Progress in treatments for colorectal cancer peritoneal metastases during the years 2010–2015. A systematic review

doi:10.1016/j.critrevonc.2016.01.017

Critical Reviews in Oncology/Hematology

Volume 100, April 2016, Pages 209-222

https://doi.org/10.1016/j.critrevonc.2016.01.017 Get rights and content

Highlights

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The treatment paradigm of colorectal cancer peritoneal metastases is rapidly evolving.
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We systematically reviewed the medical literature of the last five years.
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Survival improvements have been associated to cytoreductive surgery and HIPEC.
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Progress in epidemiology and systemic therapy of peritoneal metastases was addressed.
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Cytoreductive surgery with HIPEC is increasingly accepted as a treatment option.

Abstract

Peritoneal metastases (PM) from colorectal cancer (CRC) were traditionally associated with bad prognosis. Only recently, cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has resulted in survival improvements. A systematic literature search between January 2010 and June 2015 was performed. Studies were selected and appraised according to predetermined criteria. Nineteen cohort studies, and thirteen comparative studies of CRS/HIPEC were included. The weighted median overall survival was 31.6 months (range 16–51). Major morbidity was 17.6–52.4% (weighted average 32.6%). Mortality was 0–8.1% (weighted average 2.9%). Additional relevant topics, such as CRC-PM prevalence, results by systemic therapies, preoperative work-up, and technical aspects were summarized through a narrative review. The recent literature suggests that CRS/HIPEC is gaining acceptance as standard of care for selected CRC-PM patients. Refinement of selection criteria, and rationalization of comprehensive systemic and local-regional management is ongoing. Prevention and early treatment of PM are new and promising options.

Introduction

Colorectal cancer (CRC) is the third most common tumor worldwide (Torre et al., 2015). Recent advances, such as early diagnosis by colonoscopy, and highly effective systemic and molecularly targeted agents, have significantly improved patient survival. The use of local therapies to treat metastatic tumor regionally confined to specific organs (such as liver or lung) is a new concept that has resulted in further improvements (Brenner et al., 2014, Tomlinson et al., 2007). Peritoneal dissemination from CRC or other gastro-intestinal and gynecological malignancies is common, and it has been traditionally regarded as end-stage disease only amenable to palliation by systemic chemotherapy (sCT), or supportive care (Sugarbaker and Ryan, 2012). In recent years, better knowledge of the natural history and patterns of tumor dissemination has made increasingly clear that involvement of peritoneal surfaces by CRC may either occur in the absence of hematogenous metastases, or represent the dominant clinical picture (Sugarbaker and Ryan, 2012).

Consistently with the current understanding of peritoneal carcinomatosis as a local-regional disease entity, a novel treatment approach combines aggressive cytoreductive surgery (CRS) to remove all visible tumor with hyperthermic intraperitoneal chemotherapy (HIPEC) to eradicate microscopic residual disease (Sugarbaker, 1995). The term peritoneal carcinomatosis is being abandoned in favor of peritoneal metastases (PM), that implies the possibility of cure, in contrast with the former that suggests incurable disease (Sugarbaker and Ryan, 2012). A similar paradigm shift has occurred in the management of CRC liver metastases (LM) (Tomlinson et al., 2007).

Despite a randomized trial, and a growing body of retrospective data suggesting survival benefit over historical and contemporary non-randomized controls (Verwaal et al., 2003, Weber et al., 2012), criticism still centers on the scarcity of high-quality controlled studies, high rates of life-threatening complications, and lack of standardization of the comprehensive approach (Sugarbaker and Ryan, 2012). In the recent history of peritoneal oncology, most of the conceptual evolutions and changes in treatment options have occurred during the last three decades. We reviewed the relevant advancements and promising directions emerged during the last five years in the rapidly evolving framework of CRC-PM clinical management.

Section snippets

Search strategy

A systematic search of papers reporting outcome results of CRS/HIPEC in patients with CRC-PM was conducted through the PubMed database between January 2010 and June 2015, according to PRISMA guidelines (Moher et al., 2010). The following keywords were used: colorectal cancer; peritoneal metastases; peritoneal carcinomatosis; cytoreductive surgery; HIPEC; and combinations hereof. The reference lists were searched to identify additional relevant studies. Exclusion criteria were the following:

Prevalence of colorectal peritoneal metastases

The epidemiology of CRC-PM has been addressed for the first time in population-based studies by three recent reports (Segelman et al., 2012, Lemmens et al., 2011, van Gestel et al., 2014). Among 11.124 CRC patients observed in Stockholm County between 1995 and 2007, 924 patients had synchronous or metachronous PM (8.3%). Isolated PM occurred in 585 patients (4.8%). The prevalence of synchronous PM was 4.3%. The cumulative incidence of metachronous PM was 4.2% (Segelman et al., 2012). Among

Treatment by systemic chemotherapy

There are poor literature data on sCT in CRC-PM, because of both a nihilistic attitude toward this condition, and poor accuracy of modern radiological tools in staging and response evaluation of PM. These patients are often excluded from trials because they have “non-measurable disease” (Sugarbaker and Ryan, 2012). The available information mainly come from surgical series, control arms of trials comparing CRS/HIPEC and sCT, or subset analyses of small numbers of patients with CRC-PM included

Principles of cytoreductive surgery and perioperative intraperitoneal chemotherapy

Cytoreductive surgery may be seen as a tool to maximize response to intraperitoneal chemotherapy, because locally delivered drugs penetrate in tumor tissue not more than 2–3 mm. On the other side, the role of local-regional chemotherapy is to preserve the macroscopically complete surgical response by eradicating microscopic residual disease (Sugarbaker, 1995). CRS must aim at removing all visible tumor, since the survival advantage of macroscopic cytoreduction, over minimal residual disease has

Cohort studies

The study published in 2003 by Verwaal demonstrating the superiority of CRS/HIPEC over sCT and palliative surgery still remains the only randomized trial conducted in the setting of CRC-PM (Verwaal et al., 2003). The cohort studies published during the years 2010–2015 are listed in Table 2 (Elias et al., 2010, Elias et al., 2014a, Passot et al., 2012, Simkens et al., 2015, Huang et al., 2014b, Cashin et al., 2014, Ceelen et al., 2014, Passot et al., 2014, Nikolic et al., 2014, Blackham et al.,

Prevention and early treatment of CRC-PM

It has been widely acknowledged that treatment results of established macroscopic PM are better when peritoneal disease is lower in extent, in terms of both survival and operative morbidity (Weber et al., 2012, Elias et al., 2010, Chua et al., 2009). Most CRC-PM patients are not suitable for local-regional treatment, due to extensive disease, systemic metastases, and/or poor clinical conditions (Koppe et al., 2006, Goéré et al., 2015). but, in the palliative setting, modern sCT appears to be

Treatment-related morbidity and quality of life

Patients with PM are often referred with massive tumor load or after extensive surgical and medical treatments. Their definitive management involves further demanding surgical and comprehensive procedures. Also, there appears to be a steep learning curve in performing these complex procedures (Kusamura et al., 2012). Although impressive reductions in complications have more recently occurred in high-volume centers with increasing experience, higher operative risk may be expected and needs to be

Conclusions and future directions

During the last five years, several accomplishments have greatly contributed to the progress of peritoneal oncology: (i) epidemiology of CRC-PM has been addressed in population-based studies (Segelman et al., 2012, Lemmens et al., 2011, van Gestel et al., 2014); (ii) large retrospective series have strongly suggested that sCT and targeted therapies are less effective in treating CRC-PM than hematogenous metastases (Franko et al., 2012, Klaver et al., 2012); (iii) strict selection criteria have

Conflict of interest

Dario Baratti, Shigeki Kusamura, Marcello Guaglio, Monica Niger, Marcello Deraco have no conflict of interest to disclose. Filippo Pietrantonio: consultant for Merck Serono, Bayer, Amgen; Educational Grants for Roche, Merck Serono, Amgen.

Aknowledgments

This study was partially supported by funds of the Italian Association for Cancer Research (AIRC) and the Italian health Minister. The funding sources had no role in study design, data collection, data analysis, data interpretation, writing the report, and the final decision to submit the paper for publication.

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Cited by (89)

Oncological outcomes and hospitalization cost of hyperthermic intraperitoneal chemotherapy (HIPEC) open and closed abdomen techniques: Results from two French expert centers
2024, European Journal of Surgical Oncology
Hyperthermic intraperitoneal chemotherapy (HIPEC) associated with CC0 excision is performed using either an open (OPEN_HIPEC) or closed abdominal technique (CLOSED_HIPEC). However, little data is available on the costs of this treatment, as there is no code for HIPEC in the French Classification of Medical Acts. Oncological outcomes and the mean cost of hospitalization were compared.
Between 2017 and 2021, 144 patients with peritoneal carcinomatosis (all etiologies) were included (OPEN_HIPEC, n = 70; CLOSED_HIPEC, n = 74) in this retrospective two-center study. Morbi-mortality, overall survival (OS), recurrence-free-survival (RFS) and mean cost of hospitalization were compared.
The median OS and RFS were 71.3 months [63–71.5] and 26.8 months [20–35.3] respectively, and were similar for both techniques; and after stratification by histology. Multivariate analysis adjusted on PCI score of OS identified mitomycin as a protective factor (HR = 0.31 [0.10–0.90], p = 0.032) and ASA score>2 (HR = 2.32 [1.32– 4.06], p = 0.003) and number of resection (HR = 1.21 [1.06-1.39], p = 0.006) as a risk factors of RFS. Complication rates at day 30 were similar between OPEN and CLOSED_HIPEC, 31 (44.3 %) vs 42 (56.8 %); p = 0.135. OPEN_HIPEC had more severe complications (11 (35.5 %) vs 6 (14.3 %); p = 0.034). The mean cost of hospitalization was estimated as €15,627 for OPEN_HIPEC and €14,211 for CLOSED_HIPEC for a mean length-of-stay of 12.7 and 16.7 days respectively. The mean amount received by the hospital per hospitalization was estimated at €16,399 and €15,536 respectively.
OS and RFS were similar for open and closed HIPEC. Severe complications at day 30 were more frequent in OPEN_HIPEC group. The amount received by hospital for both HIPEC techniques is sufficient.
Immunological effects of heated intraperitoneal chemotherapy can be augmented by thymosin α1
2023, International Immunopharmacology
Peritoneal metastases of colorectal carcinoma origin (PM-CRC) are treated by cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC). However, the majority of patients recur, calling for novel treatments. We explored the immunogenic changes induced by HIPEC and the possibility to use thymosin α1 (Tα1) as an immune-stimulatory agent.
We used an experimental murine model of PM-CRC combined with mitomycin (MMC)-based HIPEC. We determined immune cell infiltration into tumor metastases after HIPEC administration by means of immunohistochemistry, and determined immunogenic cell death signals in tumor cells by real-time polymerase chain reaction.
Mice with PM-CRC treated by HIPEC had increased overall survival (OS) compared to sham-treated mice (median OS 22.8 vs 18.9 days, respectively; P < 0.001). HIPEC induced increased infiltration of CD4+, CD8+, CD68 + and CD20 + cells into omental and visceral metastases at a magnitude of 40–100 %. We searched for potential immune signals induced by HIPEC by determining its effects on known immunogenic cell death proteins (heat-shock protein [HSP]-70, HSP-90 and calreticulin). HIPEC significantly increased HSP-90 mRNA expression (2.37 ± 1.5 vs 1-fold change, P < 0.05). The OS of Tα1 treated mice significantly improved compared to HIPEC-treated mice (16.3 ± 0.8 vs 14.1 ± 0.6 days, respectively, P = 0.02) and vs sham (11.8 ± 0.8 days, P = 0.007).
HIPEC induced immunogenic changes that led to increased immune cell infiltration. These changes were further augmented by Tα1 treatment. Future studies aimed at optimizing Tα1 treatment should focus upon the immune response it evokes.
Thymosin alpha 1 as an adjuvant to hyperthermic intraperitoneal chemotherapy in an experimental model of peritoneal metastases from colonic carcinoma
2022, International Immunopharmacology
Heated intraperitoneal chemotherapy (HIPEC) is currently implemented in the treatment of peritoneal metastases from colorectal carcinoma (PM-CRC) origin. However, recurrence is common and the effectiveness of HIPEC has been questioned. The aim of this study was to evaluate the use of thymosin alpha 1 (Tα1), an immunomodulatory molecule, as an adjuvant to HIPEC treatment.
We developed an experimental model of HIPEC by the induction of PM-CRC in C57BL mice and intra-abdominal perfusion of mitomycin C (MMC). Mice were treated with Tα1 at 0.6 mg/kg for 5 days after HIPEC. Clinical and immunological parameters were compared between HIPEC and HIPEC + Tα1 groups.
Treatment with Tα1 increased overall survival of mice compared to HIPEC treatment alone and sham-treated animals (16.1 ± 0.8 vs. 14.1 ± 0.6 and 11.8 ± 0.8, respectively, p = 0.02). Tα1 had no direct anti-tumor effect, as seen by lack of inhibition of tumor cell proliferation. Tα1 treatment induced a T helper (Th) 1 immune response in tumor metastases as evidenced by a significant increase of the Th1-specific markers IFN-γ and T-bet (1.21 ± 0.3 vs. 0.52 ± 0.08, p < 0.05; 0.88 ± 0.04 vs. 0.64 ± 0.14, p < 0.05, respectively). This Th1 skew was accompanied by increased CD8⁺ infiltration into omental and visceral metastases by Tα1 treatment compared to sham and HIPEC-treated animals (21.24 ± 2.16 vs. 10.45 ± 0.89 and 7.7 ± 1.3, p < 0.001; 14.12 ± 1.54 vs. 12.12 ± 0.01 and 6.64 ± 0.87, p < 0.01, respectively).
Tα1 augments the effect of HIPEC by the induction of a Th1 anti-tumor immune response. Further experiments should evaluate Tα1 and other novel immunomodulators in order to exploit the immunological opportunities created by HIPEC.
Long-term outcomes of elderly patients with peritoneal metastases of colorectal origin after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy
2022, Surgical Oncology
Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) were reportedly safe for the elderly. However, long-term survival data in this subgroup of patients are scarce. Our aim was to evaluate the peri-operative and long-term outcomes of CRS + HIPEC in colorectal peritoneal metastases (CRC-PM) in patients ≥70 years of age.
We retrospectively analyzed our combined institutional databases for patients who underwent CRS + HIPEC for CRC-PM. Clinical and pathological characteristics, as well as overall survival (OS) and progression-free survival (PFS) were compared between the groups. Tumor extent was measured by the peritoneal carcinomatosis index (PCI) and completeness of cytoreduction by the CCR score. Major morbidity was defined according to Clavien-Dindo classification.
The dataset of 159 patients included 33 elderly and 126 non-elderly patients. Clinical characteristics between the groups differed only in medical comorbidities (Charlson comorbidity index 10 vs. 7, P < 0.001) and delivery of post-HIPEC adjuvant treatment (12.5% vs. 43.8%, P = 0.004). Overall PCI and CCR0 rates were similar between the groups, as were length of stay and major morbidity and mortality rates. Long-term outcomes in the elderly group were lower than those of the non-elderly (median OS: 21.8 vs. 40.5 months, P < 0.001; median PFS: 6 vs. 8 months, P = 0.02, respectively).
CRS + HIPEC in selected elderly patients can be safe in terms of postoperative morbidity and mortality. However, despite the same surgical extents and radicality, their long-term outcomes are inferior, possibly due to under-usage of systemic chemotherapy.
Prehabilitation to improve postoperative outcomes in patients with peritoneal carcinomatosis undergoing hyperthermic intraperitoneal chemotherapy (HIPEC): A scoping review
2022, European Journal of Surgical Oncology
Citation Excerpt :
Median overall survival of patients undergoing HIPEC for peritoneal carcinomatosis from colorectal cancer is approximately 32 months with a range of 16–51. Five-year survival ranges from 22% to 51% [33]. Small studies in patients with peritoneal carcinomatosis from any origin showed a median overall survival of 18 months [27] and a five-year survival rate of 55% [34].
Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) leads to increased survival rates in patients with peritoneal carcinomatosis, but is associated with considerable morbidity and mortality rates. Prehabilitation, a process to optimize a patient's preoperative functional capacity, has a positive impact on recovery after colorectal surgery. The impact of prehabilitation in patients undergoing HIPEC is scarcely investigated. This scoping review and narrative synthesis aims to summarize and evaluate what is currently reported about the effect of prehabilitation on postoperative outcomes after HIPEC.
A literature search of studies reporting on the effect of prehabilitation on outcomes after HIPEC was performed (August 2020). Study characteristics, patient demographics, composition of prehabilitation programs, and reported outcomes used to quantify the effect of prehabilitation were recorded.
The literature search did not yield any studies on the effect of prehabilitation programs on outcomes after HIPEC. As an alternative, studies identifying modifiable risk factors for poor postoperative outcomes after HIPEC that can be targeted by prehabilitation were reviewed to evaluate starting points for prehabilitation. Fourteen studies identify the following preoperative factors: poor nutritional status, poor performance status, low health related quality of life and an history of smoking.
No research has been published on the effect of prehabilitation prior to HIPEC. This review demonstrates that preoperative modifiable risk factors for outcomes in patients undergoing HIPEC are multifactorial. A multimodal prehabilitation program prior to HIPEC, including nutritional support, psychical exercise, psychological support and smoking cessation, might therefore be a promising approach to improve postoperative outcomes.
Perianesthesia Care of the Oncologic Patient Undergoing Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy: A Retrospective Study
2021, Journal of Perianesthesia Nursing
This study was to understand the perianesthesia care for patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS  + HIPEC).
This is a retrospective study.
The perioperative electronic medical records of 189 CRS  + HIPEC surgical cases at a hospital of Western Pennsylvania from 2012 to 2018 were analyzed to study the characteristics of perianesthesia care for CRS  + HIPEC surgery.
The patients' median age was 57 (range 21-83) years, and 60% were men. The mean anesthesia time was 10.47 ± 2.54 hours. Most tumors were appendix or colorectal in origin, and the mean peritoneal cancer index score was 16.19 ± 8.76. The mean estimated blood loss was 623 ± 582 mL. The mean total intravenous crystalloid administered was 8,377 ± 4,100 mL. Fifty-two patients received packed red blood cells during surgery. Postoperatively, 100% of the patients were transferred to the intensive care unit. A majority (52%) of patients were extubated in the operating room. Median lengths of hospital and intensive care unit stays were 13 and 2 days, respectively. A majority (73%) of patients had 1 or more postoperative complications and 29% of patients experienced major postoperative complications (Clavien-Dindo grade III or higher) during the hospital stay. Prolonged hospitalization was owing to gastrointestinal dysfunctions and respiratory failure related to atelectasis and pleural effusion.
CRS  + HIPEC is a major surgery with numerous challenges to the perianesthesia care team regarding hemodynamic adjustment, pain control, and postoperative complications, which demand training and future studies from the perianesthesia care team.

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Dario Baratti, MD is an attending surgeon at the National Cancer Institute in Milan (Italy) since 2000, and a permanent staff member of the Peritoneal Malignancy Program since 2002. He graduated in Medicine in 1990 and obtained his Specialization in Digestive Surgery in 1997, at the University of Milan. He has significant experience with the treatment of peritoneal surface malignancies using cytoreductive surgery and HIPEC. He authored or co-authored 110 articles in indexed peer-reviewed journals (88 on peritoneal surface oncology, 25 as first authors), and several book chapters. He has been lecturer at two European Society of Surgical Oncology (ESSO) courses on peritoneal surface oncology. His main areas of interest are surgical oncology, treatment of peritoneal surface malignancies, soft tissue sarcoma, peritoneal mesothelioma and pseudomyxoma peritonei.

Shigeki Kusamura, MD, PhD, is presently a clinical research fellow at the Peritoneal Malignancy Program of the National Cancer Institute of Milano (Italy). He obtained his Medical Degree at the Faculty of Medical Science (1995), and his Specialization in Gynecology Oncology at the Women Hospital (1999) of the Campinas State University (Brazil). He obtained his PhD at the Campinas State University, presenting his thesis titled “Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in the Treatment of Epithelia Ovarian Cancer”, and his Specialization in Gastro-intestinal Surgery at S. Raffaele University Hospital, Milan, in 2010. His research interests include biology and treatment of peritoneal surface malignancies, gynecologic oncology scientific methodology, statistics in medicine, He is presently the principal investigator of the trial “Effects of high Intra-abdominal pressure on tissue diffusion and pharmacokinectics of cisplatin during HIPEC” funded by the Italian Association for Cancer Research (AIRC). Dr kusamura has published 106 full papers on international peer-reviewed journals (17 as first author).

Filippo Pietrantonio, MD is currently medical oncologist at the National Cancer Institute in Milan (Italy). He obtained his degree in Medicine in 2007 at the University of Parma (Italy) and his Specialization in Oncology in 2011 at the University of Milan (Italy). His field of interest is gastrointestinal oncology. Dr. Pietrantonio is investigator and scientific contributor of many trials in gastrointestinal cancer research. He is involved in clinical and translational research projects in the field of colorectal oncology, with special interest, in the identification of potential molecular predictors of benefit from systemic treatments. He is involved in multidisciplinary boards for the management of peritoneal and hepatic metastases of colorectal cancer. He authored or co-authored several papers in international journals and is member of the Editorial Board of Tumori Journal. He is member of the Scientific Committee of the Italian Association of Medical Oncologists (AIOM).

Marcello Guaglio, MD is presently a clinical research fellow at the National Cancer Institute of Milano (Italy). He graduated in Medicine and obtained his Specialization in General Surgery in 1997, at the University of Milano Bicocca. His field of interest encompasses gastrointestinal surgery, treatment of peritoneal surface malignancies using cytoreductive surgery and HIPEC. His research activity involves clinical and translational investigations in gastrointestinal tumors.

Monica Niger, MD is attending the Fellowship Training Program in Medical Oncology of the University of Milan, at the National Cancer Institute in Milan (Italy). She is committed to clinical activities and, at the same time, is currently engaged in clinical and translational research experiences focused on gastrointestinal cancers, with particular interest in the field of the identification of potential predictive factors of benefit from targeted agents and potential prognostic factors in colorectal cancer.

Marcello Deraco, MD graduated as Medical Doctor at the University of Messina (Italy). He obtained his Specialization in General Surgery at the University of Messina and in Oncology at the University of Paris X (France) in 1993. He has been visiting fellow at the Department of Surgery at the Institut G. Roussy (Villejuiff, France), the Royal Marsden Hospital (London, UK), and the Peritoneal Malignancy Program of the Washington Cancer Center (Washington, DC). Dr. Deraco is Professor at the Residency Program at the University Tor Vergata, Rome. He has dedicated the last 25 years to the advancement of peritoneal surface oncology. As the Head of the Peritoneal Malignancy Program of the National Cancer Institute of Milano (Italy), his research has involved clinical and translational investigations in peritoneal carcinomatosis, pseudomyxoma peritonei and peritoneal mesothelioma. Currently he is Principal Investigator of clinical-biological trials investigating cellular and molecular biology of peritoneal malignancies. He has been Director of the 5th International Workshop on Peritoneal Surface Malignancies. He is the President of SITILO: (Italian Society for Loco Regional Cancer Therapy), Member of the Executive Board of PSOGI (Peritoneal Surface Oncology Group International) and the Secretary GIMe (Italian Mesothelioma Group); Very recently he began Co- Director of the European School for Peritoneal Surface Oncology (ESPSO) a ESSO-PSOGI initiative. Member of several scientific societies as SSO (Society of Surgical Oncology), ESSO (European Society of Surgical Oncology) and SICO (Italian Society of Surgical Oncology).

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Progress in treatments for colorectal cancer peritoneal metastases during the years 2010–2015. A systematic review

Highlights

Abstract

Introduction

Section snippets

Search strategy

Prevalence of colorectal peritoneal metastases

Treatment by systemic chemotherapy

Principles of cytoreductive surgery and perioperative intraperitoneal chemotherapy

Cohort studies

Prevention and early treatment of CRC-PM

Treatment-related morbidity and quality of life

Conclusions and future directions

Conflict of interest

Aknowledgments

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Eur. J. Surg. Oncol.

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Surg. Oncol. Clin. N. Am.

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Eur. J. Surg. Oncol.

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Int. J. Surg.

Crit. Rev. Oncol. Hematol.

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Surg. Oncol.

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Eur. J. Surg. Oncol.

Surg. Oncol. Clin. N. Am.

Surg. Oncol. Clin. N. Am.

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Postoperative complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy affect long-term outcome of patients with peritoneal metastases from colorectal cancer: a two-center study of 101 patients

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Small bowel involvement is a prognostic factor in colorectal carcinomatosis treated with complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy

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The American Society of Peritoneal Surface Malignancies (ASPSM) multiinstitution evaluation of the Peritoneal Surface Disease Severity Score (PSDSS) in 1013 patients with colorectal cancer with peritoneal carcinomatosis