Mitomycin-C (MMC) is the most commonly used chemotherapeutic agent for hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) to treat colorectal cancer patients with peritoneal metastases. However, MMC has a side effect of myelosuppression. Particularly, severe neutropenia after CRS with HIPEC can be a life-threatening condition. Despite the postoperative risks of this side effect, the causes and risk factors for severe neutropenia after CRS followed by HIPEC is not identified so far. Therefore, in this study, we aimed to evaluate to evaluate clinical risk factors and pharmacologic properties after CRS with HIPEC using MMC in patients with colorectal cancer or appendiceal mucinous neoplasms with peritoneal metastases.
Evaluation parameters 1. Preoperative period * Obtaining informed consent * Assessment of baseline clinical characteristics: vital sign, BMI, BSA, ASA classification, ECOG, CBC, CEA level * Before 1 day of surgery, assessment of QoR-40 questionnaires 2. Intra-operative period * CRS / HIPEC * Assessment for peritoneal cancer index, complete cytoreduction score * HIPEC procedures: HIPEC was performed using MMC 35 mg/m2 at 41-43℃ for 90 min. Following the HIPEC triple method, MMC 35 mg/m2 was mixed with 3L of Physioneal PD-2 1.5% peritoneal dialysis solution and administered into the intraperitoneal cavity at 50% of the dose at the beginning of HIPEC, 25% of the dose at 30 min, and 25% of the dose at 60 min. * Intraoperative samplings of blood and peritoneal fluids during HIPEC : * Blood sampling of 5 ml at each time point (baseline, 0 (HIPEC starting point), 15, 30, 45, 60, 75, 90, 120 min) * Peritoneal fluid sampling of 5 ml at each time point (baseline, 0 (HIPEC starting point), 15, 30, 45, 60, 75, 90 min) 3. Postoperative period : Postoperative assessment until the discharge date or postoperative 14th days. * Daily assessment before discharge : vital sign, transfusion, neutropenia occurrence, adverse events, hematologic blood test (CBC, absolute neutrophil count (ANC), postoperative complications, use of G-CSF, ICU admission (If severe neutropenia occurs in the postoperative period, the patient assigns in arm I.) * CEA level: postoperative 5th day * QoR-40 questionnaires: postoperative 4th and 7th days
Study Type
OBSERVATIONAL
Enrollment
74
\- Intraoperative samplings of blood and peritoneal fluids during HIPEC : * Blood sampling of 5ml at each time point (baseline, 0 (HIPEC starting point), 15, 30, 45, 60, 75, 90, 120 min) * Peritoneal fluid sampline of 5ml at each time point (baseline, 0 (HIPEC starting point), 15, 30, 45, 60, 75, 90 min)
Division of Colon and Rectal Surgery, Department of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
Seoul, South Korea
Association between the concentration of intraoperative mitomycin-C absoprtion and severe neutropenia after CRS/HIPEC
Comparison of the pharmacologic association between occurrence of postoperative severe neutropenia, and blood absoprtion rates of MMC and the area-under-the curve (AUC) ratios during HIPEC
Time frame: 2 weeks after the discharge
Incidence of severe neutropenia
Incidence (rates)
Time frame: During 2 weeks after CRS/HIPEC
Postoperative complications
Assessment from Clavien-Dindo classification
Time frame: During 2 weeks after CRS/HIPEC
Patterns of perioperative changes of WBC, Hemoglobin, platelet, lymphocyte, neutrophil counts
Records for serologic tests
Time frame: During 2 weeks after CRS/HIPEC
Frequency of postoperative uses for G-CSF
Numbers of G-CSF uses
Time frame: During 2 weeks after CRS/HIPEC
Changes of CEA level
ng/mL
Time frame: During 2 weeks after CRS/HIPEC
Quality of Life: QoR-40 questionnaire
Answer of questionnarie
Time frame: During 2 weeks after CRS/HIPEC
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