Drug delivery systems to prevent peritoneal metastasis after surgery of digestives or ovarian carcinoma: A review.

Peritoneum represents a frequent site of metastasis especially for digestive and ovarian primary cancers. The conventional approach to treat peritoneal metastasis consists in systemic chemotherapy, but the median survival associated is only a few months. Recent therapeutic developments result in an aggressive strategy associating cytoreductive surgery (CRS) and hyperthermic intra peritoneal chemotherapy (HIPEC). However, a recent study failed to show an improvement in the overall survival and relapse free survival of this combo in comparison to CRS alone. Confronted to a lack of guidelines, several drug delivery systems (DDS) had been developed and tested in animal models to offer an effective easy-to-use solution for surgeons to prevent peritoneal metastasis. In this work, we reviewed most of the strategies used to treat peritoneal metastasis (PM) from digestive or ovarian origin and concentrated on 3 different DDS strategies: particulates DDS, non particulates DDS (including implants, films and gels) and combination of both (in particular hydrogels loaded with particles).

Radiotheranostic Agent 64Cu-cyclam-RAFT-c(-RGDfK-)4 for Management of Peritoneal Metastasis in Ovarian Cancer.

PURPOSE: Ovarian cancer peritoneal metastases (OCPMs) are a pathophysiologically heterogeneous group of tumors that are rarely curable. αVß3 integrin (αVß3) is overexpressed on tumoral neovessels and frequently on ovarian cancer cells. Here, using two clinically relevant αVß3-positive OCPM mouse models, we studied the theranostic potential of an αVß3-specific radiopeptide, 64Cu-cyclam-RAFT-c(-RGDfK-)4 (64Cu-RaftRGD), and its intra- and intertumoral distribution in relation to the tumor microenvironment. EXPERIMENTAL DESIGN: αVß3-expressing peritoneal and subcutaneous models of ovarian carcinoma (IGR-OV1 and NIH:OVCAR-3) were established in nude mice. 64Cu-RaftRGD was administered either intravenously or intraperitoneally. We performed intratumoral distribution (ITD) studies, PET/CT imaging and quantification, biodistribution assay and radiation dosimetry, and therapeutic efficacy and toxicity studies. RESULTS: Intraperitoneal administration was an efficient route for targeting 64Cu-RaftRGD to OCPMs with excellent tumor penetration. Using the fluorescence surrogate, Cy5.5-RaftRGD, in our unique high-resolution multifluorescence analysis, we found that the ITD of 64Cu-RaftRGD was spatially distinct from, but complementary to, that of hypoxia. 64Cu-RaftRGD-based PET enabled clear visualization of multiple OCPM deposits and ascites and biodistribution analysis demonstrated an inverse correlation between tumor uptake and tumor size (1.2-17.2 mm). 64Cu-RaftRGD at a radiotherapeutic dose (148 MBq/0.357 nmol) showed antitumor activities by inhibiting tumor cell proliferation and inducing apoptosis, with negligible toxicity. CONCLUSIONS: Collectively, these results demonstrate the all-in-one potential of 64Cu-RaftRGD for imaging guided radiotherapy of OCPM by targeting both tumoral neovessels and cancerous cells. On the basis of the ITD finding, we propose that pairing αVß3- and hypoxia-targeted radiotherapies could improve therapeutic efficacy by overcoming the heterogeneity of ITD encountered with single-agent treatments.

Preclinical evaluation of local prolonged release of paclitaxel from gelatin microspheres for the prevention of recurrence of peritoneal carcinomatosis in advanced ovarian cancer.

Patients with advanced ovarian cancer develop recurrence despite initial treatment response to standard treatment of surgery and intravenous/intraperitoneal (IP) chemotherapy, partly due to a limited peritoneal exposure time of chemotherapeutics. Paclitaxel-loaded genipin-crosslinked gelatin microspheres (PTX-GP-MS) are evaluated for the treatment of microscopic peritoneal carcinomatosis and prevention of recurrent disease. The highest drug load (39.2 µg PTX/mg MS) was obtained by immersion of GP-MS in aqueous PTX nanosuspension (PTXnano-GP-MS) instead of ethanolic PTX solution (PTXEtOH-GP-MS). PTX release from PTX-GP-MS was prolonged. PTXnano-GP-MS displayed a more controlled release compared to a biphasic release from PTXEtOH-GP-MS. Anticancer efficacy of IP PTX-GP-MS (PTXEtOH-GP-MS, D = 7.5 mg PTX/kg; PTXnano-GP-MS D = 7.5 and 35 mg PTX/kg), IP nanoparticular albumin-bound PTX (D = 35 mg PTX/kg) and controls (0.9% NaCl, blank GP-MS) was evaluated in a microscopic peritoneal carcinomatosis xenograft mouse model. PTXnano-GP-MS showed superior anticancer efficacy with significant increased survival time, decreased peritoneal carcinomatosis index score and ascites incidence. However, prolonged PTX release over 14 days from PTXnano-GP-MS caused drug-related toxicity in 27% of high-dosed PTXnano-GP-MS-treated mice. Dose simulations for PTXnano-GP-MS demonstrated an optimal survival without drug-induced toxicity in a range of 7.5-15 mg PTX/kg. Low-dosed PTXnano-GP-MS can be a promising IP drug delivery system to prevent recurrent ovarian cancer.

Therapy and Prophylaxis of Peritoneal Metastases from Colorectal Cancer.

Stage IV colorectal cancer is associated with high mortality, and the prognosis is significantly worse for patients have peritoneal metastases. Peritoneal carcinomatosis from colorectal cancer was considered incurable with an infaust prognosis. Median survival of untreated patients is about 6 months and palliative systemic chemotherapy can prolonge this time up to 20 months. Patients with this disease were previously only surgically treated if they had severe clinical symptoms or complications. This view has changed dramatically over the past 15 years. Aggressive cytoreductive surgery in combination with intraperitoneal chemotherapy may prolong median survival for more than 40 months in selected patients. The Peritoneal Surface Oncology Group International (PSOGI), the international authority on the treatment of peritoneal tumors, recommends cytoreduction with intraperitoneal chemotherapy as the standard of care for selected patients with moderate-to-small volume peritoneal metastases secondary to colorectal cancer. Macroscopic cytoreduction appears to be essential; however, the role of hyperthermic intraperitoneal chemotherapy and the optimal chemotherapeutic agent for intraperitoneal lavage to treat peritoneal metastases from colorectal cancer remain unclear. The results of ongoing and future clinical trials are eagerly awaited.

Prophylactic HIPEC with radical D2 gastrectomy improves survival and peritoneal recurrence rates for locally advanced gastric cancer: personal experience from a randomized case control study.

BACKGROUND: To investigate the implications of prophylactic intraoperative Hyperthermic Intraperitoneal Chemotherapy (HIPEC) with D2 radical gastrectomy for locally advanced Gastric Cancer (AGC) in a randomized case control study. METHOD: Eighty consecutive patients with locally AGC were randomly separated into 2 groups: HIPEC group (Curative Resection + intraoperative HIPEC with cisplatin 50 mg/m2 at 42.0 ± 1.0 °C for 60 min) and Control group (Curative Resection only). Intraoperative and post-operative events, clinical recovery, morbidity and the disease-free survival (DFS) rates were closely monitored. RESULTS: Among the 40 HIPEC group patients, the highest intracranial temperature recorded during the procedure was 38.2 °C but the patient made an eventless recovery. Mild renal dysfunction, hyperbilirubinemia and mild liver dysfunction were recorded in the HIPEC group but their incidences were found to be statistically insignificant when compared with the control group (P > 0.05). The initial post-operative analysis revealed shorter post-operative stay for in the HIPEC group but further analysis revealed that it was related to the incidence of postoperative complication. During a median follow-up time of 41 months, there were 9/39 and 15/38 cases of disease progression in HIPEC and Control groups respectively, with a more favorable 3-year DFS (76.9% vs 60.5%) and a lower peritoneal recurrence rate (5% vs 30%) in the HIPEC group. CONCLUSION: Prophylactic HIPEC with radical D2 Gastrectomy is safe and shows favorable survival and peritoneal recurrence rates for AGC with acceptable morbidity. Nevertheless, more structured multi-centered RCT should be carried out for more substantial evidence.

Primary curative surgery and preemptive or adjuvant hyperthermic peritoneal chemotherapy in colorectal cancer patients at high risk to develop peritoneal carcinomatosis. A systematic review.

PURPOSE: Τo evaluate all available data on the effect of preemptive intervention in patients who have curative surgery for colorectal cancer (CRC) and are at high risk to develop peritoneal carcinomatosis (PC). METHODS: The authors conducted a systematic review of all published studies from January 2000 to July 2016. Twelve studies were eventually considered for analysis, and were divided in four categories, according to different approaches for adjuvant intra-peritoneal chemotherapy: a) hyperthermic intraperitoneal chemotherapy (HIPEC), during primary surgery for CRC; b) early postoperative intraperitoneal chemotherapy (EPIC), after primary surgery for CRC; c) early re-intervention (laparotomy or laparoscopy) and HIPEC; and d) as second look laparotomy and HIPEC + cytoreductive surgery (CRS), several months after primary surgery. RESULTS: Considering prophylactic HIPEC during primary surgery, the studies that were analysed showed a peritoneal recurrence rate of 0-12.9%, a 3- and 5-year disease free survival (DFS) of 67-97.5% and 54.8-84% respectively, and a 3- and 5-year overall survival (OS) of 67-100% and 84%, respectively. These oncological results are probably better than what is expected in patients at high risk to develop PC and have only adjuvant systemic chemotherapy. Because of the great heterogeneity in inclusion criteria (risk factors for PC) and methodology of intra-peritoneal chemotherapy (different timing, different techniques, different agents), a meta-analysis was not performed. CONCLUSIONS: At present and because of the insufficient available evidence, preemptive intervention at the immediate postoperative adjuvant setting is recommended only in the setting of a registered clinical trial.

Peritoneal Metastases from Gastrointestinal Cancer.

PURPOSE OF REVIEW: Peritoneal metastases may occur from a majority of cancers that occur within the abdomen or pelvis. When cancer spread to the peritoneal surfaces is documented, a decision regarding palliation vs. an aggressive approach using cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy must be made. The perioperative chemotherapy may be hyperthermic intraperitoneal chemotherapy (HIPEC) administered in the operating room or early postoperative intraperitoneal chemotherapy (EPIC) administered in the first 4 or 5 postoperative days. RECENT FINDINGS: This decision is dependent on a well-defined group of prognostic indicators. In addition to treatment, the clinical and pathologic features of a primary cancer can be used to select perioperative treatments that may prevent cancer cells within the abdomen and pelvis from progressing to established peritoneal metastases. In some clinical situations with appendiceal and colorectal cancers, the clinical or histopathologic features may indicate that second-look surgery plus perioperative chemotherapy should occur. Peritoneal metastases should always be considered for treatment or prevention.

Palliative Management of Peritoneal Metastases.

Despite significant recent advances in the management of peritoneal carcinomatosis, this diagnosis still is accompanied frequently by a grim survival prognosis, often measured in weeks to months. The poor prognosis also is accompanied often by complications and symptoms that have a dramatic impact on quality of life and are challenging to the managing health care provider and devastating to loved ones caring for the person who is suffering. Consequently, management of carcinomatosis often revolves around palliation of symptoms such as bowel obstruction, nausea, pain, fatigue, and cachexia as well as emotional and existential concerns. This article reviews several palliative treatment options for some of the more common symptoms and complications associated with advanced, incurable peritoneal carcinomatosis. Although readers should recognize that carcinomatosis is no longer an imminent death sentence, providers caring for patients with peritoneal carcinomatosis also must be well-versed in the palliative management of this condition and recognize the utility of early palliative care referral in this setting.

Current Management and Future Opportunities for Peritoneal Metastases: Peritoneal Mesothelioma.

PURPOSE: Diffuse malignant peritoneal mesothelioma (MPM) is a rare and ultimately fatal cancer that was first described just over a century ago. It is a diffuse malignancy arising from the mesothelial lining of the peritoneum; morbidity and mortality from MPM is due to its propensity to progress locoregionally within the abdominal cavity. METHODS: The purpose of this article is to review the current state-of-the-science related to the diagnosis, staging, and treatment of MPM. RESULTS: The condition afflicts men and women equally and the peak incidence is between 55 and 60 years of age although it can arise in the young and elderly. Patients afflicted with MPM most commonly present with nonspecific abdominal symptoms that usually lead to diagnosis when the condition is relatively advanced. Historically, median overall survival for MPM patients without treatment is < 1 year. The couplet of systemic pemetrexed and cisplatin has an overall response rate of approximately 25% and a median overall survival of approximately 1 year. CONCLUSION: The available data, almost all retrospective in nature, have shown that in selected patients, operative cytoreduction (CRS) and regional chemotherapy administered as hyperthermic intraoperative peritoneal chemotherapy (HIPEC) or early postoperative intraperitoneal chemotherapy (EPIC) is associated with long-term survival. Studies on the molecular biology of MPM have yielded new insights relating to the potentially important role of the phosphoinsitide-3-kinase/mammalian target of rapamycin (PI3 K/mTOR) pathways and immune checkpoint inhibitors that may translate into new therapeutic options for patients with diffuse MPM.

Regimens of Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis from Colorectal Cancer.

Although systemic chemotherapy has been improved, peritoneal carcinomatosis remains a factor of poor prognosis in patients with colorectal cancer. In order to achieve a higher drug concentration in the peritoneal cavity, intraperitoneal chemotherapy has been performed. However, the optimal regimen for intraperitoneal chemotherapy has not been determined. In this review of intraperitoneal chemotherapy for colorectal cancer, we summarize regimens of hyperthermic intraperitoneal chemotherapy (HIPEC) and other intraperitoneal chemotherapy modalities, such as early postoperative intraperitoneal chemotherapy (EPIC) and sequential postoperative intraperitoneal chemotherapy (SPIC). Mitomycin C and oxaliplatin are the most common chemotherapeutic agents used for HIPEC. Some combination therapies such as those involving bevacizumab, H2O2, and amifostine have potential to increase HIPEC efficacy. 5-Fluorouracil is used mainly for EPIC and SPIC. Some new agents such as paclitaxel, melphalan, and various nanoparticles have been developed. These novel chemotherapeutic agents may achieve clinical implementation in the future.

Peritoneal Involvement Is More Common Than Nodal Involvement in Patients With High-Grade Appendix Tumors Who Are Undergoing Prophylactic Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Right hemicolectomy is routinely recommended in patients with histologic findings of high-grade appendix tumors after appendicectomy. Undetected peritoneal disease may be encountered at surgery. In high-grade appendix tumors with disease detected radiologically, complete cytoreduction may not be possible and outcomes poor. For these reasons, we adopted a policy of prophylactic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. OBJECTIVE: The purpose of this study was to quantify the rates of peritoneal and nodal metastatic disease in patients with high-grade appendix tumors without obvious metastatic disease and to report the long-term outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in these patients. DESIGN: Data regarding peritoneal and nodal metastatic disease were extracted from surgical and histologic records. SETTINGS: The study was conducted at a high-volume tertiary referral center for peritoneal malignancy. PATIENTS: Patients referred with histologically high-grade appendix tumors at appendicectomy, without detectable metastatic spread, between January 1994 and September 2016 were included MAIN OUTCOME MEASURES:: A total of 62 patients with high-grade pathology at appendicectomy, without clinical or radiological peritoneal disease, underwent complete cytoreduction with hyperthermic intraperitoneal chemotherapy. RESULTS: Thirty-five (57%) of 62 patients had peritoneal disease (median peritoneal cancer index 5 (range, 1-28)). Eleven (31%) of 35 had microscopic peritoneal disease. Overall, 23 (37%) of 62 had peritoneal disease beyond the confines of a standard right hemicolectomy. Nine (15%) of 62 had nodal involvement. Mean overall and disease-free survival were 110.9 (95% CI, 94.8-127.0 mo) and 102.1 months (95% CI, 84.3-119.9 mo), with 5-year overall and disease-free survival of 83.2% and 76.0%. LIMITATIONS: The retrospective nature limits the interpretation of these results. CONCLUSIONS: Complete cytoreduction was achieved in all of the patients, with excellent long-term survival. The incidence of peritoneal spread (57%) compared with nodal involvement (15%) supports cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as definitive treatment rather than prophylaxis in patients with high-grade appendix tumors, even without radiologically detectable disease. High-grade appendix tumors benefit from early aggressive operative management to deal with potential peritoneal and nodal spread and should be considered for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. See Video Abstract at http://links.lww.com/DCR/A360.

The 30-year experience-A meta-analysis of randomised and high-quality non-randomised studies of hyperthermic intraperitoneal chemotherapy in the treatment of gastric cancer.

IMPORTANCE: Hyperthermic intraperitoneal chemotherapy (HIPEC) has been used within various multimodality strategies for the prevention and treatment of gastric cancer peritoneal carcinomatosis. OBJECTIVE: To systematically evaluate the role of HIPEC in gastric cancer and clarify its effectiveness at different stages of peritoneal disease progression. DATA SOURCES: Medline and Embase databases between January 1, 1985 and June 1, 2016. STUDY SELECTION: Randomised control trials and high-quality non-randomised control trials selected on a validated tool (methodological index for non-randomised studies) comparing HIPEC and standard oncological management for the treatment of advanced stage gastric cancer with and without peritoneal carcinomatosis were considered. DATA EXTRACTION AND SYNTHESIS: A random-effects network meta-analysis. MAIN OUTCOMES AND MEASURES: The primary outcomes were overall survival and disease recurrence. Secondary outcomes were overall complications, type of complications, and sites of recurrence. RESULTS: A total of 11 RCTs and 21 non-randomised control trials (2520 patients) were included. For patients without the presence of peritoneal carcinomatosis (PC), the overall survival rates between the HIPEC and control groups at 3 or 5 years resulted in favour of the HIPEC group (risk ratio [RR] = 0.82, P = 0.01). No difference in the 3-year overall survival (RR = 0.99, P = 0.85) in but a prolonged median survival of 4 months in favour of the HIPEC group (WMD = 4.04, P < 0.001) was seen in patients with PC. HIPEC was associated with significantly higher risk of complications for both patients with PC (RR = 2.15, P < 0.01) and without (RR = 2.17, P < 0.01). This increased risk in the HIPEC group was related to systemic drugs toxicity. Anastomotic leakage rates were found to be similar between groups. CONCLUSIONS: Our study demonstrates a survival advantage of the use of HIPEC as a prophylactic strategy and suggests that patients whose disease burden is limited to positive cytology and limited nodal involvement may benefit the most from HIPEC. For patients with extensive carcinomatosis, the completeness of cytoreductive surgery is a critical prognostic factor for survival. Future RCTs should better define patient selection criteria.

Prophylactic hyperthermic intraperitoneal chemotherapy in patients with epithelial appendiceal neoplasms.

Background Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising approach for preventing peritoneal carcinomatosis in high-risk patients. We report our initial experience with prophylactic HIPEC in a series of patients with appendiceal neoplasms. Methods We retrospectively reviewed our prospectively maintained database to identify patients who underwent HIPEC in the absence of peritoneal disease. Patients with previously documented peritoneal surface disease were excluded. Data regarding clinical, operative and pathological features were analysed. Results Out of 322 HIPEC procedures performed between March 2007and August 2015, we identified 16 patients who underwent surgery with prophylactic intent. Primary diagnoses included high-grade and low-grade appendiceal neoplasms. Most patients presented originally with appendiceal perforation; all patients underwent initial surgery during which the appendix or right colon were resected. Following a median time interval of 2.2 months, a second surgery performed at our institution consisted of completion of omentectomy, partial colectomy and oophorectomy, with administration of prophylactic HIPEC (using mitomycin C). A totally laparoscopic approach was attempted and achieved in 11 patients in whom the median duration of surgery, estimated intraoperative blood loss and length of hospitalisation were 251 min, 100 cm(3) and 4 days, respectively. There were no cases of major perioperative morbidity or mortality. Conclusions Prophylactic HIPEC for appendiceal neoplasms is feasible, safe and may be performed laparoscopically. Larger studies with long-term follow-up are needed to determine whether a survival benefit is associated with this treatment.

[Clinical Evaluation of Hyperthermic Intraperitoneal Chemotherapy(HIPEC)in Colorectal Cancer Patients at High Risk of Peritoneal Recurrence].

PURPOSE: We herein report the clinical outcomes of hyperthermic intraperitoneal chemotherapy(HIPEC)in patients at high risk of colorectal peritoneal metastasis. PATIENTS AND METHODS: We enrolled 21 patients with advanced colorectal cancer who were received HIPEC between 2009 and 2014. Retrospectively, we evaluated the short-term and long-term outcomes of these cases. RESULTS: We performed HIPEC for 12 patients with primary cancer and 9 with recurrent cancer. Perioperative complications characteristic of HIPEC did not occur. Seventeen patients(81%)had postoperative recurrence, 5 of whom had a peritoneal recurrence, and all of them already had synchronous peritoneal metastasis at the time of HIPEC. Patients with a higher peritoneal cancer index(PCI)had a tendency towards a higher rate of peritoneal recurrence than those with a lower PCI(11[median]vs 4; p=0.08).

[Effects of Banxia Xiexin Decoction Containing Serum on Proliferation, Invasion and Metastasis of Gastric Cancer Peritoneal Metastasis Cell Line GC9811-P].

Objective To observe the effects of Banxia Xiexin Decoction (BXD) containing ser- um on proliferation, invasion and metastasis of in vitro human gastric cancer peritoneum cell strain GC9811-P (which has high metastatic potential). Methods BXD containing serum was prepared. GC9811-P cells were inoculated in the E-Plate 96 and CIM Plate 16, and then 0, 25, 50, 100 µL/mL BXD containing serums were added respectively. Meanwhile, GC9811-P cells were stained by Diff-Quik stai- ning method. Inhibition of BXD containing serum on cell index (CI) for proliferation of GC9811-P cells, invasion and metastasis were observed by real time cellular analysis (RTCA) and Diff-Quik staining method. Results BXD containing serum could obviously inhibit the proliferation of GC9811-P cells. The Cl approximated to 0 after 70 h. Most stained Diff-Quik cells died. Cell migration curve showed that 25, 50, 100 µL/mL BXD containing serums could obviously inhibit the capacities for cell migration of GC9811-P cells in concentration dependent manner. The number of migration cells was reduced more obviously, as com- pared with 0 µL/mL BXD containing serum (P <0. 05). Conclusion BXD containing serums could inhibit the proliferation, invasion and metastasis of GC9811-P cells, which might be associated with blocking peritoneal metastasis of gastric cancer.

Long-term results after proactive management for locoregional control in patients with colonic cancer at high risk of peritoneal metastases.

PURPOSE: A major problem in treating patients with peritoneal spread from colorectal cancer is that at diagnosis wide peritoneal involvement often precludes all curative attempts. A possible solution is to identify those patients at risk for peritoneal metastases and intervene early to prevent locoregional disease spread before it develops and, thus, to improve outcome. METHODS: We analyzed long-term results from a previous study and compared outcomes in 25 patients with advanced colon cancer considered at high risk for peritoneal spread (pT3/pT4 and mucinous or signet ring cell histology) prospectively included and managed with a proactive surgical approach including target organ resection for peritoneal spread plus hyperthermic intraperitoneal chemotherapy (HIPEC) and in 50 retrospectively well-matched controls who underwent standard surgical resection during the same period and in the same hospital by different surgical teams. RESULTS: At 48 months after the study closed, peritoneal metastases and local recurrence developed significantly less often in proactively managed patients than in controls (4 vs 28%) (p < 0.03). Patients in the proactive group also survived longer than control patients (median overall survival 59.5 vs 52 months). Despite similar morbidity, Kaplan-Meier survival curves disclosed significantly longer disease-free and overall survival in the proactive than in the control group (p < 0.05 and <0.04). CONCLUSIONS: In patients with advanced colon cancer at risk for peritoneal recurrence, the proactive surgical approach plus HIPEC seems to achieve good locoregional control preventing peritoneal spread thus improving outcome without increasing morbidity. These advantages merit investigation in a multicentric randomized trial.

Feasibility of adjuvant laparoscopic hyperthermic intraperitoneal chemotherapy in a short stay setting in patients with colorectal cancer at high risk of peritoneal carcinomatosis.

INTRODUCTION: Treatment of peritoneal carcinomatosis (PC) of colorectal cancer (CRC) origin is relatively ineffective and associated with morbidity. This raises the question whether we should focus on prevention of the development of PC. We determined the feasibility of adjuvant laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) in a short stay setting. METHODS: A prospective single centre pilot study was conducted between January 2011 and July 2012. Ten patients at risk of developing PC of CRC origin were included. Laparoscopic HIPEC using Mitomycin-C (90 min; inflow temperature 42-43 °C) was performed within several weeks after primary resection of CRC and was considered feasible when postoperative hospital stay was three days or shorter in at least six patients, and if a maximum of one conversion and one re-admission within 30 days occurred. RESULTS: HIPEC was performed after a median of 6 weeks (range 3-9 weeks). Postoperatively, five patients were discharged at day one, four patients at day two and one patient at day three. Laparoscopic adhesiolysis resulted in small bowel injury in one patient, but no conversion to open surgery and no postoperative complications were observed. One patient was readmitted within 30 days due to a clostridium infection. The postoperative course was uneventful for the remaining patients. CONCLUSION: Adjuvant laparoscopic HIPEC appeared to be feasible in a short stay setting based on this small pilot study. The necessity of adhesiolysis determines the complexity of the procedure and requires an operating team with experience in minimally invasive abdominal surgery.

Intraperitoneal chemotherapy as adjuvant treatment to prevent peritoneal carcinomatosis of colorectal cancer origin: a systematic review.

BACKGROUND: Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) origin is associated with poor outcome. This systematic review evaluates the available evidence about adjuvant (hyperthermic) intraperitoneal chemotherapy ((H)IPEC) to prevent the development of PC. METHODS: A systematic search of literature was conducted in August 2013 in PubMed, Embase, and the Cochrane database for studies on (H)IPEC to prevent PC in patients who underwent curative surgery for primary CRC. RESULTS: Seven comparative studies and five cohort studies were selected. Treatment schedules varied between repeated fluoropyrimidine-based IPEC administration in the ambulatory setting to intra-operative (H)IPEC procedures using mitomycin-C or oxaliplatin. The reported rates of major complications related to adjuvant (H)IPEC was low. Four out of five evaluable comparative studies reported a significant difference in the incidence of PC in favour of (H)IPEC. All three comparative studies reporting on survival after intra-operative (H)IPEC showed a significant survival benefit in favour of the experimental arm. Substantial heterogeneity in patient selection, treatment protocols, and treatment effect evaluation among studies was observed. CONCLUSIONS: The currently available evidence about adjuvant (H)IPEC in high-risk CRC is limited and subject to bias, but points towards improved oncological outcome and supports further randomised studies.