Does Hospital Operative Volume Influence the Outcomes of Patients After Heated Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis?

BACKGROUND: For some cancer operations, center volume is associated with improved patient outcomes. Whether this association is true for cytoreductive surgery/heated intraperitoneal chemotherapy (CRS/HIPEC) is unclear. Given the rapidly expanding use of CRS/HIPEC, the aim of this analysis was to determine whether a volume-outcome relationship exists for this strategy. METHODS: The Vizient Clinical Database® was queried for CRS/HIPEC cases from January 2020 through December 2022. Low-, medium-, and high-volume designations were made by sorting hospitals by case volume and creating equal tertiles based on total number of cases. Analysis was performed via one-way ANOVA with post-hoc Tukey test, as indicated. RESULTS: In the 36-month study period, 5165 cases were identified across 149 hospitals. Low- (n = 113), medium- (n = 25), and high-volume (n = 11) centers performed a median of 4, 21, and 47 cases per annum, respectively. Most cases were performed for appendiceal (39.3%) followed by gynecologic neoplasms (20.4%). Groups were similar with respect to age, gender, race, comorbidities, and histology. Low-volume centers were more likely to utilize the ICU post-operatively (59.6% vs. 40.5% vs. 36.3%; p = 0.02). No differences were observed in morbidity (9.4% vs. 7.1% vs. 9.0%, p = 0.71), mortality (0.9% vs. 0.6% vs. 0.7%, p = 0.93), length of stay (9.3 vs. 9.4 vs. 10 days, p = 0.83), 30-day readmissions (5.6% vs. 5.6% vs. 5.6%, p = 1.0), or total cost among groups. CONCLUSIONS: No association was found between CRS/HIPEC hospital volume and post-operative outcomes. These data suggest that in academic medical centers with HIPEC programs, outcomes for commonly treated cancers are not associated with hospital volume.

Outcomes Following Cytoreductive Surgery and Hyperthermic Intraoperative Thoraco-Abdominal Chemotherapy with Diaphragm Resection for Peritoneal Carcinomatosis: A Retrospective Cohort Study.

PURPOSE: We aimed to evaluate the safety and efficacy of hyperthermic intraoperative thoraco-abdominal chemotherapy (HITAC) and cytoreductive surgery (CRS) for peritoneal carcinomatosis (PC) patients who underwent diaphragm resection. METHODS: PC patients who underwent CRS with diaphragm resection were selected from a prospectively established database and were divided into hyperthermic intraperitoneal chemotherapy (HIPEC) and HITAC groups. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were compared between the two groups. RESULTS: Of 1168 CRS + HIPEC/HITACs, 102 patients were enrolled-61 HITAC patients and 41 HIPEC patients. In the HITAC and HIPEC groups, the incidence of grade III-V AEs was 29.5% versus 34.1% (p = 0.621). The pleural progression rates were 13.2 versus 18.9% (p = 0.462) and the median overall survival (OS) was 50.5 versus 52.7 months (p = 0.958). Median time to progression (TTP) in thoracic disease was not reached. There was no significant difference in perioperative AEs, TTP, and OS for total patients and the completeness of cytoreduction (CC) score subgroups (p > 0.05). Age ≥ 60 years (hazard ratio [HR] 4.162, p = 0.026) was an independent risk factor influencing pleural progression, and primary malignant peritoneal mesothelioma (MPM; HR 2.749, p = 0.016) and the presence of two or more serious AEs (SAEs; HR 7.294, p = 0.001) were independent risk factors influencing OS. CONCLUSIONS: HITAC can be performed in carefully selected PC patients who underwent diaphragm resection, with no worsening of the safety profile and a possible benefit for pleural progression. In those patients, age ≥ 60 years is associated with a shorter TTP of thoracic disease, while primary MPM and two or more perioperative SAEs are associated with worse OS.

Quality-of-Life Outcomes for Patients Taking Opioids and Psychotropic Medications Before Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: The impact of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) on quality of life (QoL) for patients taking opioids and psychotropic medications preoperatively is unclear. METHODS: This study retrospectively reviewed a CRS-HIPEC single-center prospectively maintained database for 2012-2016. Demographics and clinical data on opioids/psychotropic medication use were collected via chart review. The study collected QoL outcomes at baseline, then 3, 6, and 12 months postoperatively via the Center for Epidemiologic Studies Depression Scale (CES-D), Brief Pain Inventory, Functional Assessment of Cancer Therapy, and 36-Item Short-Form Health Survey. Differences in QoL between the groups were calculated using repeated measures analysis of variance regression. Descriptive statistics and Kaplan-Meier analyses were performed. RESULTS: Of 388 patients, 44.8% were taking opioids/psychotropic medications preoperatively. At baseline, those taking opioids/psychotropic medications preoperatively versus those not taking these medications had significantly worse QoL. By 1 year postoperatively, the QoL measures did not differ significantly except for emotional functioning (e.g., no medications vs. opioids/psychotropic medications: CES-D, 5.6 vs. 10.1). Median survival did not differ significantly (opioids/psychotropic medications vs. no medications: 52.3 vs. 60.6 months; p = 0.66). At 1 year after surgery, a greater percentage of patients were taking opioids, psychotropic medications, or both than at baseline (63.2% vs. 44.8%; p < 0.001). CONCLUSION: Despite worse baseline QoL, patients who took opioids/psychotropic medications had QoL scores 1 year postoperatively similar to the scores of those who did not except in the emotional domains. These data point to the potential utility of a timed psychosocial intervention to enhance emotional adaptation and further support the role of CRS-HIPEC in improving QoL.

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

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

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.

Extended-duration antibiotics are not associated with a reduction in surgical site infection in patients with ovarian cancer undergoing cytoreductive surgery with large bowel resection.

OBJECTIVE(S): To evaluate whether extended dosing of antibiotics (ABX) after cytoreductive surgery (CRS) with large bowel resection for advanced ovarian cancer is associated with reduced incidence of surgical site infection (SSI) compared to standard intra-operative dosing and evaluate predictors of SSI. METHODS: A retrospective single-institution cohort study was performed in patients with stage III/IV ovarian cancer who underwent CRS from 2009 to 2017. Patients were divided into two cohorts: 1) standard intra-operative dosing ABX and 2) extended post-operative ABX. All ABX dosing was at the surgeon's discretion. The impact of antibiotic duration on SSI and other postoperative outcomes was assessed using univariate and multivariable Cox regression models. RESULTS: In total, 277 patients underwent cytoreductive surgery (CRS) with large bowel resection between 2009 and 2017. Forty-nine percent (n = 137) received standard intra-operative ABX and 50.5% (n = 140) received extended post-operative ABX. Rectosigmoid resection was the most common large bowel resection in the standard ABX (89.9%, n = 124) and extended ABX groups (90.0%, n = 126), respectively. No significant differences existed between age, BMI, hereditary predisposition, or medical comorbidities (p > 0.05). No difference was appreciated in the development of superficial incisional SSI between the standard ABX and extended ABX cohorts (10.9% vs. 12.9%, p = 0.62). Of patients who underwent a transverse colectomy, a larger percentage of patients developed a superficial SSI versus no SSI (21% vs. 6%, p = 0.004). CONCLUSION(S): In this retrospective study of patients with advanced ovarian cancer undergoing CRS with LBR, extended post-operative ABX was not associated with reduced SSI, and prolonged administration of antibiotics should be avoided unless clinically indicated.

Splenectomy as a part of cytoreductive surgery in ovarian cancer: systematic review and meta-analysis.

OBJECTIVE: The role of splenectomy on cytoreductive surgery in patients with ovarian cancer remains controversial. We conducted this meta-analysis to evaluate the safety and impact of survival outcome of splenectomy in patients with ovarian cancer. METHODS: In this meta-analysis we analyzed studies published in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials. gov that appeared in our search from inception to November 10, 2023. RESULT: This meta-analysis included 10 studies, totaling 6297 patients, comprising one prospective and nine retrospective analyses. The results indicated no significant disparity in overall survival and mortality (OR 1.14, 95% CI 0.69 to 1.87, p=0.62) between the splenectomy cohort and the no splenectomy (required) cohort. Furthermore, relative to the no splenectomy (required) cohort, the splenectomy group showed a heightened incidence of overall post-operative complications (odds ratio (OR) 1.66, 95% CI 1.65 to 2.61, p=0.03), an extended duration of hospitalization (mean difference (MD) 2.88 days, 95% CI 2.09 to 3.67), an increased interval from surgery to the initiation of adjuvant chemotherapy (MD 4.44 days, 95% CI 2.41 to 6.07, p<0.0001), and a greater probability of undergoing reoperation (OR 4.7, 95% CI 1.91 to 11.55, p=0.0007). However, concerning the occurrence of specific post-operative complications such as anastomotic leakage (OR 0.97, 95% CI 0.33 to 2.84, p=0.95), pancreatic fistula (OR 3.25, 95% CI 0.63 to 16.7, p=0.16), abdominal abscess (OR 1.75, 95% CI 0.25 to 12.33, p=0.57), sepsis (OR 1.46, 95% CI 0.77 to 2.77, p=0.25), and thrombotic events (OR 1.82, 95% CI 0.93 to 3.57, p=0.08), no significant differences were observed between the two cohorts. CONCLUSION: Splenectomy does not impact the overall survival and mortality of patients with ovarian cancer. Thus, it can be considered an acceptably safe procedure to obtain optimal cytoreduction. However, caution should be taken when selecting patients for splenectomy because it is associated with an increased incidence of overall post-operative complications, prolonged hospital stays, delayed initiation of adjuvant chemotherapy, and an increased probability of requiring subsequent surgical interventions.

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.

Procalcitonin and C-reactive protein as early markers of anastomotic leakage in intestinal resections for advanced ovarian cancer (EDMOCS).

INTRODUCTION: Serum levels of procalcitonin and C-reactive protein (CRP) have been used to predict anastomotic leakage after colorectal surgery, but information is scarce in advanced ovarian cancer (AOC) surgery with bowel resection. This study aimed to assess the predictive value of procalcitonin and CRP in detecting anastomotic leakage after AOC surgery with bowel resection. The study also aimed to determine the optimal postoperative reference values and the best day for evaluating these markers. MATERIAL AND METHODS: This prospective, observational and multicentric trial included 92 patients with AOC undergoing debulking surgery with bowel resection between 2017 and 2020 in 10 reference hospitals in Spain. Procalcitonin and CRP levels were measured at baseline and on postoperative days 1-6. Receiver operating characteristic analysis was performed to evaluate the predictive value of procalcitonin and CRP at each postoperative day. Sensitivity, specificity, positive and negative predictive values were calculated. RESULTS: Anastomotic leakage was detected in six patients (6.5%). Procalcitonin and CRP values were consistently higher in patients with anastomotic leakage at all postoperative days. The maximum area under the curve (AUC) for procalcitonin was observed at postoperative day 1 (AUC = 0.823) with a cutoff value of 3.8 ng/mL (83.3% sensitivity, 81.3% specificity). For CRP, the maximum AUC was found at postoperative day 3 (AUC = 0.833) with a cutoff level of 30.5 mg/dL (100% sensitivity, 80.4% specificity). CONCLUSIONS: Procalcitonin and C-reactive protein are potential biomarkers for early detection of anastomotic leakage after ovarian cancer surgery with bowel resection. Further prospective studies with a larger sample size are needed to confirm these findings.

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.

Intraoperative urinary tract resection and construction in CRS + HIPEC procedures: a single center retrospective analysis.

INTRODUCTION: The safety and efficacy of CRS + HIPEC combined with urinary tract resection and reconstruction are controversial. This study aims to summarize the clinicopathological features and to evaluate the safety and survival prognosis of CRS + HIPEC combined with urinary tract resection and reconstruction. METHODS: The patients who underwent urinary tract resection and reconstruction as part of CRS surgery were retrospectively selected from our disease-specific database for analysis. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were studied using a descriptive approach and the K-M analysis with log-rank comparison. RESULTS: Forty-nine patients were enrolled. Perioperative serious AEs (SAEs) were observed in 11 patients (22.4%), with urinary SAEs occurring in 3 patients (6.1%). Additionally, there were 23 cases (46.8%) involving urinary adverse events (UAEs). The median overall survival (OS) in the entire cohort was 59.2 (95%CI: 42.1-76.4) months. The median OS of the UAE group and No-UAE group were 59.2 months (95%CI not reached), and 50.5 (95%CI: 11.5 to 89.6) months, respectively, with no significant difference (P = 0.475). Furthermore, there were no significant differences in OS based on the grade of UAEs or the number of UAEs (P = 0.562 and P = 0.622, respectively). CONCLUSION: The combination of CRS + HIPEC with urinary tract resection and reconstruction is associated with a high incidence of Grade I-II UAEs, which do not have an impact on OS. The safety profile of this combined technique is acceptable. However, this is a retrospective single-center single-arm analysis, with limitations of generalizability and potential selection bias. The findings need high-level validation.

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.

Predictors of Blood Transfusion in Patients Undergoing Cytoreductive Surgeries for Ovarian Malignancy.

OBJECTIVES: The aims of this study were to describe the baseline estimated blood loss (EBL) in surgery and transfusion rate in patients undergoing cytoreductive surgeries for ovarian malignancy, and identify perioperative variables associated with blood loss and transfusion. METHODS: A retrospective cohort study at a single institution was performed that included patients with known or suspected ovarian malignancy undergoing cytoreductive surgery between 2016 and 2021. t tests, χ2 tests, and multiple logistic regression analyses were used. RESULTS: Among 44 patients meeting inclusion criteria, 61% received perioperative blood transfusion. There were significant differences in EBL and preoperative hemoglobin levels between patients who did and did not receive transfusion (EBL 442.6 vs 236.8 mL, P = 0.0008; preoperative hemoglobin 10.2 vs 11.2 g/dL, P = 0.049). After adjusting for preoperative hemoglobin, the risk of transfusion increased for each additional 200 mL of EBL (odds ratio [OR] 3.8, 95% confidence interval [CI] 1.5-9.5). Stratified by race, the association between EBL and transfusion risk remained statistically significant only for non-Latinx White patients (OR 6.1, 95% CI 1.7-21.9), who made up 77% of the study population, but not for patients of other races and ethnicities (OR 1.0, 95% CI 0.16-6.42). CONCLUSIONS: Perioperative blood transfusion is common in patients undergoing cytoreductive surgery. In this study, EBL and preoperative hemoglobin levels were significantly associated with transfusion receipt. Clinicians should optimize hemoglobin levels and intraoperative blood conservation strategies to reduce the need for transfusion. The results also highlight the importance of considering racial and ethnic differences when developing strategies to reduce transfusion risk.

Clinical characteristics and outcomes of children with newly diagnosed acute myeloid leukemia and hyperleukocytosis managed with different cytoreductive methods.

BACKGROUND: Hyperleukocytosis in patients with acute myeloid leukemia (AML) has been associated with worse outcomes. For cytoreduction, leukapheresis has been used but its clinical utility is unknown, and low-dose cytarabine (LD-cytarabine) is used as an alternative method. METHODS: Children with newly diagnosed AML treated between 1997 and 2017 in institutional protocols were studied. Hyperleukocytosis was defined as a leukocyte count of ≥100 × 109 /L at diagnosis. Clinical characteristics, early complications, survival data, and effects of cytoreductive methods were reviewed. Among 324 children with newly diagnosed AML, 49 (15.1%) presented with hyperleukocytosis. Initial management of hyperleukocytosis included leukapheresis or exchange transfusion (n = 16, considered as one group), LD-cytarabine (n = 18), hydroxyurea (n = 1), and no leukoreduction (n = 14). RESULTS: Compared with patients who received leukapheresis, the percentage decrease in leukocyte counts following intervention was greater among those who received LD-cytarabine (48% vs. 75%; p = .02), with longer median time from diagnosis to initiation of protocol therapy (28.1 vs. 95.2 hours; p < .001). The incidence of infection was higher in patients (38%) who had leukapheresis than those who receive LD-cytarabine (0%) or leukoreduction with protocol therapy (14%) (p = .008). No differences were noted in the outcomes among the intervention groups. Although patients with hyperleukocytosis had higher incidences of pulmonary and metabolic complications than did those without, no early deaths occurred, and the complete remission, event-free survival, overall survival rates, and outcomes of both groups were similar. CONCLUSION: LD-cytarabine treatment appears to be a safe and effective means of cytoreduction for children with AML and hyperleukocytosis.

Postoperative Respiratory Failure Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy is Associated with Volume of Intraoperative Crystalloid Administration and Worse Survival.

BACKGROUND: Postoperative respiratory failure (PRF) is associated with increased morbidity after surgery. This retrospective study explores preoperative and perioperative risk factors associated with PRF in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) and the resultant impact on survival. METHODS: We identified all patients who underwent CRS/HIPEC at our institution between 2007 and 2017. PRF was defined as mechanical ventilation for more than 48 h after surgery or reintubation not related to an additional procedure within the first 30 days postoperatively. The relationship between clinicopathologic variables and PRF was examined using Kaplan-Meier log-rank survival analysis and multivariable Cox regression models with 90-day, 1-year and 5-year overall survival (OS). RESULTS: Overall, 314 patients underwent CRS/HIPEC, of whom 24 patients (7.6%) developed PRF. On univariable analysis, chronic obstructive pulmonary disease (COPD) was the only preoperative risk factor associated with PRF (p = 0.049). Of the intraoperative risk factors, diaphragmatic resection (p = 0.008), Peritoneal Cancer Index (PCI) > 20 (p < 0.001), and volume of intraoperative crystalloid (p < 0.001) were all associated with PRF. On multivariable Cox regression, only intraoperative crystalloid was significantly associated with PRF (p < 0.001), with a volume above 5.3 L (area under the curve [AUC] 0.77) having a high predictive accuracy for PRF. Five-year OS was significantly decreased in patients with PRF (30.2% vs. 52.6%, hazard ratio 2.6, 95% confidence interval 1.5-4.4; p < 0.001). CONCLUSIONS: Liberal intraoperative crystalloid volume resuscitation is a potential independent, modifiable intraoperative risk factor for PRF following CRS/HIPEC that may contribute to decreased long-term OS.

Safety of Nephrectomy Performed During CRS/HIPEC: A Propensity Score-Matched Study.

BACKGROUND: Surgeons may hesitate to perform nephrectomy (NE) during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) due to a potential increase in morbidity. However, no data are available regarding the impact of NE on outcomes, so the authors decided to assess its safety during CRS/HIPEC. METHODS: A single-center propensity score-matched study was conducted using a prospective database (1994-2021). The study included patients who underwent NE during CRS/HIPEC with completeness of cytoreduction (CC) of 0, 1, or 2. Control subjects (no-NE) were selected in a 1:3 ratio using propensity score-matching weighted by age, histology, peritoneal cancer index (PCI), CC-0 or CC-1 rate, and length of surgery. RESULTS: Among 828 patients, 13 NE and 39 no-NE control subjects were identified. The indications for NE included tumor involvement of the ureter, hilum, and/or kidney with preserved (n = 8), decreased (n = 2), or absent (n = 3) function. NE patients received more intraoperative intravenous (IV) fluids (16,000 vs 11,500 mL; p = 0.045) and had a greater urine output (3200 vs 1913 mL; p = 0.008). NE patients received mitomycin C (40 mg for 90 min) or melphalan (50 mg/m2 for 90 min) without reduction of dose or time. Major morbidity (p = 0.435) and mortality (p = 1.000) were comparable between the two groups. No postoperative acute kidney injury was seen in either group. Adjuvant chemotherapy was administered to 46.2% of the NE and 35.9% of the no-NE patients (p = 0.553), with similar starting times (p = 0.903) between the groups. CONCLUSIONS: Nephrectomy performed during CRS/HIPEC does not seem to increase postoperative morbidity or to delay adjuvant chemotherapy, and NE can be performed if required for complete cytoreduction. The NE patients in our cohort did not have a reduction of mitomycin C or melphalan dose or perfusion time.

Randomized Controlled Trial Investigating Perioperative Immunonutrition for Patients Undergoing Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

BACKGROUND: Immunonutrition has been shown to reduce hospital stay and postoperative morbidity in patients undergoing gastrointestinal, and head and neck surgery. However, its use has not been demonstrated in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). This study aims to determine the effectiveness of perioperative immunonutrition on patients undergoing CRS-HIPEC in reducing length of hospitalization and postoperative complications. PATIENTS AND METHODS: From April 2017 to December 2018, patients undergoing CRS-HIPEC for peritoneal metastases in a single center were enrolled in a randomized controlled trial. Patients with evidence of intestinal obstruction or with diabetes mellitus were excluded. Patients were randomly assigned in a 1:1 fashion to receive perioperative oral immunonutrition or standard nutritional feeds. Length of hospital stay and rates of wound infection and complications were recorded and compared between the two groups in an intention-to-treat manner. RESULTS: A total of 62 patients were recruited and randomized into two groups. Compliance to nutritional feeds in the preoperative period was significantly higher in the standard nutrition group (95.2% versus 75.4%, p = 0.004). There was no difference in postoperative compliance rates. Length of hospital stay and rates of wound infection and postoperative complications were higher in the standard nutrition group when compared with patients on immunonutrition (15.5 versus 11.1 days, p = 0.186; 19% versus 9.7%, p = 0.473; 16% versus 9.7%, p = 0.653; respectively). CONCLUSIONS: Patients undergoing CRS-HIPEC who received perioperative immunonutrition had shorter hospitalization and less wound infections and postoperative complications, although the differences with the standard nutrition group were not statistically significant. Potential benefits of perioperative immunonutrition need to be further evaluated in larger studies.

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

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

A Multicenter Phase 1 Trial Evaluating Nanoliposomal Irinotecan for Heated Intraperitoneal Chemotherapy Combined with Cytoreductive Surgery for Patients with Peritoneal Surface Disease.

BACKGROUND: Nanoliposomal irinotecan (nal-IRI) is a promising novel hyperthermic intraperitoneal chemotherapy (HIPEC) agent given its enhanced efficacy against gastrointestinal tumors, safety profile, thermo-synergy, and heat stability. This report describes the first in-human phase 1 clinical trial of nal-IRI during cytoreductive surgery (CRS) and HIPEC. METHODS: Patients with peritoneal surface disease (PSD) from appendiceal and colorectal neoplasms were enrolled in a 3 + 3 dose-escalation trial using nal-IRI (70-280 mg/m2) during HIPEC for 30 min at 41 ± 1 °C. The primary outcome was safety. The secondary outcomes were pharmacokinetics (PK) and disease-free survival. Adverse events (AEs) categorized as grade 2 or higher were recorded. The serious AEs (SAEs) were mortality, grade ≥ 3 AEs, and dose-limiting toxicity (DLT). Irinotecan and active metabolite SN38 were measured in plasma and peritoneal washings. RESULTS: The study enrolled 18 patients, who received nal-IRI during HIPEC at 70 mg/m2 (n = 3), 140 mg/m2 (n = 6), 210 mg/m2 (n = 3), and 280 mg/m2 (n = 6). No DLT or mortality occurred. The overall morbidity for CRS/HIPEC was 39% (n = 7). Although one patient experienced neutropenia, no AE (n = 131) or SAE (n = 3) was definitively attributable to nal-IRI. At 280 mg/m2, plasma irinotecan and SN38 measurements showed maximum concentrations of 0.4 ± 0.6 µg/mL and 3.0 ± 2.4 ng/mL, a median time to maximum concentration of 24.5 and 26 h, and areas under the curve of 22.6 h*µg/mL and 168 h*ng/mL, respectively. At the 6-month follow-up visit, 83% (n = 15) of the patients remained disease-free. CONCLUSIONS: In this phase 1 HIPEC trial (NCT04088786), nal-IRI was observed to be safe, and PK profiling showed low systemic absorption overall. These data support future studies testing the efficacy of nal-IRI in CRS/HIPEC.

Influence of Extraperitoneal Metastases on the Curative-Intent Management of Colorectal Peritoneal Metastases.

BACKGROUND: Selected patients with colorectal cancer peritoneal metastasis (CRPM) and extraperitoneal disease could be treated radically with a multimodal approach combining complete cytoreductive surgery, thermoablation, radiotherapy, and systemic and intraperitoneal chemotherapy. The impact of extraperitoneal metastatic sites (EPMS) in this setting remains unclear. PATIENTS AND METHODS: Patients with CRPM undergoing complete cytoreduction in 2005-2018 were grouped in: peritoneal disease only (PDO), one EPMS (1 + EPMS), two or more EPMS (2 + EPMS). A retrospective analysis compared overall survival (OS) and postoperative outcomes. RESULTS: Of 433 patients, 109 had 1 + EPMS and 31 had 2 + EPMS. Overall, 101 patients had liver metastasis, 19 lung metastasis, and 30 retroperitoneal lymph node (RLN) invasion. The median OS was 56.9 months. There was no significant OS difference between PDO and 1 + EPMS groups (64.6 and 57.9 months, respectively), whereas OS was lower in the 2 + EPMS group (29.4 months, p = 0.005). In multivariate analysis, 2 + EPMS [hazard ratio (HR) 2.86, 95% confidence interval (CI) 1.33-6.12, p = 0.007], Sugarbaker's Peritoneal Carcinomatosis Index (PCI) > 15 (HR 3.86, 95% CI 2.04-7.32, p < 0.001), poorly differentiated tumors (HR 2.62, 95% CI 1.21-5.66, p = 0.015), and BRAF mutation (HR 2.10, 95% CI 1.11-3.99, p = 0.024) were independent poor prognostic factors, while adjuvant chemotherapy was beneficial (HR 0.33, 95% CI 0.20-0.56, p < 0.001). Patients with liver resection did not show higher severe complication rates. CONCLUSION: In patients with CRPM selected for a radical surgical approach, limited extraperitoneal disease involving one site, notably the liver, does not seem to significantly impair postoperative results. RLN invasion appeared as a poor prognostic factor in this population.