Vahan Kepenekian

What made hyperthermic intraperitoneal chemotherapy an effective curative treatment for peritoneal surface malignancy: A 25‐year experience with 1,125 procedures

To review our 25‐year experience with hyperthermic intra‐peritoneal chemotherapy (HIPEC).

Ninety-day post-operative morbidity and mortality using the National Cancer Institute’s common terminology criteria for adverse events better describe post-operative outcome after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Abstract Background: The post-operative morbidity and mortality after CRS-HIPEC has been widely evaluated. However, there is a major discrepancy between rates reported due to different metrics and time of analysis used. Objective: To evaluate the legitimacy of 90-day morbidity and mortality based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.0 classification as criteria of quality for cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). Methods: A prospective database of all patients undergoing CRS-HIPEC for peritoneal carcinomatosis between 2004 and 2015 was queried for 90-day morbidity and mortality and survival. Results: Among 881 patients, the 90-day major complication rate based on NCI-CTCAE classification and Clavien-Dindo’s classification were 51% (n = 447 patients) and 25% (n = 222 patients), respectively. Among patients who presented with a 90-day complication based on the NCI-CTCAE classification, 50% (n = 225 patients) presented a medical complication not reported by Clavien-Dindo’s classification. After surgery, 24 patients (2.7%) died of post-operative complications, for only 10 (42%) of them the death occurred within 30-day after surgery. Occurrence of major complication based on either NCI-CTCAE classification, Clavien-Dindo’s classification or the medical complication not reported by Clavien-Dindo’s classification all negatively impacts the overall survival. Conclusion: Among commonly reported morbidity’s classification, 90-day morbidity based on NCI-CTCAE classification represents a legitimate metric of CRS-HIPEC quality. Post-operative morbidity after CRS-HIPEC should be reported using 90-day NCI-CTCAE classification.

No impact on long-term survival of prolonged ICU stay and re-admission for patients undergoing cytoreductive surgery with HIPEC.

BACKGROUND Cytoreductive surgery (CRS) and Hyperthermic intraperitoneal chemotherapy (HIPEC) are promising new approaches of peritoneal metastases. However these surgical procedures are associated with a high morbidity rate thus intensive care (IC) management following serious complications may be warranted for these patients. The impact of the prolonged IC stay or re-admission on long-term survival remains unknown. METHODS We retrospectively analysed 122 consecutive HIPEC procedures over a one year period (2010-2011) in a single academic hospital. We analysed complications that would lead to prolonged stay or re-admission into ICU and analysed long term follow-up in patients whether they required intensive care (ICU group) or not (Control group). RESULTS ICU group represented 26.2% of the cohort mainly due to septic or haemorrhagic shock. Among them acute kidney injury and respiratory failure were present in 50% and 47% respectively. Cohort overall mortality rate was of 5.7%. Patients were followed for 4 years and survival analysis was performed adjusting for main confounding factors in a Cox survival model. Survival was not different between groups, with a median survival of 38 months [32; 44] vs. 33 months [26; 39] in the ICU group and Control group respectively. CONCLUSION Prolonged stay or re-admission into ICU does not seem to statistically impact long term prognosis of patients undergoing CRS with HIPEC.

Survival outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from gastric cancer: a systematic review

Abstract Background: The current treatment of choice for peritoneal carcinomatosis from gastric cancer is systemic chemotherapy. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a new aggressive form of loco-regional treatment that is currently being used in pseudomyxoma peritoneii, peritoneal mesothelioma and peritoneal carcinomatosis from colorectal cancer. It is still under investigation for its use in gastric cancer. Methods: The literature between 1970 and 2016 was surveyed systematically through a review of published studies on the treatment outcomes of CRS and HIPEC for peritoneal carcinomatosis from gastric cancer. Results: Seventeen studies were included in this review. The median survival for all patients ranged from 6.6 to 15.8 months. The 5-years overall survival ranged from 6 to 31%. For patients with complete cytoreduction, the median survival was 11.2 to 43.4 months and the 5-years overall survival was 13 % to 23%. Important prognostic factors were found to be a low peritoneal carcarcinomatosis index (PCI) score and the completeness of cytoreduction. Conclusion: The current evidence suggests that CRS and HIPEC has a role to play in the treatment of peritoneal carcinomatosis from gastric cancer. Long term survival has been shown for a select group of patients. However, further studies are needed to validate these results.

Impact of hyperthermic intraperitoneal chemotherapy on Hsp27 protein expression in serum of patients with peritoneal carcinomatosis

Despite the strong rationale for combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal carcinomatosis, thermotolerance and chemoresistance might result from heat shock protein overexpression. The aim of the present study was thus to determine whether the heat shock protein 27 (Hsp27), a potential factor in resistance to treatment, could have a higher level in serum from patients under this combined therapy. Patients receiving CRS plus HIPEC for peritoneal carcinomatosis (group 1), patients with cancer or a history of cancer undergoing abdominal surgery (group 2), and patients without malignancies undergoing abdominal surgery (group 3) were included. Hsp27 serum levels were determined before and at different times following CRS and HIPEC using enzyme-linked immunosorbent assay. In group 1 (n = 25), the high Hsp27 levels, observed at the end of surgery compared with before (p < 0.0001), decreased during HIPEC, but remained significantly higher than before surgery (p < 0.0005). In groups 2 (n = 11) and 3 (n = 15), surgery did not significantly increase Hsp27 levels. A targeted molecular strategy, inhibiting Hsp27 expression in tumor tissue, could significantly reduce resistance to the combined CRS plus HIPEC treatment. This approach should be further assessed in a clinical phase I trial.