Colorectal Peritoneal Carcinomatosis Research Articles

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancy.

Peritoneal surface malignancies have historically presented a treatment challenge for clinicians. Not infrequently, epithelial cancers can seed the peritoneal cavity. Neoplasms of the appendix can result in peritoneal dissemination of disease and pseudomyxoma peritonei; in colon cancer, up to 25% with recurrent disease will develop a peritoneal surface predominant pattern of recurrence (1), and among those resected advanced gastric cancer, the majority of patients who recur in the first five years following surgery will develop peritoneal disease (2). Among the approximately 21,290 cases of ovarian cancer cases estimated to be diagnosed in 2015 (3), most will present in an advanced disease state, many with evidence of peritoneal carcinomatosis. In addition to epithelial derived cancers, 10-15% of the approximately 2,500 cases of malignant mesothelioma diagnosed in the U.S. will develop in the peritoneal cavity (4). For all these tumor histologies, cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been considered in the treatment algorithm for selected patients. Over time, CRS/HIPEC has seen an increased utilization in treating select patients with peritoneal disease patterns previously considered inoperable, and has been associated with favorable survival outcomes. In patients with colorectal peritoneal carcinomatosis, a recent retrospective study of 539 patients undergoing a complete cytoreduction reported a median overall survival of 32.6 months (5). No doubt these observed improved outcomes compared to historical cohorts are multifactorial, reflecting improvements in systemic therapies, refinements in surgical techniques and perioperative care, and a better understanding of tumor biology contributing to better patient selection for surgery. Nonetheless, the remarkably favorable data are compelling and speak for the importance of consideration of CRS/ HIPEC in the context of a multidisciplinary approach for patients with peritoneal surface malignancy. This issue of Journal of Gastrointestinal Oncology (JGO) focuses on CRS/HIPEC and its application for various cancers. A paper led by the editors highlight some of the important historical developments in the evolution of CRS and HIPEC. Dr. Paul Sugarbaker and colleagues share their extensive expertise discussing surgical techniques of CRS/ HIPEC and pharmacology of intraperitoneal chemotherapy, while Dr. Goodman provides an excellent review of the selection of chemotherapeutic agents used for this procedure. Dr. Low presents an interesting summary on the use of MRI in the pre-operative evaluation and surveillance of patients being considered for or treated with CRS/HIPEC. Finally, each of the five tumor histologies discussed above is considered in depth in a separate manuscript, including two original papers studying CRS/HIPEC for high grade appendiceal cancer and ovarian cancer. Also in this issue is an important section on quality issues pertaining to CRS/HIPEC, including a review paper discussing the morbidity and mortality associated with the procedure. These procedures can be extensive, and not without risk, and consideration of these factors in the clinical decision making is essential. Dr. Lambert provides a very thoughtful synopsis of the palliative role of CRS/HIPEC, and Dr. Turaga discusses the impact of surgical volume in centers of these procedures on surgical outcomes. Dr. Votanopoulos presents a review of the indications and outcomes following repeat HIPEC surgery, which can be sometimes considered in select patients. Finally, Dr. Nash discusses current

Predictors of Severe Morbidity After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Patients With Colorectal Peritoneal Carcinomatosis.

Severe morbidity after cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is, besides the obvious short-term consequences, associated with impaired long-term outcomes. The risk factors for severe morbidity in patients with peritoneal carcinomatosis (PC) of colorectal origin are poorly defined. This study aimed to identify risk factors for severe morbidity after CRS + HIPEC in patients with colorectal PC. Patients with colorectal PC who underwent CRS + HIPEC between 2007 and 2015 were categorized and compared between those with and those without severe morbidity. Risk factors were identified using logistic regression analysis. Morbidity was graded according to the Clavien-Dindo classification, with grade 3 or higher indicating severe morbidity. This study included 211 patients, of whom 53 patients (25.1%) experienced morbidity of grade 3 or higher. The identified risk factors for severe morbidity were extensive prior surgery [odds ratio (OR) 4.3], a positive recent smoking history (OR 4.0), a poor physical performance status (OR 2.9), and extensive cytoreduction (OR 1.2 per additional resection). Patients with a greater number of risk factors more often had severe morbidity and higher reoperation, readmission, and mortality rates. Furthermore, an internally validated preoperative prediction model for severe morbidity with an area under the curve of 70% was constructed. The current study identified risk factors for severe morbidity after CRS + HIPEC in patients with colorectal PC. Patients with a combination of risk factors have a substantial risk of severe morbidity and therefore should be carefully selected for CRS + HIPEC. The preoperative decision model can be a valuable additional tool in this process of patient selection.

Impacts of low peritoneal cancer index on the survival outcomes of patient with peritoneal carcinomatosis of colorectal origin

IntroductionThe combination of cytoreductive surgery (CRS) and perioperative chemotherapy (PIC) have been proposed as an innovative technique for peritoneal carcinomatosis and is currently considered as a standard treatment for colorectal peritoneal carcinomatosis (CRPC) in selected patients. Peritoneal cancer index (PCI) has been suggested to be the most important prognostic factors for the outcomes of patients with CRPC. In this paper, we have studied patients with CRPC and a very low PCI of 5 or less and their survival outcomes. MethodsThis is a retrospective study of prospectively collected data of 60 consecutive patients with CRPC and PCI ≤ 5, who underwent CRS and PIC by the same surgical team at St George hospital in Sydney, Australia between January 1996 and April 2015. Clinical outcomes of these patients were analysed. ResultsHospital mortality was 0%. 14 patients (23.4%) had grade III/IV morbidity. The median follow-up was 22.2 months (range = 0.1–104.2). The median survival was 80.6 months (95% confidence interval (CI) = 35.1–126.1), with an overall 1-year, 3-year, and 5-year survival rate of 96.1%, 72.6% and 54.7% respectively. Among 60 patients, 31 patients experienced the recurrence of the disease (51.7%). The median disease-free survival was 10.8 months (95% CI = 7.2–14.4). ConclusionThis innovative approach combining CRS and PIC has shown encouraging outcomes and offers hope for patients with CRPC. Our results suggest that CRS and PIC can be performed safely to provide significant survival benefits for patients with low volume of disease. Early referral to specialist centre for evaluation is warranted for better survival outcomes.

Feeding tube placement during cytoreductive surgery and heated intraperitoneal chemotherapy does not improve postoperative nutrition and is associated with longer length of stay and higher readmission rates

BackgroundPatients with colorectal cancer and peritoneal carcinomatosis (CRC/PC) may benefit from cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC). Nutritional support is frequently required for patients after CRS/HIPEC. It remains unclear if placement of feeding access is of benefit in regard to improving postoperative nutrition in this patient population. Materials and methodsPatients with CRC/PC who underwent complete cytoreduction were evaluated. Preoperative and postoperative nutritional data and discharge outcomes were retrospectively recorded. The presence of a feeding tube and PCI scores were recorded by review of operative notes. Readmission rates were calculated for patients at 30 d and 60 d after discharge from hospital. ResultsForty-one patients underwent CRS/HIPEC, 25 had feeding tube placement at the time of surgery. Weight loss was common after HIPEC as 38 of 41 patients demonstrated weight loss. The mean weight loss was 7.6%. total parenteral nutrition was required at discharge in four patients (7.9%); three of these patients had feeding access placed. There was no difference in the degree of weight loss between groups (7.1 ± 3.7% no tube versus 7.9 ± 5.8% patients with tube; P = 0.608). The mean decrease in albumin was 12.7% but was not significantly different in patients with feeding access and those without (10.0% versus 14.75%; P = 0.773). Sixty-day readmission rates were higher in patients with feeding tubes (36% compared with 0%, P < 0.01). ConclusionsSignificant nutritional loss is common after CRS/HIPEC for patients with CRC/PC. Feeding tube placement does not prevent this and appears to be related to higher readmission rates and longer length of stay.

Treatment-Related Mortality After Cytoreductive Surgery and HIPEC in Patients with Colorectal Peritoneal Carcinomatosis is Underestimated by Conventional Parameters.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) as treatment for patients with colorectal peritoneal carcinomatosis (PC) is regarded as an extensive procedure. The risk of postoperative mortality after major abdominal surgery might be substantially higher than described by the 30-day mortality. This study aims to identify causes of 1-year mortality, thereby assessing a more accurate treatment-related mortality rate after CRS + HIPEC. All subsequent patients with colorectal PC treated with CRS + HIPEC with complete macroscopic cytoreduction in two tertiary hospitals between April 2005 and April 2013 were included in this study. Causes of 1-year mortality were carefully analyzed and patient data were compared between patients who died or did not die within 12 months after CRS + HIPEC. Of the 245 included patients, 34 (13.9 %) died within 12 months after CRS + HIPEC. The overall treatment-related mortality rate was 4.9 % (n = 12), and the 30-day and in-hospital mortality rates were 1.6 % (n = 4) and 2.4 % (n = 6), respectively. Furthermore, 18 patients (7.3 %) died due to early recurrent disease. Three patients (1.2 %) died of cardiovascular events, unrelated to CRS + HIPEC. The 1-year mortality group had more extensive peritoneal disease (p = 0.02) and the operative time in this group was longer (p < 0.001). Overall treatment-related mortality was considerably higher than described by the 30-day and in-hospital mortality rate. However, even though complete macroscopic cytoreduction was achieved in every patient, the main cause of 1-year mortality was early recurrent disease. Both findings are valuable in preoperative patient selection, as well as in preoperative counseling of patients undergoing a CRS + HIPEC procedure.

P0035 Palliative chemotherapy compared with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for patients with colorectal peritoneal carcinomatosis

Background Cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) prolong survival in selected patients with colorectal peritoneal carcinomatosis. However, this modality of treatment is not standard therapy, and many patients are offered palliative chemotherapy (PC) instead. We hypothesise that PC is suboptimal as complications from the peritoneal disease often disrupts or prevents the PC. We compared overall survival between patients treated with PC and patients undergoing CRS and HIPEC, and we analysed morbidity in those receiving PC. Methods We performed a retrospective review of a prospectively maintained database at the National Cancer Centre Singapore from January 2008, to December 2013. 34 patients underwent CRS and HIPEC, 21 patients were treated with PC. Secondary outcomes were frequency of disruption of chemotherapy, need for surgery or invasive interventions, and duration of hospitalisation for complications of peritoneal disease. Findings Median overall survival for patients receiving PC was 1.7 years (95% confidence interval (CI) 0.7–2.1), but that of CRS and HIPEC was not reached. This was in spite of a longer median follow-up time for patients undergoing CRS and HIPEC of 2.2 years (0.2–7.2) compared with 1.1 years (0.0–3.8) with PC. The hazard of death for a patient treated with PC was 5.5 times that of a patient who underwent CRS and HIPEC (p < 0.05). Of the PC group, 71.4% had chemotherapy disruptions; 60.0% due to complications of peritoneal disease. 14.3% of patients required emergency surgery with stoma creation for intestinal obstruction, and 23.8% of patients required abdominal cope loop and ureteric stent insertion. Median total duration of unforeseen hospitalisation post-CRS and HIPEC was 11 days (0–149), compared with 21 days (0–85) in the PC group. Interpretation CRS and HIPEC prolonged survival compared with PC in selected patients with CLR peritoneal carcinomatosis. Patients treated with PC have significant morbidity from disease progression, which disrupts planned chemotherapy and results in significantly longer hospitalisation compared with CRS and HIPEC. Cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) prolong survival in selected patients with colorectal peritoneal carcinomatosis. However, this modality of treatment is not standard therapy, and many patients are offered palliative chemotherapy (PC) instead. We hypothesise that PC is suboptimal as complications from the peritoneal disease often disrupts or prevents the PC. We compared overall survival between patients treated with PC and patients undergoing CRS and HIPEC, and we analysed morbidity in those receiving PC. We performed a retrospective review of a prospectively maintained database at the National Cancer Centre Singapore from January 2008, to December 2013. 34 patients underwent CRS and HIPEC, 21 patients were treated with PC. Secondary outcomes were frequency of disruption of chemotherapy, need for surgery or invasive interventions, and duration of hospitalisation for complications of peritoneal disease. Median overall survival for patients receiving PC was 1.7 years (95% confidence interval (CI) 0.7–2.1), but that of CRS and HIPEC was not reached. This was in spite of a longer median follow-up time for patients undergoing CRS and HIPEC of 2.2 years (0.2–7.2) compared with 1.1 years (0.0–3.8) with PC. The hazard of death for a patient treated with PC was 5.5 times that of a patient who underwent CRS and HIPEC (p < 0.05). Of the PC group, 71.4% had chemotherapy disruptions; 60.0% due to complications of peritoneal disease. 14.3% of patients required emergency surgery with stoma creation for intestinal obstruction, and 23.8% of patients required abdominal cope loop and ureteric stent insertion. Median total duration of unforeseen hospitalisation post-CRS and HIPEC was 11 days (0–149), compared with 21 days (0–85) in the PC group. CRS and HIPEC prolonged survival compared with PC in selected patients with CLR peritoneal carcinomatosis. Patients treated with PC have significant morbidity from disease progression, which disrupts planned chemotherapy and results in significantly longer hospitalisation compared with CRS and HIPEC.

Improving Anti-Tumor Activity of Curcumin by Polymeric Micelles in Thermosensitive Hydrogel System in Colorectal Peritoneal Carcinomatosis Model.

In this work, we prepared an in situ gel-forming composite drug delivery system (DDS) to treat colorectal peritoneal carcinomatosis. The composite DDS was based on curcumin loaded polymeric micelles (Cur-M) and thermosensitive hydrogel. Cur-M had a particle size of 27.1 ± 1.3 nm with polydisperse index of 0.149 ± 0.017, and the drug loading and encapsulation efficiency of Cur-M were 14.82 ± 0.07 and 98.83 ± 0.45%, respectively. The prepared Cur-M in thermosensitive hydrogel system (Cur-H) was a free-flowing sol at ambient temperature, and converted into non-flowing gel at body temperature, serving as a drug depot. In vitro drug release behavior suggested that Cur-H and Cur-M could release Cur in an extent period, and Cur-H showed a slower cumulative release rate. In addition, compared with free Cur, Cur-M showed higher cytotoxicity and apoptotic induction efficiency. Furthermore, colorectal peritoneal carcinomatosis mouse model was used to evaluate the anti-tumor activity of Cur-H, and the results suggested that Cur-H could inhibit tumor growth and metastasis, and prolonged survival of tumor-bearing mice. Immunohistochemical and immunofluorescent staining of tumor tissues in each group were conducted. The results demonstrated that tumors in Cur-H group showed lower proliferation activity, more apoptotic cells, and fewer microvessels. Besides, pharmacokinetic studies of Cur-H and Cur-M by intraperitoneal administration were performed. Compared with Cur-M, Cur-H showed a higher AUC and longer t½. Thus, the above results suggested that Cur-H may have potential applications in colorectal peritoneal carcinomatosis.

P0130 Quality of life in patients with colorectal carcinomatosis peritonei after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

<h3>Background</h3> An increasing number of patients with colorectal cancer are presenting with peritoneal carcinomatosis and more centres are performing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). While morbidity and mortality are shown to be acceptable after surgery, quality of life should be assessed. <h3>Methods</h3> 21 patients who had CRS and HIPEC from 2001 to 2012 for colorectal peritoneal carcinomatosis and who were still alive at follow up were included. The EORTC QLQ-CR29 was administered to the patients. Scores at baseline and at 6months and 12months after CRS and HIPEC were summarised by median and interquartile range, and changes were tested using the Wilcoxon matched-pairs signed-rank test. <h3>Findings</h3> After a median follow-up of 12months, there was no statistical difference in scores when comparing by age, sex, recurrence, PCI score, and presence of complications. There was no significant change in most scores, but body image score improved at 6months, while sexual interest scores and urinary frequency scores worsened at 6 and 12months, respectively. <h3>Interpretation</h3> Our study shows that colorectal peritoneal carcinomatosis patients can achieve a good quality of life after CRS and HIPEC, with improvement in body image scores.

Hyperthermic intraperitoneal chemotherapy + early postoperative intraperitoneal chemotherapy versus hyperthermic intraperitoneal chemotherapy alone: assessment of survival outcomes for colorectal and high-grade appendiceal peritoneal carcinomatosis

BackgroundCytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have improved survival for colorectal and high-grade appendiceal carcinomatosis. We compared the overall and recurrence-free survival (OS and RFS) of patients treated with HIPEC with mitomycin c and early postoperative intraperitoneal chemotherapy (EPIC) with fluorouracil versus HIPEC alone using oxaliplatin and simultaneous IV infusion of fluorouracil. MethodsNinety-three patients with colorectal or high-grade appendiceal carcinomatosis were treated with CRS and HIPEC + EPIC or HIPEC alone. OS and RFS were analyzed using Kaplan–Meier curves and log-rank testing. ResultsSurvival did not differ between HIPEC regimens. The 3-year OS and RFS rates were 50% and 21% for HIPEC + EPIC and 46% and 6% for HIPEC alone (P = .72 and P = .89, respectively). HIPEC + EPIC patients experienced more grade III/IV complications (43.2% vs 19.6%, P = .01). ConclusionsThere was no difference in OS and RFS between colorectal and high-grade appendiceal adenocarcinoma patients treated with CRS and HIPEC + EPIC versus HIPEC alone. However, HIPEC + EPIC patients suffered greater morbidity, making HIPEC alone the preferable regimen.

Cytoreductive surgery and HIPEC in treatment of colorectal peritoneal carcinomatosis: experiment or standard care? A survey among oncologic surgeons and medical oncologists.

Controversy still exists regarding the position of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with peritoneal metastasis of colorectal carcinoma. The goal of the current study was to evaluate the opinions about this treatment among Dutch oncologic surgeons and medical oncologists. An online survey was sent to all known Dutch oncologic surgeons (n = 459) and medical oncologists (n = 363) representing the respective departments of 84 hospitals. A comparison was made between surgeons and oncologists. 185 eligible responses were received from 71 hospitals, resulting in a response rate of 23 % for individuals and a response rate of 85 % for hospitals. Overall, 65 % of respondents regarded CRS+HIPEC as effective with sufficient evidence, 29 % responded that CRS+HIPEC is probably effective without sufficient evidence, and 7 % of respondents regards HIPEC as probably ineffective. Medical oncologists were less convinced of the effectiveness of CRS+HIPEC than surgeons (P = 0.006). Of all the respondents, 68 % indicated that they regard CRS+HIPEC as a standard treatment for patients with peritoneal dissemination of colorectal carcinoma (77 % of surgeons vs 54 % of oncologists, P = 0.001). Additionally, 68 % of respondents regard CRS+HIPEC as potentially curative (77 % of surgeons vs 54 % of oncologists, P = 0.001). Approximately 30 % of physicians who treat colorectal carcinoma do not regard CRS+HIPEC as standard care. Surgeons appear to be significantly more in favor of this treatment than medical oncologists. This study shows that efforts should be made to improve knowledge and increase acceptance of CRS and HIPEC in colorectal cancer treatment among medical oncologists and surgeons.

Skeletal Muscle Depletion is Associated with Severe Postoperative Complications in Patients Undergoing Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis of Colorectal Cancer.

In patients undergoing colorectal cancer surgery, skeletal muscle depletion (sarcopenia) is associated with impaired postoperative recovery and decreased survival. This study aimed to determine whether skeletal muscle depletion can predict postoperative complications for patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for peritoneal carcinomatosis of colorectal cancer. All consecutive patients with an available preoperative computed tomography (CT) scan who underwent CRS-HIPEC for peritoneal carcinomatosis of colorectal cancer in two centers were analyzed. Skeletal muscle mass was determined using the L3 muscle index on the preoperative CT scan. The cutoff values defined by Prado et al. were used to classify the patients as sarcopenic or nonsarcopenic. Of the study's 206 patients, 90 (43.7 %) were classified as sarcopenic. The sarcopenic patients underwent significantly more reoperations than the nonsarcopenic patients (25.6 vs. 12.1 %; p = 0.012). The mean L3 muscle index was significantly lower for the patients who experienced severe postoperative complications than for the patients without severe postoperative complications (85.6 vs. 110.2 cm(2)/m(2); p = 0.008). In a multivariable logistic regression model, L3 muscle index was the only parameter independently associated with the risk of severe postoperative complications (odds ratio 0.93; 95 % confidence interval 0.87-0.99; p = 0.018). Skeletal muscle mass depletion, assessed using CT-based muscle mass measurements, is associated with an increased risk of severe postoperative complications in patients undergoing CRS-HIPEC for colorectal peritoneal carcinomatosis and could therefore be used in preoperative risk assessment.

Trends in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of synchronous peritoneal carcinomatosis of colorectal origin in the Netherlands

BackgroundPopulation-based data on the percentage of colorectal cancer (CRC) patients with synchronous peritoneal carcinomatosis (PC) being treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are currently lacking. The current population-based study describes trends in the use of CRS–HIPEC in the Netherlands, one of the first countries where CRS and HIPEC was introduced. MethodsAll patients diagnosed with synchronous PC of CRC between 2005 and 2012 were extracted from the Netherlands Cancer Registry (n = 4623). Patients with primary appendiceal cancer were excluded resulting in a study population of 4430 patients. Trends in the use of CRS–HIPEC over time were analyzed by means of a Cochrane–Armitage trend test. Survival proportions were calculated as the time between diagnosis and date of death or last follow-up (January 2014). ResultsOf the total 4430 patients with synchronous PC, 297 (6.4%) underwent treatment with CRS–HIPEC. The proportion of colorectal PC patients receiving CRS–HIPEC increased significantly over time from 3.6% in 2005–2006 to 9.7% in 2011–2012 (p < 0.0001). Overall median survival (MS) for patients treated with CRS–HIPEC was 32.3 months, whereas MS rates were respectively 12.6, 6.1 and 1.5 for months palliative chemotherapy with/without surgery, palliative surgery and best supportive care. ConclusionThe proportion of patients diagnosed with synchronous PC from CRC treated with CRS–HIPEC has increased significantly over time and currently almost 10% of PC patients are treated with CRS–HIPEC. Median survival in this population based group is 32.3 months.

Gene therapy using therapeutic and diagnostic recombinant oncolytic vaccinia virus GLV-1h153 for management of colorectal peritoneal carcinomatosis

Peritoneal carcinomatosis (PC) is a terminal progression of colorectal cancer (CRC). Poor response to cytoreductive operation and chemotherapy coupled with the inability to reliably track disease progression by the use of established diagnostic methods, make this a deadly disease. We examined the effectiveness of the oncolytic vaccinia virus GLV-1h153 as a therapeutic and diagnostic vehicle. We believe that viral expression of the human sodium iodide transporter (hNIS) provides both real-time monitoring of viral therapy and effective treatment of colorectal peritoneal carcinomatosis (CRPC). Infectivity and cytotoxic effect of GLV-1h153 on CRC cell lines was assayed in vitro. Viral replication was examined by standard viral plaque assays. Orthotopic CRPC xenografts were generated in athymic nude mice and subsequently administered GLV-1h153 intraperitoneally. A decrease in tumor burden was assessed by mass. Orthotopic tumors were visualized by single-photon emission computed tomography/computed tomography after Iodine ((131)I) administration and by fluorescence optical imaging. GLV-1h153 infected and killed CRC cells in a time- and concentration-dependent manner. Viral replication demonstrated greater than a 2.35 log increase in titer over 4 days. Intraperitoneal treatment of orthotopic CRPC xenografts resulted in a substantial decrease in tumor burden. Infection of orthotopic xenografts was therapeutic and facilitated monitoring by (131)I-single-photon emission computed tomography/computed tomography via expression of hNIS in infected tissue. GLV-1h153 kills CRC in vitro effectively and decreases tumor burden in vivo. We demonstrate that GLV-1h153 can be used as an agent to provide accurate delineation of tumor burden in vivo. These findings indicate that GLV-1h153 has potential for use as a therapeutic and diagnostic agent in the treatment of CRPC.

Cytoreductive Surgery and HIPEC for Colorectal Cancer: Facing the Facts and Addressing the Issues to Allow for Widespread Acceptance

60% of colorectal cancers are diagnosed at an advanced stage. Curative strategies involving multimodality treatment with surgical resection and chemotherapy have been employed for liver and lung metastases from colorectal cancer. Peritoneal metastases are diagnosed synchronously in 10-15% of all newly diagnosed colorectal cancer, and in 40-70% of patients who suffer a recurrence. They are the sole sites of metastases in 10-30% of these cases. An understanding of peritoneal metastases must take into consideration the following: 1. Peritoneal metastases do not respond to systemic chemotherapy in the same fashion as liver and lung metastases 2. Peritoneal disease causes many local problems, resulting in disruption of planned chemotherapy 3. CRS and HIPEC actually works for peritoneal disease and 4. Peritoneal disease is usually not detected on state-of-the-art imaging modalities. Despite mounting evidence of the effectiveness of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) at prolonging survival in selected patients with colorectal peritoneal carcinomatosis, there remains a reluctance to explore this combined treatment modality. This is likely to be a result of the perceived morbidity and mortality of such a procedure, with most medical oncologists and colorectal surgeons being unfamiliar with the combined treatment. As with all complex procedures, a learning curve is observed, with proficiency likely only after 25 cases and at a high volume centre, with more than 30 cases annually.An effective management strategy employing CRS and HIPEC for selected patients with colorectal peritoneal carcinomatosis can only be achieved if a concerted effort is made to understand this disease and address the concerns regarding this treatment.

In situ gel-forming dual drug delivery system for synergistic combination therapy of colorectal peritoneal carcinomatosis

A novel local drug delivery system composed of docetaxel loaded micelles and an oxaliplatin loaded hydrogel was fabricated and proved to be potentially useful in the treatment of colorectal peritoneal carcinomatosis.

Serious Postoperative Complications Affect Early Recurrence After Cytoreductive Surgery and HIPEC for Colorectal Peritoneal Carcinomatosis.

The prognosis of patients with peritoneally metastasized colorectal cancer has improved significantly with the introduction of cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS+HIPEC). Although a macroscopically complete resection is achieved in nearly every patient, recurrence rates are high. This study aims to identify risk factors for early recurrence, thereby offering ways to reduce its occurrence. All patients with colorectal peritoneal carcinomatosis treated with CRS+HIPEC and a minimum follow-up of 12months, in April 2014, were analyzed. Patient data were compared between patients with or without recurrence within 12months after CRS+HIPEC. Risk factors were determined using logistic regression analysis. Postoperative complications were graded according to the serious adverse events (SAEs) score, with grade 3 or higher indicating complications requiring intervention. A complete macroscopic cytoreduction was achieved in 96% of all patients treated with CRS+HIPEC. Forty-six of 133 patients (35%) developed recurrence within 12months. An SAE ≥3 after CRS+HIPEC was the only significant risk factor found for early recurrence (odds ratio 2.3; p=0.046). Median survival in the early recurrence group was 19.3months compared with 43.2months in the group without early recurrence (p<0.001). Patients with an SAE ≥3 showed a reduced survival compared with patients without such complications (22.1 vs. 31.0months, respectively; p=0.02). Early recurrence after CRS+HIPEC is associated with a significant reduction in overall survival. This study identifies postoperative complications requiring intervention as the only significant risk factor for early recurrence, independent of the extent of peritoneal disease, highlighting the importance of minimizing the risk of postoperative complications.

45. Colorectal peritoneal carcinomatosis treated by completed surgery + systemic chemotherapy: Futility of HIPEC?

Background: Cytoreductive peritoneal surgery (CPS) associated with hyperthermic intraperitoneal chemotherapy (HIPEC) is considered as the standard treatment for colorectal peritoneal carcinomatosis (CPC). Complete CPS efficacy has been demonstrated but evidence supporting HIPEC’s role is lacking.

425. Survival prognostic factors in patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy: A single institution experience

425. Survival prognostic factors in patients with colorectal peritoneal carcinomatosis treated with cytoreductive surgery and intraoperative hyperthermic intraperitoneal chemotherapy: A single institution experience

50. Cytoreductive surgery and HIPEC in treatment of colorectal peritoneal carcinomatosis: Experimental or standard care? A survey of surgical oncologists and medical oncologists

50. Cytoreductive surgery and HIPEC in treatment of colorectal peritoneal carcinomatosis: Experimental or standard care? A survey of surgical oncologists and medical oncologists

Poor outcome after cytoreductive surgery and HIPEC for colorectal peritoneal carcinomatosis with signet ring cell histology.

Signet ring cell cancer (SRCC) patients have a poor oncologic outcome. The aim of this study was to determine whether the potential drawbacks of hyperthermic intraperitoneal chemotherapy (HIPEC) outweigh the benefits in patients with peritoneally metastasized SRCC. Patients with peritoneal carcinomatosis (PC) of colorectal origin referred to two tertiary centers between April 2005 and December 2013 were identified and retrospectively analyzed. Data were compared between SRCC histology and other differentiations. Three-hundred-fifty-one patients were referred for CRS+HIPEC among which 20 (5.7%) patients were identified with SRCC histology. CRS + HIPEC was performed in 16 of these 20 (80%) and 252 out of the 331 remaining patients (76.1%). A higher proportion of patients in the SRCC-group were diagnosed with N2 stage (62.5% vs. 36.1%, P=0.04). A macroscopic complete resection was achieved in 87.5% and 97.2% respectively (P=0.04). Median survival was 14.1 months compared to 35.1 months (P<0.01). Recurrence occurred in 68.8% of the SRCC patients and in 43.7% of the other histology patients (P=0.05). Patients with SRCC and PC treated with CRS+HIPEC have a poor median survival only slightly reaching over 1 year. In the presence of other relative contraindications, SRCC histology should refrain a surgeon from performing CRS and HIPEC.