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Introduction A laparoscopic approach for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (L-CRS+HIPEC) in highly selected patients has been reported in small cohorts with a demonstrable reduction in length of stay and post-operative morbidity. This study aims to analyse individual patient data from these international centres collected through the Peritoneal Surface Oncology Group International (PSOGI) L-CRS+HIPEC registry. Methods An international registry was designed through a networking database (REDCAP®). All centres performing L-CRS+HIPEC were invited through PSOGI to submit data on their cases. Patient's characteristics, postoperative outcomes and survival were analysed. Results Ten international centres contributed a total of 143 L-CRS+HIPEC patients during the study period. The most frequent indication was low grade pseudomyxoma peritonei in 79/143 (55%). Other indications were benign multicyst mesothelioma in 21/143(14%) and peritoneal metastasis from colon carcinoma in 18/143 (12,5%) and ovarian carcinoma in 13/143 (9%). The median PCI was 3 (2-5). The median length of stay was 6 (5-10) days, with 30-day major morbidity rate of 8.3% and 30-day mortality rate of 0.7%. At a median follow-up of 37 (16-64) months 126/143 patients (88.2%) were free of disease. Conclusions Analysis of these data demonstrates that L-CRS+HIPEC is a safe and feasible procedure in highly selected patients with limited peritoneal disease when performed at experienced centres. While short to midterm outcomes are encouraging in patients with less invasive histology, longer follow up is required before recommending it for patients with more aggressive cancers with peritoneal dissemination.

Peritoneal dissemination of low-grade appendiceal mucinous neoplasms (LAMNs), sometimes referred to as pseudomyxoma peritonei, can result in significant morbidity and mortality. Little is known about the natural history of localized (non-disseminated) LAMNs. The goal of this study was to evaluate the risk of peritoneal recurrence in patients with localized LAMNs. We performed a multi-institutional retrospective review of patients with pathologically confirmed localized LAMNs. Baseline characteristics, pathology, and follow-up data were collected. The primary endpoint was the rate of peritoneal recurrence. We identified 217 patients with localized LAMNs. Median age was 59 years (11–95) and 131 (60%) patients were female. Surgical management included appendectomy for 124 (57.1%) patients, appendectomy with partial cecectomy for 26 (12.0%) patients, and colectomy for 67 (30.9%) patients. Pathology revealed perforation in 46 patients (37.7% of 122 patients with perforation status mentioned in the report), extra-appendiceal acellular mucin (EAM) in 49 (22.6%) patients, and extra-appendiceal neoplastic cells (EAC) in 13 (6.0%) patients. Median follow-up was 51.1 months (0–271). Seven (3.2%) patients developed a peritoneal recurrence, with a median time to recurrence of 14.4 months (2.5–47.0). Seven (15.2%) patients with histologic evidence of perforation had recurrence, versus no patients (0%) without perforation (p

Low-grade appendiceal mucinous neoplasms (LAMN) are commonly managed by community surgeons at diagnosis. There is variability in the treatment of LAMN, both by community and specialist providers. We assessed current management practices for LAMN across surgeons with expertise in peritoneal surface malignancies (PSM). An online survey was sent to 106 international surgeons specializing in PSM. The survey assessed demographics, favored pre-referral management, and definitive management practices for LAMN. The response rate was 40% (67% USA, 33% international). Respondents had performed a median of 18 (interquartile range [IQR] 7.75–29) HIPEC cases in the last year, of which 10 (IQR 4–20) were for LAMN. Ninety-three percent reported more than half of LAMN referrals had already undergone surgery—an estimated 50% appendectomy and 20% right hemicolectomy (RH). No surgeon respondents supported performing right hemicolectomy before referral. For LAMN confined to the appendix, 86% of respondents would definitively treat with appendectomy. In the presence of mucinous implants, 24% would observe after appendectomy and 76% would proceed with HIPEC. All would perform HIPEC if implants contained tumor cells. When LAMN involved the appendiceal base, 67% of respondents would proceed with partial cecectomy, while 33% favored RH. Pre-referral management of LAMN is not standardized and 20% of patients were referred to a surgeon who performs CRS/HIPEC after a right hemicolectomy that would not have been recommended. Management of LAMN by surgeons who treat PSM is also variable. Long-term data and identification of prognostic features are necessary to generate consensus on the optimal management of these complex patients.

The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of desmoplastic small round cell tumor, breast, and gastrointestinal stromal tumor specifically related to peritoneal surface malignancy. These guidelines are developed with input from leading experts including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

The Chicago Consensus Working Group provides multidisciplinary recommendations for palliative care specifically related to peritoneal surface malignancies. These guidelines are developed with input from leading experts including surgical oncologists, medical oncologists, gynecologic oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of neuroendocrine tumors specifically related to the management of peritoneal surface malignancy. These guidelines are developed with input from leading experts, including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

Ovarian cancer peritoneal carcinomatosis requires a multimodal-treatment approach. Current treatment considerations are analyzed in this update and include the management of recurrent malignant ascites and the understanding of its pathophysiology, the role of peritoneal washing cytology in detecting peritoneal metastases, capsular invasion and ovarian cancer histologic type, interpretation of pretreatment Ca-125 levels at different time points of ovarian cancer therapeutic management, characteristics of 10-year survivors of high-grade ovarian cancer, and the role of lymphadenectomy in ovarian cancer peritoneal carcinomatosis. This update also includes current considerations on the role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in ovarian cancer peritoneal carcinomatosis as well as relevant ongoing phase III randomized controlled trial protocols. The results of the study showed that patients with advanced ovarian cancer who undergo a complete resection need not also undergo systematic lymphadenectomy.

Peritoneal dissemination of low-grade appendiceal mucinous neoplasms (LAMNs), sometimes referred to as pseudomyxoma peritonei, can result in significant morbidity and mortality. Little is known about the natural history of localized (non-disseminated) LAMNs.The goal of this study was to evaluate the risk of peritoneal recurrence in patients with localized LAMNs.We performed a multi-institutional retrospective review of patients with pathologically confirmed localized LAMNs. Baseline characteristics, pathology, and follow-up data were collected. The primary endpoint was the rate of peritoneal recurrence.We identified 217 patients with localized LAMNs. Median age was 59 years (11-95) and 131 (60%) patients were female. Surgical management included appendectomy for 124 (57.1%) patients, appendectomy with partial cecectomy for 26 (12.0%) patients, and colectomy for 67 (30.9%) patients. Pathology revealed perforation in 46 patients (37.7% of 122 patients with perforation status mentioned in the report), extra-appendiceal acellular mucin (EAM) in 49 (22.6%) patients, and extra-appendiceal neoplastic cells (EAC) in 13 (6.0%) patients. Median follow-up was 51.1 months (0-271). Seven (3.2%) patients developed a peritoneal recurrence, with a median time to recurrence of 14.4 months (2.5-47.0). Seven (15.2%) patients with histologic evidence of perforation had recurrence, versus no patients (0%) without perforation (p 0.001); five (10.2%) patients with EAM versus two (1.2%) patients without EAM (p = 0.007), and one (7.7%) patient with EAC versus six (2.9%) patients without EAC (p = 0.355) had recurrence.This multi-institutional study represents the largest reported series of patients with localized LAMNs. In the absence of perforation or extra-appendiceal mucin or cells, recurrence was extremely rare; however, patients with any of these pathologic findings require careful follow-up.

Low-grade appendiceal mucinous neoplasms (LAMN) are commonly managed by community surgeons at diagnosis. There is variability in the treatment of LAMN, both by community and specialist providers. We assessed current management practices for LAMN across surgeons with expertise in peritoneal surface malignancies (PSM).An online survey was sent to 106 international surgeons specializing in PSM. The survey assessed demographics, favored pre-referral management, and definitive management practices for LAMN.The response rate was 40% (67% USA, 33% international). Respondents had performed a median of 18 (interquartile range [IQR] 7.75-29) HIPEC cases in the last year, of which 10 (IQR 4-20) were for LAMN. Ninety-three percent reported more than half of LAMN referrals had already undergone surgery-an estimated 50% appendectomy and 20% right hemicolectomy (RH). No surgeon respondents supported performing right hemicolectomy before referral. For LAMN confined to the appendix, 86% of respondents would definitively treat with appendectomy. In the presence of mucinous implants, 24% would observe after appendectomy and 76% would proceed with HIPEC. All would perform HIPEC if implants contained tumor cells. When LAMN involved the appendiceal base, 67% of respondents would proceed with partial cecectomy, while 33% favored RH.Pre-referral management of LAMN is not standardized and 20% of patients were referred to a surgeon who performs CRS/HIPEC after a right hemicolectomy that would not have been recommended. Management of LAMN by surgeons who treat PSM is also variable. Long-term data and identification of prognostic features are necessary to generate consensus on the optimal management of these complex patients.

The peritoneal surface is a common failure site for gastrointestinal and gynecologic tumors. For chemotherapeutic agents to effectively kill malignant cells in peritoneal implants, agents must first reach the target. The inability of the drug to reach the target is a basic mechanism of drug resistance. Chemotherapy delivered intravenously encounters the following resistances: (a) distribution through vascular space, (b) transport across microvascular wall, (c) transport through the interstitial space, (d) transport across the cell membrane, and (e) actual incorporation. This last step is complicated by the low vascularization of the peritoneum. The intraperitoneal route seems more logical as this route bypasses the first compartment, and the peritoneal cavity can absorb almost all agents and mediates the transfer of intraperitoneally administered chemotherapy, with agents entering the systemic circulation either by diffusion into the vascular compartment or by absorption through peritoneal lymphatics. In addition, the peritoneal-plasma barrier allows dose intensification providing high concentrations of the therapeutic agent while minimizing systemic toxicity. Traditionally, the selection of drugs for intraperitoneal administration has been based on beneficial pharmacokinetic and pharmacodynamic parameters, a good tolerance profile, and proven effectiveness with systemic administration. However, the process appears to be more complex. In this chapter, we will discuss how the tumor microenvironment plays a crucial role and the effects of hyperthermia, try to understand the molecular basis of drug effectiveness/resistance at the gene as well as the protein level, and explain why high concentrations of the therapeutic agent at the level of the tumor do not necessarily translate into greater efficacy.

Minimally invasive surgery is playing an increasing role in the treatment of patients with gastrointestinal and gynaecological malignancies as the data show reduced morbidity, faster recovery and similar oncological outcome when compared to open procedures. The American Society of Peritoneal Surface Malignancies (ASPSM) conducted a retrospective study to analyse peritonectomy procedures and HIPEC done via the laparoscopic route. A database with standard clinical and pathological parameters was set up and distributed amongst ASPSM members. Rate of relapse, morbidity and mortality were the primary endpoints of the study. A total of 90 patients from 7 centres around the world were identified. Sixty percent were female. Mean age was 50 years. Peritoneal carcinomatosis from appendiceal origin was the most common diagnosis in a 64.9% of patients and colon origin was diagnosed in 16.5% of patients. Mean peritoneal cancer index (PCI) was 4.1 (0–10). Forty-one percent of patients had a bowel resection. Mean operative time was 4.7 h (2.5–8). All patients had a complete cytoreduction and HIPEC. Grade 3 and 4 morbidity was 3.0 and 6.5%, respectively. The most common reason for re-operation was an internal hernia in 2 out of 5 cases. Operative mortality and re-admission rates were 0 and 5%, respectively. Mean hospital stay was 7.4 days (1–18). At a mean follow-up of 31.6 months, 15/90 patients have a disease relapse but loco-regional relapse was identified in only five patients. Analysis of these data suggests that minimally invasive approach for peritonectomy procedures and HIPEC is feasible, safe and should be considered as part of the armamentarium for highly selected patients with peritoneal surface malignancies with limited tumour burden, defined as PCI of 10 or less and borderline tumours as low-grade pseudomyxoma and benign multicystic mesothelioma.

Background The field of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has suffered from a lack of clinical trials to validate its expanding use. Objective To evaluate published and ongoing clinical trials seeking to better define role of CRS/HIPEC in the treatment of peritoneal surface malignancies. Methods Systematic review by PubMed search was performed using terms "Clinical trial," "intraperitoneal chemotherapy," and "HIPEC." ClinicalTrials.gov and EudraCT registries were searched for active clinical trials. Eligibility included CRS/HIPEC trials investigating adult patient populations from published clinical reports and/or trials currently accruing or at completion. Results Thirteen published trials and 57 active clinical trials were included for review. Conclusions Published and ongoing U.S. and international clinical trials for CRS and HIPEC are defining important parameters that include improving patient selection, strategic sequences of treatment, cytoreductive strategies, chemotherapeutics, optimal hyperthermic temperature and timing, and toxicity profiles. Main barriers or limitations to trial development remain patient enrollment, trial design, and oncologic community collaboration. Overall progress is positive with increasing number of clinical trials throughout the world. Collaboration between surgeons and the wider oncologic community will be crucial to validate this important treatment strategy.

The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of peritoneal mesothelioma. These guidelines are developed with input from leading experts, including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness of the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

The Chicago Consensus Working Group provides the following multidisciplinary recommendations for the care of patients with peritoneal surface malignancies. This article focuses on the standards of a peritoneal surface malignancy center, standards of billing and coding, standards of operative reports for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, standards of cytoreductive surgery training, and standards of intraoperative chemotherapy preparation. These guidelines are developed with input from leading experts, including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of ovarian neoplasms specifically related to the management of peritoneal surface malignancy. These guidelines are developed with input from leading experts, including surgical oncologists, medical oncologists, gynecologic oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

The Chicago Consensus Working Group provides multidisciplinary recommendations for the management of peritoneal surface malignancies of various causes. These guidelines are developed with input from leading experts including surgical oncologists, medical oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness of the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence. This article serves as an introduction to this effort.

Cytoreductive surgery and heated intraperitoneal chemotherapy (CS/HIPEC) is performed for selected indications at a limited number of specialized centers worldwide. Currently there is no standardized approach to the perioperative care process. We sought to capture current practices in the perioperative management of patients who undergo CS/HIPEC at high-volume centers.Surgeon members of the American Society of Peritoneal Surface Malignancies working at high-volume CS/HIPEC centers (10 cases/year) were invited to complete an online survey. The survey included questions relating to preoperative preparation of patients, intraoperative practices, and postoperative care.Ninety-seven surgeons from five continents completed the survey (response rate 55%). The majority (80%) practiced in academic environments. Most respondents (68%) indicated that a formal preoperative preparatory pathway for CS/HIPEC surgery existed at their centers, but few (26%) had used enhanced recovery protocols in this group of patients. Whereas the intraoperative technical practices of the CS/HIPEC procedure were relatively consistent across respondents, there was little agreement on pre- and postoperative care practices, including use of mechanical bowel preparation, nutritional supplementation, methods of perioperative analgesia, timing of physical therapy and ambulation, nasogastric tube and Foley removal, intravenous fluids, blood transfusion parameters, and postoperative use of deep-vein thrombosis prophylaxis and antibiotics.Perioperative care practices for CS/HIPEC are widely variable nationally and internationally. Standardization of such practices offers an opportunity to incorporate evidence-based interventions and may enhance patient outcomes and improve care standards across all centers that offer this procedure.

The long-term survival of patients with peritoneal carcinomatosis of colorectal origin has been achieved with cytoreductive surgery, which removes all macroscopic implants, combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The current technology for administering intraperitoneal heated chemotherapy is expensive and, for some institutions, unaffordable. We conducted this study to assess the temperature stability provided by a modified, inexpensive system, to offer a simple and low cost alternative to the standard HIPEC delivery equipment. Ten patients with histologically diagnosed peritoneal metastases of adenocarcinoma or pseudomyxoma peritonei underwent cytoreductive surgery and received HIPEC with 5-fluorouracil for 90 min, delivered via our modified system. The temperature was recorded from two probes: one in the inflow catheter and one in the outflow catheter. The intra-abdominal temperature was monitored meticulously to maintain it at between 41 and 42 °C. All patients underwent cytoreductive surgery and HIPEC using our modified delivery system. Temperature stability was achieved in all patients, with a mean of 41.4°. There were no thermal injuries associated with any of the ten perfusions. The mean hospital stay was 15 days and the median survival was 30 months. Analysis of this data demonstrates that the uniform delivery of HIPEC at 41° with this modified system is feasible and safe. The outcome of the patients treated with cytoreductive surgery and HIPEC with this modified system compares favorably to other published series. Its low cost and simple design will give more patients with peritoneal carcinomatosis access to this treatment.

Ovarian cancer peritoneal carcinomatosis requires a multimodal-treatment approach. Current treatment considerations are analyzed in this update and include the management of recurrent malignant ascites and the understanding of its pathophysiology, the role of peritoneal washing cytology in detecting peritoneal metastases, capsular invasion and ovarian cancer histologic type, interpretation of pretreatment Ca-125 levels at different time points of ovarian cancer therapeutic management, characteristics of 10-year survivors of high-grade ovarian cancer, and the role of lymphadenectomy in ovarian cancer peritoneal carcinomatosis. This update also includes current considerations on the role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in ovarian cancer peritoneal carcinomatosis as well as relevant ongoing phase III randomized controlled trial protocols.

Appendiceal mucoceles (AMs) are rare mucin-containing neoplasms with malignant potential. Lack of evidence-based data exists defining clinicopathological features for management. MEDLINE search between 1995 and 2015 was performed using search criteria "Appendix mucocele." Systematic review of patient-, pathologic-, and treatment-related characteristics was performed and data analyzed. Among 276 cases of non-perforated AMs, 163 (59%) patients were female, with variable and nonspecific presentation. Patients were treated with appendectomy (52.1%), right hemicolectomy (17.6%), partial cecectomy (17.2%), and ileocecetomy (13.1%). Pathologic evaluation revealed the following: cystadenoma/low-grade appendiceal mucinous neoplasm (54%), unspecified/benign (25%), retention cyst (14.1%), cystadenocarcinoma (4.2%), and mucosal hyperplasia (2.9%). All 11 (4.2%) patients with cystadenocarcinoma were female (P = 0.004), odds ratio for malignancy 1.07 times higher for women. Synchronous colonic malignancy was reported in three patients (27%) with cystadenocarcinoma (P = 0.007), odds ratio of 12.1. AMs have low risk for malignancy. Treatment should begin with appendectomy-only and subsequently guided by pathologic diagnosis.

One of the most effective mechanisms to contain the spread of an infectious disease through a population is the implementation of quarantine policies. However, its efficiency is affected by different aspects, for example, the structure of the underlining social network where highly connected individuals are more likely to become infected; therefore, the speed of the transmission of the decease is directly determined by the degree distribution of the network. Another aspect that influences the effectiveness of the quarantine is the self-protection processes of the individuals in the population, that is, they try to avoid contact with potentially infected individuals. In this paper, we investigate the efficiency of quarantine and self-protection processes in preventing the spreading of infectious diseases over complex networks with a power-law degree distribution [ P(k)∼k-ν] for different ν values. We propose two alternative scale-free models that result in power-law degree distributions above and below the exponent ν = 3 associated with the conventional Barabasi-Albert model. Our results show that the exponent ν determines the effectiveness of these policies in controlling the spreading process. More precisely, we show that for the ν exponent below three, the quarantine mechanism loses effectiveness. However, the efficiency is improved if the quarantine is jointly implemented with a self-protection process driving the number of infected individuals significantly lower.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have gained momentum as a viable treatment option for primary or recurrent malignancies with peritoneal metastasis (PM). Despite significant progress over the last 30 years, this field has lacked in high-quality randomized, controlled trials, with most data supporting the use of CRS and HIPEC coming from smaller retrospective and prospective trials. Ultimately, validation of treatment efficacy and outcomes will require large, collaborative, well-organized, outcomes-based studies. Thus far, the use of CRS and HIPEC in metastatic gastric, ovarian, pancreatic, and other gastrointestinal malignancies has spurred further development of a growing number of prospective clinical trials to study outcomes and survival benefit. This chapter summarizes some of the notable, completed clinical trials and current trials being conducted.

Background Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are gaining acceptance as treatment for selected patients with colorectal cancer with peritoneal carcinomatosis (CRCPC). Tremendous variations exist in the HIPEC delivery. Methods The American Society of Peritoneal Surface Malignancies (ASPSM) examined the overall survival in patients with CRCPC who underwent a complete cytoreduction and HIPEC with Oxaliplatin vs. Mitomycin C (MMC), stratifying them by the Peritoneal Surface Disease Severity Score (PSDSS). Results Median overall survival (OS) of 539 patients with complete cytoreduction was 32.6 months, 32.7 months for the MMC group and 31.4 months for the Oxaliplatin group (P = 0.925). However, when stratified by PSDSS, median OS rates in PSDSS I/II patients were 54.3 months in those receiving MMC vs. 28.2 months in those receiving oxaliplatin (P = 0.012), whereas in PSDSS III/IV patients, median OS rates were 19.4 months in those receiving MMC vs. 30.4 months in those receiving Oxaliplatin (P = 0.427). Conclusion These data suggest that MMC might be a better agent for HIPEC delivery than Oxaliplatin in patients with CRCPC, favorable histologies and low burden of disease (PSDSS I/II) undergoing complete cytoreduction. Propsective studies are warranted, which stratify patients by their PSDSS and randomize them to HIPEC with MMC vs. Oxaliplatin. J. Surg. Oncol. 2014 110:779–785. © 2014 Wiley Periodicals, Inc.

Introduction Most classifications of mucinous appendiceal neoplasms (MAN) do not take into consideration the type of primary tumor or the burden of peritoneal disease. Materials and Methods We conducted a retrospective evaluation of 229 patients with MAN. The severity of their disease was analyzed with the Peritoneal Surface Disease Severity Score (PSDSS) on a five-point scale that included: (1) the primary appendiceal tumor, (2) the type of peritoneal dissemination, and (3) the burden of disease. Overall survival was analyzed according to five tiers of estimated disease severity based on the above parameters. Results There were 19, 67, 59, 43, and 41 patients with PSDSS 0, I, II, III, and IV, respectively. One hundred seventy-three patients underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Overall survival was 80.0 months in this group with 5-year survival of 100%, 79.2%, 23.3%, and 6.9% in patients with PSDSS I, II, III, and IV, respectively (P

The American Society of Peritoneal Surface Malignancies (ASPSM) is a consortium of cancer centers performing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC). This is a position paper from the ASPSM on the standardization of the delivery of HIPEC.A survey was conducted of all cancer centers performing HIPEC in the United States. We attempted to obtain consensus by the modified method of Delphi on seven key HIPEC parameters: (1) method, (2) inflow temperature, (3) perfusate volume, (4) drug, (5) dosage, (6) timing of drug delivery, and (7) total perfusion time. Statistical analysis was performed using nonparametric tests.Response rates for ASPSM members (n = 45) and non-ASPSM members (n = 24) were 89 and 33 %, respectively. Of the responders from ASPSM members, 95 % agreed with implementing the proposal. Majority of the surgical oncologists favored the closed method of delivery with a standardized dual dose of mitomycin for a 90-min chemoperfusion for patients undergoing cytoreductive surgery for peritoneal carcinomatosis of colorectal origin.This recommendation on a standardized delivery of HIPEC in patients with colorectal cancer represents an important first step in enhancing research in this field. Studies directed at maximizing the efficacy of each of the seven key elements will need to follow.

Chemotherapy hyperthermic intraperitoneal chemotherapy (HIPEC) is playing an ever increasing role in the management of colorectal cancer (CRC) with peritoneal metastases (PM) as results approach those of surgical resection of liver metastases. Selection criteria for treatment type, sequence and timing of currently available therapies remain ill-defined.We review the current published literature analyzing outcomes by treatments with surgery, systemic chemotherapy, cytoreductive surgery (CRS) and HIPEC, and ongoing clinical trials. A clinical pathway that incorporates all currently available therapies, determining the timing and sequence of such therapies was constructed.Most of the literature on outcome data comes from studies reporting the results of CRS and HIPEC with large series showing a median survival of 32-47 months. Meanwhile, the vast majority of patients, over 90% in the United States, are being treated with palliative systemic therapies following the NCCN guidelines.Cooperation between medical and surgical oncologists represents an unmet need in oncology when it comes to patients with CRC with PM. The presented clinical pathway constitutes a feasible and much needed first step to start this cooperation.

Background Peritoneal metastases remain an under addressed problem for which this review serves to investigate the efficacy of systemic chemotherapy and radical surgical treatments in this disease entity. Methods The literature between 1995 and June 2009 was surveyed systematically through a review of published studies on the treatment outcomes of metastatic colorectal cancer to the peritoneum on the Medline and PubMed databases. Results A total of 2,492 patients from 19 studies were reviewed. One thousand and eighty-four patients treated with complete cytoreductive surgery (CCS) and hyperthermic intraperitoneal chemotherapy (HIPEC) and 1,408 patients were treated with palliative surgery and/or systemic chemotherapy. For CCS HIPEC, the overall survival ranged between 20 and 63 (median 33) months, and 5-year survival ranged between 17% and 51% (median 40%). For palliative surgery and/or systemic chemotherapy, the overall survival ranged between 5 and 24 (median 12.5) months, and 5-year survival ranged between 13% and 22% (median 13%). Conclusion Systemic therapies have not proved effective and randomised clinical trials have not sufficiently addressed patient subpopulations with metastatic disease of this entity. Current evidence have demonstrated the efficacy associated with CCS HIPEC for which should now be embraced as the standard of care. J. Surg. Oncol. 2013;107:566–573. © 2012 Wiley Periodicals, Inc.

Tumor involvement of the peritoneum-peritoneal carcinomatosis-is a heterogeneous form of cancer that had been generally regarded as a sign of systemic tumor disease and as a terminal condition. The multimodal treatment approach for patients with peritoneal carcinomatosis, which had been conceived and developed, consists of what is known as cytoreductive surgery, followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Depending on the tumor mass as assessed intraoperatively and the histopathological differentiation, patients who undergo cytoreductive surgery and HIPEC have a significant survival benefit. Mean increases in the survival period ranging from six months to up to four years have now been reported. In view of the substantial logistic effort and the extent of the surgery involved, this treatment approach represents a major challenge both for patients and for surgical oncologists, as well as for the members of the overall interdisciplinary structure required, which includes oncology, anesthesiology and intensive care, psycho-oncology, and patient management. The surgical procedures alone may take 8-14 hr. The present paper provides an overview of the basis for the approach and the use of specialized classifications and quantitative prognostic indicators.

Introduction. Increasing numbers of patients with pseudomyxoma peritonei (PMP) of appendiceal origin are being evaluated with a low tumor burden. We explored a minimally invasive approach for this group of patients.Materials and Methods. We designed a protocol in which patients with a PMP diagnosis would have a diagnostic laparoscopy. If limited carcinomatosis (PCI ≤ 10) is identified, the procedure will continue laparoscopically. If extensive carcinomatosis (PCI > 10) is found, then the procedure will be converted to an open approach.Results. From December 2008 to December 2011, 19 patients had a complete cytoreduction and HIPEC: 18 of them (95%) were done laparoscopically and 1 of them (5%) was converted to an open procedure. Mean PCI was 4.2. Grade 3 morbidity was 0, and one patient (5%) experienced a grade 4 complication, needing a reoperation for an internal hernia. There were no mortalities. Mean length of hospital stay was 5.3 days. At a mean follow-up of 17 months (1–37) all 19 patients are alive and free of disease.Conclusion. This study demonstrates that cytoreductive surgery and HIPEC via the laparoscopic route is feasible and safe and should be offered to patients with limited pseudomyxoma peritonei of appendiceal origin.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are being widely used in the treatment of patients with peritoneal surface malignancies. The open procedure has been associated with high grade III and IV morbidity and prolonged hospitalization.Patients with peritoneal surface malignancies and no gross evidence of carcinomatosis on the computed tomographic scan were enrolled to undergo laparoscopic CRS and HIPEC. We aimed to assess the feasibility, safety, and outcome of this procedure. Postoperative complications were reported according to the National Cancer Institute Common Toxicity Criteria.From October 2008 to January 2010, 14 patients were enrolled into the protocol. Amongst these 14 patients, one patient was found with extensive carcinomatosis at the time of laparoscopy and had no surgical procedure. Thirteen patients had a complete cytoreduction and HIPEC, 10 (77%) laparoscopically and 3 (23%) were converted to an open procedure. There was one grade 3 morbidity (10%) and one patient (10%) in the laparoscopy group experienced a grade 4 complication, needing a reoperation for an internal hernia. Mean length of hospital stay was 6 days for those completed laparoscopically, 8 days for those converted to an open procedure and 8 days for a matched cohort of patients with an upfront open procedure.This initial investigative stage demonstrates the feasibility and safety of cytoreductive surgery and HIPEC via the laparoscopic route in selected patients with low-tumor volume and no small bowel involvement mainly from appendiceal malignancies. Longer follow-up and additional studies are required to evaluate its long-term efficacy.

To evaluate the role of modern systemic therapies and its role as palliative or curative therapy for patients with colorectal peritoneal carcinomatosis with an emphasis on patient selection with the colorectal Peritoneal Surface Disease Severity Score (PSDSS). From three specialized treatment centers, patients with colorectal peritoneal carcinomatosis were identified between December 1988 to December 2009 to receive best supportive care, standard, or modern systemic therapies. Intent was classified as palliative or curative (if treated by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy). Patients were stratified according to the PSDSS. Survival was estimated by the Kaplan–Meier method. Palliative and curative treatment achieved a median survival of 9 (95% confidence interval [95% CI] 5.9–12.8) and 38 (95% CI 30.2–45.2) months, respectively (P

Background Evaluation of peritoneal metastases by computed tomography (CT) scans is challenging and has been reported to be inaccurate. Methods A multi-institutional prospective observational registry study of patients with peritoneal carcinomatosis from colorectal cancer was conducted and a subset analysis was performed to examine peritoneal cancer index (PCI) based on CT and intraoperative exploration. Results Fifty-two patients (mean age 52.6 ± 12.4 years) from 16 institutions were included in this study. Inaccuracies of CT-based assessment of lesion sizes were observed in the RUQ (P = 0.004), LLQ (P

Background: KRAS mutated colorectal cancers (CRC) are reported to be associated with a poor response to anti-EGFR monoclonal antibody therapy and poor prognosis. We studied the rates of KRAS mutated tumors in patients with peritoneal carcinomatosis from CRC and investigated the association of KRAS status with specific clinicopathologic factors. Methods: A retrospective observational study of tumor specimens from 23 patients with peritoneal carcinomatosis from CRC was performed using standard genomic DNA sampling techniques to identify KRAS mutations. Correlation between clinicopathologic factors and KRAS mutation status was performed using the Fisher exact test or χ 2 test, as appropriate. Results: Eleven (48%) of 23 patients had KRAS mutations. There were no statistically significant correlations in patient demographics, tumor pathology, surgical evaluation, treatments, or survival outcomes for peritoneal carcinomatosis between patients with KRAS mutations or wild-type KRAS status. Conclusion: The prevalence of KRAS mutation in CRC patients with peritoneal carcinomatosis is 48% in this preliminary study and clinicopathologic factors appear to be independent of mutation status.

The current treatment of peritoneal surface malignancies (PSMs) is moving from a nihilistic approach, into a combined modality approach offering selected patients long-term survival. As primary PSM are rare, extrapolation of data from clinical trials of related disease is necessary to develop treatment guidelines. Secondary PSM are more common, and therefore, treatment guidelines should be developed based on prospective clinical trials. We reviewed the published and ongoing clinical trials studying the treatment of PSM.

Cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy have achieved good long-term results in patients with complete surgical eradication of their peritoneal dissemination but at the expense of significant perioperative morbidity and mortality. The high complication rate has been attributed to the steep learning curve associated with this procedure. We report on the current literature regarding the learning curve for this procedure and the key components that determine the success in learning this new skill. J. Surg. Oncol. 2009;100:293–296. © 2009 Wiley-Liss, Inc.

Primary signet-ring cell carcinoma (SRC) of colorectal and appendiceal origin is a rare entity with an aggressive biology and clinical behavior. The majority of patients develop peritoneal carcinomatosis (PC) early in the disease. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may potentially improve survival.An observational study of 33 patients with SRC of colorectal or appendiceal origin was identified through a retrospective review of two peritoneal surface malignancy databases between January 1997 and December 2008. Survival analysis was performed using the Kaplan-Meier method.Thirty-three patients (18 women (55%); mean age at diagnosis of carcinomatosis, 49 (standard deviation = 12) years) were identified to have SRC, with 15 cases of colorectal and 18 of appendiceal origin. For patients with colonic SRC who underwent complete CRS and HIPEC versus systemic chemotherapy only, the median survival was 13 and 18 months (P = 0.75). For patients with appendiceal SRC who underwent complete CRS and HIPEC versus systemic chemotherapy only, the median survival was 27 and 15 months (P = 0.12).There seems to be less survival benefits after a complete CRS and HIPEC as a curative treatment for PC from colorectal SRC compared with that for non-SRC colorectal adenocarcinoma. However, in patients with appendiceal SRC, long-term survival is a reality after treatment.