Negative Pressure Wound Therapy to Reduce Surgical Site Infections after CRS/HIPEC.

BACKGROUND: Surgical site infections (SSIs) are a common cause of morbidity after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancy. Negative pressure wound therapy (NPWT) has been proposed as a method to reduce the rates of SSIs; however, there is paucity in the literature on the efficacy in this population. The goal of this study was to determine whether routine use of NPWT in patients undergoing CRS/HIPEC could reduce the risk of developing SSI. METHODS: We performed a retrospective before-after study to assess the rates of SSI with NPWT compared with a standard postoperative surgical dressing (SSD) in all patients undergoing CRS/HIPEC from November 2013 to December 2021 at a single tertiary care center. The primary outcome was rate of SSI. A multivariate logistic regression analysis was performed to evaluate for risk factors for SSI. RESULTS: A total of 178 patients were treated with CRS/HIPEC over the study period. Seventy patients had placement of SSD, and 108 patients had placement of NPWT. Rates of SSI were 11.4% (8/70) and 5.6% (6/108) in the two groups, respectively (p = 0.16). On multivariate analysis, patients treated with NPWT had a significantly lower risk of developing an SSI (OR 0.24 [0.06, 0.92], p = 0.037). Patients living >50 km from the hospital had significantly higher risk of developing SSI (OR 2.03 [1.09, 3.78], p = 0.026). CONCLUSIONS: These results suggest that routine use of NPWT can reduce the risk of developing an SSI in patients undergoing CRS/HIPEC for peritoneal malignancy.

Risk factors of chronic kidney disease in cisplatin-based hyperthermia intraperitoneal chemotherapy.

PURPOSE: Cisplatin is commonly prescribed in hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancy. Acute kidney injury (AKI) is regarded as a common complication after HIPEC combined with cytoreductive surgery (CRS). However, post-HIPEC chronic kidney disease (CKD) is scarce and less investigated. This study aims to investigate the incidence of CKD following cisplatin-based HIPEC and to analyse the associated risk factors. MATERIALS AND METHODS: From January 2016 to August 2021, a total of 55 patients treated with CRS and cisplatin-based HIPEC for peritoneal carcinomatosis were categorized retrospectively into groups, with and without CKD. Demographics, comorbidity, surgery, postoperative management, and complications were collected to evaluate risk factors for cisplatin-based HIPEC-related CKD. Univariate and multivariate analyses were conducted to confirm the correlation between different variables and CKD occurrence. RESULTS: Of the 55 patients, 24 (43.6%) patients developed AKI and 17 (70.8%) patients of these AKI patients progressed to CKD. Multivariate regression analysis identified intraoperative use of parecoxib (Odds Ratio (OR) = 4.39) and intraoperative maximum temperature > 38.5°C (OR = 6.40) as major risk factors for cisplatin-based HIPEC-related CKD occurrence. Though type II diabetes mellitus and intraoperative complications were the independent risk factors of AKI following cisplatin-based HIPEC, but they were not shown in CKD analysis. CONCLUSION: Intraoperative use of parecoxib during cisplatin-based HIPEC emerged as a significant risk factor for postoperative CKD. Clinicians should exercise caution in prescribing parecoxib during HIPEC procedures. Additionally, maintaining intraoperative body temperature below 38.5°C might be crucial to mitigate the risk of CKD development. This study underscores the importance of identifying and preventing specific risk factors to improve long-term renal outcomes in patients undergoing cisplatin-based HIPEC.

Incidence of incisional hernia in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: an observational clinical study from a tertiary oncology referral care center in India.

BACKGROUND: An incisional hernia (IH) after major abdominal surgery is an unwanted complication particularly following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC). The frequency of IH among patients treated with CRS and HIPEC remains unexpectedly high in various studies. This study aimed to analyze the incidence, determine the factors contributing to the occurrence of IH, and develop methods to reduce the incidence of IH. METHODS: We retrospectively analyzed data from a prospectively maintained structured computerized comprehensive database of 360 patients who had undergone CRS and HIPEC after January 2013 and completed two years of follow-up before December 2023. All patients were followed for a minimum period of two years with physical examination and radiological imaging when required and the occurrence of IH was documented. We used SPSS software version 24 to analyze the data using appropriate statistical tests. We set a significance threshold of p < 0.05. RESULTS: Within two years of undergoing CRS and HIPEC, 25 patients (6.9%) out of 360 developed IH, indicating an annual incidence rate of 3.5%. The mean duration of hospitalization for the CRS/HIPEC procedure was 8.4 ± 4.13 days. Fifty-two (14.4%) patients experienced early post-operative surgical complications. The development of IH in our series was significantly associated with obesity (76% vs. 8.4%, P = 0.001), the occurrence of early post-operative surgical complications (48% vs. 12%, P = 0.001), mainly category III complications (44% vs. 7.1%), category IV complications (24% vs. 2.9%) according to Clavien-Dindo classification, post neoadjuvant chemotherapy status (72% vs. 87%, P = 0.045) and need for bowel anastomosis (32% vs. 11%, P = 0.002). CONCLUSION: The lower incidence of IH following CRS and HIPEC in our patient cohort than in the literature can be attributed to a combination of factors, including the use of meticulous surgical techniques and the use of an abdominal binder postoperatively, particularly in obese patients.

Analysis of causes and prognostic impact of tube occlusion during hyperthermic intraperitoneal chemotherapy for appendiceal pseudomyxoma peritonei.

BACKGROUND: Appendiceal pseudomyxoma peritonei (PMP), a rare tumor from mucinous appendiceal origins, is treated with Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). However, tubing blockages during HIPEC treatment pose a common challenge, impeding the smooth progression of therapy. Few studies to date have explored the incidence and risk factors of tube occlusion during HIPEC in patients with appendiceal PMP, as well as its adverse impact on postoperative complications. METHODS: From October 2017 to June 2023, a total of 80 patients with appendiceal PMP undergoing combined CRS and HIPEC were included in this study. Tubing blockage events were strictly defined, with patients experiencing blockages during HIPEC treatment allocated to the study group, while those with unobstructed perfusion were assigned to the control group. A comparative analysis was conducted between the two groups regarding post-HIPEC health assessments and occurrence of complications. Risk factors for luminal occlusion during closed HIPEC procedures were identified through univariate and multivariate analysis of data from 303 HIPEC treatments. RESULTS: Tubing blockages occurred in 41 patients (51.3%). The study group experienced prolonged gastrointestinal decompression time (4.1 ± 3.0 vs. 2.5 ± 1.7 days, P = 0.003) and prolonged time to bowel movement (6.1 ± 2.3 vs. 5.1 ± 1.8 days, P = 0.022) compared to the control group. There was no significant difference in the incidence of complications between the two groups. The 1-year survival rate postoperatively was 97%, and the 3-year survival rate was 81%, with no association found between tubing blockage and poorer survival. Additionally, In 303 instances of HIPEC treatment among these 80 patients, tube occlusion occurred in 89 cases (89/303, 29.4%). Multivariable logistic regression analysis revealed age, diabetes, hypertension, and pathology as independent risk factors for tube occlusion. CONCLUSION: Tubing blockages are a common occurrence during HIPEC treatment, leading to prolonged postoperative gastrointestinal functional recovery time. When patients are elderly and have concomitant hypertension and diabetes, along with a histological type of low-grade mucinous tumor, the risk of tube occlusion increases. However, this study did not find a significant correlation between tubing blockage and the incidence of postoperative complications or overall patient survival.

Incidence, risk factors, and outcomes of the transition of HIPEC-induced acute kidney injury to acute kidney disease: a retrospective study.

BACKGROUND: Acute kidney injury (AKI) is recognized as a common complication following cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Characterized by prolonged renal function impairment, acute kidney disease (AKD) is associated with a higher risk of chronic kidney disease (CKD) and mortality. METHODS: From January 2018 to December 2021, 158 patients undergoing CRS-HIPEC were retrospectively reviewed. Patients were separated into non-AKI, AKI, and AKD cohorts. Laboratory parameters and perioperative features were gathered to evaluate risk factors for both HIPEC-induced AKI and AKD, with the 90-day prognosis of AKD patients. RESULTS: AKI developed in 21.5% of patients undergoing CRS-HIPEC, while 13.3% progressed to AKD. The multivariate analysis identified that ascites, GRAN%, estimated glomerular filtration rate (eGFR), and intraoperative (IO) hypotension duration were associated with the development of HIPEC-induced AKI. Higher uric acid, lessened eGFR, and prolonged IO hypotension duration were more predominant in patients proceeding with AKD. The AKD cohort presented a higher risk of 30 days of in-hospital mortality (14.3%) and CKD progression (42.8%). CONCLUSIONS: Our study reveals a high incidence of AKI and AKI-to-AKD transition. Early identification of risk factors for HIPEC-induced AKD would assist clinicians in taking measures to mitigate the incidence.

Morbidity after secondary cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for ovarian cancer: An analysis of a randomized phase II trial.

OBJECTIVE: To assess postoperative complications after secondary cytoreductive surgery (SCS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC), we conducted an exploratory analysis of patients with platinum-sensitive recurrent ovarian cancer enrolled in a randomized phase II trial. METHODS: Complications occurring within 30 days of surgery were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0; only hemoglobin and platelet levels were assessed. Patients were grouped by CTCAE grade ≥ 3 and < 3 complications. RESULTS: Among 83 eligible patients, 33 (40%) had grade ≥ 3 complications and 50 (60%) had grade < 3 complications; anemia and abdominal infections were the most common. There were no perioperative mortalities. Time to initiation of postoperative chemotherapy for patients with grade ≥ 3 and grade < 3 events was 34 days (range, 18-60) and 31 days (range, 21-43), respectively (P = .017). Median progression-free survival (PFS) did not significantly differ between patients with grade ≥ 3 and grade < 3 complications (11.2 months [95% CI: 9.3-14.4] vs 14.9 months [95% CI: 11.3-16.5], respectively; P = .186), nor did median overall survival (OS) (46.9 months [95% CI: 34-NE] vs 68.2 months [95% CI: 52.1-NE], respectively; P = .053). CONCLUSION: Postoperative complications following SCS with or without HIPEC were associated with slight delays in chemotherapy initiation but did not significantly impact oncologic outcomes.

Serum procalcitonin improves diagnosis of infectious complications after CRS/HIPEC.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improve the survival of selected patients with peritoneal metastasis. A major cause of treatment-related morbidity after CRS/HIPEC is infection and sepsis. HIPEC alters the diagnostic sensitivity and specificity of blood and serum markers and therefore has an impact on early diagnosis of postoperative complications. This study aimed to assess the sensitivity and specificity of blood and serum markers after CRS/HIPEC. METHODS: Patients from two centers, operated between 2009 and 2017, were enrolled in this study. Perioperative blood samples were analyzed for white blood cells (WBC), C-reactive protein (CRP), and procalcitonin (PCT); postoperative complications were graded according to Clavien-Dindo and infectious complications according to CDC criteria. RESULTS: Overall, n=248 patients were included with peritoneal metastasis from different primary tumors treated by CRS/HIPEC. Depending on the applied HIPEC protocol, patients presented a suppressed WBC response to infection. In addition, a secondary and unspecific CRP elevation in absence of an underlining infection, and pronounced after prolonged perfusion for more than 60 min. PCT was identified as a highly specific - although less sensitive - marker to diagnose infectious complications after CRS/HIPEC. DISCUSSION/CONCLUSION: Sensitivity and specificity of WBC counts and CRP values to diagnose postoperative infection are limited in the context of HIPEC. PCT is helpful to specify suspected infection. Overall, diagnosis of postoperative complications remains a clinical diagnosis, requiring surgical expertise and experience.

Hyperthermic intraperitoneal chemotherapy does not increase risk of major complication or failure to rescue in cytoreductive surgery.

INTRODUCTION: Failure to rescue (FTR) is defined as death after a major complication. We evaluated FTR after cytoreductive surgery (CRS) with and without hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: The ACS NSQIP database 2005-2018 was reviewed for all cases of CRS. Propensity score matching was used to compare outcomes between those undergoing CRS alone and those undergoing CRS/HIPEC. Patients were matched on age, sex, ascites, diabetes, hypertension and resection of liver, pancreas, colon/rectum, diaphragm, stomach, small bowel, and/or spleen. RESULTS: Thirty nine thousand one hundred and twenty-six patients underwent CRS; 38,387 underwent CRS alone; 739 underwent CRS/HIPEC. After matching there were 726 patients in each arm. Patients undergoing CRS/HIPEC had higher risk of reintubation (25 [3.4%] vs. 13 [1.8%] p = 0.049), urinary tract infection UTI (44 [6.1%] vs. 25 [3.4%] p = 0.019) and sepsis (73 [10.1%] vs. 44 [6.1%] p = 0.005). Patients in the CRS arm required more transfusions (229 [31.5%] vs. 176 [24.2%] p = 0.002). There was no significant difference in FTR between the CRS and CRS/HIPEC groups (11 [4.0%] vs. 6 [2.3%] p = 0.258), nor in the pooled incidence of major complications (275 [37.9%] vs. 262 [36.1%] p = 0.48). CONCLUSION: CRS/HIPEC is associated with increased rates of reintubation, UTI, and sepsis while CRS alone was associated with increased transfusion. However, the addition HIPEC to CRS did not increase the risk of pooled major complication or FTR.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial.

BACKGROUND: The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery has been associated with encouraging survival results in some patients with colorectal peritoneal metastases who were eligible for complete macroscopic resection. We aimed to assess the specific benefit of adding HIPEC to cytoreductive surgery compared with receiving cytoreductive surgery alone. METHODS: We did a randomised, open-label, phase 3 trial at 17 cancer centres in France. Eligible patients were aged 18-70 years and had histologically proven colorectal cancer with peritoneal metastases, WHO performance status of 0 or 1, a Peritoneal Cancer Index of 25 or less, and were eligible to receive systemic chemotherapy for 6 months (ie, they had adequate organ function and life expectancy of at least 12 weeks). Patients in whom complete macroscopic resection or surgical resection with less than 1 mm residual tumour tissue was completed were randomly assigned (1:1) to cytoreductive surgery with or without oxaliplatin-based HIPEC. Randomisation was done centrally using minimisation, and stratified by centre, completeness of cytoreduction, number of previous systemic chemotherapy lines, and timing of protocol-mandated systemic chemotherapy. Oxaliplatin HIPEC was administered by the closed (360 mg/m2) or open (460 mg/m2) abdomen techniques, and systemic chemotherapy (400 mg/m2 fluorouracil and 20 mg/m2 folinic acid) was delivered intravenously 20 min before HIPEC. All individuals received systemic chemotherapy (of investigators' choosing) with or without targeted therapy before or after surgery, or both. The primary endpoint was overall survival, which was analysed in the intention-to-treat population. Safety was assessed in all patients who received surgery. This trial is registed with ClinicalTrials.gov, NCT00769405, and is now completed. FINDINGS: Between Feb 11, 2008, and Jan 6, 2014, 265 patients were included and randomly assigned, 133 to the cytoreductive surgery plus HIPEC group and 132 to the cytoreductive surgery alone group. After median follow-up of 63·8 months (IQR 53·0-77·1), median overall survival was 41·7 months (95% CI 36·2-53·8) in the cytoreductive surgery plus HIPEC group and 41·2 months (35·1-49·7) in the cytoreductive surgery group (hazard ratio 1·00 [95·37% CI 0·63-1·58]; stratified log-rank p=0·99). At 30 days, two (2%) treatment-related deaths had occurred in each group.. Grade 3 or worse adverse events at 30 days were similar in frequency between groups (56 [42%] of 133 patients in the cytoreductive surgery plus HIPEC group vs 42 [32%] of 132 patients in the cytoreductive surgery group; p=0·083); however, at 60 days, grade 3 or worse adverse events were more common in the cytoreductive surgery plus HIPEC group (34 [26%] of 131 vs 20 [15%] of 130; p=0·035). INTERPRETATION: Considering the absence of an overall survival benefit after adding HIPEC to cytoreductive surgery and more frequent postoperative late complications with this combination, our data suggest that cytoreductive surgery alone should be the cornerstone of therapeutic strategies with curative intent for colorectal peritoneal metastases. FUNDING: Institut National du Cancer, Programme Hospitalier de Recherche Clinique du Cancer, Ligue Contre le Cancer.

Evaluation of exposure risk for healthcare personnel performing the open technique HIPEC procedure using cisplatin.

OBJECTIVE: To perform an evaluation of the risk to healthcare personnel of exposure to cisplatin during a Hyperthermic Intraperitoneal Chemotherapy (HIPEC) procedure in an operating room environment. METHODS: Breathing zone air samples were taken from the operating room (OR) before, during and after the procedure of HIPEC filter membrane adsorption and the liquid impact method was applied to collect air samples. The samples of surface wipe from the floor of the OR were taken after the procedure. Inductively coupled plasma mass spectrometry(ICP-MS) was used to detect the content of cisplatin in all the samples. RESULTS: Thirty-six air samples and three surface wipes were collected from three different locations of healthcare personnel breathing zones. All the breathing zone air samples were negative for cisplatin; however, cisplatin contamination was detected on three surface wipes from the floor, but in a lowconcentration(≤ 2.25 ng). CONCLUSION: The results suggest that the risk of inhalation of cisplatin was extremely low for the healthcare personnel during the procedure of HIPEC, but the contamination of the OR floor should be taken into consideration.

Impact of intra-operative factors upon peri-operative outcomes in women undergoing hyperthermic intraperitoneal chemotherapy for gynecologic cancer.

OBJECTIVES: To evaluate the incidence of intra-operative metabolic and electrolyte abnormalities and subsequent impact on peri-operative outcomes in women with gynecologic cancer undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). METHODS: An IRB-approved single institution retrospective cohort study was performed in women with gynecologic cancer who underwent CRS + HIPEC. Patient demographics, intra-operative electrolyte and metabolic values and peri-operative outcomes were recorded. To assess the association of pH and lactate upon post-operative outcomes, patients were divided in four quartiles for both variables and univariate analysis was performed. RESULTS: 100 consecutive women who underwent CRS + HIPEC from 2017 to 2020 were identified. Intra-operative blood transfusion and pressor support were required in 40% and 86%, respectively. The rate of ICU admission was 17%. Longer operative time (7.0 vs. 5.3 h, p = 0.002), increased blood loss (400.0 vs. 200.0 mL, p = 0.02) and transfusion (70.6% vs. 34.1%, p = 0.005) were associated with ICU admission. Compared to patients in the highest quartile of pH, lower median pH, (7.211 vs. 7.349, p < 0.001) was associated with increased rates of ICU admission, prolonged intubation (36.0% vs. 0.0%, p < 0.05, respectively) and any post-operative complication (72.0% vs. 28.0%, p = 0.01). Similarly, need for prolonged intubation (40% vs. 0%, p = 0.04) and VTE (13.0% vs. 0%, p = 0.01) were increased in women with the highest quartile of lactate levels compared to the lowest (4.7 vs 1.9, p < 0.001). CONCLUSIONS: Intra-operative acidosis is associated with higher incidence of ICU admission and peri-operative complications following CRS + HIPEC in women with gynecologic cancer. These data support the importance of adequate intra-operative resuscitation and timely correction of hemodynamic and metabolic abnormalities.

Anastomotic leak following interval debulking surgery with or without hyperthermic intraperitoneal chemotherapy in women with advanced epithelial ovarian Cancer.

OBJECTIVE(S): To evaluate the incidence and associated risk factors for anastomotic failure following interval debulking surgery (IDS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) in women with advanced ovarian cancer. METHODS: We performed a retrospective cohort study in women with stage III/IV high-grade ovarian cancer treated with neoadjuvant chemotherapy followed by IDS with colorectal resection and HIPEC from 2017 to 2020. These patients were compared to a historical control cohort who underwent IDS with colorectal resection without HIPEC from 2009 to 2016. Data was collected for demographics, surgical variables, and perioperative outcomes. The univariate analysis compared progression-free survival and overall survival. RESULTS: 61 women were identified; 21 (34.4%) underwent IDS with HIPEC from 2017 to 2020, and 40 underwent IDS alone from 2009 to 2016. None of the patients who had IDS with HIPEC had protective ileostomy, compared to 10.0% of those who received had IDS alone (n = 4)(p = 0.29). The cumulative incidence of anastomotic leak rate was 8.2% (n = 5). There was no significant difference in anastomotic leak rate for women who underwent IDS with HIPEC (9.5%, n = 2) versus without HIPEC (7.5%, n = 3) (p = 0.99). While there was no difference in PFS (12.2 vs. 13.3 months, log-rank p = 0.31), OS (9.4 vs. 40.6 months, log-rank p = 0.013) was significantly decreased following postoperative anastomotic leak. CONCLUSIONS: In this retrospective series of women with advanced ovarian cancer, HIPEC was not associated with increased risk for anastomotic leak at the time of IDS with colorectal resection and reanastomosis. While further study is needed, HIPEC alone should not preclude colorectal resection or dictate practices for colonic diversion in IDS.

Modified frailty index predicts postoperative complications in women with gynecologic cancer undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

OBJECTIVE(S): To evaluate the impact of frailty on postoperative complications following cytoreductive surgery (CRS) with hyperthermic intra-peritoneal chemotherapy (HIPEC) in women with advanced or recurrent gynecologic cancer. METHODS: An IRB-approved single-institution prospective registry was queried for women who underwent CRS with HIPEC for advanced or recurrent gynecologic cancer from 1/1/2014-12/31/2020. Frailty was defined as a modified Frailty Index (mFI) score of ≥2. Logistic regression was used to assess the impact of mFI upon the rate of moderate or higher (≥ grade 2) Accordion postoperative complications. RESULTS: Of 141 women, 81.6% (n = 115) were non-frail with mFI of 0-1 and 18.4% (n = 26) were frail with mFI ≥2. The incidence of ≥ grade 2 complications was 21.2% (n = 14) for mFI = 0, 26.5% (n = 13) for mFI = 1, 64.7% (n = 11) for mFI = 2 and 100.0% (n = 9) for patients with mFI ≥3. The incidence of re-operation (1.7% vs. 11.5%, p = 0.044), ICU admission (13.2% vs. 34.6%, p = 0.018), acute kidney injury (6.3% vs. 30.8%, p = 0.001), and respiratory failure (0.9% vs. 19.2%, p < 0.001) were significantly lower amongst non-frail vs. frail women. On multivariable analysis, mFI ≥2 was associated with significantly increased ≥ grade 2 complications versus mFI of 0-1 (OR 9.4, 95% CI 3.3, 26.4, p < 0.001). Age (OR 1.04, 95% CI 1.00, 1.09, p = 0.07), surgical indication (recurrent vs. primary) (OR 0.71, 95% CI 0.30, 1.7, p = 0.44) and Surgical Complexity Score of Intermediate or High vs. Low (OR 1.5, 95% CI 0.67, 3.5, p = 0.31) were not associated with ≥grade 2 complications. CONCLUSIONS: Frailty, defined by the modified frailty index, is predictive of ≥grade 2 postoperative complications following CRS with HIPEC in women with gynecologic cancer. Frailty screening before CRS with HIPEC may assist patient selection and improve postoperative outcomes.

Sclerosing Encapsulating Peritonitis in a Pediatric Patient Treated With Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Sclerosing encapsulating peritonitis (SEP) is a rare chronic inflammatory condition characterized by small bowel encapsulation by a thick fibrocollagenous membrane. Patients with SEP often present with nonspecific symptoms, such as abdominal pain and distension, however some patients may present with symptoms suggestive of intestinal obstruction. Secondary SEP has been reported in patients undergoing peritoneal dialysis and has been recently described in adults following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). OBSERVATIONS: We report a clinical case of a 13-year-old female who presented with worsening abdominal pain and distension and persistent emesis who was found to have SEP 13 months following CRS and HIPEC for management of desmoplastic small round cell tumor and subsequently required operative intervention. CONCLUSION: Although there have been published reports of adult patients experiencing cases of SEP following CRS/HIPEC, this is the first published case of secondary SEP occurring in a pediatric oncology patient.

Effect of Cilastatin on Cisplatin-Induced Nephrotoxicity in Patients Undergoing Hyperthermic Intraperitoneal Chemotherapy.

Cisplatin is one of the most widely used chemotherapeutic agents in oncology, although its nephrotoxicity limits application and dosage. We present the results of a clinical study on prophylaxis of cisplatin-induced nephrotoxicity in patients with peritoneal carcinomatosis undergoing cytoreduction and hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC-cisplatin). Prophylaxis was with imipenem/cilastatin. Cilastatin is a selective inhibitor of renal dehydropeptidase I in the proximal renal tubule cells that can reduce the nephrotoxicity of cisplatin. Unfortunately, cilastatin is not currently marketed alone, and can only be administered in combination with imipenem. The study has a retrospective part that serves as a control (n = 99 patients receiving standard surgical prophylaxis) and a prospective part with imipenem/cilastatin prophylaxis corresponding to the study group (n = 85 patients). In both groups, we collected specific data on preoperative risk factors of renal damage, fluid management, hemodynamic control, and urine volume during surgery (including the hyperthermic chemotherapy perfusion), as well as data on hemodynamic and renal function during the first seven days after surgery. The main finding of the study is that cilastatin may exert a nephroprotective effect in patients with peritoneal carcinomatosis undergoing cytoreduction and hyperthermic intraperitoneal cisplatin perfusion. Creatinine values remained lower than in the control group (ANOVA test, p = 0.037). This translates into easier management of these patients in the postoperative period, with significantly shorter intensive care unit (ICU) and hospital stay.

Current status of hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer in the United States.

OBJECTIVES: 1.) To compare frequency of HIPEC use in ovarian cancer treatment before and after publication of the phase III study by van Driel et al. in January 2018. 2.) To compare associated rates of hospital-based outcomes, including length of stay, intensive care unit (ICU) admission, complications, and costs in ovarian cancer surgery with or without HIPEC. METHODS: We queried Vizient's administrative claims database of 550 US hospitals for ovarian cancer surgeries from January 2016-January 2020 using ICD-10 diagnosis and procedure codes. Sodium thiosulfate administration was used to identify HIPEC cases according to the published protocol. Student t-tests and relative risk (RR) were used to compare continuous variables and contingency tables, respectively. RESULTS: 152 ovarian cancer patients had HIPEC at 39 hospitals, and 20,014 ovarian cancer patients had surgery without HIPEC at 256 hospitals. Following the trial publication, 97% of HIPEC cases occurred. During the index admission, HIPEC patients had longer median length of stay (8.4 vs. 5.7 days, p < 0.001) and higher percentage of ICU admissions (63.1% vs. 11.0%, p < 0.001) and complication rates (RR = 1.87, p = 0.002). Index admission direct costs ($21,825 vs. $12,038, p < 0.001) and direct cost index (observed/expected costs) (1.87 vs. 1.11, p < 0.001) were also greater in the HIPEC patients. No inpatient deaths or 30-day readmissions were identified after HIPEC. CONCLUSIONS: Use of HIPEC for ovarian cancer increased in the US after publication of a phase III clinical trial in a high-impact journal, though the absolute number of cases remains modest. Incorporation of HIPEC was associated with increased cost, hospital length of stay, ICU admission, and hospital-acquired complication rates. Further studies are needed in order to evaluate long-term outcomes, including morbidity and survival.

Severe Hypocalcemia and Transient Hypoparathyroidism After Hyperthermic Intraperitoneal Chemotherapy.

Dear Editors,Hypocalcemia is not unusual in patients hospitalized for critical illness and has also been described after general surgery in addition to head and neck surgical procedures 1 2 3. Hypocalcemic events commonly occur in the setting of massive blood transfusion, albumin deficiency, vitamin D deficiency, and/or hypomagnesemia. In the absence of these factors, only slight decreases in calcium levels within the normal range have been reported during surgical procedures 1. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) causing asymptomatic hypocalcemia has only been reported in two previous studies 4 5. The etiology is unclear. We here report a patient who developed severe symptomatic hypocalcemia likely as a result of a profound inflammatory reaction with transient hypoparathyroidism after HIPEC.

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 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.

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) might increase the risk of anastomotic leakage compared to HIPEC: an experimental study.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) and hyperthermic intraperitoneal chemotherapy (HIPEC) are technics proposed to treat patients with peritoneal carcinomatosis, in different settings. There is some concern about an over-risk of anastomotic leakage (AL) with PIPAC jeopardizing a combination with cytoreductive surgery. This study used a healthy swine model to compare the postoperative AL rate between PIPAC and HIPEC with digestive resection and to analyze macrocirculation and microcirculation parameters. METHODS: Segmental colonic resection with a handsewn anastomosis was performed on 16 healthy pigs; 8 pigs had a PIPAC procedure with 7.5 mg/m2 cisplatin (PIPAC group), and 8 pigs had a closed HIPEC procedure with 70 mg/m2 cisplatin and 42 °C as the target intraperitoneal temperature (HIPEC group). Pigs were kept alive for 8 days, then sacrificed and autopsied to look for AL, which was defined as local abscess or digestive fluid leakage when pressure was applied to the anastomosis. Food intake, weight, and core temperature were monitored postoperatively. Macrocirculation (heart rate, systolic blood pressure) and microcirculation parameters (percentage of perfused vessels, perfused vessels density, DeBacker score) were evaluated intraoperatively at five timepoints. Results were compared between pigs with AL and those without. RESULTS: The HIPEC group had no AL, but 3 of 8 pigs (37.5%) had AL in the PIPAC group (p = 0.20). Heart rate and core temperature showed perioperative increases in the HIPEC group. Intraoperatively, heart rate was higher in the HIPEC group at the two last timepoints (123 vs. 93 bpm, p = 0.031, and 110 vs. 85 bpm, p = 0.010, at timepoints 3 and 4, respectively). Other macrocirculatory and microcirculatory parameters showed no significant differences. CONCLUSION: In this healthy swine model, PIPAC might have increased AL incidence compared to HIPEC. This potential over-risk did not seem to be related to changes in the microcirculation. PIPAC should probably not be used with digestive resection and should be avoided in cases of perioperative serosal injury.