Objective:To improve patient selection for cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) by evaluating various preoperatively assessable clinicopathological parameters as markers for survival after CRS and HIPEC.Summary Background Data:Peritoneal metastases (PMs)

Clinicopathological Parameters in Patient Selection for Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Cancer Metastases: A Meta-analysis

In selected patients with colorectal peritoneal carcinomatosis (PC), cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) may improve survival. We aimed to assess whether neoadjuvant chemotherapy with or without bevacizumab is indicated in this patient population. Colorectal PC patients were treated with CRS and HIPEC using oxaliplatin (200–460 mg/m2) or mitomycin C (35 mg/m2). Postoperative outcome and long-term survival were prospectively recorded. The impact of clinical variables on overall survival (OS) was assessed using univariate and Cox multivariate analysis. Between October 2002 and May 2012, 166 patients were treated with CRS and HIPEC. Neoadjuvant chemotherapy alone was administered to 21 % and neoadjuvant chemotherapy with bevacizumab to 16 % of patients. Postoperative mortality and major morbidity were 2.4 and 35 %, respectively. Half of the patients received adjuvant chemotherapy. After a median follow-up of 18 months, OS was 27 months (95 % confidence interval 20.8–33.2). On univariate analysis, OS was associated with extent of disease (P < 0.001), neoadjuvant chemotherapy with bevacizumab (P = 0.021), completeness of cytoreduction (CC) (P < 0.001), and adjuvant chemotherapy (P = 0.04), but not with primary disease site, synchronous presentation, or chemoperfusion drug. In multivariate Cox regression, independent predictors of OS were CC (hazard ratio 0.29, P < 0.001) and neoadjuvant therapy containing bevacizumab (hazard ratio 0.31, P = 0.019). Long-term OS after CRS and HIPEC for colorectal cancer is associated with CC and neoadjuvant therapy containing bevacizumab. This regimen merits prospective study in patients with resectable PC of colorectal origin.

Neoadjuvant Chemotherapy with Bevacizumab May Improve Outcome after Cytoreduction and Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) for Colorectal Carcinomatosis

Competition of charge-mediated and specific binding by peptide-tagged cationic liposome-DNA nanoparticles in vitro and in vivo.

Careful selection of patients with colorectal peritoneal metastases (PM) for cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is crucial. It remains unknown whether the time of onset of colorectal PM (synchronous vs metachronous) influences surgical morbidity and survival outcomes after CRS with HIPEC. Patients with histologically proven colorectal PM who underwent CRS with HIPEC between February 2006 and December 2017 in two Dutch tertiary referral hospitals were retrospectively included from a prospectively maintained database. The onset of colorectal PM was classified as synchronous (PM diagnosed at the initiational presentation with colorectal cancer) or metachronous (PM diagnosed after initial curative colorectal resection). Major postoperative complications (Clavien–Dindo grade ≥ 3), overall survival (OS), and disease-free survival (DFS) were compared between patients with synchronous colorectal PM and those with metachronous colorectal PM using Kaplan–Meier analyses, proportional hazard analyses, and a multivariate Cox regression analysis. The study enrolled 433 patients, of whom 231 (53%) had synchronous colorectal PM and 202 (47%) had metachronous colorectal PM. The major postoperative complication rate and median OS were similar between the patients with synchronous colorectal PM and those with metachronous colorectal PM (26.8% vs 29.7%; p = 0.693 and 34 vs 33 months, respectively; p = 0.819). The median DFS was significantly decreased for the patients with metachronous colorectal PM and those with synchronous colorectal PM (11 vs 15 months; adjusted hazard ratio, 1.63; 95% confidence interval, 1.18–2.26). Metachronous onset of colorectal PM is associated with early recurrence after CRS with HIPEC compared with synchronous colorectal PM, without a difference in OS or major postoperative complications. Time to onset of colorectal PM should be taken into consideration to optimize patient selection for this major procedure.

/pdf/impact-of-synchronous-versus-metachronous-onset-of-41cbo9bqfz.pdf

Impact of Synchronous Versus Metachronous Onset of Colorectal Peritoneal Metastases on Survival Outcomes After Cytoreductive Surgery (CRS) with Hyperthermic Intraperitoneal Chemotherapy (HIPEC): A Multicenter, Retrospective, Observational Study.

Although intraperitoneal chemotherapy (IPC) has been suggested as a promising method for the management of peritoneal dissemination (PD) of ovarian or colorectal cancers, the actual clinical use of this method has been restricted due to such problems as poor drug penetration into the tumor and high side effects. It is, therefore, necessary to develop new strategies to improve the efficacy of this approach. In the present work, a new strategy is proposed based on intraperitoneal (IP) injection of thermosensitive liposomal doxorubicin (TSL-Dox) with triggered release by mild hyperthermia induced by high intensity focused ultrasound (HIFU). A computational model is developed to evaluate the proposed drug delivery system. Results show an order of magnitude increase in drug penetration depth into the tumor compared to the conventional IP delivery. Furthermore, the effects of thermal conditions applied to the tumor, TSL size, tumor vessel permeability, and tumor size are investigated. Results indicate an improved efficiency of the drug delivery by expanding the heated region, yet, it increases the risk of unintentional TSL drug load release in the peritoneal cavity. Results also indicate that smaller TSLs have better treatment outcome. However, there is a significant reduction in treatment efficacy for TSLs with sizes smaller than the vessel wall pore size. Thus, tuning the size of TSL should be based on the tumor microvascular permeability. The simulation results suggest that the TSL-Dox delivery system in smaller tumors is far advantageous than larger ones. Results of our model can be used as guidelines for future preclinical studies.

Numerical modeling of high-intensity focused ultrasound-mediated intraperitoneal delivery of thermosensitive liposomal doxorubicin for cancer chemotherapy.

Purpose
Recurrent disease following complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a relevant clinical scenario. We aimed to determine risk factors for recurrence.

Risk factors for recurrence following complete cytoreductive surgery and HIPEC in colorectal cancer-derived peritoneal surface malignancies

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Risk factors for recurrence following complete cytoreductive surgery and HIPEC in colorectal cancer-derived peritoneal surface malignancies