/QALY. However, there is substantial uncertainty in view of the current available data on effectiveness. Results from the ongoing phase III PERISCOPE II trial are therefore crucial for further decisions on treatment policy and its cost-effectiveness.

Patterns of Recurrence in Appendix Cancer After Complete Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy.

It is thought that low-grade (LG) appendiceal cancer (AC) demonstrates predominantly intraperitoneal recurrence (IPR) after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC), whereas high-grade (HG) tumors progress both intra- and extraperitoneally (EPR). However, evidence supporting this conception is lacking; therefore, we assessed recurrence in various AC histologies. A retrospective, cohort study was conducted by using a single-center database (1998-2022). Recurrence patterns (IPR, EPR, combined) were identified for LG, HG, high-grade with signet ring cells (SRC), and goblet cell carcinoma (GCC). We included 432 complete (CC-0/1) CRS/HIPECs: 200 LG, 114 HG, 72 SRC, and 46 GCC. Median follow-up was 78 (95% confidence interval [CI] 70-86) months. Overall, 34% (n = 148) of patients recurred. IPR was the most common (LG 16%, HG 27%, SRC 36%, GCC 26%) with median time to recurrence (MTR) of 21 (IQR: 12-40) months. EPR (liver, lung, pleura, lymph nodes, or bones) occurred in LG 3%, HG 9%, SRC 22%, and GCC 7%. MTR was 11 (IQR: 4-16) months. Combined pattern occurred in LG 0%, HG 8%, SRC 7%, and GCC 0%. MTR was 13 (IQR: 7-18) months. Iterative surgery was performed in 53% IPR, 18% EPR, and 51% combined. Median post-recurrence survival was longer after IPR compared with EPR and combined recurrence: 36 (95% CI 25-47) versus 13 (95% CI 7-19) and 18 (95% CI 6-30) months (p < 0.01). After complete CRS/HIPEC, IPR was the predominant pattern in all AC histologies and occurred later. Post-recurrence survival after IPR was longer. Knowing AC recurrence patterns can help to understand its biology and plan follow-up and post-relapse management.

Risk factors for gastrointestinal perforation and anastomotic leak in patients submitted to cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC)

BackgroundGastrointestinal leak is one of the most feared complications after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) and harbors significant postoperative morbidity and mortality. We aim to identify risk-factors for anastomotic leak (AL) and gastrointestinal perforation (GP) to optimize postoperative outcomes of this population. MethodsWe performed a retrospective analysis of 1043 consecutive patients submitted to CRS in a single institution. Potential risk factors for AL and GP, both related to patient overall condition, disease status and surgical technique were reviewed. ResultsAnastomotic leaks were identified in 5.2% of patients, and GPs in 7.0%. The independent risk-factors for AL were age at surgery (OR1.40; CI95% 1.10–1.79); peritoneal cancer index (PCI) (OR1.04, CI95% 1.01–1.07); Cisplatin dose >240 mg during HIPEC (OR3.53; CI95% 1.47–8.56) and the presence of colorectal (CR) or colo-colic (CC) anastomosis (OR5.09; CI95% 2.71–9.53, and 4.58; CI95% 1.22–17.24 respectively). Male gender and intraoperative red blood cell transfusions were the only independent risk factors for GP identified (OR1.70; CI95% 1.04–2.78 and 1.06; CI95% 1.01–1.12, respectively). Regarding 30-day and 90-day postoperative mortality, independent risk-factors were mainly related to patient's overall condition. ConclusionGastrointestinal leaks are a frequent source of postoperative morbidity, mainly at the expense of GP. A careful and systematic intraoperative revision of all potential gastrointestinal injuries is equally critical to perfecting anastomotic fashioning techniques to decrease gastrointestinal complication rates. We identified multiple risk-factors for AL and GP related to disease status and patient condition. Our study suggests that patient-related conditions are of paramount relevance, highlighting the importance of patient selection and preoperative patient optimization.

Predicting Severe Complications from Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy: A Data-Driven, Machine Learning Approach to Augment Clinical Judgment.

CRS-HIPEC provides oncologic benefit in well-selected patients with peritoneal carcinomatosis; however, it is a morbid procedure. Decision tools for preoperative patient selection are limited. We developed a risk score to predict severity of 90day complications for cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Adults who underwent CRS-HIPEC at the University of Pittsburgh Medical Center (March 2001-April 2020) were analyzed as part of this study. Primary endpoint was severe complications within 90days following CRS-HIPEC, defined using Comprehensive Complication Index (CCI) scores as a dichotomous (determined using restricted cubic splines) and continuous variable. Data were divided into training and test sets. Several machine learning and traditional algorithms were considered. For the 1959 CRS-HIPEC procedures included, CCI ranged from 0 to 100 (median 32.0). Adjusted restricted cubic splines model defined severe complications as CCI > 61. A minimum of 20 variables achieved optimal performance of any of the models. Linear regression achieved the highest area under the receiving operator characteristic curve (AUC, 0.74) and outperformed the NSQIP Surgical Risk calculator (AUC 0.80 vs. 0.66). Factors most positively associated with severe complications included peritoneal carcinomatosis index score, symptomatic status, and undergoing pancreatectomy, while American Society of Anesthesiologists 2 class, appendiceal diagnosis, and preoperative albumin were most negatively associated with severe complications. This study refines our ability to predict severe complications within 90days of discharge from a hospitalization in which CRS-HIPEC was performed. This advancement is timely and relevant given the growing interest in this procedure and may have implications for patient selection, patient and referring provider comfort, and survival.

Prolonged hyperthermic intraperitoneal chemotherapy duration with 90 minutes cisplatin might increase overall survival in gastric cancer patients with peritoneal metastases.

Advanced gastric cancer with synchronous peritoneal metastases (GC-PM) is associated with a poor prognosis. Although cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is a promising approach, only a limited number of Western studies exist. To investigate the clinicopathological outcomes of patients who underwent CRS-HIPEC for GC-PM. A retrospective analysis of patients with GC-PM was conducted. All patients were seen at the Department of General and Visceral Surgery, Hospital Barmherzige Brüder, Regensburg, Germany between January 2011 and July 2021 and underwent CRS-HIPEC. Preoperative laboratory results, the use of neoadjuvant trastuzumab, and the details of CRS-HIPEC, including peritoneal carcinomatosis index, completeness of cytoreduction, and surgical procedures were recorded. Disease-specific (DSS), and overall survival (OS) of patients were calculated. A total of 73 patients were included in the study. Patients treated with neoadjuvant trastuzumab (n = 5) showed longer DSS (P = 0.0482). Higher white blood cell counts (DSS: P = 0.0433) and carcinoembryonic antigen levels (OS and DSS: P < 0.01), and lower hemoglobin (OS and DSS: P < 0.05) and serum total protein (OS: P = 0.0368) levels were associated with shorter survival. Longer HIPEC duration was associated with more advantageous median survival times [60-min (n = 59): 12.86 mo; 90-min (n = 14): 27.30 mo], but without statistical difference. To obtain additional data from this observation, further separation of the study population was performed. First, propensity score-matched patient pairs (n = 14 in each group) were created. Statistically different DSS was found between patient pairs (hazard ratio = 0.2843; 95% confidence interval: 0.1119-0.7222; P = 0.0082). Second, those patients who were treated with trastuzumab and/or had human epidermal growth factor receptor 2 positivity (median survival: 12.68 mo vs 24.02 mo), or had to undergo the procedure before 2016 (median survival: 12.68 mo vs 27.30 mo; P = 0.0493) were removed from the original study population. Based on our experience, CRS-HIPEC is a safe and secure method to improve the survival of advanced GC-PM patients. Prolonged HIPEC duration may serve as a good therapy for these patients.

Overall survival and morbidity are not associated with advanced age for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a single centre experience.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has enabled better prognosis for patients with peritoneal surface malignancies. However, in older age groups, short -and long-term outcomes are still perceived as poor. We evaluated patients aged 70 and over and determine if age is a predictor of morbidity, mortality and overall survival (OS). A retrospective cohort analysis was performed on CRS/HIPEC patients and categorised by age. The primary outcome was overall survival. Secondary outcomes included morbidity, mortality, hospital and incentive care unit (ICU) stay and early postoperative intraperitoneal chemotherapy (EPIC). A total of 1,129 patients were identified with 134 aged 70+ and 935 under 70. There was no difference in OS (p=0.175) or major morbidity (p=0.051). Advanced age was associated with higher mortality (4.48 vs. 1.11 %, p=0.010), longer ICU stay (p<0.001) and longer hospitalisation (p<0.001). The older group was less likely to achieve complete cytoreduction (61.2 vs. 73 %, p=0.004) and receive EPIC (23.9 vs. 32.7 %, p=0.040). In patients undergoing CRS/HIPEC, age of 70 and above does not impact OS or major morbidity but is associated with increased mortality. Age alone should not be a limiting factor in selecting CRS/HIPEC patients. Careful multi-disciplinary approach is needed when considering those of advanced age.

The robotic future of minimally invasive cytoreduction and hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been increasingly utilized for peritoneal surface malignancies. This has been commonly utilized for a variety of neoplasms, but, especially mucinous neoplasms of the appendix, ovarian cancer, gastric cancer, colorectal cancer and mesothelioma. Traditionally, CRS/HIPEC has been performed as an open, extensive operation associated with prolonged hospitalization. However, when the peritoneal carcinomatosis index (PCI) is small (<10), minimally invasive approaches can be considered. Such less invasive approaches may be associated with improved postoperative recovery, less complications while preserving oncologic outcomes. The robotic platform offers distinct advantages over laparoscopy with superior visualization and ergonomics which account for its increased utilization in oncologic surgery. Herein, we review available data on minimally invasive approaches to CRS/HIPEC procedures, focusing on patient selection and comparative studies to open CRS/HIPEC. We summarize the existing initial studies on robotically assisted CRS/HIPEC and provide technical insights about our approach to robotically assisted CRS/HIPEC. Current data suggests that treatment of peritoneal surface malignancies with minimally invasive CRS/HIPEC is feasible in selected cases and is associated with improved postoperative recovery. The robotically assisted platform for CRS/ HIPEC deserves further investigation and may improve outcomes after this procedure in the future for carefully selected patients with low PCI.

Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer with Peritoneal Carcinomatosis: Additional Information Helps to Optimize Patient Selection before Surgery

(1) Background: The prognosis of gastric cancer-associated peritoneal carcinomatosis (GCPC) is poor, with a median survival time of less than six months, and current systemic chemotherapy, including targeted therapy, is ineffective. Despite growing evidence that cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for GCPC improves overall survival (OS), optimal patient selection remains unclear. We aimed to evaluate preoperative clinical factors and identify indicative factors for predicting postoperative OS in patients with GCPC undergoing CRS-HIPEC. (2) Methods: We retrospectively reviewed 44 consecutive patients with GCPC who underwent CRS-HIPEC between May 2015 and May 2021. Data on demographics and radiologic assessment were collected and analyzed. (3) Results: Elevated preoperative serum neutrophil-to-lymphocyte ratio > 4.4 (p = 0.003, HR = 3.70, 95% CI = 1.55-8.79) and number of computed tomography risks > 2 (p = 0.005, HR = 3.26, 95% CI = 1.33-7.98) were independently indicative of OS post-surgery. A strong correlation was observed between intraoperative peritoneal cancer index score and number of computed tomography risks (r = 0.534, p < 0.0001). Two patients after CRS-HIPEC ultimately achieved disease-free survival for more than 50 months. (4) Conclusions: Our experience optimizes GCPC patients' selection for CRS-HIPEC, may help to improve outcomes in the corresponding population, and prevent futile surgery in inappropriate patients.

Effect of opioid-free anesthesia on post-operative period in cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a propensity score matched study

Background Postoperative pain after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is important. It appears essential to reduce postoperative pain and morphine consumption. Methods Retrospective study in a university hospital comparing patient benefiting from CRS-HIPEC under opioid-free anesthesia (OFA; dexmedetomidine) to those anesthetized with opioid anesthesia (OA; remifentanil) using a propensity score matching method. The main objective was the impact of OFA on postoperative morphine consumption in the first 24 h after surgery. Results 102 patients were included, matching on the propensity score allowed selecting 34 unique pairs analyzed. Morphine consumption was lower in the OFA group than in the OA group (3.0 [0.00–11.0] mg/24 h vs. 13.0 [2.5–25.0] mg/24 h; p = 0.02). In multivariable analysis, OFA was associated with a reduction of 7.2 [0.5–13.9] mg of postoperative morphine (p = 0.04). The rate of renal failure with a KDIGO-score > 1 was lower in the OFA group than in the OA group (12% vs. 38%; p = 0.01). There was no difference between groups concerning length of surgery/anesthesia, norepinephrine infusion, volume of fluid therapy, post-operative complications, rehospitalization or ICU readmission within 90 days, mortality, and postoperative rehabilitation. Conclusion Our results suggest that OFA for CRS-HIPEC patients appears safe and is associated with less postoperative morphine use and acute kidney injury.

Long-Term Survival in Patients Treated with Cytoreduction and Heated Intraperitoneal Chemotherapy for Peritoneal Mesothelioma at a Single High-Volume Center.

Malignant peritoneal mesothelioma (MPM) is a rare diagnosis with a dismal prognosis if untreated. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is shown to significantly improve survival. Our institution is uniquely positioned to report long-term outcomes in MPM with CRS-HIPEC, due to our robust peritoneal surface disease program existing over the past three decades. Our prospectively maintained, single-institution database of CRS-HIPEC cases was reviewed, identifying 111 consecutive patients with MPM over 28 years (1993-2021). Prognostic, operative, and pathologic factors were reviewed. Overall survival (OS) and conditional survival (CS) analyses were performed. The average age was 55.1 years; 58.6% of patients were male; 17 of 111 patients (15.3%) had a second CRS-HIPEC. At first CRS-HIPEC, the average PCI score was 18.7, andthe perfusate drugs were platinum-based (72.1%) and mitomycin C (27.9%). The resection statusat first CRS-HIPEC was R2a (46.4%), followed by R0-1 (29.1%), and R2b-c (24.5%). Median OS was 3.3 years for the entire cohort, with 75th and 25th percentiles at 10.7 months and 10.6 years. Median CS was improved if patients survived to the 1-year postoperative mark (4.9 years, p < 0.01) and trended toward further improvement with each passing year. If 3-year postoperative survival was achieved, the median CS improved to 6.1 years. This represents one of the largest and lengthiest, single-center, longitudinal, case series of peritoneal mesothelioma treated with CRS-HIPEC. The OS suggests efficacy for CRS-HIPEC for MPM. Long-term survival improves significantly after patients achieve the 1-year, postoperative mark.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy with Intra-Operative Radiotherapy for Patients with Locally Advanced or Locally Recurrent Rectal Cancer and Peritoneal Metastases.

Purpose: To assess the safety and long-term outcome of a multimodality treatment consisting of radical surgery, intra-operative radiotherapy (IORT), and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for patients with locally advanced rectal cancer (LARC) or locally recurrent rectal carcinoma (LRRC) and peritoneal metastases (PM). Methods: The present study was a single-center cohort study, including all consecutive patients undergoing this treatment in a tertiary referral center for LARC, LRRC, and PM. Postoperative complications, intensive care stay (ICU stay), and re-admission rates were assessed as well as disease-free survival (DFS) and overall survival (OS). Results: A total of 14 LARC and 16 LRRC patients with PM were included in the study. The median ICU stay was 1 day, and 57% of patients developed a severe postoperative complication. No 90-day mortality was observed. Median DFS was 10.0 months (Interquartile Range 7.1-38.7), and median OS was 31.0 months (Interquartile Range 15.9-144.3). Conclusions: As postoperative complications and survival were in line with treatments that are accepted for LARC or LRRC and PM as separate procedures, we conclude that combined treatment with IORT and CRS-HIPEC should be considered as a treatment option for selected patients with LARC or LRRC and peritoneal metastases in tertiary referral centers.