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

BACKGROUND: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Distance Traveled and Disparities in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: The impact of distance traveled on cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) outcomes needs further investigation. METHODS: This retrospective study reviewed a prospectively managed single-center CRS/HIPEC 1992-2022 database. Zip codes were used to calculate distance traveled and to obtain data on income and education via census data. Patients were separated into three groups based on distance traveled in miles (local: ≤50 miles, regional: 51-99 miles, distant: ≥100 miles). Descriptive statistics, Kaplan-Meier method, and Cox regression were performed. RESULTS: The 1614 patients in the study traveled a median distance of 109.5 miles (interquartile range [IQR], 53.36-202.29 miles), with 23% traveling locally, 23.9% traveling regionally, and 53% traveling distantly. Those traveling distantly or regionally tended to be more white (distant: 87.8%, regional: 87.2%, local: 83.2%), affluent (distant: $61,944, regional: $65,014, local: $54,390), educated (% without high school diploma: distant: 10.6%, regional: 11.5%, local: 13.0%), less often uninsured (distant: 2.3%, regional: 4.6%, local: 5.2%) or with Medicaid (distant: 3.3%, regional: 1.3%, local: 9.7%). They more often had higher Peritoneal Carcinomatosis Index (PCI) scores (distant: 15.4, regional: 15.8, local: 12.7) and R2 resections (distant: 50.3%, regional: 52.2%, local: 40.5%). Median survival did not differ between the groups, and distance traveled was not a predictor of survival. CONCLUSION: More than 50% of the patients traveled farther than 100 miles for treatment. Although regionalization of CRS/HIPEC may be appropriate given the lack of survival difference based on distance traveled, those who traveled further had fewer health care disparities but higher PCI scores and more R2 resections, which raises concerns about access to care for the underserved, time to treatment, and surgical quality.

Influence of insurance status on the postoperative outcomes of cytoreductive surgery and HIPEC.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is increasingly performed for peritoneal surface malignancies but remains associated with significant morbidity. Scant research is available regarding the impact of insurance status on postoperative outcomes. METHODS: Patients undergoing CRS/HIPEC between 2000 and 2017 at 12 participating sites in the US HIPEC Collaborative were identified. Univariate and multivariate analyses were used to compare the baseline characteristics, operative variables, and postoperative outcomes of patients with government, private, or no insurance. RESULTS: Among 2268 patients, 699 (30.8%) had government insurance, 1453 (64.0%) had private, and 116 (5.1%) were uninsured. Patients with government insurance were older, more likely to be non-white, and comorbid (p < 0.05). Patients with government (OR: 2.25, CI: 1.50-3.36, p < 0.001) and private (OR: 1.69, CI: 1.15-2.49, p = 0.008) insurance had an increased risk of complications on univariate analysis. There was no independent relationship on multivariate analysis. An American Society of Anesthesiologists score of 3 or 4, peritoneal carcinomatosis index score >15, completeness of cytoreduction score >1, and nonhome discharge were factors independently associated with a postoperative complication. CONCLUSION: While there were differences in postoperative outcomes between the three insurance groups on univariate analysis, there was no independent association between insurance status and postoperative complications after CRS/HIPEC.

Preoperative cardiopulmonary exercise testing improves risk assessment of morbidity and length of stay following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are the standard treatment for selected patients with peritoneal malignancy. The optimal means of assessing risk prior to these complex operations is not known. This study explored the associations between preoperative cardiopulmonary exercise testing (CPET) variables and postoperative outcomes following elective CRS and HIPEC. This study included patients who underwent routine preoperative CPET prior to elective CRS and HIPEC at Royal Prince Alfred Hospital in Sydney between July 2017 and July 2020. CPET was performed using a cycle ergometer and measured peak oxygen uptake (VO2 peak) and anaerobic threshold (AT). Outcomes included in-hospital morbidity, length of intensive care unit (ICU) stay and hospital stay. The associations between preoperative CPET variables and postoperative morbidity were assessed using univariate and multivariate analyses. A total of 129 patients were included. Mean age was 56 years (standard deviation (SD) 12.5 years), and colorectal cancer was the most common indication for CRS and HIPEC. The overall complication rate was 69%, and two (1.6%) patients died in hospital. Patients who did not develop any postoperative complication had slightly higher preoperative AT and VO2 peak and shorter length of hospital stay. Data in this study support the role of CPET prior to CRS and HIPEC as an adjunct to improve risk assessment.

In-Hospital Mortality and Complication Rates According to Health Insurance Data in Patients Undergoing Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies in Germany.

BACKGROUND: Morbidity and in-hospital mortality rates of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in Germany are not known. METHODS: From 2009 to 2018 all patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in Germany were retrospectively analyzed regarding morbidity and in-hospital mortality rates according to nationwide hospital billing data based on diagnosis-related groups (DRG). The "failure to rescue" (FTR) index, characterizing patients who died after severe but potentially manageable complications, was calculated. RESULTS: In total, 8463 patients were included and analyzed. Female sex predominated (1.5:1). Colonic origin of peritoneal metastasis was highest throughout all years, reaching its highest level in 2017 (55%; n = 563) and its lowest level in 2012 (40%; n = 349). Median length of hospital stay reached its maximum in 2017 at 23.9 days and its minimum in 2010 at 22.0 days. Analysis of the total FTR index showed a noticeable improvement over the years, reaching its lowest values in 2017 (9.8%) and 2018 (8.8%). The FTR index for sepsis, peritonitis, and pulmonary complications significantly improved over time. Of the 8463 included patients, 290 died during hospital stay, reflecting an in-hospital mortality rate of 3.4%. CONCLUSION: In-hospital mortality after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy is reasonably low compared with other surgical procedures. The improvement in the FTR index reflects efforts to centralize treatment at specialized high-volume centers.

Assessment of Image-Guided Intratumoral Delivery of Immunotherapeutics in Patients With Cancer.

Importance: Direct intratumoral delivery of immunotherapies is a compelling approach to overcoming barriers to systemic immunotherapy efficacy. While the use of intratumoral delivery of immunotherapy drugs is increasing rapidly in both the investigational and standard of care domains, the feasibility and safety of these interventions, particularly for deeper lesions that require image-guidance, remain unknown. Objective: To address current knowledge gaps in image-guided techniques for intratumoral immunotherapy delivery and the safety of these interventions. Design, Setting, and Participants: This case series study was performed at a single tertiary cancer center over a 2-year period from January 2016 to January 2018. Patients were followed until January 2019. All patients who underwent image-guided intratumoral delivery of immunotherapy agents in the standard of care, off-label, or investigational setting during the study period were included. Data were analyzed from February 1 to June 1, 2019. Exposures: Image-guided biopsies and intratumoral injections of immunotherapies across several clinical trials as well as standard of care talimogene laherparepvec therapy. Main Outcomes and Measures: Technical success, defined as the delivery of the prescribed injectate volume in its entirety, for image-guided biopsy and injections and procedure-related adverse events. Results: A total of 85 patients (median [interquartile range] age, 61 [47-71] years; 42 [52%] men) underwent 498 encounters during the study period. These encounters comprised 327 image-guided intratumoral investigational agent injections in 67 patients in clinical trials, including 33 patients with melanoma (50%), 14 patients with sarcoma (21%), 3 patients with ovarian cancer (4.5%), 2 patients with breast cancer (3%), and 2 patients with colon cancer (3%). An additional 18 patients with melanoma underwent 113 image-guided talimogene laherparepvec injections. There were no adverse events reported related to the technical component of the procedure, specifically needle insertion or biopsy. Serious adverse events (Common Terminology Criteria for Adverse Events score ≥3), including dyspnea and severe flu-like symptoms developing within 24 hours of the injection and requiring hospitalization, occurred after 3 of 327 investigational agent injections (2%) and 4 of 113 talimogene laherparepvec injections (4%). Conclusions and Relevance: The findings of this case series study suggest that intratumoral injections of immunotherapies were feasible across a range of histological conditions and target organs. Immediate postdelivery anticipated adverse events occurred in a small number of instances. Performing physicians should have the necessary safeguards in place to respond as needed. Optimal methods for intratumoral drug delivery remain unresolved, and efforts to standardize drug delivery techniques are required.

Impact of extent of disease on 1-year healthcare costs in patients who undergo cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: retrospective observational cohort study.

BACKGROUND: The goal of this retrospective observational study was to determine the impact of the extent of peritoneal disease on 1-year healthcare costs in patients with colorectal peritoneal metastases (PM) who undergo cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). The extent of peritoneal disease, expressed by the Peritoneal Cancer Index (PCI), directly affects the complexity of CRS + HIPEC and ultimately survival outcomes. The impact of the PCI on treatment-related healthcare costs remains unknown. METHODS: Data from patients with colorectal PM who underwent CRS + HIPEC between January 2012 and November 2017 were extracted retrospectively from an institutional database. Patients were divided into four subgroups with PCI scores ranging from 0 to 20. Treatment-related costs up to 1 year after CRS + HIPEC were obtained from the financial department. Differences in costs and survival outcomes were compared using the χ2 test and Kruskal-Wallis H test. RESULTS: Seventy-three patients were included (PCI 0-5, 22 patients; PCI 6-10, 19 patients; PCI 11-15, 17 patients; PCI 16-20, 15 patients). Median (i.q.r.) costs were significantly increased for the PCI 11-15 and PCI 16-20 groups (€51 029 (42 500-58 575) and €46 548 (35 194-60 533) respectively) compared with those for the PCI 0-5 and PCI 6-10 groups (€33 856 (25 293-42 235) and €39 013 (30 519-51 334) respectively) (P = 0·009). CONCLUSION: Treatment-related healthcare costs are significantly increased among patients with extensive tumour burden (PCI score 10 or above) who undergo CRS + HIPEC for the treatment of colorectal PM.

ANTECEDENTES: El objetivo de este estudio observacional retrospectivo fue determinar el impacto de la extensión de la enfermedad peritoneal sobre los costes de atención médica al año en pacientes con metástasis peritoneales (peritoneal metastases, PM) de origen colorrectal que se someten a cirugía citorreductora con quimioterapia intraperitoneal hipertérmica (cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, CRS + HIPEC). La extensión de la enfermedad peritoneal, expresada por el índice de carcinomatosis peritoneal (peritoneal cancer index, PCI), afecta directamente a la complejidad de la CRS + HIPEC y, en última instancia, a los resultados de supervivencia. El impacto de la PCI en los costes de la atención médica relacionados con el tratamiento sigue siendo desconocido. MÉTODOS: Los datos de pacientes con PM de origen colorrectal que se sometieron a CRS + HIPEC entre enero de 2012 y noviembre de 2017 se extrajeron retrospectivamente de una base de datos institucional. Los pacientes se dividieron en cuatro subgrupos con PCI que variaron de 0 a 20. Los costes relacionados con el tratamiento hasta un año después de la CRS + HIPEC se obtuvieron del departamento financiero. Las diferencias en los costes y los resultados de supervivencia se compararon mediante los tests χ2 y de Kruskal-Wallis H. RESULTADOS: Se incluyeron 73 pacientes (PCI 0-5, 22 pacientes; PCI 6-10, 19 pacientes; PCI 11-15, 17 pacientes y PCI 16-20, 15 pacientes). Los costes medios aumentaron significativamente para los grupos PCI 11−15 y PCI 16−20 (51.029€ (rango intercuartílico, RIQ) 42.500€−58575€)) y 46.548€ (RIQ 35.194€-60.533€), respectivamente)) en comparación con los de los grupos PCI 0−5 y PCI 6-10 (33.856€ (RIQ 25.293€−42.23€) y 39.013€ (RIQ 30.519€-51.334€), respectivamente, P = 0,009). CONCLUSIÓN: Los costes de la atención médica relacionados con el tratamiento aumentan significativamente entre los pacientes con una carga tumoral extensa (es decir, PCI ≥ 10) que se someten a CRS + HIPEC para el tratamiento de PM de origen colorrectal.

What Drives High Costs of Cytoreductive Surgery and HIPEC: Patient, Provider or Tumor?

INTRODUCTION: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is utilized for peritoneal malignancies and is associated with significant resource use. To address potentially modifiable factors contributing to excessive cost, we sought to determine predictors of high cost of care for patients undergoing CRS/HIPEC. METHODS: An institutional CRS/HIPEC database was queried for adult patients from 2014 to 2018. Cost was defined as cost for the index hospitalization, and high-cost cases were defined as > 75th percentile for cost. Bivariate analyses for cost were performed, and all significant tumor, patient, and surgeon-specific variables were entered in a linear regression for cost. A separate linear regression was performed for length of stay (LOS). RESULTS: In total, 59 patients underwent 61 CRS/HIPEC procedures. The median direct variable cost was $20,509 (16,395-25,240). Median length of stay (LOS) was 8 (7-11.5) days and ICU stay was 1 (1-1.5) day. LOS, length of ICU stay and operative time were predictive of cost. Factors associated with increased LOS were Clavien-Dindo grade II complications and ostomy creation. Patient-related factors, including age and BMI, tumor-related factors, such as PCI and CCR, and surgeon were not predictive of cost nor LOS. DISCUSSION: Our results, the first to identify predictors of high cost of CRS/HIPEC-related care in the US, reveal cost was largely related to length and intensity of care. In turn, these drivers were influenced by complications and operative factors. Future work will focus on identifying an appropriate ERAS protocol following CRS/HIPEC and selection of those patients that may avoid routine ICU admission.

Sequencing in management of in-transit melanoma metastasis: Diphencyprone versus isolate limb infusion.

BACKGROUND: In-transit metastases (ITMs) in melanoma are associated with poor prognosis, however a significant proportion of these patients survive for extended periods without further disease progression. We routinely use locoregional treatment e.g. Diphencyprone (DPCP) and/or isolated limb infusion (ILI) as long-term palliation. This study aimed to identify correct sequencing of these therapies based on disease burden and progression. METHOD: Retrospective evaluation of all melanoma patients with ITMs treated with DPCP/ILI/both from 2010 to 2017 at our Cancer Centre was performed. Patients were initially assessed in a multidisciplinary setting and empirically prescribed DPCP for low-disease burden, ILI for high-disease burden. Patient demographics, tumour characteristics, response to therapy, ITM progression and patient outcomes were analysed. RESULTS: 78 patients (M:F = 30:48), aged 47-95years (median 74years) treated with DPCP/ILI/both (n = 44/21/13) were identified. Progression-free survival (PFS) was significantly increased in patients responsive to DPCP or ILI as initial treatment. Patients who failed on DPCP and subsequently treated with ILI had a significantly increased PFS compared to DPCP alone (p = 0.026, HR = 0.048). This was not the case with patients who were treated with DPCP following failed ILI. All patients who failed to respond to the initial therapy progressed within 6 months. CONCLUSION: Our study shows that careful stratification ITM patients according to disease burden is fundamental to optimal outcomes. High-disease burden patients benefit from initial ILI; low-disease burden patients should commence on DPCP. ILI can be considered in DPCP patients who fail early. Systemic therapy should be considered when locoregional therapies fail after 12 months or after rapid relapse following ILI.

Cost-Effectiveness Analysis of Cytoreductive Surgery and HIPEC Compared With Systemic Chemotherapy in Isolated Peritoneal Carcinomatosis From Metastatic Colorectal Cancer.

BACKGROUND: Cost-effectiveness evaluations of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis (PC) from metastatic colorectal cancer (mCRC) in the United States are lacking. METHODS: The authors developed a Markov model to evaluate the cost-effectiveness of CRS/HIPEC compared with systemic chemotherapy for isolated PC from mCRC from a societal perspective in the United States. The systemic treatment regimens consisted of FOLFOX, FOLFIRI, bevacizumab, cetuximab, and pantitumumab. The model inputs including costs, probabilities, survival, progression, and utilities were taken from the literature. The cycle length for the model was 2 weeks, and the time horizon was 7 years. A discount rate of 3% was applied. The model was tested for internal and external validation, and robustness was established with univariate sensitivity and probabilistic sensitivity analyses (PSA). The primary outcomes were total costs, quality-adjusted life-years (QALYs), life-years (LYs), and incremental cost-effectiveness ratio (ICER). A willingness-to-pay (WTP) threshold of $100,000 per QALY was assumed. RESULTS: The ICER for treatment with CRS/HIPEC compared with systemic chemotherapy was $91,034 per QALY gained ($74,098 per LY gained). The univariate sensitivity analysis showed that the total costs for treatment with CRS/HIPEC had the largest effect on the calculated ICER. The CRS/HIPEC treatment was a cost-effective strategy during the majority of simulations in the PSA. The average ICER for 100,000 simulations in the PSA was $70,807 per QALY gained. The likelihood of CRS/HIPEC being a cost-effective strategy at the WTP threshold was 87%. CONCLUSIONS: The CRS/HIPEC procedure is a cost-effective treatment for isolated PC from mCRC in the United States.

Cost Effectiveness of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Management of Colorectal Peritoneal Carcinomatosis.

BACKGROUND: Peritoneal carcinomatosis from colorectal cancer is a stage 4 disease for which palliative chemotherapy has traditionally been considered the mainstay of treatment. Since the development of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) by Sugarbaker, this combined method treatment has resulted in improved survival outcomes with acceptable morbidity for selected patients with peritoneal carcinomatosis. This study examined the cost effectiveness of CRS and HIPEC compared with palliative chemotherapy for patients with peritoneal carcinomatosis from colorectal cancer within the context of the Singaporean health care system. METHODS: A retrospective review of patients with peritoneal carcinomatosis from histologically proven colorectal cancer treated at the National Cancer Centre Singapore (NCCS) was conducted. RESULTS: The average cost of CRS and HIPEC per patient was S$83,680.26, and the median overall survival period was 47 months. The calculated cost per life year attained for a patient who underwent CRS and HIPEC was S$21,365.19 per life year. In comparison, the average cost of palliative chemotherapy was S$44,478.87, with a median overall survival of 9 months, and the calculated cost per life year attained for a patient in this treatment group was S$59,305.16 per life year. CONCLUSION: The findings show that CRS and HIPEC results in prolonged survival for selected patients with colorectal peritoneal carcinomatosis and a lower cost per life year attained than for the traditionally used palliative chemotherapy. It should logically be the preferred treatment of choice for selected patients with colorectal peritoneal metastasis.

External Validation of the Simplified Preoperative Assessment for Low-Grade Mucinous Adenocarcinoma of the Appendix.

BACKGROUND: MD Anderson Cancer Center developed a computed tomography (CT)-based preoperative assessment tool simplified preoperative assessment for appendix tumor (SPAAT) for predicting incomplete cytoreduction (IC) in low-grade mucinous adenocarcinoma (LGMA) of the appendix, based on preoperative CT scans. This study independently evaluates the tool's performance. METHODS: Seventy-six preoperative CT scans of LGMA patients were evaluated by two surgeons unfamiliar with the patients' medical history. Scores were assigned based on SPAAT criteria, with a SPAAT ≥3 predictive of IC. Binary regression analyses and area under the receiver operating characteristic (AUROC) curve analyses were performed. Patients with splenic resection were excluded due to the structure of the SPAAT assessment tool. RESULTS: Seventy-six LGMA patients underwent attempted cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Of 68 patients, 58 had complete cytoreduction and 10 had IC; 8 patients were ineligible due to prior splenectomy. The mean SPAAT score was 0.8, with six patients having SPAAT scores ≥3. SPAAT scores ≥3 were predictive of IC, with a hazard ratio (HR) of 19 (95% confidence interval 2.8-124.1) (p = 0.002). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value were 40, 97, 50, and 90%, respectively. A SPAAT score ≥3 was not associated with worse survival prognosis. Median follow-up was 2.4 years and AUROC curve was 71%. SPAAT components with respective HR and p-values were foreshortening of the bowel mesentery (29.5; p = 0.004), and scalloping of the pancreas (9; p = 0.008), spleen (4.3; p = 0.04), portal vein (3.1; p = 0.4), and liver (2.1; p = 0.3). CONCLUSION: A SPAAT score ≥3 predicted IC based on a binary regression model. The clinical value of this score is controversial due to low sensitivity and PPV.

Operating personnel safety during the administration of Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

Cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is increasingly used in the treatment of peritoneal malignancies. The administration of HIPEC after complete cytoreduction offers the combination of the pharmacokinetic advantages inherent to the intraperitoneal delivery of cytotoxic chemotherapy, with the direct cytotoxic effects of hyperthermia, and has been reported to offer significantly improved patient outcomes. As a result, this novel method disseminates rapidly, with many surgical teams having developed peritoneal malignancy treatment programs. Protocols are needed for the introduction, handling, and management of chemotherapeutic agents in the operating room to minimize risk to the staff involved in the procedure. The personnel exposure during CRS and HIPEC may arise from different routes, such as air contamination, direct contact, manipulation of perfusates or chemotherapy solutions, and manipulation of objects/tissues exposed to chemotherapeutics. Guidelines for safe administration of HIPEC including environmental contamination risk management, personal protective equipment, and occupational health issues are yet to be established. This review summarizes the existing evidence regarding the safety considerations of HIPEC administration.

Enterocutaneous fistula in patients with peritoneal malignancy following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Incidence, management and outcomes.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an effective treatment for peritoneal carcinomatosis (PC) from multiple origins, however is associated with increased complications compared to conventional gastrointestinal surgery. The aetiology of enterocutaneous fistulas (ECF) in most cases is a result of various contributing factors and therefore remains a major clinical problem, occurring in 4-34% of patients post-CRS. The aim of this study was to analyze the incidence and outcome of ECF following CRS/HIPEC. METHOD: From April 1999 to September 2015, 53 patients of 918 CRS/HIPEC procedures developed an ECF. Patient, operative and postoperative data were retrospectively analyzed to determine aetiology, classification outcome and possible contributing factors were reviewed on univariate and multivariate analysis. RESULTS: We report a 5.8% ECF rate, diagnosed at a median of 13 days. The mortality rate was 5.7% and other morbidity was significantly increased (p = 0.0001). Twenty-five (47.2%), 8 (15.1%) and 20 patients (37.7%) had low, moderate and high output ECF respectively. Patients that had a CC2 cytoreduction, abdominal VAC or smoked had a higher risk of fistula (p = 0.004, p < 0.0001, p = 0.008). Spontaneous closure was achieved in 49.2% with conservative treatment (median 29 days) and 33.9% underwent surgical intervention. Preoperative serum albumin <35 g/L (p = 0.04), PCI>17 (p = 0.025) and operation >8.6 h s (p = 0.001) were independent risk factors on multivariate analysis. Overall and 5-year survival was significantly reduced (p < 0.0001,p = 0.016). CONCLUSION: CRS/HIPEC remains an effective treatment modality for PC in selected patients with a comparable ECF incidence to reported elective gastrointestinal surgery rates. This study identifies multiple risk factors that should be considered in patients undergoing CRS/HIPEC.

Cytoreduction with hyperthermic intraperitoneal chemotherapy: an appraisal of outcomes and cost at a newly established peritoneal malignancy program.

BACKGROUND: Outcome measures after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for peritoneal carcinomatosis in established centers are well defined. However, results from newly emerging US centers have not been reported. METHODS: This is a retrospective review of a prospectively maintained database of patients with peritoneal malignancies undergoing CRS/HIPEC. RESULTS: Fifty-six patients underwent exploratory laparotomy with 36 receiving CRS/HIPEC over 36 months. The median peritoneal cancer index score was 18, and the cytoreduction 0/1 rate was 92%. Postoperative major morbidity was 16.7% with one perioperative death. The median length of hospital stay and intensive care unit days were 9 and 3 days, respectively. Disease-free survival in high-grade vs low-grade tumors was 12.6 and 31.0 months (P, .03), respectively. Average direct cost for patients undergoing CRS/HIPEC was $25,917. CONCLUSIONS: Our emerging center's short-term results are comparable with established programs with a trend toward more selective intraoperative judgment on who undergoes CRS/HIPEC.

"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.

Evaluation of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in a community setting: A cost-utility analysis of a hospital's initial experience and reflections on the health care system.

BACKGROUND: The combination of Cytoreductive Surgery (CRS) plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC) has been gaining a considerable interest by surgeons throughout the United States due to the significant survival improvement it provides for peritoneal surface malignancies and the ability to reproduce comparable clinical results in numerous health care centers. However, CRS plus HIPEC has not been sufficiently investigated from the economic standpoint in the United States where a wide variety of health care insurers exists. This study was conducted to analyze hospital/surgeon cost and reimbursement data at a community hospital offering a new peritoneal surface malignancy program, and expand the discussion to analyze future healthcare implementation on this procedure in the United States. METHODS: This is a retrospective economic analysis of an initial CRS plus HIPEC experience at a community non-teaching medical center. This study was conducted using hospital/surgeon cost and reimbursement based on the Office of Finance data at Edward Hospital Cancer Center (Naperville, IL). All patients who underwent CRS and HIPEC between June 2013 and August 2014 were included in this analysis. We aimed to assess CRS plus HIPEC purely from the financial perspective on the initial admission regardless of the patients' advancement of the disease or postoperative adverse events. RESULTS: Twenty-five patients underwent 26 CRS plus HIPEC procedures. Twelve patients had private insurance plans (PRV) whereas 13 were covered by public insurers (PUB). Median overall length of stay (LOS) was 10 days (PRV 10 days vs. PUB 11 days; P = 0.76.) Average hospital cost was $38,369 (PRV $37,093 vs. PUB $39,463; P = 0.67), and average reimbursement for our patient population was $45,243 (PRV $48,954 vs. PUB $42,062; P = 0.53). It was noted that CRS plus HIPEC generated more net profit in patients with private insurance than in those with public plans, however, not statistically significant ($11,861 vs. $2,599 per patient, respectively; P = 0.38). Evaluating surgeon's data, average surgeon's charge was $29,139 (PRV $28,440 vs. PUB $29,737; P = 0.80), and average patients' payment was $8,126 (PRV 9,234 vs. PUB 7,176; P = 0.47). CONCLUSION: CRS plus HIPEC is profitable in the community setting for both the hospital and surgeon. Both private and public insurers reimbursed profitably, though with a greater profit margin from private insurers. As CRS plus HIPEC is becoming more widely recognized as a standard of care for patients with peritoneal surface malignancy, it is increasingly important to understand and report its associated costs and variability in insurance coverage, especially in light of the current healthcare structure changes in the United States. It is strongly encouraged to report and present a wider scope of CRS plus HIPEC economic experiences in a variety of hospital settings to provide further evidence for future healthcare implementations in the United States. J. Surg. Oncol. 2016;113:544-547. © 2016 Wiley Periodicals, Inc.

Use Patterns and Costs of Isolated Limb Perfusion and Infusion in the Treatment of Regional Metastatic Melanoma: A Retrospective Database Analysis.

INTRODUCTION: Isolated limb perfusion and infusion (ILP/ILI) are therapies for regional metastatic melanoma that allow high doses of anticancer drugs to be delivered directly into the circulation of an affected limb, thereby minimizing systemic drug toxicity. This procedure can lead to high response rates and is recommended in patients with Stage III unresectable metastatic melanoma. However, limited information is available on patterns of use and costs. This study examined patterns of ILP/ILI use and associated costs in patients with melanoma in the United States (US). METHODS: Retrospective, observational study, using administrative claims data from the MarketScan(®) databases, was performed in patients with a diagnosis of melanoma (ICD-9-CM: 172.xx, V10.82) who underwent ILP/ILI (CPT-4: 36823) between January 1, 2002 and March 31, 2013. Patient characteristics, use patterns, length of hospital stay, and costs (per 2014 US $) of ILP/ILI were assessed. RESULTS: One hundred and thirteen patients met the study criteria and were included in the analysis. Mean age was 61.4 years (standard deviation [SD] 13.8) and 38.9% of patients were male; the mean baseline Charlson Comorbidity Index was 0.19; 34.5% of patients were Medicare beneficiaries. The majority of patients (87.6%) had melanoma of the lower limb, 11.5% of the upper limb, and 0.9% of both limbs; 60.2% had lymph node metastasis and 56.6% had skin metastasis. Four patients (3.5%) underwent multiple ILP/ILI. The mean (± SD) length of hospital stay was 5.6 (± 3.5) days and the mean (± SD) cost was US$36,758 (± 27,124) per ILP/ILI procedure. CONCLUSIONS: Isolated limb perfusion and infusion in patients with melanoma were associated with long hospital stays and high costs. These results provide useful source data for the economic evaluation of treatment options for regional metastatic melanoma. FUNDING: This study was funded by Amgen, Inc.

Histological response assessment following neoadjuvant isolated limb perfusion in patients with primary, localised, high-grade soft tissue sarcoma.

PURPOSE: Histological response assessment following neoadjuvant treatment can help identify patients at a higher risk for systemic disease progression. Our goal was to evaluate whether mitotic count and the amount of viable tumour following neoadjuvant isolated limb perfusion (ILP) for primary, locally advanced, non-metastatic, high-grade extremity soft tissue sarcoma correlate with prognosis. PATIENTS AND METHODS: This study is a retrospective analysis of 61 patients who underwent neoadjuvant ILP followed by surgical resection with curative intent between 2001 and 2011. Non-parametric analyses were carried out with the Mann-Whitney U and the Wilcoxon signed-rank test. Survival curves were calculated with the Kaplan-Meier method and compared with the log-rank test. RESULTS: The median follow-up was 44 months for all patients and 55 months for survivors. The amount of viable tumour after ILP had no correlation with overall (OS) (P = 0.227) or event-free (EFS) (P = 0.238) survival probability. Patients with a low mitotic count after ILP had a significantly higher OS (P < 0.001), EFS (P = 0.002) and post-relapse survival probability (P = 0.030) compared to patients with an intermediate or high mitotic count. CONCLUSIONS: The mitotic count following ILP for primary, high-grade, locally advanced, non-metastatic soft tissue sarcoma appears to significantly correlate with prognosis. If these results are validated in a prospective setting, they could provide a rationale for the design of adjuvant systemic chemotherapy trials with the goal of improving the prognosis of patients with an intermediate or high mitotic count after ILP.

Hyperthermic intraperitoneal chemotherapy + early postoperative intraperitoneal chemotherapy versus hyperthermic intraperitoneal chemotherapy alone: assessment of survival outcomes for colorectal and high-grade appendiceal peritoneal carcinomatosis.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have improved survival for colorectal and high-grade appendiceal carcinomatosis. We compared the overall and recurrence-free survival (OS and RFS) of patients treated with HIPEC with mitomycin c and early postoperative intraperitoneal chemotherapy (EPIC) with fluorouracil versus HIPEC alone using oxaliplatin and simultaneous IV infusion of fluorouracil. METHODS: Ninety-three patients with colorectal or high-grade appendiceal carcinomatosis were treated with CRS and HIPEC + EPIC or HIPEC alone. OS and RFS were analyzed using Kaplan-Meier curves and log-rank testing. RESULTS: Survival did not differ between HIPEC regimens. The 3-year OS and RFS rates were 50% and 21% for HIPEC + EPIC and 46% and 6% for HIPEC alone (P = .72 and P = .89, respectively). HIPEC + EPIC patients experienced more grade III/IV complications (43.2% vs 19.6%, P = .01). CONCLUSIONS: There was no difference in OS and RFS between colorectal and high-grade appendiceal adenocarcinoma patients treated with CRS and HIPEC + EPIC versus HIPEC alone. However, HIPEC + EPIC patients suffered greater morbidity, making HIPEC alone the preferable regimen.