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.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in Elderly is Safe and Effective.

INTRODUCTION: An increasing proportion of elderly patients (EP) are undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC). They have increased comorbidities and perioperative risk. Current literature is deficient in describing the outcomes of EP undergoing CRS/HIPEC. MATERIALS AND METHODS: A retrospective review of our prospectively maintained CRS/HIPEC database analyzed perioperative and oncological outcomes of EP (>70 y) compared to younger patients (YP) (<60 y). RESULTS: Of 500 CRS/HIPEC patients, 62 EP and 210 YP were included. Median age was 73 y in EP and 46 y in YP. Demographic, clinical, operative, and perioperative outcomes were similar between groups. American Society of Anesthesiologists > 3 was more prevalent in the EP with 88.2% versus 54.8% in the YP (P < 0.001). Comorbidities were higher in the EP with 87.1% versus 39.0% in the YP (P < 0.001). Peritoneal Cancer Index score was similar with a median of 9. All postoperative and severe complications were similar with 55.2% and 17.1% in the YP and 64.5% and 21.0% in the EP (P = 0.242; P = 0.448). Postoperative mortality was similar with 1.5% in the YP and 5.0% in the EP (P = 0.134). In colorectal primary patients, median overall and disease-free survival was 61.8 and 12.9 mo in the YP and 64.6 and 11.3 mo in the EP (P = 0.363; P = 0.845). CONCLUSIONS: Despite a significant age difference, increased comorbidities, worse American Society of Anesthesiologists, and similar Peritoneal Cancer Index burden, we found no significant differences in perioperative complications or oncological benefit in elderly CRS/HIPEC patients. EP appear to have similar perioperative and oncological outcomes as YP.

Efficacy and tolerability of chemosaturation in patients with hepatic metastases from uveal melanoma.

BACKGROUND: Patients with hepatic metastatic uveal melanoma still have a poor outcome. PURPOSE: To evaluate overall survival (OS), progression-free survival (PFS), and response predictors in these patients treated with chemosaturation by percutaneous hepatic perfusion with melphalan (CS-PHP). MATERIAL AND METHODS: Between June 2015 and March 2020, a total of 29 patients (median age 69.7 years; age range 30-81 years; 60% women; median BMI 25.7 kg/m2; range 18.7-35.3kg/m2; 1-6 procedures per patient) were treated with 53 CS-PHPs. All patients received cross-sectional imaging for initial and follow-up examinations. Baseline tumor load, extrahepatic tumor load, tumor response, PFS, and OS were assessed. Non-parametric statistics were used. RESULTS: After the initial CS-PHP, a partial response was observed in 11 patients (41%), stable disease in 12 patients (44%) and progressive disease in 4 patients (15%); two patients died before the response was evaluated. After initial CS-PHP, median OS was 12.9 ± 7.4 months and median PFS was 7.1 ± 7.4 months. OS after one year was 50%. After the second CS-PHP, median PFS was 7.9 ± 5.7 months. Seven patients had a liver tumor burden >25%, associated with a significantly shorter OS (6.0 ± 2.4 vs. 14.1 ± 12.7 months; P = 0.008). At the time of first CS-PHP, 41% (12/29) of the patients had extrahepatic metastases that did not affect OS (11.1 ± 8.4 months vs. 12.9 ± 13.6 months; P = 0.66). CONCLUSION: CS-PHP is a safe and effective treatment for the hepatic metastatic uveal melanoma, especially for patients with a hepatic tumor burden <25%.

Fertility after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: A call to action.

INTRODUCTION: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly accepted as the best therapeutic option in primary and some secondary peritoneal malignancies. The ramifications of this procedure on fertility are unknown. The aim of this study was to assess the current association of CRS/HIPEC with fertility following surgery. METHODS: A review of patients who underwent CRS/HIPEC between 2009 and 2018 was performed. Female patients were included if they were between ages 18-50 at the time of surgery. Gynecologic and obstetric history before and following CRS/HIPEC was collected by phone interview. RESULTS: Of 48 eligible participants, 21 completed the survey. Sixty-five percent of women underwent a total abdominal hysterectomy before or during CRS. Twenty-nine percent of these women recall fertility counseling before CRS/HIPEC, while 14.3% saw a fertility specialist for consultation, and only one patient proceeded with oocyte cryopreservation before treatment. There were no pregnancies reported following treatment with CRS/HIPEC. CONCLUSION: Few patients after CRS/HIPEC retain child-bearing potential, partly due to the high rate of hysterectomy and oophorectomy at time of surgery. Efforts towards improved preoperative counseling, increased oocyte cryopreservation, and evaluating the safety of preserving reproductive organs at the time of surgery are needed.

Elevated Maximum Core Body Temperature During Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) is Associated with Increased Postoperative Complications.

BACKGROUND: Hyperthermia enhances the cytotoxicity of chemotherapeutic agents used during cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC). However, this may result in an elevated core body temperature (CBT), with unintended effects on surgical morbidity. This study evaluates the relationship of maximum CBT during CRS/HIPEC on postoperative outcomes. METHODS: A retrospective review of patients undergoing CRS/HIPEC from January 2011 to July 2017 was performed. Outcomes were stratified according to maximum CBT reached during HIPEC. Primary study endpoints were 30-day morbidity and 30-day complication severity. RESULTS: Overall, 135 consecutive CRS/HIPEC cases were reviewed; 36 (27%) had a maximum CBT ≥ 39.5 °C during the 90-min HIPEC. CBT ≥ 39.5 °C was associated with an increase in 30-day postoperative complications (58% vs. 34%, p = 0.01) and severe Clavien-Dindo grade III or higher complications (22% vs. 11%, p = 0.04). On multivariate analysis, the adjusted odds ratio of having any complication was 3.77 (95% confidence interval [CI] 1.56-9.14) and a Clavien-Dindo grade III or higher complication was 3.46 (95% CI 1.10-10.95) when maximum CBT reached 39.5 °C. Flow rates ≥ 2.35 L/min were associated with lower average CBT (p = 0.05) and improved peritoneal heating (p = 0.02). CONCLUSION: Maximum CBT ≥ 39.5 °C is associated with an increased risk of postoperative morbidity. Higher flow rates are associated with improved intraperitoneal heating, lower CBT, and may contribute to optimizing the therapeutic benefit of HIPEC.

Predictors of Anastomotic Failure After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Does Technique Matter?

BACKGROUND: Anastomotic failure (AF) after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) remains a dreaded complication. Whether specific factors, including anastomotic technique, are associated with AF is poorly understood. METHODS: Patients who underwent CRS-HIPEC including at least one bowel resection between 2000 and 2017 from 12 academic institutions were reviewed to determine factors associated with AF (anastomotic leak or enteric fistula). RESULTS: Among 1020 patients who met the inclusion criteria, the median age was 55 years, 43.9% were male, and the most common histology was appendiceal neoplasm (62.3%). The median Peritoneal Cancer Index was 14, and 93.2% of the patients underwent CC0/1 resection. Overall, 82 of the patients (8%) experienced an AF, whereas 938 (92.0%) did not. In the multivariable analysis, the factors associated with AF included male gender (odds ratio [OR], 2.2; p < 0.01), left-sided colorectal resection (OR 10.0; p = 0.03), and preoperative albumin (OR 1.8 per g/dL; p = 0.02).Technical factors such as method (stapled vs hand-sewn), timing of anastomosis, and chemotherapy regimen used were not associated with AF (all p > 0.05). Anastomotic failure was associated with longer hospital stay (23 vs 10 days; p < 0.01), higher complication rate (90% vs 59%; p < 0.01), higher reoperation rate (41% vs 9%; p < 0.01), more 30-day readmissions (59% vs 22%; p < 0.01), greater 30-day mortality (9% vs 1%; p < 0.01), and greater 90-day mortality (16% vs 8%; p = 0.02) as well as shorter median overall survival (25.6 vs 66.0 months; p < 0.01). CONCLUSIONS: Among patients undergoing CRS-HIPEC, AF is independently associated with postoperative morbidity and worse long-term outcomes. Because patient- and tumor-related, but not technical, factors are associated with AF, operative technique may be individualized based on patient considerations and surgeon preference.

Oncologic outcomes and morbidity following heated intraperitoneal chemotherapy at cytoreductive surgery for primary epithelial ovarian cancer: A systematic review and meta-analysis.

OBJECTIVES: Heated intraperitoneal chemotherapy (HIPEC) has not been universally adopted at the time of interval cytoreductive surgery for primary epithelial ovarian cancer (EOC) despite evidence of a 12-month overall survival (OS) benefit in a recent landmark randomized trial. We performed a systematic review and meta-analysis to assess oncologic outcomes and perioperative morbidity following HIPEC among primary EOC patients. METHODS: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, from inception to August 2019, for observational and randomized studies of primary EOC patients undergoing HIPEC. We assessed risk of bias using the Institute of Health Economics Quality Appraisal Checklist for single-arm cohort studies, Newcastle-Ottawa Scale for comparative cohort studies, and Cochrane Collaboration's Tool for randomized trials. We qualitatively summarized survival outcomes and calculated the pooled proportion of 30-day grade III-IV morbidity and postoperative death. RESULTS: We identified 35 articles including 2252 primary EOC patients; one study was a randomized trial, and only six studies included a comparator group of surgery alone. The timing, temperature, and chemotherapeutic agents used for HIPEC differed across studies. Reported OS was highly variable (3-year OS range: 46-77%); three comparative cohort studies and the sole randomized trial reported statistically significant survival benefits for HIPEC over surgery alone, while two comparative cohort studies did not. The pooled proportions for grade III-IV morbidity and postoperative death at 30 days were 34% (95% CI 20-52) and 0% (95% CI 0-5) respectively. CONCLUSION: One randomized trial suggests that HIPEC at time of interval cytoreductive surgery should be considered in patients with primary EOC. However, there is significant heterogeneity in literature with respect to an appropriate HIPEC regimen, short- and long-term outcomes. High-quality prospective randomized trials are urgently needed to clarify the role of HIPEC in the first-line treatment of primary EOC.

Over 12 Years Single Institutional Experience Performing Percutaneous Hepatic Perfusion for Unresectable Liver Metastases.

Patients with unresectable hepatic metastases, from uveal or ocular melanoma, are challenging to treat with an overall poor prognosis. Although over the past decade significant advances in systemic therapies have been made, metastatic disease to the liver, especially from uveal melanoma, continues to be a poor prognosis. Percutaneous hepatic perfusion (PHP) is a safe, viable treatment option for these patients. PHP utilizes high dose chemotherapy delivered directly to the liver while minimizing systemic exposure and can be repeated up to 6 times. Isolation of the hepatic vasculature with a double-balloon catheter allows for high concentration cytotoxic therapy to be administered with minimal systemic adverse effects. A detailed description of the multidisciplinary treatment protocol used at an institution with over 12 years of experience is discussed and recommendations are given. A dedicated team of a surgical or medical oncology, interventional radiology, anesthesiology and a perfusionist allows PHP to be repeatedly performed as a safe treatment strategy for unresectable hepatic metastases.

Impact of Perfusate Glucose Concentration on Perioperative Outcomes in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a common treatment for peritoneal surface malignancies but no standard carrier solution currently exists for the procedure. This study compared a standard low-dextrose perfusate to a higher-dextrose dialysate that has previously shown favorable impact on perioperative patient outcomes in trauma settings. MATERIALS AND METHODS: A single-center retrospective study identified patients undergoing CRS/HIPEC from 2008 to 2019 with recorded dextrose concentration of administered perfusate. An institutional shift to a higher-dextrose solution was made in late 2015. Comparisons of preoperative factors, intraoperative and postoperative glucose levels, and postoperative outcomes were made using the chi-square test, Fisher's exact test, Wilcoxon rank sum test, or repeated measures analysis of variance. RESULTS: There were 97 patients in the study, 73 (75%) in the low-dextrose group and 24 (25%) in the high-dextrose group. There was no significant difference in peak intraoperative blood glucose levels between the 1.5% (mean 230 mg/dL) and the 2.5% group (mean 199 mg/dL, P = 0.15). Daily postoperative glucose values were also not statistically different (repeated measures analysis of variance, P = 0.18). Median length of stay was slightly lower for the high-dextrose group (10 d, interquartile range 8-15) than that for the low-dextrose group (12 d, interquartile range 9-17), but was not statistically significant (P = 0.29). Return of bowel function and resumption of diet were similar between the groups. The high-dextrose group had a lower rate of overall complications (20.8%) than the low-dextrose group (49.3%, P = 0.0143). Ninety-day mortality was equivalent between the two groups (2.7% low-dextrose, 4.2% high-dextrose, P = 1.0). CONCLUSIONS: Use of 2.5% dextrose-containing perfusate appears safe for CRS/HIPEC operations, does not negatively impact intraoperative or postoperative glucose levels, and may be associated with a decreased risk of complications.

Predictors of Non-home Discharge after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Using a national database of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) recipients, we sought to determine risk factors for nonhome discharge (NHD) in a cohort of patients. METHODS: Patients undergoing CRS/HIPEC at any one of 12 participating sites between 2000 and 2017 were identified. Univariate analysis was used to compare the characteristics, operative variables, and postoperative complications of patients discharged home and patients with NHD. Multivariate logistic regression was used to identify independent risk factors of NHD. RESULTS: The cohort included 1593 patients, of which 70 (4.4%) had an NHD. The median [range] peritoneal cancer index in our cohort was 14 [0-39]. Significant predictors of NHD identified in our regression analysis were advanced age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.05-1.12; P < 0.001), an American Society of Anesthesiologists (ASA) score of 4 (OR, 2.87; 95% CI, 1.21-6.83; P = 0.017), appendiceal histology (OR, 3.14; 95% CI 1.57-6.28; P = 0.001), smoking history (OR, 3.22; 95% CI, 1.70-6.12; P < 0.001), postoperative total parenteral nutrition (OR, 3.14; 95% CI, 1.70-5.81; P < 0.001), respiratory complications (OR, 7.40; 95% CI, 3.36-16.31; P < 0.001), wound site infections (OR, 3.12; 95% CI, 1.58-6.17; P = 0.001), preoperative hemoglobin (OR, 0.81; 95% CI, 0.70-0.94; P = 0.006), and total number of complications (OR, 1.41; 95% CI, 1.16-1.73; P < 0.001). CONCLUSIONS: Early identification of patients at high risk for NHD after CRS/HIPEC is key for preoperative and postoperative counseling and resource allocation, as well as minimizing hospital-acquired conditions and associated health care costs.

Impact of Perfusate Concentration on Hyperthermic Intraperitoneal Chemotherapy Efficacy and Toxicity in a Rodent Model.

BACKGROUND: Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be beneficial in treating limited peritoneal carcinomatosis (PC) from colorectal cancer (CRC). Perfusate volume directly affects treatment concentration and therefore is a key parameter defining HIPEC; yet little is known about the impact of perfusate concentration on systemic toxicity and treatment morbidity. MATERIALS AND METHODS: PC was induced through intraperitoneal injection of human CRC cell lines. A novel perfusion model was developed to treat athymic nude mice with continuous circulation of adequately miniaturized volumes of heated perfusate. Oxaliplatin HIPEC was performed applying different volumes of perfusate with fixed doses or fixed concentrations. Early postoperative mortality and morbidity were assessed as well as long-term survival. In addition, antiproliferative and proapoptotic effects of HIPEC were determined in vitro and in vivo. RESULTS: Perfusate concentration crucially affected the toxicity of fixed-dose oxaliplatin HIPEC as indicated by postoperative weight loss and early postoperative mortality. Applying different perfusate volumes at a fixed concentration did not influence toxicity. Adequately miniaturized HIPEC with oxaliplatin did not exert relevant cytotoxic effects toward PC arising from human CRC cells in vivo. CONCLUSIONS: We describe a novel murine model that adequately miniaturizes all physical parameters of HIPEC as applied in humans. HIPEC drug concentration is a crucial parameter determining excess toxicity and should be better standardized. HIPEC with oxaliplatin fails to induce relevant antitumor activity or to improve survival in this murine model of PC from CRC.

Acute kidney injury after platinum-based transcatheter arterial chemoembolization and transarterial infusion chemotherapy in patients with hepatocellular carcinoma.

BACKGROUNDS: The incidence of acute kidney injury and the association between acute kidney injury and prognosis have been reported about transcatheter arterial chemoembolization using anthracycline. However, the incidence of acute kidney injury after platinum-based transarterial chemoembolization or transarterial infusion chemotherapy remains unclear. The aim of this study was to investigate association between acute kidney injury after platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy and prognosis in patients with hepatocellular carcinoma. METHODS: We retrospectively analysed 270 sessions in 129 patients who underwent platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy. Acute kidney injury was diagnosed according to the criteria established by the International Club of Ascites. The incidence of acute kidney injury, risk factors for serum creatinine elevation and association between acute kidney injury and prognosis were assessed. RESULTS: Fifteen cases of acute kidney injury (5.6%, 15/270) developed in 14 patients (10.8%, 14/129). Ascites (coefficient: 0.059, P = 0.006), low estimated glomerular filtration rate (coefficient: -0.008, P = 0.029), diabetes (coefficient: 0.072, P < 0.001) and high albumin-bilirubin grade (albumin-bilirubin grade 2: coefficient: 0.053, P = 0.004; and albumin-bilirubin grade 3: coefficient: 0.103, P < 0.001) were significantly associated with an elevation in serum creatinine levels after transcatheter arterial chemoembolization/transarterial infusion chemotherapy. The development of acute kidney injury was associated with poor prognosis (hazard ratio: 3.18, 95%CI: 1.411-7.171, P = 0.005). Patients with acute kidney injury had a significantly lower survival rate than patients without acute kidney injury (log-rank test; P = 0.034). CONCLUSIONS: The incidence of acute kidney injury after platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy was consistent with that after transcatheter arterial chemoembolization using anthracycline, and the development of acute kidney injury was associated with poor prognosis. Ascites, diabetes, low estimated glomerular filtration rate and high albumin-bilirubin grade were risk factors for serum creatinine elevation after platinum-based transcatheter arterial chemoembolization/transarterial infusion chemotherapy.

Anesthesia and Pain Management for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Desmoplastic Small Round Cell Tumors in Children, Adolescents, and Young Adults.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive sarcoma. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may improve survival. METHODS: A retrospective review of anesthetic management and postoperative pain control strategies after CRS/HIPEC for DSRCT from 2013 to 2017 was performed. RESULTS: The review analyzed 10 CRS/HIPEC procedures performed for nine DSRCT patients with a median age of 19 years (range 10-24 years). Six of these patients were Caucasian, and seven were men. The median operative duration was 551 min (range 510-725 min), and the median anesthesia duration was 621 min (range 480-820 min). Postoperative mechanical ventilation was necessary in 5 patients for a median duration of 1 day (range 0-2 days). The median intraoperative intravenous fluid administration was 13 ml/kg/h (range 6.3-24.4 ml/kg/h), and the colloid administration was 12 ml/kg (range 0.0-53.0 ml/kg). The median blood loss was 15 ml/kg (range 6.3-77.2 ml/kg). Nine patients received intraoperative transfusion with a median red blood cell transfusion volume of 14 ml/kg (range 10.1-58.5 ml/kg). The median intraoperative urine output was 2 ml/kg/h (range 0.09-8.40 ml/kg/h), and half of the patients received intraoperative diuretics. Cisplatin was used during HIPEC for eight surgeries. Acute kidney injury was observed in two patients, one of whom required short-term dialysis. Epidural infusions were used in eight cases for a median of 4 days (range 3-5 days). Postoperative intravenous opioid use (morphine equivalent) was 0.67 mg/kg/day (range 0.1-9.2 mg/kg/day) administered for a median of 11 days (range 2-35 days). CONCLUSION: Cytoreduction and HIPEC for DSRCT are associated with significant perioperative fluid requirements and potentially challenging pain management. Renal protective strategies should be considered for reduction of cisplatin-associated nephrotoxicity. Further investigation for a more effective, less systemically toxic HIPEC agent is warranted.

Response and Toxicity of Repeated Isolated Limb Perfusion (re-ILP) for Patients With In-Transit Metastases of Malignant Melanoma.

BACKGROUND: Isolated limb perfusion (ILP) is a safe and well-established treatment for in-transit metastases of melanoma. In case of relapse or disease progression, ILP can be repeated (re-ILP). This study aimed retrospectively to analyze a large consecutive series of re-ILP and compare clinical outcomes with first-time ILP. METHOD: Between 2001 and 2015, 290 consecutive patients underwent 380 ILPs. Of these, 90 were re-ILPs including 68 second ILPs, 16 third ILPs, 4 fourth ILPs, and two fifth ILPs. The study evaluated response (using World Health Organization [WHO] criteria), local toxicity (using the Wieberdink scale), and complications (using Clavien-Dindo). RESULTS: The results were compared between the first ILP, the second ILP, and the third to fifth ILP. The overall response rate was respectively 83%, 80% and 68%, with a complete response (CR) rate of 60%, 41%, and 59%. In the re-ILP group, the patients with a CR after the first ILP had a 65% CR rate after the second ILP compared with 8% for the patients without a CR (p = 0.001). The risk for local toxicity or complications was not increased after re-ILP. The median overall survival periods were respectively 34, 41, and 93 months (p = 0.02). CONCLUSION: As a therapeutic option, ILP can be repeated safely for in-transit metastases of melanoma, achieving similar high response rates without increasing complications or toxicity. Re-ILP is mainly indicated for patients who already had a CR after the first ILP, whereas other treatment options should be considered for primary non-responders.

Incidence, Risk Factors, and Prevention Strategies for Venous Thromboembolism after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: The risk factors and incidence of venous thromboembolism (VTE) are not well defined in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). We sought to characterize the incidence, risk factors, and pharmacothromboprophylaxis strategies for VTE after CRS/HIPEC. PATIENTS AND METHODS: We performed a retrospective study of CRS/HIPEC procedures at our institution from 8/2007 to 11/2017, examining the 60-day VTE incidence. Baseline, potential risk factor, and prevention strategy data were collected. Univariate and multivariate regression analysis was used to determine risk factors associated with 60-day VTEs. RESULTS: We identified 25 60-day VTEs among 447 CRS/HIPEC procedures (5.6%). VTEs were discovered on median postoperative day 20 (range 2-59); pulmonary emboli (68%) were the most common type of VTE. The 60-day VTE rate was 10.2% before versus 4.9% after initiation of a policy to discharge patients on pharmacothromboprophylaxis (p = 0.10). Patients with 60-day VTEs had longer average length of stay (14 vs. 11 days, p = 0.01) and higher 60-day mortality rate (4% vs. 0.2%, p = 0.02) than those without VTEs. Caprini score (odds ratio [OR] 1.53, 95% confidence interval [CI] 1.10-2.15, p = 0.01), preoperative serum albumin level (OR 0.40, 95% CI 0.16-1.00, p = 0.05), and 60-day non-VTE serious morbidity (OR 3.45, 95% CI 1.25-9.51, p = 0.02) were risk factors associated with 60-day VTEs on multivariate analysis. CONCLUSIONS: VTEs are relatively common after CRS/HIPEC and are associated with high Caprini scores, low serum albumin levels, and additional inpatient comorbidities. They result in longer length of stay and higher mortality rate. Compliance with current guidelines for extended postoperative thromboprophylaxis was likely associated with reduced VTE rate.

Pleuropulmonary Recurrence Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemoperfusion for Appendiceal Pseudomyxoma Peritonei.

BACKGROUND: The aim of this study was to identify factors associated with pleuropulmonary disease recurrence following cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS/HIPEC) for appendiceal pseudomyxoma peritonei (PMP) and to evaluate the oncologic impact of pleuropulmonary disease recurrence compared with isolated peritoneal recurrence. METHODS: From a prospective database, we identified patients who developed pleuropulmonary recurrence, isolated peritoneal recurrence, or no recurrence following CRS/HIPEC for appendiceal PMP. Clinicopathologic, perioperative, and oncologic data associated with the index CRS/HIPEC procedure were reviewed. The Kaplan-Meier method was used to estimate survival. Multivariate analyses identified associations with recurrence and survival. RESULTS: Of 382 patients undergoing CRS/HIPEC, 61 (16%) developed pleuropulmonary recurrence. Patients who developed a pleuropulmonary recurrence were more likely to have high-grade (American Joint Committee on Cancer [AJCC] grade 2/3) tumors (74% vs. 56%, p = 0.02) and increased operative blood loss (1651 vs. 1201 ml, p = 0.05) and were more likely to have undergone diaphragm stripping/resection (79% vs. 48%, p < 0.01) compared with patients with an abdominal recurrence. In a multivariate analysis, pleuropulmonary recurrence after CRS/HIPEC was associated with diaphragm stripping/resection, incomplete cytoreduction, and higher AJCC tumor grade. There was a trend towards reduced survival in patients with pleuropulmonary recurrence compared with patients with isolated peritoneal recurrence (median overall survival 45 vs. 53 months, p = 0.87). CONCLUSION: Pleuropulmonary recurrence of appendiceal PMP following CRS/HIPEC is common and may negatively impact survival. Formal protocols for surveillance and therapeutic intervention need to be studied and implemented to improve oncologic outcomes.

Murine Models of Intraperitoneal Perfusion for Disseminated Colorectal Cancer.

BACKGROUND: Reproduction of the perfusion used in therapy (hyperthermic intraperitoneal chemotherapy) procedures preclinically represents a valuable asset for investigating new therapeutic agents that may improve patient outcomes. This article provides technical descriptions of our execution of closed and open "coliseum" abdominal perfusion techniques in a mouse model of peritoneal carcinomatosis of colorectal cancer. MATERIALS AND METHODS: BALB/c mice presenting with disseminated colorectal cancer (CT26-luciferin cells) underwent 30-min perfusions mimicking either the closed perfusion or the coliseum perfusion technique. Disease burden was monitored by bioluminescence signaling using an in vivo imaging system. Perfusion circuits consisted of single inflow lines with either a single or dual outflow line. RESULTS: Twelve mice presenting with disseminated disease underwent the closed perfusion technique. Surgical complications included perfusate leakage and organ constriction/suction into the outflow line(s). Nine mice underwent the coliseum perfusion technique with surgical debulking, using bipolar cauterization to remove tumors attached to the peritoneum. All mice survived the coliseum perfusion with limited intraoperative complications. CONCLUSIONS: Fewer intraoperative complications were experienced with our coliseum perfusion technique than the closed perfusion. The methods described here can be used as a guideline for developing future perfusion murine models for investigating perfusion models useful for delivery of chemotherapy or other tumor-sensitization agents, including selective targeted agents, nanoparticles, and heat.

Adequate nephroprotection reduces renal complications after hyperthermic intrathoracic chemotherapy.

BACKGROUND AND OBJECTIVES: Hyperthermic intrathoracic chemotherapy (HITOC) is used for the treatment of malignant pleural tumors. Although HITOC proved to be safe, postoperative renal failure due to nephrotoxicity of intrapleural cisplatin remains a concern. METHODS: This single-center study was performed retrospectively in patients who underwent pleural tumor resection and HITOC between September 2008 and December 2018. RESULTS: A total of 84 patients (female n = 33; 39.3%) with malignant pleural tumors underwent surgical cytoreduction with subsequent HITOC (60 minutes; 42°C). During the study period, we gradually increased the dosage of cisplatin (100-150 mg/m2 BSA n = 36; 175 mg/m2 BSA n = 2) and finally added doxorubicin (cisplatin 175 mg/m2 BSA/doxorubicin 65 mg; n = 46). All patients had perioperative fluid balancing. The last 54 (64.3%) patients also received perioperative cytoprotection. Overall 29 patients (34.5%) experienced renal insufficiency. Despite higher cisplatin concentrations, patients with cytoprotection showed significantly lower postoperative serum creatinine levels after 1 week (P = .006) and at discharge (P = .020). Also, they showed less intermediate and severe renal insufficiencies (5.6% vs 13.3%). CONCLUSIONS: Adequate perioperative fluid management and cytoprotection seem to be effective in protecting renal function. This allows the administration of higher intracavitary cisplatin doses without raising the rate of renal insufficiencies.

[A single-center clinical analysis of 65 cases of pseudomyxoma peritonei from appendiceal origin in the early stage].

Objective: To analyze the efficacy and safety of cytoreduction surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP) in the early stage. Methods: The clinical data, including pathological features, recurrence and survival of 65 PMP patients in the early stage underwent CRS combined with HIPEC in Aerospace Center Hospital from January, 2011 to December, 2018 were retrospectively analyzed. Results: 65 patients with early stage PMP underwent CRS+ HIPEC. Among these patients, 25 were males and 40 were females, and the mean age was 52.5 years. The median peritoneal cancer index was 3 (0-16). The score of completeness of cytoreduction (CC) of 63 patients (96.9%) was 0, and 2 patients (3.1%) was 1. No perioperative death occurred, the incidence of surgical complications above grade 3 was 3.1%. Three patients relapsed during the follow-up period, including 1 patient with low-grade PMP, 1 patient with high-grade PMP, and 1 patient with high-grade PMP accompanied by signet ring cell. The 5-year disease-free survival rate of the whole group was 92.4%. Conclusions: PMP patients in the early stage treated by CRS combined with HIPEC can achieve benefit and safety. A close long-term follow-up is necessary.

The Comprehensive Complication Index: a New Measure of the Burden of Complications After Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) are complex surgeries with multiple comorbidities. The Clavien-Dindo classification (CDC) is the most commonly used method to report surgical morbidity, but limits it to the highest-grade complication. The Comprehensive Complication Index (CCI) is a score ranging from 0 to 100, calculated using all 30-day complications and their treatment after abdominal surgery. The aim of this study is to assess the CCI's validity in the HIPEC patient population. METHODS: A review of our institutional cytoreduction database from 2009 to 2015 was undertaken. Patient demographics, pathology, Peritoneal Carcinomatosis Index (PCI), complications and their treatments, and length of stay (LOS) were reviewed. The CCI was calculated for each patient. Linear regression was used to assess whether the CCI and CDC were predictors of LOS. RESULTS: Of 157 patients reviewed, 110 (70.1%) underwent HIPEC. The majority were female (77, 66.9%), and the mean age was 53.7 years. Mean PCI was 13.2 [interquartile range (IQR) 7-18]. Median CDC was grade 2 (IQR 0-2), and only 9.8% had CDC of grade 4 or higher. Mean CCI was 21.4, while the median was 20.9 (IQR 0-30.8). Mean LOS was 16.2 days, while the median was 11 days (IQR 8-15 days). The CCI strongly correlated with LOS with coefficient of 0.46 [95% confidence interval (CI) 0.38-0.54, p = 0.000]. CONCLUSIONS: The CCI is an adequate tool to capture all complications and their overall burden in patients having undergone HIPEC. This study shows that the CCI can predict LOS and could be used to quantify and compare the burden of multiple complications.