Cytoreduction and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal metastases from colorectal cancer in the Czech Republic in 2018.

BACKGROUND: For highly selected patients with peritoneal metastases (PM) from colorectal cancer (CRC), an aggressive surgical approach with intraperitoneal chemotherapy may be beneficial. This management may prolong overall survival, which is well documented by the results of a number of clinical trials. In the Czech Republic, five specialized centers of surgical oncology are able to perform cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC). All of these centers provided accurate information on the number of CRS procedures in 2018 in the PM CRC indication. The estimation of the prevalence of peritoneal metastases from CRC is based on data from the Czech National Cancer Registry. PURPOSE: To determine the number of cytoreductive procedures performed in patients with peritoneal metastases from CRC in the Czech Republic in 2018, and to compare it with the number of patients who could hypothetically benefit from this procedure according to statistical data. RESULTS: Twenty-five CRS/HIPEC procedures were performed on patients with peritoneal metastases from CRC in 2018 in the Czech Republic. However, based on the prevalence of peritoneal metastases from CRC in the Czech Republic, cytoreduction with intraperitoneal chemotherapy (CRS/HIPEC) could probably bring benefit to a minimum of 150 patients a year in the Czech Republic. CONCLUSION: In the Czech Republic in 2018, the cytoreduction and HIPEC procedures for peritoneal metastases from CRC were performed in significantly fewer cases than would correspond to the estimated number of potentially curable patients.To increase the awareness of this issue and improve the number of potentially curative cytoreductive procedures, there will be necessary better awareness and closer cooperation among specialized centers, general surgeons, and clinical oncologists.

Can Elderly Patients with Peritoneal Metastasis Induced by Appendiceal or Colorectal Tumours Benefit from Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC)?

PURPOSE: Cytoreductive surgery (CRS) added with hyperthermic intraperitoneal chemotherapy (HIPEC) can improve the survival rate of certain patients with peritoneal metastasis (PM). However, the perioperative safety and long-term survival of this intricate and possibly life-threatening procedure in elderly patients (≥65 years) remain controversial. METHODS: Patients with PM due to appendiceal or colorectal tumours who underwent CRS/HIPEC were evaluated systematically at the National Cancer Center of China and the Huanxing Cancer Hospital between June 2017 and June 2019. The recruited subjects were retrospectively categorized into elderly (age ≥65) and non-elderly (age<65) groups according to their age. Clinical and pathological features, postoperative outcomes, and prognoses were gathered and analysed. RESULTS: Both groups had similar overall morbidity (56.0% vs 38.7%, P=0.130) and grade 3/4 morbidity (28.0% vs 20.0%, P=0.403) after CRS/HIPEC. However, more patients in the elderly group suffered from ileus postoperatively (16.0% vs 2.6%, P=0.033). After a follow-up period of a median of 20 months, it was concluded that elderly patients had significantly worse 3-year overall survival (OS) than non-elderly patients (16.3% vs 51.4%, P=0.001). Independent prognostic factors were identified to be a high peritoneal carcinomatosis index (PCI) score (HR, 1.10, 95% CI, 1.04-1.16; P=0.001) and age ≥65 (HR, 2.42, 95% CI, 1.32-4.45; P=0.004) were independent prognostic factors through cox regression analysis. CONCLUSION: CRS and HIPEC are related with an elevated prevalence of postoperative ileus but not with the overall morbidity or the grade 3/4 morbidity in elderly patients. However, since worse survival outcomes were observed more commonly in elderly patients compared to younger patients from CRS+HIPEC, this complex and potentially life-threatening procedure should be considered carefully in patients aged ≥65 years.

Hyperthermic intraperitoneal chemotherapy in locally advanced and recurrent ovarian carcinoma: surgical and oncological outcomes in the Indian public healthcare system.

This study analyzed the surgical outcomes after initial implementation of a cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) program in government settings in India. Methods: Ovarian cancer patients undergoing cytoreductive surgery and HIPEC from May 2015 to April 2019 were identified from a prospectively maintained database. Treatment characteristics and surgical outcomes were analyzed. Results: The study identified 101 patients. The mean peritoneal cancer index (PCI) was 7 ± 6, with higher PCI scores in primary and recurrent cases. Major morbidities were recorded in 24.7% of patients. High PCI score, completeness of cytoreduction and major morbidities were independent predictors of overall survival in multivariate analysis. Conclusion: The application of HIPEC in limited-resource settings is feasible with acceptable major morbidities. This program should receive similar priority in government systems.

Optimal oncologic and perioperative outcomes of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy are attainable at a community center.

BACKGROUND: CRS with HIPEC is a complex operation that has shown survival benefit in patients with a variety of primary and metastatic peritoneal surface malignancies. While optimal oncologic and perioperative outcomes have been defined by expert consensus and demonstrated at university-affiliated, academic centers, similar results have never been presented from a non-university-affiliated, community center in the literature to date. METHODS: All cases of CRS with HIPEC performed at a non-university-affiliated, community center were retrospectively reviewed and analyzed. Oncologic and perioperative outcomes were compared Chicago Working Group benchmarks and with results from university-affiliated, academic centers recently published in high-impact-factor, peer-reviewed journals. RESULTS: All 112 cases completed over 5 years were reviewed. 3 were excluded from analysis since they were palliative HIPEC procedures for distressing ascites-related symptoms only without CRS. A wide variety of tumors were treated. Average PCI was 18±9.1. Median PCI was 14. CC 0-1 was achieved in 89% of patients. Average length of stay was 11.6±9.3 days. Serious perioperative morbidity, defined as a Clavien-Dindo Grade III or IV complication, was observed in 22% of patients. The frequency of major complications decreased after the first year. There were no perioperative deaths. CONCLUSIONS: Optimal oncologic and perioperative outcomes of CRS and HIPEC are attainable at a non universityaffiliated, community center. A multidisciplinary team and high clinical volume are necessary to obtain these results.

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.

Institutional variation in recovery after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: An opportunity for enhanced recovery pathways.

BACKGROUND: Variations in care have been demonstrated both within and among institutions in many clinical settings. By standardizing perioperative practices, Enhanced Recovery After Surgery (ERAS) pathways reduce variation in perioperative care. We sought to characterize the variation in cytoreductive surgery (CRS)/heated intraperitoneal chemotherapy (HIPEC) perioperative practices among experienced US medical centers. METHODS: Data from the US HIPEC Collaborative represents a retrospective multi-institutional cohort study of CRS and CRS/HIPEC procedures performed from 12 major academic institutions. Patient characteristics and perioperative practices were reported and compared. Institutional variation was analyzed using hierarchical mixed-effects linear (continuous outcomes) or logistic (binary outcomes) regression models. RESULTS: A total of 2372 operations were included. CRS/HIPEC was performed most commonly for appendiceal histologies (64.2%). The rate of complications (overall 56.3%, range: 31.8-70.9) and readmissions (overall 20.6%, range: 8.9-33.3) varied by institution (P < .001). Institution-level variation in perioperative practice patterns existed among measured ERAS pathway process/outcomes (P < .001). The percentages of variation with each process/outcome measure attributable solely to institutional practices ranged from 0.6% to 66.6%. CONCLUSIONS: Significant variation exists in the perioperative care of patients undergoing CRS/HIPEC at major US academic institutions. These findings provide a strong rationale for the investigation of best practices in CRS/HIPEC patients.

Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Versus Surgery Without HIPEC for Goblet-Cell Carcinoids and Mixed Adenoneuroendocrine Carcinomas: Propensity Score-Matched Analysis of Centers in the Netherlands and Belgium.

BACKGROUND: The value of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with peritoneally metastasized goblet-cell carcinoids (GCCs) and mixed adenoneuroendocrine carcinomas (MANECs) is currently unclear. We compared outcomes of CRS-HIPEC to surgery alone for peritoneally metastasized GCCs and MANECs. PATIENTS AND METHODS: Two cohorts were obtained from the Netherlands Cancer Registry (n = 569): patients with peritoneally metastasized GCCs and MANECs treated with CRS-HIPEC in Dutch and Belgian centers (n = 45), and patients treated with surgery alone. Primary outcome was overall survival (OS). Secondary outcomes were morbidity and hospital mortality. After propensity score matching, OS was compared in univariate and multivariate analyses. A systematic literature review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines from database inception to June 25, 2018. RESULTS: After matching for sex, tumor stage, lymph node stage, and liver metastases, CRS-HIPEC was associated with improved median OS in the combined GCC and MANEC group and the separate GCC subgroup in univariate (GCC + MANEC: 39 vs. 12 months, P < .001; GCC: 39 vs. 12 months, P = .017) and multivariate analysis (GCC + MANEC: hazard ratio 4.27, 95% confidence interval 1.88-9.66, P = .001; GCC: hazard ratio 2.77, 95% confidence interval 1.06-7.26, P = .038). Acceptable grade III-IV morbidity (17.5%) and mortality (0) were seen after CRS-HIPEC. The literature review supported these findings. CONCLUSION: CRS-HIPEC is associated with substantial survival benefit in patients with peritoneally metastasized GCCs and MANECs compared to surgery alone and is a safe treatment option. These data support centralized care of GCC and MANEC patients with peritoneal spread in expert centers offering CRS-HIPEC.

Readmissions After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: a US HIPEC Collaborative Study.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) results in significant morbidity and readmissions. Previous studies have been limited by single-institution design or lack of tumor details in the database used. METHODS: The 12-institution US HIPEC Collaborative Database was queried between 1999 and 2017. Preoperative and intraoperative patient and tumor details were analyzed for associations with readmissions. RESULTS: A total of 2017 of 2372 cases were included in the analysis. The 30-day readmission rate was 15.9% (n = 321). Common indications for readmission included failure to thrive (29.9%), infection (23.6%), and ileus/bowel obstruction (15.1%). The readmitted cohort had more complications, including intra-abdominal abscess (21.2% vs 6.2%), ileus (28.0% vs 17.2%), anastomotic leak (11.2% vs 2.2%), enteric fistula (5.6% vs 1.5%), deep venous thrombosis (6.2% vs 2.5%), and pulmonary embolism (6.9% vs 2.5%). Factors independently associated with readmission (p < 0.05) included ECOG score ≥ 3 (OR 3.4), depression (OR 2.4), total parenteral nutrition (OR 3.6), low anterior resection or partial colectomy (OR 2.0), and stoma creation (OR 2.2). Factors not associated included neoadjuvant chemotherapy, peritoneal cancer index, and completeness of cytoreduction. Readmission rate between 31 and 90 days was 3.9% (n = 78). Independent predictors (p < 0.05) included operative time (OR 1.1), low anterior resection or partial colectomy (OR 1.7), and stoma creation (OR 2.2). CONCLUSIONS: In the largest study to date examining readmissions after CRS-HIPEC, 30-day readmission rate was 15.9%. Tumor factors failed to predict readmission, whereas preoperative functional status and depression along with individual cytoreductive procedures predicted readmission. Patients with these risk factors or postoperative complications may benefit from closer post-discharge monitoring.